Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Effect of vitamin D supplementation on inflammation: protocol for a systematic review Vitamin D supplementation in the treatment of atopic dermatitis: a clinical trial study. Randomized trial of vitamin D supplementation for winter-related atopic dermatitis in children. A systematic review protocol examining the effect of vitamin D supplementation on endothelial function A randomized controlled double-blind investigation of the effects of vitamin D dietary supplementation in subjects with atopic dermatitis. Sources of evidence for systematic reviews of interventions in diabetes. The vitamin E debate: implications for ongoing trials of pre‐eclampsia prevention Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis Maternal vitamin D supplementation during pregnancy The Effects of Oral Vitamin D Supplement on Atopic Dermatitis: A Clinical Trial with Staphylococcus aureus Colonization Determination. Issues related to the conduct of systematic reviews: a focus on the nutrition field. Herbal and dietary therapies for primary and secondary dysmenorrhoea. Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials. 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) Comparative trial of moisturizer containing licochalcone A vs. hydrocortisone lotion in the treatment of childhood atopic dermatitis: a pilot study. Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol Antipruritic effects of the probiotic strain LKM512 in adults with atopic dermatitis. Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations. Probiotic Supplement Reduces Atopic Dermatitis in Preschool Children No effect of mobile phone-like RF exposure on patients with atopic dermatitis. Increased food allergy and vitamin D: randomized, double-blind, placebo-controlled trial.
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 Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 BACKGROUND The role of vitamin D in Atopic Dermatitis ( AD ) is ambiguous and clinical trials are needed to assess the role of vitamin D in the treatment of AD . The aim of this clinical trial study to evaluate the effect of vitamin D supplementation on patients with AD . MATERIAL AND METHODS sixty AD patients were included in a r and omized , double-blind , placebo-controlled trial study . They were r and omly divided into two groups and treated for 60 days : group vitamin D ( n=30 ) , and placebo group ( n=30 ) . The two groups were as follows : Group D , 1600 IU cholecalciferol ( vitamin D ) and second group placebo . The severity of AD was evaluated based on SCORAD ( Scoring Atopic Dermatitis ) and TIS ( Three Item Severity score ) value by the same trained physician before and after the trial . RESULTS According to SCORAD and TIS value index in the vitamin D group showed significant improvement in patients with mild , moderate and severe AD ( P<0.05 ) and in patients who the intake placebo , this improvement did n't showed ( P>0.05 ) . CONCLUSION Results mention that supplementation with oral vitamin D dramatically improved disease severity in AD patients BACKGROUND Epidemiologic and pre clinical data , and a small r and omized trial in Boston , suggest that vitamin D supplementation may improve winter-related atopic dermatitis ( AD ) . OBJECTIVE To determine the effect of vitamin D supplementation on winter-related AD . METHODS We performed a r and omized , double-blind , placebo-controlled trial of Mongolian children with winter-related AD ( clinical trials.gov identifier : NCT00879424 ) . Baseline eligibility included age 2 to 17 years , AD score 10 to 72 using the Eczema Area and Severity Index ( EASI ) , and winter-related AD ( eg , history of AD worsening during the fall-to-winter transition ) . Subjects were enrolled in Ulaanbaatar during winter and r and omly assigned to oral cholecalciferol ( 1000 IU/day ) versus placebo for 1 month . All children and parents received emollient and patient education about AD and basic skin care . The main outcomes were changes in EASI score and in Investigator 's Global Assessment . RESULTS The 107 enrolled children had a mean age of 9 years ( SD 5 ) , and 59 % were male . Their median age of AD onset was 3 months ( interquartile range 2 months to 1 year ) and mean EASI score at baseline 21 ( SD 9 ) . One-month follow-up data were available for 104 ( 97 % ) children . Compared with placebo , vitamin D supplementation for 1 month produced a clinical ly and statistically significant improvement in EASI score ( adjusted mean change : -6.5 vs -3.3 , respectively ; P = .04 ) . Moreover , change in Investigator 's Global Assessment favored vitamin D over placebo ( P = .03 ) . There were no adverse effects in either group . CONCLUSION Vitamin D supplementation improved winter-related AD among Mongolian children , a population likely to have vitamin D deficiency in winter Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 BACKGROUND Subjects with atopic dermatitis ( AD ) have defects in antimicrobial peptide ( AMP ) production possibly contributing to an increased risk of infections . In laboratory models , vitamin D can alter innate immunity by increasing AMP production . OBJECTIVE To determine if AD severity correlates with baseline vitamin D levels , and to test whether supplementation with oral vitamin D alters AMP production in AD skin . METHODS This was a multi-centre , placebo-controlled , double-blind study in 30 subjects with AD , 30 non-atopic subjects , and 16 subjects with psoriasis . Subjects were r and omized to receive either 4000 IU of cholecalciferol or placebo for 21 days . At baseline and day 21 , levels of 25-hydroxyvitamin D ( 25OHD ) , cathelicidin , HBD-3 , IL-13 , and Eczema Area and Severity Index ( EASI ) and Rajka-Langel and scores were obtained . RESULTS At baseline , 20 % of AD subjects had serum 25OHD below 20 ng/mL. Low serum 25OHD correlated with increased Fitzpatrick Skin Type and elevated BMI , but not AD severity . After 21 days of oral cholecalciferol , mean serum 25OHD increased , but there was no significant change in skin cathelicidin , HBD-3 , IL-13 or EASI scores . CONCLUSIONS This study illustrated that darker skin types and elevated BMI are important risk factors for vitamin D deficiency in subjects with AD , and highlighted the possibility that seasonality and locale may be potent contributors to cathelicidin induction through their effect on steady state 25OHD levels . Given the molecular links between vitamin D and immune function , further study of vitamin D supplementation in subjects with AD is warranted AIMS To analyse the effect on systematic review s in diabetes interventions of including only trials that are indexed in medline , and to assess the impact of adding trials from other data bases and the grey literature . METHODS All systematic review s of diabetes interventions which included a meta- analysis of r and omized controlled trials , and were published since 1996 , were selected . The impact on the meta- analysis of including only those trials indexed in medline , and the effect of then adding trials from other sources , was assessed . Where possible this was measured quantitatively , by redoing the meta- analysis , otherwise a qualitative estimate was made . RESULTS Forty-four systematic review s met our inclusion criteria . There were 120 articles reporting trial data which were not indexed in medline . These came from 52 % of the review s. In 34 % of the review s , basing a meta- analysis on a search of only medline would miss trials that could affect the result . Sources of non- medline data which had the biggest effect on the meta-analyses were journal articles from central and embase ( mainly in Diabetes , Nutrition and Metabolism ) and unpublished data ( mainly from industry ) . The exceptions were journal articles on herbal medicine , mostly indexed in Chinese language data bases . CONCLUSIONS A search of only the medline data base is insufficient for systematic review s of diabetes , because in about 34 % of review s the missed trials could affect the results of the meta- analysis . It is recommended that central ( on the Cochrane Library ) also be search ed . Scanning meeting abstract s , and seeking unpublished data are also recommended if the intervention has only recently been introduced A potential role for oxidative stress in the pathophysiology of pre-eclampsia was first proposed by Stark in 1993 . Synthesis of free radicals by a dysfunctional placenta , and possibly by maternal leucocytes and endothelium , seems to play a central role in this association . Free radicals , through oxidative damage of biomolecules and lipid peroxidation , can initiate maternal vascular endothelial dysfunction and leucocyte activation . A comprehensive review of the role of oxidative stress in pre-eclampsia has been recently published . Antioxidants such as vitamin C and vitamin E have been proposed as potential therapeutic or prophylactic treatment for pre-eclampsia .  This suggestion was supported by the observation that women with pre-eclampsia have lower plasma vitamin C concentrations . Both in vitro and in vivo studies suggest that there is an interaction between vitamin C and vitamin E , with vitamin C possibly exerting a ‘ redox ’ recycling effect on oxidised vitamin E within lipoproteins and membranes . The vitamin C to E ratio may be of central importance in protecting against the damaging effects of reactive oxygen species . To date , three placebo-controlled trials have assessed the effect of vitamins C and E on  pre-eclampsia .  Although no benefits were found when supplementation was given to women with diagnosed pre-eclampsia , a combination of 1 g/day of vitamin C and 400 IU/day of vitamin E given as prophylaxis to high risk women demonstrated a reduction in the risk of pre-eclampsia from 17 % in the control group to 8 % in the active treatment group . In this same double-masked r and omised controlled trial , women receiving vitamins C and E showed a reduction in biological markers of oxidative stress . Since this report , a number of multicentre r and omised clinical trials have been initiated both in low risk and in high risk population s , with the goal of testing the hypothesis that antioxidants reduce the incidence of pre-eclampsia ( Table 1 ) . In the UK , a multicentre trial is currently recruiting pregnant women with diabetes . The NIH has funded two antioxidant trials , one that is under way in Brazil and the second that is being conducted among nulliparous women in the NICHD Maternal Fetal Medicine Network . The International Trial of Antioxidants for the Prevention of Preeclampsia ( INTAPP ) , funded by the Canadian Institutes of Health Research , is enrolling nulliparas without additional risk factors ( Stratum I ) and multiparas and nulliparas with clinical risk factors for gestational hypertension ( Stratum II ) . Collectively , these trials should provide an answer to the question of the role of antioxidants in the prevention of pre-eclampsia and its related disorders . Recently , a meta- analysis of 19 clinical trials of  vitamin E  , for the most part secondary prevention trials , conducted in elderly population s at increased risk for a number of diseases ranging from lung or gastrointestinal cancer to cardiovascular disease , Alzheimer ’s disease or cataract , was published in the Annals of Internal Medicine . The authors of the meta- analysis concluded that high doses of vitamin E may be associated with an increased risk of all-cause mortality . What are the implication s of this meta- analysis for the ongoing pre-eclampsia prevention trials ? It is the responsibility of the Principal Investigators , the Steering Committees and Data Safety Monitoring Committees ( DSMC ) of ongoing clinical trials to take into account information generated from studies that arise in the course of their trial . They must assess the quality of the new evidence and determine how this information influences the balance of risks to benefits of the ongoing trials . In the case of the Canadian trial , both the DSMC and the hospital Ethics Committee have review ed the information and made their recommendations to the trial Steering Committee . The following is our evaluation of the quality of the evidence of the meta- analysis by Miller et al. , and its implication s for ongoing clinical trials of antioxidants in the prevention of pre-eclampsia Abstract Background : Atopic dermatitis is a chronically relapsing , highly pruritic and inflammatory skin disease . This study was done to assess the effects of vitamins D and E supplementation on the clinical manifestation of atopic dermatitis . Methods : Forty-five atopic dermatitis patients were included in a r and omized , double-blind , placebo-controlled trial . They were r and omly divided into four groups and treated for 60 days : group P ( n = 11 ) , vitamins D and E placebos ; group D ( n = 12 ) , 1600 IU vitamin D3 plus vitamin E placebo ; group E ( n = 11 ) , 600 IU synthetic all-rac-α-tocopherol plus vitamin D placebo ; and group DE ( n = 11 ) , 1600 IU vitamin D3 plus 600 IU synthetic all-rac-α-tocopherol .  Serum 25(OH ) vitamin D and plasma α-tocopherol were determined before and after the trial . The clinical improvement was evaluated with SCORing Atopic Dermatitis ( SCORAD ) . Data were analyzed by analysis of variance ( ANOVA ) and Kruskal-Wallis tests . Results : SCORAD was reduced after 60 days in groups D , E and DE by 34.8 % , 35.7 % and 64.3 % , respectively ( p = 0.004 ) . Objective SCORAD also showed significant improvement . There was a positive correlation between SCORAD and intensity , objective , subjective and extent ( p < 0.001 ) . We found a significant negative association between plasma α-tocopherol and SCORAD , intensity , objective and extent ( p = 0.02 ) . Conclusion : This study supports the contributing and beneficial effects of vitamins D and E in the treatment of atopic dermatitis Introduction Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring . A wealth of observational studies have reported on both obstetric outcomes and complications , including pre-eclampsia , gestational diabetes , mode and timing of delivery . Many foetal and childhood outcomes are also linked to vitamin D status , including measures of foetal size , body composition and skeletal mineralization , in addition to later childhood outcomes , such as asthma . Sources of data Synthesis of systematic and narrative review s. Areas of agreement and controversy The findings are generally inconsistent in most areas , and , at present , there is a lack of data from high- quality intervention studies to confirm a causal role for vitamin D in these outcomes . In most areas , the evidence tends towards maternal vitamin D being of overall benefit , but often does not reach statistical significance in meta-analyses . Growing points and areas timely for developing research The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia ; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily . High- quality r and omized placebo-controlled trials , such as the UK-based MAVIDOS trial , will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes BACKGROUND An increase in Staphylococcus aureus skin colonization in atopic dermatitis patients result ed from the reduction of cathelicidin production in these patients . Recently , an in vivo study demonstrated that vitamin D could stimulate cathelicidin production . Oral supplements of vitamin D might be beneficial in atopic dermatitis . OBJECTIVE To determine the effects of oral vitamin D supplements on clinical impact including Staphylococcus aureus skin colonization evaluation in atopic dermatitis patients . MATERIAL AND METHOD Twenty-four atopic dermatitis patients were included in this double-blind , placebo-controlled study . They were r and omly assigned into 2 groups for oral 2,000 IUs/day of vitamin D , supplement and placebo . The lesional swab culture for S. aureus was done at week 0 , 2 and 4 . Clinical outcomes were assessed by SCORAD score , mexameter for erythema index and konometer for conductance were done at week 0 , 2 and 4 . Serum vitamin D levels were also determined at week 0 and 4 . RESULTS Twenty patients completed the protocol .  S. aureus skin colonization , SCORAD score and erythema index were significantly reduced from baseline to week 4for vitamin D treated group comparing with placebo ( p = 0.022 , 0.028 and 0.014 , respectively ) . There was an inverse correlation between serum vitamin D levels with S. aureus skin colonization and SCORAD score ( r = -1.0 , p < 0.001 ) . CONCLUSION Oral vitamin D supplement could reduce skin colonization of S. aureus and demonstrated the clinical improvement of patients with atopic dermatitis Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition Background Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological complaint . Common treatment for dysmenorrhoea is medical therapy such as nonsteroidal anti-inflammatories ( NSAIDs ) or oral contraceptive pills ( OCPs ) which both work by reducing myometrial activity ( contractions of the uterus ) . The efficacy of conventional treatments such as nonsteroidals is considerable , however the failure rate is still often 20 - 25 % . Many consumers are now seeking alternatives to conventional medicine and research into the menstrual cycle suggests that nutritional intake and metabolism may play an important role in the cause and treatment of menstrual disorders . Herbal and dietary therapies number among the more popular complementary medicines yet there is a lack of taxonomy to assist in classifying them . In the US , herbs and other phytomedicinal products ( medicine from plants ) have been legally classified as dietary supplements since 1994 . Included in this category are vitamins , minerals , herbs or other botanicals , amino acids and other dietary substances . For the purpose of this review we use the wider term herbal and dietary therapies to include the assorted herbal or dietary treatments that are classified in the US as supplements and also the phytomedicines that may be classified as drugs in the European Union . Objectives To determine the efficacy and safety of  herbal and dietary therapies  for the treatment of  primary and secondary dysmenorrhoea  when compared to each other , placebo , no treatment or other conventional treatments ( e.g. NSAIDS ) . Search methods Electronic search es of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials , CCTR , MEDLINE , EMBASE , CINAHL , Bio extracts , and PsycLIT were performed to identify relevant r and omised controlled trials ( RCTs ) . The Cochrane Complementary Medicine Field 's Register of controlled trials ( CISCOM ) was also search ed . Attempts were also made to identify trials from the National Research Register , the Clinical Trial Register and the citation lists of review articles and included trials . In most cases , the first or corresponding author of each included trial was contacted for additional information . Selection criteria The inclusion criteria were RCTs of herbal or dietary therapies as treatment for primary or secondary dysmenorrhoea vs each other , placebo , no treatment or conventional treatment . Interventions could include , but were not limited to , the following ; vitamins , essential minerals , proteins , herbs , and fatty acids . Exclusion criteria were : mild or infrequent dysmenorrhoea or dysmenorrhoea from an IUD . Data collection and analysis Seven trials were included in the review . Quality assessment and data extraction were performed independently by two review ers . The main outcomes were pain intensity or pain relief and the number of adverse effects . Data on absence from work and the use of additional medication was also collected if available . Data was combined for meta- analysis using Peto odds ratios for dichotomous data or weighted mean difference for continuous data . A fixed effects statistical model was used . If data suitable for meta- analysis could not be extracted , any available data from the trial was extracted and presented as descriptive data . Main results MAGNESIUM :  Three small trials were included that compared magnesium and placebo . Overall magnesium was more effective than placebo for pain relief and the need for additional medication was less . There was no significant difference in the number of adverse effects experienced . VITAMIN B6 : One small trial of vitamin B6 showed it was more effective at reducing pain than both placebo and a combination of magnesium and vitamin B6 . MAGNESIUM AND VITAMIN B6 : Magnesium was shown to be no different in pain outcomes from both vitamin B6 and a combination of vitamin B6 and magnesium by one small trial . The same trial also showed that a combination of magnesium and vitamin B6 was no different from placebo in reducing pain .  VITAMIN B1 : One large trial showed vitamin B1 to be more effective than placebo in reducing pain .  VITAMIN E : One small trial comparing a combination of vitamin E ( taken daily ) and ibuprofen ( taken during menses ) versus ibuprofen ( taken during menses ) alone showed no difference in pain relief between the two treatments . OMEGA-3 FATTY ACIDS : One small trial showed fish oil ( omega-3 fatty acids ) to be more effective than placebo for pain relief . JAPANESE HERBAL COMBINATION : One small trial showed the herbal combination to be more effective for pain relief than placebo , and less additional pain medication was taken by the treatment group . Authors ' conclusions Vitamin B1 is shown to be an effective treatment for dysmenorrhoea taken at 100 mg daily , although this conclusion is tempered slightly by its basis on only one large RCT . Results suggest that magnesium is a promising treatment for dysmenorrhoea . It is unclear what dose or regime of treatment should be used for magnesium therapy , due to variations in the included trials , therefore no strong recommendation can be made until further evaluation is carried out . Overall there is insufficient evidence to recommend the use of any of the other herbal and dietary therapies considered in this review for the treatment of primary or secondary dysmenorrhoea Nutraceuticals have generated interest as a way to mitigate the cognitive decline in older adults . The aim of this systematic review was to determine the evidence for these cl aims from the scientific literature in r and omised , double-blinded , controlled trials ( duration : ≥1 year ; participants : n≥100 ; age(mean ) : ≥65 years ) . Following Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines , we search ed four electronic data bases ( PubMed , Scopus , CINAHL and Web of Science ) and identified twenty-five studies published between the 15·June·2006 and 14·June·2016 . Interventions included B-vitamins , n-3 fatty acids , antioxidant vitamins and herbs . Of the B-vitamin studies , four found benefits to cognition with supplementation . The first of these B-vitamin studies , in individuals with mild cognitive impairment ( n 266 ; duration = 2 years ) , included benefit to executive function ( P=0·015 ) and improvements in the Mini-Mental State Examination ( MMSE ) among participants with baseline homocysteine above 11·3 µmol/l ( P<0·001 ) . In the same sample , the second study found cognitive benefits  of B-vitamins dependent on the higher baseline plasma n-3 fatty acid status . The third B-vitamin study ( n 900 ; duration = 2 years ) reported improved performance in immediate ( P=0·046 ) and delayed recall ( P=0·013 ) , whereas the fourth study ( n 856 ; duration = 2 years ) reported slower rate of cognitive decline in the MMSE ( P=0·05 ) . One study investigating DHA treatment ( n 402 ; duration = 1·5 years ) revealed the slower rate of cognitive change in apoE e4 non-carriers ( P=0·03 ) . As only five included studies revealed notable benefits , presently based on the specific compounds explored here , there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly . Future long-term trials of nutraceuticals should investigate interactions with lifestyle , blood biomarkers and genetic risk factors 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 BACKGROUND Although moisturizer usage has been considered a mainstay of treatment for atopic dermatitis ( AD ) patients , few clinical studies have been investigated . Recently , moisturizers containing non-steroidal anti-inflammatory agents , such as licochalcone A ( LA ) and vitamin B(12 ) are of emerging interest . OBJECTIVE To compare the effectiveness of moisturizer containing LA with hydrocortisone ( HC ) lotion in treatment of childhood AD . Methods The r and omized , controlled , investigator-blinded 6-week study was conducted . Patients were administered with twice-daily application of LA lotion on one side of the body and HC lotion on the opposite side . The clinical outcome was assessed by the scoring of atopic dermatitis ( SCORAD ) index . The relapse rate was comparatively analysed by survival analysis . RESULTS From 30 patients enrolled , 26 patients completed the protocol . The mean age of the children was 5.8 years . The average baseline SCORAD score is about 28 on both sides . The response rates of both agents were equal to 73.33 % . There is no statistical significant group difference in reduction of SCORAD score . Although we observed more rapid resolution of oedema and erythema in areas treated with HC lotion , both agents exhibited no significant difference . The relapse rate of HC group was higher than in LA group ; however , there was no significant difference . No side-effect was observed from both agents . CONCLUSION The effectiveness of LA lotion is equal to that of HC lotion . It was suggested that moisturizer containing LA could be used both for treatment of acute and maintenance phase in mild-to-moderate childhood AD The National Institutes of Health 's consensus conference ( 1 ) defined osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture . Bone strength reflects the integration of two main features : bone density and bone quality .Bone quality refers to architecture , turnover , damage accumulation ( e.g. , microfractures ) , and mineralization . Although osteoporosis can affect any bone , the hip , spine , and wrist are most likely to be affected . Osteoporosis affects an estimated 44 million Americans or 55 % of people 50 years of age or older . Another 34 million Americans are estimated to have low bone mass , meaning that they are at an increased risk for osteoporosis . Osteoporosis can be diagnosed by the occurrence of fragility fracture . In patients without fragility fracture , osteoporosis is often diagnosed by low bone density .  Dual x-ray absorptiometry ( DXA ) is the current gold st and ard test for diagnosing osteoporosis in people without an osteoporotic fracture .  Dual x-ray absorptiometry results are scored as st and ard deviations ( SDs ) from a young healthy norm ( usually female ) and reported as T-scores . For example , a T-score of 2 indicates a bone mineral density that is 2 SDs below the comparative norm . The international reference st and ard for the description of osteoporosis in postmenopausal women and in men age 50 years or older is a femoral neck bone mineral density of 2.5 SD or more below the young female adult mean ( 2 ) . Low bone density , as measured by DXA , is an imperfect predictor of fracture risk , identifying fewer than half the people who go on to have an osteoporotic fracture . Screening guidelines for women are well established ( 3 ) , and the American College of Physicians ( ACP ) recently published guidelines on screening for men ( 4 ) . This guideline presents the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis . Medications used to treat osteoporosis may affect different parts of the skeletal system differently , and efficacy for vertebral fractures does not necessarily imply efficacy for nonvertebral fractures . The target audience for this guideline is all clinicians and the target patient population is all adult men and women with low bone density or osteoporosis . These recommendations are based on the systematic evidence review by MacLean and colleagues ( 5 ) and the Agency for Healthcare Research and Quality sponsored Southern California Evidence -Based Practice Center evidence report ( 6 ) . The drugs currently approved for prevention of osteoporosis include alendronate , ib and ronate , risedronate , zoledronic acid , estrogen , and raloxifene . The drugs currently approved for treatment of osteoporosis include alendronate , ib and ronate , risedronate , calcitonin , teriparatide , zoledronic acid ( in postmenopausal women ) , and raloxifene . Testosterone , pamidronate , and etidronate are not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Methods The literature search done by MacLean and colleagues for the systematic review ( 5 ) included studies from MEDLINE ( 1966 to December 2006 ) , the ACP Journal Club data base , the Cochrane Central Register of Controlled Trials ( no date limits ) , the Cochrane Data base of Systematic Review s ( no date limits ) , Web sites of the United Kingdom National Institute of Health and Clinical Excellence ( no date limits ) , and the United Kingdom Health Technology Assessment Program ( January 1998 to December 2006 ) . The review ers limited their search to English- language publications and human studies . They derived evidence for comparative benefits of various treatments exclusively from r and omized , controlled trials , whereas they included evidence from other types of studies for short- and long-term harms . Two physicians independently abstract ed data about study population s , interventions , follow-up , and outcome ascertainment by using a structured form . For each group within a r and omized trial , a statistician extracted the sample size and number of persons reporting fractures . Two review ers , under the supervision of the statistician , independently abstract ed information about adverse events . The statistician or the principal investigator resolved disagreements . This guideline is based on an evaluation of 76 r and omized , controlled trials , 4 of which were identified in the up date d search , and 24 meta-analyses that were included in the efficacy analyses . The analyses of adverse events included 491 articles , representing 417 r and omized trials , 25 other controlled clinical trials , 11 open-label trials , 31 large observational studies , and 9 case reports of osteonecrosis among bisphosphonate users . MacLean and colleagues ' background article ( 5 ) includes details about the methods used for the systematic evidence review . The ACP rates the evidence and recommendations by using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) system with minor modifications ( Table 1 ) . In addition , the evidence review ers used predefined criteria to assess the quality of systematic review s and r and omized trials , based on internal and external validity assessment s detailed in the Quality of Reporting of Meta-Analyses ( QUOROM ) statement ( 7 ) . Table 1 . The American College of Physicians ' Guideline Grading System The objective of this guideline is to synthesize the evidence for the following questions : What are the comparative benefits in fracture reduction among and also within the following treatments for low bone density :  bisphosphonates , specifically alendronate , risedronate , etidronate , ib and ronate , pamidronate , and zoledronic acid ; calcitonin ; estrogen for women ; teriparatide ; selective estrogen receptor modulators ( SERMs ) , specifically raloxifene and tamoxifen ; testosterone for men ; vitamins and minerals , specifically vitamin D and calcium ; and the combination of calcium plus vitamin D ? How does fracture reduction result ing from treatments vary among individuals with different risks for fracture as determined by bone mineral density ( borderline , low , or severe ) , previous fractures ( prevention vs. treatment ) , age , sex , glucocorticoid use , and other factors ( such as community-dwelling vs. institutionalized or vitamin Ddeficient vs. not ) ? What are the short- and long-term harms ( adverse effects ) of these therapies , and do these vary by specific sub population s ? Comparative Benefits of Drugs versus Placebo in Fracture Reduction Evidence from 24 meta-analyses ( 830 ) and 35 additional r and omized trials published after the meta-analyses ( 3165 ) described the effect of 9 of the 14 agents ( alendronate , etidronate , risedronate , calcitonin , estrogen , teriparatide , raloxifene , calcium , and vitamin D ) on fracture incidence . For 4 agents ( ib and ronate , pamidronate , zoledronic acid , and tamoxifen ) , the review ers found no meta-analyses and instead gathered the evidence from 14 r and omized trials ( 6679 ) . No studies were found that reported fracture rates for testosterone . Three r and omized trials ( 35 , 80 , 81 ) and 1 meta- analysis ( 82 ) evaluated the combination of calcium plus vitamin D  on fractures .  Bisphosphonates Good- quality evidence showed that alendronate , etidronate , ib and ronate , and risedronate prevent vertebral fractures . In addition , evidence from good- quality studies demonstrated that both alendronate and risedronate prevent nonvertebral and hip fractures . Two large r and omized trials showed that zoledronic acid prevents vertebral and nonvertebral fractures in high-risk population s and reduces the risk for hip fracture ( 67 , 74 ) . Ib and ronate has not been shown to reduce nonvertebral fractures ( 68 ) . Of the 6 fairly small trials that looked at vertebral fractures , 1 demonstrated a statistically significant reduction in fractures with pamidronate relative to placebo ( 0.14 [ 95 % CI , 0.03 to 0.72 ] ) ( 73 ) . However , after these data were pooled , the pooled risk estimate for fractures for pamidronate relative to placebo was not significant ( 0.52 [ CI , 0.21 to 1.24 ] ) ( 6 ) . Calcitonin Fair- quality evidence shows that calcitonin reduces vertebral fractures ( 83 , 84 ) . Good- quality evidence indicates that calcitonin does not reduce nonvertebral fractures ( 13 , 16 ) . Estrogen Good- quality evidence shows that estrogen reduces the incidence of vertebral ( 29 , 85 ) , nonvertebral ( 86 ) , and hip fractures ( 85 ) . Teriparatide Good- quality evidence shows that teriparatide prevents vertebral fractures . The evidence related to teriparatide preventing nonvertebral fractures is mixed ; 1 large r and omized trial showed a reduction in nonvertebral fractures ( 34 ) but 2 small trials did not ( 87 , 88 ) . SERMs Good- quality evidence shows that raloxifene prevents vertebral fractures , but that tamoxifen has no effect on vertebral fractures ( 8991 ) . In addition , both raloxifene and tamoxifen had no effect on hip fractures ( 91 ) . Tamoxifen is not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Testosterone No studies reported fracture rates for testosterone . Calcium and Vitamin D In the studies evaluated by MacLean and colleagues ( 5 ) , the evidence for the effect of calcium alone on reduction of fractures is complex . Most studies of pharmacologic agents for osteoporosis include calcium and vitamin D as part of the treatment regimen . Evidence from 1 meta- analysis ( 27 ) and several r and omized trials ( 35 , 48 , 51 , 92 ) showed no significant difference between calcium and placebo in preventing vertebral , nonvertebral , and hip fractures in postmenopausal women . However , nonadherence to therapy may influence this result , and 1 trial with a prespecified analysis of adherent patients found a reduction in fracture risk ( 48 ) . A recent meta- analysis ( 82 ) concluded that the relative risk ( RR ) for fracture with calcium alone was 0.90 ( CI , 0.80 to 1.00 ) , but it did not include a modestly large trial with negative results ( 35 ) . MacLean and colleagues ( 5 ) Background To improve quality of care and patient outcomes , health system decision-makers need to identify and implement effective interventions . An increasing number of systematic review s document the effects of quality improvement programs to assist decision-makers in developing new initiatives . However , limitations in the reporting of primary studies and current meta- analysis methods ( including approaches for exploring heterogeneity ) reduce the utility of existing syntheses for health system decision-makers . This study will explore the role of innovative meta- analysis approaches and the added value of enriched and up date d data for increasing the utility of systematic review s of complex interventions . Methods / Design We will use the data set from our recent systematic review of 142 r and omized trials of diabetes quality improvement programs  to evaluate novel approaches for exploring heterogeneity . These will include exploratory methods , such as multivariate meta-regression analyses and all-subsets combinatorial meta- analysis . We will then up date our systematic review to include new trials and enrich the data set by surveying authors of all included trials . In doing so , we will explore the impact of variables not , reported in previous publications , such as details of study context , on the effectiveness of the intervention . We will use innovative analytical methods on the enriched and up date d data set to identify key success factors in the implementation of  quality improvement interventions  for diabetes . Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results . Discussion This study will inform future systematic review s of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta- analysis . It will also result in an up date d comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes . Systematic review registration PROSPERO registration no. BACKGROUND Evidence suggests that intestinal microbiota play an important role in the pathogenesis of atopic dermatitis ( AD ) through induction of immunosuppression and immune tolerance ; however , the exact underlying mechanism is unclear . Few studies to date have examined the effects of probiotics on adult-type AD . OBJECTIVE To examine the effects of the probiotic Bifidobacterium animalis subsp lactis LKM512 on adult-type AD and the expression of metabolites that are known to be influenced by gut microbiota in fecal sample s. METHODS Forty-four patients were r and omly assigned to receive LKM512 or a placebo and underwent medical examinations . Fecal microbiota were analyzed with real-time polymerase chain reaction . Metabolomic analysis was conducted to search for antipruritic metabolites produced by intestinal bacteria using feces derived from 3 patients whose itch scores had improved using capillary electrophoresis with time-of-flight mass spectrometry . Antipruritic effects of kynurenic acid were observed using AD-induced NC/Nga mice . RESULTS LKM512 administration alleviated itch in AD patients compared with controls and improved the dermatology-specific quality -of-life scores when compared with the controls . Administration of LKM512 also increased the expression of the antipruritic and antinociceptive metabolite kynurenic acid ( KYNA ) in patients whose itch score had improved after LKM512 treatment . In mouse experiments , scratching behavior counts tended to be decreased by KYNA injection when compared with no treatment . CONCLUSION LKM512 administration may exert antipruritic effects by increasing KYNA production . LKM512 could therefore be a potentially effective therapeutic c and i date for the reduction of pruritus . TRIAL REGISTRATION umin.ac.jp/ctr Identifier : UMIN000005695 OBJECTIVE There are several examples in nutrition of discordance between the results of observational studies and r and omized controlled trials ( RCTs ) . We hypothesized that this discordance is attributable to differences in the translational paths of nutrient-disease associations . Translational paths can be assessed using citation analysis . STUDY DESIGN AND SETTING We compared the characteristics of citation networks using examples , where RCTs and observational studies agreed ( long-chain n-3 polyunsaturated fatty acids [ n-3 PUFA ] ) or disagreed ( vitamin E ) . We performed systematic review s in each example , constructed citation networks , and compared them with respect to the number of articles and citation relationships between them , as well as the distribution of articles ' hub and authority scores . RESULTS For n-3 PUFA , meta-analyses of 14 RCTs and 10 observational studies both suggested that higher intake was associated with lower cardiovascular mortality . For vitamin E , the meta- analysis of 14 RCTs excluded a clinical ly significant effect , whereas 14 observational studies reported a significant inverse association . The respective citation networks consisted of 392 ( n-3 PUFA ) and 351 ( vitamin E ) articles . No differences between the characteristics of the two networks were identified . There was no evidence that the observational studies pre date d RCTs in the translational process in either example . CONCLUSION In the two examples , citation network characteristics do not predict concordance in the results of observational studies and RCTs Abstract Background : The role of probiotics in the treatment of atopic dermatitis ( AD ) remains controversial . A recent systematic review of the available evidence called for further clinical trials with new probiotic formulations . Objective : To assess the clinical efficacy and impact of Lactobacillus acidophilus DDS-1 , Bifidobacterium lactis UABLA-12 with fructo-oligosaccharide on peripheral blood lymphocyte subsets in preschool children with moderate-to-severe AD . Method : R and omized , double-blind , placebo-controlled , prospect i ve trial of 90 children aged 1–3 years with moderate-to-severe AD who were treated with a mixture of L. acidophilus DDS-1 , B. lactis UABLA-12 with fructo-oligosaccharide at a dosage of 5 billion colony-forming units twice daily for 8 weeks versus placebo . The primary outcome measure was the percentage change in Scoring of Atopic Dermatitis ( SCORAD ) value . Other outcome measures were changes in Infant Dermatitis Quality Of Life ( IDQOL ) and Dermatitis Family Impact ( DFI ) scores , frequency and amount of topical corticosteroid used , and lymphocyte subsets in peripheral blood measured by laser flow cytometry . Results : At the final visit , the percentage decrease in SCORAD was 33.7 % in the probiotic group compared with 19.4 % in the placebo group ( p = 0.001 ) . Children receiving probiotic showed a greater decrease in the mean [ SD ] SCORAD score than did children from the placebo group at week 8 ( −14.2 [ 9.9 ] vs −7.8 [ 7.7 ] , respectively ; p = 0.001 ) . IDQOL and DFI scores decreased significantly from baseline by 33.0 % and 35.2 % in the probiotic group and by 19.0 % and 23.8 % in the placebo group , respectively ( p = 0.013 , p = 0.010 ) . Use of topical corticosteroids during the 8-week trial period averaged 7.7 g less in probiotic patients ( p = 0.006 ) . CD3 , CD16 , and CD22 lymphocyte subsets remained unchanged , whereas the percentage of CD4 , and the percentage and absolute count of CD25 decreased , and the percentage and absolute count of CD8 increased in the probiotic group at week 8 ( p < 0.007 vs placebo ) . There was a significant correlation between CD4 percentage , CD25 percentage , CD25 absolute count , and SCORAD values ( r = 0.642 , r = 0.746 , r = 0.733 , respectively ; p < 0.05 ) in the probiotic group at week 8 . Conclusion : The administration of a probiotic mixture containing L. acidophilus DDS-1 , B. lactis UABLA- 12 , and fructo-oligosaccharide was associated with significant clinical improvement in children with AD , with corresponding lymphocyte subset changes in peripheral blood . The efficacy of probiotic therapy in adults with AD requires further investigation This study investigates the effect of exposure to a mobile phone-like radiofrequency ( RF ) electromagnetic field on people with atopic dermatitis ( AD ) . Fifteen subjects with AD were recruited and matched with 15 controls without AD . The subjects were exposed for 30 min to an RF field at 1 W/kg via an indoor base station antenna attached to a 900 MHz GSM mobile phone .  Blood sample s for ELISA analysis of the concentration of substance P ( SP ) , tumor necrosis factor receptor 1 ( TNF R1 ) , and brain derived neurotrophic factor ( BDNF ) in serum were drawn before and after the provocation ( exposure/sham ) . Baseline heart rate and heart rate variability , local blood flow , and electrodermal activity were also recorded . No significant differences between the subject groups were found for baseline neurophysiological data . The cases displayed a serum concentration of TNF R1 significantly higher than the control subjects and a significantly lower serum concentration of BDNF in the baseline condition . For SP there was no difference between groups . However , no effects related to RF exposure condition were encountered for any of the measured substances . As to symptoms , a possible correlation with exposure could not be evaluated , due to too few symptom reports . The result of the study does not support the hypothesis of an effect of mobile phone-like RF exposure on serum levels of SP , TNF R1 , and BDNF in persons with AD BACKGROUND To eluci date whether maternal vitamin D supplementation during lactation improves infantile eczema and other subsequent allergic disorders , a r and omized , double-blind , placebo-controlled trial was performed . METHODS Mothers ( n = 164 ) of infants with facial eczema at 1 month check-up were r and omly assigned to receive vitamin D3 supplements ( n = 82 ; 800 IU/day ) or placebo ( n = 82 ) for 6 weeks from May 2009 to January 2011 . The primary outcome was infantile eczema quantified on Scoring Atopic Dermatitis ( SCORAD ) index at 3 month check-up , and the secondary outcomes were atopic dermatitis , food allergy , and wheeze diagnosed by doctors up to 2 years of age . RESULTS There was no significant difference in SCORAD at 3 month check-up between the two groups . Doctor-diagnosed food allergy was significantly more common up to age 2 years in the vitamin D group ( 10/39 , 25.7 % ) than in the placebo group ( 3/40 , 7.5 % ; risk ratio ( RR ) , 3.42 ; 95 % confidence interval [ CI ] : 1.02 - 11.77 ; P = 0.030 ) . Moreover , at least one secondary outcome was also significantly more common in the vitamin D group ( 17/39 , 43.6 % ) than in the placebo group ( 7/40 , 17.5 % ; RR , 2.49 ; 95%CI : 1.16 - 5.34 ; P = 0.012 ) . CONCLUSIONS Vitamin D supplementation may not decrease the severity of infantile eczema at 3 months of age , but may rather increase the risk of later food allergy up to 2 years of age . Because a large number of subjects was lost to follow up , further study is needed to confirm the findings
Vitamin D has a potentially significant role for improving the symptoms of AD .
The results from this study suggest that vitamin D supplementation may help ameliorate the severity of AD , and can be considered as a safe and tolerable therapy .
OBJECTIVES Despite the evidence supporting the use of vitamin D supplements for managing atopic dermatitis ( AD ) , no meta- analysis providing definite conclusions in this field has been reported .
The purpose of the present study was to conduct a systematic review and meta- analysis of all controlled studies of vitamin D for treating AD to eluci date the efficacy of vitamin D for alleviating the symptoms of AD .