title: The effect of vitamin D supplementation on blood pressure in patients with elevated blood pressure and vitamin D deficiency: a randomized, double-blind, placebo-controlled trial Plasma 25-Hydroxyvitamin D Levels and Risk of Incident Hypertension 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients Effect of weekly vitamin D supplements on mortality, morbidity, and growth of low birthweight term infants in India up to age 6 months: randomised controlled trial Effect of treatment with dydrogesterone or calcium plus vitamin D on the severity of premenstrual syndrome. Vitamin D Intake and Risk of Incident Hypertension: Results From Three Large Prospective Cohort Studies Effect of Vitamin D Supplementation on Blood Pressure in Blacks Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Serum 25-Hydroxyvitamin D Levels Are Strongly Related to Systolic Blood Pressure But Do Not Predict Future Hypertension Effects of Vitamin D Supplementation on Plasma Aldosterone and Renin-A Randomized Placebo-Controlled Trial. Serum 25-Hydroxyvitamin D Concentrations and Depressive Symptoms among Young Adult Men and Women Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study: A Randomized Clinical Trial Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Annual high-dose vitamin D3 and mental well-being: randomised controlled trial. Vitamin D and nifedipine in the treatment of Chinese patients with grades I-II essential hypertension: a randomized placebo-controlled trial. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies Vitamin D and calcium intake in relation to type 2 diabetes in women. Randomized placebo-controlled trial of high-dose prenatal third-trimester vitamin D3 supplementation in Bangladesh: the AViDD trial 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) Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial Association between depressive symptoms and 25-hydroxyvitamin D in middle-aged and elderly Chinese. Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth. Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. Low Serum 25-Hydroxyvitamin D Level and Risk of Upper Respiratory Tract Infection in Children and Adolescents Are Clinical Trials the “Gold Standard” for Cancer Prevention Research? Effects of Vitamin D Supplementation on Cognitive and Emotional Functioning in Young Adults – A Randomised Controlled Trial Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial Calcium plus vitamin D supplementation and the risk of colorectal cancer. Vitamin D status has a linear association with seasonal infections and lung function in British adults. Vitamin D3 enhances mood in healthy subjects during winter Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL). Calcium plus vitamin D supplementation and the risk of fractures. The Effect of 2 Different Single Injections of High Dose of Vitamin D on Improving the Depression in Depressed Patients With Vitamin D Deficiency: A Randomized Clinical Trial Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. Randomized controlled trials of vitamin D and cancer incidence: A modeling study Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Low vitamin D levels are associated with symptoms of depression in young adult males The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Vitamin D supplementation and depression in the women's health initiative calcium and vitamin D trial. Vitamin D Supplementation in Pregnancy: A Controlled Trial of Two Methods Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Human Interventions to Characterize Novel Relationships Between the Renin–Angiotensin–Aldosterone System and Parathyroid Hormone A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). Seasonal mood changes in 250 normal women Obstetric and neonatal outcomes of maternal vitamin D supplementation: results of an open-label, randomized controlled trial of antenatal vitamin D supplementation in Pakistani women. The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. Standardizing serum 25-hydroxyvitamin D data from four Nordic population samples using the Vitamin D Standardization Program protocols: Shedding new light on vitamin D status in Nordic individuals Dose Response to Vitamin D Supplementation in Postmenopausal Women Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms Effect of treatment of vitamin D deficiency and insufficiency during pregnancy on fetal growth indices and maternal weight gain: a randomized clinical trial.
abstract: Objectives The present evidence indicates a reverse correlation between vitamin D status and blood pressure ( BP ) . The present study determined the effect of oral vitamin D supplementation on BP in patients with elevated BP and vitamin D deficiency . Material s and methods In this r and omized , double-blind , placebo-controlled trial , 42 out patients with elevated BP and vitamin D deficiency were assigned r and omly to two groups : the vitamin D-supplemented group ( VDG ) , who received one capsule containing 50 000 IU of cholecalciferol weekly , and the placebo group ( PG ) , who received one similar capsule containing oral liquid paraffin as placebo for 8 weeks . The systolic ( SBP ) and diastolic ( DBP ) blood pressures , mean arterial blood pressure ( MAP ) , pulse pressure , serum 25-hydroxyvitamin D , parathormone , calcium , phosphorus , magnesium , sodium , and potassium were measured before and after the intervention . Results In all , 92.7 % of the VDG recovered from vitamin D deficiency . At the end of the intervention , the mean SBP and DBP , and the MAP decreased significantly in VDG compared with the PG , whereas at the beginning of the intervention , there was no significant difference between the two groups . The mean changes in SBP ( −6.4±5.3 vs. 0.9±3.7 mmHg , PV<0.001 ) , DBP ( −2.4±3.7 vs. 1.0±2.7 mmHg , PV=0.003 ) , and MAP ( −3.7±3.6 vs. 0.9±2.5 mmHg , PV<0.001 ) were lower in the VDG than PG . Conclusion The findings of the study showed that the weekly administration of 50 000 IU of oral vitamin D for 8 weeks as an adjunct supplement of antihypertensive drugs in patients with vitamin D deficiency could help prevent vitamin D deficiency and aid control of SBP , DBP , and MAP Hydroxylation of 25(OH)D to 1,25-dihydroxyvitamin D and signaling through the vitamin D receptor occur in various tissues not traditionally involved in calcium homeostasis . Laboratory studies indicate that 1,25-dihydroxyvitamin D suppresses renin expression and vascular smooth muscle cell proliferation ; clinical studies demonstrate an inverse association between ultraviolet radiation , a surrogate marker for vitamin D synthesis , and blood pressure . We prospect ively studied the independent association between measured plasma 25-hydroxyvitamin D [ 25(OH)D ] levels and  risk of incident hypertension  and also the association between predicted plasma 25(OH)D levels and risk of incident hypertension .  Two prospect i ve cohort studies including 613 men from the Health Professionals ’ Follow-Up Study and 1198 women from the Nurses ’ Health Study with measured 25(OH)D levels were followed for 4 to 8 years . In addition , 2 prospect i ve cohort studies including 38 388 men and 77 531 women with predicted 25(OH)D levels were followed for 16 to 18 years . During 4 years of follow-up , the multivariable relative risk of incident hypertension among men whose measured plasma 25(OH)D levels were < 15 ng/mL ( ie , vitamin D deficiency ) compared with those whose levels were ≥30 ng/mL was 6.13 ( 95 % confidence interval [ CI ] : 1.00 to 37.8 ) . Among women , the same comparison yielded a relative risk of 2.67 ( 95 % CI : 1.05 to 6.79 ) . The pooled relative risk combining men and women with measured 25(OH)D levels using the r and om-effects model was 3.18 ( 95 % CI : 1.39 to 7.29 ) . Using predicted 25(OH)D levels in the larger cohorts , the multivariable relative risks comparing the lowest to highest deciles were 2.31 ( 95 % CI : 2.03 to 2.63 ) in men and 1.57 ( 95 % CI : 1.44 to 1.72 ) in women . Plasma 25(OH)D levels are inversely associated with risk of incident hypertension BACKGROUND Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans . METHODS We assessed prospect ively whether plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations are associated with risk of coronary heart disease . A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study ; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection . The blood sample s were returned between April 1 , 1993 , and November 30 , 1999 ; 99 % were received between April 1 , 1993 , and November 30 , 1995 . During 10 years of follow-up , 454 men developed nonfatal myocardial infa rct ion or fatal coronary heart disease . Using risk set sampling , controls ( n = 900 ) were selected in a 2:1 ratio and matched for age , date of blood collection , and smoking status . RESULTS After adjustment for matched variables , men deficient in 25(OH)D ( < or=15 ng/mL [ to convert to nanomoles per liter , multiply by 2.496 ] ) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D ( > or=30 ng/mL ) ( relative risk [ RR ] , 2.42 ; 95 % confidence interval [ CI ] , 1.53 - 3.84 ; P < .001 for trend ) . After additional adjustment for family history of myocardial infa rct ion , body mass index , alcohol consumption , physical activity , history of diabetes mellitus and hypertension , ethnicity , region , marine omega-3 intake , low- and high-density lipoprotein cholesterol levels , and triglyceride levels , this relationship remained significant ( RR , 2.09 ; 95 % CI , 1.24 - 3.54 ; P = .02 for trend ) . Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels ( 22.6 - 29.9 ng/mL : RR , 1.60 [ 95 % CI , 1.10 - 2.32 ] ; and 15.0 - 22.5 ng/mL : RR , 1.43 [ 95 % CI , 0.96 - 2.13 ] , respectively ) . CONCLUSION Low levels of 25(OH)D are associated with higher risk of myocardial infa rct ion in a grade d manner , even after controlling for factors known to be associated with coronary artery disease Background For adults , vitamin D intake of 100 mcg ( 4000 IU)/day is physiologic and safe . The adequate intake ( AI ) for older adults is 15 mcg ( 600 IU)/day , but there has been no report focusing on use of this dose . Methods We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded , r and omized trial . In Study 1 , 64 out patients ( recruited if summer 2001 25(OH)D < 61 nmol/L ) were given 15 or 100 mcg/day vitamin D in December 2001 . Biochemical responses were followed at subsequent visits that were part of clinical care ; 37 patients completed a wellbeing question naire in December 2001 and February 2002 . Subjects for Study 2 were recruited if their 25(OH)D was < 51 nmol/L in summer 2001 . 66 out patients were given vitamin D ;  51 completed a wellbeing question naire in both December 2002 and February 2003 . Results In Study 1 , basal summer 25-hydroxyvitamin D [ 25(OH)D ] averaged 48 ± 9 ( SD ) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group , and 112 ± 41 nmol/L for the 100 mcg/day group . Both doses lowered plasma parathyroid hormone with no effect on plasma calcium . Between December and February , wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group ( 1-tail Mann-Whitney p = 0.036 ) . In Study 2 , 25(OH)D averaged 39 ± 9 nmol/L , and winter wellbeing scores improved with both doses of vitamin D ( two-tail p < 0.001 ) . Conclusion The highest AI for vitamin D  brought summertime 25(OH)D to > 40 nmol/L , lowered PTH , and its use was associated with improved wellbeing . The 100 mcg/day dose produced greater responses . Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients , we can not rule out a placebo wellbeing response , particularly for those on the lower dose . This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin Objective To investigate whether vitamin D supplementation can decrease the mortality and morbidity of low birthweight infants in low income countries . Design R and omised controlled trial . Setting Large government hospital in New Delhi , India . Participants 2079 low birthweight infants born at term ( > 37 weeks ’ gestation ) . Main outcome measures Primary outcome was admission to hospital or death during the first six months of life . Main secondary outcome was growth . Interventions Weekly vitamin D supplements for six months at a dose of one recommended nutrient intake per day ( 35 µg/week ) . Infants were visited weekly at home for observed supplementation and were brought to the clinic monthly for clinical examination and anthropometric measurements . Results Between group differences were not significant for death or hospital admissions ( 92 among 1039 infants in the vitamin D group v 99 among 1040 infants in the placebo group ; adjusted rate ratio 0.93 , 95 % confidence interval 0.68 to 1.29 ; P=0.68 ) , or referral to the outpatient clinic for moderate morbidity  . Vitamin D supplementation result ed in better vitamin D status as assessed by plasma calcidiol levels at six months . In adjusted analyses , vitamin D treatment significantly increased st and ard deviation ( z ) scores at six months for weight , length , and arm circumference and decreased the proportion of children with stunted growth ( length for age z score ≤2 ) or with arm circumference z scores of 2 or less . Conclusion A weekly dose of vitamin D result ed in better vitamin D status and benefited the classic vitamin D function of bone growth but did not decrease the incidence of severe morbidity or death among young low birthweight infants . Trial registration Clinical Trials.gov NCT00415402 OBJECTIVE To compare the effects of dydrogesterone and calcium plus vitamin D in women with severe premenstrual syndrome ( PMS ) . METHOD In this r and omized , double-blind , placebo-controlled study , 180 Shiraz University students with PMS used question naires daily to rate their symptoms for 2 menstrual cycles . Then , the students were r and omly assigned to take a tablet containing either 5 mg of dydrogesterone , 500 mg of calcium plus 200 mg of vitamin D , or a placebo twice daily from the 15th to the 24th day of the cycle for 2 more cycles , and to use the same question naires during the intervention cycles . The collected data were then analyzed by repeated-measurement design and multilevel modeling tests . RESULT Treatment with dydrogesterone or calcium plus vitamin D  decreased symptom severity in a similar way ( by 4.64 % and 4.20 % , respectively ) and placebo was associated with a 3.42 % decrease . CONCLUSION Treatment with dydrogesterone or calcium plus vitamin D had a similar effect on symptom severity in women with PMS Emerging evidence suggests an inverse relation between vitamin D and  blood pressure . We examined the independent association between intake of vitamin D and the risk of incident hypertension among participants of 3 large and independent prospect i ve cohorts : Nurses Health Study I ( NHS I ; n=77 436 ) , NHS II ( n=93 803 ) , and Health Professionals ’ Follow-up Study ( HPFS ; n=38 074 ) .  Relative risks and 95 % confidence intervals for incident hypertension were computed according to quintiles of vitamin D intake using Cox proportional hazards regression and adjusted for relevant covariates . Each cohort was followed for ≥8 years . Vitamin D intake was not associated with the risk of developing hypertension . The multivariable relative risk estimates for the highest compared with lowest quintile of intake were 0.98 ( 0.93 to 1.04 ) in NHS I , 1.13 ( 0.99 to 1.29 ) in NHS II , and 1.03 ( 0.93 to 1.15 ) in HPFS . When we compared participants who consumed ≥1600 to < 400 IU per day and those who consumed ≥1000 to < 200 IU per day , no association was found . We conclude that higher intake of vitamin D is not associated with a lower risk of incident hypertension Blacks have significantly higher rates of hypertension than whites , and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 ( cholecalciferol ) supplementation on  blood pressure in blacks . During 2 winters from 2008 to 2010 , 283 blacks ( median age , 51 years ) were r and omized into a 4-arm , double-blind trial for 3 months of placebo , 1000 , 2000 , or 4000 international units of cholecalciferol per day . At baseline , 3 months , and 6 months , systolic and diastolic pressure and 25-hydroxyvitamin D were measured . The 3-month follow-up was completed in 250 ( 88 % ) participants . The difference in systolic pressure between baseline and 3 months was + 1.7 mm Hg for those receiving placebo , −0.66 mm Hg for 1000 U/d , −3.4 mm Hg for 2000 U/d , and −4.0 mm Hg for 4000 U/d of cholecalciferol ( −1.4 mm Hg for each additional 1000 U/d of cholecalciferol ; P=0.04 ) . For each 1-ng/mL increase in plasma 25-hydroxyvitamin D , there was a significant 0.2-mm Hg reduction in systolic pressure ( P=0.02 ) . There was no effect of cholecalciferol supplementation on diastolic pressure ( P=0.37 ) . Within an unselected population of blacks , 3 months of oral vitamin D3 supplementation significantly , yet modestly , lowered systolic pressure . Future trials of vitamin D supplementation  on blood pressure are needed to confirm these promising results , particularly among blacks , a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension 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 Vitamin D receptors have been detected in vascular smooth muscle cells , and 1,25-dihydroxyvitamin D inhibits the renin mRNA expression . Epidemiological studies show an inverse relation between serum 25-hydoxyvitamin D levels and blood pressure , and low serum 25-hydoxyvitamin D levels are reported to be predictors of future development of hypertension . This may indicate an important role for vitamin D in blood pressure regulation . In the present study , 25-hydoxyvitamin D was measured in sera collected in 1994 from 4125 subjects who did not use blood pressure medication , and thereafter measurement was repeated in 2008 for 2385 of these subjects . In sera from 1994 there was a significant decrease in age , body mass index , and systolic blood pressure and a significant increase in physical activity score across increasing 25-hydoxyvitamin D quartiles . After adjusting for sex , age , body mass index , and physical activity , the difference in systolic blood pressure between the lowest and highest serum 25-hydoxyvitamin D quartiles was 3.6 mm Hg . After adjustment for confounders , serum 25-hydoxyvitamin D from 1994 did not predict future hypertension or increase in blood pressure , nor was there any significant association between change in serum 25-hydoxyvitamin D from 1994 to 2008 and change in blood pressure . Our results do not support a causal role for vitamin D in blood pressure regulation , and large r and omized clinical trials , preferably including subjects with hypertension and /or low serum 25-hydoxyvitamin D levels , are greatly needed to clarify whether vitamin D supplementation affects the blood pressure Increasing evidence describes a possible interplay between vitamin D insufficiency with increased aldosterone . The authors sought to evaluate the effect of vitamin D supplementation on plasma aldosterone concentration ( PAC ) in patients with hypertension and 25-hydroxyvitamin D[25(OH)D ] insufficiency . The Styrian Vitamin D Hypertension Trial was a single-center , double-blind , placebo-controlled r and omized clinical trial conducted from 2011 to 2014 . Two hundred patients with arterial hypertension and 25(OH)D levels < 30 ng/mL were enrolled . Study participants were r and omized to receive either 2800 IU of vitamin D3 or placebo . The present investigation is a post hoc analysis using analysis of covariance adjusting for baseline differences . A total of 188 participants ( mean±st and ard deviation age , 60.1±11.3 years ; 47 % women ; 25(OH)D , 21.2±5.6 ng/mL ) completed the trial . Mean differences between baseline and follow-up PAC in the control and intervention arm were + 3.3 ng/dL and + 0.9 ng/dL , respectively ( P=.04 ) . The findings indicate that vitamin D3 supplementation  significantly decreases PAC in patients with arterial hypertension and 25(OH)D insufficiency There has been an increased interest in the role of vitamin D in depression ; however , there have been few studies conducted in younger population groups . Our aim was to investigate the association between vitamin D status and depressive symptoms in a non- clinical young adult sample living in Dunedin , New Zeal and . A cross-sectional sample of 615 young adults completed a question naire including demographics and the  Centre  for Epidemiological Studies Depression Scale ( CES-D ) . Height , weight and a blood sample for 25-hydroxyvitamin D [ 25(OH)D ] was obtained . Serum 25(OH)D was used to predict depression scores , adjusting for potential confounders including time spent outdoors for 13 consecutive days , BMI , age , sex and ethnicity . Prevalence of low vitamin D was high even in this age group , and serum 25(OH)D was negatively associated with depression symptoms before and after adjustment . When investigating the relationship between the presence versus absence of depressive symptoms and quartiles of 25(OH)D , participants in the lowest quartile were more likely to report depressive symptoms compared with those in the highest quartile . Although our findings suggest that vitamin D is a predictor of depression symptomatology , even when controlling for time spent outdoors , a r and omised controlled trial in this young adult target group is needed to confirm the association Importance Cohort studies have reported increased incidence of cardiovascular disease ( CVD ) among individuals with low vitamin D status . To date , r and omized clinical trials of vitamin D supplementation have not found an effect , possibly because of using too low a dose of vitamin D. Objective To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population . Design , Setting , and Participants The Vitamin D Assessment Study is a r and omized , double-blind , placebo-controlled trial that recruited participants mostly from family practice s in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up until July 2015 . Participants were community-resident adults aged 50 to 84 years . Of 47 905 adults invited from family practice s and 163 from community groups , 5110 participants were r and omized to receive vitamin D3 ( n = 2558 ) or placebo ( n = 2552 ) . Two participants retracted consent , and all others ( n = 5108 ) were included in the primary analysis . Interventions Oral vitamin D3 in an initial dose of 200 000 IU , followed a month later by monthly doses of 100 000 IU , or placebo for a median of 3.3 years ( range , 2.5 - 4.2 years ) . Main Outcomes and Measures The primary outcome was the number of participants with incident CVD and death , including a prespecified subgroup analysis in participants with vitamin D deficiency ( baseline deseasonalized 25-hydroxyvitamin D [ 25(OH)D ] levels < 20 ng/mL ) . Secondary outcomes were myocardial infa rct ion , angina , heart failure , hypertension , arrhythmias , arteriosclerosis , stroke , and venous thrombosis . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 2969 ( 58.1 % ) were male , and 4253 ( 83.3 % ) were of European or other ethnicity , with the remainder being Polynesian or South Asian .  Mean ( SD ) baseline deseasonalized 25(OH)D concentration was 26.5 ( 9.0 ) ng/mL , with 1270 participants ( 24.9 % ) being vitamin D deficient . In a r and om sample of 438 participants , the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group . The primary outcome of CVD occurred in 303 participants ( 11.8 % ) in the vitamin D group and 293 participants ( 11.5 % ) in the placebo group , yielding an adjusted hazard ratio of 1.02 ( 95 % CI , 0.87 - 1.20 ) . Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes . Conclusions and Relevance Monthly high-dose vitamin D supplementation does not prevent CVD . This result does not support the use of monthly vitamin D supplementation for this purpose . The effects of daily or weekly dosing require further study . Trial Registration clinical trials.gov Identifier : Aims Circulating 25-hydroxyvitamin D ( 25OHD ) levels < 75 nmol/L are associated with a nonlinear increase in mortality risk . Such 25OHD levels are common in heart failure ( HF ) . We therefore examined whether oral vitamin D supplementation reduces mortality in patients with advanced HF . Methods and results Four hundred HF patients with 25OHD levels < 75 nmol/L were r and omized to receive 4000 IU vitamin D daily or matching placebo for 3 years . Primary endpoint was all-cause mortality . Key secondary outcome measures included hospitalization , resuscitation , mechanical circulatory support ( MCS ) implant , high urgent listing for heart transplantation , heart transplantation , and hypercalcaemia . Initial 25OHD levels were on average < 40 nmol/L , remained around 40 nmol/L in patients assigned to placebo and plateaued around 100 nmol/L in patients assigned to vitamin D. Mortality was not different in patients receiving vitamin D ( 19.6 % ; n = 39 ) or placebo ( 17.9 % ; n = 36 ) with a hazard ratio ( HR ) of 1.09 [ 95 % confidence interval ( CI ) : 0.69 - 1.71 ; P = 0.726 ] . The need for MCS implant was however greater in patients assigned to vitamin D ( 15.4 % , n = 28 ) vs. placebo [ 9.0 % , n = 15 ; HR : 1.96 ( 95 % CI : 1.04 - 3.66 ) ; P = 0.031 ] . Other secondary clinical endpoints were similar between groups . The incidence of hypercalcaemia was 6.2 % ( n = 10 ) and 3.1 % ( n = 5 ) in patients receiving vitamin D or placebo ( P = 0.192 ) . Conclusion A daily vitamin D dose of 4000 IU did not reduce mortality in patients with advanced HF but was associated with a greater need for MCS implants . Data indicate caution regarding long-term supplementation with moderately high vitamin D doses . Trial Registration Information clinical trials.gov Idenitfier : NCT01326650 BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women OBJECTIVES Low vitamin D status has been shown to be associated with hypertension . We planned to research the effect of vitamin D and nifedipine in the treatment of patients with essential hypertension . METHODS Patients with grade s I-II essential hypertension were enrolled in this single-center , double-blind ,  placebo-controlled trial in Beijing . All patients received a conventional antihypertensive drug ( nifedipine , 30 mg/d ) . One hundred and twenty-six patients were r and omly assigned to receive vitamin D ( n=63 , 2000 IU/d ) or a placebo ( n=63 ) as an add-on to nifedipine , by the method of permutated block r and omization . Ambulatory blood pressure monitoring was performed at baseline ( month 0 ) , at month 3 and at month 6 . RESULTS In vitamin D supplementation group , there was a significant increase in mean 25-hydroxyvitamin D levels from baseline ( 19.4 ± 11.6 ng/ml ) to 6 months ( 34.1 ± 12.2 ng/ml ; p<0.001 ) . At 6 months , the primary end points , a difference in the fall of 24-h mean blood pressure , between the groups was -6.2 mmHg ( 95 % CI -11.2 ; -1.1 ) for systolic blood pressure ( p<0.001 ) and -4.2 mmHg ( 95 % CI -8.8 ; -0.3 ) for diastolic blood pressure ( p<0.001 ) under intention to treat analysis . In patients with vitamin D < 30 ng/ml at baseline ( n=113 ) , 24-h mean blood pressure decreased by 7.1/5.7 mmHg ( p<0.001 ) . Safety and tolerability were similar among the two groups . CONCLUSIONS Vitamin D supplementation can reduce blood pressure in patients with hypertension , it can be an adjuvant therapy for patients with grade s I-II essential hypertension . CLINICAL TRIAL REGISTRATION This study was registered in the Chinese Clinical Trial Registry , it is available in Website : http://www.chictr.org/cn/ ; REGISTRATION NUMBER ChiCTR-ONC-13003840 The need , safety , and effectiveness of vitamin D supplementation during pregnancy remain controversial . In this r and omized , controlled trial , women with a singleton pregnancy at 12 to 16 weeks ' gestation received 400 , 2000 , or 4000 IU of vitamin D(3 ) per day until delivery . The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [ 25(OH)D ] concentration at delivery , with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3 ) [ 1,25(OH)(2)D(3 ) ] production . Of the 494 women enrolled , 350 women continued until delivery : Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different ( p < 0.0001 ) , and the percent who achieved sufficiency was significantly different by group , greatest in 4000-IU group ( p < 0.0001 ) . The relative risk ( RR ) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups ( RR = 1.52 , 95 % CI 1.24 - 1.86 ) , the 4000- and the 400-IU groups ( RR = 1.60 , 95 % CI 1.32 - 1.95 ) but not between the 4000- and . 2000-IU groups ( RR = 1.06 , 95 % CI 0.93 - 1.19 ) . Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3 ) concentrations throughout pregnancy ( p < 0.0001 ) , with maximal production of 1,25(OH)(2)D(3 ) in all strata in the 4000-IU group . There were no differences between groups on any safety measure . Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels . It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race , whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations , especially in African Americans BACKGROUND Ergocalciferol ( vitamin D(2 ) ) supplementation plays a role in fall prevention , but the effect in patients living in the community in sunny climates remains uncertain . We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling . METHODS A 1-year population -based , double-blind , r and omized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth , Australia ( latitude , 32 degrees S ) , with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year . Participants were r and omized to receive ergocalciferol , 1000 IU/d , or identical placebo ( hereinafter , ergocalciferol and control groups , respectively ) . Both groups received calcium citrate , 1000 mg/d . Fall data were collected every 6 weeks . RESULTS Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height , which was significantly different between the 2 groups ( ergocalciferol group , 53.0 % ; control group , 62.9 % ; odds ratio [ OR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.37 - 0.99 ) . When those who fell were grouped by the season of first fall or the number of falls they had , ergocalciferol treatment reduced the risk of having the first fall in winter and spring ( ergocalciferol group , 25.2 % ; control group , 35.8 % ; OR , 0.55 ; 95 % CI , 0.32 - 0.96 ) but not in summer and autumn , and reduced the risk of having 1 fall ( ergocalciferol group , 21.2 % ; control group , 33.8 % ; OR , 0.50 ; 95 % CI , 0.28 - 0.88 ) but not multiple falls . CONCLUSION Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium , which is associated with a 19 % reduction in the relative risk of falling , mostly in winter Background Diabetes and vitamin D deficiency are global epidemics . Research ers have long been exploring the role of potentially modifiable factors to manage type 2 diabetes . We conducted a systematic review of prospect i ve studies and r and omized controlled trials that involved vitamin D supplementation and specifically intended to study glycemic outcomes related to type 2 diabetes . Methods Two authors independently search ed Medline and PubMed for longitudinal studies that had assessed the effect of vitamin D supplements on glycemic control , insulin resistance and beta-cell dysfunction in patients with diabetes . Results Seventeen r and omized control trials and seven longitudinal studies with a minimum follow-up of one month were included . Results of the various short-term studies ( follow up ≤ 3 months ) suggested that vitamin D supplementation had a positive impact on glycemic control and metabolic parameters such as insulin resistance and beta cell dysfunction . However , the evidence was weak due to the low method ological quality of the studies . There was no significant effect on HbA1c , beta cell function and insulin resistance in the long-term studies ( follow up > 3 months ) . There existed heterogeneity in the methodology of the studies , inclusion criteria , mode of supplementation of vitamin D and the duration of follow up . Conclusions Current evidence based on r and omized controlled trials and longitudinal studies do not support the notion that vitamin D supplementation can improve hyperglycemia , beta cell secretion or insulin sensitivity in patients with type 2 diabetes . Large-scale trials with proper study design , optimal vitamin D supplementation and longer follow up need to be conducted OBJECTIVE The purpose of this study was to prospect ively examine the association between vitamin D and calcium intake and risk of type 2 diabetes .  RESEARCH DESIGN AND METHODS In the Nurses ' Health Study , we followed 83,779 women who had no history of diabetes , cardiovascular disease , or cancer at baseline for the development of type 2 diabetes .  Vitamin D and calcium intake from diet and supplements was assessed every 2 - 4 years . During 20 years of follow-up , we documented 4,843 incident cases of type 2 diabetes . RESULTS After adjusting for multiple potential confounders , there was no association between total vitamin D intake and type 2 diabetes . However , the relative risk ( RR ) of type 2 diabetes was 0.87 ( 95 % CI 0.75 - 1.00 ; P for trend = 0.04 ) comparing the highest with the lowest category of vitamin D intake from supplements . The multivariate RRs of type 2 diabetes were 0.79 ( 0.70 - 0.90 ; P for trend < 0.001 ) comparing the highest with the lowest category of calcium intake from all sources and 0.82 ( 0.72 - 0.92 ; P for trend < 0.001 ) comparing the highest with the lowest category of calcium intake from supplements . A combined daily intake of > 1,200 mg calcium and > 800 IU vitamin D was associated with a 33 % lower risk of type 2 diabetes with RR of 0.67 ( 0.49 - 0.90 ) compared with an intake of < 600 mg and 400 IU calcium and vitamin D , respectively . CONCLUSIONS The results of this large prospect i ve study suggest a potential beneficial role for both vitamin D and calcium intake in reducing the risk of type 2 diabetes Background Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes ; however , the benefits of vitamin D supplementation during pregnancy remain unknown . Methods We conducted a double-blind placebo-controlled r and omized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal ( cord blood ) serum 25-hydroxyvitamin D ( 25(OH)D ) concentration ( primary biochemical efficacy outcome ) and maternal serum calcium concentration ( primary safety measure ) . Eligibility criteria were pregnant women aged 18 to < 35 years , at 26 to 29 weeks gestation , and residing in Dhaka , Bangladesh . 160 women were r and omized by 1:1 allocation to one of two parallel intervention groups ; placebo ( n = 80 ) or 35,000 IU/week of vitamin D3 ( n = 80 ) until delivery . All participants , study personnel and study investigators were blind to treatment allocation . Results Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline ( 45 vs. 44 nmol/L ; p = 0.66 ) , but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery ( 134 vs. 38 nmol/L ; p < 0.001 ) and newborns ( cord blood : 103 vs. 39 ; p < 0.001 ) . In the vitamin D group , 95 % of neonates and 100 % of mothers attained 25(OH)D > 50 nmol/L , versus 21 % mothers and 19 % of neonates in the placebo group . No participants met criteria for hypercalcemia , there were no known supplement-related adverse events , and major pregnancy outcomes were similar between groups . Conclusions Antenatal 3rd-trimester vitamin D3 supplementation ( 35,000 IU/week ) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns . Doses up to 35,000 IU/week may be cautiously used in further research aim ed at establishing the clinical effects and safety of vitamin D3 supplementation in pregnancy . Trial registration This trial was registered at Clinical Trials.gov ( NCT01126528 ) 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 Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections . This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections . Methodology / Findings In this prospect i ve cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults , blinded to the nature of the substance being measured . The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations . The incidence of infection in participants with different concentrations of vitamin D was determined . One hundred ninety-five ( 98.5 % ) of the enrolled participants completed the study . Light skin pigmentation , lean body mass , and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant ( p<0.0001 ) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill . Conclusions / Significance Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby , at least during the fall and winter in temperate zones . The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections , including influenza , in the general population and in sub population s with lower 25-hydroxyvitamin D concentrations , such as pregnant women , dark skinned individuals , and the obese Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33 BACKGROUND Vitamin D deficiency is recently speculated to play a role in the development of depression . Nevertheless , few studies have explored the association between blood 25-hydroxyvitamin D [ 25(OH)D ] concentrations and depression in the general population . Therefore , we aim ed to determine this association in middle-aged and elderly Chinese . METHODS We conducted a population -based cross-sectional study in 2005 in Beijing and Shanghai , China . Participants included 3262 community residents aged 50 - 70 . Depressive symptoms were defined as a Center for Epidemiological Studies of Depression Scale ( CES-D ) score of 16 or higher . Circulating 25(OH)D concentrations were measured by radioimmunoassay . RESULTS The prevalence of depressive symptoms was lower in the top tertile of 25(OH)D concentrations compared to the lowest tertile ( 7.2 % vs. 11.1 % ) in the study population ( odds ratio , 0.62 ; 95 % confidence interval , 0.46 - 0.83 ; P for trend=0.002 ) . This association was substantially attenuated after controlling for various confounding factors , and disappeared after including geographic location in the model . Stratified analysis by location did not find any association between depressive symptoms and 25(OH)D levels among participants from either Beijing or Shanghai . LIMITATIONS Due to the cross-sectional study design , causal relation remains unknown . CONCLUSIONS Depressive symptoms are not associated with 25(OH)D concentrations in middle-aged and elderly Chinese . Further prospect i ve studies are required to determine whether they are correlated In a double-blind trial of vitamin D supplements in pregnant Asian women calciferol ( ergocalciferol , 1000 IU/day ) was administered to 59 women and placebo to 67 controls during the last trimester . The two groups had similar distributions of maternal age , height , parity , number of vegetarians , countries of origin , and sex and gestation of the infants . At entry to the trial maternal serum 25-hydroxy vitamin D ( 25-OHD ) concentrations were low in both treatment and control groups and significantly lower in vegetarians than non-vegetarians . Mothers in the treatment group gained weight faster in the last trimester than those in the control group , and at term they and their infants all had adequate plasma 25-OHD concentrations , Mothers and infants in the control group , however , had low plasma concentrations of 25-OHD and calcium and raised plasma alkaline phosphatase ( bone isoenzyme ) activity . Five of these infants developed symptomatic hypocalcaemia . Almost twice as many infants in the control group were small for gestational age ( 29 % v 15 % ) , but there were no significant differences between the two groups of infants in antropometric measurements . Infants in the control group , however , had larger fontanelles , suggesting impaired ossification of the skull . Because of the benefits to mothers and infants in the treatment group and the absence of side effects , vitamin D supplements should be given to all pregnant Asian women in the United Kingdom Summary Background Vitamin D has a role in regulating immune function , and its deficiency is a suggested risk factor for childhood pneumonia . Our aim was to assess whether oral supplementation of vitamin D3 ( cholecalciferol ) will reduce the incidence and severity of pneumonia in a high-risk infant population . Methods We did a r and omised placebo-controlled trial to compare oral 100 000 IU ( 2·5 mg ) vitamin D3 with placebo given to children aged 1–11 months in Kabul , Afghanistan . R and omisation was by use of a computer-generated list . Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months . Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically . Our primary outcome was the first or only episode of radiologically confirmed pneumonia . Our analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00548379 . Findings 1524 children were assigned to receive vitamin D3 and 1522 placebo .  There was no significant difference between the incidence of first or only pneumonia between the vitamin D ( 0·145 per child per year , 95 % CI 0·129–0·164 ) and the placebo group ( 0.137 , 0·121–0·155 ) ; the incidence rate ratio was 1·06 ( 95 % CI 0·89–1·27 ) . From 652 children during five separate periods of testing serum calcifediol , only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group — a toxic level . Interpretations Quarterly bolus doses of oral vitamin D3 supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting . Funding Wellcome Trust and British Council BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma  25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day Respiratory tract infections ( RTIs ) are very common worldwide . We prospect ively demonstrate an association between low serum 25-hydroxyvitamin D level and increased risk of laboratory-confirmed viral upper RTI  in children . Future studies should evaluate the role of supplementation to reduce RTIs Most cancer epidemiologists would cite results from a r and omized clinical trial as both the ultimate arbiter of controversial findings from observational studies and the basis for cancer control interventions . Indeed , we consider a trial definitive when its intervention demonstrably lowers Background Epidemiological research links vitamin D status to various brain-related outcomes . However , few trials examine whether supplementation can improve such outcomes and none have examined effects on cognition . This study examined whether Vitamin D supplementation led to improvements in diverse measures of cognitive and emotional functioning , and hypothesised that supplementation would lead to improvements in these outcomes compared to placebo . Methods /Principal Findings Healthy young adults were recruited to a parallel-arm , double-blind trial conducted at The University of Queensl and . Participants were r and omly allocated to receive Vitamin D ( one capsule daily , containing 5000 IU cholecalciferol ) or identical placebo capsule for six weeks . All participants and outcome assessors were blinded to group assignment . Primary outcome measures assessed at baseline and 6 weeks were working memory , response inhibition and cognitive flexibility . Secondary outcomes were : hallucination-proneness , psychotic-like experiences , and ratings of depression , anxiety and anger .  128 participants were recruited , r and omised and included in primary analyses ( vitamin D n = 63 ; placebo n = 65 ) . Despite significant increases in vitamin D status in the active group , no significant changes were observed in working memory ( F = 1.09 ; p = 0.30 ) , response inhibition ( F = 0.82 ; p = 0.37 ) , cognitive flexibility ( F = 1.37 ; p = 0.24 ) or secondary outcomes . No serious adverse effects were reported . Conclusions Our findings indicate that vitamin D supplementation does not influence cognitive or emotional functioning in healthy young adults . Future controlled trials in targeted population s of interest are required to determine whether supplementation can improve functioning in these domains . Australian and New Zeal and Clinical Trials Registry ; ACTRN12610000318088 BACKGROUND Seasonal Affective Disorder ( SAD ) is a sub-type of depression that only occurs during the winter months . A reduction in vitamin D may be linked to SAD . Since vitamin D deficiency has been reported to be common in older people , vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group . OBJECTIVE To assess the effect of vitamin D supplementation on the mental health of older women . SETTING Primary care in three areas of the UK ( Herts , Newcastle , York ) . SUBJECTS Women aged 70 years or more recruited to the trial in the months May-October . INTERVENTION Eligible women were r and omised to receive calcium and vitamin D supplementation or no supplementation . OUTCOME MEASURE At baseline and the six monthly assessment the mental component score ( MCS ) , calculated from the SF-12 question naire was used to assess participants ' subjective psychological well-being . RESULTS A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October ( 1205 woman in the control group and 912 women in the intervention group ) . Of these women , 1621 had a  MCS score at baseline and six months . Comparison of the six month mean MCS scores , adjusting for baseline MCS score and age , showed there was no significant difference between the two scores ( p = 0.262 ) . CONCLUSIONS Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores BACKGROUND Results of several epidemiologic and clinical studies have suggested that there is an excess risk of hypertension and diabetes mellitus in persons with suboptimal intake of vitamin D.  METHODS We examined the association between serum levels of  25-hydroxyvitamin D ( 25[OH]D )  and select cardiovascular disease risk factors in US adults . A secondary analysis was performed with data from the Third National Health and Nutrition Examination Survey , a national probability survey conducted by the National Center for Health Statistics between January 1 , 1988 , and December 31 , 1994 , with oversampling of persons 60 years and older , non-Hispanic black individuals , and Mexican American individuals . RESULTS There were 7186 male and 7902 female adults 20 years and older with available data in the Third National Health and Nutrition Examination Survey . The mean 25(OH)D level in the overall sample was 30 ng/mL ( 75 nmol/L ) . The 25(OH)D levels were lower in women , elderly persons ( > or=60 years ) , racial/ethnic minorities , and participants with obesity , hypertension , and diabetes mellitus . The adjusted prevalence of hypertension ( odds ratio [ OR ] , 1.30 ) , diabetes mellitus ( OR , 1.98 ) , obesity ( OR , 2.29 ) , and high serum triglyceride levels ( OR , 1.47 ) was significantly higher in the first than in the fourth quartile of serum 25(OH)D levels ( P<.001 for all ) . CONCLUSIONS Serum 25(OH)D levels are associated with important cardiovascular disease risk factors in US adults . Prospect i ve studies to assess a direct benefit of cholecalciferol ( vitamin D ) supplementation on cardiovascular disease risk factors are warranted OBJECTIVES The objective of the present study was to examine the cross-sectional relation between serum 25-hydroxyvitamin D [ 25-(OH ) D ] levels and  depression in overweight and obese subjects and to assess the effect of vitamin D supplementation on depressive symptoms . DESIGN Cross-sectional study and r and omized double blind controlled trial of 20,000 or 40,000 IU vitamin D per week versus placebo for 1 year . SETTING A total of 441 subjects ( body mass index 28 - 47 kg m(-2 ) , 159 men and 282 women , aged 21 - 70 years ) recruited by advertisements or from the out-patient clinic at the University Hospital of North Norway . MAIN OUTCOME MEASURES Beck Depression Inventory ( BDI ) score with subscales 1 - 13 and 14 - 21 . RESULTS Subjects with serum 25(OH)D levels < 40 nmol L(-1 ) scored significantly higher ( more depressive traits ) than those with serum 25(OH)D levels > or = 40 nmol L(-1 ) on the BDI total [ 6.0 ( 0 - 23 ) versus 4.5 ( 0 - 28 ) ( median and range ) ] and the BDI subscale 1 - 13 [ 2.0 ( 0 - 15 ) versus 1.0 ( 0 - 29.5 ) ] ( P < 0.05 ) . In the two groups given vitamin D , but not in the placebo group , there was a significant improvement in BDI scores after 1 year . There was a significant decrease in serum parathyroid hormone in the two vitamin D groups without a concomitant increase in serum calcium . CONCLUSIONS It appears to be a relation between serum levels of 25(OH)D and symptoms of depression . Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship Importance Evidence suggests that low vitamin D status may increase the risk of cancer . Objective To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of  cancer among older women . Design , Setting , and Participants A 4-year , double-blind , placebo-controlled , population -based r and omized clinical trial in 31 rural counties ( June 24 , 2009 , to August 26 , 2015—the final date of follow-up ) . A total of 2303 healthy postmenopausal women 55 years or older were r and omized , 1156 to the treatment group and 1147 to the placebo group . Duration of treatment was 4 years . Interventions The treatment group ( vitamin D3 + calcium group ) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium ; the placebo group received identical placebos . Main Outcomes and Measures The primary outcome was the incidence of all-type cancer ( excluding nonmelanoma skin cancers ) , which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling . Results Among 2303 r and omized women ( mean age , 65.2 years [ SD , 7.0 ] ; mean baseline serum 25-hydroxyvitamin D level , 32.8 ng/mL [ SD , 10.5 ] ) , 2064 ( 90 % ) completed the study . At year 1 , serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group . A new diagnosis of cancer was confirmed in 109 participants , 45 ( 3.89 % ) in the vitamin D3 + calcium group and 64 ( 5.58 % ) in the placebo group ( difference , 1.69 % [ 95 % CI , −0.06 % to 3.46 % ] ; P = .06 ) . Kaplan-Meier incidence over 4 years was 0.042 ( 95 % CI , 0.032 to 0.056 ) in the vitamin D3 + calcium group and 0.060 ( 95 % CI , 0.048 to 0.076 ) in the placebo group ; P = .06 . In unadjusted Cox proportional hazards regression , the hazard ratio was 0.70 ( 95 % CI , 0.47 to 1.02 ) . Adverse events potentially related to the study included renal calculi ( 16 participants in the vitamin D3 + calcium group and 10 in the placebo group ) , and elevated serum calcium levels ( 6 in the vitamin D3 + calcium group and 2 in the placebo group ) . Conclusions and Relevance Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL , supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years . Further research is necessary to assess the possible role of vitamin D in cancer prevention . Trial Registration clinical trials.gov Identifier : BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer  among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this null finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . ) Higher vitamin D concentrations have been proposed as a protective ' seasonal stimulus ' against influenza , and there are suggestions for associations with other aspects of respiratory health . The aim of the present study was to investigate the relationship of current vitamin D status ( measured by 25-hydroxyvitamin D , 25(OH)D ) with  respiratory infections and lung function .  We used cross-sectional data from 6789 participants in the nationwide 1958 British birth cohort who had measurements of 25(OH)D , lung function ( forced expiratory volume in 1 s ( FEV1 ) and forced vital capacity ( FVC ) ) and respiratory infections available from the age of 45 years . In this population , the prevalence of respiratory infections had a strong seasonal pattern in the opposite direction to the pattern for 25(OH)D concentrations . Each 10 nmol/l increase in 25(OH)D was associated with a 7 % lower risk of infection ( 95 % CI 3 , 11 % ) after adjustment for adiposity , lifestyle and socio-economic factors . For FEV1 and FVC , each 10 nmol/l increase in 25(OH)D was associated with 8 ( 95 % CI 3 , 13 ) ml and 13 ( 95 % CI 7 , 20 ) ml higher volume , respectively , after controlling for covariates . Associations of 25(OH)D with FEV1 and FVC were only slightly attenuated after further adjustment for infection and other respiratory illness . In conclusion , vitamin D status had a linear relationship with respiratory infections and lung function . R and omised controlled trials are warranted to investigate the role of vitamin D supplementation on respiratory health and to establish the underlying mechanisms Abstract Mood changes synchronised to the seasons exist on a continuum between individuals , with anxiety and depression increasing during the winter months . An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder ( SAD ) with carbohydrate craving , hypersomnia , lethargy , and changes in circadian rhythms also evident . It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3 , the hormone of sunlight , leading to changes in brain serotonin . Forty-four healthy subjects were given 400 IU , 800 IU , or no vitamin D3 for 5 days during late winter in a r and om double-blind study . Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect . Results are discussed in terms of their implication s for seasonality , SAD , serotonin , food preference , sleep , and circadian rhythms BACKGROUND Recent studies suggest a role for vitamin D in innate immunity , including the prevention of respiratory tract infections ( RTIs ) . We hypothesize that serum 25-hydroxyvitamin D ( 25[OH]D ) levels are inversely associated with self-reported recent upper RTI ( URTI ) . METHODS We performed a secondary analysis of the Third National Health and Nutrition Examination Survey , a probability survey of the US population conducted between 1988 and 1994 . We examined the association between 25(OH)D level  and  recent URTI in 18 883 participants 12 years and older . The analysis adjusted for demographics and clinical factors ( season , body mass index , smoking history , asthma , and chronic obstructive pulmonary disease ) . RESULTS The median serum 25(OH)D level was 29 ng/mL ( to convert to nanomoles per liter , multiply by 2.496 ) ( interquartile range , 21 - 37 ng/mL ) , and 19 % ( 95 % confidence interval [ CI ] , 18%-20 % ) of participants reported a recent URTI . Recent URTI was reported by 24 % of participants with 25(OH)D levels less than 10 ng/mL , by 20 % with levels of 10 to less than 30 ng/mL , and by 17 % with levels of 30 ng/mL or more ( P < .001 ) . Even after adjusting for demographic and clinical characteristics , lower 25(OH)D levels were independently associated with recent URTI ( compared with 25[OH]D levels of > or = 30 ng/mL : odds ratio [ OR ] , 1.36 ; 95 % CI , 1.01 - 1.84 for < 10 ng/mL and 1.24 ; 1.07 - 1.43 for 10 to < 30 ng/mL ) . The association between 25(OH)D level and URTI seemed to be stronger in individuals with asthma and chronic obstructive pulmonary disease ( OR , 5.67 and 2.26 , respectively ) . CONCLUSIONS Serum 25(OH)D levels are inversely associated with recent URTI . This association may be stronger in those with respiratory tract diseases . R and omized controlled trials are warranted to explore the effects of vitamin D supplementation on RTI Evidence for a role of supplemental vitamin D and marine omega-3 fatty acids in preventing cancer and cardiovascular disease ( CVD ) remains inconclusive and insufficient to inform nutritional recommendations for primary prevention . The VITamin D and Omega-A 3 TriaL ( VITAL ) is an ongoing nationwide , r and omized , double-blind , placebo-controlled clinical trial design ed to fill this knowledge gap . The study population consists of 25,874 U.S. adults without cancer or CVD at baseline , who were selected only on age ( men aged ≥50 and women aged ≥55 ) , with an oversampling of African Americans ( n=5,107 ) . In a 2 × 2 factorial design , participants were r and omized to one of four supplement groups : [ 1 ] active vitamin D3 ( cholecalciferol ; 2000 IU/d ) and active marine omega-3 fatty acids ( Omacor ® fish oil , eicosapentaenoic acid [ EPA ] and docosahexaenoic acid [ DHA ] , 1g/d ) ; [ 2 ] active vitamin D and omega-3 placebo ; [ 3 ] vitamin D placebo and active marine omega-3 fatty acids ; or [ 4 ] vitamin D placebo and omega-3 placebo . The mean length of the r and omized treatment period will be 5 years . The r and omization was successful , as evidence d by similar distributions of baseline demographic , health , and behavioral characteristics across treatment groups . The similar distribution of known potential confounders across treatment groups strongly suggests that unmeasured or unknown potential confounders are also equally distributed . VITAL is expected to provide important information on the benefit-risk balance of vitamin D and omega-3 fatty acid supplementation when taken for the primary prevention of cancer and CVD BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo .  Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) Abstract The correlation between vitamin D deficiency and depression has recently been put forward and result ed in controversial findings . The present study was conducted to find out the effect of 2 single injections of 150,000 and 300,000 IU of vitamin D on improving the depression in depressed patients with vitamin D deficiency . This clinical trial study was carried out during 2011–2012 in Yazd , Islamic Republic of Iran . A total of 120 patients who had a Beck Depression Inventory II score of 17 + and were affected with vitamin D deficiency were r and omly assigned to 3 groups of 40 . They included G300 , G150 , and NTG . G300 and G150 received an intramuscular single dose of 300,000 and 150,000 IU of vitamin D , respectively , and the NTG group received nothing . After 3 months of intervention , the depression state , serum vitamin D , calcium , phosphorus , and parathormone were measured . The median of serum vitamin D after intervention were 60.2 , 54.6 , and 28.2 nmol/L ( P < 0.001 ) for the G300 , G150 , and NTG , respectively . Percentages of vitamin D deficiency after intervention were 18 , 20 , and 91.2 for the groups , respectively . The serum calcium mean showed a statistically significant increase in just the 2 test groups receiving vitamin D. There was only significant difference in mean of Beck Depression Inventory II test score between G300 and NTG ( P = 0.003).The results of the study revealed that first , the correction of vitamin D deficiency improved the depression state , and second , a single injection dose of 300,000 IU of vitamin D was safe and more effective than a 150,000-IU dose IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled  r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure < 90 mm Hg ) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were r and omized into the trial from June 1 , 2009 , through May 31 , 2011 . INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) .  Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P < .001 ) . No significant treatment effect was seen for mean ( 95 % CI ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858 OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group .  Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation Calcium supplementation is effective in reducing blood pressure in various states of hypertension , including pregnancy-induced hypertension and preeclampsia . In addition , calcitropic hormones are associated with blood pressure . The hypothesis is that short-term therapy with calcium and vitamin D(3 ) may improve blood pressure as well as secondary hyperparathyroidism more effectively than calcium monotherapy . The effects of 8 weeks of supplementation with vitamin D(3 ) ( cholecalciferol ) and calcium on blood pressure and biochemical measures of bone metabolism were studied . The sample consisted of 148 women ( mean + /- SD age , 74 + /- 1 yr ) with a 25-hydroxycholecalciferol ( 25OHD(3 ) ) level below 50 nmol/L. They received either 1200 mg calcium plus 800 IU vitamin D(3 ) or 1200 mg calcium/day . We measured intact PTH , 25OHD(3 ) , 1,25-dihydroxyvitamin D(3 ) , blood pressure , and heart rate before and after treatment . Compared with calcium , supplementation with vitamin D(3 ) and calcium result ed in an increase in serum 25OHD(3 ) of 72 % ( P < 0.01 ) , a decrease in serum PTH of 17 % ( P = 0.04 ) , a decrease in systolic blood pressure ( SBP ) of 9.3 % ( P = 0.02 ) , and a decrease in heart rate of 5.4 % ( P = 0.02 ) . Sixty subjects ( 81 % ) in the  vitamin D(3 ) and calcium group compared with 35 ( 47 % ) subjects in the calcium group showed a decrease in SBP of 5 mm Hg or more ( P = 0.04 ) . No statistically significant difference was observed in the diastolic blood pressures of the calcium-treated and calcium- plus vitamin D(3)-treated groups ( P = 0.10 ) . Pearson coefficients of correlation between the change in PTH and the change in SBP were 0.49 ( P < 0.01 ) for the vitamin D(3 ) plus calcium group and 0.23 ( P < 0.01 ) for the calcium group . A short-term supplementation with vitamin D(3 ) and calcium is more effective in reducing SBP than calcium alone . Inadequate vitamin D(3 ) and calcium intake could play a contributory role in the pathogenesis and progression of hypertension and cardiovascular disease in elderly women Although geographic ecological studies and observational studies find that ultraviolet B exposure and 25-hydroxyvitamin D [ 25(OH)D ] concentrations are inversely correlated with 15–20 types of cancer , few r and omized controlled trials ( RCTs ) of vitamin D support those findings . The poor design of some RCTs may account for that lack of support . Most vitamin D RCTs to date have considered the vitamin D dose , rather than initial , final , or changes in , serum 25(OH)D concentrations . Here a model is developed for use in design ing and analyzing vitamin D RCTs with application to cancer incidence . The input variables of the model are  vitamin D dose , baseline and achieved 25(OH)D concentrations , known rates of cancer for the population  , and numbers of participants for the treatment and placebo arms is estimated — vitamin D dosage and numbers of participants are varied to achieve desired hazard ratio significance , using information from two  vitamin D RCTs on cancer incidence conducted in Nebraska with good agreement between the model estimates and reported hazard ratios . Further improvements to the conduct of vitamin D RCTs would be to start the trial with a moderate bolus dose to achieve the desired 25(OH)D concentrations , and bloodspot 25(OH)D assay use in summer and winter annually to monitor seasonal and long-term changes in 25(OH)D concentration and compliance , and to allow dosage adjustment for achievement of desired vitamin D status Seasonal Affective Disorder ( SAD ) is prevalent when vitamin D stores are typically low . Broad-spectrum light therapy includes wavelengths between 280 - 320 nm which allow the skin to produce vitamin D. This study was design ed to test the hypothesis that vitamin D deficiency might play a role in SAD . A prospect i ve , r and omized controlled trial was conducted in a group of 15 subjects with SAD . Eight subjects received 100,000 I.U. of vitamin D and seven subjects received phototherapy . At the onset of treatment and after 1 month of therapy subjects were administered the Hamilton Depression scale , the SIGH-SAD , and the SAD-8 depression scale . All subjects also had serum levels of 25-hydroxyvitamin D ( 25-OH D ) measured before and 1 week after intervention therapy . All subjects receiving vitamin D improved in all outcome measures . The phototherapy group showed no significant change in depression scale measures . Vitamin D status improved in both groups ( 74 % vitamin D group , p < 0.005 and 36 % phototherapy group , p < 0.01 ) . Improvement in 25-OH D was significantly associated with improvement in depression scale scores ( r2=0.26 ; p=0.05 ) . Vitamin D may be an important treatment for SAD . Further studies will be necessary to confirm these findings Objective : To compare the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder . Methods : In the present double-blind , r and omized , placebo-controlled trial , 42 patients with a diagnosis of major depressive disorder based on DSM-IV criteria were r and omly assigned into two groups to receive daily either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for 8 weeks . Depression severity was assessed at 2-week intervals using the 24-item Hamilton Depression Rating Scale ( HDRS ) as a primary outcome measure and the 21-item Beck Depression Inventory ( BDI ) as a secondary outcome measure . Serum 25(OH ) vitamin D was measured at baseline and after intervention . Results : Forty patients completed the trial . A two-way repeated- measures analysis of variance showed that depression severity based on HDRS and BDI decreased significantly after intervention , with a significant difference between the two groups . The vitamin D + fluoxetine combination was significantly better than fluoxetine alone from the fourth week of treatment . Conclusions : In the present 8-week trial , the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms BACKGROUND In cross-sectional studies , low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease . This study aim ed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality . METHODS Prospect i ve cohort study of 3258 consecutive male and female patients ( mean [ SD ] age , 62 [ 10 ] years ) scheduled for coronary angiography at a single tertiary center . We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings . The main outcome measures were all-cause and cardiovascular deaths . RESULTS During a median follow-up period of 7.7 years , 737 patients ( 22.6 % ) died , including 463 deaths from cardiovascular causes . Multivariate-adjusted hazard ratios ( HRs ) for patients in the lower two 25-hydroxyvitamin D quartiles ( median , 7.6 and 13.3 ng/mL [ to convert 25-hydroxyvitamin D levels to nanomoles per liter , multiply by 2.496 ] ) were higher for all-cause mortality ( HR , 2.08 ; 95 % confidence interval [ CI ] , 1.60 - 2.70 ; and HR , 1.53 ; 95 % CI , 1.17 - 2.01 ; respectively ) and for cardiovascular mortality ( HR , 2.22 ; 95 % CI , 1.57 - 3.13 ; and HR , 1.82 ; 95 % CI , 1.29 - 2.58 ; respectively ) compared with patients in the highest 25-hydroxyvitamin D quartile ( median , 28.4 ng/mL ) . Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile . These effects were independent of coronary artery disease , physical activity level , Charlson Comorbidity Index , variables of mineral metabolism , and New York Heart Association functional class . Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation ( C-reactive protein and interleukin 6 levels ) , oxidative burden ( serum phospholipid and glutathione levels ) , and cell adhesion ( vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels ) . CONCLUSIONS Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality . A causal relationship has yet to be proved by intervention trials using vitamin Objective : Results from studies examining associations between serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations and depressive symptoms are equivocal . We investigated the relationship between serum 25(OH)D concentrations and symptoms of depression , anxiety and stress in a cross-sectional analysis of a population -based sample of young adults participating in the Western Australian Pregnancy Cohort ( Raine ) Study . Methods : Participants provided a blood sample at the 20-year follow-up ( March 2010-April 2012 ) for the  measurement of serum 25(OH)D concentrations .  Mental health symptoms were assessed using the  21-item Depression Anxiety Stress Scales ( DASS-21 ) . Associations between serum 25(OH)D concentrations and total DASS-21 scores and subscale scores of depression , anxiety and stress were explored in males and females using negative binomial regression , adjusting for age , race , body mass index ( BMI ) and physical activity ( n=735 ) . Models examining subscale scores were also adjusted for the other subscale scores . Results : After adjusting for confounders , an increase in serum 25(OH)D concentrations of 10 nmol/L decreased total DASS-21 scores in males by 9 % ( rate ratio ( RR ) 0.91 ; 95%CI 0.87,0.95 ; p<0.001 ) and depression subscale scores in males by 8 % ( RR 0.92 ; 95%CI 0.87,0.96 ; p=0.001 ) . However , in adjusted models there were no significant associations between serum 25(OH)D concentrations and symptoms of anxiety and stress in males . There were no significant associations between serum 25(OH)D concentrations and symptoms of depression , anxiety and stress in females . Conclusions : We found an association between serum 25(OH)D concentrations and symptoms of depression , but not anxiety and stress , in males . R and omised controlled trials are necessary to determine any benefit of vitamin D supplementation in the prevention and treatment of depressive symptoms in young adults Data from laboratory studies , observational research , and /or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease ( CVD ) , but primary prevention trials with adequate dosing in general population s ( i.e. , unselected for disease risk ) are lacking . The ongoing VITamin D and OmegA-3 TriaL ( VITAL ) is a large r and omized , double-blind , placebo-controlled , 2 x 2 factorial trial of vitamin D ( in the form of vitamin D(3 ) [ cholecalciferol ] , 2000 IU/day ) and marine omega-3 fatty acid ( Omacor fish oil , eicosapentaenoic acid [EPA]+docosahexaenoic acid [ DHA ] , 1g/day ) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 U.S. men aged ≥ 50 and women aged ≥ 55 . The mean treatment period will be 5 years . Baseline blood sample s will be collected in at least 16,000 participants , with follow-up blood collection in about 6000 participants . Yearly follow-up question naires will assess treatment compliance ( plasma biomarker measures will also assess compliance in a r and om sample of participants ) , use of non- study drugs or supplements , occurrence of endpoints , and cancer and vascular risk factors . Self-reported endpoints will be confirmed by medical record review by physicians blinded to treatment assignment , and deaths will be ascertained through national registries and other sources . Ancillary studies will investigate whether these agents affect risk for diabetes and glucose intolerance ; hypertension ; cognitive decline ; depression ; osteoporosis and fracture ; physical disability and falls ; asthma and other respiratory diseases ; infections ; and rheumatoid arthritis , systemic lupus erythematosus , thyroid diseases , and other autoimmune disorders While observational studies have suggested that vitamin D deficiency increases risk of depression , few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms . The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3 ) combined with 1,000 mg of elemental calcium on measures of depression in a r and omized , double-blinded US trial comprising 36,282 postmenopausal women . The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at r and omization ( 1995 - 2000 ) . Two years later , women again reported on their antidepressant use , and 2,263 completed a second Burnam scale . After 2 years , women r and omized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms ( Burnam score ≥0.06 ) of 1.16 ( 95 % confidence interval : 0.86 , 1.56 ) compared with women in the placebo group . Supplementation was not associated with antidepressant use ( odds ratio = 1.01 , 95 % confidence interval : 0.92 , 1.12 ) or continuous depressive symptom score . Results stratified by  baseline vitamin D and calcium intake , solar irradiance , and other factors were similar . The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3 ) along  with calcium and depression in older women . Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression & NA ; A r and omized study was conducted to evaluate the effects of single‐dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France . The women were divided into three r and omized groups : one ( N = 21 ) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy , one ( N = 27 ) was given a single oral dose of 5 mg at the seventh month of pregnancy , and one ( N = 29 ) acted as a control . Venous plasma sample s were obtained at delivery from the women and from cord blood , and levels of calcium , 25‐OHD , and 1,25(OH)2D were determined . No significant difference in plasma calcium concentration was found among the three groups , but within each group plasma calcium concentrations were higher in the cord sample s than in the respective maternal sample s. The levels of the two metabolites measured were consistently lower in the cord sample s than in the respective maternal sample s. Cord 25‐OHD concentrations correlated with those of maternal plasma . No significant modification of maternal calciuria or of the birth weight of term infants was observed . 25‐OHD concentrations were greater in maternal and cord plasma from treated mothers , but only a slight difference was observed between the supplemented groups . 1,25(OH)2D concentrations were not significantly different in the three groups . A single 5‐mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors ’ region . ( Obstet Gynecol 68:300 , 1986 CONTEXT Vitamin D or calcium supplementation may have effects on  vascular disease and cancer .  OBJECTIVE Our objective was to investigate whether vitamin D or calcium supplementation affects mortality , vascular disease , and cancer in older people . DESIGN AND SETTING The study included long-term follow-up of participants in a two by two factorial , r and omized controlled trial from 21 orthopedic centers in the United Kingdom . PARTICIPANTS Participants were 5292 people ( 85 % women ) aged at least 70 yr with previous low-trauma fracture . INTERVENTIONS Participants were r and omly allocated to daily vitamin D(3 ) ( 800 IU ) , calcium ( 1000 mg ) , both , or placebo for 24 - 62 months , with a follow-up of 3 yr after intervention . MAIN OUTCOME MEASURES All-cause mortality , vascular disease mortality , cancer mortality , and cancer incidence were evaluated . RESULTS In intention-to-treat analyses , mortality [ hazard ratio ( HR ) = 0.93 ; 95 % confidence interval ( CI ) = 0.85 - 1.02 ] , vascular disease mortality ( HR = 0.91 ; 95 % CI = 0.79 - 1.05 ) , cancer mortality ( HR = 0.85 ; 95 % CI = 0.68 - 1.06 ) , and cancer incidence ( HR = 1.07 ; 95 % CI = 0.92 - 1.25 ) did not differ significantly between participants allocated vitamin D and those not . All-cause mortality ( HR = 1.03 ; 95 % CI = 0.94 - 1.13 ) , vascular disease mortality ( HR = 1.07 ; 95 % CI = 0.92 - 1.24 ) , cancer mortality ( HR = 1.13 ; 95 % CI = 0.91 - 1.40 ) , and cancer incidence ( HR = 1.06 ; 95 % CI = 0.91 - 1.23 ) also did not differ significantly between participants allocated calcium and those not . In a post hoc statistical analysis adjusting for compliance , thus with fewer participants , trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated , although all results remain nonsignificant . CONCLUSIONS Daily vitamin D or calcium supplementation did not affect mortality , vascular disease , cancer mortality , or cancer incidence BACKGROUND Frequent use of personal , non protocol calcium supplements obscured an adverse effect of coadministered calcium and vitamin D ( CaD ) on cardiovascular risk in the Women 's Health Initiative ( WHI ) . OBJECTIVE We investigated the effects of the use of personal calcium or vitamin D supplements on other outcomes in the WHI CaD Study ( WHI CaD ) by using the WHI limited-access clinical trials data set . DESIGN The WHI CaD was a 7-y , r and omized , placebo-controlled trial of CaD ( 1 g Ca/400 IU vitamin D daily ) in 36,282 community-dwelling , postmenopausal women . The incidence of total cancer ( excluding nonmelanoma skin cancers ) , breast and colorectal cancers , hip and total fracture , and mortality was assessed by using Cox proportional hazards models . RESULTS In the WHI CaD , interactions between the use of either personal calcium or vitamin D supplements and CaD were found for total , breast , and colorectal cancers but not for fracture or mortality .  In 15,646 women ( 43 % ) who were not taking personal calcium or vitamin D supplements at r and omization , CaD significantly decreased the risk of total , breast , and invasive breast cancers by 14 - 20 % and nonsignificantly reduced the risk of colorectal cancer by 17 % . In women taking personal calcium or vitamin D supplements , CaD did not alter cancer risk ( HR : 1.06 - 1.26 ) . CONCLUSIONS For women in the WHI CaD who were not taking personal calcium or vitamin D supplements at r and omization , CaD decreased the risk of total , breast , and colorectal cancers and did not change the risk of fractures or total mortality . The nonskeletal effects of CaD may be more important than the skeletal effects and should be considered when evaluating these supplements . The WHI CaD trial is registered at clinical trials.gov as NCT00000611 Observational studies in primary hyperaldosteronism suggest a positive relationship between aldosterone and parathyroid hormone ( PTH ) ; however , interventions to better characterize the physiological relationship between the renin – angiotensin – aldosterone system ( RAAS ) and PTH are needed . We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without primary hyperaldosteronism .  PTH was measured before and after study ( 1 ) low-dose angiotensin II ( Ang II ) infusion ( 1 ng/kg per minute ) and captopril administration ( 25 mg × 1 ) ; study ( 2 ) high-dose Ang II infusion ( 3 ng/kg per minute ) ; study ( 3 ) blinded crossover r and omization to aldosterone infusion ( 0.7 µg/kg per hour ) and vehicle ; and study ( 4 ) blinded r and omization to spironolactone ( 50 mg/daily ) or placebo for 6 weeks . Infusion of Ang II at 1 ng/kg per minute acutely increased aldosterone ( + 148 % ) and PTH ( + 10.3 % ) , whereas Ang II at 3 ng/kg per minute induced larger incremental changes in aldosterone ( + 241 % ) and PTH ( + 36 % ; P<0.01 ) . Captopril  acutely decreased aldosterone ( −12 % ) and PTH ( −9.7 % ; P<0.01 ) . In contrast , aldosterone infusion robustly raised serum aldosterone ( + 892 % ) without modifying PTH . However , spironolactone therapy during 6 weeks modestly lowered PTH when compared with placebo ( P<0.05 ) . In vitro studies revealed the presence of Ang II type I and mineralocorticoid receptor mRNA and protein expression in normal and adenomatous human parathyroid tissues . We observed novel pleiotropic relationships between RAAS components and the regulation of PTH in individuals without primary hyperaldosteronism : the acute modulation of PTH by the RAAS seems to be mediated by Ang II , whereas the long-term influence of the RAAS on PTH may involve aldosterone . Future studies to evaluate the impact of RAAS inhibitors in treating PTH-mediated disorders are warranted OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( < 12 ng/mL ) at baseline . CONCLUSION Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people A 1-year prospect i ve study of seasonal mood changes was conducted in 250 female Boston area residents , aged 43 to 72 , who were participants in a study of vitamin D supplementation .  Each woman completed the Profile of Mood States question naire at four study visits . There were significant changes over the year in scores for Tension-Anxiety , Depression-Dejection , Anger-Hostility , Fatigue-Inertia , and Confusion-Bewilderment . These scores were all highest or " worst " in the fall and lowest in the spring or summer . Worse mood scores were associated with fewer hours of sleep . Serum thyroxine was positively associated with higher Depression-Dejection scores in August through November and with higher ( better ) Vigor-Activity scores in February through May. Supplementation with 400 IU of vitamin D did not appear to affect levels or changes in mood scores OBJECTIVE The objective of the study was to determine whether vitamin D ( vitD ) supplementation during pregnancy affects obstetric and neonatal outcomes . SETTING The study was conducted at a university hospital in Karachi , Pakistan . METHODS The study was a single-center , open-label , r and omized , controlled trial of routine care ( group A , 200 mg ferrous sulfate and 600 mg calcium daily ) vs vitD supplementation ( group B , 4000 IU vitamin D3 daily ) , started at 20 weeks and continued till delivery . Maternal serum sample s of 25-hydroxyvitamin D ( 25OHD ) were collected at baseline and delivery . Neonatal vitD status was assessed in cord blood or in neonatal serum sample s within 48 hours of birth . Obstetric outcomes included gestational hypertension , gestational diabetes , and preterm labor , and neonatal well-being included small for gestational age , birth weight , length , head circumference , and 1- and 5-minute Apgar scores . RESULTS Of 207 gravidae enrolled , 193 completed the trial .  Maternal age , vitD status , and gestational age at enrollment were comparable between the two groups . At delivery , maternal 25OHD was increased in group B ( 18.3 ± 11 ng/dL vs 8.82 ± 11.84 ng/dL ( P = .001 ) compared with group A ( 6.9 ± 7.0 ng/dL vs 6.32 ± 3.97 ng/dL , P = .06 ) . The obstetric outcomes were comparable between the two groups ( P > .05 ) . Neonatal 25OHD levels were significantly higher in group B compared with group A ( 19.22 ± 12.19 ng/dL vs 6.27 ± 5.2 ng/dL ) . There was positive correlation between maternal and neonatal 25OHD levels ( r = 0.83 , P = .001 ) . One- and 5-minute Apgar scores were significantly higher in group B ( 7.10 ± 0.66 vs 6.90 ± 0.50 , P = .026 , and 8.53 ± 0.68 vs 8.33 ± 0.81 , P = .051 , respectively ) . Neonatal anthropometric parameters were comparable between the two groups ( P > .05 ) . CONCLUSION Maternal vitD supplementation improved maternal and neonatal vitD status This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine ( IOM ) . An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes . The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health , consistent with a cause- and -effect relationship and providing a sound basis for determination of intake requirements . For extraskeletal outcomes , including cancer , cardiovascular disease , diabetes , and autoimmune disorders , the evidence was inconsistent , inconclusive as to causality , and insufficient to inform nutritional requirements . R and omized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative . Based on bone health , Recommended Dietary Allowances ( RDAs ; covering requirements of ≥97.5 % of the population ) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age . For vitamin D , RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older , corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml ( 50 nmol/liter ) , meet the requirements of at least 97.5 % of the population . RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer . Higher values were not consistently associated with greater benefit , and for some outcomes U-shaped associations were observed , with risks at both low and high levels . The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated . Urgent research and clinical priorities were identified , including re assessment of laboratory ranges for 25-hydroxyvitamin D , to avoid problems of both undertreatment and overtreatment BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo .  Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people AIMS To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels . METHODS Double-blind , parallel group , placebo-controlled r and omized trial . A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter , when levels of circulating 25-hydroxyvitamin D were likely to be lowest . Patients were enrolled if their baseline 25-hydroxyvitamin D level was < 50 nmol/l .  Endothelial function and blood pressure were measured and fasting blood sample s were taken at baseline and 8 weeks after administration of vitamin D. RESULTS Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels < 50 nmol/l . Thirty-four subjects completed the study , with a mean age of 64 years and a baseline 25-hydroxyvitamin D level of 38.3 nmol/l .  Vitamin D supplementation  increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation ( FMD ) of the brachial artery by 2.3 % . The improvement in FMD remained significant after adjusting for changes in blood pressure .  Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo ; this did not correlate with change in FMD . CONCLUSIONS Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotl and . A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency OBJECTIVE To examine the association of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment in a r and omized , double-blind , placebo-controlled trial . METHODS Adult primary care patients in Duluth , Minnesota , were screened for vitamin D deficiency in February 2007 . Participants completed question naires pertaining to a variety of symptoms , vitamin D intake , and selected medical conditions . Patients with mild to moderate vitamin D deficiency ( 25-hydroxyvitamin D [ 25(OH)D ] , 10 - 25 ng/mL ) participated in a r and omized controlled trial ( RCT ) of vitamin D replacement and its effect on symptoms . Participants were r and omly assigned to receive 50 000 units of cholecalciferol ( vitamin D3 ) weekly or placebo for 8 weeks . Patients with severe vitamin D deficiency ( 25[OH]D < 10 ng/mL ) were treated in an unblinded fashion , and symptoms were reevaluated post treatment . RESULTS A total of 610 patients underwent initial screening , and 100 patients with mild to moderate vitamin D deficiency participated in the RCT . Thirty-eight severely deficient patients were treated in an unblinded fashion . On initial screening , 46.2 % of participants were deficient in vitamin D. Self-reported vitamin D supplementation , milk intake , celiac disease , gastric bypass , and chronic pancreatitis were predictive of vitamin D status . Severely deficient participants reported increased musculoskeletal symptoms , depression ( including seasonal ) , and higher ( worse ) scores on a fibromyalgia assessment question naire . In the RCT , the treated group showed significant improvement in fibromyalgia assessment scores ( P = 0.03 ) , whereas the placebo-treated participants did not . Severely deficient patients did not show symptom improvement over the 8-week trial period or when followed up 1 year later . CONCLUSIONS Compared with participants in the placebo group , patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score , but did not show significant improvement in most musculoskeletal symptoms or in activities of daily living Abstract Knowledge about the distributions of serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations in representative population sample s is critical for the quantification of vitamin D deficiency as well as for setting dietary reference values and food-based strategies for its prevention . Such data for the European Union are of variable quality making it difficult to estimate the prevalence of vitamin D deficiency across member states . As a consequence of the widespread , method -related differences in measurements of serum 25(OH)D concentrations , the Vitamin D St and ardization Program ( VDSP ) developed protocol s for st and ardizing existing serum 25(OH)D data from national surveys around the world . The objective of the present work was to apply the VDSP protocol s to existing serum 25(OH)D data from a Danish , a Norwegian , and a Finnish population -based health survey and from a Danish r and omized controlled trial . A specifically-selected subset ( n 100–150 ) of bio-banked serum sample s from each of the studies were reanalyzed for 25(OH)D by LC-MS/MS and a calibration equation developed between old and new 25(OH)D data , and this equation was applied to the entire data -sets from each study . Compared to estimates based on the original serum 25(OH)D data , the percentage vitamin D deficiency ( < 30 nmol/L ) decreased by 21.5 % in the Danish health survey but by only 1.4 % in the Norwegian health survey ; but was relatively unchanged ( 0 % and 0.2 % ) in the Finish survey or Danish RCT , respectively , following VDSP st and ardization . In conclusion , st and ardization of serum 25(OH)D concentrations is absolutely necessary in order to compare serum 25(OH)D concentrations across different study population s , which is needed to quantify and prevent vitamin D deficiency BACKGROUND Serum 25-hydroxyvitamin D ( 25-[OH]D ) is considered the best biomarker of clinical vitamin D status . OBJECTIVE To determine the effect of increasing oral doses of vitamin D(3 ) on serum 25-(OH)D and serum parathyroid hormone ( PTH ) levels in postmenopausal white women with vitamin D insufficiency ( defined as a 25-[OH]D level ≤50 nmol/L ) in the presence of adequate calcium intake . These results can be used as a guide to estimate the Recommended Dietary Allowance ( RDA ) ( defined as meeting the needs of 97.5 % of the population ) for vitamin D(3 ) . DESIGN R and omized , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00472823 ) SETTING Creighton University Medical Center , Omaha , Nebraska . PARTICIPANTS 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year . INTERVENTION Participants were r and omly assigned to receive placebo or vitamin D(3 ) , 400 , 800 , 1600 , 2400 , 3200 , 4000 , or 4800 IU once daily . Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg . MEASUREMENTS The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months . RESULTS The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3 ) . The RDA of vitamin D(3 ) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d . A mixed-effects model predicted that 600 IU of vitamin D(3 ) daily could also meet this goal . Compared with participants with a normal body mass index ( < 25 kg/m(2 ) ) , obese women ( ≥30 kg/m(2 ) ) had a 25-(OH)D level that was 17.8 nmol/L lower . Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3 ) ( P = 0.012 ) . Depending on the criteria used , hypercalcemia occurred in 2.8 % to 9.0 % and hypercalciuria in 12.0 % to 33.0 % of participants ; events were unrelated to dose . LIMITATION Findings may not be generalizable to other age groups or persons with substantial comorbid conditions . CONCLUSION A vitamin D(3 ) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5 % of women ; however , a model predicted the same response with a vitamin D(3 ) dosage of 600 IU/d . These results can be used as a guide for the RDA of vitamin D(3 ) , but prospect i ve trials are needed to confirm the clinical significance of these results . PRIMARY FUNDING SOURCE National Institute on Aging Objective The aim of this study was to examine the effect of hormone therapy and calcitriol on  depression in older postmenopausal women and to determine whether the response was associated with polymorphisms of estrogen receptor & agr ; and vitamin D receptor . Methods In a double-blind placebo-controlled prospect i ve trial involving 489 postmenopausal older women , a secondary analysis of depression was done . The Geriatric Depression Scale was used to screen for depression . We used binary logistic regression to examine the effect of treatment on depression and one-way analysis of variance to find a relationship between gene polymorphisms and depression . Results There was no effect of hormone therapy ( odds ratio [ OR ] , 1.65 ; 95 % CI , 0.66 - 4.12 ; P = 0.277 ) , calcitriol ( OR , 1.15 ; 95 % CI , 0.43 - 3.11 ; P = 0.772 ) , or hormone therapy with calcitriol ( OR , 1.01 ; 95 % CI , 0.36 - 2.80 ; P = 0.979 ) on depression . Neither the polymorphisms of estrogen receptor & agr ; ( XbaI-&bgr ; = 0.093 ; CI , −0.337 to 1.350 ; P = 0.239 and PvuII-&bgr ; = −0.064 ; CI , −1.171 to 0.491 , P = 0.421 ) nor those of vitamin D receptor ( BsmI-&bgr ; = 0.044 , CI −2.546 to 3.030 , P = 0.865 and TaqI-&bgr ; = −0.015 , CI −2.900 to 2.738 , P = 0.955 ) were associated with depression . Conclusion In older postmenopausal women , there was no effect of hormone therapy and calcitriol either individually or in combination with depression . Estrogen receptor & agr ; and vitamin D receptor polymorphisms are not associated with depression or the response to intervention in older postmenopausal women . Additional trials are required to confirm these findings OBJECTIVE To determine whether treatment of low serum vitamin D in pregnant women improves fetal growth indices . STUDY DESIGN In this open-label r and omized clinical trial , 130 Iranian pregnant women ( 24 - 26 weeks of gestation ) with vitamin D deficiency or insufficiency [ 25(OH)D < 30ng/ml ] were divided at r and om into an intervention group and a control group . The control group received 200 mg calcium plus a multivitamin ( containing vitamin D3 400U ) each day , and the intervention group received 200 mg calcium plus a multivitamin ( containing vitamin D3 400U ) each day , plus vitamin D3 ( 50,000U ) each week for 8 weeks . At delivery , maternal and cord blood 25(OH)D levels , maternal weight gain , neonatal length , neonatal weight and neonatal head circumference were compared between two groups . Serum vitamin D was measured using enzyme-linked immunosorbent assay . A multivariate regression analysis was performed to examine the independent effect of maternal vitamin D level on fetal growth indices . RESULTS Mean ( ±st and ard deviation ) length ( intervention group : 49±1.6 cm ; control group : 48.2±1.7 cm ; p=0.001 ) , head circumference ( intervention group : 35.9±0.7 cm ; control group : 35.3±1.0 cm ; p=0.001 ) and weight ( intervention group : 3429±351.9 g ; control group : 3258.8±328.2 g ; p=0.01 ) were higher in the intervention group compared with the control group . Mean maternal weight gain was higher in the intervention group compared with the control group ( 13.3±2.4 kg vs 11.7±2.7 kg ; p=0.006 ) . Multivariate regression analysis for maternal weight gain , neonatal length , neonatal weight and neonatal head circumference showed an independent correlation with maternal vitamin D level . CONCLUSION Treatment of low serum vitamin D during pregnancy improves fetal growth indices and maternal weight gain
target: The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels
background: Background A large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D ( 25OHD ) levels on non-skeletal outcomes .
  We performed a systematic quantitative review on characteristics of r and omized clinical trials ( RCTs ) included in meta-analyses ( MAs ) on non-skeletal effects of vitamin D supplementation .