Introduction

The aims of this evidence report are to

summarize the current evidence on the health

effects of soy and its isoflavones on the following:

cardiovascular diseases, menopausal symptoms,

endocrine function, cancer, bone health,

reproductive health, kidney diseases, cognitive

function, and glucose metabolism. In addition,

safety issues and drug interactions of using soy

and its isoflavones, as reported in the literature,

are summarized. This report also summarizes the

formulations of soy products and/or soy food

used in clinical trials. The report was requested

and funded by the National Center for

Complementary and Alternative Medicine

(NCCAM) and the Office of Dietary

Supplements at the National Institutes of Health

(NIH) and was conducted through the

Evidence-based Practice Center (EPC) program

at the Agency for Healthcare Research and

Quality (AHRQ).

There is increasing interest in soy and health

since the U.S. Food and Drug Administration

approved a health claim in October 1999 for use

on food labels stating that a daily diet containing

25 grams of soy protein, also low in saturated fat

and cholesterol, may reduce the risk of heart

disease. This claim was based on the beneficial

results in reducing plasma low-density

lipoprotein (LDL) levels from dozens of human

controlled clinical trials.1 The health claim,

however, covers only soy protein, since research

results surrounding soy isoflavones were

controversial.2 This report summarizes the

current evidence on the health effects of soy and

its isoflavones.

Methods

Key Questions

Five general questions are addressed in this

report:

1. In the clinical trial literature, what

formulations of soy were used? At what

dose? For what purpose(s) (e.g., trial

endpoints)?

2. Does current clinical trial evidence indicate

that whole soy products and individual

constituents of soy have an effect on: 

a. Cardiovascular events, risk factors, and

measures; 

b. Menopausal symptoms;

c. Endocrine function;

d. Cancer and tumor-related biomarkers; 

e. Osteoporosis and osteoporosis risk

factors; 

f. Reproductive health; 

g. Kidney function; and 

h. Other outcomes, based on results of Key

Question 1, above?

3. What is the scientific evidence of a doseresponse effect of different forms of soy and

Evidence Report/Technology Assessment

Number 126

Effects of Soy on Health Outcomes

Summary

Authors: Balk E, Chung M, Chew P, Ip S, Raman G, Kupelnick B, 

Tatsioni A, Sun Y, Wolk B, DeVine D, Lau J

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

individual constituents of soy for the conditions specified

in Key Question 1?

4. What are the frequency and type(s) of adverse events

associated with consumption of soy that are reported in

the scientific literature (both trials and epidemiology)?

5. What is the scientific evidence of a dose-response effect of

whole soy products and individual soy constituents on

their safety?

Approach to Analyzing the Literature

Inclusion Criteria

This report encompasses several health conditions and many

outcomes of interest. Therefore, specific inclusion criteria were

needed for each of the health conditions and sometimes for

different outcomes of the same health condition. The common

inclusion criteria for studies analyzed in this report consist of:

human subjects 13 years and older; prospective studies

including randomized controlled trials, cohorts, crossover and

non-randomized comparison studies; at least five subjects in

the soy arm; any health condition; quantification of the

amount of soy; and reported outcomes of interest. In general,

the minimum duration for all serum marker, urine marker,

and vascular outcome studies was 4 weeks (exceptions are

noted below, under “Specific Inclusion Criteria for Health

Conditions Examined”). 

For assessments of adverse events, we also included

prospective observation studies and case-control studies, with

no limitations on study size or duration, or quantification of

soy product.

Health Conditions of Interest

In addition to the health conditions of interest listed under

Key Question 3, the Technical Expert Panel (TEP) convened

by the EPC suggested the category of neurocognitive

outcomes. NCCAM was also interested in knowing about

research that might have been done in other health conditions.

Therefore, our literature search was conducted to broadly

include soy studies for any health conditions. We screened all

citations to identify health conditions not on the list agreed

upon with the TEP. During our review process, we included

the additional category of endocrine function.

Soy Products (and Controls) Considered

We accepted studies that used soy supplements and foods

that quantified the amount of soy ingredients or products. We

categorized various soy products and soy food into the

following groups:

• Refined soy products

- Isolated soy protein with isoflavones

- Isolated soy protein without isoflavones

- Textured soy protein 

- Soy-derived isoflavone

■ Genistein/genistin

■ Daidzein/daidzin

■ Glycitein/glycitin

• Soy/soya food products (ingested amount must be

quantified)

- Whole soy beans (edamame)

- Soy flour

- Soy drink (soy milk)

- Tofu (bean curd)

- Miso

- Other processed soy bean products (tempeh, natto,

okara, etc.)

For the purpose of this report, all study arms with a soy

product of any type were considered to be soy interventions.

Only study arms with a non-soy intervention were categorized

as controls. 

Specific Inclusion Criteria for Health Conditions

Examined

In addition to the common inclusion criteria listed above,

with input from TEP members we established the following

additional criteria and specific outcomes for each of the

specific health conditions.

Cardiovascular Outcomes: These included total

cholesterol, LDL, high density lipoprotein (HDL),

triglycerides, lipoprotein(a) [Lp(a)], blood pressure (BP), Creactive protein (CRP), homocysteine, endothelial function,

systemic arterial compliance, and oxidized LDL. We also

sought studies of clinical cardiovascular outcomes (e.g., death,

myocardial infarction, angina) but found none. The list of

outcomes was determined in consultation with the TEP, based

on expert opinion of the likelihood of an effect on the

outcomes, clinical importance, and estimates of the numbers

of studies likely to be available.

Because of the relatively large number of available studies

reporting on lipids, triglycerides, and blood pressure, it was

decided with the TEP to limit inclusion of these studies to

randomized controlled trials with a minimum of 10 subjects

consuming a soy product. For all cardiovascular outcomes, we

required a minimum duration of 4 weeks.
Menopausal Symptoms: Studies evaluated perimenopausal women, post-menopausal women, or women on

breast cancer therapies with menopausal symptoms. A

minimum duration of 4 weeks was required for studies of

menopausal symptoms.

Endocrine Function: We included in our analyses the

following endocrine markers: testosterone, follicle stimulating

hormone (FSH), total estradiol and thyroid stimulating

hormone (TSH). In addition, we evaluated menstrual cycle

outcomes. The decisions for which outcomes to investigate

were based on expert opinion of the likelihood of an effect on

the outcomes, clinical importance, and estimates of the

numbers of studies likely to be available. Studies that did not

report numerical data on effect for these outcomes were not

summarized; however, these studies were maintained in the

database. For all endocrine outcomes, we required a minimum

duration of 4 weeks (or one menstrual cycle).

Cancer and Tumor-Related Biomarkers: To evaluate

whether soy may prevent cancer or reduce cancer risk factors,

we included only studies that recruited subjects without a

diagnosis of cancer. We limited our analyses to studies with

tumor-related biomarkers or cancer risk factors as outcomes

and to studies of clinical cancer outcomes (e.g., diagnosis of

prostate cancer). We did not include studies that used soy

products as “treatments” for cancer. The only outcome that

fulfilled these criteria was testosterone. The studies that

reported testosterone as an outcome in men without diagnoses

of cancer were analyzed in the endocrine section. The decision

to investigate only testosterone was based on expert opinion of

the likelihood of an effect on the outcomes and of its clinical

importance. For all tumor-related biomarkers, we broadened

the eligibility criteria to include a minimum duration of 1

week.

Bone Endpoints: For bone resorption and/or formation

biomarkers, the general inclusion criteria were used, including

a minimum duration of 4 weeks. Because effects on bone

mineral density occur slowly over time, we used minimum

study duration of 1 year, although we did briefly review studies

with a duration less than 1 year.

Miscellaneous Outcomes: For all other outcomes

(neurocognitive, kidney, glucose metabolism), the general

inclusion criteria were used in combination with the restriction

to populations without the related specific diseases or

conditions.

Literature Search Strategy

We conducted a comprehensive literature search to address

the key questions.* Primary literature searches for English

language publications on soy studies were conducted in

EMBASE on March 25, 2004; in MEDLINE® on April 20,

2004; and in CAB Abstracts on June 24, 2004. Search terms

included subject headings and textwords with filters to limit

the publications to English language and primary studies of

the adult and adolescent human populations. Subject headings

and textwords were selected so that the same set could be

applied to each of the different databases. A supplemental

search was performed in MEDLINE on April 30, 2004, to

retrieve articles using the textword “miso.” A search update was

performed in MEDLINE In-Process & Other Non-Indexed

Citations and MEDLINE on September 30, 2004, and in

CAB Abstracts on October 4, 2004. A search of the

TOXLINE® database was conducted in March 31, 2005, to

identify additional reports of adverse events in humans.

Additional sources of published and unpublished data were

sought by contacting members of the TEP and from reference

lists of selected review articles and meta-analyses.

Reporting of Evidence

Methodological Quality Grade

We used a three-category grading system (A, B, C) to

denote the methodological quality of each study. This system

defines a generic grading system that is applicable to varying

study designs, including randomized controlled trials, cohort,

and case-control studies:

A: Least bias; results are valid; a study that mostly adheres to

the commonly held concepts of high quality.

B: Susceptible to some bias but not sufficient to invalidate

the results; a study that does not meet all the criteria in

category A.

C: Significant bias that may invalidate the results; a study

with serious errors in design, analysis, or reporting.

Applicability Grade

In this report, the focus is on the U.S. population and on

specific subgroups within that population (i.e., postmenopausal women, peri-menopausal women, pre-menopausal

women, men, and people with relevant medical histories such

as breast cancer). Even though a study may focus on a specific

3

* Appendix A (Search Strategy) is available electronically at

www.ahrq.gov/clinic/tp/soytp.htm.
4

target population, limited study size, eligibility criteria, and the

patient recruitment process may result in a narrow population

sample that is of limited applicability, even to the target

population. To address this issue, we categorized studies within

a target population into one of three levels of applicability,

which are defined as follows: sample is representative of the

target population; sample is representative of a relevant

subgroup of the target population but not the entire

population; sample is representative of a narrow subgroup of

subjects only and is of limited applicability to other subgroups.

Meta-analysis

Meta-analysis was performed for several cardiovascular

outcomes. We used the random effects model for continuous

outcomes to combine studies. We also performed several

random effects model meta-regression analyses to explore

possible reasons for discrepancies across studies and to address

Key Questions related to dose-response.

Results

Soy Products

Soy supplements were used in about three-quarters of all the

trials analyzed in this report; soy foods were used in the

remaining trials. In this report, soy milk was categorized as a

soy supplement. Among the soy supplement trials, 57 percent

used soy protein with isoflavones, 36 percent used isoflavones

alone, and 6 percent used soy protein without isoflavones. In

about one-half of the soy foods trials, textured soy protein was

used. Soy flour was used in about one-quarter of the soy foods

trials. There are 146 separate treatment arms of soy

supplementations and 68 separate treatment arms of soy foods

or diets. Across studies, the total isoflavones ranged from 0 mg

to 185 mg per day, and the total protein intake from soy

ranged from 0 g to 154 g per day. It is notable that the median

soy product dose across studies (36 g soy protein per day) was

equivalent to over a pound of tofu daily or about 3 soy protein

shakes daily.

Cardiovascular Endpoints

No study evaluated clinical cardiovascular events. A total of

68 randomized studies reported data on total cholesterol,

LDL, HDL, and/or triglycerides. The total isoflavones ranged

from 0 mg to 185 mg per day, with a median of 80 mg.

Among studies with soy protein, the total protein intake from

soy ranged from 14 to 113 g per day, with a median of 36 g.

There is a great deal of heterogeneity in the effects found on

lipoprotein and triglyceride levels. Overall, the majority of

studies reported small to moderate effects on the lipids, despite

a wide range of net effects for total cholesterol, LDL, and

triglycerides. Sixty-one studies reported data on the effect of

consumption of soy products on total cholesterol levels. The

median net change compared to control was approximately –5

(interquartile range –10, +1) mg/dL decrease (about –2.5

percent). A meta-analysis of 52 studies that reported data on

the effect of soy consumption on LDL levels yielded a

statistically significant net decrease of 5 (95-percent confidence

interval [CI] –8 to –3) mg/dL (about –3 percent). A metaanalysis of 56 studies that reported data on the effect of soy

consumption on HDL levels found a statistically

nonsignificant net change of +0.6 (95-percent CI –0.5, +1.8)

mg/dL. A meta-analysis combining 54 studies that reported

data on the effect of soy consumption on triglyceride levels

yielded a net change of –8 (95-percent CI –11, –5) mg/dL

(about –6 percent). Across studies, there is the possible

suggestion that higher doses of soy protein are associated with

greater LDL reduction among those with elevated baseline

LDL (although not if studies with minimal soy protein doses

are excluded) but not with HDL or triglycerides. Dose of

isoflavones was not associated with effect for any lipid. Higher

baseline LDL or triglycerides may also be associated with net

effect for these two lipids; the effect of baseline HDL is

unclear. For all lipids, in individual studies the effect of dose

and baseline was generally inconsistent.

A total of 22 studies reported data on the effect of

consumption of soy products on systolic and diastolic BP.

Overall, across studies, there was no discernible effect. 

Some of the well-known emerging risk factors for

cardiovascular disease included for analysis in this report are:

Lp(a), CRP, homocysteine, endothelial function, systemic

arterial compliance, and oxidized LDL. The total numbers of

studies that reported data on the effect of soy consumption

are: 18 studies on Lp(a), 3 on CRP, 5 on homocysteine, 10 on

endothelial function, 3 on systemic arterial compliance, and 13

on oxidized LDL. Across these studies, there is no discernible

effect based on the type of soy products. The majority of

studies were of poor quality with a narrow range of

applicability. Given the limited evidence and poor quality of

studies, no conclusions could be drawn on the beneficial or

harmful effects of consumption of soy protein on these

putative risk factors for cardiovascular disease.

Menopausal Symptoms

A total of 21 trials examined the effects of soy and/or its

isoflavones on hot flashes and night sweats in women. These
trials generally measured frequency and severity of the

symptoms. However, the investigators used a large number of

vasomotor symptom scores or indexes that employed a variety

of frequency intervals. These factors made meta-analyses

unsuitable and limited the comparisons of results across

studies. Furthermore, many of the studies had high withdrawal

or dropout rates, which were frequently uneven between soy

treatment and control arms, further limiting the validity of

these trials. Overall, the effects of soy protein and/or its

isoflavones are inconsistent across studies. Every trial found a

decrease in hot flash frequencies or scores in both the

treatment groups and the control groups. Thus, the results are

difficult to interpret. A third of the studies found no or

worsening effects compared to control; two-thirds showed that

soy protein and/or its isoflavones either nonsignificantly or

significantly decreased hot flash frequencies or scores compared

to control in post-menopausal women. The evidence of a

benefit was stronger among the randomized trials of isoflavone

supplements, which mostly showed positive results—the net

reduction in weekly hot flash frequency ranged from 7 percent

to 40 percent. However, these trials are mostly rated as poor

quality due to high dropout rates. Only four studies evaluated

the effect of soy consumption on menopausal symptoms in

peri-menopausal women or those receiving breast cancer

therapy. Among these studies there is no evidence that soy

consumption is better than control to reduce menopausal

symptoms.

Endocrine Function

Measures of endocrine function from 50 trials were reported

in 47 articles. Five studies with a total of 179 participants

reported testosterone levels in healthy males before and after

soy consumption. Four of these trials found a statistically

nonsignificant decrease in testosterone levels. The small total

number of subjects, as well as the low quality of these studies,

precluded any meaningful conclusion. No statistically

significant effect was found on FSH level, which is commonly

measured in the initial evaluation of male and female

infertility; results were conflicting. 

Twelve studies reported estradiol levels at the follicular phase

in 434 pre-menopausal women. The overall effect of soy on

estradiol levels was not consistent. Most of the studies showed

a trend for soy to reduce estradiol, although they failed to

demonstrate a statistically significant effect. Six randomized

trials reported the effect of soy on TSH. No overall effect of

soy on TSH and thyroid function is clear.

An additional 11 trials (in 10 publications) evaluated the

effect of soy on menstrual cycle length in pre-menopausal

women. A wide range of soy interventions were used in these

trials, making a conclusion on the effects from soy difficult.

These trials did not show statistically significant changes in

menstrual cycle length after treatments of soy and/or its

isoflavones.

Cancer and Tumor-Related Biomarkers

Twenty-four trials evaluated subjects without a history of

cancer for effects of soy on tumor-related biomarkers. No

study reported the development of cancer as an outcome.

Most studies measured the effect of soy on estrogens and

estrogen metabolites as well as on estrogenicity indicators.

There were also trials that evaluated correlations between soy

and possible cellular pathways of cancer prevention. No causal

relationship could be established between these markers and

cancer because they do not represent known risk factors for

cancer disease. Only four studies reported on testosterone level,

which is a risk factor for prostate cancer and is discussed above

under “Endocrine Function.”

Bone Endpoints

Overall, 31 studies evaluated various markers of bone

health, including bone mineral density (BMD), bone

formation biomarkers (bone specific alkaline phosphatase and

osteocalcin) and bone resorption biomarkers (urinary

hydroxyproline, urinary cross-linked N-telopeptide, urinary

pyridinoline, and urinary deoxypyridinoline).

Because there are few long-term randomized trials and a

wide variety of soy interventions used across studies, it is

difficult to draw an overall conclusion about the effects of soy

on bone outcomes. Overall, among the five studies of 1-year

minimum duration, no consistent effect on BMD was seen

with soy consumption. Studies of shorter duration likewise

found no effect of soy. Similar to the results for BMD, studies

of bone formation biomarkers generally found no effect of soy

consumption when compared to control. While a number of

studies reported reductions in two markers of bone

resorption—urinary pyridinoline and deoxypyridinoline—no

effects were found on the other markers of bone resorption,

and the effects were not consistent across studies. For these

markers, there is no clear evidence of a dose effect for either

soy isoflavones or soy protein.

Only one study found a consistent effect on these markers.

The study differed from other studies in that it evaluated a

unique formulation of soy genistein and that it excluded

subjects with denser femoral neck BMD. 

5
Kidney Function, Neurocognitive Function,

and Glucose Metabolism

Only one small study in patients with type 2 diabetes

assessed the effect of soy on kidney function. No statistically

significant change in glomerular filtration rate was seen after 8

weeks of soy protein diet. Four studies examined the effects of

soy on cognitive function of post-menopausal women and

college students of both sexes. Overall, no statistically

significant or consistent effect was noted on neurocognitive

functions such as verbal episodic memory. Six studies evaluated

the effect of soy on fasting blood glucose. No statistically

significant changes were reported. 

Adverse Events

In general, the rates of adverse events reported were greater

in the soy treatment arms than in their respective control arms,

but adverse events related to soy consumption were generally

minor. Overall, soy products including isoflavones were well

tolerated in the trials we examined.

The most frequently reported adverse events among a total

of 3,518 subjects in 49 studies (including 5 nonrandomized

and 3 pharmacokinetic studies) that reported adverse events

were gastrointestinal in nature. These were reported in 33 of

41 comparison studies of soy diets, soy proteins, isoflavones,

and phytoestrogen supplements. Most of the gastrointestinal

adverse events were reported in soy diet and soy protein trials,

especially the 12 studies that used purified isoflavone

interventions in dosages ranging from 40 to 100 mg/day. The

amount of soy protein in these trials ranged from 20 to 60

g/day, but there was no clear dose relationship between the

amount consumed and subsequent adverse events. Menstrual

complaints, reported in 15 studies, were also common. Six of

these studies used purified isoflavone interventions in dosages

ranging from 40 to 80 mg/day. However, most women in

these studies were post-menopausal, and the controls

frequently included hormone therapy regimens. Other adverse

events included musculoskeletal complaints, headache,

dizziness, and rashes. In addition, there were somewhat more

withdrawals from the soy arms due to taste aversion.

Limitations

Despite the large number of trials that have been

performed, the health effects of soy for many conditions that

have been studied remain uncertain. The methodological

quality of over half the studies (about 55 percent) evaluated in

this report was poor (Grade C). One-third of the poor-quality

studies were either uncontrolled single-cohort studies,

nonrandomized comparative studies, or comparative studies

for which it was unclear whether they were randomized.

Another third of the poor-quality studies had dropout rates

that exceeded 20 percent or unequal dropout rates between the

soy and control arms. Other reasons that studies were graded

poor quality included lack of reporting of baseline data;

inadequate accounting of important confounders; major

discrepancies between text, tables, and/or figures or

irreconcilable data that indicate likely improper statistical

analysis; and substantial missing data.

There was also great heterogeneity among studies,

particularly among the interventions analyzed. Comparisons

across the myriad types of soy are intrinsically very difficult.

This difficulty was compounded by the use of soy both as a

supplement and as an integral part of the diet; furthermore, for

numerous studies, it is difficult to distinguish between

supplement and diet. It is likely that studies of supplements

and diet are not easily comparable. Most studies involved a

small number of study subjects and were of short duration.

About one-half of studies were of less than 12 weeks duration

and about one-third were shorter than 6 weeks. Few studies

directly compared soy products, mostly comparing soy protein

with varying amounts of soy isoflavones. Only one performed

a factorial design study comparing both present and absent soy

protein and present and absent soy isoflavones, thus allowing

analysis of the effect of both soy protein and soy product. The

universal issue of possible publication bias, where negative

studies are less likely to be published and are more likely to be

published later, is a potential concern. However, for most

outcomes, the majority of studies reported negative outcomes,

and there was no obvious evidence of publication bias among

the lipid studies (where there is evidence of a positive effect).

Conclusions

Most of the studies evaluated the effects of soy on various

biomarkers or measures, not clinical outcomes, although

several of the endpoints, such as blood pressure, LDL, and

bone mineral density, do have known meaningful correlations

with clinical outcomes. Cardiovascular surrogate endpoints

were assessed by the largest number of studies. Overall, soy was

found to have a small effect on lipids. However, the duration

of these studies was generally short, and it is uncertain whether

the results would be sustained. No study evaluated clinical

cardiovascular disease.

6
Reduction of hot flashes by soy was seen in trials involving

post-menopausal and peri-menopausal women. Most of the

trials lasted only 3 to 4 months; thus the long-term benefits

remain unclear. In addition, different measurements were used

to assess benefits across studies, making comparisons and

synthesis difficult. Soy phytoestrogens are seen by some as an

alternative to estrogen therapy to treat post-menopausal

symptoms. However, the estrogenic effect of soy in potentially

promoting tumor recurrence raises concern for its use by breast

cancer survivors. The current literature provides no data to

address this issue.

The evidence does not support an effect of soy products on

endocrine function, menstrual cycle length, or bone health,

although evidence was often limited and of poor quality. No

study evaluated clinical endocrine or bone disease.

This report was limited to human studies, and thus was

unable to fully respond to biological or biochemical

hypotheses of benefits or harms of phytoestrogens suggested by

various animal, in vitro, or assay detection studies: the

correlations between specific nutrients and their effects remain

unclear. While the evidence does suggest a greater likelihood of

adverse events with soy consumption, these were mostly minor

in nature. There were a limited number of studies with

duration of 1 year or longer; thus the long-term adverse effect

of soy in a large population is uncertain.

For all outcomes, including adverse events, there is no

conclusive evidence of a dose-response effect for either soy

protein or isoflavone. However, for LDL reduction, there is a

suggestion of a possible dose-response effect for soy protein.

Future Research

This report dealt with a broad range of health conditions

and endpoints; thus it is difficult to focus research

recommendations on a specific area. As is the case with most

bodies of evidence regarding medical fields, better quality, wellreported, larger, and longer duration studies are needed to

address the questions of interest. Future studies should fully

report the components of soy products being tested; compare

different doses, soy products, and populations; more closely

evaluate the effects of different soy components, including

non-protein, non-isoflavone components; fully consider the

types of foods being replaced by soy products and the controls

being used; and use the CONSORT statement as a guide to

designing and reporting studies.3,4

Conducting clinical trials in the area of health effects of

food substances is fraught with difficulties. There is a complex

interplay among the various components and potentially active

substances within the foods and with other foods. Dietary

variations, as well as other lifestyle and clinical variations

among individuals, are also complex. Controlling for these

factors is difficult within a trial. Interpreting discrepant results

among trials is even more difficult. Isoflavones are believed to

be the key active substance in soy, but this is by no means

certain. Little data suggest that the amount of soy isoflavones is

associated with an incremental effect, and studies of soy

protein with little or no isoflavones frequently had similar

effects as isoflavone studies. Difficulties with attempting to

ascribe a food health benefit to a specific component of the

food are highlighted by the recent spate of disappointing

results from antioxidant trials, which suggest that the

evaluation of potential nutrient benefits may need a paradigm

different from the traditional clinical trial model. 

The bioavailability of an ingested nutrient may also be an

important factor in the determination of the beneficial effect.

Several factors may affect the bioavailability of ingested

nutrients: (1) absorption rate, which is affected by the

interactions with competitive nutrients, the usual diet

compositions, and types of foods or supplements; (2)

incorporation rate into the blood stream, in which complex

mechanisms might be involved, such as the functions of

facilitated transporters, receptors on the membrane, or cellular

binding proteins; (3) metabolism of the intestinal bacterial

environment. Any one of these factors alone does not

determine the bioavailability. In order to gain insights on the

question of dose-response relationship, we need information

not only on the soy isoflavone contents, including types and

amount, but also on the bioavailability of the ingested soy

isoflavones.

Unfortunately, studies that attempt to control for the

myriad factors that interfere with clear interpretation of the

effect of food products such as soy tend to be highly artificial,

with little applicability to the average person. Clarity is needed

to define what study questions are of interest. Metabolic

laboratory studies or investigations of highly structured or

restricted diets (such as those where soy protein constitutes the

bulk of daily protein consumption) are of potential value only

to possibly determine which components of soy are bioactive

or to determine what extremes of diet may be necessary to

achieve a benefit. Studies that substitute practical amounts of

soy products into average people’s diets would better address

7
8

the question of whether people should make the effort to

include more soy in their diets, but these studies will invariably

be difficult to interpret. An exception to this may be studies of

soy isoflavone supplements (e.g., nonfood capsules), which

may be interpreted more like usual drug trials.

Carefully controlled efficacy studies (those conducted under

the artificial conditions of a clinical trial) may still be useful to

pin down the relative effects of various components of soy.

Once this is better clarified, more practical effectiveness studies

that aim to test the value of an intervention in more real-world

scenarios with feasible interventions might be more important.

Availability of the Full Report

The full evidence report from which this summary was

taken was prepared for the Agency for Healthcare Research

and Quality (AHRQ) by the Tufts-New England Medical

Center Evidence-based Practice Center under Contract No.

290-02-0022. It is expected to be available in August 2005. At

that time, printed copies may be obtained free of charge from

the AHRQ Publications Clearinghouse by calling 800-358-

9295. Requesters should ask for Evidence Report/Technology

Assessment No. 126, Effects of Soy on Health Outcomes. In

addition, Internet users will be able to access the report and

this summary online through AHRQ’s Web site at

www.ahrq.gov.

Suggested Citation

Balk E, Chung M, Chew P, Ip S, Raman G, Kupelnick B,

Tatsioni A, Sun Y, Wolk B, DeVine D, Lau J. Effects of Soy

on Health Outcomes. Summary, Evidence Report/Technology

Assessment No. 126. (Prepared by the Tufts-New England

Medical Center Evidence-based Practice Center under

Contract No. 290-02-0022.) AHRQ Publication No. 

05-E024-1. Rockville, MD: Agency for Healthcare Research

and Quality. July 2005.

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2. Henkel J. Soy: health claims for soy protein, questions about other

components. FDA Consumer [magazine] 2000; 34(3). 

3. Moher D, Schulz KF, Altman DG, for the CONSORT group. The

CONSORT Statement: Revised Recommendations for Improving

the Quality of Reports of Parallel-Group Randomized Trials. Ann

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AHRQ Pub. No. 05-E024-1

Corrected August 2005

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