Evidence Report/Technology Assessment 

Number 192 

Lactose Intolerance and Health 

Prepared for: 

Agency for Healthcare Research and Quality 

U.S. Department of Health and Human Services 

540 Gaither Road 

Rockville, MD 20850 

www.ahrq.gov 

Contract No. HHSA 290-2007-10064-I 

Prepared by: 

Minnesota Evidence-based Practice Center, Minneapolis, MN 

Investigators 

Timothy J. Wilt, M.D., M.P.H. 

Aasma Shaukat, M.D., M.P.H. 

Tatyana Shamliyan, M.D., M.S. 

Brent C. Taylor, Ph.D., M.P.H. 

Roderick MacDonald, M.S. 

James Tacklind, B.S. 

Indulis Rutks, B.S. 

Sarah Jane Schwarzenberg, M.D. 

Robert L. Kane, M.D. 

Michael Levitt, M.D. 

AHRQ Publication No. 10-E004 

February 2010 
This report is based on research conducted by the Minnesota Evidence-based Practice Center 

(EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, 

MD (Contract No. HHSA 290-2007-10064-I). The findings and conclusions in this document are 

those of the authors, who are responsible for its content, and do not necessarily represent the 

views of AHRQ. No statement in this report should be construed as an official position of AHRQ 

or of the U.S. Department of Health and Human Services. 

The information in this report is intended to help clinicians, employers, policymakers, and others 

make informed decisions about the provision of health care services. This report is intended as a 

reference and not as a substitute for clinical judgment. 

This report may be used, in whole or in part, as the basis for the development of clinical practice 

guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage 

policies. AHRQ or U.S. Department of Health and Human Services endorsement of such 

derivative products may not be stated or implied. 
This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders. 

Suggested Citation: 

Wilt TJ, Shaukat A, Shamliyan T, Taylor BC, MacDonald R, Tacklind J, Rutks I, 

Schwarzenberg SJ, Kane RL, and Levitt M. Lactose Intolerance and Health. No. 192 (Prepared 

by the Minnesota Evidence-based Practice Center under Contract No. HHSA 290-2007-10064-I.) 

AHRQ Publication No. 10-E004. Rockville, MD. Agency for Healthcare Research and Quality. 

February 2010. 

No investigators have any affiliations or financial involvement (e.g., employment, 

consultancies, honoraria, stock options, expert testimony, grants or patents received or 

pending, or royalties) that conflict with material presented in this report. 

ii 
 

 

Preface 

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based 

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public- and private-sector organizations in their efforts to improve the 

quality of health care in the United States. This report was requested by the Office of Medical 

Applications of Research (OMAR) at the National Institutes of Health (NIH). The reports and 

assessments provide organizations with comprehensive, science-based information on common, 

costly medical conditions, and new health care technologies. The EPCs systematically review the 

relevant scientific literature on topics assigned to them by AHRQ and conduct additional 

analyses when appropriate prior to developing their reports and assessments. 

To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release. 

AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality. 

We welcome written comments on this evidence report. They may be sent to the Task Order 

Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, 

Rockville, MD 20850, or by email to epc@ahrq.gov. 

Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H. 

Director Director, Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality 

Beth A. Collins Sharp, R.N., Ph.D. Stephanie Chang, M.D., M.P.H. 

Director, EPC Program EPC Program Task Order Officer 

Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality 

Jennifer Croswell, M.D., M.P.H. Susanne Olkkola, M.Ed., M.P.A. 

Acting Director Senior Advisor, Consensus Development Program 

Consensus Development Program Office of Medical Applications of Research 

Office of Medical Applications of Research National Institutes of Health 

National Institutes of Health 

iii 
Acknowledgments 

We wish to thank the librarian, Judith Stanke, for her contributions to the literature search, 

Marilyn Eells for her outstanding work in the preparation and text editing of this report; 

Stephanie Chang, M.D., AHRQ Task Order Officer, for her patience and guidance; our 

Technical Expert Panel members for their helpful recommendations, and the reviewers for their 

comments and suggestions. 

iv 
Structured Abstract   

Objectives: We systematically reviewed evidence to determine lactose intolerance (LI) 

prevalence, bone health after dairy-exclusion diets, tolerable dose of lactose in subjects with 

diagnosed LI, and management. 

Data Sources: We searched multiple electronic databases for original studies published in 

English from 1967-November 2009. 

Review Methods: We extracted patient and study characteristics using author’s definitions of 

LI and lactose malabsorption. We compared outcomes in relation to diagnostic tests, including 

lactose challenge, intestinal biopsies of lactase enzyme levels, genetic tests, and symptoms. 

Fractures, bone mineral content (BMC) and bone mineral density (BMD) were compared in 

categories of lactose intake. Reported symptoms, lactose dose and formulation, timing of 

lactose ingestion, and co-ingested food were analyzed in association with tolerability of lactose. 

Symptoms were compared after administration of probiotics, enzyme replacements, lactosereduced milk and increasing lactose load. 

Results: Prevalence was reported in 54 primarily nonpopulation based studies (15 from the 

United States). Studies did not directly assess LI and subjects were highly selected. LI 

magnitude was very low in children and remained low into adulthood among individuals of 

Northern European descent. For African American, Hispanic, Asian, and American Indian 

populations LI rates may be 50 percent higher in late childhood and adulthood. Small doses of 

lactose were well tolerated in most populations. Low level evidence from 55 observational 

studies of 223,336 subjects indicated that low milk consumers may have increased fracture risk. 

Strength and significance varied depended on exposure definitions. Low level evidence from 

randomized controlled trials (RCTs) of children (seven RCTs) and adult women (two RCTs) 

with low lactose intake indicated that dairy interventions may improve BMC in select 

populations. Most individuals with LI can tolerate up to 12 grams of lactose, though symptoms 

became more prominent at doses above 12 grams and appreciable after 24 grams of lactose; 50 

grams induced symptoms in the vast majority. A daily divided dose of 24 grams was generally 

tolerated. We found insufficient evidence that use of lactose reduced solution/milk, with lactose content 

of 0-2 grams, compared to a lactose dose of greater than 12 grams, reduced symptoms of lactose 

intolerance. Evidence was insufficient for probiotics (eight RCTs), colonic adaptation (two 

RCTs) or varying lactose doses (three RCTs) or other agents (one RCT). Inclusion criteria, 

interventions, and outcomes were variable. Yogurt and probiotic types studied were variable 

and results either showed no difference in symptom scores or small differences in symptoms 

that may be of low clinical relevance. 

Conclusions: There are race and age differences in LI prevalence. Evidence is insufficient to 

accurately assess U.S. population prevalence of LI. Children with low lactose intake may have 

beneficial bone outcomes from dairy interventions. There was evidence that most individuals 

with presumed LI or LM can tolerate 12-15 grams of lactose (approximately 1 cup of milk). 

There was insufficient evidence regarding effectiveness for all evaluated agents. Additional 

research is needed to determine LI treatment effectiveness. 

v 

 

 

 

 

 

 

 

 

 

 

Contents 

Executive Summary.......................................................................................................................1 

Evidence Report.........................................................................................................................17 

Chapter 1. Introduction ...............................................................................................................19 

 Lactase Deficiency.................................................................................................................20 

 Lactose Malabsorption...........................................................................................................21 

 Lactose Intolerance ................................................................................................................21 

Treatment of Lactose Intolerance .................................................................................... 22 

Health Outcomes of Dairy Exclusion Diets..................................................................... 22 

Tolerable Dose of Lactose ............................................................................................... 23 

Strategies of Manage Individuals with Diagnosed Lactose Intolerance.......................... 25 

Key Questions Addressed in this Report ............................................................................... 26 

Chapter 2. Methods.....................................................................................................................27 

Criteria for Inclusion/Exclusion of Studies in Reviewing and Searching for the 

Evidence: Literature Search Strategies for Identification of Relevant Studies to 

Overview................................................................................................................................27 

 Analytic Framework ........................................................................................................ 27 

Answer the Key Questions.................................................................................................. 28 

 General Inclusion Criteria................................................................................................ 28 

Key Question 1: What is the prevalence of lactose intolerance? How does this differ 

by race, ethnicity, and age?........................................................................................... 28 

Key Question 2: What are the health outcomes of dairy exclusion diets?....................... 30 

Key Question 3: What amount of daily lactose intake is tolerable in subjects with 

lactose intolerance?.......................................................................................................32 

Key Question 4: What strategies are effective in managing individuals with 

diagnosed lactose intolerance?......................................................................................33 

Assessment of Methodological Quality of Individual Studies .............................................. 33 

 Data Synthesis........................................................................................................................34 

Grading the Evidence for Each Key Question.......................................................................34 

Assess Study Quality and Strength of Evidence.............................................................. 34 

Chapter 3. Results .......................................................................................................................37 

Key Question 1: What is the prevalence of lactose intolerance? How does this differ by 

race, ethnicity, and age?......................................................................................................37 

 Description of Study Characteristics ............................................................................... 37 

 Lactose Intolerance ..........................................................................................................37 

 Lactose Malabsorption.....................................................................................................39 

Lactase Nonpersisters (Adult-type Hypolactasia Biopsy) ............................................... 40 

 Summary..........................................................................................................................42 

Key Question 2: What are the health outcomes of dairy exclusion diets?............................. 67 

 Association Between GI Symptoms and Dairy Exclusion Diets..................................... 67 

vii 
 

 

 

 

 Association Between Milk Intake With Genetic Polymorphism, Lactose 

Intolerance, or Malabsorption....................................................................................... 67 

 Association Between Genetic Polymorphism, Milk Intake, or Self Reported Lactose 

 Association Between Lactose Intake and Metabolism and Bone Mineral Content or 

Studies Comparing Symptoms Resulting from the Ingestion of One Dosage of 

 Commercially Available Lactase/Lactose Hydrolyzed Milk or Nonlactose Solutions . 118 

 Association Between Dairy Exclusion Diets and Bone Health ....................................... 67 

 Association Between Lactose Intake and Metabolism and Bone Fractures .................... 69 

Diet...................................................................................................................................69 

 Genetic Polymorphism..................................................................................................... 70 

 Lactose Intolerance ..........................................................................................................71 

 Lactose Malabsorption.....................................................................................................71 

 Association Between Lactose Intake and Metabolism with Osteoporosis ......................72 

Intolerance.....................................................................................................................72 

Density ..........................................................................................................................73 

Key Question 3: What amount of daily lactose intake is tolerable in subjects with 

lactose intolerance?...........................................................................................................107 

Characteristics of Included Studies................................................................................ 107 

 Overview of Findings ....................................................................................................108 

Experimental Studies of the Tolerance of Individual Subjects to Lactose .................... 108 

Studies Using a Range of Dosage of Lactose ................................................................109 

Lactose Versus that of a Lactose Reduced or Lactose Free Treatment ......................111 

Key Question 4: What strategies are effective in managing individuals with diagnosed 

lactose intolerance?...........................................................................................................118 

 Prebiotics and Probiotics................................................................................................120 

 Incremental Lactose for Colonic Adaptation................................................................. 120 

 Other Strategies.................................................................................................................... 121 

 Studies on Management Strategies in Subjects with IBS and LM/LI ........................... 121 

Chapter 4. Discussion ............................................................................................................... 147 

Summary and Discussion..................................................................................................... 147
 

Key Question 5: What are the future research needs for understanding and managing 

lactose intolerance?...........................................................................................................149 

 Key Question 1 .............................................................................................................. 149 

 Key Question 2 .............................................................................................................. 149 

 Key Question 3 .............................................................................................................. 149 

 Key Question 4 .............................................................................................................. 150 

References and Included Studies............................................................................................... 151 

List of Acronyms/Abbreviations................................................................................................ 157 

viii 
Tables 

Table 1 Recommended calcium intake by age group ............................................................. 22 

Table 2 Calcium content in common foods............................................................................ 23 

Table 3 Prevalence of lactose intolerance symptoms following challenge ............................ 44 

Table 4 Prevalence of lactose intolerance by self report ........................................................50 

Table 5 Prevalence of lactose malabsorption by challenge .................................................... 53 

Table 6 Prevalence of hypolactasia......................................................................................... 62 

Table 7 Prevalence of adult-type hypolactasia genotype........................................................ 64 

Table 8 Association between lactose intolerance and bone outcomes.................................... 76 

Table 9 Association between low lactose diets and bone fractures........................................ 80 

Table 10 Association between vegan diet (lactose free) and incident fracture of bones 

other than the digits or ribs, results from the Oxford cohort of the European 

Prospective Investigation into Cancer and Nutrition (EPIC-Oxford)........................ 87 

Table 11 Association between genetic polymorphism and bone fractures............................... 88 

Table 12 Association between lactose intolerance or malabsorption and bone fractures......... 89 

Table 13 Association between low lactose diets, lactose intolerance or malabsorption, and 

osteoporosis................................................................................................................91 

Table 14 Bone health outcomes in children and adolescents with low lactose diets (results 

from randomized controlled clinical trials of dairy products) ................................... 93 

Table 15 Percent change in osteodensitometric values after administration of dairy 

products in children consuming low lactose diets (RCTs) ......................................101 

Table 16 Association between lactose intake and metabolism and BMC .............................. 102 

Table 17 Effect of increased dairy intake on bone health in young and pre-menopausal 

women consuming low lactose diets (results from individual RCTs)..................... 106 

Table 18 Summary of study characteristics for blinded lactose intolerance treatment 

studies ...................................................................................................................... 125 

Table 19 Occurrence of gastrointestinal symptoms in randomized trials............................... 126 

Figures 

Figure 1 Analytic framework ...................................................................................................27 

Figure 2 Reference flow diagram.............................................................................................43 

Figure 3 Association between milk intake and history of any fracture....................................83 

Figure 4 Association between milk intake and hip fracture.....................................................84 

Figure 5 Association between milk intake and osteoporotic bone fractures............................85 

Figure 6 Association between dairy calcium intake (mg/day) and bone fractures .................. 86 

Figure 7 Association between genetic polymorphism TT vs. C/C and positive tests for 

lactose malabsorption, crude odds ratios from two Austrian observational 

population based studies of genetic screening for osteoporosis ................................ 92 

Figure 8 Bone mineral content from RCTs of dairy product use in children and 

adolescents with low lactose diets. Total body..........................................................97 

Figure 9 Bone mineral content from RCTs of dairy product use in children and 

adolescents with low lactose diets. Femoral neck .....................................................98 

ix 
 

Figure 10 Bone mineral content from RCTs of dairy product use in children and 

adolescents with low lactose diets. Total hip............................................................. 99 

Figure 11 Bone mineral content from RCTs of dairy product use in children and 

adolescents with low lactose diets. Lumbar spine ................................................... 100 

Figure 12 Symptomatic response of adult lactose malabsorbers to lactose ingested with 

nutrients other than milk .......................................................................................... 117 

Figure 13 Symptomatic response of adult lactose malabsorbers to lactose ingested without 

nutrients other than milk .......................................................................................... 117 

Figure 14 Percentage of subjects reporting abdominal pain .................................................... 123 

Figure 15 Abdominal pain based on symptom scores.............................................................. 124 

Appendixes and evidence tables cited in this report are available at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/lactoseint/lactint.pdf. 

x 
Executive Summary 

Introduction 

Milk and milk products contain high concentrations of the disaccharide lactose (galactose 

and glucose linked by a beta-galactoside bond). Intestinal absorption of lactose requires that the 

disaccharide be hydrolyzed to its component monosaccharides, both of which are rapidly 

transported across the small bowel mucosa. A brush border beta-galactosidase, lactase, carries 

out this hydrolysis. While infants virtually always have high concentrations of lactase, sometime 

after weaning a genetically programmed reduction in lactase synthesis results in very low lactase 

activity in some adult subjects, a situation known as lactase nonpersistence. 

Lactase nonpersistence results in incomplete digestion of an ingested load of lactose; hence 

lactose is malabsorbed and reaches the colon. If sufficient lactose enters the colon, the subject 

may experience symptoms of abdominal pain, bloating, excess flatulence, and diarrhea, a 

condition known as lactose intolerance (LI). Diseases of the small bowel mucosa (infection, 

celiac disease) may also be associated with low brush border lactase, with resultant lactose 

malabsorption (LM) and LI. 

The terminology involved in lactose absorption/intolerance is as follows: 

a) Lactase nonpersistence (or lactase insufficiency) – indicates that brush border lactase 

activity is only a small fraction of the infantile level, a condition documented by analysis 

of brush border biopsies. Recently it has been shown that a genotype (C/C) of the lactase 

promoter gene is responsible for lactase nonpersistence, and demonstration of this 

genotype can be used as indirect evidence of lactase nonpersistence. 

b) Lactose malabsorption – indicates that a sizable fraction of a dosage of lactose is not 

absorbed in the small bowel and thus is delivered to the colon. Since such malabsorption 

is virtually always a result of low levels of lactase, there is a nearly a one to one 

relationship of lactase nonpersistence (or deficiency) and LM. LM is objectively 

demonstrated via measurements of hydrogen H2 breath or blood glucose concentrations 

following ingestion of a lactose load. 

c) Lactose intolerance – indicates that malabsorbed lactose produces symptoms (diarrhea, 

abdominal discomfort, flatulence, or bloating). It should be stressed that this 

symptomatic response to LM is linked to the quantity of lactose malabsorbed (as well as 

other variables), i.e., ingestion of limited quantities of lactose does not cause 

recognizable symptoms in lactose malabsorbers, while very large doses commonly 

induce appreciable LI symptoms. As a result, the prevalence of lactase nonpersistence or 

LM could far exceed the prevalence of LI symptoms in population groups ingesting 

modest quantities of lactose. 

A public health problem may arise when large numbers of individuals diagnose themselves 

as being lactose intolerant. However, these self-identified lactose intolerant individuals may 

actually be lactase persisters. Some of these lactase persisters (and even lactase nonpersisters) 

may mistakenly ascribe the symptoms of undiagnosed irritable bowel syndrome (IBS) or other 

intestinal disorders to LI. Given that the relatively nonspecific abdominal symptoms caused by 

IBS and LM are extremely susceptible to the placebo effect, reliable demonstration of LI 

requires double-blind methodology. 

1 
The problem may become intergenerational when self-diagnosed lactose intolerant parents 

place their children on lactose restricted diets (even in the absence of symptoms) or use 

enzymatic replacement in the belief that the condition is hereditary. Children and adults with LI 

may avoid dietary milk intake to reduce symptoms of intolerance. Since the avoidance of milk 

and milk containing products can result in a dietary calcium intake that is below recommended 

levels of 1,000 milligrams (mg) per day for men and women and 1,300 mg for adolescents, 

osteoporosis and associated fractures secondary to inadequate dietary calcium is the perceived 

major potential health problem associated with real or assumed LI. 

Current dietary recommendations suggest consuming 3 cups/day of fat-free or low-fat milk 

or equivalent milk products. This amount is equivalent to about 50 grams of lactose, which we 

defined to be the threshold of minimum tolerance. We defined LI to be present when ingestion of 

50 grams of lactose (or less) as a single dose by a lactose malabsorbing subject induces 

gastrointestinal symptoms not observed when the subject ingests an indistinguishable placebo. 

Because ingesting smaller portions over the course of the day may minimize potential 

problems with larger acute lactose loads, the above definition of lactose intolerance may miss 

lactose malabsorbers who ingest smaller dosages of lactose. The prevalence of clinically 

important lactose intolerance requires demonstration that the quantity of lactose that subjects 

actually ingest (or wish to ingest) causes symptoms in placebo-controlled experiments. 

Treatment to reduce lactose exposure, while maintaining calcium intake from dairy products, 

consists of a lactose restricted diet or the use of milk in which the lactose has been prehydrolyzed via treatment with lactase supplements. Lactase supplements taken at the time of 

milk ingestion also are commercially available. 

This report was commissioned as background material for a National Institutes of Health 

(NIH) and Office of Medical Applications of Research (OMAR) Consensus Development 

Conference on Lactose Intolerance and Health to address the following key questions: 

Key Questions Addressed in this Report 

1. What is the prevalence of lactose intolerance? How does this differ by race, ethnicity, and age? 

2. What are the health outcomes of dairy exclusion diets? 

• In true lactase nonpersisters 

• In undiagnosed or self-identified lactose intolerant individuals. 

• How does this differ by age and ethnicity? 

• Health outcomes to include: Bone health – osteoporosis, fracture, bone density, bone 

mass; and gastrointestinal symptoms – abdominal pain, diarrhea, nausea, flatulence, 

bloating. 

3. What amount of daily lactose intake is tolerable in subjects with diagnosed lactose 

intolerance?
 

• How does this differ by age and ethnicity? 

• What are the diagnostic standards used? 

4. What strategies are effective in managing individuals with diagnosed lactose intolerance? 

• Commercially-available lactase 

• Prebiotics and probiotics 

• Incremental lactose loads for colonic adaptation 

• Other dietary strategies 

5. What are the future research needs for understanding and managing lactose intolerance? 

2 
Methods 

We searched several databases including MEDLINE® via PubMed® and via Ovid, the 

Cochrane Library of randomized controlled clinical trials, BIOSIS Previews®, Biological 

Abstracts®, Global Health, Food Science and Technology Abstracts®, and Commonwealth 

Agricultural Bureau International databases, to find studies published in English between 1967 

and November 2009. We included observations that examined prevalence, symptoms, and 

outcomes of LI in different age, gender, racial, and ethnic groups. We excluded populations with 

other gastrointestinal disorders, including individuals diagnosed with IBS, inflammatory or 

infectious bowel diseases, or milk allergies. We excluded children younger than 4 years of age. 

We synthesized the results using the exact definitions the authors used for LI and LM. We 

defined LI to be present when ingestion of 50 grams of lactose (or less) as a single dose by a 

lactose malabsorbing subject induces gastrointestinal symptoms not observed when the subject 

ingests an indistinguishable placebo. Since the symptomatic response to lactose likely increases 

with increasing dosages, this definition is also intimately related to the dose of lactose 

administered. 

For question 2 we operationalized dairy exclusion diets by including studies that compared 

outcomes among populations reporting, or randomized, to consume diets very low in or free 

from lactose. We included the following populations: general, vegans, lactase nonpersisters, 

diagnosed or self-identified lactose intolerant or lactose malabsorber. For bone health outcomes 

we analyzed bone fractures and osteoporosis, bone mineral content (BMC), and bone mineral 

density (BMD). For gastrointestinal outcomes we assessed gastrointestinal symptoms at different 

categories of lactose intake. Dietary recall may be unreliable, and our search identified few 

studies meeting these criteria. Therefore, we included studies that examined the association 

between individuals classified as lactose intolerant, lactose malabsorbers, or lactase deficient and 

health outcomes even if they did not specifically state the amount of lactose/dairy consumed. We 

included these studies because evidence suggested that these populations were likely to consume 

diets low in lactose. We provide quantitative estimation of lactose intake expressed in differences 

between consumed and recommended dietary calcium. We included randomized controlled trials 

(RCTs) that evaluated the effect of lactose free diets on outcomes to assess if lactose intake 

resulted in improved bone health. We excluded the studies of patients with milk allergies, 

irritable bowel syndrome, chronic diarrhea, gastroenteritis, or other diagnosed gastrointestinal 

diseases. 

Osteoporosis was defined according to World Health Organization criteria1-3 as a BMD 2.5 

standard deviation or more below the young average value in women and men.4

 Osteopenia was 

defined as a BMD 1-2.5 standard deviation below the population average.5 

We used reference data on femur bone mineral content and density of noninstitutionalized 

adults in the United States from the third National Health and Nutrition Examination Survey that 

collected dual energy x-ray absorptiometry in a nationally representative sample of 14,646 men 

and women 20 years of age and older.6 

For Key Question 3 we included double-blind RCTs and analyzed the tolerable dose of 

lactose given in single or multiple doses. Findings from these studies (and for question 4) 

provided information regarding the short-term gastrointestinal outcomes among subjects 

diagnosed with LI or LM. 

For Key Question 4 we included randomized double blind controlled trials of probiotics, 

enzyme replacement therapies with lactase from nonhuman sources, administration of lactose 

3 
reduced milk, and regimes of increases in dietary lactose load. We evaluated the efficacy of 

therapeutic agents and strategies in alleviating symptoms among individuals with diagnosed 

lactose malabsorption. 

We judged level of evidence using modified GRADE criteria. Inconsistency in direction or 

magnitude of the association or inconsistent adjustment for known confounding factors reduced 

level of evidence. We also determined low level of evidence and confidence when data came 

from a single study. We judged moderate level of evidence for statistically heterogeneous results 

from several small RCTs because further research is likely to have an important impact on our 

confidence in the estimate of effect and may change the estimate. 

Results 

Key Question 1: What is the prevalence of lactose intolerance? How 

does this differ by race, ethnicity, and age? 

A total of 54 articles met inclusion criteria, including 15 articles from the United States. 

Studies did not directly assess LI in a blinded lactose challenge but instead assessed unblinded 

subjective LI symptoms, an inability to fully absorb lactose (lactose malabsorption), or lactase 

nonpersistence. The data available tended to be from highly selected populations and was not 

likely representative of the overall U.S. population. We report results according to the following 

conditions: lactose intolerance, lactose malabsorption, or lactase nonpersistence. Within these 

conditions we further describe findings according to assessment method and populations studied. 

Lactose intolerance. 

Symptoms following blinded lactose challenge. We identified no studies that reported on the 

prevalence of LI based on our “gold-standard” definition; i.e., gastrointestinal symptoms that are 

more prevalent and severe after ingestion of 50 grams of lactose (or less) as a single dose by a 

lactose malabsorbing subject that are not observed when the subject ingests an indistinguishable 

placebo. 

Symptoms following nonblinded lactose challenge. We identified 21 studies that reported LIrelated symptoms (abdominal pain, bloating, excess flatulence, and diarrhea) following a 

nonblinded lactose challenge.7-28 Few assessed U.S. populations. No studies were published in 

the last 30 years. There were four older U.S. convenience sample studies13,18,26,27 that reported 

results on different subpopulations. One study of healthy Caucasian volunteers with no history of 

milk intolerance reported that symptoms were rare and confined primarily to those with biopsy 

determined hypolactasia.18 In another study on healthy adults,26 Hispanics were 43 percent more 

likely to report symptoms following a lactose challenge compared to white non-Hispanics.26 

Similarly, in healthy children27 the rate of symptoms was twice as high among Hispanic children 

(41 percent versus 20 percent in non-Hispanic). The fourth U.S. study included African 

American (n=69) and Caucasian (n=30) children between the ages of 4 and 9 years old. The 

overall frequency of symptoms following a challenge was quite low in young children, but the 

rate increased with age and was higher in African American children compared to Caucasian 

children.13 Age up to adulthood was a consistent predictor of LI-related symptoms. Racial and 

ethnic variation was present, but the variation in symptoms reported following a challenge did 

not seem as extreme as the racial and ethnic variation seen in lactose malabsorption and 

prevalence of lactase nonpersistence. 

4 
 

 

Symptoms without lactose challenge. We identified seven studies reporting baseline selfreported symptoms in 6,161 people.29-35 There was only one U.S. population-based study.35 This 

study included only self-reported LI with no additional confirmation of the diagnosis. Overall, 

U.S. estimated prevalence of self-reported LI was 12 percent from this study, with estimates of 8 

percent in European Americans, 10 percent in Hispanic Americans, and 20 percent in African 

Americans. The rest of the self-reported studies’ results provide little evidence to address our 

research questions about population prevalence and the impact of age and ethnicity. Overall, the 

prevalence of self-reported symptoms was typically lower than the prevalence of symptoms 

following a lactose challenge. 

Lactose malabsorption. 

Determined by hydrogen breath test following lactose challenge. We identified 31 studies 

evaluating participants from a wide range of ages and ethnicities that reported LM prevalence as 

defined by subjects with a positive hydrogen breath test.7,8,11,12,14-17,20-25,28,30,32,36-48 None of the 

U.S. studies were representative population-based studies. All U.S. studies focused on reporting 

results in populations of patients with gastrointestinal (GI) symptoms at baseline,36,42,47,48 with 

the exception of one three decade old study of American Indians30 and one convenience sample 

of adults from the Army, senior centers, nursing homes, and a university.44 

Within the U.S. studies of patients with GI symptoms at baseline, the prevalence of LM in 

Caucasian adult populations ranged from 6 to 24 percent.42,44,47 Some data suggested high levels 

of LM among American Indians, but this effect was substantially attenuated among those with 

American Indian and Caucasian mixed ancestry.30 One study showed that the prevalence of LM 

may be greater than 70 percent in African Americans, around 50 percent in Hispanic Americans, 

and even higher for Asian Americans.49 Age is an important contributor to the rate of LM, since 

nearly every population group identified showed low rates of LM in the youngest age groups, 

particularly those less than 6 years of age.16,17,23,28,39,45,46 In populations with high adult rates of 

LM, rates peaked between 10 and 16 years of age. 

Lactase nonpersisters (adult-type hypolactasia). 

Biopsy identification. We identified five studies that reported on the prevalence of lactase 

persistence as diagnosed by biopsy assays.18,50-53 These estimates ranged from 6 percent to 34 

percent among Caucasians, to 75 percent among nonwhites; however, there was little to no 

correlation with symptoms of LI. It is difficult to generalize these findings to create population 

estimates or understand their clinical relevance. 

Genetic Test Association. The most commonly reported genetic mutation for adult-type 

hypolactasia is the single nucleotide polymorphism (SNP) of the lactase (LCT) gene. The C 

allele is the globally most prevalent allele, while the less common T allele is dominantly 

associated with lactase persistence.54 Nine studies were identified that reported genotype 

frequencies for LCT -13910C>T SNP mutation, indicating a genetic predisposition for 

hypolactasia, or lactose nonpersistence.29,45,55-61 None of these studies were of U.S. populations. 

There were no obvious differences in genotype by age group.55,56 In North European studies, 

Caucasians had frequencies between 10-20 percent for the homozygous C/C genotype.29,55-57,59,61 

Key Question 2: What are the health outcomes of dairy exclusion 

diets? 

We identified 55 publications of observational studies of 223,336 subjects that reported 

symptoms or bone health outcomes in relation to lactose intake. The absence of specific 

5 
 

 

 

documentation of the amount of lactose consumed over long periods of time hampered synthesis, 

so indirect associations between bone outcomes and proxy variables for lower lactose 

consumption were assessed. We also found seven RCTs of 1,207 children on low lactose diets 

(less than 50 percent of the recommended calcium intake), and two RCTs of adult women (34-73 

percent of recommended calcium intake) 62,63 that provide direct evidence of lactose intake on 

bone health. African American women were enrolled in one study.64 We identified no studies 

that specifically addressed gastrointestinal symptoms after long-term (>1 month) dairy exclusion 

diets. In evidence presented for key questions 3 and 4 we report on short-term gastrointestinal 

symptoms after blinded administration of lactose free diets or differing doses of lactose intake 

among subjects diagnosed with LI or LM. We included indirect evidence of the effect of dairy 

exclusion diets on health outcomes in populations that are presumed to have low dairy intake 

(e.g., vegans, individuals with LI/LM or lactase nonpersistence), even if the studies did not 

report on the amount of dairy consumed. 

Lactose and calcium. Children and adults with self-reported symptoms of milk intolerance 

and diagnosed LM reported (or were assumed to be consuming) lactose free or low lactose diets. 

Limited evidence suggest that adults with C/C genotype may report reduced milk intake.59,65-67 

The association was more consistent for women.68,69 Young adults with C/C genotype reported 

not drinking milk two times more often than those with TT genotype.70 The association may 

diminish with aging.71,72 

Dietary calcium intake was 47 percent of that recommended in children and 30 percent in 

women who followed a vegan diet. Among those with LI, children consumed 45 percent and 

women 37 percent of the recommended dietary calcium. During the transition to young 

adulthood, adolescents with LI had decreased dairy calcium intake.73 Among those with LM, 

adults consume 44 percent and women 50 percent of the recommended dietary calcium. Daily 

calcium intake was 32 percent of that recommended in women with LM and LI. Young adults 

with C/C genotype had lower than recommended calcium intake when compared to those with 

TT genotype.70 Women with C/C genetic polymorphism consumed 48 percent of the 

recommended dairy calcium from all sources and 34 percent from milk. Men with C/C genetic 

polymorphism consumed 58 percent of the recommended dairy calcium from all sources and 1.3 

percent from milk. Children with C/C genetic polymorphism consumed 80 percent of the 

recommended dietary calcium. 

We evaluated GI symptoms and bone health in vegans (lactose free), in healthy adults with 

low lactose intake and an unknown proportion of subjects with undiagnosed LI, and in 

populations with lactase deficiency, LI, or LM who followed low lactose diet. 

Association between GI symptoms and dairy exclusion diets. We identified no studies that 

addressed the long-term impact (>1 month) of dairy exclusion diets on GI symptoms in the 

general population, vegans, or those diagnosed with LI or LM. Limited evidence suggested that 

long-term lactose free diet resulted in improved symptoms in patients with IBS and lactose 

malabsorption.74 A degree of clinical improvement, however, was not associated with severity of 

clinical symptoms during hydrogen diagnostic tests in patients with IBS and no history of milk 

intolerance.75 Therefore, severity of clinical symptoms during hydrogen diagnostic tests could 

not predict favorable responses to long-term lactose free diets. Postmenopausal Austrian women 

with TT genotype (lactase persistence) had lower odds of aversion to milk consumption than 

women with C/C genotype.68,69 Among children who avoided milk, those diagnosed with lactose 

intolerance had much greater odds of milk related symptoms.76 

6 
In key questions 3 and 4 we report short-term GI outcomes from blinded RCTs among 

subjects with diagnosed LI or controls fed short-term diets containing varying doses of lactose or 

lactose free diets. 

Association between lactose intake and metabolism and bone fractures. We found low 

levels of evidence from observational studies that low milk consumers had fractures more 

frequently than populations with higher milk consumption. Inconsistency in magnitude of the 

association and lack of consistent adjustment for all known confounding factors lowered the 

level of evidence.76-88 The magnitude varied depending on definitions of exposure. Studies did 

not analyze all levels of exposure, including milk and dairy calcium intake, genetic 

polymorphism, perceived milk intolerance, and positive tests for lactose maldigestion. We found 

low levels of evidence from two industry sponsored studies that children who avoid milk intake 

for more than 4 months had increased risk of bone fractures.76,89 

A single study found that odds of the annual incidence of distal forearm fracture in 

prepubertal children with a history of long-term milk avoidance more than doubled.76 Another 

study reported that the age-adjusted odds of history of any fracture were more than three times 

higher among children with lactose free diets compared to the general population.89 We found 

low levels of inconsistent evidence from three studies of 44,552 adults (not stratified by gender) 

that those with low lifetime or childhood milk intake had increased odds of any or osteoporotic 

fracture.80 Evidence from nine studies of 111,485 adult women suggested an increase in risk of 

fracture in association with low dairy intake. The magnitude of the association varied across the 

studies. Variability in definitions of lactose intake and types of fracture may contribute to 

inconsistency in the results of the studies. While all nine studies found increased odds of fracture 

in women with lower dairy intake; only five reported a significant association.77-79,81,82,84-87 We 

found no significant association between any osteoporotic or hip fracture and low milk intake 

among male participants in large well designed observational studies.83,88 One large cohort 

reported that vegans had increased relative risk of fractures compared to the general population.90

 Genetic predisposition. We found no studies that examined the association of low versus 

regular lactose diet and bone outcomes in those with genetic diagnosis, probably because of high 

prevalence of low lactose diet in this population However, we found studies that compared bone 

outcomes in subjects with C/C genotype (true lactase nonpersisters) and TT genotype (lactase 

persisters). The association between a single nucleotide polymorphism of the LCT gene at 

chromosome 2q21-22 (associated with lactase deficiency and reduced lactose intake) and 

fractures in adults was examined in five publications.29,65,68,69,91 Evidence of the association 

between bone fracture and lactase deficiency from three studies of 895 postmenopausal women 

were inconsistent in direction and effect size.29,68,69 One population-based study “Vantaa 85+” of 

601 Finnish elderly found that those with C/C genotype (lactase deficient) had more than a 

threefold increase in crude odds of hip and nearly a twofold increase in crude odds of wrist 

fracture when compared to TT genotype (lactase persistent and reporting lower odds of milk 

aversion).65 The Austrian Study Group on Normative Values on Bone Metabolism did not find a 

significant association between genetic polymorphism and bone fracture in elderly men.91

 Lactose intolerance: One study reported that children who avoided drinking cow's milk 

because of perceived milk intolerance did not have higher rates of fracture compared to milk 

avoiders who did not report symptoms of intolerance.89 Finnish postmenopausal women with 

lactose intolerance (and presumed lower lactose intake) did not have greater risk of any, 

vertebral, or nonvertebral fracture when compared to healthy women.29 Austrian men and 

women with self-reported symptoms of LI (and presumed lower lactose intake) during the 

7 
 

 

 

 

hydrogen breath test had a 96 percent increase in crude odds of any fracture.92 Estonian men and 

women with self-reported milk intolerance had increased crude odds of osteoporotic fracture.67 

Association between lactose intake and osteopenia, osteoporosis, bone mineral density, 

and bone mineral content. Low level evidence indicates that adults with lactose free or low 

lactose diets had osteopenia more often than controls.5,93,94 Postmenopausal Taiwanese women 

consuming lactose free diets had a twofold increase in adjusted odds of femoral neck osteopenia 

compared to nonvegan vegetarians.93 Italian adults with symptoms of LI and positive hydrogen 

test (assumed to consume low lactose diets) had a large increase in crude odds of osteopenia.5 

Women with different lactase genetic polymorphism (assumed to vary in lactose intake 

according to lactase gene presence) had the same odds of osteoporosis.29,69 

Four studies demonstrated that children from Europe,95 Asia,96 or New Zealand76,97 with 

lactose free or low lactose diets had reduced BMC and BMD.76,95-97

 Genetic polymorphism. We found low levels evidence that women with C/C genotype 

(lactase nonpersistent who consumed 48 percent of recommended calcium) had lower BMD 

compared to TT (lactase persistent) genotype.68,69 Bone outcomes did not differ by genotype in 

either gender.57,67

 Lactose intolerance. We found low levels of evidence that children and adults with selfreported milk intolerance (reduced dairy intake with 45 percent of recommended calcium intake) 

had reduced BMC and BMD. Children98 and adolescent girls99 from the United States with 

lactose intolerance had an inconsistent reduction in BMC. Adults with self-reported milk 

intolerance had consistent reduction in BMD5,67,100 and BMC.5 

Role of diet: bone health outcomes by intake of dairy and calcium. We found moderate 

level RCT evidence that increased lactose intake resulted in improved BMC of the lumbar spine 

and femoral neck in prepubertal children with low baseline milk intake (less than 50 percent of 

recommended calcium intake). Lactose effects were causal and direct but the effect sized varied 

across studies and lowered the level of evidence. Dairy intervention with 1,794 or 1,067 mg of 

calcium per day compared to 400-879 mg of calcium per day for 12 months resulted in a 

significant increase in total body BMC in boys and girls from Hong Kong.101 One RCT that 

included pre-pubertal children with very low baseline milk intake reported significant increases 

in total body BMC after dairy administration that provided 1,200 mg of calcium per day.102 The 

effect, however, was not significant at 18 months of followup.102 The U.S.103 and British104 RCTs 

that included only girls consuming half of the recommended daily calcium did not demonstrate 

significant improvement in total body BMC. Study design, population, race/ethnicity, gender, 

and baseline milk intake could explain inconsistency between studies in lumbar spine BMC. 

Lumbar spine BMC was increased in three RCTs,101,102,105 while two trials did not report 

significant changes.106,107 Children from Hong Kong with very low baseline calcium intake had 

the greatest increase in lumbar spine BMC.101 Dairy intervention increased lumbar spine BMC in 

girls105 but not in boys.106 The improvement in bone mineral density was less evident. Dairy 

interventions did not increase BMD in girls in two RCTs that reported absolute levels of the 

outcome.103,105 Dairy interventions increased BMD from baseline in one RCT of Finnish girls,107 

while British girls104 and children from New Zealand102 or Hong Kong101 did not have significant 

changes in BMD. Dairy intervention did not result in a significant increase in total spine BMD at 

6 months in young women.62 In one small RCT (n=59) of premenopausal U.S. women, dairy 

intervention reduced age-related decline over a 3-year period in vertebral BMD.63 Observational 

studies reported that children with very low milk intake had reduced BMD when compared to the 

reference population.76,96,97 Long term milk avoiders had lower BMC.76,95-97 

8 
Key Question 3: What amount of daily lactose intake is tolerable in 

subjects with diagnosed lactose intolerance? 

Twenty-eight randomized crossover trials were included. Half of the trials included lactose 

digesting controls. The vast majority of studies of LI were small (<30 subjects) with trial 

populations ranging between six and 150 subjects. Women constituted 55 percent of the subjects, 

and the mean age was 37 years (20 studies reporting). Seven trials included children or 

adolescents, four exclusively. Among the 20 studies reporting race or ethnicity, 33 percent of the 

subjects were white, 30 percent Hispanic, 20 percent black, and ten percent Asian. Studies did 

not report outcomes stratified by these baseline factors. In 11 studies abdominal symptoms 

compatible with malabsorption of lactose prior to study entry were not required for participation. 

Lactose malabsorption was diagnosed following lactose tolerance tests by the hydrogen breath 

test in 13 of the studies,108-120 and blood glucose test in 11 studies.121-131 Diagnosis based on 

urinary galactose concentration was reported in one study132 and biochemical method of 

diagnosis was not reported in three trials.133-135 Half of the trials included lactose digesting 

controls.110-113,116,120,122,125-129,133,135 

While subjects were routinely tested for LM, only a few studies then tested the intolerant 

subjects in blinded fashion with increasing doses of lactose administered throughout the day to 

determine the daily tolerable dosage of lactose. Most studies utilized a single dose of lactose and 

a lactose-free control administered in water or milk without food, frequently in not totally 

blinded fashion (i.e., the taste of low lactose milk differs from milk). The statistical rating of 

symptoms may not indicate clinical significance. The probability that a given dose of lactose 

induces more symptoms than the control treatment has been assessed by standard statistical tests 

of the differences between group means. No attention has been paid to the possibility of outliers. 

Results were heterogeneous in terms of patient populations, interventions, assessment methods, 

and outcome definitions, thus precluding pooling. Most studies used hydrogen H2 breath testing 

to identify lactose malabsorbers which can incorrectly classify subjects. The problem is 

compounded because studies do not clearly distinguish between individuals with and without 

symptoms, suggestive of LI individuals who undergo the testing. 

The one study that investigated symptoms when lactose was ingested for 1 week with each of 

the three meals showed that up to 70 grams of lactose/day could be tolerated without appreciable 

symptoms.118 Studies testing the tolerance of lactose malabsorbing subjects to a single dose of 

lactose yielded discordant results. Several studies indicated that subjects with “lactose 

intolerance” can ingest from 10-15 grams of lactose (comparable to approximately one cup of 

milk), particularly if taken with food, with no or minor symptoms.113,116,119,120,126,127,130,131,134,135 

When the dosage of lactose was increased to 18-25 grams, once again, the finding of intolerance 

varied between studies. Five trials reported that intolerance becomes more prominent, with single 

doses of 20 grams or greater usually yielding appreciable symptoms.119,127,129,130,134 Lactose may 

be better tolerated when ingested with other nutrients versus administration of an aqueous 

solution of lactose or milk as a single test dose without other nutrients. When taken with other 

nutrients, symptoms appear to be minimal with daily lactose dosages of less than 20 grams (1. 7 

cups of milk), while many subjects experience severe symptoms with dosages of 50 grams. In 

contrast, when lactose/milk is administered as a single test dose without other nutrients, dosages 

of 12 grams may be symptomatic. Two trials demonstrated that if 20-24 grams of lactose is 

distributed throughout the day and given with meals, many lactose malabsorbers will tolerate this 

dosage.111,132 Studies with comparable lactose doses reporting high frequency of appreciable 

9 
intolerance symptoms supplied lactose in a single dose without food.124,133,134 No studies 

determined if lactose malabsorbers of differing ethnicities have differing tolerance to lactose. 

Likewise, there was no data on the relationship of age or sex to the quantity of lactose that can be 

tolerated by lactose intolerant subjects. 

Key Question 4: What strategies are effective in managing individuals 

with diagnosed lactose intolerance? 

For individuals wishing to consume milk and milk products that exceed the amount of lactose 

that they are able to tolerate, we examined the strategy of consuming lactose reduced/hydrolyzed 

formulations. A total of 37 unique randomized studies (26 on lactase/lactose hydrolyzed milk 

supplements and lactose reduced milk, eight on probiotics, two on incremental lactose dose for 

colonic adaptation, and one on other agents) met inclusion criteria. The quality of the studies was 

low, with almost no study reporting adequate allocation concealment. Generally, studies had 

small sample sizes, and reporting of symptoms was variable or not reported: composite scores of 

four to five symptoms or individual symptoms such as abdominal pain, diarrhea, bloating, and 

flatulence were reported, either as means or proportion. 

Lactase/lactose hydrolyzed milk. The 26 articles represented 28 unique trials. There was 

one study representing two trials that tested lactase supplements Lactodigest, DairyEase, and 

Lactaid,136 while the remaining 25 studies reported on lactose reduced or hydrolyzed milk by 

adding a lactase enzyme such as beta-galactosidase to the milk. Studies enrolled between six and 

150 subjects. Women constituted 56 percent of the subjects (n=23 studies). The mean age of 

subjects was 37 years of age with a range between 10 and 77 (n=19 studies). Six trials included 

children or adolescents.109,114,123,126,127,135 One trial enrolled elderly subjects (mean age 77 

years).116 Within the 19 studies reporting race or ethnicity, 40 percent of the subjects were white, 

30 percent Hispanic, 20 percent black, and 9 percent Asian.109-116,123,126-130,133-135,137 Sixteen 

studies utilized commercial lactase products or hydrolyzed milk,108-111,113-115,121-125,128,130,133,135 

two used milk products with lactose removed by ultrafiltration or chromatographically,112,134 and 

three assessed nonlactose solutions.116,126,127 

Unclear or unreported methods of lactose removal were noted in two trials.129,132 Subjects in 

18 studies reported abdominal symptoms compatible with malabsorption of lactose prior to study 

entry.108-114,121,123-125,128,130,132,134,136-138 Abdominal symptoms were not required for study 

participation (based solely on biochemical diagnosis) or subjects were not reported to experience 

symptoms following ingestion of lactose in ten studies.115,116,122,126,127,129,130,133,135,136 LM was 

diagnosed following lactose tolerance tests by the hydrogen H2 breath test in 11 of the studies108­

116,136 and blood glucose test in 13 studies.121-130,137,138 Diagnosis based on urinary galactose 

concentration was reported in one study132 and biochemical method of diagnosis was not 

reported in three trials.133-135 Over half the trials included lactose digesting controls.110­

113,116,122,125-129,133,135,137 Among the 18 studies that enrolled symptomatic subjects at baseline, 13 

utilized lactose doses greater than 12 grams, comparable to one cup of milk.108,110,111,114,121,123­

125,128,130,132,134,136,137 Hydrolyzed lactose doses typically ranged from 0-2 grams per dose. In most 

of the studies, the lactose dose was consumed in a single serving. In six trials, the lactose dose 

was administered over multiple intervals per day for at least part of the study.110,111,122,125,128,132 

We found insufficient evidence that lactose reduced solution/milk, with lactose content of 0-2 

grams, reduced symptoms of lactose intolerance. Seven studies, representing nine comparisons 

that enrolled individuals who had symptoms compatible with LI reported inconsistent results that 

10 
lactose reduced preparations decreased overall symptom scores compared to controls. None of the 

four studies reported a significant improvement in overall symptoms compared to control 

preparations of up to 12 grams of lactose. However, as noted in key question 3, doses of 12 grams 

of lactose or less are well tolerated and produce minimal to no symptoms. When compared to 

controls given greater than 12 grams of lactose, only two out of five trials reported statistically 

significant reductions in overall symptoms with lactose reduced/hydrolyzed milk. Results for 

individual symptoms of abdominal pain, diarrhea, flatulence, and bloating were also inconsistent. 

When we examined all included studies, regardless of symptom history, we found 

insufficient information from 16 (19 comparisons), mostly low quality, trials regarding the effect 

of hydrolyzed milk, lactase, or non-lactose preparations in reducing GI symptoms compared to 

lactose controls. Because these studies enrolled subjects with and without a prior history of GI 

symptoms compatible with LI (and did not provide results stratified by prior symptom history) 

they have very low applicability to the question to be addressed. Some studies did report 

substantial reductions (improvement from moderate and severe to mild or none, or an absolute 

reduction of at least 50 percent) in abdominal pain/cramping109,112,123,125,134 and diarrhea136 with 

use of lactose reduced solution/milk, with lactose content of 0-2 grams, compared to a lactose 

dose of 12 grams or more. However, even in studies where symptoms were reduced statistically 

significant reductions were not consistently observed among all symptoms reported, or only a 

subset of symptoms were reported. For example, the overall symptom score was significantly 

reduced by 60 percent with 591 milliliters (ml) of lactose reduced milk containing 7.5 grams of 

lactose compared to a similar amount of milk with 30 grams of lactose130 and by 13 percent with 

low lactose skim milk with 0.8-6.5 grams of lactose compared to skim milk with 6.1-49 grams of 

lactose,122 but the subjects in both studies were not symptomatic at enrollment, and improvement 

in individual symptoms was not provided. Mean and total symptom scores were also reduced, 

from 3.7 to 0.36 with 70 percent hydrolyzed milk compared to placebo with 20 grams of 

lactose,108 but subjects were also not symptomatic at enrollment, and improvement in individual 

symptoms was not provided. One study reported a score of 46 for skim milk with 11.3 grams of 

lactose, which was reduced to a score of 17 with low lactose milk with 3.2 grams of lactose, but 

the difference was not statistically significant.134 Similar reductions were seen in summed scores 

for abdominal pain from 43 with milk containing 25 grams of lactose to 1 with lactose 

hydrolyzed milk containing 1.25 grams of lactose123 and a mean score for abdominal pain from 

7.5 with milk containing 12 grams of lactose to 4.1 with milk containing lactase,109 both in 

children. Again, neither study required subjects to be symptomatic at baseline. One study showed 

a statistically significant reduction in abdominal pain from moderate to none or mild with low 

lactose milk containing 2.9 grams of lactose compared to skim milk containing 28.5 grams of 

lactose.125 One trial found a significantly greater percentage of subjects reporting abdominal pain 

and bloating compared to the 0.5 gram and 1.5 gram doses, respectively.112 Compared to 

placebo, use of lactase supplement Lactodigest, DairyEase, or Lactaid in doses of two to four 

capsules/tablets when taken with 400 ml of 2 percent milk containing 20 grams of lactose 

reduced overall symptom scores in subjects not symptomatic at enrollment. However, more 

relevant to the clinical question of treatment for individuals with symptoms compatible with LI 

who desire to consume lactose beyond the “minimally tolerable dose,” these products did not 

reduce symptoms when administered with a dose of 50 grams of lactose in subjects who had 

symptoms compatible with LI.136 Generally, studies had small sample sizes and reporting of 

symptoms was variable: composite scores of four to five symptoms or individual symptoms such 

11 
as abdominal pain, diarrhea, bloating, and flatulence were reported, either as means or 

proportion, making pooling estimates difficult. 

Prebiotics and probiotics. Trials were generally small, enrolling between nine and 28 

subjects. Among the five studies reporting gender, women constituted 34 percent of the 

subjects.139-143 Two studies enrolled only male subjects.142,143 Subjects were typically young to 

middle-aged adults (between 18 and 45 years old), and only one study enrolled subjects older 

than 60 years of age.144 Half of the studies reported race or ethnicity. White subjects comprised 

two trials,140,141 one study evaluated black African immigrants to France142 and one trial was 

conducted in Taiwan.117 Five of the studies were conducted in the United States,139,140,143-145 and 

two in France.141,142 Five trials assessed probiotic test products, prepared by adding strains of 

lactobacillus acidophilus, lactobacillus bulgaricus, or bifidobacterium longum to milk prior to 

consumption.117,139,140,144,145 Four studies evaluated yogurt products.141-143,145 Lactose 

malabsorption was diagnosed by the hydrogen breath test in all studies. 

We found insufficient evidence to determine the effectiveness of yogurt or probiotics to 

improve LI symptoms. The inclusion criteria were variable; the type, source, and concentration 

of yogurt and probiotics studied were variable; and no two studies studied the same agent. 

Results either did not show a difference in symptom score or reported clinically insignificant 

differences, mostly in symptoms of flatulence. Symptoms of abdominal pain, diarrhea, or overall 

score were not improved, which may be more clinically relevant to the patients and their 

providers. Only one study noted that the enrolled subjects reported symptoms compatible with 

malabsorption of lactose prior to study entry144 and reported a symptom score of 40 in groups 

given milk or acidophilus milk. In the remaining studies, study entry was based solely on 

hydrogen H2 breath tests, and subjects were not reported to experience symptoms following 

ingestion of lactose. Lactose doses in the control tests were between 10 and 20 grams. Overall 

symptom score was reduced from 12.5 with 2 percent milk containing 20 grams of lactose to 2.8 

with the same milk formulation but with added lactobacillus at 109 cfu/ml117 and from fairly 

strong to mild with 400 ml of bulgofilus milk (Ofilus bacteria+L. bulgaircus) compared to 

control (10 grams lactulose in 250 ml water), both with 18 grams of lactose.141 Reductions in 

other symptoms, such as abdominal pain and diarrhea, were either not reported, not significantly 

different, or of lower clinical significance or relevance. The inclusion criteria were variable, the 

type, source, and concentration of yogurt and probiotics studied were variable, and no two 

studies studied the same agent. 

Other strategies. We identified three small short-term studies.118,146,147 We found insufficient 

evidence that incremental doses of lactose reduce LI symptoms. We found one cross-over study 

evaluating 10 days of incremental doses of lactose versus dextrose for colonic adaptation among 

20 subjects with LM diagnosed on hydrogen breath tests.118 Most subjects had mild symptoms, 

even with high doses of lactose consumption. Flatulence but not abdominal pain and diarrhea 

were reduced. The second study evaluated colonic adaptation to lactose by comparing symptoms 

among 46 adults with lactose malabsorption that were fed either 34 grams of lactose or sucrose in 

a double blind fashion for 13 days.146 The overall clinical score and individual mean scores for 

pain, flatulence, bloating, and borborygmi also improved, but the improvement seen in lactose 

and sucrose groups was similar, suggesting a placebo response. One additional study of 40 

subjects with malabsorption on breath hydrogen testing evaluated rifaximin compared to lactose 

free diets and placebo.147 Rifaximin and lactose free diets resulted in similar reductions in 

abdominal pain, diarrhea, bloating, and distension compared to their respective baseline values. 

There were no data directly comparing rifaximin to placebo or lactose-free diets. 

12 
Summary and Discussion 

Our evidence synthesis reached the following major conclusions: (1) Reliable estimates of 

prevalence rates for LI in the United States are not currently available, though there is some 

evidence that the magnitude of LI will be very low in young children and remain low into 

adulthood for most populations of Northern European descent. For African American, Hispanic, 

Asian, and American Indian populations the rates of LI will likely be higher in late childhood 

and adulthood. (2) Evidence regarding the effect of dairy exclusion diets on long-term GI and 

bone health outcomes is relatively sparse in quantity and low in quality. Evidence does not 

strongly indicate that dairy-free diets are independently associated with poor long-term bone 

health outcomes, and there is no direct information on long-term GI outcomes among individuals 

consuming dairy-free diets. However, results from genetic association tests consistently reported 

decreased consumption of milk in adults with the C/C genotype compared to those with at least 

one T allele, suggesting that individuals with lactase nonpersistence avoid milk, presumably to 

reduce dairy induced GI symptoms. (3) The majority of individuals diagnosed with LI can likely 

tolerate up to 12 grams (equivalent to 1 cup of milk) at a given sitting with minimal to no 

symptoms, especially if consumed with other foods. (4) Treatment with lactose reduced milk 

products may result in clinically important improvements in selected GI symptoms in selected 

individuals diagnosed with LI or LM, but there is very little high quality data on the effect of 

incremental lactose loads. 

Our findings have important research and clinical implications. With regard to LI prevalence 

estimates, most of the identified research assessed subjective symptoms in an unblinded fashion 

or an inability of individuals to fully absorb lactose irrespective of symptoms or lactase 

nonpersistence. Available data tended to be from highly selected populations and not likely 

representative of the overall U.S. population. Additional genetic association studies may provide 

a useful method to assess LI in epidemiologic studies. Dietary history assessing dairy 

consumption and symptoms linked to results from testing for the lactase gene might obviate the 

need for blinding of lactose intake. 

Our findings that there is not a strong or consistent association on bone health with dairy 

intake is supported by a previous evidence report that concluded that the majority of findings 

concerning vitamin D, calcium, or a combination of both nutrients on the different health 

outcomes (including bone health) were inconsistent. Because the major long-term health concern 

of dairy exclusion diets is the potential for intake of calcium below recommended dietary levels, 

future research is required to clarify whether populations that consume dairy-free diets have 

adverse bone health outcomes, particularly fractures. We found that dairy interventions in 

healthy children with low baseline milk intakes may result in short but not long-term 

improvement of bone mineral content and density. Adults with lactose free or low lactose diet 

may have increased risk of bone fractures. Low and inconsistent evidence suggested that adults 

with milk intolerance and malabsorption had greater odds of fractures and worse bone outcomes. 

Adult women with low childhood and lifetime milk intake, lactose malabsorption, and C/C 

genotype had greater risk of osteoporosis and fractures. However, studies did not find significant 

association with lactose metabolism and bone health in men. There was little data on African 

Americans. Additional information would be important because African Americans have a 

higher prevalence of LI and likely lower consumption of dairy products, yet they have lower 

rates of bone health outcomes of interest for this report. Children with low baseline calcium 

13 
consumption may benefit from increased lactose intake. It is not clear if increased milk 

consumption in healthy adult women with low childhood and lifetime milk intake, LM, or C/C 

genotype reduces the risk of osteoporosis and fractures. 

Our findings can aid patients and practitioners in clinical management of individuals 

diagnosed with lactose intolerance. The preponderance of evidence indicates individuals 

diagnosed with LI can be informed that they can ingest 12 grams of lactose (1 cup of milk) as a 

single dose (particularly if taken with food) with no or minor symptoms. Therefore, most 

individuals (either self or clinically diagnosed) can consume a sufficient amount of dairy 

products each day to meet minimum recommendations without incurring GI symptoms. 

However, as the dose is increased above 12 grams, these individuals can be informed that 

intolerance becomes more prominent, with single doses of 24 grams usually yielding appreciable 

symptoms. There is some evidence that if 24 grams of lactose are distributed throughout the day, 

many lactose malabsorbers will tolerate this dosage. Lactose in a dose of 50 grams induces 

symptoms in the vast majority of subjects. No studies assessed if lactose malabsorbers of 

differing ethnicities have differing tolerance to lactose. There was no data on the relationship of 

age or sex to the quantity of lactose that can be tolerated. 

Advice regarding additional management strategies is hampered from the lack of study 

uniformity in design and methodology. We caution that the criterion of being symptomatic at 

baseline was found in only a few studies. This makes comparison of symptoms at the end of trial 

difficult across studies. Most studies had an 8-hour recording period, and it is difficult to 

generalize these findings to individuals with chronic relapsing remitting problems with a 

constellation of symptoms. While it seems logical that consuming lactose reduced products (i.e. 

to less than 12 grams of lactose) would reduce or prevent LI symptoms, the evidence was 

insufficient that products, as tested, provide this effect. 

Key Question 5: What are the future research needs for 

understanding and managing lactose intolerance? 

We recommend that future prevalence studies be derived from population-based samples that 

include adequate distributions across ages and ethnic variation in order to assess the effects of 

these factors. Efforts are needed to account for possible placebo effects in the reporting of 

symptoms. The best mechanisms available for accounting for placebo effects would be to 

conduct blinded challenges with and without lactose and to assign the difference in reported 

symptoms as the true prevalence due to the lactose challenge. Double blind placebo controlled 

RCTs of individuals examining the effect of treatment strategies that enroll subjects with clearly 

documented LI are needed. Standardized, validated outcome reports are needed. Additional work 

on what constitutes a meaningful challenge dose should also be conducted. We recommend that 

research on lactose intolerance take into account the prevalence of symptoms that might be 

expected following doses of lactose that would be consumed during a normal diet (e.g., 1 cup or 

12 grams) as compared to extreme doses of lactose that are comparable to getting a full day’s 

worth of calcium from a one-time consumption of milk (50 gram load at a single sitting). 

We recommend that future research investigate the association between lactose and dietary 

calcium intake and patient outcomes in patients with lactose intolerance lactose free diet 

compared to age, gender, and race/ethnicity matched controls. We recommend that the sources of 

dietary calcium from nondairy products and from nutritional supplements be examined 

separately and in interaction with other dietary patterns (food synergy).148-150 Bone health in 

14 
treated patients with LI is unknown. Length and doses of dairy products, probiotics, and plant 

calcium sources, as well as patient adherence to the recommended treatment regimes may 

modify the association and should be examined in future research. We recommend that future 

studies examine intermediate outcomes such as improvement in bone density and mineral 

content but, more importantly, clinical outcomes such as the incidence of osteoporosis and 

fractures. We recommend that other health outcomes include obesity, diabetes, cardiovascular 

diseases, and cancer in treated and untreated lactose intolerant patients in comparison with the 

general population. 

Additional studies are required to accurately diagnose the overlapping symptoms of LI from 

other GI disorders (especially IBS), determine the health consequences of low lactose diets, and 

identify methods to improve patient and provider information about the diagnosis and 

management of LI versus other GI symptom based conditions (especially functional bowel or 

celiac disease) versus LM. 

It is not clear to what extent restriction in intake of milk is from symptoms of LI versus 

reasons unrelated to symptoms, such as taste, caloric intake, or cultural factors. To the extent that 

milk avoidance is unrelated to LI, lactose reduced milk is not going to enhance ingestion. Thus, 

we believe a crucial question is to determine to what extent symptoms of LI limit the ingestion of 

milk or milk related products. Information on this could be obtained by studies in which lactose 

malabsorbers to avoid milk are provided with lactose containing and lactose hydrolyzed diets to 

determine if ingestion of milk and milk related products is increased by reduction of lactose 

content. To the extent that milk intake is reduced due to lactose intolerance symptoms, the next 

important question to answer is if there are long-term health consequences of limiting lactose 

intake. 

15 

Evidence Report
 

Chapter 1. Introduction 

Milk and milk products contain high concentrations of the disaccharide lactose (galactose 

and glucose linked by a beta-galactoside bond). Intestinal absorption of lactose requires that the 

disaccharide be hydrolyzed to its component monosaccharides, both of which are rapidly 

transported across the small bowel mucosa. A brush border beta-galactosidase, lactase, carries 

out this hydrolysis. While infants virtually always have high concentrations of lactase, sometime 

after weaning a genetically programmed reduction in lactase synthesis results in very low lactase 

activity in some adult subjects, a situation known as lactase nonpersistence. 

Lactase nonpersistence results in incomplete digestion of an ingested load of lactose, hence 

lactose is malabsorbed and reaches the colon. If sufficient lactose enters the colon, the subject 

may experience symptoms of abdominal pain, bloating, excess flatulence, and diarrhea, a 

condition known as lactose intolerance (LI). Diseases of the small bowel mucosa (infection, 

celiac disease) may also be associated with low brush border lactase, with resultant lactose 

malabsorption (LM) and LI. 

The terminology involved in lactose absorption/intolerance is as follows: 

a) Lactase nonpersistence (or lactase insufficiency) – indicates that brush border lactase 

activity is only a small fraction of the infantile level, a condition documented by analysis 

of brush border biopsies. Recently it has been shown that a genotype (C/C) of the lactase 

promoter gene is responsible for lactase nonpersistence, and demonstration of this 

genotype can be used as indirect evidence of lactase nonpersistence. 

b) Lactose malabsorption – indicates that a sizable fraction of a dosage of lactose is not 

absorbed in the small bowel and thus is delivered to the colon. Since such malabsorption 

is virtually always a result of low levels of lactase, there is a nearly one to one 

relationship of lactase nonpersistence (or deficiency) and LM. LM is objectively 

demonstrated via measurements of breath H2 or blood glucose concentrations following 

ingestion of a lactose load. 

c) Lactose intolerance – indicates that malabsorbed lactose produces symptoms (diarrhea, 

abdominal discomfort, flatulence, or bloating). It should be stressed that this 

symptomatic response to LM is linked to the quantity of lactose malabsorbed (as well as 

other variables), i.e., ingestion of limited quantities of lactose does not cause 

recognizable symptoms in lactose malabsorbers, while very large doses commonly 

induce appreciable LI symptoms. As a result, the prevalence of lactase nonpersistence or 

LM could far exceed the prevalence of LI symptoms in population groups ingesting 

modest quantities of lactose. 

A public health problem may arise when large numbers of individuals diagnose themselves 

as being lactose intolerant. However, these self-identified lactose intolerant individuals may 

actually be lactase persisters. Some of these lactase persisters (and even lactase nonpersisters) 

may mistakenly ascribe the symptoms of undiagnosed irritable bowel syndrome (IBS) or other 

intestinal disorders to LI. Given that the relatively nonspecific abdominal symptoms caused by 

IBS and lactose malabsorption are extremely susceptible to the placebo effect, reliable 

demonstration of LI requires double-blind methodology. 

The problem may become intergenerational when self-diagnosed lactose intolerant parents 

place their children on lactose restricted diets (even in the absence of symptoms) or use 

Appendixes and evidence tables cited in this report are available at http://www.ahrq.gov/downloads/pub/evidence/pdf/lactoseint/lactint.pdf. 

19 
enzymatic replacement in the belief that the condition is hereditary. Children and adults with 

lactose intolerance may avoid dietary milk intake to reduce symptoms of intolerance. Since the 

avoidance of milk and milk containing products can result in a dietary calcium intake that is 

below recommended levels of 1,000 milligrams (mg) per day for men and women and 1,300 mg 

for adolescents, osteoporosis and associated fractures secondary to inadequate dietary calcium is 

the perceived major potential health problem associated with real or assumed lactose intolerance. 

Current dietary recommendations suggest consuming 3 cups/day of fat-free or low-fat milk 

or equivalent milk products. This amount is equivalent to about 50 grams of lactose, which we 

defined to be the threshold of minimum tolerance. We defined LI to be present when ingestion of 

50 grams of lactose (or less) as a single dose by a lactose malabsorbing subject induces 

gastrointestinal (GI) symptoms not observed when the subject ingests an indistinguishable 

placebo. 

Because ingesting smaller portions over the course of the day may minimize potential 

problems with larger acute lactose loads, the above definition of LI may miss lactose 

malabsorbers who ingest smaller dosages of lactose. The prevalence of clinically important LI 

requires demonstration that the quantity of lactose that subjects actually ingest (or wish to ingest) 

causes symptoms in placebo controlled experiments. 

Treatment to reduce lactose exposure, while maintaining calcium intake from dairy products, 

consists of a lactose restricted diet or the use of milk in which the lactose has been prehydrolyzed via treatment with lactase supplements. Lactase supplements taken at the time of 

milk ingestion also are commercially available. 

This report was commissioned as background material for a National Institutes of Health 

(NIH) and Office of Medical Applications of Research (OMAR) Consensus Development 

Conference on Lactose Intolerance and Health to address the following key questions: 

Understanding the terminology of lactose-related “problems” is important and outlined as 

follows: 

1. Lactase deficiency – low concentrations of lactase in the small intestinal brush border 

relative to the concentrations observed in infants. 

2. Lactose malabsorption – failure of the small bowel to absorb the bulk of an ingested 

load of lactose. 

3. Lactose intolerance – a symptomatic response to malabsorption of lactose. 

Lactase Deficiency 

There are multiple causes of lactase deficiency. Congenital lactase deficiency, a very rare 

condition in which lactase synthesis is negligible at birth, results from the inheritance of two 

defective alleles of the lactase transcribing gene located on chromosome 2. Secondary lactase 

deficiency occurs in diseases that damage the brush border, such as celiac disease or intestinal 

infections. This deficiency usually is reversible with recovery from the disease. Lactase 

nonpersistence is a condition in which lactase synthesis is normal at birth and throughout 

infancy. However, after weaning, lactase synthesis declines, and by adulthood brush border 

lactase concentrations are only about 10 percent of the infantile level. This nonpersistence of 

lactase synthesis, which occurs despite continued exposure to milk or lactose, is present in about 

70 percent of the world’s adult population. This review will focus solely on the problems 

associated with lactase nonpersistence. 

20 
Lactase nonpersistence versus persistence has been shown to be a function of a lactose 

promoter region located upstream from the lactase gene. In lactose nonpersistent subjects the 

activity of this promoter is programmed to decline markedly after weaning, with a resultant 

decline in lactase synthesis. Several population groups, most prominently individuals of northern 

European extraction, have mutations of this promoter which permits it to remain active 

throughout life. In northern Europeans, a single nucleotide thymine for cytosine substitution in 

the promoter region allows this gene to retain activity throughout adulthood with resultant 

lactase persistence. Lactose nonpersisters have a C/C genotype whereas persisters have a C/T or 

T/T genotype (the C→T mutation is a dominant trait). 

Direct assessment of brush border lactase levels requires analysis of biopsies of small bowel 

mucosa via either measurement of enzymatic activity or histochemical staining for lactase. 

Genetic assessment of the C/T promoter area recently has become available. The complexity and 

expense of these techniques has limited their application, and information concerning the lactase 

nonpersistence/persistence state of individuals largely has been inferred from measurements of 

lactose absorption. The Digestive Diseases Clearinghouse of the National Institute of Diabetes, 

Digestive and Kidney Diseases states that 30 million to 50 million individuals in this country and 

about 4 billion people worldwide are lactase nonpersisters. Many of these individuals belong to 

minority groups such as Asians, African Americans, Hispanics, Native Americans, Alaskan 

Natives, and Pacific Islanders. However, lactase nonpersistence is also observed in a sizable 

fraction of Caucasians of southern European and Mediterranean origin. 

Lactose Malabsorption 

Multiple tests have been employed to assess the ability of a subject to absorb lactose. Such 

testing initially employed measurements of the rise in blood glucose observed after ingestion of a 

large (50 gram) dose of lactose, the lactose content of one quart of cow’s milk. A rise of blood 

glucose of <20 mg was used as evidence of lactose malabsorption. This test largely has been 

supplanted by the hydrogen H2 breath test, which assesses breath H2 concentration following 

ingestion of a 50 gram dose of lactose. A rise in breath H2 signifies that lactose has reached the 

colonic bacteria and hence was malabsorbed. Various lactose dosages, times of breath collection, 

and breath H2 increases have been employed in this test, and the accuracy of hydrogen H2 breath 

testing for lactose malabsorption has never been precisely determined. Nevertheless, this simple 

noninvasive test has been widely employed and much of our knowledge concerning the 

prevalence of lactose malabsorption in various population groups, as well as the ability of 

individual patients to absorb lactose, has been obtained via hydrogen H2 breath testing. 

Lactose Intolerance 

Lactose intolerance indicates that malabsorption of lactose results in symptoms of diarrhea, 

flatulence, bloating, or abdominal discomfort. While LM and LI frequently are used 

interchangeably, the demonstration that an individual malabsorbs lactose does not necessarily 

indicate that the subject will be symptomatic. The likelihood that a lactose malabsorber will 

perceive symptoms after ingestion of lactose is a function of many variables, including the 

dosage of lactose, lactase activity of the mucosa, foods co-ingested with lactose, the lactose 

fermentation pathways of the colonic flora, and the sensitivity of an individual’s colon to lactose 

malabsorption. Of particular importance is the dosage of lactose. Intolerance to supra21 
 

physiological loads of lactose (such as were employed in the lactose tolerance test) does not 

necessarily indicate that subjects will be symptomatic with a smaller, more physiological dosage. 

Thus, the dosage of lactose that causes symptoms is a major consideration in determining the 

importance of lactose as a clinical problem. Another important question is the extent to which the 

colon of select individuals might be particularly sensitive to lactose and/or its bacterial 

metabolites; e.g., are patients with IBS unusually susceptible to lactose induced symptoms? 

Treatment of Lactose Intolerance 

LI may be self-diagnosed or diagnosed by a clinician based on historical information and/or 

the demonstration of lactose malabsorption. Blinded evaluation to document the role of lactose in 

a patient’s symptomatology is not employed. As a result, the subject’s unblinded response to a 

reduction in lactose intake is the standard means of establishing the diagnosis of lactose 

intolerance. Treatment to reduce lactose exposure consists of a lactose restricted diet or the use 

of lactase supplements. The former may involve the avoidance of milk and milk-containing 

foods or the use of milk in which the lactose has been pre-hydrolyzed via treatment with lactase. 

Lactase supplements taken at the time of milk ingestion also are commercially available. 

Health Outcomes of Dairy Exclusion Diets 

As described above, gastrointestinal symptoms are the main presenting clinical symptoms of 

LI and a major reason that individuals are presumed to be lactose intolerant. In attempts to 

reduce these symptoms, many exclude dairy from their diet. Others avoid dairy for cultural or 

health belief reasons (vegans), even if they do not have symptoms of LI. Osteoporosis and 

associated fractures secondary to inadequate dietary calcium is the perceived major long-term 

health outcome of interest associated with real or assumed LI, since the avoidance of milk and 

milk containing products usually results in a dietary calcium intake that is well below 

recommended levels of 1,000 mg per day for men and women and 1,300 mg for adolescents. 

Women who are pregnant or breastfeeding need between 1,000 and 1,300 mg of calcium daily. 

Because dairy foods are the major source of dietary calcium intake (in the absence of 

supplementation), dietary recommendations suggest consuming 3 cups/day of fat-free or low-fat 

milk or equivalent milk products. This amount could be ingested over the course of the day (e.g., 

1 cup three times per day with each meal) to minimize potential problems with larger acute 

lactose loads. The recommended calcium intake by age group is shown in Table 1. Table 2 

shows examples of calcium content in common foods. 

Table 1. Recommended calcium intake by age group 

Amount of Calcium to Consume Daily, Age Group Age Group in Milligrams (mg) 

0-6 months 210 mg 

7-12 months 270 mg 

1-3 years 500 mg 

4-8 years 800 mg 

9-18 years 1,300 mg 

19-50 years 1,000 mg 

51-70+ years 1,200 mg 

Source: Adapted from Dietary Reference Intakes, 2004, Institute of Medicine, National Academy of Sciences. 

22 
 

Table 2. Calcium content in common foods 

Nonmilk Products Calcium Content 

Rhubarb, frozen, cooked, 1 cup 348 mg 

Sardines, with bone, 3 oz. 325 mg 

Spinach, frozen, cooked, 1 cup 291 mg 

Salmon, canned, with bone, 3 oz. 181 mg 

Soy milk, unfortified, 1 cup 61 mg 

Orange, 1 medium 52 mg 

Broccoli, raw, 1 cup 41 mg 

Pinto beans, cooked, 1⁄2 cup 40 mg 

Lettuce greens, 1 cup 20 mg 

Tuna, white, canned, 3 oz. 12 mg 

Milk and Milk Products 

Yogurt, with active and live cultures, plain, low-fat, vitamin D-fortified, 1 cup 415 mg 

Milk, reduced fat, vitamin D-fortified, 1 cup 285 mg 

Swiss cheese, 1 oz. 224 mg 

Cottage cheese, 1⁄2 cup 87 mg 

Ice cream, 1⁄2 cup 84 mg 

Source: Adapted from U.S. Department of Agriculture, Agricultural Research Service. 2008. USDA National Nutrient 

Database for Standard Reference, Release 21. 

Tolerable Dose of Lactose 

Symptoms induced by lactose malabsorption (lactose intolerance) result from: (a) fluid 

osmotically “held” in the gut by nonabsorbed lactose and its bacterial metabolites and (b) gases 

released by the bacterial fermentation of lactose. Thus, unlike an allergic reaction that may be 

triggered by trivial doses of the allergen, a symptomatic response to LM requires that the mass of 

lactose reaching the colon be sufficient to hold enough water to induce diarrhea and/or permit 

gas production of a magnitude that causes abdominal pain, distention, or flatulence. It follows 

that very low doses of lactose should be tolerated without symptoms, while very large doses 

should routinely induce symptoms. Defining the dosage that is tolerable in lactose malabsorbers 

is crucial to determining the clinical importance of LM as well the prevalence of LI. 

A variety of physiological differences between individuals indicates that there may be sizable 

individual differences in the dose of lactose that are tolerated by subjects with LM. Lactase 

nonpersistent subjects retain a low, but readily measureable, concentration of lactase in the brush 

border of their small bowel, and intubation studies have shown that these subjects are capable of 

absorbing variable amounts (mean: about 40 percent) of a 12 gram dose of lactose. The kinetics 

of this digestion have not been studied, but it seems likely that the 12 gram dose of lactose 

saturates the digestive activity of the gut, such that the percentage absorption would decline with 

increasing lactose loads. The tests employed to diagnose LM are qualitative and provide no 

information on the actual quantity of lactose not absorbed. It is possible that there are appreciable 

differences in the residual lactase activity of lactase nonpersistent subjects, with resultant sizable 

differences in their ability to digest and absorb a given dose of lactose. Differences in small 

bowel transit time (partially a function of gastric emptying) could affect the ability of this limited 

lactase activity to act on luminal lactose. 

If the osmotic load created by nonabsorbed lactose was simply a function of the amount of 

lactose reaching the colon, the potential for nonabsorbed lactose to increase fecal water and 

induce diarrhea would be predictable: a gram of lactose is equivalent to 3 mosms and fecal water 

23 
is isotonic (about 300 mosm/l). Thus, 12 grams of lactose (36 mosm), the quantity in 1 cup of 

milk, would osmotically hold 36/300 of a liter of fluid in the lumen or about 120 ml. Normally, 

humans excrete about 100 ml of fecal water each day, and increasing this quantity by 120 ml 

would yield a loose stool but not severe diarrhea. However, the vast majority of malabsorbed 

lactose is fermented by the colonic bacteria to short chain organic acids, which are rapidly taken 

up by the colonic mucosa. When relatively low amounts of lactose reach the colon, fermentation 

and subsequent absorption of lactose metabolites may be sufficiently rapid to remove all lactose 

and its metabolites from the fecal stream, thus protecting the subject from lactose-induced 

diarrhea. However, as the lactose load increases, the production of bacterial metabolites may 

outstrip the ability of the colonic mucosa to remove these metabolites. In this situation, bacterial 

metabolism increases the osmotic load over that of lactose with a resultant increase in fecal 

volume. Thus, differences in fecal bacterial metabolism, colonic mucosal function, and colonic 

transit time influence the susceptibility of individual subjects to develop diarrhea following 

malabsorption of lactose. 

Colonic bacteria ferment lactose via gas producing and nongas producing pathways. 

Adaption of the colonic flora via a shift to nongas producing pathways is considered to be the 

explanation for the decreased H2 excretion that occurs following daily exposure to large doses of 

lactose. This fermentation pathway could reduce the distention and flatulence noted with lactose 

malabsorption. The quantitatively important gases directly released during fermentation of 

lactose are carbon dioxide (CO2) and hydrogen gas (H2). The third quantitatively important gas 

resulting from fermentation is methane (CH4), a product of methanogenic bacteria that utilize 

preformed H2 and CO2 to synthesize CH4, a reaction that results in a fivefold reduction in gas 

volume (1 CO2 + 4 H2 → 2 H2O + 1 CH4). In addition, several other bacterial reactions utilize 

H2, and H2 released from fecal material is only a small fraction of that produced. After leaving 

the feces, CO2 is very rapidly absorbed across the intestinal mucosa; H2 and CH4 are also 

absorbed, albeit at a slower rate than CO2. The luminal gases that escape metabolism and 

absorption are excreted per the anus and thus have the potential to increase flatus volume and 

frequency. Since there are individual differences in the gas producing and consuming reactions, 

it would be expected that the volume of luminal gas resulting from malabsorption of a given 

quantity of lactose might vary widely from one subject to the next. 

Lastly, individuals differ in their response to colonic distention. Subjects with a 

“hypersensitive” colon may rapidly propel nonabsorbed lactose and its metabolites through the 

colon with resultant diarrhea and flatulence, while slower transit in the less sensitive colon could 

allow for more complete absorption of the metabolites, hence no diarrhea or flatulence. 

Similarly, the hypersensitive colon might perceive discomfort with a degree of distention that 

was imperceptible to subjects with a less sensitive colon. 

The above theoretical discussion suggests that there could be wide individual differences in 

the daily dose of lactose that is tolerable to subjects with lactose nonpersistence. Elucidation of 

this tolerable dose can only be obtained from a study of the subjective response of subjects to 

ingestion of known dosages of lactose. Some of the many factors that could influence the results 

of such studies are: 

1. Psychological – The perception of symptoms such as bloating and discomfort resulting 

from dietary manipulations is very susceptible to psychological factors. Thus, reliable 

testing requires placebo controlled, double-blind methodology. 

24 
2. Form that lactose is administered or restricted – The dietary load of lactose, rather than 

that of milk, should be manipulated to ensure that intolerance symptoms result from 

lactose rather than some nonlactose fraction of milk. 

3. Timing of lactose ingestion – Distributing lactose ingestion throughout the day very 

likely results in fewer symptoms than a similar quantity of lactose taken as a single dose. 

4. Food co-ingested with lactose – Food co-ingested with lactose would tend to reduce the 

rate of gastric emptying, which would slow the rate that lactose is presented to the small 

bowel and, hence, increase the fraction of lactose digested and slow the rate of 

presentation of unabsorbed lactose to the colon. 

5. Amount of lactose routinely ingested in diet – Some studies indicate that chronic 

ingestion of appreciable doses of lactose increases tolerance to lactose. 

6. “Sensitivity” of the colon – Subjects with a “hypersensitive” colon (i.e., IBS subjects) 

might be more susceptible to lactose-induced symptoms than are subjects who do not 

have IBS. 

Strategies to Manage Individuals with Diagnosed Lactose Intolerance 

Lactose is a simple disaccharide composed of glucose and galactose linked by a beta 1,4 

bond. Intestinal brush border synthesizes lactase, an enzyme that is able to cleave the beta 1,4 

bond. This hydrolysis is required for the intestinal absorption of lactose. 

Probiotics are live microorganisms that are ingested to prevent or treat disease. The current 

definition by the Food and Drug Administration and the World Health Organization is “Live 

microorganisms which, when administered in adequate amounts, confer a health benefit on the 

host.” These microorganisms are a heterogeneous group that are nonpathogenic and have betagalactosidase or lactase intracellularly and may aid in the digestion of lactose ingested by the 

host. These microorganisms can be added to food products, such as milk and yogurt, or used as 

supplements. Examples of commonly used probiotics include lactobacillus, bifidobacterium, and 

saccharomyces. Enzyme replacement therapy with lactase from nonhuman sources to hydrolyze 

lactose in another important approach to preventing lactose intolerance. There are multiple 

commercially available lactase supplements containing variable amounts of beta-galactosidase 

from a variety of sources. In addition, lactose reduced milk is also available commercially, with 

lactose content of 5 percent to 90 percent of regular milk. 

Probiotics and lactase supplements are often regulated as dietary supplements rather than 

pharmaceuticals or biological agents. Hence, there is no requirement to demonstrate efficacy, 

purity, potency, or safety prior to marketing probiotics and supplements. The access to the World 

Wide Web and direct consumer marketing has inundated the public with promotional 

information, while scientific evidence to support use has been largely overlooked. 

Another approach in management of lactose intolerance is to increase the lactose load 

steadily in one’s diet, giving the colon time to adapt. This is supported by the observation that 

introduction of lactose to diet causes temporary and transient symptoms in individuals.49 Since 

lactase from intestinal brush border is not an inducible enzyme, the reduction in symptoms may 

be explained by colonic adaptation. The time frame is approximately 1 week, as shown by 

Perman et al.151 that demonstrated increased beta-galactosidase activity and lactulose catabolism 

in the feces of healthy adults who consumed 40 gm lactulose per day for 1 week. 

Other strategies for management of lactose intolerance include gut decontaminating agents 

and anti-microbials, such as rifaximin. 

25 
Key Questions Addressed in this Report 

1. What is the prevalence of lactose intolerance? How does this differ by race, ethnicity, and 

age? 

2. What are the health outcomes of dairy exclusion diets? 

• In true lactase nonpersisters. 

• In undiagnosed or self-identified lactose-intolerant individuals. 

• How does this differ by age and ethnicity? 

• Health outcomes to include: Bone health – osteoporosis, fracture, bone density, bone 

mass; and gastrointestinal symptoms - abdominal pain, diarrhea, nausea, flatulence, 

bloating. 

3. What amount of daily lactose intake is tolerable in subjects with diagnosed lactose 

intolerance? 

• How does this differ by age and ethnicity? 

• What are the diagnostic standards used? 

4. What strategies are effective in managing individuals with diagnosed lactose intolerance? 

• Commercially available lactase 

• Prebiotics and probiotics 

• Incremental lactose loads for colonic adaptation 

• Other dietary strategies 

5. What are the future research needs for understanding and managing lactose intolerance? 

26 
Chapter 2. Methods 

Overview 

Analytic Framework 

We followed the analytic framework (modified from the U.S. Preventive Services Task 

Force)8

 to determine causality between treatments and patient outcomes and adverse events in 

patient subpopulations, including age, race, and ethnic subgroups. Probabilities of diagnosis, 

treatment, and outcomes were analyzed based on the published literature. 

Figure 1. Analytic framework 

Figure 1 describes target population and also includes individuals with self reported LI 

(regardless of symptoms) as well as individuals with clinically diagnosed LI, which may include 

those with lactose malabsorption, lactase nonpersistence, etc. Figure 1 also gives information 

about research questions: 

KQ1. What is the prevalence of lactose intolerance?
 

KQ2. What are the intermediate and clinical outcomes of lactose free or low lactose diets?
 

KQ3. What amount of daily lactose intake is tolerable in subjects with diagnosed lactose 

intolerance? 

KQ4. What are the intermediate, clinical, and adverse outcomes after treatments for lactose 

intolerance? 

In the clinical situation, a graduated definition of a potentially lactose intolerant subject, 

might be as follows: 

1. The quantity of lactose routinely ingested by the individual that causes symptoms. 

Appendixes and evidence tables cited in this report are available at http://www.ahrq.gov/downloads/pub/evidence/pdf/lactoseint/lactint.pdf. 

27 
2. The quantity of lactose ingested in some situations by the individual causes the above 

symptoms.3. The quantity of lactose that the individual would like to ingest (but does 

not due to fear of symptoms) causes the above symptoms. 

4. The quantity of lactose ingested in the course of obtaining 1,500 mg/day of calcium 

entirely via lactose-containing dairy products causes the above symptoms. 

A confounding problem is that factors other than simply the quantity of lactose ingested 

might influence a subject’s symptomatic response, i.e., the form in which lactose is ingested (ice 

cream versus milk, etc.), the coingestion of nonlactose containing foods, the nonspecificity of 

symptoms, and the large placebo response potentially observed. 

Criteria for Inclusion/Exclusion of Studies in Reviewing and 

Searching for the Evidence: Literature Search Strategies for 

Identification of Relevant Studies to Answer the Key 

Questions 

General Inclusion Criteria 

We included original observational studies that examined prevalence, symptoms, and 

outcomes in different age, gender, racial, and ethnic groups; published in the English language; 

randomized controlled clinical trials (RCTs) that examined different treatment options or doses 

of lactose loads in patients with LI or LM; and large observational studies in individuals with LI, 

LM, lactase nonpersistence, or reduced dairy intake that performed at least one strategy to reduce 

bias. We limited our search to studies published from 1967 to November 2009. We excluded 

studies that were published in non English languages and small case reports or descriptive case 

series with less than 100 subjects unless there are no reliable data from other higher quality 

studies. Because this report is to be used for a U.S. NIH Consensus Conference report we 

emphasized U.S. based population studies. We excluded populations with other GI disorders, 

including individuals diagnosed with IBS, inflammatory or infectious bowel diseases, or milk 

allergies. We excluded children younger than 4 years of age. 

Key Question 1: What is the prevalence of lactose intolerance? How 

does this differ by race, ethnicity, and age? 

 Study eligibility. We included studies if: (1) they were original research articles, (2) they 

presented prevalence data related to nonacute LI or LM, including self-reported symptoms, 

symptoms following a lactose challenge, symptoms following a placebo controlled and blinded 

lactose challenge, lactose malabsorption via a hydrogen breath test following a lactose challenge, 

hypolactasia defined by biopsy or genetic tests for adult-type hypolactasia, (3) the study 

population was not primarily secondary lactose intolerance related to other conditions or 

treatments, and (4) only results for those greater than 1 year of age. Since the focus of this report 

is to provide evidence most relevant for a U.S. population, all studies with a sample size greater 

than 50 that met the previous criteria were included if the study reported results from a U.S. 

28 
population. Only larger studies (at least 100 participants) of populations outside of the United 

States were included. 

To the extent that evidence of reliable estimates of LI is missing, we reviewed the evidence 

of prevalence of lactose malabsorption, lactase nonpersistence (adult-type hypolactasia) and selfreported symptoms following lactose consumption. 

Population. We included persons older than 4 years of age. 

Conditions. We defined lactose intolerance to be present when ingestion of 50 grams of 

lactose (or less) as a single dose by a lactose malabsorbing subject induces GI symptoms 

(abdominal pain, bloating, diarrhea, nausea, flatulence) not observed when the subject ingests an 

indistinguishable placebo. The 50 gram dose of lactose, the quantity present in a quart of milk, 

was selected because this quantity of milk provides the maximal recommended daily intake of 

calcium (1,500 mg), and this dosage approaches the maximal daily volume of milk likely to be 

ingested by most Americans (http://digestive.niddk.nih.gov/ddiseases/pubs/lactoseintolerance/). 

As discussed previously, LI defined in this way does not indicate that intolerance symptoms 

necessarily will be recognizable when these subjects ingest smaller dosages of lactose (as does 

the vast majority of the U.S. population). The prevalence of clinically important LI requires 

demonstration that the quantity of lactose that subjects actually ingest (or wish to ingest) causes 

symptoms in placebo-controlled experiments. We excluded congenital lactase deficiency, 

developmental lactase deficiency among pre-term infants, milk allergies commonly seen in 

infants, and acute lactose intolerance (<30-60 days duration) due to such things as antibiotic use 

or illness. 

 Disease severity. Lactose malabsorption is the physiologic problem that manifests as LI and 

is attributable to an imbalance between the amount of ingested lactose and the capacity for 

lactase to hydrolyze the disaccharide.7

 LM indicates that a sizable fraction of a dosage of lactose 

is not absorbed in the small bowel and thus is delivered to the colon. We defined severity of LM 

according to the amount of consumed lactose (desired or required to meet established dietary 

needs) before experiencing clinical symptoms of LI. Since such malabsorption virtually always 

is a result of low levels of lactase, there is a nearly one to one relationship of lactase 

nonpersistence (or deficiency) and LM. LM is objectively demonstrated via measurements of 

breath H2 or blood glucose concentrations following ingestion of a lactose load. We analyzed 

severity of lactose intolerance according to criteria from diagnostic tests: lactose intolerance 

breath test: increase from baseline in hydrogen + methane (in parts per million [ppm]) by 20-38 

ppm as mild and >39 as severe LI. 

We defined lactase nonpersistence according to presence of lactase enzyme on intestinal 

biopsy and according to the presence of the C/C genotype of the lactase promoter gene with 

genetic testing using restriction fragment length polymorphism or by DNA Sequencing to detect 

single-nucleotide polymorphisms (C-13910T, G-22018A) located upstream of the lactase gene 

within the gene MCM6. 

We reviewed differences in prevalence estimates based on different definitions of LI: 

• Primary lactase deficiency, a genetically determined decrease or absence of lactase is 

noted, while all other aspects of both intestinal absorption and brush border enzymes are 

normal. Primary lactase deficiency is attributable to relative or absolute absence of 

lactase that develops in childhood at various ages in different racial groups and is the 

most common cause of LM and LI. Primary lactase deficiency is also referred to as adulttype hypolactasia, lactase nonpersistence, or hereditary lactase deficiency. 

29 
• We excluded individuals if secondary lactase deficiency occurs in association with small 

intestinal mucosal disease with abnormalities in both structure and function of other 

brush border enzymes and transport processes. Secondary lactase deficiency is often seen 

in celiac sprue. 

Comorbidities, patient demographics. We attempted to review differences in prevalence in 

individuals of different age groups defined as: Preschool Children: 4-5 years, Children: 6-12 

years, Adolescents: 13-18 years, Adults: 19-44 years, Middle Aged: 45-64 years, Aged: 65+ 

years, and Elderly Adults: 80 and over. 

We attempted to review differences in prevalence of LI in patients of different raceethnicity groups defined as: Continental Africans, Asians and Europeans, African Americans, 

Arabs, Caucasians, Arabs, Asian Americans, and Hispanic Americans. We included studies of 

patients with LI and all comorbidities except acute diseases, treatment of which could cause 

secondary LI. 

Outcomes. 

Prevalence of LI. We reported prevalence according to: (a) patient reported diagnosis of LI, 

(b) clinician diagnosis of LI, and (c) absolute difference in prevalence of individuals with 

symptoms as derived from randomized controlled blinded trials conducted in subjects diagnosed 

with LI. We compared outcomes between individuals with a diagnosis of LI receiving blinded 

lactose (at varying doses) and control interventions, as well as the outcome from blinded RCTs, 

comparing outcomes in subjects with diagnosed LI versus control subjects. We assessed the 

prevalence of LM by evaluating studies using breath hydrogen measures. 

Glucose tolerance testing is rarely used clinically today, and studies assessing this method for 

evaluating LM were excluded. Studies assessing only intestinal biopsies were reviewed for 

quality and applicability. 

A critical aspect of this question was to clearly define and differentiate between: (1) lactase 

nonpersisters, (2) lactose malabsorbers, and (3) lactose intolerance. 

LI is the key component of this question and conference. Identifying a gold-standard 

definition of LI is critical and difficult. There is no objective laboratory test (intestinal biopsies 

are rarely done and only assess lactase enzyme levels; physiologic tests: e.g., hydrogen breath 

tests measure LM to a laboratory challenge and need to be evaluated to determine whether they 

accurately identify clinically relevant LI. 

We defined LI to be present when ingestion of 50 grams of lactose (or less) as a single dose 

by a lactose malabsorbing subject induces gastrointestinal symptoms not observed when the 

subject ingests an indistinguishable placebo. 

We evaluated prevalence according to different populations and methods of assessment with 

a particular focus on presence or absence of specific symptoms among individuals participating 

in blinded RCTs evaluating LI. While assessing prevalence in RCTs typically is not done to 

assess prevalence, we believe that patient reported symptoms and resolution of symptoms in the 

absence of placebo controlled trials are not reliable. 

Key Question 2: What are the health outcomes of dairy exclusion 

diets? 

Population. We included populations that consumed or were likely to consume dairy free or 

low dairy diets and reported on long-term GI and bone outcomes. We excluded individuals with 

30 
irritable bowel syndrome or other GI disorders, such as infectious or inflammatory diarrhea. We 

excluded populations with children under age 4. 

 Interventions. We defined dairy exclusion diets as low lactose diets that generally eliminate 

only milk and milk products or lactose free diets that eliminate all lactose products, including 

foods that are prepared with milk, both at home and in commercially packaged foods. We 

included studies with the following comparators: placebo or regular diet. We defined 

interventions when patients followed lactose free diets prescribed by health care professionals. 

We defined exposure when subjects followed low lactose or lactose free diets without 

recommendations from health care professionals. We included indirect evidence of the effect of 

dairy exclusion on health outcomes by including studies of populations known or suspected of 

having low dairy intake (e.g., diagnosis of LI/LM, lactase nonpersistence based on intestinal 

biopsy or genetic test association for lactase nonpersistence) even in the absence of specific 

documentation of amount of lactose intake. We assessed associations between lactose intake and 

factors associated with low lactose intake on GI symptoms or bone health, including clinical 

(fracture) and intermediate outcomes (osteoporosis, bone mineral density, and content). 

Outcomes. 

Primary bone outcomes. Fracture. 

Secondary bone outcomes. Osteoporosis, bone density, bone content. 

Primary gastrointestinal outcomes. Abdominal pain, diarrhea, nausea, flatulence, bloating. 

Osteoporosis was defined according to World Health Organization Criteria1-3 as a BMD 2.5 

standard deviation or more below the young average value in women and men.4

 Osteopenia was 

defined as a BMD 1-2.5 standard deviation below the population average.5 

We used reference data on femur bone mineral content and density of noninstitutionalized 

adults in the United States from the third National Health and Nutrition Examination Survey that 

collected dual energy x-ray absorptiometry in the nationally representative sample of 14,646 men 

and women 20 years of age and older.6 

Adverse events. All published adverse events. 

Timing. We included prospective and retrospective studies with duration of followup long 

enough to detect long-term differences in outcomes (5 years for fractures, 1-2 years for 

secondary bone outcomes, and greater than 1 month for GI symptoms). We evaluated the impact 

of lactose exclusion diets on shorter-term (<1 month) patient reported GI symptoms from 

observational and interventional studies among individuals with both LI and non LI controls. GI 

outcomes from RCTs with shorter duration followup are reported in Key Questions 3 and 4. 

Setting. We included studies in primary and specialty outpatient settings and population 

based settings. 

Co-interventions. We reviewed co-interventions in studies that reported patient outcomes 

after low lactose and lactose free diets. 

We conducted a literature search to identify three types of studies: 

1.	 Studies in patients with LI who followed lactose free diets. 

2.	 Studies that examined patient outcomes among healthy populations consuming dairy 

exclusion (or very low dairy) diets (e.g., vegans). 

3.	 Meta-analyses and systematic reviews that synthesized the association between dairy 

(dietary Ca++) intake and patient outcomes. 

Confounding factors. We analyzed the adjustment for the known factors that could 

confound the association between lactose intake and bone health, including age, gender, race, 

menopausal status in women, external calcium supplementation, renal function, and smoking. 

31 
We abstracted how systematic reviews addressed the adjustment for confounding for the 

association between low milk intake and bone fractures. 

The main long-term health concern related to lactose exclusion diets from this report was 

predominately related to potentially low calcium and vitamin D intake associated with these 

diets. We also assessed the impact of dietary or supplemental calcium and/or vitamin D. We 

reviewed whether the studies that examined patient outcomes in association with low dietary 

milk intake addressed calcium intake from other sources and supplementation with Ca++ or 

vitamin D. This provided us with contextual information regarding the potential role of low 

lactose or lactose free diet on bone health independent of other sources of Ca++ or vitamin D. 

Key Question 3: What amount of daily lactose intake is tolerable in 

subjects with diagnosed lactose intolerance? 

Population. Our target population was limited to subjects with self or clinically diagnosed 

LI. We focused on populations with clinically diagnosed LI. We defined genetic testing as 

reference methods to diagnose primary LI. We defined LI breath tests as methods for assessing 

LM. We defined self reported LI as the presence of self described clinical symptoms occurring 

only when they ingested lactose and relieved when they eliminated/reduced lactose or used 

products to hydrolyze lactose prior to ingestion. We quantified the type and severity of 

symptoms and the amount and type of lactose causing patient reported symptoms. A presumptive 

working diagnosis of LI was GI symptoms associated with the ingestion of foods containing a 

quantity of lactose that is either desired by the individual or considered necessary to meet 

national minimal daily dietary standards, and that resolve upon elimination or marked reduction 

of these lactose containing foods or when using products to hydrolyze lactose prior to ingestion 

and return upon lactose rechallenge provided in a blinded fashion. We defined self reporting as 

index methods to diagnose LI. 

 Interventions. We evaluated individual daily or weekly intake of lactose stratified by the 

presence or absence of index diagnostic tests for LI. 

Comparators. Placebo, inactive comparator, lactose dose response. 

Outcomes. 

Primary outcomes. Our primary outcomes included the prevalence and severity of GI 

symptoms, particularly abdominal pain, diarrhea, nausea, flatulence, and/or bloating. We 

assessed for the percentage reporting these outcomes as well as scores reported on symptom 

questionnaires. 

Timing. Short term (≤1 month) long-term (>6 months). 

Settings. Primary and specialty outpatient settings, population based settings. 

Because there was strong evidence of a placebo response, we relied on an evaluation of 

results from blinded RCTs, including dosing studies to determine the threshold amounts that 

caused symptoms in subjects with self or clinician diagnosed LI (with or without laboratory 

evidence of LM) ingesting different doses of lactose versus controls and the outcomes among 

individuals ingesting lactose with a diagnosis of LI versus non LI controls. Where possible, we 

attempted to categorize findings according to age, ethnicity, and patient reported baseline LI 

severity and whether symptoms differed between subjects diagnosed with LI (self versus 

clinician) and controls. 

We characterized the diagnostic standards used in these studies (e.g., patient reported 

symptoms and breath hydrogen (measure of LM not LI). If there are gaps in evidence related to 

32 
amount and type of daily lactose intake, symptoms were defined as patient reported: 

gas/flatulence, abdominal pain, bloating, and diarrhea. 

Key Question 4: What strategies are effective in managing individuals 

with diagnosed lactose intolerance? 

Study inclusion. We included randomized double blind controlled trials that evaluated 

probiotics, enzyme replacement therapies with lactase from nonhuman sources, administration of 

lactose reduced milk, and regimes of increases in dietary lactose load for improvement of GI 

symptoms in individuals with presumed LI or LM. 

Population. Subjects with presumed LI, LM, or controls and greater than 4 years of age. We 

also included double blind randomized trials that enrolled subjects with IBS and LM or LI. These 

were reported as a separate group. We excluded individuals with presumed IBS alone and other 

likely causes of acute GI symptoms (e.g., infectious, antibiotic, or inflammatory associated 

bowel disease). 

 Interventions. We evaluated the following interventions: 

• Commercially available lactase 

• Prebiotics and probiotics 

• Incremental lactose loads for colonic adaptation 

• Other dietary strategies 

Comparators. Placebo, usual care, no active treatment, or active control. 

Outcomes. 

 Primary outcomes. Disease specific and overall quality of life. 

 Secondary outcomes. Frequency and severity of specific GI items of disease specific quality 

of life questionnaires: abdominal pain, diarrhea, nausea, flatulence, bloating. 

 Adverse events. We evaluated all published adverse events.

 Timing. We analyzed all eligible studies regardless of followup duration. 

Settings. We included primary and specialty outpatient settings and population based 

settings. 

Assessment of Methodological Quality of Individual Studies 

We rated the quality of studies according to recommendations from the Methods Guide for 

Comparative Effectiveness Reviews. We used the following ratings of Quality of Individual 

Studies: 

• Well designed and conducted (good; low risk of bias). A study that adheres mostly to the 

commonly held concepts of high quality, including the following: a formal randomized 

controlled study; clear description of the population, setting, interventions, and 

comparison groups; appropriate measurement of outcomes; appropriate statistical and 

analytic methods and reporting; no reporting errors; low dropout rate; and clear reporting 

of dropouts. 

• Fair. These studies are susceptible to some bias, but it is not sufficient to invalidate the 

results. They do not meet all the criteria required for a rating of good quality because they 

have some deficiencies, but no flaw is likely to cause major bias. The study may be 

missing information, making it difficult to assess limitations and potential problems. 

33 
 

• Poor (high risk of bias). These studies have significant flaws that imply biases of various 

types that may invalidate the results. They have serious errors in design, analysis, or 

reporting; large amounts of missing information; or discrepancies in reporting. 

We assessed for external validity (applicability) according to the Methods Guide for 

Comparative Effectiveness Reviews. 

Data Synthesis 

We summarized evidence into summary tables with qualitative analysis of the results for 

prevalence of LI by subgroups for Key Question 1. We did not pool results for Key Question 

1.We attempted to calculate odds ratio with 95 percent confidence interval (CI) or absolute risk 

differences from the reported number of events in RCTs as well as the number needed to treat to 

achieve one event of the outcome if the data are homogeneous enough to permit pooling. All 

additional calculations were performed at 95 percent confidence levels. 

We calculated minimum difference in continuous variables from the reported sample size, 

means, and standard deviations. We calculated crude odds ratios from the reported number of 

subjects with and without outcomes among compared categories of exposure. Calculations were 

performed using STATA software,152 SAS 9.2,153 and Meta-analyst software (available at 

https://research.tufts-nemc.org/metaanalyst/) at the 95 percent confidence level. 

Attributable risk was calculated as the outcome events rate in patients exposed to different 

clinical interventions.9-11 The number needed to treat to prevent one symptomatic event was 

calculated as the reciprocal to the absolute risk differences in rates of outcomes events in the 

active and control groups: 1/(control group event rate - treatment group event rate).10-12 We did 

not pool data related to Key Questions 1 or 2. 

For Key Questions 3 and 4 if symptoms associated with lactose malabsorption (abdominal 

pain and frequency of diarrhea) data were appropriate for pooling, they were analyzed using 

RevMan 5.0 software using a random effects model.154 Standardized mean differences (symptom 

effect sizes) were calculated with the generic inverse variance method due to the crossover study 

design of the trials. 

Grading the Evidence for Each Key Question 

Assess Study Quality and Strength of Evidence 

On the basis of the quality checklist(s) developed for articles relevant to the various key 

questions, we assigned a quality score to each article. We used methods for assessing study 

quality and strength of evidence according to the Methods Guide for comparative Effectiveness 

Reviews that is conceptually similar to the GRADE (Grades of Recommendation Assessment, 

Development, and Evaluation) system of evidence rating.13,14 Specifically, we assessed four 

domains: risk of bias, consistency, directness, and precision. When appropriate, we also include 

dose response association, presence of confounders that would diminish an observed effect, 

strength of association, and publication. 

Quality of evidence across studies for each outcome. We graded the quality of evidence 

for primary outcomes across studies as illustrated below: 

34 
Overall ranking of evidence. 

Grade Definition 

High High confidence that the evidence reflects the true effect. Further research is 

very unlikely to change our confidence in the estimate of effect. 

Moderate Moderate confidence that the evidence reflects the true effect. Further research 

may change our confidence in the estimate of effect and may change the 

estimate. 

Low Low confidence that the evidence reflects the true effect. Further research is 

likely to change the confidence in the estimate of effect and is likely to change 

the estimate. 

Insufficient Evidence either is unavailable or does not permit a conclusion. 

35 

Chapter 3. Results 

All work was conducted under the guidance of a Technical Expert Panel (TEP), whose 

members are identified in Appendix A. Figure 2 shows the inclusion/exclusion criteria and 

number and reasons for study inclusion and exclusion. The search strategies for the research 

questions are described in Appendix B. Excluded references are shown in Appendix C. 

Key Question 1: What is the prevalence of lactose 

intolerance? How does this differ by race, ethnicity, and age? 

Description of Study Characteristics 

Our search strategy identified 2,450 articles from abstracts or full articles that were obtained 

to determine study eligibility. Each article was read by one extractor and was included for further 

review if the article either appeared to meet the inclusion criteria or if inclusion was uncertain. In 

cases where inclusion was not obvious, additional review by a senior investigator occurred. 

A total of 54 articles met inclusion criteria (Figure 2). These articles include populations from 

the United States, as well as populations for Northern, Central, and Southern Europe, the Middle 

East, Central America, South America, Africa, Asia, and Australia. As described in our methods 

section, we over represented studies from the United States in order to make this review more 

relevant to U.S. populations. Although the majority of research has occurred outside the United 

States, our review includes 15 studies from the United States, with a total of 4,817 participants. 

Only one randomly selected or population representative study of the United States was 

identified, and this study only included self reported LI on a questionnaire with no lactose 

challenge or objective confirmation.35 The vast majority of studies are convenience samples, 

which make extrapolation of results to the general public difficult to impossible. 

Lactose Intolerance 

Symptoms following blinded lactose challenge. We identified no studies in the United 

States or elsewhere that reported on the prevalence of LI based on our “gold-standard” definition 

of LI. Since abdominal symptoms can be caused by a large number of factors unrelated to lactose 

and biases in attributing abdominal symptoms following unblinded challenges of lactose, it is 

difficult to accurately identify the prevalence of symptoms truly attributable to lactose. This is 

made even more difficult since studies have rarely tried to obtain samples of participants that are 

representative of the overall U.S. population. Because of these limitations, we were unable to 

accurately define the true prevalence of LI or estimate the extent to which the true prevalence of 

LI differs depending on race/ethnicity or age. 

The prevalence of symptoms estimated from studies not using blinded challenges is defined 

for the remainder of the report as “symptoms” so as to intentionally distinguish these results 

from the prior mentioned “gold standard” definition of prevalence of LI. 

Symptoms following nonblinded lactose challenge. We identified 21 studies that reported 

LI related symptoms (abdominal pain, bloating, excess flatulence, and diarrhea) following a 

Appendixes and evidence tables cited in this report are available at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/lactoseint/lactint.pdf. 

37 
 

challenge of lactose.7-28 Detailed information about each of these studies, included in Table 3, is 

stratified into three different groups based on whether the participants self reported prior LI 

related symptoms prior to the challenge. Studies include results on a total of 8,174 people from 

various samples collected on every continent except Antarctica. 

There is, however, little data available specifically from the United States to answer this 

question, and the data that are available offer little information about the overall prevalence of 

people who would report symptoms of LI if they were given a lactose challenge; moreover, these 

data are particularly limited for providing information on the impact of race/ethnicity and age on 

prevalence of symptoms. No U.S. studies from the past 30 years were identified. Four older, U.S. 

studies of convenience samples were identified.13,18,26,27 Newcomer reported results on a 

population of healthy Caucasian volunteers with no history of milk intolerance.18 This study 

reported no overall prevalence of symptoms following the lactose challenge, but it did report that 

all six of the participants with biopsy determined hypolactasia reported symptoms, while only 4 

percent (2/57) of participants with normal lactase levels reported symptoms. U.S. studies of 

healthy volunteers from Texas reported results in adults26 and children27 for Hispanic and white 

non Hispanic participants. In adults, Hispanics were 43 percent more likely to report symptoms 

following a lactose challenge compared to white non Hispanics (Hispanics 67 percent versus non 

Hispanics 47 percent).26 Similarly, in children the rate of symptoms was much higher among 

Hispanic children (41 percent versus 20 percent in non Hispanic); however, even among Hispanic 

children, the majority did not experience symptoms and among Hispanic children less than 6 years 

old symptoms were rare (18 percent).27 The fourth U.S. study included black (n=69) and white 

(n=30) children between the ages of 4 and 9 years old.13 This study provided some information that 

is consistent with studies reported in other countries, showing the overall frequency of symptoms 

following a challenge is quite low in young children, but the rate increases with age and is 

significantly higher in black children compared to white children. Specific estimates of the 

prevalence in age or race strata are impossible, since confidence intervals were very wide. 

Larger and more recent studies have been conducted outside of the United States, and these 

studies do provide more information, suggesting that there are substantial differences in the 

prevalence of reported symptoms depending on both the age and ethnicity of the population. 

These non U.S. populations included a total of nearly 7,260 participants from 16 different 

countries (Table 3).7-12,14-17,19-25,28 The results in Table 3 are separated according to whether the 

primary population does or does not have symptoms at baseline. 

Many of the studies only reported symptoms in subgroups of their populations; for example, 

only in people who had positive breath hydrogen tests (LM) or only in people who reported 

previously having symptoms. Studies that reported results in people both with and without LM, 

reported significantly greater frequency of symptoms (typically around twice as high) in those 

with positive breath hydrogen tests compared to those with negative tests.11,15,22,25 

Two studies reported doses of approximately 50 grams of lactose versus 12 grams of lactose 

and found much lower rates of symptoms with lower doses.15,16 While dose studies were 

uncommon, these dose results suggest that even among people positive for LM, symptoms might 

only occur in a minority of people when the dose is approximately one glass of milk. This might 

be particularly true for young children.15,16 

Older age is a consistent predictor of increased symptoms following a lactose 

challenge.13,16,19,23,28,155 For almost all populations it appears as though very few children 

younger than 6 experience symptoms following lactose challenges. There was some evidence 

that children of African or Asian decent may experience increased frequencies of symptoms in 

38 
childhood at younger ages compared to other populations, but even these studies still showed 

that the majority of young children did not experience symptoms.23,28,53 

Symptoms without lactose challenge. Self reported history of LI related symptoms without 

empirical evidence of symptoms following a lactose challenge is very difficult to interpret. We 

identified seven studies reporting baseline self-reported symptoms representing 6,161 people.29-34 

35 Study characteristics from the identified studies are provided in Table 4. The population based 

nationally representative sample of U.S. adults by Nicklas and colleagues provides some 

evidence regarding the prevalence self-reported LI.35 This study included 1,084 respondents 19 

to 70 years of age, of which 486 were European American, 355 were African American, and 243 

were Hispanic American. Data from this survey were combined with U.S. Census Bureau data to 

estimate an overall age adjusted prevalence of self reported LI of 12 percent. The specific 

racial/ethnic estimates were 8 percent for Caucasian adults, 20 percent for African American 

adults, and 10 percent for Hispanic Americans. This study did not attempt to validate the self 

reported results with either laboratory tests or clinician diagnoses. 

Among non U.S. studies, one additional population based random sample of 1,978 Iranian 

adults showed a population self reported prevalence of 28 percent with no variation by age.34 The 

generalizability of this one non U.S. study is difficult to put into a broader context without 

similar studies reporting different racial and ethnic populations and with greater variations in 

age. 

Other than the one population based random sample in the United States, the rest of the self 

reported studies’ results provide little evidence to address our research questions about 

population prevalence and the impact of age and ethnicity. Overall, the prevalence of self 

reported symptoms was typically lower than the prevalence of symptoms following a lactose 

challenge. 

Lactose Malabsorption 

Determined by hydrogen breath test following lactose challenge. Prevalence of LM, as 

diagnosed via a hydrogen breath test following a lactose challenge, has been frequently assessed 

in a wide range of studies from around the world. We identified 31 studies, including a total of 

nearly 12,000 participants from a wide range of ages and ethnicities.7,8,10-12,14-17,20-25,28,30,32,36-42,44­

48,156 The study characteristics from the identified studies are provided in Table 5. The studies in 

Table 5 are stratified into three different groups based on whether the participants self reported 

LI related symptoms prior to the challenge. Unfortunately, none of the U.S. studies were 

representative population based studies. In fact, all of the U.S. studies identified focused on 

reporting results in populations of patients with GI symptoms at baseline,36,42,47,48 with the 

exception of one three decade old study of American Indians30 and one convenience sample of 

adults from the Army, senior centers, nursing homes, and a university.44 

Within the U.S. studies, the prevalence of LM in Caucasian adult populations ranged from 6 

percent to 24 percent.42,44,47 There were also some data suggesting high levels of LM among 

American Indians, but this effect was substantially attenuated among those with American Indian 

and Caucasian mixed ancestry.30 Few data were eligible for this review for other racial and 

ethnic groups within U.S. populations, but a prior review of smaller and older studies using 

blood glucose tests suggested that the prevalence of LM may be greater than 70 percent in 

African Americans, around 50 percent in Hispanic Americans, and even higher for Asian 

39 
Americans.49 Data for various racial and ethnic groups within the United States can likely be best 

understood by looking at the LM rates in the ancestral homelands of each of these ethnic groups. 

The high prevalence of LM in the majority of non Northern European countries has been 

well known for decades. Earlier reviews captured many of the smaller and earlier studies, 

particularly those that used blood glucose tests.49 The focus of this current review was more on 

LI as compared to LM. Similar to what has previously been reported, we found a wide range of 

LM rates that tended to be lowest among groups of Northern European ancestry, and relatively 

high in most other regions. Clearly, race and ethnicity have significant effects on the prevalence 

of LM; however, it is difficult to put precise estimates around the prevalence of LM for any 

group. In general, the majority of adults from populations with Northern European ancestry are 

able to digest lactose; whereas, the majority of adults who are Asian, African, American Indian, 

or from Sicily, Italy, (and actually much of the rest of the world) are unable to adequately digest 

50 gram challenges of lactose. However, it is important to note that for many regions there is 

significant heterogeneity within the population in the ability of adults to digest lactose. This is 

particularly true within some regions in Africa,37,38 but it has also been seen in other areas, such 

as in Italy.11 However, much of the within country variation seen around the world is likely due 

to immigration that has occurred during the past couple of centuries. 

Age is clearly an important contributor to the rate of LM, since nearly every population 

group identified, even those with high adult rates of LM, showed low rates of LM in the 

youngest age groups, particularly those less than 6 years of age.16,17,23,28,39,45,46 In populations 

with high adult rates of LM, rates often seemed to nearly peak between 10 and 16 years of age. 

Not unexpectedly, the dose of the lactose challenge appears to be an important factor in the 

reported prevalence of lactose malabsorption. Studies that included a lower dose challenge 

appeared to identify significantly fewer case of malabsorption.12,16,23,41,46 Unfortunately, these 

lower dose studies were primarily only conducted in children, with the exception of a study of 

adults from Norway that found a 4 percent prevalence of LM following a 25 gram lactose 

challenge12 and a study from Spain that found, compared to the standard challenge, a single 

serving of milk and a single serving of yogurt were much less frequently malabsorbed (33 

percent, 14 percent, and 4 percent, respectively).16 

Lactase Nonpersisters (Adult-type Hypolactasia Biopsy) 

Biopsy identification. Five studies were identified that reported on the prevalence of lactase 

persistence as diagnosed by biopsy assays.18,50-53 Generalizing results from these studies is more 

difficult since the studies were performed primarily in convenience samples of patients who had 

biopsy tissue available, often for clinical purposes, and these studies were all conducted decades 

ago (Table 6). The earliest study is the only study that provides estimates on lactase 

nonpersistence in a population of healthy U.S. Caucasians not thought to be intolerant to milk or 

to have GI symptoms.53 This study, among adults with a mean age of 39 years, found 6 percent 

(6/100) had lactase activity ≤0.5 units per gram, and from these data the authors estimated that a 

population prevalence of hypolactasia would be between 1.3 percent to 10.3 percent (95 percent 

confidence level) for asymptomatic Caucasian adults. 

One additional study from the United Kingdom provides a comparison of the prevalence of 

hypolactasia in four different groups of British adults who had biopsy jejunal tissue available: 

white subjects with normal histopathic biopsy, nonwhite subjects with normal histopathic biopsy, 

subjects with diarrhea following gastric surgery, and subjects with irritable bowel syndrome.50 

40 
There were no statistically significant differences in the frequencies of hypolactasia for white 

subjects (7/150; 5 percent), subjects with diarrhea following gastric surgery (3/36, 8 percent), or 

subjects with IBS (16/200, 8 percent); however, the prevalence of hypolactasia was substantially 

higher in the nonwhite subjects (15/29, 75 percent). The three remaining studies offer little data 

on the population prevalence of hypolactasia, since the study samples were highly selected for 

patients with clinical GI symptoms.51-53 The first study found that both white children (ages 6 to 

14) with recurrent abdominal pain and white children with chronic diarrhea had similar 

frequencies of hypolactasia—31 percent (8/26) and 36 percent (16/61), respectively.51 Similarly, 

another study found children with IBS had a similar frequency (p-value=0.16) of hypolactasia 

(40 percent, 45/112) compared to children with chronic abdominal pain (30 percent, 34/112).52 

This study did report that within children with IBS, the nine black children had a significantly 

higher prevalence of hypolactasia compared to the 103 white children (78 percent versus 37 

percent, respectively). The last study included a sample of 250 U.S. subjects with biopsy samples 

taken over a several year period with varied clinical reasons.53 This study did have a sample with 

both age (2-81) and racial (white=209 and black=39) diversity; however, the hypolactasia results 

were not stratified by race. The overall prevalence of hypolactasia in the sample was 34 percent, 

but without race or age stratification it is difficult to generalize these findings to create any 

meaningful population estimates. 

Genetic test association. Adult-type hypolactasia is thought to be an inherited autosomal 

recessive trait leading to decreased lactase activity in the intestinal mucosa. The most commonly 

reported genetic mutation for adult-type hypolactasia is the single nucleotide polymorphism 

(SNP) located 13,910 base pairs upstream of the lactase (LCT) gene of which the C allele is the 

globally most prevalent allele, while the less common T allele is associated with lactase 

persistence.54 

Nine studies were identified that reported genotype frequencies for adult-type hypolactasialinked LCT -13910C>T SNP mutation.29,45,55-57,59-61,91 These studies included a total of 8,581 

participants; however, none of these studies were of U.S. populations, and the majority of the 

people included in these studies had Northern European ancestry (Table 7). Not unexpectedly, 

there were no obvious differences in genotype by age group.55,56 In North European studies, 

Caucasians had frequencies between 10-20 percent for the homozygous C/C genotype.29,55-57,59,61 

The frequency of the C/C genotype was somewhat higher in the one study from Austria (C/C=27 

percent). Two studies reported results for the Italian regions of Sardinia45,60 and Apulia60 where 

the prevalence of the C/C genotype was between 80 percent and 90 percent. One study from 

Finland reported results in a subgroup of 65 children from Africa in which the prevalence of the 

C/C genotype was 95 percent. 

Results from genetic association tests consistently reported decreased consumption of milk 

(often on the order of twofold lower) in adults with the C/C genotype compared to those with at 

least one T allele.56,57,59,61,91 These differences were smaller in healthy children.59 The relative 

differences in calcium intake from all dairy and overall calcium intake were smaller than the 

differences in milk consumption.29,57,59,91 All of these studies were from populations in Finland 

with generally high dairy consumption, except for one study in Austrian men where milk 

consumption was low in all men.91 

41 
Summary 

There are few data available from recent U.S. studies regarding any of the outcomes we 

reviewed. The data that were available tended to be highly selected and not likely representative 

of the overall U.S. population. Finally, the outcomes that have been reported do not directly 

assess LI, but instead assess either an inability to fully absorb lactose or somewhat subjective 

symptoms that are prone to biased reporting. This lack of data may in part be due to the fact that 

LI is a difficult condition to define. The lack of a clear, clinically meaningful, and commonly 

accepted definition of LI may partly explain the limited information available for characterizing 

the U.S. population prevalence. 

While precise estimates of the U.S. prevalence of LI are not possible, there is evidence that 

the magnitude of LI will be very low in young children and likely remain low into adulthood for 

most populations of Northern European decent. For African American, Hispanic, Asian, and 

American Indian populations the rates of LI will likely be higher in late childhood and 

adulthood; however, smaller doses of lactose might be generally well tolerated in most 

populations. 

42 
Combined search results = 2,455 

references* 

Q1 (prevalence) = 

54 references 

Q2 (outcomes) = 

67 references 

Included = 160 references** Other = 33 references 

Q3 (daily intake) = 

28 references 

Excluded (2,295 references): 

Not relevant to key questions = 1,286 references 

Not lactose intolerance study = 460 references 

Not eligible outcomes = 224 references 

Ineligible number of subjects = 102 references 

Not target population = 65 references 

Review article = 51 references 

Not original research = 30 references 

Not English language = 17 reference 

Comment = 12 references 

Not eligible exposure = 11 references 

Q4 (management) = 

40 references 

Figure 2. Reference flow diagram 

* Searches of PubMed®, MEDLINE® (OVID), and the Cochrane Central Register of Controlled Trials (CENTRAL) 

were combined and duplicate listings were removed. 

**	 The total number of included references is not a sum of eligible references for each question because of 

overlapping eligibility. 

43 
Table 3. Prevalence of lactose intolerance symptoms following challenge 

Number Author, Year	 Diagnostic Challenge Prevalenc

Subject Selection Subject Characteristics Country	 Methods 

Inclusion/Exclusion 

Asymptomatic at baseline Ahmad, 19847 N=414 Mean age: 28.3 (range 18-48) Challenge: 50 g lactose/400 ml Overall: NA 

Pakistan (N. Males: n=404 water Subject selection: healthy, well- Subgroup Panjab) Females: n=10 nourished Pakistani adults Symptoms (gas and/or In malabsor

Race/ethnicity: Panjabi diarrhea) Inclusion/exclusion: NA 

Bolin, 1970157 N=100 Mean age: NA (18-40) Challenge: 50 g lactose/400 ml Overall: 6/10

Australia Males: n=62 water Subject selection: healthy adults Subgroups Females: n=38 Symptoms (abdominal pain, Males: 0/62 

Inclusion/exclusion: NA Race/ethnicity: Australians diarrhea) Females: 6/

Bujanover, N=110 198510 Subject selection: healthy Israel subjects 

Inclusion/exclusion: All were antibiotic and drug free 1 month prior to entrance; all were consuming dairy products. 

Mean age: 6 years 7 months (4 months-15 years) Males: n=61 Females: n=49 Race/ethnicity: Israeli Jews 

Challenge: 2 g/kg lactose up to 50 g (10% solution) Symptoms: abdominal pain, diarrhea or soft stool with increased number of bowel movements, nausea and vomiting, flatulence, borborygmi 

Overall: NA Subgroups In malabsorBy age 

Years 0-3 3-6 6-12 12-16 

44 

Burgio, 198411 N=308 Mean age: 43.2 Challenge: 50 g lactose/400 ml Overall: 71/3

Italy Males: n=116 of boiled tap water Subject selection: healthy Italian Subgroups Females: n=192 adults Symptoms: abdominal Milk intolera

Race/ethnicity: Italians of distention, colics, borborygmi, 51/177 (29%

Inclusion/exclusion: NA Sicilian, N. Italian descent flatulence Milk intolera

(15%) 

Ladas, 199115 N=150 (baseline symptoms Mean age: NA (5-12) 

Greece n=43) Males: n=72 

Females: n=78 Subject selection: Greek children 

selected by their teacher- Race/ethnicity: Greeks assigned number Exclusion: One child was excluded because of a known milk allergy (atopic dermatitis). 

Challenge: 

2 g lactose/kg to a maximum of 50 g and 0.240 L of milk (12 g
 lactose) Symptoms: colicky pain, abdominal distention with flatulence and diarrhea, as well as the frequency and consistency of bowel movements 

2 g lactose/kIn absorbersIn malabsor0.240 L of mIn absorbersIn malabsorAge 5: 5/17 Age 12: 8/10 
Table 3. Prevalence of lactose intolerance symptoms following challenge (continued) 

Author, Year 

Country 

Leis, 199716 

Spain 

Number 

Subject Selection 

Inclusion/Exclusion 

N=850 Subject selection: healthy subjects from Galicia Spain with no history of GI illness Inclusion/exclusion: 1) not eaten or drunk anything for at least 12 hours; 2) not smoked for at least 6 hours (and did not smoke during the test); 3) not slept or done heavy physical exercise for at least 1 hour; 4) cooperated readily in the test, without hyperventilation or crying; 5) no antibiotics or laxatives for at least 15 days, and had not used any other drug on the day of the test; and 6) had gotten a positive breath hydrogen test after ingestion of 1 g/kg body weight of lactulose, so the enteric 

Subject Characteristics 

Mean age: NA Males: n=397 Females: 453 Race/ethnicity: Galician Spaniards 

Diagnostic Challenge 

Methods 

Challenge: 2 g lactose/kg up to 50 g 250 ml of milk 250 ml of yogurt Symptoms (vomiting, nausea, diarrhea, belching, flatulence, abdominal pain, distension) 

Prevalenc

Overall: NA Subgroups In malabsor150/276 (54Ages 3-5: 0/Ages 6-13: 3Ages 14-18: Ages 19-24: Ages 25-60: Age >60: 6/In malabsor

(18.5%) Ages 3-5: 0/

Ages 6-13: Ages 14-18: Ages 19-24: Ages 25-60: Age >60: 1/6 

bacterial flora was able to produce hydrogen 

45 

Newcomer, N=100 Mean age: 38.5 (20-63) Challenge: 50 g lactose/500 ml Overall: NA 196718 Males: 37 (20-63) water Subject selection: healthy Subgroups USA Females: 40 (21-62) Caucasian volunteers Symptoms: diarrhea, cramping, In malabsor

Males: n=50 bloating, borborygmi, flatulence In absorbers

Inclusion: no history of milk Females: n=50
 

intolerance Race/ethnicity: Caucasian 

Rosado, 199419 

Mexico 

N=926 Subject selection: randomly selected subjects from 3 regions Inclusion/exclusion: healthy, taken no meds, antibiotics for last 3 weeks, <60 years old 

Mean age: 14.9 N. Mexico: 14.1 C. Mexico: 15.8 S. Mexico: 14.3 Males: NA Females: NA Race/ethnicity: Mayan, “mixed” 

Challenge: 240 or 360 ml of whole intact cow's milk (12 or 18 g of lactose, respectively) Symptoms: headache, gas, flatulence, abdominal cramps, leg pain, diarrhea 

Overall: 151Subgroups: 

Years <4 

4 to <8 8 to <13 Adult 
Table 3. Prevalence of lactose intolerance symptoms following challenge (continued) 

Number Author, Year Diagnostic Challenge Prevalenc

Subject Selection Subject Characteristics Country Methods 

Inclusion/Exclusion 

Segal, 198321 N=115 Mean age: 32.5 Challenge: 50 g lactose/400 ml Overall: 32/1

South Africa Males: NA water Subject selection: healthy adult Females: NA volunteers Symptoms: abdominal 

Race/ethnicity: Zulu, Xhosa, discomfort, borborygmi, Exclusion: GI symptoms Sotho, Tswana, Swazi, diarrhea 

Shangaan 

Ting, 198823 

Republic of China (Taiwan) 

N=726 Subject selection: subjects in good health, without diarrhea or antibiotic therapy for at least 1 week prior to study Inclusion/exclusion: NA 

Mean age: NA (3-18) Males: NA Females: NA Race/ethnicity: Chinese 

Challenge: 0.5 g lactose/kg Symptoms: abdominal pain, diarrhea, and/or flatulence 

Overall: NA Subgroups 

Age (years3 4 

5 6 7 9, 10 8 11, 12 13, 14 15, 16 17, 18 

46 

Wang, 198425 N=641 Mean age: 22.9 (16-46) Challenge: 50 g lactose Overall: 287

China Subject selection: healthy, wellnourished, volunteers Males: n=447 Females: n=194 Symptoms: gas and/or diarrhea Subgroups Absorbers: 1

Inclusion/exclusion: NA Race/ethnicity: Han, Mongols, and Kazakhs from N. China Malabsorbe

Yang, 200028 

China 

N=1168 Subject selection: Healthy subjects recruited from schools in large cities. Inclusion/exclusion: diarrhea, chronic constipation or other GI problems, no use of any drugs 1 week prior to test, good general health without signs of acute or chronic illness 

Overall mean age: 8.0 (3-13) Males: n=610 Females: n=558 Race/ethnicity: Chinese 

Challenge: 25 g lactose or 50 g milk Symptoms: bloating, pain, diarrhea 

Overall: 296Subgroups: 

Years 3-5 7, 8 11-13 
Table 3. Prevalence of lactose intolerance symptoms following challenge (continued) 

Number Author, Year Diagnostic Challenge Prevalenc

Subject Selection Subject Characteristics Country Methods 

Inclusion/Exclusion 

Symptomatic at baseline Beyerlein, 20088 

Switzerland Hermans, 199714 

The Netherlands 

N=1,127 Subject selection: data from all patients referred for H2-BT 

between 1999 and 2005 were collected prospectively Inclusion/exclusion: patients were asked to fast and refrain from smoking for at least 6 hours prior to the test. Patients were also asked to discontinue use of antibiotics 1 week and laxatives 1 day before the hydrogen breath test N=309 Subject selection: Consecutive adult patients with suspected LM underwent a lactose tolerance test. Exclusion: Subjects who were treated with antibiotic drugs or underwent bowel preparation for an endoscopic or a radiological investigation within 4 weeks before the test, as well as those with diabetes mellitus, were excluded from the study. 

Farup, 200412 N=187 (Irritable bowel syndrome 

Norway Group n=82, Controls n=105) 

Subject selection: A populationbased, case-controlled, health study. Persons with irritable bowel syndrome (Rome II criteria) and alarm symptoms were invited to follow up. Also invited was a group of healthy Norwegians to participate in the study as a control group. Exclusion: organic disease 

Mean age: 39.8 (7-87) Males: n=320 Females: n=807 Race/ethnicity: “Swiss,” “nonSwiss” Mean age: 42 Males: n=130 Females: n=179 Race/ethnicity: NA 

Challenge: 50 g lactose Symptoms: nausea, abdominal pain, borborygmi, bloating and diarrhea Challenge: 50 g lactose Symptoms: Total symptom score was 0-8, with 8 being most severe. Each symptom (bloating, flatulence, abdominal distension, diarrhea) was scored with 0 (no complaints), 1 (moderate), 2 (severe), with diarrhea always scored as a 2. 

Overall: 326

Subgroup: Swiss: 241/7Non-Swiss: 

Overall: 220Subgroups 

Total sympscore (0-8) 

0 1 2 3 4 

47 

Symptomatic and asymptomatic at baseline 

Mean age: 47 Males: n=49 Females: n=138 Race/ethnicity: Norwegians 

Challenge: 25 g lactose Symptoms: abdominal pain/discomfort, borborygmi, bloating, diarrhea, or constipation 

Overall: N/A Subgroups Irritable bowControls: 21Total symptoIrritable bowControls (n=
Table 3. Prevalence of lactose intolerance symptoms following challenge (continued) 

Author, Year 

Country 

Garza, 197613 

Number 

Subject Selection 

Inclusion/Exclusion 

N=99 

Subject Characteristics 

Mean age: NA (4-9) 

Diagnostic Challenge 

Methods 

Challenge: 2 g lactose/kg to a 

Prevalenc

Overall: NA 

USA Sample: healthy White and Black 

children Inclusion/exclusion: NA 

Males: NA Females: NA Race/ethnicity White: n=30 Black: n=69 

maximum of 50 g Symptoms 

Subgroups 

Age Blacks 4,5 6,7 

8,9 Whites 4,5 6,7 8,9 

Maggi, 198717 

Uruguay 

N=200 Subject selection: randomly selected volunteer subjects were 

Mean age: NA (0-86) Males: n=100 Females: n=100 

Challenge: 2 g lactose/kg body weight or 50 g lactose/m2 body 

surface 

Overall: 65/2Subgroups In LM in sub

prospectively studied Race/ethnicity Symptoms (40%) Inclusion/exclusion: NA Whites: n=184 

48

Blacks: n=16 

Seakins, 198720 

Samoa, New Zealand, Cook Islands Socha, 198422 

Poland 

N=207 Subject selection: Samoan children were studied in four locations, two in W. Samoa and two in New Zealand. White children were studied in the Cook Islands and New Zealand. Inclusion/exclusion: NA N=275 (historical milk intolerance, n=15) Subject selection: healthy Polish adolescents and adults Inclusion/exclusion: NA 

Mean age: NA (6-13) Males: n=NA Females: n=NA Race/ethnicity Somoans: n=139  Whites: n=68 Mean age: 29.1 (16-59) Males: n=61 Females: n=214 Race/ethnicity: NA 

Challenge: 10 g lactose/100 ml orange flavored, carbohydratefree cordial Symptoms from milk (abdominal bloating and pain, flatulence, and diarrhea) Challenge: 50 g lactose/400 ml water Symptoms: abdominal pain and distension, flatulence, borborygmi, nausea, diarrhea 

Overall: 24/2

Subgroups Samoans: 1Whites: 8/68 

Overall: 110

Subgroups In malabsorIn absorbersIn historical (88.6%) In historical (32.4%) 
Table 3. Prevalence of lactose intolerance symptoms following challenge (continued) 

Number Author, Year Diagnostic Challenge Prevalenc

Subject Selection Subject Characteristics Country Methods 

Inclusion/Exclusion 

Vernia 200424 

Italy Woteki, 197627 

USA Woteki,197726 USA 

N=402 Subject selection: consecutive IBS patients diagnosed by Rome criteria Inclusion/exclusion: NA N=339 Subject selection: normal and healthy as described by school nurse Exclusion: known GI diseases, or diabetes; secondary lactase deficiency N=419 Subject selection: volunteers were solicited from within the San Antonio area Exclusion: diabetes, digestive or liver diseases, previous GI surgery (excepting appendectomy) 

Mean age: 35.1 Males: n=120 Females: n=282 Race/ethnicity: NA Mean age: 7.5 (2-14) 

Males: “approximately equal numbers” Females: “approximately equal
 numbers” 

Race/ethnicity
 Mexican American: n=282 Anglo American: n=51 

Challenge: 0.5 g lactose/kg up to a maximum of 25 g Symptoms Challenge: 2 g lactose/kg up to a maximum of 50 g Symptoms 

Overall (self breath test): Subgroups Symptoms aconsumers: Symptoms amilk intolera(75.6%) Overall: 126Subgroups Mexican AmAnglo Amer<0.005 

Age 

group 

Mexican A2-5 6-9 10-14 Total Anglo Ame2-5 6-9 10-14 Total 

49 

Mean age: 32.6 (18-94) Males: NA Females: NA Race/ethnicity Mexican-American: n=277 Anglo American: n=142 

Challenge: 50 g lactose Symptoms 

Overall: 253

Subgroups Mexican-AmAnglo Amer
Table 4. Prevalence of lactose intolerance by self report 

Number Author, Year Subject Selection Subject Characteristics Diagnostic Methods Prevalence of L

Country Inclusion/Exclusion 

Symptomatic and asymptomatic at baseline Ennattah, 200529 N=564 

Finland Subject selection: crosssectional, cohort study of 

population-based, postmenopausal women (n=453), women with osteoporotic fractures (n=52), and a control group of women without osteoporosis (n=59) Inclusion/exclusion: NA 

Johnson, 197830 N=109 

USA Sample: Native Americans 

with full and mixed blood from various tribes from the American Great Basin and South West Excluded: subjects with diabetes or a recent history of diarrhea or intestinal surgery 

Johnson 198031 N=1,452 USA (Hawaii), Subject selection: Republic of Questionnaire administered China (Taiwan), to students in the U.S., Japan, Republic Taiwan, and Japan of Korea (S. Korea), Peoples’ Inclusion/exclusion: NA Republic of China 

Mean age: 70 (62-85) Mean age (population-based cohort): 69 (62-78) Males: n=0 Females: n=564 Race/ethnicity: Finns Mean age: >18 years Males: NA Females: NA Race/ethnicity: Native Americans

50 

Mean age: NA Males: NA Females: NA Race/ethnicity: 

Hawaii subjects Caucasians: n=177  Chinese: n=58 Filipino: n=49 

Hapa-Haole (either 1⁄2 Chinese, Japanese or Korean & 1⁄2 European): n=22 Hawaiian (or partial): n=52 

 Japanese: n=366 Homeland Chinese: n=296 

Self report Overall (population-ba

(16%) 

Self report Overall: 30/109 (27.5%Self report Overall: NA 

Subgroups Retrospective childhopopulations that conspresent 

National/ethnic group Hawaiian Caucasian 29

Asian/Pacific Rim† 

Foreign Asian* 

*Chinese (N=296), Ja
51 

Table 4. Prevalence of lactose intolerance by self report (continued) 

Author, Year 

Country 

Number 

Subject Selection 

Inclusion/Exclusion 

Subject Characteristics Diagnostic Methods Prevalence of L

Homeland Japanese: n=192 Homeland Koreans: n=240 

Korean (N=240). †Hawaiian Chinese (N

Hapa-Haole (N=22), H(N=52). Self-reported symptomfrom populations that milk at present 

National/Ethnic Group Hawaiian Caucasian 22Asian/Pacific Rim† 

Foreign Asian* 

*Chinese (N=296), JaKorean (N=240). †Hawaiian Chinese (N

Hapa-Haole (N=22), H

Kokkonen 200132 

Finland 

N=260 Subject selection: Fifty-six 10­year-old subjects (n=56) who manifested cow’s milk allergy before 1 year of age, compared to a group (n=204) randomly selected agematched school children. 

Mean age (subjects with cow’s milk allergy): 10.5 (9­11) Males: n=35 Females: n=21 Race/ethnicity: Finns 

Self report Overall 

Cow’s milk allergy GrControls: 18/204 (9%

Children underwent a blind, placebo-controlled milk challenge. Inclusion: children with abdominal pain or reported complaints compatible with lactose intolerance (e.g., flatulence, diarrhea, abdominal pain) 
Table 4. Prevalence of lactose intolerance by self report (continued) 

Author, Year 

Country 

Nicklas, 200935 

USA 

Number 

Subject Selection 

Inclusion/Exclusion 

N=1,084 Subject selection: participants were selected from a representative sample of randomly generated telephone numbers from a commercial provider Inclusion: NA 

Subject Characteristics 

Mean age: NA Males: n=351 Females: n=733 Race/ethnicity European Americans: n=486 African Americans: n=355 Hispanic Americans: n=243 

Diagnostic Methods 

Self report 

Prevalence of L

Overall (age adjustedSubgroups (age adjusEuropean AmericansAfrican Americans: 19Hispanic Americans: European American mEuropean American fAfrican American malAfrican American femHispanic American mHispanic American fe

Paajanen 200533 

Finland 

52 

Saberi-Firoozi 200734 

Iran 

N=827 (Controls n=29) Subject selection: Study group was drawn from a population-based cohort of children living in northern Finland, who were initially recruited in 1994 for a study of risk factors for Type 1 diabetes. Inclusion/exclusion: celiac disease, A–class antibodies to tissue transglutaminase, Type I diabetes N=1978 Subject selection: healthy cohort in Shiraz, Iran, chosen by cluster randomization Inclusion/exclusion: NA 

Mean age: NA (16-21) (from original cohort of 3,652) Males: n=367 Females: n=460 Race/ethnicity: Finns Mean age: 49.9 Males: n=709 Females: n=1,269 Race/ethnicity: Iranians 

Self report Overall (self-diagnose

diagnosed LI): 108/8210.8%-15.4%) 

Self report (questionnaire— subjective symptoms by Rome II criteria) 

Overall LI: 562/1978 (Subgroups 

Gender Male  FemAge groups  35-4 45-5 55-6 65-7

≥ 75 

*P=0.015 
Table 5. Prevalence of lactose malabsorption by challenge 

Number Author, Year Diagnostic Challenge Subject Selection Subject Characteristics Prevalence 

Country Methods Inclusion/Exclusion 

Asymptomatic at baseline Ahmad, 19847 N=414 Mean age: 28.3 (18-48) Challenge: 50 g lactose/400 ml Overall: 216/4

Pakistan (N. Males: n=404 water Subject selection: healthy, well- Panjab) Females: n=10 nourished Pakistani adults Hydrogen breath test 

Race/ethnicity: Panjabi Inclusion/exclusion: NA 

Bayoumi, N=563 Mean age: NA Challenge: 50 g lactose/400 ml Overall: 310/5

198138 Males: n=549 water Subject selection: healthy Sudan Females: n=14 Sudanese adults Hydrogen breath test 

Race/ethnicity: Sudanese Inclusion/exclusion: NA 

Bayoumi, N=585 Mean age: 21.4 (14-50) Challenge: NA Overall: 261/5

198237 Males: 483 Subject selection: healthy, well Hydrogen breath test Subgroups Sudan Females: n=102 nourished adults Age group 

Race/ethnicity: NE. and S. 14-1

Inclusion/exclusion: NA Sudanese 19-3

30+ 

53 

Beyerlein, 20088 

Switzerland 

N=1127 Subject selection: Data from all patients referred for hydrogen breath test were collected prospectively. Inclusion/exclusion: Patients were asked to fast and refrain from smoking for at least 6 hours prior to the test. Furthermore, patients were asked to discontinue use of antibiotics 1 week and laxatives 1 day before the hydrogen breath test. 

Mean age: 39.8 (7-87) Challenge: 50 g of lactose Overall: 376/1Males: n=320 dissolved in 300 ml of water Subgroup Females: n=807 Hydrogen breath test Swiss: 23%, Race/ethnicity: “Swiss,” “non- Non-Swiss: 54Swiss” 
Table 5. Prevalence of lactose malabsorption by challenge (continued) 

Number Author, Year Diagnostic Challenge Subject Selection Subject Characteristics Prevalence 

Country Methods Inclusion/Exclusion 

Bujanover, 198510 

Israel 

N=110 Subject selection: healthy subjects Inclusion/exclusion: All were antibiotic and drug free 1 month prior to entrance; all were consuming dairy products. 

Mean age: 6 years 7 months (4 months-15 years) Males: n=61 Females: n=49 Race/ethnicity: Israeli Jews 

Challenge: 2 g/kg lactose up to 50 g (10% solution) Hydrogen breath test 

Overall: 68/11

Subgroups And symptomAge 

Years 0-3 0/3-6 136-12 3012-16 22

Burgio, N=308 Mean age: 43.2 Challenge: 50 g lactose/400 ml Overall: 177/2198411 Males: n=116 water Subject selection: healthy Subgroups Italy Females: n=192 Italian adults Hydrogen breath test N. Italy: 106/2

Race/ethnicity: Italians of Sicily: 71/100 

Inclusion/exclusion: NA Sicilian, N. Italian descent 

54 

Czeizel, N=820 Mean age: 26.2 (16-54) Challenge: 50 g lactose Overall: 323/8198340 Males: n=260 Subject selection: healthy adult Hydrogen breath test Subgroups Hungary Females: n=560 and adolescent Hungarian Magyars: 198

subjects Race/ethnicity: Magyars Matyos: 63/17

(n=535), Matyo (n=172), and Romai: 63/113 

Inclusion/exclusion: NA Romai (n=113) 

Debrot, N=729 Mean age: 8.9 (8-10) Challenge: 0.5 g lactose/kg Overall: 97/69199041 Males: NA body weight Subject selection: children aged Curaçao, Females: NA 8-10 years who attended Hydrogen breath test (n=692) Netherlands elementary schools in Curaçao Race/ethnicity: “Blacks” Antilles 

Inclusion/exclusion: NA 

Leis, 199716 

Spain 

N=850 Subject selection: healthy subjects from Galicia Spain with no history of GI illness Inclusion/exclusion: 1) not eaten or drunk anything for at least 12 hours; 2) not smoked for at least 6 hours (& did not smoke during the test); 3) not slept or done heavy physical exercise for at least 1 hour; 4) cooperated 

Mean age: NA Males: n=397 Females: 453 Race/ethnicity: Galician Spaniards 

Challenge: (1) 2 g lactose/kg up to 50 g (2) 250 ml of milk, (3) 250 ml of yogurt Hydrogen breath test 

Overall (2 g la

Overall (250 mOverall (250 m

Subgroups (2 In symptomatIn asymptomaAges 3-5: 9/95 Ages 6-13: 76Ages 14-18: 7Ages 19-24: 4Ages 25-60: 5
Table 5. Prevalence of lactose malabsorption by challenge (continued) 

Number Author, Year Diagnostic Challenge Subject Selection Subject Characteristics Prevalence 

Country Methods Inclusion/Exclusion 

Segal, 198321 N=115 Mean age: 32.5 Challenge: 50 g cow’s milk/400 Overall: 90/11

South Africa Males: NA ml water Subject selection: healthy adult Females: NA volunteers Hydrogen breath test 

Race/ethnicity: Zulu, Xhosa, Exclusion: GI symptoms Sotho, Tswana, Swazi, 

Shangaan 

Tadesse, 199146 

Hong Kong 

55 

Ting, 198823 

Republic of China (Taiwan) 

readily in the test, without hyperventilation or crying; 5) had not taken antibiotics or laxatives for at least 15 days, and had not used any other drug on the day of the test; and 6) had gotten a positive breath hydrogen test after ingestion of 1 g/kg body weight of lactulose, so the enteric bacterial flora was able to produce hydrogen N=320 (outcomes were for 276; 44 were noncompliant) Subject selection: Subjects from primary and secondary school were invited to participate. Exclusion: GI complaints, no antibiotic treatment for last month before entry N=726 Subject selection: subjects in good health, without diarrhea or antibiotic therapy for at least 1 week prior to study Inclusion/exclusion: NA 

Median age: 11.4 (6.5-18.3) Males: n=134 Females: n=142 Race/ethnicity: Chinese Mean age: NA (3-18) Males: NA Females: NA Race/ethnicity: Chinese 

Challenge: 5 ml cow’s milk/kg body weight (~0.25g lactose/kg body weight) Hydrogen breath test Challenge: 0.5 ml lactose/kg body weight Hydrogen breath test 

Age >60: 15/6

Ages 3-5: 0/8 

Ages 6-13: 6/7Ages 14-18: 1Ages 19-24: 4Ages 25-60: 0Age >60: 6/14 

Overall: 35/27Subgroups Age 

Years 

6, 7 0/28, 9 3/610, 11 3/512, 13 3/314, 15 1516-18 11Total 35

Overall: NA Age 

Years n

3 

4 

5 6 137 558 29, 10 4

11, 12 5
Table 5. Prevalence of lactose malabsorption by challenge (continued) 

Number Author, Year	 Diagnostic Challenge Subject Selection Subject Characteristics Prevalence 

Country	 Methods Inclusion/Exclusion 

13, 14 515, 16 417, 18 3

Wang, 198425 N=641 Mean age: 22.9 (16-46) Challenge: 50 g lactose Overall: 552/6

China Males: n=447 Subject selection: healthy, well- Symptoms: gas and/or diarrhea Subgroups Females: n=194 nourished, volunteers Han: 229/248

Race/ethnicity: Han, Mongols, Mongols: 174/

Inclusion/exclusion: NA and Kazakhs from N. China Kazakhs: 149

Yang, 200028 

China 

N=1168 Subject selection: healthy subjects recruited from schools in large cities. Inclusion/exclusion: diarrhea, chronic constipation or other GI problems, no use of any drugs 1 week prior to test, good general health without signs of acute or chronic illness 

Overall mean age: NA (3-13) Males: n=610 Females: n=558 Race/ethnicity: Chinese 

Challenge: 50 g lactose Hydrogen breath test 

Overall: 835/1Subgroup: Ag

Years 

3-5 1507, 8 35011-13 335

56 

Symptomatic at baseline Barr, 197936 

USA 

Challenge: 2 g lactose/kg up to Overall: 32/80 50 g Subgroups Hydrogen breath test White: 16/59 (

Black: 12/16 (Hispanic: 4/5 

N=80 Subject selection: children seen at a general medicine clinic during a 12-month period Inclusion: symptomatic for a primary complaint of intermittent abdominal pain of unexplained origin, more than 3 episodes of pain in <3 months, and of sufficient severity to affect activity Excluded: children with transient GI dysfunction 

Mean age: 9.6 (4-15) Males: NA Females: NA Race/ethnicity White: n=59 Black: n=16 Hispanic: n=5 

Hermans, N=309 Mean age: 42 Challenge: 50 g lactose Overall: 122/3

199714 Males: n=130 Subject selection: Consecutive Hydrogen breath test The Females: n=179 adult patients with suspected Netherlands LM underwent a lactose Race/ethnicity: NA 

tolerance test. 
Table 5. Prevalence of lactose malabsorption by challenge (continued) 

Number Author, Year Diagnostic Challenge Subject Selection Subject Characteristics Prevalence 

Country Methods Inclusion/Exclusion 

Exclusion: Subjects who were treated with antibiotic drugs or underwent bowel preparation for an endoscopic or a radiological investigation within 4 weeks before the test as well as those with diabetes mellitus were excluded from the study. 

Kokkonen, 200132 

Finland Montes, 1993156 

USA 

N=260 Subject selection: 10-year-old subjects with cow’s milk allergy before 1 year of age, and compared to a group of 204 randomly selected age-matched school children Inclusion: children who had abdominal pain or reported complaints compatible with lactose intolerance (e.g., flatulence, diarrhea, abdominal pain) N=494 Subject selection: (Group 1) children of diverse ethnic backgrounds from Maryland or Pennsylvania (n=385); also reviewed were the lactose hydrogen breath test results of 109 lactose-malabsorbing patients (Group 2) tested at home or in a physician's office. Eighty-nine of these subjects were children (81.6%). Inclusion: GI complaints, such as diarrhea and abdominal pain 

Mean age: 10.5 (9-11) Males: n=35 Females: n=21 Race/ethnicity: Finns 

57 

Group 1 (n=385) Mean age: NA (2.5-21) Males: NA Females: NA 

Group 2 (n=109) Mean age: 8.6 (1-16) Adults: n=20 (Mean age 43.2) Children: n=89
 Race/ethnicity: NA 

Challenge: 2 g lactose/kg in 250 ml water Hydrogen breath test Challenge: 2 g lactose/kg up to 50 g Hydrogen breath test 

Overall Study group: 8Controls: 6/20Overall: 252/4

Subgroup Group 1: 70/3

Newcomer, N=80 Overall mean age: 50.3 (26-82) Challenge: 50 g lactose/500 ml Overall: 5/80 198342 Males: n=16 water Subject selection: healthy USA Females: n=64 Caucasian volunteers with no Hydrogen breath test 
Table 5. Prevalence of lactose malabsorption by challenge (continued) 

Author, Year 

Country 

Number 

Subject Selection 

Inclusion/Exclusion 

Subject Characteristics Diagnostic Challenge Methods Prevalence 

history of intolerance to milk Race/ethnicity: “White, nonInclusion: irritable bowel 

syndrome 

Jewish, NW European background” 

Tolliver, 199447 

USA 

N=196 Subject selection: Subjects who met the International Congress of Gastroenterology criteria for IBS were prospectively sampled by hematological, biochemical and metabolic lab testing, as well as evaluation of colon. Inclusion: Patients had to meet the International Congress of Gastroenterology criteria for Irritable Bowel Syndrome. 

Mean age: 43.7 (18-76) Males: n=38 (19%) Females: n=158 (81%) Race/ethnicity: NA 

Challenge: 50 g lactose/200 ml Overall: 48/19water Hydrogen breath test 

Vernia, 200324 

Italy 

N=402 Subject selection: consecutive IBS patients diagnosed by Rome 

Mean age: 35.1 Males: n=120 Females: n=282 

Self report Overall: 290/4

Subgroups Self-reported 

criteria Race/ethnicity: NA (68.6%) 

Inclusion/exclusion: NA Self-reported 

152/201 (75.6

58 

Webster, 199548 

US 

N=137 Subject selection: Subjects were referred for specialty evaluation of recurrent abdominal pain of at least 3 months' duration. Inclusion/exclusion: NA 

Carroccio, N=323 (historical self-reported 199839 tolerants (n=274) and Italy intolerants (n=49) 

Subject selection: a randomized sample of the general population in a small center in Sicily; subjects were then divided into self-reported 

Mean age: 9.6 (6-18) Males: n=53 Females: n=84 Race/ethnicity: Caucasians (n=114) and African Americans (n=23) 

Symptomatic and asymptomatic at baseline 

Median age: 44 (5-85) Males: n=150 Females: n=173 Race/ethnicity: Sicilians 

Challenge: 1 g lactose/kg lactose 10% aqueous solution) up to 50 g Hydrogen breath test Challenge: 1 g lactose/kg was administered to children weighing 25 kg hydrogen breath test; a standard dose of 25 g was given to all the other subjects, suspended in 250 to 300 ml of water Hydrogen breath test 

Overall: 33/13Subgroups African AmeriCaucasians: 2Overall: 117/3Subgroup: Ag

Years n

6-16 17/7

17-64 54/65-85 46/

Self-reported 
Table 5. Prevalence of lactose malabsorption by challenge (continued) 

Author, Year 

Country 

Number 

Subject Selection 

Inclusion/Exclusion 

Subject Characteristics Diagnostic Challenge Methods Prevalence 

Farup, 200412 

Norway 

tolerants & intolerants Inclusion/exclusion: known intestinal disease, episodes of diarrhea, consumption of antibiotics or laxatives during the 3 weeks prior to the investigation N=187 (IBS Group n=82, Controls n=105) Subject selection: A populationbased, case-controlled, health study. Persons with IBS (Rome II criteria) and alarm symptoms were invited to follow up. Also invited were a group of healthy Norwegians to participate in the study as a control group. 

Mean age: 47 Males: n=49 Females: n=138 Race/ethnicity: Norwegians 

Challenge: 25 g lactose Hydrogen breath test 

Only 5/49 (10post challenge Overall: 7/179 Subgroups (aIBS group: 3/7Controls: 4/10

Exclusion: organic disease 

Johnson, 197830 

USA Ladas, 199115 Greece 

N=109 Sample: Native Americans with full and mixed blood from various tribes from the American Great Basin and South West Excluded: subjects with diabetes, or a recent history of diarrhea or intestinal surgery N=150 (baseline symptoms n=43) 

Subject selection: Greek children by their teacher-assigned number Exclusion: One child was excluded from the study because of a known milk allergy (atopic dermatitis). 

59Mean age: >18 years Males: NA 

Females: NA Race/ethnicity: Native Americans Mean age: NA (5-12) Males: n=72 Females: n=78 Race/ethnicity: Greeks 

Challenge: 50 g lactose/250 ml water Hydrogen breath test Challenge: 2 g lactose/kg to a maximum of 50 g or 0.240 L of milk Hydrogen breath test 

Overall: 98/10

Subgroup Full-blooded: European adm

Overall: 68/14

Subgroups History of sym
Table 5. Prevalence of lactose malabsorption by challenge (continued) 

Number Author, Year	 Diagnostic Challenge Subject Selection Subject Characteristics Prevalence 

Country	 Methods Inclusion/Exclusion 

Maggi, 198717 

Uruguay Rao, 199444 

USA 

N=200 Subject selection: randomly selected volunteer subjects were prospectively studied Inclusion/exclusion: NA N=97 (or 98) Subject selection: randomly selected volunteers from the U.S. Army, senior citizens' centers, nursing homes, and a university 

Mean age: NA (0-86) Males: n=100 Females: n=100 Race/ethnicity “White”: n=184 “Black”: n=16 

60Mean age: NA (20-89) Males: n=48 

Females: n=50
 

Race/ethnicity
 White: n=46 (north central European descent) Black: n=52 (African descent) 

Challenge: 2 g lactose/kg body weight or 50 g lactose/m2 body 

surface Hydrogen breath test Challenge: 16.5 g lactose (360 ml milk) Hydrogen breath test 

Overall: 113/2

Subgroups In subjects > 2

Age Group 

0-4 

5-9 10-14 15-19 20-29 30-39 40-49 50-59 60-69 >70 

Race 

White 

Black 

Overall: 34/98 Subgroups 

Age group (y

<50 (n=58) Total for age X2 Race P=0

≥50 (n=40) 

Total for age All ages all BAll ages all WAll ages all mAll ages all fTotal for all a

X2 Race P<0.
Table 5. Prevalence of lactose malabsorption by challenge (continued) 

Author, Year 

Country 

Seakins, 198720

 Samoa, New Zealand, Cook Islands 

Number 

Subject Selection 

Inclusion/Exclusion 

N=207 Subject selection: Samoan children were studied in four locations, two in W. Samoa and two in New Zealand. White 

Subject Characteristics 

Mean age: NA (6-13) Males: n=NA Females: n=NA Race/ethnicity Somoans: n=139 

Diagnostic Challenge 

Methods 

Challenge: 10 g lactose/100 ml orange flavored, carbohydratefree cordial Hydrogen breath test 

Prevalence 

Overall: 74/20Subgroups Samoans: 65/Whites: 9/68 (

children were studied in the Whites: n=68 Cook Islands and New Zealand. Inclusion/exclusion: NA 

Schirru, 200745 

Italy (Sardinia) 

N=383 Subject selection: hydrogen breath testing and genotyping of the C/T-13910 variant were performed in 392 patients in Cagliari, Italy Exclusion: celiac disease, milk allergy, Crohn’s disease 

Mean age: NA (3-19) Males: n=184 Females: n=208 (Number of females, males, and age range are from the original cohort of 392 subjects) Race/ethnicity: Sardinians 

Challenge: 2 g/kg body weight to a maximum of 50 g Hydrogen breath test 

Overall: 272/3Subgroups 

Age (yrs) 

 

Age (yrs) 

 

61 

Age (yrs) 

 

Socha, 198422 N=275 Mean age: 29.1 (16-59) Challenge: 50 g lactose/400 ml Overall: 103/2

Poland Subject selection: healthy 

Polish adolescents & adults 

Males: n=61 Females: n=214 

water Hydrogen breath test 

Inclusion/exclusion: NA Race/ethnicity: NA 
Table 6. Prevalence of hypolactasia 

Number 

Study Subject Selection Subject Characteristics Diagnostic Methods Prevalence o

Inclusion/Exclusion 

Asymptomatic at baseline Newcomer, N=100 Mean age: 38.5 (20-63) Biopsy Overall (≤0.5 U): 6% 

196718 Subject selection: Healthy Males mean age: 37 (20-63) 

US Caucasians Females mean age: 40 (21-62)
 

Exclusion: Intolerance to milk Males: n=50 and/or GI symptoms Females: n=50
 

Race/ethnicity: Caucasians 

Asymptomatic and symptomatic at baseline 

62 

Ferguson, N=406 198450 Subject selection: 

UK 1) retrospective evaluation of 

White, adult subjects who had had a jejunal biopsy performed (n=150) 2) non White British (n=20) 3) investigated because of diarrhea after gastric surgery (n=36) 4) subjects with irritable bowel syndrome (n=200) Inclusion/exclusion: For the 150 White British sample only those that had no significant intestinal disease; all had normal histopathic jejunal biopsy 

Lebenthal, N=156 198151	 Subject selection: in a caseUSA controlled study, White children 

(n=95) with recurrent abdominal pain, plus 61 age- and racematched Controls who had undergone diagnostic intestinal biopsies primarily for chronic diarrhea Inclusion: diagnosis of recurrent abdominal pain 

Mean age: NA Males: NA Females: NA Race/ethnicity: “White” British, and non White British (Indian, Chinese, Black, Arab) Mean age: NA (6-14) Males: NA Females: NA Race/ethnicity: White 

Biopsy Groups: White British 

disease: 7/150 (4.7%Non White British: 15/Diarrhea after gastric IBS group: 16/200 (8%

Biopsy Overall: 24/87 (27.6%

Subgroups White children: 8/26 (Controls: 16/61 (26.4%
Table 6. Prevalence of hypolactasia (continued) 

Number 

Study Subject Selection 

Inclusion/Exclusion 

Subject Characteristics Diagnostic Methods Prevalence o

Welsh, 197053 

N=250 Sample: Intestinal specimens 

Mean age: NA (2-81) Males: n=169 

Biopsy Overall (duodenojejun

Overall (isolated lacta

USA from patients without celiac Females: n=81 procedures)): 9/250 (3

sprue. Race/ethnicity Inclusion/exclusion: NA White: n=209 

Black: n=39 American Indian: n=2 

Symptomatic at baseline Pfefferkorn N=224 (patients with IBD 

200252	 n=112, patients with chronic US abdominal pain n=112) 

Sample: retrospective and descriptive analysis of pediatric and adolescent patients with IBS were compared to a random sample of age- and gender-matched controls who were being evaluated for abdominal pain Inclusion/exclusion: 

Mean age (IBS): 12.7 Biopsy Mean age (controls): 12.4 (1.9­18.7) Males: n=60 Females: n=52 Race/ethnicity White: n=103 Black: n=9 

Overall: NA 

Subgroups IBS: 45/112 (40%) Chronic abdominal paP=0.16 Among 112 with IBD Whites: 38/103 (37%) African Americans: 7/

63 
Table 7. Prevalence of adult-type hypolactasia genotype 

Number Author, Year Subject Selection Subject Characteristics Diagnostic Methods Prevalence of H

Country Inclusion/Exclusion 

Asymptomatic and symptomatic at baseline Almon, 200755 N=1,082 

Sweden Subject selection: 

randomly selected children (n=690), and elderly, nonrandomly selected subjects (n=392) Inclusion/exclusion: NA 

Anthoni, 2007158 N=1,900 

Finland Subject selection: Finnish 

adults attending lab investigations in primary health clinic Inclusion/exclusion: NA 

Mean age: (children were aged either 9 or 15; adults were born between 1920­1932) Males: NA Females: NA Race/ethnicity: Swedes (“Caucasians,” “nonCaucasians”) 

Blood genotyping 

Mean age: “working age” Blood genotyping Males: NA Females: NA 

Overall (C/C): 117/1082 (10.8%Subgroups 

C/C 

Genotype 

Children 97/690 

(14) 

Adults 20/392 

(5) 

Caucasians 61/635 

(10) 

Non Caucasians 36/55 

(65) 

Overall: 342/1,900 (18%) Subgroups 

 

Genotype 

 

C/C 341/1900 (18) 

C/T 901/1900 (47) 

T/T 658/1900 (35) 

Total 1900 (100) 

64 

Ennattah, 200457 

Finland 

N=234 Subject selection: Finnish army male recruits and men of similar age who had postponed their military service not related to health 

Mean age: NA (18.3-20.6) Males: n=234 Females: n=0 Race/ethnicity: Finns 

Blood genotyping Overall (C/C): 40/234 (17.1%) 

Inclusion/exclusion: NA 
Table 7. Prevalence of adult-type hypolactasia genotype (continued) 

Number Author, Year Subject Selection Subject Characteristics Diagnostic Methods Prevalence of H

Country Inclusion/Exclusion 

65 

Gugatschka, N=239 200791 Subject selection: Men Austria from a population based 

cohort were invited into study Exclusion: liver or kidney disease, primary hyperparathyroidism, longterm use of corticosteroids, other possible causes of secondary osteoporosis, consumption of bone-active meds, severe nicotine or alcohol abuse 

Overall mean age: 70 (62- Blood genotyping Overall: 85) C/C 

Genotype Mean age (pop-based n/

cohort): 69 (62-78) 81/453 21Males: n=0 (17.9) (4Females: n=564 Race/ethnicity: Finns 

Ennattah, 200529 

Finland 

N=564 Subject selection: crosssectional, cohort study of population-based women (n=453), women with osteoporotic fractures (n=52), and a control group of women without osteoporosis (n=59) Inclusion/exclusion: Historical lactose intolerance (n=72) 

Mean age: 61 (50-85) Blood genotyping Overall: 

Males: n=239 Females: n=0 Genotype C/C 

n

Race/ethnicity: Austrians 65/239 (27) 13

Lehtimäki, 200659 

Finland 

N=3596 (in 1980) Subject selection: prospective, crosssectional cohort study of randomly selected Finnish children (n=3,596) in 1980, with reexamination in 1983, 1986, and 2001 (after a 21-year followup period) Inclusion/exclusion: NA 

Mean age: 10.5 (3-18) 

(1980) Males: n=1,015 (2002) Females: n=1,250 (2002) Race/ethnicity: Finns 

Blood genotyping Overall (2002): 

C/C 

Genotype  399/2265 1

(17.6) 
Table 7. Prevalence of adult-type hypolactasia genotype (continued) 

Number Author, Year Subject Selection Subject Characteristics Diagnostic Methods	 Prevalence of H

Country Inclusion/Exclusion 

Piepoli, 200760	 N=254 (there were also 

Italy (Sardinia 124 subjects with and Apulia) colorectal cancer, but not 

reported) Subject selection: two different healthy populations were randomly collected: unrelated Apulians and Sardinians Inclusion/exclusion: NA 

Schirru, 200745 N=383 Italy (Sardinia) Subject selection: 

hydrogen breath testing and genotyping of the C/T-13910 variant were performed in 392 patients in Cagliari, Italy Exclusion: celiac disease, milk allergy, Crohn’s disease 

Mean age: 31.9 (1-73) Males: n=194 Females: n=60 Race/ethnicity: Italians Mean age: NA (range 3-19) Males: n=184 Females: n=208 (Number of females, males, and age range are from the original cohort of 392 subjects) Race/ethnicity: Sardinians 

66 

Symptomatic at baseline 

Mean age: 8.5 (0.1-20.2) 

Africans: 6.9 (0.1-15.6) Finns: 9 (0.6-20.2) other Whites) 6.9 (1.9-10.9) 

Males: n=162  Africans: n=31 Finns: n=125 

other Whites: n=6 

Females: n=167  Africans: n=34 Finns: n=127 

other Whites: n=6 

Race/ethnicity: Africans (n=65); Finns (n=252); other Whites (n=12) 

Blood genotyping Overall: 

C/C C/T 

n/N (%

214/254 (84) 37/254 (

Blood genotyping Overall: 344/383 (89.8%) 

Subgroups 

Age 3, 4 5, 6 

n/

C/C 31/35 (89) 39/43 (91) 

Age 9 10, 11 

n/

C/C 42/45 (93) 56/62 (90) 

Blood genotyping Overall (C/C): 108/329 (32.8%) 

Subgroups 

Race C/C 

 

Finns 37/252 

(14.7) 

African s 

62/65 

(95.4) 

Other Whites 

9/12 

(75.0) 

Rasinperä, 200461 

Finland 

N=329 Subject selection: Children undergoing upper GI endoscopy because of abdominal complaints Exclusion: children receiving chemotherapy, with GI anomalies, or villous height to crypt depth ratio of < 2:1 
Key Question 2. What are the health outcomes of dairy 

exclusion diets? 

Association Between GI Symptoms and Dairy Exclusion Diets 

We identified no studies that addressed the long-term impact (>1 month) of dairy exclusion 

diets on GI symptoms in the general population, vegans, or those diagnosed with LI or LM. 

Studies that reported symptoms in patients with milk allergies, IBS, or other diseases were 

beyond the scope of our review. In Key Questions 3 and 4 we report short-term GI outcomes 

from blinded RCTs among subjects with diagnosed LI or controls fed short-term diets containing 

varying doses of lactose or lactose free diets. We found low levels of indirect evidence that 

populations susceptible to LI avoid dairy consumption, presumably in an effort to reduce dairy 

induced GI symptoms. Postmenopausal Austrian women with TT genotype (lactase persistence) 

had lower odds of aversion to milk consumption than women with C/C genotype.68,69 Among 

children who avoided milk, those diagnosed with LI had much greater odds of milk related 

symptoms.76 

Association Between Milk Intake With Genetic Polymorphism, Lactose 

Intolerance, or Malabsorption 

As noted in Key Question 1, results from genetic association tests consistently reported 

decreased consumption of milk (often on the order of twofold lower) in adults with the C/C 

genotype compared to those with at least one T allele.56,57,59,61,91 These differences were smaller 

in healthy children.59 The relative differences in calcium intake from all dairy and overall 

calcium intake were smaller than the differences in milk consumption.29,57,59,91 All of these 

studies were from populations in Finland with generally high dairy consumption, except for one 

study in Austrian men where milk consumption was low in all men.91 The Finnish 

Cardiovascular Risk in Young Finns Study demonstrated that those with C/C genotype had 

lower than recommended calcium intake among young women (crude OR 1.91, 95 percent CI 

1.12; 3.23) and men (crude OR 2.00, 95 percent CI 1.36; 2.95).70 Young women with C/C 

genotype had a 524 percent increase in odds of following a lactose free diet (OR 6.24, 95 percent 

CI 3.46; 11.24).70 Young men with C/C genotype had a 144 percent relative increase in odds of a 

lactose free diet when compared to those with T/T genotype (OR 2.44, 95 percent CI 1.22; 

4.87).70 

Children and adults with self reported symptoms of milk intolerance and diagnosed LM 

reported (or were assumed to be consuming) lactose free or low lactose diets.59,65-67 The 

association was more consistent for women.68,69 The association may diminish with aging.71,72 

The American prospective “Project EAT: Eating Among Teens” study reported that adolescents 

with self-perceived lactose intolerance reported decreased dietary calcium intake during the 

transition to young adulthood.73 

Association Between Dairy Exclusion Diets and Bone Health 

We identified 55 publications of observational studies of 223,336 subjects (Appendix Table 

D1) that examined the association between lactose intake or factors associated with low lactose 

67 
 

 

 

intake (i.e., diagnosis of LI/LM or biopsy or genetic test association for lactase nonpersistence in 

the absence of specific documentation of the amount of lactose intake) on bone health including 

clinical (fracture) and intermediate outcomes (osteoporosis, bone mineral density, and content). 

The absence of specific documentation of the amount of lactose consumed over long periods of 

time hampered synthesis so indirect associations between bone outcomes and proxy variables for 

lower lactose consumption were assessed. We identified seven RCTs of 1,207 children, and two 

RCTs of adult women62,63 that demonstrated causal effect of lactose intake on bone health. 

African American women were enrolled in one study.64 

Sample sizes varied from a minimum of 19 to a maximum of 77,761 subjects, average = 

4,06140,61±12,451 subjects. We identified 13 observational studies of 9,577 children or 

adolescents with an average sample size of 737±1,146 subjects.59,70,73,76,89,95-99,159-161 

Adult men and women (N = 80,726) were examined in 11 publications with an average 

sample size of 7,339±14,826 subjects.5,65,67,83,88,90,92,94,100,162,163 Adult men (N=751) were 

examined in three publications with an average sample size of 250±24.57,66,91 

The majority of the studies included women. We identified 28 publications of 132,282 

women with an average sample size of 4,724±14,707.29,64,68,69,71,72,77-82,84-87,93,164-174 

The majority of the studies (N=32) were cross-sectional evaluations that included on average 

1,364 subjects. From 55 publications identified, 14 studies were prospective design, seven were 

case-control studies, one was a meta-analysis of the individual subject data, and one was a 

prospective observation of the placebo arm in an RCT. The majority of the studies were 

sponsored by grants from nonprofit resources, 29 studies enrolled an average of 5,929±15,418 

subjects. Few (N=7) studies reported combined support from industry and grants, and one study 

was supported by industry alone. A large proportion of the studies (18/55) did not provide any 

information about funding sources. 

U.S. studies represented 27 percent of all included studies (15/55) and enrolled an average of 

7,324±19,795subjects. Studies from North European countries constituted 30 percent of the 

publications (seven from Austria, ten from Finland, and one from Sweden). Studies from the 

United Kingdom represented 6 percent of all eligible (3/55) but had larger sample sizes 

averaging around 25,475±20,363. Asian populations were examined in five studies; two were 

conducted in Taiwan, one in Hong Kong, one in China, and one in Japan. African American 

women were enrolled in one study.64 Other publications either did not report race or ethnical 

distribution of the subjects or enrolled predominately Caucasians. 

Lactose metabolism was addressed in 29 publications.5,29,57,59,64-69,71,72,88,91,92,94,96,98­

100,159,162,164-170 The wide variety of definitions of milk intolerance and absence of the gold 

standard to diagnose LI hampered synthesis of evidence. Authors defined self reported 

symptoms as “perceived milk intolerance”99 or relied on clinical diagnosis that was made based 

on a positive hydrogen LI test and self reported symptoms after dairy consumption.66,91,92,100,168 

Authors assessed symptoms during or after oral LI tests in few studies.5,64,166,167 

Trained interviewers who were blinded to the results of oral LI tests assessed symptoms in 

one study.72 Two studies used blood glucose examination after oral lactose intake to diagnose 

malabsorption.162,170 Several studies obtained a hydrogen breath test after oral lactose intake 

without evaluating the symptoms of intolerance.71,98,164,165,169 

One early study defined LI as positive oral lactose tolerance tests, positive glucose tolerance 

tests, and jejunal biopsy with impaired lactase activity.94 The remaining 23 publications 

evaluated the outcomes among populations with different dairy intake but unknown lactose 

68 
metabolism.76-87,89,90,93,95,97,160,163,171-174 Randomized trials examined the effects of increased dairy 

administration in populations with baseline low lactose intake. 

We synthesized the evidence of the association between lactose diet and metabolism on 

clinical (fracture) and intermediate outcomes (osteoporosis, bone mineral density [BMD], and 

content) in children and adults. We provided the methodological characteristics of the studies 

when differences in results could be contributed to external or internal validity of the studies. 

Association Between Lactose Intake and Metabolism and Bone 

Fractures 

A low level of inconsistent evidence was available from observational studies that low milk 

consumers had fractures more often than higher milk consumers (Table 8). There are no data 

according to race. Observational studies with different quality provided low level evidence that 

childhood milk avoidance was associated with increased risk of bone fractures. Adults with C/C 

genotype, symptoms of milk intolerance, or diagnosed LM had reduced lactose intake and 

increased odds of bone fracture. One large cohort reported that vegans had an increased relative 

risk of fractures. The effects of lactose free or low lactose diet were more evident in women. 

Diet 

We found a low level of evidence that children who avoid milk intake had increased odds of 

bone fractures (Table 8). 

The association between lactose intake and bone fracture was examined in 13 publications.76­

88 The Oxford cohort of the European Prospective Investigation into Cancer and Nutrition 

(EPIC-Oxford) compared risk of fracture among vegans and dairy consumers (Table 9).90 

Children. Low levels of evidence from two industry sponsored studies of prepubertal 

children from New Zealand found a significant association between lactose free diets and 

increased odds of bone fractures.76,89 Prepubertal children with a history of long-term milk 

avoidance had greater than a threefold increase in odds of the annual incidence of distal forearm 

fracture (age adjusted odds ratio 3.59, 95 percent CI 1.77; 7.29).76 Age adjusted odds of history 

of any fracture were four times higher (OR 4.13, 95 percent CI 1.61; 10.56) among children with 

lactose free diets when compared to the general population.89

 Adults. We found a low level of inconsistent evidence in three studies of 44,552 adults that 

those with low lifetime or childhood milk intake had increased odds of any or osteoporotic 

fracture.80,83,88 The largest meta-analyses of individual data from 39,563 adults, participants in 

the European Vertebral Osteoporosis Study (EVOS/EPOS), the Canadian Multicentre 

Osteoporosis Study (CaMos), the Dubbo Osteoporosis Epidemiology Study (DOES), the 

Rotterdam Study, the Sheffield Study, and a cohort from Gothenburg, demonstrated a borderline 

nonsignificant 10 percent increase in relative risk of osteoporotic fracture in those who consume 

less than one glass of milk per day (multivariate adjusted RR 1.10, 95 percent CI 1.00; 1.21).88 

The adjustment for body mineral density, however, attenuated the association to nonsignificant. 

Women. Low level evidence from nine publications of 111,485 adult women suggested an 

inconsistent increase in risk of fracture in association with low dairy intake.77-79,81,82,84-87 

Variability in definitions of lactose intake and types of fracture contributed to inconsistency 

in the results of the studies. All studies found increased odds of fracture in women with lower 

dairy intake; however, only five reported a significant association. For instance, an American 

69 
 

study of 5,398 college alumnae, 2,622 former college athletes, and 2,776 non-athletes found a 92 

percent increase in multivariate adjusted odds of the first fracture after 40 years of age in low 

milk consumers when compared to the rest of the population (OR 1.92, 95 percent CI 

1.15;3.16).79 The third National Health and Nutritional Examination Survey demonstrated that 

older women with dairy intake of less versus more than two servings per day had greater crude 

odds of osteoporotic fracture.85 The European Mediterranean Osteoporosis Study showed that 

women with low lifetime intake of milk had 46 percent increased relative risk of hip fracture (RR 

1.46, 95 percent CI 1.21; 1.76).82 

In contrast, the Nurses' Health Study of 77,761 women who had never used calcium 

supplements did not detect a significant association between milk or dairy calcium intake and 

risk of hip fracture at 12 years of followup.84 Moreover, the same study reported a 93 percent 

increase in relative risk of hip fracture among women with dairy calcium intake of >550 mg/day 

versus <175 mg/day (multivariate adjusted RR 1.93, 95 percent CI 1.09; 3.42). Elderly female 

participants in the Study of Osteoporotic Fractures, who rarely or never consumed dairy calcium 

during their adolescence, had a 77 percent increase in relative risk of fractured proximal humerus 

(multivariate adjusted RR 1.77, 95 percent CI 1.12; 2.80) with no differences in risk of fractured 

distal forearm.77 Three studies did not find a significant association between lifetime81,87 or 

adolescent milk intake78 and odds of bone fracture. 

Men. One meta-analysis of individual data from 15,825 male participants in the 

EVOS/EPOS, CaMos, DOES, Rotterdam Study, and Sheffield Study, and a cohort from 

Gothenburg, did not detect a significant association between any osteoporotic or hip fracture in 

88 men.

Type of fracture. Low lactose intake was associated with a history of any fracture in 

prepubertal children and elderly women (Figure 3).80,86,87,89 The association between low lactose 

intake and risk of hip fracture was significant in two studies of seven that examined this 

relationship (Figure 4).78,79,81-84,88 

Osteoporotic fractures were not associated with lactose intake in the three studies that 

examined the relationship (Figure 5).85,86,88 

Dairy calcium intake. Evidence from published studies did not suggest a significant 

association between dairy calcium intake and bone fractures. Low calcium intake was not 

associated with fracture in 50 prepubertal children (Appendix Table D3 and Figure 6),89 960 

Italian women,81 or 4,342 adults from the National Health and Nutrition Examination Survey 

(NHANES) I Epidemiologic Follow-Up Study cohort.174 

Vegan diet. We found one study, the Oxford cohort of the European Prospective 

Investigation into Cancer and Nutrition (EPIC-Oxford), that compared relative risk of bone 

fracture among vegan vegetarians (lactose free diet) with meat and dairy consumers (Table 10).90 

Multivariate adjusted relative risk of incident fracture of bones other than the digits or ribs was 

30 percent higher in vegan adults (RR 1.30, 95 percent 1.02; 1.66) but not significant in women 

or men separately. 

Genetic Polymorphism 

A single nucleotide polymorphism of the LCT gene at chromosome 2q21-22 in association 

with fractures was examined in five publications.29,65,68,69,91 

Children. We did not find studies that examined bone fractures in children with genetic 

polymorphism. 

70 
 

 

Women. Evidence of the association between bone fracture and genetic polymorphism from 

three studies of 895 postmenopausal women was inconsistent in direction and effect size (Table 

11).29,68,69 

A cross sectional Austrian study demonstrated that women with TT genotype had reduced 

crude odds of fracture (OR 0.26, 95 percent CI 0.13; 0.54).68 Another smaller prospective 

Austrian study, however, did not find a significant association between genetic polymorphism 

with interim vertebral or nonvertebral bone fractures.69 In contrast, a Finnish study reported 

greater crude odds of any and nonvertebral fractures in women with TT genotype when 

compared to C/C genotype.29 The authors did discuss why their results showed negative 

association between C/C genotype and bone fractures. They did not calculate odds ratios but 

compared fractures in three categories of genotype (TT, C/C, and TC). Authors reported a 

nonsignificant p value from χ

2

 tests, and concluded no differences in fractures in relation to 

genetic pattern.29 

Adults. One population-based study “Vantaa 85+” of 601 Finnish elderly found that those 

with C/C genotype had a fourfold increase in crude odds of hip (OR 4.22, 95 percent CI 2.16; 

8.26) and nearly threefold increase in crude odds of wrist fracture (OR 2.82, 95 percent CI 1.42; 

5.59) when compared to TT genotype.65 

Men. The Austrian Study Group on Normative Values on Bone Metabolism did not find a 

significant association between genetic polymorphism and bone fracture in elderly men.91 

Lactose Intolerance 

We synthesized the evidence with the exact definitions of lactose intolerance that were 

obtained by the primary investigators in the studies. 

Children. Children who avoided drinking cow's milk because of perceived milk intolerance 

did not have higher rates of fracture when compared to those milk avoiders who did not report 

symptoms of intolerance (Table 12).89 

Adults. Austrian men and women with self reported symptoms of lactose intolerance during 

the hydrogen breath test had twofold increased crude odds of any fracture (OR 1.96, 95 percent 

CI 1.11; 3.48).92 Estonian men and women with self reported milk intolerance had increased 

crude odds of osteoporotic fracture (OR 2.69, 95 percent CI 1.25; 5.78).67 

Women. Finnish postmenopausal women with lactose intolerance did not have greater risk 

of any, vertebral, or nonvertebral fracture.29 

Lactose Malabsorption 

We synthesized the evidence of the association between LM that was diagnosed with 

objective breath hydrogen or blood glucose test and bone fractures (Table 12). As noted above, 

while we did not have information on dairy intake, we assumed that individuals with 

documented LM have lower dairy intake than absorbers. 

Adults. Austrian adults with positive hydrogen breath test had an increase in crude odds of 

any fracture when compared to lactose absorbers (OR 2.63, 95 percent CI 1.52; 4.54).92 Adults 

with severe LI (ΔH2 >60ppm) had greater than threefold increase in crude odds of vertebral 

fractures when compared to lactose absorbers (OR 3.62, 95 percent CI 1.93; 6.79).92 

Women. We found a low level of evidence that women with LM may have increased risk of 

bone fractures (Table 8).164,167,170 

71 
 

The Finnish Kuopio Osteoporosis Risk Factor and Prevention Study demonstrated that 

women with positive versus negative lactose tolerance test had 33 percent greater odds of any 

fracture (multivariate adjusted OR 1.33, 95 percent C 1.08; 1.64) after adjustment for age, body 

mass index (BMI), number of chronic health disorders, and menopausal and smoking status.167 

Smaller case control studies of women failed to detect significant associations. One Finnish 

study of 18 elderly women with spinal fragility fractures, 28 elderly women with hip fractures, 

and 35 population controls did not find differences in crude odds of fracture when women with 

positive blood glucose tests were compared to those with negative tests.170 Elderly female 

malabsorbers from New Zealand did not have greater age adjusted odds of fracture when 

compared to those with negative breath hydrogen tests.164 

Association Between Lactose Intake and Metabolism with 

Osteoporosis 

Studies examined different populations, used different definitions of impaired lactose 

metabolism, and evaluated osteoporosis at different bone sites and with varying fracture 

definitions. Adults with lactose free or low lactose diets had osteopenia more often (Table 13). 

Adults. Two studies addressed the odds of osteoporosis in association with lactose intake and 

reported different results, depending on ethnicity of the subjects and definitions of exposure. The 

study of Asian adults in Taiwan did not find a significant association between low milk intake 

and odds of osteoporosis.163 The U.S. study reported a significant increase in odds of 

osteoporosis in adults with LI or LM.94

 Women. Postmenopausal Taiwanese women with lactose free diets had a fourfold increase 

in adjusted odds of femoral neck when compared to nonvegan vegetarians (multivariate adjusted 

OR 3.94, 95 percent CI 1.21; 12.82).93 Italian adults with symptoms of LI and positive hydrogen 

test an increase in crude odds of osteopenia.5

 Women with different genetic polymorphism had 

the same odds of osteoporosis.29,69 

Two small studies totaling 124 women examined crude odds of osteoporosis by LI and LM 

status.168,169 An Austrian study reported a large significant increase in crude odds of idiopathic 

osteoporosis among malabsorbers (OR 36.56, 95 percent CI 8.02; 166.69) and those with milk 

intolerance (OR 32.31, 95 percent CI 6.97; 149.75).168 In contrast, an Italian study of 

postmenopausal women did not find a significant association between osteoporosis and lactose 

intolerance or malabsorption.169 

The magnitude and significance of the association varied, depending on definitions of 

exposure. Studies did not analyze all levels of exposure, including milk and dairy calcium intake, 

genetic polymorphism, perceived milk intolerance, and positive tests for lactose maldigestion. To 

address the issue of correlated definitions of exposure, we analyzed, when possible, the odds of 

lactose free diet in children and adults with genetic polymorphism or lactose malabsorption. 

Association Between Genetic Polymorphism, Milk Intake, or Self 

Reported Lactose Intolerance 

Available evidence suggested that children and adults with self reported symptoms of milk 

intolerance and diagnosed LM reported lactose free or low lactose diets. Adults with C/C 

genotype reported reduced milk intake. The association was more consistent for women. The 

association may diminish with aging. 

72 
 

We identified five publications that examined genetic polymorphism in association with 

lactose intake.59,65-67,70 One study of children and adolescence, the Cardiovascular Risk in Young 

Finns Study, found that dietary intake of milk and milk products was significantly lower for girls 

with the C/C.59 The same study did not report significant difference in milk intake among boys 

(Appendix Table D4). During the transition to young adulthood, however, both genders with C/C 

genotype did not drink milk (OR 1.86, 95 percent CI 1.34; 2.59 among women and 2.00, 95 

percent CI 1.36; 2.95 among men).70 The odds of following a low lactose or milk free diet at 24­

39 years of age were also significantly higher in those with C/C genotype (OR 6.24, 95 percent 

CI 3.46; 11.24 in females and 2.44, 95 percent CI 1.22; 4.87 in males).70 

Among adults, one study of Austrian men reported that milk tolerance and consumption were 

higher in those with TT genetic polymorphism compared to T/C or C/C types.66 Two studies of 

adults also reported that those with TT type had greater odds of using milk products (OR 2.06, 

95 percent CI 1.38; 3.06)65 and greater daily milk intake.67 

Two studies demonstrated smaller odds of positive tests for lactose malabsorption in adults 

with T/T when compared to C/C genotypes (Figure 7).66,69 

The odds of self reported symptoms of lactose intolerance were higher in women with C/C 

genetic polymorphism (Appendix Table D5).68,69 Men with different genotypes, however, had 

the same frequency of milk related clinical symptoms.57,66,91 

Studies demonstrated that children and adults diagnosed with LM had clinical symptoms 

more often than controls (Appendix Table D5). Adult malabsorbers reported symptoms of LI 

more often when compared to absorbers (OR 107.98, 95 percent CI 6.34; 1838.99).5 The 

association was dose response shaped with a greater than threefold increase in odds of 

symptomatic LI in adults with moderate (OR 3.58, 95 percent CI 1.43; 9.00) and with a six fold 

increase in those with severe LM (ΔH2 >60ppm) when compared to lactose absorbers (OR 6.22, 

95 percent CI 2.87; 13.51).92 Postmenopausal lactose malabsorbers had milk-related clinical 

symptoms more often; however, the results did not achieve statistical significance.71,72 

Summary. Observational studies with different quality provided low level evidence that 

childhood milk avoidance may be associated with increased risk of bone fractures. Selected adult 

populations with C/C genotype, symptoms of milk intolerance, or diagnosed LM and reduced 

lactose intake may have increased odds of bone fracture. One large cohort reported that vegan 

vegetarians had increased relative risk of fractures. The effects of lactose free or low lactose diet 

were more evident in women. 

Association Between Lactose Intake and Metabolism and Bone 

Mineral Content or Density 

We summarize here the results from seven RCTs in children,101-107 two RCTs of women,62,63 

and 28 observational studies reporting bone mineral density or content.5,57,66-69,71,72,76,91-93,95­

100,159-162,165-167,169,171,172 

The studies suggest that children and adults with lactose free or low lactose diets may have 

reduced bone mineral content (BMC) and bone mineral density (BMD). The actual differences, 

however, varied across the studies, depending on the populations, definitions of exposure, time 

of followup, and measured bones (Table 8). 

Diet. 

Children. We found a moderate level of evidence from RCTs that increased lactose intake 

resulted in improved BMC of lumbar spine and femoral neck in prepubertal children with low 

73 
 

baseline milk intake (Table 14). Dairy intervention with 1,794 or 1,067 mg calcium per day for 

12 months resulted in significant increases in total body BMC in boys and girls from Hong Kong 

(Figure 8).101 This open label trial included 344 boys and girls 10.0 ± 3 years of age with very 

low baseline milk intake of 35.6 percent of the recommended daily calcium consumption.101 One 

RCT that included prepubertal children with very low baseline milk intake of 30.8 percent from 

that recommended also reported a significant increase in total body BMC after dairy 

administration that provided 1,200 mg calcium per day.102 The effect, however, was not 

significant at 18 months of followup.102 The U.S.103 and British104 RCTs that included only girls 

consuming half the recommended daily calcium did not demonstrate significant improvement in 

total body BMC. 

The same pattern was seen in BMC of femoral neck. Children with very low baseline 

calcium intake (36 percent from the recommended) experienced significant increase in BMC.101 

Children that consumed half of the recommended calcium did not have a noticeable increase in 

BMC (Figure 9).106,107 The effects of dairy interventions on total hip BMC were significant in all 

three RCTs that examined the association (Figure 10). 

Design, population gender, and baseline milk intake could explain study inconsistencies in 

increased lumbar spine BMC. Lumbar spine BMC was increased in three RCTs,101,102,105 while 

two trials did not report significant changes in this outcome106,107 (Figure 11). Children from 

Hong Kong with very low baseline calcium intake had the greatest increase in lumbar spine 

BMC.101 This evidence suggests that dairy intervention increased lumbar spine BMC in girls105 

but not in boys106 because trials did not differ by country (both trials were conducted in 

Switzerland), baseline milk intake, and design (both trials were double blinded). Neither absolute 

levels of BMC nor changes from baseline in BMC or BMD differed in boys after dairy 

intervention (1,607 mg calcium/day) when compared to placebo (747 mg calcium/day) 

(Appendix Table D6).106 

The improvement in BMD was less evident. Dairy interventions did not increase BMD in 

girls in two RCTs that reported absolute levels of the outcome.103,105 Dairy interventions 

increased BMD from baseline in one RCT of Finnish girls,107 while British girls104 and children 

from New Zealand102 or Hong Kong101 did not have significant changes in BMD (Table 15). 

In contrast with RCTs, observational studies (Table 16) reported that children with very low 

milk intake had reduced BMD compared to the reference population.76,96,97 Long term milk 

avoiders had lower BMC.76,95-97 Studies did not address all confounding factors. 

Adults. A low level of evidence in one study suggested that low milk consumers (<4dL/day) 

had decreased BMD when compared to high milk consumers (>4dL/day).67 

Women. Inconsistent evidence of the association between low lactose diets and bone 

outcomes were limited to two RCTs62,63 and two observational studies.93,171 Dairy intervention 

resulted in a short term increase (6 months) in total spine BMD in young women with high 

adherence to their diet.62 Intention to treat analysis did not detect a significant improvement in 

BMD (Table 17). Dairy intervention reduced age related decline over a 3-year period in vertebral 

bone mineral density in pre-menopausal women.63 Asian women that followed a lactose free 

vegan diet had the same BMD as milk consumers (Appendix Table D7).93,171

 Lactose intolerance. We found low levels of evidence that children and adults with self 

reported milk intolerance (assumed low dairy intake) had reduced BMC or BMD (Table 8). 

American children98 and adolescent girls99 with LI had an inconsistent reduction in BMC (Table 

16). Adults with self reported milk intolerance had a consistent reduction in BMD5,67,100 and 

BMC.5

 A small observation of 58 postmenopausal Italian women, however, did not report a 

74 
significant difference in BMD in those with symptoms of LI when compared to healthy 

asymptomatic milk consumers.169

 Lactose malabsorption. We found low levels of evidence that, when compared to absorbers, 

children with diagnosed LM (and therefore assumed to be have low dairy intake) had lower 

BMC.99 LM in women was associated with inconsistent reduction in BMD72,166,167,169 with no 

differences in BMC.71 The studies of adults did not find a difference in either BMD5,92,162 or in 

BMC5

 in malabsorbers compared to the general population. 

 Genetic polymorphism. We found low levels of evidence that women with C/C genotype 

had lower BMD when compared to TT genotype.68,69 

Bone outcomes did not differ by genotype in adults67 or in men.57 Bone density did not differ 

by genotype in either gender (Appendix Table D8). However, one prospective Cardiovascular 

Risk in Young Finns study demonstrated that at 12 years of followup young men with C/C 

genotype tended to have greater bone loss when compared to those with T/T genotype (bone 

mineral density in lumbar spine p=0.081).161 

75 
Table 8. Association between lactose intolerance and bone outcomes 

Exposure Number of Studies/Patients Bone Mineral Density (BMD) or Content (BMC) Level of Evidence Number of Studies/Patients Fractu

Osteopor

Osteop

Children Diet 7 RCTs/1,207 children 

(mean age range 7-11 years old) Chan, 1995103 

Bonjour, 1997105 Cadogan, 1997104 

Lau, 2004101 

Gibbons, 2004102 

Chevalley, 2005106 Cheng, 2005107 

Inconsistent increase in BMC of lumbar spine and femoral neck at 12, and 18 months after increased dairy intake. Results did not persist at 24 months of followup 

Moderate 2 /100, New Zealand 

Black, 200276 

Goulding, 200489 

Milk avoideincrease in adjusted o259 (OR 395% CI 1.77.29)- 3134.13, 95% 10.56) 

4/940 Parsons, 199795 

Du, 200296 

Black, 200276 

Rockell, 200597 

BMC Inconsistent reduction in BMC among milk avoiders 

Low 

3/745 Du, 200296 Black, 200276 

Rockell, 200597 

BMD Consistent reduction in milk avoiders 

Low 

Dairy Ca++ Lactose malabsorption Lactose intolerance Genotype 

1/152 

Vatanparast, 2005160 

1/291 Matlik, 200799 2/310 Stallings, 199498 

Matlik, 200799 

1/358 

19168163 

For every additional 1 mg Ca++ for boys, 0.017 g increase in total body BMC NS for girls Inconsistent reduction in BMC Inconsistent reduction in BMC During the transition to young adulthood men but not women 

LowLow LowLow 

1/50 

Goulding, 200489 

1/50 

Goulding, 200489 

NS NS among milk avoideperceived symptoms 

with C/C genotype tended to have greater bone loss 

76 
Table 8. Association between lactose intolerance and bone outcomes (continued) 

Exposure 

Adult women 

Number of 

Studies/Patients 

Bone Mineral 

Density (BMD) or 

Content (BMC) 

Level of 

Evidence 

Number of 

Studies/Patients 

Fractu

Osteopor

Osteop

Diet 2 RCTs/496 adult women 

(mean age range 28-35 years old) Woo, 200762 

Baran, 199063 

Short term increase (6 months) in total spine BMD in young women with high adherence to increased lactose diet. Reduced decline in vertebral BMD in pre-menopausal 

Low 9/111,485 

Kelsey, 199277 

Nieves, 199278 Wyshak, 198979 Tavani, 199581 Johnell, 199582 

Feskanich, 199784 

Turner, 199885 

Johansson, 200487 

Kalkwarf, 200386 

Inconsistenevidence tlifetime milis associatincreased fracture 

women. 

Dairy Ca++ 1/960 

Tavani, 199581 

NS 

Vegan diet Lactose malabsorption 

2/443 

Lau, 1998171 

Chiu, 199793 1/80 Goulding, 199971 

BMD in Asian women NS BMC NS 

Low Low

1/ 26, 749 Appleby, 200790 

1/258 Chiu, 199793 

 3/11761 

Honkanen, 1997167 

Wheadon, 1991164 

Harma, 1988170 

NS Osteopenia Increased adjusted o294% (OR 95% CI 1.212.82) Inconsistenincrease in and adjust

4/13,748 Honkanen, 1997167 

Honkanen, 1996166 Corazza, 1995169 

Horowitz, 198772 

BMD Inconsistent reduction 

Low 2/124 

Finkenstedt, 1986168 

Corazza, 1995169 

OsteoporoInconsistenincrease in odds 

Lactose intolerance 

1/58 Corazza, 1995169 

BMD NS 

Low 1/564 

Enattah, 200529 

NS 

2/124 Finkenstedt, 1986168 

Corazza, 1995169 

OsteoporoInconsistenincrease in odds 

Genetic polymorphism 

2/331 Obermayer-Pietsch, 200468 

Obermayer-Pietsch, 200769 

BMD Consistent reduction among individuals with C/C genotype 

Low 3/895 

Obermayer-Pietsch, 200468 

Obermayer-Pietsch, 

Inconsistenevidence twomen witgenotype h

77 
Table 8. Association between lactose intolerance and bone outcomes (continued) 

Bone Mineral Fractu

Number of Level of Number of 

Exposure Density (BMD) or Osteopor

Studies/Patients Evidence Studies/Patients 

Content (BMC) Osteop

200769 increased Enattah, 200529 odds of fra2/637 Osteoporo

Enattah, 200529 NS 

Obermayer-Pietsch, 200769 

Adults Diet 1/367 BMD Low 3/44,552 Inconsisten

Kull, 200967	 Significant reduction Cumming, 199480 increase in 

in low milk Fujiwara, 199783 lifetime or consumers Kanis, 200588 osteoporot

fracture in with low lifchildhood intake 

1/404 Osteoporo

Shaw, 1993163 NS in thos

low milk in

78Dairy Ca++ 1/4342 NS 

Looker, 1993174 

Vegan Diet 1/34,696 Increase in 

Appleby, 200790 adjusted re

risk by 30% 1.30, 95% 1.66) 

Lactose 1/103 BMC Low 1/218 malabsorption Di Stefano, 20025 NS Kudlacek, 200292 

Increase in odds of ovfactures by (OR 2.63, 1.52; 4.54) crude odds verterbral fby 262% (O3.62, 95% 6.79) in thosevere LM 

3/350 BMD Low 1/103 Osteopenia 

Di Stefano, 20025 NS Di Stefano, 20025 Increase in 

Alhava, 1977162 odds by 67Kudlacek, 200292 7.77, 95% 

27.44)-959 
Table 8. Association between lactose intolerance and bone outcomes (continued) 

Bone Mineral Fractu

Number of Level of Number of 

Exposure Density (BMD) or Osteopor

Studies/Patients Evidence Studies/Patients 

Content (BMC) Osteop

79 

10.59, 95% 2.66; 42.20with LI sym

Lactose intolerance Genetic polymorphism Adult males Diet Vegan diet Genetic polymorphism 

1/103 Di Stefano, 20025 

3/536 DiStefano, 20025 

Kull, 200967 

Segal, 2003100 

1/367 Kull, 200967 

1/234 Enattah, 200457 

1/234 Enattah, 200457 

Reduction in BMC BMD Consistent reduction BMD NS BMC NS BMD NS 

Low 

LowLowLow Low 

2/585 

Kudlacek, 200292 

Kull, 200967 

1/32 

Birge, 196794 

1/601 

Enattah, 200565 

1/15,825 Kanis, 200588 1/404 Shaw, 1993163 

1/7,947 Appleby, 200790 

1/239 Gugatschka, 200791 

Increased odds by 961.96 95% 3.48)169% 2.69, 95% 5.78) OsteoporoIncrease in odds by 657.56, 95% 43.98) Elderly witgenotype h322% increcrude odds 4.22, 95% 2.17; 8.33) NS OsteoporoNS in men low milk inNS NS 

Bold = statistically significant 
Table 9. Association between low lactose diets and bone fractures 

Study Comparison Outcome Estimate 

Black, 200276 

Country: New Zealand Prepubertal children with a history of long-term milk avoidance Ca++ intake difference in comparison groups: NR/NR 

80 

Johnell, 199582 Low lifetime intake of milk vs. Hip fracture Adjusted for age, center, BMI RR 

Country: Sweden above the low
 Women Milk intake >5 glasses/day vs. Adjusted for age, center, BMI RR Ca++ intake difference in never or sometimes comparison groups: NR/Y 

Tavani, 199581 Milk intake (drinks/week) >7 vs. Hip fracture Adjusted for age, education, smoking Country: Italy <7 status, total alcohol consumption, anPostmenopausal women Cheese intake, portions/week estrogen replacement therapy OR Ca++ intake difference in 4-6 vs. <4
 comparison groups: NR/NR Cheese intake (portions/week) 

4-6 vs. >6 

Fujiwara, 199783 Milk intake >5/week vs. Hip fracture Adjusted for age, sex, BMI, alcohol 

Country: Japan <1/week intake, for women-parity RR 

Adults Ca++ intake difference in comparison groups: NR/NR Kalkwarf, 200386 Child milk intake <1 Lifetime fracture Adjusted for age and weight OR 

Country: USA serving/week vs. >I serving/day Osteoporotic fracture 

Non-Hispanic, white women Adolescent milk intake: <1 Lifetime fracture 

Ca++ intake difference in serving/week vs. >I serving/day Osteoporotic fracture 

comparison groups: NR/NR Childhood and adolescence Lifetime fracture 

≤1/week vs. >1/week Osteoporotic fracture 

Kanis, 200588 Low milk intake (<1 glass/day) Osteoporotic fracture in Adjusted for current time, current age

Country: UK vs. >1 glass/day males milk intake and milk intake times 

Adults Osteoporotic fracture in current age RR 

Ca++ intake difference in females comparison groups: NR/NR Hip fracture in males 

Goulding, 200489 

Country: New Zealand Prepubertal children with a history of long-term milk avoidance Ca++ intake difference in comparison groups: NR/NR 

Milk avoiders vs. general Annual incidence of distal Age adjusted OR 

population forearm fracture Family members avoiding milk vs. not 

History of fracture Crude OR 

Milk avoiders 0-13 years old vs. general population 

Age adjusted OR 
Table 9. Association between low lactose diets and bone fractures (continued) 

Study Comparison Outcome Estimate 

Hip fracture in females Osteoporotic fracture in Adjusted for current time, current ageall ages milk intake and milk intake times 

current age, and BMD RR Adjusted for the same variables as above but not BMD RR 

Hip fracture in all ages Adjusted for current time, current age

milk intake and milk intake times current age, and BMD RR Adjusted for the same variables as above but not BMD RR 

Johansson, 200487 Intake of milk (score 0–5) from Fracture Crude RR 

Country: UK never, occasional, and 1-2, 3-4, Elderly women to 5 glasses/day Ca++ intake difference in comparison groups: NR/NR 

81 

Cumming, 199480 Country: Australia Elderly women and men Ca++ intake difference in comparison groups: NR/NR Feskanich, 199784 Country: USA Middle aged women Ca++ intake difference in comparison groups: NR/NR 

11.5 units of dairy products/week vs. 0 units at age 20 11.5 units of dairy products/week vs. 0 units at age 50 11.5 units of dairy products/week vs. 0 units at current age 

Fracture Adjusted for age and sex OR 

2-6 glasses of milk/week vs. <1 Hip Fractures Adjusted for age; body mass index; 

2-6 glasses of milk/week vs. <1 Dairy calcium intake >550/day vs.<175 

Forearm fractures 

Hip fractures 

menopausal status and use of postmenopausal estrogen; cigarette smoking; amount of vigorous activity

Dairy calcium intake >550/day vs.<175 

Forearm fractures use of thyroid hormone medication a

thiazide diuretics; and alcohol, caffei

Milk consumption during Hip fractures and total energy intakes. RR 

teenage years 2-6 glasses/ week vs. <1 glass/week Milk consumption during Adjusted for questionnaire time perioteenage years >3 glasses/day age; body mass index; menopausal vs. <1 glass/week status and use of postmenopausal Milk consumption during teenage years 2-6 glasses/ 

Forearm fractures hormones; cigarette smoking; and 

adult (1980) milk consumption. RR 

week vs. <1 glass/week Milk consumption during teenage years >3 glasses/day vs. <1 glass/week 
Table 9. Association between low lactose diets and bone fractures (continued) 

Study Comparison Outcome Estimate 

Kelsey, 199277 Country: USA Older women Ca++ intake difference in comparison groups: NR/NR 

Calcium intake from milk in Fracture of distal forearm 

adolescence: rarely or never Fracture of proximal vs. all others humerus Dietary Ca++ in year before Fracture of distal forearm baseline > vs. <5,000 mg/week Dietary Ca++ in year before Fracture of proximal baseline > vs. <5,000 mg/week humerus 

Adjusted for age, poor visual acuity, number of falls in the year before baseline, frequent walking, recent decline in health status, insulindependent diabetes mellitus, indicators of neuromuscular weaknesRR 

Turner, 199885 Dairy intake < vs. >2 Osteoporotic fracture Crude OR 

Country: USA servings/day Older women Ca++ intake difference in comparison groups: NR/NR Nieves, 199278 Milk intake in adolescence, >7 Hip fracture Matching by age and hospital, adjust

Country: USA glasses/week vs. none for BMI OR 

Middle aged women Ca++mg/day during the last Matching for hospital and age and thCa++ intake difference in year >1,000 vs. <400 following potential confounders: 

comparison groups: NR/NR Quetelet index, estrogen use, and 

presence of chronic disease OR 

82 

Wyshak, 198979Country: USA Low milk diet vs. not First fracture after 40 

Women years of age Ca++ intake difference in comparison groups: NR/NR 

Adjusted for current consumption of nonalcoholic carbonated beverages; current consumption of alcoholic beverages; age; current dietary restrictions, smoking history; pregnancy history; currently exercisinregularly; and use of hormones for menopausal symptoms OR 

Bold = statistically significant 
83 

Figure 3. Association between milk intake and history of any fracture 

Lactose free diet Prepubertal children, New Zealand Low childhood and adolescence milk intake Women, 3d National Health and Nutrition Examination Survey Low adolescence milk intake Women, 3d National Health and Nutrition Examination Survey Elderly women and men, Australia Low childhood milk intake Women, 3d National Health and Nutrition Examination Survey Low lifetime milk intake Elderly women and men, Australia Study 

4.13 (1.61, 1.60 (1.17, 2.07 (1.27, 3.20 (1.30, 1.72 (0.84, 2.10 (1.00, ES (95% C

0.1 1 10.6 
Low lifetime intake of milk 

The Nurses' Health Study Women, Mediterranean Osteoporosis Study (the MEDOS Study) Women, former college athletes, USA Men in the pooled cohorts* Women in the pooled cohorts* Adults of all ages in the pooled cohorts* Adults, the Adult Health Study, Japan Postmenopausal women, Italy Low adolescence intake of milk The Nurses' Health Study Middle aged women, USA Study 

.25 1 

Figure 4. Association between milk intake and hip fracture * The European Vertebral Osteoporosis Study (EVOS/EPOS study), the Canadian Multicentre Osteoporosis Study (CaMos), the Dubbo 

Epidemiology Study (DOES), the Rotterdam Study, the Sheffield Study and a cohort from Gothenburg. 

84 
85 

Figure 5. Association between milk intake and osteoporotic bone fractures 

0.3 1 3 

*The European Vertebral Osteoporosis Study (EVOS/EPOS study), the Canadian Multicentre Osteoporosis Study (CaMos), the Dubbo O

Study (DOES), the Rotterdam Study, the Sheffield Study and a cohort from Gothenburg 

Low childhood and adolescence milk intake in elderly women 3rd National Health and Nutrition Examination Survey Low childhood milk intake in elderly women 3rd National Health and Nutrition Examination Survey Low adolescence milk intake in elderly women 3rd National Health and Nutrition Examination Survey Low lifetime milk intake Adults in the pooled cohorts* 

Men in the pooled cohorts* Women in the pooled cohorts* Study 

1.19 1.39 1.59 1.06 1.11 1.09 ES (
Figure 6. Association between dairy calcium intake (mg/day) and bone fractures 

86 

History of fracture in prepubertal children with a history of long-term milk avoidance <300 vs. >300 mg/day Hip fracture in the NHANES I Epidemiologic Followup Study <400 vs. >1,000 mg/day in men <400 vs. >1,000 mg/day in women <400 vs. >1,000 mg/day in late menopausal women Hip fracture in postmenopausal women, Italy >1,026 vs. <443 mg/day Study Comparison groups of daily Ca++ intake 

1.26 (0.34, 4.65) 0.51 (0.20, 1.10) 0.91 (0.50, 1.60) 0.73 (0.30, 1.60) 1.20 (0.80, 2.00) 

Relative measure of the 

association 

(95% CI) 

.2 1 5 
Table 10. Association between vegan diet (lactose free) and incident fracture of bones other than the digits 

or ribs, results from the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition 

(EPIC-Oxford)90 

Comparison Estimate Mean (95%CI) 

Vegan men vs. meat eaters: men Adjusted for age RR 1.30 (0.85; 2.00) 

Vegan women vs. meat eaters women 1.28 (0.95; 1.72) 

Vegan adults vs. meat eaters: adults 1.37 (1.07; 1.74) 

Vegan men vs. meat eaters: men Adjusted for age, smoking, alcohol consumption, 1.19 (0.76; 1.85) 

Vegan women vs. meat eaters women 

Vegan adults vs. meat eaters adults 

body mass index, exercise, physical activity at 

work, marital status and for women parity and use 

of hormone replacement therapy RR 

1.21 (0.89; 1.64) 

1.30 (1.02; 1.66) 

Vegan men vs. meat eaters men Adjusted for age, smoking, alcohol consumption, 1.20 (0.73; 1.98) 

Vegan women vs. meat eaters women 

Vegan adults vs. meat eaters adults 

body mass index, exercise, physical activity at 

work, marital status and for women parity and use 

of hormone replacement therapy, energy and 

1.05 (0.76; 1.44) 

1.15 (0.89; 1.49) 

calcium intake RR 

Vegan men consuming at least 525 mg/day Adjusted for age, smoking, alcohol consumption, 0.80 (0.42; 1.51) 

calcium vs. meat eaters body mass index, exercise, physical activity at 

Vegan women consuming at least 525 

mg/day calcium vs. meat eaters 

work, marital status and for women parity and use 

of hormone replacement therapy RR 

0.96 (0.61; 1.51) 

Vegan adults consuming at least 525 1.00 (0.69; 1.44) 

mg/day calcium vs. meat eaters 

Bold = statistically significant 

87 
Table 11. Association between genetic polymorphism and bone fractures 

88 

Study

Gugatschka, 200791 

 Comparison 

T/T vs. C/T 

Outcome 

Fractures (number) 

Estimate 

Crude mean difference 

Country: Austria Elderly male 

T/T vs. C/C 

Ca++ intake difference in comparison groups: -21/Y Obermayer-Pietsch, 200468 

Country: Austria Postmenopausal women Ca++ intake difference in 

T/T vs. C/C T/C vs. C/C T/T vs. TC 

Bone fracture incidence Crude OR 

comparison groups: 0.55/Y Gugatschka, 200791 C/T vs. C/C Fractures (number) Crude mean difference 

Country: Austria Elderly male Ca++ intake difference in comparison groups: 14/N Obermayer-Pietsch, 200769 T/T vs. C/C Interim nonvertebral bone Crude OR 

Country: Austria fractures Postmenopausal women Ca++ intake difference in 

T/T vs. C/C Interim vertebral fractures 

comparison groups: 349/Y Enattah, 200565 

Country: Finland Elderly Ca++ intake difference in comparison groups: NR/NR 

T/T vs. C/C C/T vs. C/C T/T vs. C/T 

Fracture of hip Fracture of wrist Fracture of hip Fracture of wrist Fracture of hip 

Crude OR 

Enattah, 200529 Country: Finland Postmenopausal women Ca++ intake difference in 

T/T vs. C/C 

Fracture of wrist History of any fracture Vertebral Nonvertebral 

Crude OR 

comparison groups: NR/NR Bold = statistically significant 
89 

Table 12. Association between lactose intolerance or malabsorption and bone fractures 

Study Comparison Outcome Estimate 

Symptomatic lactose intolerance Goulding, 200489 Symptoms to cow milk vs. History of fracture Crude OR 

Country: New Zealand none Prepubertal children with a history of long-term milk avoidance Ca++ intake difference in comparison groups: NR/NR Enattah, 200529 Lactose intolerance vs. none History of any fracture Crude OR 

Country: Finland Postmenopausal women Ca++ intake difference in 

Vertebral Nonvertebral 

comparison groups: NR/NR Kudlacek, 200292 

Country: Austria 

Self reported symptoms of LI vs. none 

Fracture Crude OR 

Adults Ca++ intake difference in comparison groups: NR/NR Kull, 200967 

Country: Estonia 

Self-reported LI vs. none Fracture occurring after the age 

of 25 

Crude OR 

Adults Ca++ intake difference in comparison groups: NR/NR Diagnosed with objective tests lactose malabsorption Honkanen, 1997167 

Country: Finland Perimenopausal women Ca++ intake difference in comparison groups: -280/Y 

Positive vs. negative lactose tolerance test 

Wheadon, 1991 Malabsorbers vs. none (age 164 

A fracture since age of 15 Any fracture Wrist, radius Any fracture Wrist Nonwrist History of fracture 

Crude OR Adjusted for age, BMI, number of chronic health disorders, menopausstatus (postmenopausal/other), and smoking status OR Age matched OR 

Country: New Zealand matched controls) Elderly New Zealand women with hip fractures Ca++ intake difference in comparison groups: 317/N Kudlacek, 200292 

Malabsorbers vs. none (young controls) Malabsorbers vs. none (all controls) Moderate lactose All fractures 

Crude OR Crude OR Crude mean difference 

Country: Austria Adults 

malabsorption vs. none Severe lactose malabsorption 

Vertebral fractures/patient 

All fractures 
Table 12. Association between lactose intolerance or malabsorption and bone fractures (continued) 

Study

Ca++ intake difference in comparison groups: NR/NR Harma, 1988170 

Country: Finland Elderly women Ca++ intake difference in comparison groups: NR/NR 

 Comparison 

vs. none Severe lactose malabsorption vs. moderate Lactose malabsorption vs. none Moderate lactose malabsorption vs. none Severe lactose malabsorption vs. none Severe lactose malabsorption vs. moderate LM (positive blood glucose test) vs. none LM (positive blood glucose test) vs. none 

Outcome 

Vertebral fractures/patient All fractures Vertebral fractures/patient Overall fractures Vertebral fracture per individual Verterbral fracture per individual Verterbral fracture per individual Spinal fracture Hip fracture 

Estimate 

Crude OR Age and sex matching OR 

Bold = statistically significant 

90 
Study Comparison Outcome Estimate 

Osteopenia 

Di Stefano, 20025 Lactose malabsorption vs. normal lactose Lumbar Crude OR 

Country: Italy absorption Femoral neck 

Adults Lactose malabsorption with intolerance Lumbar 

symptoms vs. absorbers Femoral neck Lactose malabsorption without intolerance Lumbar symptoms vs. absorbers Femoral neck Lactose malabsorption with intolerance Lumbar symptoms vs. lactose malabsorption without Femoral neck symptoms 

Chiu, 199793 Long-term vegan vegetarian practice vs. non Lumbar spine OR adjusted for age, BMI, vigorous 

Country: Taiwan long-term vegan and nonvegan vegetarians physical activity, calcium, protein, 

postmenopausal Taiwanese Long-term vegan vegetarian practice vs. Femoral neck and kcal women short -term vegan and nonvegan vegetarians 

Osteoporosis 

Birge, 196794 History of milk intolerance Osteoporosis Crude OR 

Country: USA Adults 50 years or over Sha 93

91 163 w, 19 Milk intake > vs.<2times/week: women Osteoporosis Crude OR 

Country: Taiwan Milk intake > vs.<2times/week: men 

Adults Enattah, 200529 T/T vs. C/C Osteoporosis Crude OR 

Country: Finland C/T vs. C/C Postmenopausal women T/T vs. C/T Obermayer-Pietsch, 200769 T/T vs. C/C Osteoporosis Crude OR 

Country: Austria 

Postmenopausal women 

Finkenstedt, 1986168 LI vs. none Osteoporosis Crude OR 

Country: Austria 

Women Birge, 196794 Positive vs. negative lactose tolerance test Osteoporosis Crude OR 

Country: USA

Adults 50 year


 

s or over 

Finkenstedt, 1986168 LM vs. none Osteoporosis Crude OR 

Country: Austria 

Women Corazza, 1995169 Osteoporosis Crude OR 

Country: Italy 

postmenopausal women LI (clinical diagnosis) vs. none Bold = statistically significant Table 13. Association between low lactose diets, lactose intolerance or malabsorption, and osteoporosis 
Figure 7. Association between genetic polymorphism TT vs. C/C and positive tests for lactose malabsorption, 

crude odds ratios from two Austrian observational population based studies of genetic screening for 

osteoporosis66,69 

Postmenopausal women 

Positive breath test 

Positive blood glucose test 

Positive at least one test 

Adult males 

Positive breath test 

Positive blood glucose test 

Study 

0.06 (0.02, 0.19) 

0.32 (0.12, 0.88) 

4.14 (0.41, 41.82) 

0.03 (0.00, 0.24) 

0.02 (0.00, 0.42) 

ES (95% CI) 

0.001 1 100 

92 
Table 14. Bone health outcomes in children and adolescents with low lactose diets (results from randomized controlled clinica

% Recommended Outcome 

Daily Values of Ca++ Ca++mg/Day in Outcome Mean ± S

Skeletal Site in Control Group with Active vs. Mean ± SD In Control G

Low Lactose Diet / Control Group in Active Group with Low Lac

Months of Followup Diet 

Bone Mineral Content (BMC) 

Total body BMC Chan, 1995103 56.0 / 12 1,068 vs. 463 1,695.00±317.00 1617.00±152.

Country: USA Masking: Open label Sample: 48 Gender: 48 females Age: 11±1 Cadogan, 1997104 54.1 / 18 1,125 vs. 703 428.00±88.00 391.00±107.0

Country: UK Masking: Open label Sample: 82 Gender: 82 females Age: 12.2 years±3 Lau, 2004101 35.6 / 12 1,794 vs. 463 1,143.80±146.10 1,058.10±152

Country: Hong Kong 35.6 / 12 1,067 vs. 463 1,092.50±153.30 1,058.10±152Masking: Open label 35.6 / 18 1,794 vs. 463 1,218.00±146.10 1,147.40±152Sample: 344 35.6 / 18 1,067 vs. 463 1,185.40±153.30 1,147.40±152Gender: 181 males/143 females 

Age: 10.0 years±3 

93 

Gibbons, 2004102 

Country: New Zealand Masking: The children were blinded to the study product Sample: 154 Gender: 75 males/79 females Age: 9.4 years±1 

30.8 / 12 1,200 vs.400 1,394.00±23.00 1,383.00±29.0

30.8 / 18 1,200 vs.400 1,428.00±23.00 1,429.00±29.0

Total hip BMC Lau, 2004101 

Country: Hong Kong Masking: Open label Sample: 344 Gender: 181 males/143 females 

35.6 / 12 35.6 / 12 35.6 / 18 35.6 / 18 

1,794 vs. 463 

1,067 vs. 463 

1,794 vs. 463 

1,067 vs. 463 

17.50±3.07 

16.60±2.46 

18.97±3.07 

18.62±2.46 

16.10±2.64 

16.10±2.64 

17.92±2.69 

17.92±2.69 

Age: 10.0 years±3 
Table 14. Bone health outcomes in children and adolescents with low lactose diets (results from randomized controlled clinica

(continued) Gibbons, 2004102 

Country: New Zealand Masking: The children were blinded to the study product Sample: 154 Gender: 75 males/79 females Age: 9.4 years±1 

% Recommended Outcome 

Daily Values of Ca++ Ca++mg/Day in Outcome Mean ± S

Skeletal Site in Control Group with Active vs. Mean ± SD In Control G

Low Lactose Diet / Control Group in Active Group with Low Lac

Months of Followup Diet 

30.8 / 12 1,200 vs.400 19.10±0.40 19.00±0.50 

94 

Total femur BMC Cheng, 2005107 51.6 / 24 1,680 vs.671 25.90±3.20 26.20±3.90 

Country: Finland Masking: DB Sample: 195 Gender: 196 females Age: 11.3 years±7 Femoral shaft BMC Bonjour, 1997105 

Country: Switzerland Masking: DB 

87.9 / 12 74.7 / 12 

1,723 vs.879 1,607 vs. 747 

0.89±0.06 

4.50±2.20 

0.65±0.07 

4.00±0.21 

Sample: 149 Gender: 149 females Age: 7.9 years±06 Femoral neck BMC Lau, 2004101 

Country: Hong Kong Masking: Open label Sample: 344 Gender: 181 males/143 females 

35.6 / 12 35.6 / 12 35.6 / 18 35.6 / 18 

1,794 vs. 463 

1,067 vs. 463 

1,794 vs. 463 

1,067 vs. 463 

1.81±0.27 

1.76±0.27 

1.92±0.27 

1.85±0.27 

1.71±0.26 

1.71±0.26 

1.81±0.26 

1.81±0.26 

Age: 10.0 years±3 Chevalley, 2005106 74.7 / 12 1,607 vs. 747 1.59±0.18 1.64±0.22 

Country: Switzerland Masking: DB Sample: 235 Gender: 235 males Age: 7.4 years±4 
Table 14. Bone health outcomes in children and adolescents with low lactose diets (results from randomized controlled clinica

(continued) 

% Recommended Outcome 

Daily Values of Ca++ Ca++mg/Day in Outcome Mean ± S

Skeletal Site in Control Group with Active vs. Mean ± SD In Control G

Low Lactose Diet / Control Group in Active Group with Low Lac

Months of Followup Diet 

Cheng, 2005107 51.6 / 24 1,680 vs.671 3.99±0.40 3.95±0.05 

Country: Finland Masking: DB Sample: 195 Gender: 196 females Age: 11.3 years±7 Lumbar spine BMC Bonjour, 1997105 87.9 / 12 1,723 vs.879 1.78±0.20 1.30±0.18 

Country: Switzerland Masking: DB Sample: 149 Gender: 149 females Age: 7.9 years±0.6 Lau, 2004101 35.6 / 12 1,794 vs. 463 27.47±4.06 26.29±4.13 

Country: Hong Kong 35.6 / 12 1,067 vs. 463 27.71±5.07 26.29±4.13 Masking: Open label 35.6 / 18 1,794 vs. 463 31.65±4.06 28.81±4.13 Sample: 344 35.6 / 18 1,067 vs. 463 30.60±5.07 28.81±4.13 Gender: 181 males/143 females Age: 10.0 years±3 

95 

Gibbons, 2004102 

Country: New Zealand Masking: The children were blinded to the study product Sample: 154 Gender: 75 Males/79 Females Age: 9.4 years±1 

30.8 / 12 1,200 vs.400 28.80±1.00 27.40±1.00 

30.8 / 18 1,200 vs.400 28.50±1.00 28.80±1.00 

Chevalley, 2005106 74.7 / 12 1,607 vs. 747 1.97±0.80 1.99±0.81 

Country: Switzerland Masking: DB Sample: 235 Gender: 235 males Age: 7.4 years±4 Cheng, 2005107 51.6 / 24 1,680 vs.671 34.20±5.60 34.00±5.60 

Country: Finland Masking: DB Sample: 195 Gender: 196 females Age: 11.3 years±7 
Table 14. Bone health outcomes in children and adolescents with low lactose diets (results from randomized controlled clinica

(continued) 

96 

% Recommended Outcome 

Daily Values of Ca++ Ca++mg/Day in Outcome Mean ± S

Skeletal Site in Control Group with Active vs. Mean ± SD In Control G

Low Lactose Diet / Control Group in Active Group with Low Lac

Months of Followup Diet 

Bone Mineral Density (BMD) 

Femoral trochanter BMD Bonjour, 1997105 87.9 / 12 1,726 vs.879 530.00±59.33 514.00±58.24 

Country: Switzerland Masking: DB Sample: 149 Gender: 149 females Age: 7.9 years±0.6 Femoral neck BMD Bonjour, 1997105 67.6 / 12 1,725 vs.879 656.00±81.58 635.00±65.52 Country: Switzerland Masking: DB Sample: 149 Gender: 149 females Age: 7.9 years±0.6 Femoral diaphysis Bonjour, 1997105 

BMD 

87.9 / 12 1,727 vs.879 1098.00±96.41 1077.00±87.3

Country: Switzerland Masking: DB Sample: 149 Gender: 149 females Age: 7.9 years±0.6 Lumbar spine Chan, 1995103 

BMD 

56.0 / 12 1,069 vs. 463 0.77±0.09 0.75±0.08 

Country: USA Masking: Open label Sample: 48 Gender: 48 females Age: 11±1 Bold- statistically significant difference at 95% confidence level 
Figure 8. Bone mineral content from RCTs of dairy product use in children and adolescents with low lactose 

diets. Total body 

Daily Ca++ intake in active vs. control group (country) 

WMD (95% CI) 

12 months 

1,067 vs. 463 (Hong Kong) 

1,200 vs. 400 (New Zealand) 

1,417 vs. 728 (USA) 

1,794 vs. 463 (Hong Kong) 

18 months 

1,067 vs. 463 (Hong Kong) 

1,125 vs. 703 (UK) 

1,200 vs. 400 (New Zealand) 

1,794 vs. 463 (Hong Kong) 

34.40 (2.14, 66.66) 

11.00 (2.73, 19.27) 

78.00 (-62.65, 218.65) 

85.70 (54.19, 117.21) 

38.00 (5.74, 70.26) 

37.00 (-5.41, 79.41) 

-1.00 (-9.27, 7.27) 

70.60 (39.09, 102.11) 

-219 0 219 

97 
Figure 9. Bone mineral content from RCTs of dairy product use in children and adolescents with low lactose 

diets. Femoral neck 

Daily Ca++ intake in active vs. control group (country) 

WMD (95% CI) 

NOTE: Weights are from random effects analysis 

. 

. 

. 

12 months 

1,067 vs. 463 (Hong Kong) 

1,607 vs. 747 (Switzerland) 

1,794 vs. 463 (Hong Kong) 

18 months 

1,067 vs. 463 (Hong Kong) 

1,794 vs. 463 (Hong Kong) 

24 months 

1,680 vs. 671 (Finland) 

0.05 (-0.01, 0.11) 

-0.05 (-0.10, 0.00) 

0.10 (0.04, 0.16) 

0.04 (-0.02, 0.10) 

0.11 (0.05, 0.17) 

0.04 (-0.04, 0.12) 

-0.2 0 0.2 

98 
12 months 

1,067 vs. 463 (Hong Kong) 0.50 (-0.04, 1.04) 

1,200 vs. 400 (New Zealand) 0.10 (-0.04, 0.24) 

1,794 vs. 463 (Hong Kong) 1.40 (0.79, 2.01) 

18 months 

1,067 vs. 463 (Hong Kong) 0.70 (0.16, 1.24) 

1,200 vs. 400 (New Zealand) 1.20 (1.06, 1.34) 

1,794 vs. 463 (Hong Kong) 1.05 (0.44, 1.66) 

-2 0 2 

Figure 10. Bone mineral content from RCTs of dairy product use in children and adolescents with low lactose 

diets. Total hip 

Daily Ca++ intake in active vs. control group (country) WMD (95% CI) 

99 
Figure 11. Bone mineral content from RCTs of dairy product use in children and adolescents with low lactose 

diets. Lumbar spine 

Daily Ca++ intake in active vs. control group (country) 

WMD (95% CI) 

12 months 

1,067 vs. 463 (Hong Kong) 

1,200 vs. 400 (New Zealand) 

1,607 vs. 747 (Switzerland) 

1,723 vs. 879mg/day (Switzerland) 

1,794 vs. 463 (Hong Kong) 

18 months 

1,067 vs. 463 (Hong Kong) 

1,200 vs. 400 (New Zealand) 

1,794 vs. 463 (Hong Kong) 

24 months 

1,680 vs. 671 (Finland) 

1.42 (0.44, 2.40) 

1.40 (1.08, 1.72) 

-0.02 (-0.23, 0.19) 

0.48 (0.42, 0.54) 

1.18 (0.31, 2.05) 

1.79 (0.81, 2.77) 

-0.30 (-0.62, 0.02) 

2.84 (1.97, 3.71) 

0.20 (-1.37, 1.77) 

-4 0 4 

100 
Table 15. Percent change in osteodensitometric values after administration of dairy products in children 

consuming low lactose diets (RCTs) 

Study 

Sample 

Gibbons, 2004102 

Outcome 

Bone mineral density, total body 

Active, 

Mean STD 

9.40±8.60 

Control, 

Mean STD 

8.90±9.84 

Mean Difference 

(95% CI) 

0.50 (-2.41; 3.41) 

74 Bone mineral density, lumbar spine 16.30±16.34 16.80±18.78 -0.50 (-6.05; 5.05) 

Bone mineral density, hip 14.00±16.34 12.40±17.89 1.60 (-3.81; 7.01) 

Bone mineral density, Trochanter 15.80±18.93 14.90±19.68 0.90 (-5.20; 7.00) 

Bone mineral density, femoral neck 15.40±16.34 15.30±15.21 0.10 (-4.90; 5.10) 

Cadogan, 1997104 

Lumbar spine L1-L4 volumetric density 

Bone mineral density, lumbar spine 

54.30±55.92 

17.90±6.80 

60.50±65.29 

16.20±6.70 

-6.20 (-25.36; 12.96) 

1.70 (-1.23; 4.63) 

44 

Cheng, 2005107 

48 

Bone mineral density 

Bone mineral density in femoral neck (g) 

38.10±1.40 

26.50±1.40 

35.00±1.40 

22.40±1.50 

3.10 (2.54; 3.66) 

4.10 (3.52; 4.68) 

Bone mineral content total femur (g) 36.90±1.60 33.60±1.60 3.30 (2.66; 3.94) 

Bone mineral density, spine L2-4 (g) 52.40±2.20 47.00±2.20 5.40 (4.52; 6.28) 

Bone cross-sectional area, radius (mm2) 26.20±2.00 21.30±2.00 4.90 (4.10; 5.70) 

Bone mineral content radius (mg/mm) 25.90±1.90 22.20±2.00 3.70 (2.92; 4.48) 

Volumetric bone mineral density, radius 

(mg/cm3) 

3.07±1.50 1.99±1.50 1.08 (0.48; 1.68) 

Bone mineral density, tibia (mg/mm) 25.20±1.00 22.70±1.00 2.50 (2.10; 2.90) 

Lau, 2004101 

Volumetric bone mineral density, tibia 

(mg/cm3) 

Bone mineral content, total hip 

8.30±0.60 

24.42±11.40 

7.76±0.60 

22.77±11.60 

0.54 (0.30; 0.78) 

1.65 (-1.39; 4.69) 

100 Bone mineral density, total hip 7.28±4.10 6.34±4.20 0.94 (-0.16; 2.04) 

Bone mineral content, femoral neck 10.01±11.40 10.64±12.04 -0.63 (-3.72; 2.46) 

Bone mineral density, femoral neck 6.16±4.60 5.40±4.75 0.76 (-0.47; 1.99) 

Bone mineral content, spine 20.88±9.40 19.23±9.39 1.65 (-0.83; 4.13) 

Bone mineral density, spine 8.05±5.20 7.01±5.30 1.04 (-0.35; 2.43) 

Bone mineral content, total body 17.02±6.50 16.88±6.63 0.14 (-1.59; 1.87) 

Bone mineral density, total body 3.06±2.60 2.39±2.65 0.67 (-0.02; 1.36) 

Bone mineral content, total hip 25.89±12.02 22.77±11.60 3.12 (0.01; 6.23) 

Bone mineral density, total hip 7.41±4.24 6.34±4.20 1.07 (-0.04; 2.18) 

Bone mineral content, femoral neck 13.16±12.22 10.64±12.04 2.52 (-0.67; 5.71) 

Bone mineral density, femoral neck 6.48±4.95 5.40±4.75 1.08 (-0.20; 2.36) 

Bone mineral content, spine 21.51±9.70 19.23±9.39 2.28 (-0.23; 4.79) 

Bone mineral density, spine 8.37±5.45 7.01±5.30 1.36 (-0.06; 2.78) 

Bone mineral content, total body 18.46±6.77 16.88±6.63 1.58 (-0.18; 3.34) 

Bone mineral density, total body 2.87±2.73 2.39±2.65 0.48 (-0.23; 1.19) 

Bold- statistically significant differences at 95% confidence level 

101 
Table 16. Association between lactose intake and metabolism and BMC 

Study 

Difference in Daily Ca++ Comparison Outcome Estimate 

Intake in Comparison Groups 

Low lactose diets Vatanparast, 2005160 Calcium intake by mg/d, Total-body BMC in boys Adjusted for height, body 0

Country: Canada increment 1mg/day mass, physical activity, intake 

Children and adolescents Calcium intake by mg/d, Total-body BMC in girls of calcium, and intake of N

Ca++ intake difference in increment 1mg/day vegetables and fruit 

comparison groups: NR/NR Parsons, 199795 

Country: The Netherlands Adolescents Ca++ intake difference in comparison groups: -488/Y 

102Rockell, 200597 

Country: New Zealand Prepubertal children with a history of long-term milk avoidance Ca++ intake difference in comparison groups: 182/Y Black, 200276 

Country: New Zealand Prepubertal children with a history of long-term milk avoidance Ca++ intake difference in comparison groups: NR/NR 

Vegan type diet vs. regular diet in BMC, total body girls Vegan type diet vs. regular diet in BMC, Total body boys BMC, Spine L1–L4 

BMC, Femoral neck BMC, Trochanter BMC, Radius 33% 

Vegan type diet vs. regular diet in BMC, Spine L1–L4 

girls BMC, Femoral neck 

BMC, Trochanter BMC, Radius 33% 

Adjusted for bone area, weight, height, percent body lean, age, and puberty 

-2-3-8-8

-3

-6-4-8-5-5

Milk avoiders, at 2 years of Total body BMC (g) Crude 2

followup vs. baseline Baseline vs. reference population Total body BMC (kg) -0

At 2 years of followup vs. Total body BMC (kg) Age adjusted -0

reference population Baseline vs. reference population UD radius BMC Crude -0

33% radius BMC -0Lumbar spine (L2–4) BMC -0Femoral neck BMC -0Hip trochanter BMC -0

At 2 years of followup vs. UD radius BMC Age adjusted -0reference population	 33% radius BMC -0

Lumbar spine (L2–4) BMC 0Femoral neck BMC 0Hip trochanter BMC 0

Age adjusted z scores in milk Total-body BMC (g) Age adjusted -0

avoiders vs. reference healthy children 
Table 16. Association between lactose intake and metabolism and BMC (continued) 

103 

Study 

Difference in Daily Ca++ 

Intake in Comparison Groups 

Du, 200296 

Country: China Adolescent Girls Ca++ intake difference in comparison groups: NR/NR 

Comparison 

Increase in milk intake by 1 g/day 

Outcome 

BMC at distal one-third ulna BMC at distal one-third radius BMC at distal one-tenth ulna 

Estimate 

Adjusted for physical activity, body weight, age, and socio-economic status regression coefficient 

000

BMC at distal one-tenth radius 

0

No milk consumers vs. Low milk group (<22±18 g/day) 

BMC (g/cm); distal onethird radius BMC (g/cm); distal onethird ulna 

Crude -0

0

BMC (g/cm); distal onetenth radius -0BMC (g/cm); distal onetenth ulna -0

No milk consumers vs. High milk group (>128±165 g/day) 

BMC (g/cm); distal onethird radius BMC (g/cm); distal onethird ulna 

Crude -0

-0

BMC (g/cm); distal onetenth radius -0BMC (g/cm); distal onetenth ulna -0

Low milk group (<22±18 g/day) vs. High milk group (>128±165 g/day) 

BMC (g/cm); distal onethird radius BMC (g/cm); distal onethird ulna 

Crude 0

0

BMC (g/cm); distal onetenth radius 0BMC (g/cm); distal onetenth ulna 0

Genetic polymorphism Enattah, 200457 

Country: Finland Young men Ca++ intake difference in comparison groups: NR/NR 

T/T vs. C/C C/T vs. C/C 

Lumbar spine BMC (g) Femoral neck BMC (g) Trochanter BMC (g) Total hip BMC (g) Lumbar spine BMC (g) Femoral neck BMC (g) Trochanter BMC (g) 

Crude Crude 

2

0

0

2

1

-0

-0
Table 16. Association between lactose intake and metabolism and BMC (continued) 

104 

Study 

Difference in Daily Ca++ 

Intake in Comparison Groups 

Comparison Outcome Estimate 

Total hip BMC (g) 0

T/T vs. C/T Lumbar spine BMC (g) Crude 0

Femoral neck BMC (g) 0

Trochanter BMC (g) 0

Total hip BMC (g) 1

Lactose intolerance Stallings, 199498 

Country: USA 

Lactose intolerance vs. none BMC, g/cm adjusted for 

body size in LI subjects 

Crude regression coefficient 0

Prepubertal children Ca++ intake difference in 

Lactose intolerance vs. none BMC, g/cm Crude -0

comparison groups: -383/Y Di Stefano, 20025 

Country: Italy Adults 

Lactose intolerance vs. none Lactose intolerance vs. none 

BMC (g): Lumbar spine 

BMC (g): Femoral neck 

Crude -2

-1

Ca++ intake difference in comparison groups: -240/Y Matlik, 200799Country: USA Perceived Lactose intolerance vs. Total body BMC, g Adjusted for location -6

10- to 13-Year-Old Female Adolescents Ca++ intake difference in comparison groups: 168/Y 

none Spine (L2–L4) BMC, g 

Total hip BMC, g Femoral neck BMC, g 

(California or Indiana), race/ethnic group (Asian, Hispanic, or non-Hispanic white), and age (years), BMI 

-2-0-0

and Tanner score 

Total body BMC, g Crude -9

Spine (L2–L4) BMC, g -3Total hip BMC, g -Femoral neck BMC, g -0

Lactose malabsorption Di Stefano, 20025 Lactose malabsorption vs. none BMC (g): Lumbar spine Crude -0

Country: Italy Adults 

BMC (g): Femoral neck 0

Ca++ intake difference in comparison groups: -54/Y Matlik, 200799 

Country: USA 

Lactose malabsorption vs. none Total body BMC, g, adjusted for location, 

race/ethnic group, and age. 

3

10- to 13-year-old Diet models were also female adolescents adjusted for weight, , BMI and Ca++ intake difference in Tanner score comparison groups: 9/N Spine (L2–L4) BMC, g -0

Total hip BMC, g 0Femoral neck BMC, g 0
Table 16. Association between lactose intake and metabolism and BMC (continued) 

105 

Study 

Difference in Daily Ca++ 

Intake in Comparison Groups 

Comparison Outcome Estimate 

Total body BMC, g Crude -9Spine (L2–L4) BMC, g -0Total hip BMC, g -0

Goulding, 199971 Malabsorbers vs. absorbers at 

Femoral neck BMC, g BMC, g/cm2 ultradistal Adjusted for age, body 

-00

Country: New Zealand Middle age and older women Ca++ intake difference in comparison groups: NR/NR 

baseline radius 

BMC, g/cm2 33% radius 

BMC, g/cm2 , L2-4 BMC, g/cm2, neck of femur BMC, g/cm2, trochanter BMC, g/cm2 

weight, menopausal status, calcium intake regression coefficient 

0

-0

0

0

0

Total body mineral content -5

Malabsorbers vs. absorbers at 

(g) BMC, g/cm2 ultradistal 0

baseline at 12 months of followup radius 

BMC, g/cm2 33% radius 

BMC, g/cm2 , L2-4 BMC, g/cm2, neck of femur BMC, g/cm2, trochanter BMC, g/cm2 

00

-0

-0

0

Bold – statistically significant 
Table 17. Effect of increased dairy intake on bone health in young62 and pre-menopausal63 women consuming low lactose diets 

RCTs) 

Outcome Outcome Ca++mg/day in Active Study Outcome Mean ± STD in Mean ± STD in 

vs. Control Group Active Control 

Woo, 200762 

Country: China Masking: Open label Sample: 441 Gender: Female Age: 28±8 Baran, 199063 

Country: USA Masking: Open label Sample: 59 Gender: Female Age: 35.7-37 

Outcome: BMD Total spine; % change from baseline Outcome: BMD, Total hip; % change from baseline Outcome: BMD, whole body; % change from baseline Outcome: BMD, vertebral ; % change from baseline 

1,446 vs. 446 (45% of recommended daily values) 

1.49±NR 1.20±NR 0.25±NR 0.25±NR 0.60±NR 0.75±NR 

962 vs.892 (89% of -0.40±0.90 -2.90±0.80 recommended daily values) 

Total signifin the protocsignifthe mboth iprotoc

The v

womecalciu3-yeacontradensideclinsignifthe suand 3

106 
Key Question 3: What amount of daily lactose intake is 

tolerable in subjects with diagnosed lactose intolerance? 

Optimally, studies of this question would employ the following methodology. 

1. A large, randomly recruited group of subjects with a wide range of age and ethnicity 

would be tested for lactose malabsorption (the assumption being that subjects who do not 

malabsorb lactose cannot be lactose intolerant). 

2. The lactose malabsorbers would undergo double-blind testing with a maximal 

physiological dose of lactose (50 grams) or an identical placebo to identify which subjects 

had appreciably more symptoms with lactose than the placebo. This study would identify 

subjects for further study with lower, more physiological dosages of lactose. 

3. Subjects with lactose intolerance would then be tested in double-blind fashion with a 

range of doses of lactose or identical placebo in an attempt to determine at what dosage 

lactose symptoms convert from tolerable to intolerable. To simulate a true life situation, 

the lactose would be administered with meals throughout the day. The subjects would 

provide a global assessment of their symptoms as well as a daily severity assessment of 

various symptoms on a numerical scale. The dose of lactose that induced a global rating of 

unacceptable (“intolerable”), or a significant increase in symptom score relative to the 

rating of the placebo, would be determined. The numerical scoring system would be 

converted to biological relevance, i.e., what difference in symptom score differentiates 

“tolerable” versus “intolerable.” 

4. Lastly, data would be analyzed to determine if the tolerable dose of lactose in 

malabsorbers is influenced by age and ethnicity. 

Characteristics of Included Studies 

Twenty-eight randomized (to treatment order), crossover, trials were included (Appendix Table 

D9).108-115,117-135 Nearly all trials reported utilizing a double blinded approach, but three studies 

were single blinded or did not attempt to mask the tastes of the test preparations.115,130,131 Trial 

populations ranged between six and 150 subjects. Women constituted 55 percent of the subjects 

(n=22 studies). The mean age of subjects was 37 years of age with a range between 10 and 77 

(n=20 studies). Seven trials included children or adolescents, four exclusively.109,114,120,123,126,127,135 

One trial enrolled elderly subjects (mean age 77 years).116 Within the 20 studies reporting race or 

ethnicity, 34 percent of subjects were white, 30 percent Hispanic, 20 percent black, 8 percent 

Asian, and 7 percent other.109-116,118,120,123,126-131,133-135 One study was exclusively American 

Indians.120 Fifteen studies were conducted in the United States,109-111,113,114,116,118-120,125-127,130,131,135 

eight in Europe,108,112,121-124,132,134 three in Latin America,128,129,133 one in Asia,117 and one in 

Australia.115 Sixteen studies utilized commercial lactase products or hydrolyzed milk,108-111,113­

115,121-125,128,130,133,135 two used milk products with lactose removed by ultrafiltration or 

chromatographically,112,134 and three assessed nonlactose solutions.116,126,127 An unclear or 

unreported method of lactose removal was noted in two trials.129,132 One trial involved 

probiotics,117 one was a colonic adaptation study,118 and three trials assessed varying levels of 

daily lactose (added to water or in sugar packets to be added to breakfast).119,120,131 In 11 studies, 

abdominal symptoms compatible with malabsorption of lactose prior to study entry were not 

required for study participation (based solely on biochemical diagnosis) or subjects were not 

reported to experience symptoms following ingestion of lactose.115-117,120,122,126,127,129,130,133,135 

107 
Lactose malabsorption was diagnosed following lactose tolerance tests by the hydrogen breath test 

in 13 of the studies,108-120 and blood glucose test in 11 studies.121-131 Diagnosis based on urinary 

galactose concentration was reported in one study132 and biochemical method of diagnosis was not 

reported in three trials.133-135 Half of the trials included lactose digesting controls.110-113,116,120,122,125­

129,133,135 

Overview of Findings 

Existing studies do not fulfill the ideal criteria described above. The vast majority of studies of 

LI have been small (<30 subjects). While age and ethnicity of the subjects is often provided, 

tolerance to lactose of these subgroups of subjects has not been studied. While subjects are 

routinely tested for LM, only a few studies have then tested the intolerant subjects in blinded 

fashion with increasing doses of lactose administered throughout the day to determine the daily 

tolerable dosage of lactose. Most studies have utilized a single dose of lactose and a lactose free 

control administered in water or milk without food, frequently in not totally blinded fashion (i.e., 

the taste of low lactose milk differs from milk). The statistical rating of symptoms is rarely related 

to biological significance. The probability that a given dose of lactose induces more symptoms 

than the control treatment has been assessed by standard statistical tests of the differences between 

group means. No attention has been paid to the possibility of outliers, i.e., selected subjects who 

consistently might be particularly sensitive to lactose induced symptoms. In contrast to the massive 

amount of data on LM and ethnicity, published data do not allow one to determine if the daily 

tolerable dose of lactose in lactose malabsorbers differs by age and ethnicity. Thus, it can be 

stated, a priori, that it is not possible to provide reliable answers to many of the questions raised in 

this section of the report. Results were heterogeneous in terms of patient populations, 

interventions, assessment methods, and outcome definitions, thus precluding pooling. We provide 

a description of the individual studies and their results stratified by key study design characteristics 

of interest. 

Experimental Studies of the Tolerance of Individual Subjects to 

Lactose 

A wide variety of methodologies have been employed to assess the ability of subjects to 

tolerate lactose. The vast majority of studies initially dosed a group of volunteers with a high (30 

grams to 50 grams) dose of lactose, and the subjects were classified as malabsorbers or absorbers 

based on breath H2 measurements or blood glucose rise. In addition, the malabsorbing subjects 

were characterized as being lactose tolerant or intolerant based on the reporting of appreciable 

(variable from one study to the next) symptoms reported during this testing. A blinded control was 

virtually never employed during this portion of the study; thus, it is possible that some of the 

subjects categorized as lactose intolerant might have had similar symptoms following ingestion of 

a lactose free control solution. 

In some studies only the lactose intolerant individuals were then tested in some sort of blinded 

fashion with a dosage or dosages of lactose, while in other studies both the lactose tolerant and the 

intolerant subjects were tested. The lactose free or lactose reduced milks that served as the controls 

usually were produced by prehydrolysis of milk with lactase, a process that produces a milk 

sweeter than that of conventional milk (glucose and galactose released from lactose is sweeter than 

lactose). Some studies did not blind for this taste difference, while other studies employed a 

108 
variety of methods to disguise this taste difference, including the addition of an artificial sweetener 

to milk, chocolate, and commercial lactose free dietary supplements. A sizable variability of the 

response of malabsorbers to the placebo was observed in various studies, ranging from nil in some 

studies to very appreciable in others. In addition, there was large inter-study variability in the 

response of the absorbers/lactose tolerant to the lactose containing or lactose free treatments. A 

striking example of the potential for nonlactose induced symptoms in this testing was provided by 

the study of Haverberg, et al.,126 in which 32 percent of lactose absorbers reported symptoms after 

ingestion of 480 ml of lactose free milk. A further example of the potential importance for taste 

blinding was the study of Reasoner, et al.,125 in which the addition of 0.2 percent glucose to milk 

reduced the symptomatic response to milk. Presumably this low concentration of glucose induced 

its effect via an influence of the taste of the milk rather than lactose digestion/absorption. Some 

studies have administered lactose (or low lactose controls) with meals, while most studies have 

employed a single dose of milk or control ingested without food (usually in the morning after 

arising). The former is more physiological, while the latter eliminated the confounding effect of 

other food on symptom response. 

Studies Using a Range of Dosages of Lactose 

The study of Hertzler and Savaiano118 provided the literature’s most optimistic appraisal of the 

daily dosage of lactose that is tolerable by lactose intolerant subjects. Eighteen healthy young adult 

subjects with self diagnosed LI were demonstrated to be lactose malabsorbers. In a randomized, 

double blind crossover study, subjects received either sucrose or lactose for a 10-day period with a 

2-day washout between feeding of the opposite sugar. The initial daily dosage of the sugar (lactose 

or sucrose) was 42 grams in evenly divided doses with meals, and this dose was incrementally 

increased to 70 grams/day over the 10-day period. Comparison of the daily symptom records 

showed no statistically significant difference between the sucrose and lactose feeding periods for 

any dosage of the sugars. Thus, subjects had negligible symptoms at the initiation of lactose 

feeding (42 grams per day) and by the end of the 10-day period, were tolerating 70 grams (almost 

1.5 quarts of milk) per day. If the results of this study of 18 self diagnosed lactose intolerant 

subjects could be extrapolated to the universe of lactose intolerant individuals, LI would not 

represent an appreciable clinical problem, provided lactose was routinely ingested in divided doses 

with meals. The investigators attributed the apparent extraordinary tolerance to lactose at the end 

of the feeding period to adaptation of the colonic flora towards bacteria that ferment lactose via 

nongas producing pathways. Lactose ingestion was associated with a nonsignificantly greater 

flatus and diarrhea severity score on virtually each of the 10 days of the study, and a statistical 

analysis of the sum of the 10-day records, if provided, may have demonstrated a significant (but 

small) increase in symptoms with lactose. 

 Stephenson et al.,131 studied 14 healthy young adult subjects who were intolerant to a 50 gram 

dose of lactose. The subjects were then fed increasing dosages of lactose in water or in milk, with 

tolerance to lactose defined as two or less mild symptoms following lactose ingestion. All subjects 

tolerated the 15 gram dose, the vast majority tolerated 30 grams, while only 5/14 tolerated a 50 

gram or greater dosage. Thus, 30 grams was the usual tolerable dose. Subjects were not blinded 

nor were the dosages of lactose randomly assigned. 

Newcomer et. al.120 randomly fed 59 Native American lactose malabsorbers (three children and 

56 adults) dosages of lactose ranging from 0-18 grams with a sweet roll and 8 ounces of Ensure® 

to disguise the difference in tastes of the test meals. Any symptom greater than slight was 

109 
considered an appreciable problem. There was no significant correlation between the dosage of 

lactose and the frequency of appreciable symptoms up to a dosage of 18 grams of lactose. Jones, et 

al.130 fed variable doses of lactose in the form of milk or lactose reduced milk with breakfast to 16 

lactose malabsorbers. Symptoms were comparable for 7.5 grams and 15 grams lactose dosages, but 

a significant increase in symptoms was observed with 30 grams. In a second study in this paper (15 

subjects) symptoms were similar for placebo and milks containing 10 grams of lactose; however, 

symptoms increased significantly (p<0.05) when lactose dosage was increased to 25 grams. No 

effort was made to disguise the taste of the milk. This study shows that up to 15 grams of milk is 

tolerated by an unselected group of lactose malabsorbers, whereas 25 (or 30 grams) yields a 

statistically significant increase in symptoms. 

In a study by Cavalli-Sforza, et al.122 40 adult lactose malabsorbers were randomly fed four 

different doses of lactose, each test period lasting 4 days. Dosages were 125, 250, 500, and 1,000 

ml/day of milk or lactose hydrolyzed milk. A significant positive correlation between increasing 

dosage and symptoms was observed with milk. The percentage of subjects reporting symptoms 

with the 125 ml, 250 ml, 500 ml, 1,000 ml dosages were about 30 percent, 45 percent, 55 percent, 

and 65 percent, respectively. The symptomatic response to low lactase milk was about 10 percent 

less at each dosage. Symptoms seldom were severe. This study suggests that the frequency of mild 

symptoms increases with increasing dosage of lactose over the range of 125 ml of milk (6 grams of 

lactose) to 1,000 ml of milk (50 grams of lactose), with no clear-cut threshold for tolerance versus 

intolerance. Given the sizable percentage reporting symptoms with lactose hydrolyzed milk, 

lactose was only partially responsible for this symptom response. 

Hertzler et al.119 fed 13 healthy adult lactose malabsorbers varying dosages of lactose (0 to 20 

grams) in water without other food. Authors masked taste differences with aspartame. A 

statistically significant increase in symptoms was observed when the dose of lactose reached 20 

grams, although mean symptom severity score was less than “slight.” Results suggest that the 

ability of lactose malabsorbers to ingest lactose without detectable symptoms occurs between a 12 

gram and 20 gram dosage of lactose when the sugar is administered in water without other food. 

Two studies of adolescents investigated the response to 240 and 480 ml of lactose-containing 

and lactose-free milk. Haverberg, et al.126 studied 43 lactose absorbers and 67 malabsorbers where 

the flavors were disguised with chocolate. There was no significant difference in symptomatic 

response of malabsorbers and absorbers to the 240 ml (12 grams lactose) dose nor was the 

response of malabsorbers to the two types significantly different. These comparisons showed 

greater differences for the 480 ml dosages. It was calculated for the lactose malabsorbers that the 

lactose content of 240 ml and 480 ml of milk might have induced symptoms in 5 percent and 24 

percent of the subjects, respectively. The majority of the symptoms reported after milk ingestion 

by these subjects (particularly with the 240 ml milk dosage) were caused by factors other than LI. 

Kwon et al.,127 using similar methodology to that of Haverberg et al.,126 studied 45 malabsorbers 

and 42 absorbers. With the 240 ml dosage of milk, a higher percentage of absorbers (19 percent) 

had symptoms with the lactose containing milk than did malabsorbers (9 percent). However, with 

480 ml of milk, a greater percentage of malabsorbers (27 percent) had symptoms versus absorbers 

(17 percent) and a greater percentage of the lactose malabsorbers had symptoms with the lactose 

containing (27 percent) than with the lactose free milk (16 percent). Statistical significance was not 

computed. This study showed that lactose malabsorbers tolerate the lactose content (11 grams) of 

240 ml of milk, but a percentage of these subjects (about 16 percent) apparently experience lactose 

induced symptoms from a 22 gram dose of lactose (480 ml of milk). 

110 
Lybeck-Sorenson et al.134 tested 35 well nourished Latin American malabsorbers with 250 ml 

or 500 ml of lactose-containing and a low lactose milk from which 86 percent of the lactose had 

been removed. The products were said to be similar in taste and consistency. Doses of lactose fed 

(with a light breakfast) were 1.6 grams (250 ml, lactose- reduced milk), 3.2 grams (500 ml, lactose 

reduced milk), 11.3 grams (250 ml milk), 22.5 grams (500 ml milk), and 50 grams (lactose 

tolerance test). The respective median symptom scores for these lactose loads were 0.3, 0.2, 0.5, 

1.1, and 6.1, with a maximal score of 12. No significant increase in symptoms was noted between 

conventional and low lactose milk at the 250 ml dosage, while a significant increase was noted 

with the 500 ml dosage, although symptoms tended to be slight (score 1.1 out of 12). When the 

lactose dosage was increased to 50 grams (1,000 ml of milk), symptoms became appreciable (score 

6.1 out of 12), although there was no control for this phase of the study. This study demonstrates 

that 11.3 grams of lactose was tolerated, 22.5 grams yielded mild symptoms, and 50 grams was 

clearly intolerable. 

Lisker et al.129 studied 97 lactose malabsorbing, healthy adult Mexican subjects. The subjects 

received 250 ml of milks containing 0 grams, 12.5 grams, and 37.5 grams of lactose, with taste 

difference disguised with chocolate. Compared to the lactose free preparation, the 12.5 gram dose 

induced a highly significant increase in symptoms (16 percent were severe) and the 37.5 gram dose 

resulted in very severe symptoms in 71 percent of subjects. This is the only study using multiple 

dosages of lactose in which appreciable symptoms were observed with 12 grams of lactose. 

Vesa et al.112 tested 39 lactose malabsorbers with 250 ml of lactose free milk to which lactose 

was added in quantities of 0, 0.5, 1.5, and 7 grams. Symptoms were not significantly different for 

the various doses, showing that malabsorbers can tolerate small amounts of lactose (7 grams), such 

as might be used in coffee or cereal. 

The above studies involving the feeding of incremental dosages of lactose to determine the 

amount of lactose tolerated by lactose intolerant subjects were all carried out with adult subjects, 

and no data were provided to correlate tolerance with age or ethnicity. All but one of the studies 

assessed tolerance to a single dose of lactose (frequently without food) and thus provided no data 

on the daily dosage of lactose that might be tolerated, assuming tolerance is improved if lactose 

intake is distributed throughout the day with meals. The one study that investigated symptoms 

when lactose was ingested for 1 week with each of the three meals showed that up to 70 grams of 

lactose/day could be tolerated without appreciable symptoms.118 The results of single feeding 

studies generally demonstrated that a 12 gram dose of lactose (one cup of milk) produces 

negligible symptoms with intolerance occurring at dosage ranging between 20 and 50 grams of 

lactose. 

Studies Comparing Symptoms Resulting from the Ingestion of One 

Dosage of Lactose Versus that of a Lactose Reduced or Lactose Free 

Treatment 

Adult and adolescent studies: Evaluating daily dosage of approximately 12 grams of 

lactose (250 ml of milk). Suarez et al.113 recruited 30 subjects who self reported extreme 

intolerance to milk. Nine of these subjects were demonstrated to be lactose absorbers via breath 

testing. This finding, which was observed in other studies, demonstrates the tendency of subjects 

to misdiagnose themselves as lactose intolerant. For 1-week periods, the lactose malabsorbers 

ingested 250 ml/day of conventional milk with their usual breakfast and during another week they 

receive 250/ml of lactose hydrolyzed milk, the taste difference masked with an artificial sweetener. 

111 
There were no statistically significant differences in symptoms (gas, flatulence, abdominal 

discomfort, bloating) between the two testing periods. A surprising finding of this study was that 

symptoms were trivial during both testing periods, despite the pre-study perception of the subjects 

that lactose induced severe symptoms. 

The finding of negligible symptoms with 12 grams of lactose was also observed by Rorick et 

al.116 in a study of 87 healthy elderly subjects (mean age 77). Either 240 ml of milk or 240 ml of 

lactose free milk (taste disguised with chocolate) was fed to 64 lactose absorbers and 23 lactose 

malabsorbers without food. The percentage of subjects with symptoms was similar (about 70 

percent) for the absorbers and the malabsorbers. The percentage of subjects reporting symptoms to 

lactose-containing but not lactose-free milk (i.e., “lactose intolerance”) was actually higher for the 

lactose absorbers versus the malabsorbers. 

 Paige et al.135 studied 22 African American adolescent malabsorbers. Subjects received three 

240 ml treatments: whole milk (12 grams of lactose), 50 percent lactose hydrolyzed milk (6 grams 

of lactose), and 90 percent lactose hydrolyzed milk (1.2 grams of lactose). Symptoms were 

reported by 3/22 subjects after ingestion of conventional milk, but two of these three subjects also 

had symptoms after ingestion of the 90 percent hydrolyzed milk. Thus, 1/22 subjects may have had 

symptoms attributable to LI. 

In contrast, several groups have reported appreciable symptoms after ingestion of 

approximately 12 grams of lactose. Johnson, et al.114 fed 315 ml of milk (about 15 grams of 

lactose) or lactose free milk (taste difference disguised with artificial sweetener) to 45 lactose 

malabsorbing, young adult African Americans. Symptoms were reported by 100 percent of 

subjects with the lactose containing milk; however, 33 percent had symptoms with lactose free 

milk as well. Thus, 67 percent of this group of African American subjects appeared to have 

symptoms attributable to lactose, although the severity of symptoms was not studied. Brand et 

al.115 compared the symptomatic response of six lactose absorbers to conventional milk with that 

of lactose reduced milk with no blinding for taste differences. Five subjects had at least one 

symptom of flatulence, diarrhea, or cramps with conventional milks, whereas no subjects reported 

symptoms with 95 percent hydrolyzed milk. Symptom severity was recorded but not presented, 

other than that mild to moderate diarrhea was reported by three of the six subjects. Reasoner et 

al.125 studied nine milk intolerant individuals (defined as responding to a 50 gram lactose challenge 

with a positive breath test and appreciable symptoms). While multiple milks were tested, the three 

types pertinent to this study were conventional skim milk, conventional skim milk with added 

glucose (0.2 percent), and low lactose milk (approximately 80 percent lactose hydrolyzed). Taste 

differences were not disguised. The average scores for pain and gas were statistically significantly 

higher (“moderate”) for untreated skim milk versus the lactose hydrolyzed milk where symptoms 

were slight. No significant difference was observed for flatulence. Of interest, symptoms with the 

skim milk containing 0.2 percent glucose, added to simulate the taste of the hydrolyzed milk, 

induced less symptoms than did the skim milk. Although not analyzed statistically, differences 

between this milk and lactose hydrolyzed milk appeared to be insignificant. 

Daily dosage of 18 to 25 grams of lactose (350 ml to 500 ml of milk). Suarez et al.111 studied 

the symptoms of 32 lactose malabsorbers when they ingested 240 ml of milk or lactose free milk 

with breakfast and dinner for 1-week periods (24 grams of lactose daily x 7 days with lactosecontaining milk). Differences in milk flavors were disguised with artificial sweetener. While each 

of the symptoms was scored higher during the lactose ingestion period, none of the difference 

reached statistical significance. Mean symptom scores for gas, bloating, abdominal pain, and 

diarrhea were trivial with both types of milk. Of interest, symptoms during both the 24 gram 

112 
lactose and the zero lactose test periods were significantly higher if, prior to testing, the subjects 

deemed themselves to be lactose intolerant. 

Vesa et al.132 studied 30 Estonian malabsorbers. Subjects ingested 200 ml of conventional or 

lactose free milk twice daily (with breakfast and before lunch) for 2-day test periods (about 20 

grams of lactose daily). No significant differences in symptoms were observed between the periods 

when subjects ingested lactose-containing versus lactose free milk. 

Lin et al.117 fed 400 ml of milk (20 grams of lactose) to 20 healthy malabsorbers with a placebo 

or one of four different commercial beta-galactosidase preparations. The numerical ratings of 

symptoms of gas, “stomach” pain, and diarrhea were significantly less when each of the betagalactosidase preparations was ingested with milk compared to milk ingested with placebo. 

However, the symptoms seemingly were relatively minor with a severity score, out of a maximum 

of 40, being 7.85 for gas and only 1.55 and 1.20 for “stomach pain” and diarrhea, respectively. 

 Montalto et al.108 studied 30 lactose malabsorbers who ingested 400 ml of milk (about 20 

grams of lactose). The treatments consisted of conventional milk, milk pretreated with lactase, and 

milk taken 5 minutes after ingestion of a commercial beta-galactosidase preparation. The 

treatments were not blinded. Symptoms were significantly (p<0.001) higher for tests in which the 

milk was ingested without pretreatment with lactase. The mean overall symptom severity score 

when conventional milk was ingested without lactase was about 4, apparently out of a maximum 

of 12. 

Rosado et al.133 studied 25 Mexican malabsorbers who ingested 360 ml of milk (18 grams of 

lactose) with and without pretreatment of the milk with a commercial beta-galactosidase. The 

study was not blinded. Symptoms were observed in 12 of 25 subjects with untreated milk and four 

of 12 with enzyme treated milk, and the median symptom grade in the 12 subjects ingesting 

untreated milk was “major.” A sizable reduction (p<0.01, paired t test) was observed in severity 

score with beta-galactosidase treated milk. 

Rask Pedersen et al.124 studied 11 Danes with lactose malabsorption. Subjects received 500 ml 

of milk (25 grams of lactose) or lactose hydrolyzed milk without other food, apparently with no 

blinding for taste differences. Symptoms of diarrhea and flatulence were severe in 5/12 with milk 

and only 1/12 with lactose hydrolyzed milk, and statistical analysis showed the reduction in 

symptoms was significant (p<0.02). 

Summary of results with 18-25 grams of lactose. The results of studies performed with 18 to 

25 grams of lactose ranged from excellent tolerance by malabsorbers111,132 to a high frequency of 

appreciable intolerance symptoms.108,124,133 The two studies111,132 in which tolerance was observed 

supplied lactose in divided doses with meals, while studies that showed appreciable intolerance 

supplied lactose as a single dose without food. These few observations suggest that a daily dose of 

18 to 25 grams of lactose may be tolerable to lactose malabsorbers if lactose intake is distributed 

throughout the day with meals. 

Lactose dosage greater than 25 grams/day. Suarez et al110 enrolled 62 women, 31 lactose 

absorbers and 31 lactose malabsorbers, in a study to determine the tolerance to a diet that supplied 

1,300 mg of calcium per day in the form of dairy products. To this end, for 1-week periods, each 

day the subjects ingested 480 ml of milk (240 ml at breakfast, 240 ml at dinner), 240 ml of yogurt 

at lunch, and 56 grams of hard cheese. One week the subjects ingested conventional products that 

had a total lactose content of 34 grams, and in another week the lactose in the milk and yogurt 

prehydrolyzed via treatment with beta-galactosidase (this diet contained 2 grams of lactose per 

day). Subjects rated symptoms twice daily on a zero to five scale. Perception of rectal gas, 

frequency of gas passages, bloating, and frequency of bowel movements all were significantly (p 

113 
<0.05) greater when the lactose malabsorbers ingested the lactose rich diet. However, the mean 

symptom score seldom exceeded “slight.” No significant differences were observed between the 

two treatment weeks by the lactose absorbers. Despite the higher symptom severity scores 

recorded during the high lactose week, when queried as to the week they perceived their symptoms 

were greater, 15 identified the high lactose week, eight the low lactose week, and eight noted no 

difference (p = 0.21). Two-thirds of the malabsorbers felt that the symptoms during the high 

lactose week were less severe than they anticipated. A roughly equal percentage (about 50 percent) 

of lactose absorbers and malabsorbers indicated a willingness to obtain their calcium via the 

lactose rich diet, and conversely about 50 percent in each group indicated that they would prefer to 

obtain their daily calcium requirement via ingestion of calcium tablets. This study suggests that if 

dairy products are supplied as two cups of milk (distributed throughout the day), yogurt, and hard 

cheese, LI is not a major impediment to the daily ingestion of 34 grams of lactose. 

Cheng et al.128 studied 15 Chilean penitentiary inmates who were lactose malabsorbers. For 30 

days the subjects ingested a baseline diet which included 500 ml of low lactose milk taken twice 

daily at 8:30 am and 4:30 pm. On three occasions on weeks 2, 3, and 4 of this regimen, 

conventional milk sweetened with 5 percent sucrose was substituted for the low lactose milk. A 

marked increase in the frequency and severity of abdominal pain, diarrhea, distension, and 

flatulence (p <0.001 for each symptom) was observed on the days that conventional milk was 

substituted for the low lactose milk. No such increase in symptoms was observed in lactose 

absorbers. Although probably not perfectly blinded, this study indicated that in subjects ingesting a 

diet low in lactose, 50 grams of lactose in two divided doses during the day yields severe 

intolerance symptoms. 

Xeno et al.121 dosed lactose malabsorbers with 100 grams of lactose in water, with a placebo or 

tablet, or a tablet containing beta-galactosidase. Symptoms were rated on a zero to four scale. 

While symptoms appeared to be more severe during the placebo phase of the study, no statistical 

analysis of the results was performed. Severe symptoms with the placebo were reported for 

abdominal cramping (3/8), bloating (1/8), flatulence (2/8), and diarrhea (2/8), and 2/8 reported 

vomiting. No severe symptoms were reported when beta-galctosidase was ingested. While the 

marked intolerance to 100 grams of lactose taken as a single dose was not unexpected, this study 

was unique in its use of such a large dose of lactose. 

The studies testing the tolerance of lactose malabsorbing subjects to a single dose of lactose 

yielded discordant results. Multiple studies showed no appreciable increase in symptoms with the 

12 gram dose, while others showed appreciable symptoms. The explanation for this discrepancy is 

not clear. When the dosage of lactose was increased to 18 to 25 grams, once again, the finding of 

intolerance varied between studies. However, the difference in tolerance observed in these studies 

could be explained by the better tolerance of lactose if the ingestion of this sugar was distributed 

throughout the day as opposed to ingestion of lactose as a single dose without food. 

Studies in children. The tolerance of children to a given dose of lactose might differ from that 

of adults because of differing physiology in children and/or the greater dosage/kg of body weight. 

Gremse et al.109 studied the effect of lactose on unexplained abdominal pain in 30 children 

(mean age 11.4 ± 2.5) lactose malabsorbers. The subjects were provided with 250 ml of regular or 

lactose hydrolyzed milk (taste disguised with artificial sweetener) for 2-week periods. Their 

abdominal pain scores increased from 4.1 on lactose free milk to 7.5 on lactose containing milk, a 

difference with a p value of 0. 021. No significant differences were observed for flatulence, 

diarrhea, or bloating. The mean pain score observed with milk (7.5) appeared to be trivial, given a 

maximal possible score of 54. Only 5/30 subjects appear to have had an appreciable increase in 

114 
 

pain with introduction of lactose, and four of these subjects had the highest pain scores on the 

lactose free diet. Thus, the pain of these subjects was aggravated, but not solely caused, by lactose. 

Nielsen et al,123 studied the tolerance of nine lactose malabsorbing children (mean age 10, 

range 9-16) via the feeding of 500 ml of conventional or lactose hydrolyzed milk, with no effort to 

disguise taste differences. Symptoms of abdominal pain, flatulence, and diarrhea were very 

significantly greater after ingestion of the nonhydrolyzed milk. Thus, clear-cut LI to a 25 gram 

dose of lactose was observed in these nine children. On a lactose dosage per kg body weight basis, 

the 25 gram dose to 10 year olds was roughly equivalent to a 50 gram dose for middle age adult 

subjects. 

Summary. 

What amount of daily lactose intake is tolerable in subjects with diagnosed lactose 

intolerance? How does this differ by age and ethnicity? What are the diagnostic standards used? 

A number of problems arose when we attempted to answer these seemingly straightforward 

questions via a review of the existing literature. 

1. Patients enrolled in the studies did not have “diagnosed lactose intolerance.” The standard 

approach to the classification of patients enrolled in studies of intolerance was the 

demonstration via hydrogen breath testing or blood glucose measurements that the subject 

incompletely absorbed a sizable dosage of lactose (30 to 50 grams). While most studies 

recorded symptoms with this dosage of lactose, this information was seldom used in the 

selection of study subjects. Thus, the vast majority of the studies investigated subjects 

with proven LM, not proven LI. 

2. Although very seldom discussed in the literature, tests for LM are not 100 percent 

accurate. Most studies used H2 breath testing to identify lactose malabsorbers. It is known 

that this test has an appreciable, but not well defined, false negative rate, i.e., subjects with 

LM do not generate a diagnostic rise in breath H2. The incidence of false positives, i.e., 

production of the H2 in the small bowel with complete absorption of lactose, is not known. 

Thus, some patients were incorrectly classified as lactose malabsorbers or absorbers. 

3. The taste of conventional milk and lactose hydrolyzed milk differ. Many studies did not 

disguise this taste difference. 

4. Lactose was administered in a variety of ways in the intolerance tests. Most studies fed 

lactose in water or milk as a single does in the fasting state upon arising in the morning. 

The daily tolerable dose of lactose appears to be greater if lactose intake is distributed 

throughout the day and taken with meals. 

5. The response to lactose is primarily subjective symptoms – i.e., abdominal discomfort, 

gas, bloating – the severity of which the subjects rated on numerical scales. The finding of 

a statistically significant increase in symptoms with the lactose containing product versus 

the low lactase product was considered to provide evidence of intolerance. However, the 

biological significance of changes in numerical rating seldom was investigated. Only one 

study attempted to evaluate the association between the symptom score and the global 

assessment of symptom severity. In this study, the majority of a group of subjects who had 

a significant increase in symptom score when high and low lactose test periods were 

compared did not clearly identify the high lactose period as being particularly 

symptomatic. 

6. Some data supports the belief that the routine ingestion of lactose increases the quantity of 

lactose that is tolerable. Very few studies provided data on lactose ingestion by subjects 

prior to enrollment in controlled trials. 

115 
With the above problems in mind, the literature on this question can be summarized as follows: 

As shown in Figure 12, the majority of studies indicate that subjects with “lactose intolerance” can 

ingest 12 grams of lactose as a single dose (particularly if taken with food) with no or minor 

symptoms. In contrast, when lactose/milk is administered as a single test dose without other 

nutrients, dosages of 12 grams may be symptomatic (Figure 13). As the dose is increased above 12 

grams, intolerance becomes more prominent, with single doses of 24 grams usually yielding 

appreciable symptoms. There is some evidence that if 24 grams of lactose are distributed 

throughout the day, many lactose malabsorbers will tolerate this dosage. Lactose in a dose of 50 

grams induces symptoms in the vast majority of subjects. While the literature is laden with studies 

of the relationship of ethnicity to lactose malabsorption, no studies made it possible to determine if 

lactose malabsorbers of differing ethnicities have differing tolerance to lactose. Likewise, there 

was no data on the relationship of age or sex to the quantity of lactose that can be tolerated by 

lactose intolerant subjects. 

116 
117 

Figure 12. Symptomatic response# of adult lactose malabsorbers to lactose ingested with nutrients other than milk 

Publication Cheng, 1979128 (n=15)* ++ 

Suarez, 1998110 (n=31) + 

Vesa, 1997132 (n=30) -

Jones, 1976130 (n=16) - - ++ 

Rorick, 1979116 (n=23) -

Suarez, 1997111 (n=19) -

Suarez, 1995113 (n=21) -Newcomer, 1978120 (n=59) - - - - - - ++ 

Hertzler, 1996118 (n=18) - - - - -

Daily lactose (grams) 0 3 6 7 9 12 15 18 22 30 34 42 49 50 55 63 70 

# Symptoms indicated by: - no or trivial symptoms; + minor symptoms; ++ severe symptoms 

* n indicates number of lactose malabsorbing subjects studied Figure 13. Symptomatic response# of adult lactose malabsorbers to lactose ingested without nutrients other than milk 

Publication Rosado, 1984133 (n=25)* + 
 Kwon, 1980127 (n=45) - + 

Cavalli-Sforza, 1987122 (n=40) ± ± + 
 Reasoner, 1981125 (n=9) Rask Pedersen, 1982124 (n=17) + 
 Lybeck Sorensen, 1983134 (n=35) - - - - + 

Johnson, 1993114 (n=45) + 
 Jones, 1976130 (n=17) - + Xenos, 1998121 (n=8) 

Montalto, 2005108 (n=20) ++ 
 Hertzler, 1996118 (n=13) - - - ++ 
 Stephenson, 1974131 (n-19) - Brand, 1991115 (n=26) + 
 Daily lactose (grams) 0 2 3 6 8 10 12 13 14 15 16 17 19 20 23 24 25 29 

# Symptoms indicated by: - no or trivial symptoms; + minor symptoms; ++ severe symptoms 

* n indicates number of lactose malabsorbing subjects studied 
 

Key Question 4. What strategies are effective in managing 

individuals with diagnosed lactose intolerance? 

The details of our search strategy are presented in the methods section and in Figure 2. A total 

of 37 unique randomized studies (26 on lactase/lactose hydrolyzed milk supplements, lactose 

reduced milk, eight on probiotics, two on incremental lactose dose for colonic adaptation, and one 

on other agents) met inclusion criteria.108-147 The quality of the studies was low, with almost no 

study reporting adequate allocation concealment. Generally, studies had small sample sizes and 

reporting of symptoms was variable or not reported: composite scores of four to five symptoms or 

individual symptoms such as abdominal pain, diarrhea, bloating, and flatulence were reported, 

either as means or proportion. Many studies enrolled individuals who did not have a prior 

diagnosis of LI or did not have a prior history of LI like symptoms. 

We focused our results on strategies grouped in the following categories, discussed below: 

• Commercially available lactase/lactose hydrolyzed milk or nonlactose solutions and other 

dietary strategies 

• Prebiotics and probiotics 

• Incremental lactose for colonic adaptation 

• Other strategies 

Commercially Available Lactase/Lactose Hydrolyzed Milk, or 

Nonlactose Solutions 

 Characteristics of included studies. There was one study representing two trials that tested 

lactase supplements Lactodigest, DairyEase, and Lactaid,136 while the remaining 25 studies 

reported on lactose reduced or hydrolyzed milk by adding a lactase enzyme such as betagalactosidase to the milk. Studies enrolled between six and 150 subjects. Women constituted 56 

percent of the subjects (n=23 studies). The mean age of subjects was 37 years of age, with a range 

between 10 and 77 (n=19 studies). Six trials included children or adolescents.109,114,123,126,127,135 

One trial enrolled elderly subjects (mean age 77 years).116 Within the 19 studies reporting race or 

ethnicity, 40 percent of subjects were white, 30 percent Hispanic, 20 percent black, and 9 percent 

Asian.109-116,123,126-130,133-135,137 Nineteen studies utilized commercial lactase products or hydrolyzed 

milk,108-111,113-115,121-125,128,133,135,136 two used milk products with lactose removed by ultrafiltration 

or chromatographically,112,134 and five assessed nonlactose solutions.116,126,127,137,138 Unclear or 

unreported methods of lactose removal were noted in two trials129,132 Subjects in 18 studies 

reported abdominal symptoms compatible with malabsorption of lactose prior to study entry.108­

114,121,123-125,128,130,132,134,136-138 Abdominal symptoms were not required for study participation 

(based solely on biochemical diagnosis) or subjects were not reported to experience symptoms 

following ingestion of lactose in ten studies.115,116,122,126,127,129,130,133,135,136 LM was diagnosed 

following lactose tolerance tests by the hydrogen breath test in 11 of the studies108-116,136 and blood 

glucose test in 13 studies121-130,137,138 Diagnosis based on urinary galactose concentration was 

reported in one study132 and biochemical method of diagnosis was not reported in three trials.133-135 

Over half of the trials included lactose digesting controls.110-113,116,122,125-129,133,135,137 

Among the 18 studies that enrolled symptomatic subjects at baseline, 13 utilized lactose doses 

greater than 12 grams, comparable to one cup of milk.108,110,111,114,121,123-125,128,130,132,134,136,137 

118 
Hydrolyzed lactose doses typically ranged from zero to two grams per dose. In most of the studies, 

the lactose dose was consumed in a single serving. In six trials, the lactose dose was administered 

over multiple intervals per day for at least part of the study.110,111,122,125,128,132 

Results. We found insufficient evidence that lactose reduced solution/milk, with lactose 

content of 0-2 grams, is effective in reducing symptoms among individuals with LI. Seven studies, 

representing nine comparisons that enrolled individuals who had symptoms compatible with LI 

reported inconsistent results that lactose reduced preparations reduced overall symptom scores 

compared to controls. None of the four studies reported a significant improvement in overall 

symptoms compared to control preparations of up to 12 grams of lactose. However, as noted in key 

question 3, doses of 12 grams of lactose or less are well tolerated and produce minimal to no 

symptoms. When compared to controls given greater than 12 grams of lactose, only two out of five 

trials reported statistically significant reductions in overall symptoms with lactose reduced/ 

hydrolyzed milk. Results for individual symptoms of abdominal pain, diarrhea, flatulence, and 

bloating were also inconsistent. 

For all included studies, regardless of symptom history, information from 16 (19 comparisons), 

mostly low quality, trials was insufficient to determine the effect of hydrolyzed milk, lactase, or 

non lactose preparations in reducing GI symptoms compared to lactose controls. Some studies did 

report substantial reductions (improvement from moderate and severe to mild or none, or an 

absolute reduction of at least 50 percent) in abdominal pain/cramping109,112,123,125,134 and diarrhea136 

with use of lactose reduced solution/milk, with lactose content of 0-2 grams, compared to a lactose 

dose of 12 grams or more. However, even in studies where symptoms were reduced, statistically 

significant reductions were not consistently observed among all symptoms reported, or only a 

subset of symptoms was reported. For example, the overall symptom score was significantly 

reduced by 60 percent with 591 milliliters of lactose reduced milk containing 7.5 grams of lactose 

compared to a similar amount of milk with 30 grams of lactose,130 and by 13 percent with low 

lactose skim milk with 0.8-6.5 grams of lactose compared to skim milk with 6.1-49 grams of 

lactose,122 but the subjects in both studies were not symptomatic at enrollment, and improvement 

in individual symptoms was not provided. Mean and total symptom scores were also reduced, from 

3.7 to 0.36 with 70 percent hydrolyzed milk compared to placebo with 20 grams of lactose,108 but 

subjects were also not symptomatic at enrollment, and improvement in individual symptoms was 

not provided. One study reported a score of 46 for skim milk with 11.3 grams of lactose which was 

reduced to a score of 17 with low lactose milk with 3.2 grams of lactose, but the difference was not 

statistically significant.134 Similar reductions were seen in summed scores for abdominal pain from 

43 with milk containing 25 grams of lactose to one with lactose hydrolyzed milk containing 1.25 

grams of lactose123 and a mean score for abdominal pain from 7.5 with milk containing 12 grams 

of lactose to 4.1 with milk containing lactase,109 both in children. Again, neither study required 

subjects to be symptomatic at baseline. One study showed a statistically significant reduction in 

abdominal pain from moderate to none or mild with low lactose milk containing 2.9 grams of 

lactose compared to skim milk containing 28.5 grams of lactose.125 One trial found a significantly 

greater percentage of subjects reporting abdominal pain and bloating compared to the 0.5 grams 

and 1.5 grams doses, respectively.112 Compared to placebo, use of lactase supplement Lactodigest, 

DairyEase, or Lactaid in doses of two to four capsules/tablets when taken with 400 ml of 2 percent 

milk containing 20 grams of lactose reduced overall symptom scores in subjects not symptomatic 

at enrollment. Of greater clinical relevance to management of patients with symptoms compatible 

with LI who wish to consume doses of lactose beyond the minimally tolerable dose, these products 

were found not to reduce symptoms when administered with a dose of 50 grams of lactose in 

119 
subjects who had symptoms compatible with LI.136 Generally, studies had small sample sizes and 

reporting of symptoms was variable: composite scores of four to five symptoms or individual 

symptoms such as abdominal pain, diarrhea, bloating, and flatulence were reported, either as 

means or proportion, making pooling estimates difficult. 

Prebiotics and Probiotics 

 Characteristics of included studies. Eight randomized trials were included; (Appendix Table 

D9) seven crossover117,139-141,143-145 and one parallel group design.142 The trials were generally 

small, enrolling between nine and 28 subjects (Table 18). Among the five studies reporting gender, 

women constituted 34 percent of the subjects.139-143 Two studies enrolled only male subjects.142,143 

Subjects were typically young to middle-aged adults (between 18 and 45 years old), and only one 

study enrolled subjects older than 60 years of age.144 Half of the studies reported race or ethnicity. 

White subjects comprised two trials,140,141 one study evaluated black African immigrants to 

France,142 and one trial was conducted in Taiwan Chinese.117 Five of the studies were conducted in 

the United States,139,140,143-145 two in France,141,142 and one in Taiwan.117 Five trials assessed 

probiotic test products, prepared by adding strains of lactobacillus acidophilus, lactobacillus 

bulgaricus, or bifidobacterium longum to milk prior to consumption.117,139,140,144,145 Four studies 

evaluated yogurt products.141-143,145 LM was diagnosed by the hydrogen breath test in all studies. 

Results. We found insufficient evidence to determine the effectiveness of yogurt or probiotics 

to improve lactose intolerance symptoms (Table 19). The inclusion criteria and the studied type of 

yogurt and probiotics were variable—results either did not show a difference in symptom score, or 

reported clinically insignificant differences, mostly in the symptoms that are of low clinical 

relevance, such as flatulence. Only one study noted that the enrolled subjects reported symptoms 

compatible with malabsorption of lactose prior to study entry144 and reported no difference in 

symptom score in groups given milk or acidophilus milk (symptom score of 40 in both groups). In 

the remaining studies, study entry was based solely on breath hydrogen tests, and subjects were not 

reported to experience symptoms following ingestion of lactose. Lactose doses in the control tests 

were between 10 and 20 grams. Overall symptom score was reduced from 12.5 with 2 percent milk 

containing 20 grams of lactose to 2.8 with the same milk formulation but with added lactobacillus 

at 109

 cfu/ml.117 Similar improvements were seen with the addition of lactobacillus at 108 cfu/ml 

(overall score 3.9) and lactoacidolphilus at 109

 cfu/ml (overall score 6.5), but not with 

lactoacidolphilus at 108

 cfu/ml. Overall symptom scores improved from fairly strong to mild with 

400 ml of bulgofilus milk (Ofilus bacteria+L. bulgaircus) compared to control (lactulose 10 grams 

in 250 ml water), both with 18 grams of lactose.141 Reductions in other symptoms such as 

abdominal pain and diarrhea were either not reported, not significantly different, or of low clinical 

significance or relevance. The inclusion criteria were variable, the type, source, and concentration 

of yogurt and probiotics studied were variable, and no two studies studied the same agent. Based 

on these findings we found insufficient evidence for the use of yogurt or probiotics for lactose 

intolerance. 

Incremental Lactose for Colonic Adaptation 

We found insufficient evidence to support the role of incremental doses of lactose for lactose 

intolerance symptoms (Table 19). Two studies met our inclusion criteria.118,146 In the first one, 20 

healthy volunteers with LM on hydrogen breath testing were randomized to receive either dextrose 

120 
or lactose in a blinded fashion for 10 days and crossed over for days 12 through 21. The dose of 

lactose and dextrose was 0.6 grams/kg body weight per day, increased by 0.2 grams/kg/day to a 

maximum of 1 gram/kg/day (approximately 42 to 70 grams of lactose per day for an average 70 kg 

adult). Subjects were also given lactose challenge doses of 0.35 grams/kg on days 11 and 22. The 

authors found that symptoms of flatulence after the lactose challenge decreased by 50 percent after 

lactose feeding compared to dextrose feeding, while symptoms of abdominal pain and diarrhea did 

not differ. These results suggest that colonic adaptation may occur, but there is no appreciable 

decrease in clinically relevant symptoms of abdominal pain and diarrhea. Though subjects were 

lactose malabsorbers at baseline, average symptom scores were 1 (scale 0-5) even with the highest 

doses of lactose (70 grams), and very similar to scores were seen with sucrose. The second study 

evaluated colonic adaptation to lactose compared to sucrose in a double blinded fashion. The study 

enrolled 46 healthy volunteers in France, 21 males, 25 females, all of Asian origin, with a mean 

age of 33 (range 20-47 years) that were lactose malabsorbing by hydrogen breath testing. Subjects 

were fed their regular diet and underwent hydrogen breath testing and symptom evaluation on days 

1 and 14. For the 13 days in between, subjects were fed either 34grams of lactose or sucrose in a 

double blind fashion. The overall clinical score improved from 42 to 20 in the group randomized 

to lactose, as did the individual mean scores for pain, flatulence, bloating and borborygmi, but 

similar improvements were seen with sucrose (overall score improvement from 42 to 24), 

suggesting a placebo response. 

Other Strategies 

We found insufficient evidence regarding rifaximin for treatment of lactose intolerance. A 

single small study met inclusion criteria147 and showed reduction in symptom score after rifaximin 

treatment compared to placebo and similar to a lactose free control. The study enrolled 40 patients 

with lactose malabsorption on hydrogen breath test, 16 were randomized to 10-day treatment with 

rifaximin 800 mg/day, 16 to a 40-day lactose free diet, while eight were given 10 days of placebo. 

On a scale of 0-4, compared to baseline, there was reduced abdominal pain (2.0 versus 1.0), 

diarrhea (1.3 versus 0.2), bloating (2.5 versus 1.6), and distention (2.4 versus 1.5) at day 40 for the 

rifaximin group. Similar decreases were seen for the lactose free group. The clinical significance 

of the change in score is not clear. 

Studies on Management Strategies in Subjects with IBS and LM/LI 

We found insufficient evidence that low lactose diet or probiotics were effective in reducing 

symptoms of lactose intolerance among subjects with IBS and LM/LI. Four small, double blinded, 

trials assessed management strategies in subjects with IBS and LI/LM with conflicting 

results.144,175-177 A British study of 23 IBS subjects identified with lactose malabsorption based on 

the hydrogen breath test found patients with LI were not distinguishable from other IBS subjects 

based on GI symptoms, and treatment with a low lactose diet led to disappointing results.175 They 

concluded there was no real advantage to segregating IBS subjects with LI from other IBS 

subjects. In contrast, a Dutch study investigating the prevalence of lactose malabsorption in 70 IBS 

patients found statistically significant improvement in GI symptoms in 17 IBS subjects identified 

to have LM following 6 weeks of treatment with a low lactose diet.176 They concluded that LM 

should be excluded prior to a diagnosis of IBS. A Mexican study of 12 IBS subjects, eight of 

whom were noted to be lactase nonpersistent, found that IBS symptoms appeared to be 

121 
independent of LM following 3 months of treatment with hydrolyzed milk or placebo.177 An 

American study by Newcomer assessed whether unfermented acidophilus milk was beneficial in 

relieving symptoms in subjects with lactase deficiency or IBS.144 Sixty one subjects with IBS who 

were lactase sufficient and 18 lactase deficient (based on the hydrogen breath test) subjects each 

received lactobacillus acidophilus milk or regular milk for 2 week intervals each. Within the 

lactase deficient group, symptoms were not significantly reduced during the acidophilus milk 

period compared to the regular milk period. In subjects with IBS, acidophilus milk did not relieve 

their symptoms. These studies are summarized in Table 19, section F. 

122 
Vesa (n=30) 

Chen (n=15) 

Jarvine

n (n=27 

Jarvine

n (n=27) 

Vesa (n=39) 

Vesa (n=39) 

Vesa (n=39) 

U

nger (n=24) 

Brand (n=6) 

Brand (n=6) 

Brand (n=6) 

Vesa (n=39) 

Rask-P (n=11) 

Brand (n=6) 

Brand (n=6) 

Jarvinen (n=27) 

Jarvine

n (n=27) 

Unger (n=24) 

Vesa (n=30) 

Vesa (n=30) 

Rask-P (n=11) 

Chen (n=15) 

0 

10 

20 

30 

40 

50 

60 

70 

80 

90 

100 

0-2 g 

>2-7 g 

~12 g 

~20 g 

Lactose 

Content 

Figure 14. Percentage of subjects reporting abdominal pain 

123 
0 

1 

2 

3 

4 

5 

0-3 g 

~12 g 

~25 g 

> 25 g 

Lactose 

content 

Saurez 1998Saurez 1997Saurez 1995Jarvinen 0gJarvinen 2 gReasonerLin1 Lactogest x 2Lin 1 Lactogest x 4Lin 1 DairyEaseLin 1 LactaidSaurez 1995Jarvinen (powder milk)Jarvinen (whole milk)Saurez 1997Saurez 1998Reasoner (Skim milk)Reasoner (SM+glucose)Reasoner (acidoph milk) 

Figure 15. Abdominal pain based on symptom scores (0 = none, 1 = mild, 3 = moderate, 5 = severe) 

124 
Table 18. Summary of study characteristics for blinded LI treatment studies 

Range Number of Characteristic (Number of Subjects, Studies Reporting Percent, or Mean) 

A. Commercially-available lactase/lactose hydrolyzed milk, or nonlactose solutions 

Total number of studies 6 to 150 28 (26 publications) 

Studies with lactose tolerant controls (number of controls) 5 to 64 14 

Studies in which subjects were not noted to be symptomatic at baseline 6 to 150 10 

or symptoms were not required for study inclusion or unclear 

Studies with children (range) 9 to 150 6 (4 exclusive) 

Mean age (range) 37 (10 to 77) 19 

Gender, female – mean % (range) 56 (0 to 93) 23 

Race/ethnicity, White - mean % (range) 40 (0 to 100) 19 (1 exclusive) 

Race/ethnicity, Hispanic* - mean % (range) 30 (0 to 100) 19 (3 exclusive) 

Race/ethnicity, Black - mean % (range) 20 (0 to 100) 19 (2 exclusive) 

Race/ethnicity, Asian - mean % (range) 9 (0 to 100) 19 (1 exclusive) 

Studies conducted in the United States 11 to 110 15 

Diagnosis, hydrogen breath test 11 studies 

Diagnosis, blood sugar test 13 studies 

Diagnosis, urinary galactose test 1 study 

Noted as “double-blind” studies (some studies noted that it may not be 24 studies 

possible mask flavors of tests) 

Single blind studies 4 studies 

Multi-dose studies (test products administered more than one time/day) 6 studies 

B. Prebiotic/probiotic studies 

Total number of studies 9 to 28 8 

Studies with lactose tolerant controls (number of controls) 10 1 

Studies in which subjects were not noted to be symptomatic at 9 to 28 7 

baseline or symptoms were not required for study inclusion 

Age range of subjects 18 to 69 7 

Gender, female - mean % (range) 34 (0 to 73) 5 

(2 exclusively male) 

Race/ethnicity, White - mean % (range) 45 (0 to 100) 4 (2 exclusive) 

Race/ethnicity, black - mean % (range) 24 (0 to 100) 4 (1 exclusive) 

Race/ethnicity, Asian - mean % (range) 30 (0 to 100) 4 (1 exclusive) 

Number of studies conducted in the United States 9 to 28 5 

Diagnosis, hydrogen breath test All studies 

Noted as “double blind” studies (some studies noted that it may not be 5 studies 

possible to mask flavors of tests) 

Single blind or blinding unclear studies 3 studies 

D and E. Colonic adaptation and incremental lactose load studies/studies with different levels of lactose 

Total number of studies 13 to 59 4 

Studies with lactose tolerant controls (number of controls) 19 1 

Studies in which subjects were not noted to be symptomatic at All studies 

baseline or symptoms were not required for study inclusion 

Age range of subjects 23 (19 to 32) 3 

Gender, female - mean % (range) 46 (25 to 54) 4 

Race/ethnicity, Non-white - mean % (range) 51 (29 to 90) 2 

Asian 70% in one trial 

Race/ethnicity, White - mean % (range) 49 (10 to 71) 2 

American Indian 59 (1 exclusive) 

Number of studies conducted in the United States All studies 

Diagnosis, hydrogen breath test 3 studies 

Diagnosis, blood sugar test 1 study 

Noted as “double blind” studies (some studies noted that it may not be 2 studies 

possible to mask flavors of tests) 

Single blind or blinding unclear studies 2 studies 

*Subjects could be of any race 

125 
Table 19. Occurrence of GI symptoms in randomized trials 

I. Studies that reported subjects with symptoms at baseline in addition to LI by biochemical testing 

126 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content / Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

A. Commercially-available lactase/lactose hydrolyzed milk, or nonlactose solutions A1. Studies with doses of lactose >12 g per dose/test Montalto, 2005108 Mean clinical score (± SD) based on symptoms: 0=absent to 3=severe for bloating, 

(n=30) flatulence, diarrhea for each during test Test A –enzyme (3,000 UI), ≥70% 0.36 ± 0.55 Not NR NR NR 

added 10 hours prior to hydrolyzed p<0.001 vs. Reported 

consumption pbo (NR) 

p=0.03 vs. TB 

Test B-enzyme (6,000 UI) ≥70% 0.96 ± 0.85 NR NR NR NR 

(TB), add 5 minutes prior hydrolyzed p<0.001 vs. 

pbo 

Placebo (pbo) Saurez, 1998110 

Maldigesters (n=31) 

20 g 3.77 ± 0.79 NR NR NR NR 

Average daily severity of symptoms, (Mean ± SEM), ranked on a continuous scale f5=severe symptoms. Frequency “f” (episodes per day) reported for flatus and diar

Baseline NR NR 0.2 ± 0.1 0.4 ± 0.1 0.5 ± 0.1 

10.6 ± 2.0 f 

Lactose hydrolyzed products 2 g NR NR 0.5 ± 0.2 1.0 ± 0.3 0.8 ± 0.2 

(LH) 10.7 ± 1.3 f Conventional dairy products 34 g NR NR 0.5 ± 0.2 1.1 ± 0.2 1.3 ± 0.2 

p<0.05 vs. LH 

17.1 ± 2.1 f 

p<0.05 vs. LH 

Digesters (n=31) Baseline NR NR 0.1 ± 0.03 0.3 ± 0.1 0.4 ± 0.1 

13.7 ± 1.9 f 

Lactose hydrolyzed products 2 g NR NR 0.1 ± 0.05 0.3 ± 0.1 0.4 ± 0.1 

12.8 ± 1.5 f 

Conventional dairy products 34 g NR NR 0.1 ± 0.04 0.3 ± 0.1 0.4 ± 0.1 

14.7 ± 1.9 f 

Xenos, 1998121 

(n=8) 

Subjects reporting symptoms based on ratings (0=none to 4=severe) after consumover 24 hours 

β-D-galactosidase 100 u/ml + - NR NR 1: 1 subject 1: 3 1: 2 

100 g lactose dissolved in 2: 1 2: 2 2: 1 

water 3: 1 

Placebo + 100 g lactose 100 g NR NR 1: 1 1: 1 2: 2 

dissolved in water 2: 1 2: 2 3: 4 

3: 1 3: 1 4: 2 4: 3 4: 1 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

127 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content / Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Saurez, 1997111 Mean symptom severity scores (± SEM) ranked scale on a scale as follows: 0=none

Lactase-nonpersistent, described as 3=moderate; 4=strong; 5= severe. Data were extracted from graph. Frequency “f” (

severely LI (n=19) for flatus and diarrhea) Lactose hydrolyzed milk 0 g NR NR ~ 0.12 ± 0.05 ~ 0.14 ± 0.05 ~ 0.78 ± 0.1 ~ 0.

~9.8 ± 1.4 f 

Milk 23.6 g NR NR ~ 0.32 ± 0.1 ~ 0.27 ± 0.09 ~ 1 ± 0.1 ~ 0

~14.4 ± 2 f 

Lactase-nonpersistent who denied LI (n=13)
 

Lactose hydrolyzed milk 0 g NR NR ~ 0.05 ± 0.01 ~ 0.05 ± ~ 0.3 ± 0.09 ~ 0.

0.002 ~5.7 ± 1.9 f 

Milk 23.6 g NR NR ~ 0.09 ± 0.09 ~ 0.23 ± 0.1 ~ 0.57 ± 0.09 ~ 0.

~8 ± 1.3 f 

Vesa, 1997132 Percentage of subjects who experienced symptoms after consumption of each lac

(n=30) Lactose-free, fat-free milk 0 g NR NR 37 40 63 

Fat-free milk 19.6 g NR NR 38 45 79 

x 2 days p<0.05 vs. p<0.01 vs. 

MFP MFP 

High-fat milk 19.6 g NR NR 33 33 70 

x 2 days p<0.05 vs. 

MFP 

Milk-free period (MFP) - NR NR 27 19 41 

Johnson, 1993114 Presence of symptoms (abdominal fullness, cramps, flatulence, borborygmi, nause

(n=45) consistent with LM Lactose hydrolyzed milk 0 g NR 15 (33%) NR NR NR 

Milk 16.4 g NR 30 (67%) NR NR NR 

only milk 

15 (33%) 

both 

Lin, Study 2, 1993136 Symptom scores are expressed as the sum of mean scores rating symptoms from 

(n=11) experienced) at baseline and 4 and 8 hours after challenge L 50 g in water plus - NR NR 2.5 4.4 5.4 

Lactodigest (2 capsules) cL 50 g in water plus - NR NR 3.4 4.6 5.6 DairyEase (2 capsules) cL 50 g in water plus Lactaid (2 - NR NR 3.1 5.2 6.1 capsules) cL 50 g in water plus - NR NR 3.2 4.0 4.7 Lactodigest (4 capsules) c
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content / Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

128 

Lactose (L) 50 g in water 50 g NR NR 3.0 4.1 4.8 

plus placebo Nielsen, 1984123 

(n=9 children) 

c

Summation of observed symptoms from the scoring charts. At 10 times during the 

recorded in the scoring chart to indicate no symptoms and a 1 was recorded if sym

Lactose hydrolyzed milk 1.25 g NR NR 1 NR 15 

(LHM) Milk 25 g NR NR 43 p<0.01 vs. NR 37 37 

LHM 

Cheng, 1979128 

Intolerants n=15 

The incidence and severity of symptoms 

Lactose hydrolyzed skim milk 0.5­

1.25 g 

NR NR 279 none 

9 mild 

2 severe 

251 none 

32 mild 

7 severe 

252 none 

25 mild 

13 severe 

Skim milk 25 g NR NR 12 none 2 none 3 none 

12 mild 2 mild 4 mild 

18 severe 38 severe 35 severe 

Tolerants n=16 Lactose hydrolyzed skim milk 0.5­

1.25 g 

NR NR 324 none 

4 mild 

4 severe 

304 none 

20 mild 

8 severe 

311 none 

12 mild 

9 severe 

Skim milk 25 g NR NR 46 none 40 none 42 none 

1 mild 7 mild 5 mild 

1 severe 1 severe 1 severe 

A2. Studies with doses of lactose ≤12 g per dose/test 

Gremse, 2003109 Severity of each symptom was graded from 0=none to 4=severe. Sum of the individ

(n=30 children) was calculated for each 14-day study and averaged for all patients Järvinen, 2003138 

Milk + lactase - NR NR 4.1 ± 1.4 0.9 ± 0.4 3.3 ± 2.6 

p=0.021 vs. M 

Milk (M) 12 g NR NR 7.5 ± 2.7 1.4 ± 0.7 5.1 ± 2.8 

Subjects reporting symptoms during 8 hours after consuming chocolate samples 

(n=27) Chocolate sample consisting 0 g NR 19 (70%) 8 (30%) 16 (59%) 19 (70%) 9 

of lactose-free milk powder. Chocolate sample consisting 2 g NR 22 (81%) 8 (30%) 17 (63%) 18 (67%) 1

of low-lactose milk powder Chocolate sample consisting 12 g NR 23 (85%) 10 (37%) 19 (70%) 21 (78%) 9 

of whole milk powder Chocolate sample consisting 12 g NR 25 (93%) 10 (37%) 19 (70%) 22 (81%) 1of fresh whole milk p=0.21 across p=0.88 p=0.80 p=0.48 p

groups 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

129 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content / Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Mean (± SD) of the scores given for symptoms. Symptoms were recorded on a queranging from 0 (none) to 10 (very severe, disturbing normal life) once every hour fotwo more times (at 4 – 6 and 7 – 8 hours) until 8 hours had elapsed. 

Chocolate sample consisting 0 g 13.5 (15.8) NA 2.3 ± 5.2 4.6 ± 5.5 4.4 ± 4.6 1

of lactose-free milk powder Sum of all 

symptoms 

Chocolate sample consisting 2 g 16.6 ± 15.8 NA 2.3 ± 4.5 5.6 ± 6.3 5.1 ± 5.8 1

of low-lactose milk powder Chocolate sample consisting 12 g 17.5 ± 18.6 NA 2.9 ± 5.5 5.3 ± 5.7 5.2 ± 5.4 2

of whole milk powder Chocolate sample consisting 12 g 19.5 ± 20.8 NA 3.6 ± 6.6 5.0 ± 5.7 6.0 ± 6.4 3

of fresh whole milk p=0.59 across p=0.85 p=0.93 p=0.75 

groups 

Vesa, 1996112 Percentage of subjects who experienced symptoms after each lactose dose, either 

Maldigesters (n=39) Note: not all subjects consumption of test. Symptom score represents the sum of symptoms, based on 0

reported at the 3 hour period) severe (data were extracted from graph). 

Percentage of subjects who NR NR 14 16 47 reported daily or almost daily symptoms before the study Lactose-free milk 0 g 7.7 ± 2.3 NR 15 (3 h) 22 (3 h) 19 (3 h) 1

33 (1 d) 44 (1 d) 51 (1 d) 1

Lactose free milk plus 0.5 g 0.5 g 5.1 ± 3.7 NR 12 (3 h) 7 (3 h) 19 (3 h) 1lactose 15 (1 d) p<0.05 vs. 0 g 49 (1 d) 2

p<0.05 vs. 0 g 28 (1 d) 

Lactose free milk plus 1.5 g 1.5 g 4.1 ± 4.9 NR 18 (3 h) 19 (3 h) 23 (3 h) 1lactose 24 (1 d) 26 (1 d) 47 (1 d) 1

p<0.05 vs. 0 g 

Lactose free milk plus 7 g 7 g 6.2 ± 4.6 NR 21 (3 h) 26 (3 h) 35 (3 h) 1

lactose 33 (1 d) 38 (1 d) 51 (1 d) 2Digesters (n=15) Percentage of subjects who 

NR 

NR 0 7 27 

reported daily or almost daily symptoms before the studyLactose free milk 0 g 2 ± 1 NR 8 (3 h) 0 both time 0 (3 h) 

13 (1 d) points 40 (1 d) 1

Lactose free milk plus 0.5 g 0.5 g 2.7 ± 1.2 NR 8 (3 h) 0 both time 10 (3 h) 

lactose 13 (1 d) points 47 (1 d) 2Lactose free milk plus 1.5 g 1.5 g 3.8 ± 1.3 NR 0 (3 h) 0 both time 0 (3 h) 

lactose 7 (1 d) points 53 (1 d) 2
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

Number of Lactose Overall Subjects Abdominal Abdominal	 Bo

Study (n) / Interventions Content / Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

130 

Lactose-free milk plus 7 g 7 g 1.1 ± 2 NR 0 (3 h) 0 (3 h) 0 (3 h) 

lactose Saurez, 1995113 

Malabsorbers (n=21) 

7 (1 d) 7 (1 d) 40 (1 d) 

Severity of daily gastrointestinal symptoms over the one week period (mean ± SEM5=severe. Frequency (episodes per day reported for flatus and diarrhea) 

Lactose hydrolyzed low fat <0.5 g NR NR 0.3 ± 0.1 0.5 ± 0.1 0.9 ± 0.1 

milk 7.6 ± 1.2 f Low-fat milk 12.1 g NR NR 0.4 ± 0.1 0.6 ± 0.1 1.1 ± 0.1 

10.1 ± 1.5 f 

Absorbers (n=9) Lactose hydrolyzed low fat <0.5 g NR NR 0.4 ± 0.2 0.5 ± 0.2 1.2 ± 0.2 

milk 8.4 ± 1.9 f 

Low fat milk 12.1 g NR NR 0.6 ± 0.2 0.6 ± 0.2 0.9 ± 0.2 

11.8 ± 2.3 f 

A3. Studies with doses of lactose >12 g and ≤12.5 g per dose/test 

Lybeck Sørensen, 1983134	 Frequency of symptoms in percent following milk ingestion over 8 hours. Symptom

(n=35) accordingly: 0=no symptoms; 1=slight; 2=moderate; 3=severe. The total symptom 

the sum of the score for each person. 

Low lactose milk, 250 ml 1.6 g 26 At least ≥1 moderate or 18 29 18 

Median = 0.47 severe symptom 

6 

Low lactose milk, 500 ml 3.2 g 17 3 14 20 3 

p<0.05 vs. SM p<0.05 vs. SM 500 ml p<0.05 vs. p <0.05 vs. SM p<0

500 ml SM 500 ml 500 ml 

Median = 0.35 

Skim milk (SM), 250 ml 11.3 g 46 9 42 49 12 

Median = 0.67 

Skim milk, 500 ml 22.5 g 46 31 49 51 26 

Median = 1.14 

Rask Pedersen, 1982124 

(n=11) 

Subjects reporting symptoms. On a 24 hour diary sheet, subjects reported abdomithe following, 0=none; 1=mild/moderate; 2=severe. For diarrhea, no diarrhea=forme≤3 liquid/soft stools; severe= ≥4 liquid/soft stools. 

Low lactose milk 3.75 g NR NR 8 none NR 6 none C

3 mild/mod 4 mild/mod with 

0 severe 0 severe 

Milk 25 g NR NR 7 none NR 1 none C

2 mild/mod 5 mild/mod with 

2 severe 5 severe 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

131 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content / Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Reasoner, 1981125 Symptom scores based on the occurrence and severity of symptoms experienced 

Milk intolerant group (n=9) 0-0.33=none to mild; 0.34-0.66=moderate; 0.67-1=severe. Low lactose milk ~2.9 g NR NR 0.16 0.23 0.40 

p<0.05 vs. SM p <0.05 vs. n

SM 

Skim milk (SM) ~28.5 g NR NR 0.35 0.26 0.57 

n

Skim milk plus glucose ~28.5 g NR NR 0.21 0.31 0.45 

n

Sweet acidophilus milk ~28.5 g NR NR 0.20 0.40 0.50 

n

Milk tolerant group (n=5) Low lactose milk ~2.9 g NR NR No symptoms 0.06 0.32 No 

reported p <0.04 vs. SM sym

Skim milk (SM) ~28.5 g NR NR 0.12 0.51 repo

Skim milk plus glucose ~28.5 g NR NR 0.06 0.25 

p <0.01 vs. SM 

Sweet acidophilus milk ~28.5 g NR NR none 0.31 

Unger, 1981178 

Malabsorbers (n=24) 

p <0.03 vs. SM 

Subjects reporting symptoms during 24 hours after consumption 

Lactose-free chocolate dairy NR 3 NR NR NR 

drink, 240 ml (12.5%) Lactose free chocolate dairy NR 2 NR NR NR drink, 480 ml (8) Lactose containing chocolate 10.8 g NR 8 NR NR NR dairy drink, 240 ml (33) Lactose containing chocolate 21.6 g NR 10 NR NR NR dairy drink, 480 ml (42) 

Absorbers (n=75) Lactose free chocolate dairy NR unclear NR NR NR 

drink, 240 ml Lactose free chocolate dairy NR unclear NR NR NR 

drink, 480 ml Lactose containing chocolate 10.8 g NR unclear NR NR NR 

dairy drink, 240 ml Lactose containing chocolate 21.6 g NR unclear NR NR NR 

dairy drink, 480 ml 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

132 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content / Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Jones, 1976, Part II130 Symptoms scores and subjects reporting symptoms of bloating, gas, diarrhea and 

(n=17) symptoms, 1=mild, 2=moderate, 3=severe, summed Aqueous lactose 250 ml 25 g 46 13 (76.5%) NR NR NR Regular skim milk 500 ml 25 g 45 15 (88.2%) NR NR NR Regular whole milk 500 ml 25 g 39 12 (70.6%) NR NR NR 

60% reduced skim milk 500 10 g 14 6 (35.3%) NR NR NR 

ml 60% reduced lactose whole 10 g 9 7 (41.2%) NR NR NR 

milk 500 ml Placebo 250 ml (saccharin, 0 g 9 6 (35.3%) NR NR NR 

lemon juice water) II. Studies in which subjects were not noted to be symptomatic at baseline or symptoms were not required for study inclusion 

measures only) 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content/ Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Lin, Study 1, 1993136 Symptom scores, expressed as the mean of the sum of scores rating symptoms (gas

(n=20) cramps and diarrhea) from 0 (none) to 5 (severe) for each hour from baseline to 8 hr Low fat milk plus Lactodigest (2 20 g 4.75 NR 1.30 NR 2.95 p<0.05 

capsules) p<0.05 vs. pbo vs. pbo 

Low fat milk plus DairyEase (2 20 g 2.75 NR 0.35 NR 2.25 p<0.05 capsules) p<0.05 vs. pbo vs. pbo 

Low fat milk plus Lactaid (2 20 g 2.60 NR 0.35 NR 2.10 p<0.05 capsules) p<0.05 vs. pbo vs. pbo 

Low fat milk plus Lactodigest (4 20 g 1.25 NR 0.20 p< 0.05 vs. NR 1.0 p <0.05 capsules) p<0.05 vs. pbo, pbo vs. pbo 

Lactodigest 

Low fat milk plus placebo (pbo) 20 g 10.45 NR 1.55 NR 7.85 

Brand, 1991115 Number of subjects who reported specific symptoms over 4 hours after consumption 

(n=6) 95% lactose reduced milk <0.25 g NR At least ≥1 0 NR 0 

symptom 

0 

80% lactose reduced milk 1 g NR 1 1 NR 1 

(Cotee) 80% lactose reduced milk 1 g NR 1 0 NR 1 

(Balance) 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

133 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content/ Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

50% lactose reduced milk 2.4 g NR 1 1 NR 0 

Whole milk 4.8 g NR 5 4 NR 3 

Cavalli-Sforza, 1987122 Percentages of the total number of tests for symptom) response (diarrhea, flatulence

Malabsorbers (n=40) pain) during the 24 hours after consuming the milk test. Symptoms were rated none=

severe=3 in intensity. A total for the 4 symptoms could range from 0 to 12. 

Low lactose skim milk (all 0.8-6.5 0: 64.8%; 1: 11.3%; 2: 8.2%; NR NR NR 

quantities) 3: 4.4%; 4: 5.0%; >4: 6.3% Number of tests: 159 Overall % with symptoms: 35.2%
 

p<0.05 vs. SM for presence/ absence of symptoms; p<0.05 vs. SM for intensity of symptoms 

Skim milk (SM) (all quantities) 6.1-49 0: 51.3%; 1: 15.4%; 2: 16%; NR NR NR 

Number of tests: 156 3: 9%; 4: 1.9%; >4: 6.4% 

Overall % with symptoms: 48.7% 

Low lactose whole milk (all 0.6-5 0: 62.5%; 1: 16.9%; 2: 11.2%; NR NR NR quantities) 3: 3.8%; 4: 3.8%; >4: 1.8% Number of tests: 160 Overall % with symptoms: 37.5% 

p ns vs. whole milk 

Whole milk (all quantities) 6.4-51 0: 51%; 1: 17.2%; 2: 20.5%; NR NR NR 

Number of tests: 151 3: 4.0%; 4: 4.6%; >4: 2.7% 

Overall % with symptoms: 49% 

Absorbers (n=31)) Low- lactose skim milk (all 0.8-6.5 0: 71.2%; 1: 5.1%; 2: 5.9%; NR NR NR 

quantities) 3: 8.5%; 4: 3.4%; >4: 5.9% Number of tests: 118 Overall % with symptoms: 28.8%
 

p ns vs. SM 

Skim milk (SM) (all quantities) 6.1-49 0: 75.4%; 1: 10.7%; 2: 5.7%; NR NR NR 

Number of tests: 122 3: 3.3%; 4: 1.6%; >4: 3.3% 

Overall % with symptoms: 24.6% 

Low lactose whole milk (all 0.6-5 0: 78%; 1: 4.1%; 2: 12.6%; NR NR NR 

quantities) 3: 0.9%; 4: 1.7%; >4: 2.7% Number of tests: 118 Overall % with symptoms: 22% 

p ns vs. whole milk 

Whole milk (all quantities) 6.4-51 0: 77.2%; 1: 5.9%; 2: 6.8%; NR NR NR 

Number of tests: 118 3: 2.6%; 4: 1.7%; >4: 5.9% 

Overall % with symptoms: 22.8% 

Malabsorbers (n=40) Number of subjects reporting symptoms based on the quantity of the 4 milk types Low lactose skim milk 125 ml 0.81 g NR 8/40 NR NR NR 

(20%) 

Low lactose skim milk 250 ml 1.6 g NR 11/40 NR NR NR 

(27.5%) 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

134 

Study (n) / Interventions 

Lactose 

Content/ 

Day 

Overall 

Symptom 

Score 

Number of 

Subjects 

Reporting 

Symptoms 

Abdominal 

Pain/Cramps 

Abdominal 

Bloating Flatulence Bo

(o

Low lactose skim milk 500 ml 3.25 g NR 18/40 NR NR NR 

(45%) 

Low lactose skim milk 1000 ml 6.5 g NR 18/36 NR NR NR 

(50%) 

p <0.025 

across 

groups 

Skim milk 125 ml 6.4 g NR 13/40 NR NR NR 

(32.5%) 

Skim milk 250 ml 12.75 g NR 18/40 NR NR NR 

(45%) 

Skim milk 500 ml 25.5 g NR 19/39 NR NR NR 

(48.7%) 

Skim milk 1000 ml 51 g NR 23/34 NR NR NR 

(67.6%) 

p <0.05 across 

groups 

Low lactose whole milk 125 ml 0.63 g NR 8/40 NR NR NR 

(20%) 

Low lactose whole milk 250 ml 1.25 g NR 12/40 NR NR NR 

(30%) 

Low lactose whole milk 500 ml 2.5 g NR 17/40 NR NR NR 

(42.5%) 

Low lactose whole milk 1,000 ml 5 g NR 21/37 NR NR NR 

(56.8%) 

p <0.01 across 

groups 

Whole milk 125 ml 6.1 g NR 12/38 NR NR NR 

(31.6%) 

Whole milk 250 ml 12.3 g NR 17/38 NR NR NR 

(44.7%) 

Whole milk 500 ml 24.5 g NR 21/37 NR NR NR 

(56.8%) 

Whole milk 1,000 ml 49 g NR 23/36 NR NR NR 

(63.9%) 

p <0.05 

across 

groups 

Absorbers (n=31) Low lactose skim milk 125 ml 0.81 g NR 7/31 NR NR NR 

(22.6%) 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

135 

Study (n) / Interventions 

Lactose 

Content/ 

Day 

Overall 

Symptom 

Score 

Number of 

Subjects 

Reporting 

Symptoms 

Abdominal 

Pain/Cramps 

Abdominal 

Bloating Flatulence Bo

(o

Low lactose skim milk 250 ml 1.6 g NR 8/31 NR NR NR 

(25.8%) 

Low lactose skim milk 500 ml 3.25 g NR 8/28 NR NR NR 

(27.6%) 

Low lactose skim milk 1000 ml 6.5 g NR 9/25 NR NR NR 

(36%) 

ns (not 

significant) 

across groups 

Skim milk 125 ml 6.4 g NR 4/31 NR NR NR 

(12.9%) 

Skim milk 250 ml 12.75 g NR 5/31 NR NR NR 

(16.1%) 

Skim milk 500 ml 25.5 g NR 9/31 NR NR NR 

(29%) 

Skim milk 1,000 ml 51 g NR 10/27 NR NR NR 

(37%) 

ns across 

groups 

Low lactose whole milk 125 ml 0.63 g NR 3/31 NR NR NR 

(9.7%) 

Low lactose whole milk 250 ml 1.25 g NR 4/30 NR NR NR 

(13.3%) 

Low lactose whole milk 500 ml 2.5 g NR 9/29 NR NR NR 

(31%) 

Low lactose whole milk 1,000 ml 5 g NR 8/26 NR NR NR 

(30.8%) 

ns across 

groups 

Whole milk 125 ml 6.1 g NR 2/31 NR NR NR 

(6.5%) 

Whole milk 250 ml 12.3 g NR 7/31 NR NR NR 

(22.6%) 

Whole milk 500 ml 24.5 g NR 8/29 NR NR NR 

(27.6%) 

Whole milk 1,000 ml 49 g NR 9/25 NR NR NR 

(36%) 

ns across 

groups 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

136 

Number of Lactose Overall Subjects Abdominal Abdominal	 Bo

Study (n) / Interventions Content/ Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Rosado, 1984133 Subjects reporting symptoms. A numerical score was given for the presence or abse

Malabsorbers (n=25) (abdominal cramps, gas/flatulence, vomiting, and/or diarrhea), 0=absent to 3=severe

was always marked a 3. Total points were then summed for each of the 3 treatment p

minor symptoms, ≥4 = major. 

Lactose prehydrolyzed milk 18 g NR 24 none NR NR NR 

1 minor 0 major 

Milk plus Lactaid 18 g NR 21 none NR NR NR 

4 minor 0 major 

Milk 18 g NR 13 none NR NR NR 

5 minor 7 major 

Absorbers (n=25) Lactose prehydrolyzed milk 18 g NR 24 none NR NR NR 

0 minor 1 major 

Milk plus Lactaid 18 g NR 22 none NR NR NR 

2 minor 1 major 

Milk 18 g NR 22 none NR NR NR 

2 minor 1 major 

Haverberg, 1980126 Number of subjects reporting GI symptoms during 24 hours after consumption. Occu

Malabsorbers (n=67) ≥2 mild GI symptoms or ≥1 moderate or severe symptom was noted as a positive res

Lactose free chocolate dairy NR 12 (18%) NR NR NR drink, 240 ml Lactose free chocolate dairy NR 15 (22) NR NR NR drink, 480 ml Lactose containing chocolate 10.8 g NR 19 (28) NR NR NR 

dairy drink, 240 ml Lactose containing chocolate 21.6 g NR 26 (39) NR NR NR 

dairy drink, 480 ml Absorbers (n=43) Lactose-free chocolate dairy NR 7 (16) NR NR NR 

drink, 240 ml Lactose-free chocolate dairy NR 14 (32) NR NR NR 

drink, 480 ml Lactose containing chocolate 10.8 g NR 7 (16) NR NR NR 

dairy drink, 240 ml 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content/ Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

137 

Lactose-containing chocolate 21.6 g NR 8 (19) NR NR NR 

dairy drink, 480 ml Kwon, 1980127 

Malabsorbers (n=45 adolescents) 

Number of subjects reporting GI symptoms during 24 hours after consumption 

Lactose free chocolate dairy NR 12 (27%) NR NR NR 

drink, 240 ml Lactose free chocolate dairy NR 7 (16) NR NR NR 

drink, 480 ml Lactose containing chocolate 10.8 g NR 4 (9) NR NR NR 

dairy drink, 240 ml Lactose containing chocolate 21.6 g NR 12 (27) NR NR NR 

dairy drink, 480 ml Absorbers (n=42 adolescents) Lactose free chocolate dairy NR 7 (17) NR NR NR 

drink, 240 ml Lactose free chocolate dairy NR 7 (17) NR NR NR 

drink, 480 ml Lactose-containing chocolate 10.8 g NR 8 (19) NR NR NR 

dairy drink, 240 ml Lactose containing chocolate 21.6 g NR 7 (17) NR NR NR 

dairy drink, 480 ml Rorick, 1979116 

Malabsorbers (n=23) 

Number of subjects reporting intolerance to test drinks during the afternoon after cosymptoms is based on only the subjects who reported symptoms, 7 in the malabsorbabsorber group and subjects could be intolerant to both test drinks. 

Intolerant to only lactose free NR 2 1 mild 4, 3 mild 6, 3 mild 

chocolate dairy drink cramps 1 moderate, 3 moderate 

Intolerant to only lactose 10.8 g NR 0 1 mild 2, both mild 5, 3 mild 

containing chocolate dairy drink cramps 2 moderate Intolerant to both test drinks 0 to NR 5 Not applicable NA NA 

10.8 g (NA) 

Tolerant to both test drinks 0 to NR 16 NA NA NA 

10.8 g 

Absorbers (n=64) Intolerant to only lactose free NR 6 1 mild 5, 8, 5 mild 

chocolate dairy drink cramps 4 mild 1 moderate 

1 severe 2 severe 

Intolerant to only lactose 10.8 g NR 7 1 mild 6, 10, 7 mild 

containing chocolate dairy drink cramps 5 mild 2 moderate 

1 moderate 1 severe 

Intolerant to both test drinks 0 to NR 5 NA NA NA 

10.8 g 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

Number of Lactose Overall Subjects Abdominal Abdominal Bo

Study (n) / Interventions Content/ Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

138 

Tolerant to both test drinks 0 to NR 46 NA NA NA 

Lisker, 1978129 

Lactase-deficient subjects (n=97) 

10.8 g 

Number of subjects reporting symptoms. Symptoms were rated according: 1+ if mild

marked. Symptoms were scored as severe if diarrhea was present or if a cumulative (abdominal cramps, bloating, flatulence) was 4+. Cumulative rating less than 4+ was 

Lactose free milk 0 g NR 1 mild NR NR NR 

96 absent 

Regular milk 12.5 g NR 16 severe NR NR NR 

20 mild 

61 absent 

Regular milk plus additional 25 g 37.5 g NR 69 severe NR NR NR 

lactose 12 mild 

16 absent 

Lactase -sufficient subjects (n=53) Lactose free milk 0 g NR 53 absent NR NR NR 

Regular milk 12.5 g NR 1 severe NR NR NR 

1 mild 

51 absent 

Regular milk plus additional 25 g 37.5 g NR 2 severe NR NR NR 

lactose 2 mild 

49 absent 

Paige, 1975135 

Lactose malabsorbers (n=22) 

Number of subjects reporting symptoms during 90 minutes after consumption. Sympmentioned were recorded. Subjects were not specifically asked if they developed any associated with lactose intolerance. 

90% hydrolyzed milk 1.2 g NR 3 NR NR NR 

50% hydrolyzed milk 6 g NR 0 (n=18) NR NR NR Whole milk 12 g NR 3 NR NR NR 

Lactose absorbers (n=10) 90% hydrolyzed milk 1.2 g NR 0 NR NR NR 

50% hydrolyzed milk 6 g NR 0 NR NR NR 

Whole milk 12 g NR 0 NR NR NR Jones, 1976, Part I130 Subjects reporting symptoms of bloating, gas, diarrhea and cramps using scale: 0=no symptom

(n=16) 3=severe, summed Regular skim milk 591.5 ml 30 g 35 15 (93.8%) NR NR NR 

50% lactose reduced skim milk 15 g 17 12 (75%) NR NR NR 

591.5 ml 75% lactose reduced skim milk 7.5 g 13 5 (31.3%) NR NR NR 

591.5 ml 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

B. Prebiotics or probiotics I. Studies that reported subjects with symptoms at baseline in addition to lactose intolerance by testing 

139 

Number of Lactose Overall Subjects Abdominal Abdominal Bor

Study (n) / Interventions Content/ Symptom Flatulence 

Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Newcomer, 1983144 Mean symptom score over 10wk for diarrhea + pain + gas + borborygmi, averaged and compa

(n=18) from graph) 1. 720 ml 2% milk NR 40 NR NR NR NR 

2. 720 ml 2% unfermented NR 40 NR NR NR NR acidophilus milk with LA at cell concentration 106 cfu/ml 

II. Studies in which subjects were not noted to be symptomatic at baseline or symptoms were not required for study inclusion 

measures only) 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bor

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (or 

Day Score Symptoms 

Lin, 1998117 Mean symptom score over 8 hours, 0-5 from none to severe for abdominal pain, gas and diarr

(n=20) compared to control. 1. 400 ml milk with LA at cell 20 g 9.8 NR NR NR NR 

concentration 108 cfu/ml 

2. 400 ml milk with LA at cell 20 g 6.5 (p<.05) NR NR NR NR 

concentration 109 cfu/ml 

3. 400 ml of milk with LB at 108 20 g 3.9 (p<.05) NR NR NR NR 

cfu/ml 4. 400 ml of milk with L.B at 109 20 g 2.8 (p<.05) NR NR NR NR cfu/ml 2% milk 20 g 12.5 NR NR NR NR 

Mustapha, 1997139 Subjects rated symptoms (mean ± SEM) on a 0-5 (none to severe) scale for each hour from ho

(n=11) each of the diets. Diarrhea was monitored 24 hours after diet. Control 15 g NR NR NR 7.44 ± 1.8 9.93 ± 1.73 7.8

ATC 4356 milk (highest B-gal 15 g NR NR NR 5.31 ± 1.18 7.80 ± 1.18 6.7

activity) B Milk 15 g NR NR NR 5.16 ± 1.2 8.68 ± 1.41 6.4

N1 Milk (lowest B-gal activity) 15 g NR NR NR 5.15 ± 1.39 6.87 ± 1.65 6.9

(p<0.05 vs. 

control) 

E Milk 15 g NR NR NR 4.57 ± 1.64 8.40 ± 1.75 5.9

(p<0.05 vs. 

control) 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

140 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bor

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (or 

Day Score Symptoms 

Jiang, 1996140 Mean ranked scale of symptoms (± SEM) for abdominal pain, flatulence, borborygmi, diarrhea 

(n=15) 1=slight, 2=mild, 3=moderate, 4=moderately severe, 5= severe summed for hours 1-8. flatus fr

of gas passages over 8 hours 

1. 400 ml 2% milk with NR NR NR 5.6 ± 1.8 6.0 ± 1.8 7.0 ± 1.7 8.

B.longum B6 from m-MRS broth containing lactose 2.400 ml 2% milk with B.longum NR NR NR 3.8 ±1.5 7.3 ± 2.0 13.2 ± 2.1 8.B6 from Sanofi biomed as a concentrated frozen culture 3. 400 ml of bifidus milk with NR NR NR 4.4 ± 2.0 6.1 ± 2.6 11.8 ± 2.0 9.B.longum ATC/C 15708 from mMRS broth containing lactose One meal 400 ml of 2% milk NR NR NR 7 ± 1.8 6.1 ± 2.2 9.2 ± 1.9 9.

Vesa, 1996141 Ranked scale of symptoms for abdominal pain, flatulence, diarrhea, bloating and sum score: 0

(n=15, results on 14 reported) 2=moderate, 3=fairly strong, 4=very strong, summed for hours 1-8. Also measured HB post intControl: Lactulose 10gm in 250 18 g 3±0.95 NR 0.42 ±0.19 1.33 ± 0.41 1±0.37 

ml water 1. Ofilus (Yoplait, France; has L. 18 g 1.58±0.76 NR 0.25±0.25 0.58 ± 0.26 0.5±0.36 

acidophilus and bifidobacterium) 320 ml 2. Bulgofilus (ofilus bacteria + L. 18 g 1.17 ± 0.59 NR 0 0.42 ± 0.29 0.5±0.34 bulgaricus) 400 ml (p<0.05) (p<0.05) 

3. Yoplait yogurt 500 ml Lerebours, 1989142 

(n=16, only 2 with symptoms of 

18 g 2.17±0.95 NR 0.25±0.18 0.92 ± 0.48 0.5±0.36 

Subjects reporting symptoms. No subjects reported diarrhea, pain or flatulence 

LI) 125 g 3x/day of yogurt 18 g NR 0/8 0 NR 0 

125 g 3x/day of fermented then 18 g NR 0/8 0 NR 0 pasteurized milk Martini, 1987143 

(n=16) 

Subjects reporting gastrointestinal distress symptoms after consuming milk and various yogu

Unflavored yogurt 455 g 20 g NR 0/8 0/8 NR NR 

Strawberry flavored yogurt 465 g 20 g NR 0/9 0/9 NR NR 

Ice milk 410 g 20 g NR 0/9 0/9 NR NR 

Ice cream 400 g 20 g NR 0/9 0/9 NR NR 

Unflavored yogurt FY-1 410 g 20 g NR 0/8 0/8 NR NR 

Unflavored yogurt FY-2 410 g 20 g NR 0/8 0/8 NR NR Unflavored yogurt FY-3 410 g 20 g NR 0/8 0/8 NR NR 

Whole milk 415 g 20 g NR 3/8 3/8 (38%) NR NR 

(38%) 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

141 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bor

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (or 

Day Score Symptoms 

Savaiano, 1984145 Subjects reported symptoms after consumption of 2 types of yogurt (regular and pasteurized) 

(n=9) (regular, sweet acidophilus and buttermilk). Scale not reported. Yogurt 500 gm 20 g NR NR 0 NR 0 

410 g milk 20 g NR NR 1 NR 3 

420 g sweet acidophilus milk 20 g NR NR 0 NR 4 

465 g cultured milk (buttermilk) 20 g NR NR 4 NR 8 

 500 g pasteurized yogurt 20 g NR NR 0 NR 0 

C. Other therapies 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bor

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (or 

Day Score Symptoms 

Cappello 2005147 Symptoms score referred to the 5 days preceding each evaluation and scored as: 0=absent; 1

symptom but easily tolerated); 2=moderate; 3=severe; and 4=very severe at baseline (b), 10 an

Rifaximin x 10 days (n=14) NA NR NR 2.0 ± 1.1 b 

0.6 ± 0.7 10d 

1 ± 1.2 40d 

p <0.05 vs. b 

at 10 and 40d 

2.5 ± 1 b 

1.6 ± 0.9 10d 1.6 ± 0.9 40d 

*p <0.05 vs. b 

at 10 and 40d 

NR 2.4 

1.4 ± 1.5 ± 

p <0

at 10 

Placebo x 10 days (n=5) NA NR NR 1.0 ± 1.4 b 

1.0 ± 1.4 10d 0.7 ± 0.9 40d 

2.8 ± 1.0 b 

2.7 ± 0.5 10d 2.7 ± 1.2 40d 

NR 1.6 

1.5 ± 1.7 ± 

Lactose-free diet x 40 days (n=13) 

0 g NR NR 

1.3 ± 1.0 b 

0.7 ± 1.0 10d 0.5 ± 0.7 40d 

p <0.05 vs. b 

at 10 and 40d 

2.5 ± 1.1 b 

1.9 ± 1.3 

10d 

1.8 ± 1.2 

40d 

p <0.05 vs. b 

at 10 and 40d 

NR 1.8 

1.1.

p <0

at 10 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

142 

D. Colonic adaptation studies 

Number of Lactose Overall Abdominal Study (n) / Subjects Abdominal Bo

Content/ Symptom Pain/Cramp Flatulence 

Interventions Reporting Bloating (o

Day Score s Symptoms 

Hertzler, 1996118 Symptoms rating after lactose (L) or dextrose feeding periods (mean ± SEM). The 

(n=20) score for any individual symptom would be 40 (a “5” rating each hour for 8 hours

Dextrose: 0.6 g • kg body wt-1 • d-1 , then NR NR 2.3 ± 0.9 NR 8.1 ± 1.6 F

increased by 0.2-g/kg every other day up to a frmaximum of 1.0 g • kg-1 • d-1. p=0.25 vs. L 

2

p=0

Lactose: 0.6 g • kg body wt-1 • d-1 , then NR NR 2.6 ± 0.9 NR 4.5 ± 1.0 

increased by 0.2-g/kg every other day up to a maximum of 1.0 g • kg-1 • d-1. 

Briet , 1997146 Every hour, subjects reported any occurrence of abdominal pain, borborygmus, f

(n=46) distension, and graded each symptom5 as absent = 0, mild = 1, moderate = 2, or s

clinical score was calculated for each subject by summing the scores for each sy

Sucrose 17 g plus 50 g aspartame (to mask NR NR NR NR taste) twice daily (34 g sucrose total) over 13 24.2 ± 12.8 days (days 2 to 14). Lactose 17 g plus 50 g aspartame (to mask 20.2 ± 13.9 NR NR NR NR taste) twice daily (34 g lactose total) over 13 p=ns between days (days 2 to 14). groups E. Incremental lactose load studies or studies examining different levels of lactose 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bo

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Hertzler, 1996119 Symptoms rating (mean ± SEM) after lactose (L) or dextrose feeding periods. The 

(n=13) score for any individual symptom would be 40 (a “5” rating each hour for 8 hours

Lactose (dissolved in 240 ml 0 g NR NR 1.7 ± 0.8 NR 3.4 ± 1.0 F

water) fr

4

Lactose 2 g NR NR 1.7 ± 0.9 NR 3.8 ± 1.4 4

Lactose 6 g NR NR 1.2 ± 0.5 NR 1.9 ± 0.9 5

Lactose 12 g NR NR 3.4 ± 0.8 NR 3.5 ± 1.3 4

Lactose 20 g NR NR 5.3 ± 1.8 NR 6.6 ± 1.8 9

Symptom ranking (mean ± SEM) after lactose (L) or dextrose feeding periods. Tre(least symptoms) through 5 (most symptoms). 

Lactose (dissolved in 240 ml 0 g NR NR 2.4 ± 0.3 NR 2.7 ± 0.3 F

water) fr

2
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bo

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

143 

Lactose 2 g NR NR 2.5 ± 0.2 NR 3.0 ± 0.3 2

Lactose 6 g NR NR 2.4 ± 0.2 NR 1.9 ± 0.2 2

p≤0.05 for 0- p≤0.05 vs. 2, 

6 g vs. 12 12, 20 g 

and 20 g 

Lactose 12 g NR NR 3.8 ± 0.3 NR 3.2 ± 0.4 3

Lactose 20 g NR NR 3.9 ± 0.3 NR 4.2 ± 0.3 4

p≤0.05 vs. all p≤0

other 

treatments tr

Newcomer, 1978120 Number of subjects reporting symptoms. A subject was considered to have a positive sympto

(n=59) had ≥1 loose stools or had a grade 2+ or higher in at least one of the following symptoms: abd

bloating or gas, borborygmi, flatulence. 1+=slight; 2+=mild; 3+=moderate; 4+=severe. 

Breakfast 1 0 g NR 56 ≤+1 NR NR NR 

3 ≥+2 

(1 +3) 

Breakfast 2 3 g NR 57 ≤+1 NR NR NR 

2 ≥+2 

(1 +4) 

Breakfast 3 6 g NR 53 ≤+1 NR NR NR 

6 ≥+2 

(1 +4) 

Breakfast 4 9 g NR 52 ≤+1 NR NR NR 

7 ≥+2 

(1 +3, 

1 +4) 

Breakfast 5 12 g NR 56 ≤+1 NR NR NR 

3 ≥+2 

(1 +4) 

Breakfast 6 18 g NR 56 ≤+1 NR NR NR 

3 ≥+2 

(1 +3, 

1 +4) 

Stephenson, 1974131 Subjects reporting symptoms of diarrhea, gas, bloating and cramps according to scale: 1=mil

(n=16 LI subjects that got summed for the 4 symptoms symptoms with 50 g lactose in water test dose) Lactose in water 15 g NR 7% NR NR NR 

Lactose in water 30 g NR 58% NR NR NR 

Lactose in water 50 g NR 14% NR NR NR 

Lactose in milk 15 g NR 20% NR NR NR 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bo

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

144 

Lactose in milk 30 g NR 66% NR NR NR 

Lactose in milk 50 g NR 7% NR NR NR 

Lactose in water 100 g NR 14% NR NR NR 

Lactose in water 150 g NR 7% NR NR NR 

Lactose in water 200 g NR 0 NR NR NR 

Lactose in milk 100 g NR 7% NR NR NR 

Lactose in milk 150 g NR 0 NR NR NR 

Lactose in milk 200 g NR 0 NR NR NR 

Stephenson, 1974131 Subjects reporting symptoms of diarrhea, gas, bloating and cramps according to scale: 1=mil

(n=19 lactose tolerant subjects summed for the 4 symptoms that did not get symptoms with 50 g lactose in water test dose) Lactose in water 15 g NR 0 NR NR NR 

Lactose in water 30 g NR 5% NR NR NR 

Lactose in water 50 g NR 16% NR NR NR 

Lactose in milk 15 g NR 0 NR NR NR 

Lactose in milk 30 g NR 13% NR NR NR 

Lactose in milk 50 g NR 6% NR NR NR Lactose in water 100 g NR 21% NR NR NR 

Lactose in water 150 g NR 32% NR NR NR 

Lactose in water 200 g NR 26% NR NR NR 

Lactose in milk 100 g NR 31% NR NR NR Lactose in milk 150 g NR 31% NR NR NR Lactose in milk 200 g NR 19% NR NR NR F. Studies with IBS subjects 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bo

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Parker, 2001175 Symptom score based on eight variables: abdominal pain, number of daily bowel 

(n=33 IBS subjects, only 23 completed 3 defecate, consistency of feces, flatulence, headache, abdominal distension and g

weeks of low lactose diet. 7 of 9 of subjects symptom, except urgency, was scored from 0 to 4, with 0 being no symptoms and improving on the diet were double-blind, Urgency was scored from 0 to 3. The maximum cumulative score was 31. placebo-controlled challenges Lactose challenges 0 to 15 g	 During the double blind, placebo controlled challenges, two of the seven (29%) showed 

higher levels of lactose. The remaining five were inconclusive but 5/7 (71%) had worsenof lactose 
Table 19. Occurrence of GI symptoms in randomized trials (continued) 

145 

Number of Lactose Overall Study (n) / Subjects Abdominal Abdominal Bo

Content/ Symptom Flatulence 

Interventions Reporting Pain/Cramps Bloating (o

Day Score Symptoms 

Böhmer, 1996176 Cumulative score with a total score of 18. Subjects scored symptoms (pain, flatul

(n=70 IBS subjects total) diarrhea, mucus, incomplete evacuation) from 0=no complaints, 1=mild; 2=moder

maximum. 

Lactose malabsorbers based on hydrogen breath test (n=17) Baseline score 19.1 13.6 3 weeks after lactose restricted <9 g 7.3 (p<0.001 diet vs. baseline 6 weeks after lactose restricted <9 g 4.2 (p<0.001 diet vs. baseline Lactose absorbers based on hydrogen breath test (n=53) 

Baseline score 19.1 13.1 3 weeks after lactose restricted <9 g 11.6 diet 6 weeks after lactose restricted <9 g 11.8 

diet Lisker, 1989177 Diary record of symptoms filled out daily. Symptoms included constipation, diarr

(n=12, 8 were lactose nonpersistent based on abdominal distension, and flatulence.
 hydrogen breath test)
 Placebo or hydrolyzed milk IBS symptoms appeared to be independent of lactose malabsorption following 3 monthNewcomer, 1983144 Symptom (diarrhea, abdominal pain/cramps, gas/flatus, rumbling, constipation) d

(n=89 total) Scored as following: 0=no trouble; 1=slight trouble; 2=mild; 3=moderate; 4=sever

better, same, worse. Diarrhea was yes/no, # stools per day. 

Lactase deficient group (n=18) Unaltered milk NR, mean There was no significant difference in symptoms during the acidolphilus and unaltered m

11⁄2 symptoms increased significantly with both acidolphilus and unaltered milks compared t

glasses/d period. 

Acidolphilus milk NR, mean 

11⁄2 

glasses/d 

IBS group (n=61) Unaltered milk NR, mean Symptoms were not helped by the ingestion of acidophilus milk. 

11⁄2 

glasses/d 

Acidolphilus milk NR, mean 

11⁄2 

glasses/d 

Chapter 4. Discussion 

Summary and Discussion 

Our evidence synthesis has the following major conclusions: (1) Reliable estimates of U.S. 

prevalence rates for LI are not currently available, though there is some evidence that the 

magnitude of LI will be very low in young children and remain low into adult ages for most 

populations of Northern European descent. For African American, Hispanic, Asian, and American 

Indian populations the rates of LI will likely be higher in late childhood and adulthood. (2) 

Evidence regarding the effect of dairy exclusion diets on long-term GI and bone health outcomes 

is relatively sparse in quantity and low in quality. The evidence does not strongly indicate that 

dairy free diets are independently associated with poor long-term bone health outcomes, and there 

is no direct information on long-term GI outcomes among individuals consuming dairy free diets. 

However, results from genetic association tests consistently reported decreased consumption of 

milk in adults with the C/C genotype compared to those with at least one T allele, suggesting that 

individuals with lactase nonpersistence avoid milk presumably to reduce dairy induced GI 

symptoms. (3) The majority of symptomatic individuals diagnosed with LI can likely tolerate up to 

12 grams (equivalent of 1 cup of milk) at a given setting with minimal to no symptoms, especially 

if consumed with other foods. (4) Although reduced lactose consumption is logical and a 

biologically plausible treatment plan, evidence was insufficient to determine if lactose reduced 

milk products result in clinically important improvements in GI symptoms in individuals 

diagnosed with LI who wish to consume doses of lactose that exceed 12 grams per serving. There 

was also insufficient evidence on the effects of other treatment options, including probiotics and 

incremental lactose loads. 

Our findings have important research and clinical implications. With regard to LI prevalence 

estimates, most of the identified research assessed subjective symptoms in an unblinded fashion, 

an inability of individuals to fully absorb lactose, irrespective of symptoms or lactase 

nonpersistence. Data available tended to be from highly selected populations and not likely 

representative of the overall U.S. population. Racial and ethnic variation was clearly present, but 

the variation in symptoms reported following a challenge does not seem as extreme as the racial 

and ethnic variation seen in lactose malabsorption and prevalence of hypolactasia. This is likely 

due in part to the fact the GI symptoms are commonly caused by factors unrelated to LI, so the 

effects due to lactose are likely attenuated by symptoms caused by nonlactose factors. Also, many 

people who malabsorb lactose do not report symptoms. Additional genetic association studies may 

provide a useful method to assess LI in epidemiologic studies. Dietary history assessing dairy 

consumption and symptoms linked to results from testing for the lactase gene might obviate the 

need for blinding of lactose intake. 

Dietary lactose intake and supplemental calcium consumption were recorded in a few 

observational studies. We found inconsistent increased risk of bone fracture in populations with 

documented or assumed low lactose intake. Poor documentation of dietary intake may contribute 

to inconsistency in results of observational studies. A recently published systematic review of the 

association between vitamin D and dietary calcium also found that inconsistent dietary analysis 

hampered synthesis of evidence.179 The authors could not find consistent evidence that increased 

dietary or supplemental vitamin D and calcium intake improves bone health. Because the major 

Appendixes and evidence tables cited in this report are available at http://www.ahrq.gov/downloads/pub/evidence/pdf/lactoseint/lactint.pdf. 

147 
long-term health concern of dairy exclusion diets beyond GI symptoms is the potential for intake 

of calcium below recommended dietary levels, future research is needed to accurately assess longterm bone health outcomes in populations that consume dairy free diets. We found that dairy 

interventions in healthy children with low baseline milk intake may result in short but not longterm improvement of bone mineral content and density. Adults with lactose free or low lactose diet 

may have increased risk of bone fractures. Low and inconsistent evidence suggested that adults 

with milk intolerance and malabsorption had greater odds of fractures and worse bone outcomes. 

Adult women with low childhood and lifetime milk intake, LM, and C/C genotype had greater risk 

of osteoporosis and fractures. However, studies did not find significant association with lactose 

metabolism and bone health in men. There was little data on African Americans. Additional 

information would be important because African Americans have a higher prevalence of LI, likely 

lower consumption of dairy products, yet have lower rates of bone health outcomes of interest for 

this report. Children with low baseline calcium consumption may benefit from increased lactose 

intake. It is not clear if increased milk consumption in healthy adult women with low childhood 

and lifetime milk intake, LM, or C/C genotype reduces the risk of osteoporosis and fractures. 

Our findings can aid patients and practitioners in clinical management of individuals diagnosed 

with LI. The preponderance of evidence indicates individuals diagnosed with LI can be informed 

that they can ingest 12 grams of lactose (one cup of milk) as a single dose (particularly if taken 

with food) with no or minor symptoms. Therefore, most individuals diagnosed (either self or 

clinically), can consume a sufficient amount of dairy products each day to meet minimum 

recommendations without incurring GI symptoms. However, as the dose is increased above 12 

grams, these individuals can be informed that intolerance becomes more prominent, with single 

doses of 24 grams usually yielding appreciable symptoms. There is some evidence that if 24 grams 

of lactose is distributed throughout the day, many lactose malabsorbers will tolerate this dosage. 

Lactose in a dose of 50 grams induces symptoms in the vast majority of subjects. No studies 

assessed if lactose malabsorbers of differing ethnicities have differing tolerance to lactose. There 

was no data on the relationship of age or sex to the quantity of lactose that can be tolerated. 

Advice regarding additional management strategies is hampered from the lack of study 

uniformity in design and methodology. For individuals with LI who wish to consume more than 12 

grams of lactose at an individual sitting, there is insufficient evidence of clinically relevant 

reductions in overall symptoms and abdominal pain and diarrhea with consumption of lactose 

reduced milk (to content of 0-2 grams). However, we caution that the criterion of being 

symptomatic at baseline was found only in a few studies, and not all of the enrolled subjects may 

have actually been lactose intolerant. This greatly reduces the applicability of these studies to the 

clinical management of individuals with LI as well and limits the comparison of findings across 

studies. Most studies had an 8-hour recording period, and it is difficult to generalize these findings 

to individuals with chronic relapsing remitting problems with a constellation of symptoms. 

Individuals can be informed that while some studies indicated that treatments provided a statistical 

benefit, symptomatic improvement generally went from none to mild or slight, and the clinical 

significance for many individuals may be low. There is little information on the effect of these 

interventions on diarrhea and abdominal pain. 

148 
Key Question 5: What are the future research needs for 

understanding and managing lactose intolerance? 

Key Question 1 

In order to accurately assess the population prevalence of lactose, future studies will need to be 

derived from population based samples that include adequate distributions across ages and ethnic 

variation in order to map the effects of these important factors. Effort will also need to be made to 

account for possible placebo effects in reporting symptoms. The best mechanisms available for 

accounting for placebo effects would be to conduct blinded challenges with and without lactose 

and to assign the difference in reported symptoms and the true prevalence due to the lactose 

challenge. Additional work on what constitutes a meaningful challenge dose should also be 

conducted. For the research to be clinically meaningful, research on LI should take into account 

the prevalence of symptoms that might be expected following doses of lactose that would be 

consumed during a normal diet as compared to extreme doses of lactose that are comparable to 

getting a recommended daily intake of calcium from a one-time consumption of milk. 

Key Question 2 

We were unable to identify long-term studies that assess the impact of dairy exclusion diets on 

GI symptoms, especially if blinding individuals to dairy exclusion. Studies evaluating individuals 

diagnosed with IBS and gluten intolerance are needed. Future research should investigate the 

association between dietary calcium and patient outcomes in patients with LI and lactose free 

diets. The target populations for investigational research should include children, elderly, gender 

and ethnic subgroups, and patients with genetic polymorphism. The sources of dietary calcium 

from nondairy products and from nutritional supplements should be examined separately and in 

interaction with other dietary patterns (food synergy).148-150 Despite the widespread perception that 

low intake of dairy products and associated low vitamin D and calcium intake can lead to poor 

health outcomes, bone health in patients with LI is unknown. Length and doses of dairy products, 

probiotics, and plant calcium sources, as well as patient adherence to the recommended treatment 

regimes, may modify the association and should be examined in future research. Future research 

should prioritize patient outcomes, including bone fractures and intermediate outcomes of bone 

density and mineral content. Other health outcomes, including obesity, diabetes, cardiovascular 

diseases, and cancer, should be examined in treated and untreated lactose intolerant patients in 

comparison with the general population. In children with LI, incidence of infection and allergic 

diseases should be evaluated in long-term observational studies and in randomized controlled 

clinical trials of available treatment options. 

Key Question 3 

Future research needs to examine if lactose malabsorbers of differing ethnicities have differing 

tolerance to lactose. Additionally, blinded RCTs should enroll and provide outcomes among 

subjects according to age and gender to determine if the quantity of lactose that can be tolerated by 

lactose intolerant subjects varies by these characteristics. Reporting of outcomes in a standardized 

149 
validated fashion and determining clinically significant as well as statistically significant 

differences are needed. 

Key Question 4 

Few studies have tested the hypotheses that incremental lactose loads for colonic adaptation is 

beneficial. Furthermore, studies that have examined different products to prevent LM used a wide 

variety of patients, interventions, comparisons, and outcomes. Pooling results is difficult, and 

determining generalized estimates of clinically relevant effect sizes was generally not feasible. 

Future research is needed employing standardized interventions with blinded controls and reported 

validated outcomes in a standardized fashion. 

In summary, while probiotics, lactose reduced milks, and lactase supplements hold great 

promise and high public acceptance, evidence of efficacy and effectiveness in specific populations 

is lacking. Rigorous scientific data to support their use is lacking, and there is also a dearth of 

information on their safety. Probiotics are generally considered effective and safe. Using the 

approach, “they can’t hurt and may help” is potentially erroneous as safety and efficacy, 

particularly long-term use, are not known. 

The connection between bench and bedside application needs to be made. A large body of 

literature exists on physiological and experimental measurement of LM, but few studies evaluate 

the symptomatic response of agents. Also, the correlation between measurement of hydrogen 

breath excretion, colonic bacterial fermentation, and lactase activity and other physiological 

measurements with symptomatic improvement needs to be studied and reported. 

Need for blinded randomized clinical studies. LI is well recognized by the medical and lay 

community and is often blamed for being the cause of diarrhea, abdominal pain, bloating, and 

flatulence. Patients self diagnose the condition and drastically reduce or stop their intake of lactose 

or use supplements to help digest lactose. This has the variable effect of reducing or alleviating 

symptoms. However, given the subjective nature of symptoms and the large placebo effect of any 

dietary manipulation, it is unclear if the response is a ‘placebo effect’ or due to use of supplements. 

The literature on efficacy of hydrolyzed milk, probiotics, and supplements to help digest lactose is 

fraught with this problem. Rigorous double blinded placebo controlled studies are required to 

demonstrate efficacy, and larger long-term studies demonstrating effectiveness are needed. There 

also needs to be rigorous long-term safety data of these agents. Outcomes reported in a 

standardized validated fashion and that determine clinically significant as well as statistically 

significant differences are needed. 

150 
 

 

 

 

 

 

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Vigorita VJ, Lane M, Suda MK, et al. Differences 

between lactase deficient and non-lactase deficient 

174. 

175. 

Looker AC, Harris TB, Madans JH, et al. Dietary calcium 

and hip fracture risk: the NHANES I Epidemiologic 

Follow-Up Study. Osteoporos Int 1993 Jul; 3(4):177-84. 

Parker TJ, Woolner JT, Prevost AT, et al. Irritable bowel 

166. 

women with spinal osteoporosis. Clin Orthop Relat Res 

1987 Feb; (215):248-53. 

Honkanen R, Pulkkinen P, Jarvinen R, et al. Does lactose 

intolerance predispose to low bone density? A population176. 

syndrome: is the search for lactose intolerance justified? 

Eur J Gastroenterol Hepatol 2001 Mar; 13(3):219-25. 

Bohmer CJ, Tuynman HA. The clinical relevance of 

lactose malabsorption in irritable bowel syndrome. Eur J 

167. 

based study of perimenopausal Finnish women. Bone 

1996 Jul; 19(1):23-8. 

Honkanen R, Kroger H, Alhava E, et al. Lactose 

intolerance associated with fractures of weight-bearing 

177. 

Gastroenterol Hepatol 1996 Oct; 8(10):1013-6. 

Lisker R, Solomons NW, Perez Briceno R, et al. Lactase 

and placebo in the management of the irritable bowel 

syndrome: a double-blind, cross-over study. Am J 

168. 

bones in Finnish women aged 38-57 years. Bone 1997 

Dec; 21(6):473-7. 

Finkenstedt G, Skrabal F, Gasser RW, et al. Lactose 

absorption, milk consumption, and fasting blood glucose 

178. 

Gastroenterol 1989 Jul; 84(7):756-62. 

Unger M, Scrimshaw NS. Comparative tolerance of adults 

of differing ethnic backgrounds to lactose-free and 

lactose-containing dairy drinks. Nutr Res Vol 1; 1981: 

169. 

concentrations in women with idiopathic osteoporosis. Br 

Med J (Clin Res Ed) 1986 Jan 18; 292(6514):161-2. 

Corazza GR, Benati G, Di Sario A, et al. Lactose 

intolerance and bone mass in postmenopausal Italian 

179. 

227-33. 

Chung M, United States. Agency for Healthcare Research 

and Quality., Tufts-New England Medical Center. 

Evidence-based Practice Center. Vitamin D and calcium : 

170. 

women. Br J Nutr 1995 Mar; 73(3):479-87. 

Harma M, Alhava E. Is lactose malabsorption a risk factor 

in fractures of the elderly? Ann Chir Gynaecol 1988; 

77(5-6):180-3. 

a systematic review of health outcomes. Rockville, MD: 

Agency for Healthcare Research and Quality; 2009. 

171. Lau EM, Kwok T, Woo J, et al. Bone mineral density in 

Chinese elderly female vegetarians, vegans, lactovegetarians and omnivores. Eur J Clin Nutr 1998 Jan; 

52(1):60-4. 

156 
List of Acronyms and Abbreviations 

AHRQ Agency for Healthcare Research and Quality 

BMC Bone mineral content 

BMD Bone mineral density 

BMI Body mass index 

CaMos Canadian Multicentre Osteoporosis Study 

CH4 Methane 

CI Confidence interval 

Co2 Carbon dioxide 

DOES Dubbo Osteoporosis Epidemiology Study 

EPC Evidence-based Practice Center 

EPIC European Prospective Investigation into Cancer and Nutrition 

EPOS European Prospective Osteoporosis Study 

EVOS European Vertebral Osteoporosis Study 

g Gram 

GI Gastrointestinal 

GRADE Grades of Recommendation Assessment, Development, and Evaluation 

H2 Hydrogen gas 

IBS Irritable bowel syndrome 

kg Kilogram 

L Liter 

LCT Lactase gene 

LI Lactose intolerance 

LM Lactose malabsorption 

mg Milligram 

ml Milliliter 

NHANES National Health and Nutrition Examination Survey 

NIH National Institutes of Health 

OMAR Office of Medical Applications of Research 

OR Odds ratio 

ppm Parts per million 

RCT Randomized controlled trial 

SNP Single nucleotide polymorphism 

TEP Technical Expert Panel 

157
 
Appendix A. Technical Expert Panel Members and Affiliation 

TEP Member Affiliation 

Melvin Heyman, MD School of Medicine 

University of California 

San Francisco, California 

Jay Perman, MD College of Medicine 

Chandler Medical Center 

Lexington, Kentucky 

Frederick Suchy, MD Pediatric Gastroenterology 

Mount Sinai Hospital 

New York, New York 

158
 
-------------------------------------------------------------------------------- 

-------------------------------------------------------------------------------- 

Appendix B. Search Strings 

Q1 

Database: Ovid MEDLINE(R) 

Search Strategy: 

1 lactose intoleran*.mp. or exp Lactose Intolerance/ (2726) 

2 milk intoleran*.mp. (286) 

3 lactose malabsor*.mp. (493) 

4 exp Lactase/ or lactase deficien*.mp. (961) 

5 prevalen*.mp. or exp Prevalence/ (325492) 

6 exp Population/ or population.mp. (682952) 

7 exp Lactose Tolerance Test/ (313) 

8 4 or 1 or 3 or 7 or 2 (3490) 

9 6 or 5 (914652) 

10 8 and 9 (515) 

11 exp Cohort Studies/ (694867) 

12 11 or 5 (980226) 

13 8 and 12 (424) 

14 limit 13 to (english language and humans) (365) 

15 remove duplicates from 14 (362) 

Q2 

Database: Ovid MEDLINE(R) 

Search Strategy: 

1 exp Lactose Intolerance/dh [Diet Therapy] (185) 

2 limit 1 to english language (131) 

3 exp epidemiologic studies/ (1121620) 

4 3 and 2 (12) 

5 (lactose restricted or lactose free).mp. (242) 

6 dairy exclusion.mp. (0) 

7 dairy free.mp. (9) 

8 7 or 5 (251) 

9 8 and 3 (36) 

10 limit 9 to english language (28) 

11 4 or 10 (35) 

159
 
-------------------------------------------------------------------------------- 

Database: Ovid MEDLINE(R) 

Search Strategy: 

1 exp lactose/df (9) 

2 hypolactas$.mp. (181) 

3 (lactose adj2 free).mp. [mp=title, original title, abstract, name of substance word, subject 

heading word] (273) 

4 (dairy adj2 free).mp. [mp=title, original title, abstract, name of substance word, subject 

heading word] (42) 

5 (dairy adj2 exclu$).mp. (12) 

6 low lactose.mp. (123) 

7 limited lactose.mp. (2) 

8 (lactose adj2 restrict$).mp. (38) 

9 (dairy adj2 restrict$).mp. (19) 

10 exp Lactose Intolerance/ (2478) 

11 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 (2902) 

12 exp Diet/ (144995) 

13 dh.fs. (29635) 

14 diet$.mp. (372626) 

15 13 or 12 or 14 (405928) 

16 11 and 15 (933) 

17 exp Bone Density/ (28018) 

18 exp "Bone and Bones"/ (382334) 

19 exp Osteoporosis/ (33396) 

20 exp Fractures, Bone/ (108442) 

21 exp Bone Diseases/ (318865) 

22 21 or 18 or 19 or 17 or 20 (653576) 

23 22 and 16 (51) 

24 exp Treatment Outcome/ (371740) 

25 "Outcome and Process Assessment (Health Care)"/ (16843) 

26 outcome$.mp. (801020) 

27 25 or 24 or 26 (813119) 

28 27 and 16 (45) 

29 ep.fs. (828160) 

30 exp Epidemiologic Studies/ (1087836) 

31 exp Epidemiologic Methods/ (2978476) 

32 30 or 31 or 29 (3265926) 

33 32 and 16 (290) 

34 33 or 28 or 23 (341) 

35 limit 34 to (english language and humans) (298) 

36 limit 35 to journal article (293) 

37 limit 35 to (case reports or comment or editorial or letter or "review") (66) 

38 36 not 37 (232) 

160
 
MEDLINE® via Pubmed 

Search "Diet, Vegetarian"[Mesh] AND calcium Limits: Humans, Journal Article, English 158 

Search "Diet, Vegetarian"[Mesh] AND relative risk AND dairy Limits: Humans, Journal 20 

Article, English, All Adult: 19+ years, Preschool Child: 2-5 years, Child: 6-12 years, 

Adolescent: 13-18 years 

Search "Diet, Vegetarian"[Mesh] AND relative risk Limits: Humans, Journal Article, English, 279 

All Adult: 19+ years, Preschool Child: 2-5 years, Child: 6-12 years, Adolescent: 13-18 years 

Search "Diet, Vegetarian"[Mesh] AND lactose Limits: Humans, Journal Article, English, All 4 

Adult: 19+ years, Preschool Child: 2-5 years, Child: 6-12 years, Adolescent: 13-18 years 

Search "Diet, Vegetarian"[Mesh] AND lactose free Limits: Humans, Journal Article, English, 0 

All Adult: 19+ years, Preschool Child: 2-5 years, Child: 6-12 years, Adolescent: 13-18 years 

Search "Diet, Vegetarian"[Mesh] AND cancer Limits: Humans, Journal Article, English, All 156 

Adult: 19+ years, Preschool Child: 2-5 years, Child: 6-12 years, Adolescent: 13-18 years 

Search "Diet, Vegetarian"[Mesh] AND bone Limits: Humans, Journal Article, English, All 46 

Adult: 19+ years, Preschool Child: 2-5 years, Child: 6-12 years, Adolescent: 13-18 years 

Search avoidance AND "Calcium, Dietary"[Mesh] AND "Dairy Products"[Mesh] Limits: 8 

Humans, Journal Article, English 

Search intolerance AND "Calcium, Dietary"[Mesh] AND "Dairy Products"[Mesh] Limits: 35 

Humans, Journal Article, English 

Search "Calcium, Dietary"[Mesh] AND "Dairy Products"[Mesh] Limits: Humans, Journal 517 

Article, English 

Search "Calcium, Dietary"[Mesh] AND relative risk AND lactose intolerance Limits: 22 

Humans, Journal Article, English 

Scirus 

1-10 of 23 hits for"Lactose-free diet" (fracture) 

161
 
-------------------------------------------------------------------------------- 

-------------------------------------------------------------------------------- 

Q3 

Database: Ovid MEDLINE(R) 

Search Strategy: 

1 exp epidemiologic studies/ (1121620) 

2 exp lactose intolerance/ (2583) 

3 exp Lactose Tolerance Test/ (329) 

4 3 and 2 (268) 

5 1 and 4 (19) 

6 limit 5 to english language (18) 

7 exp lactose/ad (469) 

8 7 and 2 (117) 

9 8 and 1 (13) 

10 limit 9 to english language (13) 

11 6 or 10 (27) 

12 lactose intake.mp. (63) 

13 1 and 12 and 2 (8) 

14 limit 13 to english language (6) 

15 11 or 14 (30) 

Q4 

Database: Ovid MEDLINE(R) 

Search Strategy: 

1 exp epidemiologic studies/ (1121620) 

2 exp Lactose Intolerance/dh, su, dt, th [Diet Therapy, Surgery, Drug Therapy, Therapy] (413) 

3 1 and 2 (20) 

4 limit 3 to english language (16) 

5 exp lactose intolerance/ (2583) 

6 limit 5 to "therapy (optimized)" (114) 

7 1 and 6 (11) 

8 limit 7 to english language (11) 

9 4 or 8 (24) 

MEDLINE® via Pubmed 

"Probiotics"[Mesh] AND "lactose intolerance" Limits: Humans, Journal Article, English 45 

probiotics 

Search lactose-free AND "lactose intolerance" Limits: Humans, Journal Article, English 55 

162
 
-------------------------------------------------------------------------------- 

Q5 

Database: Ovid MEDLINE(R) 

Search Strategy: 

1 exp Lactose Intolerance/ (2583) 

2 td.fs. (203594) 

3 1 and 2 (4) 

4 from 3 keep 1 (1) 

5 future research.mp. (21817) 

6 research need$.mp. (2549) 

7 trend$.mp. (147898) 

8 1 and 5 (2) 

9 6 and 1 (0) 

10 1 and 7 (14) 

11 8 or 4 or 10 (17) 

12 from 11 keep 1-2,11-13 (5) 

13 further investigation.mp. (26459) 

14 1 and 13 (6) 

15 from 14 keep 2,4-5 (3) 

16 12 or 15 (7) 

17 understanding.mp. (243623) 

18 1 and 17 (14) 

19 from 18 keep 1,3 (2) 

20 from 18 keep 1,3,6-11,13 (9) 

21 19 or 16 or 20 (16) 

The broader preliminary literature search in MEDLINE® via Pubmed can be summarized as 

follows: 

Relevant MeSH terms Number 

identified 

"Lactose Intolerance"[Mesh] 2461 

"Lactose Intolerance"[Mesh] NOT review NOT comment Limits: Humans, Journal 

Article, English 

1355 

"Lactose Intolerance"[Mesh] AND "Epidemiologic Studies"[Mesh] Limits: Humans, 

English 

122 

"Lactose Intolerance"[Mesh] Limits: Humans, Randomized Controlled Trial, English 84 

Additionally, the Cochrane Central Register of Controlled Trials (CENTRAL) was searched using 

the terms “lactose OR lactase”, which yielded 792 references. 

163 
 

Appendix C. List of Excluded Studies 

1. Lactase deficiency. N Engl J Med 1965 Nov 11; 273(20):1108-9. Not relevant to key 

questions 

2. Synthetic foods and deficiency states. Lancet 1965 Nov 6; 2(7419):937-8. Not relevant to key 

questions 

3. Primary intestinal lactase deficiency. Nutr Rev 1967 Sep; 25(9):265-70. Not relevant to key 

questions 

4. Recurrent abdominal pain. Pediatrics 1970 Dec; 46(6):968-75. Not relevant to key questions 

5. Correspondence re iron fortified formulas. Pediatrics 1971 Jul; 48(1):152-6 passim. Not 

relevant to key questions 

6. Background information on lactose and milk intolerance. A statement of the Food and 

Nutrition Board Division of Biology and Agriculture, National Research Council. Nutr Rev 

1972 Aug; 30(8):175-6. Review 

7. Lactose intolerance in Greeks. Lancet 1973 Feb 17; 1(7799):367-8. Not relevant to key 

questions 

8. American Academy of Pediatrics Committee on Nutrition. Should milk drinking by children 

be discouraged? Pediatrics 1974 Apr; 53(4):576-82. Not relevant to key questions 

9. Editorial: Lactase deficiency. Lancet 1975 Nov 8; 2(7941):910-1. Editorial 

10. Editorial: When does lactose malabsorption matter in adults? Br Med J 1975 May 17; 

2(5967):351-2. Editorial 

11. Soy-based formulas for infants. Med Lett Drugs Ther 1976 Nov 19; 18(24):104. Not relevant 

to key questions 

12. The lactose intolerance test and milk consumption. Nutr Rev 1976 Oct; 34(10):302-4. Not 

relevant to key questions 

13. Clinical case presentation: diarrhea following tube feeding. JPEN J Parenter Enteral Nutr 

1978; 2(1):41-2. Not relevant to key questions 

14. From the NIH: Recurrent abdominal pain in a healthy school-aged child can be lactose 

intolerance. JAMA 1979 Dec 14; 242(24):2670. Not relevant to key questions 

15. Metabolic bone disease as a result of lactase deficiency. Nutr Rev 1979 Mar; 37(3):72-3. 

Comment 

16. Efficacy and indications of ursodeoxycholic acid treatment for dissolving gallstones. A 

multicenter double-blind trial. Tokyo Cooperative Gallstone Study Group. Gastroenterology 

Vol 78; 1980: 542-8. Not lactose intolerance study 

17. Treatment of lactose intolerance. Med Lett Drugs Ther 1981 Jul 24; 23(15):67-8. Not relevant 

to key questions 

18. Soy-protein formulas: recommendations for use in infant feeding. Pediatrics 1983 Sep; 

72(3):359-63. Not relevant to key questions 

19. Nonpharmacological approaches to the control of high blood pressure. Final report of the 

Subcommittee on Nonpharmacological Therapy of the 1984 Joint National Committee on 

Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 1986 May; 

8(5):444-67. Guideline 

20. American Academy of Pediatrics Committee on Nutrition: Practical significance of lactose 

intolerance in children: supplement. Pediatrics 1990 Oct; 86(4):643-4. Not relevant to key 

questions 

164
 
21. Evaluation of an algorithm for the treatment of persistent diarrhoea: a multicentre study. 

International Working Group on Persistent Diarrhoea. Bulletin of the World Health 

Organization 1996; 74(5):479-89. Not relevant to key questions 

22. More lactose in your life? Health News 1999 Jan 5; 5(1):6. Not relevant to key questions 

23. Milk: got proof? We assess the evidence behind the dairy industry's ads and critics' claims. 

Consum Rep 2001 Sep; 66(9):62-3. Not relevant to key questions 

24. Information from your family doctor. Lactose intolerance. Am Fam Physician 2002 May 1; 

65(9):1855-6. Not relevant to key questions 

25. Probiotics: using bacteria to improve health. Harv Health Lett 2002 Mar; 27(5):1-3. Not 

relevant to key questions 

26. Why milk matters: questions and answers for professionals. Nutr Clin Care 2003 Oct-Dec; 

6(3):140-2. Review 

27. Got milk? No thanks! Up to 20% of Americans believe they're lactose intolerant. Just how 

intolerant varies with the person and the food. Harv Health Lett 2003 Dec; 29(2):6-7. Not 

relevant to key questions 

28. Position of the American Dietetic Association and Dietitians of Canada: vegetarian diets. Can 

J Diet Pract Res 2003 Summer; 64(2):62-81. Guideline 

29. Asthma inhalers may pose risks in the milk-allergic child. Child Health Alert 2005 Jan; 23:1­

2. Not relevant to key questions 

30. Lactose intolerance in children and adolescents. Child Health Alert 2006 Oct; 24:3. Not 

relevant to key questions 

31. I love milk, but I notice that as I get older I seem to tolerate it less--experiencing gas and 

bloating. Is this normal? Mayo Clin Womens Healthsource 2006 May; 10(5):10. Not relevant 

to key questions 

32. Aalberts JS, Weegels PL, van der Heijden L, et al. Calcium supplementation: effect on blood 

pressure and urinary mineral excretion in normotensive male lactoovovegetarians and 

omnivores. Am J Clin Nutr 1988 Jul; 48(1):131-8. Not eligible outcomes 

33. Abate G, Taormina F, Brillante C, et al. [The effects of the carbocalcitonin + arginine-lysinelactose combination in senile involutional osteoporosis]. Minerva medica Vol 85; 1994: 253­

9. Not lactose intolerance study 

34. Abbas H. A genetic study of lactose digestion in Pakistani families. Indian J Med Sci 1984 

Jul; 38(7):129-33. Not relevant to key questions 

35. Abbas H. Primary adult hypolactasia. J Pak Med Assoc 1985 Feb; 35(2):55-7. Not relevant to 

key questions 

36. Abbas H, Ahmad M. Persistence of high intestinal lactase activity in Pakistan. Hum Genet 

1983; 64(3):277-8. Not relevant to key questions 

37. Abbott WG, Tasman-Jones C. Incidence of acquired primary hypolactasia in three New 

Zealand racial groups. N Z Med J 1985 Apr 10; 98(776):228-9. Not relevant to key questions 

38. Abdo-Bassols F, Lifshitz F, Del Castillo ED, et al. Transient lactose intolerance in premature 

infants. Pediatrics 1971 Nov; 48(5):816-21. Not relevant to key questions 

39. Abdulla M. Public health/clinical significance of inorganic chemical elements. Experientia 

Suppl 1983; 44:339-55. Not eligible outcomes 

40. Abdulla M, Andersson I, Asp NG, et al. Nutrient intake and health status of vegans. Chemical 

analyses of diets using the duplicate portion sampling technique. Am J Clin Nutr 1981 Nov; 

34(11):2464-77. Not relevant to key questions 

165
 
 

41. Abelow BJ, Holford TR, Insogna KL. Cross-cultural association between dietary animal 

protein and hip fracture: a hypothesis. Calcif Tissue Int 1992 Jan; 50(1):14-8. Secondary data 

analysis 

42. Abraham G, Varsha P, Mathew M, et al. Malnutrition and nutritional therapy of chronic 

kidney disease in developing countries: the Asian perspective. Adv Ren Replace Ther 2003 

Jul; 10(3):213-21. Review 

43. Abraham JM, Levin B, Oberholzer VG, et al. Glucose-galactose malabsorption. Arch Dis 

Child 1967 Dec; 42(226):592-7. Not relevant to key questions 

44. Abramowitz A, Granot E, Tamir I, et al. Two-hour lactose breath hydrogen test. J Pediatr 

Gastroenterol Nutr 1986 Jan; 5(1):130-3. Not relevant to key questions 

45. Abrams SA, Griffin IJ, Davila PM. Calcium and zinc absorption from lactose-containing and 

lactose-free infant formulas. The American journal of clinical nutrition Vol 76; 2002: 442-6. 

Not lactose intolerance 

46. Acheson KJ, Ravussin E, Schoeller DA, et al. Two-week stimulation or blockade of the 

sympathetic nervous system in man: influence on body weight, body composition, and twenty 

four-hour energy expenditure. Metabolism: clinical and experimental Vol 37; 1988: 91-8. Not 

lactose intolerance study 

47. Acosta PB. Availability of essential amino acids and nitrogen in vegan diets. Am J Clin Nutr 

1988 Sep; 48(3 Suppl):868-74. Review 

48. Addolorato G, Marsigli L, Capristo E, et al. Anxiety and depression: a common feature of 

health care seeking patients with irritable bowel syndrome and food allergy. HepatoGastroenterology 1998 Sep-Oct; 45(23):1559-64. No prevalence data 

49. Afzal N, Thomson M. Diarrhoea and gastroenteritis in the infant and young child. J Fam 

Health Care 2002; 12(6):146-50. Review 

50. Agampodi SB, Agampodi TC, Piyaseeli UK. Breastfeeding practices in a public health field 

practice area in Sri Lanka: a survival analysis. Int Breastfeed J 2007; 2:13. Not relevant to key 

questions 

51. Agarwal MM, Khandelwal N, Mandal AK, et al. Factors affecting bone mineral density in 

patients with prostate carcinoma before and after orchidectomy. Cancer 2005 May 15; 

103(10):2042-52. Not eligible target population 

52. Agarwal MM, Rana SV, Mandal AK, et al. Lactose intolerance in prostate cancer patients: 

incidence and associated factors. Scandinavian Journal of Gastroenterology 2008 Mar; 

43(3):270-6. No prevalence data 

53. Aggett PJ, More J, Thorn JM, et al. Evaluation of the trace metal supplements for a synthetic 

low lactose diet. Arch Dis Child 1983 Jun; 58(6):433-7. Not relevant to key questions 

54. Agte V, Chiplonkar S, Joshi N, et al. Apparent absorption of copper and zinc from composite 

vegetarian diets in young Indian men. Ann Nutr Metab 1994; 38(1):13-9. Not relevant to key 

questions 

55. Aguilo A, Tauler P, Fuentespina E, et al. Antioxidant diet supplementation influences blood 

iron status in endurance athletes. International journal of sport nutrition and exercise 

metabolism Vol 14; 2004: 147-60. Not lactose intolerance study 

56. Agustina R, Lukito W, Firmansyah A, et al. The effect of early nutritional supplementation 

with a mixture of probiotic, prebiotic, fiber and micronutrients in infants with acute diarrhea 

in Indonesia. Asia Pacific journal of clinical nutrition Vol 16; 2007: 435-42. Not lactose 

intolerance study 

166
 
57. Ahlskog JE, Muenter MD, Bailey PA, et al. Parkinson's disease monotherapy with controlledrelease MK-458 (PHNO): double-blind study and comparison to carbidopa/levodopa. Clinical 

neuropharmacology Vol 14; 1991: 214-27. Not lactose intolerance study 

58. Aires CP, Tabchoury CM, Del BCAA, et al. Cariogenicity of sweetners containing lactose - 

in situ study in root dentine (AADR Abstract Annual Meeting March 7-10 2001). Journal of 

Dental Research Vol 80; 2001: 119 (Abs No 665). Not lactose intolerance study 

59. Aires CP, Tabchoury CP, Del BCAA, et al. Effect of a lactose-containing sweetener on root 

dentine demineralization in situ. Caries research Vol 36; 2002: 167-9. Not lactose intolerance 

study 

60. Alarcon P, Montoya R, Perez F, et al. Clinical trial of home available, mixed diets versus a 

lactose-free, soy-protein formula for the dietary management of acute childhood diarrhea. 

Journal of pediatric gastroenterology and nutrition Vol 12; 1991: 224-32. Not lactose 

intolerance study 

61. Albani S, Avanzini MA, Plebani A, et al. Diagnostic value of a lymphocyte stimulation test in 

cow milk protein intolerance. Ann Allergy 1989 Dec; 63(6 Pt 1):489-92. Not relevant to key 

questions 

62. Alexander D, Ball MJ, Mann J. Nutrient intake and haematological status of vegetarians and 

age-sex matched omnivores. Eur J Clin Nutr 1994 Aug; 48(8):538-46. Not relevant to key 

questions 

63. Alexander FW. Chronic diarrhoea of unknown cause with response to steroids. Proc R Soc 

Med 1973 Nov; 66(11):1067-8. Not relevant to key questions 

64. Alford SC. Lactose intolerance in Asians. Nature 1969 Feb 8; 221(5180):562-3. Not relevant 

to key questions 

65. Alfven G. One hundred cases of recurrent abdominal pain in children: diagnostic procedures 

and criteria for a psychosomatic diagnosis.[erratum appears in Acta Paediatr. 2003 

May;92(5):641]. Acta Paediatrica 2003; 92(1):43-9. No prevalence data 

66. Al-Habbal MJ, Al-Habbal Z, Huwez FU. A double-blind controlled clinical trial of mastic 

and placebo in the treatment of duodenal ulcer. Clin Exp Pharmacol Physiol Vol 11; 1984: 

541-4. Not lactose intolerance study 

67. Allan SJ, Kavanagh GM, Herd RM, et al. The effect of inositol supplements on the psoriasis 

of patients taking lithium: a randomized, placebo-controlled trial. The British journal of 

dermatology Vol 150; 2004: 966-9. Not lactose intolerance study 

68. Allen UD, McLeod K, Wang EE. Cow's milk versus soy-based formula in mild and moderate 

diarrhea: a randomized, controlled trial. Acta paediatrica (Oslo, Norway : 1992) Vol 83; 

1994: 183-7. Not relevant to key questions 

69. Alm L. Effect of fermentation on lactose, glucose, and galactose content in milk and 

suitability of fermented milk products for lactose intolerant individuals. J Dairy Sci 1982 

Mar; 65(3):346-52. Not relevant to key questions 

70. Almeida JA, Kim R, Stoita A, et al. Lactose malabsorption in the elderly: role of small 

intestinal bacterial overgrowth. Scandinavian Journal of Gastroenterology 2008; 43(2):146­

54. Ineligible number of subjects 

71. Almendingen K, Trygg K, Hofstad B, et al. Results from two repeated 5 day dietary records 

with a 1 y interval among patients with colorectal polyps. European journal of clinical 

nutrition Vol 55; 2001: 374-9. Not lactose intolerance study 

72. Almy TP. Editorial: Evolution, lactase levels, and global hunger. N Engl J Med 1975 May 29; 

292(22):1183-4. Editorial 

167
 
73. Alpers DH, Gerber JE. Monosaccharide inhibition of human intestinal lactase. J Lab Clin 

Med 1971 Aug; 78(2):265-74. Not relevant to key questions 

74. Al-Sanae H, Saldanha W, Sugathan TN, et al. Comparison of lactose intolerance in healthy 

Kuwaiti and Asian volunteers. Medical Principles & Practice 2003 Jul-Sep; 12(3):160-3. 

Ineligible number of subjects 

75. Alvarez-Coca J, Perez-Miranda M, Iritia M, et al. Usefulness of urinary galactose for 

diagnosis of hypolactasia. J Clin Gastroenterol 1996 Jul; 23(1):79-80. Not relevant to key 

questions 

76. Alves MN, Ferrari-Auarek WM, Pinto KM, et al. Effects of caffeine and tryptophan on rectal 

temperature, metabolism, total exercise time, rate of perceived exertion and heart rate. 

Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas 

e biológicas / Sociedade Brasileira de Biofísica ... [et al.] Vol 28; 1995: 705-9. Not lactose 

intolerance study 

77. Alzate H, Gonzalez H, Guzman J. Lactose intolerance in South American Indians. Am J Clin 

Nutr 1969 Feb; 22(2):122-3. Not relevant to key questions 

78. Ambroszkiewicz J, Klemarczyk W, Gajewska J, et al. Serum concentration of biochemical 

bone turnover markers in vegetarian children. Adv Med Sci 2007; 52:279-82. Not eligible 

exposure 

79. Ameen VZ, Powell GK. Quantitative fecal carbohydrate excretion in premature infants. The 

American journal of clinical nutrition Vol 49; 1989: 1238-42. Not lactose intolerance study 

80. Ameen VZ, Shivpuri C, King RC. Total fecal carbohydrate (CHO) and short chain fatty acid 

(SCFA) excretion in prematures fed 100% lactose (L) vs 50% lactose plus 50% glucose 

polymers (GP). Pediatric Research Vol 23; 1988: 297a. Not lactose intolerance study 

81. Anand AN, Seshadri S. A quantitative model for prediction of iron bioavailability from 

Indian meals: an experimental study. Int J Food Sci Nutr 1995 Nov; 46(4):335-42. Not 

eligible outcomes 

82. Anderson B, Vullo C. Did malaria select for primary adult lactase deficiency? Gut 1994 Oct; 

35(10):1487-9. Not relevant to key questions 

83. Anderson TW, Reid DB. A double-blind trial of vitamin E in angina pectoris. The American 

journal of clinical nutrition Vol 27; 1974: 1174-8. Not lactose intolerance study 

84. Andersson DE, Nygren A. Four cases of long-standing diarrhoea and colic pains cured by 

fructose-free diet--a pathogenetic discussion. Acta Med Scand 1978; 203(1-2):87-92. Not 

relevant to key questions 

85. Andersson-Wenckert I, Blomquist HK, Fredrikzon B. Oral health in coeliac disease and cow's 

milk protein intolerance. Swed Dent J 1984; 8(1):9-14. Not relevant to key questions 

86. Andiran F, Dayi S, Mete E. Cows milk consumption in constipation and anal fissure in 

infants and young children. J Paediatr Child Health 2003 Jul; 39(5):329-31. Not relevant to 

key questions 

87. Andrews BF, Cook LN. Low birth-weight infants fed a new carbohydrate-free formula with 

different sugars. I. Growth and clinical course. The American journal of clinical nutrition Vol 

22; 1969: 845-50. Not lactose intolerance study 

88. Angelides AG, Davidson M. Lactose intolerance and diarrhea: are they related? Pediatr Ann 

1985 Jan; 14(1):62-3, 6-7, 70-1 passim. Not relevant to key questions 

89. Anh NT, Thuc TK, Welsh JD. Lactose malabsorption in adult Vietnamese. Am J Clin Nutr 

1977 Apr; 30(4):468-9. Not relevant to key questions 

168
 
90. Anonymous. Intal compound for asthma. Drug & Therapeutics Bulletin Vol 6; 1968: 37-8. 

Not lactose intolerance study 

91. Ansari Z, Malik AS, Dutta AK, et al. Prevalence of sugar intolerance in diarrhoea of infancy 

and childhood. Indian Pediatrics 1979 Oct; 16(10):879-85. No prevalence data 

92. Anslow JA, Balm TK, Hooper JW, et al. Minimization of gastric damage with enteric-coated 

aspirin granules compared to buffered aspirin. Pharmacology Vol 30; 1985: 40-4. Not lactose 

intolerance study 

93. Anthoni S, Elg P, Haahtela T, et al. Should milk-specific IgE antibodies be measured in 

adults in primary care? Scandinavian Journal of Primary Health Care 2008 Dec; 26(4):197­

202. No prevalence data 

94. Antia FP. Lactase deficiency a realistic approach. J Assoc Physicians India 1979 Feb; 

27(2):152-4. Not relevant to key questions 

95. Antonowicz I, Reddy V, Khaw KT, et al. Lactase deficiency in patients with cystic fibrosis. 

Pediatrics 1968 Sep; 42(3):492-500. Not relevant to key questions 

96. Arashima S, Matsuda I, Sato N, et al. Intestinal disaccharidase activity in an infant with 

lactose intolerance. Helv Paediatr Acta 1971 Jun; 26(2):215-9. Not relevant to key questions 

97. Araya M, Baiocchi N, Espinoza J, et al. Persistent diarrhoea in the community. 

Characteristics and risk factors. Acta Paediatr Scand 1991 Feb; 80(2):181-9. Not relevant to 

key questions 

98. Ariyoshi Y, Ota K, Taguchi T, et al. [Anti-emetic effect and safety of ondansetron tablet in 

double-blind comparison with placebo]. Gan to kagaku ryoho. Cancer & chemotherapy Vol 

19; 1992: 2057-70. Not lactose intolerance study 

99. Arlettaz A, Portier H, Lecoq AM, et al. Effects of short-term prednisolone intake during 

submaximal exercise. Medicine and science in sports and exercise Vol 39; 2007: 1672-8. Not 

lactose intolerance study 

100. Armitstead J, Kelly D, Walker-Smith J. Evaluation of infant feeding in acute gastroenteritis. 

Journal of pediatric gastroenterology and nutrition Vol 8; 1989: 240-4. Not relevant to key 

questions 

101. Arnold AJ, Simpson JG, Jones HE, et al. Suppression of histamine-induced pruritus by 

hydroxyzine and various neuroleptics. Journal of the American Academy of Dermatology Vol 

1; 1979: 509-12. Not lactose intolerance study 

102. Aro A, Pelkonen R, Leino U. Glucose and insulin responses to meals containing milk, 

lactose, glucose or fructose in subjects with non-insulin-dependent diabetes. Diabète & 

métabolisme Vol 13; 1987: 603-6. Not relevant to key questions 

103. Arola H. The strip test for hypolactasia also works without ethanol. Scand J Gastroenterol 

1988 Sep; 23(7):851-5. Not relevant to key questions 

104. Arola H, Koivula T, Jokela H, et al. Simple urinary test for lactose malabsorption. Lancet 

1982 Sep 4; 2(8297):524-5. Not relevant to key questions 

105. Arola H, Koivula T, Jokela H, et al. Comparison of indirect diagnostic methods for 

hypolactasia. Scand J Gastroenterol 1988 Apr; 23(3):351-7. Not relevant to key questions 

106. Arola H, Koivula T, Jokela H, et al. Strip test is reliable in common prevalences of 

hypolactasia. Scandinavian Journal of Gastroenterology 1987 May; 22(4):509-12. No 

prevalence data 

107. Arola H, Sillanaukee P, Aine E, et al. Galactitol is not a cause of senile cataract. Graefes Arch 

Clin Exp Ophthalmol 1992; 230(3):240-2. Not relevant to key questions 

169
 
108. Arrigoni E, Marteau P, Briet F, et al. Tolerance and absorption of lactose from milk and 

yogurt during short-bowel syndrome in humans. Am J Clin Nutr 1994 Dec; 60(6):926-9. Not 

relevant to key questions 

109. Arthur AB, Clayton BE, Cottom DG, et al. Importance of disaccharide intolerance in the 

treatment of coeliac disease. Lancet 1966 Jan 22; 1(7430):172-4. Not relevant to key 

questions 

110. Arunachalam K, Gill HS, Chandra RK. Enhancement of natural immune function by dietary 

consumption of Bifidobacterium lactis (HN019). European journal of clinical nutrition 2000 

Mar; 54(3):263-7. Not relevant to key questions 

111. Arvanitakis C, Chen GH, Folscroft J, et al. Lactase deficiency--a comparative study of 

diagnostic methods. American Journal of Clinical Nutrition 1977 Oct; 30(10):1597-602. 

Ineligible number of subjects 

112. Ashraf H, Ahmed S, Fuchs GJ, et al. Persistent diarrhoea: associated infection and response 

to a low lactose diet. Journal of tropical pediatrics 2002 Jun; 48(3):142-8. Not relevant to key 

questions 

113. Asmawi MZ, Seppo L, Vapaatalo H, et al. Hypolactasia & lactose intolerance among three 

ethnic groups in Malaysia. Indian Journal of Medical Research 2006 Dec; 124(6):697-704. 

Not eligible test for lactose malabsorption 

114. Asp NG. Human small-intestinal -galactosidases. Separation and characterization of three 

forms of an acid -galactosidase. Biochem J 1971 Jan; 121(2):299-308. Not relevant to key 

questions 

115. Asp NG, Berg NO, Dahlqvist A, et al. The activity of three different small-intestinal ­

galactosidases in adults with and without lactase deficiency. Scand J Gastroenterol 1971; 

6(8):755-62. Not relevant to key questions 

116. Asp NG, Dahlqvist A. Multiplicity of intestinal beta-galactosidases. Contribution of each 

enzyme to the total lactase activity in normal and lactose-intolerant patients. Acta Paediatr 

Scand 1971 May; 60(3):364-5. Not relevant to key questions 

117. Asp NG, Dahlqvist A. Human small intestine -galactosidases: specific assay of three different 

enzymes. Anal Biochem 1972 Jun; 47(2):527-38. Not relevant to key questions 

118. Asp NG, Dahlqvist A. Intestinal beta-galactosidases in adult low lactase activity and in 

congenital lactase deficiency. Enzyme 1974; 18(1):84-102. Not relevant to key questions 

119. Asp NG, Dahlqvist A, Koldovsky O. Human small-intestinal beta-galactosidases. Separation 

and characterization of one lactase and one hetero beta-galactosidase. Biochem J 1969 Sep; 

114(2):351-9. Not relevant to key questions 

120. Asp NG, Dahlqvist A, Kuitunen P, et al. Complete deficiency of brush-border lactase in 

congenital lactose malabsorption. Lancet 1973 Aug 11; 2(7824):329-30. Not relevant to key 

questions 

121. Atkins D, Briss PA, Eccles M, et al. Systems for grading the quality of evidence and the 

strength of recommendations II: pilot study of a new system. BMC Health Serv Res 2005 

Mar 23; 5(1):25. Not relevant to key questions 

122. Atkins D, Eccles M, Flottorp S, et al. Systems for grading the quality of evidence and the 

strength of recommendations I: critical appraisal of existing approaches The GRADE 

Working Group. BMC Health Serv Res 2004 Dec 22; 4(1):38. Not relevant to key questions 

123. Auld G, Boushey CJ, Bock MA, et al. Perspectives on intake of calcium-rich foods among 

Asian, Hispanic, and white preadolescent and adolescent females. J Nutr Educ Behav 2002 

Sep-Oct; 34(5):242-51. Not eligible outcomes 

170
 
124. Auricchio S. Lactase deficiency phenotype has not been selected by malaria.[comment]. 

Italian Journal of Gastroenterology & Hepatology 1998 Oct; 30(5):494-5. No prevalence data 

125. Aurisicchio LN, Pitchumoni CS. Lactose intolerance. Recognizing the link between diet and 

discomfort. Postgraduate Medicine 1994 1994 Jan; 95(1):113-6. Not original research 

126. Avni EF, Van Gansbeke D, Rodesch P, et al. Sonographic demonstration of malabsorption in 

neonates. J Ultrasound Med 1986 Feb; 5(2):85-7. Not relevant to key questions 

127. Aziz EM. Neonatal pneumatosis intestinalis associated with milk intolerance. Am J Dis Child 

1973 Apr; 125(4):560-2. Not relevant to key questions 

128. Babb RR. Coffee, sugars, and chronic diarrhea. Why a dietary history is important. Postgrad 

Med 1984 Jun; 75(8):82, 6-7. Not relevant to key questions 

129. Baer D. Lactase deficiency and yogurt. Soc Biol 1970 Jun; 17(2):143. Not relevant to key 

questions 

130. Bahk YW, Ahn GS. Lactose intolerance in the Koreans. Mod Med Asia 1977 Mar; 13(3):7-8. 

Not relevant to key questions 

131. Bahna SL. Cow's milk allergy versus cow milk intolerance. Annals of Allergy, Asthma, & 

Immunology 2002 Dec; 89(6 Suppl 1):56-60. No prevalence data 

132. Bain HW. Chronic vague abdominal pain in children. Pediatr Clin North Am 1974 Nov; 

21(4):991-1000. Not relevant to key questions 

133. Bakan R, Birmingham CL, Aeberhardt L, et al. Dietary zinc intake of vegetarian and 

nonvegetarian patients with anorexia nervosa. Int J Eat Disord 1993 Mar; 13(2):229-33. Not 

relevant to key questions 

134. Bakken AF. Letter: Intestinal lactase deficiency as a factor in the diarrhea of light-treated 

jaundiced infants. N Engl J Med 1976 Mar 11; 294(11):615. Not relevant to key questions 

135. Bakken AF. Temproary intestinal lactase deficiency in light-treated jaundiced infants. Acta 

Paediatr Scand 1977 Jan; 66(1):91-6. Not relevant to key questions 

136. Bakken AF. The application of the "Lojda" method for intestinal lactase in intestinal biopsies 

from jaundiced newborn infants. Histochemistry 1977 Mar 4; 51(2-3):253-5. Not relevant to 

key questions 

137. Bakken AF, Motzfeldt C. Intestinal lactase deficiency in newborns with cystic fibrosis-­

dietary consequences. Monogr Paediatr 1979; 10:5-7. Not relevant to key questions 

138. Bakry F, Sunoto, Hendardji H, et al. The severity of lactose intolerance in Indonesian 

children. Paediatr Indones 1973 Jul-Aug; 13(7):185-90. Not relevant to key questions 

139. Balanza E, Taboada G. The frequency of lactase phenotypes in Aymara children. J Med 

Genet 1985 Apr; 22(2):128-30. Not relevant to key questions 

140. Ball D, Maughan RJ. Blood and urine acid-base status of premenopausal omnivorous and 

vegetarian women. Br J Nutr 1997 Nov; 78(5):683-93. Not eligible outcomes 

141. Balslev I, Kramhoft J, Backer OG. Lactose malabsorption before and after truncal and 

selective vagotomy. Scand J Gastroenterol Suppl 1971; 9:71-4. Not relevant to key questions 

142. Bampoe V, Sapsford RJ, Avigad S, et al. Lactase degradation by human enteric bacteria. 

Lancet 1979 Jul 21; 2(8134):125-7. Not relevant to key questions 

143. Banai J, Surjan L, Szanto I, et al. Jejunoscopic lactose provocation. Gastroenterol Jpn 1984 

Apr; 19(2):127-30. Not relevant to key questions 

144. Bandera EV, Kushi LH, Moore DF, et al. Consumption of animal foods and endometrial 

cancer risk: a systematic literature review and meta-analysis. Cancer Causes Control 2007 

Nov; 18(9):967-88. Not eligible outcomes 

171
 
145. Barbeau A, Mars H, Botez MI, et al. Amantadine-HCl (Symmetrel) in the management of 

Parkinson's disease: a double-blind cross-over study. Canadian Medical Association journal 

Vol 105; 1971: 42-6 passim. Not lactose intolerance study 

146. Barillas C, Solomons NW. Effective reduction of lactose maldigestion in preschool children 

by direct addition of beta-galactosidases to milk at mealtime. Pediatrics 1987 May; 

79(5):766-72. Not relevant to key questions 

147. Barillas-Mury C, Solomons NW. Test-retest reproducibility of hydrogen breath test for 

lactose maldigestion in preschool children. J Pediatr Gastroenterol Nutr 1987 Mar-Apr; 

6(2):281-5. Not relevant to key questions 

148. Barnes GL. Management of sugar intolerance in children. N Z Med J 1976 Mar 10; 

83(559):149-51. Not relevant to key questions 

149. Barnes GL, Doyle LW, Hewson PH, et al. A randomised trial of oral gammaglobulin in lowbirth-weight infants infected with rotavirus. Lancet Vol 1; 1982: 1371-3. Not lactose 

intolerance study 

150. Baron ML. Assisting families in making appropriate feeding choices: cow's milk protein 

allergy versus lactose intolerance. Pediatr Nurs 2000 Sep-Oct; 26(5):516-20. Not relevant to 

key questions 

151. Barr RG, Hanley J, Patterson DK, et al. Breath hydrogen excretion in normal newborn infants 

in response to usual feeding patterns: evidence for "functional lactase insufficiency" beyond 

the first month of life. Journal of Pediatrics 1984 Apr; 104(4):527-33. Ineligible number of 

subjects 

152. Barr RG, Kushner DC. Roentgenographic observation of gas-fluid levels in the colon of 

children with abdominal pain and malabsorption of lactose. Can Med Assoc J 1985 May 15; 

132(10):1158-60. Not relevant to key questions 

153. Barr RG, Watkins JB, Perman JA. Mucosal function and breath hydrogen excretion: 

comparative studies in the clinical evaluation of children with nonspecific abdominal 

complaints. Pediatrics 1981 Oct; 68(4):526-33. Not relevant to key questions 

154. Barr RG, Wooldridge J, Hanley J. Effects of formula change on intestinal hydrogen 

production and crying and fussing behavior. J Dev Behav Pediatr 1991 Aug; 12(4):248-53. 

Not relevant to key questions 

155. Barrett-Connor E, Chang JC, Edelstein SL. Coffee-associated osteoporosis offset by daily 

milk consumption. The Rancho Bernardo Study. Jama 1994 Jan 26; 271(4):280-3. Not 

eligible outcomes 

156. Barrie H. Lactose malabsorption. Dev Med Child Neurol 1977 Jun; 19(3):402-3. Not relevant to 

key questions 

157. Barsotti G, Morelli E, Cupisti A, et al. A low-nitrogen low-phosphorus Vegan diet for patients 

with chronic renal failure. Nephron 1996; 74(2):390-4. Not eligible target population 

158. Bartholomew C, Pong OY. Lactose intolerance in East Indians of Trinidad. Trop Geogr Med 

1976 Dec; 28(4):336-8. Not relevant to key questions 

159. Bartlett K, Dobson JV, Eastham E. A new method for the detection of hydrogen in breath and 

its application to acquired and inborn sugar malabsorption. Clin Chim Acta 1980 Dec 8; 

108(2):189-94. Not relevant to key questions 

172
 
160. Bartrop RW, Hull D. Transient lactose intolerance in infancy. Arch Dis Child 1973 Dec; 

48(12):963-6. Not relevant to key questions 

161. Basford RL, Henry JB. Lactose intolerance in the adult. Postgrad Med 1967 Jan; 41(1):A70­

7. Not relevant to key questions 

162. Basran GS, Darbyshire JH, Nunn AJ, et al. Inhaled lactose-free sodium cromoglycate powder 

in the treatment of recurrent asthma. British journal of diseases of the chest Vol 78; 1984: 

254-60. Not lactose intolerance study 

163. Bassindale T, Cowan DA, Dale S, et al. Effects of oral administration of androstenedione on 

plasma androgens in young women using hormonal contraception. The Journal of clinical 

endocrinology and metabolism Vol 89; 2004: 6030-8. Not lactose intolerance study 

164. Batar I. Study of the efficacy of combined ColpoCleaner and Diflucan therapy. Magyar 

Noorvosok Lapja Vol 65; 2002: 41-4. Not lactose intolerance study 

165. Bates CJ, Evans PH, Allison G, et al. Biochemical indices and neuromuscular function tests 

in rural Gambian schoolchildren given a riboflavin, or multivitamin plus iron, supplement. 

The British journal of nutrition Vol 72; 1994: 601-10. Not lactose intolerance study 

166. Bayar N, Böke B, Turan E, et al. Efficacy of amitriptyline in the treatment of subjective 

tinnitus. The Journal of otolaryngology Vol 30; 2001: 300-3. Not lactose intolerance study 

167. Bayless TM. Recognition of lactose intolerance. Hosp Pract 1976 Oct; 11(10):97-102. Not 

relevant to key questions 

168. Bayless TM. Lactose intolerance in the adolescent. J Adolesc Health Care 1982 Aug; 3(1):65­

8. Not relevant to key questions 

169. Bayless TM, Huang SS. Inadequate intestinal digestion of lactose. Am J Clin Nutr 1969 Mar; 

22(3):250-6. Not relevant to key questions 

170. Bayless TM, Huang SS. Recurrent abdominal pain due to milk and lactose intolerance in 

school-aged children. Pediatrics 1971 Jun; 47(6):1029-32. Not relevant to key questions 

171. Bayless TM, Paige DM. Lactose intolerance. Curr Concepts Nutr 1979; 8:79-90. Not relevant 

to key questions 

172. Bayless TM, Paige DM, Ferry GD. Lactose intolerance and milk drinking habits. 

Gastroenterology 1971 Apr; 60(4):605-8. Not relevant to key questions 

173. Bayless TM, Partin JS, Rosensweig NS. Absence of milk antibodies in milk intolerance in 

adults. JAMA 1967 Jul 3; 201(1):128. Not relevant to key questions 

174. Bayless TM, Rosensweig NS. A racial difference in incidence of lactase deficiency. A survey 

of milk intolerance and lactase deficiency in healthy adult males. JAMA 1966 Sep 19; 

197(12):968-72. Not relevant to key questions 

175. Bayless TM, Rosensweig NS, Christopher N, et al. Milk intolerance and lactose tolerance 

tests. Gastroenterology 1968 Mar; 54(3):475-7. Not relevant to key questions 

176. Bayless TM, Rothfeld B, Massa C, et al. Lactose and milk intolerance: clinical implications. 

N Engl J Med 1975 May 29; 292(22):1156-9. Not eligible test for lactose malabsorption 

177. Beal D, Gillis JS. Methylphenidate hydrochloride and judgmental behavior in hyperkinetic 

children. Curr Ther Res, Clin Exp Vol 26; 1979: 931-9. Not lactose intolerance study 

178. Beau JP, Fontaine O, Garenne M. Management of malnourished children with acute 

diarrhoea and sugar intolerance. J Trop Pediatr 1989 Dec; 35(6):281-4. Not relevant to key 

questions 

179. Beau JP, Fontaine O, Garenne M. Management of malnourished children with acute 

diarrhoea and sugar intolerance. J Trop Pediatr 1990 Apr; 36(2):86-9. Not relevant to key 

questions 

173
 
180. Beck IT, Da Costa LR, Beck M. Sugar absorption by small bowel biopsy samples from 

patients with primary lactase deficiency and with adult celiac disease. Am J Dig Dis 1976 

Nov; 21(11):946-52. Not relevant to key questions 

181. Bedine MS, Bayless TM. Intolerance of small amounts of lactose by individuals with low 

lactase levels. Gastroenterology 1973 Nov; 65(5):735-43. Not relevant to key questions 

182. Beeken WL. Remediable defects in Crohn disease: a prospective study of 63 patients. 

Archives of Internal Medicine 1975 May; 135(5):686-90. No prevalence data 

183. Beeken WL, Kanich RE. Microbial flora of the upper small bowel in Crohn's disease. 

Gastroenterology 1973 Sep; 65(3):390-7. Not relevant to key questions 

184. Beilin LJ, Burke V. Vegetarian diet components, protein and blood pressure: which nutrients 

are important? Clin Exp Pharmacol Physiol 1995 Mar; 22(3):195-8. Review 

185. Bell RR, Draper HH, Bergan JG. Sucrose, lactose, and glucose tolerance in northern Alaskan 

Eskimos. Am J Clin Nutr 1973 Nov; 26(11):1185-90. Not relevant to key questions 

186. Bellati U, Liberati M. [Experience regarding the use of arginine-lysine-lactose treatment in 

menopausal osteoporosis]. Minerva medica Vol 85; 1994: 327-32. Not lactose intolerance 

study 

187. Benetos A, Xiao YY, Cuche JL, et al. Arterial effects of salt restriction in hypertensive 

patients. A 9-week, randomized, double-blind, crossover study. Journal of hypertension Vol 

10; 1992: 355-60. Not lactose intolerance study 

188. Bengtsson U, Knutson TW, Knutson L, et al. Increased levels of hyaluronan and albumin 

after intestinal challenge in adult patients with cow's milk intolerance. Clinical and 

experimental allergy : journal of the British Society for Allergy and Clinical Immunology Vol 

26; 1996: 96-103. Not relevant to key questions 

189. Ben-Yoseph Y, Momoi T, Baylerian MS, et al. Km defect in neuraminidase of dysmorphic 

type sialidosis with and without beta-galactosidase deficiency. Clin Chim Acta 1982 Aug 18; 

123(3):233-40. Not relevant to key questions 

190. Berezin S, Bhole A, Wu TC, et al. Abdominal distention associated with lactose 

malabsorption in a premature infant. N Y State J Med 1985 May; 85(5):227. Not relevant to 

key questions 

191. Berezin S, Schwarz SM, Glassman M, et al. Gastrointestinal milk intolerance of infancy.[see 

comment]. American Journal of Diseases of Children 1989 Mar; 143(3):361-2. Ineligible 

number of subjects 

192. Berg A, Eriksson M, Barany F, et al. Hydrogen concentration in expired air analyzed with a 

new hydrogen sensor, plasma glucose rise, and symptoms of lactose intolerance after oral 

administration of 100 gram lactose. Scand J Gastroenterol 1985 Sep; 20(7):814-22. Not 

relevant to key questions 

193. Berg NO, Borulf S, Jakobsson I, et al. How to approach the child suspected of malabsorption. 

Experience from a prospective investigation of suspected malabsorption in children 1968­

1976 in Malmo. Acta Paediatr Scand 1978 Jul; 67(4):403-11. Not relevant to key questions 

194. Berg NO, Dahlqvist A, Lindberg T. A boy with severe infantile gastrogen lactose intolerance 

and acquired lactase deficiency. Acta Paediatrica Scandinavica 1979 Sep; 68(5):751-8. 

Ineligible number of subjects 

195. Berg SB. Think before you drink milk. Dent Assist 1986 Jul-Aug; 55(4):21-2. Comment 

196. Bergoz R, Griessen M, Infante F, et al. Significance of duodenal disaccharidases. A 

comparative study of duodenal and jejunal values. Digestion 1981; 22(2):108-12. Not 

relevant to key questions 

174
 
197. Berkey CS, Rockett HR, Willett WC, et al. Milk, dairy fat, dietary calcium, and weight gain: 

a longitudinal study of adolescents. Arch Pediatr Adolesc Med 2005 Jun; 159(6):543-50. Not 

eligible outcomes 

198. Berlin CM, Jr., Tinker DE. Kwashiorker in a child in central Pennsylvania. A seven-year 

follow-up. American Journal of Diseases of Children 1982 Sep; 136(9):822-4. Not relevant to 

key questions 

199. Bernardes-Silva CF, Pereira AC, de Fatima Alves da Mota G, et al. Lactase persistence/nonpersistence variants, C/T_13910 and G/A_22018, as a diagnostic tool for lactose intolerance 

in IBS patients. Clin Chim Acta 2007 Nov-Dec; 386(1-2):7-11. Not relevant to key questions 

200. Bernhardt MK, Southard KA, Batterson KD, et al. The effect of preemptive and/or 

postoperative ibuprofen therapy for orthodontic pain. American journal of orthodontics and 

dentofacial orthopedics : official publication of the American Association of Orthodontists, 

its constituent societies, and the American Board of Orthodontics Vol 120; 2001: 20-7. Not 

lactose intolerance study 

201. Bernier GM, Gunderman JR, Ruymann FB. Kappa-chain deficiency. Blood 1972 Dec; 

40(6):795-805. Not relevant to key questions 

202. Bernstein CN, Ament M, Artinian L, et al. Milk tolerance in adults with ulcerative colitis. 

Am J Gastroenterol 1994 Jun; 89(6):872-7. Not relevant to key questions 

203. Bernstein JA, Bernstein DI, Stauder T, et al. A cross-sectional survey of sensitization to 

Aspergillus oryzae-derived lactase in pharmaceutical workers. Journal of Allergy & Clinical 

Immunology 1999 Jun; 103(6):1153-7. No prevalence data 

204. Berry GT, Nissim I, Gibson JB, et al. Quantitative assessment of whole body galactose 

metabolism in galactosemic patients. European journal of pediatrics 1997 Aug; 156(Suppl 

1):S43-9. Not relevant to key questions 

205. Besigye E, Kajubi SK. Experience with a radiological method of diagnosing lactase 

deficiency. East Afr Med J 1969 Oct; 46(10):564-71. Not relevant to key questions 

206. Bhan MK, Arora NK, Ghai OP, et al. Lactose and milk intolerance in recurrent abdominal 

pain of childhood. Indian J Pediatr 1982 Mar-Apr; 49(397):199-202. Not relevant to key 

questions 

207. Bhan MK, Arora NK, Khoshoo V, et al. Comparison of a lactose-free cereal-based formula 

and cow's milk in infants and children with acute gastroenteritis. Journal of pediatric 

gastroenterology and nutrition Vol 7; 1988: 208-13. Not relevant to key questions 

208. Bhatia BD, Banerjee D, Agarwal DK, et al. Dietary intakes of urban and rural pregnant, 

lactating and non-pregnant, non-lactating vegetarian women of Varanasi. Indian J Med Res 

1981 Nov; 74:680-7. Not eligible outcomes 

209. Bhatnagar R, Sharma YR, Vajpayee RB, et al. Does milk have a cataractogenic effect? 

Weighing of clinical evidence. Digestive Diseases & Sciences 1989 Nov; 34(11):1745-50. No 

prevalence data 

210. Bhatnagar S, Bhan MK, Singh KD, et al. Efficacy of milk-based diets in persistent diarrhea: a 

randomized, controlled trial. Pediatrics Vol 98; 1996: 1122-6. Not relevant to key questions 

211. Bhattacharya RD, Patel TS, Pandya CB. Reference values of urinary electrolyte excretion in 

respect of a vegetarian diet. A chronobiological study. Panminerva Med 1985 Apr-Jun; 

27(2):83-7. Not eligible outcomes 

212. Bhttacharyya AK, Chaudhuri AD, Chatterjee S, et al. Milk intolerance in irritable colon 

syndrome. Bull Calcutta Sch Trop Med 1971 Jul; 19(3):55-6. Not relevant to key questions 

175
 
213. Bhutta ZA, Nizami SQ, Isani Z. Lactose intolerance in persistent diarrhoea during childhood: 

the role of a traditional rice-lentil (Khitchri) and yogurt diet in nutritional management. J Pak 

Med Assoc 1997 Jan; 47(1):20-4. Not relevant to key questions 

214. Bianchi Porro G, Parente F, Sangaletti O. Lactose intolerance in adults with chronic 

unspecific abdominal complaints. Hepato-Gastroenterology 1983 Dec; 30(6):254-7. Not 

population based study 

215. Bianchi Porro G, Petrillo M, Parente F, et al. Recurrent abdominal pain and lactose 

intolerance. Br Med J (Clin Res Ed) 1981 Aug 15; 283(6289):501. Not relevant to key 

questions 

216. Biar J. Milk intolerance. J Med Liban 1969; 22(1):66-71. Not relevant to key questions 

217. Biddulph J. Standardized management of diarrhoea in young children. Paediatr Indones 1971 

Sep-Oct; 11(5):37-46. Not relevant to key questions 

218. Bilir S. Acquired disaccharide intolerance in children with malnutrition. Am J Clin Nutr 1972 

Jul; 25(7):664-71. Not relevant to key questions 

219. Biller JA, King S, Rosenthal A, et al. Efficacy of lactase-treated milk for lactose-intolerant 

pediatric patients. J Pediatr 1987 Jul; 111(1):91-4. Not relevant to key questions 

220. Binder HJ. The pathophysiology of diarrhea. Hosp Pract (Off Ed) 1984 Oct; 19(10):107-13, 

16-8. Not lactose intolerance study 

221. Binder JH, Gryboski JD, Thayer WR, Jr., et al. Intolerance to milk in ulcerative colitis. A 

preliminary report. Am J Dig Dis 1966 Nov; 11(11):858-64. Not relevant to key questions 

222. Binnington HB, Keating JP, Ternberg JL. Proceedings: Gastroschisis. Arch Surg 1974 Apr; 

108(4):455-9. Not relevant to key questions 

223. Binns J, Stevens HNE, McEwen J, et al. The tolerability of multiple oral doses of 

Pulsincapregistered trade mark capsules in healthy volunteers. Journal of Controlled Release. 

Vol 38; 1996: 151-8. Not lactose intolerance study 

224. Birch EE, Castan~eda YS, Wheaton DH, et al. Visual maturation of term infants fed longchain polyunsaturated fatty acid-supplemented or control formula for 12 months. American 

Journal of Clinical Nutrition Vol 81; 2005: 871-9. Not lactose intolerance study 

225. Bircher J, Haemmerli UP, Williams R. Lactulose in the treatment of portal-systemic 

encephalopathy. Report of a symposium. Gastroenterology Vol 58; 1970: 595-7. Not lactose 

intolerance study 

226. Birkhed D, Fuchs G. Influence of sugar content in soft bread on pH of human dental plaque. 

Acta Odontologica Scandinavica Vol 33; 1975: 59-66. Not lactose intolerance study 

227. Birkhed D, Imfeld T, Edwardsson S. pH changes in human dental plaque from lactose and 

milk before and after adaptation. Caries-Res Vol 27; 1993: 43-50. Not lactose intolerance 

study 

228. Birlouez-Aragon I, Ravelontseheno L, Villate-Cathelineau B, et al. Disturbed galactose 

metabolism in elderly and diabetic humans is associated with cataract formation. J Nutr 1993 

Aug; 123(8):1370-6. Not relevant to key questions 

229. Biskup H, Heine WE, Wutzke KD. Gastric emptying and intestinal transit time of high- and 

low caloric formulas. Aktuelle Ernahrungsmedizin Vol 24; 1999: 238-41. Not lactose 

intolerance study 

230. Bjarnason I. Intestinal permeability. Gut 1994 Jan; 35(1 Suppl):S18-22. Not relevant to key 

questions 

176
 
231. Blair J, Fitzgerald JF. Non-specific infantile diarrhea. J Indiana State Med Assoc 1973 Sep; 

65(9):791-3. Not relevant to key questions 

232. Blair J, Fitzgerald JF. Treatment of nonspecific diarrhea in infants. Clin Pediatr (Phila) 1974 

Apr; 13(4):333-4. Not relevant to key questions 

233. Blaney DJ, Cook CH. Topical use of tetracycline in the treatment of acne: a double-blind 

study comparing topical and oral tetracycline therapy and placebo. Archives of dermatology 

Vol 112; 1976: 971-3. Not lactose intolerance study 

234. Blankenship RM, Greenburg BR, Lucas RN, et al. Familial sea-blue histiocytes with acid 

phosphatemia. A syndrome resembling Gaucher disease: the Lewis variant. JAMA 1973 Jul 

2; 225(1):54-6. Not eligible target population 

235. Blass EM. Milk-induced hypoalgesia in human newborns. Pediatrics Vol 99; 1997: 825-9. 

Not relevant to key questions 

236. Blum AL, Haemmerli UP, Lorenz-Meyer H. Is phlorizin or its aglycon the inhibitor of 

intestinal glucose transport? A study in normal and lactase deficient man. Eur J Clin Invest 

1975 Jun 12; 5(3):285-8. Not relevant to key questions 

237. Blumenthal I, Kelleher J, Littlewood JM. Recurrent abdominal pain and lactose intolerance in 

childhood. Br Med J (Clin Res Ed) 1981 Jun 20; 282(6281):2013-4. Not relevant to key 

questions 

238. Bode JC. [Lactose enemas plus placebo tablets vs neomycin tablets plus starch enemas in 

acute portal systemic encephalopathy A double-blind randomized contolled study]. Zeitschrift 

für Gastroenterologie Vol 19; 1981: 744. Not lactose intolerance study 

239. Bode S, Gudmand-Hoyer E. Incidence and clinical significance of lactose malabsorption in 

adult coeliac disease. Scand J Gastroenterol 1988 May; 23(4):484-8. Not relevant to key 

questions 

240. Bodlaj G, Stocher M, Hufnagl P, et al. Genotyping of the lactase-phlorizin hydrolase -13910 

polymorphism by LightCycler PCR and implications for the diagnosis of lactose intolerance. 

Clin Chem 2006 Jan; 52(1):148-51. Not relevant to key questions 

241. Boellner SW, Beard AG, Panos TC. Impairment of intestinal hydrolysis of lactose in 

newborn infants. Pediatrics 1965 Oct; 36(4):542-50. Not relevant to key questions 

242. Boey CC. Lactase deficiency among Malaysian children with recurrent abdominal pain. 

Journal of Paediatrics & Child Health 2001 Apr; 37(2):157-60. Ineligible number of subjects 

243. Bohmer CJ, Tuynman HA. The clinical relevance of lactose malabsorption in irritable bowel 

syndrome. European Journal of Gastroenterology & Hepatology 1996 Oct; 8(10):1013-6. 

Ineligible number of subjects 

244. Bojarski C, Epple HJ, Kirstein FW, et al. Patients with dyspepsia benefit from eradication 

of Helicobacter pylori if other organic causes for dyspepsia were carefully ruled out. Zeitschrift für 

Gastroenterologie Vol 38; 2000: 211-9. Not lactose intolerance study 

245. Bolin TD. Use of oral sodium cromoglycate in persistent diarrhoea. Gut Vol 21; 1980: 848­

50. Not lactose intolerance study 

246. Bolin TD, Crane GG, Davis AE. Lactose intolerance in various ethnic groups in South-East 

Asia. Australas Ann Med 1968 Nov; 17(4):300-6. Not relevant to key questions 

247. Bolin TD, Davis AE. Asian lactose intolerance and its relation to intake of lactose. Nature 

1969 Apr 26; 222(5191):382-3. Not relevant to key questions 

248. Bolin TD, Davis AE. Lactose intolerance in Australian-born Chinese. Australas Ann Med 

1970 Feb; 19(1):40-1. Not relevant to key questions 

249. Bolin TD, Davis AE. Primary lactase deficiency: genetic or acquired? Gastroenterology 1972 

177
 
Feb; 62(2):355-7. Not relevant to key questions 

250. Bolin TD, Davis AE, Duncombe VM. A prospective study of persistent diarrhoea. Australian 

& New Zealand Journal of Medicine 1982 Feb; 12(1):22-6. No prevalence data 

251. Bolin TD, Davis AE, Levey J, et al. Aboriginal health on Mornington Island, 1972. Med J 

Aust 1975 Feb 22; 1(3 Suppl):29-31. Not relevant to key questions 

252. Bolin TD, Davis AE, Seah CS, et al. Lactose intolerance in Singapore. Gastroenterology 1970 

Jul; 59(1):76-84. Not relevant to key questions 

253. Bond JH, Levitt MD. Quantitative measurement of lactose absorption. Gastroenterology 1976 

Jun; 70(6):1058-62. Not relevant to key questions 

254. Bondesson E, Asking L, Borgström L, et al. In vitro and in vivo aspects of quantifying 

intrapulmonary deposition of a dry powder radioaerosol. International journal of 

pharmaceutics Vol 232; 2002: 149-56. Not lactose intolerance study 

255. Bondesson E, Bengtsson T, Borgström L, et al. Dose delivery late in the breath can increase 

dry powder aerosol penetration into the lungs. Journal of aerosol medicine : the official 

journal of the International Society for Aerosols in Medicine Vol 18; 2005: 23-33. Not 

lactose intolerance study 

256. Boner AL, Niero E, Grigolini C, et al. Inhibition of exercise-induced asthma by three forms 

of sodium cromoglycate. European journal of respiratory diseases Vol 66; 1985: 21-4. Not 

lactose intolerance study 

257. Bongers ME, de LF, Reitsma JB, et al. The clinical effect of a new infant formula in term 

infants with constipation: a double-blind, randomized cross-over trial. Nutrition journal Vol 

6; 2007: 8. Not lactose intolerance 

258. Booth IW. Dietary management of acute diarrhoea in childhood. Lancet 1993 Apr 17; 

341(8851):996-7. Not relevant to key questions 

178
 
259. Borg M, Phillips AD, Smith MW, et al. Enteric disease in early childhood inhibits 

microvillus expression by potential stem cells. Clin Sci (Lond) 1993 Apr; 84(4):377-9. Not 

relevant to key questions 

260. Born P, Sekatcheva M, Rosch T, et al. Carbohydrate malabsorption in clinical routine: a 

prospective observational study. Hepato-Gastroenterology 2006 Sep-Oct; 53(71):673-7. 

Ineligible number of subjects 

261. Bosch S, Kalde S, Kuhlbusch R, et al. Treatment of lactose intolerance with a new aspergillus 

lactose preparation. Aktuelle Ernahrungsmedizin Klinik Und Praxis. Vol 20; 1995: 310-5. 

Not relevant to key questions 

262. Bose DP, Welsh JD. Lactose malabsorption in Oklahoma Indians. Am J Clin Nutr 1973 Dec; 

26(12):1320-2. Ineligible number of subjects 

263. Bott C, Rudolph MW, Schneider AR, et al. In vivo evaluation of a novel pH- and time-based 

multiunit colonic drug delivery system. Alimentary pharmacology & therapeutics Vol 20; 

2004: 347-53. Not lactose intolerance study 

264. Boudraa G, Benbouabdellah M, Hachelaf W, et al. Effect of feeding yogurt versus milk in 

children with acute diarrhea and carbohydrate malabsorption. Journal of pediatric 

gastroenterology and nutrition Vol 33; 2001: 307-13. Not relevant to key questions 

265. Boudraa G, Touhami M, Pochart P, et al. Effect of feeding yogurt versus milk in children 

with persistent diarrhea. Journal of pediatric gastroenterology and nutrition Vol 11; 1990: 

509-12. Not relevant to key questions 

266. Boudraa GBM, Soltana R, Touhami M. Effets compares du yaourt et du lait, au cours des 

diarrhees prolongees du nourrisson et de l'enfant, avec malabsorption ou intolerance au 

lactose. Arch Fr Pediatr Vol 49; 1992: 583-. Not relevant to key questions 

267. Bourlioux P, Bouley C, Ashwell M. New aspects of the functionalities of probiotics. Forum 

Nutr 2003; 56:355-6. Not relevant to key questions 

268. Bowen J, Noakes M, Trenerry C, et al. Energy intake, ghrelin, and cholecystokinin after 

different carbohydrate and protein preloads in overweight men. The Journal of clinical 

endocrinology and metabolism Vol 91; 2006: 1477-83. Not lactose intolerance study 

269. Bowie MD. Effect of lactose-induced diarrhoea on absorption of nitrogen and fat. Arch Dis 

Child 1975 May; 50(5):363-6. Not relevant to key questions 

270. Bowie MD, Hill ID, Mann MD. Response of severe infantile diarrhoea to soya-based feeds. 

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde Vol 73; 1988: 

343-5. Not relevant to key questions 

271. Boyd LD, Palmer C, Dwyer JT. Managing oral health related nutrition issues of high risk 

infants and children. J Clin Pediatr Dent 1998 Fall; 23(1):31-6. Not relevant to key questions 

272. Bozzani A, Penagini R, Velio P, et al. Lactose malabsorption and intolerance in Italians. 

Clinical implications. Dig Dis Sci 1986 Dec; 31(12):1313-6. Not relevant to key questions 

273. Bradfield RB, Jelliffe DB, Ifekwunigwe A. Letter: Milk intolerance and mainutrition. Lancet 

1975 Aug 16; 2(7929):325. Not relevant to key questions 

274. Braham R, Dawson B, Goodman C. The effect of glucosamine supplementation on people 

experiencing regular knee pain. British journal of sports medicine Vol 37; 2003: 45-9; 

discussion 9. Not lactose intolerance study 

275. Brand J, Mitchell JD. Faecal fat losses and cow's milk lactose. Lancet 1980 Jan 26; 

1(8161):207. Not relevant to key questions 

276. Brand JC, Darnton-Hill I. Lactase deficiency in Australian school children. Medical Journal 

of Australia 1986 Oct 6; 145(7):318-22. Ineligible number of subjects 

179
 
277. Brand JC, Darnton-Hill I, Gracey MS, et al. Lactose malabsorption in Australian Aboriginal 

children. American Journal of Clinical Nutrition 1985 Mar; 41(3):620-2. Ineligible number of 

subjects 

278. Brand JC, Gracey MS, Spargo RM, et al. Lactose malabsorption in Australian Aborigines. 

Am J Clin Nutr 1983 Mar; 37(3):449-52. Not relevant to key questions 

279. Brand JC, Miller JJ, Vorbach EA, et al. A trial of lactose hydrolysed milk in Australian 

Aboriginal children. Med J Aust 1977 Nov 26; 2(4 Suppl):10-3. Not relevant to key questions 

280. Brasseur D, Mandelbaum I, Vis HL. Effects of an episode of severe malnutrition and age on 

lactose absorption by recovered infants and children. Am J Clin Nutr 1980 Feb; 33(2):177-9. 

Not relevant to key questions 

281. Brink EJ, van BEC, Dekker PR, et al. Urinary excretion of magnesium and calcium as an 

index of absorption is not affected by lactose intake in healthy adults. The British journal of 

nutrition Vol 69; 1993: 863-70. Not eligible target population 

282. Brockis JG, Levitt AJ, Cruthers SM. The effects of vegetable and animal protein diets on 

calcium, urate and oxalate excretion. Br J Urol 1982 Dec; 54(6):590-3. Not eligible outcomes 

283. Bronsky E, Bucholtz GA, Busse WW, et al. Comparison of inhaled albuterol powder and 

aerosol in asthma. The Journal of allergy and clinical immunology Vol 79; 1987: 741-7. Not 

lactose intolerance study 

284. Broom J, Jones K. Causes and prevention of diarrhoea in patients receiving enteral nutritional 

support. J Hum Nutr 1981 Apr; 35(2):123-7. Not relevant to key questions 

285. Brouwers FM, Van Der Werf S, Bleijenberg G, et al. The effect of a polynutrient supplement 

on fatigue and physical activity of patients with chronic fatigue syndrome: a double-blind 

randomized controlled trial. QJM 2002 Oct; 95(10):677-83. Not lactose intolerance 

286. Brown KH. Dietary management of acute diarrheal disease: contemporary scientific issues. 

Journal of Nutrition 1994 Aug; 124(8 Suppl):1455S-60S. Not original research 

287. Brown KH, Black RE, Parry L. The effect of diarrhea on incidence of lactose malabsorption 

among Bangladeshi children. Am J Clin Nutr 1980 Oct; 33(10):2226-7. Not relevant to key 

questions 

288. Brown KH, Gastañaduy AS, Saavedra JM, et al. Effect of continued oral feeding on clinical 

and nutritional outcomes of acute diarrhea in children. The Journal of pediatrics Vol 112; 

1988: 191-200. Not lactose intolerance study 

289. Brown KH, Khatun M, Parry L, et al. Nutritional consequences of low dose milk supplements 

consumed by lactose-malabsorbing children. American Journal of Clinical Nutrition 1980 

May; 33(5):1054-63. Ineligible number of subjects 

290. Brown KH, Parry L, Khatun M, et al. Lactose malabsorption in Bangladeshi village children: 

relation with age, history of recent diarrhea, nutritional status, and breast feeding. American 

Journal of Clinical Nutrition 1979 Sep; 32(9):1962-9. Not eligible test for lactose 

malabsorption 

291. Brown KH, Peerson JM, Fontaine O. Use of nonhuman milks in the dietary management of 

young children with acute diarrhea: a meta-analysis of clinical trials. Pediatrics 1994 Jan; 

93(1):17-27. Not relevant to key questions 

292. Brown KH, Perez F, Gastañaduy AS. Clinical trial of modified whole milk, lactosehydrolyzed whole milk, or cereal-milk mixtures for the dietary management of acute 

childhood diarrhea. Journal of pediatric gastroenterology and nutrition Vol 12; 1991: 340-50. 

Not relevant to key questions 

180
 
293. Brown KH, Perez F, Peerson JM, et al. Effect of dietary fiber (soy polysaccharide) on the 

severity, duration, and nutritional outcome of acute, watery diarrhea in children. Pediatrics 

Vol 92; 1993: 241-7. Not lactose intolerance study 

294. Brown PT, Bergan JG. The dietary status of "new" vegetarians. J Am Diet Assoc 1975 Nov; 

67(5):455-9. Not eligible outcomes 

295. Brown RS, Di SPT, Beaver WT, et al. The administration of folic acid to institutionalized 

epileptic adults with phenytoin-induced gingival hyperplasia. A double-blind, randomized, 

placebo-controlled, parallel study. Oral surgery, oral medicine, and oral pathology Vol 71; 

1991: 565-8. Not lactose intolerance study 

296. Bruening K, Kemp FW, Simone N, et al. Dietary calcium intakes of urban children at risk of 

lead poisoning. Environ Health Perspect 1999 Jun; 107(6):431-5. Not eligible target 

population 

297. Brummer RJ, Karibe M, Stockbrugger RW. Lactose malabsorption. Optimalization of 

investigational methods. Scandinavian Journal of Gastroenterology - Supplement 1993; 

200:65-9. No prevalence data 

298. Brunser O, Araya M, Espinoza J, et al. [Trial of milk with low-lactose contents in acute 

diarrhea]. Rev Chil Pediatr Vol 61; 1990: 94-9. Not English language 

299. Bryant GD, Chu YK, Lovitt R. Incidence and aetiology of lactose intolerance. Med J Aust 

1970 Jun 27; 1(26):1285-8. Not relevant to key questions 

300. Buchanan GR, Martin V, Levine PH, et al. The effects of "anti-platelet" drugs on bleeding 

time and platelet aggregation in normal human subjects. American journal of clinical 

pathology Vol 68; 1977: 355-9. Not lactose intolerance study 

301. Buchman AL, Moukarzel AA, Bhuta S, et al. Parenteral nutrition is associated with intestinal 

morphologic and functional changes in humans. Jpen: Journal of Parenteral & Enteral 

Nutrition Vol 19; 1995: 453-60. Not relevant to key questions 

302. Bueno MA. Protriptyline: relationship between plasma concentrations and the clinical effect 

in depressed male patients. <ORIGINAL> PROTRIPTILINA: RELACION ENTRE LAS 

CONCENTRACIONES PLASMATICAS Y EL EFECTO CLINICO EN PACIENTES 

HOMBRES DEPRIMIDOS. Revcolombpsiquiatr Vol 5; 1976: 431-8. Not lactose intolerance 

study 

303. Buhac I, Balint JA. Practical therapeutics. Diarrhea and constipation. Am Fam Physician 

1975 Nov; 12(5):149-59. Not relevant to key questions 

304. Bujanover Y, Schwartz G, Milbauer B, et al. Lactose malabsorption is not a cause of diarrhea 

during phototherapy. J Pediatr Gastroenterol Nutr 1985 Apr; 4(2):196-8. Not relevant to key 

questions 

305. Bulhoes AC, Goldani HA, Oliveira FS, et al. Correlation between lactose absorption and the 

C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adulttype hypolactasia. Braz J Med Biol Res 2007 Nov; 40(11):1441-6. Not relevant to key 

questions 

306. Bull NL, Barber SA. Food and nutrient intakes of vegetarians in Britain. Hum Nutr Appl Nutr 

1984 Aug; 38(4):288-93. Not relevant to key questions 

307. Buller HA, Grand RJ. Lactose intolerance. Annual Review of Medicine 1990; 41:141-8. Not 

original research 

308. Buning C, Genschel J, Jurga J, et al. Introducing genetic testing for adult-type hypolactasia. 

Digestion 2005; 71(4):245-50. Not relevant to key questions 

181
 
309. Buning C, Ockenga J, Kruger S, et al. The C/C(-13910) and G/G(-22018) genotypes for 

adult-type hypolactasia are not associated with inflammatory bowel disease. Scandinavian 

Journal of Gastroenterology 2003 May; 38(5):538-42. No prevalence data 

310. Burger J, Kirchner M, Bramanti B, et al. Absence of the lactase-persistence-associated allele 

in early Neolithic Europeans. Proc Natl Acad Sci U S A 2007 Mar 6; 104(10):3736-41. Not 

eligible target population 

311. Burgin-Wolff A, Bertele RM, Berger R, et al. A reliable screening test for childhood celiac 

disease: fluorescent immunosorbent test for gliadin antibodies. A prospective multicenter 

study. Journal of Pediatrics 1983 May; 102(5):655-60. No prevalence data 

312. Burke V. Gastrointestinal symptoms and cow's milk allergy. Aust Paediatr J 1972 Oct; 

8(5):231-2. Not relevant to key questions 

313. Bursey RF. Burning issues. A guide for patients. Lactose intolerance. Can J Gastroenterol 

1999 Mar; 13(2):107. Not relevant to key questions 

314. Burton BK, Ben-Yoseph Y, Nadler HL. Lactosyl ceramidosis: deficient activity of neutral 

beta-galactosidase in liver and cultivated fibroblasts? Clin Chim Acta 1978 Sep 15; 

88(3):483-93. Not relevant to key questions 

315. Busk HE, Dahlerup B, Lytzen T, et al. The incidence of lactose malabsorption in ulcerative 

colitis. Scandinavian Journal of Gastroenterology 1975; 10(3):263-5. No prevalence data 

316. Buttery JE, Ratnaike RN. Can ethanol be omitted from the lactose absorption test? Clin 

Biochem 1995 Dec; 28(6):599-601. Not relevant to key questions 

317. Buttery JE, Ratnaike RN, Chamberlain BR. A visual screening method for lactose 

maldigestion. Ann Clin Biochem 1994 Nov; 31 ( Pt 6):566-7. Not relevant to key questions 

318. Bye A, Kaasa S, Ose T, et al. The influence of low fat, low lactose diet on diarrhoea during 

pelvic radiotherapy. Clin-Nutr Vol 11; 1992: 147-53. Not relevant to key questions 

319. Bye A, Ose T, Kaasa S. The effect of a low fat, low lactose diet on nutritional status during 

pelvic radiotherapy. Clin-Nutr Vol 12; 1993: 89-95. Not relevant to key questions 

320. Bye A, Ose T, Kaasa S. Quality of life during pelvic radiotherapy. Acta obstetricia et 

gynecologica Scandinavica Vol 74; 1995: 147-52. Not eligible target population 

321. Bye A, Ose T, Kaasa S. Food choice and nutrient intake among patients on a low-fat, lowlactose diet: Experience from a prospective randomized study. Journal of Human Nutrition & 

Dietetics Vol 12; 1999: 273-85. Not eligible target population 

322. Bye A, Ose T, Sundfor K, et al. Effect of low-lactose/low-fat diet during pelvic radiotherapy 

[abstract]. Clin-Nutr Vol 10; 1991: 12-3. Not relevant to key questions 

323. Bye A, Tropé C, Loge JH, et al. Health-related quality of life and occurrence of intestinal side 

effects after pelvic radiotherapy--evaluation of long-term effects of diagnosis and treatment. 

Acta oncologica (Stockholm, Sweden) Vol 39; 2000: 173-80. Not eligible target population 

324. Bye C, Clubley M, Peck AW. Drowsiness, impaired performance and tricyclic 

antidepressants drugs. British journal of clinical pharmacology Vol 6; 1978: 155-62. Not 

lactose intolerance study 

325. Bye CE, Claridge R, Peck AW, et al. Evidence for tolerance to the central nervous effects of 

the histamine antagonist, triprolidine, in man. Eur J Clin Pharmacol Vol 12; 1977: 181-6. Not 

lactose intolerance study 

326. Bye CE, Clubley M, Henson T, et al. Changes in the human light reflex as a measure of the 

anticholinergic effects of drugs. A comparison with other measures. European journal of 

clinical pharmacology Vol 15; 1979: 21-5. Not lactose intolerance study 

182
 
327. Byers KG, Savaiano DA. The myth of increased lactose intolerance in African-Americans. J 

Am Coll Nutr 2005 Dec; 24(6 Suppl):569S-73S. Review 

328. Caballero B, Solomons NW, Torun B. Fecal reducing substances and breath hydrogen 

excretion as indicators of carbohydrate malabsorption. J Pediatr Gastroenterol Nutr 1983; 

2(3):487-90. Not relevant to key questions 

329. Caballero B, Solomons NW, Torun B, et al. Calcium metabolism in children recovering from 

severe protein-energy malnutrition. Journal of pediatric gastroenterology and nutrition Vol 5; 

1986: 740-5. Not lactose intolerance study 

330. Cade JE, Burley VJ, Greenwood DC. The UK Women's Cohort Study: comparison of 

vegetarians, fish-eaters and meat-eaters. Public Health Nutr 2004 Oct; 7(7):871-8. Not 

eligible outcomes 

331. Caldwell EF, Mayor LR, Thomas MG, et al. Diet and the frequency of the alanine:glyoxylate 

aminotransferase Pro11Leu polymorphism in different human populations. Hum Genet 2004 

Nov; 115(6):504-9. Not relevant to key questions 

332. Caldwell JL, Prazinko BF, Rowe T, et al. Improving daytime sleep with temazepam as a 

countermeasure for shift lag. Aviation, space, and environmental medicine Vol 74; 2003: 

153-63. Not lactose intolerance study 

333. Calkins BM, Whittaker DJ, Nair PP, et al. Diet, nutrition intake, and metabolism in 

populations at high and low risk for colon cancer. Nutrient intake. Am J Clin Nutr 1984 Oct; 

40(4 Suppl):896-905. Not eligible outcomes 

334. Calloway DH, Chenoweth WL. Utilization of nutrients in milk- and wheat-based diets by 

men with adequate and reduced abilities to absorb lactose. I. Energy and nitrogen. Am J Clin 

Nutr 1973 Sep; 26(9):939-51. Not relevant to key questions 

335. Calloway DH, Murphy EL, Bauer D. Determination of lactose intolerance by breath analysis. 

Am J Dig Dis 1969 Nov; 14(11):811-5. Not relevant to key questions 

336. Cammà C, Fiorello F, Tinè F, et al. Lactitol in treatment of chronic hepatic encephalopathy. 

A meta-analysis. Digestive diseases and sciences Vol 38; 1993: 916-22. Not lactose 

intolerance study 

337. Campbell AK, Waud JP, Matthews SB. The molecular basis of lactose intolerance. Sci Prog 

2005; 88(Pt 3):157-202. Not relevant to key questions 

338. Candan S, Sapci T, Turkmen M, et al. Sucralfate in accelerating post-tonsillectomy wound 

healing. Marmara Medical Journal Vol 10; 1997: 79-83. Not lactose intolerance study 

339. Capano G, Guandalini S, Guarino A, et al. Enteric infections, cow's milk intolerance and 

parenteral infections in 118 consecutive cases of acute diarrhoea in children. Eur J Pediatr 

1984 Sep; 142(4):281-5. Not relevant to key questions 

340. Capel LH, McKelvie P. Disodium cromoglycate in hayfever. Lancet Vol 1; 1971: 575-6. Not 

lactose intolerance study 

341. Cappello G, Spezzaferro M, Grossi L, et al. Peppermint oil (Mintoil) in the treatment of 

irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial. 

Dig Liver Dis 2007 Jun; 39(6):530-6. Not lactose intolerance 

342. Capristo E, Mingrone G, Addolorato G, et al. Effect of a vegetable-protein-rich polymeric 

diet treatment on body composition and energy metabolism in inactive Crohn's disease. Eur J 

Gastroenterol Hepatol 2000 Jan; 12(1):5-11. Not relevant to key questions 

343. Cardinal BJ, Engels HJ. Ginseng does not enhance psychological well-being in healthy, 

young adults: results of a double-blind, placebo-controlled, randomized clinical trial. Journal 

of the American Dietetic Association Vol 101; 2001: 655-60. Not lactose intolerance study 

183
 
344. Carey WB. "Colic"--primary excessive crying as an infant-environment interaction. Pediatric 

clinics of North America 1984 Oct; 31(5):993-1005. Review 

345. Carlson SJ, Rogers RR, Lombard KA. Effect of a lactase preparation on lactose content and 

osmolality of preterm and term infant formulas. JPEN J Parenter Enteral Nutr 1991 Sep-Oct; 

15(5):564-6. Not relevant to key questions 

346. Carpentier G, D'Hondt F, Molla AM, et al. Lactose intolerance following measles. Lancet 

1970 Oct 3; 2(7675):725-6. Not relevant to key questions 

347. Carrera E, Nesheim MC, Crompton DW. Lactose maldigestion in Ascaris-infected preschool 

children. American Journal of Clinical Nutrition 1984 Feb; 39(2):255-64. Ineligible number 

of subjects 

348. Carrier J, Fernandez-Bolanos M, Robillard R, et al. Effects of caffeine are more marked on 

daytime recovery sleep than on nocturnal sleep. Neuropsychopharmacology : official 

publication of the American College of Neuropsychopharmacology Vol 32; 2007: 964-72. 

Not lactose intolerance study 

349. Carroccio A, Montalto G, Custro N, et al. Evidence of very delayed clinical reactions to cow's 

milk in cow's milk-intolerant patients. Allergy 2000 Jun; 55(6):574-9. Not lactose intolerance 

350. Carroccio A, Scalici C, Maresi E, et al. Chronic constipation and food intolerance: a model of 

proctitis causing constipation. Scandinavian Journal of Gastroenterology 2005 Jan; 40(1):33­

42. Ineligible number of subjects 

351. Carter JP, Furman T, Hutcheson HR. Preeclampsia and reproductive performance in a 

community of vegans. South Med J 1987 Jun; 80(6):692-7. Not relevant to key questions 

352. Casaburi R, Briggs DD, Jr., Donohue JF, et al. The spirometric efficacy of once-daily dosing 

with tiotropium in stable COPD: A 13-week multicenter trial. Chest Vol 118; 2000: 1294­

302. Not lactose intolerance study 

353. Casellas F, Malagelada JR. Applicability of short hydrogen breath test for screening of 

lactose malabsorption. Dig Dis Sci 2003 Jul; 48(7):1333-8. Not relevant to key questions 

354. Caskey DA, Payne-Bose D, Welsh JD, et al. Effects of age on lactose malabsorption in 

Oklahoma Native Americans as determined by breath H2 analysis. Am J Dig Dis 1977 Feb; 

22(2):113-6. Not relevant to key questions 

355. Caspary WF. Breath tests. Clin Gastroenterol 1978 May; 7(2):351-74. Not relevant to key 

questions 

356. Caspary WF. Diarrhoea associated with carbohydrate malabsorption. Clin Gastroenterol 1986 

Jul; 15(3):631-55. Not relevant to key questions 

357. Castiglia PT. Lactose intolerance. J Pediatr Health Care 1994 Jan-Feb; 8(1):36-8. Not 

relevant to key questions 

358. Castillo-Durán C, Perales CG, Hertrampf ED, et al. Effect of zinc supplementation on 

development and growth of Chilean infants. The Journal of pediatrics Vol 138; 2001: 229-35. 

Not lactose intolerance study 

359. Castillo-Duran C, Solomons NW. Studies on the bioavailability of zinc in humans. IX. 

Interaction of beef-zinc with iron, calcium and lactose. Nutrition Research Vol 11; 1991: 429­

38. Not lactose intolerance study 

360. Castillo-Duran C, Venegas G, Villalobos JC, et al. Trace mineral balance in acute diarrhea of 

infants. Association to etiological agents and lactose content of formula. Nutrition Research 

Vol 18; 1998: 799-808. Not relevant to key questions 

184
 
361. Cavaliere H, Medeiros-Neto G. The anorectic effect of increasing doses of L-tryptophan in 

obese patients. Eating and weight disorders : EWD Vol 2; 1997: 211-5. Not lactose 

intolerance study 

362. Cavalli-Sforza LT, Menozzi P, Strata A. A model and program for study of a tolerance curve: 

application to lactose absorption tests. Int J Biomed Comput 1983 Jan; 14(1):31-41. Not 

relevant to key questions 

363. Cavalli-Sforza LT, Strata A, Barone A, et al. Primary adult lactose malabsorption in Italy: 

regional differences in prevalence and relationship to lactose intolerance and milk 

consumption. American Journal of Clinical Nutrition 1987 Apr; 45(4):748-54. Not eligible 

test for lactose malabsorption 

364. Ceriani R, Zuccato E, Fontana M, et al. Lactose malabsorption and recurrent abdominal pain 

in Italian children. J Pediatr Gastroenterol Nutr 1988 Nov-Dec; 7(6):852-7. Not relevant to 

key questions 

365. Ceuterick C, Martin JJ. Diagnostic role of skin or conjunctival biopsies in neurological 

disorders. An update. J Neurol Sci 1984 Aug; 65(2):179-91. Not relevant to key questions 

366. Chakrabarti AK, Johnson SC, Samantray SK, et al. Osteomalacia, myopathy and basilar 

impression. J Neurol Sci 1974 Oct; 23(2):227-35. Not eligible target population 

367. Chalfin D, Holt PR. Lactase deficiency in ulcerative colitis, regional enteritis, and viral 

hepatitis. Am J Dig Dis 1967 Jan; 12(1):81-7. Not relevant to key questions 

368. Challacombe DN, Richardson JM, Edkins S. Anaerobic bacteria and deconjugated bile salts 

in the upper small intestine of infants with gastrointestinal disorders. Acta Paediatr Scand 

1974 Jul; 63(4):581-7. Not relevant to key questions 

369. Chan GM, McMurry M, Westover K, et al. Effects of increased dietary calcium intake upon 

the calcium and bone mineral status of lactating adolescent and adult women. Am J Clin Nutr 

1987 Aug; 46(2):319-23. Not eligible outcomes 

370. Chandra RK, Pawa RR, Ghai OP. Sugar intolerance in malnourished infants and children. Br 

Med J 1968 Dec 7; 4(5631):611-3. Not relevant to key questions 

371. Chandra RK, Pawa RR, Ghai OP. Disaccharide intolerance in the aetiology of chronic and-or 

recurrent diarrhoea in young children. Indian J Med Res 1969 Apr; 57(4):713-7. Not relevant 

to key questions 

372. Chandra RK, Singh G, Shridhara B. Effect of feeding whey hydrolysate, soy and 

conventional cow milk formulas on incidence of atopic disease in high risk infants. Annals of 

allergy Vol 63; 1989: 102-6. Not relevant to key questions 

373. Chandrasekaran R, Kumar V, Moorthy B. Combined lactose-D-xylose tolerance test in 

infancy. Digestion 1976; 14(3):281-4. Not relevant to key questions 

374. Chang MH, Hsu HY, Chen CJ, et al. Lactose malabsorption and small-intestinal lactase in 

normal Chinese children. J Pediatr Gastroenterol Nutr 1987 May-Jun; 6(3):369-72. Not 

relevant to key questions 

375. Chao CK, Sibley E. PCR-RFLP genotyping assay for a lactase persistence polymorphism 

upstream of the lactase-phlorizin hydrolase gene. Genet Test 2004 Summer; 8(2):190-3. Not 

relevant to key questions 

376. Charney M, McCracken RD. Intestinal lactase deficiency in adult nonhuman primates: 

implications for selection pressures in man. Soc Biol 1971 Dec; 18(4):416-21. Not relevant to 

key questions 

185
 
377. Cheetham PS. An explanation for variations in the clinical and biochemical symptoms of 

lysosomal-enzyme deficiency diseases such as GM1 gangliosidosis [proceedings]. Biochem 

Soc Trans 1979 Oct; 7(5):980-2. Not relevant to key questions 

378. Cheetham PS, Dance NE, Robinson D. A benign deficiency of typeB beta-galactosidase in 

human liver. Clin Chim Acta 1978 Feb 1; 83(1-2):67-74. Not relevant to key questions 

379. Chen F, Cole P, Mi Z, et al. Dietary trace elements and esophageal cancer mortality in 

Shanxi, China. Epidemiology 1992 Sep; 3(5):402-6. Not eligible outcomes 

380. Chen ST, Domala Z. Milk tolerance among malnourished school children in Malaysia. Asia 

Pac J Public Health 1989; 3(4):274-7. Not relevant to key questions 

381. Cherry FF, Cooper MD, Stewart RA, et al. Cow versus soy formulas. Comparative evaluation 

in normal infants. Am J Dis Child 1968 Jun; 115(6):677-92. Not relevant to key questions 

382. Chesta J, Antezana C. [Effects of neomycin on intestinal digestion, absorption and 

fermentation of carbohydrates in patients with liver cirrhosis: evidence for an alternative 

therapeutic mechanism in hepatic encephalopathy]. Revista médica de Chile Vol 122; 1994: 

365-71. Not lactose intolerance study 

383. Chiang BL, Sheih YH, Wang LH, et al. Enhancing immunity by dietary consumption of a 

probiotic lactic acid bacterium (Bifidobacterium lactis HN019): optimization and definition 

of cellular immune responses. European journal of clinical nutrition Vol 54; 2000: 849-55. 

Not relevant to key questions 

384. Chilson BD, Knickrehm ME. Nutrient intake of college students under two systems of board 

charges--a la carte vs. contract. J Am Diet Assoc 1973 Nov; 63(5):543-5. Not eligible 

outcomes 

385. Chintu C, Simukoko RB, Snook CR. Lactose tolerance tests in normal healthy Zambian 

children--a preliminary report. J Trop Med Hyg 1978 Feb-Mar; 81(2-3):46-7. Not relevant to 

key questions 

386. Cho E, Smith-Warner SA, Spiegelman D, et al. Dairy foods, calcium, and colorectal cancer: a 

pooled analysis of 10 cohort studies. J Natl Cancer Inst 2004 Jul 7; 96(13):1015-22. Not 

eligible outcomes 

387. Cho YW, Oh SY, Han HC, et al. Comparative bronchodilatory activity of cetiedil citrate 

monohydrate, theophylline, orciprenaline and placebo in adult asthmatics. International 

journal of clinical pharmacology and biopharmacy Vol 16; 1978: 402-7. Not lactose 

intolerance study 

388. Choi YK, Johlin FC, Jr., Summers RW, et al. Fructose intolerance: an under-recognized 

problem. American Journal of Gastroenterology 2003 Jun; 98(6):1348-53. No prevalence 

data 

389. Choy EH, Scott DL, Kingsley GH, et al. Control of rheumatoid arthritis by oral tolerance. 

Arthritis and rheumatism Vol 44; 2001: 1993-7. Not lactose intolerance study 

390. Christensen MF. Prevalence of lactose intolerance in children with recurrent abdominal pain. 

Archives of Disease in Childhood 1978 Aug; 53(8):693. Not original research 

391. Christensen MF. Prevalence of lactose intolerance in children with recurrent abdominal pain. 

Pediatrics 1980 Mar; 65(3):681-2. No prevalence data 

392. Christman NT, Hamilton LH. A new chromatographic instrument for measuring trace 

concentrations of breath-hydrogen. J Chromatogr 1982 May 14; 229(2):259-65. Not relevant 

to key questions 

186
 
393. Christomanou H, Jaffe S, Martinius J, et al. Biochemical, genetic, psychometric, and 

neuropsychological studies in heterozygotes of a family with globoid cell leucodystrophy 

(Krabbe's disease). Hum Genet 1981; 58(2):179-83. Not relevant to key questions 

394. Christopher NL, Bayless TM. Role of the small bowel and colon in lactose-induced diarrhea. 

Gastroenterology 1971 May; 60(5):845-52. Not relevant to key questions 

395. Chua CP. A rational approach to infant feeding in the management of sugar intolerance 

associated with infantile enteritis. Med J Malaysia 1975 Dec; 30(2):98-101. Not relevant to 

key questions 

396. Chua KL, Seah CS. Lactose intolerance: hereditary or acquired? Effect of prolonged milk 

feeding. Singapore Med J 1973 Mar; 14(1):29-33. Not relevant to key questions 

397. Chugh JC, Dhatt PS, Singh H, et al. Disaccharide intolerance & ICC. VII. Effect of steroid 

therapy on lactosuria. Indian Pediatr 1987 Feb; 24(2):163-5. Not relevant to key questions 

398. Chung CM, Kong YF. No evidence of lactase deficiency related to phototherapy of jaundiced 

infants. N Engl J Med 1976 Dec 23; 295(26):1483. Not relevant to key questions 

399. Chung MH, McGill DB. Lactase deficiency in Orientals. Gastroenterology 1968 Feb; 

54(2):225-6. Not relevant to key questions 

400. Cicco R, Holzman IR, Brown DR, et al. Glucose polymer tolerance in premature infants. 

Pediatrics 1981 Apr; 67(4):498-501. Not relevant to key questions 

401. Ciclitira PJ, Machell RJ, Farthing JG, et al. Double-blind controlled trial of cimetidine in the 

healing of gastric ulcer. Gut Vol 20; 1979: 730-4. Not lactose intolerance study 

402. Cirla AM, Sforza N, Roffi GP, et al. Preseasonal intranasal immunotherapy in birch-alder 

allergic rhinitis. A double-blind study. Allergy Vol 51; 1996: 299-305. Not lactose 

intolerance study 

403. Clarke AD, Podmore DA. The enzymatic determination of lactic acid in faeces in glycosidase 

deficiency. Clin Chim Acta 1966 Jun; 13(6):725-30. Not relevant to key questions 

404. Clemente YF, Tapia CC, Comino AL, et al. [Lactose-free formula versus adapted formula in 

acute infantile diarrhea]. Anales españoles de pediatría Vol 39; 1993: 309-12. Not English 

language 

405. Cline MJ, Williams HE, Smith LH, Jr. Lactose intolerance. Calif Med 1967 Oct; 107(4):350­

4. Not relevant to key questions 

406. Clubley M, Bye CE, Henson T, et al. A technique for studying the effects of drugs on human 

sweat gland activity. Eur J Clin Pharmacol Vol 14; 1978: 221-6. Not lactose intolerance 

study 

407. Cochet B, Jung A, Griessen M, et al. Effects of lactose on intestinal calcium absorption in 

normal and lactase-deficient subjects. Gastroenterology 1983 May; 84(5 Pt 1):935-40. Not 

eligible outcomes 

408. Cochran M, Nordin BE. Panhypopituitarism, testicular atrophy, alactasia, corticosteroidinduced osteoporosis and systemic lupus erythematosus induced by methoin. Proc R Soc Med 

1968 Jul; 61(7):656. Not eligible target population 

187
 
409. Coda BA, Mackie A, Hill HF. Influence of alprazolam on opioid analgesia and side effects 

during steady-state morphine infusions. Pain Vol 50; 1992: 309-16. Not lactose intolerance 

study 

410. Coello-Ramirez P, Gutierres-Topete G, Lifshitz F. Pneumatosis intestinalis. Am J Dis Child 

1970 Jul; 120(1):3-9. Not relevant to key questions 

411. Coello-Ramirez P, Larrosa-Haro A. Gastrointestinal occult hemorrhage and gastroduodenitis 

in cow's milk protein intolerance. J Pediatr Gastroenterol Nutr 1984 Mar; 3(2):215-8. Not 

relevant to key questions 

412. Coello-Ramirez P, Lifshitz F. Enteric microflora and carbohydrate intolerance in infants with 

diarrhea. Pediatrics 1972 Feb; 49(2):233-42. Not relevant to key questions 

413. Cohen L. Lactase deficiency: helping patients cope. J Pract Nurs 1991 Dec; 41(4):59-61. Not 

relevant to key questions 

414. Cohen MB, Mezoff AG, Laney DW, et al. Use of a single solution for oral rehydration and 

maintenance therapy of infants with diarrhea and mild to moderate dehydration. Pediatrics 

Vol 95; 1995: 639-45. Not relevant to key questions 

415. Cole ET, Scott RA, Connor AL, et al. Enteric coated HPMC capsules designed to achieve 

intestinal targeting. International journal of pharmaceutics Vol 231; 2002: 83-95. Not lactose 

intolerance study 

416. Collomp K, Le PB, Portier H, et al. Effects of acute salbutamol intake during a Wingate test. 

International journal of sports medicine Vol 26; 2005: 513-7. Not lactose intolerance study 

417. Colomina MJ, Puig L, Godet C, et al. Prevalence of asymptomatic cardiac valve anomalies in 

idiopathic scoliosis. Pediatric Cardiology 2002 Jul-Aug; 23(4):426-9. No prevalence data 

418. Colton T, Gosselin RE, Smith RP. The tolerance of coffee drinkers to caffeine. Clinical 

pharmacology and therapeutics Vol 9; 1968: 31-9. Not lactose intolerance study 

419. Condon JR, Nassim JR, Millard FJ, et al. Calcium and phosphorus metabolism in relation to 

lactose tolerance. Lancet 1970 May 16; 1(7655):1027-9. Not eligible outcomes 

420. Condon JR, Westerholm P, Tanner NC. Lactose malabsorption and postgastrectomy milk 

intolerance, dumping, and diarrhoea. Gut 1969 Apr; 10(4):311-4. Not eligible target 

population 

421. Conley ME, Anolik R. The baby who refused to walk. Hospital Practice (Office Edition) 

1981 Dec; 16(12):109. Ineligible number of subjects 

422. Cook GC. Jejunal disaccharidiases in Uganda. East Afr Med J 1966 Nov; 43(11):554-7. Not 

relevant to key questions 

423. Cook GC. Malabsorption. Br Med J 1967 Mar 11; 1(5540):613-7. Not relevant to key 

questions 

424. Cook GC. Lactase activity in newborn and infant Baganda. Br Med J 1967 Mar 4; 

1(5539):527-30. Not relevant to key questions 

188
 
425. Cook GC. Defects of sugar absorption. Some observations on racial lactase deficiency. Proc 

R Soc Med 1968 Nov; 61(11 Part 1):1102-4. Not relevant to key questions 

426. Cook GC. Some factors influencing absorption rates of the digestion products of protein and 

carbohydrate from the proximal jejunum of man and their possible nutritional implications. 

Gut 1974 Mar; 15(3):239-45. Not relevant to key questions 

427. Cook GC. Serum cholesterol concentration in Arabs in Riyadh Saudi Arabia, and its relation 

to adult hypolactasia. Trop Geogr Med 1976 Dec; 28(4):339-42. Not relevant to key questions 

428. Cook GC. Breath hydrogen concentrations after oral lactose and lactulose in tropical 

malabsorption and adult hypolactasia. Trans R Soc Trop Med Hyg 1978; 72(3):277-81. Not 

relevant to key questions 

429. Cook GC. Intestinal lactase status of adults in Papua New Guinea. Ann Hum Biol 1979 JanFeb; 6(1):55-8. Not relevant to key questions 

430. Cook GC, Dahlqvist A. Jejunal hetero-beta-galactosidase activities in Ugandans with lactase 

deficiency. Gastroenterology 1968 Sep; 55(3):328-32. Not relevant to key questions 

431. Cook GC, Howells GR. Lactosuria in the African with lactase deficiency. Am J Dig Dis 1968 

Jul; 13(7):634-7. Not relevant to key questions 

432. Cook GC, Kajubi SK. Tribal incidence of lactase deficiency in Uganda. Lancet 1966 Apr 2; 

1(7440):725-9. Not relevant to key questions 

433. Cook GC, Lakin A, Whitehead RG. Absorption of lactose and its digestion products i the 

normal and malnourished Ugandan. Gut 1967 Dec; 8(6):622-7. Not relevant to key questions 

434. Cook GC, Lee FD. The jejunum after kwashiorkor. Lancet 1966 Dec 10; 2(7476):1263-7. Not 

relevant to key questions 

435. Cooke WT. Common problems of malabsorption. Practitioner 1976 Jun; 216(1296):637-41. 

Not relevant to key questions 

436. Cooke WT, Asquith P, Ruck N, et al. Rickets, growth, and alkaline phosphatase in urban 

adolescents. Br Med J 1974 May 11; 2(5914):293-7. Not eligible target population 

437. Cooper BT. Lactase deficiency and lactose malabsorption. Dig Dis 1986; 4(2):72-82. Not 

relevant to key questions 

438. Cooper GS, Busby MG, Fairchild AP. Measurement of lactose consumption reliability and 

comparison of two methods. Annals of Epidemiology Vol 5; 1995: 473-7. Not eligible 

outcomes 

439. Corazza GR, Benati G, Sorge M, et al. beta-Galactosidase from Aspergillus niger in adult 

lactose malabsorption: a double-blind crossover study. Aliment Pharmacol Ther 1992 Feb; 

6(1):61-6. Not relevant to key questions 

440. Corazza GR, Ginaldi L, Furia N, et al. The impact of HIV infection on lactose absorptive 

capacity. Journal of Infection 1997 Jul; 35(1):31-5. Ineligible number of subjects 

441. Corazza GR, Sorge M, Strocchi A, et al. Methodology of the H2 breath test. II. Importance of 

the test duration in the diagnosis of carbohydrate malabsorption. Ital J Gastroenterol 1990 

Oct; 22(5):303-5. Not relevant to key questions 

442. Cordano A, Grahma GG. Copper deficiency complicating severe chronic intestinal 

malabsorption. Pediatrics 1966 Oct; 38(4):596-604. Not eligible target population 

443. Coremans G, Geypens B, Vos R, et al. Influence of continuous isobaric rectal distension on 

gastric emptying and small bowel transit in young healthy women. Neurogastroenterology 

and motility : the official journal of the European Gastrointestinal Motility Society Vol 16; 

2004: 107-11. Not lactose intolerance 

189
 
444. Coremans G, Vos R, Margaritis V, et al. Small doses of the unabsorbable substance 

polyethylene glycol 3350 accelerate oro-caecal transit, but slow gastric emptying in healthy 

subjects. Digestive and liver disease : official journal of the Italian Society of 

Gastroenterology and the Italian Association for the Study of the Liver Vol 37; 2005: 97-101. 

Not lactose intolerance 

445. Corkey C, Mindorff C, Levison H, et al. Comparison of three different preparations of 

disodium cromoglycate in the prevention of exercise-induced bronchospasm: a double-blind 

study. The American review of respiratory disease Vol 125; 1982: 623-6. Not lactose 

intolerance study 

446. Costongs GM, Bos LP, Engels LG, et al. A new method for chemical analysis of faeces. Clin 

Chim Acta 1985 Aug 30; 150(3):197-203. Not relevant to key questions 

447. Cox JA, Elliott FG. Primary adult lactose intolerance in the Kivu Lake area: Rwanda and the 

Bushi. Am J Dig Dis 1974 Aug; 19(8):714-24. Not relevant to key questions 

448. Coyne MJ, Rodriguez H. Carbohydrate malabsorption in black and Hispanic dialysis patients. 

Am J Gastroenterol 1986 Aug; 81(8):662-5. Not relevant to key questions 

449. Craig O. The radiology of small bowel lesions. Postgrad Med J 1970 Jan; 46(531):44-51. Not 

relevant to key questions 

450. Craig RP. The quantitative evaluation of the use of oral proteolytic enzymes in the treatment 

of sprained ankles. Injury Vol 6; 1975: 313-6. Not lactose intolerance study 

451. Cramer DW, Xu H, Sahi T. Adult hypolactasia, milk consumption, and age-specific fertility. 

American Journal of Epidemiology 1994 Feb 1; 139(3):282-9. Not original research 

452. Crawford MA. Lactase deficiency. Nature 1969 Aug 16; 223(5207):742. Not relevant to key 

questions 

453. Creagan ET, Moertel CG, O'Fallon JR, et al. Failure of high-dose vitamin C (ascorbic acid) 

therapy to benefit patients with advanced cancer. A controlled trial. The New England journal 

of medicine Vol 301; 1979: 687-90. Not lactose intolerance study 

454. Crisp J, Ostrander C, Giannini A, et al. Cromolyn sodium therapy for chronic perennial 

asthma. A double-blind study of 40 children. JAMA : the journal of the American Medical 

Association Vol 229; 1974: 787-9. Not lactose intolerance study 

455. Crittenden RG, Bennett LE. Cow's milk allergy: a complex disorder. J Am Coll Nutr 2005 

Dec; 24(6 Suppl):582S-91S. Not eligible target population 

456. Croagh C, Shepherd SJ, Berryman M, et al. Pilot study on the effect of reducing dietary 

FODMAP intake on bowel function in patients without a colon. Inflammatory Bowel 

Diseases 2007 Dec; 13(12):1522-8. Ineligible number of subjects 

457. Cuddenec Y, Delbruck H, Flatz G. Distribution of the adult lactase phenotypes--lactose 

absorber and malabsorber--in a group of 131 army recruits. Gastroenterol Clin Biol 1982 Oct; 

6(10):776-9. Not relevant to key questions 

458. Curtis JA, Kooh SW, Fraser D, et al. Nutritional rickets in vegetarian children. Can Med 

Assoc J 1983 Jan 15; 128(2):150-2. Not eligible target population 

459. Cuvelier A, Muir JF, Benhamou D, et al. Dry powder ipratropium bromide is as safe and 

effective as metered-dose inhaler formulation: a cumulative dose-response study in chronic 

obstructive pulmonary disease patients. Respiratory care Vol 47; 2002: 159-66. Not lactose 

intolerance study 

460. Czernichow B, Cui SW, Goldstein L, et al. Delayed effects of protracted or single yoghurt 

and saccharomyces boulaardii ingestion on lactose absorption in a lactase deficiency Chinese 

population [abstract]. Clin-Nutr Vol 12; 1993: 45. Not relevant to key questions 

190
 
461. Czerwenka H, Maly J, Quatember R, et al. [Clinical and test psychological studies with a 

geriatric agent]. Wiener medizinische Wochenschrift (1946) Vol 120; 1970: 217-24. Not 

lactose intolerance study 

462. Dady IM, Thomas AG, Miller V, et al. Inflammatory bowel disease in infancy: an increasing 

problem? Journal of Pediatric Gastroenterology & Nutrition 1996 Dec; 23(5):569-76. 

Ineligible number of subjects 

463. Dagan R, Gorodischer R, Moses S, et al. Lactose-free formulae for infantile diarrhoea. Lancet 

Vol 1; 1980: 207. Not relevant to key questions 

464. Dagnelie PC, van Staveren WA. Macrobiotic nutrition and child health: results of a 

population-based, mixed-longitudinal cohort study in The Netherlands. Am J Clin Nutr 1994 

May; 59(5 Suppl):1187S-96S. Not eligible outcomes 

465. Dagnelie PC, van Staveren WA, Roos AH, et al. Nutrients and contaminants in human milk 

from mothers on macrobiotic and omnivorous diets. Eur J Clin Nutr 1992 May; 46(5):355-66. 

Not relevant to key questions 

466. Dagnelie PC, Vergote FJ, van Staveren WA, et al. High prevalence of rickets in infants on 

macrobiotic diets. Am J Clin Nutr 1990 Feb; 51(2):202-8. Not eligible target population 

467. Dahlqvist A. Sugar malabsorption. Scand J Clin Lab Invest Suppl 1967; 100:96. Not relevant 

to key questions 

468. Dahlqvist A. Assay of intestinal disaccharidases. Enzymol Biol Clin (Basel) 1970; 11(1):52­

66. Not relevant to key questions 

469. Dahlqvist A. The role of enzymes in the digestive tract. Prog Clin Biol Res 1981; 77:883-91. 

Not relevant to key questions 

470. Dahlqvist A, Asp NG. Accurate assay of low intestinal lactase activity with a fluorometric 

method. Anal Biochem 1971 Dec; 44(2):654-7. Not relevant to key questions 

471. Dahlqvist A, Hammond JB, Crane RK, et al. Intestinal lactase deficiency and lactose 

intolerance in adults. Preliminary report. Gastroenterology 1968 Apr; 54(4):Suppl:807-10. 

Not relevant to key questions 

472. Dahlqvist A, Lindberg T, Meeuwisse G, et al. Intestinal dipeptidases and disaccharidases in 

children with malabsorption. Acta Paediatr Scand 1970 Nov; 59(6):621-30. Not relevant to 

key questions 

473. Dahlstrom KA, Danielsson L, Kalin M, et al. Chronic non-specific diarrhea of infancy 

successfully treated with trimethoprim-sulfamethoxazole. Scandinavian journal of 

gastroenterology 1989 Jun; 24(5):589-92. Not relevant to key questions 

474. Dahlström KA, Danielsson L, Kalin M, et al. Chronic non-specific diarrhea of infancy 

successfully treated with trimethoprim-sulfamethoxazole. Scandinavian journal of 

gastroenterology Vol 24; 1989: 589-92. Not relevant to key questions 

475. Danchaivijitr A, Nakornchai S, Thaweeboon B, et al. The effect of different milk formulas on 

dental plaque pH. International journal of paediatric dentistry / the British Paedodontic 

Society [and] the International Association of Dentistry for Children Vol 16; 2006: 192-8. 

Not eligible outcomes 

476. Dandona P, Mohiuddin J, Weerakoon JW, et al. Persistence of parathyroid hypersecretion 

after vitamin D treatment in Asian vegetarians. J Clin Endocrinol Metab 1984 Sep; 

59(3):535-7. Not eligible outcomes 

477. Danovitch SH. Gastrointestinal function after forty. Am Fam Physician 1984 Feb; 29(2):205­

10. Not relevant to key questions 

191
 
478. Darling P, Lepage G, Tremblay P, et al. Protein quality and quantity in preterm infants 

receiving the same energy intake. American journal of diseases of children (1960) Vol 139; 

1985: 186-90. Not relevant to key questions 

479. Davey GK, Spencer EA, Appleby PN, et al. EPIC-Oxford: lifestyle characteristics and 

nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK. 

Public Health Nutr 2003 May; 6(3):259-69. Not eligible outcomes 

480. Davidson GP. Lactase deficiency. Diagnosis and management. Med J Aust 1984 Sep 29; 

141(7):442-4. Not relevant to key questions 

481. Davidson GP. Cow's milk protein intolerance: diagnosis and management. Aust Fam 

Physician 1986 Feb; 15(2):204, 7. Not relevant to key questions 

482. Davidson GP, Goodwin D, Robb TA. Incidence and duration of lactose malabsorption in 

children hospitalized with acute enteritis: study in a well-nourished urban population. J 

Pediatr 1984 Oct; 105(4):587-90. Not relevant to key questions 

483. Davidson GP, Robb TA. Value of breath hydrogen analysis in management of diarrheal 

illness in childhood: comparison with duodenal biopsy. J Pediatr Gastroenterol Nutr 1985 

Jun; 4(3):381-7. Not relevant to key questions 

484. Davie I, Masson AH. An assessment of the analgesic efficacy of oral pentazocine. British 

journal of anaesthesia Vol 42; 1970: 169-73. Not lactose intolerance study 

485. Davis AE. Irritable colon syndrome and lactose intolerance. Aust N Z J Med 1971 Nov; 

1(4):420-1. Not relevant to key questions 

486. Davis AE. Alactasia. Med J Aust 1972 Aug 19; 2(8):431-2. Not relevant to key questions 

487. Davis AE, Bolin T. Lactose intolerance in asians. Nature 1967 Dec 23; 216(5121):1244-5. 

Not relevant to key questions 

488. Davis AE, Bolin TD. Lactose intolerance in Asians. Gut 1969 Jan; 10(1):78. Not relevant to 

key questions 

489. Davis FA, Stefoski D, Rush J. Orally administered 4-aminopyridine improves clinical signs 

in multiple sclerosis. Annals of neurology Vol 27; 1990: 186-92. Not lactose intolerance 

study 

490. Davis JW, Novotny R, Ross PD, et al. Anthropometric, lifestyle and menstrual factors 

influencing size-adjusted bone mineral content in a multiethnic population of premenopausal 

women. J Nutr 1996 Dec; 126(12):2968-76. Not eligible outcomes 

491. Dawson B, Trapp RG. Basic & Clinical Biostatistics (LANGE Basic Science). 3rd ed. New 

York: Lange Medical Books-McGraw-Hill; 2004. Custom 3 

492. D'Azzo A, Hoogeveen A, Reuser AJ, et al. Molecular defect in combined beta-galactosidase 

and neuraminidase deficiency in man. Proc Natl Acad Sci U S A 1982 Aug; 79(15):4535-9. 

Not relevant to key questions 

493. de Gast-Bakker DA, van Vliet I, Alles M, et al. Intestinal permeability and lactase activity in 

premature infants receiving enteral IGF-I supplementation, a randomized controlled trial. 

Pediatric research Vol 55; 2004: 99. Not relevant to key questions 

494. De Giorgio R, Barbara G, Stanghellini V, et al. Diagnosis and therapy of irritable bowel 

syndrome. Aliment Pharmacol Ther 2004 Jul; 20 Suppl 2:10-22. Not relevant to key questions 

495. De Haan P, Lerk CF. The megaloporous system: A novel principle for zero-order drug 

delivery I. In vitro and in vivo performance. International Journal of Pharmaceutics Vol 31; 

1986: 15-24. Not lactose intolerance study 

496. De Preter V, Geboes K, Verbrugghe K, et al. The in vivo use of the stable isotope-labelled 

192
 
biomarkers lactose-[15N]ureide and [2H4]tyrosine to assess the effects of pro- and prebiotics 

on the intestinal flora of healthy human volunteers. The British journal of nutrition Vol 92; 

2004: 439-46. Not lactose intolerance 

497. De Preter V, Vanhoutte T, Huys G, et al. Effect of lactulose and Saccharomyces boulardii 

administration on the colonic urea-nitrogen metabolism and the bifidobacteria concentration 

in healthy human subjects. Alimentary pharmacology & therapeutics Vol 23; 2006: 963-74. 

Not lactose intolerance 

498. De Ritis F, Balestrieri GG, Ruggiero G, et al. High incidence of lactase activity deficiency in 

small bowel of adults in the Naples area. Pol Arch Med Wewn 1970 Apr-May; 4(4):539-42. 

Not relevant to key questions 

499. De Ritis F, Balestrieri GG, Ruggiero G, et al. High frequency of lactase activity deficiency in 

small bowel of adults in the Neapolitan area. Enzymol Biol Clin (Basel) 1970; 11(3):263-7. 

Not relevant to key questions 

500. de Villiers FP. A standardized milk tolerance test. J Clin Gastroenterol 1987 Jun; 9(3):320-3. 

Not relevant to key questions 

501. de Villiers FP. Relationship between milk lactose tolerance and body mass in teenage Tswana 

schoolchildren. South African Medical Journal Suid-Afrikaanse Tydskrif Vir Geneeskunde 

1988 Nov 19; 74(10):499-501. Ineligible number of subjects 

502. de Villiers FP. The effect of lactose maldigestion on the stools of young Tswana children. J 

Trop Pediatr 1995 Feb; 41(1):54-6. Not relevant to key questions 

503. de Vizia B, Poggi V, Conenna R, et al. Iron absorption and iron deficiency in infants and 

children with gastrointestinal diseases. Journal of Pediatric Gastroenterology & Nutrition 

1992 Jan; 14(1):21-6. No prevalence data 

504. de Vrese M, Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv Biochem Eng 

Biotechnol 2008; 111:1-66. Not relevant to key questions 

505. de Vrese M, Stegelmann A, Richter B, et al. Probiotics--compensation for lactase 

insufficiency. Am J Clin Nutr 2001 Feb; 73(2 Suppl):421S-9S. Not relevant to key questions 

506. De Vries HA, Adams GM. Electromyographic comparison of single doses of exercise and 

meprobamate as to effects on muscular relaxation. American journal of physical medicine 

Vol 51; 1972: 130-41. Not lactose intolerance study 

507. de Vries TW, Wierdsma N, van Ede J, et al. Dieting in children referred to the paediatric 

outpatient clinic. European journal of pediatrics 2001 Oct; 160(10):595-8. Not relevant to key 

questions 

508. Dearlove J, Dearlove B, Pearl K, et al. Dietary lactose and the child with abdominal pain. Br 

Med J (Clin Res Ed) 1983 Jun 18; 286(6382):1936. Not relevant to key questions 

193
 
509. Dearlove J, Dearlove B, Pearl K, et al. A measure of aggression among working-class youths. 

Br-Med-J-Clin-Res-Ed Vol 286; 1983: 1936. Not relevant to key questions 

510. Debongnie JC, Newcomer AD, McGill DB, et al. Absorption of nutrients in lactase 

deficiency. Dig Dis Sci 1979 Mar; 24(3):225-31. Not relevant to key questions 

511. Degenhardt DP, Hodgkinson R. Ethaverine in the treatment of angina pectoris. British Heart 

Journal Vol 16; 1954: 142-6. Not lactose intolerance study 

512. DeGrandpre RJ, Bickel WK, Higgins ST. Emergent equivalence relations between 

interoceptive (drug) and exteroceptive (visual) stimuli. Journal of the experimental analysis of 

behavior Vol 58; 1992: 9-18. Not lactose intolerance study 

513. Dehkordi N, Rao DR, Warren AP, et al. Lactose malabsorption as influenced by chocolate 

milk, skim milk, sucrose, whole milk, and lactic cultures. J Am Diet Assoc 1995 Apr; 

95(4):484-6. Not relevant to key questions 

514. Demetree JW, Safer LF, Artis WM. The effect of zinc on the sebum secretion rate. Acta 

dermato-venereologica Vol 60; 1980: 166-69. Not lactose intolerance study 

515. Den Tandt WR, Hooghwinkel GJ. Brain lysosomal enzymes in generalized gangliosidosis 

and metachromatic leukodystrophy. Acta Neurol (Napoli) 1980 Feb; 2(1):10-4. Not relevant 

to key questions 

516. Densupsoontorn N, Jirapinyo P, Thamonsiri N, et al. Lactose intolerance in Thai adults. J 

Med Assoc Thai 2004 Dec; 87(12):1501-5. Not relevant to key questions 

517. Dent CE, Gupta MM. Plasma 25-hydroxyvitamin-D-levels during pregnancy in Caucasians 

and in vegetarian and non-vegetarian Asians. Lancet 1975 Nov 29; 2(7944):1057-60. Not 

eligible outcomes 

518. Dent CE, Round JM, Rowe DJ, et al. Effect of chapattis and ultraviolet irradiation on 

nutritional rickets in an Indian immigrant. Lancet 1973 Jun 9; 1(7815):1282-4. Not eligible 

target population 

519. Dent CE, Smith R. Nutritional osteomalacia. Q J Med 1969 Apr; 38(150):195-209. Not 

eligible target population 

520. Desai AB, Gandhi RA, Vani GB. Lactose intolerance. Indian Pediatr 1969 Jul; 6(7):457-62. 

Not relevant to key questions 

521. Desai HG. Editorial: Intestinal disaccharidases. J Assoc Physicians India 1974 Dec; 

22(12):918-20. Editorial 

522. Desai HG, Antia FP. Lactose load and abdominal symptoms: should milk be withdrawn from 

healthy subjects with low lactase levels? Gastroenterology 1973 Jan; 64(1):136-8. Not 

relevant to key questions 

523. Desai HG, Chitre AV, Jeejeebhoy KN. Lactose loading. A simple test for detecting intestinal 

lactase. Evaluation of different methods. Gastroenterologia 1967; 108(4):177-88. Not relevant 

to key questions 

194
 
524. Desai HG, Gupte UV, Pradhan AG, et al. Incidence of lactase deficiency in control subjects 

from India. Role of hereditary factors. Indian J Med Sci 1970 Nov; 24(11):729-36. Not 

relevant to key questions 

525. Desai HG, Pereira E, Jeejeebhoy KN. Disaccharidases in jejunal and ileal mucosa in Indian 

subjects. Indian J Med Sci 1969 Oct; 23(10):538-42. Not relevant to key questions 

526. Deutschmann HA, Weger M, Weger W, et al. Search for occult secondary osteoporosis: 

impact of identified possible risk factors on bone mineral density. Journal of Internal 

Medicine 2002 Nov; 252(5):389-97. No prevalence data 

527. Dewit O, Boudraa G, Touhami M, et al. Breath hydrogen test and stools characteristics after 

ingestion of milk and yogurt in malnourished children with chronic diarrhoea and lactase 

deficiency. J Trop Pediatr 1987 Aug; 33(4):177-80. Not relevant to key questions 

528. Dhatt PS, Aggarwal RK, Saini AS, et al. Disaccharide intolerence and Indian childhood 

cirrhosis. IV. Relationship of melituria to lactose administration. Indian Pediatr 1982 Jul; 

19(7):583-9. Not relevant to key questions 

529. Dhonukshe-Rutten RA, van Dusseldorp M, Schneede J, et al. Low bone mineral density and 

bone mineral content are associated with low cobalamin status in adolescents. Eur J Nutr 

2005 Sep; 44(6):341-7. Not eligible exposure 

530. Dhume RR, Dhume RA. A comparative study of the driving effects of dextroamphetamine 

and yogic meditation on muscle control for the performance of balance on balance board. 

Indian journal of physiology and pharmacology Vol 35; 1991: 191-4. Not lactose intolerance 

study 

531. Di Camillo M, Marinaro V, Argnani F, et al. Hydrogen breath test for diagnosis of lactose 

malabsorption: the importance of timing and the number of breath samples. Canadian Journal 

of Gastroenterology 2006 Apr; 20(4):265-8. No prevalence data 

532. Di Nola F, Soranzo ML, Bosio G, et al. [Pharmacokinetic and clinical research on a new 

antibiotic combination (amoxicillin and flucloxacillin in equivalent-weight dose)]. Minerva 

medica Vol 68; 1977: 917-28. Not lactose intolerance study 

533. Di Stefano M, Miceli E, Mazzocchi S, et al. Visceral hypersensitivity and intolerance 

symptoms in lactose malabsorption. Neurogastroenterol Motil 2007 Nov; 19(11):887-95. Not 

relevant to key questions 

534. Di Stefano M, Missanelli A, Miceli E, et al. Hydrogen breath test in the diagnosis of lactose 

malabsorption: accuracy of new versus conventional criteria. J Lab Clin Med 2004 Dec; 

144(6):313-8. Not relevant to key questions 

535. Di Stefano M, Veneto G, Malservisi S, et al. Lactose malabsorption and intolerance in the 

elderly. Scandinavian Journal of Gastroenterology 2001 Dec; 36(12):1274-8. Ineligible 

number of subjects 

195
 
536. Diamond S. Double-blind study of metaxalone; use as skeletal-muscle relaxant. JAMA : the 

journal of the American Medical Association Vol 195; 1966: 479-80. Not lactose intolerance 

study 

537. Díaz S, Croxatto HB, Pavez M, et al. Clinical assessment of treatments for prolonged 

bleeding in users of Norplant implants. Contraception Vol 42; 1990: 97-109. Not lactose 

intolerance study 

538. Díaz-Sánchez V, Antúnez O, Vargas L, et al. Absorption of oral ethinylestradiol is delayed by 

its eutectic mixture with cholesterol. Contraception Vol 43; 1991: 45-53. Not lactose 

intolerance study 

539. Diestelhorst M, Grunthal S, Süverkrüp R. Dry Drops: a new preservative-free drug delivery 

system. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes 

Archiv für klinische und experimentelle Ophthalmologie Vol 237; 1999: 394-8. Not lactose 

intolerance study 

540. Dill JE, Levy M, Wells RF, et al. Lactase deficiency in Mexican-American males. Am J Clin 

Nutr 1972 Sep; 25(9):869-70. Not relevant to key questions 

541. Dinnerstein AJ, Halm J. Modification of placebo effects by means of drugs: effects of aspirin 

and placebos on self-rated moods. Journal of abnormal psychology Vol 75; 1970: 308-14. Not 

lactose intolerance study 

542. DiPalma JA, Collins MS. Enzyme replacement for lactose malabsorption using a beta-Dgalactosidase. J Clin Gastroenterol 1989 Jun; 11(3):290-3. Not relevant to key questions 

543. DiPalma JA, Narvaez RM. Prediction of lactose malabsorption in referral patients. Dig Dis 

Sci 1988 Mar; 33(3):303-7. Not relevant to key questions 

544. Dissanayake AS, Truelove SC, Whitehead R. Jejunal mucosal recovery in coeliac disease in 

relation to the degree of adherence to a gluten-free diet. The Quarterly journal of medicine 

Vol 43; 1974: 161-85. Not relevant to key questions 

545. Donaldson RM, Jr. The muddle of diets for gastrointestinal disorders. JAMA 1973 Sep 3; 

225(10):1243. Not relevant to key questions 

546. Donovan GK, Torres-Pinedo R. Chronic diarrhea and soy formulas. Inhibition of diarrhea by 

lactose. American journal of diseases of children (1960) Vol 141; 1987: 1069-71. Not 

relevant to key questions 

547. Donovan UM, Gibson RS. Dietary intakes of adolescent females consuming vegetarian, semivegetarian, and omnivorous diets. J Adolesc Health 1996 Apr; 18(4):292-300. Not relevant to 

key questions 

548. Doron S, Gorbach SL. Probiotics: their role in the treatment and prevention of disease. Expert 

Rev Anti Infect Ther 2006 Apr; 4(2):261-75. Not relevant to key questions 

549. Dossetor JF, Whittle HC. Protein-losing enteropathy and malabsorption in acute measles 

enteritis. Br Med J 1975 Jun 14; 2(5971):592-3. Not relevant to key questions 

550. Douwes AC, Fernandes J, Degenhart HJ. Improved accuracy of lactose tolerance test in 

children, using expired H2 measurement. Arch Dis Child 1978 Dec; 53(12):939-42. Not 

relevant to key questions 

551. Douwes AC, Fernandes J, Jongbloed AA. Diagnostic value of sucrose tolerance test in 

children evaluated by breath hydrogen measurement. Acta Paediatr Scand 1980 Jan; 

69(1):79-82. Not relevant to key questions 

552. Douwes AC, Oosterkamp RF, Fernandes J, et al. Sugar malabsorption in healthy neonates 

estimated by breath hydrogen. Arch Dis Child 1980 Jul; 55(7):512-5. Not relevant to key 

questions 

196
 
553. Douwes AC, Schaap C, van der Klei-van Moorsel JM. Hydrogen breath test in 

schoolchildren. Arch Dis Child 1985 Apr; 60(4):333-7. Not relevant to key questions 

554. Doxiadis S, Papageorgiadis G. Lactose intolerance in Greeks. Lancet 1973 Feb 3; 

1(7797):271. Not relevant to key questions 

555. Drapeau C, Hamel-Hébert I, Robillard R, et al. Challenging sleep in aging: the effects of 200 

mg of caffeine during the evening in young and middle-aged moderate caffeine consumers. 

Journal of sleep research Vol 15; 2006: 133-41. Not lactose intolerance study 

556. Drewitt PN, Butterworth KR, Springall CD, et al. Toxicity threshold of quinine hydrochloride 

following low-level repeated dosing in healthy volunteers. Food and chemical toxicology : an 

international journal published for the British Industrial Biological Research Association Vol 

31; 1993: 235-45. Not lactose intolerance study 

557. Drube HC, Hansen HT, Klein UE, et al. Disaccharidase activity of the jejunal mucosa in 

normal subjects and patients after partial gastrectomy. Ger Med Mon 1967 Sep; 12(9):418-21. 

Not relevant to key questions 

558. Duan LP, Braden B, Clement T, et al. Clinical evaluation of a miniaturized desktop breath 

hydrogen analyzer. Z Gastroenterol 1994 Oct; 32(10):575-8. Not relevant to key questions 

559. Dufourmentel C, Pailheret JP, Raulo Y. [Double-blind trial of a new therapeutic agent with 

wound healing properties]. Annales de chirurgie plastique Vol 19; 1974: 139-46. Not lactose 

intolerance study 

560. Dughera L, Elia C, Navino M, et al. Effects of symbiotic preparations on constipated irritable 

bowel syndrome symptoms. Acta Bio-Medica de l Ateneo Parmense 2007 Aug; 78(2):111-6. 

No prevalence data 

561. Duncan A, Park RP, Lee FD, et al. A retrospective assessment of the clinical value of jejunal 

disaccharidase analysis. Scand J Gastroenterol 1994 Dec; 29(12):1111-6. Not relevant to key 

questions 

562. Duncan IW, Scott EM. Lactose intolerance in Alaskan Indians and Eskimos. Am J Clin Nutr 

1972 Sep; 25(9):867-8. Not relevant to key questions 

563. Dupont C, Moreno JL, Barau E, et al. Effect of diosmectite on intestinal permeability changes 

in acute diarrhea: a double-blind placebo-controlled trial. Journal of pediatric 

gastroenterology and nutrition Vol 14; 1992: 413-9. Not eligible target population 

197
 
564. Duteil L, Queille C, Poncet M, et al. Processing and statistical analysis of laser Doppler data 

applied to the assessment of systemic anti-inflammatory drugs. Journal of dermatological 

science Vol 2; 1991: 376-82. Not lactose intolerance study 

565. Dwyer JT. Health aspects of vegetarian diets. Am J Clin Nutr 1988 Sep; 48(3 Suppl):712-38. 

Review 

566. Dwyer JT, Dietz WH, Jr., Hass G, et al. Risk of nutritional rickets among vegetarian children. 

Am J Dis Child 1979 Feb; 133(2):134-40. Not eligible outcomes 

567. Eaglstein WH, Feinstein RJ, Halprin KM, et al. Systemic antibiotic therapy of secondary 

infected dermatitis. Archives of dermatology Vol 113; 1977: 1378-9. Not lactose intolerance 

study 

568. Eastham EJ, Walker WA. Effect of cow's milk on the gastrointestinal tract: a persistent 

dilemma for the pediatrician. Pediatrics 1977 Oct; 60(4):477-81. Not relevant to key questions 

569. Easton CJ, Bauer LO. Beneficial effects of thiamine on recognition memory and P300 in 

abstinent cocaine-dependent patients. Psychiatry research Vol 70; 1997: 165-74. Not lactose 

intolerance study 

570. Eastwood MA, Walton BA, Brydon WG, et al. Faecal weight, constituents, colonic motility, 

and lactose tolerance in the irritable bowel syndrome. Digestion 1984; 30(1):7-12. Not 

relevant to key questions 

571. Ebbesen F, Edelsten D, Hertel J. Gut transit time and lactose malabsorption during 

phototherapy. II. A study using raw milk from the mothers of the infants. Acta Paediatr Scand 

1980 Jan; 69(1):69-71. Not relevant to key questions 

572. Ebbesen F, Edelsten D, Hertel J. Gut transit time and lactose malabsorption during 

phototherapy. I. A study using lactose-free human mature milk. Acta Paediatr Scand 1980 

Jan; 69(1):65-8. Not relevant to key questions 

573. Ebrahim S. The use of numbers needed to treat derived from systematic reviews and metaanalysis. Caveats and pitfalls. Eval Health Prof 2001 Jun; 24(2):152-64. Not relevant to key 

questions 

574. Eddington ND, Ashraf M, Augsburger LL, et al. Identification of formulation and 

manufacturing variables that influence in vitro dissolution and in vivo bioavailability of 

propranolol hydrochloride tablets. Pharm Dev Technol Vol 3; 1998: 535-47. Not lactose 

intolerance study 

575. Edwards AM, Chambers A. Comparison of a lactose-free formulation of sodium 

cromoglycate and sodium cromoglycate plus lactose in the treatment of asthma. Current 

medical research and opinion Vol 11; 1989: 283-92. Not lactose intolerance study 

576. Eerikainen S, Leino J, Harjula M, et al. Use of a hard gelatin capsule as a rectal dosage form. 

S.T.P. Pharma Pratiques. Vol 6; 1996: 435-40. Not lactose intolerance study 

577. Egarter C, Eppel W, Vogel S, et al. A pilot study of hormone replacement therapy with 

tibolone in women with mastopathic breasts. Maturitas Vol 40; 2001: 165-71. Not lactose 

intolerance study 

578. Egger M, Smith GD, Altman DG. Systematic Reviews in Health Care. London: NetLibrary, 

Inc. BMJ Books; 2001. Custom 3 

579. Eichenberger JR, Hadorn B, Schmidt BJ. A semi-elemental diet with low osmolarity and high 

content of hydrolyzed lactalbumin in the treatment of acute diarrhea in malnourished 

children. Arquivos de gastroenterologia Vol 21; 1984: 130-5. Not relevant to key questions 

580. Elbary AA, El-laithy HM, Tadros MI. Promising ternary dry powder inhaler formulations of 

cromolyn sodium: formulation and in vitro-in vivo evaluation. Archives of pharmacal 

198
 
research Vol 30; 2007: 785-92. Not lactose intolerance study 

581. el-Ebrashy N, Shaheen MH, Wasfi AA, et al. Side effects of IV fructose load in diabetics. J 

Egypt Med Assoc 1974; 57(9-10):406-14. Not relevant to key questions 

582. Eley B. Metabolic complications of antiretroviral therapy in HIV-infected children. Expert 

Opinion On Drug Metabolism & Toxicology 2008 Jan; 4(1):37-49. Not original research 

583. Ellestad-Sayed JJ, Haworth JC. Disaccharide consumption and malabsorption in Canadian 

Indians. Am J Clin Nutr 1977 May; 30(5):698-703. Not relevant to key questions 

584. Ellestad-Sayed JJ, Haworth JC, Hildes JA. Disaccharide malabsorption and dietary patterns in 

two Canadian Eskimo communities. Am J Clin Nutr 1978 Aug; 31(8):1473-8. Ineligible 

number of subjects 

585. Ellestad-Sayed JJ, Levitt MD, Bond JH. Milk intolerance in Manitoba Indian school children. 

American Journal of Clinical Nutrition 1980 Oct; 33(10):2198-201. No prevalence data 

586. Elliott RB, Maxwell GM. Predominance of lactase of small molecular size in duodenal and 

jejunal mucosa of Australian aboriginal children. Aust J Exp Biol Med Sci 1966 Dec; 

44(6):709-13. Not relevant to key questions 

587. Elliott RB, Maxwell GM, Vawser N. Lactose maldigestion in Australian Aboriginal children. 

Med J Aust 1967 Jan 14; 1(2):46-9. Not relevant to key questions 

588. Ellis FR, Holesh S, Ellis JW. Incidence of osteoporosis in vegetarians and omnivores. Am J 

Clin Nutr 1972 Jun; 25(6):555-8. Not target population 

589. Elwood PC, Pickering JE, Hughes J, et al. Milk drinking, ischaemic heart disease and 

ischaemic stroke II. Evidence from cohort studies. Eur J Clin Nutr 2004 May; 58(5):718-24. 

Not eligible outcomes 

590. Emberlin JC, Lewis RA. A double blind, placebo-controlled cross over trial of cellulose 

powder by nasal provocation with Der p1 and Der f1. Current medical research and opinion 

Vol 23; 2007: 2423-31. Not lactose intolerance study 

591. Enattah NS, Jensen TG, Nielsen M, et al. Independent introduction of two lactase-persistence 

alleles into human populations reflects different history of adaptation to milk culture. 

American Journal of Human Genetics 2008 Jan; 82(1):57-72. Ineligible number of subjects 

592. Enattah NS, Sahi T, Savilahti E, et al. Identification of a variant associated with adult-type 

hypolactasia. Nature Genetics 2002 Feb; 30(2):233-7. No prevalence data 

593. Enattah NS, Trudeau A, Pimenoff V, et al. Evidence of still-ongoing convergence evolution 

of the lactase persistence T-13910 alleles in humans. Am J Hum Genet 2007 Sep; 81(3):615­

25. Not relevant to key questions 

594. Enck P, Kremer A, Kuhlbusch R, et al. Prevalence of lactose malabsorption among patients 

with functional bowel disorders. Zeitschrift fur Gastroenterologie 1990 May; 28(5):239-41. 

Ineligible number of subjects 

595. Engels HJ, Fahlman MM, Wirth JC. Effects of ginseng on secretory IgA, performance, and 

recovery from interval exercise. Medicine and science in sports and exercise Vol 35; 2003: 

690-6. Not lactose intolerance study 

596. Englert DM, Guillory JA. For want of lactase. Am J Nurs 1986 Aug; 86(8):902-6. Not 

relevant to key questions 

597. Epstein E, Ugel AR. Effects of topical mechlorethamine on skin lesions of psoriasis. Archives 

of dermatology Vol 102; 1970: 504-6. Not lactose intolerance study 

598. Erasmus HD, Ludwig-Auser HM, Paterson PG, et al. Enhanced weight gain in preterm 

infants receiving lactase-treated feeds: a randomized, double-blind, controlled trial. The 

Journal of pediatrics Vol 141; 2002: 532-7. Not eligible target population 

199
 
599. Ercan N, Nuttall FQ, Gannon MC, et al. Effects of glucose, galactose, and lactose ingestion 

on the plasma glucose and insulin response in persons with non-insulin-dependent diabetes 

mellitus. Metab. Clin. Exp. Vol 42; 1993: 1560-7. Not relevant to key questions 

600. Erinoso HO, Hoare S, Spencer S, et al. Is cow's milk suitable for the dietary supplementation 

of rural Gambian children? 1. Prevalence of lactose maldigestion. Annals of Tropical 

Paediatrics 1992; 12(4):359-65. Subjects less than 4 years old 

601. Escoboza PM, Fernandes MI, Peres LC, et al. Adult-type hypolactasia: clinical, morphologic 

and functional characteristics in Brazilian patients at a university hospital. Journal of 

Pediatric Gastroenterology & Nutrition 2004 Oct; 39(4):361-5. Not population based study 

602. Eto Y, Owada M, Kitagawa T, et al. Neurochemical abnormality in I-cell disease: chemical 

analysis and a possible importance of beta-galactosidase deficiency. J Neurochem 1979 Feb; 

32(2):397-405. Not relevant to key questions 

603. Evans R. Therapeutic diets for children. Nursing (Lond) 1980 Apr; (12):527-30. Not relevant 

to key questions 

604. Evans WO, Witt NF. The interaction of high altitude and psychotropic drug action. 

Psychopharmacologia Vol 10; 1966: 184-8. Not lactose intolerance study 

200
 
605. Ewe K, Ueberschaer B, Press AG, et al. Effect of lactose, lactulose and bisacodyl on 

gastrointestinal transit studied by metal detector. Alimentary pharmacology & therapeutics 

Vol 9; 1995: 69-73. Not relevant to key questions 

606. Fagundes-Neto U, Scaletsky IC. The gut at war: the consequences of enteropathogenic 

Escherichia coli infection as a factor of diarrhea and malnutrition. Sao Paulo medical journal 

= Revista paulista de medicina 2000 Jan 6; 118(1):21-9. Review 

607. Fagundes-Neto U, Viaro T, Lifshitz F. Tolerance to glucose polymers in malnourished infants 

with diarrhea and disaccharide intolerance. Am J Clin Nutr 1985 Feb; 41(2):228-34. Not 

relevant to key questions 

608. Fahr K, Nutzenadel W. Lactose-free diet by acute enteritis in infants. Monatsschrift fur 

Kinderheilkunde Vol 124; 1976: 389-90. Not relevant to key questions 

609. Faiz S, Panunti B, Andrews S. The epidemic of vitamin D deficiency. Journal of the 

Louisiana State Medical Society 2007 Jan-Feb; 159(1):17-20; quiz Ineligible number of 

subjects 

610. Fajardo O, Naim HY, Lacey SW. The polymorphic expression of lactase in adults is 

regulated at the messenger RNA level.[see comment]. Gastroenterology 1994 May; 

106(5):1233-41. Ineligible number of subjects 

611. Falcoz C, Oliver R, McDowall JE, et al. Bioavailability of orally administered micronised 

fluticasone propionate. Clinical pharmacokinetics Vol 39; 2000: 9-15. Not lactose intolerance 

study 

612. Farnworth ER. The evidence to support health claims for probiotics. J Nutr 2008 Jun; 

138(6):1250S-4S. Not relevant to key questions 

613. Fayad IM, Hashem M, Hussein A, et al. Comparison of soy-based formulas with lactose and 

with sucrose in the treatment of acute diarrhea in infants. Archives of pediatrics & adolescent 

medicine Vol 153; 1999: 675-80. Not relevant to key questions 

614. Fehily AM, Coles RJ, Evans WD, et al. Factors affecting bone density in young adults. Am J 

Clin Nutr 1992 Sep; 56(3):579-86. Not eligible outcomes 

615. Feigenberg M, Sotman JW. A toddler with a malabsorption syndrome. Am J Nurs 1975 Jun; 

75(6):978-9. Not relevant to key questions 

616. Feitelson M, Fitz P, Rovezzi-Carroll S, et al. Enteral nutrition practices: similarities and 

differences between dietitians and physicians in Connecticut. Journal of the American 

Dietetic Association 1987 Oct; 87(10):1363-8. Not relevant to key questions 

617. Ferencík M, Ebringer L, Mikes Z, et al. [Successful modification of human intestinal 

microflora with oral administration of lactic acid bacteria]. Bratislavské lekárske listy Vol 

100; 1999: 238-45. Not English language 

618. Ferguson A, Downie WW. Gastrointestinal amyloidosis in psoriatic arthritis. Ann Rheum Dis 

1968 May; 27(3):245-8. Not relevant to key questions 

201
 
619. Fernandes J, Vos CE, Douwes AC, et al. Respiratory hydrogen excretion as a parameter for 

lactose malabsorption in children. Am J Clin Nutr 1978 Apr; 31(4):597-602. Not relevant to 

key questions 

620. Fernandez-Banares F, Rosinach M, Esteve M, et al. Sugar malabsorption in functional 

abdominal bloating: a pilot study on the long-term effect of dietary treatment. Clin Nutr 2006 

Oct; 25(5):824-31. Not relevant to key questions 

621. Ferrara M, Coppola L, Coppola A, et al. Iron deficiency in childhood and adolescence: 

retrospective review. Hematology 2006 Jun; 11(3):183-6. No prevalence data 

622. Ferrari AM, Montano A, Ferolla MC, et al. [Acute diarrheal disease. Refeeding with a low 

lactose milk.]. Arch. Pediatr. Uruguay Vol 58; 1987: 221-3. Not English language 

623. Ferris B, Green OC. Pregnanediol excretion by newly born infants. Am J Dis Child 1968 Jun; 

115(6):693-7. Not relevant to key questions 

624. Ficicioglu C, Thomas N, Yager C, et al. Duarte (DG) galactosemia: a pilot study of 

biochemical and neurodevelopmental assessment in children detected by newborn screening. 

Molecular Genetics & Metabolism 2008 Dec; 95(4):206-12. Not relevant to key questions 

625. Fiddes PJ, Baume P. Disaccharidase deficiency in regional enteritis. Australas Ann Med 1967 

Nov; 16(4):339-42. Not relevant to key questions 

626. Fielding JF. The half-hour lactose "tolerance" test in adults. Ir Med J 1980 Jan; 73(1):21-2. 

Not relevant to key questions 

627. Fielding JF. The value of a second oral lactose tolerance test in detecting hypolactasia. Ir J 

Med Sci 1981 Jul; 150(7):210-2. Not relevant to key questions 

628. Fielding JF, Baynes S, Fottrell PJ. The lactose tolerance test and intestinal lactase activity. Ir 

J Med Sci 1983 May; 152(5):196-8. Not relevant to key questions 

629. Fielding JF, Harrington MG, Fottrell PF. The incidence of primary hypolactasia amongst 

native Irish. Ir J Med Sci 1981 Sep; 150(9):276-7. Not relevant to key questions 

630. Fielding JF, Harrington MG, Fottrell PF. Hypolactasia and the irritable bowel syndrome in 

Ireland. Ir Med J 1982 Oct; 75(10):377-8. Not relevant to key questions 

631. Fields JZ, Turk A, Durkin M, et al. Increased gastrointestinal symptoms in chronic 

alcoholics. American Journal of Gastroenterology 1994 Mar; 89(3):382-6. No prevalence 

data 

632. Figueroa RB, Melgar E, Jo N, et al. Intestinal lactase deficiency in an apparently normal 

Peruvian population. Am J Dig Dis 1971 Oct; 16(10):881-9. Not relevant to key questions 

633. Filippski GK, Tsaplin I, Voznenko AA. [Urinary lactose determination]. Klinicheskaia 

laboratornaia diagnostika; 1994: 40. Not English language 

634. Filippvski GK, Klimov L. [Glycoprotein hexoses in feces of infants with lactose intolerance]. 

Klinicheskaia laboratornaia diagnostika; 1995: 20-1. Not English language 

635. Finch PJ, Ang L, Colston KW, et al. Blunted seasonal variation in serum 25-hydroxy vitamin 

D and increased risk of osteomalacia in vegetarian London Asians. Eur J Clin Nutr 1992 Jul; 

46(7):509-15. Not eligible target population 

636. Fine A, Willoughby E, McDonald GS, et al. A family with intolerance to lactose and cold 

milk. Ir J Med Sci 1968 Jul; 7(7):321-6. Not relevant to key questions 

637. Finley DA, Dewey KG, Lonnerdal B, et al. Food choices of vegetarians and nonvegetarians 

during pregnancy and lactation. J Am Diet Assoc 1985 Jun; 85(6):678-85. Not relevant to key 

questions 

638. Finley DA, Lonnerdal B, Dewey KG, et al. Inorganic constituents of breast milk from 

vegetarian and nonvegetarian women: relationships with each other and with organic 

202
 
constituents. J Nutr 1985 Jun; 115(6):772-81. Not relevant to key questions 

639. Fiocchi A, Restani P, Leo G, et al. Clinical tolerance to lactose in children with cow's milk 

allergy. Pediatrics 2003 Aug; 112(2):359-62. Not relevant to key questions 

640. Fischer TJ, Guilfoile TD, Kesarwala HH, et al. Adverse pulmonary responses to aspirin and 

acetaminophen in chronic childhood asthma. Pediatrics Vol 71; 1983: 313-8. Not lactose 

intolerance study 

641. Fischer-Rasmussen W, Kjaer SK, Dahl C, et al. Ginger treatment of hyperemesis gravidarum. 

European journal of obstetrics, gynecology, and reproductive biology Vol 38; 1991: 19-24. 

Not lactose intolerance study 

642. Fisher M. Vegan pregnancy. Midwifery Today Int Midwife 1999 Winter; (52):30-3. Not 

eligible outcomes 

643. Fisher SE, Markowitz J, Lifshitz F. Food intolerance in childhood. Compr Ther 1984 May; 

10(5):5-11. Not relevant to key questions 

644. Flasch H, Asmussen B, Heinz N. [Enhanced bioavailability of digoxin from silica matrix 

formulations (author's transl)]. Arzneimittel-Forschung Vol 28; 1978: 326-30. Not lactose 

intolerance study 

645. Flaten MA, Simonsen T, Olsen H. Drug-related information generates placebo and nocebo 

responses that modify the drug response. Psychosomatic Medicine Vol 61; 1999: 250-5. Not 

lactose intolerance study 

646. Flaten MA, Simonsen T, Zahlsen K, et al. Stimulant and relaxant drugs combined with 

stimulant and relaxant information: a study of active placebo. Psychopharmacology Vol 176; 

2004: 426-34. Not lactose intolerance study 

647. Flatz G. Ethnic differences in reactions to drugs and xenobiotics. Problems perceived in Asia. 

Prog Clin Biol Res 1986; 214:55-7. Not relevant to key questions 

648. Flatz G, Bernsau I, Behrens A. Lactose absorption and malabsorption in healthy German 

children: improved phenotypic resolution by simultaneous determination of breath hydrogen 

and carbon dioxide. Eur J Pediatr 1982 Jul; 138(4):304-6. Not relevant to key questions 

649. Flatz G, Henze HJ, Palabiyikoglu E, et al. Distribution of the adult lactase phenotypes in 

Turkey. Trop Geogr Med 1986 Sep; 38(3):255-8. Not relevant to key questions 

650. Flatz G, Howell JN, Doench J, et al. Distribution of physiological adult lactase phenotypes, 

lactose absorber and malabsorber, in Germany. Hum Genet 1982; 62(2):152-7. Not relevant 

to key questions 

651. Flatz G, Kuhnau W, Naftali D. Breath hydrogen test for lactose absorption capacity: 

importance of timing of hydrogen excretion and of high fasting hydrogen concentration. Am J 

Clin Nutr 1984 May; 39(5):752-5. Not relevant to key questions 

652. Flatz G, Lie GH. Effect of acetylsalicylic acid on symptoms and hydrogen excretion in the 

disaccharide tolerance test with lactose or lactulose. Am J Clin Nutr 1982 Feb; 35(2):273-6. 

Not relevant to key questions 

653. Flatz G, Rotthauwe HW. Evidence against nutritional adaption of tolerance to lactose. 

Humangenetik 1971; 13(2):118-25. Not relevant to key questions 

654. Flatz G, Rotthauwe HW. Lactose nutrition and natural selection. Lancet 1973 Jul 14; 

2(7820):76-7. Comment 

655. Flatz G, Rotthauwe HW. The human lactase polymorphism: physiology and genetics of 

lactose absorption and malabsorption. Prog Med Genet 1977; 2:205-49. Not relevant to key 

questions 

656. Flatz G, Saengudom C. Lactose tolerance in Asians: a family study. Nature 1969 Nov 29; 

203
 
224(5222):915-6. Not relevant to key questions 

657. Flatz G, Saengudom C, Sanguanbhokhai T. Lactose intolerance in Thailand. Nature 1969 Feb 

22; 221(5182):758-9. Not relevant to key questions 

658. Flatz G, Schildge C, Sekou H. Distribution of adult lactase phenotypes in the Tuareg of 

Niger. Am J Hum Genet 1986 Apr; 38(4):515-9. Not relevant to key questions 

659. Fleming SC. Evaluation of a hand-held hydrogen monitor in the diagnosis of intestinal lactase 

deficiency. Ann Clin Biochem 1990 Sep; 27 ( Pt 5):499-500. Not relevant to key questions 

660. Fluge G, Aksnes L. Influence of cow's milk proteins and gluten on human duodenal mucosa 

in organ culture. J Pediatr Gastroenterol Nutr 1990 Nov; 11(4):481-8. Not relevant to key 

questions 

661. Flynn MA, Irvin W, Krause G. The effect of folate and cobalamin on osteoarthritic hands. J. 

Am. Coll. Nutr. Vol 13; 1994: 351-6. Not lactose intolerance study 

662. Forget P, Lombet J, Grandfils C, et al. Lactase insufficiency revisited. J Pediatr Gastroenterol 

Nutr 1985 Dec; 4(6):868-72. Not relevant to key questions 

663. Förster H, Mehnert H, Beck J. [The effect of various orally administered carbohydrates on the 

blood sugar level]. Klinische Wochenschrift Vol 45; 1967: 50-1. Not lactose intolerance 

study 

204
 
664. Fortner BR, Danziger RE, Rabinowitz PS, et al. The effect of ascorbic acid on cutaneous and 

nasal response to histamine and allergen. The Journal of allergy and clinical immunology Vol 

69; 1982: 484-8. Not lactose intolerance study 

665. Fosbrooke AD, Wharton BA. "Added lactose" and "added sucrose" cow's milk formulae in 

nutrition of low birthweight babies. Archives of disease in childhood Vol 50; 1975: 409-18. 

Not relevant to key questions 

666. Foster DN. A proposed mechanism for acquired lactose tolerance in adults with hypolactasia. 

East Afr Med J 1974 Jan; 51(1):26-32. Not relevant to key questions 

667. Fowkes FG, Ferguson A. Self-diagnosed irritable bowel syndrome and milk intolerance in 

white and non-white doctors. Scott Med J 1981 Jan; 26(1):41-4. Not relevant to key questions 

668. Fowler W. Studies in non-gonococcal urethritis therapy. The long-term value of tetracycline. 

The British journal of venereal diseases Vol 46; 1970: 464-8. Not lactose intolerance study 

669. Fox R, Leen CL, Dunbar EM, et al. Acute gastroenteritis in infants under 6 months old. Arch 

Dis Child 1990 Sep; 65(9):936-8. Not relevant to key questions 

670. Fox ZR, Brickman HF, Beaudry PH, et al. Response to disodium cromoglycate in children 

with chronic asthma. Canadian Medical Association journal Vol 106; 1972: 975-9. Not 

lactose intolerance study 

671. Fradkin A, Yahav J, Zemer D, et al. Colchicine-induced lactose malabsorption in patients 

with familial Mediterranean fever. Israel Journal of Medical Sciences 1995 Oct; 31(10):616­

20. Ineligible number of subjects 

672. Fraser NG, Murray D, Alexander JO. Structure and function of the small intestine in 

dermatitis herpetiformis. Br J Dermatol 1967 Oct; 79(10):509-18. Not relevant to key 

questions 

673. Fratello F, Curcio G, Ferrara M, et al. Can an inert sleeping pill affect sleep? Effects on 

polysomnographic, behavioral and subjective measures. Psychopharmacology Vol 181; 2005: 

761-70. Not lactose intolerance study 

674. Freedman DJ, Tacket CO, Delehanty A, et al. Milk immunoglobulin with specific activity 

against purified colonization factor antigens can protect against oral challenge with 

enterotoxigenic Escherichia coli. The Journal of infectious diseases Vol 177; 1998: 662-7. 

Not relevant to key questions 

675. Freeland-Graves J. Mineral adequacy of vegetarian diets. Am J Clin Nutr 1988 Sep; 48(3 

Suppl):859-62. Review 

676. Freeland-Graves JH, Bodzy PW, Eppright MA. Zinc status of vegetarians. J Am Diet Assoc 

1980 Dec; 77(6):655-61. Not eligible outcomes 

677. Freeman HJ. Gene therapy for lactose intolerance. Can J Gastroenterol 1999 Apr; 13(3):209­

10. Not relevant to key questions 

205
 
678. Freiburghaus AU, Schmitz J, Schindler M, et al. Protein patterns of brush-border fragments in 

congenital lactose malabsorption and in specific hypolactasia of the adult. N Engl J Med 1976 

May 6; 294(19):1030-2. Not relevant to key questions 

679. French AB, Cook HB, Pollard HM. Nutritional problems after gastrointestinal surgery. Med 

Clin North Am 1969 Nov; 53(6):1389-402. Not eligible target population 

680. Friedland N. "Normal" lactose tolerance test. Arch Intern Med 1965 Dec; 116(6):886-8. Not 

relevant to key questions 

681. Friedman LS. By the way, doctor. There seem to be many products, such as stool softeners, to 

help with constipation. But are there any remedies for loose, poorly formed stools--a problem 

my husband has? The first suggestion is always to eat more fiber, but that hasn't helped my 

husband. Harv Health Lett 2004 Feb; 29(4):8. Not relevant to key questions 

682. Fries JH. Food allergy: current concerns. Ann Allergy 1981 May; 46(5):260-3. Not relevant 

to key questions 

683. Frissora CL, Koch KL. Symptom overlap and comorbidity of irritable bowel syndrome with 

other conditions. Current Gastroenterology Reports 2005 Aug; 7(4):264-71. No prevalence 

data 

684. Frith PA, Ruffin RE, Juniper EF, et al. Inhibition of allergen-induced asthma by three forms 

of sodium cromoglycate. Clinical allergy Vol 11; 1981: 67-77. Not lactose intolerance study 

685. Frostell G. Effects of mouth rinses with sucrose, glucose, fructose, lactose, sorbitol and 

Lycasin on the pH of dental plaque. Odontologisk revy Vol 24; 1973: 217-26. Not lactose 

intolerance study 

686. Fry AC, Kraemer WJ, Stone MH, et al. Endocrine and performance responses to high volume 

training and amino acid supplementation in elite junior weightlifters. International journal of 

sport nutrition Vol 3; 1993: 306-22. Not lactose intolerance study 

687. Fryburg DA. N(G)-monomethyl-L-arginine inhibits the blood flow but not the insulin- like 

response of forearm muscle to IGF-I. Possible role of nitric oxide in muscle protein synthesis. 

Journal of Clinical Investigation Vol 97; 1996: 1319-28. Not lactose intolerance study 

688. Fukuda M, Hirota M, Sato S. Bone lesions and dental caries after gastrectomy--evaluation of 

milk intolerance and operative procedure. Jpn J Surg 1986 Jan; 16(1):36-41. Not eligible 

target population 

689. Fukuda M, Shibata H, Hatakeyama K, et al. Difference in calcium metabolism following 

Billroth-I and Billroth-II procedures for gastric and duodenal ulcers. Jpn J Surg 1979 Dec; 

9(4):295-303. Not eligible target population 

690. Fukuda M, Tamura T. A controlled clinical trial of adrenochrome monoaminoguanidine 

methansulfonate in diabetic retinopathy. Jpn J Clin Ophthal Vol 32; 1978: 1470-4. Not 

lactose intolerance study 

206
 
691. Fukuda Y, et al. [Evaluation of the Antitussive Effect of Perocan: A Double-Blind 

Comparison with Lactose Placebo]. Rinsho to Kenkyu (The Japanese Journal of Clinical and 

Experimental Medicine) Vol 50; 1973: 882-92. Not lactose intolerance study 

692. Fulton JR, Hutton CW, Stitt KR. Preschool vegetarian children. Dietary and anthropometric 

data. J Am Diet Assoc 1980 Apr; 76(4):360-5. Not relevant to key questions 

693. Fung WP, Kho KM. The importance of milk intolerance in patients presenting with chronic 

(nervous) diarrhoea. Aust N Z J Med 1971 Nov; 1(4):374-6. Not relevant to key questions 

694. Furuya T, Suzuki Y. GM1-Gangliosidosis: a molecular abnormality of acid betagalactosidase in fibroblasts. J Inherit Metab Dis 1984; 7(3):145-6. Not relevant to key 

questions 

695. Fusch C, Skopnik H, Wirth S, et al. Double-blind, randomised, placebo-controlled study to 

evaluate the nutritional efficacy of Omneo 1. Final study results. Pediatrika Vol 21; 2001: 49­

54. Not relevant to key questions 

696. Gaab MR, Rode CP, Schakel EH, et al. [Effect of the Ca antagonist nimodipine on global and 

regional cerebrovascular circulation]. Klinische Wochenschrift Vol 63; 1985: 8-15. Not lactose 

intolerance study 

697. Gabr M, El-Beheiry F, Soliman AA, et al. Lactose tolerance in normal Egyptian infants and 

children and in protein calorie malnutrition. Gaz Egypt Paediatr Assoc 1977 Jan; 26(1):27-33. 

Not relevant to key questions 

698. Gaeini AA, Rahnama N, Hamedinia MR. Effects of vitamin E supplementation on oxidative 

stress at rest and after exercise to exhaustion in athletic students. The Journal of sports 

medicine and physical fitness Vol 46; 2006: 458-61. Not lactose intolerance study 

699. Gaffney PT, Buttenshaw RL, Thomas MJ, et al. Faster assay of H2 in breath by dedicated 

instruments compared with conventional gas chromatography. Clin Chem 1986 Sep; 

32(9):1784-8. Not relevant to key questions 

700. Gallagher CR, Molleson AL, Caldwell JH. Lactose intolerance and fermented dairy products. 

J Am Diet Assoc 1974 Oct; 65(4):418-9. Not relevant to key questions 

701. Gannage MH, Abikaram G, Nasr F, et al. Osteomalacia secondary to celiac disease, primary 

hyperparathyroidism, and Graves' disease. Am J Med Sci 1998 Feb; 315(2):136-9. Not 

eligible target population 

702. Gao KP, Mitsui T, Fujiki K, et al. Effect of lactase preparations in asymptomatic individuals 

with lactase deficiency--gastric digestion of lactose and breath hydrogen analysis. Nagoya J 

Med Sci 2002 May; 65(1-2):21-8. Not relevant to key questions 

703. Gao X, Wilde PE, Lichtenstein AH, et al. Meeting adequate intake for dietary calcium 

without dairy foods in adolescents aged 9 to 18 years (National Health and Nutrition 

Examination Survey 2001-2002). Journal of the American Dietetic Association 2006 Nov; 

106(11):1759-65. Not relevant to key questions 

704. Gaón D, Chekherdemian M, Harwicz R, et al. [Effect of cimetidine on lactose activity in 

patients with duodenal ulcer]. Acta gastroenterologica Latinoamericana Vol 11; 1981: 285­

90. Not English language 

705. Gaón D, Doweck Y, Gómez ZA, et al. [Lactose digestion by milk fermented with 

Lactobacillus acidophilus and Lactobacillus casei of human origin]. Medicina Vol 55; 1995: 

237-42. Not English language 

706. Garcia-Paredes J, Truelove SC. Disaccharidase levels in the small intestine in patients with 

diarrhoea following vagotomy and pyloroplasty. Gut 1971 Feb; 12(2):107-9. Not relevant to 

key questions 

207
 
707. Gardiner AJ, Tarlow MJ, Sutherland IT, et al. Lactose malabsorption during gastroenteritis, 

assessed by the hydrogen breath test. Arch Dis Child 1981 May; 56(5):364-7. Not relevant to 

key questions 

708. Gearhart HL, Bose DP, Smith CA, et al. Determination of lactose malabsorption by breath 

analysis with gas chromatography. Anal Chem 1976 Feb; 48(2):393-8. Not relevant to key 

questions 

709. Geboes KP, Luypaerts A, Rutgeerts P, et al. Inulin is an ideal substrate for a hydrogen breath 

test to measure the orocaecal transit time. Alimentary pharmacology & therapeutics Vol 18; 

2003: 721-9. Not lactose intolerance 

710. Gendrel D, Dupont C, Richard-Lenoble D, et al. Feeding lactose-intolerant children with a 

powdered fermented milk. Journal of Pediatric Gastroenterology & Nutrition 1990 Jan; 

10(1):44-6. Ineligible number of subjects 

711. Gendrel D, Dupont C, Richard-Lenoble D, et al. Milk lactose malabsorption in Gabon 

measured by the breath hydrogen test. Journal of Pediatric Gastroenterology & Nutrition 

1989 May; 8(4):545-7. Ineligible number of subjects 

712. Gendrel D, Richard-Lenoble D, Kombila M, et al. Influence of intestinal parasitism on 

lactose absorption in well-nourished African children. Am J Trop Med Hyg 1992 Feb; 

46(2):137-40. Not relevant to key questions 

713. Gerasimidis K, McGrogan P, Hassan K, et al. Dietary modifications, nutritional supplements 

and alternative medicine in paediatric patients with inflammatory bowel disease. Alimentary 

Pharmacology & Therapeutics 2008 Jan 15; 27(2):155-65. Not relevant to key questions 

714. Gerstenfeld TS, Wing DA. Rectal misoprostol versus intravenous oxytocin for the prevention 

of postpartum hemorrhage after vaginal delivery. American journal of obstetrics and 

gynecology Vol 185; 2001: 878-82. Not lactose intolerance study 

715. Ghadirian P, Shatenstein B, Verdy M, et al. The influence of dairy products on plasma uric 

acid in women. European journal of epidemiology 1995 Jun; 11(3):275-81. Not relevant to 

key questions 

716. Ghahremani GG, Bowie JD. Volvulus of the splenic flexure: report of a case. Dis Colon 

Rectum 1974 Jan-Feb; 17(1):100-2. Not relevant to key questions 

208
 
717. Ghai OP, Bhan MK, Arora NK, et al. Practical implication of milk intolerance in diarrhea. 

Indian Pediatr 1982 Jan; 19(1):89-93. Not relevant to key questions 

718. Ghai OP, Kumar L, Kumar V. Disaccharide intolerance in malnutrition. Indian Pediatr 1969 

Jun; 6(6):364-73. Not relevant to key questions 

719. Ghoshal UC, Abraham P, Bhatt C, et al. Epidemiological and clinical profile of irritable 

bowel syndrome in India: report of the Indian Society of Gastroenterology Task Force.[see 

comment]. Indian Journal of Gastroenterology 2008 Jan-Feb; 27(1):22-8. No prevalence data 

720. Gibbons IS. Disaccharides and cystic fibrosis of the pancreas. Arch Dis Child 1969 Feb; 

44(233):63-8. Not relevant to key questions 

721. Gibbs SE, D'Esposito M. A functional MRI study of the effects of bromocriptine, a dopamine 

receptor agonist, on component processes of working memory. Psychopharmacology Vol 

180; 2005: 644-53. Not lactose intolerance study 

722. Gibney SF, Munroe V, Nurse GT, et al. Lactose absorption in a Western Massim population. 

Ann Hum Biol 1981 Sep-Oct; 8(5):477-80. Not relevant to key questions 

723. Gibson G. Human evolution: thrifty genes and the dairy queen. Curr Biol 2007 Apr 17; 

17(8):R295-6. Not relevant to key questions 

724. Gibson JB, Berry GT, Palmieri MJ, et al. Sugar nucleotide concentrations in red blood cells 

of patients on protein- and lactose-limited diets: effect of galactose supplementation. 

American Journal of Clinical Nutrition 1996 May; 63(5):704-8. Not relevant to key questions 

725. Gibson RS, Donovan UM, Heath AL. Dietary strategies to improve the iron and zinc nutriture 

of young women following a vegetarian diet. Plant Foods Hum Nutr 1997; 51(1):1-16. Not 

relevant to key questions 

726. Gilat T. Lactase--an adaptable enzyme? Gastroenterology 1971 Feb; 60(2):346-7. Not 

relevant to key questions 

727. Gilat T. Lactase deficiency: the world pattern today. Isr J Med Sci 1979 Apr; 15(4):369-73. 

Not relevant to key questions 

728. Gilat T, Benaroya Y, Gelman-Malachi E, et al. Genetics of primary adult lactase deficiency. 

Gastroenterology 1973 Apr; 64(4):562-8. Not relevant to key questions 

729. Gilat T, Dolizky F, Gelman-Malachi E, et al. Lactase in childhood--a non-adaptable enzyme. 

Scand J Gastroenterol 1974; 9(4):395-8. Not relevant to key questions 

730. Gilat T, Kuhn R, Gelman E, et al. Lactase deficiency in Jewish communities in Israel. Am J 

Dig Dis 1970 Oct; 15(10):895-904. Not relevant to key questions 

731. Gilat T, Malachi EG, Shochet SB. Lactose tolerance in an Arab population. Am J Dig Dis 

1971 Mar; 16(3):203-6. Not relevant to key questions 

732. Gilat T, Russo S, Gelman-Malachi E, et al. Lactase in man: a nonadaptable enzyme. 

Gastroenterology 1972 Jun; 62(6):1125-7. Not relevant to key questions 

733. Gill HS, Guarner F. Probiotics and human health: a clinical perspective. Postgrad Med J 2004 

Sep; 80(947):516-26. Review 

734. Gill HS, Rutherfurd KJ, Cross ML. Dietary probiotic supplementation enhances natural killer 

cell activity in the elderly: an investigation of age-related immunological changes. Journal of 

clinical immunology Vol 21; 2001: 264-71. Not relevant to key questions 

735. Gilliland SE, Kim HS. Effect of viable starter culture bacteria in yogurt on lactose utilization 

in humans. J Dairy Sci 1984 Jan; 67(1):1-6. Not relevant to key questions 

736. Giovannetti S, Barsotti G, Gretz N, et al. Treatment and prevention of uremic osteodystrophy. 

Contrib Nephrol 1989; 72:66-72. Not eligible target population 

737. Gismondo MR, Drago L, Lombardi A. Review of probiotics available to modify 

209
 
gastrointestinal flora. Int J Antimicrob Agents 1999 Aug; 12(4):287-92. Not relevant to key 

questions 

738. Glinghammar B, Venturi M, Rowland IR, et al. Shift from a dairy product-rich to a dairy 

product-free diet: influence on cytotoxicity and genotoxicity of fecal water--potential risk 

factors for colon cancer. American Journal of Clinical Nutrition 1997 Nov; 66(5):1277-82. 

Not eligible outcomes 

739. Godard C, Bustos M, Muñoz M, et al. Value of a chicken-based formula for refeeding of 

children with protracted diarrhea and malnutrition in a developing country. Journal of 

pediatric gastroenterology and nutrition Vol 9; 1989: 473-80. Not relevant to key questions 

740. Godfrey S, Konig P. Inhibition of exercise induced asthma by different pharmacological 

pathways. Thorax Vol 31; 1976: 137-43. Not lactose intolerance study 

741. Godfrey S, Silverman M. Demonstration by placebo response in asthma by means of exercise 

testing. Journal of psychosomatic research Vol 17; 1973: 293-7. Not lactose intolerance study 

742. Godfrey S, Zeidifard E, Brown K, et al. The possible site of action of sodium cromoglycate 

assessed by exercise challenge. Clinical science and molecular medicine Vol 46; 1974: 265­

72. Not lactose intolerance study 

743. Goepp JG, Katz S, Cuervo E, et al. Comparison of two regimens of feeding and oral 

electrolyte solutions in infants with diarrhea. Journal of pediatric gastroenterology and 

nutrition Vol 24; 1997: 374-9. Not relevant to key questions 

744. Goldberg D. A psychiatric study of patients with diseases of the small intestine. Gut 1970 

Jun; 11(6):459-65. Not relevant to key questions 

745. Goldberg DP. A one-year survey of the prevalence of psychiatric illness in patients with 

disease of the small intestine. Gut 1968 Dec; 9(6):725. No prevalence data 

746. Goldberg JP, Folta SC, Must A. Milk: can a "good" food be so bad? Pediatrics 2002 Oct; 

110(4):826-32. Comment 

210
 
747. Goldfarb AH, Bloomer RJ, McKenzie MJ. Combined antioxidant treatment effects on blood 

oxidative stress after eccentric exercise. Medicine and science in sports and exercise Vol 37; 

2005: 234-9. Not lactose intolerance study 

748. Goldin BR. Health benefits of probiotics. Br J Nutr 1998 Oct; 80(4):S203-7. Not relevant to 

key questions 

749. Goldstein R, Braverman D, Stankiewicz H. Carbohydrate malabsorption and the effect of 

dietary restriction on symptoms of irritable bowel syndrome and functional bowel complaints. 

Isr Med Assoc J 2000 Aug; 2(8):583-7. Not relevant to key questions 

750. Gonzalez A, Neri M, Campollo O, et al. Treatment of acute portalsystemic encephalopathy 

(PSE) grades III and IV with sodium benzoate and lactose [AASLD abstract]. Hepatology 

Vol 16; 1992: 249a. Not lactose intolerance study 

751. Gonzalez A, Neri M, Campollo O, et al. Treatment of acute portalsystemic encephalopathy 

(PSE) grades III and IV with sodium benzoate and lactose [IASL abstract]. Hepatology Vol 

19; 1994: 67i. Not lactose intolerance study 

752. Gonzalez de la Reguera I, Subira ML, Oehling A. The role of sensitizing proteins in milk 

allergy. Allergol Immunopathol (Madr) 1978 May-Jun; 6(3):225-30. Not relevant to key 

questions 

753. Goodchild CS, Robinson A, Nadeson R. Antinociceptive properties of neurosteroids IV: pilot 

study demonstrating the analgesic effects of alphadolone administered orally to humans. 

British journal of anaesthesia Vol 86; 2001: 528-34. Not lactose intolerance study 

754. Goodlin RC. Letter: Maternal nutrition. Obstet Gynecol 1974 Jan; 43(1):157-9. Not relevant 

to key questions 

755. Goossens D, Jonkers D, Stobberingh E, et al. Probiotics in gastroenterology: indications and 

future perspectives. Scandinavian Journal of Gastroenterology - Supplement 2003; (239):15­

23. No prevalence data 

756. Gorbach SL, Neale G, Levitan R, et al. Alterations in human intestinal microflora during 

experimental diarrhoea. Gut 1970 Jan; 11(1):1-6. Not relevant to key questions 

757. Gorduza EV, Indrei LL, Gorduza VM. Nutrigenomics in postgenomic era. Revista medicochirurgicala a Societatii de Medici si Naturalisti din Iasi 2008 Jan-Mar; 112(1):152-64. 

Review 

758. Gounder DS, Pullon HW, Ockelford PA, et al. Clinical manifestations of the 

thrombocytopenia and absent radii (TAR) syndrome. Aust N Z J Med 1989 Oct; 19(5):479­

82. Not eligible target population 

759. Gozalo RF, Colas SC, Senent SC, et al. Long-term modification on histamine-induced 

bronchoconstriction by disodium cromoglycate and ketotifen versus placebo. Allergy Vol 40; 

1985: 242-9. Not lactose intolerance study 

760. Gracey M. Some paediatric problems of Australian Aborigines. Paediatr Indones 1973 Jan; 

13(1):1-10. Not relevant to key questions 

211
 
761. Graham GG. Letter: Protein advisory group's recommendations deplored. Pediatrics 1975 

Feb; 55(2):295-6. Not relevant to key questions 

762. Graham GG, Baertl JM, Cordano A, et al. Lactose-free, medium-chain triglyceride formulas 

in severe malnutrition. Am J Dis Child 1973 Sep; 126(3):330-5. Not relevant to key questions 

763. Grange AO, Santosham M, Ayodele AK, et al. Evaluation of a maize-cowpea-palm oil diet 

for the dietary management of Nigerian children with acute, watery diarrhea. Acta paediatrica 

(Oslo, Norway : 1992) Vol 83; 1994: 825-32. Not relevant to key questions 

764. Granot E, Simcha A, Tamir I, et al. Lactose breath hydrogen analysis in infants with 

congenital heart disease. Isr J Med Sci 1987 Nov; 23(11):1158-60. Not relevant to key 

questions 

765. Grant JD, Bezerra JA, Thompson SH, et al. Assessment of lactose absorption by 

measurement of urinary galactose. Gastroenterology 1989 Oct; 97(4):895-9. Not relevant to 

key questions 

766. Grases F, Costa-Bauza A, Prieto RM. Renal lithiasis and nutrition. Nutr J 2006; 5:23. Review 

767. Gravelle IH, Marsden RT. Radiological assessment of hypolactasia in ulcerative colitis. Br J 

Radiol 1969 Jun; 42(498):416-8. Not relevant to key questions 

768. Gray GM. Malabsorption of carbohydrate. Fed Proc 1967 Sep; 26(5):1415-9. Not relevant to 

key questions 

769. Gray GM. Congenital and adult intestinal lactase deficiency. N Engl J Med 1976 May 6; 

294(19):1057-8. Not relevant to key questions 

770. Gray GM. Absorption and malabsorption of dietary carbohydrate. Curr Concepts Nutr 1980; 

9:43-53. Not relevant to key questions 

771. Gray GM, Conklin KA, Townley RR. Sucrase-isomaltase deficiency. Absence of an inactive 

enzyme variant. N Engl J Med 1976 Apr 1; 294(14):750-3. Not relevant to key questions 

772. Gray GM, Santiago NA. Intestinal beta-galactosidases. I. Separation and characterization of 

three enzymes in normal human intestine. Journal of Clinical Investigation 1969 Apr; 

48(4):716-28. No prevalence data 

773. Gray GM, Santiago NA, Colver EH, et al. Intestinal beta-galactosidases. II. Biochemical 

alteration in human lactase deficiency. Journal of Clinical Investigation 1969 Apr; 48(4):729­

35. Ineligible number of subjects 

774. Gray GM, Walter WM, Jr., Colver EH. Persistent deficiency of intestinal lactase in 

apparently cured tropical sprue. Gastroenterology 1968 Apr; 54(4):552-8. Not relevant to key 

questions 

775. Grazioli B, Matera G, Laratta C, et al. Giardia lamblia infection in patients with irritable 

bowel syndrome and dyspepsia: a prospective study. World Journal of Gastroenterology 2006 

Mar 28; 12(12):1941-4. No prevalence data 

212
 
776. Green TJ, Issenman RM, Jacobson K. Patients' diets and preferences in a pediatric population 

with inflammatory bowel disease. Canadian Journal of Gastroenterology 1998 Nov-Dec; 

12(8):544-9. Not relevant to key questions 

777. Gregorio GV, Rogacion JM, Gabriel EP, et al. Nutritional intervention in acute diarrhea: is a 

lactose-free formula essential? Southeast Asian Journal of Tropical Medicine & Public Health 

1992 Jun; 23(2):235-45. No prevalence data 

778. Gremse DA, Nguyenduc GH, Sacks AI, et al. Irritable bowel syndrome and lactose 

maldigestion in recurrent abdominal pain in childhood. South Med J 1999 Aug; 92(8):778-81. 

Not relevant to key questions 

779. Gribbin M, Walker-Smith J, Wood C. Delayed recovery following acute gastroenteritis. Acta 

Paediatrica Belgica 1976 Jul-Sep; 29(3):167-76. No prevalence data 

780. Griessen M, Cochet B, Infante F, et al. Calcium absorption from milk in lactase-deficient 

subjects. Am J Clin Nutr 1989 Feb; 49(2):377-84. Not eligible outcomes 

781. Griffin MP, Hansen JW. Can the elimination of lactose from formula improve feeding 

tolerance in premature infants?[see comment]. Journal of Pediatrics 1999 Nov; 135(5):587­

92. No prevalence data 

782. Grimbacher B, Peters T, Peter HH. Lactose-intolerance may induce severe chronic eczema. 

Int Arch Allergy Immunol 1997 Aug; 113(4):516-8. Not relevant to key questions 

783. Groothuis JR, Berman S, Chapman J. Effect of carbohydrate ingested on outcome in infants 

with mild gastroenteritis. Journal of Pediatrics 1986 Jun; 108(6):903-6. No prevalence data 

784. Gross MD. Effect of sucrose on hyperkinetic children. Pediatrics Vol 74; 1984: 876-8. Not 

lactose intolerance study 

785. Guarner F, Perdigon G, Corthier G, et al. Should yoghurt cultures be considered probiotic? Br 

J Nutr 2005 Jun; 93(6):783-6. Not relevant to key questions 

786. Gudmand-Hoyer E. Lactose malabsorption in patients operated upon for peptic ulcer. Scand J 

Gastroenterol 1969; 4(8):705-11. Not relevant to key questions 

787. Gudmand-Hoyer E. The clinical significance of disaccharide maldigestion. American Journal 

of Clinical Nutrition 1994 Mar; 59(3 Suppl):735S-41S. Not original research 

788. Gudmand-Hoyer E, Asp NG, Skovbjerg H, et al. Lactose malabsorption after bypass 

operation for obesity. Scand J Gastroenterol 1978; 13(6):641-7. Not relevant to key questions 

789. Gudmand-Hoyer E, Dahlqvist A, Jarnum S. Specific small-intestinal lactase deficiency in 

adults. Scand J Gastroenterol 1969; 4(4):377-86. Not relevant to key questions 

790. Gudmand-Hoyer E, Dahlqvist A, Jarnum S. The clinical significance of lactose 

malabsorption. Am J Gastroenterol 1970 May; 53(5):460-73. Not relevant to key questions 

791. Gudmand-Hoyer E, Folke K. Radiological detection of lactose malabsorption. Scand J 

Gastroenterol 1970; 5(7):565-71. Not relevant to key questions 

792. Gudmand-Hoyer E, Jarnum S. Diagnosis of lactose malabsorption. Gastroenterology 1968 

Feb; 54(2):323-4. Not relevant to key questions 

793. Gudmand-Hoyer E, Jarnum S. Milk intolerance following gastric surgery. Scand J 

Gastroenterol 1969; 4(2):127-32. Not relevant to key questions 

794. Gudmand-Hoyer E, Jarnum S. Incidence and clinical significance of lactose malabsorption in 

ulcerative colitis and Crohn's disease. Gut 1970 Apr; 11(4):338-43. Not relevant to key 

questions 

795. Gudmand-Hoyer E, Riis P, Wulff HR. The significance of lactose malabsorption in the 

irritable colon syndrome. Scand J Gastroenterol 1973; 8(3):273-8. Not relevant to key 

questions 

213
 
796. Gudmand-Hoyer E, Simony K. Individual sensitivity to lactose in lactose malabsorption. Am J 

Dig Dis 1977 Mar; 22(3):177-81. Not relevant to key questions 

797. Gudmand-Hoyer E, Skovbjerg H. Disaccharide digestion and maldigestion. Scandinavian 

Journal of Gastroenterology - Supplement 1996; 216:111-21. Not original research 

798. Gudmand-Hoyer E, Soeberg B. Disaccharidase activity in the small intestinal mucosa in cases 

with acute enteritis. Scand J Gastroenterol 1974; 9(4):405-9. Not relevant to key questions 

799. Guevara G, Jiminez R, Kranz P, et al. Lactase enzyme-treated cow's milk based formula does 

not alter course of acute diarrheal illness in babies. Pediatric Research Vol 31/4; 1992: 107a. 

Not relevant to key questions 

800. Guiheneuc P, Ginet J, Grolleau JY, et al. [Study of the effects of isaxonine on retrograde axon 

degeneration induced by vincristine in man (author's transl)]. La Nouvelle presse médicale 

Vol 11; 1982: 1257-61. Not lactose intolerance study 

801. Gulati VK, Desai S, Khatri PK, et al. Aqueous penetration of orally administered 

ciprofloxacin in humans. International Ophthalmology Vol 18; 1994: 221-4. Not lactose 

intolerance study 

802. Gulick EE, Johnson S. Infant health of mothers with multiple sclerosis. Western Journal of 

Nursing Research 2004 Oct; 26(6):632-49. No prevalence data 

803. Gumand-Hoyer E, Simony K. [Individual sensitivity to lactose in lactose malabsorption]. 

Ugeskrift for laeger Vol 137; 1975: 2064-8. Not English language 

804. Gunn TR, Stunzner D. A comparative trial of casein or whey-predominant formulae in 

healthy infants. The New Zealand medical journal Vol 99; 1986: 843-6. Not relevant to key 

questions 

805. Gunther S, Patterson RE, Kristal AR, et al. Demographic and health-related correlates of 

herbal and specialty supplement use. Journal of the American Dietetic Association 2004 Jan; 

104(1):27-34. No prevalence data 

806. Gupta D, Ghoshal UC, Misra A, et al. Lactose intolerance in patients with irritable bowel 

syndrome from northern India: a case-control study. J Gastroenterol Hepatol 2007 Dec; 

22(12):2261-5. Not relevant to key questions 

807. Gupta I, Gupta V, Parihar A, et al. Effects of Boswellia serrata gum resin in patients with 

bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. 

European journal of medical research Vol 3; 1998: 511-4. Not lactose intolerance study 

808. Gupta MM, Round JM, Stamp TC. Spontaneous cure of vitamin-D deficiency in Asians 

during summer in Britain. Lancet 1974 Apr 6; 1(7858):586-8. Not eligible outcomes 

809. Gupta PS, Misra RC, Ramachandran KA, et al. Lactose intolerance in adults. J Assoc 

Physicians India 1970 Sep; 18(9):765-8. Not relevant to key questions 

810. Gupta PS, Misra RC, Sacheti CK, et al. Lactase activity in irritable colon syndrome. J Assoc 

Physicians India 1971 Jul; 19(7):507-10. Not relevant to key questions 

811. Gupta PS, Misra RC, Sarin GS, et al. Intestinal disaccharidases activity in normal adult 

population in tropics. J Trop Med Hyg 1971 Oct; 74(10):225-9. Not relevant to key questions 

812. Gupta R, Gupta S. Dietary management of lactose intolerance--lactase treated milk versus 

soya milk. Indian J Med Sci 1993 Jan; 47(1):1-7. Not relevant to key questions 

813. Gupta RC, Sarin GS, Misra RC, et al. Intestinal disaccharidases in intestinal tuberculosis. J 

Indian Med Assoc 1975 May 16; 64(10):262-4. Not relevant to key questions 

814. Gupta SK, Chong SK, Fitzgerald JF. Disaccharidase activities in children: normal values and 

comparison based on symptoms and histologic changes. J Pediatr Gastroenterol Nutr 1999 

Mar; 28(3):246-51. Not relevant to key questions 

214
 
815. Gupta SK, Gupta RC, Seth AK, et al. Reversal of fluorosis in children. Acta paediatrica 

Japonica; Overseas edition Vol 38; 1996: 513-9. Not lactose intolerance study 

816. Gwee KA, Graham JC, McKendrick MW, et al. Psychometric scores and persistence of 

irritable bowel after infectious diarrhoea.[see comment]. Lancet 1996 Jan 20; 347(8995):150­

3. No prevalence data 

817. Habte D, Sterky G, Hjalmarsson B. Lactose malabsorption in Ethiopian children. Acta 

Paediatr Scand 1973 Nov; 62(6):649-54. Not relevant to key questions 

818. Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute 

mountain sickness. Lancet Vol 2; 1976: 1149-55. Not lactose intolerance study 

819. Haderstorfer B, Psycholgin D, Whitehead WE, et al. Intestinal gas production from bacterial 

fermentation of undigested carbohydrate in irritable bowel syndrome. Am J Gastroenterol 

1989 Apr; 84(4):375-8. Not relevant to key questions 

820. Haffejee IE. Persistent diarrhoea following gastroenteritis. Journal of diarrhoeal diseases 

research 1990 Dec; 8(4):143-6. Not relevant to key questions 

215
 
821. Haffejee IE. Cow's milk-based formula, human milk, and soya feeds in acute infantile 

diarrhea: a therapeutic trial. Journal of pediatric gastroenterology and nutrition Vol 10; 1990: 

193-8. Not relevant to key questions 

822. Haider T, Husain Q. Concanavalin A layered calcium alginate-starch beads immobilized beta 

galactosidase as a therapeutic agent for lactose intolerant patients. Int J Pharm 2008 Jul 9; 

359(1-2):1-6. Not relevant to key questions 

823. Hajek P, Belcher M. Improved CO monitors for validating smoking abstinence by expired-air 

carbon monoxide levels. British Journal of Addiction 1991 Aug; 86(8):1029-30. No 

prevalence data 

824. Hakala P, Karvetti RL. Weight reduction on lactovegetarian and mixed diets. Changes in 

weight, nutrient intake, skinfold thicknesses and blood pressure. Eur J Clin Nutr 1989 Jun; 

43(6):421-30. Not relevant to key questions 

825. Halimun EM, Sunoto, Suharjono. Sugar intolerance in post neonatal surgery. Paediatr 

Indones 1973 Nov; 13(11):289-92. Not relevant to key questions 

826. Hall RT, Callenbach JC, Sheehan MB, et al. Comparison of calcium- and phosphorussupplemented soy isolate formula with whey-predominant premature formula in very low 

birth weight infants. J Pediatr Gastroenterol Nutr Vol 3; 1984: 571-6. Not eligible target 

population 

827. Halliday R, Callaway E, Lannon R. The effects of clonidine and yohimbine on human 

information processing. Psychopharmacology Vol 99; 1989: 563-6. Not lactose intolerance 

study 

828. Halpern GM, Prindiville T, Blankenburg M, et al. Treatment of irritable bowel syndrome 

with Lacteol Fort: a randomized, double-blind, cross-over trial. The American journal of 

gastroenterology Vol 91; 1996: 1579-85. Not relevant to key questions 

829. Halpern GM, Van de Water J, Delabroise AM, et al. Comparative uptake of calcium from 

milk and a calcium-rich mineral water in lactose intolerant adults: implications for treatment 

of osteoporosis. Am J Prev Med 1991 Nov-Dec; 7(6):379-83. Not eligible outcomes 

830. Halpin TC, Byrne WJ, Ament ME. Colitis, persistent diarrhea, and soy protein intolerance. 

Journal of Pediatrics 1977 Sep; 91(3):404-7. No prevalence data 

831. Halsas M, Hietala J, Veski P, et al. Morning versus evening dosing of ibuprofen using 

conventional and time-controlled release formulations. International Journal of Pharmaceutics 

Vol 189; 1999: 179-85. Not lactose intolerance study 

832. Hamer S, Collinson G. Achieving Evidence-based Practice: A Handbook for Practitioners. 

2nd ed. New York: Bailliere Tindall Elsevier; 2005. Custom 3 

833. Hamilton I, Hill A, Bose B, et al. Small intestinal permeability in pediatric clinical practice. J 

Pediatr Gastroenterol Nutr 1987 Sep-Oct; 6(5):697-701. Not relevant to key questions 

216
 
834. Hamilton M, Bush M, Bye C, et al. A comparison of triprolidine and cyclizine on histamine 

(H1) antagonism, subjective effects and performance tests in man. British journal of clinical 

pharmacology Vol 13; 1982: 441-4. Not lactose intolerance study 

835. Hamilton MJ, Smith PR, Peck AW. Effects of bupropion, nomifensine and dexamphetamine 

on performance, subjective feelings, autonomic variables and electroencephalogram in 

healthy volunteers. British journal of clinical pharmacology Vol 15; 1983: 367-74. Not 

lactose intolerance study 

836. Hamilton-Miller JM. Probiotics and prebiotics in the elderly. Postgrad Med J 2004 Aug; 

80(946):447-51. Not relevant to key questions 

837. Hamm LR, Sorrells SC, Harding JP, et al. Additional investigations fail to alter the diagnosis 

of irritable bowel syndrome in subjects fulfilling the Rome criteria. Am J Gastroenterol 1999 

May; 94(5):1279-82. Not relevant to key questions 

838. Hammer HF, Petritsch W, Pristautz H, et al. Evaluation of the pathogenesis of flatulence and 

abdominal cramps in patients with lactose malabsorption. Wien Klin Wochenschr 1996; 

108(6):175-9. Not relevant to key questions 

839. Hammer HF, Petritsch W, Pristautz H, et al. Assessment of the influence of hydrogen 

nonexcretion on the usefulness of the hydrogen breath test and lactose tolerance test. Wiener 

Klinische Wochenschrift 1996; 108(5):137-41. Ineligible number of subjects 

840. Hanafy MM, Seddik Y, El-Khateeb S, et al. Lactose absorption in protein-calorie 

malnutrition. Gaz Egypt Paediatr Assoc 1973 Oct; 21(4):9-13. Not relevant to key questions 

841. Hanger HC, Smart EJ, Merrilees MJ, et al. The prevalence of malnutrition in elderly hip 

fracture patients. New Zealand Medical Journal 1999 Mar 26; 112(1084):88-90. Letter 

842. Hannington E. Preliminary report on tyramine headache. British medical journal Vol 2; 1967: 

550-1. Not lactose intolerance study 

843. Harland BF, Peterson M. Nutritional status of lacto-ovo vegetarian Trappist monks. J Am 

Diet Assoc 1978 Mar; 72(3):259-64. Not relevant to key questions 

844. Harland BF, Smith SA, Howard MP, et al. Nutritional status and phytate:zinc and phytate x 

calcium:zinc dietary molar ratios of lacto-ovo vegetarian Trappist monks: 10 years later. J 

Am Diet Assoc 1988 Dec; 88(12):1562-6. Not target population 

845. Harms HK, Bertele-Harms RM, Bruer-Kleis D. Enzyme-substitution therapy with the yeast 

Saccharomyces cerevisiae in congenital sucrase-isomaltase deficiency. N Engl J Med 1987 

May 21; 316(21):1306-9. Not relevant to key questions 

846. Harris RP, Helfand M, Woolf SH, et al. Current methods of the US Preventive Services Task 

Force: a review of the process. Am J Prev Med 2001 Apr; 20(3 Suppl):21-35. Not relevant to 

key questions 

217
 
847. Harrison GG, Graver EJ, Vargas M, et al. Growth and adiposity of term infants fed wheypredominant or casein-predominant formulas or human milk. Journal of pediatric 

gastroenterology and nutrition Vol 6; 1987: 739-47. Not relevant to key questions 

848. Harrison M. Letter: Sugar malabsorption in cow's milk protein intolerance. Lancet 1974 Mar 

2; 1(7853):360-1. Not relevant to key questions 

849. Harrison M, Kilby A, Walker-Smith JA, et al. Cows' milk protein intolerance: a possible 

association with gastroenteritis, lactose intolerance, and IgA deficiency. Br Med J 1976 Jun 

19; 1(6024):1501-4. Not relevant to key questions 

850. Harrison M, Walker-Smith JA. Reinvestigation of lactose intolerant children: lack of 

correlation between continuing lactose intolerance and small intestinal morphology, 

disaccharidase activity, and lactose tolerance tests. Gut 1977 Jan; 18(1):48-52. Not relevant to 

key questions 

851. Harrison V, Fawcus S, Jordaan E. Magnesium supplementation and perinatal hypoxia: 

outcome of a parallel group randomised trial in pregnancy. BJOG : an international journal of 

obstetrics and gynaecology Vol 114; 2007: 994-1002. Not lactose intolerance study 

852. Hart J, Hill HM, Bye CE, et al. The effects of low doses of amylobarbitone sodium and 

diazepam on human performance. British journal of clinical pharmacology Vol 3; 1976: 289­

98. Not lactose intolerance study 

853. Harvey CB, Hollox EJ, Poulter M, et al. Lactase haplotype frequencies in Caucasians: 

association with the lactase persistence/non-persistence polymorphism. Ann Hum Genet 1998 

May; 62(Pt 3):215-23. Not relevant to key questions 

854. Harvey-Berino J, Gold BC, Lauber R, et al. The impact of calcium and dairy product 

consumption on weight loss. Obesity research 2005 Oct; 13(10):1720-6. Not relevant to key 

questions 

855. Harzer G, Dieterich I, Haug M. Effects of the diet on the composition of human milk. Ann 

Nutr Metab Vol 28; 1984: 231-9. Not relevant to key questions 

856. Harzer K. The two human lactosylceramidases and their respective enzyme activity 

deficiency diseases: inhibition studies using p-nitrophenyl-beta-D-galactoside. Hum Genet 

1978 Apr 24; 41(3):341-5. Not relevant to key questions 

857. Hass CJ, Collins MA, Juncos JL. Resistance training with creatine monohydrate improves 

upper-body strength in patients with Parkinson disease: a randomized trial. 

Neurorehabilitation and neural repair Vol 21; 2007: 107-15. Not lactose intolerance study 

858. Hassan NA, al-Ani MR, Lafta AM, et al. Value of breath hydrogen test in detection of 

hypolactasia in patients with chronic diarrhoea. J Chromatogr 1990 Aug 24; 530(1):102-7. 

Not relevant to key questions 

859. Hastings K, Hilker DM. An investigation of milk-drinking habits of University of Hawaii 

students as a possible indication of lactose intolerance. Hawaii Med J 1976 Jul; 35(7):197-9. 

Not relevant to key questions 

860. Havala S, Dwyer J. Position of the American Dietetic Association: vegetarian diets. J Am 

Diet Assoc 1993 Nov; 93(11):1317-9. Guideline 

861. He M, Antoine JM, Yang Y, et al. [Influence of live flora on lactose digestion in male adult 

lactose-malabsorbers after dairy products intake]. Wei sheng yan jiu = Journal of hygiene 

research Vol 33; 2004: 603-5. Not English language 

862. He T, Priebe MG, Harmsen HJ, et al. Colonic fermentation may play a role in lactose 

intolerance in humans. J Nutr 2006 Jan; 136(1):58-63. Not relevant to key questions 

863. He T, Priebe MG, Vonk RJ, et al. Identification of bacteria with beta-galactosidase activity in 

218
 
faeces from lactase non-persistent subjects. FEMS Microbiol Ecol 2005 Nov 1; 54(3):463-9. 

Not relevant to key questions 

864. He T, Priebe MG, Welling GW, et al. Effect of lactose on oro-cecal transit in lactose digesters 

and maldigesters. Eur J Clin Invest 2006 Oct; 36(10):737-42. Not relevant to key questions 

865. He T, Priebe MG, Zhong Y, et al. Effects of yogurt and bifidobacteria supplementation on the 

colonic microbiota in lactose-intolerant subjects. Journal of Applied Microbiology 2008 Feb; 

104(2):595-604. Ineligible number of subjects 

866. He T, Roelofsen H, Alvarez-Llamas G, et al. Differential analysis of protein expression of 

Bifidobacterium grown on different carbohydrates. J Microbiol Methods 2007 May; 

69(2):364-70. Not relevant to key questions 

867. Heather DJ, Howell L, Montana M, et al. Effect of a bulk-forming cathartic on diarrhea in 

tube-fed patients. Heart Lung 1991 Jul; 20(4):409-13. Not relevant to key questions 

868. Heckmann SM, Hujoel P, Habiger S, et al. Zinc gluconate in the treatment of dysgeusia--a 

randomized clinical trial. Journal of dental research Vol 84; 2005: 35-8. Not lactose 

intolerance study 

869. Heiss H. [Clinical and experimental contribution on the question of the lactogenic effect of 

Galega officinalis]. Wiener medizinische Wochenschrift (1946) Vol 118; 1968: 546-8. Not 

English language 

870. Heizer WD. Normal and abnormal intestinal absorption by humans. Environmental Health 

Perspectives 1979 Dec; 33:101-6. No prevalence data 

871. Hendrickse RG, Wooldridge MA, Russell A. Lactulose in baby milks causing diarrhoea 

simulating lactose intolerance. Br Med J 1977 May 7; 1(6070):1194-5. Not relevant to key 

questions 

872. Henriksson R, Franzén L, Sandström K, et al. Effects of active addition of bacterial cultures 

in fermented milk to patients with chronic bowel discomfort following irradiation. Supportive 

care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 

Vol 3; 1995: 81-3. Not eligible target population 

873. Heresbach D, Flourie B, Briet F, et al. Effect of colonic fermentation on respiratory gas 

exchanges measured in the postabsorptive state. American Journal of Clinical Nutrition Vol 

62; 1995: 973-8. Not relevant to key questions 

874. Hermann J, Arquitt A, Stoecker B. Effects of chromium supplementation on plasma lipids, 

apolipoproteins, and glucose in elderly subjects. Nutr Res Vol 14; 1994: 671-4. Not relevant 

to key questions 

875. Hernandez-Rauda R, Martinez-Garcia S. Osteoporosis-related life habits and knowledge 

about osteoporosis among women in El Salvador: a cross-sectional study. BMC 

Musculoskelet Disord 2004 Aug 26; 5:29. Not eligible outcomes 

876. Hernell O, West C. Do we need personalized recommendations for infants at risk of 

developing disease? Nestle Nutrition Workshop Series Paediatric Programme 2008; 62:239­

49; discussion 49-52. Not original research 

877. Herrera JA, Arevalo-Herrera M, Herrera S. Prevention of preeclampsia by linoleic acid and 

calcium supplementation: a randomized controlled trial. Obstetrics and gynecology Vol 91; 

1998: 585-90. Not lactose intolerance study 

878. Herrera JA, Arévalo-Herrera M, Shahabuddin AK, et al. Calcium and conjugated linoleic acid 

reduces pregnancy-induced hypertension and decreases intracellular calcium in lymphocytes. 

American journal of hypertension : journal of the American Society of Hypertension Vol 19; 

2006: 381-7. Not lactose intolerance study 

219
 
879. Herskovic T. Protein malnutrition and the small intestine. Am J Clin Nutr 1969 Mar; 

22(3):300-4. Not relevant to key questions 

880. Hertzler SR, Clancy S. Kefir improves lactose digestion and tolerance in adult lactose 

maldigesters. Journal of Parenteral and Enteral Nutrition Vol 27; 2003: S26-s7. Not relevant 

to key questions 

881. Hertzler SR, Clancy SM. Kefir improves lactose digestion and tolerance in adults with lactose 

maldigestion. J Am Diet Assoc 2003 May; 103(5):582-7. Not relevant to key questions 

882. Hertzler SR, Savaiano DA, Levitt MD. Fecal hydrogen production and consumption 

measurements. Response to daily lactose ingestion by lactose maldigesters. Dig Dis Sci 1997 

Feb; 42(2):348-53. Not relevant to key questions 

883. Hessels J, Eidhof HH, Steggink J, et al. Assessment of hypolactasia and site-specific 

intestinal permeability by differential sugar absorption of raffinose, lactose, sucrose and 

mannitol. Clin Chem Lab Med 2003 Aug; 41(8):1056-63. Not relevant to key questions 

884. Heubi J, Karasov R, Reisinger K, et al. Randomized multicenter trial documenting the 

efficacy and safety of a lactose-free and a lactose-containing formula for term infants. Journal 

of the American Dietetic Association Vol 100; 2000: 212-7. Not relevant to key questions 

885. Hewson P, Oberklaid F, Menahem S. Infant colic, distress, and crying. Clin Pediatr (Phila) 

1987 Feb; 26(2):69-76. Not relevant to key questions 

886. Heyman M. Effect of lactic acid bacteria on diarrheal diseases. J Am Coll Nutr 2000 Apr; 

19(2 Suppl):137S-46S. Not relevant to key questions 

220
 
887. Heyman MB. Lactose intolerance in infants, children, and adolescents. Pediatrics 2006 Sep; 

118(3):1279-86. Review 

888. Hicks SM, Walker AF, Gallagher J, et al. The significance of "nonsignificance" in 

randomized controlled studies: a discussion inspired by a double-blinded study on St. John's 

wort (Hypericum perforatum L.) for premenstrual symptoms. Journal of alternative and 

complementary medicine (New York, N.Y.) Vol 10; 2004: 925-32. Not lactose intolerance 

study 

889. Hiele M. Georges Brohee Prize 1988-1989. Assimilation of nutritional carbohydrates: 

influence of hydrolysis. Acta Gastroenterol Belg 1991 Jan-Feb; 54(1):3-11. Not relevant to 

key questions 

890. Hiele M, Ghoos Y, Rutgeerts P, et al. 13CO2 breath test using naturally 13C-enriched lactose 

for detection of lactase deficiency in patients with gastrointestinal symptoms. Journal of 

Laboratory & Clinical Medicine 1988 Aug; 112(2):193-200. Ineligible number of subjects 

891. Higgins EA, Chiles WD, McKenzie JM, et al. Effects of altitude and two decongestantantihistamine preparations on physiological functions and performance. Aviation, space, and 

environmental medicine Vol 50; 1979: 154-8. Not lactose intolerance study 

892. Higgins ST, Roll JM, Bickel WK. Alcohol pretreatment increases preference for cocaine over 

monetary reinforcement. Psychopharmacology Vol 123; 1996: 1-8. Not lactose intolerance 

study 

893. Higham MA, Sharara AM, Magee RP, et al. Determination of the minimum dose of lactose 

that can be sensed during inhalation [abstract]. European Respiratory Journal. Supplement. 

Vol 8; 1995: 97s. Not lactose intolerance study 

894. Higham MA, Sharara AM, Magee RP, et al. Determination of the minimum dose of lactose 

drug carrier that can be sensed during inhalation. British journal of clinical pharmacology Vol 

40; 1995: 281-2. Not lactose intolerance study 

895. Hijazi S, El-Khateeb M, Abdulatif D. Lactose malabsorption in Jordanian infants and young 

children. Acta Paediatr Scand 1981 Sep; 70(5):759-60. Not relevant to key questions 

896. Hijazi SS, Abulaban A, Ammarin Z, et al. Distribution of adult lactase phenotypes in 

Bedouins and in urban and agricultural populations of Jordan. Trop Geogr Med 1983 Jun; 

35(2):157-61. Not relevant to key questions 

897. Hilb A. Metabolic study on a patient with nutritional vitamin D deficiency. J Hum Nutr 1977 

Oct; 31(5):359-61. Not eligible target population 

898. Hildebrandt J, Herrmann U. [Selective proximal vagotomy with and without pyloroplasty in 

uncomplicated chronic duodenal ulcer. Results of a randomized clinical study 5 and 10 years 

following surgery]. Zentralblatt für Chirurgie Vol 117; 1992: 36-40. Not lactose intolerance 

study 

221
 
899. Hildebrandt J, Lauschke G, Wolff H, et al. [Selective proximal vagotomy with and without 

pyloroplasty--results of a randomized clinical study of duodenal ulcer 5 and 8 years after 

surgery]. Zentralblatt für Chirurgie Vol 113; 1988: 827-36. Not lactose intolerance study 

900. Hill AM, Coates AM, Buckley JD, et al. Can EGCG reduce abdominal fat in obese subjects? 

Journal of the American College of Nutrition Vol 26; 2007: 396s-402s. Not lactose 

intolerance study 

901. Hines C, Jr. Milk intolerance--mimic of the irritable bowel syndrome. J La State Med Soc 

1977 May; 129(5):125-7. Not relevant to key questions 

902. Hirota N, Sone Y, Tokura H. Effect of post-prandial posture on orocecal transit time and 

digestion of milk lactose in humans. Journal of physiological anthropology and applied 

human science Vol 23; 2004: 75-80. Not lactose intolerance 

903. Hirota T, Nara M, Ohguri M, et al. Effect of diet and lifestyle on bone mass in Asian young 

women. Am J Clin Nutr 1992 Jun; 55(6):1168-73. Not eligible outcomes 

904. Hirschhorn N, Molla A, Molla AM. Reversible jejunal disaccharidase deficiency in cholera 

and other acute diarrheal diseases. Johns Hopkins Med J 1969 Dec; 125(6):291-300. Not 

relevant to key questions 

905. Hjelt K, Paerregaard A, Krasilnikoff PA. Giardiasis causing chronic diarrhoea in suburban 

Copenhagen: incidence, physical growth, clinical symptoms and small intestinal abnormality. 

Acta Paediatrica 1992 Nov; 81(11):881-6. Ineligible number of subjects 

906. Hjelt K, Paerregaard A, Petersen W, et al. Rapid versus gradual refeeding in acute 

gastroenteritis in childhood: energy intake and weight gain. Journal of pediatric 

gastroenterology and nutrition Vol 8; 1989: 75-80. Not relevant to key questions 

907. Ho MW, Povey S, Swallow D. Lactase polymorphism in adult British natives: estimating 

allele frequencies by enzyme assays in autopsy samples. Am J Hum Genet 1982 Jul; 

34(4):650-7. Not relevant to key questions 

908. Hobbs SH. Attitudes, practices, and beliefs of individuals consuming a raw foods diet. 

Explore (NY) 2005 Jul; 1(4):272-7. Not relevant to key questions 

909. Hodgson JM, Puddey IB, Beilin LJ, et al. Effects of isoflavonoids on blood pressure in 

subjects with high-normal ambulatory blood pressure levels: a randomized controlled trial. 

Am J Hypertens 1999 Jan; 12(1 Pt 1):47-53. Not eligible target population 

910. Hoeksema HL, De Wit J, Westerveld A. The genetic defect in the various types of human 

beta-galactosidase deficiency. Hum Genet 1980 Feb; 53(2):241-7. Not relevant to key 

questions 

911. Hoeksema HL, van Diggelen OP, Galjaard H. Intergenic complementation after fusion of 

fibroblasts from different patients with beta-galactosidase deficiency. Biochim Biophys Acta 

1979 Jan 12; 566(1):72-9. Not relevant to key questions 

222
 
912. Hoffman JJ. A double-blind crossover clinical trial of an OTC diuretic in the treatment of 

premenstrual tension and weight gain. Curr-Ther-Res,-Clin-Exp Vol 26; 1979: 575-80. Not 

lactose intolerance study 

913. Hogarth FW. Should zinc be added to textured vegetable protein? J Hum Nutr 1981 Oct; 

35(5):379-82. Comment 

914. Hogenauer C, Hammer HF, Mellitzer K, et al. Evaluation of a new DNA test compared with 

the lactose hydrogen breath test for the diagnosis of lactase non-persistence. Eur J 

Gastroenterol Hepatol 2005 Mar; 17(3):371-6. Not relevant to key questions 

915. Hoghton MA, Mittal NK, Sandhu BK, et al. Effects of immediate modified feeding on 

infantile gastroenteritis. The British journal of general practice : the journal of the Royal 

College of General Practitioners Vol 46; 1996: 173-5. Not relevant to key questions 

916. Hohenauer L. [Dietary treatment of acute gastroenteritis in infants]. Monatsschrift 

Kinderheilkunde : Organ der Deutschen Gesellschaft für Kinderheilkunde Vol 131; 1983: 

729-32. Not English language 

917. Holtug K, Clausen MR, Hove H, et al. The colon in carbohydrate malabsorption: short-chain 

fatty acids, pH, and osmotic diarrhoea. Scand J Gastroenterol 1992 Jul; 27(7):545-52. Not 

relevant to key questions 

918. Holzel A. Defects of sugar absorption. Sugar malabsorption and sugar intolerance in 

childhood. Proc R Soc Med 1968 Nov; 61(11 Part 1):1095-9. Not relevant to key questions 

919. Holzel A. Malabsorption. Midwife Health Visit Community Nurse 1978 Mar; 14(3):79-81. 

Not relevant to key questions 

920. Hongladarom GC, Russell M. An ethnic difference--lactose intolerance. Nurs Outlook 1976 

Dec; 24(12):764-5. Not relevant to key questions 

921. Honkanen O, Nordberg M, Eerikainen S, et al. Bioavailability of metoclopramide from orally 

and rectally administered novel hydroxypropyl methylcellulose capsules containing different 

diluents: A comparison with corresponding gelatine capsules. S.T.P. Pharma Sciences Vol 

12; 2002: 299-307. Not lactose intolerance study 

922. Honkanen O, Seppa H, Eerikainen S, et al. Bioavailability of ibuprofen from orally and 

rectally administered hydroxypropyl methyl cellulose capsules compared to corresponding 

gelatine capsules. S.T.P. Pharma Sciences Vol 11; 2001: 181-5. Not lactose intolerance study 

923. Hoogeveen A, d'Azzo A, Brossmer R, et al. Correction of combined betagalactosidase/neuraminidase deficiency in human fibroblasts. Biochem Biophys Res 

Commun 1981 Nov 16; 103(1):292-300. Not relevant to key questions 

924. Hoogeveen AT, Verheijen FW, d'Azzo A, et al. Genetic heterogeneity in human 

neuraminidase deficiency. Nature 1980 Jun 12; 285(5765):500-2. Not relevant to key 

questions 

925. Hoogeveen AT, Verheijen FW, Galjaard H. The relation between human lysosomal betagalactosidase and its protective protein. J Biol Chem 1983 Oct 25; 258(20):12143-6. Not 

relevant to key questions 

926. Horak F, Matthes H. The protective action of fluocortin butylester (FCB) in the nasal antigen 

provocation test: a controlled double-blind, crossover study. Annals of allergy Vol 48; 1982: 

305-8. Not lactose intolerance study 

927. Horsmans Y, Solbreux PM, Daenens C, et al. Lactulose improves psychometric testing in 

cirrhotic patients with subclinical encephalopathy. Alimentary pharmacology & therapeutics 

Vol 11; 1997: 165-70. Not lactose intolerance study 

928. Horton GE, Wruble LD. Lactose intolerance syndrome mimicking milk--allergy and/or 

223
 
functional bowel disorders: four cases. Ann Allergy 1966 Dec; 24(12):698-704. Not relevant 

to key questions 

929. Hosny M, Eldin SG, Hosny H. Combined lidocaine 1% and hydroxypropyl methylcellulose 

2.25% as a single anesthetic/ viscoelastic agent in phacoemulsification. Journal of cataract 

and refractive surgery Vol 28; 2002: 834-6. Not lactose intolerance study 

930. Host A, Husby S, Osterballe O. A prospective study of cow's milk allergy in exclusively 

breast-fed infants. Incidence, pathogenetic role of early inadvertent exposure to cow's milk 

formula, and characterization of bovine milk protein in human milk. Acta Paediatrica 

Scandinavica 1988 Sep; 77(5):663-70. Ineligible number of subjects 

931. Hove H, Nordgaard-Andersen I, Mortensen PB. Effect of lactic acid bacteria on the intestinal 

production of lactate and short-chain fatty acids, and the absorption of lactose. Am J Clin 

Nutr 1994 Jan; 59(1):74-9. Not relevant to key questions 

932. Hove H, Norgaard H, Mortensen PB. Lactic acid bacteria and the human gastrointestinal 

tract. Eur J Clin Nutr 1999 May; 53(5):339-50. Not relevant to key questions 

933. Howard FM, O'Halloran ET, Creagh A. Diarrhoea: after rehydration, what next? Human 

Nutrition - Applied Nutrition 1985 Feb; 39(1):53-61. Not relevant to key questions 

934. Howell JN, Mellmann J, Ehlers P, et al. Intestinal disaccharidase activities and activity ratios 

in a group of 60 adult German subjects. Hepatogastroenterology 1980 Jun; 27(3):208-12. Not 

relevant to key questions 

935. Howell JN, Schockenhoff T, Flatz G. Population screening for the human adult lactase 

phenotypes with a multiple breath version of the breath hydrogen test. Hum Genet 1981; 

57(3):276-8. Not relevant to key questions 

936. Howell JN, Von der Fecht R, Flatz G. Hydrogen breath test for lactose tolerance adapted to 

population screening. Clin Chim Acta 1980 Apr 25; 103(2):229-31. Not relevant to key 

questions 

224
 
937. Hrboticky N, Leiter LA, Anderson GH. Effects of L-tryptophan on short term food intake in 

lean men. Nutr Res Vol 5; 1985: 595-607. Not lactose intolerance study 

938. Hrboticky N, Leiter LA, Anderson GH. Menstrual cycle effects on the metabolism of 

tryptophan loads. The American journal of clinical nutrition Vol 50; 1989: 46-52. Not lactose 

intolerance study 

939. Hu JF, Zhao XH, Jia JB, et al. Dietary calcium and bone density among middle-aged and 

elderly women in China. Am J Clin Nutr 1993 Aug; 58(2):219-27. Not eligible outcomes 

940. Huang SS, Bayless TM. Lactose intolerance in healthy children. N Engl J Med 1967 Jun 8; 

276(23):1283-7. Not relevant to key questions 

941. Huang SS, Bayless TM. Milk and lactose intolerance in healthy Orientals. Science 1968 Apr 

5; 160(823):83-4. Not relevant to key questions 

942. Huempel M, Wendt H, Dogs G, et al. Intraindividual comparison of pharmacokinetic 

parameters of d norgestrel, lynestrenol and cyproterone acetate in 6 women. Contraception 

Vol 16; 1977: 199-215. Not lactose intolerance study 

943. Huncharek M, Muscat J, Kupelnick B. Impact of dairy products and dietary calcium on bonemineral content in children: results of a meta-analysis. Bone 2008 Aug; 43(2):312-21. Not 

relevant to key questions 

944. Hunt IF, Murphy NJ, Henderson C, et al. Bone mineral content in postmenopausal women: 

comparison of omnivores and vegetarians. Am J Clin Nutr 1989 Sep; 50(3):517-23. Not 

eligible outcomes 

945. Hunt JR, Matthys LA, Johnson LK. Zinc absorption, mineral balance, and blood lipids in 

women consuming controlled lactoovovegetarian and omnivorous diets for 8 wk. Am J Clin 

Nutr 1998 Mar; 67(3):421-30. Not relevant to key questions 

946. Hunt T, Geetha R, Warga E. The bioavailability of desogestrel/ethinyl estradiol tablets 

relative to the oral solution. Clinical Drug Investigation Vol 15; 1998: 507-14. Not lactose 

intolerance study 

947. Hurlemann R, Matusch A, Hawellek B, et al. Emotion-induced retrograde amnesia varies as a 

function of noradrenergic-glucocorticoid activity. Psychopharmacology Vol 194; 2007: 261­

9. Not lactose intolerance study 

948. Hursh LM. Milk has something for every body? JAMA 1975 May 5; 232(5):539-40. 

Comment 

949. Hussein L, Ezzilarab A. The frequency distribution of lactose malabsorption among adult 

populations from the eastern and western Egyptian deserts. Biochemical Genetics 1994 Oct; 

32(9-10):331-42. No prevalence data 

950. Hussein L, Flatz SD, Kuhnau W, et al. Distribution of human adult lactose phenotypes in 

Egypt. Human Heredity 1982; 32(2):94-9. Not eligible test for lactose malabsorption 

951. Hutt MS. Epidemiology of chronic intestinal disease in middle Africa. Isr J Med Sci 1979 

Apr; 15(4):314-7. Not relevant to key questions 

225
 
952. Hyams JS, Krause PJ, Gleason PA. Lactose malabsorption following rotavirus infection in 

young children. J Pediatr 1981 Dec; 99(6):916-8. Not relevant to key questions 

953. Hyams JS, Stafford RJ, Grand RJ, et al. Correlation of lactose breath hydrogen test, intestinal 

morphology, and lactase activity in young children. J Pediatr 1980 Oct; 97(4):609-12. Not 

relevant to key questions 

954. Hyams JS, Treem WR, Justinich CJ, et al. Characterization of symptoms in children with 

recurrent abdominal pain: resemblance to irritable bowel syndrome.[see comment]. Journal of 

Pediatric Gastroenterology & Nutrition 1995 Feb; 20(2):209-14. No prevalence data 

955. Hyman FC, Collins WE, Taylor HL, et al. Instrument flight performance under the influence 

of certain combinations of antiemetic drugs. Aviation, space, and environmental medicine 

Vol 59; 1988: 533-9. Not lactose intolerance study 

956. Hyo S, Fujieda S, Kawada R, et al. The efficacy of short-term administration of 3 

antihistamines vs placebo under natural exposure to Japanese cedar pollen. Annals of allergy, 

asthma & immunology : official publication of the American College of Allergy, Asthma, & 

Immunology Vol 94; 2005: 457-64. Not lactose intolerance study 

957. Iancu T, Elian E. The intestinal microvillus. Ultrastructural variability in coeliac disease and 

cow's milk intolerance. Acta Paediatr Scand 1976 Jan; 65(1):65-73. Not relevant to key 

questions 

958. Ibrahim SA, O'Sullivan DJ. Use of chemical mutagenesis for the isolation of food grade betagalactosidase overproducing mutants of bifidobacteria, lactobacilli and Streptococcus 

thermophilus. J Dairy Sci 2000 May; 83(5):923-30. Not relevant to key questions 

959. Imokawa S, Satou A, Taniguchi M, et al. [Amlexanox has an acute bronchodilator effect in 

patients with aspirin-induced asthma (AIA)]. Nihon Ky?bu Shikkan Gakkai zasshi Vol 31; 

1993: 976-82. Not lactose intolerance study 

960. Imtiaz F, Savilahti E, Sarnesto A, et al. The T/G 13915 variant upstream of the lactase gene 

(LCT) is the founder allele of lactase persistence in an urban Saudi population. Journal of 

Medical Genetics 2007 Oct; 44(10):e89. Subjects less than 4 years old 

961. Ingram CJ, Elamin MF, Mulcare CA, et al. A novel polymorphism associated with lactose 

tolerance in Africa: multiple causes for lactase persistence? Human Genetics 2007 Feb; 

120(6):779-88. No prevalence data 

962. Ingram CJ, Mulcare CA, Itan Y, et al. Lactose digestion and the evolutionary genetics of 

lactase persistence. Hum Genet 2009 Jan; 124(6):579-91. Not relevant to key questions 

963. Inui K, Wenger DA. Biochemical, immunological, and structural studies on a sphingolipid 

activator protein (SAP-1). Arch Biochem Biophys 1984 Sep; 233(2):556-64. Not relevant to 

key questions 

226
 
964. Iqbal TH, Wood GM, Lewis KO, et al. Prevalence of primary lactase deficiency in adult 

residents of west Birmingham. BMJ 1993 May 15; 306(6888):1303. Not population based 

study 

965. Isbell RG, Carlson HC, Hoffman HN, 2nd. Roentgenologic-pathologic correlation in 

malabsorption syndromes. Am J Roentgenol Radium Ther Nucl Med 1969 Sep; 107(1):158­

69. Not relevant to key questions 

966. Ish-Horowicz M, Korman SH, Shapiro M, et al. Asymptomatic giardiasis in children. 

Pediatric Infectious Disease Journal 1989 Nov; 8(11):773-9. No prevalence data 

967. Ishimori A. Safety experience with sucralfate in Japan. Journal of clinical gastroenterology 

Vol 3; 1981: 169-73. Not lactose intolerance study 

968. Isokoski M, Jussila J, Sarna S. A simple screening method for lactose malabsorption. 

Gastroenterology 1972 Jan; 62(1):28-32. Not relevant to key questions 

969. Isokoski M, Sahi T, Villako K, et al. Epidemiology and genetics of lactose malabsorption. 

Ann Clin Res 1981 Jun; 13(3):164-8. Not relevant to key questions 

970. Isselbacher KJ. Malabsorption syndromes including disease of pancreatic and biliary origin. 

Curr Concepts Nutr 1980; 9:93-104. Not relevant to key questions 

971. Itoh H, Naito T, Takeyama M. Effects of histamine H<inf>2</inf>-receptor antagonists on 

human plasma levels of calcitonin gene-related peptide, substance P and vasoactive intestinal 

peptide. Journal of Pharmacy & Pharmacology Vol 54; 2002: 1559-63. Not lactose 

intolerance study 

972. Iyngkaran N, Davis K, Robinson MJ, et al. Cows' milk protein-sensitive enteropathy: an 

important contributing cause of secondary sugar intolerance in young infants with acute 

infective enteritis. Arch Dis Child 1979 Jan; 54(1):39-43. Not relevant to key questions 

973. Iyngkaran N, Yadav M, Boey CG, et al. Effect of continued feeding of cows' milk on 

asymptomatic infants with milk protein sensitive enteropathy. Archives of Disease in 

Childhood 1988 Aug; 63(8):911-5. Subjects less than 4 years old 

974. Jackson AA, Golden MH. The human rumen. Lancet 1978 Oct 7; 2(8093):764-7. Not 

relevant to key questions 

975. Jackson KA, Savaiano DA. Lactose maldigestion, calcium intake and osteoporosis in 

African-, Asian-, and Hispanic-Americans. J Am Coll Nutr 2001 Apr; 20(2 Suppl):198S207S. review 

976. Jackson RT, Latham MC. Lactose and milk intolerance in Tanzania. East Afr Med J 1978 Jul; 

55(7):298-302. Not relevant to key questions 

977. Jackson RT, Latham MC. Lactose malabsorption among Masai children of East Africa. Am J 

Clin Nutr 1979 Apr; 32(4):779-82. Not relevant to key questions 

978. Jacobsen ST, Hull CK, Crawford AH. Nutritional rickets. Journal of pediatric orthopedics 

1986 Nov-Dec; 6(6):713-6. Not eligible target population 

227
 
979. Jahn HU, Ullrich R, Schneider T, et al. Immunological and trophical effects of 

Saccharomyces boulardii on the small intestine in healthy human volunteers. Digestion 1996; 

57(2):95-104. Ineligible number of subjects 

980. James JA, Clark C, Ward PS. Screening Rastafarian children for nutritional rickets. Br Med J 

(Clin Res Ed) 1985 Mar 23; 290(6472):899-900. Not eligible outcomes 

981. James JE. The influence of user status and anxious disposition on the hypertensive effects of 

caffeine. International journal of psychophysiology : official journal of the International 

Organization of Psychophysiology Vol 10; 1990: 171-9. Not lactose intolerance study 

982. James WP. Intestinal absorption in protein-calorie malnutrition. Lancet Vol 1; 1968: 333-5. 

Not relevant to key questions 

983. James WP. Sugar absorption and intestinal motility in children when malnourished and after 

treatment. Clin Sci 1970 Aug; 39(2):305-18. Not relevant to key questions 

984. James WP. Comparison of three methods used in assessment of carbohydrate absorption in 

malnourished children. Arch Dis Child 1972 Aug; 47(254):531-6. Not relevant to key 

questions 

985. Jamison JR, Davies NJ. Chiropractic management of cow's milk protein intolerance in infants 

with sleep dysfunction syndrome: a therapeutic trial. Journal of Manipulative & Physiological 

Therapeutics 2006 Jul-Aug; 29(6):469-74. Not relevant to key questions 

986. Janas LM, Picciano MF, Hatch TF. Indices of protein metabolism in term infants fed either 

human milk or formulas with reduced protein concentration and various whey/casein ratios. 

The Journal of pediatrics Vol 110; 1987: 838-48. Not relevant to key questions 

987. Janelle KC, Barr SI. Nutrient intakes and eating behavior scores of vegetarian and 

nonvegetarian women. J Am Diet Assoc 1995 Feb; 95(2):180-6, 9, quiz 7-8. Not relevant to 

key questions 

988. Janket SJ, Manson JE, Sesso H, et al. A prospective study of sugar intake and risk of type 2 

diabetes in women. Diabetes care Vol 26; 2003: 1008-15. Not lactose intolerance study 

989. Jardini L, Findlay R, Burgi E, et al. Auditory changes associated with moderate blood 

salicylate levels. Rheumatology and rehabilitation Vol 17; 1978: 233-6. Not lactose 

intolerance study 

990. Jarnum S, Kristensen M. Lactose malabsorption and lactose-induced enteric loss of protein in 

regional enteritis. Nucl Med (Stuttg) 1967:223-9. Not relevant to key questions 

991. Jarrett EC, Holman GH. Lactose absorption in the premature infant. Archives of Disease in 

Childhood Vol 41; 1966: 525-7. Not relevant to key questions 

992. Jarvela I, Enattah NS, Kokkonen J, et al. Assignment of the locus for congenital lactase 

deficiency to 2q21, in the vicinity of but separate from the lactase-phlorizin hydrolase gene. 

Am J Hum Genet 1998 Oct; 63(4):1078-85. Not relevant to key questions 

993. Jarvela IE. Molecular genetics of adult-type hypolactasia. Annals of Medicine 2005; 

37(3):179-85. No prevalence data 

994. Jarvis JK, Miller GD. Overcoming the barrier of lactose intolerance to reduce health 

disparities. J Natl Med Assoc 2002 Feb; 94(2):55-66. Review 

995. Jasani MK, Downie WW, Samuels BM, et al. Ibuprofen in rheumatoid arthritis. Clinical 

study of analgesic and anti-inflammatory activity. Annals of the rheumatic diseases Vol 27; 

1968: 457-62. Not lactose intolerance study 

996. Jeans WD. An evaluation of radiological signs in small bowel examinations in children. Clin 

Radiol 1972 Jan; 23(1):78-86. Not relevant to key questions 

997. Jelliffe DB. Intolerance to lactose in mother's milk? Lancet 1972 Oct 7; 2(7780):760. Not 

228
 
relevant to key questions 

998. Jenista JA, Chapman D. Medical problems of foreign-born adopted children. Am J Dis Child 

1987 Mar; 141(3):298-302. Not relevant to key questions 

999. Jenkins C, Breslin AB, Marlin GE. The role of alpha and beta adrenoceptors in airway 

hyperresponsiveness to histamine. The Journal of allergy and clinical immunology Vol 75; 

1985: 364-72. Not lactose intolerance study 

1000. Jenkins T, Gibney SF, Nurse GT, et al. Persistent high intestinal lactase activity in Papua 

New Guinea. Lactose absorption curves in two populations. Ann Hum Biol 1981 Sep-Oct; 

8(5):447-51. Not relevant to key questions 

1001. Jenkins T, Lehmann H, Nurse GT. Public health and genetic constitution of the San 

("Bushmen"): carbohydrate metabolism and acetylator status of the Kung of Tsumkwe in the 

North-western Kalahari. Br Med J 1974 Apr 6; 2(5909):23-6. Not relevant to key questions 

1002. Jenkins T, Nurse GT. Biomedical studies on the desert dwelling huntergatherers of 

Southern Africa. Prog Med Genet 1976; 1:211-81. Not relevant to key questions 

1003. Jennings W, Rowland R, Hecker R, et al. The significance of lowered jejunal 

disaccharidase levels. Aust N Z J Med 1976 Dec; 6(6):556-60. Not relevant to key questions 

1004. Jersky J, Kinsley RH. Lactose deficiency in the South African Bantu. S Afr Med J 1967 

Dec 16; 41(46):1194-6. Not relevant to key questions 

1005. Jewell DP, Truelove SC. Circulating antibodies to cow's milk proteins in ulcerative colitis. 

Gut 1972 Oct; 13(10):796-801. Not relevant to key questions 

1006. Jiang TA, Ye RY. Studies on small intestinal mucosal morphology lactase activity and 

lactose hydrolysis rate in childhood with diarrhea. Chin Med J (Engl) 1991 Jun; 104(6):476­

9. Not relevant to key questions 

1007. Johansson G, Callmer E, Gustafsson JA. Validity of repeated dietary measurements in a 

dietary intervention study. Eur J Clin Nutr 1992 Oct; 46(10):717-28. Not eligible outcomes 

229
 
1008. Johansson G, Holmen A, Persson L, et al. Long-term effects of a change from a mixed diet 

to a lacto-vegetarian diet on human urinary and faecal mutagenic activity. Mutagenesis 1998 

Mar; 13(2):167-71. Not relevant to key questions 

1009. Johansson G, Holmen A, Persson L, et al. The effect of a shift from a mixed diet to a lactovegetarian diet on human urinary and fecal mutagenic activity. Carcinogenesis 1992 Feb; 

13(2):153-7. Not eligible outcomes 

1010. Johnson AO, Semenya JG, Buchowski MS, et al. Adaptation of lactose maldigesters to 

continued milk intakes. Am J Clin Nutr 1993 Dec; 58(6):879-81. Not relevant to key 

questions 

1011. Johnson JD, Simoons FJ, Hurwitz R, et al. Lactose malabsorption among the Pima indians 

of Arizona. Gastroenterology 1977 Dec; 73(6):1299-304. Not eligible test for lactose 

malabsorption 

1012. Johnson RC, Ayau EP, Ching CA, et al. Environmental influences on lactose tolerance. 

Behav Genet 1987 Jul; 17(4):313-30. Not relevant to key questions 

1013. Johnson RC, Bowman KS, Schwitters SY, et al. Ethnic, familial, and environmental 

influences on lactose tolerance. Hum Biol 1984 May; 56(2):307-16. Not relevant to key 

questions 

1014. Johnson RC, Cole RE, Ahern FM. Genetic interpretation of racial/ethnic differences in 

lactose absorption and tolerance: a review. Hum Biol 1981 Feb; 53(1):1-13. Not relevant to 

key questions 

1015. Johnson RC, Schwitters SY, Cole RE, et al. A family study of lactose tolerance. Behav 

Genet 1981 Jul; 11(4):369-72. Not relevant to key questions 

1016. Johnson RM, Brummett R, Schleuning A. Use of alprazolam for relief of tinnitus. A 

double-blind study. Archives of otolaryngology--head & neck surgery Vol 119; 1993: 842-5. 

Not lactose intolerance study 

1017. Johnston PK. Getting enough to grow on. Am J Nurs 1984 Mar; 84(3):336-9. Comment 

1018. Jones DV, Latham MC. Lactose intolerance in young children and their parents. Am J Clin 

Nutr 1974 Jun; 27(6):547-9. Not relevant to key questions 

1019. Jones DV, Latham MC. The implications of lactose intolerance in children. J Trop Pediatr 

Environ Child Health 1974 Oct; 20(5):261-71. Not relevant to key questions 

1020. Jones VA, McLaughlan P, Shorthouse M, et al. Food intolerance: a major factor in the 

pathogenesis of irritable bowel syndrome. Lancet 1982 Nov 20; 2(8308):1115-7. Not relevant 

to key questions 

1021. Jonkers D, Stockbrugger R. Review article: Probiotics in gastrointestinal and liver diseases. 

Aliment Pharmacol Ther 2007 Dec; 26 Suppl 2:133-48. Not relevant to key questions 

1022. Jonsson B, Gardsell P, Johnell O, et al. Life-style and different fracture prevalence: a crosssectional comparative population-based study. Calcif Tissue Int 1993 Jun; 52(6):425-33. Not 

eligible outcomes 

230
 
1023. Joos G, Vincken W, Aumann J, et al. Comparison of the bronchodilator effect of fenoterolipratropium bromide delivered as lactose powder capsule to metered dose inhaler in asthma 

[abstract]. European Respiratory Journal. Supplement. Vol 8; 1995: 426s. Not lactose 

intolerance study 

1024. Joseph F, Jr., Rosenberg AJ. Low breath hydrogen production in post-diarrheic infants. 

Acta Paediatr Scand 1991 Aug-Sep; 80(8-9):792-4. Not relevant to key questions 

1025. Josephson RV, Rupp JW, Chambers JF. Needs assessment of enteral nutrition support 

products. Journal of the American Dietetic Association 1985 Nov; 85(11):1485-7. Not 

relevant to key questions 

1026. Juambeltz JC, Kula K, Perman J. Nursing caries and lactose intolerance. Journal of 

Dentistry for Children 1993 Nov-Dec; 60(4):377-84. No prevalence data 

1027. Jung AL, Carr SL. A soy protein formula and a milk-based formula. A comparative 

evaluation in milk-tolerant infants showed no significant nutritional differences. Clin Pediatr 

(Phila) 1977 Nov; 16(11):982-5. Not relevant to key questions 

1028. Jussila J. Milk intolerance and lactose malabsorption in hospital patients and young 

servicemen in Finland. Ann Clin Res 1969 Nov; 1(3):199-207. Not relevant to key questions 

1029. Jussila J. The lactose tolerance test with intravenous administration of ethanol. Ann Clin 

Res 1969 May; 1(1):50-6. Not relevant to key questions 

1030. Jussila J. Diagnosis of lactose malabsorption by the lactose tolerance test with peroral 

ethanol administration. Scand J Gastroenterol 1969; 4(4):361-8. Not relevant to key questions 

1031. Jussila J, Isokoski M, Launiala K. Prevalence of lactose malabsorption in a Finnish rural 

population. Scandinavian Journal of Gastroenterology 1970; 5(1):49-56. Not eligible test for 

lactose malabsorption 

1032. Jussila J, Launiala K, Gorbatow O. Lactase deficiency and a lactose-free diet in patients 

with "unspecific abdominal complaints". Acta Med Scand 1969 Sep; 186(3):217-22. Not 

relevant to key questions 

1033. Jussila J, Mattila MJ, Takki S. Drug absorption during lactose-induced intestinal symptoms 

in patients with selective lactose malabsorption. Ann Med Exp Biol Fenn 1970; 48(1):33-7. 

Not relevant to key questions 

1034. Jussila J, Sivula A, Salmi HJ. Effect of ulcer surgery on disaccharidase activities of the 

small bowel and on lactose absorption. Scandinavian Journal of Gastroenterology 1972; 

7(4):315-20. No prevalence data 

1035. Jutzy RV. Clinical studies of Norpace (Part IV). Angiology 1975 Jan; 26(1 Pt 2):138-9. Not 

relevant to key questions 

1036. Kagaya M, Iwata M, Toda Y, et al. Circadian rhythm of breath hydrogen in young women. 

J Gastroenterol 1998 Aug; 33(4):472-6. Not relevant to key questions 

231
 
1037. Kahn A, Francois G, Sottiaux M, et al. Sleep characteristics in milk-intolerant infants. 

Sleep 1988 Jun; 11(3):291-7. Not relevant to key questions 

1038. Kahn A, Mozin MJ, Rebuffat E, et al. Milk intolerance in children with persistent 

sleeplessness: a prospective double-blind crossover evaluation.[see comment]. Pediatrics 

1989 Oct; 84(4):595-603. Ineligible number of subjects 

1039. Kahn HA, Sempos CT. Statistical Methods in Epidemiology (Monographs in 

Epidemiology and Biostatistics). USA: Oxford University Press; 1989. Custom 3 

1040. Kailasapathy K, Chin J. Survival and therapeutic potential of probiotic organisms with 

reference to Lactobacillus acidophilus and Bifidobacterium spp. Immunol Cell Biol 2000 

Feb; 78(1):80-8. Not relevant to key questions 

1041. Kalis B. [Assessment by transcutaneous PO2 measurement of the treatment of venous 

ulcers with naftidrofuryl]. Journal Des Maladies Vasculaires Vol 9; 1984: 133-6. Not lactose 

intolerance study 

1042. Kaminski M, Boal R. An effect of ascorbic acid on delayed-onset muscle soreness. Pain 

Vol 50; 1992: 317-21. Not lactose intolerance study 

1043. Kammann J, Dornbach G, Vollenberg C, et al. [Controlled clinical study of two 

viscoelastic substances]. Fortschritte der Ophthalmologie : Zeitschrift der Deutschen 

Ophthalmologischen Gesellschaft Vol 88; 1991: 438-41. Not lactose intolerance study 

1044. Kanabar D. Infantile colic. J Fam Health Care 2004; 14(2):suppl 1-2. Review 

1045. Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following 

reduction of lactose load with lactase. J Hum Nutr Diet 2001 Oct; 14(5):359-63. Not eligible 

target population 

1046. Kanaghinis T, Hatzioannou J, Deliargyris N, et al. Primary lactase deficiency in Greek 

adults. Am J Dig Dis 1974 Nov; 19(11):1021-7. Not relevant to key questions 

1047. Kaplan NM. Non-drug treatment of hypertension. Ann Intern Med 1985 Mar; 102(3):359­

73. Not eligible target population 

1048. Kaplan NM. Dietary aspects of the treatment of hypertension. Annu Rev Public Health 

1986; 7:503-19. Not eligible target population 

1049. Kar P, Tandon RK. Lactose intolerance in Nagaland. Indian J Med Res 1985 Sep; 82:254­

6. Not relevant to key questions 

1050. Karhu M, Kuikka J, Kauppinen T, et al. Pulmonary deposition of lactose carriers used in 

inhalation powders. International journal of pharmaceutics Vol 196; 2000: 95-103. Not 

lactose intolerance study 

1051. Karlowski TR, Chalmers TC, Frenkel LD, et al. Ascorbic acid for the common cold. A 

prophylactic and therapeutic trial. JAMA : the journal of the American Medical Association 

Vol 231; 1975: 1038-42. Not lactose intolerance study 

1052. Karofsky PS. Infantile colic. J Fam Pract 1984 Jul; 19(1):107-8, 11-2, 14 passim. Not 

relevant to key questions 

232
 
1053. Kasper H, Kuhn HA. The small-intestinal function in ulcerative colitis. Am J Proctol 1970 

Aug; 21(4):253-7. Not relevant to key questions 

1054. Katch VL, Moorehead CP, Becque MD, et al. Reduced short-term thermic effects of a meal 

in obese adolescent girls. European journal of applied physiology and occupational 

physiology Vol 65; 1992: 535-40. Not lactose intolerance study 

1055. Kato T, Okada S, Yutaka T, et al. beta-Galactosidase deficient-type mucolipidosis: a 

complementation study of neuraminidase in somatic cell hybrids. Biochem Biophys Res 

Commun 1979 Nov 14; 91(1):114-7. Not relevant to key questions 

1056. Kato T, Okada S, Yutaka T, et al. Induction of beta-galactosidase in beta-galactosidasealpha-neuraminidase deficiency: effects of leupeptin and sucrose. Biochem Int 1983 Feb; 

6(2):267-73. Not relevant to key questions 

1057. Katz AJ, Falchuk ZM. Definitive diagnosis of gluten-sensitive enteropathy. Use of an in 

vitro organ culture model. Gastroenterology 1978 Oct; 75(4):695-700. Not relevant to key 

questions 

1058. Kaur K, Mahmood S, Mahmood A. Hypolactasia as a molecular basis of lactose 

intolerance. Indian Journal of Biochemistry & Biophysics 2006 Oct; 43(5):267-74. No 

prevalence data 

1059. Kay CD, Morrison JD. The effects of ingestion of 60 mg pyridostigmine bromide on 

contrast sensitivity in man. Human toxicology Vol 7; 1988: 347-52. Not lactose intolerance 

study 

1060. Keet MP, Moodie AD, Wittmann W, et al. Kwashiorkor: a prospective ten-year follow-up 

study. S Afr Med J 1971 Dec 25; 45(49):1427-49. Not eligible target population 

1061. Kefenie H, Berhane R. Lactose tolerance test in 193 subjects in Ethiopia. Ethiop Med J 

1987 Apr; 25(2):65-9. Not relevant to key questions 

1062. Kelsay JL, Frazier CW, Prather ES, et al. Impact of variation in carbohydrate intake on 

mineral utilization by vegetarians. Am J Clin Nutr 1988 Sep; 48(3 Suppl):875-9. Not relevant 

to key questions 

1063. Kemp JP, Hill MR, Vaughan LM, et al. Pilot study of bronchodilator response to inhaled 

albuterol delivered by metered-dose inhaler and a novel dry powder inhaler. Annals of 

allergy, asthma & immunology : official publication of the American College of Allergy, 

Asthma, & Immunology Vol 79; 1997: 322-6. Not lactose intolerance study 

1064. Keohane PP, Attrill H, Jones BJ, et al. The roles of lactose and clostridium difficile in the 

pathogenesis of enteral feeding associated diarrhoea. Clin-Nutr Vol 1; 1983: 259-64. Not 

relevant to key questions 

1065. Kerber M, Oberkanins C, Kriegshauser G, et al. Hydrogen breath testing versus LCT 

genotyping for the diagnosis of lactose intolerance: a matter of age? Clin Chim Acta 2007 

Aug; 383(1-2):91-6. Not relevant to key questions 

233
 
1066. Kerr FA, Szabadi E. Comparison of the effects of chronic administration of ciclazindol and 

desipramine on pupillary responses to tyramine, methoxamine and pilocarpine in healthy 

volunteers. British journal of clinical pharmacology Vol 19; 1985: 639-47. Not lactose 

intolerance study 

1067. Keshavarzian A, Iber FL, Dangleis MD, et al. Intestinal-transit and lactose intolerance in 

chronic alcoholics. Am J Clin Nutr 1986 Jul; 44(1):70-6. Not relevant to key questions 

1068. Keusch GT. Subclinical malabsorption in Thailand. I. Intestinal absorption in Thai 

children. Am J Clin Nutr 1972 Oct; 25(10):1062-6. Not relevant to key questions 

1069. Keusch GT, Plaut AG, Troncale FJ. Subclinical malabsorption in Thailand. II. Intestinal 

absorption in American military and Peace Corps personnel. Am J Clin Nutr 1972 Oct; 

25(10):1067-79. Not relevant to key questions 

1070. Keusch GT, Troncale FJ, Miller LH, et al. Acquired lactose malabsorption in Thai children. 

Pediatrics 1969 Apr; 43(4):540-5. Not relevant to key questions 

1071. Keusch GT, Troncale FJ, Thavaramara B, et al. Lactase deficiency in Thailand: effect of 

prolonged lactose feeding. Am J Clin Nutr 1969 May; 22(5):638-41. Not relevant to key 

questions 

1072. Khan NA, McAlister FA, Rabkin SW, et al. The 2006 Canadian Hypertension Education 

Program recommendations for the management of hypertension: Part II - Therapy. Canadian 

Journal of Cardiology 2006 May 15; 22(7):583-93. Not relevant to key questions 

1073. Khoshoo V, Bhan MK, Arora NK, et al. Leucocyte migration inhibition in cow's milk 

protein intolerance. Acta Paediatr Scand 1986 Mar; 75(2):308-12. Not relevant to key 

questions 

1074. Kien CL, Liechty EA. Effects of lactose intake on nutrient absorption and nutritional status 

in premature infants (PI). Pediatric Research Vol 25; 1989: 117a. Not relevant to key 

questions 

1075. Kien CL, Liechty EA, Mullett MD. Contribution of low-molecular-weight compounds to 

the fecal excretion of carbohydrate energy in premature infants. Gastroenterology Vol 99; 

1990: 165-74. Not relevant to key questions 

1076. Kien CL, Liechty EA, Mullett MD. Effects of lactose intake on nutritional status in 

premature infants. Journal of Pediatrics Vol 116; 1990: 446-9. Not relevant to key questions 

1077. Kien CL, Liechty EA, Myerberg DZ, et al. Dietary carbohydrate assimilation in the 

premature infant: evidence for a nutritionally significant bacterial ecosystem in the colon. The 

American journal of clinical nutrition Vol 46; 1987: 456-60. Not relevant to key questions 

1078. Kien CL, Liechty EA, Myerberg DZ, et al. Effects in premature infants of normalizing 

breath H2 concentrations with CO2: increased H2 concentration and reduced interaliquot 

variation. J Pediatr Gastroenterol Nutr 1987 Mar-Apr; 6(2):286-9. Not relevant to key 

questions 

234
 
1079. Kien CL, McClead RE, Cordero L. Effects of lactose intake on lactose digestion and 

colonic fermentation in preterm infants. The Journal of pediatrics Vol 133; 1998: 401-5. Not 

relevant to key questions 

1080. Kien CL, Sumners JE, Stetina JS, et al. A method for assessing carbohydrate energy 

absorption and its application to premature infants. The American journal of clinical nutrition 

Vol 36; 1982: 910-6. Not relevant to key questions 

1081. Kies CV. Mineral utilization of vegetarians: impact of variation in fat intake. Am J Clin 

Nutr 1988 Sep; 48(3 Suppl):884-7. Not eligible target population 

1082. Kikuchi K, Matahira Y. Oral N-acetylglucosamine supplementation improves skin 

conditions of female volunteers: Clinical evaluation by a microscopic three-dimensional skin 

surface analyzer. Journal of Applied Cosmetology Vol 20; 2002: 143-52. Not lactose 

intolerance study 

1083. Kim HS, Gilliland SE. Lactobacillus acidophilus as a dietary adjunct for milk to aid lactose 

digestion in humans. J Dairy Sci 1983 May; 66(5):959-66. Not relevant to key questions 

1084. King F. Intolerance to lactose in mother's milk? Lancet 1972 Aug 12; 2(7772):335. Not 

relevant to key questions 

1085. King T. Comparison of symptoms after the consumption of milk or lactose-hydrolysed 

milk by people with self-reported severe lactose intolerance. Clin Nutr 1996 Apr; 15(2):97-8. 

Not relevant to key questions 

1086. Kingfisher CP, Millard AV. "Milk makes me sick but my body needs it": conflict and 

contradiction in the establishment of authoritative knowledge. Med Anthropol Q 1998 Dec; 

12(4):447-66. Not relevant to key questions 

1087. Kirkpatrick C, Buck H, Ellis S. Assessment of adrenal suppression from two new dry 

powder inhaler formulations of budesonide delivered by Clickhaler compared with the 

Pulmicort Turbuhaler. Journal of aerosol medicine : the official journal of the International 

Society for Aerosols in Medicine Vol 16; 2003: 31-6. Not lactose intolerance study 

1088. Kirschner BS, DeFavaro MV, Jensen W. Lactose malabsorption in children and 

adolescents with inflammatory bowel disease. Gastroenterology 1981 Nov; 81(5):829-32. No 

prevalence data 

1089. Kirsner JB. Clinical observations on malabsorption. Med Clin North Am 1969 Sep; 

53(5):1169-94. Not relevant to key questions 

1090. Klauser AG, Voderholzer WA, Schindlbeck NE, et al. Functional diagnostic work-up in 

patients with irritable bowel syndrome. Zeitschrift fur Gastroenterologie 1996 May; 

34(5):273-8. Not population based study 

1091. Kleerekoper M, Peterson E, Nelson D, et al. Identification of women at risk for developing 

postmenopausal osteoporosis with vertebral fractures: role of history and single photon 

absorptiometry. Bone Miner 1989 Sep; 7(2):171-86. Not eligible outcomes 

235
 
1092. Kleessen B, Sykura B, Zunft H, et al. Effects of insulin and lactose on fecal microflora, 

microbial activity, and bowel habit in elderly constipated persons. American Journal of 

Clinical Nutrition Vol 65; 1997: 1397-402. Not relevant to key questions 

1093. Klein UE, Walpurger G. Biochemical and enzyme-cytochemical findings in the human 

small intestinal mucosa in malabsorption syndromes. Digestion 1971; 4(4):205-15. Not 

relevant to key questions 

1094. Klesges RC, Harmon-Clayton K, Ward KD, et al. Predictors of milk consumption in a 

population of 17- to 35-year-old military personnel. J Am Diet Assoc 1999 Jul; 99(7):821-6; 

quiz 7-8. Not relevant to key questions 

1095. Kline AH, Assemi M. Lactose intolerance with lactosuria. Tex Med 1968 Jul; 64(7):36-9. 

Not relevant to key questions 

1096. Klorman R, Brumaghim JT, Salzman LF, et al. Effects of methylphenidate on processing 

negativities in patients with attention-deficit hyperactivity disorder. Psychophysiology Vol 

27; 1990: 328-37. Not lactose intolerance study 

1097. Klotz AP, Lubos MC. Gastrointestinal symptoms and intestinal lactase deficiencies--a 

word of caution. Am J Dig Dis 1967 Apr; 12(4):421-3. Not relevant to key questions 

1098. Klug RM. AIDS beyond the hospital. 2. Children with AIDS. Am J Nurs 1986 Oct; 

86(10):1126-32. Not relevant to key questions 

1099. Kneepkens CM, Hoekstra JH. Malabsorption of carbohydrates. Nestle Nutr Workshop Ser 

Pediatr Program 2005; 56:57-69; discussion -71. Not relevant to key questions 

1100. Knodell RG, Tate MA, Akl BF, et al. Vitamin C prophylaxis for posttransfusion hepatitis: 

lack of effect in a controlled trial. The American journal of clinical nutrition Vol 34; 1981: 

20-3. Not lactose intolerance study 

1101. Knopp RH, Brandt K, Arky RA. Effects of aspartame in young persons during weight 

reduction. Journal of toxicology and environmental health Vol 2; 1976: 417-28. Not lactose 

intolerance study 

1102. Knudsen KB, Welsh JD, Kronenberg RS, et al. Effect of a nonlactose diet on human 

intestinal disaccharidase activity. Am J Dig Dis 1968 Jul; 13(7):593-7. Not relevant to key 

questions 

1103. Kobayashi A, Kawai S, Obe Y, et al. Effects of dietary lactose and lactase preparation on 

the intestinal absorption of calcium and magnesium in normal infants. The American journal 

of clinical nutrition Vol 28; 1975: 681-3. Not eligible target population 

1104. Kochhar R, Mehta SK, Goenka MK, et al. Lactose intolerance in idiopathic ulcerative 

colitis in north Indians. Indian J Med Res 1993 Apr; 98:79-82. Not relevant to key questions 

1105. Kocian J, Skala I, Bakos K. Calcium absorption from milk and lactose-free milk in healthy 

subjects and patients with lactose intolerance. Digestion 1973 Nov; 9(4):317-24. Not eligible 

outcomes 

236
 
1106. Kocian J, Vulterinova M, Bejblova O, et al. Influence of lactose intolerance on the bones of 

patients after partial gastrectomy. Digestion 1973; 8(4):324-35. Not eligible target population 

1107. Koetse HA, Klaassen D, van der Molen AR, et al. Combined LDI/SAT test to evaluate 

intestinal lactose digestion and mucosa permeability. Eur J Clin Invest 2006 Oct; 36(10):730­

6. Not relevant to key questions 

1108. Koetse HA, Vonk RJ, Gonera-De Jong GB, et al. Low lactase activity in a small-bowel 

biopsy specimen: should dietary lactose intake be restricted in children with small intestinal 

mucosal damage? Scand J Gastroenterol 2006 Jan; 41(1):37-41. Not relevant to key questions 

1109. Kohlenberg-Mueller K, Raschka L. Calcium balance in young adults on a vegan and 

lactovegetarian diet. J Bone Miner Metab 2003; 21(1):28-33. not eligible outcomes 

1110. Kokke FT, van ERM, van OFM, et al. [A new biscuit free of cow's milk, chicken egg 

protein, lactose and gluten for children with food hypersensitivity]. Nederlands tijdschrift 

voor geneeskunde Vol 138; 1994: 2549-52. Not English language 

1111. Kokkonen J, Haapalahti M, Tikkanen S, et al. Gastrointestinal complaints and diagnosis in 

children: a population-based study. Acta Paediatr 2004 Jul; 93(7):880-6. Not relevant to key 

questions 

1112. Kokkonen J, Mottonen M, Karttunen TJ, et al. Mucosal pathology of the upper 

gastrointestinal tract associated with intensive chemotherapy in children: vitamin A 

supplements do not prevent lesions. Pediatric Hematology & Oncology 2002 Apr-May; 

19(3):181-92. Ineligible number of subjects 

1113. Kokkonen J, Simila S. Cow's milk intolerance with melena. Eur J Pediatr 1980 Dec; 

135(2):189-94. Not relevant to key questions 

1114. Kolars JC, Levitt MD, Aouji M, et al. Yogurt--an autodigesting source of lactose. N Engl J 

Med 1984 Jan 5; 310(1):1-3. Not relevant to key questions 

1115. Koller WC, Block GA, Ahlskog JE, et al. Effect of MK-458 (HPMC) in Parkinson's 

disease previously untreated with dopaminergic drugs. A double-blind, placebo-controlled 

multicenter study. Clinical neuropharmacology Vol 14; 1991: 322-9. Not lactose intolerance 

study 

1116. Kondo T, Liu F, Toda Y. Milk is a useful test meal for measurement of small bowel transit 

time. J Gastroenterol 1994 Dec; 29(6):715-20. Not relevant to key questions 

1117. Konstantynowicz J, Nguyen TV, Kaczmarski M, et al. Fractures during growth: potential 

role of a milk-free diet. Osteoporos Int 2007 Dec; 18(12):1601-7. Not relevant to key 

questions 

1118. Kopp-Hoolihan L. Prophylactic and therapeutic uses of probiotics: a review. Journal of the 

American Dietetic Association 2001 Feb; 101(2):229-38; quiz 39-41. Not original research 

237
 
1119. Kordansky D, Adkinson NF, Jr., Norman PS, et al. Asthma improved by nonsteroidal antiinflammatory drugs. Annals of Internal Medicine Vol 88; 1978: 508-11. Not lactose 

intolerance study 

1120. Kordansky DW, Rosenthal RR, Norman PS. The effect of vitamin C on antigen-induced 

bronchospasm. The Journal of allergy and clinical immunology Vol 63; 1979: 61-4. Not 

lactose intolerance study 

1121. Korede O. Effect of supplementation with water-soluble vitamins on erythrocyte alanine 

aminotransferase activity of healthy adolescents. Annals of nutrition & metabolism Vol 35; 

1991: 77-81. Not lactose intolerance study 

1122. Koskinen S. Long-term follow-up of health in blood donors with primary selective IgA 

deficiency. Journal of Clinical Immunology 1996 May; 16(3):165-70. No prevalence data 

1123. Kosnai I, Kuitunen P, Savilahti E, et al. Mast cells and eosinophils in the jejunal mucosa of 

patients with intestinal cow's milk allergy and celiac disease of childhood. J Pediatr 

Gastroenterol Nutr 1984 Jun; 3(3):368-72. Not relevant to key questions 

1124. Kosonen H, Rimpela A, Rauma AL, et al. Consumption of special diet among Finnish 

adolescents in 1979-2001: repeated national cross-sectional surveys. Sozial- und 

Praventivmedizin 2005; 50(3):142-50. No prevalence data 

1125. Kowalski R. Lactose intolerance how widespread? Nurs Care 1977 May; 10(5):30, 4. Not 

relevant to key questions 

1126. Kozlov AI. Hypolactasia in the indigenous populations of northern Russia. Int J 

Circumpolar Health 1998 Jan; 57(1):18-21. Not relevant to key questions 

1127. Krasilnikoff PA, Gudman-Hoyer E, Moltke HH. Diagnostic value of disaccharide tolerance 

tests in children. Acta Paediatr Scand 1975 Sep; 64(5):693-8. Not relevant to key questions 

1128. Krawczyk M, Wolska M, Schwartz S, et al. Concordance of genetic and breath tests for 

lactose intolerance in a tertiary referral centre. Journal of Gastrointestinal & Liver Diseases 

2008 Jun; 17(2):135-9. Ineligible number of subjects 

1129. Kresse H, von Figura K, Klein U, et al. Enzymic diagnosis of the genetic 

mucopolysaccharide storage disorders. Methods Enzymol 1982; 83:559-72. Not relevant to 

key questions 

1130. Kretchmer N. Lactose and lactase. Sci Am 1972 Oct; 227(4):71-8. Not relevant to key 

questions 

1131. Kretchmer N. The geography and biology of lactose digestion and malabsorption. Postgrad 

Med J 1977; 53 Suppl 2:65-72. Not relevant to key questions 

1132. Kretchmer N, Ransome-Kuti O. Lactose intolerance: an international problem. Proc Inst 

Med Chic 1970 Nov; 28(6):213-7. Not relevant to key questions 

1133. Kretchmer N, Ransome-Kuti O, Hurwitz R, et al. Intestinal absorption of lactose in 

Nigerian ethnic groups. Lancet 1971 Aug 21; 2(7721):392-5. Not relevant to key questions 

238
 
1134. Kretchmer N, Sunshine P. Intestinal disaccharidase deficiency in the sea lion. 

Gastroenterology 1967 Jul; 53(1):123-9. Not relevant to key questions 

1135. Krishnaswamy K, Prasad MP, Krishna TP, et al. A case study of nutrient intervention of 

oral precancerous lesions in India. European journal of cancer. Part B, Oral oncology Vol 

31b; 1995: 41-8. Not lactose intolerance study 

1136. Kristinsson JO, Valdimarsson O, Steingrimsdottir L, et al. Relation between calcium 

intake, grip strength and bone mineral density in the forearms of girls aged 13 and 15. J Intern 

Med 1994 Oct; 236(4):385-90. Not eligible exposure 

1137. Kromhout D. Epidemiology of cardiovascular diseases in Europe. Public Health Nutr 2001 

Apr; 4(2B):441-57. Review 

1138. Kromhout D. Diet and cardiovascular diseases. J Nutr Health Aging 2001; 5(3):144-9. 

Review 

1139. Kudoh A, Ishihara H, Matsuki A. Effect of carbamazepine on pain scores of unipolar 

depressed patients with chronic pain: a trial of off-on-off-on design. The Clinical journal of 

pain Vol 14; 1998: 61-5. Not lactose intolerance study 

1140. Kudoh T, Wenger DA. Diagnosis of metachromatic leukodystrophy, Krabbe disease, and 

Farber disease after uptake of fatty acid-labeled cerebroside sulfate into cultured skin 

fibroblasts. J Clin Invest 1982 Jul; 70(1):89-97. Not relevant to key questions 

1141. Kuitunen P, Kosnai I, Savilahti E. Morphometric study of the jejunal mucosa in various 

childhood enteropathies with special reference to intraepithelial lymphocytes. Journal of 

Pediatric Gastroenterology & Nutrition 1982; 1(4):525-31. Ineligible number of subjects 

1142. Kukuruzovic RH, Brewster DR. Milk formulas in acute gastroenteritis and malnutrition: a 

randomized trial. J Paediatr Child Health 2002 Dec; 38(6):571-7. Not eligible target 

population 

1143. Kulaputana O, Thanakomsirichot S, Anomasiri W. Ginseng supplementation does not 

change lactate threshold and physical performances in physically active Thai men. Journal of 

the Medical Association of Thailand = Chotmaihet thangphaet Vol 90; 2007: 1172-9. Not 

lactose intolerance study 

1144. Kullisaar T, Songisepp E, Mikelsaar M, et al. Antioxidative probiotic fermented goats' milk 

decreases oxidative stress-mediated atherogenicity in human subjects. British Journal of 

Nutrition Vol 90; 2003: 449-56. Not relevant to key questions 

1145. Kulski JK, Hartmann PE, Martin JD, et al. Effects of bromocriptine mesylate on the 

composition of the mammary secretion in non-breast-feeding women. Obstetrics and 

gynecology Vol 52; 1978: 38-42. Not lactose intolerance study 

1146. Kumar V, Chandrasekaran R, Bhaskar R. Carbohydrate intolerance associated with acute 

gastroenteritis. A prospective study of 90 well-nourished indian infants. Clinical Pediatrics 

1977 Dec; 16(12):1123-7. No prevalence data 

239
 
1147. Kuokkanen M, Butzow R, Rasinpera H, et al. Lactase persistence and ovarian carcinoma 

risk in Finland, Poland and Sweden. International Journal of Cancer 2005 Oct 20; 117(1):90­

4. No prevalence data 

1148. Kuokkanen M, Kokkonen J, Enattah NS, et al. Mutations in the translated region of the 

lactase gene (LCT) underlie congenital lactase deficiency. Am J Hum Genet 2006 Feb; 

78(2):339-44. Not relevant to key questions 

1149. Kuokkanen M, Myllyniemi M, Vauhkonen M, et al. A biopsy-based quick test in the 

diagnosis of duodenal hypolactasia in upper gastrointestinal endoscopy. Endoscopy 2006 Jul; 

38(7):708-12. Not relevant to key questions 

1150. Kuriyama M, Ariga T, Ando S, et al. Urinary sialyloligosaccharides in adult type sialidosis: 

occurrence of two positional isomers. Jpn J Exp Med 1981 Apr; 51(2):129-32. Not relevant to 

key questions 

1151. Kuriyama M, Someya F, Yamada T, et al. Radioassay method of neuraminidase towards 

N-acetylneuraminosyl hexasaccharides. Clin Chim Acta 1982 Feb 26; 119(1-2):73-80. Not 

relevant to key questions 

1152. Kwinta P, Mitkowska Z, Kruczek P, et al. [Influence of the lactose free and lactose 

containing diet on prevalence of gram-negative sepsis and feeding intolerance in very low 

birth weight infants: double-blind randomized trial]. Przegla?d lekarski Vol 59; 2002: 63-6. 

Not English language 

1153. Kwok T, Woo J, Kwan M. Does low lactose milk powder improve the nutritional intake 

and nutritional status of frail older Chinese people living in nursing homes? Journal of 

Nutrition, Health & Aging 2001; 5(1):17-21. Ineligible number of subjects 

1154. Kwok TC, Chan TY, Woo J. Relationship of urinary sodium/potassium excretion and 

calcium intake to blood pressure and prevalence of hypertension among older Chinese 

vegetarians. Eur J Clin Nutr 2003 Feb; 57(2):299-304. not eligible outcomes 

1155. Labayen I, Forga L, Gonzalez A, et al. Relationship between lactose digestion, 

gastrointestinal transit time and symptoms in lactose malabsorbers after dairy consumption. 

Aliment Pharmacol Ther 2001 Apr; 15(4):543-9. Not relevant to key questions 

1156. Lacassie Y, Weinberg R, Monckeberg F. Poor predictability of lactose malabsorption from 

clinical symptoms for Chilean populations. Am J Clin Nutr 1978 May; 31(5):799-804. Not 

relevant to key questions 

1157. Ladas S, Papanikos J, Arapakis G. Lactose malabsorption in Greek adults: correlation of 

small bowel transit time with the severity of lactose intolerance. Gut 1982 Nov; 23(11):968­

73. No prevalence data 

1158. Ladas SD, Grammenos I, Tassios PS, et al. Low-dose lactose, fructose and sorbitol 

malabsorption and intolerance does not often coexist in normal adults [abstract]. Gut Vol 45; 

1999: A290. Not relevant to key questions 

1159. Ladas SD, Grammenos I, Tassios PS, et al. Coincidental malabsorption of lactose, fructose, 

and sorbitol ingested at low doses is not common in normal adults. Dig Dis Sci 2000 Dec; 

45(12):2357-62. Not relevant to key questions 

1160. Ladas SD, Haritos DN, Raptis SA. Honey may have a laxative effect on normal subjects 

because of incomplete fructose absorption. The American journal of clinical nutrition Vol 62; 

1995: 1212-5. Not relevant to key questions 

1161. Lader M. Comparison of amphetamine sulphate and caffeine citrate in man. 

Psychopharmacologia Vol 14; 1969: 83-94. Not lactose intolerance study 

1162. Lagarde D, Chappuis B, Billaud PF, et al. Evaluation of pharmacological aids on physical 

240
 
performance after a transmeridian flight. Medicine and science in sports and exercise Vol 33; 

2001: 628-34. Not lactose intolerance study 

1163. Lamberg-Allardt C, Karkkainen M, Seppanen R, et al. Low serum 25-hydroxyvitamin D 

concentrations and secondary hyperparathyroidism in middle-aged white strict vegetarians. 

Am J Clin Nutr 1993 Nov; 58(5):684-9. Not eligible target population 

1164. Lami F, Callegari C, Tatali M, et al. Efficacy of addition of exogenous lactase to milk in 

adult lactase deficiency. Am J Gastroenterol 1988 Oct; 83(10):1145-9. Not relevant to key 

questions 

1165. Langlais PJ, Mair RG, Whalen PJ, et al. Memory effect of DL-threo-3,4­

dihydroxyphenylserine (DOPS) in human Korsakoff's disease. Psychopharmacology Vol 95; 

1988: 250-4. Not lactose intolerance study 

1166. Lanng C, Mortensen D, Friis M, et al. Gastrointestinal dysfunction in a community sample 

of subjects with symptoms of irritable bowel syndrome. Digestion 2003; 67(1-2):14-9. No 

prevalence data 

1167. Lanzkowsky P, Karayalcin G, Miller F, et al. Disaccharidase values in iron-deficient 

infants. J Pediatr 1981 Oct; 99(4):605-8. Not relevant to key questions 

1168. Larsson CL, Johansson GK. Dietary intake and nutritional status of young vegans and 

omnivores in Sweden. Am J Clin Nutr 2002 Jul; 76(1):100-6. Not relevant to key questions 

1169. Larsson CL, Johansson GK. Young Swedish vegans have different sources of nutrients 

than young omnivores. J Am Diet Assoc 2005 Sep; 105(9):1438-41. Not relevant to key 

questions 

1170. Larsson SC, Orsini N, Wolk A. Milk, milk products and lactose intake and ovarian cancer 

risk: a meta-analysis of epidemiological studies. Int J Cancer 2006 Jan 15; 118(2):431-41. 

Not eligible outcomes 

1171. Launiala K. The mechanism of diarrhoea in congenital disaccharide malabsorption. Acta 

Paediatr Scand 1968 Sep; 57(5):425-32. Not relevant to key questions 

1172. Launiala K, Kuitunen P, Visakorpi JK. Disaccharidases and histology of duodenal mucosa 

in congenital lactose malabsorption. Acta Paediatr Scand 1966 May; 55(3):257-63. Not 

relevant to key questions 

1173. Launiala K, Sahi T, Isokoski M, et al. Lactose malabsorption in school-children. Acta 

Paediatr Scand 1971 May; 60(3):365-6. Not relevant to key questions 

1174. Lawlor-Smith C, Lawlor-Smith L. Lactose intolerance. Breastfeed Rev 1998 May; 6(1):29­

30. Review 

1175. Lawriw B, I, Barbee JG. Effect of diazepam upon verbal recall associated with simple 

picture recognition. Psychol Rep Vol 60; 1987: 1139-49. Not lactose intolerance study 

1176. Laws HF, 2nd. Effect of lactase on infantile colic.[comment]. Journal of Pediatrics 1991 

Jun; 118(6):993-4. No prevalence data 

1177. Leahy SC, Higgins DG, Fitzgerald GF, et al. Getting better with bifidobacteria. J Appl 

Microbiol 2005; 98(6):1303-15. Not relevant to key questions 

1178. Lebenthal E. Lactose malabsorption and milk consumption in infants and children. Am J 

Dis Child 1979 Jan; 133(1):21-3. Not relevant to key questions 

1179. Lebenthal E. Impact of digestion and absorption in the weaning period on infant feeding 

practices. Pediatrics 1985 Jan; 75(1 Pt 2):207-13. Not relevant to key questions 

1180. Lebenthal E, Antonowicz I, Shwachman H. Correlation of lactase activity, lactose 

tolerance and milk consumption in different age groups. Am J Clin Nutr 1975 Jun; 28(6):595­

600. Not relevant to key questions 

241
 
1181. Lebenthal E, Tsuboi K, Kretchmer N. Characterization of human intestinal lactase and 

hetero-beta-galactosidases of infants and adults. Gastroenterology 1974 Dec; 67(6):1107-13. 

Not relevant to key questions 

1182. Leblanc JC, Yoon H, Kombadjian A, et al. Nutritional intakes of vegetarian populations in 

France. Eur J Clin Nutr 2000 May; 54(5):443-9. Not relevant to key questions 

1183. Lechin F, Van Der Dijs B, Bentolila A, et al. Antidiarrheal effects of dihydroergotamine. J 

Clin Pharmacol 1977 May-Jun; 17(5-6):339-49. Not relevant to key questions 

1184. Ledochowski M, Murr C, Lass-Florl C, et al. Increased serum amylase and lipase in 

fructose malabsorbers. Clin Chim Acta 2001 Sep 25; 311(2):119-23. Not relevant to key 

questions 

1185. Ledochowski M, Sperner-Unterweger B, Fuchs D. Lactose malabsorption is associated 

with early signs of mental depression in females: a preliminary report. Dig Dis Sci 1998 Nov; 

43(11):2513-7. Not relevant to key questions 

1186. Lee CK. Disaccharidase deficiency and malabsorption of carbohydrates. Singapore Med J 

1984 Feb; 25(1):6-13. Not relevant to key questions 

1187. Lee CM, Hardy CM. Cocoa feeding and human lactose intolerance. Am J Clin Nutr 1989 

May; 49(5):840-4. Not relevant to key questions 

1188. Lee JH, Griffiths WJ, Zantout I, et al. Adequacy of endoscopic biopsy specimens for 

disaccharidase assays. Am J Dig Dis 1978 Dec; 23(12):1129-31. Not relevant to key 

questions 

242
 
1189. Lee MF, Krasinski SD. Human adult-onset lactase decline: an update. Nutr Rev 1998 Jan; 

56(1 Pt 1):1-8. Review 

1190. Lee WS, Boey CC. Chronic diarrhoea in infants and young children: causes, clinical 

features and outcome. Journal of Paediatrics & Child Health 1999 Jun; 35(3):260-3. Ineligible 

number of subjects 

1191. Leese PT, White KD, Frampton M, et al. Absence of increased fecal blood loss in adult 

volunteers after oral administration of conventional tablets and osmotic tablets of albuterol. 

Curr Ther Res Clin Exp Vol 48; 1990: 440-50. Not lactose intolerance study 

1192. Leffler DA, Dennis M, Hyett B, et al. Etiologies and predictors of diagnosis in 

nonresponsive celiac disease. Clin Gastroenterol Hepatol 2007 Apr; 5(4):445-50. Not relevant 

to key questions 

1193. Lehtimaki T, Hutri-Kahonen N, Kahonen M, et al. Adult-type hypolactasia is not a 

predisposing factor for the early functional and structural changes of atherosclerosis: the 

Cardiovascular Risk in Young Finns Study. Clinical science 2008 Nov; 115(9):265-71. Not 

relevant to key questions 

1194. Lehtniemi A, Lindholm R. [The effect of Lactobacillus products on lactose intolerance]. 

Duodecim; lääketieteellinen aikakauskirja Vol 111; 1995: 1027-31. Not English language 

1195. Lehtniemi A, Lindholm RK. Alleviation of symptoms of lactase-deficient patients during 

lactose challenge after administration of enteric coated lactobacilli- preparation.[abstract]. 

Scand J of Gastroenterol Vol 30; 1995: 114. Not relevant to key questions 

1196. Leichter J. Lactose tolerance in a Jewish population. Am J Dig Dis 1971 Dec; 16(12):1123­

6. Not relevant to key questions 

1197. Leichter J. Lactose tolerance in a Slavic population. Am J Dig Dis 1972 Jan; 17(1):73-6. 

Not relevant to key questions 

1198. Leichter J. Comparison of whole milk and skim milk with aqueous lactose solution in 

lactose tolerance testing. Am J Clin Nutr 1973 Apr; 26(4):393-6. Not relevant to key 

questions 

1199. Leichter J, Lee M. Lactose intolerance in Canadian West Coast Indians. Am J Dig Dis 

1971 Sep; 16(9):809-13. Not relevant to key questions 

1200. Leino J, Honkanen O, Kokkonen M, et al. Evaluation of hard gelatin capsules as a rectal 

dosage form for a freely water-soluble model drug, metoclopramide hydrochloride. S.T.P 

Pharma Sciences Vol 13; 2003: 141-5. Not lactose intolerance study 

1201. Leitzmann C. Vegetarian diets: what are the advantages? Forum Nutr 2005; (57):147-56. 

Review 

1202. Leitzmann P, Heine W, Wutzke KD, et al. Blood glucose, gastric emptying and oro-coecal 

transit time after a conventional breakfast vs. a Kollath breakfast. Zeitschrift fur 

Ernahrungswissenschaft Vol 37; 1998: 31-7. Not lactose intolerance study 

243
 
1203. Lembcke B, Fölsch UR, Caspary WF, et al. Influence of metronidazole on the breath 

hydrogen response and symptoms in acarbose-induced malabsorption of sucrose. Digestion 

Vol 25; 1982: 186-93. Not relevant to key questions 

1204. Lembcke B, Kraus B, Lankisch PG. Small intestinal function in chronic relapsing 

pancreatitis. Hepato-Gastroenterology 1985 Jun; 32(3):149-51. Ineligible number of subjects 

1205. Lembcke B, Schneider H, Lankisch PG. Is the assay of disaccharidase activity in small 

bowel mucosal biopsy relevant for clinical gastroenterologists? Klin Wochenschr 1989 Jun 1; 

67(11):568-75. Not relevant to key questions 

1206. Lember M, Tamm A, Piirsoo A, et al. Lactose malabsorption in Khants in western Siberia. 

Scandinavian Journal of Gastroenterology 1995 Mar; 30(3):225-7. Ineligible number of 

subjects 

1207. Lemire I, Cartier A, Malo JL, et al. Effect of sodium cromoglycate on histamine inhalation 

tests. The Journal of allergy and clinical immunology Vol 73; 1984: 234-9. Not lactose 

intolerance study 

1208. Lerch MM, Rieband HC, Feldberg W, et al. Concordance of indirect methods for the 

detection of lactose malabsorption in diabetic and nondiabetic subjects. Digestion 1991; 

48(2):81-8. No prevalence data 

1209. Lerebours E, N'Djitoyap C, Lavoine A, et al. [Absorption of lactose and intestinal lactosic 

activities after acute and chronic intake of yoghourt in subjects with lactasis deficiency]. 

Gastroenterologie Clinique et Biologique Vol 11; 1987: 24a. Not relevant to key questions 

1210. Leslie J, MacLean WC, Jr., Graham GG. Effect of an episode of severe malnutrition and 

age on lactose absorption by recovered infants and children. Am J Clin Nutr 1979 May; 

32(5):971-4. Not relevant to key questions 

1211. Leung SS, Lee RH, Sung RY, et al. Growth and nutrition of Chinese vegetarian children in 

Hong Kong. J Paediatr Child Health 2001 Jun; 37(3):247-53. not eligible outcomes 

1212. Leveille GA. United States food and nutrition issues--roles of dairy foods. J Dairy Sci 1979 

Oct; 62(10):1665-72. Not relevant to key questions 

1213. Levenson DI, Bockman RS. A review of calcium preparations. Nutr Rev 1994 Jul; 

52(7):221-32. Review 

1214. Levin B, Abraham JM, Burgess EA, et al. Congenital lactose malabsorption. Arch Dis 

Child 1970 Apr; 45(240):173-7. Not relevant to key questions 

1215. Levin N, Rattan J, Gilat T. Mineral intake and blood levels in vegetarians. Isr J Med Sci 

1986 Feb; 22(2):105-8. Not relevant to key questions 

1216. Levitt MD. Intestinal gas. Postgrad Med 1975 Jan; 57(1):77-81. Not relevant to key 

questions 

1217. Levitt MD, Donaldson RM. Use of respiratory hydrogen (H2) excretion to detect 

carbohydrate malabsorption. J Lab Clin Med 1970 Jun; 75(6):937-45. Not relevant to key 

questions 

244
 
1218. Levri KM, Ketvertis K, Deramo M, et al. Do probiotics reduce adult lactose intolerance? A 

systematic review. J Fam Pract 2005 Jul; 54(7):613-20. Review 

1219. Lewindon PJ, Robb TA, Moore DJ, et al. Bowel dysfunction in cystic fibrosis: importance 

of breath testing. Journal of Paediatrics & Child Health 1998 Feb; 34(1):79-82. No 

prevalence data 

1220. Lewinsky RH, Jensen TG, Moller J, et al. T-13910 DNA variant associated with lactase 

persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro. Hum Mol 

Genet 2005 Dec 15; 14(24):3945-53. Not relevant to key questions 

1221. Lewith G, Brown PK, Tyrell DA. Controlled study of the effects of a homoeopathic 

dilution of influenza vaccine on antibody titres in man. Complementary medical research Vol 

3; 1989: 22-4. Not lactose intolerance study 

1222. Liebman WM. Recurrent abdominal pain in children: lactose and sucrose intolerance, a 

prospective study. Pediatrics 1979 Jul; 64(1):43-5. Ineligible number of subjects 

1223. Liebman WM. Infantile colic. Association with lactose and milk intolerance. JAMA 1981 

Feb 20; 245(7):732-3. Not relevant to key questions 

1224. Lifschitz CH, Abrams SA. Addition of rice cereal to formula does not impair mineral 

bioavailability. Journal of pediatric gastroenterology and nutrition Vol 26; 1998: 175-8. Not 

eligible target population 

1225. Lifschitz CH, Bautista A, Gopalakrishna GS, et al. Absorption and tolerance of lactose in 

infants recovering from severe diarrhea. J Pediatr Gastroenterol Nutr 1985 Dec; 4(6):942-8. 

Not relevant to key questions 

1226. Lifschitz CH, Smith EO, Garza C. Delayed complete functional lactase sufficiency in 

breast-fed infants. J Pediatr Gastroenterol Nutr 1983; 2(3):478-82. Not relevant to key 

questions 

1227. Lifshitz F. Carbohydrate problems in paediatric gastroenterology. Clin Gastroenterol 1977 

May; 6(2):415-29. Not relevant to key questions 

1228. Lifshitz F, Coello-Ramirez P, Contreras-Gutierrez ML. The response of infants to 

carbohydrate oral loads after recovery from diarrhea. J Pediatr 1971 Oct; 79(4):612-7. Not 

relevant to key questions 

1229. Lifshitz F, Coello-Ramirez P, Gutierrez-Topete G, et al. Carbohydrate intolerance in 

infants with diarrhea. J Pediatr 1971 Nov; 79(5):760-7. Not relevant to key questions 

1230. Lifshitz F, Fagundes-Neto U, Ferreira VC, et al. The response to dietary treatment of 

patients with chronic post-infectious diarrhea and lactose intolerance. Journal of the 

American College of Nutrition 1990 Jun; 9(3):231-40. Ineligible number of subjects 

1231. Lim E, Ali ZA, Attaran R, et al. Evaluating routine diuretics after coronary surgery: a 

prospective randomized controlled trial. The Annals of thoracic surgery Vol 73; 2002: 153-5. 

Not lactose intolerance study 

245
 
1232. Lin CL, Fang TC, Gueng MK. Vascular dilatory functions of ovo-lactovegetarians 

compared with omnivores. Atherosclerosis 2001 Sep; 158(1):247-51. Not relevant to key 

questions 

1233. Lin LH, See M, Wang NK. Breath hydrogen test for assessment of lactose malabsorption 

following rotavirus gastroenteritis. J Formos Med Assoc 1990 Dec; 89(12):1072-6. Not 

relevant to key questions 

1234. Lin MY, Savaiano D, Harlander S. Influence of nonfermented dairy products containing 

bacterial starter cultures on lactose maldigestion in humans. J Dairy Sci 1991 Jan; 74(1):87­

95. Not relevant to key questions 

1235. Lingström P, Birkhed D. Effect of buccal administration of a lactose-containing 

nitroglycerin tablet (Suscard) on plaque pH. Scandinavian journal of dental research Vol 102; 

1994: 324-8. Not lactose intolerance study 

1236. Liong MT. Probiotics: a critical review of their potential role as antihypertensives, immune 

modulators, hypocholesterolemics, and perimenopausal treatments. Nutr Rev 2007 Jul; 

65(7):316-28. Not relevant to key questions 

1237. Lisker R, Aguilar L, Lares I, et al. Double blind study of milk lactose intolerance in a 

group of rural and urban children. Am J Clin Nutr 1980 May; 33(5):1049-53. Not relevant to 

key questions 

1238. Lisker R, Aguilar L, Zavala C. Intestinal lactase deficiency and milk drinking capacity in 

the adult. Am J Clin Nutr 1978 Sep; 31(9):1499-503. Not relevant to key questions 

1239. Lisker R, Amador A, Meza-Calix A. Intestinal lactase deficiency and milk drinking habits. 

Rev Invest Clin 1976 Apr-Jun; 28(02):109-12. Not relevant to key questions 

1240. Lisker R, Cervantes G, Pérez-Briceño R, et al. Lack of relationship between lactose 

absorption and senile cataracts. Annals of ophthalmology Vol 20; 1988: 436-8. Not relevant 

to key questions 

1241. Lisker R, Gonzalez B, Daltabuit M. Recessive inheritance of the adult type of intestinal 

lactase deficiency. Am J Hum Genet 1975 Sep; 27(5):662-4. Not relevant to key questions 

1242. Lisker R, Lopez HG, Mora MA, et al. Correlation in the diagnosis of intestinal lactase 

deficiency between the radiological method and the lactose tolerance test. Rev Invest Clin 

1975 Jan-Mar; 27(1):1-5. Not relevant to key questions 

1243. Lisker R, Lopez-Habib G, Daltabuit M, et al. Lactase deficiency in a rural area of Mexico. 

Am J Clin Nutr 1974 Jul; 27(7):756-9. Not relevant to key questions 

1244. Lisker R, Moreno-Terrazas O. [Double blind study of milk lactose intolerance in a group of 

rural children]. Revista de Investigacion Clinica Vol 32; 1980: 363-8. Not relevant to key 

questions 

1245. Lisker R, Solomons NW, Perez Briceno R, et al. Lactase and placebo in the management of 

the irritable bowel syndrome: a double-blind, cross-over study. American Journal of 

Gastroenterology 1989 Jul; 84(7):756-62. Ineligible number of subjects 

246
 
1246. Littman A. Isolated lactase deficit in the adult: a present view. JAMA 1966 Mar 14; 

195(11):954-5. Not relevant to key questions 

1247. Littman A, Cady AB, Rhodes J. Lactase and other disaccharidase deficiencies in a hospital 

population. Isr J Med Sci 1968 Jan-Feb; 4(1):110-6. Not relevant to key questions 

1248. Liu HY, Tsao MU, Moore B, et al. Bovine milk protein-induced intestinal malabsorption of 

lactose and fat in infants. Gastroenterology 1968 Jan; 54(1):27-34. Not relevant to key 

questions 

1249. Lloyd B, Halter RJ, Kuchan MJ, et al. Formula tolerance in postbreastfed and exclusively 

formula-fed infants. Pediatrics Vol 103; 1999: E7. Not relevant to key questions 

1250. Lloyd T, Schaeffer JM, Walker MA, et al. Urinary hormonal concentrations and spinal 

bone densities of premenopausal vegetarian and nonvegetarian women. Am J Clin Nutr 1991 

Dec; 54(6):1005-10. not eligible exposure 

1251. Lloyd-Still J. Gastroenteritis with secondary disaccharide intolerance. An outbreak in a 

premature unit. Acta Paediatr Scand 1969 Mar; 58(2):147-50. Not relevant to key questions 

1252. Lobley RW, Burrows PC, Warwick R, et al. Simultaneous assessment of intestinal 

permeability and lactose tolerance with orally administered raffinose, lactose and Larabinose. Clin Sci (Lond) 1990 Aug; 79(2):175-83. Not relevant to key questions 

1253. Lojda Z. Suitability of the azocoupling reaction with 1-naphthyl-beta-D-glucoside for the 

histochemical demonstration of lactase (lactase-beta-glucosidase complex) in human 

enterobiopsies. Histochemistry 1975 Jun 9; 43(4):349-53. Not relevant to key questions 

1254. London DR, Cuatrecasas P, Birge SJ, Jr., et al. Metabolism of lactose by intestinal mucosa 

from normal and lactase-deficient subjects. Br Med J 1967 Mar 4; 1(5539):524-6. Not 

relevant to key questions 

1255. Longmore J, Szabadi E, Bradshaw CM. Comparison of the effects of binodaline and 

amitriptyline on peripheral autonomic functions in healthy volunteers. British journal of 

clinical pharmacology Vol 19; 1985: 295-300. Not lactose intolerance study 

1256. Lopez-Gonzalez MA, Moliner-Peiro F, Alfaro-Garcia J, et al. Sulpiride plus hydroxyzine 

decrease tinnitus perception. Auris, nasus, larynx Vol 34; 2007: 23-7. Not lactose intolerance 

study 

1257. Lopez-Gonzalez MA, Santiago AM, Esteban-Ortega F. Sulpiride and melatonin decrease 

tinnitus perception modulating the auditolimbic dopaminergic pathway. The Journal of 

otolaryngology Vol 36; 2007: 213-9. Not lactose intolerance study 

1258. Lorenz-Meyer H, Blum AL, Haemmerli HP, et al. A second enzyme defect in acquired 

lactase deficiency: lack of small-intestinal phlorizin-hydrolase. Eur J Clin Invest 1972 Aug; 

2(5):326-31. Not relevant to key questions 

1259. Loriaux SM, Deijen JB, Orlebeke JF, et al. The effects of nicotinic acid and xanthinol 

nicotinate on human memory in different categories of age. A double blind study. 

Psychopharmacology Vol 87; 1985: 390-5. Not lactose intolerance study 

1260. Lorist MM, Snel J. Caffeine effects on perceptual and motor processes. 

Electroencephalography and clinical neurophysiology Vol 102; 1997: 401-13. Not lactose 

intolerance study 

1261. Lorist MM, Snel J, Kok A. Influence of caffeine on information processing stages in well 

rested and fatigued subjects. Psychopharmacology Vol 113; 1994: 411-21. Not lactose 

intolerance study 

1262. Lorist MM, Snel J, Kok A, et al. Acute effects of caffeine on selective attention and visual 

search processes. Psychophysiology Vol 33; 1996: 354-61. Not lactose intolerance study 

247
 
1263. Lovelace HY, Barr SI. Diagnosis, symptoms, and calcium intakes of individuals with selfreported lactose intolerance. J Am Coll Nutr 2005 Feb; 24(1):51-7. Not relevant to key 

questions 

1264. Low-Beer TS. Chronic diarrhoea: diagnosis, mechanisms and treatment. Ir J Med Sci 1973 

May; 142(3 Suppl):67-73. Not relevant to key questions 

1265. Lowe JC, Garrison RL, Reichman AJ, et al. Effectiveness and safety of T3 

(Triiodothyronine) therapy for euthyroid fibromyalgia: A double-blind placebo-controlled 

response-driven crossover study. Clinical Bulletin of Myofascial Therapy Vol 2; 1997: 31-57. 

Not lactose intolerance study 

1266. Lowe JC, Reichman AJ, Yellin J. The process of change during T3 treatment for euthyroid 

fibromyalgia: A double-blind placebo-controlled crossover study. Clinical Bulletin of 

Myofascial Therapy Vol 2; 1997: 91-124. Not lactose intolerance study 

1267. Lozano JM, Cespedes JA. Lactose vs. lactose free regimen in children with acute 

diarrhoea: a randomized controlled trial. Archivos Latinoamericanos de Nutricion 1994 Mar; 

44(1):6-11. Not relevant to key questions 

1268. Lubos MC, Gerrard JW, Buchan DJ. Disaccharidase activities in milk-sensitive and celiac 

patients. J Pediatr 1967 Mar; 70(3):325-31. Not relevant to key questions 

1269. Lucassen PL, Assendelft WJ, Gubbels JW, et al. Effectiveness of treatments for infantile 

colic: systematic review. Bmj Vol 316; 1998. Not relevant to key questions 

1270. Ludan AC. Current management of acute diarrheas in the Philippines. J Singapore Paediatr 

Soc 1987; 29 Suppl 1:153-8. Not relevant to key questions 

1271. Ludvigsson JF. Effect of gastroenteritis during pregnancy on neonatal outcome. European 

Journal of Clinical Microbiology & Infectious Diseases 2001 Dec; 20(12):843-9. No 

prevalence data 

1272. Luke B. Lactose intolerance during pregnancy: significance and solutions. MCN Am J 

Matern Child Nurs 1977 Mar-Apr; 2(2):93-6. Not relevant to key questions 

248
 
1273. Lund-Hansen T, Hoyer PE, Andersen H. A quantitative cytochemical assay of betagalactosidase in single cultured human skin fibroblasts. Histochemistry 1984; 81(4):321-30. 

Not relevant to key questions 

1274. Lundquist G, Hedenstedt S. Jejunal transposition in stomach surgery: indications and 

results. Acta Chirurgica Scandinavica - Supplementum 1975; 457:1-83. No prevalence data 

1275. Luyken R. Studies on milk intolerance. A review of literature for Latin America. Paediatr 

Indones 1971 Nov-Dec; 11(6):233-50. Not relevant to key questions 

1276. Luyken R. Medical research in Kenya. III. Nutrition. Trop Geogr Med 1977 Jun; 

29(2):S25-30. Not relevant to key questions 

1277. Luyken R, Luyken-Koning FW. Lactose intolerance in Kenya. Proc Nutr Soc 1972 May; 

31(1):6A. Not relevant to key questions 

1278. Luyken R, Luyken-Koning FW, Immikhuizen MJ. Lactose intolerance in Surinam. Trop 

Geogr Med 1971 Mar; 23(1):54-8. Not relevant to key questions 

1279. Lyytikainen A, Lamberg-Allardt C, Kannas L, et al. Food consumption and nutrient intakes 

with a special focus on milk product consumption in early pubertal girls in Central Finland. 

Public health nutrition 2005 May; 8(3):284-9. Not relevant to key questions 

1280. Macdonald MJ, Horowitz R, Duncan TG. Use of the lactose-ethanol tolerance test in 

diabetes. Am J Med Sci 1975 Mar-Apr; 269(2):193-9. Not relevant to key questions 

1281. Machiels F, De Maeseneer M, Van Snick A, et al. A rare cause of rickets in a young child. 

J Belge Radiol 1995 Oct; 78(5):276-7. Case Reports 

1282. MacLean WC, Jr., Graham GC. Evaluation of a low-lactose nutritional supplement in 

malnourished children. J Am Diet Assoc 1975 Dec; 67(6):558-64. Not relevant to key 

questions 

1283. MacPhee IT, Sircus W, Farmer ED, et al. Use of steroids in treatment of aphthous 

ulceration. British medical journal Vol 2; 1968: 147-9. Not lactose intolerance study 

1284. Madsen PO, Pedersen JF, Knuth OE. Endocrine treatment of cancer of the prostate. 

Wisconsin medical journal Vol 69; 1970: 177-81. Not lactose intolerance study 

1285. Madzarovova N. Activity of intestinal disaccharidases. Rev Czech Med 1969; 15(4):212­

34. Review 

1286. Maesen FP, Smeets JJ, Sledsens TJ, et al. Tiotropium bromide, a new long-acting 

antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive 

pulmonary disease (COPD). Dutch Study Group. The European respiratory journal : official 

journal of the European Society for Clinical Respiratory Physiology Vol 8; 1995: 1506-13. 

Not lactose intolerance study 

1287. Maffei HV, Daher SR, Moreira FL. Carbohydrate malabsorption in infants with diarrhea: 

diagnostic and evolutive aspects. Arq Gastroenterol 1984 Jul-Sep; 21(3):136-42. Not relevant 

to key questions 

1288. Maffei HV, Metz G, Bampoe V, et al. Lactose intolerance, detected by the hydrogen breath 

test, in infants and children with chronic diarrhoea. Arch Dis Child 1977 Oct; 52(10):766-71. 

Not relevant to key questions 

1289. Mahé S, Marteau P, Huneau JF, et al. Intestinal nitrogen and electrolyte movements 

following fermented milk ingestion in man. The British journal of nutrition Vol 71; 1994: 

169-80. Not eligible target population 

1290. Maki KC, Davidson MH, Malik KC, et al. Cholesterol lowering with high-viscosity 

hydroxypropylmethylcellulose. The American journal of cardiology Vol 84; 1999: 1198-203. 

Not lactose intolerance study 

249
 
1291. Maldonado J, Gil A, Narbona E, et al. Special formulas in infant nutrition: a review. Early 

Hum Dev 1998 Dec; 53 Suppl:S23-32. Not relevant to key questions 

1292. Malik GM, Khuroo MS, Ahmed SZ. Incidence of lactose intolerance in Kashmir. J Assoc 

Physicians India 1977 Sep; 25(9):623-5. Not relevant to key questions 

1293. Mallinson CN. Effect of pancreatic insufficiency and intestinal lactase deficiency on the 

gastric emptying of starch and lactose. Gut 1968 Dec; 9(6):737. Not relevant to key questions 

1294. Maluenda C, Phillips AD, Briddon A, et al. Quantitative analysis of small intestinal 

mucosa in cow's milk-sensitive enteropathy. J Pediatr Gastroenterol Nutr 1984 Jun; 3(3):349­

56. Not relevant to key questions 

1295. Mandell HN. Lactose intolerance--a case of bovine revenge? Med Times 1978 Apr; 

106(4):71-7. Not relevant to key questions 

1296. Mann MD, Hill ID, Bowie MD. Absorption and retention in acute diarrhoea. European 

journal of clinical nutrition Vol 44; 1990: 629-35. Not relevant to key questions 

1297. Marangella M, Bianco O, Martini C, et al. Effect of animal and vegetable protein intake on 

oxalate excretion in idiopathic calcium stone disease. Br J Urol 1989 Apr; 63(4):348-51. Not 

eligible target population 

1298. Mardirossian G, Cooper SA. Comparison of the analgesic efficacy of flurbiprofen and 

aspirin for postsurgical dental pain. Journal of oral and maxillofacial surgery : official journal 

of the American Association of Oral and Maxillofacial Surgeons Vol 43; 1985: 106-9. Not 

lactose intolerance study 

1299. Margetts BM, Beilin LJ, Vandongen R, et al. Vegetarian diet in mild hypertension: a 

randomised controlled trial. Br Med J (Clin Res Ed) 1986 Dec 6; 293(6560):1468-71. Not 

eligible outcomes 

1300. Marien P, Molla AM, Eggermont E. Coeliac disease in childhood. Problems in differential 

diagnosis. Acta Gastroenterol Belg 1986 Jul-Aug; 49(4):387-92. Not relevant to key questions 

1301. Marino DD, King JC. Nutritional concerns during adolescence. Pediatr Clin North Am 

1980 Feb; 27(1):125-39. Review 

1302. Mark LC. Letter: Avoiding the pain of veinpuncture. N Engl J Med 1976 Mar 11; 

294(11):614. Not relevant to key questions 

1303. Marrs DC. Milk drinking by the elderly of three races. J Am Diet Assoc 1978 May; 

72(5):495-8. Not relevant to key questions 

1304. Marsh AA, Finger EC, Buzas B, et al. Impaired recognition of fear facial expressions in 5­

HTTLPR S-polymorphism carriers following tryptophan depletion. Psychopharmacology Vol 

189; 2006: 387-94. Not lactose intolerance study 

1305. Marsh AG, Ford DL, Christensen DK. Metabolic response of adolescent girls to a lactoovo-vegetarian diet. J Am Diet Assoc 1967 Nov; 51(5):441-6. Not eligible outcomes 

1306. Marsh AG, Sanchez TV, Midkelsen O, et al. Cortical bone density of adult lacto-ovovegetarian and omnivorous women. J Am Diet Assoc 1980 Feb; 76(2):148-51. Not target 

population 

1307. Marteau P, Boutron-Ruault MC. Nutritional advantages of probiotics and prebiotics. Br J 

Nutr 2002 May; 87 Suppl 2:S153-7. Not relevant to key questions 

1308. Marteau P, Flourie B, Pochart P, et al. Effect of the microbial lactase (EC 3.2.1.23) activity 

in yoghurt on the intestinal absorption of lactose: An in vivo study in lactase-deficient 

humans. British Journal of Nutrition Vol 64; 1990: 71-9. Not relevant to key questions 

1309. Marteau P, Messing B, Arrigoni E, et al. Do patients with short-bowel syndrome need a 

lactose-free diet? Nutrition 1997 Jan; 13(1):13-6. Not relevant to key questions 

250
 
1310. Marteau P, Seksik P, Jian R. Probiotics and intestinal health effects: a clinical perspective. 

Br J Nutr 2002 Sep; 88 Suppl 1:S51-7. Not relevant to key questions 

1311. Marteau PR. Probiotics in clinical conditions. Clin Rev Allergy Immunol 2002 Jun; 

22(3):255-73. Not relevant to key questions 

1312. Martini MC, Bollweg GL, Levitt MD, et al. Lactose digestion by yogurt beta-galactosidase: 

influence of pH and microbial cell integrity. Am J Clin Nutr 1987 Feb; 45(2):432-6. Not 

relevant to key questions 

1313. Martini MC, Kukielka D, Savaiano DA. Lactose digestion from yogurt: influence of a meal 

and additional lactose. Am J Clin Nutr 1991 May; 53(5):1253-8. Not relevant to key 

questions 

1314. Martini MC, Lerebours EC, Lin WJ, et al. Strains and species of lactic acid bacteria in 

fermented milks (yogurts): effect on in vivo lactose digestion. Am J Clin Nutr Vol 54; 1991: 

1041-6. Not relevant to key questions 

1315. Martini MC, Savaiano DA. Reduced intolerance symptoms from lactose consumed during 

a meal. Am J Clin Nutr 1988 Jan; 47(1):57-60. Not relevant to key questions 

1316. Marvel ME, Bertino JS. Comparative effects of an elemental and a complex enteral feeding 

formulation on the absorption of phenytoin suspension. JPEN. Journal of parenteral and 

enteral nutrition Vol 15; 1991: 316-8. Not relevant to key questions 

1317. Mascart-Lemone F, Van Pachterbeek T, Duchateau J, et al. Serum IgA anti-gliadin 

antibodies (monomeric versus dimeric) in childhood coeliac disease. Acta Gastroenterol Belg 

1986 Jul-Aug; 49(4):415-22. Not relevant to key questions 

1318. Mascolo R, Saltzman JR. Lactose intolerance and irritable bowel syndrome. Nutrition 

Reviews 1998 Oct; 56(10):306-8. Not original research 

1319. Massler M. Geriatric nutrition. I: Osteoporosis. Calcif Tissue Int 1979 Sep; 42(3):252-4. 

Comment 

1320. Mathur GP, Gandhi KK, Mathur S, et al. Lactobacillus therapy. Indian Pediatr 1991 Feb; 

28(2):199-204. Not relevant to key questions 

1321. Matsumura T, Kuroume T, Amada K. Close relationship between lactose intolerance and 

allergy to milk protein. J Asthma Res 1971 Sep; 9(1):13-29. Not relevant to key questions 

1322. Mattar R, Monteiro Mdo S, Villares CA, et al. Single nucleotide polymorphism C/T(­

13910), located upstream of the lactase gene, associated with adult-type hypolactasia: 

validation for clinical practice. Clin Biochem 2008 May; 41(7-8):628-30. Not relevant to key 

questions 

1323. Matthews SB, Waud JP, Roberts AG, et al. Systemic lactose intolerance: a new perspective 

on an old problem. Postgrad Med J 2005 Mar; 81(953):167-73. Not relevant to key questions 

1324. Mattila MJ, Palva E, Seppälä T, et al. Actions and interactions with alcohol of drugs on 

psychomotor skills: comparison of diazepam and gamma-hydroxybutyric acid. Archives 

internationales de pharmacodynamie et de thérapie Vol 234; 1978: 236-46. Not lactose 

intolerance study 

1325. Maulén-Radován I, Brown KH, Acosta MA, et al. Comparison of a rice-based, mixed diet 

versus a lactose-free, soy-protein isolate formula for young children with acute diarrhea. The 

Journal of pediatrics Vol 125; 1994: 699-706. Not relevant to key questions 

1326. Mavromichalis J, Brueton MJ, McNeish AS, et al. Evaluation of the intraepithelial 

lymphocyte count in the jejunum in childhood enteropathies. Gut 1976 Aug; 17(8):600-3. Not 

relevant to key questions 

1327. Max MB, Schafer SC, Culnane M, et al. Amitriptyline, but not lorazepam, relieves 

251
 
postherpetic neuralgia. Neurology Vol 38; 1988: 1427-32. Not lactose intolerance study 

1328. Maxwell GM, Elliott RB. Nutritional state of Australian aboriginal children. Am J Clin 

Nutr 1969 Jun; 22(6):716-24. Not relevant to key questions 

1329. Maxwell JD, McKiddie MT, Ferguson A, et al. Plasma insulin response to oral carbohydrate 

in patients with glucose and lactose malabsorption. Gut 1970 Nov; 11(11):962-5. Not relevant 

to key questions 

1330. May DC, Jarboe CH, Ellenburg DT, et al. The effects of erythromycin on theophylline 

elimination in normal males. Journal of clinical pharmacology Vol 22; 1982: 125-30. Not 

lactose intolerance study 

1331. Mayer PJ, Beeken WL. The role of urinary indican as a predictor of bacterial colonization 

in the human jejunum. Am J Dig Dis 1975 Nov; 20(11):1003-9. Not relevant to key questions 

1332. Mayne AJ, Brown GA, Sule D, et al. Postnatal development of disaccharidase activities in 

jejunal fluid of preterm neonates. Gut 1986 Nov; 27(11):1357-61. Ineligible number of 

subjects 

1333. McBean LD, Miller GD. Allaying fears and fallacies about lactose intolerance. Journal of 

the American Dietetic Association 1998 Jun; 98(6):671-6. Not original research 

1334. McCarthy OR. The prevention of exercise induced asthma. British journal of diseases of 

the chest Vol 66; 1972: 133-40. Not lactose intolerance study 

1335. McCarty MF. A moderately low phosphate intake may provide health benefits analogous to 

those conferred by UV light - a further advantage of vegan diets. Med Hypotheses 2003 NovDec; 61(5-6):543-60. Not eligible exposure 

1336. McCarty MF. Sub-optimal taurine status may promote platelet hyperaggregability in 

vegetarians. Med Hypotheses 2004; 63(3):426-33. Not relevant to key questions 

1337. McClean P, Lynch AB, Dodge JA. Comparison of three regimens in the management of 

acute gastroenteritis in infants. Alimentary pharmacology & therapeutics Vol 4; 1990: 457­

64. Not relevant to key questions 

1338. McClure RJ, Newell SJ. Randomized controlled study of digestive enzyme activity 

following trophic feeding. Acta Paediatrica 2002; 91(3):292-6. No prevalence data 

1339. McConnell EA. Myths & facts ... about lactose intolerance. Nursing 1999 Mar; 29(3):71. 

Not relevant to key questions 

1340. McCracken RD. Adult lactose tolerance. JAMA 1970 Sep 28; 213(13):2257-60. Not 

relevant to key questions 

1341. McCracken RD. Origins and implications of the distribution of adult lactase deficiency in 

human populations. J Trop Pediatr Environ Child Health 1971 Mar; 17(1):7-10. Not relevant 

to key questions 

1342. McDonagh TJ. Lactose intolerance: a newly recognized cause of gastrointestinal symptoms 

seen in the practice of occupational medicine. J Occup Med 1969 Feb; 11(2):57-64. Not 

relevant to key questions 

1343. McDonald GS, Willoughby E, Weir DG. The incidence of lactase deficiency following 

partial gastrectomy. Ir J Med Sci 1969 Oct; 8(10):481-8. Not relevant to key questions 

1344. McDonald GS, Willoughby E, Weir DG, et al. Milk intolerance in clinical practice. J Ir 

Med Assoc 1966 Dec; 59(354):179-83. Not relevant to key questions 

1345. McDonough FE, Hitchins AD, Wong NP, et al. Modification of sweet acidophilus milk to 

improve utilization by lactose-intolerant persons. Am J Clin Nutr 1987 Mar; 45(3):570-4. Not 

relevant to key questions 

1346. McGee T. For parents. Planning a vegetarian diet. Diabetes Self Manag 2002 Jul-Aug; 

252
 
19(4):53-4, 6, 9. Parent education 

253
 
1347. McGill CR, Fulgoni VL, 3rd, DiRienzo D, et al. Contribution of dairy products to dietary 

potassium intake in the United States population. Journal of the American College of 

Nutrition 2008 Feb; 27(1):44-50. Not relevant to key questions 

1348. McGill DB, Newcomer AD. Comparison of venous and capillary blood samples in lactose 

tolerance testing. Gastroenterology 1967 Sep; 53(3):371-4. Not relevant to key questions 

1349. McGrath PJ, Feldman W. Clinical approach to recurrent abdominal pain in children. J Dev 

Behav Pediatr 1986 Feb; 7(1):56-63. Not relevant to key questions 

1350. McGrath PJ, Goodman JT, Firestone P, et al. Recurrent abdominal pain: a psychogenic 

disorder? Arch Dis Child 1983 Nov; 58(11):888-90. Not relevant to key questions 

1351. McIntyre BA, Philp RB, Inwood MJ. Effect of ibuprofen on platelet function in normal 

subjects and hemophiliac patients. Clinical pharmacology and therapeutics Vol 24; 1978: 

616-21. Not lactose intolerance study 

1352. McMahan S, South C, Crespin S. Lactose intolerance. Strategies for symptom 

management. Adv Nurse Pract 2002 Jun; 10(6):71-4. Not relevant to key questions 

1353. McMahon FG, Vargas R, Leese P, et al. Controlled-release dosage forms and 

gastrointestinal blood loss: Four clinical studies. Int. J. Pharm. Vol 91; 1993: 75-84. Not 

lactose intolerance study 

1354. McMichael HB. The irrelevancies of disaccharidase assays. Acta Hepatogastroenterol 

(Stuttg) 1972 Jul-Aug; 19(4):281-90. Not relevant to key questions 

1355. McMichael HB, Webb J, Dawson AM. Jejunal disaccharidases and some observations on 

the cause of lactase deficiency. Br Med J 1966 Oct 29; 2(5521):1037-41. Not relevant to key 

questions 

1356. McMichael HB, Webb J, Dawson AM. The absorption of maltose and lactose in man. Clin 

Sci 1967 Aug; 33(1):135-45. Not relevant to key questions 

1357. McNair A, Olsen J. Disaccharidase activity in chronic renal failure. Acta Med Scand 1974 

Jan-Feb; 195(1-2):93-6. Not relevant to key questions 

1358. McNeill AD, Owen LA, Belcher M, et al. Abstinence from smoking and expired-air carbon 

monoxide levels: lactose intolerance as a possible source of error. Am J Public Health 1990 

Sep; 80(9):1114-5. Not relevant to key questions 

1359. McNeish AS, Sweet EM. Lactose intolerance in childhood coeliac disease. Assessment of 

its incidence and importance. Arch Dis Child 1968 Aug; 43(230):433-7. Not relevant to key 

questions 

1360. Meador KJ, Nichols ME, Franke P, et al. Evidence for a central cholinergic effect of highdose thiamine. Annals of neurology Vol 34; 1993: 724-6. Not lactose intolerance study 

1361. Medow MS, Glassman MS, Schwarz SM, et al. Respiratory methane excretion in children 

with lactose intolerance. Dig Dis Sci 1993 Feb; 38(2):328-32. Not relevant to key questions 

254
 
1362. Medow MS, Thek KD, Newman LJ, et al. Beta-galactosidase tablets in the treatment of 

lactose intolerance in pediatrics. Am J Dis Child 1990 Nov; 144(11):1261-4. Not relevant to 

key questions 

1363. Meeusen R, Piacentini MF, Van DES, et al. Exercise performance is not influenced by a 5­

HT reuptake inhibitor. International journal of sports medicine Vol 22; 2001: 329-36. Not 

lactose intolerance study 

1364. Mehuys E, Remon JP, Korst A, et al. Human bioavailability of propranolol from a matrixin-cylinder system with a HPMC-Gelucire core. Journal of controlled release : official journal 

of the Controlled Release Society Vol 107; 2005: 523-36. Not lactose intolerance study 

1365. Meloni G, Ogana A, Mannazzu MC, et al. High prevalence of lactose absorbers in patients 

with presenile cataract from northern Sardinia. British Journal of Ophthalmology 1995 Jul; 

79(7):709. No prevalence data 

1366. Meloni GF, Colombo C, La Vecchia C, et al. High prevalence of lactose absorbers in 

Northern Sardinian patients with type 1 and type 2 diabetes mellitus. American Journal of 

Clinical Nutrition 2001 Mar; 73(3):582-5. No prevalence data 

1367. Meloni GF, Colombo C, La Vecchia C, et al. Lactose absorption in patients with ovarian 

cancer. Am J Epidemiol 1999 Jul 15; 150(2):183-6. Not eligible target population 

1368. Meloni T, Colombo C, Ogana A, et al. Lactose absorption in patients with glucose 6­

phosphate dehydrogenase deficiency with and without favism. Gut 1996 Aug; 39(2):210-3. 

Ineligible number of subjects 

1369. Meloni T, Colombo C, Ruggiu G, et al. Primary lactase deficiency and past malarial 

endemicity in Sardinia.[see comment]. Italian Journal of Gastroenterology & Hepatology 

1998 Oct; 30(5):490-3. Ineligible number of subjects 

1370. Mendis BL, Wijesiriwardena BC, Sheriff MH, et al. Irritable bowel syndrome. Ceylon 

Medical Journal 1982 Dec; 27(4):171-81. No prevalence data 

1371. Menon MPS, Sharma VC, Shivpuri DN. Effect of cromolyn sodium (DSCG) on allergen 

induced asthma. Indjchest Disallied Sci Vol 18; 1976: 83-9. Not lactose intolerance study 

1372. Meretoja J. Inherited syndrome with corneal snowflake dystrophy, oculocutaneous 

pigmentary disturbances, pseudoexfoliation and malabsorption. Statistical data of some 

symptoms. Ophthalmic Research 1987; 19(5):245-54. No prevalence data 

1373. Mermelstein NH. Food allergies and other food sensitivities. ASDC J Dent Child 1986 JulAug; 53(4):296-9. Not relevant to key questions 

1374. Meshitsuka K. Intranasal administration of antihistamine for nasal allergy. Otolaryngology 

(Tokyo) Vol 54; 1982: 213-7. Not lactose intolerance study 

1375. Messina V, Mangels AR. Considerations in planning vegan diets: children. J Am Diet 

Assoc 2001 Jun; 101(6):661-9. Review 

255
 
1376. Messina V, Melina V, Mangels AR. A new food guide for North American vegetarians. 

Can J Diet Pract Res 2003 Summer; 64(2):82-6. Not relevant to key questions 

1377. Metalidis C, Knockaert DC, Bobbaers H, et al. Involuntary weight loss. Does a negative 

baseline evaluation provide adequate reassurance? European Journal of Internal Medicine 

2008 Jul; 19(5):345-9. No prevalence data 

1378. Metneki J, Czeizel A, Flatz SD, et al. A study of lactose absorption capacity in twins. Hum 

Genet 1984; 67(3):296-300. Not relevant to key questions 

1379. Metz G, Blendis LM, Jenkins DJ. Letter: H2 breath test for lactase deficiency. N Engl J 

Med 1976 Mar 25; 294(13):730. Not relevant to key questions 

1380. Metz G, Jenkins DJ, Peters TJ, et al. Breath hydrogen as a diagnostic method for 

hypolactasia. Lancet 1975 May 24; 1(7917):1155-7. Not relevant to key questions 

1381. Metz GL, Blendis LM, Jenkins JA. Proceedings: Alveolar H2 in the diagnosis of 

carbohydrate malabsorption. Gut 1975 May; 16(5):398. Not relevant to key questions 

1382. Miadonna A, Cottini M, Candiani C, et al. Modulation of allergen-induced nasal symptoms 

and mediator release by treatment with N-acetyl-aspartyl-glutamate (ZY15106). European 

journal of clinical pharmacology Vol 46; 1994: 127-31. Not lactose intolerance study 

1383. Miadonna A, Milazzo N, Salmaso C, et al. N-acetyl-aspartyl-glutamic acid inhibits cellular 

recruitment and mediator release during the late allergen-induced nasal reaction. European 

journal of clinical pharmacology Vol 54; 1998: 515-20. Not lactose intolerance study 

1384. Micallef J, Gavaudan G, Burle B, et al. A study of a topiramate pre-treatment on the effects 

induced by a subanaesthetic dose of ketamine on human reaction time. Neuroscience letters 

Vol 369; 2004: 99-103. Not lactose intolerance study 

1385. Michaelsson K, Holmberg L, Ljunghall S, et al. Effect of prefracture versus postfracture 

dietary assessment on hip fracture risk estimates. Int J Epidemiol 1996 Apr; 25(2):403-10. not 

eligible outcomes 

1386. Miettinen P, Pasanen P, Lahtinen J, et al. The long-term outcome after negative appendix 

operation. Annales Chirurgiae et Gynaecologiae 1995; 84(3):267-70. No prevalence data 

1387. Mihatsch WA, von SP, Fahnenstich H, et al. Randomized, multicenter trial of two different 

formulas for very early enteral feeding advancement in extremely-low-birth-weight infants. 

Journal of pediatric gastroenterology and nutrition Vol 33; 2001: 155-9. Not relevant to key 

questions 

1388. Milla PJ, Moynahan EJ. Acrodermatitis enteropathica with lactose intolerance. Proc R Soc 

Med 1972 Jul; 65(7):600-1. Not relevant to key questions 

256
 
1389. Miller JJ, McVeagh P, Fleet GH, et al. Effect of yeast lactase enzyme on "colic" in infants 

fed human milk. J Pediatr 1990 Aug; 117(2 Pt 1):261-3. Not relevant to key questions 

1390. Miller TL, Orav EJ, Martin SR, et al. Malnutrition and carbohydrate malabsorption in 

children with vertically transmitted human immunodeficiency virus 1 infection. 

Gastroenterology 1991 May; 100(5 Pt 1):1296-302. Not relevant to key questions 

1391. Milne MD. Hereditary disorders of intestinal transport. Biomembranes 1974; 4B(0):961­

1013. Not relevant to key questions 

1392. Minami R, Wagatsuma K, Ishikawa Y, et al. Complementation analysis of betagalactosidase deficiency by means of histochemical method. Tohoku J Exp Med 1985 Jun; 

146(2):181-7. Not relevant to key questions 

1393. Minenna MF, Palieri A, Panella C, et al. Gastro-oesophageal reflux disease and lactose 

malabsorption: Casual comorbidity or neglected association? Digestive & Liver Disease 2006 

Jun; 38(6):437-8. Not original research 

1394. Minoia C, Apostoli P, Maranelli G, et al. Urinary chromium levels in subjects living in two 

north Italy regions. Sci Total Environ 1988 Jun 1; 71(3):527-31. Not relevant to key questions 

1395. Mishkin B, Yalovsky M, Mishkin S. Increased prevalence of lactose malabsorption in 

Crohn's disease patients at low risk for lactose malabsorption based on ethnic origin. 

American Journal of Gastroenterology 1997 Jul; 92(7):1148-53. No prevalence data 

1396. Mishkin D, Sablauskas L, Yalovsky M, et al. Fructose and sorbitol malabsorption in 

ambulatory patients with functional dyspepsia: comparison with lactose 

maldigestion/malabsorption. Digestive Diseases & Sciences 1997 Dec; 42(12):2591-8. No 

prevalence data 

1397. Mishkin S. Dairy sensitivity, lactose malabsorption, and elimination diets in inflammatory 

bowel disease. American Journal of Clinical Nutrition 1997 Feb; 65(2):564-7. Not original 

research 

1398. Misra S, Sabui TK, Basu S, et al. A prospective study of rotavirus diarrhea in children 

under 1 year of age. Clinical Pediatrics 2007 Oct; 46(8):683-8. Ineligible number of subjects 

1399. Missmer SA, Smith-Warner SA, Spiegelman D, et al. Meat and dairy food consumption 

and breast cancer: a pooled analysis of cohort studies. Int J Epidemiol 2002 Feb; 31(1):78-85. 

Not eligible outcomes 

1400. Mitchell JD, Brand J, Halbisch J. Weight-gain inhibition by lactose in Australian 

Aboriginal children. A controlled trial of normal and lactose hydrolysed milk. Lancet 1977 

Mar 5; 1(8010):500-2. Not relevant to key questions 

1401. Mitchell KJ, Bayless TM, Paige DM, et al. Intolerance of eight ounces of milk in healthy 

lactose-intolerant teen-agers. Pediatrics 1975 Nov; 56(5):718-21. Ineligible number of 

subjects 

257
 
1402. Mittal SK, Mital HS, Dwivedi KK, et al. Lactose malabsorption in irritable colon 

syndrome. J Assoc Physicians India 1981 Sep; 29(9):751-6. Not relevant to key questions 

1403. Mittal SK, Mittal HS, Dwivvedi KK, et al. Lactose malabsorption in healthy adults. J 

Assoc Physicians India 1979 Feb; 27(2):95-8. Not relevant to key questions 

1404. Mobassaleh M, Montgomery RK, Biller JA, et al. Development of carbohydrate absorption 

in the fetus and neonate. Pediatrics 1985 Jan; 75(1 Pt 2):160-6. Not relevant to key questions 

1405. Mokhtar NA, Ghaly IM. Lactose intolerance, a cause of recurrent diarrhea in Kuwait. 

Gazette of the Egyptian Paediatric Association 1974 Apr; 22(2):113-8. Subjects less than 4 

years old 

1406. Mombelli B, Gismondo MR. The use of probiotics in medical practice. Int J Antimicrob 

Agents 2000 Dec; 16(4):531-6. Not relevant to key questions 

1407. Montalto M, Curigliano V, Santoro L, et al. Management and treatment of lactose 

malabsorption. World J Gastroenterol 2006 Jan 14; 12(2):187-91. Not relevant to key 

questions 

1408. Montalto M, Gallo A, Santoro L, et al. Low-dose lactose in drugs neither increases breath 

hydrogen excretion nor causes gastrointestinal symptoms. Aliment Pharmacol Ther 2008 Oct 

15; 28(8):1003-12. Not relevant to key questions 

1409. Montaño GML, Orea M. [Frequency of urticaria and angioedema induced by food 

additives]. Revista alergia México Vol 36; 1989: 15-8. Not relevant to key questions 

1410. Montes RG, Bayless TM, Saavedra JM, et al. Effect of milks inoculated with Lactobacillus 

acidophilus or a yogurt starter culture in lactose-maldigesting children. J Dairy Sci 1995 Aug; 

78(8):1657-64. Not relevant to key questions 

1411. Montes RG, Perman JA. Lactose intolerance. Pinpointing the source of nonspecific 

gastrointestinal symptoms. Postgraduate Medicine 1991 Jun; 89(8):175-8. No prevalence 

data 

1412. Moodie PM. Medical aspects of Aboriginal health. Aust Fam Physician 1977 Oct; 

6(10):1309-17. Not relevant to key questions 

1413. Moore DJ, Robb TA, Davidson GP. Breath hydrogen response to milk containing lactose in 

colicky and noncolicky infants.[see comment]. Journal of Pediatrics 1988 Dec; 113(6):979­

84. No prevalence data 

1414. Moore LG, Cymerman A, Huang SY, et al. Propranolol does not impair exercise oxygen 

uptake in normal men at high altitude. Journal of applied physiology (Bethesda, Md. : 1985) 

Vol 61; 1986: 1935-41. Not lactose intolerance study 

1415. Moore TJ, McKnight JA. Dietary factors and blood pressure regulation. Endocrinol Metab 

Clin North Am 1995 Sep; 24(3):643-55. Review 

258
 
1416. Morales C, Peñarrocha M, Bagán JV, et al. Immunological study of Melkersson-Rosenthal 

syndrome. Lack of response to food additive challenge. Clinical and experimental allergy : 

journal of the British Society for Allergy and Clinical Immunology Vol 25; 1995: 260-4. Not 

lactose intolerance study 

1417. Morley D, Woodland M, Cuthbertson WF. Controlled trial of pyrimethamine in pregnant 

women in an african village. Bmj Vol 1; 1964: 667-8. Not lactose intolerance study 

1418. Morrison WJ, Christopher NL, Bayless TM, et al. Low lactase levels: evaluation of the 

radiologic diagnosis. Radiology 1974 Jun; 111(3):513-8. Not relevant to key questions 

1419. Moscato G, Rossi G, Dellabianca A, et al. Local immunotherapy by inhalation of a powder 

extract in asthma due to house dust mite Dermatophagoides pteronyssinus: a double-blind 

comparison with parenteral immunotherapy. Journal of investigational allergology & clinical 

immunology : official organ of the International Association of Asthmology (INTERASMA) 

and Sociedad Latinoamericana de Alergia e Inmunología Vol 1; 1991: 383-94. Not lactose 

intolerance study 

1420. Moskovitz M, Curtis C, Gavaler J. Does oral enzyme replacement therapy reverse 

intestinal lactose malabsorption? Am J Gastroenterol 1987 Jul; 82(7):632-5. Not relevant to 

key questions 

1421. Mota-Hernandez F, Gordillo-Paniagua G, Muñoz-Arizpe R, et al. Prednisone versus 

placebo in membranoproliferative glomerulonephritis: long-term clinicopathological 

correlations. The International journal of pediatric nephrology Vol 6; 1985: 25-8. Not lactose 

intolerance study 

1422. Mottes M, Belpinati F, Milani M, et al. Genetic testing for adult-type hypolactasia in Italian 

families. Clin Chem Lab Med 2008; 46(7):980-4. Not relevant to key questions 

1423. Motulsky AG. Human genetic variation and nutrition. Am J Clin Nutr 1987 May; 45(5 

Suppl):1108-13. Not relevant to key questions 

1424. Moukarzel AA, Lesicka H, Ament ME. Irritable bowel syndrome and nonspecific diarrhea 

in infancy and childhood--relationship with juice carbohydrate malabsorption. Clinical 

Pediatrics 2002 Apr; 41(3):145-50. Ineligible number of subjects 

1425. Moya M, Cortés E, Juste M, et al. [Absorptive pattern of individual fatty acids and total fat 

in full term babies. Its stability in the absence of lactose]. Anales españoles de pediatría Vol 

48; 1998: 515-21. Not relevant to key questions 

1426. Moya M, Cortes E, Vento M, et al. Impaired absorption of calcium in term babies on 

lactose free formula (LFF) with vitamin D repletion [abstract]. Pediatric Research Vol 28; 

1990: 309. Not relevant to key questions 

259
 
1427. Moya M, Lifschitz C, Ameen V, et al. A metabolic balance study in term infants fed 

lactose-containing or lactose-free formula. Acta Paediatrica 1999 Nov; 88(11):1211-5. 

Ineligible number of subjects 

1428. Moynahan EJ, Barnes PM. Zinc deficiency and a synthetic diet for lactose intolerance. 

Lancet 1973 Mar 24; 1(7804):676-7. Not relevant to key questions 

1429. Moynihan P. Dietary therapy in chronically sick children: dental health considerations. 

Quintessence Int 2006 Jun; 37(6):444-8. Not relevant to key questions 

1430. Moynihan PJ, Wright WG, Walton AG. A comparison of the relative acidogenic potential 

of infant milk and soya infant formula: a plaque pH study. International journal of paediatric 

dentistry / the British Paedodontic Society [and] the International Association of Dentistry for 

Children Vol 6; 1996: 177-81. Not eligible outcomes 

1431. Mueller OT, Shows TB. Human beta-galactosidase and alpha-neuraminidase deficient 

mucolipidosis: genetic complementation analysis of the neuraminidase deficiency. Hum 

Genet 1982; 60(2):158-62. Not relevant to key questions 

1432. Mujika I, Chatard JC, Lacoste L, et al. Creatine supplementation does not improve sprint 

performance in competitive swimmers. Medicine and science in sports and exercise Vol 28; 

1996: 1435-41. Not lactose intolerance study 

1433. Munck LK, Kjeldsen J, Philipsen E, et al. Incomplete remission with short-term 

prednisolone treatment in collagenous colitis: a randomized study. Scandinavian journal of 

gastroenterology Vol 38; 2003: 606-10. Not lactose intolerance study 

1434. Munir M. Protracted diarrhea in infants and young children. A clinical evaluation with 

special reference to the role of infection. Paediatr Indones 1982 May-Jun; 22(5-6):89-98. Not 

relevant to key questions 

1435. Munir M. Determinants of chronic diarrhea in infants in Manado. Paediatr Indones 1985 

Jan-Feb; 25(1-2):22-32. Not relevant to key questions 

1436. Munir M. Infantile diarrhoea: breast and bottle feeding compared with special reference to 

their clinical role. Paediatrica Indonesiana 1985 May-Jun; 25(5-6):100-6. No prevalence data 

1437. Murphy MS, Sood M, Johnson T. Use of the lactose H2 breath test to monitor mucosal 

healing in coeliac disease. Acta Paediatr 2002; 91(2):141-4. Not relevant to key questions 

1438. Murphy S, Khaw KT, May H, et al. Milk consumption and bone mineral density in middle 

aged and elderly women. Bmj 1994 Apr 9; 308(6934):939-41. not eligible outcomes 

1439. Murray RD, Boutton TW, Klein PD, et al. Comparative absorption of [13C]glucose and 

[13C]lactose by premature infants. Am J Clin Nutr 1990 Jan; 51(1):59-66. Not relevant to key 

questions 

1440. Murtagh J. Test for lactose intolerance. Aust Fam Physician 1993 Jul; 22(7):1272. Not 

relevant to key questions 

260
 
1441. Murthy MS, Haworth JC. Intestinal lactase deficiency among east Indians. An adaptive 

rather than a genetically inherited phenomenon? Am J Gastroenterol 1970 Mar; 53(3):246-51. 

Not relevant to key questions 

1442. Mustadjab I, Munir M. Lactose intolerance in pateints with gastroenteritis between 0--2 

years of age. Paediatr Indones 1976 Nov-Dec; 16(11-12):415-29. Not relevant to key 

questions 

1443. Mutalik S, Naha A, Usha AN, et al. Preparation, in vitro, preclinical and clinical 

evaluations of once daily sustained release tablets of aceclofenac. Archives of pharmacal 

research Vol 30; 2007: 222-34. Not lactose intolerance study 

1444. Mutch PB. Food guides for the vegetarian. Am J Clin Nutr 1988 Sep; 48(3 Suppl):913-9. 

Review 

1445. Myers VH, Champagne CM. Nutritional effects on blood pressure. Curr Opin Lipidol 2007 

Feb; 18(1):20-4. Not relevant to key questions 

1446. Myles S, Bouzekri N, Haverfield E, et al. Genetic evidence in support of a shared EurasianNorth African dairying origin. Hum Genet 2005 Jun; 117(1):34-42. Not relevant to key 

questions 

1447. Myo K, Bolin TD, Khin Mar O, et al. Ineffectiveness of breath methane excretion as a 

diagnostic test for lactose malabsorption. Journal of Pediatric Gastroenterology & Nutrition 

1999 May; 28(5):474-9. No prevalence data 

1448. Nacey KA. Infant colic. J Emerg Nurs 1993 Feb; 19(1):65-6. Not relevant to key questions 

1449. Nadasdi M. Tolerance of a milk-based formula by infants. Clin Ther 1992 Mar-Apr; 

14(2):242-6. Not relevant to key questions 

1450. Nadasdi M. Tolerance of a soy formula by infants and children. Clin Ther 1992 Mar-Apr; 

14(2):236-41. Not relevant to key questions 

1451. Nagano T, Itoh H, Hayashi T, et al. Effect of pilocarpine on levels of substance P and 

alpha-calcitonin gene-related peptide in human saliva. Pharmacy & Pharmacology 

Communications Vol 5; 1999: 571-4. Not lactose intolerance study 

1452. Nagy L, Mozsik G, Garamszegi M, et al. Lactose-poor milk in adult lactose intolerance. 

Acta Med Hung 1983; 40(4):239-45. Not relevant to key questions 

1453. Nagy L, Tapsonyi Z, Mozsik G, et al. Efficacy testing of beta-galactosidase with H2 breath 

test in patients with carbohydrate malabsorption. Acta Med Hung 1987; 44(1):31-42. Not 

relevant to key questions 

1454. Nahum LH. Lactose deficiency and the "irritable-colon syndrome". Conn Med 1966 Mar; 

30(3):153-4. Not relevant to key questions 

1455. Naidoo BT, Chunterpurshad I, Mahyoodeen AB, et al. The use of a soy isolate based 

formula in the treatment of infantile diarrhoea. J Int Med Res 1981; 9(3):232-5. Not relevant 

to key questions 

261
 
1456. Nakade S, Komaba J, Ohno T, et al. Bioequivalence study of two limaprost alfadex 5 

microg tablets in healthy subjects: moisture-resistant tablet (dextran formulation) versus 

standard tablet (lactose formulation). International journal of clinical pharmacology and 

therapeutics Vol 46; 2008: 42-7. Not lactose intolerance study 

1457. Nakamoto K, Watanabe S, Kudo H, et al. Nutritional characteristics of middle-aged 

Japanese vegetarians. J Atheroscler Thromb 2008 Jun; 15(3):122-9. Not relevant to key 

questions 

1458. Nakamura K, Takahashi H, Shimai S, et al. Effects of immersion in tepid bath water on 

recovery from fatigue after submaximal exercise in man. Ergonomics Vol 39; 1996: 257-66. 

Not lactose intolerance study 

1459. Nakate T, Yoshida H, Ohike A, et al. Formulation development of inhalation powders for 

FK888 with carrier lactose using Spinhaler and its absorption in healthy volunteers. Journal 

of controlled release : official journal of the Controlled Release Society Vol 97; 2004: 19-29. 

Not lactose intolerance study 

1460. Nandi NA, Parham ES. Milk drinking by the lactose intolerant. Comparison of Caucasian 

and Oriental adults. J Am Diet Assoc 1972 Sep; 61(3):258-61. Not relevant to key questions 

1461. Nanji AA, Denardi FG. Primary adult lactose intolerance protects against development of 

inflammatory bowel disease. Medical Hypotheses 1986 Jan; 19(1):1-6. No prevalence data 

1462. Nasrallah SM. Lactose intolerance in the Lebanese population and in "Mediterranean 

lymphoma". American Journal of Clinical Nutrition 1979 Oct; 32(10):1994-6. Ineligible 

number of subjects 

1463. Neale G. Defects of sugar absorption. The diagnosis, incidence and significance of 

disaccharidase deficiency in adults. Proc R Soc Med 1968 Nov; 61(11 Part 1):1099-102. Not 

relevant to key questions 

1464. Neale G. The geographical incidence of lactase deficiency. Pathol Microbiol (Basel) 1973; 

39(3):238-47. Not relevant to key questions 

1465. Neaverson MA. The clinical significance of lactose intolerance. Aust Fam Physician 1980 

Oct; 9(10):747-50. Not relevant to key questions 

1466. Nedkova-Bratanova N. Radiologic changes of the small intestine in combined enzymic 

deficiency (gluten intolerance and lactase deficiency). Digestion 1968; 1(1):43-51. Not 

relevant to key questions 

1467. Nei M, Saitou N. Genetic relationship of human populations and ethnic differences in 

reaction to drugs and food. Prog Clin Biol Res 1986; 214:21-37. Not relevant to key questions 

1468. Nelson CD, Waggoner DD, Donnell GN, et al. Verbal dyspraxia in treated galactosemia. 

Pediatrics 1991 Aug; 88(2):346-50. Not relevant to key questions 

262
 
1469. Neumeister A, Hu XZ, Luckenbaugh DA, et al. Differential effects of 5-HTTLPR 

genotypes on the behavioral and neural responses to tryptophan depletion in patients with 

major depression and controls. Archives of general psychiatry Vol 63; 2006: 978-86. Not 

lactose intolerance study 

1470. Neumeister A, Nugent AC, Waldeck T, et al. Neural and behavioral responses to 

tryptophan depletion in unmedicated patients with remitted major depressive disorder and 

controls. Archives of general psychiatry Vol 61; 2004: 765-73. Not lactose intolerance study 

1471. New SA. Do vegetarians have a normal bone mass? Osteoporos Int 2004 Sep; 15(9):679­

88. Review 

1472. New SA, Bolton-Smith C, Grubb DA, et al. Nutritional influences on bone mineral density: 

a cross-sectional study in premenopausal women. Am J Clin Nutr 1997 Jun; 65(6):1831-9. 

not eligible outcomes 

1473. Newcomer AD. Disaccharidase deficiencies. Mayo Clin Proc 1973 Sep; 48(9):648-52. Not 

relevant to key questions 

1474. Newcomer AD. Lactase deficiency. J Med Soc N J 1980 Feb; 77(2):127-8. Not relevant to 

key questions 

1475. Newcomer AD, Gordon H, Thomas PJ, et al. Family studies of lactase deficiency in the 

American Indian. Gastroenterology 1977 Nov; 73(5):985-8. Not relevant to key questions 

1476. Newcomer AD, Hodgson SF, McGill DB, et al. Lactase deficiency: prevalence in 

osteoporosis. Annals of Internal Medicine 1978 Aug; 89(2):218-20. Ineligible number of 

subjects 

1477. Newcomer AD, McGill DB. Incidence of lactase deficiency in ulcerative colitis. 

Gastroenterology 1967 Dec; 53(6):890-3. Not relevant to key questions 

1478. Newcomer AD, McGill DB, Thomas PJ, et al. Prospective comparison of indirect methods 

for detecting lactase deficiency. New England Journal of Medicine 1975 Dec 11; 

293(24):1232-6. Ineligible number of subjects 

1479. Newcomer AD, Thomas PJ, McGill DB, et al. Lactase deficiency: a common genetic trait 

of the American Indian. Gastroenterology 1977 Feb; 72(2):234-7. Not relevant to key 

questions 

1480. Newman S, Malik S, Hirst R, et al. Lung deposition of salbutamol in healthy human 

subjects from the MAGhaler dry powder inhaler. Respiratory medicine Vol 96; 2002: 1026­

32. Not lactose intolerance study 

1481. Ngan P, Wilson S, Shanfeld J, et al. The effect of ibuprofen on the level of discomfort in 

patients undergoing orthodontic treatment. American journal of orthodontics and dentofacial 

orthopedics : official publication of the American Association of Orthodontists, its 

constituent societies, and the American Board of Orthodontics Vol 106; 1994: 88-95. Not 

lactose intolerance study 

263
 
1482. Nguyen KN, Welsh JD, Manion CV, et al. Effect of fiber on breath hydrogen response and 

symptoms after oral lactose in lactose malabsorbers. Am J Clin Nutr 1982 Jun; 35(6):1347­

51. Not relevant to key questions 

1483. Nguyen MT. Effect of cow milk on pulmonary function in atopic asthmatic patients. 

Annals of Allergy, Asthma, & Immunology 1997 Jul; 79(1):62-4. No prevalence data 

1484. Nicolaescu T, Stoiculescu P, Bittman E, et al. Chronic dysenzymatic enteropathy; its 

relationship to chronic functional colopathy. Rom Med Rev 1970 Oct-Dec; 14(4):18-23. 

Review 

1485. Nielsen FH, Milne DB, Gallagher S, et al. Moderate magnesium deprivation results in 

calcium retention and altered potassium and phosphorus excretion by postmenopausal 

women. Magnesium research : official organ of the International Society for the Development 

of Research on Magnesium Vol 20; 2007: 19-31. Not lactose intolerance study 

1486. Nielsen FH, Penland JG. Boron supplementation of peri-menopausal women affects boron 

metabolism and indices associated with macromineral metabolism, hormonal status and 

immune function. Journal of Trace Elements in Experimental Medicine Vol 12; 1999: 251­

61. Not lactose intolerance study 

1487. Nilsson M, Stenberg M, Frid AH, et al. Glycemia and insulinemia in healthy subjects after 

lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and 

incretins. Am J Clin Nutr Vol 80; 2004: 1246-53. Not relevant to key questions 

1488. Nilsson TK, Johansson CA. A novel method for diagnosis of adult hypolactasia by 

genotyping of the -13910 C/T polymorphism with Pyrosequencing technology. Scand J 

Gastroenterol 2004 Mar; 39(3):287-90. Not relevant to key questions 

1489. Nilsson TK, Olsson LA. Simultaneous genotyping of the three lactose tolerance-linked 

polymorphisms LCT -13907C>G, LCT -13910C>T and LCT -13915T>G with 

Pyrosequencing technology. Clin Chem Lab Med 2008; 46(1):80-4. Not relevant to key 

questions 

1490. Nin F, Fukui T, Sakai K, et al. Effects of bromazepam (Lexotan(Reg.trademark)) as a 

premedicant in the preoperative night. Hiroshima J. Anesth. Vol 16; 1980: 29-34. Not lactose 

intolerance study 

1491. Nizami SQ, Bhutta ZA, Molla AM. Efficacy of traditional rice-lentil-yogurt diet, lactose 

free milk protein-based formula and soy protein formula in management of secondary lactose 

intolerance with acute childhood diarrhoea. Journal of Tropical Pediatrics 1996 Jun; 

42(3):133-7. Ineligible number of subjects 

1492. Nordio S, Lamedica GM, Berio A, et al. Disaccharidase activities of duodenal mucosa in 

children. (Normal subjects, coeliac DISEASE, malnutrition, cystic fibrosis of pancreas, other 

chronic enteropathies). Ann Paediatr 1966; 206(4):287-312. Review 

264
 
1493. Nordstrom C, Dahlqvist A. Quantitative distribution of some enzymes along the villi and 

crypts of human small intestine. Scand J Gastroenterol 1973; 8(5):406-16. Not relevant to key 

questions 

1494. Northrop-Clewes CA, Lunn PG, Downes RM. Lactose maldigestion in breast-feeding 

Gambian infants. J Pediatr Gastroenterol Nutr 1997 Mar; 24(3):257-63. Not relevant to key 

questions 

1495. Nose O, Iida Y, Kai H, et al. Breath hydrogen test for detecting lactose malabsorption in 

infants and children. Prevalence of lactose malabsorption in Japanese children and adults. 

Archives of Disease in Childhood 1979 Jun; 54(6):436-40. Ineligible number of subjects 

1496. Nurse GT, Jenkins T. Letter: Lactose intolerance in San populations. Br Med J 1974 Sep 

28; 3(5934):809. Not relevant to key questions 

1497. Nurse GT, Jenkins T. Health and the Hunter-Gatherer. Biomedical studies on the hunting 

and gathering populations of Southern Africa. Monogr Hum Genet 1977; 8:1-126. Not 

relevant to key questions 

1498. Nyulasi IB, Metz G. Methods of introducing nasoenteric feeding. A prospective 

randomized study. Medical Journal of Australia 1984 Oct 13; 141(8):496-8. Not relevant to 

key questions 

1499. Oberlander TF, Barr RG, Young SN, et al. Short-term effects of feed composition on 

sleeping and crying in newborns. Pediatrics Vol 90; 1992: 733-40. Not relevant to key 

questions 

1500. Ochs HD, Ament ME, Davis SD. Giardiasis with malabsorption in X-linked 

agammaglobulinemia. N Engl J Med 1972 Aug 17; 287(7):341-2. Not relevant to key 

questions 

1501. Ochs HD, Ament ME, Davis SD. Structure and function of the gastrointestinal tract in 

primary immunodeficiency syndromes (IDS) and in granulocyte dysfunction. Birth Defects 

Orig Artic Ser 1975; 11(1):199-207. Not relevant to key questions 

1502. O'Connell S, Walsh G. Physicochemical characteristics of commercial lactases relevant to 

their application in the alleviation of lactose intolerance. Appl Biochem Biotechnol 2006 

Aug; 134(2):179-91. Not relevant to key questions 

1503. Ohler J, Grinspoon L, Shader R, et al. Behavioral correlates of the guessing game. Side 

effects and double-blind studies. Archives of general psychiatry Vol 15; 1966: 279-87. Not 

lactose intolerance study 

1504. Ohura T, Kobayashi K, Tazawa Y, et al. Clinical pictures of 75 patients with neonatal 

intrahepatic cholestasis caused by citrin deficiency (NICCD). Journal of inherited metabolic 

disease 2007 Apr; 30(2):139-44. Not relevant to key questions 

1505. Ojantakanen S, Hannula AM, Marvola M. Bioavailability of ibuprofen from hard gelatin 

capsules containing sodium bicarbonate, lactose or dicalcium phosphate. Acta Pharmaceutica 

Fennica Vol 99; 1990: 119-27. Not lactose intolerance study 

265
 
1506. Ojetti V, Gabrielli M, Migneco A, et al. Regression of lactose malabsorption in coeliac 

patients after receiving a gluten-free diet. Scandinavian journal of gastroenterology 2008; 

43(2):174-7. Not relevant to key questions 

1507. Ojetti V, La Mura R, Zocco MA, et al. Quick test: a new test for the diagnosis of duodenal 

hypolactasia. Dig Dis Sci 2008 Jun; 53(6):1589-92. Not relevant to key questions 

1508. Ojetti V, Nucera G, Migneco A, et al. High prevalence of celiac disease in patients with 

lactose intolerance. Digestion 2005; 71(2):106-10. No prevalence data 

1509. Okada S, Kato T, Miura S, et al. Hypersialyloligosacchariduria in mucolipidoses: a method 

for diagnosis. Clin Chim Acta 1978 Jun; 86(2):159-67. Not relevant to key questions 

1510. Okada S, Kato T, Yabuuchi H, et al. The complementation of beta-galactosidase in fused 

cells of mucolipidosis II with another variants of beta-galactosidase deficiency using new 

single cell enzyme assay. Biochem Biophys Res Commun 1979 May 28; 88(2):559-62. Not 

relevant to key questions 

1511. O'Keefe SJ, Adam JK. Primary lactose intolerance in Zulu adults. S Afr Med J 1983 May 

14; 63(20):778-80. Not relevant to key questions 

1512. O'Keefe SJ, Adam JK, Cakata E, et al. Nutritional support of malnourished lactose 

intolerant African patients. Gut 1984 Sep; 25(9):942-7. Not relevant to key questions 

1513. O'Keefe SJ, O'Keefe EA, Burke E, et al. Milk-induced malabsorption in malnourished 

African patients. Am J Clin Nutr 1991 Jul; 54(1):130-5. Not relevant to key questions 

1514. O'Keefe SJ, Young GO, Rund J. Milk tolerance and the malnourished African. Eur J Clin 

Nutr 1990 Jul; 44(7):499-504. Not relevant to key questions 

1515. Olafsdottir E, Aksnes L, Fluge G, et al. Faecal calprotectin levels in infants with infantile 

colic, healthy infants, children with inflammatory bowel disease, children with recurrent 

abdominal pain and healthy children. Acta Paediatrica 2002; 91(1):45-50. Ineligible number 

of subjects 

1516. Olatunbosun DA, Adadevoh BK. Lactose intolerance in Nigerian children. Acta Paediatr 

Scand 1972 Nov; 61(6):715-9. Not relevant to key questions 

1517. Olatunbosun DA, Adadevoh BK. Plasma insulin response to oral lactose and glucosegalactose in patients with lactose intolerance. Ghana Med J 1973 Dec; 12(4):370-4. Not 

relevant to key questions 

1518. Olatunbosun DA, Kwaku Adadevoh B. Lactase deficiency in Nigerians. Am J Dig Dis 

1971 Oct; 16(10):909-14. Not relevant to key questions 

1519. Olden KW. Diagnosis of irritable bowel syndrome. Gastroenterology 2002 May; 

122(6):1701-14. Not original research 

1520. Olds LC, Sibley E. Lactase persistence DNA variant enhances lactase promoter activity in 

vitro: functional role as a cis regulatory element. Hum Mol Genet 2003 Sep 15; 12(18):2333­

40. Not relevant to key questions 

1521. Oliver MF. Thrombosis and oestrogens. Lancet Vol 2; 1967: 510-1. Not lactose intolerance 

study 

1522. Olives JP, Mundelengolo JM, Le TO, et al. Diarrhees aigues communes du nourrisson: 

faut-il avoir peur du lactose? Arch Fr Pediatr Vol 45; 1988: 591-. Not relevant to key 

questions 

1523. Olsen WA. Carbohydrate digestion and absorption. Clinically significant abnormalities. 

Postgrad Med 1972 Apr; 51(4):149-52. Not relevant to key questions 

1524. O'Malley BW, Li D, McQuone SJ, et al. Combination nonviral interleukin-2 gene 

immunotherapy for head and neck cancer: from bench top to bedside. The Laryngoscope Vol 

266
 
115; 2005: 391-404. Not lactose intolerance study 

1525. Onbasi K, Gunsar F, Sin AZ, et al. Common variable immunodeficiency (CVID) 

presenting with malabsorption due to giardiasis. Turkish Journal of Gastroenterology 2005 

Jun; 16(2):111-3. No prevalence data 

1526. Onwulata CI, Rao DR, Vankineni P. Relative efficiency of yogurt, sweet acidophilus milk, 

hydrolyzed-lactose milk, and a commercial lactase tablet in alleviating lactose maldigestion. 

Am J Clin Nutr 1989 Jun; 49(6):1233-7. Not relevant to key questions 

1527. Ooms ME, Lips P, Van Lingen A, et al. Determinants of bone mineral density and risk 

factors for osteoporosis in healthy elderly women. J Bone Miner Res 1993 Jun; 8(6):669-75. 

not eligible exposure 

1528. Orrego F, Quintana C. Darwin's illness: a final diagnosis. Notes Rec R Soc Lond 2007 Jan 

22; 61(1):23-9. Not relevant to key questions 

1529. Orris L, Shalita AR, Sibulkin D, et al. Oral zinc therapy of acne. Absorption and clinical 

effect. Archives of dermatology Vol 114; 1978: 1018-20. Not lactose intolerance study 

1530. Osterlund P, Ruotsalainen T, Peuhkuri K, et al. Lactose intolerance associated with 

adjuvant 5-fluorouracil-based chemotherapy for colorectal cancer. Clin Gastroenterol Hepatol 

2004 Aug; 2(8):696-703. Not eligible target population 

1531. Osterwalder P, Bircher AJ, Wuthrich B. Cow's milk allergy as delayed-type reaction. 

Allergologie Vol 21; 1998: 73-7. Not relevant to key questions 

1532. Osvaath P, Kerese I, Szendrey A. Use of chestnut in the feeding of infants allergic to cow's 

milk or intolerant to lactose. Allergol Immunopathol (Madr) 1976 Nov-Dec; 4(6):413-8. Not 

relevant to key questions 

1533. Outila TA, Karkkainen MU, Seppanen RH, et al. Dietary intake of vitamin D in 

premenopausal, healthy vegans was insufficient to maintain concentrations of serum 25­

hydroxyvitamin D and intact parathyroid hormone within normal ranges during the winter in 

Finland. J Am Diet Assoc 2000 Apr; 100(4):434-41. Not eligible exposure 

1534. Ouwehand A, Vesterlund S. Health aspects of probiotics. IDrugs 2003 Jun; 6(6):573-80. 

Not relevant to key questions 

267
 
1535. Ouwehand AC, Salminen S, Isolauri E. Probiotics: an overview of beneficial effects. 

Antonie Van Leeuwenhoek 2002 Aug; 82(1-4):279-89. Not relevant to key questions 

1536. Ozkaya O, Sezik M, Kaya H, et al. Placebo-controlled randomized comparison of vaginal 

with rectal misoprostol in the prevention of postpartum hemorrhage. The journal of obstetrics 

and gynaecology research Vol 31; 2005: 389-93. Not lactose intolerance study 

1537. Ozmen S, Turhan NO, Seckin NC. Gardnerella-associated vaginitis: Comparison of three 

treatment modalities. Turkish Journal of Medical Sciences Vol 28; 1998: 171-3. Not lactose 

intolerance study 

1538. Ozolek JA, Cook LA, Mimouni FB, et al. Bone mineralization over the first eight months 

of life in infants fed a lactose free formula. Pediatric Research Vol 2; 1995: 315. Not eligible 

target population 

1539. Paajanen L, Tuure T, Poussa T, et al. No difference in symptoms during challenges with 

homogenized and unhomogenized cow's milk in subjects with subjective hypersensitivity to 

homogenized milk. The Journal of dairy research Vol 70; 2003: 175-9. Not lactose 

intolerance 

1540. Paerregaard A, Hjelt K, Christiansen L, et al. Postenteritis enteropathy in infancy. A 

prospective study of 10 patients with special reference to growth pattern, long-term outcome 

and incidence. Acta Paediatrica Scandinavica 1990 Nov; 79(11):1045-51. Not relevant to key 

questions 

1541. Paerregaard A, Vilien M, Krasilnikoff PA, et al. Supposed coeliac disease during childhood 

and its presentation 14-38 years later. Scandinavian Journal of Gastroenterology 1988 Jan; 

23(1):65-70. Ineligible number of subjects 

1542. Paes IC, Searl P, Rubert MW, et al. Intestinal lactase deficiency and saccharide 

malabsorption during oral neomycin administration. Gastroenterology 1967 Jul; 53(1):49-58. 

Not relevant to key questions 

1543. Paganini-Hill A, Chao A, Ross RK, et al. Exercise and other factors in the prevention of 

hip fracture: the Leisure World study. Epidemiology 1991 Jan; 2(1):16-25. not eligible 

outcomes 

1544. Paige DM, Bayless TM, Dellinger WS, Jr. Relationship of milk consumption to blood 

glucose rise in lactose intolerant individuals. Am J Clin Nutr 1975 Jul; 28(7):677-80. Not 

relevant to key questions 

1545. Paige DM, Bayless TM, Ferry GD, et al. Lactose malabsorption and milk rejection in 

Negro children. Johns Hopkins Med J 1971 Sep; 129(3):163-9. Not relevant to key questions 

1546. Paige DM, Bayless TM, Graham GG. Milk programs: helpful or harmful to Negro 

children? Am J Public Health 1972 Nov; 62(11):1486-8. Not relevant to key questions 

1547. Paige DM, Bayless TM, Graham GG. Pregnancy and lactose intolerance. Am J Clin Nutr 

1973 Mar; 26(3):238-40. Not relevant to key questions 

1548. Paige DM, Bayless TM, Mellitis ED, et al. Lactose malabsorption in preschool black 

children. Am J Clin Nutr 1977 Jul; 30(7):1018-22. Not relevant to key questions 

1549. Paige DM, Bayless TM, Mellits ED, et al. Effects of age and lactose tolerance on blood 

glucose rise with whole cow and lactose-hydrolyzed milk. J Agric Food Chem 1979 Jul-Aug; 

27(4):677-80. Not relevant to key questions 

1550. Paige DM, Graham GG. Etiology of lactase deficiency: another perspective. 

Gastroenterology 1971 Nov; 61(5):798-9. Not relevant to key questions 

1551. Paige DM, Graham GG. School milk programs and Negro children: a nutritional dilemma. 

J Sch Health 1974 Jan; 44(1):8-10. Not relevant to key questions 

268
 
1552. Paige DM, Leonardo E, Cordano A, et al. Lactose intolerance in Peruvian children: effect 

of age and early nutrition. Am J Clin Nutr 1972 Mar; 25(3):297-301. Not relevant to key 

questions 

1553. Paige DM, Leonardo E, Nakashima J, et al. Response of lactose-intolerant children to 

different lactose levels. Am J Clin Nutr 1972 May; 25(5):467-9. Not relevant to key questions 

1554. Paige DM, Mellits ED, Chiu FY, et al. Blood glucose rise after lactose tolerance testing in 

infants. Am J Clin Nutr 1978 Feb; 31(2):222-5. Not relevant to key questions 

1555. Paige DM, Witter FR, Bronner YL, et al. Lactose digestion in pregnant African-Americans. 

Public Health Nutrition 2003 Dec; 6(8):801-7. Secondary lactose intolerance 

1556. Palacios S, Castelo-Branco C, Cifuentes I, et al. Changes in bone turnover markers after 

calcium-enriched milk supplementation in healthy postmenopausal women: a randomized, 

double-blind, prospective clinical trial. Menopause (New York, N.Y.) Vol 12; 2005: 63-8. 

Not lactose intolerance study 

1557. Palma D, Oliva CA, Taddei JA, et al. [Acute diarrhea: stool water loss in hospitalized 

infants and its correlation with etiologic agents and lactose content in the diet]. Arquivos de 

gastroenterologia Vol 34; 1997: 186-95. Not relevant to key questions 

1558. Palma M, Rosado JL, López P, et al. [Lactose intolerance. Its definition, its prevalence in 

Mexico, and its implications in milk consumption]. Revista de investigación clínica; organo 

del Hospital de Enfermedades de la Nutrición Vol 48; 1996: 25-31. Not English language 

1559. Pan J, Takeshita T, Morimoto K. Acute caffeine effect on repeatedly measured P300. 

Environmental Health & Preventive Medicine Vol 5; 2000: 13-7. Not lactose intolerance 

study 

1560. Papadaki A, Vardavas C, Hatzis C, et al. Calcium, nutrient and food intake of Greek 

Orthodox Christian monks during a fasting and non-fasting week. Public Health Nutr 2008 

Oct; 11(10):1022-9. Not eligible outcomes 

1561. Park RH, Duncan A, Russell RI. Hypolactasia and Crohn's disease: a myth. American 

Journal of Gastroenterology 1990 Jun; 85(6):708-10. Ineligible number of subjects 

1562. Parker TJ, Woolner JT, Prevost AT, et al. Irritable bowel syndrome: is the search for 

lactose intolerance justified? Eur J Gastroenterol Hepatol 2001 Mar; 13(3):219-25. Not 

relevant to key questions 

1563. Parnes HL, Fung E, Schiffer CA. Chemotherapy-induced lactose intolerance in adults. 

Cancer 1994 Sep 1; 74(5):1629-33. Ineligible number of subjects 

1564. Parra D, Martinez JA. Amino acid uptake from a probiotic milk in lactose intolerant 

subjects. Br J Nutr 2007 Oct; 98 Suppl 1:S101-4. Not relevant to key questions 

1565. Parra MD, Martinez de Morentin BE, Cobo JM, et al. Acute calcium assimilation from 

fresh or pasteurized yoghurt depending on the lactose digestibility status. J Am Coll Nutr 

2007 Jun; 26(3):288-94. Not eligible outcomes 

1566. Parrott AC, Golding JF, Pethybridge RJ. The effects of single and repeated doses of oral 

scopolamine, cinnarizine, and placebo upon psychological performance and physiological 

functioning. Hum Psychopharmacol Vol 5; 1990: 207-16. Not lactose intolerance study 

1567. Parry SD, Barton JR, Welfare MR. Is lactose intolerance implicated in the development of 

post-infectious irritable bowel syndrome or functional diarrhoea in previously asymptomatic 

people? European Journal of Gastroenterology & Hepatology 2002 Nov; 14(11):1225-30. No 

prevalence data 

1568. Parsons TJ, van Dusseldorp M, Seibel MJ, et al. Are levels of bone turnover related to 

lower bone mass of adolescents previously fed a macrobiotic diet? Exp Clin Endocrinol 

269
 
Diabetes 2001; 109(5):288-93. not eligible outcomes 

1569. Parvez S, Malik KA, Ah Kang S, et al. Probiotics and their fermented food products are 

beneficial for health. Journal of Applied Microbiology 2006 Jun; 100(6):1171-85. No 

prevalence data 

1570. Patel Y, Boyd PA, Chamberlain P, et al. Follow-up of children with isolated fetal 

echogenic bowel with particular reference to bowel-related symptoms. Prenatal Diagnosis 

2004 Jan; 24(1):35-7. No prevalence data 

1571. Patel YT, Minocha A. Lactose intolerance: diagnosis and management. Comprehensive 

Therapy 2000; 26(4):246-50. Not original research 

1572. Patil DH, Grimble GK, Silk DB. Lactitol, a new hydrogenated lactose derivative: intestinal 

absorption and laxative threshold in normal human subjects. The British journal of nutrition 

Vol 57; 1987: 195-9. Not relevant to key questions 

1573. Patrick MK. Vomiting and diarrhoea. Aust Fam Physician 1994 Oct; 23(10):1913, 6-9. Not 

relevant to key questions 

1574. Patwari AK, Anand VK, Aneja S, et al. Persistent diarrhea: management in a diarrhea 

treatment unit. Indian Pediatrics 1995 Mar; 32(3):277-84. No prevalence data 

1575. Paul VK, Singh M, Srivastava LM, et al. Macronutrient and energy content of breast milk 

of mothers delivering prematurely. Indian journal of pediatrics Vol 64; 1997: 379-82. Not 

relevant to key questions 

270
 
1576. Pauwels S, Fiasse R, Tome G, et al. A simplified method of measuring breath hydrogen by 

end-expiratory sampling for diagnosis of lactose malabsorption. Acta Clin Belg 1985; 

40(3):174-8. Not relevant to key questions 

1577. Payne DL, Welsh JD, Manion CV, et al. Effectiveness of milk products in dietary 

management of lactose malabsorption. Am J Clin Nutr 1981 Dec; 34(12):2711-5. Not 

relevant to key questions 

1578. Payne-Bose D, Welsh JD, Gearhart HL, et al. Milk and lactose-hydrolyzed milk. Am J Clin 

Nutr 1977 May; 30(5):695-7. Not relevant to key questions 

1579. Pearson AD, Craft AW, Pledger JV, et al. Small bowel function in acute lymphoblastic 

leukaemia. Arch Dis Child 1984 May; 59(5):460-5. Not relevant to key questions 

1580. Peck AW, Adams R, Bye C, et al. Residual effects of hypnotic drugs: evidence for 

individual differences on vigilance. Psychopharmacologia Vol 47; 1976: 213-6. Not lactose 

intolerance study 

1581. Pederzini F, Faraguna D, Giglio L, et al. Development of a screening system for cystic 

fibrosis: meconium or blood spot trypsin assay or both? Acta Paediatrica Scandinavica 1990 

Oct; 79(10):935-42. No prevalence data 

1582. Pei J, Yang T, Liu Z. [Study on effect of acupoint sticker of TTS-ST93-1 in treating motion 

sickness]. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese 

journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, 

Zhongguo Zhong yi yan jiu yuan zhu ban Vol 18; 1998: 464-7. Not lactose intolerance study 

1583. Pelchat ML, Rozin P. The special role of nausea in the acquisition of food dislikes by 

humans. Appetite 1982 Dec; 3(4):341-51. Not relevant to key questions 

1584. Pelletier X, Laure-Boussuge S, Donazzolo Y. Hydrogen excretion upon ingestion of dairy 

products in lactose-intolerant male subjects: importance of the live flora. Eur J Clin Nutr 

2001 Jun; 55(6):509-12. Not relevant to key questions 

1585. Pelto L, Impivaara O, Salminen S, et al. Milk hypersensitivity in young adults. European 

Journal of Clinical Nutrition 1999 Aug; 53(8):620-4. No prevalence data 

1586. Pelto L, Salminen S, Lilius EM, et al. Milk hypersensitivity--key to poorly defined 

gastrointestinal symptoms in adults. Allergy 1998 Mar; 53(3):307-10. Not relevant to key 

questions 

1587. Pena AS, Truelove SC. Hypolactasia and the irritable colon syndrome. Scand J 

Gastroenterol 1972; 7(5):433-8. Not relevant to key questions 

1588. Pena AS, Truelove SC. Hypolactasia and ulcerative colitis. Gastroenterology 1973 Mar; 

64(3):400-4. Not relevant to key questions 

1589. Pena AS, Truelove SC, Lumsden K, et al. Hypolactasia and the irritable colon syndrome. 

Gut 1969 Dec; 10(12):1052-3. Not relevant to key questions 

271
 
1590. Penny ME, Brown KH. Lactose feeding during persistent diarrhoea. Acta Paediatr Suppl 

1992 Sep; 381:133-8. Not relevant to key questions 

1591. Penny ME, Paredes P, Brown KH. Clinical and nutritional consequences of lactose feeding 

during persistent postenteritis diarrhea. Pediatrics Vol 84; 1989: 835-44. Not relevant to key 

questions 

1592. Perlow W, Baraona E, Lieber CS. Symptomatic intestinal disaccharidase deficiency in 

alcoholics. Gastroenterology 1977 Apr; 72(4 Pt 1):680-4. Not relevant to key questions 

1593. Perman JA, Modler S, Olson AC. Role of pH in production of hydrogen from 

carbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J Clin Invest 1981 Mar; 

67(3):643-50. Not relevant to key questions 

1594. Perrin B, Malo JL, Cartier A, et al. Occupational asthma in a pharmaceutical worker 

exposed to hydralazine. Thorax 1990 Dec; 45(12):980-1. Not relevant to key questions 

1595. Pesola GR, Hogg JE, Eissa N, et al. Hypertonic nasogastric tube feedings: do they cause 

diarrhea? Critical care medicine 1990 Dec; 18(12):1378-82. Not eligible target population 

1596. Peters TJ, Batt RM, Heath JR, et al. The micro-assay of intestinal disaccharidases. 

Biochem Med 1976 Apr; 15(2):145-8. Not relevant to key questions 

1597. Petrarulo M, Marangella M, Bianco O, et al. Ion-chromatographic determination of Ltartrate in urine samples. Clin Chem 1991 Jan; 37(1):90-3. Not relevant to key questions 

1598. Petrella RJ, DiSilvestro MD, Hildebrand C. Effects of hyaluronate sodium on pain and 

physical functioning in osteoarthritis of the knee: a randomized, double-blind, placebocontrolled clinical trial. Archives of internal medicine Vol 162; 2002: 292-8. Not lactose 

intolerance study 

1599. Pettersson R, Dahlqvist A, Hattevig G, et al. Borderline galactosemia. Acta Paediatr Scand 

1980 Nov; 69(6):735-9. Not relevant to key questions 

1600. Pettersson T, Wegelius O, Skrifvars B. Gastro-intestinal disturbances in patients with 

severe rheumatoid arthritis. Acta Med Scand 1970 Jul-Aug; 1-2(1):139-44. Not relevant to 

key questions 

1601. Pettifor JM, Hansen JD. Letter: Lactose intolerance in San populations. Br Med J 1974 Jul 

20; 3(5924):173. Not relevant to key questions 

1602. Pettoello Mantovani M, Guandalini S, Ecuba P, et al. Lactose malabsorption in children 

with symptomatic Giardia lamblia infection: feasibility of yogurt supplementation. J Pediatr 

Gastroenterol Nutr 1989 Oct; 9(3):295-300. Not relevant to key questions 

1603. Pettoello-Mantovani M, Guandalini S, diMartino L, et al. Prospective study of lactose 

absorption during cancer chemotherapy: feasibility of a yogurt-supplemented diet in lactose 

malabsorbers. Journal of Pediatric Gastroenterology & Nutrition 1995 Feb; 20(2):189-95. 

Ineligible number of subjects 

272
 
1604. Peuhkuri K, Nevala R, Vapaatalo H, et al. Ibuprofen augments gastrointestinal symptoms 

in lactose maldigesters during a lactose tolerance test. Aliment Pharmacol Ther 1999 Sep; 

13(9):1227-33. Not relevant to key questions 

1605. Peuhkuri K, Poussa T, Korpela R. Comparison of a portable breath hydrogen analyser 

(Micro H2) with a Quintron MicroLyzer in measuring lactose maldigestion, and the 

evaluation of a Micro H2 for diagnosing hypolactasia. Scand J Clin Lab Invest 1998 May; 

58(3):217-24. Not relevant to key questions 

1606. Peuhkuri K, Vapaatalo H, Korpela R. Wide variations in the testing of lactose tolerance: 

results of a questionnaire study in Finnish health care centres. Scand J Clin Lab Invest 2000 

Jul; 60(4):291-7. Not relevant to key questions 

1607. Peuhkuri K, Vapaatalo H, Nevala R, et al. Influence of the pharmacological modification 

of gastric emptying on lactose digestion and gastrointestinal symptoms. Aliment Pharmacol 

Ther 1999 Jan; 13(1):81-6. Not relevant to key questions 

1608. Peuhkuri K, Vapaatalo H, Nevala R, et al. Temperature of a test solution influences 

abdominal symptoms in lactose tolerance tests. Scand J Clin Lab Invest 2000 Feb; 60(1):75­

80. Not relevant to key questions 

1609. Phillips MC, Briggs GM. Milk and its role in the American diet. J Dairy Sci 1975 Nov; 

58(11):1739-63. Not relevant to key questions 

1610. Phillips SF. Relationship of diarrhea to maldigestion and malabsorption. Mayo Clin Proc 

1973 Sep; 48(9):660-2. Not relevant to key questions 

1611. Phillips T, Macdonald I, Keyser A. Some metabolic effects of ingesting galactose, before 

and after a high-lactose diet. Proc Nutr Soc 1978 May; 37(1):24A. Not relevant to key 

questions 

1612. Piacentini MF, Meeusen R, Buyse L, et al. Hormonal responses during prolonged exercise 

are influenced by a selective DA/NA reuptake inhibitor. British journal of sports medicine 

Vol 38; 2004: 129-33. Not lactose intolerance study 

1613. Piccirillo JF, Finnell J, Vlahiotis A, et al. Relief of idiopathic subjective tinnitus: is 

gabapentin effective? Archives of otolaryngology--head & neck surgery Vol 133; 2007: 390­

7. Not lactose intolerance study 

1614. Piche T, Zerbib F, Bruley DVS, et al. Modulation by colonic fermentation of LES function 

in humans. American Journal of Physiology - Gastrointestinal & Liver Physiology Vol 278; 

2000: G578-g84. Not lactose intolerance study 

1615. Pickett CK, Regensteiner JG, Woodard WD, et al. Progestin and estrogen reduce sleepdisordered breathing in postmenopausal women. Journal of applied physiology (Bethesda, 

Md. : 1985) Vol 66; 1989: 1656-61. Not lactose intolerance study 

1616. Pieters JJ, van Rens R. Lactose malabsorption and milk tolerance in Kenyan school-age 

children. Trop Geogr Med 1973 Dec; 25(4):365-71. Not relevant to key questions 

273
 
1617. Pimentel M, Kong Y, Park S. Breath testing to evaluate lactose intolerance in irritable 

bowel syndrome correlates with lactulose testing and may not reflect true lactose 

malabsorption. American Journal of Gastroenterology 2003 Dec; 98(12):2700-4. Ineligible 

number of subjects 

1618. Piper DW. Milk in treatment of gastric disease. Am J Clin Nutr 1969 Feb; 22(2):191-5. Not 

relevant to key questions 

1619. Pirk F, Skala I. Functional response of the digestive tract to the ingestion of milk in 

subjects suffering from lactose intolerance. Digestion 1972; 5(2):89-99. Not relevant to key 

questions 

1620. Pirk F, Skala I, Vulterinova M. Milk intolerance after gastrectomy. Digestion 1973; 

9(2):130-7. Not relevant to key questions 

1621. Pironi L, Callegari C, Cornia GL, et al. Lactose malabsorption in adult patients with 

Crohn's disease. American Journal of Gastroenterology 1988 Nov; 83(11):1267-71. Ineligible 

number of subjects 

1622. Pitcairn G, Lunghetti G, Ventura P, et al. A comparison of the lung deposition of 

salbutamol inhaled from a new dry powder inhaler, at two inhaled flow rates. Int J Pharm Vol 

102; 1994: 11-8. Not lactose intolerance study 

1623. Placzek M, Walker-Smith JA. Comparison of two feeding regimens following acute 

gastroenteritis in infancy. J Pediatr Gastroenterol Nutr 1984 Mar; 3(2):245-8. Not relevant to 

key questions 

1624. Pochart P, Dewit O, Desjeux JF, et al. Viable starter culture, beta-galactosidase activity, 

and lactose in duodenum after yogurt ingestion in lactase-deficient humans. Am J Clin Nutr 

1989 May; 49(5):828-31. Not relevant to key questions 

1625. Pock-Steen OC. The role of gluten, milk, and other dietary proteins in chronic or 

intermittent dyspepsia. Clin Allergy 1973 Dec; 3(4):373-83. Not relevant to key questions 

1626. Pollack RL, Mueller DH. Nutritionally speaking. Pa Dent J (Harrisb) 1983 May-Jun; 

50(3):28. Not relevant to key questions 

1627. Ponz dLM, Roncucci L, Di DP, et al. Lactose and vitamin A,E,C on prevention of relapse 

of adenomatous polyps of the large intestine. Tumori Vol 75; 1989: 72. Not lactose 

intolerance study 

1628. Poon WB, Ho WL, Yeo CL. Survey on parenting practices among Chinese in Singapore. 

Singapore Med J 2007 Nov; 48(11):1006-11. Not relevant to key questions 

1629. Popescu CM. Experimental use of prostaglandin E2 (Dinoprost) in the treatment of 

duodenal ulcer in humans. Prostaglandins, leukotrienes, and medicine Vol 21; 1986: 97-105. 

Not lactose intolerance study 

1630. Portincasa P, Di Ciaula A, Vacca M, et al. Beneficial effects of oral tilactase on patients 

with hypolactasia. Eur J Clin Invest 2008 Nov; 38(11):835-44. Not relevant to key questions 

1631. Portnoy J, Bagstad K, Kanarek H, et al. Premedication reduces the incidence of systemic 

reactions during inhalant rush immunotherapy with mixtures of allergenic extracts. Annals of 

allergy Vol 73; 1994: 409-18. Not lactose intolerance study 

1632. Potter NL, Lazarus JA, Johnson JM, et al. Correlates of language impairment in children 

with galactosaemia. Journal of inherited metabolic disease 2008 Aug; 31(4):524-32. Not 

relevant to key questions 

1633. Powell GK. Enterocolitis in low-birth-weight infants associated with milk and soy protein 

intolerance. Journal of Pediatrics 1976 May; 88(5):840-4. Ineligible number of subjects 

1634. Powell ML, Weisberger M, Gural R, et al. Comparative bioavailability and 

274
 
pharmacokinetics of three formulations of albuterol. Journal of pharmaceutical sciences Vol 

74; 1985: 217-9. Not lactose intolerance study 

1635. Preger L, Amberg JR. Sweet diarrhea. Roentgen diagnosis of disaccharidase deficiency. 

Am J Roentgenol Radium Ther Nucl Med 1967 Oct; 101(2):287-95. Not relevant to key 

questions 

1636. Premchander KV, Sundaravalli N, Panchatcharam M, et al. Pattern of sugar intolerance in 

children following chronic or recurrent diarrhoea: a preliminary report. Indian Pediatr 1976 

Mar; 13(3):177-86. Not relevant to key questions 

1637. Prentice A. Diet, nutrition and the prevention of osteoporosis. Public Health Nutr 2004 

Feb; 7(1A):227-43. Review 

1638. Pribila BA, Hertzler SR, Martin BR, et al. Improved lactose digestion and intolerance 

among African-American adolescent girls fed a dairy-rich diet. J Am Diet Assoc 2000 May; 

100(5):524-8; quiz 9-30. Not relevant to key questions 

1639. Priebe MG, Wachters-Hagedoorn RE, Stellaard F, et al. Oro-cecal transit time: influence of 

a subsequent meal. European Journal of Clinical Investigation Vol 34; 2004: 417-21. Not 

lactose intolerance study 

1640. Prieto L, Juyol M, Paricio A, et al. Oral challenge test with sodium metabisulfite in steroiddependent asthmatic patients. Allergologia et immunopathologia Vol 16; 1988: 393-6. Not 

lactose intolerance study 

1641. Prieto L, Pastor A, Palop A, et al. [Rhinitis with intolerance to non-steroidal antiinflammatory agents. Report of 3 cases]. Allergologia et immunopathologia Vol 14; 1986: 

147-53. Not lactose intolerance study 

1642. Prince R, Devine A, Dick I, et al. The effects of calcium supplementation (milk powder or 

tablets) and exercise on bone density in postmenopausal women. J Bone Miner Res 1995 Jul; 

10(7):1068-75. not eligible outcomes 

1643. Prinsloo JG, Laubscher NF, Kruger H, et al. The effect of different sugars and two levels of 

fat intake on diarrhoea in Bantu children. South African medical journal = Suid-Afrikaanse 

tydskrif vir geneeskunde Vol 47; 1973: 821-8. Not relevant to key questions 

1644. Prinsloo JG, Wittmann W, Pretorius PJ, et al. Effect of different sugars on diarrhoea of 

acute kwashiorkor. Arch Dis Child 1969 Oct; 44(237):593-9. Not relevant to key questions 

275
 
1645. Puche RC, Feldman S. Relative importance of urinary sulfate and net acid excretion as 

determinants of calciuria in normal subjects. Medicina (B Aires) 1992; 52(3):220-4. Not 

eligible outcomes 

1646. Qin LQ, Xu JY, Wang PY, et al. Milk consumption is a risk factor for prostate cancer: 

meta-analysis of case-control studies. Nutr Cancer 2004; 48(1):22-7. Not eligible outcomes 

1647. Qin LQ, Xu JY, Wang PY, et al. Milk consumption is a risk factor for prostate cancer in 

Western countries: evidence from cohort studies. Asia Pac J Clin Nutr 2007; 16(3):467-76. 

Not eligible outcomes 

1648. Quak SH. Lactose intolerance in Asian children. J Paediatr Child Health 1994 Apr; 

30(2):91-2. Not relevant to key questions 

1649. Quak SH, Low PS, Quah TC, et al. Oral refeeding following acute gastro-enteritis: a 

clinical trial using four refeeding regimes. Annals of tropical paediatrics Vol 9; 1989: 152-5. 

Not relevant to key questions 

1650. Quak SH, Raman GV, Low PS, et al. Lactase insufficiency in Chinese children detected by 

oral milk and lactose challenge. Ann Trop Paediatr 1987 Jun; 7(2):100-3. Not relevant to key 

questions 

1651. Quak SH, Tan SP. Use of soy-protein formulas and soyfood for feeding infants and 

children in Asia. American Journal of Clinical Nutrition 1998 Dec; 68(6 Suppl):1444S-6S. 

No prevalence data 

1652. Raadal M, Coldwell SE, Kaakko T, et al. A randomized clinical trial of triazolam in 3- to 

5-year-olds. Journal of dental research Vol 78; 1999: 1197-203. Not lactose intolerance study 

1653. Rab SM, Baseer A. High intestinal lactase concentration in adult Pakistanis. Br Med J 1976 

Feb 21; 1(6007):436. Not relevant to key questions 

1654. Rachelefsky GS, Coulson A, Siegel SC, et al. Aspirin intolerance in chronic childhood 

asthma: Detected by oral challenge. Pediatrics Vol 56; 1975: 443-8. Not lactose intolerance 

study 

1655. Rachlis A, Gill J, Baril JG, et al. Effectiveness of step-wise intervention plan for managing 

nelfinavir-associated diarrhea: a pilot study. HIV clinical trials Vol 6; 2005: 203-12. Not 

lactose intolerance 

1656. Radomyska B. [Effectiveness of the screening programme for galactosemia. New strategy 

in Poland]. Medycyna wieku rozwojowego 2001 Jan-Mar; 5(1):51-8. Not relevant to key 

questions 

1657. Rahimi AG, Delbruck H, Haeckel R, et al. Persistence of high intestinal lactase activity 

(lactose tolerance) in Afghanistan. Human Genetics 1976 Sep 10; 34(1):57-62. Not eligible 

test for lactose malabsorption 

1658. Raimondi F, Indrio F, Crivaro V, et al. Neonatal hyperbilirubinemia increases intestinal 

protein permeability and the prevalence of cow's milk protein intolerance. Acta Paediatrica 

2008 Jun; 97(6):751-3. Ineligible number of subjects 

276
 
1659. Rajah R, Pettifor JM, Noormohamed M, et al. The effect of feeding four different formulae 

on stool weights in prolonged dehydrating infantile gastroenteritis. Journal of pediatric 

gastroenterology and nutrition Vol 7; 1988: 203-7. Not relevant to key questions 

1660. Rana S, Bhasin DK, Gupta D, et al. Assessment of optimal dose of lactose for lactose 

hydrogen breath test in Indian adults. Indian J Gastroenterol 1995 Jan; 14(1):13-4. Not 

relevant to key questions 

1661. Rana SV, Bhasin DK, Naik N. Lactose malabsorption in apparently healthy adults in 

northern India, assessed using lactose hydrogen breath test. Indian Journal of 

Gastroenterology 2004 Mar-Apr; 23(2):78. Ineligible number of subjects 

1662. Rana SV, Bhasin DK, Naik N, et al. Lactose maldigestion in different age groups of north 

Indians. Trop Gastroenterol 2004 Jan-Mar; 25(1):18-20. Not relevant to key questions 

1663. Rana SV, Bhasin DK, Vinayak VK. Prospective evaluation of lactose malabsorption by 

lactose hydrogen breath test in individuals infected with Entamoeba histolytica and passing 

cysts. British Journal of Nutrition 2004 Aug; 92(2):207-8. Ineligible number of subjects 

1664. Rana SV, Bhasin DK, Vinayak VK. Lactose hydrogen breath test in Giardia lambliapositive patients. Dig Dis Sci 2005 Feb; 50(2):259-61. Not relevant to key questions 

1665. Rana SV, Mandal AK, Kochhar R, et al. Lactose intolerance in different types of irritable 

bowel syndrome in north Indians. Tropical Gastroenterology 2001 Oct-Dec; 22(4):202-4. 

Ineligible number of subjects 

1666. Rangecroft L, de San Lazaro C, Scott JE. A comparison of the feeding of the postoperative 

newborn with banked breast-milk or cow's-milk feeds. J Pediatr Surg 1978 Feb; 13(1):11-2. 

Not relevant to key questions 

1667. Ransome OJ, Roode H. Early introduction of milk feeds in acute infantile gastro-enteritis. 

A controlled study. South African Medical Journal Suid-Afrikaanse Tydskrif Vir 

Geneeskunde 1984 Jan 28; 65(4):127-8. Ineligible number of subjects 

1668. Ransome-Kuti O. Lactose intolerance--a review. Postgrad Med J 1977; 53 Suppl 2:73-87. 

Not relevant to key questions 

1669. Ransome-Kuti O, Kretchmer N, Johnson JD, et al. A genetic study of lactose digestion in 

Nigerian families. Gastroenterology 1975 Mar; 68(3):431-6. Not relevant to key questions 

1670. Rao RM, Reddy GP, Grim CE. Relative role of genes and environment on BP: twin studies 

in Madras, India. J Hum Hypertens 1993 Oct; 7(5):451-5. Not relevant to key questions
 

1671. Raper NR, Hill MM. Vegetarian diets. Nutr Rev 1974 Jul; 32(0):suppl 1:29-33. Comment 

277
 
1672. Rasinpera H, Saarinen K, Pelkonen A, et al. Molecularly defined adult-type hypolactasia in 

school-aged children with a previous history of cow's milk allergy. World Journal of 

Gastroenterology 2006 Apr 14; 12(14):2264-8. Secondary lactose intolerance 

1673. Rasmussen DD, Ishizuka B, Quigley ME, et al. Effects of tyrosine and tryptophan 

ingestion on plasma catecholamine and 3,4-dihydroxyphenylacetic acid concentrations. J Clin 

Endocrinol Metab Vol 57; 1983: 760-3. Not lactose intolerance study 

1674. Rasmussen M, Michalsen H, Lie SO, et al. Intestinal retinol esterification and serum retinol 

in children with cystic fibrosis. J Pediatr Gastroenterol Nutr 1986 May-Jun; 5(3):397-403. 

Not relevant to key questions 

1675. Rastogi M, Misra RC, Srivastava PN, et al. Intestinal disaccharidases in primary protein 

malnutrition in adults. Trop Geogr Med 1974 Jun; 26(2):133-6. Not relevant to key questions 

1676. Ratner D, Schneeyour A, Eshel E, et al. Does milk intolerance affect seronegative arthritis 

in lactase-deficient women? Isr J Med Sci 1985 Jun; 21(6):532-4. Not relevant to key 

questions 

1677. Ratner D, Shneyour A, Eshel E, et al. Elevated IgM in dietary migraine with lactase 

deficiency. Isr J Med Sci 1984 Aug; 20(8):717-9. Not relevant to key questions 

1678. Ratner D, Shoshani E, Dubnov B. Milk protein-free diet for nonseasonal asthma and 

migraine in lactase-deficient patients. Isr J Med Sci 1983 Sep; 19(9):806-9. Not relevant to 

key questions 

1679. Rautio M, Eerola E, Vaisanen-Tunkelrott ML, et al. Reclassification of Bacteroides 

putredinis (Weinberg et al., 1937) in a new genus Alistipes gen. nov., as Alistipes putredinis 

comb. nov., and description of Alistipes finegoldii sp. nov., from human sources. Syst Appl 

Microbiol 2003 Jun; 26(2):182-8. Not relevant to key questions 

1680. Read NW, Davies RJ, Holdsworth CD, et al. Electrical assessment of functional lactase 

activity in conscious man. Gut 1977 Aug; 18(8):640-3. Not relevant to key questions 

1681. Read NW, Krejs GJ, Read MG, et al. Chronic diarrhea of unknown origin. 

Gastroenterology 1980 Feb; 78(2):264-71. Not relevant to key questions 

1682. Rebello T, Hodges RE, Smith JL. Short-term effects of various sugars on antinatriuresis 

and blood pressure changes in normotensive young men. The American journal of clinical 

nutrition Vol 38; 1983: 84-94. Not lactose intolerance study 

1683. Recker RR, Heaney RP. The effect of milk supplements on calcium metabolism, bone 

metabolism and calcium balance. Am J Clin Nutr 1985 Feb; 41(2):254-63. Not eligible 

outcomes 

1684. Reddy V, Bhaskaram P. Treatment of severe protein energy malnutrition. Indian Pediatr 

1982 Mar; 19(3):243-8. Not relevant to key questions 

1685. Reddy V, Pershad J. Lactase deficiency in Indians. Am J Clin Nutr 1972 Jan; 25(1):114-9. 

Not relevant to key questions 

1686. Reed JA, Anderson JJ, Tylavsky FA, et al. Comparative changes in radial-bone density of 

elderly female lacto-ovovegetarians and omnivores. Am J Clin Nutr 1994 May; 59(5 

Suppl):1197S-202S. Not target population 

1687. Regan PT, DiMagno EP. The medical management of malabsorption. Mayo Clin Proc 

1979 Apr; 54(4):267-74. Not relevant to key questions 

1688. Register UD, Sonnenberg LM. The vegetarian diet. Scientific and practical considerations. 

J Am Diet Assoc 1973 Mar; 62(3):253-61. Review 

1689. Rehnberg O. Antrectomy and gastroduodenostomy with or without vagotomy in peptic 

ulcer disease. A prospective study with a 5-year follow-up. Acta Chirurgica Scandinavica - 

278
 
Supplementum 1983; 515:1-63. No prevalence data 

1690. Rehnberg O, Olbe L. Early dumping reaction after partial gastrectomy and its relation to 

preoperative apomorphine testing. Acta Chirurgica Scandinavica 1985; 151(6):565-9. No 

prevalence data 

1691. Reiner EB, 2nd, Patterson M. Intestinal disaccharidase content. South Med J 1966 Mar; 

59(3):311-4. Not relevant to key questions 

1692. Rejman F. Postgastrectomy syndrome. EFFECTS OF PARTIAL GASTRECTOMY 

ON BONE METABOLISM. Ann Chir Gynaecol Fenn Suppl 1970; 170:45-50. Not eligible target 

population 

1693. Renaud J, Bourassa M, Douglas VI, et al. Methylphenidate and motor organization in 

children with ADHD [abstract]. 150th Annual Meeting of the American Psychiatric 

Association; 1997 May 17-22; San Diego, CA; 1997. Not lactose intolerance study 

1694. Resbeut M, Marteau P, Cowen D, et al. A randomized double blind placebo controlled 

multicenter study of mesalazine for the prevention of acute radiation enteritis. Radiotherapy 

& Oncology 1997 Jul; 44(1):59-63. Not eligible target population 

1695. Retta TM, Afre GM, Randall OS. Dietary management of blood pressure. J Assoc Acad 

Minor Phys 1994; 5(4):147-51. Review 

1696. Reusser ME, DiRienzo DB, Miller GD, et al. Adequate nutrient intake can reduce 

cardiovascular disease risk in African Americans. J Natl Med Assoc 2003 Mar; 95(3):188-95. 

Review 

1697. Rey J, Schmitz J, Rey F, et al. Cellular differentiation and enzymatic deficits. Lancet 1971 

Jul 24; 2(7717):218. Not relevant to key questions 

1698. Rhee YS, Hermann JR, Burnham K, et al. The effects of chromium and copper 

supplementation on mitogen-stimulated T cell proliferation in hypercholesterolaemic 

postmenopausal women. Clinical and experimental immunology Vol 127; 2002: 463-9. Not 

lactose intolerance study 

1699. Rhoades RB, Leifer KN, Cohan R, et al. Suppression of histamine-induced pruritus by 

three antihistaminic drugs. The Journal of allergy and clinical immunology Vol 55; 1975: 

180-5. Not lactose intolerance study 

1700. Ribeiro JHC, Lifshitz F. Alanine-based oral rehydration therapy for infants with acute 

diarrhea. The Journal of pediatrics Vol 118; 1991: S86-90. Not lactose intolerance study 

1701. Richards AJ, Condon JR, Mallinson CN. Lactose intolerance following extensive small 

intestinal resection. Br J Surg 1971 Jul; 58(7):493-4. Not relevant to key questions 

1702. Rickett JW, Jackson BT. Topical ampicillin in the appendicectomy wound: report of 

double-blind trial. British medical journal Vol 4; 1969: 206-7. Not lactose intolerance study 

1703. Ridefelt P, Hakansson LD. Lactose intolerance: lactose tolerance test versus genotyping. 

Scandinavian Journal of Gastroenterology 2005 Jul; 40(7):822-6. Ineligible number of 

subjects 

1704. Rider JA. Placebo gastric analysis. The American journal of gastroenterology Vol 56; 

1971: 364-70. Not lactose intolerance study 

1705. Rinaldi E, Albini L, Costagliola C, et al. High frequency of lactose absorbers among adults 

with idiopathic senile and presenile cataract in a population with a high prevalence of primary 

adult lactose malabsorption. Lancet 1984 Feb 18; 1(8373):355-7. Secondary lactose 

intolerance 

1706. Ringrose RE, Thompson JB, Welsh JD. Lactose malabsorption and steatorrhea. Am J Dig 

Dis 1972 Jun; 17(6):533-8. Not relevant to key questions 

279
 
1707. Risch HA, Jain M, Marrett LD, et al. Dietary lactose intake, lactose intolerance, and the 

risk of epithelial ovarian cancer in southern Ontario (Canada). Cancer Causes Control 1994 

Nov; 5(6):540-8. Not eligible outcomes 

1708. Ritschel WA, Johnson RD, Young DG. Evaluation of a controlled release osmotic pump 

type of dosage form for chlorpheniramine maleate. Eur J Pharm Biopharm Vol 40; 1994: 

122-7. Not lactose intolerance study 

1709. Rittmann LS, Tennant LL, O'Brien JS. Dog GM1 gangliosidosis: characterization of the 

residual liver acid beta-galactosidase. Am J Hum Genet 1980 Nov; 32(6):880-9. Not relevant 

to key questions 

1710. Ritzenthaler KL, McGuire MK, McGuire MA, et al. Consumption of conjugated linoleic 

acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating 

women. Journal of Nutrition Vol 135; 2005: 422-30. Not lactose intolerance study 

1711. Rizkalla SW, Luo J, Kabir M, et al. Chronic consumption of fresh but not heated yogurt 

improves breath-hydrogen status and short-chain fatty acid profiles: a controlled study in 

healthy men with or without lactose maldigestion. Am J Clin Nutr 2000 Dec; 72(6):1474-9. 

Not relevant to key questions 

1712. Robb TA, Goodwin DA, Davidson GP. Faecal hydrogen production in vitro as an indicator 

for in vivo hydrogen producing capability in the breath hydrogen test. Acta Paediatr Scand 

1985 Nov; 74(6):942-4. Not relevant to key questions 

1713. Roberfroid MB. Prebiotics and probiotics: are they functional foods? Am J Clin Nutr 2000 

Jun; 71(6 Suppl):1682S-7S; discussion 8S-90S. Not relevant to key questions 

1714. Roberson CM. Lactose intolerance. Ala Nurse 2004 Dec-2005 Feb; 31(4):23-4; quiz 4. 

Comment 

280
 
1715. Roberts SB, Hajduk CL, Howarth NC, et al. Dietary variety predicts low body mass index 

and inadequate macronutrient and micronutrient intakes in community-dwelling older adults. 

J Gerontol A Biol Sci Med Sci 2005 May; 60(5):613-21. Not relevant to key questions 

1716. Robertson WG, Peacock M, Heyburn PJ, et al. Should recurrent calcium oxalate stone 

formers become vegetarians? Br J Urol 1979 Dec; 51(6):427-31. Not eligible outcomes 

1717. Rodgers AL, Lewandowski S. Effects of 5 different diets on urinary risk factors for 

calcium oxalate kidney stone formation: evidence of different renal handling mechanisms in 

different race groups. J Urol 2002 Sep; 168(3):931-6. Not eligible outcomes 

1718. Rodriguez M, Daniels B, Gunawardene S, et al. High frequency of vitamin D deficiency in 

ambulatory HIV-Positive patients. AIDS Research & Human Retroviruses 2009 Jan; 25(1):9­

14. No prevalence data 

1719. Rodriguez-Rodriguez E, Aparicio A, Perea JM, et al. [Aproximation of the diet to the 

Mediterranean profile and repercusion in the body weight control]. Nutricion Clinica y 

Dietetica Hospitalaria Vol 26; 2006: 9-17. Not lactose intolerance study 

1720. Roe DA. Prediction of the cause, effects, and prevention of drug-nutrient interactions using 

attributes and attribute values. Drug Nutr Interact 1985; 3(4):187-9. Not relevant to key 

questions 

1721. Roelofs RI, de AGS, Law PK, et al. Treatment of Duchenne's muscular dystrophy with 

penicillamine. Results of a double-blind trial. Archives of neurology Vol 36; 1979: 266-8. 

Not lactose intolerance study 

1722. Roggero P, Offredi ML, Mosca F, et al. Lactose absorption and malabsorption in healthy 

Italian children: do the quantity of malabsorbed sugar and the small bowel transit time play 

roles in symptom production? Journal of Pediatric Gastroenterology & Nutrition 1985 Feb; 

4(1):82-6. Ineligible number of subjects 

1723. Rolfe RD. The role of probiotic cultures in the control of gastrointestinal health. J Nutr 

2000 Feb; 130(2S Suppl):396S-402S. Not relevant to key questions 

1724. Romer H, Olivero E, Gomez-rodriguez G, et al. Effect of carbohydrate composition of 

semi-elemental diets on the nutritional recovery of children with chronic diarrhea. Nutr Rep 

Int Vol 40; 1989: 843-52. Not relevant to key questions 

1725. Ropert A, Cherbut C, Rozé C, et al. Colonic fermentation and proximal gastric tone in 

humans. Gastroenterology Vol 111; 1996: 289-96. Not relevant to key questions 

1726. Rosado JL. [Importance of nutritional status in digestion capacity and lactose tolerance]. 

Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición Vol 

48; 1996: 45-50. Not relevant to key questions 

281
 
1727. Rosado JL, Allen LH, Solomons NW. Milk consumption, symptom response, and lactose 

digestion in milk intolerance. Am J Clin Nutr 1987 Jun; 45(6):1457-60. Not relevant to key 

questions 

1728. Rosado JL, Deodhar AD, Bourges H, et al. The effect of the digestion products of lactose 

(glucose and galactose) on its intraintestinal, in vivo hydrolysis by exogenous microbial betaD-galactosidase. J Am Coll Nutr 1986; 5(3):281-90. Not relevant to key questions 

1729. Rosado JL, López P, Palma M. [Poor digestion and intolerance to lactose in Mexican 

adults. Importance of evaluating them with regular doses of milk]. Revista de investigación 

clínica; organo del Hospital de Enfermedades de la Nutrición Vol 46; 1994: 203-8. Not 

relevant to key questions 

1730. Rosado JL, Morales M, Pasquetti A. Lactose digestion and clinical tolerance to milk, 

lactose-prehydrolyzed milk and enzyme-added milk: a study in undernourished continuously 

enteral-fed patients. JPEN J Parenter Enteral Nutr 1989 Mar-Apr; 13(2):157-61. Not relevant 

to key questions 

1731. Rosado JL, Morales M, Pasquetti A, et al. Nutritional evaluation of a lactose-hydrolyzed 

milk-based enteral formula diet. I. A comparative study of carbohydrate digestion and clinical 

tolerance. Rev Invest Clin 1988 Apr-Jun; 40(2):141-7. Not relevant to key questions 

1732. Rosado JL, Solomons NW. Sensitivity and specificity of the hydrogen breath-analysis test 

for detecting malabsorption of physiological doses of lactose. Clin Chem 1983 Mar; 

29(3):545-8. Not relevant to key questions 

1733. Rosado JL, Solomons NW, Allen LH. Lactose digestion from unmodified, low-fat and 

lactose-hydrolyzed yogurt in adult lactose-maldigesters. Eur J Clin Nutr 1992 Jan; 46(1):61­

7. Not relevant to key questions 

1734. Rosanelli K, Hofler K. [Comparative studies on the rearing of premature infants with 

various milk mixtures]. Wiener Medizinische Wochenschrift Vol 115; 1965: 160-4. Not 

relevant to key questions 

1735. Rosenberg IH, Solomons NW, Schneider RE. Malabsorption associated with diarrhea and 

intestinal infections. Am J Clin Nutr 1977 Aug; 30(8):1248-53. Not relevant to key questions 

1736. Rosenkranz W, Hadorn B, Muller W, et al. Distribution of human adult lactase phenotypes 

in the population of Austria. Hum Genet 1982; 62(2):158-61. Not relevant to key questions 

1737. Rosenquist CJ. Lactose-barium study as a screening test for lactase deficiency. West J Med 

1975 Apr; 122(4):319. Not relevant to key questions 

1738. Rosenquist CJ, Heaton JW, Jr., Friedland GW, et al. Assessment of a radiographic method 

for diagnosis of intestinal lactase deficiency: a prospective study. Investigative Radiology 

1971 Jan-Feb; 6(1):40-3. Ineligible number of subjects 

1739. Rosenquist CJ, Heaton JW, Jr., Gray GM, et al. Intestinal lactase deficiency. Diagnosis by 

routine upper gastrointestinal radiography. Radiology 1972 Feb; 102(2):275-7. Not relevant 

to key questions 

1740. Rosensweig NS. Adult human milk intolerance and intestinal lactase deficiency. A review. 

J Dairy Sci 1969 May; 52(5):585-7. Not relevant to key questions 

1741. Rosensweig NS. Adult lactase deficiency: genetic control or adaptive response? 

Gastroenterology 1971 Mar; 60(3):464-7. Not relevant to key questions 

1742. Rosensweig NS. Lactose feeding and lactase deficiency. Am J Clin Nutr 1973 Nov; 

26(11):1166-7. Not relevant to key questions 

1743. Rosensweig NS. Other carbohydrate intolerances. Curr Concepts Nutr 1979; 8:91-6. Not 

relevant to key questions 

282
 
1744. Rosensweig NS, Dawkins AT, Jr., Bayless TM. Lactase activity before and after acute 

febrile bacterial illness. Gastroenterology 1967 Jan; 52(1):50-3. Not relevant to key questions 

1745. Rossi E, Hadorn B. Congenital enzyme deficiencies of the small intestine: molecular basis 

and nutritional and therapeutic implications. J Pediatr Gastroenterol Nutr 1983; 2 Suppl 

1:S321-7. Not relevant to key questions 

1746. Rossiter MA, Palmer T, Evans K, et al. The short-term response to a drink of milk, lactose 

or casein in children with apparently normal gastrointestinal tracts. The British journal of 

nutrition Vol 32; 1974: 605-13. Not relevant to key questions 

1747. Rothman D, Habte D, Latham M. The effect of lactose on diarrhoea in the treatment of 

kwashiorkor. J Trop Pediatr 1980 Oct; 26(5):193-7. Not relevant to key questions 

1748. Rotthauwe HW, el-Schallah MO, Flatz G. Lactose intolerance in Arabs. Humangenetik 

1971; 13(4):344-6. Not relevant to key questions 

1749. Rouse IL, Beilin LJ, Armstrong BK, et al. Vegetarian diet, blood pressure and 

cardiovascular risk. Aust N Z J Med 1984 Aug; 14(4):439-43. Not relevant to key questions 

1750. Rouse IL, Beilin LJ, Mahoney DP, et al. Nutrient intake, blood pressure, serum and urinary 

prostaglandins and serum thromboxane B2 in a controlled trial with a lacto-ovo-vegetarian 

diet. J Hypertens 1986 Apr; 4(2):241-50. Not relevant to key questions 

1751. Rowland I. Probiotics and benefits to human health--the evidence in favour. Environ 

Microbiol 1999 Oct; 1(5):375-6. Not relevant to key questions 

1752. Roy P, Aubert-Jacquin C, Avart C, et al. [Benefits of a thickened infant formula with 

lactase activity in the management of benign digestive disorders in newborns]. Archives de 

pédiatrie : organe officiel de la Sociéte française de pédiatrie Vol 11; 2004: 1546-54. Not 

English language 

1753. Roy PK, Venzon DJ, Shojamanesh H, et al. Zollinger-Ellison syndrome. Clinical 

presentation in 261 patients. Medicine 2000 Nov; 79(6):379-411. No prevalence data 

1754. Rozen GS, Rennert G, Rennert HS, et al. Calcium intake and bone mass development 

among Israeli adolescent girls. J Am Coll Nutr 2001 Jun; 20(3):219-24. Not eligible outcomes 

283
 
1755. Rozen P, Shafrir E. Behavior of serum free fatty acids and glucose during lactose tolerance 

tests. Isr J Med Sci 1968 Jan-Feb; 4(1):100-9. Not relevant to key questions 

1756. Rudolf M, Arulanantham K, Greenstein RM. Unsuspected nutritional rickets. Pediatrics 

1980 Jul; 66(1):72-6. Not eligible target population 

1757. Rudzeviciene O, Narkeviciute I, Eidukevicius R. Lactose malabsorption in young 

Lithuanian children with atopic dermatitis. Acta Paediatrica 2004 Apr; 93(4):482-6. 

Secondary lactose intolerance 

1758. Rugg GAJ, Roberts GJ, Wright WG. Effect of human milk on plaque pH in situ and 

enamel dissolution in vitro compared with bovine milk, lactose, and sucrose. Caries-Res Vol 

19; 1985: 327-34. Not eligible outcomes 

1759. Rugg-Gunn AJ, Wright WG. The effect of human milk on plaque pH and enamel 

dissolution compared with cow's milk, lactose and sucrose (JDR Divisional Abstract). Journal 

of Dental Research Vol 62; 1983: 426 (Abs 105). Not relevant to key questions 

1760. Ruijter J, Lorist MM, Snel J. The influence of different doses of caffeine on visual task 

performance. Journal of Psychophysiology Vol 13; 1999: 37-48. Not lactose intolerance 

study 

1761. Rumessen JJ, Gudmand-Hoyer E, Bachmann E, et al. Diagnosis of bacterial overgrowth of 

the small intestine. Comparison of the 14C-D-xylose breath test and jejunal cultures in 60 

patients. Scand J Gastroenterol 1985 Dec; 20(10):1267-75. Not relevant to key questions 

1762. Russo F, De Carne M, Buonsante A, et al. Hypolactasia and metabolic changes in postmenopausal women. Maturitas 1997 Apr; 26(3):193-202. Ineligible number of subjects 

1763. Russo G, Mollica F, Mazzone D, et al. Congenital lactose intolerance of gastrogen origin 

associated with cataracts. Acta Paediatr Scand 1974 May; 63(3):457-60. Not relevant to key 

questions 

1764. Rutherford PJ, Davidson DC, Matthai SM. Dietary calcium in galactosaemia. Journal of 

Human Nutrition & Dietetics 2002 Feb; 15(1):39-42. Not relevant to key questions 

1765. Saavedra JM. Clinical applications of probiotic agents. Am J Clin Nutr 2001 Jun; 

73(6):1147S-51S. Not relevant to key questions 

1766. Saavedra JM, Perman JA. Current concepts in lactose malabsorption and intolerance. Annu 

Rev Nutr 1989; 9:475-502. Not relevant to key questions 

1767. Sacerdote C, Guarrera S, Smith GD, et al. Lactase persistence and bitter taste response: 

instrumental variables and mendelian randomization in epidemiologic studies of dietary 

factors and cancer risk. Am J Epidemiol 2007 Sep 1; 166(5):576-81. Not relevant to key 

questions 

1768. Sadre M, Ghassemi H. Milk intolerance among Iranian school children. J Trop Pediatr 

1981 Dec; 27(6):312-4. Not relevant to key questions 

1769. Sadre M, Karbasi K. Lactose intolerance in Iran. American Journal of Clinical Nutrition 

1979 Sep; 32(9):1948-54. Ineligible number of subjects 

1770. Sahi T. Lactose malabsorption in Finnish-speaking and Swedish-speaking populations in 

Finland. Scand J Gastroenterol 1974; 9(3):303-8. Not relevant to key questions 

1771. Sahi T. The inheritance of selective adult-type lactose malabsorption. Scand J 

Gastroenterol Suppl 1974; 30:1-73. Not relevant to key questions 

1772. Sahi T. Intestinal lactase polymorphisms and dairy foods. Hum Genet Suppl 1978; (1):115­

23. Not relevant to key questions 

1773. Sahi T. Genetics and epidemiology of adult-type hypolactasia. Scandinavian Journal of 

Gastroenterology - Supplement 1994; 202:7-20. Not original research 

284
 
1774. Sahi T, Isokoski M, Jussila J, et al. Population surveys of lactose malabsorption. 

Preliminary report. Acta Sociomed Scand 1970; 2(2):161-5. Not relevant to key questions 

1775. Sahi T, Isokoski M, Jussila J, et al. Lactose malabsorption in Finnish children of school 

age. Acta Paediatr Scand 1972 Jan; 61(1):11-6. Not relevant to key questions 

1776. Sahi T, Isokoski M, Jussila J, et al. Recessive inheritance of adult-type lactose 

malabsorption. Lancet 1973 Oct 13; 2(7833):823-6. Not relevant to key questions 

1777. Sahi T, Jussila J, Penttila IM, et al. Serum lipids and proteins in lactose malabsorption. Am 

J Clin Nutr 1977 Apr; 30(4):476-81. Not relevant to key questions 

1778. Sahi T, Launiala K. More evidence for the recessive inheritance of selective adult type 

lactose malabsorption. Gastroenterology 1977 Aug; 73(2):231-2. Ineligible number of 

subjects 

1779. Sahi T, Launiala K. Manifestation and occurrence of selective adult-type lactose 

malabsorption in Finnish teenagers. A follow-up study. American Journal of Digestive 

Diseases 1978 Aug; 23(8):699-704. Not original research 

1780. Sahi T, Launiala K, Laitinen H. Hypolactasia in a fixed cohort of young Finnish adults. A 

follow-up study. Scandinavian Journal of Gastroenterology 1983 Oct; 18(7):865-70. Not 

original research 

1781. Sakuraba H, Aoyagi T, Suzuki Y. Galactosialidosis (beta-galactosidase-neuraminidase 

deficiency): a possible role of serine-thiol proteases in the degradation of beta-galactosidase 

molecules. Clin Chim Acta 1982 Nov 10; 125(3):275-82. Not relevant to key questions 

1782. Sakuraba H, Suzuki Y, Fukuoka K, et al. beta-Galactosidase--neuraminidase deficiency. 

Deficiency of a freeze-labile neuraminidase in leukocytes and fibroblasts. J Inherit Metab Dis 

1982; 5(2):79-80. Not relevant to key questions 

1783. Salazar de Sousa J, da Silva A, Pereira MV, et al. Cow's milk protein-sensitive 

enteropathy: number and timing of biopsies for diagnosis. J Pediatr Gastroenterol Nutr 1986 

Mar-Apr; 5(2):207-9. Not relevant to key questions 

285
 
1784. Salazar-Lindo E, Figueroa-Quintanilla D, Caciano MI, et al. Effectiveness and safety of 

Lactobacillus LB in the treatment of mild acute diarrhea in children. Journal of pediatric 

gastroenterology and nutrition Vol 44; 2007: 571-6. Not lactose intolerance 

1785. Salazar-Lindo E, Miranda-Langschwager P, Campos-Sanchez M, et al. Lactobacillus casei 

strain GG in the treatment of infants with acute watery diarrhea: a randomized, double-blind, 

placebo controlled clinical trial [ISRCTN67363048]. BMC Pediatrics 2004 Sep 2; 4:18. No 

prevalence data 

1786. Salminen E, Karonen SL, Salminen S. Blood glucose and plasma insulin responses to fat 

free milk and low-lactose fat free milk in healthy human volunteers. Z Ernahrungswiss 1987 

Mar; 26(1):52-5. Not relevant to key questions 

1787. Salmon PR, Read AE, McCarthy CF. An isotope technique for measuring lactose 

absorption. Gut 1969 Aug; 10(8):685-9. Ineligible number of subjects 

1788. Saltzman JR, Russell RM, Golner B, et al. A randomized trial of Lactobacillus acidophilus 

BG2FO4 to treat lactose intolerance. Am J Clin Nutr 1999 Jan; 69(1):140-6. Not relevant to 

key questions 

1789. Salvioli G, Lugli R, Pradelli JM. Relationships between squalene and cholesterol in bile: 

Effect of ursodeoxycholic acid administration in patients with radiolucent gallstones. Metab 

Clin Exp Vol 33; 1984: 641-5. Not lactose intolerance study 

1790. Sandberg DH. Intolerance to lactose in Negro children. Pediatrics 1970 Oct; 46(4):646. Not 

relevant to key questions 

1791. Sanders ME, Klaenhammer TR. Invited review: the scientific basis of Lactobacillus 

acidophilus NCFM functionality as a probiotic. Journal of dairy science 2001 Feb; 84(2):319­

31. Review 

1792. Sanders SW, Tolman KG, Reitberg DP. Effect of a single dose of lactase on symptoms and 

expired hydrogen after lactose challenge in lactose-intolerant subjects. Clin Pharm 1992 Jun; 

11(6):533-8. Not relevant to key questions 

1793. Sanders T. Good nutrition for the vegetarian mother. Mod Midwife 1994 Apr; 4(4):23-6. 

Not relevant to key questions 

1794. Sanders TA. Growth and development of British vegan children. Am J Clin Nutr 1988 Sep; 

48(3 Suppl):822-5. Not relevant to key questions 

1795. Sanders TA, Key TJ. Blood pressure, plasma renin activity and aldosterone concentrations 

in vegans and omnivore controls. Hum Nutr Appl Nutr 1987 Jun; 41(3):204-11. Not relevant 

to key questions 

1796. Sanders TA, Purves R. An anthropometric and dietary assessment of the nutritional status 

of vegan preschool children. J Hum Nutr 1981 Oct; 35(5):349-57. Not relevant to key 

questions 

1797. Sandhu BK, Isolauri E, Walker-Smith JA, et al. A multicentre study on behalf of the 

European Society of Paediatric Gastroenterology and Nutrition Working Group on Acute 

Diarrhoea. Early feeding in childhood gastroenteritis. Journal of Pediatric Gastroenterology & 

Nutrition 1997 May; 24(5):522-7. No prevalence data 

1798. Sandler RB, Slemenda CW, LaPorte RE, et al. Postmenopausal bone density and milk 

consumption in childhood and adolescence. Am J Clin Nutr 1985 Aug; 42(2):270-4. Not 

eligible outcomes 

1799. Sannolo N, Vajro P, Dioguardi G, et al. Gas chromatographic quantitation of breath 

hydrogen and carbon monoxide for clinical investigation in adults and in children. J 

Chromatogr 1983 Sep 9; 276(2):257-65. Not relevant to key questions 

286
 
1800. Santosham M, Fayad IM, Hashem M, et al. A comparison of rice-based oral rehydration 

solution and "early feeding" for the treatment of acute diarrhea in infants. The Journal of 

pediatrics Vol 116; 1990: 868-75. Not relevant to key questions 

1801. Santosham M, Foster S, Reid R, et al. Role of soy-based, lactose-free formula during 

treatment of acute diarrhea. Pediatrics Vol 76; 1985: 292-8. Not relevant to key questions 

1802. Santosham M, Goepp J, Burns B, et al. Role of a soy-based lactose-free formula in the 

outpatient management of diarrhea. Pediatrics Vol 87; 1991: 619-22. Not relevant to key 

questions 

1803. Sarri K, Linardakis M, Codrington C, et al. Does the periodic vegetarianism of Greek 

Orthodox Christians benefit blood pressure? Prev Med 2007 Apr; 44(4):341-8. Not relevant 

to key questions 

1804. Sasaki Y, Iio M, Kameda H, et al. Measurement of 14C-lactose absorption in the diagnosis 

of lactase deficiency. J Lab Clin Med 1970 Nov; 76(5):824-35. Not relevant to key questions 

1805. Sastre J, Lluch-Bernal M, Quirce S, et al. A double-blind, placebo-controlled oral 

challenge study with lyophilized larvae and antigen of the fish parasite, Anisakis simplex. 

Allergy Vol 55; 2000: 560-4. Not lactose intolerance study 

1806. Sategna-Guidetti C, Cruto E, Capobianco P. Breath hydrogen excretion after lactose and 

whole milk ingestion. A prospective comparison in lactase deficiency. Journal of Clinical 

Gastroenterology 1989 Jun; 11(3):287-9. Ineligible number of subjects 

1807. Savaiano D. Lactose intolerance: a self-fulfilling prophecy leading to osteoporosis? Nutr 

Rev 2003 Jun; 61(6 Pt 1):221-3. Review 

1808. Savaiano DA, Boushey CJ, McCabe GP. Lactose intolerance symptoms assessed by metaanalysis: a grain of truth that leads to exaggeration. J Nutr Vol 136; 2006: 1107-13. Not 

eligible outcomes 

1809. Savaiano DA, Kotz C. Recent advances in the management of lactose intolerance. ASDC J 

Dent Child 1989 May-Jun; 56(3):228-33. Not relevant to key questions 

1810. Savilahti E, Launiala K, Kuitunen P. Jejunal disaccharidases in children with selective IgA 

deficiency. Scand J Gastroenterol 1973; 8(5):417-9. Not relevant to key questions 

1811. Savilahti E, Launiala K, Kuitunen P. Congenital lactase deficiency. A clinical study on 16 

patients. Archives of Disease in Childhood 1983 Apr; 58(4):246-52. Ineligible number of 

subjects 

287
 
1812. Savilahti E, Pelkonen P, Visakorpi JK. IgA deficiency in children. A clinical study with 

special reference to intestinal findings. Arch Dis Child 1971 Oct; 46(249):665-70. Not 

relevant to key questions 

1813. Savino F. Focus on infantile colic. Acta Paediatr 2007 Sep; 96(9):1259-64. Not relevant to 

key questions 

1814. Sawicki W. Pharmacokinetics of verapamil and norverapamil from controlled release 

floating pellets in humans. European Journal of Pharmaceutics & Biopharmaceutics Vol 53; 

2002: 29-35. Not lactose intolerance study 

1815. Scaglione F, Ferrara F, Dugnani S, et al. Immunomodulatory effects of two extracts of 

Panax ginseng C.A. Meyer. Drugs under experimental and clinical research Vol 16; 1990: 

537-42. Not lactose intolerance study 

1816. Schachter EN, Brown S, Lach E, et al. Histamine blocking agents in healthy and asthmatic 

subjects. Chest Vol 82; 1982: 143-7. Not lactose intolerance study 

1817. Schade DS, Eaton RP, George S, et al. Metabolic effects of clofibrate in insulin-dependent 

ketosis-prone diabetic man. Metabolism: clinical and experimental Vol 27; 1978: 461-8. Not 

lactose intolerance study 

1818. Schaefer O. Adverse reactions to drugs and metabolic problems perceived in Northern 

Canadian Indians and Eskimos. Progress in Clinical & Biological Research 1986; 214:77-83. 

No prevalence data 

1819. Scharff L. Recurrent abdominal pain in children: a review of psychological factors and 

treatment. Clinical Psychology Review 1997; 17(2):145-66. Not original research 

1820. Schirru E, Corona V, Usai-Satta P, et al. Genetic testing improves the diagnosis of adult 

type hypolactasia in the Mediterranean population of Sardinia. European Journal of Clinical 

Nutrition 2007 Oct; 61(10):1220-5. Ineligible number of subjects 

1821. Schlimmer P. Formoterol Turbuhaler 6 mug vs. Formoterol Aerolizer 12 mug. Atemwegsund Lungenkrankheiten Vol 26; 2000: 263-8. Not lactose intolerance study 

1822. Schmidt BJ, Costa CVD, Oshiro CGS, et al. [Evaluation of a low lactose formula food in 

children with diahrreic syndrome]. Rev Paul Pediatr Vol 8; 1990: 91-6. Not relevant to key 

questions 

1823. Schmidt P, Freund E, de MC, et al. Bronchodilatory response to three batches of 

fenoterol/ipratropium lactose based powder capsules with different fine particle fractions in 

asthmatic patients [abstract]. European Respiratory Journal. Supplement. Vol 9; 1996: 204s. 

Not lactose intolerance study 

1824. Schmidt W, Schneider T, Heise W, et al. Mucosal abnormalities in microsporidiosis. AIDS 

1997 Nov; 11(13):1589-94. No prevalence data 

288
 
1825. Schneider RE, Corona E, Rosales F, et al. Effect of temperature on the lactose hydrolytic 

capacity of a lactase derived from Kluyveromyces lactis. Am J Clin Nutr 1990 Feb; 

51(2):197-201. Not relevant to key questions 

1826. Schnuth ML. You and your vegetarian patients. RDH 1994 Apr; 14(4):12-4, 6, 8 passim. 

Comment 

1827. Schramm P. [Clinical experiences with collagenase powder on ulcers of different origin]. 

Aktuelle Dermatologie Vol 15; 1989: 146-9. Not lactose intolerance study 

1828. Schrander JJ, Dellevoet JJ, Arends JW, et al. Small intestinal mucosa IgE plasma cells and 

specific anti-cow milk IgE in children with cow milk protein intolerance. Annals of Allergy 

1993 May; 70(5):406-9. Subjects less than 4 years old 

1829. Schrander JJ, Oudsen S, Forget PP, et al. Follow up study of cow's milk protein intolerant 

infants. European Journal of Pediatrics 1992 Oct; 151(10):783-5. No prevalence data 

1830. Schrander JJ, Unsalan-Hooyen RW, Forget PP, et al. [51Cr]EDTA intestinal permeability 

in children with cow's milk intolerance. J Pediatr Gastroenterol Nutr 1990 Feb; 10(2):189-92. 

Not relevant to key questions 

1831. Schrander JJ, van den Bogart JP, Forget PP, et al. Cow's milk protein intolerance in infants 

under 1 year of age: a prospective epidemiological study. European Journal of Pediatrics 

1993 Aug; 152(8):640-4. Subjects less than 4 years old 

1832. Schroeder DJ, Collins WE, Elam GW. Effects of some motion sickness suppressants on 

static and dynamic tracking performance. Aviation, space, and environmental medicine Vol 

56; 1985: 344-50. Not lactose intolerance study 

1833. Schuette SA, Yasillo NJ, Thompson CM. The effect of carbohydrates in milk on the 

absorption of calcium by postmenopausal women. Journal of the American College of 

Nutrition Vol 10; 1991: 132-9. Not eligible outcomes 

1834. Schuh KJ, Schubiner H, Johanson CE. Discrimination of intranasal cocaine. Behavioural 

Pharmacology Vol 11; 2000: 511-5. Not lactose intolerance study 

1835. Schulpis KH, Papassotiriou I, Tsakiris S. 8-hydroxy-2-desoxyguanosine serum 

concentrations as a marker of DNA damage in patients with classical galactosaemia. Acta 

Paediatrica 2006 Feb; 95(2):164-9. Not relevant to key questions 

1836. Schwachman H, Lebenthal E. Letter: Lactose tolerance in children. N Engl J Med 1975 

Aug 7; 293(6):305-6. Not relevant to key questions 

1837. Schwartz RH, Puglese J, Schwartz DM. Use of a short course of prednisone for treating 

middle ear effusion. A double-blind crossover study. The Annals of otology, rhinology & 

laryngology. Supplement Vol 89; 1980: 296-300. Not lactose intolerance study 

289
 
1838. Sciarretta G, Giacobazzi G, Verri A, et al. Hydrogen breath test quantification and clinical 

correlation of lactose malabsorption in adult irritable bowel syndrome and ulcerative colitis. 

Digestive Diseases & Sciences 1984 Dec; 29(12):1098-104. Ineligible number of subjects 

1839. See MC, Birnbaum AH, Schechter CB, et al. Double-blind, placebo-controlled trial of 

famotidine in children with abdominal pain and dyspepsia: global and quantitative 

assessment. Digestive diseases and sciences Vol 46; 2001: 985-92. Not lactose intolerance 

study 

1840. Seetharam B, Perrillo R, Alpers DH. Effect of pancreatic proteases on intestinal lactase 

activity. Gastroenterology 1980 Nov; 79(5 Pt 1):827-32. Not relevant to key questions 

1841. Segall JJ. Hypothesis is lactose a dietary risk factor for ischaemic heart disease?[see 

comment][reprint in Int J Epidemiol. 2008 Dec;37(6):1204-8; discussion 1209-16; PMID: 

18725363]. International Journal of Epidemiology 1980 Sep; 9(3):271-6. Not original 

research 

1842. Segall JJ. Hypothesis is lactose a dietary risk factor for ischaemic heart disease? 

International Journal of Epidemiology 1980 Sep; 9(3):271-6. Duplicate listing 

1843. Segall JJ. Dietary lactose as a possible risk factor for ischaemic heart disease: review of 

epidemiology.[see comment]. International Journal of Cardiology 1994 Oct; 46(3):197-207. 

Not original research 

1844. Segall JJ. Digestive and nutritional factors may explain lower prevalence of coronary 

disease in indigenous peoples. BMJ 2003 Aug 23; 327(7412):449-50. No prevalence data 

1845. Senewiratne B, Thambipillai S, Perera H. Intestinal lactase deficiency in Ceylon (Sri 

Lanka). Gastroenterology 1977 Jun; 72(6):1257-9. Not eligible test for lactose malabsorption 

1846. Seppanen S, Niittynen L, Poussa T, et al. Removing lactose from milk does not delay 

bowel function or harden stool consistency in lactose-tolerant women. European journal of 

clinical nutrition 2008 Jun; 62(6):727-32. Not relevant to key questions 

1847. Seppo L, Tuure T, Korpela R, et al. Can primary hypolactasia manifest itself after the age 

of 20 years? A two-decade follow-up study. Scandinavian Journal of Gastroenterology 2008; 

43(9):1082-7. No prevalence data 

1848. Seriki O, Adcock KJ. Lactose intolerance in infancy as a cuase for failure to thrive. West 

Afr Med J Niger Pract 1968 Feb; 17(1):14-6. Not relevant to key questions 

1849. Sethi SK, Khuffash FA, al-Nakib W. Microbial etiology of acute gastroenteritis in 

hospitalized children in Kuwait. Pediatric Infectious Disease Journal 1989 Sep; 8(9):593-7. 

No prevalence data 

1850. Sewell AC. Simple laboratory determination of excess oligosacchariduria. Clin Chem 1981 

Feb; 27(2):243-5. Not relevant to key questions 

290
 
1851. Sewell AC. The simple detection of neuraminic acid-containing urinary oligosaccharides in 

patients with glycoprotein storage diseases. J Inherit Metab Dis 1983; 6(4):153-7. Not 

relevant to key questions 

1852. Sewell AC, Gehler J, Spranger J. Urinary oligosaccharide screening in patients with betagalactosidase deficiency. Eur J Pediatr 1980 May; 133(3):269-71. Not relevant to key 

questions 

1853. Shah KA, Needham TE. Correlation of urinary excretion with in vitro dissolution using 

several dissolution methods for hydrochlorothiazide formulations. J Pharm Sci Vol 68; 1979: 

1486-90. Not lactose intolerance study 

1854. Shahani KM, Chandan RC. Nutritional and healthful aspects of cultured and culturecontaining dairy foods. J Dairy Sci 1979 Oct; 62(10):1685-94. Not relevant to key questions 

1855. Shakur BH, Kemhadjian EL, Myers JD, et al. Minimum dose of inhaled lactose sensed by 

asthmatic patients. American Journal of Respiratory and Critical Care Medicine Vol 157; 

1998: A637. Not lactose intolerance study 

1856. Shane AL. Applications of probiotics for neonatal enteric diseases. J Perinat Neonatal Nurs 

2008 Jul-Sep; 22(3):238-43. Not relevant to key questions 

1857. Sharma AD. Disulfiram and low nickel diet in the management of hand eczema: a clinical 

study. Indian journal of dermatology, venereology and leprology Vol 72; 2006: 113-8. Not 

lactose intolerance study 

1858. Shatin R. Evolution and lactase deficiency. Gastroenterology 1968 May; 54(5):992. Not 

relevant to key questions 

1859. Shaw AD, Davies GJ. Lactose intolerance: problems in diagnosis and treatment. J Clin 

Gastroenterol 1999 Apr; 28(3):208-16. Not relevant to key questions 

1860. Sheih YH, Chiang BL, Wang LH, et al. Systemic immunity-enhancing effects in healthy 

subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus 

HN001. Journal of the American College of Nutrition Vol 20; 2001: 149-56. Not lactose 

intolerance study 

1861. Sheppard D, Nadel JA, Boushey HA. Inhibition of sulfur dioxide-induced 

bronchoconstriction by disodium cromoglycate in asthmatic subjects. The American review 

of respiratory disease Vol 124; 1981: 257-9. Not lactose intolerance study 

1862. Shermak MA, Saavedra JM, Jackson TL, et al. Effect of yogurt on symptoms and kinetics 

of hydrogen production in lactose-malabsorbing children. Am J Clin Nutr 1995 Nov; 

62(5):1003-6. Not relevant to key questions 

1863. Sherr HP. When diarrhea persists. Med Times 1980 Aug; 108(8):76-89. Not relevant to key 

questions 

1864. Shibata Y, Yamamoto Y, Fujii M, et al. A novel method for predicting disintegration time 

in the mouth of rapidly disintegrating tablet by compaction analysis using TabAll. Chemical 

& pharmaceutical bulletin Vol 52; 2004: 1394-5. Not lactose intolerance study 

291
 
1865. Shimomura Y, Maeda K, Nagasaki M, et al. Attenuated response of the serum triglyceride 

concentration to ingestion of a chocolate containing polydextrose and lactitol in place of 

sugar. Bioscience, biotechnology, and biochemistry Vol 69; 2005: 1819-23. Not lactose 

intolerance study 

1866. Shiner M. Ultrastructural features of allergic manifestations in the small intestine of 

children. Scand J Gastroenterol Suppl 1981; 70:49-64. Not relevant to key questions 

1867. Shishehbor F, Roche HM, Gibney MJ. The effect of acute carbohydrate load on the 

monophasic or biphasic nature of the postprandial lipaemic response to acute fat ingestion in 

human subjects. The British journal of nutrition Vol 80; 1998: 411-8. Not lactose intolerance 

study 

1868. Shore L. Disodium cromoglycate (Rynacrom) in the treatment of nasal allergy in children. 

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde Vol 46; 1972: 

279-81. Not lactose intolerance study 

1869. Shows TB, Mueller OT, Honey NK, et al. Genetic heterogeneity of I-cell disease is 

demonstrated by complementation of lysosomal enzyme processing mutants. Am J Med 

Genet 1982 Jul; 12(3):343-53. Not relevant to key questions 

1870. Shrier I, Szilagyi A, Correa JA. Impact of lactose containing foods and the genetics of 

lactase on diseases: an analytical review of population data. Nutrition & Cancer 2008 MayJun; 60(3):292-300. Not original research 

1871. Shulman, R J, Schanler, et al. Early feeding in preterm infants increases lactase activity. 

Pediatric Research Vol 39; 1996: 320a. Not eligible target population 

1872. Shulman RJ, Feste A, Ou C. Absorption of lactose, glucose polymers, or combination in 

premature infants. The Journal of pediatrics Vol 127; 1995: 626-31. Not relevant to key 

questions 

1873. Shulman RJ, Lifschitz CH, Langston C, et al. Human milk and the rate of small intestinal 

mucosal recovery in protracted diarrhea. The Journal of pediatrics Vol 114; 1989: 218-24. 

Not relevant to key questions 

1874. Shulman RJ, Schanler RJ, Lau C, et al. Early feeding, feeding tolerance, and lactase 

activity in preterm infants. Journal of Pediatrics 1998 Nov; 133(5):645-9. No prevalence data 

1875. Shulman RJ, Wong WW, Smith EO. Influence of changes in lactase activity and smallintestinal mucosal growth on lactose digestion and absorption in preterm infants. American 

Journal of Clinical Nutrition 2005 Feb; 81(2):472-9. Ineligible number of subjects 

1876. Shuster S, Marks J. Dermatitis herpetiformis and the coeliac syndrome. Proc R Soc Med 

1969 Oct; 62(10):985-6. Not relevant to key questions 

292
 
1877. Shwachman H, Lloyd-Still JD, Khaw KT, et al. Protracted diarrhea of infancy treated by 

intravenous alimentation. II. Studies of small intestinal biopsy results. American Journal of 

Diseases of Children 1973 Mar; 125(3):365-8. Subjects less than 4 years old 

1878. Sicherer SH. I've always thought I was allergic to milk, but now I'm told that I have a food 

intolerance, not an allergy. What's the difference? Health News 2002 Jun; 8(6):12. Not 

relevant to key questions 

1879. Siegel M, Krantz B, Lebenthal E. Effect of fat and carbohydrate composition on the gastric 

emptying of isocaloric feedings in premature infants. Gastroenterology Vol 89; 1985: 785-90. 

Not relevant to key questions 

1880. Siener R, Hesse A. Influence of a mixed and a vegetarian diet on urinary magnesium 

excretion and concentration. Br J Nutr 1995 May; 73(5):783-90. Not eligible outcomes 

1881. Sill V, Bartuschka B, Villiger B, et al. [Changes in specific airway resistance after powder 

inhalation of formoterol or salmeterol in moderate bronchial asthma]. Pneumologie (Stuttgart, 

Germany) Vol 53; 1999: 4-9. Not lactose intolerance study 

1882. Silvennoinen J, Lamberg-Allardt C, Karkkainen M, et al. Dietary calcium intake and its 

relation to bone mineral density in patients with inflammatory bowel disease. Journal of 

internal medicine 1996 Nov; 240(5):285-92. Not eligible target population 

1883. Silverman M, Connolly NM, Balfour-Lynn L, et al. Long-term trial of disodium 

cromoglycate and isoprenaline in children with asthma. British medical journal Vol 3; 1972: 

378-81. Not lactose intolerance study 

1884. Silvestre MA, Morbach CA, Brans YW, et al. A prospective randomized trial comparing 

continuous versus intermittent feeding methods in very low birth weight neonates. The 

Journal of pediatrics Vol 128; 1996: 748-52. Not lactose intolerance study 

1885. Simakachorn N, Tongpenyai Y, Tongtan O, et al. Randomized, double-blind clinical trial 

of a lactose-free and a lactose-containing formula in dietary management of acute childhood 

diarrhea. Journal of the Medical Association of Thailand = Chotmaihet thangphaet Vol 87; 

2004: 641-9. Not eligible target population 

1886. Simila S, Kokkonen J, Kouvalainen K. Use of lactose-hydrolyzed human milk in 

congenital lactase deficiency. J Pediatr 1982 Oct; 101(4):584-5. Not relevant to key questions 

1887. Simons FE. A comparison of beclomethasone, salmeterol, and placebo in children with 

asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. The 

New England journal of medicine Vol 337; 1997: 1659-65. Not lactose intolerance study 

1888. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in 

biological and cultural interrelations. I. Review of the medical research. Am J Dig Dis 1969 

Dec; 14(12):819-36. Not relevant to key questions 

293
 
1889. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biologic 

and cultural interrelations. II. A culture historical hypothesis. Am J Dig Dis 1970 Aug; 

15(8):695-710. Not relevant to key questions 

1890. Simoons FJ. Progress report. New light on ethnic differences in adult lactose intolerance. 

Am J Dig Dis 1973 Jul; 18(7):595-611. Not relevant to key questions 

1891. Simoons FJ. The geographic hypothesis and lactose malabsorption. A weighing of the 

evidence. American Journal of Digestive Diseases 1978 Nov; 23(11):963-80. Not original 

research 

1892. Simoons FJ. A geographic approach to senile cataracts: possible links with milk 

consumption, lactase activity, and galactose metabolism. Digestive Diseases & Sciences 1982 

Mar; 27(3):257-64. No prevalence data 

1893. Simoons FJ, Johnson JD, Kretchmer N. Perspective on milk-drinking and malabsorption of 

lactose. Pediatrics 1977 Jan; 59(1):98-108. Not relevant to key questions 

1894. Sipski M, Alexander C, Guo X, et al. Cardiovascular effects of sildenafil in men with SCIs 

at and above T6. Topics in Spinal Cord Injury Rehabilitation Vol 8; 2003: 26-34. Not lactose 

intolerance study 

1895. Skala I, Lamacova V. Diets in lactose intolerance. Nutr Metab 1971; 13(3):200-6. Review 

1896. Skala I, Lamacova V, Pirk F. Lactose-free milk as a solution of problems associated with 

dietetic treatment of lactose intolerance. Digestion 1971; 4(6):326-32. Not relevant to key 

questions 

1897. Skogsdal Y, Eriksson M, Schollin J. Analgesia in newborns given oral glucose. Acta 

paediatrica (Oslo, Norway : 1992) Vol 86; 1997: 217-20. Not lactose intolerance study 

1898. Skovbjerg H, Gudmand-Hoyer E, Fenger HJ. Immunoelectrophoretic studies on human 

small intestinal brush border proteins--amount of lactase protein in adult-type hypolactasia. 

Gut 1980 May; 21(5):360-4. Not relevant to key questions 

1899. Slapke J, Hummel S, Wischnewsky GG, et al. Protease inhibitor prevents 

bronchoconstriction in man. European journal of respiratory diseases Vol 68; 1986: 29-34. 

Not lactose intolerance study 

1900. Smith A, Sturgess W, Rich N, et al. The effects of idazoxan on reaction times, eye 

movements and the mood of healthy volunteers and patients with upper respiratory tract 

illnesses. Journal of psychopharmacology (Oxford, England) Vol 13; 1999: 148-51. Not 

lactose intolerance study 

1901. Smith AH, Pearce NE, Joseph JG. Major colorectal cancer aetiological hypotheses do not 

explain mortality trends among Maori and non-Maori New Zealanders. Int J Epidemiol 1985 

Mar; 14(1):79-85. Not eligible outcomes 

1902. Smith AM. Veganism and osteoporosis: a review of the current literature. Int J Nurs Pract 

2006 Oct; 12(5):302-6. Review 

1903. Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int 

J Epidemiol 2004 Feb; 33(1):30-42. Review 

1904. Smith TC. That villain milk. T. C. G. Smith, MB, ChB, describes the problem of milk 

intolerance in babies. Nurs Mirror Midwives J 1976 Apr 22; 142(17):67-8. Not relevant to 

key questions 

1905. Smith TM, Kolars JC, Savaiano DA, et al. Absorption of calcium from milk and yogurt. 

American Journal of Clinical Nutrition 1985 Dec; 42(6):1197-200. No prevalence data 

1906. Snook CR, Mahmoud JN, Chang WP. Lactose tolerance in adult Jordanian Arabs. Trop 

Geogr Med 1976 Dec; 28(4):333-5. Not relevant to key questions 

294
 
1907. Soenarto Y, Suprapto, Sutrisno DS, et al. Milk lactose: the amount tolerated in post 

diarrheal children. J Trop Pediatr Environ Child Health 1979 Aug; 25(4):104-6. Not relevant 

to key questions 

1908. Soeparto P, Noerasid H, Subianto, et al. Disaccharide intolerance in infants during the 

diarrheal stage of acute gastroenteritis. Paediatr Indones 1977 May-Jun; 17(5-6):161-7. Not 

relevant to key questions 

1909. Soeparto P, Stobo E, Walker-Smith JA. Stool chromatography for sugar in children with 

diarrhoea. Gut 1970 Nov; 11(11):980. Not relevant to key questions 

1910. Soeparto P, Subijanto MS, Noerasid H. Prolonged diarrhoea following acute gastro 

enteritis. Paediatr Indones 1982 May-Jun; 22(5-6):83-8. Not relevant to key questions 

1911. Soeparto P, Subijanto MS, Satjadibrata K. Low lactose milk (L.L.M.) on refeeding infants 

with gastroenteritis. Paediatr Indones 1977 Mar-Apr; 17(3-4):85-94. Not relevant to key 

questions 

1912. Solomons NW. The hydrogen breath test and gastrointestinal disorders. Compr Ther 1981 

Aug; 7(8):7-15. Not relevant to key questions 

1913. Solomons NW, Barillas C. The cut-off criterion for a positive hydrogen breath test in 

children: a reappraisal. Journal of Pediatric Gastroenterology & Nutrition 1986 Nov-Dec; 

5(6):920-5. No prevalence data 

1914. Solomons NW, Garcia-Ibanez R, Viteri FE. Reduced rate of breath hydrogen excretion 

with lactose tolerance tests in young children using whole milk. Am J Clin Nutr 1979 Apr; 

32(4):783-6. Not relevant to key questions 

1915. Solomons NW, Garcia-Ibanez R, Viteri FE. Hydrogen breath test of lactose absorption in 

adults: the application of physiological doses and whole cow's milk sources. Am J Clin Nutr 

1980 Mar; 33(3):545-54. Not relevant to key questions 

1916. Solomons NW, Garcia-Ibañez R, Viteri FE. Reduced rate of breath hydrogen excretion 

with lactose tolerance tests in young children using whole milk. The American journal of 

clinical nutrition Vol 32; 1979: 783-6. Not relevant to key questions 

1917. Solomons NW, Guerrero AM, Torun B. Effective in vivo hydrolysis of milk lactose by 

beta-galactosidases in the presence of solid foods. Am J Clin Nutr 1985 Feb; 41(2):222-7. 

Not relevant to key questions 

295
 
1918. Solomons NW, Guerrero AM, Torun B. Dietary manipulation of postprandial colonic 

lactose fermentation: II. Addition of exogenous, microbial beta-galactosidases at mealtime. 

Am J Clin Nutr 1985 Feb; 41(2):209-21. Not relevant to key questions 

1919. Solomons NW, Guerrero AM, Torun B. Dietary manipulation of postprandial colonic 

lactose fermentation: I. Effect of solid foods in a meal. Am J Clin Nutr 1985 Feb; 41(2):199­

208. Not relevant to key questions 

1920. Solomons NW, Rosenthal A. Intestinal metabolism of a random-bonded polyglucose 

bulking agent in humans: In vitro and in vivo studies of hydrogen evolution. J. Lab. Clin. 

Med. Vol 105; 1985: 585-92. Not relevant to key questions 

1921. Solomons NW, Torun B, Caballero B, et al. The effect of dietary lactose on the early 

recovery from protein-energy malnutrition. I. Clinical and anthropometric indices. Am J Clin 

Nutr 1984 Sep; 40(3):591-600. Not relevant to key questions 

1922. Solomons NW, Viteri F, Rosenberg IH. Development of an interval sampling hydrogen 

(H2) breath test for carbohydrate malabsorption in children: evidence for a circadian pattern 

of breath H2 concentration. Pediatr Res 1978 Aug; 12(8):816-23. Not relevant to key 

questions 

1923. Solomons NW, Viteri FE, Hamilton LH. Application of a simple gas chromatographic 

technique for measuring breath hydrogen. J Lab Clin Med 1977 Nov; 90(5):856-62. Not 

relevant to key questions 

1924. Somayaji BN. Functional and metabolic effects of vagotomy and pyloroplasty. Q J Med 

1970 Jul; 39(155):441-60. Not relevant to key questions 

1925. Soontornchai S, Sirichakwal P, Puwastien P, et al. Lactitol tolerance in healthy Thai adults. 

European Journal of Nutrition 1999 Oct; 38(5):218-26. Ineligible number of subjects 

1926. Southgate DA, Barrett IM. The intake and excretion of calorific constituents of milk by 

babies. The British journal of nutrition Vol 20; 1966: 363-72. Not relevant to key questions 

1927. Sowers MF, Winterfeldt E. Lactose intolerance among Mexican Americans. Am J Clin 

Nutr 1975 Jul; 28(7):704-5. Not relevant to key questions 

1928. Spanidou EP, Petrakis NL. Lactose intolerance in Greeks. Lancet 1972 Oct 21; 

2(7782):872-3. Not relevant to key questions 

1929. Sparks JW, Avery GB, Fletcher AB, et al. Parenteral galactose therapy in the glucoseintolerant premature infant. The Journal of pediatrics Vol 100; 1982: 255-9. Not lactose 

intolerance study 

1930. Specker BL. Nutritional concerns of lactating women consuming vegetarian diets. Am J 

Clin Nutr 1994 May; 59(5 Suppl):1182S-6S. Not eligible target population 

1931. Specker BL, Tsang RC, Ho M, et al. Effect of vegetarian diet on serum 1,25­

dihydroxyvitamin D concentrations during lactation. Obstet Gynecol 1987 Dec; 70(6):870-4. 

Not eligible outcomes 

296
 
1932. Spencer J, Welbourn RB. Milk intolerance following gastric operations with special 

reference to lactase deficiency. Br J Surg 1968 Apr; 55(4):261-4. Not relevant to key 

questions 

1933. Sperotto G, Barison EM, Baldacci ER, et al. Use of undiluted whole cow's milk is effective 

for the routine treatment of children with acute diarrhea and severe dehydration. Arq 

Gastroenterol Vol 35; 1998: 132-7. Not relevant to key questions 

1934. Spicher T, Orgül S, Gugleta K, et al. The effect of losartan potassium on choroidal 

hemodynamics in healthy subjects. Journal of glaucoma Vol 11; 2002: 177-82. Not lactose 

intolerance study 

1935. Spollett GR. Nutritional management of common gastrointestinal problems. Nurse 

practitioner forum 1994 Mar; 5(1):24-7. Not relevant to key questions 

1936. Spoor TC, Hammer M, Belloso H. Traumatic hyphema. Failure of steroids to alter its 

course: a double-blind prospective study. Archives of ophthalmology Vol 98; 1980: 116-9. 

Not lactose intolerance study 

1937. Srinivasan R, Minocha A. When to suspect lactose intolerance. Symptomatic, ethnic, and 

laboratory clues. Postgraduate Medicine 122-3, 1998 Sep; 104(3):109-11. Not original 

research 

1938. St James-Roberts I. Infant crying and sleeping: helping parents to prevent and manage 

problems. Primary Care; Clinics in Office Practice 2008 viii; Sep; 35(3):547-67. Review 

1939. Ståhlberg MR, Savilahti E. Infantile colic and feeding. Archives of disease in childhood 

Vol 61; 1986: 1232-3. Not relevant to key questions 

1940. Stallings VA. Calcium and bone health in children: a review. Am J Ther 1997 Jul-Aug; 

4(7-8):259-73. Review 

1941. Stanfield JP. The diarrhoea--malnutrition circle. J Trop Pediatr Afr Child Health 1966 Dec; 

12(3):53-4. Not relevant to key questions 

1942. Stanley ED, Jackson GG, Dirda VA, et al. Effect of a topical interferon inducer on 

rhinovirus infections in volunteers. The Journal of infectious diseases Vol 133; 1976: A121­

7. Not lactose intolerance study 

1943. Stanton C, Gardiner G, Meehan H, et al. Market potential for probiotics. Am J Clin Nutr 

2001 Feb; 73(2 Suppl):476S-83S. Not relevant to key questions 

1944. Steen KH, Reeh PW, Kreysel HW. Topical acetylsalicylic, salicylic acid and indomethacin 

suppress pain from experimental tissue acidosis in human skin. Pain Vol 62; 1995: 339-47. 

Not lactose intolerance study 

1945. Steen LSL, Southard KA, Law AS, et al. An evaluation of preoperative ibuprofen for 

treatment of pain associated with orthodontic separator placement. American journal of 

orthodontics and dentofacial orthopedics : official publication of the American Association of 

Orthodontists, its constituent societies, and the American Board of Orthodontics Vol 118; 

2000: 629-35. Not lactose intolerance study 

297
 
1946. Stegmann H, Kindermann W. Comparison of prolonged exercise tests at the individual 

anaerobic threshold and the fixed anaerobic threshold of 4 mmol.l(-1) lactate. International 

journal of sports medicine Vol 3; 1982: 105-10. Not lactose intolerance study 

1947. Stemmermann GN, Nomura A, Chyou PH. The influence of dairy and nondairy calcium on 

subsite large-bowel cancer risk. Dis Colon Rectum 1990 Mar; 33(3):190-4. Not eligible 

exposure 

1948. Stenström B. Oral contraception using a sequential method. A clinical investigation. Acta 

obstetricia et gynecologica Scandinavica Vol 47; 1968: 443-50. Not lactose intolerance study 

1949. Stephenson LS. Helminth parasites, a major factor in malnutrition. World Health Forum 

1994; 15(2):169-72. No prevalence data 

1950. Stephenson LS, Latham MC. Rapid and portable methods of lactose tolerance test 

administration. Am J Clin Nutr 1975 Aug; 28(8):888-93. Not relevant to key questions 

1951. Stephenson LS, Latham MC. Letter: Lactose tolerance tests as a predictor of milk 

tolerance. Am J Clin Nutr 1975 Feb; 28(2):86-8. Not relevant to key questions 

1952. Stephenson LS, Latham MC, Jones DV. Milk consumption by black and by white pupils in 

two primary schools. J Am Diet Assoc 1977 Sep; 71(3):258-62. Not relevant to key questions 

1953. Sterchi EE, Mills PR, Fransen JA, et al. Biogenesis of intestinal lactase-phlorizin hydrolase 

in adults with lactose intolerance. Evidence for reduced biosynthesis and slowed-down 

maturation in enterocytes. J Clin Invest 1990 Oct; 86(4):1329-37. Not relevant to key 

questions 

1954. Sterky G, Freij L, Gobezi A, et al. Milk intolerance in young Ethiopian school children. 

Ethiop Med J 1973 Jan; 11(1):25-32. Not relevant to key questions 

1955. Stoopler M, Frayer W, Alderman MH. Prevalence and persistence of lactose malabsorption 

among young jamaican children. American Journal of Clinical Nutrition 1974 Jul; 27(7):728­

32. Subjects less than 4 years old 

1956. Storer EH. Postvagotomy diarrhea. Surg Clin North Am 1976 Dec; 56(6):1461-8. Not 

relevant to key questions 

1957. Stott JR, Barnes GR, Wright RJ, et al. The effect on motion sickness and oculomotor 

function of GR 38032F, a 5-HT3-receptor antagonist with anti-emetic properties. British 

journal of clinical pharmacology Vol 27; 1989: 147-57. Not lactose intolerance study 

1958. Strand FT. Primary prevention of insulin-dependent diabetes mellitus: simple approaches 

using thermal modification of milk. Med Hypotheses 1994 Feb; 42(2):110-4. Not relevant to 

key questions 

1959. Strandhagen E, Lia A, Lindstrand S, et al. Fermented milk (ropy milk) replacing regular 

milk reduces glycemic response and gastric emptying in healthy subjects. Scand. J. Nutr. 

Naringsforsk. Vol 38; 1994: 117-21. Not relevant to key questions 

298
 
1960. Stratiki Z, Costalos C, Sevastiadou S, et al. The effect of a bifidobacter supplemented 

bovine milk on intestinal permeability of preterm infants. Early human development Vol 83; 

2007: 575-9. Not lactose intolerance 

1961. Strisciuglio P, Creek KE, Sly WS. Complementation, cross correction, and drug correction 

studies of combined beta-galactosidase neuraminidase deficiency in human fibroblasts. 

Pediatr Res 1984 Feb; 18(2):167-71. Not relevant to key questions 

1962. Strocchi A, Corazza GR, Anania C, et al. Quality control study of H2 breath testing for the 

diagnosis of carbohydrate malabsorption in Italy. The "Tenue Club" Group.[see comment]. 

Italian Journal of Gastroenterology & Hepatology 1997 Apr; 29(2):122-7. No prevalence data 

1963. Stryker JA, Bartholomew M. Failure of lactose-restricted diets to prevent radiation-induced 

diarrhea in patients undergoing whole pelvis irradiation. Int J Radiat Oncol Biol Phys 1986 

May; 12(5):789-92. Not relevant to key questions 

1964. Suarez F, Levitt M. Assessing food intolerance: don't lose control. Gut 1997 Nov; 

41(5):715-6. Not relevant to key questions 

1965. Suarez FL, Savaiano DA. Lactose digestion and tolerance in adult and elderly AsianAmericans. Am J Clin Nutr 1994 May; 59(5):1021-4. Not relevant to key questions 

1966. Suarez FL, Savaiano DA, Levitt MD. Review article: the treatment of lactose intolerance. 

Aliment Pharmacol Ther 1995 Dec; 9(6):589-97. Not relevant to key questions 

1967. Suarez FL, Springfield J, Furne JK, et al. Gas production in human ingesting a soybean 

flour derived from beans naturally low in oligosaccharides. The American journal of clinical 

nutrition Vol 69; 1999: 135-9. Not lactose intolerance study 

1968. Suarez FL, Zumarraga LM, Furne JK, et al. Nutritional supplements used in weightreduction programs increase intestinal gas in persons who malabsorb lactose. J Am Diet 

Assoc 2001 Dec; 101(12):1447-52. Not relevant to key questions 

1969. Sudarmo SM, Ranuh RG, Rochim A, et al. Management of infant diarrhea with highlactose probiotic-containing formula. The Southeast Asian journal of tropical medicine and 

public health Vol 34; 2003: 845-8. Not eligible target population 

1970. Suharjono. Intestinal biopsy and coeliac disease. Paediatrica Indonesiana 1971 May-Jun; 

11(3):116-34. No prevalence data 

1971. Suharjono, Sunoto, Budiarso A, et al. Lactose malabsorption in "healthy" Indonesian preschool children. Paediatr Indones 1971 Nov-Dec; 11(6):251-4. Not relevant to key questions 

1972. Sullivan PB. Food allergy and food intolerance in childhood. Indian Journal of Pediatrics 

1999; 66(1 Suppl):S37-45. No prevalence data 

299
 
1973. Sun HM, Qiao YD, Chen F, et al. The lactase gene -13910T allele can not predict the 

lactase-persistence phenotype in north China. Asia Pac J Clin Nutr 2007; 16(4):598-601. Not 

relevant to key questions 

1974. Sun QQ, Xu SS, Pan JL, et al. Huperzine-A capsules enhance memory and learning 

performance in 34 pairs of matched adolescent students. Zhongguo yao li xue bao = Acta 

pharmacologica Sinica Vol 20; 1999: 601-3. Not lactose intolerance study 

1975. Sung YF, Kutner MH, Cerine FC, et al. Comparison of the effects of acupuncture and 

codeine on postoperative dental pain. Anesthesia and analgesia Vol 56; 1977: 473-8. Not 

lactose intolerance study 

1976. Sungkapalee T, Puntukosit P, Eunsuwan O, et al. Incidence and clinical manifestations of 

rotavirus infection among children with acute diarrhea admitted at Buri Ram Hospital, 

Thailand. Southeast Asian J Trop Med Public Health 2006 Nov; 37(6):1125-31. Not relevant 

to key questions 

1977. Sunoto, Suharjono, Lembong CM, et al. Lactose loading test on protein calorie 

malnutrition. Paediatr Indones 1973 Feb; 13(2):43-8. Not relevant to key questions 

1978. Sunoto, Suharjono, Mangiwa J, et al. Lactose intolerance in chronic diarrhea among 

Indonesian children. Paediatr Indones 1971 Sep-Oct; 11(5):1-6. Not relevant to key questions 

1979. Sunoto S, Sutedjo. Two years study on sugar intolerance in Indonesian children. Paediatr 

Indones 1973 Sep-Oct; 13(9):241-9. Not relevant to key questions 

1980. Sureda A, Batle JM, Tauler P, et al. Vitamin C supplementation influences the antioxidant 

response and nitric oxide handling of erythrocytes and lymphocytes to diving apnea. 

European journal of clinical nutrition Vol 60; 2006: 838-46. Not lactose intolerance study 

1981. Surjone A, Sebodo T, Sunarto J, et al. Lactose intolerance among healthy adults. Paediatr 

Indones 1973 Feb; 13(2):49-54. Not relevant to key questions 

1982. Surjono A, Surjantoro, Sadjimin T, et al. Lactose tolerance test on Indonesian newborn 

infants. Paediatr Indones 1973 Jan; 13(1):11-6. Not relevant to key questions 

1983. Sussman S, Grossman M, Magoffin R, et al. Dexamethasone (16 alpha methyl, 9 alpha 

fluoroprednisolone) in obstructive respiratory tract infections in children. Pediatrics Vol 34; 

1964: 851-5. Not lactose intolerance study 

1984. Sutanto AH, Sa'at R, Siregar H. Steatorrhoea in acute enteritis. Paediatr Indones 1982 NovDec; 22(11-12):217-21. Not relevant to key questions 

1985. Sutedjo. Cow's milk (lactose) intolerance among Indonesian doctors of the Dr. Tjipto 

Mangunkusumo General Hospital and Medical School, University of Indonesia. Paediatr 

Indones 1971 Mar-Apr; 11(2):43-6. Not relevant to key questions 

1986. Suter CB. Letter: Lactose malabsorption. Am J Clin Nutr 1975 Apr; 28(4):308-9. Not 

relevant to key questions 

300
 
1987. Suthutvoravut U, Tontisirin K, Varavithya W, et al. Wheat extract and milk mixture as a 

milk substitute for children with milk intolerance. J Diarrhoeal Dis Res 1984 Sep; 2(3):168­

72. Not relevant to key questions 

1988. Sutnick MR. Vegetarian diets. Prim Care 1975 Jun; 2(2):309-15. Not relevant to key 

questions 

1989. Sutton RE, Hamilton JR. Tolerance of young children with severe gastroenteritis to dietary 

lactose: a controlled study. Can Med Assoc J 1968 Nov 23; 99(20):980-2. Not relevant to key 

questions 

1990. Suzuki K, Tanaka H, Yamanaka T, et al. The specificity of beta-galactosidase in the 

degradation of gangliosides. Adv Exp Med Biol 1980; 125:307-18. Not relevant to key 

questions 

1991. Suzuki Y, Fukuoka K. Neuraminidase in mucolipidoses: normal activity in frozen autopsy 

tissues from three patients with I-cell disease and adult beta-galactosidase deficiency. Clin 

Chim Acta 1979 Dec 3; 99(2):107-12. Not relevant to key questions 

1992. Suzuki Y, Fukuoka K, Sakuraba H, et al. Galatosialidosis (beta-galactosidaseneuraminidase deficiency): clinical and biochemical studies on 13 patients. Adv Exp Med 

Biol 1982; 152:241-51. Not relevant to key questions 

1993. Suzuki Y, Sakuraba H, Hayashi K, et al. Beta-galactosidase-neuraminidase deficiency: 

restoration of beta-galactosidase activity by protease inhibitors. J Biochem 1981 Jul; 

90(1):271-3. Not relevant to key questions 

1994. Svennerholm L. Diagnosis of the sphingolipidoses with labelled natural substrates. Adv 

Exp Med Biol 1978; 101:689-706. Not relevant to key questions 

1995. Svenonius E, Arborelius M, Wiberg R, et al. Prevention of exercise-induced asthma by 

drugs inhaled from metered aerosols. Allergy Vol 43; 1988: 252-7. Not lactose intolerance 

study 

1996. Swagerty DL, Jr., Walling AD, Klein RM. Lactose intolerance. Am Fam Physician 2002 

May 1; 65(9):1845-50. Not relevant to key questions 

1997. Szajewska H, Kantecki M, Albrecht P, et al. Carbohydrate intolerance after acute 

gastroenteritis--a disappearing problem in Polish children. Acta Paediatrica 1997 Apr; 

86(4):347-50. Not original research 

1998. Szilagyi A. Review article: lactose--a potential prebiotic. Aliment Pharmacol Ther 2002 

Sep; 16(9):1591-602. Not relevant to key questions 

1999. Szilagyi A. Redefining lactose as a conditional prebiotic. Canadian Journal of 

Gastroenterology 2004 Mar; 18(3):163-7. Review 

2000. Szilagyi A, Cohen A, Vinokuroff C, et al. Deadaption and readaptation with lactose, but no 

cross-adaptation to lactulose: a case of occult colonic bacterial adaptation. Can J 

Gastroenterol 2004 Nov; 18(11):677-80. Not relevant to key questions 

2001. Szilagyi A, Lerman S, Barr RG, et al. Reversible lactose malabsorption and intolerance in 

Graves' disease. Clin Invest Med 1991 Jun; 14(3):188-97. Not relevant to key questions 

2002. Szilagyi A, Malolepszy P, Hamard E, et al. Comparison of a real-time polymerase chain 

reaction assay for lactase genetic polymorphism with standard indirect tests for lactose 

maldigestion. Clin Gastroenterol Hepatol 2007 Feb; 5(2):192-6. Not relevant to key questions 

2003. Szilagyi A, Malolepszy P, Yesovitch S, et al. Inverse dose effect of pretest dietary lactose 

intake on breath hydrogen results and symptoms in lactase nonpersistent subjects. Dig Dis Sci 

2005 Nov; 50(11):2178-82. Not relevant to key questions 

2004. Szilagyi A, Nathwani U, Vinokuroff C, et al. Evaluation of relationships among national 

301
 
colorectal cancer mortality rates, genetic lactase non-persistence status, and per capita yearly 

milk and milk product consumption. Nutr Cancer 2006; 55(2):151-6. Not eligible outcomes 

2005. Szilagyi A, Nathwani U, Vinokuroff C, et al. The effect of lactose maldigestion on the 

relationship between dairy food intake and colorectal cancer: a systematic review. Nutr 

Cancer 2006; 55(2):141-50. Not eligible outcomes 

2006. Szilagyi A, Rivard J, Fokeeff K. Improved parameters of lactose maldigestion using 

lactulose. Dig Dis Sci 2001 Jul; 46(7):1509-19. Not relevant to key questions 

2007. Szilagyi A, Salomon R, Martin M, et al. Lactose handling by women with lactose 

malabsorption is improved during pregnancy. Clin Invest Med 1996 Dec; 19(6):416-26. Not 

relevant to key questions 

2008. Szilagyi A, Salomon R, Seidman E. Influence of loperamide on lactose handling and oralcaecal transit time. Aliment Pharmacol Ther 1996 Oct; 10(5):765-70. Not relevant to key 

questions 

2009. Szilagyi A, Torchinsky A, Calacone A. Possible therapeutic use of loperamide for 

symptoms of lactose intolerance. Can J Gastroenterol 2000 Jul-Aug; 14(7):581-7. Not 

relevant to key questions 

2010. Szustkiewicz C, Demetriou J. Detection of some clinically important carbohydrates in 

plasma and urine by means of thin-layer chromatography. Clin Chim Acta 1971 May; 

32(3):355-9. Not relevant to key questions 

2011. Tadesse K, Leung DT, Yuen RC. The status of lactose absorption in Hong Kong Chinese 

children. Acta Paediatrica 1992 Aug; 81(8):598-600. Not original research 

2012. Tadesse K, Smith D, Eastwood MA. Breath hydrogen (H2) and methane (CH4) excretion 

patterns in normal man and in clinical practice. Quarterly Journal of Experimental Physiology 

Vol 65; 1980: 85-97. Not relevant to key questions 

2013. Tag CG, Oberkanins C, Kriegshauser G, et al. Evaluation of a novel reverse-hybridization 

StripAssay for typing DNA variants useful in diagnosis of adult-type hypolactasia. Clin Chim 

Acta 2008 Jun; 392(1-2):58-62. Not relevant to key questions 

2014. Taif B. Myths about milk. J Pract Nurs 1975 Nov; 25(11):16-7. Not relevant to key 

questions 

302
 
2015. Tamir I, Levtow O, Dolizki F, et al. Changes in plasma free fatty acid concentration 

following oral lactose tolerance tests as a test for lactose absorption in infants and children. 

Am J Dig Dis 1974 Aug; 19(8):745-50. Not relevant to key questions 

2016. Tamm A. Management of lactose intolerance. Scand J Gastroenterol Suppl 1994; 202:55­

63. Not relevant to key questions 

2017. Tamura A, Shiomi T, Hachiya S, et al. Low activities of intestinal lactase suppress the 

early phase absorption of soy isoflavones in Japanese adults. Clin Nutr 2008 Apr; 27(2):248­

53. Not relevant to key questions 

2018. Tandon R, Mandell H, Spiro HM, et al. Lactose intolerance in Jewish patients with 

ulcerative colitis. Am J Dig Dis 1971 Sep; 16(9):845-8. Not relevant to key questions 

2019. Tandon RK, Goel U, Mukherjee SN, et al. Lactose intolerance during pregnancy in 

different Indian communities. Indian J Med Res 1977 Jul; 66(1):33-8. Not relevant to key 

questions 

2020. Tandon RK, Joshi YK, Singh DS, et al. Lactose intolerance in North and South Indians. 

Am J Clin Nutr 1981 May; 34(5):943-6. Not relevant to key questions 

2021. Tangpricha V, Koutkia P, Rieke SM, et al. Fortification of orange juice with vitamin D: a 

novel approach for enhancing vitamin D nutritional health. The American journal of clinical 

nutrition Vol 77; 2003: 1478-83. Not lactose intolerance study 

2022. Tari MG, Mancino M, Monti G. Immunotherapy by inhalation of allergen in powder in 

house dust allergic asthma--a double-blind study. Journal of investigational allergology & 

clinical immunology : official organ of the International Association of Asthmology 

(INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología Vol 2; 1992: 59­

67. Not lactose intolerance study 

2023. Tarlo SM, Broder I. Tartrazine and benzoate challenge and dietary avoidance in chronic 

asthma. Clinical Allergy Vol 12; 1982: 303-12. Not lactose intolerance study 

2024. Tarshish P, Bernstein J, Tobin JN, et al. Treatment of mesangiocapillary 

glomerulonephritis with alternate-day prednisone--a report of the International Study of 

Kidney Disease in Children. Pediatric nephrology (Berlin, Germany) Vol 6; 1992: 123-30. 

Not lactose intolerance study 

2025. Tasman-Jones C. Medium chain triglycerides in the therapy of small bowel Crohn's 

disease. N Z Med J 1971 Apr; 73(467):214-5. Not relevant to key questions 

2026. Taylan B, Capan Y, Guven O, et al. Design and evaluation of sustained-release and buccal 

adhesive propranolol hydrochloride tablets. Journal of Controlled Release. Vol 38; 1996: 11­

20. Not lactose intolerance study 

2027. Taylor C. Lactose intolerance in infants. Nursing Times 2006 Apr 25-May 1; 102(17):43-4. 

Not original research 

303
 
2028. Taylor C, Hodgson K, Sharpstone D, et al. The prevalence and severity of intestinal 

disaccharidase deficiency in human immunodeficiency virus-infected subjects. Scandinavian 

journal of gastroenterology Vol 35; 2000: 599-606. Not lactose intolerance study 

2029. Taylor D, O'Toole K, Auble T, et al. The psychometric and cardiac effects of 

pseudoephedrine and antihistamines in the hyperbaric environment. South Pacific Underwater 

Medicine Society Journal Vol 31; 2001: 50-7. Not lactose intolerance study 

2030. Taylor HA, Stevenson RE, Parks SE. Beta-galactosidase deficiency: studies of two patients 

with prolonged survival. American Journal of Medical Genetics 1980; 5(3):235-45. Ineligible 

number of subjects 

2031. Teegarden D, Lyle RM, Proulx WR, et al. Previous milk consumption is associated with 

greater bone density in young women. Am J Clin Nutr 1999 May; 69(5):1014-7. not eligible 

outcomes 

2032. Teesalu S, Vihalemm T, Vaasa IO. Nutrition in prevention of osteoporosis. Scandinavian 

Journal of Rheumatology - Supplement 1996 discussion 83; 103:81-2. Not relevant to key 

questions 

2033. Tepper BJ, Trail AC, Shaffer SE. Diet and physical activity in restrained eaters. Appetite 

1996 Aug; 27(1):51-64. Not relevant to key questions 

2034. Terezhalmy GT, Bottomley WK, Pelleu GB. The use of water-soluble bioflavonoidascorbic acid complex in the treatment of recurrent herpes labialis. Oral surgery, oral 

medicine, and oral pathology Vol 45; 1978: 56-62. Not lactose intolerance study 

2035. Terrio K, Auld GW. Osteoporosis knowledge, calcium intake, and weight-bearing physical 

activity in three age groups of women. J Community Health 2002 Oct; 27(5):307-20. Not 

eligible target population 

2036. Tesar R, Notelovitz M, Shim E, et al. Axial and peripheral bone density and nutrient 

intakes of postmenopausal vegetarian and omnivorous women. Am J Clin Nutr 1992 Oct; 

56(4):699-704. Not eligible exposure 

2037. Teuri U, Vapaatalo H, Korpela R. Fructooligosaccharides and lactulose cause more 

symptoms in lactose maldigesters and subjects with pseudohypolactasia than in control 

lactose digesters. Am J Clin Nutr 1999 May; 69(5):973-9. Not relevant to key questions 

2038. Theofilopoulos N, Szabadi E, Bradshaw CM. Comparison of the effects of ranitidine, 

cimetidine and thioridazine on psychomotor functions in healthy volunteers. Br J Clin 

Pharmacol Vol 18; 1984: 135-44. Not lactose intolerance study 

2039. Tholstrup T, Høy CE, Andersen LN, et al. Does fat in milk, butter and cheese affect blood 

lipids and cholesterol differently? Journal of the American College of Nutrition Vol 23; 2004: 

169-76. Not lactose intolerance study 

2040. Thomas E, von Unruh GE, Hesse A. Influence of a low- and a high-oxalate vegetarian diet 

on intestinal oxalate absorption and urinary excretion. Eur J Clin Nutr 2008 Sep; 62(9):1090­

7. Not eligible outcomes 

2041. Thomas FB, Caldwell JH, Greenberger NJ. Steatorrhea in thyrotoxicosis. Relation to 

hypermotility and excessive dietary fat. Ann Intern Med 1973 May; 78(5):669-75. Not 

eligible target population 

2042. Thomas S, Walker-Smith JA, Senewiratne B, et al. Age dependency of the lactase 

persistence and lactase restriction phenotypes among children in Sri Lanka and Britain. 

Journal of Tropical Pediatrics 1990 Apr; 36(2):80-5. Not population based study 

2043. Thompson D, Bailey DM, Hill J, et al. Prolonged vitamin C supplementation and recovery 

from eccentric exercise. European journal of applied physiology Vol 92; 2004: 133-8. Not 

304
 
lactose intolerance study 

2044. Thompson D, Williams C, McGregor SJ, et al. Prolonged vitamin C supplementation and 

recovery from demanding exercise. International journal of sport nutrition and exercise 

metabolism Vol 11; 2001: 466-81. Not lactose intolerance study 

2045. Thompson JR, Sanders I. Lactose-barium small bowel study. Efficacy as a screening 

method. Am J Roentgenol Radium Ther Nucl Med 1971 Oct; 113(2):255-7. Not relevant to 

key questions 

2046. Thompson JR, Sanders I. Lactose-barium small bowel study. Efficacy as a screening 

method. Am J Roentgenol Radium Ther Nucl Med 1972 Oct; 116(2):276-8. Not relevant to 

key questions 

2047. Thompson M, Anderson M. Studies of gastrointestinal blood loss during ibuprofen therapy. 

Rheumatology and physical medicine Vol 10; 1970: Suppl 10:104-7. Not lactose intolerance 

study 

2048. Thompson SJ, Leigh L, Christensen R, et al. Immediate neurocognitive effects of 

methylphenidate on learning-impaired survivors of childhood cancer. Journal of clinical 

oncology : official journal of the American Society of Clinical Oncology Vol 19; 2001: 1802­

8. Not lactose intolerance study 

2049. Thong-Ngam D, Suwangool P, Prempracha J, et al. Lactose intolerance and intestinal villi 

morphology in Thai people. Journal of the Medical Association of Thailand 2001 Aug; 

84(8):1090-6. Ineligible number of subjects 

2050. Thoren P, Wallin A, Whitehead PJ, et al. The effect of different concentrations of lactose 

powder on the airway function of adult asthmatics. Respiratory medicine Vol 95; 2001: 870­

5. Not lactose intolerance study 

2051. Thorne MG, Bradbeer WH. Disodium chromoglycate in the treatment of perennial allergic 

rhinitis. Acta allergologica Vol 27; 1972: 307-20. Not lactose intolerance study 

2052. Tillotson JL, Grandits GA, Bartsch GE, et al. Chapter 10. Relation of dietary carbohydrates 

to blood lipids in the special intervention and usual care groups in the Multiple Risk Factor 

Intervention Trial. American Journal of Clinical Nutrition Vol 65; 1997: 314s-26s. Not 

lactose intolerance study 

305
 
2053. Ting CW, Wu TC, Hwang B. Hydrogen breath test with physiological dose of lactose in 

children and adolescents. J Singapore Paediatr Soc 1987; 29 Suppl 1:170-1. Not relevant to 

key questions 

2054. Tinmouth J, Kandel G, Tomlinson G, et al. The effect of dairy product ingestion on human 

immunodeficiency virus-related diarrhea in a sample of predominantly gay men: a 

randomized, controlled, double-blind, crossover trial. Archives of internal medicine Vol 166; 

2006: 1178-83. Not relevant to key questions 

2055. Tishkoff SA, Reed FA, Ranciaro A, et al. Convergent adaptation of human lactase 

persistence in Africa and Europe. Nat Genet 2007 Jan; 39(1):31-40. Not relevant to key 

questions 

2056. Toaff R, Ashkenazi H, Schwartz A, et al. Effects of oestrogen and progestagen on the 

composition of human milk. Journal of reproduction and fertility Vol 19; 1969: 475-82. Not 

lactose intolerance study 

2057. Tolboom JJ, Kabir H, Molatseli P, et al. Lactose malabsorption and giardiasis in Basotho 

school children. Acta Paediatrica Scandinavica 1987 Jan; 76(1):60-5. Ineligible number of 

subjects 

2058. Tolboom JJ, Moteete M, Kabir H, et al. Incomplete lactose absorption from breast milk 

during acute gastroenteritis. Acta Paediatr Scand 1986 Jan; 75(1):151-5. Not relevant to key 

questions 

2059. Tolboom JJ, Ralitapole-Maruping AP, Mothebe M, et al. Carbohydrate malabsorption in 

children with severe protein energy malnutrition. Trop Geogr Med 1984 Dec; 36(4):355-65. 

Not relevant to key questions 

2060. Tolliver BA, Jackson MS, Jackson KL, et al. Does lactose maldigestion really play a role in 

the irritable bowel? J Clin Gastroenterol 1996 Jul; 23(1):15-7. Not relevant to key questions 

2061. Tontisirin K, Tejavej A, Siripoonya P, et al. Effect of phototherapy on nutrients utilization 

in newborn infants with jaundice. Journal of the Medical Association of Thailand = 

Chotmaihet thangphaet Vol 72; 1989: 177-82. Not lactose intolerance study 

2062. Tootla R, Kotru G, Connolly MA, et al. Asthma inhalers and subsurface enamel 

demineralisation: an in situ pilot study. European journal of paediatric dentistry : official 

journal of European Academy of Paediatric Dentistry Vol 6; 2005: 139-43. Not lactose 

intolerance study 

2063. Tootla R, Toumba KJ, Duggal MS. An evaluation of the acidogenic potential of asthma 

inhalers. Archives of oral biology Vol 49; 2004: 275-83. Not lactose intolerance study 

2064. Tormo R, Bertaccini A, Conde M, et al. Methane and hydrogen exhalation in normal 

children and in lactose malabsorption. Early Hum Dev 2001 Nov; 65 Suppl:S165-72. Not 

relevant to key questions 

2065. Torun B, Solomons NW, Caballero B, et al. The effect of dietary lactose on the early 

recovery from protein-energy malnutrition. II. Indices of nutrient absorption. Am J Clin Nutr 

1984 Sep; 40(3):601-10. Not eligible target population 

306
 
2066. Torun B, Solomons NW, Viteri FE. Lactose malabsorption and lactose intolerance: 

implications for general milk consumption. Arch Latinoam Nutr 1979 Dec; 29(4):445-94. Not 

relevant to key questions 

2067. Toseland PA. Specific determination of plasma and urinary lactose. J Clin Pathol 1968 Jan; 

21(1):112-3. Not relevant to key questions 

2068. Touhami M, Boudraa G, Mary JY, et al. [Clinical consequences of replacing milk with 

yogurt in persistent infantile diarrhea]. Annales de pédiatrie Vol 39; 1992: 79-86. Not 

relevant to key questions 

2069. Treem WR, Ahsan N, Sullivan B, et al. Evaluation of liquid yeast-derived sucrase enzyme 

replacement in patients with sucrase-isomaltase deficiency. Gastroenterology Vol 105; 1993: 

1061-8. Not lactose intolerance study 

2070. Tremaine WJ, Newcomer AD, Riggs BL, et al. Calcium absorption from milk in lactasedeficient and lactase-sufficient adults. Dig Dis Sci 1986 Apr; 31(4):376-8. Not eligible 

outcomes 

2071. Trinchieri A, Nespoli R, Ostini F, et al. A study of dietary calcium and other nutrients in 

idiopathic renal calcium stone formers with low bone mineral content. Journal of Urology 

1998 Mar; 159(3):654-7. Not eligible target population 

2072. Tripp-Reimer T, Pollack RB. Lactase deficiency. Nursing 1977 Nov; 7(11):82, 5. Not 

relevant to key questions 

2073. Troelsen JT, Olsen J, Moller J, et al. An upstream polymorphism associated with lactase 

persistence has increased enhancer activity. Gastroenterology 2003 Dec; 125(6):1686-94. Not 

relevant to key questions 

2074. Troncon LE, de Oliveira RB, Collares EF, et al. Gastric emptying of lactose and glucosegalactose in patients with low intestinal lactase activity. Arq Gastroenterol 1983 Jan-Mar; 

20(1):8-12. Not relevant to key questions 

2075. Troncone R, Caputo N, Florio G, et al. Increased intestinal sugar permeability after 

challenge in children with cow's milk allergy or intolerance. Allergy 1994 Mar; 49(3):142-6. 

Not relevant to key questions 

2076. Truelove SC. Medical management of ulcerative colitis. Br Med J 1968 Jun 8; 

2(5605):605-7. Not relevant to key questions 

2077. Truesdell DD, Acosta PB. Feeding the vegan infant and child. J Am Diet Assoc 1985 Jul; 

85(7):837-40. Review 

2078. Truesdell DD, Whitney EN, Acosta PB. Nutrients in vegetarian foods. J Am Diet Assoc 

1984 Jan; 84(1):28-35. Review 

2079. Tsega E, Endeshaw Y, Mengesha B, et al. The role of milk and lactose intolerance in 

Ethiopian patients with non-ulcer dyspepsia: a case control study. Ethiop Med J 1989 Jul; 

27(3):135-45. Not relevant to key questions 

307
 
2080. Tsuchiya J, Barreto R, Okura R, et al. Single-blind follow-up study on the effectiveness of 

a symbiotic preparation in irritable bowel syndrome. Chinese journal of digestive diseases 

Vol 5; 2004: 169-74. Not lactose intolerance study 

2081. Tsuji S, Yamada T, Ariga T, et al. Carrier detection of sialidosis with partial betagalactosidase deficiency by the assay of lysosomal sialidase in lymphocytes. Ann Neurol 

1984 Feb; 15(2):181-3. Not relevant to key questions 

2082. Tuncbilek E, Turun R, Say B. Lactose intolerance in Turkey. Lancet 1973 Jul 21; 

2(7821):151. Not relevant to key questions 

2083. Tuohy KM, Ziemer CJ, Klinder A, et al. A human volunteer study to determine the 

prebiotic effects of lactulose powder on human colonic microbiota. Microbial Ecology in 

Health & Disease Vol 14; 2002: 165-73. Not lactose intolerance study 

2084. Turner SJ, Daly T, Hourigan JA, et al. Utilization of a low-lactose milk. Am J Clin Nutr 

1976 Jul; 29(7):739-44. Not relevant to key questions 

2085. Turner-McGrievy GM, Barnard ND, Cohen J, et al. Changes in nutrient intake and dietary 

quality among participants with type 2 diabetes following a low-fat vegan diet or a 

conventional diabetes diet for 22 weeks. J Am Diet Assoc 2008 Oct; 108(10):1636-45. Not 

relevant to key questions 

2086. Turner-McGrievy GM, Barnard ND, Scialli AR, et al. Effects of a low-fat vegan diet and a 

Step II diet on macro- and micronutrient intakes in overweight postmenopausal women. 

Nutrition 2004 Sep; 20(9):738-46. Not relevant to key questions 

2087. Tursi A, Brandimarte G, Giorgetti G. High prevalence of small intestinal bacterial 

overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten 

withdrawal.[see comment]. American Journal of Gastroenterology 2003 Apr; 98(4):839-43. 

Ineligible number of subjects 

2088. Tursi A, Brandimarte G, Giorgetti GM, et al. Transient lactose malabsorption in patients 

affected by symptomatic uncomplicated diverticular disease of the colon. Digestive Diseases 

& Sciences 2006 Mar; 51(3):461-5. Ineligible number of subjects 

2089. Tylavsky FA, Anderson JJ. Dietary factors in bone health of elderly lactoovovegetarian and 

omnivorous women. Am J Clin Nutr 1988 Sep; 48(3 Suppl):842-9. Not target population 

2090. Ulrich CM, Georgiou CC, Snow-Harter CM, et al. Bone mineral density in motherdaughter pairs: relations to lifetime exercise, lifetime milk consumption, and calcium 

supplements. Am J Clin Nutr 1996 Jan; 63(1):72-9. not eligible outcomes 

2091. Urbach KF. Hypnotic properties of amitriptyline: comparison with secobarbital. Anesthesia 

and analgesia Vol 46; 1967: 835-42. Not lactose intolerance study 

2092. Uribe M. Lactose to treat acute and chronic portal systemic encephalopathy. Hepatic 

encephalopathy in chronic liver failure: Plenum Press; 1984: 279-85. Not lactose intolerance 

study 

308
 
2093. Uribe M, Berthier JM, Lewis H, et al. Lactose enemas plus placebo tablets vs. neomycin 

tablets plus starch enemas in acute portal systemic encephalopathy. A double-blind 

randomized controlled study. Gastroenterology Vol 81; 1981: 101-6. Not lactose intolerance 

study 

2094. Uribe M, Campollo O, Vargas F, et al. Acidifying enemas (lactitol and lactose) vs. 

nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a doubleblind, randomized clinical trial. Hepatology (Baltimore, Md.) Vol 7; 1987: 639-43. Not 

lactose intolerance study 

2095. Uribe M, Lewis H, Moreno J, et al. Successful use of lactose enemas in acute portal 

systemic encephalopathy (PSE). A double blind controlled trial. Gastroenterology Vol 79; 

1980: 1061. Not lactose intolerance study 

2096. Uribe M, Marquez MA, Garcia-Ramos G, et al. Treatment of chronic portal-systemic 

encephalopathy with lactose in lactase-deficient patients. Digestive Diseases & Sciences 1980 

Dec; 25(12):924-8. No prevalence data 

2097. Uribe M, Morán S, Poo JL, et al. Beneficial effect of carbohydrate maldigestion induced by 

a disaccharidase inhibitor (AO-128) in the treatment of chronic portal-systemic 

encephalopathy. A double-blind, randomized, controlled trial. Scandinavian journal of 

gastroenterology Vol 33; 1998: 1099-106. Not lactose intolerance study 

2098. Uribe M, Toledo H, Perez F, et al. Lactitol, a second-generation disaccharide for treatment 

of chronic portal-systemic encephalopathy. A double-blind, crossover, randomized clinical 

trial. Digestive diseases and sciences Vol 32; 1987: 1345-53. Not lactose intolerance study 

2099. Uribe-Esquivel M, Moran S, Poo JL, et al. In vitro and in vivo lactose and lactulose effects 

on colonic fermentation and portal-systemic encephalopathy parameters. Scand J 

Gastroenterol Suppl 1997; 222:49-52. Not relevant to key questions 

2100. Vakil DV, Ayiomamitis A, Nizami N, et al. A double-blind comparative study of pelletized 

cromolyn versus cromolyn blend in the treatment of asthma. The Journal of asthma : official 

journal of the Association for the Care of Asthma Vol 22; 1985: 279-84. Not lactose 

intolerance study 

2101. Valman HB. Chronic diarrhoea. Br Med J (Clin Res Ed) 1981 Jun 27; 282(6282):2120-2. 

Not relevant to key questions 

2102. Valsecchi R, Tribbia G, Rossi A, et al. Pseudo-cross-reactivity between aspirin and 

tartrazine. G Ital Dermatol Venereol Vol 123; 1988: 177-80. Not lactose intolerance study 

2103. van Assendelft AH. Bronchospasm induced by vanillin and lactose. European journal of 

respiratory diseases Vol 65; 1984: 468-72. Not lactose intolerance study 

309
 
2104. Van Beers EH, Einerhand AW, Taminiau JA, et al. Pediatric duodenal biopsies: mucosal 

morphology and glycohydrolase expression do not change along the duodenum. Journal of 

Pediatric Gastroenterology & Nutrition 1998 Feb; 26(2):186-93. No prevalence data 

2105. Van Beers EH, Rings EH, Taminiau JA, et al. Regulation of lactase and sucrase-isomaltase 

gene expression in the duodenum during childhood. Journal of Pediatric Gastroenterology & 

Nutrition 1998 Jul; 27(1):37-46. No prevalence data 

2106. Van Bever HP, Von Berg A, Schmidt P, et al. Safety and efficacy of fenoterol/ipratropium 

lactose based powder capsules compared to fenoterol/ipratropium MDI in pediatric patients 

with asthma [abstract]. European Respiratory Journal - Supplement Vol 12; 1998: 89s. Not 

lactose intolerance study 

2107. Van Biervliet S, Eggermont E, Marien P, et al. Combined impact of mucosal damage and 

of cystic fibrosis on the small intestinal brush border enzyme activities. Acta Clinica Belgica 

2003 Jul-Aug; 58(4):220-4. Ineligible number of subjects 

2108. Van den Driessche M, Veereman-Wauters G. Functional foods in pediatrics. Acta 

Gastroenterol Belg 2002 Jan-Mar; 65(1):45-51. Not relevant to key questions 

2109. van der Horst GT, Kleijer WJ, Hoogeveen AT, et al. Morquio B syndrome: a primary 

defect in beta-galactosidase. Am J Med Genet 1983 Oct; 16(2):261-75. Not relevant to key 

questions 

2110. van der Klei-van Moorsel JM, Douwes AC, van Oeveren JP. New principle for estimation 

of hydrogen in expired air. Eur J Pediatr 1984 Feb; 141(4):221-4. Not relevant to key 

questions 

2111. Van Diggelen OP, Schram AW, Sinnott ML, et al. Turnover of beta-galactosidase in 

fibroblasts from patients with genetically different types of beta-galactosidase deficiency. 

Biochem J 1981 Oct 15; 200(1):143-51. Not relevant to key questions 

2112. van Faassen A, Hazen MJ, van den Brandt PA, et al. Bile acids and pH values in total feces 

and in fecal water from habitually omnivorous and vegetarian subjects. Am J Clin Nutr 1993 

Dec; 58(6):917-22. Not eligible outcomes 

2113. van Staveren WA, Dhuyvetter JH, Bons A, et al. Food consumption and height/weight 

status of Dutch preschool children on alternative diets. J Am Diet Assoc 1985 Dec; 

85(12):1579-84. Not relevant to key questions 

2114. VandenBergh MF, DeMan SA, Witteman JC, et al. Physical activity, calcium intake, and 

bone mineral content in children in The Netherlands. J Epidemiol Community Health 1995 

Jun; 49(3):299-304. not eligible outcomes 

2115. Varavithya W, Valyasevi A, Charuchinda S. Lactose malabsorption in Thai infants. Journal 

of Pediatrics 1971 Apr; 78(4):710-5. Subjects less than 4 years old 

310
 
2116. Varavithya W, Valyasevi A, Manu P, et al. Lactose malabsorption in Thai infants and 

children: effect of prolonged milk feeding. Southeast Asian J Trop Med Public Health 1976 

Dec; 7(4):591-5. Not relevant to key questions 

2117. Varea V, de Carpi JM, Puig C, et al. Malabsorption of carbohydrates and depression in 

children and adolescents. Journal of Pediatric Gastroenterology & Nutrition 2005 May; 

40(5):561-5. No prevalence data 

2118. Varela-Moreiras G, Antoine JM, Ruiz-Roso B, et al. Effects of yogurt and fermented-thenpasteurized milk on lactose absorption in an institutionalized elderly group. Journal of the 

American College of Nutrition 1992 Apr; 11(2):168-71. No prevalence data 

2119. Vásquez-Garibay E, Stein K, Kratzsch J, et al. Effect of nucleotide intake and nutritional 

recovery on insulin-like growth factor I and other hormonal biomarkers in severely 

malnourished children. The British journal of nutrition Vol 96; 2006: 683-90. Not lactose 

intolerance study 

2120. Vatn MH, Mogstad TE, Gjone E. A prospective study of patients with uncharacteristic 

abdominal disorders. Scand J Gastroenterol 1985 May; 20(4):407-14. Not eligible target 

population 

2121. Vazquez B, Amador A. Radiological diagnosis of lactose intolerance in children with 

chronic diarrhoea. Acta Paediatr Acad Sci Hung 1973; 14(1):51-61. Not relevant to key 

questions 

2122. Vega-Franco L, Meza C, Romero JL, et al. Breath hydrogen test in children with giardiasis. 

J Pediatr Gastroenterol Nutr 1987 May-Jun; 6(3):365-8. Not relevant to key questions 

2123. Veligati LN, Treem WR, Sullivan B, et al. Delta 10 ppm versus delta 20 ppm: a reappraisal 

of diagnostic criteria for breath hydrogen testing in children. Am J Gastroenterol 1994 May; 

89(5):758-61. Not relevant to key questions 

2124. Venderley AM, Campbell WW. Vegetarian diets: nutritional considerations for athletes. 

Sports Med 2006; 36(4):293-305. Review 

2125. Ventura A, Pineschi A, Tasso M. Cow's milk intolerance and abdominal surgery: a 

puzzling connection. Helvetica Paediatrica Acta 1986 Mar; 41(6):487-94. Ineligible number 

of subjects 

2126. Verger P, Garnier-Sagne I, Leblanc JC. Identification of risk groups for intake of food 

chemicals. Regul Toxicol Pharmacol 1999 Oct; 30(2 Pt 2):S103-8. Not eligible outcomes 

2127. Verkasalo M, Kuitunen P, Savilahti E, et al. Changing pattern of cow's milk intolerance. 

An analysis of the occurrence and clinical course in the 60s and mid-70s. Acta Paediatrica 

Scandinavica 1981; 70(3):289-95. Ineligible number of subjects 

2128. Verma M, Saxena S. Lactose intolerance in children with protein-energy malnutrition. 

Indian J Pediatr 1980 Jul-Aug; 47(387):273-7. Not relevant to key questions 

311
 
2129. Vernia P, Camillo MD, Marinaro V, et al. Effect of predominant methanogenic flora on the 

outcome of lactose breath test in irritable bowel syndrome patients. European Journal of 

Clinical Nutrition 2003 Sep; 57(9):1116-9. No prevalence data 

2130. Vernia P, Frandina C, Bilotta T, et al. Sorbitol malabsorption and nonspecific abdominal 

symptoms in type II diabetes. Metabolism: Clinical & Experimental Vol 44; 1995: 796-9. Not 

lactose intolerance study 

2131. Vernia P, Ricciardi MR, Frandina C, et al. Lactose malabsorption and irritable bowel 

syndrome. Effect of a long-term lactose-free diet. Italian Journal of Gastroenterology 1995 

Apr; 27(3):117-21. No prevalence data 

2132. Verwimp JJ, Bindels JG, Barents M, et al. Symptomatology and growth in infants with 

cow's milk protein intolerance using two different whey-protein hydrolysate based formulas 

in a Primary Health Care setting. European journal of clinical nutrition Vol 49; 1995: S39-48. 

Not relevant to key questions 

2133. Vesa T, Marteau P, Briet F, et al. Role of the Viscosity of Therapeutic Milk on 

Digestibility and Tolerance of Lactose in Adults with Hypolactasia [abstract]. Gut Vol 39; 

1996: A169. Not relevant to key questions 

2134. Vesa TH, Marteau P, Korpela R. Lactose intolerance. Journal of the American College of 

Nutrition 2000 Apr; 19(2 Suppl):165S-75S. Not original research 

2135. Vesa TH, Marteau P, Zidi S, et al. Digestion and Tolerance of Lactose from Yoghurt and 

Semi-Solid Fermented Diary Products - Is Bacterial Lactase Important? [abstract]. Gut Vol 

39; 1996: A169. Not relevant to key questions 

2136. Vesa TH, Marteau PR, Briet FB, et al. Raising milk energy content retards gastric 

emptying of lactose in lactose-intolerant humans with little effect on lactose digestion. J Nutr 

1997 Dec; 127(12):2316-20. Not relevant to key questions 

2137. Vesa TH, Marteau PR, Briet FB, et al. Effects of milk viscosity on gastric emptying and 

lactose intolerance in lactose maldigesters. Am J Clin Nutr 1997 Jul; 66(1):123-6. Not 

relevant to key questions 

2138. Vesa TH, Seppo LM, Marteau PR, et al. Role of irritable bowel syndrome in subjective 

lactose intolerance. Am J Clin Nutr 1998 Apr; 67(4):710-5. Not relevant to key questions 

2139. Vetvik K, Schrumpf E, Mowinckel P, et al. Effects of omeprazole and eradication of 

Helicobacter pylori on gastric and duodenal mucosal enzyme activities and DNA in duodenal 

ulcer patients. Scandinavian journal of gastroenterology Vol 29; 1994: 995-1000. Not lactose 

intolerance study 

2140. Viall C, Porcelli K, Teran JC, et al. A double-blind clinical trial comparing the 

gastrointestinal side effects of two enteral feeding formulas. JPEN. Journal of parenteral and 

enteral nutrition Vol 14; 1990: 265-9. Not lactose intolerance study 

312
 
2141. Vidgren M, Karkkainen A, Karjalainen P, et al. Effect of powder inhaler design on drug 

deposition in the respiratory tract. International Journal of Pharmaceutics Vol 42; 1988: 211­

6. Not lactose intolerance study 

2142. Vidgren P, Vidgren M, Laurikainen K, et al. In vitro deposition and clinical efficacy of two 

sodium cromoglycate inhalation powders. International journal of clinical pharmacology, 

therapy, and toxicology Vol 29; 1991: 108-12. Not lactose intolerance study 

2143. Vienna A, Biondi G. Culture and biology: surnames in evaluating genetic relationships 

among the ethnic minorities of Southern Italy and Sicily. Coll Antropol 2001 Jun; 25(1):189­

93. Not relevant to key questions 

2144. Vigna GB, Costantini F, Aldini G, et al. Effect of a standardized grape seed extract on lowdensity lipoprotein susceptibility to oxidation in heavy smokers. Metabolism: clinical and 

experimental Vol 52; 2003: 1250-7. Not lactose intolerance study 

2145. Villani RG, Gannon J, Self M, et al. L-Carnitine supplementation combined with aerobic 

training does not promote weight loss in moderately obese women. International journal of 

sport nutrition and exercise metabolism Vol 10; 2000: 199-207. Not lactose intolerance study 

2146. Villar J, Kestler E, Castillo P, et al. Improved lactose digestion during pregnancy: a case of 

physiologic adaptation? Obstetrics & Gynecology 1988 May; 71(5):697-700. Secondary 

lactose intolerance 

2147. Vince JD. Diarrhoea in children in Papua New Guinea. P N G Med J 1995 Dec; 38(4):262­

71. Not relevant to key questions 

2148. Vissing J, Quistorff B, Haller RG. Effect of fuels on exercise capacity in muscle 

phosphoglycerate mutase deficiency. Archives of neurology Vol 62; 2005: 1440-3. Not 

lactose intolerance study 

2149. Vitek V, Vitek K, Cowley RA. Increased urinary excretion of lactose in brain injury. Surg 

Forum 1973; 24:429-31. Not relevant to key questions 

2150. Vivatvakin B, Jongpipatvanich S, Harikul S, et al. Control study of oral rehydration 

solution (ORS)/ORS + dioctahedral smectite in hospitalized Thai infants with acute secretory 

diarrhea. The Southeast Asian journal of tropical medicine and public health Vol 23; 1992: 

414-9. Not lactose intolerance study 

2151. Vivatvakin B, Kowitdamrong E. Randomized control trial of live Lactobacillus acidophilus 

plus Bifidobacterium infantis in treatment of infantile acute watery diarrhea. Journal of the 

Medical Association of Thailand = Chotmaihet thangphaet Vol 89; 2006: S126-33. Not 

lactose intolerance study 

2152. Vlachos P, Liakakos D, Boviatsi E. Letter: Childhood lactose intolerance. N Engl J Med 

1976 Jan 15; 294(3):163-4. Not relevant to key questions 

2153. Vogelsang H, Ferenci P, Frotz S, et al. Acidic colonic microclimate--possible reason for 

false negative hydrogen breath tests. Gut 1988 Jan; 29(1):21-6. Not relevant to key questions 

2154. Volpe R, Niittynen L, Korpela R, et al. Effects of yoghurt enriched with plant sterols on 

serum lipids in patients with moderate hypercholesterolaemia. The British journal of nutrition 

Vol 86; 2001: 233-9. Not lactose intolerance study 

2155. von Scheele C. Levodopa in restless legs. Lancet Vol 2; 1986: 426-7. Not lactose 

intolerance study 

2156. von Tirpitz C, Kohn C, Steinkamp M, et al. Lactose intolerance in active Crohn's disease: 

clinical value of duodenal lactase analysis. J Clin Gastroenterol 2002 Jan; 34(1):49-53. Not 

eligible target population 

2157. von Wright A, Salminen S. Probiotics: established effects and open questions. Eur J 

313
 
Gastroenterol Hepatol 1999 Nov; 11(11):1195-8. Not relevant to key questions 

2158. Vonk RJ, Lin Y, Koetse HA, et al. Lactose (mal)digestion evaluated by the 13C-lactose 

digestion test. European Journal of Clinical Investigation 2000 Feb; 30(2):140-6. No 

prevalence data 

2159. Vonk RJ, Priebe MG, Koetse HA, et al. Lactose intolerance: analysis of underlying factors. 

Eur J Clin Invest 2003 Jan; 33(1):70-5. Not relevant to key questions 

2160. Vonk RJ, Stellaard F, Hoekstra H, et al. 13C carbohydrate breath tests. Gut 1998 Nov; 43 

Suppl 3:S20-2. Not relevant to key questions 

2161. Vukovich MD, Sharp RL, Kesl LD, et al. Effects of a low-dose amino acid supplement on 

adaptations to cycling training in untrained individuals. International journal of sport nutrition 

Vol 7; 1997: 298-309. Not lactose intolerance study 

2162. Vyhmeister IB, Register UD, Sonnenberg LM. Safe vegetarian diets for children. Pediatr 

Clin North Am 1977 Feb; 24(1):203-10. Review 

2163. Wagh MG, Ghooi RB, Shetty RK. Lactose intolerance; physiological, clinical and 

therapeutic considerations. Indian J Pediatr 1984 Nov-Dec; 51(413):671-81. Not relevant to 

key questions 

2164. Waickman FJ. Food hypersensitivity allergy or malabsorption. Laryngoscope 1977 May; 

87(5 Pt 1):661-4. Not relevant to key questions 

2165. Wald A, Chandra R, Fisher SE, et al. Lactose malabsorption in recurrent abdominal pain of 

childhood. Journal of Pediatrics 1982 Jan; 100(1):65-8. Ineligible number of subjects 

2166. Waldmann A, Koschizke JW, Leitzmann C, et al. Dietary intakes and lifestyle factors of a 

vegan population in Germany: results from the German Vegan Study. Eur J Clin Nutr 2003 

Aug; 57(8):947-55. Not relevant to key questions 

2167. Walike BC, Walike JW. Lactose content of tube feeding diets as a cause of diarrhea. 

Laryngoscope 1973 Jul; 83(7):1109-15. Not relevant to key questions 

2168. Walike BC, Walike JW. Relative lactose intolerance. A clinical study of tube-fed patients. 

JAMA 1977 Aug 29; 238(9):948-51. Not relevant to key questions 

314
 
2169. Walker AC, Harry JG. A survey of diarrhoeal disease in malnourished aboriginal children. 

Med J Aust 1972 Apr 29; 1(18):904-11. Not relevant to key questions 

2170. Walker-Smith J, Barnard J, Bhutta Z, et al. Chronic diarrhea and malabsorption (including 

short gut syndrome): Working Group Report of the First World Congress of Pediatric 

Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2002; 35 Suppl 

2:S98-105. Not relevant to key questions 

2171. Walker-Smith JA. Cow's milk intolerance as a cause of postenteritis diarrhoea. J Pediatr 

Gastroenterol Nutr 1982; 1(2):163-73. Not relevant to key questions 

2172. Walker-Smith JA, Bowdler JD. The role of radiology in the diagnosis of lactose intolerance 

in childhood. Gut 1969 Jan; 10(1):78-9. Not relevant to key questions 

2173. Wall CR, Webster J, Quirk P, et al. The nutritional management of acute diarrhea in young 

infants: effect of carbohydrate ingested. Journal of Pediatric Gastroenterology & Nutrition 

1994 Aug; 19(2):170-4. Not relevant to key questions 

2174. Wallace D, Grieco MH. Double-blind, cross-over study of cromolyn sodium inhibition of 

exercise-induced bronchospasm in adults. Annals of Allergy Vol 37; 1976: 153-63. Not 

lactose intolerance study 

2175. Wallin A, Sandstrom T. Bronchoconstriction due to inhaled lactose dry powder? 

[Abstract]. European Respiratory Journal. Supplement. Vol 8; 1995: 426s. Not lactose 

intolerance study 

2176. Walsh NE, Ramamurthy S, Schoenfeld L, et al. Analgesic effectiveness of D-phenylalanine 

in chronic pain patients. Archives of physical medicine and rehabilitation Vol 67; 1986: 436­

9. Not lactose intolerance study 

2177. Wanderer AA, St PJP, Ellis EF. Primary acquired cold urticaria. Double-blind comparative 

study of treatment with cyproheptadine, chlorpheniramine, and placebo. Archives of 

dermatology Vol 113; 1977: 1375-7. Not lactose intolerance study 

2178. Wang Y, Harvey CB, Hollox EJ, et al. The genetically programmed down-regulation of 

lactase in children. Gastroenterology 1998 Jun; 114(6):1230-6. Ineligible number of subjects 

2179. Wang Y, Harvey CB, Pratt WS, et al. The lactase persistence/non-persistence 

polymorphism is controlled by a cis-acting element. Hum Mol Genet 1995 Apr; 4(4):657-62. 

Not relevant to key questions 

2180. Wang YF, Chiu JS, Chuang MH, et al. Bone mineral density of vegetarian and nonvegetarian adults in Taiwan. Asia Pac J Clin Nutr 2008; 17(1):101-6. Not eligible exposure 

2181. Wapnick S. Milk and lactose intolerance following distal small bowel resection. Am J Clin 

Nutr 1972 Jul; 25(7):655-60. Not relevant to key questions 

315
 
2182. Ward RJ, Abraham R, McFadyen IR, et al. Assessment of trace metal intake and status in a 

Gujerati pregnant Asian population and their influence on the outcome of pregnancy. Br J 

Obstet Gynaecol 1988 Jul; 95(7):676-82. Not eligible outcomes 

2183. Warner J, Brooks SE, James WP, et al. Juvenile dermatitis herpetiformis in Jamaica: 

clinical and gastrointestinal features. Br J Dermatol 1972 Mar; 86(3):226-37. Not relevant to 

key questions 

2184. Warren S, Taylor G, Smith J, et al. Gamma scintigraphic evaluation of a novel budesonide 

dry powder inhaler using a validated radiolabeling technique. Journal of aerosol medicine : 

the official journal of the International Society for Aerosols in Medicine Vol 15; 2002: 15-25. 

Not lactose intolerance study 

2185. Waud JP, Matthews SB, Campbell AK. Measurement of breath hydrogen and methane, 

together with lactase genotype, defines the current best practice for investigation of lactose 

sensitivity. Ann Clin Biochem 2008 Jan; 45(Pt 1):50-8. Not relevant to key questions 

2186. Weaver CM, McCabe LD, McCabe GP, et al. Bone mineral and predictors of bone mass in 

white, Hispanic, and Asian early pubertal girls. Calcif Tissue Int 2007 Nov; 81(5):352-63. 

Not eligible exposure/outcomes 

2187. Weaver CM, Plawecki KL. Dietary calcium: adequacy of a vegetarian diet. Am J Clin Nutr 

1994 May; 59(5 Suppl):1238S-41S. Review 

2188. Weaver CM, Proulx WR, Heaney R. Choices for achieving adequate dietary calcium with a 

vegetarian diet. Am J Clin Nutr 1999 Sep; 70(3 Suppl):543S-8S. Not eligible outcomes 

2189. Weber K, Barth C, Schuler D, et al. [Activation of CFTR-dependent chloride channels by 

tiotropium bromide]. Atemwegs- und Lungenkrankheiten Vol 30; 2004: 38-42. Not lactose 

intolerance study 

2190. Weber W, Michaelis K, Luckow V, et al. Pharmacokinetics and bioavailability of 

pentaerithrityl tetranitrate and two of its metabolites. Arzneimittel-Forschung Vol 45; 1995: 

781-4. Not lactose intolerance study 

2191. Wedlake L, Thomas K, McGough C, et al. Small bowel bacterial overgrowth and lactose 

intolerance during radical pelvic radiotherapy: An observational study. European Journal of 

Cancer 2008 Oct; 44(15):2212-7. No prevalence data 

2192. Wehrli SL, Berry GT, Palmieri M, et al. Urinary galactonate in patients with galactosemia: 

quantitation by nuclear magnetic resonance spectroscopy. Pediatric research 1997 Dec; 

42(6):855-61. Not relevant to key questions 

2193. Weinberg RB. Apolipoprotein A-IV-2 allele: association of its worldwide distribution with 

adult persistence of lactase and speculation on its function and origin. Genetic Epidemiology 

1999 Nov; 17(4):285-97. No prevalence data 

316
 
2194. Weiskirchen R, Tag CG, Mengsteab S, et al. Pitfalls in LightCycler diagnosis of the singlenucleotide polymorphism 13.9 kb upstream of the lactase gene that is associated with adulttype hypolactasia. Clin Chim Acta 2007 Sep; 384(1-2):93-8. Not relevant to key questions 

2195. Weiss HJ, Aledort LM. Impaired platelet-connective-tissue reaction in man after aspirin 

ingestion. Lancet Vol 2; 1967: 495-7. Not lactose intolerance study 

2196. Weiss KM. The unkindest cup. Lancet 2004 May 8; 363(9420):1489-90. Not relevant to 

key questions 

2197. Weiss PA. Does milk cause cancer? Clin J Oncol Nurs 2008 Apr; 12(2):359-60. Not 

relevant to key questions 

2198. Weiss RG, Stryker JA. 14C-lactose breath tests during pelvic radiotherapy: the effect of the 

amount of small bowel irradiated. Radiology 1982 Feb; 142(2):507-10. Not relevant to key 

questions 

2199. Weizman Z. [Evaluation of a new Israel infant soy formula]. Harefuah Vol 120; 1991: 374­

6. Not relevant to key questions 

2200. Welsh JD. On the lactose tolerance test. Gastroenterology 1966 Sep; 51(3):445-6. Not 

relevant to key questions 

2201. Welsh JD. Commentary. Am J Dig Dis 1967 Apr; 12(4):424-5. Not relevant to key 

questions 

2202. Welsh JD. Diet therapy in adult lactose malabsorption: present practices. American Journal 

of Clinical Nutrition 1978 Apr; 31(4):592-6. Not relevant to key questions 

2203. Welsh JD, Cassidy D, Prigatano GP, et al. Chronic hepatic encephalopathy treated with 

oral lactose in a patient with lactose malabsorption. N Engl J Med 1974 Aug 1; 291(5):240-1. 

Not relevant to key questions 

2204. Welsh JD, Griffiths WJ. Breath hydrogen test after oral lactose in postgastrectomy patients. 

Am J Clin Nutr 1980 Nov; 33(11):2324-7. Not relevant to key questions 

2205. Welsh JD, Hall WH. Gastric emptying of lactose and milk in subjects with lactose 

malabsorption. Am J Dig Dis 1977 Dec; 22(12):1060-3. Not relevant to key questions 

2206. Welsh JD, Langdon DE. Lactose to treat hepatic encephalopathy in patient with lactose 

malabsorption. N Engl J Med 1972 Feb 24; 286(8):436. Not relevant to key questions 

2207. Welsh JD, Payne DL, Manion C, et al. Interval sampling of breath hydrogen (H2) as an 

index of lactose malabsorption in lactase-deficient subjects. Dig Dis Sci 1981 Aug; 

26(8):681-5. Not relevant to key questions 

2208. Welsh JD, Poley JR, Bhatia M, et al. Intestinal disaccharidase activities in relation to age, 

race, and mucosal damage. Gastroenterology 1978 Nov; 75(5):847-55. No prevalence data 

2209. Welsh JD, Porter MG. Reversible secondary disaccharidase deficiency. Am J Dis Child 

1967 Jun; 113(6):716-20. Not relevant to key questions 

317
 
2210. Welsh JD, Rohrer GV, Drewry R, et al. Human intestinal disaccharidase activity. II. 

Diseases of the small intestine and deficiency states. Arch Intern Med 1966 Apr; 117(4):495­

503. Not relevant to key questions 

2211. Welsh JD, Rohrer GV, Walker A. Human intestinal disaccharidase activity. I. Normal 

individuals. Arch Intern Med 1966 Apr; 117(4):488-94. Not relevant to key questions 

2212. Welsh JD, Shaw RW, Walker A. Isolated lactase deficiency producing postgastrectomy 

milk intolerance. Ann Intern Med 1966 Jun; 64(6):1253-8. Not relevant to key questions 

2213. Wemmer U. [Nutrition in infant enteritis]. Fortschritte der Medizin Vol 95; 1977: 94-8, 

102. Not relevant to key questions 

2214. Wen CP. Milk programs. Am J Public Health 1973 Aug; 63(8):669-71. Not relevant to key 

questions 

2215. Wendland BE, Greenwood CE, Weinberg I, et al. Malnutrition in institutionalized seniors: 

the iatrogenic component. Journal of the American Geriatrics Society 2003 Jan; 51(1):85-90. 

Not relevant to key questions 

2216. Werner I. Hospital food and possibilities of its improvement. Clinical aspects. Bibl Nutr 

Dieta 1973; (19):86-92. Not eligible target population 

2217. Weser E, Rubin W, Ross L, et al. Lactase deficiency in patients with the "irritable-colon 

syndrome". N Engl J Med 1965 Nov 11; 273(20):1070-5. Not relevant to key questions 

2218. Westman EC, Behm FM, Rose JE. Airway sensory replacement combined with nicotine 

replacement for smoking cessation. A randomized, placebo-controlled trial using a citric acid 

inhaler. Chest Vol 107; 1995: 1358-64. Not lactose intolerance study 

2219. Wharton B, Howells G, Phillips I. Diarrhoea in kwashiorkor. Br Med J 1968 Dec 7; 

4(5631):608-11. Not relevant to key questions 

2220. Whitcomb JE, Findling JW, Raff H, et al. Randomized trial of oral hydrocortisone and its 

effect on emergency physicians during night duty. WMJ : official publication of the State 

Medical Society of Wisconsin Vol 99; 2000: 37-41, 6. Not lactose intolerance study 

2221. Whitehead RG. Lowered energy intake and dietary macronutrient balance: potential 

consequences for micronutrient status. Nutr Rev 1995 Sep; 53(9 Pt 2):S2-8. Review 

2222. Whitehead WE, Bosmajian L, Zonderman AB, et al. Symptoms of psychologic distress 

associated with irritable bowel syndrome. Comparison of community and medical clinic 

samples. Gastroenterology 1988 Sep; 95(3):709-14. Not relevant to key questions 

2223. Whitehead WE, Holtkotter B, Enck P, et al. Tolerance for rectosigmoid distention in 

irritable bowel syndrome. Gastroenterology 1990 May; 98(5 Pt 1):1187-92. Not relevant to 

key questions 

318
 
2224. Wiecha JM, Fink AK, Wiecha J, et al. Differences in dietary patterns of Vietnamese, white, 

African-American, and Hispanic adolescents in Worcester, Mass. J Am Diet Assoc 2001 Feb; 

101(2):248-51. Not relevant to key questions 

2225. Wigg AE, Prest C, Slobodian P, et al. A system for improving vitamin D nutrition in 

residential care. The Medical journal of Australia Vol 185; 2006: 195-8. Not lactose 

intolerance study 

2226. Wilkin JK, Fortner G, Reinhardt LA, et al. Prostaglandins and nicotinate-provoked increase 

in cutaneous blood flow. Clinical pharmacology and therapeutics Vol 38; 1985: 273-7. Not 

lactose intolerance study 

2227. Wilkinson AW. The starving newborn baby. Proc Nutr Soc 1969 Mar; 28(1):61-6. Not 

relevant to key questions 

2228. Williams CA, Macdonald I. Serum galactose levels in lactose-intolerant persons receiving 

a galactose:glucose mixture. Hum Nutr Clin Nutr 1982; 36(2):149-53. Not relevant to key 

questions 

2229. Williams CA, Phillips T, Macdonald I. The influence of glucose on serum galactose levels 

in man. Metabolism: Clinical & Experimental Vol 32; 1983: 250-6. Not lactose intolerance 

study 

2230. Williams CN, Dickson RC. Cholestyramine and medium-chain triglyceride in prolonged 

management of patients subjected to ileal resection or bypass. Canadian Medical Association 

Journal 1972 Oct 7; 107(7):626-31. No prevalence data 

2231. Williams EJ, Irvine WT. Functional and metabolic effects of total and selective vagotomy. 

Lancet 1966 May 14; 1(7446):1053-7. Not relevant to key questions 

2232. Willumsen JF, Darling JC, Kitundu JA, et al. Dietary management of acute diarrhoea in 

children: effect of fermented and amylase-digested weaning foods on intestinal permeability. 

Journal of pediatric gastroenterology and nutrition Vol 24; 1997: 235-41. Not lactose 

intolerance study 

2233. Wilmers MJ, Young WF, Valman HB. Acute infective gastroenteritis. Br Med J 1969 May 

31; 2(5656):573. Not relevant to key questions 

2234. Wilson J, Riedel G. Lactose intolerance. Can Nurse 1984 Nov; 80(10):27-9. Not relevant to 

key questions 

2235. Wilson L, Taylor JD, Nash CW, et al. The combined effects of ethanol and amphetamine 

sulfate on performance of human subjects. Canadian Medical Association journal Vol 94; 

1966: 478-84. Not lactose intolerance study 

2236. Wirth FH, Numerof B, Pleban P, et al. Effect of lactose on mineral absorption in preterm 

infants. The Journal of pediatrics Vol 117; 1990: 283-7. Not eligible target population 

2237. Wisuthsarewong W, Viravan S. Diagnostic criteria for atopic dermatitis in Thai children. 

Journal of the Medical Association of Thailand 2004 Dec; 87(12):1496-500. No prevalence 

data 

319
 
2238. Wittenberg DF, Moosa A. Lactose maldigestion: increased age-related prevalence in 

institutionalized children. Journal of Pediatric Gastroenterology & Nutrition 1990 Nov; 

11(4):489-95. Ineligible number of subjects 

2239. Wittenberg DF, Moosa A. Lactose maldigestion--age-specific prevalence in black and 

Indian children. South African Medical Journal Suid-Afrikaanse Tydskrif Vir Geneeskunde 

1990 Oct 20; 78(8):470-2. Ineligible number of subjects 

2240. Wittenberg DF, Moosa A. The practical significance of lactose maldigestion in 

institutionalised black children. South African Medical Journal Suid-Afrikaanse Tydskrif Vir 

Geneeskunde 1991 Jan 19; 79(2):70-2. Ineligible number of subjects 

2241. Wolever TMS, Wong GS, Kenshole A, et al. Lactose in the diabetic diet: A comparison 

with other carbohydrates. Nutrition Research Vol 5; 1985: 1335-45. Not relevant to key 

questions 

2242. Wolfe BE, Metzger ED, Jimerson DC. Comparison of the effects of amino acid mixture 

and placebo on plasma tryptophan to large neutral amino acid ratio. Life sciences Vol 56; 

1995: 1395-400. Not lactose intolerance study 

2243. Wolfe BE, Metzger ED, Jimerson DC. Eating Behavior, Serotonin and Tryptophan 

Depletion. 149th Annual Meeting of the American Psychiatric Association. New York, New 

York, USA. 4-9th May, 1996.; 1996. Not lactose intolerance study 

2244. Wong FH, Yeung CY, Fung KW, et al. Breath hydrogen (H2) analysis in southern Chinese 

children and infants by gas chromatography and a novel automatic sampling system. 

Singapore Med J 1996 Feb; 37(1):72-81. Not relevant to key questions 

2245. Woo J, Kwok T, Ho SC, et al. Nutritional status of elderly Chinese vegetarians. Age 

Ageing 1998 Jul; 27(4):455-61. Not relevant to key questions 

2246. Wood RJ, Hanssen DA. Effect of milk and lactose on zinc absorption in lactose-intolerant 

postmenopausal women. J Nutr 1988 Aug; 118(8):982-6. Not eligible outcomes 

2247. Woodd-Walker RB, Hansen JD, Saunders SJ. The in vitro uptake of lysine and alanine by 

human jejunal mucosa in protein-calorie malnutrition, in gastroenteritis and after neomycin. 

Acta Paediatr Scand 1972 Mar; 61(2):140-4. Not relevant to key questions 

2248. Woods RK, Weiner JM, Abramson M, et al. Do dairy products induce bronchoconstriction 

in adults with asthma? Journal of Allergy & Clinical Immunology 1998 Jan; 101(1 Pt 1):45­

50. Not relevant to key questions 

2249. Woods RK, Weiner JM, Thien F, et al. The effects of monosodium glutamate in adults with 

asthma who perceive themselves to be monosodium glutamate-intolerant. The Journal of 

allergy and clinical immunology Vol 101; 1998: 762-71. Not lactose intolerance study 

320
 
2250. Woods RK, Weiner JM, Thien F, et al. Respiratory pathophysiologic responses the effects 

of monosodium glutamate in adults with asthma who perceive themselves to be monosodium 

glutamate-intolerant. Journal of Allergy and Clinical Immunology Vol 101; 1998: 762-71. 

Not lactose intolerance study 

2251. Woolf GM, Miller C, Kurian R, et al. Diet for patients with a short bowel: high fat or high 

carbohydrate? Gastroenterology Vol 84; 1983: 823-8. Not lactose intolerance study 

2252. Woolf GM, Miller C, Kurian R, et al. Nutritional absorption in short bowel syndrome. 

Evaluation of fluid, calorie, and divalent cation requirements. Digestive Diseases & Sciences 

1987 Jan; 32(1):8-15. Not relevant to key questions 

2253. Wooten WJ, Price W. Consensus report of the National Medical Association. The role of 

dairy and dairy nutrients in the diet of African Americans. J Natl Med Assoc 2004 Dec; 96(12 

Suppl):5S-31S. Concensus report 

2254. Wu VT, Brochetti D, Duncan SE. Sensory characteristics and acceptability of lactosereduced baked custards made with an egg substitute. J Am Diet Assoc 1998 Dec; 

98(12):1467-9. Not relevant to key questions 

2255. Wutzke KD, Heine WE, Plath C, et al. Evaluation of oro-coecal transit time: A comparison 

of the lactose-[13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans. 

European Journal of Clinical Nutrition Vol 51; 1997: 11-9. Not relevant to key questions 

2256. Wutzke KD, Schütt M. The duration of enzyme induction in orocaecal transit time 

measurements. European journal of clinical nutrition Vol 61; 2007: 1162-6. Not lactose 

intolerance 

2257. Wynckel A, Jaisser F, Wong T, et al. Intestinal absorption of calcium from yogurt in 

lactase-deficient subjects. Reprod Nutr Dev 1991; 31(4):411-8. Not eligible outcomes 

2258. Wytock DH, DiPalma JA. All yogurts are not created equal. Am J Clin Nutr 1988 Mar; 

47(3):454-7. Not relevant to key questions 

2259. Xiao SD, Zhang DZ, Lu H, et al. Multicenter, randomized, controlled trial of heat-killed 

Lactobacillus acidophilus LB in patients with chronic diarrhea. Advances in therapy Vol 20; 

2003: 253-60. Not lactose intolerance study 

2260. Xu SS, Cai ZY, Qu ZW, et al. Huperzine-A in capsules and tablets for treating patients 

with Alzheimer disease. Zhongguo yao li xue bao = Acta pharmacologica Sinica Vol 20; 

1999: 486-90. Not lactose intolerance study 

2261. Yabuuchi H, Okada S, Nishigaki M, et al. Studies on the pathogenesis of mucolipidosis. 

Monogr Hum Genet 1978; 10:27-31. Not relevant to key questions 

2262. Yadrick MM, Halling JF, Beyer PL, et al. Comparison of the effects of diets high and low 

in simple sugars on bowel function in healthy, lactose-tolerant men. Journal of the American 

Dietetic Association Vol 92; 1992: 1121-3. Not lactose intolerance study 

2263. Yahata H, Saito M, Sendo T, et al. Prophylactic effect of pemirolast, an antiallergic agent, 

against hypersensitivity reactions to paclitaxel in patients with ovarian cancer. International 

journal of cancer. Journal international du cancer Vol 118; 2006: 2636-8. Not lactose 

intolerance study 

2264. Yale SH, Liu K. Echinacea purpurea therapy for the treatment of the common cold: a 

randomized, double-blind, placebo-controlled clinical trial. Archives of internal medicine Vol 

164; 2004: 1237-41. Not lactose intolerance study 

2265. Yamagata S, Ishikawa M, Wada T, et al. A Multicenter Double Blind Study of 

Carbenoxolone Sodium for Patients with Gastric Ulcer in Japan, Evaluated by Group 

Comparison with Nonparametric Analysis. Rinsho Hyoka (Clinical Evaluation) Vol 4; 1976: 

321
 
247-69. Not lactose intolerance study 

2266. Yamagata S, Ishimori A, Sat H, et al. Clinical course of peptic ulcer and the effect of 

pharmacotherapy:--multi-institutional double-blind controlled study. Gastroenterologia 

Japonica Vol 10; 1975: 323-41. Not lactose intolerance study 

2267. Yanaka A, Zhang S, Sato D, et al. Geranylgeranylacetone protects the human gastric 

mucosa from diclofenac-induced injury via induction of heat shock protein 70. Digestion Vol 

75; 2007: 148-55. Not lactose intolerance study 

2268. Yáñez L, Jung H, Garza-Flores J, et al. Norethisterone-cholesterol eutectic mixture as an 

oral sustained-release hormonal preparation: bioequivalence study in humans. Contraception 

Vol 37; 1988: 349-57. Not lactose intolerance study 

2269. Yang WH, Purchase EC, Rivington RN. Positive skin tests and Prausnitz-Küstner reactions 

in metabisulfite-sensitive subjects. The Journal of allergy and clinical immunology Vol 78; 

1986: 443-9. Not lactose intolerance study 

2270. Yano K, Heilbrun LK, Wasnich RD, et al. The relationship between diet and bone mineral 

content of multiple skeletal sites in elderly Japanese-American men and women living in 

Hawaii. Am J Clin Nutr 1985 Nov; 42(5):877-88. Correlation coefficient 

2271. Yao XH, Kong BQ, Yan JX, et al. Lactose tolerance test by hydrogen breath method in 

Chinese. Chin Med J (Engl) 1987 Apr; 100(4):316-8. Not relevant to key questions 

2272. Yap I, Berris B, Kang JY, et al. Lactase deficiency in Singapore-born and Canadian-born 

Chinese. Digestive Diseases & Sciences 1989 Jul; 34(7):1085-8. Ineligible number of 

subjects 

2273. Yeh TF, Srinivasan G, Harris V, et al. Hydrocortisone therapy in meconium aspiration 

syndrome: a controlled study. The Journal of pediatrics Vol 90; 1977: 140-3. Not lactose 

intolerance study 

322
 
2274. Yeoh E, Horowitz M, Russo A, et al. A retrospective study of the effects of pelvic 

irradiation for carcinoma of the cervix on gastrointestinal function. International Journal of 

Radiation Oncology, Biology, Physics 1993 May 20; 26(2):229-37. Ineligible number of 

subjects 

2275. Yeoh E, Horowitz M, Russo A, et al. The effects of abdominal irradiation for seminoma of 

the testis on gastrointestinal function. J Gastroenterol Hepatol Vol 10; 1995: 125-30. Not 

lactose intolerance study 

2276. Yeoh E, Horowitz M, Russo A, et al. Effect of pelvic irradiation on gastrointestinal 

function: a prospective longitudinal study. American Journal of Medicine 1993 Oct; 

95(4):397-406. Ineligible number of subjects 

2277. Yeoh EK, Horowitz M, Russo A, et al. Gastrointestinal function in chronic radiation 

enteritis--effects of loperamide-N-oxide. Gut Vol 34; 1993: 476-82. Not lactose intolerance 

study 

2278. Yesovitch R, Cohen A, Szilagyi A. Failure to improve parameters of lactose maldigestion 

using the multiprobiotic product VSL3 in lactose maldigesters: a pilot study. Can J 

Gastroenterol 2004 Feb; 18(2):83-6. Not relevant to key questions 

2279. Yeung CY, Ma YP, Wong FH, et al. Automatic end-expiratory air sampling device for 

breath hydrogen test in infants. Lancet 1991 Jan 12; 337(8733):90-3. Not relevant to key 

questions 

2280. Yip I, Go VL, DeShields S, et al. Liquid meal replacements and glycemic control in obese 

type 2 diabetes patients. Obesity research Vol 9; 2001: 341s-7s. Not lactose intolerance study 

2281. Yolken RH, Hart W, Oung I, et al. Gastrointestinal dysfunction and disaccharide 

intolerance in children infected with human immunodeficiency virus. Journal of Pediatrics 

1991 Mar; 118(3):359-63. No prevalence data 

2282. Yoshida Y, Sasaki G, Goto S, et al. Studies on the etiology of milk intolerance in Japanese 

adults. Gastroenterol Jpn 1975; 10(1):29-34. Not relevant to key questions 

2283. Young DS. High pressure column chromatography of carbohydrates in the clinical 

laboratory. Am J Clin Pathol 1970 May; 53(5):803-10. Not relevant to key questions 

2284. Young EA. Jonathan E. Rhoads Lecture. Medicine, nutrition, and patient care: a panoramic 

view. Jpen: Journal of Parenteral & Enteral Nutrition 1994 Sep-Oct; 18(5):387-95. Not 

original research 

2285. Youngstedt SD, O'Connor PJ, Crabbe JB, et al. The influence of acute exercise on sleep 

following high caffeine intake. Physiology & behavior Vol 68; 2000: 563-70. Not lactose 

intolerance study 

2286. Yudkoff M, Cohn RM, Segal S. Errors of carbohydrate metabolism in infants and children: 

a survey. Clin Pediatr (Phila) 1978 Nov; 17(11):820-8. Not relevant to key questions 

323
 
2287. Zemel MB. Calcium utilization: effect of varying level and source of dietary protein. Am J 

Clin Nutr 1988 Sep; 48(3 Suppl):880-3. Comment 

2288. Zhang Y, Ojima T, Murata C. Calcium intake pattern among Japanese women across five 

stages of health behavior change. J Epidemiol 2007 Mar; 17(2):45-53. Not eligible outcomes 

2289. Zheng JJ, Gong ZL, Xue LS, et al. Lactose malabsorption and its ethnic differences in 

Hans and Uygurs. Chin Med J (Engl) 1988 Apr; 101(4):284-6. Not relevant to key questions 

2290. Zhong Y, Priebe MG, Vonk RJ, et al. The role of colonic microbiota in lactose intolerance. 

Dig Dis Sci 2004 Jan; 49(1):78-83. Not relevant to key questions 

2291. Zimmerman CL, O'Connell MB, Soria I. The effects of urine pH modification on the 

pharmacokinetics and pharmacodynamics of phenylpropanolamine. Pharmaceutical research 

Vol 7; 1990: 96-102. Not lactose intolerance study 

324
 
2292. Zittermann A, Bock P, Drummer C, et al. Lactose does not enhance calcium bioavailability 

in lactose-tolerant, healthy adults. The American journal of clinical nutrition Vol 71; 2000: 

931-6. Not eligible outcomes 

2293. Zuccato E, Andreoletti M, Bozzani A, et al. Respiratory excretion of hydrogen and 

methane in Italian subjects after ingestion of lactose and milk. Eur J Clin Invest 1983 Jun; 

13(3):261-6. Not relevant to key questions 

2294. Zuin G, Fontana M, Monti S, et al. Malabsorption of different lactose loads in children 

with human immunodeficiency virus infection. Journal of Pediatric Gastroenterology & 

Nutrition 1992 Nov; 15(4):408-12. Ineligible number of subjects 

2295. Zweig MH, Robertson EA. Why we need better test evaluations. Clinical Chemistry 1982 

Jun; 28(6):1272-6. No prevalence data 

325
 
Appendix D. Evidence Tables 

Table D1. Observational studies of lactose intolerance or malabsorption in association 

with patient outcomes.............................................................................................D-2 

Table D2. Association between low dairy Ca++ intake and bone fractures............................D-20 

Table D3. Association between lactose intake and genetic polymorphism or self reported 

lactose intolerance ................................................................................................D-21 

Table D4. Association between low lactose diets, lactose intolerance or malabsorption,
 

and clinical symptoms..........................................................................................D-22 

Table D5. Gains in osteodensitometric values in prepubertal boys consuming low lactose 

diet (74% of the recommended daily Ca++ intake) after interventions with 

dairy foods (1,607 vs. 747mg/day of Ca++) ........................................................D-24 

Table D6. Association between lactose intake and metabolism and bone mineral density 

(BMD, g/cm2) ......................................................................................................D-25 

Table D7. Association between lactose intake and metabolism and bone density (BD).........D-31 

Table D8. Evidence table for blinded lactose intolerance treatment studies: Questions 3 

and 4 .....................................................................................................................D-32 

References for Appendix D .....................................................................................................D-69 

326
 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes 

Study Subjects Diagnosis and Control for Bias 

Alhava, 19771 

Country: Finland Population: Adults Source: The Outpatient Clinic in the University of Central Hospital, Kuopio Study design: Cross-sectional Birge, 19672 

Country: USA Population: Adults 50 years or over Source: Patients referred to the National Institute of Arthritis and Metabolic Diseases Study design: Cross-sectional Buchowski, 20023 

Country: USA Population: Premenopausal lactose maldigesting African American women Source: Recruited in Meharry Medical College Study design: Cross-sectional 

Inclusion: Adults with documented positive lactose intolerance test and healthy controls Exclusion: General malabsorption, rheumatoid arthritis, other diseases that affect bone metabolism Excluded: NS Inclusion age: >19 Followup: None Mean age: 21-72 for men and 19-71 for women Inclusion: Confirmed diagnosis of osteoporosis, healthy volunteers without osteoporosis Exclusion: History of steroid therapy, malabsopriton, endocrinopathy, cancer, renal disease or lithiasis or other causes of demineralization Excluded: NR Inclusion age: >50 Followup: None Mean age: NS 

Diagnosis of LI: Lactose malabsorption as positive glucose test, max rise <1.3mmol/l Diet: Self reported Diet assessment: NS Control for bias: None Diagnosis of LI: Positive lactose tolerance test; Patients who had less than a 50% mg/dl rise in blood glucose were lactase deficient Diet: Self reported Diet assessment: Interviews conducted by a registered dietician and PI Control for bias: None 

Test: BloRace: NS Ethnicity: Test: Oratests, glujejunal bilactase aRace: NS Ethnicity: 

D327 

Inclusion: Premenopausal (self-reported frequency of menstruation in the preceding three-month period )African American women with a rise in breath hydrogen concentration of greater than 0.90 mol/L (20 ppm) after ingestion of 25 g of lactose Exclusion: NR Excluded: Seven women were excluded from final analyses; two withdrew from the study, and five women did not complete dietary records Inclusion age: Adults Followup: None Mean age: 34.1-37.1 

Diagnosis of LI: Lactose maldigestion – positive hydrogen breath testing. Lactose intolerance self reported symptoms were scored, women with scores of at least 3 on this scale after ingesting lactose-containing milk were classified as lactose intolerant. Women who scored 2 or less after drinking lactose containing milk were classified as lactose tolerant Diet: Regular diet Diet assessment: Seven-day dietary record Control for bias: Matching by age, adjustment for BMI 

Test: The severity orated by ingesting containin(Suarez eoccurrenabdominaflatulencescale as 1 trivial, 2 strong, aRace: AfEthnicity: 

Corazza, 19954 Inclusion: 83 consecutive postmenopausal Diagnosis of LI: Self reported relationship Test: Pos

Country: Italy women with suspected between the onset of abdominal symptoms, test Population: Postmenopausal osteoporosis, Caucasian, residents in the such as flatulence, abdominal pain, Race: Cawomen Bologna area diarrhea and the intake of milk, ice cream, Ethnicity: Source: Clinic based Exclusion: Ovariectomy , estrogen cheese and yoghurt and positive Hydrogen 

Study design: Cross-sectional replacement therapy, Ca supplementation, breath testing 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Di Stefano, 20025 

Country: Italy Population: Adults Source: Work place Study design: Cross-sectional Du, 20026 

Country: China Population: Adolescent Girls Source: Population based Study design: Cross-sectional 

D328 

Enattah, 20047 Country: Finland Population: Young men Source: Population based cohort The Cardiovascular Risk in Young Finns Study Study design: Cross-sectional 

gastrointestinal diseases, recent treatment with antibiotics or drugs which could modify the intestinal flora, diseases known to influence Ca and bone metabolism Excluded: 25 Inclusion age: Adults Followup: NA Mean age: 57±7 Inclusion: 103 healthy subjects (59 women, 44 men), members of medical or paramedical staff of our hospital, or were students Exclusion: NR Excluded: NR Inclusion age: Adults Followup: NA Mean age: 28± 2 Inclusion: A random sample of 649 girls, ages 12–14 years from a sample of 1,277 girls selected in 13 middle schools in the Beijing area using cluster sampling procedure by means of a socioeconomic strata Exclusion: Evidence of liver, kidney, or other disorders that may have caused abnormal bone metabolism Excluded: NR Inclusion age: 12–14 years Followup: NA Mean age: 12.9±0.6 Inclusion: Participants in a study examining the role of genes, hormones, and lifestyle factors: 234 young men, ages 18.3 to 20.6 years, 184 men were recruits of the Finnish Army, and 50 were men of similar age who had postponed their military service for reasons not related to health Exclusion: Not reported Excluded: NR Inclusion age: 18.3-20.6 

Diet: Self reported Diet assessment: Dietary diary for three consecutive days evaluated by the nutritionist blinded to the details of the study Control for bias: None Diagnosis of LI: Lactose malabsorption was defined as positive hydrogen breath test Diet: Self reported Diet assessment: Dietary diary for 3 nonconsecutive days evaluated by blinded to the study details researcher Control for bias: None Diagnosis of LI: Feeling uncomfortable after drinking milk including symptoms such as stomach upset, cramps, bloating, and diarrhea, or any minor abnormal feeling Diet: Self reported Diet assessment: Habitual food and nutrient intakes over the past year were estimated by use of a specially designed and validated semi quantitative food frequency questionnaire Control for bias: Adjustment Diagnosis of LI: Adult-type hypolactasia, caused by the lactase-phlorizin hydrolase C/C-13910 genotype Diet: Self reported Diet assessment: Calcium intake was calculated on the basis of the supply from dairy products only Control for bias: Adjustment 

Test: Selduring thperiod afabdominadiarrhea, ranked asymptommild symsymptomand 5 sevRace: CaEthnicity: Test: Not Race: CaEthnicity: Test: lactC/T-1391Race: CaEthnicity: 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Followup: NA
 

Mean age: 19.4-19.7 

Enattah, 20058 Country: Finland Population: Postmenopausal women Source: Population based cohort The Cardiovascular Risk in Young Finns Study Study design: Cross-sectional 

D329 

Enattah, 20059 Country: Finland Population: Elderly Source: Population based cohort The Cardiovascular Risk in Young Finns Study Study design: Prospective 

Inclusion: A random subset of the control group participating in an ongoing RCT of an educational program for the prevention of fractures. RCT study population was 2,181 postmenopausal women, ages 60–70 years living in Southern Finland, they were initially recruited from the population register between 1996 and 2000;.52 women 69–85 years old, participants in trials of drug treatment of osteoporosis, were included for genotyping if they had vertebral fracture or osteoporosis according to the WHO criteria of BMD (a T-score <-2.5) at either the lumbar spine or the femoral neck Exclusion: Metabolic bone disease other than postmenopausal osteoporosis, use of bone-active agents (any previous use of bisphosphonates, concomitant use of oral glucocorticoids, or hormone replacement therapy use less than 6 months before the study), diseases that affect bone turnover, history of gastrointestinal mucosal disorders (erosive gastritis, gastric ulcer or esophagitis), history of a prior thromboembolic disease, liver or kidney disease, insulin-treated diabetes, history of uterus or breast cancer, or uncontrolled hypertension. Control group was 59 healthy women of the same age Excluded: 2 women who did not answer the question about self perceived LI Inclusion age: >60 Followup: NA Mean age: 62-78 Inclusion: Vantaa 85+ population-based study of all subjects born before April 1, 1906, who were living in the city of Vantaa, Finland, on April 1, 1991; included 483 people older than 85 years of age (106 men and 377 women). Exclusion: NR 

Diagnosis of LI: Adult-type hypolactasia, caused by the lactase-phlorizin hydrolase C/C-13910 genotype Diet: Self reported Diet assessment: Calcium intake was calculated from dairy products only. The questionnaire was not validated. Control for bias: Adjustment Diagnosis of LI: Adult-type hypolactasia, caused by the lactase-phlorizin hydrolase C/C-13910 genotype Diet: Self reported Diet assessment: The data on consumption of milk was based on interviews of the participants 

Test: lactC/T-1391self repoRace: CaEthnicity: Test: lactC/T-1391Race: CaEthnicity: 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study	 Subjects Diagnosis and Control for Bias 

cohort Excluded: The data on milk product intake Control for bias: Adjustment 

was available on 399 of 483 subjects Inclusion age: 85 - 98 Followup: 8 years Mean age: 89 

Finkenstedt, 198610 

Country: Austria Population: Women Source: NS Study design: Case-control Goulding, 199911 Country: New Zealand Population: Middle age and older women Source: Population based Study design: Prospective 

Inclusion: Cases- women with "idiopathic" osteoporosis confirmed by the presence of reduced bone mineral density in plain x-ray films and either a femoral trabecular index <5 in 4 degree or the presence of spontaneous fractures of vertebrae or long bones, or both. Controls: 33 women without osteoporosis (Singh index >4) of the same ethnic origin matched for age Exclusion: Endocrine disorders, liver and renal disease, postgastrectomy states, malabsorption syndromes, rheumatoid arthritis, osteomalacia, and malignancy and patients receiving corticosteroids. Patients and controls were not taking drugs that influenced calcium or bone metabolism Excluded: NR Inclusion age: Adults Followup: NA Mean age: 54-56 

Test: Selrelated to diagnosis Race: CaEthnicity: 

D330 

Inclusion: Healthy Caucasian women ages 40-79 years Exclusion: Medications affecting bones, history of gastro-intestinal surgery, radiotherapy, hip replacement, malapsorption syndromes, hyperthyroidism, hyperparathyroidism Excluded: NR Inclusion age: 40-79 Followup: 1 year Mean age: NR 

Diagnosis of LI: Lactose malabsorption as a rise in glucose concentration of <20 mg/100 ml) after the ingestion of 50 g lactose dissolved in water Diet: Self reported Diet assessment: A questionnaire about mean daily or weekly ingestion of dairy products and about tolerance to milk in childhood and later life. The daily calcium intake derived from milk and dairy products was calculated according to standard nutritional tables Control for bias: Matching Diagnosis of LI: Lactose malabsorption: Positive hydrogen test, >10ppmH2 above baseline 60-180min after lactose load Diet: Self reported Diet assessment: Food frequency questionnaire and 4-day diet records Control for bias: Adjustment 

Test: breg oral lacRace: CaEthnicity: 

Gugatschka, 200512 Inclusion: Participants in the population- Diagnosis of LI: Lactose malabsorption was Test: Sel

Country: Austria Population: based study by the Austrian Study Group on diagnosed when the difference between related to Adult males Normative Values on Bone Metabolism and breath hydrogen concentration at baseline diagnosis Source: Population based and out-patients who had examination of bone and maximum exceeded 20 parts per Race: Ca

out-patient in the Division of metabolism and nutritional and constitutional million according to international standards Ethnicity: 

Endocrinology and Nuclear factors, response rate 56% (ppm). 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Medicine Study design: Cross-sectional Gugatschka, 200713 

Country: Austria Population: Elderly male Source: Population based and out-patient in the Division of Endocrinology and Nuclear Medicine Study design: Cross-sectional 

D331 

Harma, 198814 Country: Finland Population: Elderly women Source: Hospital based Study design: Case-control 

Exclusion: Liver or kidney disease, primary hyperparathyroidism, long-term use of corticosteroids, other possible causes of secondary osteoporosis, consumption of bone-active medication, alcoholism Excluded: Breath hydrogen test was performed in 52 women (22%) Inclusion age: Adults Followup: NA Mean age: 56±12 Inclusion: Participants in the populationbased study by the Austrian Study Group on Normative Values on Bone Metabolism and out-patients who had examination of bone metabolism and nutritional and constitutional factors, response rate 56% Exclusion: Liver or kidney disease, primary hyperparathyroidism, long-term use of corticosteroids, other possible causes of secondary osteoporosis, consumption of bone-active medication, alcoholism Excluded: Breath hydrogen test was performed in 52 women (22%) Inclusion age: Elderly Followup: NA Mean age: 61±9 Inclusion: Cases: 18 women with spinal fragility fractures and 28 women with hip fractures within one week after the fracture. Healthy controls: 35 female of the same ethnic background hospitalized for cataract surgery or other minor operations Exclusion: Institutionalized patients, previous gastric surgery, hepatic or renal failure, metabolic bone diseases, drugs altering bone metabolism Excluded: NR Inclusion age: 38-84 with spinal fractures, 64-93 with hip fractures, and 45-86 healthy controls) Followup: NA Mean age: 67-78 years 

Diet: Self reported Diet assessment: Calcium intake from dairy and other food products and self perceived lactose intolerance (nonmilk drinkers) were obtained using a questionnaire Control for bias: None Diagnosis of LI: Lactose malabsorption was diagnosed when the difference between breath hydrogen concentration at baseline and maximum exceeded 20 parts per million according to international standards (ppm). Diet: Self reported Diet assessment: Standardized calcium questionnaire Control for bias: None Diagnosis of LI: Lactose malabsorpion as positive blood glucose test (<1.3mmol/L) Diet: Self reported Diet assessment: Interview to assess daily milk consumption Control for bias: Matching 

Test: Selrelated to diagnosis Race: CaEthnicity: Test: BloRace: CaEthnicity: 

Honkanen, 199715 Inclusion: A random population sample of Diagnosis of LI: Positive lactose tolerance Test: Lac
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Country: Finland Population: Perimenopausal women Source: Population based Study design: Cross-sectional Honkanen, 199616 

Country: Finland Population: Perimenopausal women Source: Population based Study design: Cross-sectional 

D332 

Horowitz, 198717 

Country: Austria Population: Postmenopausal women Source: Clinic based Study design: Cross-sectional 

11,619 women of the 13,100 respondents who also responded to the fracture and health disorder questions. A random stratified sample of 3,222 of these 13,100 women underwent bone densitometry. Exclusion: Not reported Excluded: NR Inclusion age: NR Followup: None Mean age: 52.4± 2.9 Inclusion: A random population sample of 2,025 women 48-59 years old, who underwent spinal and femoral BMD measurement with dual x-ray absorptiometry in Kuopio, Finland, during 1989-1991 Exclusion: Not reported Excluded: NS Inclusion age: 47-56 Followup: None Mean age: 54±9 Inclusion: 48 randomly selected untreated women with postmenopausal osteoporosis from 50 to 83 years Exclusion: Recent fractures Excluded: NR Inclusion age: 50-83 Followup: NA Mean age: 65 

test Diet: Self reported Diet assessment: Dairy calcium intake was computed as the sum intake from fluid milk products (l20 mg/dL) and cheese (87 mg/ slice) in 1989. The validity of the dairy calcium intake inquiry was tested against a 4 day food record of total nutritional calcium intake 76 women, resulting in a correlation of 0.50 Control for bias: Adjustment Diagnosis of LI: Positive lactose tolerance test (serial blood glucose determinations after a 50 g oral dose of lactose). Diet: Self reported Diet assessment: Dairy calcium intake was estimated with two questions: (1) “How many deciliters of milk products (such as milk, buttermilk, processed sour milk, and yogurt) do you use daily on average?” and (2) “How many slices of cheese do you use daily on average?” Dairy calcium intake was computed as the sum of calcium derived from fluid milk products (120 mg/dL) and cheese (87 mglslice) based on the NUTRICA, a PC-program for nutritional data developed by the Social Insurance Institution of Finland. The validity of the questionnaire was tested against a 4-day food record completed by 76 women (39 LI and 37 control women) in 1990. Control for bias: Adjustment Diagnosis of LI: Lactose malabsorpion as positive hydrogen breath test, LI- self reported symptoms during and after the test Diet: Self reported Diet assessment: Questionnaire to record milk intake before the diagnosis of osteoporosis and the presence of symptoms of LI Control for bias: None 

abdominatest Race: CaEthnicity: Test: Lacabdominatest Race: CaEthnicity: Test: Breinterview of the tessymptomRace: NR Ethnicity: 

Infante, 200018 Inclusion: Thirty children followed dietary Diagnosis of LI: Medical diagnosis Test: NS 

Country: Spain advice to exclude dairy for at least 2 years: Diet: Advised Race: NS Population: Children and 10 patients with late-onset, genetically Diet assessment: Questionnaire Ethnicity: 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

adolescents Source: Clinic based Study design: Cross-sectional 

induced lactose intolerance (breath hydrogen test >20 ppm), 3 patients with short bowel syndrome, 7 with cow's milk protein allergy and l0 with hypercholesterolemia (cholesterol >200 mg/dl and low-density lipoprotein cholesterol >130 mg/ dl).14 patients received special formulas for children (lactose-free cow's milk formula, highly hydrolyzed cow's milk protein formula, soy protein isolate formula), 4 patients received liquid soy beverages, 6 patients received skim milk (1% fat), and 6 patients had exclusion of dairy products. Exclusion: NR 

commenting dairy food (or substitute)o consumption for a total of 7 days during a 4-week period Control for bias: None 

Excluded: NR 

Kanis, 200519 

Country: UK Population: Adults Source: Population based Study design: Meta-analysis of individual patient data 

Inclusion age: 2-14 years Followup: NA Mean age: 7 Inclusion: Meta-analysis of the original data from 6 prospective cohorts that recruited randomly selected from the populations in Europe, Australia, and Canada 39,563 men and women. The collaborative study to identify clinical risk factors for fracture 

included the European Vertebral Osteoporosis Study (EVOS/EPOS study), the Canadian Multicentre Osteoporosis Study (CaMos), the Dubbo Osteoporosis Epidemiology Study (DOES), the Rotterdam Study, the Sheffield Study and a cohort from Gothenburg. Exclusion: Invalidated data on milk 

Diagnosis of LI: Reference category of low milk intake <1 glass of milk/day (~250 mg calcium/ day). A threshold of <500 mg of calcium was used two studies (Rotterdam and DOES) assuming that ~50% of calcium intake is in the form of milk. Diet: Self reported Diet assessment: Validated food frequency questionnaire or dietary intake questionnaire Control for bias: Adjustment 

Test: Not Race: NS Ethnicity: 

consumption Excluded: NR Inclusion age: Adults Followup: Total 3.8 years, 151,957 person years for 39,563 subjects Mean age: Varied in the studies, the ranges 21-103 

D333 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Kudlacek, 200220 

Country: Austria Population: Adults Source: Clinical based screening Study design: Cross-sectional 

Inclusion: Healthy individuals who were referred for confirmation of suspected osteoporosis or for osteoporosis screening and estimation of risk for fracture; male female ratio, 1:4 Exclusion: Secondary osteoporosis, medical treatment, e.g., receiving hormone replacement therapy, fluorides, calcitonin, or vitamin D, other gastrointestinal diseases, e.g., celiac disease or chronic inflammatory bowel disease, a history of fracture due to severe trauma. Excluded: NR Inclusion age: NR Followup: NA Mean age: 58.2± 11.5 

D334 Kull, 200921 Country: Estonia 

Population: Adults Source: Health care based: registers of general practitioners in the region Study design: Cross-sectional Lehtimaki, 200622 Country: Finland Population: children and adolescents Source: Population based cohort The Cardiovascular Risk in Young Finns Study Study design: Prospective cohort 

Inclusion: Randomly selected from the registers healthy subjects, response rate 66% (200 F, 167 M) Exclusion: NR Inclusion age: >20 Followup: NA Mean age: 25-70 Inclusion: A random sample from the national population register, from 5 university cities in Finland and the rural municipalities in their vicinity Exclusion: Not reported Excluded: 2,265 from original 3,596 participants had genotyping exam Inclusion age: 3-18 years Followup: 21 years Mean age: 10 

Diagnosis of LI: Lactose intolerance was diagnosed with a positive hydrogen breath test. Lactose malabsorbers moderate, 20ppm <DH2 < 59ppm or was severe (DH2 >60ppm). Clinical symptoms were categorized as moderate (group 1) or severe (group 2). Symptoms during the test were scored with a self-reported questionnaire. Group 0 reported no symptoms; group 1 experienced abdominal discomfort (moderate symptoms); and group 2, severe diarrhea with abdominal cramps (severe symptoms). Diet: Self reported Diet assessment: Questionnaire to categorize as lactose exclusion (denied milk consumption), low lactose diet (1 glass per day ~ 200ml milk; 240mg calcium/day) no restrictions with regard to milk (>400ml milk; 480mg calcium/day). Control for bias: None Diagnosis of LI: Adult-type hypolactasia was diagnosed by direct sequencing of the LCT gene Diet: Self reported Diet assessment: Questionnaire about milk and dairy product consumption, selfperceived milk tolerance Control for bias: None Diagnosis of LI: Adult-type hypolactasia, caused by the lactase-phlorizin hydrolase C/C-13910 genotype Diet: Self reported Diet assessment: Dietary questionnaires, detailed dietary interviews, and a 48-hour dietary recall Control for bias: Stratification by sex and onset of LI 

Test: Hydreported Race: CaEthnicity: Test: SelintolerancsequenciRace: CaEthnicity: Test: LacC/T-1391Race: CaEthnicity: 

Matlik, 200723 Inclusion: Middle schools that had larger Diagnosis of LI: Lactose maldigestion Test: Per

Country: USA proportions of Asian or Hispanic students diagnosed with hydrogen breath testing was diagPopulation: 10-13 year old than the state average and were located (breath hydrogen levels of >20 ppm), questionn

female adolescents within a 1-hour distance from the designated perceived milk intolerance diagnosed with statemen
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Source: Participants in a sub study of the multiple-site project Adequate Calcium Today Study design: Cross-sectional study was a sub study of the Adequate Calcium Today (ACT) project, a schoolrandomized intervention project conducted at sites in 6 states 

D335 

Obermayer-Pietsch, 200724 

Country: Austria Population: Postmenopausal women Source: Participants in a genetic screening study for osteoporosis Study design: Prospective followup of the previously published study Obermayer-Pietsch, 200425 Country: Austria Population: Postmenopausal women Source: Participants in a genetic screening study for osteoporosis Study design: Cross-sectional study 

dual-energy x-ray absorptiometry (DXA) measurement site (1 site in each state).Girls were eligible if they were at least 75% Asian, Hispanic, or non-Hispanic white, as selfreported by their biological parents Exclusion: Estimated daily food calcium intakes that were 100 mg/day or 2,500 mg/day were considered improbable, and individuals with such values were excluded from any analyses using food calcium intake. Excluded: A total of 39 (13.5%) of 289 subjects were excluded Inclusion age: 10-13 years Followup: None Mean age: 11. Inclusion: Unrelated postmenopausal women who live independently Exclusion: Liver or kidney disease, primary hyperparathyroidism or other causes of bone disease Excluded: 60 Inclusion age: Adults Followup: 61±9months Mean age: 65±9 Inclusion: Unrelated postmenopausal women Exclusion: Liver or kidney disease, primary hyperparathyroidism, other causes of secondary bone disease, consumption of bone active medication Excluded: 92 Inclusion age: Adults Followup: None Mean age: 62 ± 9 

questionnaires Diet: Self reported diet Diet assessment: Calcium-specific, semi quantitative, food frequency questionnaire developed for and evaluated with Asian, Hispanic, and non-Hispanic white youths Control for bias: Adjustment Diagnosis of LI: Hydrogen breath test and glucose blood test, symptoms Diet: Self reported Diet assessment: Detailed food-frequency questionnaire on dietary calcium intake in milligrams per day Control for bias: None Diagnosis of LI: Recorded by the general practitioner during the standardized interview, self reported dislike of milk taste, and aversion to milk consumption Diet: Self reported Diet assessment: Detailed food-frequency questionnaire on dietary calcium intake in milligrams per day Control for bias: Adjustment 

group disof adolessame age groups aparticipanwere as fto milk,” (after drinhave beemake my drink it.” “strongly to “strongor “do nomissing). calculateresponseresponseabove 2; was definPMI Race: AmAsian, 76 Hispanic Test: LCT and CC Race: NR Ethnicity: Test: LCT and CC Race: NR Ethnicity: 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Segal, 200326 

Country: Israel Population: Adults Source: Clinic based Study design: Cross-sectional Stallings, 199427 

Country: USA Population: Prepubertal children Source: Children's Hospital of Philadelphia Study design: Cross sectional controlled comparison 

D336 

Vigorita, 198728 

Country: USA Population: Postmenopausal women Source: NS Study design: Cross-sectional 

Inclusion: Seventy-eight consecutive patients 20 to 78 years of age, with clinical signs of LI referred to gastroenterologists or recruited from the Gastroenterology Unit Exclusion: Ontogenesiimperfect; chronic renal failure; hypocalciuric hypercalcemia; history of recent malignancy Excluded: 12 Inclusion age: 20-78 Followup: NA Mean age: 66 patients, 49 women (18 premenopausal, 31 postmenopausal), 17 men Inclusion: Prepubertal children 6-12 years with LI diagnosed with standard breath hydrogen test within the previous 3 years, without symptoms related to LI at the time of the study. Healthy children participating in the Fels Longitudinal Study Exclusion: Significant illnesses that could affect growth or bone development including inflammatory bowel syndrome, renal failure, cardiac disease, sarcoidosis. Consume Ca++ supplement and/or>16oz milk products Excluded: One girl without suitable control Inclusion age: 6-12 years Followup: None Mean age: 9.6±1.9 Inclusion: Postmenopausal women with the osteoporotic spinal compression fracture syndrome Exclusion: Concurrent malabsorption syndromes, endocrinopathies, marrow tumor, or prior therapy Excluded: 3 women with normal and 6 women with abnormal lactose tolerance test were excluded from bone biopsy analyses Inclusion age: >53 Followup: None Mean age: 66.3-70.3 

Diagnosis of LI: Positive breath test in addition to clinical symptoms (concentration of H2 in the expired air increased by more than 20 ppm above baseline) Diet: Self reported Diet assessment: Calcium intake from dairy and other sources was evaluated using a semi-quantitative food frequency questionnaire adapted from W. Willet Control for bias: Matching by age and gender Diagnosis of LI: LI diagnosed by standard breath hydrogen test Diet: prescribed low lactose diet Diet assessment: Food frequency questionnaire of 7 days over 6 week period to evaluate adherence to prescribed diet Control for bias: Matching, Adjustment for body size Diagnosis of LI: Positive lactose tolerance test; Patients who had less than a 30% mg/dl rise in blood glucose were termed lactase deficient Diet: Self reported Diet assessment: Interviews conducted by a registered dietician using a questionnaire based on dietary preference, 24-hour recall, and weekly intake Control for bias: None 

Test: Clinconfirmed positive bRace: NS Ethnicity: Test: BreRace: NR Ethnicity: Test: OraRace: CaEthnicity: Hispanic 

Wheadon, 199129 Inclusion: Cases-women <75 years of age Diagnosis of LI: Lactose malabsorption- Test: bre

Country: New Zealand with hip fractures 6 months-2 years before breath hydrogen after a 50 g oral lactose g oral lacPopulation: Elderly New the study diagnosed with type II tolerance test of >10ppm above baseline Race: Ca
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Zealand women with hip fractures Source: NS Study design: Case-control 

osteoporosis. Controls: 16 healthy agematched women who had never had a fracture and 50 healthy young volunteers (17-30 years old) Exclusion: Previous surgery of gastrointestinal tract, baseline reasons for 

Diet: Self reported Diet assessment: Dietary calcium was estimated from a food frequency questionnaire Control for bias: Age matched controls 

Ethnicity: 

malabsorption Excluded: NR Inclusion age: Cases-<75 years old, age matched controls, healthy controls 17-30 years Followup: NA Mean age: 66±10 

Studies of low lactose diet that did not address lactose intolerance status 

D337 

Appleby, 200730 Country: UK Population: Vegetarians; adults Source: The Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford) Study design: Prospective cohort Bauer, 199331 

Country: USA Population: Older women Source: The Study of Osteoporotic Fractures Research Group Study design: Cross-sectional 

Inclusion: The Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford) general practice surgeries recruited 57,450 adults from the residential areas and several general practice surgeries in the UK Exclusion: NR Excluded: 240 participants who did not answer the question about fractures, 1,360 who reported any type of fracture before recruitment or a fracture of the digits or ribs, and 660 whose nutrient intake data were considered to be unreliable (>20% of food frequencies missing or daily energy intakes less than 800 kcal or more than 4,000 kcal for men or less than 500 kcal or more than 3,500 kcal for women). Inclusion age: NR Followup: 6 years Mean age: 46.6 Inclusion: 9,704 ambulatory, nonblack women, ages 65 years or older Exclusion: Blacks or unable to walk without the assistance of another person or who had bilateral hip replacements Excluded: NR Inclusion age: >65 Followup: NA Mean age: 71.1 

Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Food frequency questionnaire Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Checklist-interview method developed from the HANES-II survey to asses dietary Ca++ (correlation of 0.76 with calcium intake assessed by a 7-day diet diary) and milk intake Control for bias: Adjustment 

Test: Not Race: NR Ethnicity: Test: Not Race: CaEthnicity: Calcium teenager50, and aadjusted intake, wincreased 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

who dranbetween 3.1% higwith thosdrank mil

Black, 200232 

Country: New Zealand Population: Prepubertal children with a history of longterm milk avoidance Source: Population based Study design: Cross-sectional Chiu, 199733 

Country: Taiwan Population: Postmenopausal Taiwanese women Source: 10 temples in Tai-nan and Kaoshiung, two of the largest counties in southern Taiwan. Study design: Cross-sectional 

D338 

Cumming, 199434 Country: Australia Population: Elderly women and men Source: Population-based control Study design: Case-control 

Inclusion: Caucasian children ages 3–10 years with a history of prolonged milk avoidance for more than 4 months Exclusion: Gait disorders, current bone fractures, or medical diagnoses affecting bone (e.g., diabetes or malabsorptive syndromes) Excluded: None Inclusion age: Children Followup: NA Mean age: 5.9±1.9 (female) and 6.4±2.3 (male) Inclusion: 258 postmenopausal Buddhist nuns and female religious followers of Buddhism in southern Taiwan Exclusion: Disease or therapy known to affect bone metabolism Excluded: NR Inclusion age: 40–87 Followup: NA Mean age: 60.8 ± 9.2 Inclusion: Cases-patients with acute hip fracture older than 65 years of age were recruited in 12 hospitals. Controls were selected in a defined region in Sydney, Australia, using an area probability sampling method, with additional sampling from nursing homes Exclusion: NR Excluded: Exposure data was not available for 42% of cases because of impaired cognitive function and difficulties collecting proxy responses Inclusion age: >75 

Diagnosis of LI: Not diagnosed Diet: Self reported prolonged milk avoidance Diet assessment: Validated food-frequency questionnaire; current calcium intakes were estimated both by the same FFQ used at baseline and by 4-day diet records (4DDRs), which we collected just before the followup clinic appointment to avoid post interview bias. Control for bias: None Diagnosis of LI: Not addressed Diet: Vegan diet Diet assessment: Questionnaire interview to identify type of vegetarian practiced (strict vegan, lacto vegetarian, or omnivore who ate vegan diet only periodically). Longterm vegan vegetarians were defined in this study as those who had adhered to a strict vegan vegetarian diet for at least 15 years. Dietary assessment included a 24­hour recall and food frequency questionnaire Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Interview administered questionnaire, proxy responders. To assess recall bias, all participants were asked what cases hip fractures in old age. Dairy intake was categorized in units, 1 unit of dairy products was equal 1 glass of milk+0.5 servings of chees+0.5 (milk on cereal) Control for bias: Adjustment 

Test: Selrelated to Race: CaEthnicity: Sex-specscores wreference and 100 fracture oDunedin Test: Not Race: AsEthnicity: Test: Not Race: NR Ethnicity: 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Followup: NA
 

Mean age: NR
 

Feskanich, 199735 Country: USA Population: Middle aged women Source: The Nurses' Health Study Study design: Prospective cohort Fujiwara, 199736 

Country: Japan Population: Adults Source: The Adult Health Study Study design: Prospective cohort 

D339 

Goulding, 200437 

Country: New Zealand Population: Prepubertal children with a history of longterm milk avoidance Source: Population based Study design: Prospective followup of the previously published study 

Inclusion: 77,761 women, ages 34-59 years in 1980, who had never used calcium supplements were selected from the original cohort of 121,701 female registered nurses in 11 states who were 30 to 55 years of age when they returned an initial questionnaire in 1976 Exclusion: Implausibly low or high daily food intake or failure to report frequency of milk consumption (6%); a previous hip or forearm fracture or a diagnosis of coronary heart disease, stroke, cancer, or osteoporosis (6%); and reported use of calcium supplements in 1982 (9%). Excluded: 0.21 Inclusion age: 34-59 Followup: 12 years Mean age: 45.8-46.4 Inclusion: 4,869 residents in Hiroshima and Nagasaki ages 32 years who responded to the mail questionnaire survey conducted in 1979–1981. Exclusion: Incident hip fractures due to traffic accidents Excluded: 285 who lacked measurements of height and weight and 11 who were diagnosed as having hip fracture in the 1978–1980 examination were excluded Inclusion age: >32 Followup: 18 Mean age: 58.5 ± 12.2 Inclusion: Caucasian children ages 3–10 years with a history of prolonged milk avoidance for more than 4 months Exclusion: Gait disorders, current bone fractures, or medical diagnoses affecting bone (e.g., diabetes or malabsorptive syndromes) Excluded: 4 Inclusion age: Children Followup: 2 years 

Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Food-frequency questionnaire to collect four dairy items were added: cream or whipped cream, sour cream, sherbet or ice milk, and cream cheese. In validation studies the questionnaire was compared with multiple weeks of diet records, correlations were 0.81 for skim or low-fat milk, 0.62 for whole milk, and 0.57 for dietary calcium. In a reproducibility study that compared the frequency of milk consumption during their teenage years (ages 13 to 18) with data from a second administration 8 years later, the correlation was 0.71. Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Questionnaire survey about food frequency Control for bias: Adjustment Diagnosis of LI: Not diagnosed Diet: Self reported prolonged milk avoidance Diet assessment: Validated food-frequency questionnaire; current calcium intakes were estimated both by the same FFQ used at baseline and by 4-day diet records (4DDRs), which we collected just before the followup clinic appointment to avoid post interview bias. 

Test: Not Race: CaEthnicity: White Test: Not Race: AsEthnicity: Test: Selrelated to Race: CaEthnicity: Data from MultidiscDevelopm>1,000 c1972/197compara
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Mean age: 3-10 years Control for bias: None the gene

Johansson, 200438 

Country: UK Population: Elderly women Source: population based Study design: Placebo arm in RCT, prospective Johnell, 199539 

Country: Sweden Population: Women Source: The MEDOS Study. Mediterranean Osteoporosis Study Study design: Case-control 

D340 

Kalkwarf, 200340 Country: USA Population: Adults Source: Population based Study design: Cross-sectional 

Inclusion: 2,113 women >75 years of age randomly selected from Sheffield, UK, and adjacent regions who were randomized to placebo group in RCT of Ca++ supplement. 35,000 were invited, 5,873 responded (response rate 17%) Exclusion: Bone active agents, known malabsorption states, lack of compliance because of a poor mental state or concurrent illnesses, serum creatinine >0.3 mM, leukopenia (white cell count, <2 109/liter), hyper- or hypocalcemia, and elevated transaminases (greater than twice the upper reference limit). Excluded: 683 women randomized to placebo group Inclusion age: >75 Followup: 6 years Mean age: NR Inclusion: Cases: 2,086 women ages 50 years or more with hip fracture (interviewed within 14 days of fracture) in 14 centers from Portugal, Spain, France, Italy, Greece, and Turkey. Controls: 3,532 women ages 50 years or more selected from the neighborhood or population registers Exclusion: Poor mental health, concurrent illness Excluded: 80% of cases and 84% of controls were intervwied Inclusion age: >50 Followup: NA Mean age: 77.7-78.1 Inclusion: The third National Health and Nutrition Examination Survey of 3,251 nonHispanic, white women age ≥20 not institutionalized in 1988 and 1994 using a stratified, multistage probability design to select a nationally representative sample Exclusion: Unacceptable bone measurements 

Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Questionnaire to record milk intake Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Cases and controls were interviewed using a structured questionnaire on consumption of milk. Ca++ from milk in the recent past, young adulthood and childhood was assessed with 5 point scale (0-4: never, sometimes, 1-2 glasses/day, 3-4 glasses/day, >5 glasses/day) An overall score was calculated from three measurements with max 12 points. The median score was 6~ lifetime 1-2 glasses of milk/day or 240­480mg Ca++/day Control for bias: Adjustment Diagnosis of LI: Not defined Diet: Self reported Diet assessment: Milk intake during childhood was examined during the household interview with the questionnaire targeted 5 distinct age periods: childhood (5–12 years), adolescence (13–17 years), young adulthood (18–35 years), middle 

Test: Not Race: NR Ethnicity: Test: Not Race: NR Ethnicity: Test: Not Race: CaEthnicity: Among wbone minlower in tserving othan in th
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Kelsey, 199241 

Country: USA Population: Older women Source: The Study of Osteoporotic Fractures Research Group Study design: Cross-sectional 

Inclusion: 9,704 ambulatory, nonblack women, ages 65 years or older Exclusion: Blacks or unable to walk without the assistance of another person or who had bilateral hip replacements Excluded: NR Inclusion age: >65 Followup: NA Mean age: 71.1 

D341 

Lau, 199842 

Country: Hong Kong Population: Elderly Chinese vegetarian women Source: Population based Study design: Cross-sectional 

Excluded: Exclusion of fractures associated with severe trauma did not affect the results Inclusion age: Adults Followup: NA Mean age: 35±8 Inclusion: 76 vegetarian for over 30 years noninstitutionalized Buddhist women (ages 70±89 years). 250 Chinese omnivorous women, participants in a previous dietary survey, served as controls Exclusion: NR Excluded: NR Inclusion age: 70-89 Followup: NA Mean age: 79.1±5.2 

adulthood (36–65 years), and later adulthood (> 65 years). Subjects were asked to recall how often they consumed any type of milk, responses were collapsed into 4 categories: >1/day, 1/day, 1–6/week, and <1/week. Current milk intake was derived from the food-frequency questionnaire with the same categories as the historical milk intake information. Calcium intake was estimated from the 24­hour recall conducted during the MEC visit. The 24-hour recall was conducted with the use of an automated, interactive dietary data-collection system that was developed by the University of Minnesota Nutrition Coordinating Center. Food composition data were based on the US Department of Agriculture data files specific for that time period Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Checklist-interview method developed from the HANES-II survey to asses dietary Ca++ (correlation of 0.76 with calcium intake assessed by a 7-day diet diary) and milk intake Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Vegan diet Diet assessment: The 24 hour recall method administered by a single trained interviewer. Control for bias: None 

serving/dchildhood intake duassociatehip bone bone minAmong w

there was between childhood hip bone bone minTest: Not Race: CaEthnicity: Test: Not Race: AsEthnicity: 

Looker, 199343 Inclusion: Nationally representative sample Diagnosis of LI: Not addressed Test: Not 

Country: USA of the United States population: 4,342 white Diet: Self reported Race: CaPopulation: Men and men and postmenopausal women ages 50- Diet assessment: 24-hour recall and Ethnicity: posmenopausal women 74 years at baseline (1971-1975) were qualitative food frequency questionnaire to 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Source: the NHANES I Epidemiologic Follow-Up Study cohort Study design: Prospective cohort Nieves, 199244 

Country: USA Population: Middle aged women Source: Clinic based Study design: Case-control 

D342 

Parsons, 199745 

Country: The Netherlands Population: Adolescents Source: Macrobiotic families connected with the Human Nutrition Department, Wageningen University Study design: Cross-sectional 

observed through 1987 for up to 16 years of followup Exclusion: African American Excluded: NR Inclusion age: >50 Followup: 16 years Mean age: NR Inclusion: Cases: 161 white women admitted to one of 30 participating hospitals with radiologically confirmed diagnosis of a first hip fracture. Controls included 168 white women from general and orthopedic surgical services frequency-matched to cases by age group and hospital. The response rate was 61% in the case group and 56% in the controls; respondents were similar to nonrespondents with respect to age and city Exclusion: Previous hip fracture or hip replacement; cognitive impairment, death prior to interview, severe language and hearing impairments or medical instability Excluded: 143 potential cases and 44 potential controls with proxy responses Inclusion age: >45 Followup: NA Mean age: 50-103 Inclusion: 195 adolescents (103 girls, 92 boys) ages 9-15 years who followed a macrobiotic diet in childhood (43 girls, 50 boys) and 102 (60 girls, 42 boys) control subjects; response rates of the families 50% Exclusion: Poor health, taking medications that can affect bone health Excluded: 10 families failed to keep appointments 

obtain weekly frequency of dairy food consumption. Daily calcium intake was categorized: 0-405, 406-654, 655-1,003 and >1,004 for men; 0-300, 301-501, 502­776, and ≥777 for all women; 0-292, 293­

500, 501-755 and >756 for late menopausal women. Daily Ca++intake was also categorized by selected cutoff points: <400 rag/day versus >600, > 800 or >1,000 rag/day. The food frequency questionnaire assessed weekly frequency, of milk and cheese consumption in the previous 3 months. Ca++ intake index combined both measurement. Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Standardized questionnaire to all cases and controls to assess frequency of consumption of milk, cheese and dark green leafy vegetables was used to estimate calcium intake during the teen years Control for bias: Matching by age and hospital, adjustment for BMI, education, smoking, HRT, chronic disease Diagnosis of LI: Not addressed Diet: Macrobiotic children reported following a macrobiotic diet from birth onward for a period of 6.2 6 2.9 (mean 6 SD) years, in most cases subsequently adopting a vegetarian-type diet Diet assessment: Previously validated food frequency questionnaire with added questions to asses non dairy sources of 

Test: Not Race: CaEthnicity: Test: Not Race: CaEthnicity: 
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Inclusion age: >9 Ca++ Followup: NA Control for bias: Adjustment Mean age: 11.6-12.5 

Rockell, 200546 

Country: New Zealand Population: Prepubertal children with a history of longterm milk avoidance Source: Population based Study design: Prospective followup of the previously published study Shaw, 199347 Country: Taiwan Population: Adults Source: Population based Study design: Cross-sectional 

D343 

Soroko, 199448 

Country: USA Population: Older women Source: community based cohort of older women in California Study design: Cross-sectional 

Inclusion: Caucasian children ages 3–10 years with a history of prolonged milk avoidance for more than 4 months Exclusion: Gait disorders, current bone fractures, or medical diagnoses affecting bone (e.g., diabetes or malabsorptive syndromes) Excluded: 4 Inclusion age: Children Followup: 2 years Mean age: 8.1±2 Inclusion: 404 healthy volunteers (266 women and 138 men, ages 15 to 83 years) living in Lin-Kou Township Exclusion: History of hip fracture, spine disorders, adrenal gland disorders Excluded: NR Inclusion age: 15-83 Followup: NA Mean age: NR Inclusion: 624 postmenopausal White women Exclusion: No data on milk consumption history and had bone mineral density measurements Excluded: 43 Inclusion age: >60 Followup: NA Mean age: 70.6 

Diagnosis of LI: Not diagnosed Diet: Self reported prolonged milk avoidance Diet assessment: Validated food-frequency questionnaire; current calcium intakes were estimated both by the same FFQ used at baseline and by 4-day diet records (4DDRs), which we collected just before the followup clinic appointment to avoid post interview bias. Control for bias: None Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Interview with a trained technician, food frequency questionnaire of 16 calcium-rich items common for Taiwan Control for bias: None Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Standardized interview with food-frequency questionnaire to assess current dietary calcium intake and calcium supplementation history. Participants also quantified their daily milk consumption during adolescence (12 to 19 years of age), midlife (20 to 50 years of age), and older adulthood (after 50 years of age) as (1) "rarely or never" (classified as none), (2) "about every week, but not every day" (low), (3) "1 to 2 glasses per day, about every day" (medium), or (4) "3 or more glasses per day, about every meal" (high). Childhood milk intake was not queried because of expected poor recall. Control for bias: Adjustment 

Test: Selrelated to Race: CaEthnicity: Sex-specscores wreference and 100 fracture oDunedin Test: Not Race: AsEthnicity: Test: Not Race: CaEthnicity: Higher madulthood significanhigher boat the mid intertrochHigher teassociatehigher bospine and was not amineral dwrist. Anacalcium ssimilar pa
Appendix Table D1. Observational studies of lactose intolerance or malabsorption in association with patient outcomes (continued) 

Study Subjects Diagnosis and Control for Bias 

Tavani, 199549 

Country: Italy Population: Postmenopausal women Source: 4 largest teaching and general hospitals in Milan Study design: Case-control Turner, 199850 

Country: USA Population: Older women Source: The Third National Health and Nutritional Examination Survey, Phase 1 Study design: Cross-sectional Vatanparast, 200551 

Country: Canada Population: children and adolescents Source: Population based Study design: Prospective cohort 

D344 

Wyshak, 198952 Country: USA Population: Women Source: University based Study design: Cross-sectional 

Inclusion: Cases: 241 postmenopausal women (median age 64 years, range 45-74 years) admitted to hospital for fracture of the hip. Controls- 719 controls hospitalized patients for acute, non-neoplastic, nontraumatic, nondigestive, non-hormonerelated diseases Exclusion: Long-term modifications in diet Excluded: NR Inclusion age: 45-74 Followup: NA Mean age: 64 Inclusion: National sample of 953 southern women ages 50 years and older Exclusion: NR Excluded: NR Inclusion age: >50 Followup: NA Mean age: 68.8 ±11.5 Inclusion: Participants in the University of Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS)-population-based sample of children in Saskatoon.7-year longitudinal data from 85 boys and 67 girls are analyzed Exclusion: History of chronic disease or chronic medication use, medical conditions, allergies, or medication use known to influence bone metabolism or calcium balance Excluded: NR Inclusion age: 8-20 years Followup: 7 years Mean age: 11.8±0.9 for girls; 13.5±1 for boys Inclusion: 5,398 alumnae listed as currently alive by the alumnae offices of 8 colleges and two universities, response rate 71% Exclusion: NR Excluded: NR Inclusion age: >21 Followup: NA Mean age: 51.3 ±0.2 

Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Trained interviewers used a structured questionnaire to collect data on frequency of 29 food items before the onset of the disease including major sources of calcium Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Food-frequency questionnaire Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Dietary intake was assessed by serial 24-hour recalls Control for bias: Adjustment Diagnosis of LI: Not addressed Diet: Self reported Diet assessment: Questionnaire to asses any dietary restrictions including low milk intake Control for bias: Adjustment 

Test: Not Race: NR Ethnicity: Test: Not Race: 58African ATest: Not Race: CaEthnicity: For every consumewas accrTest: Not Race: NR Ethnicity: 

 NS - not specified, NA - not applicable, NR - not reported 
Appendix Table D2. Association between low dairy Ca++ intake and bone fractures 

Study

Goulding, 200437 

 Comparison 

Calcium intake below 300 

Outcome 

History of fracture 

Estimate 

Crude OR 

Country: New Zealand mg/day vs. >300mg/day Prepubertal children with a history of long-term milk avoidance Ca++ intake difference in comparison groups: NR/NR Looker, 199343 Selected calcium cut points History of fracture Adjusted for alcohol use, smoking, 

Country: USA (mg~day) <400 vs. >1,000 in physical activity, BMI, and 

Men and postmenopausal men postmenopausal hormone use in the 

women Selected calcium cut points total sample of women in addition to 

Ca++ intake difference in (mg~day) <400 vs. >1,000 in age RR 

comparison groups: NR/Y women 

Selected calcium cut points (mg~day) <400 vs., >1,000 in late menopausal women 

D-345 

Tavani, 199549 Ca++ intake >1,026mg/day vs. Hip fracture Adjusted for age, education, smokin

Country: Italy <443mg/day status, total alcohol consumption, an

Postmenopausal women estrogen replacement therapy OR Ca++ intake difference in comparison groups: NR/NR 
Appendix Table D3. Association between lactose intake and genetic polymorphism or self reported lactose intolerance 

Study Comparison Outcome Results 

Lehtimaki, 200622 T/T vs. C/C Lactose-free or low lactose Statistically insignificant after adjustm

Country: Finland C/T vs. C/C diet calcium intake, pubertal stage, age, aChildren and adolescents T/T vs. C/T 

T/T vs. C/C in women For female subjects dietary intakes oC/T vs. C/C in women products were significantly lower for T/T vs./ C/T in women 13910 genotype than the other geno

1980, 1986, and 2001. 

T/T vs. C/C in men For male subjects there were no stat

C/T vs. C/C genotype differences in the intake of 

in men 

T/T vs./ C/T in men
 years, but the consumption of milk an

significantly lower for subjects with thover the study years from 1980 to 20years of age, the consumption of mil

significantly lower for subjects with thover the study years from 1980 to 20

Estimate 

Enattah, 20059 T/T or T/C vs. C/C Use of milk products OR 2.06 

D- Country: Finland 346 Elderly Gugatschka, 200512 T/T vs. C/C Milk tolerance OR 3.79 

Country: Austria C/T vs. C/C 1.84 

Adult males T/T vs. C/T 2.07 

Kull, 200921 T/T vs. C/C Milk consumption (dL/day) Mean Difference 1.00 

Country: Estonia C/T vs. C/C 0.80 

Adults T/T vs. C/T 0.20 

Hypolactasia vs. -0.8normolactasia Self reported LI vs. none -1.4
Appendix Table D4. Association between low lactose diets, lactose intolerance or malabsorption, and clinical symptoms 

Study Comparison Outcome Crude o

Dietary preferences as a lifestyle choice Black, 200232 Bad taste of milk vs. not Presence of milk related symptoms 0.05 (0.01; 0

Country: New Zealand Lifestyle choice: The family 0.22 (0.04; 1

Prepubertal children with a history of consumed soymilk or goat milk rather 

long-term milk avoidance than cow milk vs. not Ca++ intake difference in comparison Subjects whose family member 1.26 (0.33; 4

groups: NR/NR avoided cow milk consumption vs. not Genetic polymorphism Obermayer-Pietsch, 200425 TT vs. CC Dislike of milk taste 0.83 (0.25; 2

Country: Austria Frequency of aversion to milk 0.26 (0.09; 0

Postmenopausal women consumption Ca++ intake difference in comparison Dislike of milk taste 1.54 (0.58; 4

groups: 0.55/Y Frequency of aversion to milk 0.14 (0.05; 0

consumption Dislike of milk taste 0.54 (0.20; 1

Frequency of aversion to milk 1.80 (0.56; 5

consumption 

Obermayer-Pietsch, 200724 TT vs. CC Dislike of milk taste 0.18 (0.05; 0

Country: Austria Aversion to milk consumption 0.05 (0.01; 0Postmenopausal women Ca++ intake difference in comparison groups: 349/Y Enattah, 20047 TT or C/T vs. CC Self reported lactose intolerance 0.39 (0.09; 1

Country: Finland Young men Ca++ intake difference in comparison groups: / Gugatschka, 200512 T/T vs. C/C Self-reported lactose intolerance 1.49 (0.09;2 

Country: Austria C/T vs. C/C 2.03(0.22;18Adult males T/T vs. C/T 0.73(0.08;6.7Ca++ intake difference in comparison groups: 5/N Gugatschka, 200713 T/T vs. C/C Self reported Lactose intolerance 1.35 (0.08; 2Country: Austria C/T vs. C/C 1.48 (0.15; 1Elderly male T/T vs. C/T 0.91 (0.09; 9Ca++ intake difference in comparison groups: -7/N Black, 200232 Lactose intolerance vs. none Presence of milk related symptoms 190.09 (9.92

Country: New Zealand Consulted a health professional vs. 13.50 (3.40; 

Prepubertal children with a history of not 

D347 
Appendix Table D4. Association between low lactose diets, lactose intolerance or malabsorption, and clinical symptoms (continued) 

Study Comparison Outcome Crude o

long-term milk avoidance Ca++ intake difference in comparison groups: NR/NR Objectively detected lactose malabsorption Goulding, 199911 Malabsorbers vs. absorbers Symptoms of gastrointestinal 2.06 (0.04; 1

Country: New Zealand discomfort associated with milk intake 

Middle age and older women Ca++ intake difference in comparison groups: NR/NR Kudlacek, 200220 Moderate lactose malabsorption vs. Moderate symptoms (diarrhea, 1.34 (0.59; 3

Country: Austria absorbers abdominal cramps) during the H2 Adults breath test Ca++ intake difference in comparison Moderate lactose malabsorption vs. Severe symptoms (diarrhea, 3.58 (1.43; 9groups: NR/NR absorbers abdominal cramps) during the H2 

breath test 

Severe lactose malabsorption vs. Moderate symptoms (diarrhea, 1.66 (0.86; 3absorbers abdominal cramps) during the H2 

breath test Severe symptoms (diarrhea, 6.22 (2.87; 1abdominal cramps) during the H2 breath test 

Di Stefano, 20025 Lactose malabsorption vs. absorbers Symptoms of LI 107.98 (6.34

Country: Italy Adults Ca++ intake difference in comparison groups: -54/Y Horowitz, 298717 Malabsorbers vs. absorbers History of milk intolerance 1.50 (0.31; 7

Country: Austria Postmenopausal women Ca++ intake difference in comparison groups: / 

Rockell, 200546 Baseline vs. 2 years of followup Any symptoms related to milk intake 3.30 (1.33; 8

Country: New Zealand were the reason for avoidance Prepubertal children with a history of No milk intake whatsoever 8.95 (3.00;2 long-term milk avoidance Ca++ intake difference in comparison groups: NR/NR 

D-348 
 

 

Appendix Table D5. Gains in osteodensitometric values in prepubertal boys consuming low lactose diet (74% 

of the recommended daily Ca++ intake) after interventions with dairy foods (1,607 vs. 747mg/day of Ca++)53 

Outcome 

Outcome 

Mean ±STD in Active 

Group 

Outcome 

Mean ± STD in 

Control Group 

Mean Difference (95% 

CI) 

12 months Gain in BMD 

Radial metaphysis 14.6±19.2 11.2±16.7 3.4 (-1.237; 8.037) 

Radial diaphysis 25.6±22.2 22.3±19.6 3.3 (-2.096; 8.696) 

Femoral neck 22±31.9 22.7±30 -0.7 (-8.674; 7.274) 

Femoral trochanter 25±31.3 20.5±27.5 4.5 (-3.092; 12.092) 

Femoral diaphysis 76.3±31.7 64.3±33 12 (3.675; 20.325) 

Lumbar spine (L2–L4) 25.9±18 28.1±18.5 -2.2 (-6.897; 2.497) 

12 months Gain in BMC (mg/year) 

Radial metaphysis 79±62 71±56 8 (-7.219; 23.219) 

Radial diaphysis 93±58 87±46 6 (-7.5; 19.5) 

Femoral neck 159±187 164±222 -5 (-57.752; 47.752) 

Femoral trochanter 472±198 495±211 -23 (-75.635; 29.635) 

Femoral diaphysis 4,460±2234 4,011±2119 449 (-111.669; 1009.669) 

Lumbar spine (L2–L4) 1,971±804 1,994±814 -23 (-231.214; 185.214) 

Mean of 5 appendicular skeletal sites 1,064±470 969±449 95 (-23.35; 213.35) 

Bold - statistically significant difference at 95% confidence level 

D-349 
Study 

Difference in Daily Ca++ Comparison Outcome Estimate 

Intake in Comparison Groups 

Lactose free diet 

Lau, 199842 Vegans (never consumed milk) BMD spine (L1±L4) Crude 0

Country: Hong Kong vs. lactovegetarians BMD femoral neck 0

Elderly Chinese vegetarian BMD intertrochanteric area 0women BMD ward triangle 0

Ca++ intake difference in comparison groups: -94/Y Rockell, 200546 At 2 years of followup vs. Total body BMD Crude 0

Country: New Zealand baseline 33% radius BMD 0Prepubertal children with a Lumbar spine (L2–4) BMD 0

history of long-term milk Femoral neck BMD 0

avoidance Hip trochanter BMD 0

Ca++ intake difference in UD radius, z score -0

comparison groups: 182/Y 33% radius, z score 0

Lumbar spine (L2–4), z -0score Femoral neck, z score 0Hip trochanter, z score 0Total body, z score -0

Black, 200232 Age adjusted z scores in milk Total-body BMD Age adjusted 0

Country: New Zealand avoiders vs. reference healthy Femoral neck BMD -1

Prepubertal children with a children history of long-term milk avoidance Ca++ intake difference in comparison groups: NR/NR Chiu, 199733 Long-term vegan vegetarian Lumbar spine BMD Adjusted for age, BMI (as a -0

Country: Taiwan practice vs. nonlong-term vegan Femoral neck BMD continuous variable), -0Postmenopausal Taiwanese and nonvegan vegetarians vigorous physical activity 

women (three categories), calcium, 

Ca++ intake difference in protein, and nonprotein kcal comparison groups: NR/NR (as continuous variables) 

Kull, 200921 Low milk consumption (<4dL/day) Femoral BMD (total) Crude -0

Country: Estonia vs. high (>4dL/day) Spinal BMD (L1- L4) g/cm2 -0

Adults Ca++ intake difference in comparison groups: NR/NR 

Du, 20026 No milk consumers vs. low milk BMD (g/cm2); distal one- Crude -0

Country: China group (<22±18 g/day) third radius 

Appendix Table D6. Association between lactose intake and metabolism and bone mineral density (BMD, g/cm2) 

D350 
Study 

Difference in Daily Ca++ Comparison Outcome Estimate 

Intake in Comparison Groups 

Adolecent Girls Distal one-third ulna -0

Ca++ intake difference in Distal one-tenth radius -0comparison groups: NR/NR Distal one-tenth ulna -0

No milk consumers vs. high milk Distal one-third radius -0group (>128±165 g/day) Distal one-third ulna -0

Distal one-tenth radius -0Distal one-tenth ulna -0

Lau, 199842 Vegans (never consumed milk) BMD (g=cm2) spine Crude 0

Country: Hong Kong vs. omnivores (L1±L4) Elderly Chinese vegetarian BMD (g=cm2) femoral neck -0women BMD (g=cm2) -0Ca++ intake difference in Intertrochanteric area comparison groups: NR/NR BMD (g=cm2) ward triangle -0Genetic polymorphism Obermayer-Pietsch, 200425 TT vs. CC Lumbar BMD Crude 0

Country: Austria Femoral neck 0Postmenopausal women Total hip 0Ca++ intake difference in Ward’s triangle 0comparison groups: 0.55/Y TC vs. CC Lumbar BMD 0

Femoral neck 0Total hip 0Ward’s triangle 0

TT vs. TC Lumbar BMD 0

Femoral neck 0Total hip 0Ward’s triangle 0

Obermayer-Pietsch, 200724 TT vs. CC Lumbar BMD Crude 0Country: Austria Femoral neck BMD [g/cm2] 0

Postmenopausal women Total hip BMD 0Ca++ intake difference in 

comparison groups: 349/Y Enattah, 20047 T/T vs. C/C Lumbar spine BMD (g/cm2) Crude 0

Country: Finland Femoral neck BMD (g/cm2) 0Young men Trochanter BMD 0Ca++ intake difference in Total hip BMD 0comparison groups: NR/NR BMD, lumbar spine Adjusted for age, height, 0

BMD, femoral neck weight, smoking, alcohol 0BMD, total hip consumption and current 0

exercise 

C/T vs. C/C Lumbar spine BMD Crude 0

Appendix Table D6. Association between lactose intake and metabolism and bone mineral density (BMD, g/cm2) (continued) 

D351 
Study 

Difference in Daily Ca++ Comparison Outcome Estimate 

Intake in Comparison Groups 

Femoral neck BMD 0

Trochanter BMD -0Total hip BMD 0BMD, lumbar spine Adjusted for age, height, 0BMD, femoral neck weight, smoking, alcohol 0BMD, total hip consumption and current 0

exercise 

T/T vs. C/T Lumbar spine BMD Crude 0

Femoral neck BMD 0Trochanter BMD 0Total hip BMD 0BMD, lumbar spine Adjusted for age, height, -0BMD, femoral neck weight, smoking, alcohol 0BMD, total hip consumption and current 0

exercise 

Kull, 200921 T/T vs. C/C Femoral BMD (total) Crude -0

Country: Estonia Spinal BMD (L1- L4) -0

Adults C/T vs. C/C Femoral BMD (total) -0Ca++ intake difference in Spinal BMD (L1- L4) -0

comparison groups: NR/NR T/T vs. C/T Femoral BMD (total) 0

Spinal BMD (L1- L4) 0

Hypolactasia vs. normolactasia Femoral BMD (total) 0

Spinal BMD (L1- L4) 0

Lactose intolerance Corazza, 19954 Lactose malabsorbers with BMD z score Crude -0

Country: Italy symptoms of intolerance vs. Postmenopausal women without symptoms Ca++ intake difference in comparison groups: -246/Y Di Stefano, 20025 Lactose intolerance vs. not BMD (T-score): lumbar Crude -0

Country: Italy spine Adults BMD (T-score): femoral -0Ca++ intake difference in neck 

comparison groups: -240/Y BMD (z-score): lumbar -0

spine BMD (z-score): femoral -0neck 

Corazza, 19954
 Lactose intolerace (clinical BMD z score Crude 0

Country: Italy diagnosis) vs. not 

Postmenopausal women 

Appendix Table D6. Association between lactose intake and metabolism and bone mineral density (BMD, g/cm2) (continued) 

D352 
Study 

Difference in Daily Ca++ Comparison Outcome Estimate 

Intake in Comparison Groups 

Ca++ intake difference in comparison groups: -138/NR 

Kull, 200921 Self reported lactose intolerance Femoral BMD (total) g/cm2 Crude -0

Country: Estonia vs. not Spinal BMD (L1- L4) g/cm2 -0

Adults Ca++ intake difference in 

comparison groups: NR/NR Segal, 200326 Lactose intolerance vs. healthy BMD z-Scores: femoral Matching by age and gender 0

Country: Israel population; BMD z-Scores neck in Premenopausal Adults women 

Ca++ intake difference in Hip in premenopausal 0

comparison groups: NR/NR women 

L2–L4 in premenopausal -0women Femoral neck in -0postmenopausal women Hip in postmenopausal 0women L2–L4 in Postmenopausal -0women Femoral neck in men -0Hip in men -0L2–L4 in men -1

Lactose malabsorption 

Honkanen, 199715 Positive vs. negative lactose Femoral BMD, no fractures Adjusted for age, -0

Country: Finland tolerance test Femoral BMD, wrist menopausal status, weight, -0Perimenopausal women fractures and HRT history 

Ca++ intake difference in Femoral BMD, ankle -0

comparison groups: -280/Y fractures 

Femoral BMD, tibial -0

fracture Spinal bone BMD, no -0fractures Spinal bone BMD, wrist -0fractures Spinal bone BMD, ankle -0fracture Spinal bone BMD, tibial -0fracture 

Appendix Table D6. Association between lactose intake and metabolism and bone mineral density (BMD, g/cm2) (continued) 

D353 
Appendix Table D6. Association between lactose intake and metabolism and bone mineral density (BMD, g/cm2) (continued) 

Study 

Difference in Daily Ca++ Comparison Outcome Estimate 

Intake in Comparison Groups 

Honkanen, 199616 Positive vs. negative lactose Femoral BMD Adjusted for Calcium intake, 0

Country: Finland tolerance test weight, age, years since 

perimenopausal women
 menopause, HRT 

Ca++ intake difference in
 Positive vs. negative lactose Spinal BMD Crude 0

comparison groups: -270/Y tolerance test in premenopausal 

Positive vs. negative lactose -0tolerance test in postmenopausal Positive vs. negative lactose -0tolerance test in postmenopausal, hormone replacement therapy 6 months or more Positive vs. negative lactose -0tolerance test in postmenopausal, no HRT Positive vs. negative lactose Femoral BMD -0tolerance test in premenopausal Positive vs. negative lactose -0tolerance test in postmenopausal Positive vs. negative lactose -0tolerance test in postmenopausal, hormone replacement therapy 6 months or more Positive vs. negative lactose -0tolerance test in postmenopausal, no HRT 

Di Stefano, 20025 Lactose malabsorption vs. no BMD (T-score): lumbar Crude -0

Country: Italy spine Adults BMD (T-score): femoral -0Ca++ intake difference in neck 

comparison groups: -54/Y BMD (z-score): lumbar -0

spine BMD (z-score): femoral -0neck 

Corazza, 19954 Lactose malabsroption vs. no BMD z score Crude -0

Country: Italy Postmenopausal women Ca++ intake difference in comparison groups: -2/N Alhava, 19771 Malabsorbers vs. absorbers (men Mineral density distal Crude 0

Country: Finland only) radius Adults Malabsorbers vs. absorbers Mineral density distal 0

D354 
Study 

Difference in Daily Ca++ Comparison Outcome Estimate 

Intake in Comparison Groups 

Ca++ intake difference in (women only) radius comparison groups: NR/NR

Kudlacek, 200220


 

Moderate lactose malabsorption DEXA (radial) (g/cm2) Crude 

Country: Austria 

-0

vs. no 

Adults Severe lactose malabsorption vs. DEXA (radial)(g/cm2) -0

Ca++ intake difference in no comparison groups: NR/NR Severe lactose malabsorption vs. DEXA (radial)(g/cm2) -0

moderate 

Horowitz, 198717 Lactose malabsroption vs. no BMD of the right forearm, Crude -1

Country: Austria mg/ml 

Postmenopausal women Ca++ intake difference incomparison groups: NR/N


 

R

Alhava, 19771 


 

Malabsorbers vs. absorbers (men Bone mineral linear density Crude 0

Country: Finland Adults 

only) (g/cm), distal radius 

Bone mineral linear d

Ca++

ensity 0

 intake difference in
 (g/cm), midshaft radius 

comparison groups: NR/NR
 Bone mineral linear density 0

(g/cm), midshaft ulna 

Malabsorbers vs. absorbers Bone mineral linear density 0(women only) (g/cm), distal radius 

Bone mineral linear density 0(g/cm), midshaft radius Bone mineral linear density 0(g/cm), midshaft ulna 

Bold – statistically significant 

Appendix Table D6. Association between lactose intake and metabolism and bone mineral density (BMD, g/cm2) (continued) 

D355 
Study 

Difference in Daily Ca++ Comparison Outcome Estimate 

Intake in Comparison Groups 

Honkanen, 199616 Positive vs. negative lactose Spinal BD, mg/cm Adjusted for calcium intake, 2

Country: Finland tolerance test weight, age, years since Perimenopausal women menopause, HRT Ca++ intake difference in comparison groups: -270/Y Gugatschka, 200713 T/T vs. C/T Spinal BD (L1–L4) Z score Crude 0

Country: Austria Femoral BD (total) Z score -0Elderly male Femoral BD (neck) Z score -0Ca++ intake difference in Femoral BD (trochanteric) -0

comparison groups: -221/Y Z score 

T/T vs. C/C Spinal BD (L1–L4) Z score -0

Femoral BD (total) Z score -0Femoral BD (neck) Z score -0Femoral BD (trochanteric) -0

Z score 

Gugatschka, 200512 T/T vs. C/T Spinal BD (L1–L4) Z score Crude 0

Country: Austria Femoral BD (total) Z score 0

Adult males T/T vs. C/C Spinal BD (L1–L4) Z score 0

Ca++ intake difference in Femoral BD (total) Z score 0

comparison groups: -3/N C/T vs. C/C Spinal BD (L1–L4) Z score -0

Femoral BD (total) Z score -0

Gugatschka, 200713 C/T vs. C/C Spinal BD (L1–L4) Z score Crude -0

Country: Austria Femoral BD (total) Z score -0Elderly male Femoral BD (neck) Z score 0

Ca++ intake difference in Femoral BD (trochanteric) -0comparison groups: 14/N Z score 

Bold – statistically significant 

Appendix Table D7. Association between lactose intake and metabolism and bone density (BD) 

D356 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 3 and 4 

D357 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

A. Commercially-available lactase/lactose hydrolysed milk, or non-lactose solutions Montalto, 200554 Data source: 30 Italian Mean age (range): β-d-galactosidase Placebo before 400 Clinical score bas

RCT, crossover subjects referred 43 (18-65) from mL milk (lactose on symptoms whSponsorship: not because of symptoms Gender: women Kluyveromyces content 20 g) plus severity was indicreported compatible with lactose 63%. lactis aspartame (to by a score for eacItaly intolerance with a Race/ethnicity: not 1) Test A -enzyme simulate the taste symptom (0=abseDuration of positive lactose H2 reported (3000 UI) added to of lactase-treated 1=mild; 2=modersymptom recording: breath test. Each patient Comorbidities: not 400 mL milk milk x 1 dose 3=severe). 8 hours underwent, in a random reported (lactose content 20 Conclusion(s): A 

order, three H2 breath Cointerventions: g) 10 h before milk significant reducttests. An interval of at not reported consumption x 1 of the mean clinicleast 72 hours was dose score after both tallowed among 2) Test B-enzyme (0.36 ± 0.55) and successive tests (20 g (6000 UI) added 5 B (0.96 ± 0.85) velactose), to avoid the min before 400 mL placebo (3.77 ± 0effect of colonic milk (lactose (P<0.001). acidification. content 20 g) There was also a Inclusion criteria: consumption x 1 significant reductSymptoms compatible dose after Test A versuwith lactose intolerance. Test B (P=0.03). Methods to measure outcomes: Subjects kept a diary where they recorded occurrence of intolerance symptoms for 8 hours following 

Gremse, 200355 

milk ingestion. Data source: 30 Mean age (range): 240 mL Lactose­ 240 mL Milk (lactose Symptom scores 

RCT, crossover American child subjects 11 (3-17) free milk (LFM) to content 12 g) the 14 day period Sponsorship: not with lactose mal- Gender: women which lactase 2 g 2% homogenized (mean ± SEM). 

reported digestion a positive 63%. from milk plus Severity of sympt

USA lactose H2 breath test. Race/ethnicity: Kluyveromyces aspartame (to was graded as: Duration of Inclusion criteria: black 53%, white lactis (Lactaid, simulate the taste 0=none; 1=trivial, 

symptom recording: Recurrent abdominal 47%. Pleasantville, NY) of lactase-treated 2=mild; 3= mode2 weeks pain of childhood with at Comorbidities: not was added to 2% milk) taken for 14 4=severe. Sum o
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Järvinen, 200356 

RCT, crossover Sponsorship: not reported Finland Duration of symptom recording: 8 hours 

least 3 discrete episodes of abdominal pain severe enough to affect daily activities for 3 months or more. Exclusion criteria: Organic causes of abdominal pain. Methods to measure outcomes: Subjects and/or their parents recorded their symptoms daily in a diary that was collected at weekly intervals during each study period. Data source: 27 Finnish subjects who had experienced gastrointestinal symptoms after consuming milk or food containing lactose. Inclusion criteria: lactose maldigestion based on rise in blood glucose <1.1 mmol/l within 1 hour after ingesting 50 g lactose dissolved in water. Methods to measure outcomes: Gastrointestinal symptoms including 

reported homogenized milk 

Cointerventions: (lactose content 12 not reported g) taken for 14 days 

(2 week washout period) 

Students and staff 100 g chocolate at a university. No sample consisting further information of lactose-free milk provided. powder. 

days 100 g chocolate sample consisting of low-lactose milk powder (lactose content 2 g). 100 g chocolate sample consisting of whole milk powder (lactose content 12 g). 100 g chocolate sample consisting of whole milk (lactose content 12 g). The chocolate sample was eaten in the morning 

individual sympto

scores was calcufor each 14-day speriod and averafor all subjects. Significant increaabdominal pain dthe lactose ingesperiod compared the lactose-free period. Conclusion(s): Authors conclude ingestion of 12 g lactose daily is associated with increased abdompain in susceptibchildren with lactomaldigestion. Number of subjecreporting symptoand mean symptoscores for individgastrointestinal symptoms. Conclusion(s): Numbers of subjereporting GI symptoms did nodiffer significantly after eating chocosamples. 

D-358 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Suarez, 199857 

RCT, crossover Sponsorship: Department of Veteran Affairs, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Dairy Council. USA Duration of symptom recording: 1 week 

flatulence, abdominal bloating, abdominal pain, borgorygmi and nausea were recorded on a questionnaire with a scale ranging from 0 (no symptoms) to 10 (very severe symptoms disturbing normal life) once every hour for the first 3 hours and then two more times (at 4-6 and 7-8 hours) until 8 hours had elapsed since the test meal. Data source: 31 American women subjects with lactose maldigestion a positive lactose H2 breath test plus 31 American women digester controls. Inclusion criteria: Lactose maldigestion based on an increase in the breath-hydrogen concentration of >0.45 mmol/L (10 ppm) after the oral ingestion of a 250-mL aqueous solution containing 15 g lactose (0.18 mol/L) was used as the indicator of lactose maldigestion. Exclusion criteria: Previously had gastrointestinal surgery, 

Maldigestion group (n=31): Mean age 46.9 

2.6 y 

Gender: women 100%. Race/ethnicity: Asian 29%; Hispanic 16%; black 6%; white 45%, of whom 4 were Jewish Digestion group Mean age 49.4 ±2.4 Gender: women 100%. Race/ethnicity: white 100% Prior to the study, 23 women in the lactose maldigestion group 

Lactose hydrolyzed products (LHP), lactose totaling 34 g daily. The lactose in fresh, low-fat milk was hydrolyzed by adding 1.07 g of a lactase preparation obtained from Kluyveromyces lactis 240 mL lactose hydrolyzed,1%-fat milk with breakfast and dinner; 1 serving (28 g) of a hard cheese at lunch and at dinner; and 240 mL low-fat, strawberry flavored, lactose-hydrolyzed yogurt at lunch. Subjects ingested 

between 8 and 10 o’clock after an overnight fast Conventional diary products (CDP) lactose totaling 34 g daily. 240 mL conventional, 1%­fat milk with breakfast and dinner; 1 serving (28 g) of a hard cheese at lunch and at dinner; and 240 mL (8 oz) lowfat, strawberryflavored yogurt at lunch time 

Severity of sympt(Mean ± SEM), ranked on a continuous scale 0 to 5 as follows: (no symptoms), 1 (trivial), 2 (mild), 3 (moderate), 4 (strong), or 5 (sevsymptoms). Women with lactomaldigestion reposignificantly increflatus frequency asubjective impresof rectal gas durinthe period of high lactose intake; however, bloatingabdominal pain, diarrhea, and the global perception overall symptom 

D-359 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Xenos, 199858 

RCT, crossover Sponsorship: not reported Greece Duration of symptom recording: 1 day 

had significant intercurrent illnesses, had received antibiotic therapy within the past 2 months, or allergy to aspartame, milk, yogurt, or cheese. Methods to measure outcomes: The occurrence and severity of symptoms (bloating, abdominal pain or cramps, and subjective impressions of rectal gas excretion) were self-rated by subjects on 2 occasions daily (for the periods from breakfast time to dinnertime and from dinnertime to bedtime) during the baseline and the 2 test periods. Data source: 8 Greek lactose intolerant volunteers. Inclusion criteria: Rise in blood glucose levels <1.1 mmol/L above fasting level after ingestion of lactose (1 g/kg of body weight) and if intestinal symptoms occurred. Methods to measure outcomes: Subjects completed questionnaire regarding 

and 2 in the lactose digestion group believed that the ingestion of dairy products resulted in appreciable abdominal symptoms. Mean age 32 No other data were provided. 

their regular diets with the exception of the additional dairy products. The dairy products provided <1300 mg Ca/d; it was assumed that the remainder of the diet provided <200 mg. Lactose treatment: β-D-galactosidase 100 u/mL + 100 g lactose dissolved in water. There was a washout period of 1 week between challenges. 

Matching placebo + 100 g lactose dissolved in water. 

severity were not significantly differbetween the 2 treatment periodsConclusion(s): Authors conclude the symptoms resulting from lacmaldigestion are major impedimenthe ingestion of a dairy-rich diet supplying <1500 Ca/day. Subjects reportinsymptoms based ratings (0=none t4=severe), 8 houafter lactose challenge. Conclusion(s): Subjective ratings the severity of symptoms (crampbelching, flatulendiarrhea) were significantly decreased with thlactose treatment 

D-360 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

symptoms 8 hours after consuming tests and then every 8 hours until 24 hours elapsed. Symptoms were rated from 0=none to 4=severe. 

Suarez, 199759 

RCT, crossover Sponsorship: Department of Veteran Affairs, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Dairy Council. USA Duration of symptom recording: 1 week 

Data source: 19 American symptomatic lactase-nonpersistent (S-LNP) subjects selfdescribed as “severely lactose intolerant,” plus 13 LNP subjects who denied lactose intolerance (A-LNP), and 10 lactasepersistent subjects who believed they were lactose intolerant (SLP). Inclusion criteria: Individuals who reported GI symptoms after one cup of milk. Lactose maldigestion based on an increase in the breath-hydrogen concentration of >10 ppm after the oral ingestion of a 250-mL aqueous solution containing 15 g lactose was used as the indicator of lactose malabsorption, hence LNP. Exclusion criteria: 

S-LNP Group (n=19) Mean age 34 ±22 years (range 18-43) Gender: women 53%. Race/ethnicity:
 Asian 63%; black 11%; Hispanic 5%; white 21%
 A-LNP Group (n=13) Mean age 35.9 ±11 years (range 25-69) Gender: women 38%. Race: Asian 69%; black 8%; Hispanic 15%; white 8%
 S-LP Group (n=10) Mean age 35.9 ±11 years (range 25-69) Gender: women 38%. Race/ethnicity:
 Asian 69%; black 8%; Hispanic 15%; white 8%
 

240 mL lactose hydrolyzed milk (lactose totaling 11.8 g, 23.6 daily), consumed at breakfast and dinner. The lactose in fresh, low-fat milk was hydrolyzed by adding 1.07 g of a lactase preparation obtained from Kluyveromyces lactis to 1 L milk. A washout period of 7 days between treatments. 

240 mL regular milk (lactose totaling 11.8 g, 23.6 daily), plus aspartame (to simulate the taste of lactase-treated milk, consumed at breakfast and dinner. 

compared to placMean symptom severity scores ranked scale on a scale as follows: 0=none; 1=trivial; mild; 3=moderatestrong; 5= severeExtracted from grNeither LNP grouhad a significant increased in symptoms during regular milk periocompared to the lactose hydrolyzemilk period. S-NLsubjects reported significantly greatgaseous symptomcompared to A-Nduring both feediperiods. Conclusion(s): Authors concludelactase-nonpersissubjects can toletwo cups of milk pday without appreciable symptoms. 

D-361 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

Inconsistent GI symptoms (bloating, abdominal pain, flatulence, or diarrhea), prior gastrointestinal surgery or other significant illnesses, received antibiotic therapy within the past 2 months, or inability to consume aspartame. Methods to measure outcomes: Subjects rated symptoms (bloating, borborygmi, abdominal pain or cramps, and subjective impressions of rectal gas excretion) on 4 occasions daily (morning, noon, afternoon, night) during the baseline and the 2 test periods. Subjects also recorded diarrhea, and each passage of flatus. 

Vesa, 199760 

RCT, crossover Sponsorship: Finnish Association of Agronomists Finland Duration of symptom recording: 2 days 

Data source: 30 Estonian subjects with lactose maldigestion. Inclusion criteria: Lactose maldigestion based on measuring of urinary galactose concentration after ingesting 50 g lactose with 150 mg ethanol/kg body weight, with 

Mean age (range): 46 (18-74) Gender: women 90%. Race/ethnicity: not reported Comorbidities: not reported Cointerventions: not reported 

200 mL lactose-free milk (0.1% fat) x 2 daily (lactose totaling 0 g over 2 days) 

200 mL fat-free milk (0.1% fat) x 2 daily, (lactose totaling 19.6 g over 2 days) 200 mL high-fat milk (4.9% fat) x 2 daily (lactose totaling 19.6 g over 2 days) Milk-free period over 5 days 

Percentage of subjects who experienced symptoms during test day after eaclactose dose The sum of sympwas higher during milk periods than during the milk-freperiod (P<0.01). 

D-362 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Vesa, 199661 

RCT, crossover Sponsorship: not reported Finland Duration of symptom recording: 1 day 

symptom followup during the test day. Exclusion criteria: No gastrointestinal diseases, were not on medications, on antibiotics at least two months prior to study, or had irritable bowel syndrome. Methods to measure outcomes: On test days, after consuming milk, subjects noted symptoms (flatulence, nausea, abdominal bloating, abdominal pain) on a questionnaire with a visual analog scale (VAS). Data source: 39 Finnish subjects with lactose maldigestion and 15 lactose digesters. Inclusion criteria: Lactose maldigestion based on a positive lactose H2 breath test (39%) or lactose tolerance test with ethanol (61%). Lactose maldigesters who experienced at least moderate gastrointestinal symptoms, i.e., loose stools, abdominal pain, abdominal bloating, or 

1. Lactose maldigesters (n=39) Mean age (range): 47.2 (27-70) Gender: women 62%. Race/ethnicity:
 white 100%. 2. Lactose digesters (n=15) Mean age (range): 38.3 (25-54) Gender: women 66%. Race: white 100%. Comorbidities: 5 hypertensives and one diabetic. 

200 mL fat-free, lactose-free milk x 1 serving (lactose was separated chromatographically). The taste of the milk was disguised with 0.2 g lemon flavoring and the sweetness and osmolarity of the test milks were equalized with glucose. 

200 mL fat-free, lactose-free milk x 1 serving (lactose was separated chromatographically) plus 0.1% /3­galactosidase was added to ensure that it contained no traces of lactose. Milk 1. plus 0.5 g lactose Milk 2. plus 1.5 g lactose Milk 3. plus 7 g lactose 

There were no statistically signifdifferences in the occurrence or sevof symptoms durithe fat-free milk period compared the high-fat milk period. Conclusion(s): A marked difference the fat content of did not affect the symptoms of lactintolerance. Percentage of subjects who experienced symptoms during test day after eaclactose dose. Maldigesters reposignificantly more abdominal bloatinand abdominal pathan the digestersThere was no difference in the mseverity of the reported symptombetween the test and the lactose-frmilk in the group 

D-363 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Saurez, 199562 

RCT, crossover Sponsorship: Department of Veterans Affairs, National Institute of Diabetes and Digestive and Kidney Diseases, and the University of Minnesota USA Duration of symptom recording: 1 week 

flatulence, were selected for in the study group. Exclusion criteria: No gastrointestinal diseases or on antibiotics one month prior to study. Methods to measure outcomes: On test, for 12 h after consuming milk, subjects noted symptoms (flatulence, abdominal bloating, abdominal pain, borborygmi, and loose stools) on a questionnaire with a visual analog scale (VAS) Data source: 30 American subjects who reported severe lactose intolerance with consistent related symptoms. Subjects were classified as having lactose malabsorption if their breath H2 concentrations increased by more than 10 parts per million (ppm) (0.93 x 10-6 g of 

H2 per liter of air or 0.45 μmol per liter). The ability of the colonic 

Cointerventions: not reported Lactose malabsorbers (n=21) Mean age (range): 29.4 (18-50) Gender: women 62%. Race/ethnicity: white 38%; Asian 33%, Hispanic 24%; black 5%. Lactose absorbers (n=9, those with increase in H2 <10 ppm) Mean age (range): 25.1(18-45) 

Hydrolyzed low-fat milk (HM) (lactose content <0.05 g) by adding 1.07 g of lactase from Kluyveromyces lactis (Lactaid, 

Pleasantville, NY) to 1 liter of milk at breakfast daily for a one-week period. 

Low-fat milk (lactose content 12.1 g) to plus aspartame (to simulate the taste of lactase-treated milk) at breakfast daily for a oneweek period. 

lactose maldigestof whom one-third not experience ansymptoms from athe test doses. Thsame proportion (64%) of the maldigesters experienced symptoms after bthe lactose-free mand the milk with lactose. Conclusion(s): Gastrointestinal symptoms in moslactose maldigestare not induced blactose when smaamounts (0.5-7.0 lactose are includin the diet. Intensity of daily gastrointestinal symptoms over thone week period (mean ± SEM), 0=none; 1=trivial; 2=mild; 3=moder4=strong symptomand 5=severe. Diarrhea or loose stool was defined “an urgent, waterdefecation.” In Subjects recordeeach passage of flatus. 

D-364 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

flora to produce hydrogen through fermentation in response to carbohydrate malabsorption was tested in seven of the nine subjects who were able to absorb lactose after they ingested 10 g of lactulose. 

Gender: women 56%. Race/ethnicity: white 89%; East Indian 11% Comorbidities: not reported Cointerventions: not reported. 

During the study periods, gastrointestinal symptoms were minimal. When thperiods were compared, there no statistically significant differein the severity of these four 

Exclusion criteria: Subjects were excluded if they did not report consistently having symptoms after drinking less than 240 ml of milk; if they had undergone gastro-intestinal surgery, had other major illnesses, or received antibiotic 

gastrointestinal symptoms. Conclusion(s): Pewho identify themselves as severely lactoseintolerant may mistakenly attribuvariety of abdomisymptoms to lactintolerance. Whe

therapy within the lactose intake is previous two months; or if they indicated that they could not consume 

limited to the equivalent of 240 of milk or less a d

aspartame. Methods to measure outcomes: Subjects rated the occurrence and severity of gastrosymptoms are lik

be negligible and use of lactose- digestive aids unnecessary. 

intestinal symptoms experienced during the 24-hour period after each test meal. 

Johnson, 199363 

RCT, crossover 

Data source: 45 lactosemaldigesting and Ages ranged from 12-40 in the eligible 315 mL hydrolyzed milk (lactose 315 mL milk (lactose content Presence of symptoms consis

Sponsorship: The lactose intolerant population. content 0 g) by 16.4 g) plus with lactose mal- 

D-365 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

National Dairy Board In cooperation with the National Dairy Council USA Duration of symptom recording: unclear Lin, 1993 Study 264 

RCT, crossover Sponsorship: Thompson Medical Co., Inc. and the Minnesota Agricultural Experiment Station USA Duration of symptom recording: 8 hours 

African Americans. All subjects claimed to have GI symptoms after consuming one cup of milk or less. Inclusion criteria: Subjects who had an increase in hydrogen concentration from baseline of ≥ 20 ppm. Exclusion criteria: Chronic constipation and other GI problems, regular cigarette smokers, and subjects on antibiotic therapy. Methods to measure outcomes: Subjects were to record symptoms after ingestion (time period unclear) Data source: 11 American adults similarly characterized as maldigesters as in Study 1 by breath hydrogen analysis following a 50-g lactose load and by past experience with intolerance symptoms following the consumption of dairy foods  Inclusion and exclusion criteria: Same as Study 1. Methods to measure 

Gender: not reported but mostly female (70%) in the eligible population. Race/ethnicity: black 100% Comorbidities: not reported Cointerventions: not reported Age range: 18-60 Gender: women 91%. Race/ethnicity: not reported Comorbidities: not reported Cointerventions: not reported 

adding 30 drops of lactase (Lactaid, Pleasantville, NY) to of milk. Subjects took 3 samples, either HM twice and M once or the opposite on 3 different days, assigned in a random order. 50 g of lactose dissolved in 200 ml of water plus βgalactosidase (βgal) enzyme 

preparations 1) Lactogest soft gel capsules x 2 (Thompson Medical Inc, New York, New York), 2) Lactogest capsules x 4 3) Lactaid caplets x 2 (Lactaid Inc, Pleasantville, New 

artificial sweetener (to simulate the taste of lactasetreated milk) Subjects took three samples, either M twice and HM once or the opposite on 3 different days, assigned in a random order. 50 g of lactose dissolved in 200 ml of water plus two soft gel vitamin E capsules containing 420 rag/capsule of α-tocopherol in soybean oil as a Placebo (Pharmacaps Inc, Elizabeth, New Jersey) 

absorption. 33% (n=10) reposymptoms consiswith lactose malabsorption with bHM and milk. Conclusion(s): Authors conclude the cause of milk intolerance in up 1/3rd African 

Americans claimisymptoms after ingestion of a moderate amounmilk cannot be duits lactose contenSymptom scoresexpressed as the of mean scores rasymptoms from 1 (none) to 5 (worsever experiencedbaseline and 4 anhours after challeConclusion(s): Symptom scores bloating, crampinnausea, pain, diarrhea, and flatwere not significadifferent between treatments and th

D-366 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Nielsen, 198465 

RCT, crossover Sponsorship: Danish Medical Research Council Denmark Duration of symptom recording: 1 day 

outcomes: Subjects kept a similar diary to Study 1, except that symptoms of bloating, abdominal cramps, nausea, abdominal pain, diarrhea and gas were self-scored by subjects at baseline and 4 and 8 hr on a 1-5 scale (none to worst ever experienced). Data source: 9 lactose intolerant Danish children Inclusion criteria: Subjects had to fulfill two of the following: 1) An increase in blood glucose during a lactose tolerance test (2 g of lactose per kilogram of body weight); 2) Diarrhea, borborygmus, and/or flatulence during a lactose tolerance test; 3) Low or no lactase activity in an intestinal biopsy specimen taken at the ligament of Treitz. Exclusion criteria: Subjects with acute or chronic diarrhea or other GI orders. Methods to measure outcomes: At 10 times during the 24 test 

Median age (range): 10 (9-16) Gender: female 33%. Ethnicity: 6 subjects immigrants from Korea, Pakistan, or Turkey (plus 3 native Danes) Comorbidities: No subjects had renal or endocrine disorders or hereditary diseases. Cointerventions: None received any medicine during the period of examination. 

Jersey) or 4) DairyEase chewable tablets x 2 (Glenbrook Laboratories, New York, NY) One half liter of hydrolyzed milk (HM) (lactose content 1.25 g) by adding 2 mL of lactase from Kluyveromyces fragilis (Lactozym 3000 L, Novo Industri A/S, Bagsvaerd, Denmark), given after 8 hours of fasting 

One half liter of ordinary milk (lactose content 25 g) given after 8 hours of fasting 

control. Summation of observed symptofrom the scoring charts of the 9 subjects. Conclusion(s): Children had significantly feweclinical symptoms signs within 24 hoafter consuming lactose-hydrolyzemilk compared to regular milk. 

D-367 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

periods, a 0 was recorded in the scoring chart to indicate no symptoms and a 1 was recorded if symptoms or defecation was observed by the children’s parents. 

Lybeck Sørensen, 198366 

RCT, crossover Sponsorship: Not reported Denmark Duration of symptom recording: 8 hours 

Data source: 35 Mean age (range): 250 and 500 mL 250 and 500 mL Frequency of 

symptomatic lactose 32 (20-60) low-lactose milk skim milk (SM) symptoms in percintolerant Danish adults Gender: women (lactose content 1.6 (lactose content following milk from Latin America. 54%. g), 86% of the 11.3 g). ingestion. Inclusion criteria: Race/ethnicity: lactose was Conclusion(s): Lactose intolerance Latin American removed by Ingestion of 500 mbased on a lactose 100% ultrafiltration and low-lactose milk tolerance test (not Comorbidities: not replaced with the resulted in defined), with no known reported addition of malto­ significantly fewedisorders of the Cointerventions: dextrose. symptoms compagastrointestinal tract. not reported 48 hours between to regular skim mExclusion criteria: tests. After ingestion of lactose tolerance mL low-lactose mMethods to measure there was a tendeoutcomes: Subjects to fewer symptomcompleted but the difference questionnaire not statistically concerning the significant. development of symptoms (borborygmus and meteorism, colic attacks, flatulence, and/or diarrhea) based on the following: 0=no symptoms; 1=slight; 2=moderate; 3=severe. The total symptom score was calculated as the sum of the score for each person. 

D-368 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Rask Pedersen, 198267 

RCT, crossover Sponsorship: NOVO Industries supplied the lactase and performed the HPLC analyses Denmark Duration of symptom recording: 1 day Reasoner, 198168 

RCT, crossover Sponsorship: University of Rhode Island and Shadow Research Foundation, Inc. USA Duration of symptom recording: 1 week 

Data source: 11 symptomatic lactose intolerant Danish adults. Inclusion criteria: Rise in blood glucose levels <1.4 mmol/L above fasting level after ingestion of 50 g lactose with symptoms (abdominal cramp, meteorism, and/or diarrhea). Methods to measure outcomes: On a 24 hour diary sheet, subjects reported abdominal symptoms based on the following. 0=none; 1= mild/moderate; 2= severe. For diarrhea, No diarrhea=formed stools; mild/moderate= ≤3 liquid/soft stools; severe= ≥4 liquid/soft stools. Data source: 9 symptomatic American adults from an outpatient clinic and 5 milk tolerant controls. Inclusion criteria: Subjects with a blood sugar <20 mg/100 mL after ingestion of 50 g lactose and had symptoms when challenged with 250 mL of skim milk. 

Mean age: 43 Gender: women 64%. Race/ethnicity: not reported Comorbidities: not reported Cointerventions: not reported “Milk-intolerant” (n=9) Mean age (range): 41 (22-60) Gender: women 44%. Race/ethnicity: not reported Comorbidities: 2 subjects had LI due to Crohn’s disease (one also had an intestinal 

500 mL low-lactose milk (lactose content 3.75 g), 85% hydrolyzed by adding 2 mL of lactase from Kluyveromyces fragilis (Lactozym 3000 L, Novo Industri A/S, Bagsvaerd, Denmark) to of milk x 1 dose. Low-lactose milk (lactose content ~2.9 g/d) x 1 week), 74-91% hydrolyzed with lactase (Maxilact 40,000, GB Fermentation, Des Plains, Illinois). Average weekly consumed was 1.79 L. 

500 mL ordinary milk (lactose content 25 g), x 1 dose. 1) Skim milk (lactose content ~28.5 g/d) x 1 week. Average weekly consumed was 1.58 L. 2) Skim milk + glucose (simulates the taste of lactasetreated milk) x 1 week. Average weekly consumed was 1.8 L. 

Number of subjecreporting symptoafter ingestion Conclusion(s): Thwas a significant reduction in abdominal symptafter ingestion of lactose-hydrolyzemilk compared to regular milk. Abdominal symptresponses transformed into a numerical value. Numbers correlatwith the following0.33 = none to m0.34 to 0.66 = moderate; 0.67 to = severe. Conclusion(s): Lactose-hydrolyzmilk significantly 

D-369 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Unger, 198169 

RCT, crossover Sponsorship: not reported USA Duration of symptom recording: 1 day 

Methods to measure outcomes: Subjects rated the occurrence and severity of gastrointestinal symptoms experienced during the 24-hour period after each test meal. 0=none; 1= mild; 2=moderate; and 3=severe. Number of days that the subject responded per week was totaled. A quotient was then calculated, giving a symptom index for the week. Data source: 24 American lactose malabsorbers (determined by breath hydrogen test) and 75 lactose absorbing adolescent volunteers. Subjects were to report all symptoms during breath hydrogen test period. Presence of ≥1 GI symptom was considered a positive response to lactose. Methods to measure outcomes: Symptomatology questionnaires were given to subjects each day after the test beverage was consumed. One or more 

resection), and one subject had a subtotal gastrectomy. Cointerventions: not reported “Milk-tolerant” (n=5) Mean age (range): 33 (22-48) Gender: women 60%. Race/ethnicity: not reported Mean age (range): 24 (18-46) Gender: women 49%. Race/ethnicity: white 87% (northern European n=65; southernEuropean n=8; Jewish n=14), Asian 10%, black 3%. 

240 or 480 mL lactose-free chocolate dairy drink. 

3) Sweet acidophilus milk x 1 week. Average weekly consumed was 1.50 L. 240 or 480 mL lactose-containing (lactose content 10.8-21.6 g) chocolate dairy drink. 

reduced pain and symptoms in the “Milk-intolerant” gcompared to reguskim milk. Subjects reportinsymptoms during hours after consumption. Conclusion(s): 12of lactose malabsorbers wesymptomatic afteconsuming 240 mlactose-free solutversus 33.3% afteconsuming 240 mlactose solution. 

D-370 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

relevant symptoms occurring between one and 24 hours indicated a positive response to the dairy drink for that test day. The 4 symptoms (bloating, flatulence, cramps, diarrhea) indicative of lactose intolerance were rated according: 0=none; 1=mild; 

Cheng, 197970 

RCT, crossover Sponsorship: Chile Foundation Chile Duration of symptom recording: 1 day 

2=moderate; 3=severe Data source: Chilean volunteers from the Santiago penitentiary. 15 were lactose intolerant and 16 were lactose tolerant controls. Inclusion criteria: Lactose intolerance, determined by blood glucose analysis [<20 mg/ 100 considered deficient lactase activity] and developed symptoms after ingestion of 50 g lactose. 

Lactose intolerant subjects (n=15) Mean age (range): 27 (19-34) Gender: men 100% Race/ethnicity: Latin American 100%. Lactose tolerant subjects (n=16) Mean age (range): 27 (18-38) Gender: men 100% Race/ethnicity: Latin American 100%. 

500 mL low lactose milk (lactose content 0.5 to 1.25 g), hydrolyzed with lactase (galactosidase, Maxilact, Enzyme Development Corporation, New York, NY), x 2 daily for 1 month. 

500 mL skim milk (lactose content 25 g), sweetened with sucrose to imitate taste of low-lactose milk. All subjects received at least 4 of these tests. 

Results are expressed as the number of times a score was given teach symptom duthe experiment. Conclusion(s): Lactose intoleransubjects had morsymptoms and msevere symptoms skim milk. 

Methods to measure Comorbidities: not outcomes: A standard questionnaire was applied twice daily. All symptoms, attributable or not to lactose 

reported Cointerventions: not reported 

intolerance, were recorded. No symptoms = 0, mild (symptoms 

D-371 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

present but not interfering with daily activities or <2 liquid bowel movements) = 1, severe (symptoms present and interfering with daily activities or caused great discomfort or >2 liquid bowel movements) = 2. No data on statistical analyses. 

Jones, 1976 Study 271 

Data Source: 17 American volunteers 

Mean age 24 (range 20-34) 

60% reduced skim milk 500 ml (10 g 

Regular skim milk 500 ml (25 g 

Sum of score of bloating, gas, cra

Single blind RCT no who reported symptoms Gender: women lactose) 60% lactose). Regular and diarrhea on smasking to taste, after ingesting 25 g 41% reduced lactose whole milk 500 ml 0-none, 1=mild, 2crossover lactose but not after Race/ethnicity: whole milk 500 ml (25 g lactose) moderate, 3=sevUSA placebo. Asian 41%; black (10 g lactose). Conclusion(s): 1) Duration:8 hours Inclusion criteria: LI on 18%; Latin- Placebo 250 ml Lower lactose miFunded by National basis of rise in blood American 12%; (saccharin, lemon better tolerated; Dairy Council and glucose of less than 25 Other 29% juice water) 2.) No differences NY State Agriculture mg/100mL after 50 g Comorbid: none tolerance betweeExperiment station lactose injection Co-intervention: test beverages hatch project none Studies in which subjects were not noted to be symptomatic at baseline or symptoms were not required for study inclusion (bameasures only) Lin, 1993 Study 164 Data source: 20 Age range: 25-40 400 ml of low-fat 400 ml of low-fat The difference in RCT, crossover “healthy” American Gender: women (2%) milk (lactose (2%) (lactose symptom scores Sponsorship: lactose maldigesters 50%. content 20 g) plus content 20 g) plus baseline), based Thompson Medical adults based soley on Race/ethnicity: not β-galactosidase (β­ two soft gel vitamin the summation of 

Co., Inc. and the breath hydrogen test. reported gal) enzyme E capsules observed symptoMinnesotaAgricultur Inclusion criteria: Breath Comorbidities: not preparations containing 420 from the scoring al Experiment Station USA 

hydrogen concentration to >20 ppm (>1.80 x 10 ­ 6 g H2/liter air) after 

reported Cointerventions: not reported 

1) Lactogest soft gel capsules x 2 (Thompson Medical 

rag/capsule of αtocopherol in 

soybean oil as a 

charts (on a 0 = nto 5 = severe scathe 20 subjects. 

Duration of ingestion of 400 ml of Inc, New York, NY), Placebo Conclusion(s): 

symptom recording: low-fat (2%) milk 2) Lactogest (Pharmacaps Inc, Symptoms were 

D-372 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

8 hours Brand, 199172 

RCT, crossover Sponsorship: Not reported Australia Duration of symptom recording: 4 hours 

containing approximately 20 g of lactose. 

Exclusion criteria: Pregnant or lactating, had prior gastrointestinal surgery, had illness that would interfere with the experiment, or had used antibiotics within the past 30 days. Methods to measure outcomes: Subjects kept a dairy of symptoms and selfrated gas, stomach pain and/or cramps and diarrhea and/or loose stool for each hour from 0 to 8 hours following the test meal. Scores are expressed as the mean of the sum of scores rating symptoms from 0 (none) to 5 (severe) for each hour from baseline to 8 hr after the challenge. Data source: Six healthy adult Australian subjects with lactose malabsorption. Subjects were not noted to be symptomatic at baseline. Inclusion criteria: Diagnosis of lactose malabsorption was 

Mean age (range): 

33 (29 to 44) Gender: female
 83%. Ethnicity: The 6 subjects were immigrants from Indonesia, Japan, Malaysia, and Laos. 

capsules x 4 3) Lactaid caplets x 2 (Lactaid Inc, Pleasantville, New Jersey) or 4) DairyEase chewable tablets x 2 (Glenbrook Laboratories, New York, NY) 300 mL 50% lactose reduced milk (Lacto Lo) (lactose content 2.4 g)  300 mL 80% lactose reduced milk (Cotee) (lactose content 1 g) 

Elizabeth, New Jersey) 300 mL whole milk (lactose content 4.8 g), tested twice in each individual (n = 12). After an overnight fast the subjects consumed 300 mL of each of five milk products in a 

significantly less severe with all the galactosidase products. Number of subjecwho reported spesymptoms. Conclusion(s): Thresults suggest th50% level of lactoreduction in milk be adequate to rethe signs and symptoms of milk 

D-373 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

based on the results of a challenge with 300 mL whole milk contain-ing 

Comorbidities: not reported Cointerventions: 

300 mL 80% lactose reduced milk (Balance) 

single-blind fashion and random order on separate 

intolerance in the majority of healthadults with lactos

14 g lactose after an overnight fast based on a peak breath hydrogen excretion >20 ppm. 

not reported (lactose content 1 

g) 300 mL 95% lactose reduced 

occasions 3-5 d apart. 

malabsorption. 

Methods to measure outcomes: At hourly intervals they rated their symptoms (cramps, 

milk (Digestelact) (lactose content <0.25 g) 

flatulence, and diarrhea) on a scale of 0, no symptoms; 1, mild; 2, moderate; and 3, severe. 

Cavalli-Sforza, 198673 

RCT, crossover Sponsorship: Parmalat Spa Italy Duration of symptom recording: 1 day 

Data source: 80 Italian adults, data from 71 subjects: 40 lactose malabsorbers and 30 lactose absorbers. Inclusion criteria: Adults free from gastrointestinal diseases and diabetes. All subjects were give lactose tolerance test (50 g lactose in 200 mL water). Subjects were defined as lactose malabsorber if maximum increase in 

All subjects (N=80) Mean age (range): 34 (18 to 69) Gender: female 66% Ethnicity: not reported Comorbidities: not reported Cointerventions: not reported 

Regular whole hydrolyzed milk (lactose content 0.5 g/dL) and fat content of 3.2 g. Regular skim hydrolyzed milk (lactose content 0.65 g/dL and fat content of 0.10 g.) Each type of milk was taken on 4 consecutive days in Increasing quantities: 125, 250, 500, 1000 mL. 

Regular whole milk (lactose content 4.9 g/dL) and fat content of 3.3 g. Regular skim milk (lactose content 5.10 g/dL and fat content of 0.15 g; 12.75 per milk serving) 

Symptom responthe intake of the 4 milk types, percecases. Conclusion(s): Lactose malabsohad significantly fsymptoms with skmilk vs. whole miThe authors founcontrary to earliefindings, that fat seemed to contribto milk intoleranclactose malabsorrather than reduc

blood glucose concentration above fasting level was <20 mg/dL. Methods to measure 

The larger quantities could be divided into 2 to 6 intakes during the day. 

outcomes: 

D-374 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

Questionnaire was given to subjects to indicate whether they experienced diarrhea, flatulence, bloating, or abdominal pain during the 24 hours after consuming the milk test. Symptoms were rated mild = 1, moderate = 2 or severe = 3 in intensity. A total for the 4 symptoms could 

Rosado, 198474 

range from 0 to 12. Data source: 50 Age range: 19-53 1) LactAid 1g 360 mL milk, Number of subjec

RCT Mexican adults were Gender: women combined with 360 reconstituted from reporting symptoSponsorship: enrolled, 25 lactose 64%. mL milk, powdered whole (minor or major). Limited, industries malabsorbers and 25 Race/ethnicity: reconstituted from milk (lactose Conclusion(s): provided the absorbers. Mostly Mexican powdered whole content 18 g) Addition of LactAenzymes (SugarLo Inclusion criteria: No with various milk (lactose significantly reducCo. (Pleasantville, inclusion criteria, degrees of content 18 g) symptoms of NJ) and G.B. subjects unselected. European and 2) 360 mL pre- intolerance amonFermentation Methods to measure Indian descent. hydrolyzed milk. A 25 lactose (Kingstree, SC)) outcomes: Subjects Comorbidities: NR minimum of 72 malabsorbers USA/Mexico completed symptom Cointerventions: hours between subjects. Duration of questionnaire document NR tests. symptom recording: presence or absence of 1 day 4 gastrointestinal 

symptoms (abdominal cramps, gas/flatulence, vomiting, and/or diarrhea). Absence of all 4 symptoms = lactose tolerance. 0 =absent; 1=mild; 2=moderate; 3=severe, except for diarrhea which was always marked a 3. 

D-375 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

Total points were then summed for each of the treatment periods. A score ≥4 = major symptomaology, ≤3 = minor. Exclusion criteria: recent history or concurrent use of antibiotics or recent 

Haverberg, 198075 

RCT, crossover Sponsorship: National Dairy Council USA Duration of symptom recording: 1 day 

gastrointestinal disease. Data source: 67 American lactose malabsorbing (determined by blood glucose analysis) and 43 lactose absorbing adolescent volunteers. Classification was based on biochemical vs. subjective symptomatic response to lactose. Methods to measure outcomes: Subjects reported abdominal symptoms on a questionnaire containing yes/no or multiple choice questions regarding symptoms over 24 hours after consumption. Occurrence of diarrhea, 

Age range: 14-19 Gender: not reported Race/ethnicity: black 53%, white 40%; Latin American 7%. Comorbidities: not reported Cointerventions: not reported 

240 or 480 mL lactose-free chocolate dairy drink. 

240 or 480 mL lactose-containing (lactose content 10.8-21.6 g) chocolate dairy drink. 

Number of subjecreporting symptoduring 24 hours aconsumption 18% of lactose malabsorbers wesymptomatic afteconsuming 240 mlactose-free solutversus 28% after consuming 240 mlactose solution. Conclusion(s): Results indicate tmost of the indiviwho reported GI symptoms after consuming the beverages did so to other reasons besides the lacto

≥ 2 mild GI symptoms or ≥ 1 moderate or severe 

content. 

symptom was noted as a positive response of intolerance to the test drink. 

D-376 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Kwon, 198076 

RCT, crossover Sponsorship: National Dairy Council USA Duration of symptom recording: 1 day Rorick, 197977 

RCT, crossover Sponsorship: National Dairy Council USA Duration of symptom recording: 1 day 

Data source: 45 American lactose malabsorbing (determined by blood glucose analysis) and 42 lactose absorbing adolescent volunteers. Classification was based on biochemical vs. subjective symptomatic response to lactose. Methods to measure outcomes: Subjects reported abdominal symptoms on a questionnaire containing yes/no or multiple choice questions regarding symptoms (bloating, flatulence, cramps, or diarrhea) over 24 hoursafter consumption by checking 1=none; 2= mild; 3=moderate; and 4=severe. Presence of ≥1 symptom was considered as a positive intolerant response. Data source: 87 American elderly volunteers, in which 23 were lactose malabsorbers (determined by breath hydrogen analysis after ingestion of 25 g lactose) and 64 lactose absorbers. 

All subjects (N=87) Age range: (14-19) Gender: not reported Race/ethnicity: black 30%, white 64%; Asian 6%. Comorbidities: not reported Cointerventions: not reported All subjects (N=87) Mean age (range): 77 (60-97). Gender: women 77% Race/ethnicity: Northern/western European ancestry 76% (35% of the malabsorbers), 

240 or 480 mL lactose-free chocolate dairy drink. 240 mL lactose-free chocolate dairy drink. 

240 or 480 mL lactose-containing (lactose content 10.8 or 21.6 g) chocolate dairy drink. 240 mL lactosecontaining (lactose content 10.8 g) chocolate dairy drink. 

Number of subjecreporting symptoduring 24 hours aconsumption Among lactose malabsorbers, 27were symptomatiafter consuming 2mL of lactose-free solution versus 9after consuming 2mL lactose solutioConclusion(s): Factors other thalactose malabsormay be responsibfor a significant proportion of mild symptoms of “milintolerance” in an adolescent populsimilar to this studNumber of subjecreporting intolerato test drinks bason GI symptoms during the afternoafter consumptionSymptom frequenwas not significandifferent between beverages in both 

D-377 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Lisker, 197878 

RCT, crossover Sponsorship: Programa Nacional de Alimentos of the Consejo Nacional de Ciencia Y Tecnología de México. Mexico Duration of symptom recording: 6 hours 

Inclusion criteria: Subjects with no known gastrointestinal disease. Methods to measure outcomes: Subjects were interviewed the following morning after the test and were asked to state the occurrence severity of gas, bloating, cramps, or diarrhea during the previous afternoon. Symptom severity was based as follows: none; mild (noticeable, but not troublesome); moderate (troublesome, but not seriously uncomfortable); severe (uncomfortable, could not carry out normal activities). Data source: 150 Mexican volunteers, in which 97 were lactose malabsorbers (determined by blood glucose analysis [<25 mg/dl considered deficient lactase activity] after ingestion of 50 g lactose). Inclusion criteria: Subjects with no known gastrointestinal disease, diabetes. Methods to measure 

Jewish 11% (30%), black 8% (22%), Southern Italian 5% (13%). Comorbidities: not reported Cointerventions: not reported All subjects (N=150) Mean age (range): 24 (16-50). Gender: women 41% Race/ethnicity: Mexican 100% 60 of the volunteers had previously participated in lactose malabsorption studies and were also 

250 mL lactose-free milk plus 7.1 glucose. Powdered chocolate added to mask flavors. 

250 mL regular milk (lactose content 12.5 g). 250 mL regular milk plus additional 25 g lactose added (lactose content 37.5 g). 

malabsorbers and absorbers. Conclusion(s): Authors conclude factors other than lactose malabsorappeared to be responsible for thsymptoms of intolerance reporand most may habeen psychosomin origin.  Conclusion: Authconcluded that lactose-intolerant subjects are indelactose-intolerant that the frequencabdominal symptthat occur in perswith lactose malabsorption increases directly the lactose contemilk. 

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Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Paige, 197579 

RCT, crossover Sponsorship: Maternal and Child Health Services and National Institutes of Health USA Duration of symptom recording: 90 minutes 

outcomes: Symptoms were rated according: 1+ if mild; 2+ if moderate; 3+ if marked. Symptoms were scored as severe if diarrhea was present or if a cumulative rating of other symptoms (abdominal cramps, bloating, flatulence) was 4+. Cumulative rating less than 4+ was considered mild. Data source: 22 lactosemalabsorbers and 10 lactose absorber African American volunteers. Malabsorption was based on blood sugar rise of 26 mg/mL following ingestion of lactose load (50 g/ m2 of 

body surface) Inclusion criteria: no overt gastrointestinal or metabolic disease, Methods to measure outcomes: Symptoms voluntarily mentioned were recorded. Subjects were not specifically asked if they developed any symptoms commonly associated with lactose intolerance. 

aware they could tolerate at least 250 mL of milk at one time without difficulty. Comorbidities: not reported Cointerventions: not reported All subjects (N=32) Age range: 13-19. Gender: not reported Race: black 100%. Comorbidities: not reported Cointerventions: not reported 

240 mL whole milk, 90% hydrolyzed (lactose content 1.2 g) by adding lactase from Saccharomyces lactis 240 mL.whole milk, 50% hydrolyzed (lactose content 6 g) by adding lactase from Saccharomyces lactis. 

240 mL whole milk (lactose content 12 g). 

Number of subjecreporting symptoduring 90 minutes after consumption90% hydrolyzed m(n=22): 3 includinfrom the whole mgroup) 90% hydrolyzed m(n=18): none Whole milk (n=22Conclusion(s): Authors concludehydrolyzed milk mserve as alternatimilk in subjects wlow lactase levels

Jones 1976, Study 171 

Data Source: 16 American adult 

Mean age 25 (range 23-55) 

1. 50% lactose reduced skim milk 

Regular skim milk 591 ml (50 g 

Sum of score of bloating, gas, cra

Single blind RCT no volunteers Gender: women 591 ml (30 g lactose and diarrhea on s

D-379 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

masking to taste, Inclusion criteria: LI on 31% lactose) 0-none, 1=mild, 2

crossover basis of rise in blood Race/ethnicity: 2. 75% lactose moderate, 3=sevUSA glucose of less than 25 Asian 25%; black reduced skim milk Conclusion(s): Duration:8 hours mg/100mL after 50 g 19%; Latin­ 591 ml (15 g 1) Lower lactose Funded by National lactose injection American 13%; lactose) better tolerated; Dairy Council and Methods to measure other 44% 2.) Whether milks NY State Agriculture outcome: Asked about Comorbid: none were given with oExperiment station any symptoms of Co-intervention: without food had hatch project bloating, gas, abdominal none significant effect oHypothesis: 1. milk cramps and diarrhea on symptoms with lower lactose 0-3 point scale, better tolerated than summed regular milk, 2. compare symptoms after whole, skim milk, and lactose solutions B. Prebiotics or probiotics I. Studies where subjects were reported to be symptomatic at baseline in addition to LI testing Newcomer, 198380 Data source: 28 US Range age: 18-69 Unfermented 2% milk: 3 8 oz Median of cumula

RCT, crossover volunteers Gender: NR acidophilus milk: glasses per day, s/s score over 10 

Funding: US Inclusion criteria: No Race: NR 2% milk with L. one with each meal weeks as sum of 

national diary symptoms and negative Comorbid: 5/18 acidophilus added for total of 720 diarrhea+pain+ga

council and NC hydrogen breath test cases also had IBS for approx 7x10(6) ml/day borborygmi over 

State University for controls and Co-intervention: colony/ml (one 8 oz week periods for Dairy Foundation symptoms and positive none glass with three group USA hydrogen breath test meals, 3x/day for Conclusion(s): No Duration: 10 weeks for cases (defined as H2 total of 720 ml/day) difference in tolerHypothesis: excretion of .30 ml/min of regular milk vsUnfermented after 50gm lactose plus unfermented acidophilus milk is symptoms) acidophilus milk 

better tolerated than Methods to measure regular milk outcomes: Subjects 

kept a diary for scoring 0-4; 0=no trouble, 1=slight symptoms, 2=mild s/s, 3= 

D-380 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

moderate, 4= severe) for 4-10 weeks Loss to followup: none 

II. Studies where subjects did not have symptoms of LI at baseline or not reported and only underwent breath/other testing Lin, 199881 Data source: 20 No information on 1) 400 ml of 2% 400 ml of 2% low- Symptom scores 

RCT, crossover Taiwanese subjects. age and gender low-fat milk fat milk expressed as the 

Sponsorship: Inclusion criteria: provided. containing L. mean of the sum 

National Science Maldigesters were Comorbidities: not acidophilus at a cell stomach pain, ga

Council ofTaiwan classified on the basis reported concentration of 108 and diarrhea sco

Taiwan of a rise in breath Cointerventions: CFU/ml; rated from 0 to 5 

Duration of hydrogen concentration not reported 2) 400 ml of 2% (none to severe) 

symptom recording: of >20 ppm after low-fat milk each hour from 0 

8 hours ingestion of 400 ml of containing L. hr after consump

milk containing approxi­ acidophilus at 109 of the diets. 

mately 20 g of lactose. CFU/ml; Conclusion(s): No

Methods to measure 3) 400 ml of 2% fermented milks 

outcomes: Subjects rated symptoms on a 0­5 (none to severe) scale 

low-fat milk containing L. bulgaricus at 108 

containing L. bulgaricus 449 at 

and 109 CFU/ml w

for each hour from hour CFU/ml; effective in reduc

1 to hour 8 following 4) 400 ml of 2% symptoms. 

each of the diets. low-fat milk 

containing L. bulgaricus at 109 CFU/ml. All milk products were nonfermented. 

Mustapha, 199782 Data source: 11 lactose Age range: 25-42 1) 400 mL L. 400 mL low fat milk Mean symptom 

RCT, crossover maldigesting American Gender: women acidophilus 4356 (b-gal activity 0; response 0-5 (no

Sponsorship: subjects 55%. (b-galactosidase lactose content 15 severe), summed 

Minnesota-South Inclusion criteria: Race/ethnicity: not (b-gal) activity 1.22; g) from hour 1 to ho

Dakota Diary Foods Maldigesters were reported lactose content 15­ Conclusion(s): 

Research Center classified on the basis Comorbidities: not 16 g). Acidophilus milk 

United States of a rise in breath reported 2) 400 mL L. containing L. 

Duration of hydrogen concentration Cointerventions: acidophilus B (b­ acidophilus N1 w

symptom recording: of >20 ppm after not reported gal) activity 0.81; the most effective 

D-381 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

8 hours Jiang, 199683 

RCT, crossover Sponsorship: Minnesota Agricultural Experiment Station USA Duration of symptom recording: 1 day with 3 days in b/w Hypothesis: HB after ingestion of milk with different strains of B. longum 

ingestion of 400 ml of 

milk containing approximately 18 g of lactose. None had any GI illness or had taken antibiotics in the prior three months of the study. Methods to measure outcomes: Subjects rated symptoms on a 0­5 (none to severe) scale for each hour from hour 1 to hour 8 following each of the diets. Diarrhea was monitored 24 hours after diet. 

Data source: 15 American 

volunteers Inclusion criteria: lactose maldigesters on basis of rise of >20ppm after ingestion of 400 ml of milk (16 gm lactose) on hydrogen breath test using Levitt/Donaldson method. Methods to measure outcomes: ranked scale of symptoms for abdominal pain, flatulence, borborygmi, diarrhea and meteoism: 0=none, 1=slight, 2=mild, 3=moderate, 4=moderately severe, 5= severe summed for hours 1-8. flatus frequency: mean num of 

Age range: 24-42, mean 29.7 Gender: women 8(52%). Race: white 100% Comorbidities: no GI disorders Cointerventions: not reported 

lactose content 15­16 g). 

3) 400 mL L. acidophilus N1 (lowest b-gal activity 0.50; lactose content 15­16 g). 4) 400 mL L. acidophilus E (bgal) activity 0.79; lactose content 15­16 g).
 

3 test meals: 1) 400 ml 2% milk with Bifidobacterium longum B6 from mMRS broth containing lactose 2) 400 ml 2% milk with B. longum B6 from Sanofi biomed as a concentrated frozen culture 3) 400 ml of bifidus milk with B. longum ATCC 15708 from m-MRS broth containing lactose 

One meal 400 ml of 2% milk 

the four strains in improving lactose digestion and tolerance. Mean symptom response 0-5 (nosevere), summed from hour 1 to hoConclusion(s): Consumption of mcontaining B6 growith lactose resuin significantly lesflatulence vs. milthe milk containingrown with both lactose and glucoAuthors concludethat milks containB. longum might reduce symptoms from lactose malabsorption whthe culture is growa medium containonly lactose to in

D-382 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

gas passages over 8 a higher βhours, plus hydrogen galactosidase lev

breath test mean and increase rate reading over 8 hours lactose uptake. 

Vesa, 199684 

RCT crossover France Funding: Yoplait Sodima, France Duration of symptom recording: 8 hours Hypothesis: Addition of L. bulgaricus to increase lactase activity may make milk easier to tolerate compared to yogurt and milk with L. acidohpilus and bifidobacterium Lerebours, 198985 

RCT, parallel study Sponsorship: none reported. France Duration of symptom recording: unclear 

Data source: 15 Healthy French volunteers (reported 14) Inclusion criteria: lactase deficient by hydrogen breath test Methods to measure outcomes: symptom score 0-4 (0=no symptoms, 1=mild, 2=moderate, 3= fairly strong, 4=very strong symptoms) for abdominal bloating, flatulence, abdominal pain and loose stool compared mean+/-SE and sum of symptoms Data source: 16 healthy subjects born in Cameroon. Inclusion criteria: lactose intolerance on the basis of an increase in breath hydrogen concentration >20 ppm after ingestion of 440 mL milk containing 18 g lactose. Only two subjects experienced mild flatulence after milk ingestion. Methods to measure outcomes; No methods 

Age range: 20-45 Gender: women 11 (73%) Race: 100% Caucasian Comorbidities: none Cointerventions: not reported Age range: 20-53 Gender: NR Race: black 100%. Comorbidities: not reported Cointerventions: not reported 

3 fermented dairy products each with 18gm lactose in 250 ml water: 1) Ofilus (Yoplait, France; has L. acidophilus and bifidobacterium ) 320 ml 2) Bulgofilus (ofilus bacteria+ L. bulgaricus) 400 ml 3) Yoplait yogurt 500 ml 125 g yogurt (n=8) 

three times daily (breakfast, bunch, and dinner) (lactose content 18 g/d) Meals were given over 8 consecutive days. 

Lactulose 10gm in 250 ml water 125 g fermentedthen-pasteurized milk (FPM) (n=8) without living acid bacteria times daily (breakfast, bunch, and dinner) (lactose content 18 g/d) 

Conclusion(s): Significantly less bloating with bulgofilus compato lactulose and sscore less with bulgofilus compato lactulose Presence or abseof symptoms. Conclusion(s): Although lactose malabsorption wahigher with FPM with yogurt, the subjects reported gastrointestinal distress after consuming 1PM days but it must bstressed that only subjects experienmild symptoms amilk ingestion. Th

D-383 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

Martini, 198786 

RCT crossover Sponsorship: The National Dairy Board In cooperation with the National Dairy Council USA Duration of symptom recording:8 hours 

reported. Data source: 16 American healthy subjects. Inclusion criteria: lactose intolerance on the basis of an increase in breath hydrogen concentration >20 ppm after ingestion of milk containing 20 g lactose. Methods to measure outcomes; intolerance symptoms were recorded by the subjects. 

Age range: 18-26 Gender: male 100% Race: NR Comorbidities: not reported Cointerventions: not reported 

A. Flavored products (n=9) 1) 465 g strawberry flavored yogurt (lactose content 20 g) 2) 410 g ice milk (lactose content 20 g) 3) 400 g ice cream (lactose content 20g) B. unflavored products (n=8) 1) 455 g unflavored yogurt (lactose content 20 g) 2) 410 g unflavored yogurt FY-1 (lactose content 20 g) 3) 410 g unflavored yogurt FY-2 (lactose content 20 g) 4) 410 g unflavored yogurt FY-3 (lactose content 20 g) One subject received both products. 

415 g whole milk (lactose content 20 g) 

data indicate that besides lactose digestion, other factors are involvinducing or prevegastrointestinal distress during thconsumption of dproducts by lactadeficient subjectsSubjects reportinsymptoms of gastrointestinal distress. Conclusion(s): Subjects were fresymptoms after consuming flavorand unflavored yogurts. Tolerance to frozyogurt same as focream and ice m

D-384 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Savaiano, 198487 Data source: 9 Age range: 20-28 1) 500 gm yogurt 410 gm milk No symptoms 

RCT crossover, American healthy Gender: NR 2) 420 gm sweet reported when yo

single blind (no subjects. Race: NR acidophilus milk or pasteurized yo

attempt to mask Inclusion criteria: Comorbidities: not 3) 465 gm cultured was fed. 4 and 5 

flavor or texture) lactose intolerance on reported milk (buttermilk) the nine reported 

USA the basis of an increase Cointerventions: 4) 500 gm symptoms with m

University of MN in breath hydrogen not reported pasteurized yogurt and sweet acidop

Agricultural concentration >20 ppm milk respectively. 

Experiment Station, after ingestion of milk Conclusion(s): Yo

VA, NIH containing 20 g lactose. is unique due to 

Duration of s/s Methods to measure ability to enhance 

recording: 8 hours outcomes; intolerance lactose digestion 

Hypothesis: yogurt symptoms were produces less recorded by the symptoms than subjects, scale not other milk products reported. Symptoms 

reported were diarrhea, flatulence, abdominal pain 

C. Modifications to diet or other therapies Cappello, 20088 40 symptomatic Italian Mean age: 44 1) Rifaximin 800 Placebo (n=5) x 10 Intensity of symp

RCT subjects with positive Gender: women mg/day x 10 days days at baseline, 10d aSponsorship: not breath H2 test for 80%. (n=14) 40 d (mean ± SDreported lactose intolerance Race: Not reported 2) No-milk diet x 40 Conclusion(s): ThItaly Methods to measure Comorbidities: not days (n=13) total symptom scDuration of outcomes: Subjects reported significantly improsymptom recording: filled in a questionnaire Cointerventions: after rifaximin and 40 days related to the intensity not reported lactose-free diet. 

of symptoms (bloating, abdominal pain, flatulence and diarrhea). Symptoms score referred to the 5 days preceding each evaluation and scored as: 0=absent; 1=mild (awareness of a 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

D-385 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

symptom but easily tolerated); 2=moderate; 3=severe; and 4=very severe. 

D. Colonic adaptation studies Hertzler, 199689 Data source: 20 Mean age: 30 Dextrose for days Lactose for days 1­ Symptoms rating 

RCT, crossover American lactose Gender: women 1-10 and crossed 10 and crossed lactose (L) or 

Sponsorship: The maldigesting subjects. 25%. over to the other over to the other dextrose (D) feed

National Dairy Inclusion criteria: Race: Asian 70%, feeding period for feeding period for periods (mean ± 

Board In Healthy nonsmokers black, Latin- days 12-21. days 12-21. SEM). The maxim

cooperation with the National Dairy Council 

who had not used antibiotics in the preceding 2 months and 

American, and white 10% each Comorbidities: not 

Initial dosage was 0.6 g • kg body wt-1 

• d-1 , which was 

Initial dosage was 0.6 g • kg body wt-1 

• d-1 , which was 

possible score foindividual symptowould be 40 (a “5

USA reported no history of reported increased by 0.2­ increased by 0.2­ rating each hour 

Duration of functional bowel Cointerventions: not g/kg increments g/kg increments hours). 

symptom recording: complaints. Subjects reported every other day up every other day up Conclusion(s): 

10 days were classified as 

lactose maldigesters 

to a maximum of 1.0 g • kg-1 • d-1. On 

to a maximum of 1.0 g • kg-1 • d-1. On 

Authors concludethat there is colon

based on a rise in days 11 and 22 an days 11 and 22 an adaptation to reg

breath hydrogen of >20 aqueous lactose aqueous lactose lactose ingestion 

ppm (0.9 ımol challenge (0.35 challenge (0.35 this adaptation 

hydrogen/L air) after a g/kg) was g/kg) was reduces lactose 

challenge dose of administered after administered after intolerance 

lactose (0.7 g/kg body an overnight (>12 an overnight (>12 symptoms. 

wt) administered after hours) fast. Breath hours) fast. Breath 

an overnight fast. hydrogen excretion hydrogen excretion 

Methods to measure and intolerance and intolerance 

outcomes: Subjects symptoms were symptoms were 

rated symptoms hourly monitored hourly monitored hourly 

during the breath for 8 hours after the for 8 hours after the 

hydrogen tests using a challenge dose was challenge dose 

ranked scale: 0=none, consumed was consumed. 

1=slight, 2=mild, 3=moderate, 4= moderately severe, 5= severe. Data are reported as the sum of 

D-386 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods	 Treatment-Active, Study	 Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of	 Evaluations Conclusions Criteria Followup 

hours 1-8. During the feeding periods, subjects recorded symptoms once per day each evening during the feeding periods using the same scale mentioned above. 

E. Incremental lactose loads or studies examining different levels of lactose Hertzler, 199690	 Data source: 13 Mean age: 32 Five treatment 

RCT, crossover American lactose (range 21 to 42) solutions consisting Sponsorship: maldigesting subjects. Gender: women of lactose dissolved Minnesota Inclusion criteria: 46%. in 240 mL of tap Agricultural Subjects were classified Race: NR water. Experiment Station as lactose maldigesters Comorbidities: not 1) Lactose 0 g USA based on a rise in reported 2) Lactose 2 g Duration of breath hydrogen of >20 Cointerventions: not 3) Lactose 6 g symptom recording: ppm (0.9 ımol reported 4) Lactose 12 g 1 day hydrogen/L air) during a 5) Lactose 20 g 

challenge dose of lactose (20 g) after a 12 hours fast. Methods to measure outcomes: Subjects rated symptoms of flatulence, abdominal pain, and diarrhea hours 1 through 8 following challenge dose. A ranked scale was used; 0=none, 1=slight, 2=mild, 3=moderate, 4= moderately severe, 5= severe. 

Symptoms rating each challenge d(mean ± SEM). Tmaximum possibscore for any individual symptowould be 40 (a “5rating each hour hours). Conclusion(s): Lactose maldigesmay be able to tolerate foods wit

g lactose per servsuch as hard cheand small serving(≤120 mL) of milk

Newcomer, 197891 Data source: 59 lactase Mean age (range): 6 breakfasts Number of subjec

RCT, crossover deficient American 18.7 (5-62). 44 randomly with symptoms. Sponsorship: Indians. were <18 years of distributed. Sugar 

D-387 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

National Institutes of Health and United States Public Health Service. USA Duration of symptom recording: 8 hours Stephenson, 197492 

Un-blinded RCT, attempt made to mask to taste, crossover USA Duration:8 hours Funded by National 

Inclusion criteria: lactase deficiency determined by breath hydrogen concentration to >20 mL/min after ingestion of 50 g (less for children) of lactose. Methods to measure outcomes: A subject was considered to have a positive symptomatic response if he/she had ≥1 loose stools or had a grade 2+ or higher in at least one of the following symptoms: abdominal cramps/pain, bloating or gas, borborygmi, flatulence. Symptoms were rated according: 0 = no trouble; 1+ = slight; 2+ = mild; 3+ = moderate, subject would normally avoid a breakfast causing these symptoms; 4+ = severe, subject would be unable to carry on usual activities. Data Source: n=35 U.S. adults, with and without LI on basis of rise in blood glucose of less than 20 mg/100mL after 50 g lactose ingestion Methods to measure outcome: Asked about 

age. Gender: women 47% Race/ethnicity: American Indian 100%  Median age 25 (23-55 range) Gender: women 54% Race/ethnicity: white 71%, nonwhite 29% Co-morbid: none 

packets with lactose ranging from 0 to 18 g added to 8 ounces of Ensure drink. Breakfast 1: 0 g lactose + 18 g glucose plus galactose (G+G). Breakfast 2: 3 g lactose + 15 g G+G. Breakfast 3: 6 g lactose + 12 g G+G. Breakfast 4: 9 g lactose + 9 g G+G. Breakfast 5: 12 g lactose + 6 g G+G. Breakfast 6: 18 g lactose + 0 g G+G. Day 1, all 35 got 50 gm lactose. Those with symptoms got 15, 30, 50 gm lactose in water or milk serially. Those with no symptoms got 100, 150 and 

Placebo 250 ml (saccharin, lemon juice water) 

Conclusion(s): A modest amount olactose (1-11⁄2 glaof milk), when consumed with a meal, was well tolerated by lactadeficient AmericaIndians. 

Sum of score of bloating, gas, craand diarrhea on scale: 0=none, 1=mild, 2= mode3=severe. Conclusion(s): Madults with lactos

D-388 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

Dairy Council and any symptoms of Co-intervention: 200 gm lactose in intolerance can 

NY State Agriculture bloating, gas, abdominal none water and milk tolerate up to 30 

Experiment Station cramps and diarrhea on serially lactose 

hatch project scale of mild moderate Hypothesis: Higher and severe, summed doses of lactose poorly tolerated F. Studies with irritable bowel syndrome subjects Parker, 200193 Data source: 122 British Data for the 33 Three active tests Conclusion(s): 

RCT, crossover IBS patients were subjects with were given in During double-bli

Sponsorship: NR referred for a lactose positive hydrogen random order for 7 phase, 2/7 subjec

UK hydrogen breath test. breath test. of 9 subjects (29%) developed Duration of The breath test was Mean age NR. Age improving on low- increasing sympt

symptom recording: positive in 33 (27%) and <50 years 73%; lactose diet: lactose with increasing d

1 week negative in 89 (73%). Gender: women 5 g, 10 g, or 15 g, of lactose. 

Subjects in the positive 76% and placebo mixed Although 5 of the 

group were then placed Race/ethnicity with 285 ml water were affected by 

on a low lactose diet for White 85% (n=28), and taken at lactose, 5 subjec

3 weeks. The daily Asian 9% (n=3), breakfast on 2 had worse sympt

intake of lactose from Middle-Eastern 6% consecutive days with 5 g than 10 g

this diet was <1 g. (n=2), with 5 days' rest suggesting that m

Patients improving on Comorbidities: not between each test. LM patients can 

the low lactose diet reported Symptoms scores tolerate up to 12 

were given double-blind, Cointerventions: not were completed day. 

placebo-controlled reported daily for test and Patients with lact

challenges to confirm rest days. Subjects intolerance were 

lactose intolerance. remained on low distinguishable fr

Methods to measure lactose diet during others with IBS o

outcomes: Symptom double-blind, basis of symptom

score was based on placebo-controlled and treatment wit

eight variables: test period. low lactose diet g

abdominal pain, daily disappointing resbowel movements, urgency to defecate, consistency of feces, 

D-389 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

flatulence, headache, abdominal distension, and general well-being. Each symptom was scored from 0 to 4, 0 being no symptoms and 4 most severe. Urgency was scored from 0 to 3. The maximum cumulative score = 31. 

Böhmer 199694 

Sponsorship: not reported The Netherlands Duration of symptom recording: 6 weeks 

Data source: 105 Caucasian Dutch subjects, 70 with IBS and 35 healthy controls Inclusion criteria: Subjects were screened for lactose malabsorption (LM) and were not aware of the test results. Diagnosis of IBS after exclusion of organic causes. Subjects had to fulfill at least two criteria: visible abdominal distension; 

IBS subjects (n=70 of which 17 had LM) Median age (range): 35.7 years (18 to 59) Gender: women 74% Race/ethnicity: white 100% Healthy control subjects (n=35) Median age (range): 33 years (21 to 51) Gender: women 

Lactose restricted diet 

 Cumulative symp

scores at 3 and 6 weeks, comparinIBS subjects with vs. IBS subjects without LM. Conclusion(s): thmean symptom sof the IBS with LM showed a statisticsignificant decreaafter 6 weeks of a lactose restricted 

pain relief with defecation; more frequent stools at pain onset; looser stools at 

74% Race/ethnicity: white 100% 

pain onset; passage of rectal mucus; and feeling of incomplete evacuation. Subjects were classified as lactose malabsorbers based on a rise in breath hydrogen of >20 ppm above basal level 

D-390 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

during a challenge dose of lactose (50 g) after a 12 hours fast. Methods to measure outcomes: subjects scored symptoms (pain, flatulence, distension, diarrhea, mucus, incomplete evacuation) 0=no complaints, 1=mild; 2=moderate; and 3 as severe. A maximum cumulative score = 18. 

Lisker 198995 

RCT, crossover Sponsorship: Mr. A. Kligerman, President of Sugar Lo/Lact Aid company (lactase and placebo vials) Mexico Duration of symptom recording: months: 3 months 

Data source: 12 Mexican subjects with IBS whose diets regularly included milk. Eight of the subjects were lactose maldigesters (when challenged with 12.5 lactose and diagnosed by hydrogen breath test ≥ 20 ppm). Inclusion criteria: 1) diagnosis of IBS based on chronic abdominal pain, altered bowel habits, and absence of organic disease; 2) regular diet included consumption of milk/dairy products ≥8 

oz. glass of milk daily or equivalent lactose intake; 3) patients lived close enough to center 

Mean age (range): 49 years (24 to 72) Gender: women 75% Race/ethnicity: not reported Comorbidities: not reported Cointerventions: not reported 

Treatment A group Lactase x 4 weeks, then placebo x 4 weeks, then lactase x 4 weeks. Prior to 3 month study phase there was a 1 month nonintervention, control period. Lactase (derived from Kluyveromyces lactis) was used in 

vitro (added in entirety to liter of milk the day before consumption) and in vivo (added at mealtime when consuming lactosecontaining foods away from home) 

Treatment B group Placebo x 4 weeks, then lactase x 4 weeks, then lactase x 4 weeks. Prior to 3 month study phase there was a 1 month nonintervention, control period. 

Symptoms noted better, same, or worse for each intervention montConclusion(s): Gsymptoms were fto be independenlactase treatmentthis study populawith a high prevalence of lacdeficiency, IBS symptoms appeato be independenlactose maldiges

D-391 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, 

Study Design, 

Study 

Sponsorship, 

Country, Length of 

Followup 

Subject Selection, 

Data Source, Methods 

to Measure Outcomes, 

Inclusion/Exclusion 

Criteria 

Subject 

Characteristics 

Treatment-Active, 

Adherence 

Evaluations 

TreatmentControl, 

Adherence 

Evaluations 

Outcome 

assessment

Results and 

Conclusions 

to allow adherence to frequent interviews; and 4) showed proper compliance and reliability during first (control) month. Methods to measure outcomes: Diary record of symptoms filled out daily. Symptoms included constipation, diarrhea, abdominal pain, abdominal distension, and flatulence. 

Newcomer 198380 Data source: 79 1) Lactase Lactase deficient lactase deficient Cumulative symp

RCT, crossover American subjects, 61 deficiency subjects subjects subjects indices for the 18 

Sponsorship: lactase sufficient (n=18) Acidophilus milk Unaltered milk lactase deficiency 

National Dairy subjects with IBS and Age range (18-69) (mean 11⁄2 glasses (mean 11⁄2 glasses subjects 

Council and North 18 lactase deficient (all Gender: not daily) x 1 week daily) x 1 week Conclusion(s): Th

Carolina State had histories of milk reported (either week 1 or (either week 1 or was no difference 

University Dairy intolerance) subjects. Race/ethnicity: not week 4). week 4). the tolerance of t

Foundation There were also 10 reported 2 week control lactase sufficient acidophilus and 

USA healthy controls. 2) lactase sufficient period between subjects with IBS unaltered milks in 

Duration of Inclusion criteria: subjects with IBS weeks of starting and controls lactase deficient 

symptom recording: lactase deficiency was (n=61) new treatment Unaltered milk (3 8 group. IBS subjec

1 week diagnosed by an Age range (20-82) Lactase sufficient oz. glasses daily) x were also not hel

increase in the breath Gender: not subjects with IBS 2 weeks (either by the ingestion o

hydrogen ≥0.30 ml/min reported and controls week 3 or week 7). acidophilus milk. 

above basal level after Race/ethnicity: not Acidophilus milk (3 challenge of 50 g reported 8 oz. glasses daily) lactose in 500 ml water. 3) healthy controls x 2 weeks (either IBS was diagnosed on (n=10) week 3 or week 7). the basis of a typical Age range (21-64) Three 2- week history and a minimal Gender: not control periods 

number of negative reported (milk-drinking diagnostic studies. Race/ethnicity: not periods in 

Methods to measure reported between). 

D-392 
Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

Author, Year, Subject Selection, Study Design, Treatment- Outcome Data Source, Methods Treatment-Active, Study Subject Control, assessment

to Measure Outcomes, Adherence Sponsorship, Characteristics Adherence Results and 

Inclusion/Exclusion Evaluations Country, Length of Evaluations Conclusions Criteria Followup 

outcomes: Symptom (diarrhea, abdominal pain/cramps*, gas/flatus*, rumbling*, constipation) diary at end of each day. Diarrhea was yes/no, # stools per day. Scored as following for *: 0=no trouble; 1=slight trouble; 2=mild; 3=moderate; 4=severe. Constipation was better, same, worse. 

D-393 
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Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) 

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