World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Vitamin D Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) National Institutes of Health State-of-the-Science Conference Statement: Multivitamin/Mineral Supplements and Chronic Disease Prevention Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand: a position statement. Periconceptional vitamin supplementation and neural tube defects; evidence from a case-control study in Western Australia and a review of recent publications. EMAS position statement: Vitamin D and postmenopausal health. Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Calcium intake in health maintenance – a systematic review Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial A Treatment Trial of Vitamin D Supplementation in Breast-fed Infants: Universal Supplementation Is Not Necessary for Rickets Prevention in Southern Louisiana Preoperative or postoperative therapy for resectable oesophageal cancer: an updated practice guideline. Vitamin D: do we get enough? Exercise for people with cancer: a clinical practice guideline. Effect of combined maternal and infant vitamin D supplementation on vitamin D status of exclusively breastfed infants. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics Vitamin D supplementation in breastfed infants from Montréal, Canada: 25-hydroxyvitamin D and bone health effects from a follow-up study at 3 years of age Influence of long-chain polyunsaturated fatty acid formula feeds on vitamin E status in preterm infants. EAU guidelines on renal cell carcinoma: the 2010 update. A global representation of vitamin D status in healthy populations [Optimization of calcium intake for the prevention of osteoporosis and osteoporotic fractures: a review of the evidence].
Background The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20–30 % in those with an allergic first-degree relative .  Vitamin D is involved in the regulation of the immune system and it may play a role in the development , severity and course of asthma and other allergic diseases . Objective The World Allergy Organization ( WAO ) convened a guideline panel to develop evidence -based recommendations addressing the use of vitamin D in primary prevention of allergic diseases . Methods Our WAO guideline panel identified the most relevant clinical questions and performed a systematic review of r and omized controlled trials and non-r and omized studies ( NRS ) , specifically cohort and case-control studies , of vitamin D supplementation for the prevention of allergic diseases . We also review ed the evidence about values and preferences , and re source requirements ( up to January 2015 , with an up date on January 30 , 2016 ) . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . Results Having review ed the currently available evidence , the WAO guideline panel found no support for the hypothesis that vitamin D supplementation reduces the risk of developing allergic diseases in children . The WAO guideline panel suggest not using vitamin D in pregnant women , breastfeeding mothers , or healthy term infants as a means of preventing the development of allergic diseases . This recommendation does not apply to those mothers and infants who have other indications for prophylactic or therapeutic use of vitamin D. The panel ’s recommendations are conditional and supported by very low certainty evidence . Conclusions WAO recommendations about vitamin D supplementation for the prevention of allergic diseases support parents , clinicians and other health care professionals in their decisions whether or not to use vitamin D in preventing allergic diseases in healthy , term infants OBJECTIVE : To revise the American Academy of Pediatrics practice parameter regarding the diagnosis and management of  initial urinary tract infections ( UTIs ) in febrile infants and young children . METHODS : Analysis of the medical literature published since the last version of the guideline was supplemented by analysis of data provided by authors of recent publications . The strength of evidence supporting each recommendation and the strength of the recommendation were assessed and grade d. RESULTS : Diagnosis is made on the basis of the presence of both pyuria and at least 50 000 colonies per mL of a single uropathogenic organism in an appropriately collected specimen of urine . After 7 to 14 days of antimicrobial treatment , close clinical follow-up monitoring should be maintained to permit prompt diagnosis and treatment of recurrent infections . Ultrasonography of the kidneys and bladder should be performed to detect anatomic abnormalities . Data from the most recent 6 studies do not support the use of antimicrobial prophylaxis to prevent febrile recurrent UTI in infants without vesicoureteral reflux ( VUR ) or with grade I to IV VUR . Therefore , a  voiding cystourethrography ( VCUG )  is not recommended routinely after the first UTI ; VCUG is indicated if renal and bladder ultrasonography reveals hydronephrosis , scarring , or other findings that would suggest either high- grade VUR or obstructive uropathy and in other atypical or complex clinical circumstances .  VCUG  should also be performed if there is a recurrence of a febrile UTI . The recommendations in this guideline do not indicate an exclusive course of treatment or serve as a st and ard of care ; variations may be appropriate . Recommendations about antimicrobial prophylaxis and implication s for performance of VCUG are based on currently available evidence . As with all American Academy of Pediatrics clinical guidelines , the recommendations will be review ed routinely and incorporate new evidence , such as data from the R and omized Intervention for Children With Vesicoureteral Reflux ( RIVUR ) study . CONCLUSIONS : Changes in this revision include criteria for the diagnosis of UTI and recommendations for imaging Background The prevalence of allergic diseases in infants , whose parents and siblings do not have allergy , is approximately 10 % and reaches 20–30 % in those with an allergic first-degree relative . Intestinal microbiota may modulate immunologic and inflammatory systemic responses and , thus , influence development of sensitization and allergy . Prebiotics – non-digestible oligosaccharides that stimulate growth of probiotic bacteria – have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention . Objective The World Allergy Organization ( WAO ) convened a guideline panel to develop evidence -based recommendations about the use of prebiotics in the prevention of allergy . Methods The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy . We performed a systematic review of r and omized controlled trials of prebiotics , and review ed the evidence about patient values and preferences , and re source requirements ( up to January 2015 , with an up date on July 29 , 2015 ) . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . Results Based on GRADE evidence to decision frameworks , the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants . Both recommendations are conditional and based on very low certainty of the evidence . We found no experimental or observational study of prebiotic supplementation  in pregnant women or in breastfeeding mothers . Thus , the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding , at this time . Conclusions WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents , clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy , term infants Introduction Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures . A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects . Purpose and Methods Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have review ed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases , providing recommendations and guidelines for future studies in this field . Results and conclusions Robust mechanistic evidence is available from in vitro studies and in vivo animal studies , usually employing cholecalciferol , calcidiol or calcitriol in pharmacologic rather than physiologic doses . Although many cross-sectional and prospect i ve association studies in humans have shown that low 25-hydroxyvitamin D levels ( i.e. , < 50 nmol/L ) are consistently associated with chronic diseases , further strengthened by a dose-response relationship , several meta-analyses of clinical trials have shown contradictory results . Overall , large r and omized controlled trials with sufficient doses of vitamin D are missing , and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels  > 50 nmol/L , did not simultaneously assess multiple outcomes , and did not report overall safety ( e.g. , falls ) . Thus , no recommendations can be made to date for the use of vitamin D supplementation in general , parental compounds , or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases . Moreover , attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health can not be recommended based on current evidence , since safety has yet to be confirmed . Finally , the promising findings from mechanistic studies , large cohort studies , and small clinical trials obtained for autoimmune diseases ( including type 1 diabetes , multiple sclerosis , and systemic lupus erythematosus ) , cardiovascular disorders , and overall reduction in mortality require further confirmation National Institutes of Health ( NIH ) consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1 ) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality ( AHRQ ) , 2 ) presentations by investigators working in areas relevant to the conference questions during a 2-day public session , 3 ) questions and statements from conference attendees during open discussion periods that are part of the public session , and 4 ) closed deliberations by the panel during the remainder of the second day and the morning of the third . This statement is an independent report of the panel and is not a policy statement of the NIH or the federal government . The statement reflects the panel 's assessment of medical knowledge available at the time the statement was written . Thus , it provides a snapshot in time of the state of knowledge on the conference topic . When reading the statement , keep in mind that new knowledge is inevitably accumulating through medical research . At least half of American adults take a dietary supplement , the majority of which are multivitamin/multimineral ( MVM ) supplements . As more and more Americans seek strategies for maintaining good health and preventing disease , and as the marketplace offers an increasing number of products to fulfill that desire , it is important that consumers have the best possible information to make their choices . Assessing the available scientific evidence on the benefits of MVM supplement use for chronic disease prevention , identifying the gaps in the evidence , and recommending an appropriate research agenda to meet the shortfalls are subjects considered in this report . The word vitamine was coined in 1912 , as an abbreviated term meant to capture the notion of important factors in the diet , or vital amines . This was preceded more than 150 years earlier by British navy physician James Lind 's discoveryin the first recorded controlled trialthat citrus juice , a good source of what was found 2 centuries later to be vitamin C , could prevent scurvy in sailors . In 1913 , the first vitamin was isolated : thiamin , the deficiency of which caused beriberi . Thirteen vitamins and 15 essential minerals have now been identified as important to human nutrition . Large-scale fortification of diets began in the United States with the addition of iodine to table salt in 1924 to prevent goiter , followed by the addition of vitamin D to milk in 1933 to prevent rickets and the addition of thiamin , riboflavin , niacin , and iron to flour in 1941 . Multivitamin/multimineral products providing more than vitamins A and D became available in pharmacies and grocery stores in the mid-1930s . In the early 1940s , the first MVM tablet was introduced . Although clinical deficiency of vitamins or minerals , other than iron , is now uncommon in the United States , growth in supplement use has accelerated rapidly with marketing spurred by cl aims some based on scientific studies that chronic conditions could be prevented or treated by supplement use . Annual sales of supplements to Americans are now reported at about $ 23 billion , a substantial share of which is spent on vitamins and minerals . Because of such widespread use of MVM , increasing public and medical confusion over apparently contradictory results from studies , and reports of possible adverse effects from overuse in certain circumstances , the Office of Dietary Supplements and the Office of Medical Applications of Research of the NIH convened a State-of-the-Science Conference on Multivitamin/Mineral Supplements and Chronic Disease Prevention , held on 1517 May 2006 , in Bethesda , Maryl and . The goal of the conference was to assess the evidence available on MVM use and outcomes for chronic disease prevention in the generally healthy population of adults and to make recommendations for future research . The conference focused on vitamins and minerals and did not deal with botanicals , hormones , or other supplements . It also did not address the treatment of vitamin or mineral deficiencies . Except for considerations of safety , the conference also did not review issues of primary relevance to pregnant women or children . Specifically , the conference explored the following key questions : 1 ) What are the current patterns and prevalence of the public 's use of MVM supplements ? 2 ) What is known about the dietary nutrient intake of MVM users versus nonusers ? 3 ) What is the efficacy of single vitamin/mineral supplement use in chronic disease prevention ? 4 ) What is the efficacy of MVM  in chronic disease prevention in the general population of adults ? 5 ) What is known about the safety of MVM  for the generally healthy population ? and 6 ) What are the major knowledge gaps and research opportunities regarding MVM use ? During the first 2 days of the conference , experts presented information on each of the key questions . After weighing the scientific evidence , including the data presented by the speakers and a formal evidence report commissioned through AHRQ , an independent panel prepared and presented a draft of this state-of-the-science statement addressing the conference questions . The evidence report prepared for the conference is available at www.ahrq.gov/clinic/tp/multivittp.htm . For the purpose of this statement , the term MVM refers to any supplement containing 3 or more vitamins and minerals but no herbs , hormones , or drugs , with each component at a dose less than the tolerable upper level determined by the Food and Nutrition Boardthe maximum daily intake likely to pose no risk for adverse health effects . Our review also included studies of the relationship of single-nutrient supplements and 2-nutrient supplements to certain disease outcomes . The term primary prevention refers to preventing the development of disease in a person who does not have the disease in question . The chronic conditions assessed include cancer ; age-related sensory loss ; and cardiovascular , endocrine , neurologic , musculoskeletal , gastroenterologic , renal , and pulmonary diseases . A word is warranted about the nature of the evidence base considered by the panel . The range of vitamins and minerals of possible interest was so broad that the conference planning committee chose to focus the evidence report on nutrients for which the potential for impact had been most strongly suggested and on conditions for which supplements were thought to have the most potential influence . The planning committee also limited the scope of the evidence report to consideration of r and omized , controlled trials ( RCTs ) , which are generally considered the gold st and ard for evidence -based decision making . These are studies in which participants are allocated by chance alone to receive or not to receive 1 of 2 or more clinical interventions . For example , while folate supplementation was initially shown to decrease the risk for neural tube defects in animal studies , outcome data in nonhuman models were not considered sufficient evidence on which to base policy recommendations . At the next level of evidence , observational studies in humans suggested efficacy of folate supplementation to prevent such defects . However , these were criticized because they were not r and omized and were potentially subject to bias . Not until these findings were confirmed by RCTs in humans was public policy implemented , including fortification of cereal grains with folate . An observational study is one in which the exposure or treatment of interest is not assigned to the participant by the investigator . Such studies suggested that -carotene intake might protect against the development of some types of cancer . However , RCTs of -carotene supplementation not only showed no benefit , they also found an increased risk for lung cancer in persons who smoked cigarettes or who were exposed to asbestos . These examples illustrate both the risk of relying only on observational studies and the advantage of RCTs in identifying both benefits and risks of MVM supplementation . Limiting the focus of our statement to RCTs has some inherent limitations , given the potential of other types of studies to provide important insights . Observational studies , for example , are particularly useful for generating hypotheses , defining adverse effects , and documenting long-term treatment consequences . They are often essential precursors to the well-conducted RCTs important for policy formation . Our principal recommendations focus on the compelling research activities that must be supported to better inform the decisions that millions of Americans are making each day to use or not to use MVM supplements to prevent chronic disease . At the same time , mindful of the constraints of the available evidence base , we have also taken care not to make premature recommendations about whether generally healthy Americans should or should not take MVM supplements . Because of the need for more reliable information on MVMs , we have made strong recommendations for research and for increased U.S. Food and Drug Administration ( FDA ) oversight of the MVM industry . 1 . What Are the Current Patterns and Prevalence of the Public 's Use of MVM Supplements ? More than half of American adults take dietary supplements in the belief that they will make them feel better , give them greater energy , improve their health , and prevent and treat disease . The use of supplements has been steadily increasing , and growth appears likely to continue . Currently , users spend more than $ 23 billion per year on supplements , and among this supplement-using population , MVM is the major category of supplements , used by about one third of Americans . Uncertainty remains in estimating prevalence of use because of problems defining these products ; increasing complexity in the formulation of supplements , including more non-MVM components and specialized formulas ; and varying frequency of use . It appears that use is higher Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . This is a grade I recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) The available evidence from r and omized trials is either inadequate or conflicting , and the influence of confounding variables on observed outcomes in observational studies can not be determined . As a result , the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . The USPSTF recommends against the use of beta-carotene supplements , either alone or in combination , for the prevention of cancer or cardiovascular disease . This is a grade D recommendation . The USPSTF found good evidence that -carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults . In two trials restricted to heavy smokers , -carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality . The USPSTF concludes that -carotene supplements are unlikely to provide important benefits and might cause harm in some groups . Clinical Considerations The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies , including pregnant and lactating women , children , elderly persons , and people with chronic illnesses .  Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins . Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate . With the exception of vitamins for which there is compelling evidence of net harm ( for example , beta-carotene supplementation in smokers ) , there is little reason to discourage people from taking vitamin supplements . Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet . All patients should receive information about the benefits of a diet high in fruits and vegetables , as well as information on other foods and nutrients that should be emphasized or avoided in their diet ( see the 2002 USPSTF recommendations on counseling to promote a healthy diet [ 1 ] ) . Patients who choose to take vitamins  should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine . Some vitamins , such as A and D , may be harmful in higher doses ; therefore , doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits . Vitamins and minerals sold in the United States are classified as dietary supplements , and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal ( 2 ) . Nevertheless , imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds . The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses . There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods . The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects . In 1996 , the USPSTF recommended folic acid for all women who are planning , or capable of , pregnancy ( see the 1996 USPSTF chapter on screening for neural tube defects [ 3 ] ) . Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications ( for example , folic acid supplementation for patients taking methotrexate ) . Scientific Evidence The USPSTF review s ( 4 - 6 ) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease . These review s were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases ( 7 - 9 ) . The review s focused on prospect i ve trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease . The value of vitamins naturally occurring in food , the use of vitamin supplements for the prevention of other conditions ( for example , neural tube defects ) , and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these review s. Vitamin A No prospect i ve trials have examined the effect of vitamin A supplements alone on the risk for cancer . Observational studies provide no evidence that such supplements prevent cancer in men . In women , observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer ( 10 , 11 ) . Despite efforts to adjust for confounding variables , the observational , nonr and om design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements .  No evidence from prospect i ve trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease . One good- quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality ( 12 ) . Vitamin C No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported . Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast , prostate , colon , or lung ( 12 - 14 ) . The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results ( 12 , 15 , 16 ) . Vitamin E Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease . A r and omized , controlled trial ( RCT ) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer ( 14 ) . Because prostate cancer was not a primary end point of the trial and the trial had other limitations , further evidence is needed to confirm this finding . Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate , lung , or breast cancer ( 5 ) . One study suggested that vitamin E protects against colon cancer , but the influence of confounding variables can not be fully excluded ( 17 ) . Among primary prevention trials , two good- quality trials ( 14 , 18 ) and one fair- quality trial ( 19 ) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease ( 20 ) . Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events ( 4 ) . Some prospect i ve cohort studies have suggested a significant benefit , but the results are mixed and the influence of confounding variables can not be excluded ( 4 ) . -Carotene A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung , prostate , colon , breast , or nonmelanoma skin cancer ( 14 , 21 - 25 ) . -Carotene supplements were associated with an increased risk for lung cancer among smokers , especially heavy smokers , in two RCTs ( 14 , 25 ) . Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation ( 14 , 21 , 22 , 26 - 28 ) . Antioxidant Vitamin Combinations Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results . A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants : vitamin E , vitamin C , and beta-carotene ( 29 ) . Some studies have suggested an adverse effect of antioxidant combinations on cancer , but the results may have been confounded by the inclusion of beta-carotene ( 5 ) . Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease ( 13 , 30 , 31 ) , but other studies , including well- design ed RCTs , have shown no benefit ( 29 , 32 , 33 ) . One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements  ( 34 ) . Multiple Vitamin Combinations The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements ( 35 ) . In these analyses , folic acid supplementation was associated with significantly decreased risk for colon cancer , but the protective effect requires confirmation in prospect i ve trials . There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease . Among cohort studies , one good- quality study reported a statistically significant reduction in coronary events ( 36 ) , two good- quality studies reported no statistically significant effect on mortality ( 16 , 37 ) , and one • The recommended level for serum 25-hydroxyvitamin D ( 25(OH)D ) in infants , children , adolescents and during pregnancy and lactation is ≥ 50 nmol/L. This level may need to be 10 - 20 nmol/L higher at the end of summer to maintain levels ≥ 50 nmol/L over winter and spring . • Sunlight is the most important source of vitamin D. The US recommended dietary allowance for vitamin D is 600 IU daily in children aged over 12 months and during pregnancy and lactation , assuming minimal sun exposure . • Risk factors for low vitamin D are : lack of skin exposure to sunlight , dark skin , southerly latitude , conditions affecting vitamin D metabolism and storage ( including obesity ) and , for infants , being born to a mother with low vitamin D and exclusive breastfeeding combined with at least one other risk factor . • Targeted measurement of 25(OH)D levels is recommended for infants , children and adolescents with at least one risk factor for low vitamin D and for pregnant women with at least one risk factor for low vitamin D at the first antenatal visit . • Vitamin D deficiency can be treated with daily low-dose vitamin D supplements , although barriers to adherence have been identified . High-dose intermittent vitamin D can be used in children and adolescents . Treatment should be paired with health education and advice about sensible sun exposure . Infants at risk of low vitamin D should be supplemented with 400 IU vitamin D₃ daily for at least the first year of life . • There is increasing evidence of an association between low vitamin D and a range of non-bone health outcomes , however there is a lack of data from robust r and omised controlled trials of vitamin D supplementation STUDY OBJECTIVE --The aim was to assess the association of  neural tube defects  with periconceptional vitamin supplementation . DESIGN --This was a matched , population based case-control study . SETTING --Western Australia , 1982 - 1984 . PARTICIPANTS --Mothers of 77 cases ( 93 % of those eligible ) with isolated neural tube defects , mothers of 77 matched control infants with defects other than neural tube defects ( control group I ) , and mothers of 154 liveborn , matched , control infants with no birth defects ( control group II ) participated in the study . MEASUREMENTS AND MAIN RESULTS --Information was collected by interview and self administered question naire .  Crude and adjusted odds ratios ( and their 95 % confidence intervals ) showed a small but non-significant protective effect of folate supplementation in comparisons with both control groups . The adjusted ratios for the three months before pregnancy were 0.69 ( 0.06 , 8.53 ) with control group I , and 0.11 ( 0.01 , 1.33 ) with control group II . In the first six weeks of pregnancy , the adjusted odds ratios were 0.70 ( 0.32 , 1.52 ) with control group I and 0.74 ( 0.29 , 1.88 ) with control group II . The odds ratios for  vitamin supplementation of any kind were all very close to or greater than one , and all confidence intervals embraced unity . CONCLUSIONS --These data do not provide evidence of an association between periconceptional vitamin supplementation and neural tube defects , although a protective effect of folate supplementation can not be excluded with confidence , due to the low power of the study . Of three other observational studies of vitamins and neural tube defects , two have shown an association . While further studies of this kind may be of value , evidence must now be sought from r and omised controlled trials INTRODUCTION There is emerging evidence on the widespread tissue effects of vitamin D. AIMS To formulate a position statement on the role of vitamin D in postmenopausal women . MATERIAL S AND METHODS Literature review and consensus of expert opinion . RESULTS AND CONCLUSIONS Epidemiological and prospect i ve studies have related vitamin D deficiency with not only osteoporosis but also cardiovascular disease , diabetes , cancer , infections and neurodegenerative disease . However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospect i ve studies are lacking . The major natural source of vitamin D is cutaneous synthesis through exposure to sunlight with a small amount from the diet in animal-based foods such as fatty fish , eggs and milk . Vitamin D status is determined by measuring serum 25-hydroxyvitamin D [ 25(OH)D ] levels . Optimal serum 25(OH)D levels are in the region of 30 - 90 ng/mL ( 75 - 225 nmol/L ) though there is no international consensus . Levels vary according to time of the year ( lower in the winter ) , latitude , altitude , air pollution , skin pigmentation , use of sunscreens and clothing coverage . Risk factors for low serum 25(OH)D levels include : obesity , malabsorption syndromes , medication use ( e.g. anticonvulsants , antiretrovirals ) , skin aging , low sun exposure and those in residential care . Fortified foods do not necessarily provide sufficient amounts of vitamin D. Regular sunlight exposure ( without sunscreens ) for 15 min , 3 - 4 times a week , in the middle of the day in summer generate healthy levels . The recommended daily allowance is 600 IU/day increasing to 800 IU/day in those aged 71 years and older . Supplementation can be undertaken with either vitamin D2 ( ergocalciferol ) or vitamin D3 ( cholecalciferol ) with monitoring depending on the dose used and the presence of concomitant medical conditions such as renal disease Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849 Background Calcium ( Ca ) is an essential nutrient for the human body . Despite lively research , there is uncertainty about Ca requirements in terms of desirable health outcomes including an upper intake level above which the potential for harm increases . Objectives The aim was to conduct a review to up date requirements and desirable or harmful health effects of Ca on the current scientific evidence . Methods We search ed Medline and Swemed from January 2000 to December 2011 and included all systematic review s that reported Ca supplementation or usual Ca intake on health outcomes . Meta-analyses , r and omized clinical trials and cohort studies were included in the second search between May 2009 and March 2011 and an additional search covering studies till the end of 2011 . This review concentrated on studies reporting independent effects of Ca , although a few recent trials report sole effects of Ca on health outcomes , most trials use Ca in combination with vitamin D vs. placebo . Results In total , we review ed 38 studies addressing the effects of Ca on bone , pregnancy-related outcomes , cancers , cardiovascular outcomes , obesity , and mortality .  There was a lot of heterogeneity in the study protocol s , which made it difficult to draw any strong conclusions . According to the literature , high Ca intake seems to have a small positive effect on bone mineral content ( BMC ) or bone mineral density ( BMD ) in children and postmenopausal women . We did not find any consistent evidence on the effects of Ca on bone health in premenopausal women or men . Also , the evidence that Ca supplementation reduces fracture incidence is scarce and inconsistent . Maternal diet may influence the peak bone mass of offspring but more studies are required . There was no overall effect of Ca intake on cancers . Ca was associated with a decreased risk of breast cancer and a slightly increased risk of prostate cancer in two of the three studies . No associations were found with other cancers . We found no consistent association between cardiovascular outcomes and  Ca  intake except for blood pressure . A small decrease of 2–4 mmHg in systolic blood pressure was found in pregnant and in hypertensive subjects with Ca supplementation . Review ed studies did not show consistent evidence relating Ca intake to either mortality or obesity . Conclusion Based on this evidence , there is no need to change the Nordic recommendations for Ca intake . However , due to heterogeneity in the studies it is difficult to interpret the results and provide single summary statement BACKGROUND Supplementation of vitamin A in children aged 6 - 59 months improves child survival and is implemented as global policy . Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results . We aim ed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days ( 6 months ) . METHODS We did an individually r and omised , double-blind , placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania . Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam . In Kilombero , Ulanga , and Kilosa districts , women were seen at home as part of the health and demographic surveillance system . Newborn infants were eligible for r and omisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months . We r and omly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth . Infants were r and omly assigned in blocks of 20 , and investigators , participants ' families , and data analysis teams were masked to treatment assignment . We assessed infants on day 1 and day 3 after dosing , as well as at 1 , 3 , 6 , and 12 months after birth . The primary endpoint was mortality at 6 months , assessed by field interviews . The primary analysis included only children who were not lost to follow-up . This trial is registered with the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , number ACTRN12610000636055 . FINDINGS Between Aug 26 , 2010 , and March 3 , 2013 , 31,999 newborn babies were r and omly assigned to receive vitamin A ( n=15,995 ) or placebo ( n=16,004 ; 15,428 and 15,464 included in analysis of mortality at 6 months , respectively ) . We did not find any evidence for a beneficial effect of vitamin A  supplementation on mortality in infants at 6 months ( 26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group ; risk ratio 1·10 , 95 % CI 0·95 - 1·26 ; p=0·193 ) . There was no evidence of a differential effect for vitamin A supplementation on mortality by sex ; risk ratio for mortality at 6 months for boys was 1·08 ( 0·90 - 1·29 ) and for girls was 1·12 ( 0·91 - 1·39 ) . There was also no evidence of adverse effects of supplementation within 3 days of dosing . INTERPRETATION Neonatal vitamin A supplementation did not result in any immediate adverse events , but had no beneficial effect on survival in infants in Tanzania . These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation . FUNDING Bill & Melinda Gates Foundation to WHO This study was conducted to determine if vitamin D supplementation is required to prevent rickets in breast-fed infants . Breast-feeding rates are increasing , and there are concerns about whether the vitamin D content of breast milk is sufficient . There are a few treatment trials of vitamin D supplementation in breast-fed infants ; these were conducted in northern climates . The authors therefore performed a prospect i ve clinical trial comparing vitamin D supplementation with placebo as control in southern Louisiana . Blood sample s and question naires were collected at birth , 2 , 4 , and 6 months of age . There were no cases of rickets observed , and no differences in alkaline phosphatase levels between groups . Thus , there was no evidence that vitamin D supplementation reduced rickets risk in the authors ’ study population . This suggests that the current recommendations for universal vitamin D supplementation of breast-fed infants throughout the United States may need to be revised AIMS Oesophageal cancer is an aggressive disease and the optimal therapy for patients with resectable tumours remains unclear . A systematic review and companion practice guideline were published in 2004 ; however , new evidence has become available since the publication of the original report . An up date of the literature search and a revision of the recommendations were undertaken to incorporate the new data . The following research question was addressed : should patients with resectable oesophageal cancer receive preoperative or postoperative therapy together with surgery ? The outcomes of interest were survival , adverse effects and quality of life . MATERIAL S AND METHODS The literature search of the original systematic review was up date d to April 2007 . MEDLINE , EMBASE , Cochrane Library and abstract s from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were search ed for reports of r and omised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy . After the completion of the draft systematic review and practice guideline , the report was distributed through a mailed survey to 133 health care providers in Ontario for review and feedback . RESULTS The up date d literature search yielded eight new r and omised controlled trial reports and seven new meta- analysis reports for consideration , together with the evidence review ed in the original review publication . Of the 31 practitioners who responded to the mailed survey , 80 % agreed with the draft recommendations as stated , 83 % agreed that the report should be approved as a practice guideline and 86 % indicated that they would probably use the guideline in their own practice . CONCLUSIONS Preoperative cisplatin-based chemotherapy plus radiotherapy is recommended as the preferred modality for the management of surgically resectable patients with oesophageal cancer .  Preoperative cisplatin-based chemotherapy alone is an alternative choice for the management of these patients Summary On September 29 , 2011 , acknowledged experts in the field of vitamin D , mainly European , were brought together in order to discuss the recent scientific advances in relation to vitamin D : the current requirements and associations with various health outcomes . In this article , the discussion s result ing from the meeting are summarized . Introduction Several groups at risk for developing vitamin D insufficiency have been identified . Accordingly , review s indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l . In addition to the role of vitamin D in bone health , recent studies suggest that it may play a pivotal role in other systems , e.g. , the cardiovascular system , pancreas , muscle , immune system and brain . Most evidence , however , is obtained from observational studies and yet inconclusive . Methods To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes , a workshop entitled “ Vitamin D Expert Meeting : Do we get enough ? ” , was organized . Results Despite low vitamin D levels worldwide , consensus on the definition of deficiency is not yet reached . In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects , r and omized controlled trials in these fields are warranted . The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation , in most studies co-administered with calcium , reduces fracture risk in the senior population . Conclusion To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 μg ( 800 IU ) , which is best achieved with a supplement BACKGROUND Development of this guideline was undertaken by the Exercise for People with Cancer Guideline Development Group , a group organized by Cancer Care Ontario 's Program in Evidence -Based Care ( pebc ) . The purpose of the guideline was to provide guidance for clinicians with respect to exercise for patients living with cancer , focusing on the benefits of specific types of exercise , recommendations about screening requirements for new referrals , and safety concerns . METHODS Consistent with the pebc 's st and ardized approach , a systematic search was conducted for existing guidelines , and systematic literature search es were performed in medline and embase for both systematic review s and primary literature . Content and methodology experts performed an internal review , which was followed by an external review by targeted experts and intended users . RESULTS The search identified three guidelines , eighteen systematic review s , and twenty-nine r and omized controlled trials with relevance to the topic . The present guideline provides recommendations for the duration , frequency , and intensity of exercise appropriate for people living with cancer . It also provides recommendations for pre-exercise assessment , safety concerns , and delivery models . CONCLUSIONS There is sufficient evidence to show that exercise provides benefits in quality of life and muscular and aerobic fitness for people with cancer both during and after treatment , and that it does not cause harm . The present guideline is intended to support the Canadian Society for Exercise Physiology 's Canadian physical activity guidelines . The recommendations are intended for clinicians and institutions treating cancer patients in Ontario , and for policymakers and program planners involved in the delivery of exercise programs for cancer patients Severe vitamin D deficiency in mothers and their breastfed infants is a significant health problem in the Middle East . Supplementation of the breastfed infant alone with the recommended dose of vitamin D may be insufficient in high-risk population . We investigated the effect of combined maternal and infant vitamin D supplementation on vitamin D status of the breastfed infant . We examined also the effect of supplementation on vitamin D antirachitic activity of breast milk in a subset of mothers . Healthy breastfeeding mothers ( n = 90 ) were r and omly assigned to 2000 IU daily ( group 1 ) or 60,000 IU monthly ( group 2 ) of vitamin D(2 ) , and all their infants ( n = 92 ) received 400 IU daily of vitamin D(2 ) for 3 months . Most infants had vitamin D deficiency - 25-hydroxyvitamin D [ 25(OH)D ] < or= 37.5 nmol L(-1)- at study entry .  Serum 25(OH)D concentrations at 3 months increased significantly from baseline in infants of mothers in group 1 ( 13.9 + /- 8.6 vs. 49.6 + /- 18.5 nmol L(-1 ) , P < 0.0001 ) and group 2 ( 13.7 + /- 12.1 vs. 44.6 + /- 15.0 nmol L(-1 ) , P < 0.0001 ) . Maternal and infant serum 25(OH)D concentrations correlated positively at baseline ( r = 0.36 , P = 0.01 ) and 3 months ( r = 0.46 , P = 0.002 ) . Milk antirachitic activity increased from undetectable ( < 20 IU L(-1 ) ) to a median of 50.9 IU L(-1 ) . In conclusion , combined maternal and infant vitamin D supplementation was associated with a threefold increase in infants ' serum 25(OH)D concentrations and a 64 % reduction in the prevalence of vitamin D deficiency without causing hypervitaminosis Background Prevalence of  allergic diseases in infants , whose parents and siblings do not have allergy , is approximately 10 % and reaches 20–30 % in those with an allergic first-degree relative . Intestinal microbiota may modulate immunologic and inflammatory systemic responses and , thus , influence development of sensitization and allergy . Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention . Objective The World Allergy Organization ( WAO ) convened a guideline panel to develop evidence -based recommendations about the use of probiotics in the prevention of allergy . Methods We identified the most relevant clinical questions and performed a systematic review of r and omized controlled trials of probiotics for the prevention of allergy . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . We search ed for and review ed the evidence about health effects , patient values and preferences , and re source use ( up to November 2014 ) . We followed the GRADE evidence -to-decision framework to develop recommendations . Results Currently available evidence does not indicate that probiotic supplementation  reduces the risk of developing allergy in children . However , considering all critical outcomes in this context , the WAO guideline panel determined that there is a likely net benefit from using probiotics result ing primarily from prevention of eczema . The WAO guideline panel suggests : a ) using probiotics in pregnant women at high risk for having an allergic child ; b ) using probiotics in women who breastfeed infants at high risk of developing allergy ; and c ) using probiotics in infants at high risk of developing allergy . All recommendations are conditional and supported by very low quality evidence . Conclusions WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents , clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding , and whether to give them to infants Summary Whether infant vitamin D supplementation may have long-term bone benefits is unclear . In this study , breastfed infants who received vitamin dosages greater than 400 IU/day did not have higher bone mineralization at 3 years . This study provides important data to inform pediatric public health recommendations for vitamin D. Introduction North American health agencies recommend breastfed infants should be supplemented with 400 IU of vitamin D/day to support bone health . Few studies examined the long-term benefits of early life vitamin D supplementation on bone mineralization . The objective of this study was to determine if a dose-response relationship exists between infant vitamin D supplementation , vitamin D status , and bone outcomes at 3 years of age . Methods This was a double-blind r and omized trial of 132 , 1-month-old healthy , breastfed infants from Montréal , Canada , between 2007 and 2010 . In this longitudinal analysis , 87 infants ( 66 % ) returned for follow-up at 3 years of age , between 2010 and 2013 . At 1 month of age , participants were r and omly assigned to receive oral cholecalciferol ( vitamin D3 ) supplements of 400 , 800 , 1200 , or 1600 IU/day until 12 months of age . Lumbar spine vertebrae 1–4 ( LS ) bone mineral density ( BMD ) , LS and whole body bone mineral content ( BMC ) , and mineral accretion were measured by dual-energy x-ray absorptiometry at 3 years . Results At follow-up , the treatment groups were similar in terms of diet , sun exposure , and demographics . There were no significant differences among the groups in LS or whole body BMC , BMD , or accretion . Although , 25(OH)D concentrations were not different among the groups , higher doses ( 1200 and 1600 IU/day ) achieved higher 25(OH)D area under the curve from 1 to 36 months vs. 400 IU/day . Conclusions This is the first longitudinal follow-up of an infant vitamin D dose-response study which examines bone mineralization at 3 years of age . Dosages higher than 400 IU/day do not appear to provide additional benefits to the bone at follow-up . Larger studies with more ethnically diverse groups are needed to confirm these results It has been recommended to supplement formulas for preterm infants with n-3 and n-6 long-chain polyunsaturated fatty acids ( LCP ) to improve growth , visual acuity , and neurodevelopmental performance . However , large amounts of LCP may increase lipid peroxidation and oxidative stress in preterm infants . We investigated if , under high supplementation of natural tocopherols , LCP addition to formula can be performed safely without causing tocopherol depletion in cell membranes . Thirty-one healthy preterm infants with gestational ages from 28 to 32 weeks were evaluated in a prospect i ve , r and omized study from birth to day 42 . Nine infants received an n-3 and n-6 LCP-enriched formula ( A ) , eleven infants a st and ard formula ( B ) , and eleven infants breast milk ( control group ) . Alpha- and gamma-tocopherol extracts were added to both formulas , amounting to five times the value in breast milk ( 2.3 mg/dL in both formulas versus 0.45 mg/dL in breast milk ) . Erythrocyte arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) in the phosphatidylethanolamine fraction were similar in the three groups over the study period , whereas a significant reduction of erythrocyte AA and DHA could be detected in the phosphatidylcholine fraction in all three groups from day 14 onwards , when compared to respective cord blood values , with lowest values in the st and ard formula group . Amazingly , levels of alpha- and gamma-tocopherol were higher in plasma , erythrocytes , platelets , monocytes , and polymorphonuclear leukocytes with LCP supplementation as compared to st and ard formula and breast milk from day 7 onwards , whereas in buccal mucosal cells , this was not the case until day 42 . Gammatocopherol uptake in the LCP-supplemented group was also significantly higher in all cell fractions studied from day 7 onwards . We therefore hypothesize that the LCP supplementation used in formula A improves tocopherol solubility and stability in biological membranes . Under high-dose vitamin E addition to n-3 and n-6 LCP-supplemented formula , no evidence for tocopherol depletion and furthermore , high accumulation of tocopherols , can be detected in healthy preterm infants CONTEXT AND OBJECTIVES The European Association of Urology Guideline Group for renal cell carcinoma ( RCC ) has prepared these guidelines to help clinicians assess the current evidence -based management of RCC and to incorporate the present recommendations into daily clinical practice . EVIDENCE ACQUISITION The recommendations provided in the current up date d guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials . EVIDENCE SYNTHESIS A number of recent prospect i ve r and omised studies concerning RCC are now available with a high level of evidence , whereas earlier publications were based on retrospective analyses , including some larger multicentre validation studies , meta-analyses , and well- design ed controlled studies . CONCLUSIONS These guidelines contain information for the treatment of an individual patient according to a current st and ardised general approach . Up date d recommendations concerning diagnosis , treatment , and follow-up can improve the clinical h and ling of patients with RCC Purpose This paper visualizes the available data on vitamin D status on a global map , examines the existing heterogeneities in vitamin D status and identifies research gaps . Methods A graphical illustration of global vitamin D status was developed based on a systematic review of the worldwide literature published between 1990 and 2011 . Studies were eligible if they included sample s of r and omly selected males and females from the general population and assessed  circulating 25-hydroxyvitamin D [ 25(OH)D ] levels .  Two different age categories were selected : children and adolescents ( 1–18 years ) and adults ( > 18 years ) . Studies were chosen to represent a country based on a hierarchical set of criteria . Results In total , 200 studies from 46 countries met the inclusion criteria , most coming from Europe . Forty-two of these studies ( 21 % ) were classified as representative . In children , gaps in data were identified in large parts of Africa , Central and South America , Europe , and most of the Asia/Pacific region . In adults , there was lack of information in Central America , much of South America and Africa . Large regions were identified for which the mean 25(OH)D levels were below 50 nmol/L. Conclusions This study provides an overview of 25(OH)D levels around the globe . It reveals large gaps in information in children and adolescents and smaller but important gaps in adults . In view of the importance of vitamin D to musculoskeletal growth , development , and preservation , and of its potential importance in other tissues , we strongly encourage new research to clearly define 25(OH)D status around the world One of the main focuses of lifestyle modification for the prevention of osteoporosis and osteoporotic fractures  in Japan is improvement in dietary calcium intake . However , virtually no r and omized controlled trial to assess the preventive effects of administration of calcium on the risk of fractures has been conducted in Japan . In this study , we review ed all the scientific papers currently available from medical literature data bases to propose evidence -based recommendations on the preventive procedures for osteoporosis . The result of the present systematic review gives the evidence showing that calcium supplementation or optimal dietary calcium intake increases bone density in childhood and adolescence and reduces the risk of fracture due to osteoporosis in the elderly people regardless of the gender . The evidence also supports the current health policy guiding the elderly to increase their dietary calcium intake in daily life
They do not provide any additional evidence that larger , more generous amounts of daily vitamin D beyond the customary recommended 400 IU daily dose , affect any significant outcome .
Larger amounts may lead to serum 25 hydroxy vitamin D concentrations that have been reported to be potentially associated with adverse effects .
Summary There are still many unanswered questions left , in particular whether or not more ‘ generous ’ amounts of vitamin D in infancy may improve long-term health outcomes such as prevention of osteoporosis , allergies , or cancer
Purpose of review New evidence for recommendations for vitamin D supplementation in healthy infants based upon recent literature .