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    Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. Uusi-Rasi Kirsti,Patil Radhika,Karinkanta Saija,Kannus Pekka,Tokola Kari,Lamberg-Allardt Christel,Sievänen Harri JAMA internal medicine IMPORTANCE:While vitamin D supplementation and exercise are recommended for prevention of falls for older people, results regarding these 2 factors are contradictory. OBJECTIVE:To determine the effectiveness of targeted exercise training and vitamin D supplementation in reducing falls and injurious falls among older women. DESIGN, SETTING, AND PARTICIPANTS:A 2-year randomized, double-blind, placebo-controlled vitamin D and open exercise trial conducted between April 2010 and March 2013 in Tampere, Finland. Participants were 409 home-dwelling women 70 to 80 years old. The main inclusion criteria were at least 1 fall during the previous year, no use of vitamin D supplements, and no contraindication to exercise. INTERVENTIONS:Four study groups, including placebo without exercise, vitamin D (800 IU/d) without exercise, placebo and exercise, and vitamin D (800 IU/d) and exercise. MAIN OUTCOMES AND MEASURES:The primary outcome was monthly reported falls. Injurious falls and the number of fallers and injured fallers were reported as secondary outcomes. In addition, bone density, physical functioning (muscle strength, balance, and mobility), and vitamin D metabolism were assessed. RESULTS:Intent-to-treat analyses showed that neither vitamin D nor exercise reduced falls. Fall rates per 100 person-years were 118.2, 132.1, 120.7, and 113.1 in the placebo without exercise, vitamin D without exercise, placebo and exercise, and vitamin D and exercise study groups, respectively; however, injurious fall rates were 13.2, 12.9, 6.5, and 5.0, respectively. Hazard ratios for injured fallers were significantly lower among exercisers with vitamin D (0.38; 95% CI, 0.17-0.83) and without vitamin D (0.47; 95% CI, 0.23-0.99). Vitamin D maintained femoral neck bone mineral density and increased tibial trabecular density slightly. However, only exercise improved muscle strength and balance. Vitamin D did not enhance exercise effects on physical functioning. CONCLUSIONS AND RELEVANCE:The rate of injurious falls and injured fallers more than halved with strength and balance training in home-dwelling older women, while neither exercise nor vitamin D affected the rate of falls. Exercise improved physical functioning. Future research is needed to determine the role of vitamin D in the enhancement of strength, balance, and mobility. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00986466. 10.1001/jamainternmed.2015.0225
    Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. Burt Lauren A,Billington Emma O,Rose Marianne S,Raymond Duncan A,Hanley David A,Boyd Steven K JAMA Importance:Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day. Objective:To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength. Design, Setting, and Participants:Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L. Interventions:Daily doses of vitamin D3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day. Main Outcomes and Measures:Co-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis. Results:Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (-3.9 mg HA/cm3 [95% CI, -6.5 to -1.3]) and 10 000 IU group (-7.5 mg HA/cm3 [95% CI, -10.1 to -5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of -1.2% (400 IU group), -2.4% (4000 IU group), and -3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were -1.8 mg HA/cm3 (95% CI, -3.7 to 0.1) in the 4000 IU group and -4.1 mg HA/cm3 in the 10 000 IU group (95% CI, -6.0 to -2.2), with mean percent change values of -0.4% (400 IU), -1.0% (4000 IU), and -1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12). Conclusions and Relevance:Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful. Trial Registration:ClinicalTrials.gov Identifier: NCT01900860. 10.1001/jama.2019.11889
    Vitamin D and Cardiovascular Disease: Controversy Unresolved. Al Mheid Ibhar,Quyyumi Arshed A Journal of the American College of Cardiology Vitamin D deficiency is typically caused by inadequate cutaneous synthesis secondary to decreased exposure to sunlight. Serum levels of 25-hydroxyvitamin D l <20 ng/ml are diagnostic of vitamin D deficiency. Vitamin D has various cardiovascular pleiotropic effects by activating its nuclear receptor in cardiomyocytes and vascular endothelial cells and by regulating the renin-angiotensin-aldosterone system, adiposity, energy expenditure, and pancreatic cell activity. In humans, vitamin D deficiency is associated with the following: vascular dysfunction; arterial stiffening; left ventricular hypertrophy; and worsened metrics of diabetes, hypertension, and hyperlipidemia. It is also linked with worse cardiovascular morbidity and mortality. However, meta-analyses of vitamin D supplementation trials have failed to show clear improvements in blood pressure, insulin sensitivity, or lipid parameters, thus suggesting that the link between vitamin D deficiency and cardiovascular disease may be an epiphenomenon. Ongoing larger randomized trials will clarify whether monitoring and supplementation of vitamin D play roles in cardiovascular protection. 10.1016/j.jacc.2017.05.031
    Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. Bischoff-Ferrari Heike A,Dawson-Hughes Bess,Orav E John,Staehelin Hannes B,Meyer Otto W,Theiler Robert,Dick Walter,Willett Walter C,Egli Andreas JAMA internal medicine IMPORTANCE:Vitamin D deficiency has been associated with poor physical performance. OBJECTIVE:To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline. DESIGN, SETTING, AND PARTICIPANTS:One-year, double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. INTERVENTIONS:Three study groups with monthly treatments, including a low-dose control group receiving 24,000 IU of vitamin D3 (24,000 IU group), a group receiving 60,000 IU of vitamin D3 (60,000 IU group), and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol (24,000 IU plus calcifediol group). MAIN OUTCOMES AND MEASURES:The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index. RESULTS:The study cohort comprised 200 participants (men and women ≥ 70 years with a prior fall). Their mean age was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (<20 ng/mL) at baseline. Intent-to-treat analyses showed that, while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL (P = .001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups (P = .26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60,000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24,000 IU plus calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24,000 IU group (47.9%; 95% CI, 35.8%-60.3%) (P = .048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60,000 IU group (mean, 1.47) and the 24,000 IU plus calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24,000 IU group (mean, 0.94) (P = .09). CONCLUSIONS AND RELEVANCE:Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01017354. 10.1001/jamainternmed.2015.7148
    No effect of high-dose vitamin D supplementation on glycemic status or cardiovascular risk factors in subjects with prediabetes. Sollid Stina Therese,Hutchinson Moira Y S,Fuskevåg Ole M,Figenschau Yngve,Joakimsen Ragnar M,Schirmer Henrik,Njølstad Inger,Svartberg Johan,Kamycheva Elena,Jorde Rolf Diabetes care OBJECTIVE:In observational studies, low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS:We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) randomly assigned to 20,000 IU/week vitamin D3 or placebo. An oral glucose tolerance test was performed at baseline and after 1 year. RESULTS:Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups, respectively, and increased by 45.8 nmol/L and 3.4 nmol/L, respectively. With adjustment for baseline concentrations, no differences in measures of glucose metabolism, insulin secretion or sensitivity, blood pressure, or hs-CRP were found after 1 year. There was a slight, but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group, but as there was also a decrease in HDL cholesterol, the change in the total/HDL cholesterol ratio did not differ significantly. Only analyzing subjects with 25(OH)D <50 nmol/L did not change the results. CONCLUSIONS:This study shows that vitamin D supplementation does not improve glycemic indices, blood pressure, or lipid status in subjects with IFG and/or IGT. 10.2337/dc14-0218
    Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. Manson JoAnn E,Cook Nancy R,Lee I-Min,Christen William,Bassuk Shari S,Mora Samia,Gibson Heike,Gordon David,Copeland Trisha,D'Agostino Denise,Friedenberg Georgina,Ridge Claire,Bubes Vadim,Giovannucci Edward L,Willett Walter C,Buring Julie E, The New England journal of medicine BACKGROUND:It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease, and data from randomized trials are limited. METHODS:We conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D (cholecalciferol) at a dose of 2000 IU per day and marine n-3 (also called omega-3) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes). Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. This article reports the results of the comparison of vitamin D with placebo. RESULTS:A total of 25,871 participants, including 5106 black participants, underwent randomization. Supplementation with vitamin D was not associated with a lower risk of either of the primary end points. During a median follow-up of 5.3 years, cancer was diagnosed in 1617 participants (793 in the vitamin D group and 824 in the placebo group; hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47). A major cardiovascular event occurred in 805 participants (396 in the vitamin D group and 409 in the placebo group; hazard ratio, 0.97; 95% CI, 0.85 to 1.12; P=0.69). In the analyses of secondary end points, the hazard ratios were as follows: for death from cancer (341 deaths), 0.83 (95% CI, 0.67 to 1.02); for breast cancer, 1.02 (95% CI, 0.79 to 1.31); for prostate cancer, 0.88 (95% CI, 0.72 to 1.07); for colorectal cancer, 1.09 (95% CI, 0.73 to 1.62); for the expanded composite end point of major cardiovascular events plus coronary revascularization, 0.96 (95% CI, 0.86 to 1.08); for myocardial infarction, 0.96 (95% CI, 0.78 to 1.19); for stroke, 0.95 (95% CI, 0.76 to 1.20); and for death from cardiovascular causes, 1.11 (95% CI, 0.88 to 1.40). In the analysis of death from any cause (978 deaths), the hazard ratio was 0.99 (95% CI, 0.87 to 1.12). No excess risks of hypercalcemia or other adverse events were identified. CONCLUSIONS:Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259 .). 10.1056/NEJMoa1809944
    Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily. Zittermann Armin,Ernst Jana B,Prokop Sylvana,Fuchs Uwe,Dreier Jens,Kuhn Joachim,Knabbe Cornelius,Birschmann Ingvild,Schulz Uwe,Berthold Heiner K,Pilz Stefan,Gouni-Berthold Ioanna,Gummert Jan F,Dittrich Marcus,Börgermann Jochen European heart journal 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 randomized 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:clinicaltrials.gov Idenitfier: NCT01326650. 10.1093/eurheartj/ehx235
    Research digest: vitamin D supplementation. Preiss David,Sattar Naveed The lancet. Diabetes & endocrinology 10.1016/S2213-8587(19)30007-5
    Vitamin D and cardiovascular disease prevention. Pilz Stefan,Verheyen Nicolas,Grübler Martin R,Tomaschitz Andreas,März Winfried Nature reviews. Cardiology Vitamin D is a precursor of the steroid hormone calcitriol that is crucial for bone and mineral metabolism. Both the high prevalence of vitamin D deficiency in the general population and the identification of the vitamin D receptor in the heart and blood vessels raised interest in the potential cardiovascular effects of vitamin D. Experimental studies have demonstrated various cardiovascular protective actions of vitamin D, but vitamin D intoxication in animals is known to induce vascular calcification. In meta-analyses of epidemiological studies, vitamin D deficiency is associated with an increased cardiovascular risk. Findings from Mendelian randomization studies and randomized, controlled trials (RCTs) do not indicate significant effects of a general vitamin D supplementation on cardiovascular outcomes. Previous RCTs, however, were not adequately designed to address extraskeletal events, and did not focus on vitamin D-deficient individuals. Therefore, currently available evidence does not support cardiovascular benefits or harms of vitamin D supplementation with the commonly used doses, and whether vitamin D has cardiovascular effects in individuals with overt vitamin D deficiency remains to be evaluated. Here, we provide an update on clinical studies on vitamin D and cardiovascular risk, discuss ongoing vitamin D research, and consider the management of vitamin D deficiency from a cardiovascular health perspective. 10.1038/nrcardio.2016.73
    Associations of lower vitamin D concentrations with cognitive decline and long-term risk of dementia and Alzheimer's disease in older adults. Feart Catherine,Helmer Catherine,Merle Bénédicte,Herrmann François R,Annweiler Cédric,Dartigues Jean-François,Delcourt Cécile,Samieri Cécilia Alzheimer's & dementia : the journal of the Alzheimer's Association INTRODUCTION:Hypovitaminosis D has been associated with several chronic conditions; yet, its association with cognitive decline and the risk of dementia and Alzheimer's disease (AD) has been inconsistent. METHODS:The study population consisted of 916 participants from the Three-City Bordeaux cohort aged 65+, nondemented at baseline, with assessment of vitamin D status and who were followed for up to 12 years. RESULTS:In multivariate analysis, compared with individuals with 25(OH)D sufficiency (n = 151), participants with 25(OH)D deficiency (n = 218) exhibited a faster cognitive decline. A total of 177 dementia cases (124 AD) occurred: 25(OH)D deficiency was associated with a nearly three-fold increased risk of AD (hazard ratio = 2.85, 95% confidence interval 1.37-5.97). DISCUSSION:This large prospective study of French older adults suggests that maintaining adequate vitamin D status in older age could contribute to slow down cognitive decline and to delay or prevent the onset of dementia, especially of AD etiology. 10.1016/j.jalz.2017.03.003
    Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Khaw Kay-Tee,Stewart Alistair W,Waayer Debbie,Lawes Carlene M M,Toop Les,Camargo Carlos A,Scragg Robert The lancet. Diabetes & endocrinology BACKGROUND:Adults with low concentrations of 25-hydroxyvitamin D (25[OH]D) in blood have an increased risk of falls and fractures, but randomised trials of vitamin D supplementation have had inconsistent results. We aimed to assess the effect of high-dose vitamin D supplementation on fractures and falls. METHODS:The Vitamin D Assessment (ViDA) Study was a randomised, double-blind, placebo-controlled trial of healthy volunteers aged 50-84 years conducted at one centre in Auckland, New Zealand. Participants were randomly assigned to receive either an initial oral dose of 200 000 IU (5·0 mg) colecalciferol (vitamin D) followed by monthly 100 000 IU (2·5 mg) colecalciferol or equivalent placebo dosing. The prespecified primary outcome was cardiovascular disease and secondary outcomes were respiratory illness and fractures. Here, we report secondary outcome data for fractures and post-hoc outcome data for falls. Cox proportional hazards models were used to estimate hazard ratios (HRs) for time to first fracture or time to first fall in individuals allocated vitamin D compared with placebo. The analysis of fractures included all participants who gave consent and was by intention-to-treat; the analysis of falls included all individuals who returned one or more questionnaires. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000402943. FINDINGS:Between April 5, 2011, and Nov 6, 2012, 5110 participants were recruited and randomly assigned either colecalciferol (n=2558) or placebo (n=2552). Two participants allocated placebo withdrew consent after randomisation; thus, a total of 5108 individuals were included in the analysis of fractures. The mean age of participants was 65·9 years (SD 8·3) and 2971 (58%) were men. The mean concentration of 25(OH)D in blood was 63 nmol/L (SD 24) at baseline, with 1534 (30%) having 25(OH)D concentrations lower than 50 nmol/L. Follow-up was until July 31, 2015, with a mean treatment duration of 3·4 years (SD 0·4, range 2·5-4·2). During follow-up, 2638 participants reported having a fall, 1312 (52%) of 2539 in the vitamin D group compared with 1326 (53%) of 2517 in the placebo group. The HR for falls-adjusted for age, sex, ethnic origin, history of recent fall, physical activity, and baseline 25(OH)D-was 0·99 (95% CI 0·92-1·07; p=0·82) for vitamin D compared with placebo. Non-vertebral fractures were reported in 292 individuals, 156 (6%) of 2558 in the vitamin D group and 136 (5%) of 2550 in the placebo group. The adjusted HR for fractures was 1·19 (95% CI 0·94-1·50; p=0·15) for vitamin D compared with placebo. 123 (2%) people died during the trial, 65 assigned vitamin D and 58 allocated placebo; the difference between treatment groups was not significant. INTERPRETATION:High-dose bolus vitamin D supplementation of 100 000 IU colecalciferol monthly over 2·5-4·2 years did not prevent falls or fractures in this healthy, ambulatory, adult population. Further research is needed to ascertain the effects of daily vitamin D dosing, with or without calcium. FUNDING:Health Research Council of New Zealand and Accident Compensation Corporation of New Zealand. 10.1016/S2213-8587(17)30103-1
    Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Autier Philippe,Mullie Patrick,Macacu Alina,Dragomir Miruna,Boniol Magali,Coppens Kim,Pizot Cécile,Boniol Mathieu The lancet. Diabetes & endocrinology Randomised trials reported up to Dec 31, 2012, did not confirm that vitamin D supplementation could protect from non-skeletal health conditions affecting adults, as was expected on the basis of data from observational studies. To examine whether the more recently published meta-analyses and trials would change past conclusions, we systematically reviewed meta-analyses of vitamin D supplementation and non-skeletal disorders published between Jan 1, 2013, and May 31, 2017, that included study participants of all ages, including pregnant women. We also searched for randomised trials not included in meta-analyses. We identified 87 meta-analyses, of which 52 were excluded because they contained less recent literature or were of suboptimal quality. We retrieved 202 articles on trials that were not included in meta-analyses. Recent meta-analyses reinforce the finding that 10-20 μg per day of vitamin D can reduce all-cause mortality and cancer mortality in middle-aged and older people. Although vitamin D doses were greater than those assessed in the past, we found no new evidence that supplementation could have an effect on most non-skeletal conditions, including cardiovascular disease, adiposity, glucose metabolism, mood disorders, muscular function, tuberculosis, and colorectal adenomas, or on maternal and perinatal conditions. New data on cancer outcomes were scarce. The compilation of results from 83 trials showed that vitamin D supplementation had no significant effect on biomarkers of systemic inflammation. The main new finding highlighted by this systematic review is that vitamin D supplementation might help to prevent common upper respiratory tract infections and asthma exacerbations. There remains little evidence to suggest that vitamin D supplementation has an effect on most conditions, including chronic inflammation, despite use of increased doses of vitamin D, strengthening the hypothesis that low vitamin D status is a consequence of ill health, rather than its cause. We further hypothesise that vitamin D supplementation could exert immunomodulatory effects that strengthen resistance to acute infections, which would reduce the risk of death in debilitated individuals. We identified many meta-analyses of suboptimal quality, which is of concern. Future systematic reviews on vitamin D should be based on data sharing so that data for participants with the same outcomes measured in the same way can be pooled to generate stronger evidence. 10.1016/S2213-8587(17)30357-1
    Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Keum N,Lee D H,Greenwood D C,Manson J E,Giovannucci E Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Previous meta-analyses of randomized controlled trials (RCTs) of vitamin D supplementation and total cancer incidence and mortality found inconsistent results, and most included trials administered generally low doses of vitamin D (≤1100 IU/day). We updated the meta-analysis by incorporating recent RCTs that have tested higher doses of vitamin D supplements. MATERIALS AND METHODS:PubMed and Embase were searched from the inception to November 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. RESULTS:For total cancer incidence, 10 trials were included [6537 cases; 3-10 years of follow-up; 54-135 nmol/l of attained levels of circulating 25(OH) vitamin D [25(OH)D] in the intervention group]. The summary RR was 0.98 (95% CI, 0.93-1.03; P = 0.42; I2 = 0%). The results remained null across subgroups tested, including even when attained 25(OH)D levels exceeded 100 nmol/l (RR, 0.95; 95% CI, 0.83-1.09; P = 0.48; I2 = 26%). For total cancer mortality, five trials were included [1591 deaths; 3-10 years of follow-up; 54-135 nmol/l of attained levels of circulating 25(OH)D in the intervention group]. The summary RR was 0.87 (95% CI, 0.79-0.96; P = 0.005; I2 = 0%), which was largely attributable to interventions with daily dosing (as opposed to infrequent bolus dosing). No statistically significant heterogeneity was observed by attained levels of circulating 25(OH)D (Pheterogeneity = 0.83), with RR being 0.88 (95% CI, 0.78-0.98; P = 0.02; I2 = 0%) for ≤100 nmol/l and 0.85 (95% CI, 0.70-1.03; P = 0.11; I2 = 0%) for >100 nmol/l. CONCLUSIONS:In an updated meta-analysis of RCTs, vitamin D supplementation significantly reduced total cancer mortality but did not reduce total cancer incidence. 10.1093/annonc/mdz059
    Vitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease Current Evidence. Manson JoAnn E,Bassuk Shari S,Cook Nancy R,Lee I-Min,Mora Samia,Albert Christine M,Buring Julie E, Circulation research Whether marine omega-3 fatty acid (n-3 FA) or vitamin D supplementation can prevent cardiovascular disease (CVD) in general populations at usual risk for this outcome is unknown. A major goal of VITAL (Vitamin D and Omega-3 Trial) was to fill this knowledge gap. In this article, we review the results of VITAL, discuss relevant mechanistic studies regarding n-3 FAs, vitamin D, and vascular disease, and summarize recent meta-analyses of the randomized trial evidence on these agents. VITAL was a nationwide, randomized, placebo-controlled, 2×2 factorial trial of marine n-3 FAs (1 g/d) and vitamin D (2000 IU/d) in the primary prevention of CVD and cancer among 25 871 US men aged ≥50 and women aged ≥55 years, including 5106 blacks. Median treatment duration was 5.3 years. Supplemental n-3 FAs did not significantly reduce the primary cardiovascular end point of major CVD events (composite of myocardial infarction, stroke, and CVD mortality; hazard ratio [HR], 0.92 [95% CI, 0.80-1.06]) but were associated with significant reductions in total myocardial infarction (HR, 0.72 [95% CI, 0.59-0.90]), percutaneous coronary intervention (HR, 0.78 [95% CI, 0.63-0.95]), and fatal myocardial infarction (HR, 0.50 [95% CI, 0.26-0.97]) but not stroke or other cardiovascular end points. For major CVD events, a treatment benefit was seen in those with dietary fish intake below the cohort median of 1.5 servings/wk (HR, 0.81 [95% CI, 0.67-0.98]) but not in those above ( interaction=0.045). For myocardial infarction, the greatest risk reductions were in blacks (HR, 0.23 [95% CI, 0.11-0.47]; interaction by race, 0.001). Vitamin D supplementation did not reduce major CVD events (HR, 0.97 [95% CI, 0.85-1.12]) or other cardiovascular end points. Updated meta-analyses that include VITAL and other recent trials document coronary risk reduction from supplemental marine n-3 FAs but no clear CVD risk reduction from supplemental vitamin D. Additional research is needed to determine which individuals may be most likely to derive net benefit from supplementation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01169259. 10.1161/CIRCRESAHA.119.314541
    Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Bolland Mark J,Grey Andrew,Avenell Alison The lancet. Diabetes & endocrinology BACKGROUND:The effects of vitamin D on fractures, falls, and bone mineral density are uncertain, particularly for high vitamin D doses. We aimed to determine the effect of vitamin D supplementation on fractures, falls, and bone density. METHODS:In this systematic review, random-effects meta-analysis, and trial sequential analysis, we used findings from literature searches in previously published meta-analyses. We updated these findings by searching PubMed, Embase, and Cochrane Central on Sept 14, 2017, and Feb 26, 2018, using the search term "vitamin D" and additional keywords, without any language restrictions. We assessed randomised controlled trials of adults (>18 years) that compared vitamin D with untreated controls, placebo, or lower-dose vitamin D supplements. Trials with multiple interventions (eg, co-administered calcium and vitamin D) were eligible if the study groups differed only by use of vitamin D. We excluded trials of hydroxylated vitamin D analogues. Eligible studies included outcome data for total or hip fractures, falls, or bone mineral density measured at the lumbar spine, total hip, femoral neck, total body, or forearm. We extracted data about participant characteristics, study design, interventions, outcomes, funding sources, and conflicts of interest. The co-primary endpoints were participants with at least one fracture, at least one hip fracture, or at least one fall; we compared data for fractures and falls using relative risks with an intention-to-treat analysis using all available data. The secondary endpoints were the percentage change in bone mineral density from baseline at lumbar spine, total hip, femoral neck, total body, and forearm. FINDINGS:We identified 81 randomised controlled trials (n=53 537 participants) that reported fracture (n=42), falls (n=37), or bone mineral density (n=41). In pooled analyses, vitamin D had no effect on total fracture (36 trials; n=44 790, relative risk 1·00, 95% CI 0·93-1·07), hip fracture (20 trials; n=36 655, 1·11, 0·97-1·26), or falls (37 trials; n=34 144, 0·97, 0·93-1·02). Results were similar in randomised controlled trials of high-dose versus low-dose vitamin D and in subgroup analyses of randomised controlled trials using doses greater than 800 IU per day. In pooled analyses, there were no clinically relevant between-group differences in bone mineral density at any site (range -0·16% to 0·76% over 1-5 years). For total fracture and falls, the effect estimate lay within the futility boundary for relative risks of 15%, 10%, 7·5%, and 5% (total fracture only), suggesting that vitamin D supplementation does not reduce fractures or falls by these amounts. For hip fracture, at a 15% relative risk, the effect estimate lay between the futility boundary and the inferior boundary, meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount, but uncertainty remains as to whether it might increase hip fractures. The effect estimate lay within the futility boundary at thresholds of 0·5% for total hip, forearm, and total body bone mineral density, and 1·0% for lumbar spine and femoral neck, providing reliable evidence that vitamin D does not alter these outcomes by these amounts. INTERPRETATION:Our findings suggest that vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density. There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health. This conclusion should be reflected in clinical guidelines. FUNDING:Health Research Council of New Zealand. 10.1016/S2213-8587(18)30265-1
    Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis. Barbarawi Mahmoud,Kheiri Babikir,Zayed Yazan,Barbarawi Owais,Dhillon Harsukh,Swaid Bakr,Yelangi Anitha,Sundus Saira,Bachuwa Ghassan,Alkotob Mohammad Luay,Manson JoAnn E JAMA cardiology Importance:Observational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding. Objective:We conducted a meta-analysis of randomized clinical trials that tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality. Data Sources:Literature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from each database's inception to December 15, 2018. Study Selection:Inclusion criteria were randomized clinical trials that reported the effect of long-term (≥1 year) vitamin D supplementation on CVD events and all-cause mortality. Studies that did not include cardiovascular outcomes were excluded. Data Extraction and Synthesis:Data were abstracted independently by 2 authors. Random-effects models were used to report the risk ratios (RRs) and 95% CIs. Main Outcomes and Measures:Major adverse cardiovascular events was the primary outcome, and rates of myocardial infarction, stroke or cerebrovascular accident, CVD mortality, and all-cause mortality were the secondary end points. Results:Twenty-one randomized clinical trials were included (including 83 291 patients, of whom 41 669 received vitamin D and 41 622 received placebos). The mean (SD) age of trial participants was 65.8 (8.4) years; 61 943 (74.4%) were female. Only 4 trials had prespecified CVD as a primary end point. Vitamin D supplementation compared with placebo was not associated with reduced major adverse cardiovascular events (RR, 1.00 [95% CI, 0.95-1.06]; P = .85) nor the secondary end points of myocardial infarction (RR, 1.00 [95% CI, 0.93-1.08]; P = .92), stroke (RR, 1.06 [95% CI, 0.98-1.15]; P = .16), CVD mortality (RR, 0.98 [95% CI, 0.90-1.07]; P = .68), or all-cause mortality (RR, 0.97 [95% CI, 0.93-1.02]; P = .23). Results were generally consistent by sex, baseline 25-hydroxyvitamin D level, vitamin D dosage, formulation (daily vs bolus dosing), and presence or absence of concurrent calcium administration. Conclusions and Relevance:In this updated meta-analysis, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality), or all-cause mortality. The findings suggest that vitamin D supplementation does not confer cardiovascular protection and is not indicated for this purpose. 10.1001/jamacardio.2019.1870
    Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Reid Ian R,Bolland Mark J,Grey Andrew Lancet (London, England) BACKGROUND:Findings from recent meta-analyses of vitamin D supplementation without co-administration of calcium have not shown fracture prevention, possibly because of insufficient power or inappropriate doses, or because the intervention was not targeted to deficient populations. Despite these data, almost half of older adults (older than 50 years) continue to use these supplements. Bone mineral density can be used to detect biologically significant effects in much smaller cohorts. We investigated whether vitamin D supplementation affects bone mineral density. METHODS:We searched Web of Science, Embase, and the Cochrane Database, from inception to July 8, 2012, for trials assessing the effects of vitamin D (D3 or D2, but not vitamin D metabolites) on bone mineral density. We included all randomised trials comparing interventions that differed only in vitamin D content, and which included adults (average age >20 years) without other metabolic bone diseases. We pooled data with a random effects meta-analysis with weighted mean differences and 95% CIs reported. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I(2) statistic. The primary endpoint was the percentage change in bone mineral density from baseline. FINDINGS:Of 3930 citations identified by the search strategy, 23 studies (mean duration 23·5 months, comprising 4082 participants, 92% women, average age 59 years) met the inclusion criteria. 19 studies had mainly white populations. Mean baseline serum 25-hydroxyvitamin D concentration was less than 50 nmol/L in eight studies (n=1791). In ten studies (n=2294), individuals were given vitamin D doses less than 800 IU per day. Bone mineral density was measured at one to five sites (lumbar spine, femoral neck, total hip, trochanter, total body, or forearm) in each study, so 70 tests of statistical significance were done across the studies. There were six findings of significant benefit, two of significant detriment, and the rest were non-significant. Only one study showed benefit at more than one site. Results of our meta-analysis showed a small benefit at the femoral neck (weighted mean difference 0·8%, 95% CI 0·2-1·4) with heterogeneity among trials (I(2)=67%, p<0·00027). No effect at any other site was reported, including the total hip. We recorded a bias toward positive results at the femoral neck and total hip. INTERPRETATION:Continuing widespread use of vitamin D for osteoporosis prevention in community-dwelling adults without specific risk factors for vitamin D deficiency seems to be inappropriate. FUNDING:Health Research Council of New Zealand. 10.1016/S0140-6736(13)61647-5
    Vitamin D and falls - the dosage conundrum. Gallagher J Christopher Nature reviews. Endocrinology Falls are a major health problem in elderly individuals. Although intensive physical therapy and management of hazards in the home can reduce falls by 25%, long-term practicality limits their use. Interest in vitamin D as a medical therapy has led to many trials; however, results using daily oral doses of vitamin D have been inconsistent. In the past 5 years, studies on the effect of bolus doses of vitamin D have produced surprising results. Bolus doses of vitamin D, given annually (at a dose of 300,000 IU or 500,000 IU) or monthly (at a dose of 24,000 IU or 60,000 IU) - equivalent to approximate daily doses of 800 IU, 1400 IU and 2,000 IU - result in a significant increase in the number of falls and fractures associated with serum levels of 25-hydroxyvitamin D greater than 40-45 ng/ml (equivalent to 100-112 nmol/l). These unexpected results show increased falls and fractures are adverse events related to vitamin D administration. Until further safety data is available, bolus dosing or daily doses should not exceed 3,000 IU and serum levels of 25-hydroxyvitamin D should not exceed 40-45 ng/ml (equivalent to 100-112 nmol/l) in elderly individuals. 10.1038/nrendo.2016.123
    Vitamin D Deficiency and the Risk of Cerebrovascular Disease. Kim Hyun Ah,Perrelli Andrea,Ragni Alberto,Retta Francesca,De Silva T Michael,Sobey Christopher G,Retta Saverio Francesco Antioxidants (Basel, Switzerland) Vitamin D deficiency has been clearly linked to major chronic diseases associated with oxidative stress, inflammation, and aging, including cardiovascular and neurodegenerative diseases, diabetes, and cancer. In particular, the cardiovascular system appears to be highly sensitive to vitamin D deficiency, as this may result in endothelial dysfunction and vascular defects via multiple mechanisms. Accordingly, recent research developments have led to the proposal that pharmacological interventions targeting either vitamin D deficiency or its key downstream effects, including defective autophagy and abnormal pro-oxidant and pro-inflammatory responses, may be able to limit the onset and severity of major cerebrovascular diseases, such as stroke and cerebrovascular malformations. Here we review the available evidence supporting the role of vitamin D in preventing or limiting the development of these cerebrovascular diseases, which are leading causes of disability and death all over the world. 10.3390/antiox9040327
    Non-linear associations between serum 25-OH vitamin D and indices of arterial stiffness and arteriosclerosis in an older population. van Dijk Suzanne C,Sohl Evelien,Oudshoorn Christian,Enneman Anke W,Ham Annelies C,Swart Karin M A,van Wijngaarden Janneke P,Brouwer-Brolsma Elske M,van der Zwaluw Nikita L,Uitterlinden Andre G,de Groot Lisette C P G M,Dhonukshe-Rutten Rosalie A M,Lips Paul,van Schoor Natasja M,Blom Henk J,Geleijnse Johanna M,Feskens Edith J,Smulders Yvo M,Zillikens M Carola,de Jongh Renate T,van den Meiracker Anton H,Mattace Raso Francesco U S,van der Velde Nathalie Age and ageing BACKGROUND:several studies have been pointing towards a non-linear relationship between serum 25(OH)D and cardiovascular disease. Next to vitamin D deficiency, also higher levels of 25(OH)D have been reported to be associated with increased cardiovascular risk. We aimed to investigate the nature of the relationship between serum 25(OH)D and measures of arterial stiffness and arteriosclerosis in an elderly population. DESIGN:cross-sectional. SETTING/SUBJECTS:a subgroup of the B-PROOF study was included to determine associations between serum 25(OH)D and arterial stiffness and atherosclerosis (n = 567, 57% male, age 72.6 ± 5.6 years, mean serum 25(OH)D 54.6 ± 24.1 nmol/l). METHODS:carotid intima media thickness (IMT) was assessed using ultrasonography and pulse wave velocity (PWV) was determined with applanation tonometry. Associations were tested using multivariable restricted cubic spline functions and stratified linear regression analysis. RESULTS:the associations between serum 25(OH)D and carotid IMT or PWV were non-linear. Spline functions demonstrated a difference between 25(OH)D deficient and sufficient individuals. In serum 25(OH)D sufficient participants (≥50 nmol/l; n = 287), a positive association with IMT and serum 25(OH)D was present (β 1.24; 95%CI [0.002; 2.473]). PWV levels were slightly lower in vitamin D deficient individuals, but the association with 25(OH)D was not significant. CONCLUSION:our study demonstrates that associations of serum 25(OH)D and PWV and IMT in an elderly population are not linear. In particular from serum 25(OH)D levels of 50 nmol/l and up, there is a slight increase of IMT with increasing 25(OH)D levels. 10.1093/ageing/afu095
    Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults. Miller Joshua W,Harvey Danielle J,Beckett Laurel A,Green Ralph,Farias Sarah Tomaszewski,Reed Bruce R,Olichney John M,Mungas Dan M,DeCarli Charles JAMA neurology IMPORTANCE:Vitamin D (VitD) deficiency is associated with brain structural abnormalities, cognitive decline, and incident dementia. OBJECTIVE:To assess associations between VitD status and trajectories of change in subdomains of cognitive function in a cohort of ethnically diverse older adults. DESIGN, SETTING, AND PARTICIPANTS:Longitudinal multiethnic cohort study of 382 participants in an outpatient clinic enrolled between February 2002 and August 2010 with baseline assessment and yearly follow-up visits. Serum 25-hydroxyvitamin D (25-OHD) was measured, with VitD status defined as the following: deficient, less than 12 ng/mL (to convert to nanomoles per liter, multiply by 2.496); insufficient, 12 to less than 20 ng/mL; adequate, 20 to less than 50 ng/mL; or high, 50 ng/mL or higher. Subdomains of cognitive function were assessed using the Spanish and English Neuropsychological Assessment Scales. Associations were evaluated between 25-OHD levels (as continuous and categorical [deficient, insufficient, or adequate]) and trajectories of cognitive decline. MAIN OUTCOMES AND MEASURES:Serum 25-OHD levels, cognitive function, and associations between 25-OHD levels and trajectories of cognitive decline. RESULTS:Participants (N = 382 at baseline) had a mean (SD) age of 75.5 (7.0) years; 61.8% were women; and 41.4% were white, 29.6% African American, 25.1% Hispanic, and 3.9% other race/ethnicity. Diagnosis at enrollment included 17.5% with dementia, 32.7% with mild cognitive impairment, and 49.5% cognitively normal. The mean (SD) 25-OHD level was 19.2 (11.7) ng/mL, with 26.2% of participants being VitD deficient and 35.1% insufficient. The mean (SD) 25-OHD levels were significantly lower for African American and Hispanic participants compared with white participants (17.9 [15.8] and 17.2 [8.4] vs 21.7 [10.0] ng/mL, respectively; P < .001 for both). The mean (SD) 25-OHD levels were similarly lower in the dementia group compared with the mild cognitive impairment and cognitively normal groups (16.2 [9.4] vs 20.0 [10.3] and 19.7 [13.1] ng/mL, respectively; P = .006). The mean (SD) follow-up was 4.8 (2.5) years. Rates of decline in episodic memory and executive function among VitD-deficient (episodic memory: β = -0.04 [SE = 0.02], P = .049; executive function: β = -0.05 [SE = 0.02], P = .01) and VitD-insufficient (episodic memory: β = -0.06 [SE = 0.02], P < .001; executive function: β = -0.04 [SE = 0.02], P = .008) participants were greater than those with adequate status after controlling for age, sex, education, ethnicity, body mass index, season of blood draw, vascular risk, and apolipoprotein E4 genotype. Vitamin D status was not significantly associated with decline in semantic memory or visuospatial ability. Exclusion of participants with dementia did not substantially affect the associations between VitD status and rates of cognitive decline. CONCLUSIONS AND RELEVANCE:Low VitD status was associated with accelerated decline in cognitive function domains in ethnically diverse older adults, including African American and Hispanic individuals who exhibited a high prevalence of VitD insufficiency or deficiency. It remains to be determined whether VitD supplementation slows cognitive decline. 10.1001/jamaneurol.2015.2115
    Vitamin D and white matter abnormalities in older adults: a quantitative volumetric analysis of brain MRI. Annweiler Cédric,Bartha Robert,Karras Spyridon N,Gautier Jennifer,Roche Frédéric,Beauchet Olivier Experimental gerontology BACKGROUND:Vitamin D insufficiency is associated with brain changes. Our objective was to investigate whether vitamin D insufficiency was associated with a greater volume in mm(3) of white matter abnormalities (WMA) in older adults. METHODS:Seventy-five Caucasian older community-dwellers (mean, 70.9 ± 5.0 years; 48%female) received a blood test and brain MRI. The volumes of total white matter (WM) and WMA were measured from T1-weighted MR images using automatic, accurate and reproducible segmentation of the brain provided by FreeSurfer. Vitamin D insufficiency was defined a priori as serum 25-hydroxyvitamin D<50 nmol/L. Age, gender, body mass index, mean arterial pressure, use of anti-vascular drugs, education level, Mini-Mental State Examination score, Instrumental Activities of Daily Living score, serum calcium concentration, estimated glomerular filtration rate, and season of evaluation were used as potential confounders. RESULTS:Participants with vitamin D insufficiency (n = 29) had a greater volume of WMA than the others (4233 ± 4359 mm(3) versus 2658 ± 1544 mm(3), P = 0.028), even after normalization for WM volume (P = 0.031). Vitamin D insufficiency was cross-sectionally associated with an increased ratio of WMA volume to WM volume (fully adjusted β = 0.35, P = 0.047). CONCLUSIONS:Vitamin D insufficiency was associated with increased WMA volume in the studied sample of older adults. These findings may provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency. 10.1016/j.exger.2015.01.049
    Effects of Vitamin D on Blood Pressure, Arterial Stiffness, and Cardiac Function in Older People After 1 Year: BEST-D (Biochemical Efficacy and Safety Trial of Vitamin D). Tomson Joseph,Hin Harold,Emberson Jonathan,Kurien Rijo,Lay Michael,Cox Jolyon,Hill Michael,Arnold Linda,Leeson Paul,Armitage Jane,Clarke Robert Journal of the American Heart Association BACKGROUND:The relevance of vitamin D for prevention of cardiovascular disease is uncertain. The BEST-D (Biochemical Efficacy and Safety Trial of vitamin D) trial previously reported effects of vitamin D on plasma markers of vitamin D status, and the present report describes the effects on blood pressure, heart rate, arterial stiffness, and cardiac function. METHODS AND RESULTS:This was a randomized, double-blind, placebo-controlled trial of 305 older people living in United Kingdom, who were allocated vitamin D 4000 IU (100 μg), vitamin D 2000 IU (50 μg), or placebo daily. Primary outcomes were plasma concentrations of 25-hydroxy-vitamin D and secondary outcomes were blood pressure, heart rate, and arterial stiffness in all participants at 6 and 12 months, plasma N-terminal prohormone of brain natriuretic peptide levels in all participants at 12 months, and echocardiographic measures of cardiac function in a randomly selected subset (n=177) at 12 months. Mean (SE) plasma 25-hydroxy-vitamin D concentrations were 50 (SE 2) nmol/L at baseline and increased to 137 (2.4), 102 (2.4), and 53 (2.4) nmol/L after 12 months in those allocated 4000 IU/d, 2000 IU/d of vitamin D, or placebo, respectively. Allocation to vitamin D had no significant effect on mean levels of blood pressure, heart rate, or arterial stiffness at either 6 or 12 months, nor on any echocardiographic measures of cardiac function, or plasma N-terminal prohormone of brain natriuretic peptide concentration at 12 months. CONCLUSIONS:The absence of any significant effect of vitamin D on blood pressure, arterial stiffness, or cardiac function suggests that any beneficial effects of vitamin D on cardiovascular disease are unlikely to be mediated through these mechanisms. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrialsregister.eu/ctr-search/search. Unique identifier: EudraCT number: 2011-005763-24a. 10.1161/JAHA.117.005707
    Vitamin D and walking speed in older adults: Systematic review and meta-analysis. Annweiler Cedric,Henni Samir,Walrand Stéphane,Montero-Odasso Manuel,Duque Gustavo,Duval Guillaume T Maturitas Vitamin D is involved in musculoskeletal health. There is no consensus on a possible association between circulating 25-hydroxyvitamin D (25OHD) concentrations and walking speed, a 'vital sign' in older adults. Our objective was to systematically review and quantitatively assess the association of 25OHD concentration with walking speed. A Medline search was conducted on June 2017, with no limit of date, using the MeSH terms "Vitamin D" OR "Vitamin D Deficiency" combined with "Gait" OR "Gait disorders, Neurologic" OR "Walking speed" OR "Gait velocity". Fixed-effect meta-analyses were performed to compute: i) mean differences in usual and fast walking speeds and Timed Up and Go test (TUG) between participants with severe vitamin D deficiency (≤25nmol/L) (SVDD), vitamin D deficiency (≤50nmol/L) (VDD), vitamin D insufficiency (≤75nmol/L) (VDI) and normal vitamin D (>75nmol/L) (NVD); ii) risk of slow walking speed according to vitamin D status. Of the 243 retrieved studies, 22 observational studies (17 cross-sectional, 5 longitudinal) met the selection criteria. The number of participants ranged between 54 and 4100 (0-100% female). Usual walking speed was slower among participants with hypovitaminosis D, with a clinically relevant difference compared with NVD of -0.18m/s for SVDD, -0.08m/s for VDD and -0.12m/s for VDI. We found similar results regarding the fast walking speed (mean differences -0.04m/s for VDD and VDI compared with NVD) and TUG (mean difference 0.48s for SVDD compared with NVD). A slow usual walking speed was positively associated with SVDD (summary OR=2.17[95%CI:1.52-3.10]), VDD (OR=1.38[95%CI:1.01-1.89]) and VDI (OR=1.38[95%CI:1.04-1.83]), using NVD as the reference. In conclusion, this meta-analysis provides robust evidence that 25OHD concentrations are positively associated with walking speed among adults. 10.1016/j.maturitas.2017.07.012
    Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging. Giallauria Francesco,Milaneschi Yuri,Tanaka Toshiko,Maggio Marcello,Canepa Marco,Elango Palchamy,Vigorito Carlo,Lakatta Edward G,Ferrucci Luigi,Strait James The Journal of clinical endocrinology and metabolism CONTEXT:The importance of vitamin D for bone health has long been acknowledged. Recent evidence suggests that vitamin D can also play a role in reducing the risk of several other diseases, including cardiovascular disease. OBJECTIVE:The aim of this study is to test the hypothesis that 25-hydroxyvitamin D (25-OH D) is an independent cross-sectional correlate of central arterial stiffness in a normative aging study population. DESIGN AND SETTINGS:We conducted a cross-sectional analysis. SUBJECTS:We studied 1228 healthy volunteers (50% males; age, 70±12 yr) of the Baltimore Longitudinal Study of Aging. MAIN OUTCOME MEASURES:We measured carotid-femoral pulse wave velocity (PWV) and 25-OH D levels. RESULTS:We found a significant inverse association between PWV and 25-OH D levels (adjusted r2=0.27; β=-0.43; P=0.001). After adjusting for age, gender, ethnicity, season of blood draw, estimated glomerular filtration rate, physical activity level, cardiovascular risk factors score (smoking, visceral obesity, hypercholesterolemia, hypertension, and diabetes), calcium/vitamin D supplementation, serum calcium, and PTH levels, the association between PWV and 25-OH D levels was only slightly reduced and remained statistically significant (adjusted r2=0.34; β=-0.34; P=0.04). CONCLUSIONS:Vitamin D levels are inversely associated with increased arterial stiffness in a normative aging population, irrespective of traditional risk factor burden. Further research is needed to understand the mechanism of this association and to test the hypothesis that vitamin D supplementation can reduce arterial stiffness. 10.1210/jc.2012-1584
    The VITAH Trial-Vitamin D Supplementation and Cardiac Autonomic Tone in Patients with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled Trial. Mann Michelle C,Exner Derek V,Hemmelgarn Brenda R,Hanley David A,Turin Tanvir C,MacRae Jennifer M,Wheeler David C,Sola Darlene Y,Ramesh Sharanya,Ahmed Sofia B Nutrients End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine the effects of oral vitamin D supplementation on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring hemodialysis were recruited from January 2013-March 2015 and randomized 1:1 to either conventional (0.25 mcg alfacalcidol plus placebo 3×/week) or intensive (0.25 mcg alfacalcidol 3×/week plus 50,000 international units (IU) ergocalciferol 1×/week) vitamin D for six weeks. The primary outcome was the change in LF:HF. There was no difference in LF:HF from baseline to six weeks for either vitamin D treatment (conventional: = 0.9 vs. baseline; intensive: = 0.07 vs. baseline). However, participants who remained vitamin D-deficient (25-hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF (conventional: = 13, ∆LF:HF: 0.20 ± 0.06, < 0.001 vs. insufficient and sufficient vitamin D groups; intensive: = 8: ∆LF:HF: 0.15 ± 0.06, < 0.001 vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient after treatment. Our findings potentially suggest that while activated vitamin D, with or without additional nutritional vitamin D, does not appear to improve cardiac autonomic tone in hemodialysis patients with insufficient or sufficient baseline vitamin D levels, supplementation in patients with severe vitamin D deficiency may improve cardiac autonomic tone in this higher risk sub-population of ESKD. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01774812. 10.3390/nu8100608
    Effect of vitamin D supplementation on serum lipid profiles: a systematic review and meta-analysis. Dibaba Daniel T Nutrition reviews CONTEXT:Vitamin D deficiency is highly prevalent across the world. The existing evidence suggests vitamin D may have beneficial effects on serum lipid profiles and thus cardiovascular health. OBJECTIVE:The objective of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on serum lipid profiles. DATA SOURCE:Original randomized controlled trials (RCTs) examining the effect of vitamin D supplementation on serum lipid profiles and published before July 2018 were identified by searching online databases, including PubMed, Google Scholar, and ScienceDirect, using a combination of relevant keywords. DATA EXTRACTION:Data on study characteristics, effect size, measure of variation, type of vitamin D supplementation, and duration of follow-up were extracted by the author. DATA ANALYSIS:PRISMA guidelines for systematic reviews were followed. Random effects (DerSimonian and Laird [D-V)] models were used to pool standardized mean differences in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides between the active and the placebo arms of RCT studies. Between-study heterogeneities were assessed using Cochrane Q and I2, and publication bias was assessed using Begg's test, Egger's test, and funnel plot. RESULTS:A total of 41 RCTs comprising 3434 participants (n = 1699 in the vitamin D supplementation arm and n = 1735 in the placebo arm) were identified and included in the meta-analysis. Approximately 63.4% of study participants were women, with 14 studies conducted entirely among women. Approximately 24% of the trials had follow-up duration >6 months, whereas the remaining 76% had follow-up duration of <6 months. The standardized mean differences (SMDs) and 95% confidence intervals (CIs) for comparing the change from baseline to follow-up between the vitamin D supplementation arm and the placebo (control) arm were as follows: total cholesterol = -0.17 (-0.28 to -0.06); LDL cholesterol = -0.12 (-0.23 to -0.01); triglycerides = -0.12 (-0.25 to 0.01); and HDL cholesterol = -0.19 (-0.44 to 0.06). After removing a trial that was an outlier based on the magnitude of the effect size, the SMD for triglycerides was -0.15 (-0.24 to -0.06) and that for HDL cholesterol was -0.10 (-0.28 to 0.09). The improvements in total cholesterol and triglycerides were more pronounced in participants with baseline vitamin D deficiency. CONCLUSIONS:Vitamin D supplementation appeared to have a beneficial effect on reducing serum total cholesterol, LDL cholesterol, and triglyceride levels but not HDL cholesterol levels. Vitamin D supplementation may be useful in hypercholesterolemia patients with vitamin D insufficiency who are at high risk of cardiovascular diseases. 10.1093/nutrit/nuz037
    Vitamin D modulates airway smooth muscle function in COPD. Banerjee Audreesh,Panettieri Reynold Current opinion in pharmacology COPD is a disease manifested as persistent airflow obstruction with an enhanced inflammatory response in the airways and lungs to noxious particles and gases which evokes symptoms of dyspnea on exertion, cough and mucus production. Airway smooth muscle plays a central role in the COPD diathesis and is implicated in many aspects of COPD pathogenesis. Vitamin D deficiency has been associated with COPD severity and studies suggest a role for Vitamin D as a treatment for COPD. In this review, we describe the effects of 1,25-dihydroxyvitamin D on airway smooth muscle function, including agonist-induced shortening, secretion of inflammatory mediators, and myocyte hypertrophy and hyperplasia. 10.1016/j.coph.2012.01.014
    Relationship between serum vitamin D and forced expiratory volume in patients with chronic obstructive pulmonary disease (COPD). Monadi Mahmoud,Heidari Behzad,Asgharpour Masumeh,Firouzjahi Alireza,Monadi Mohsen,Ghazi Mirsaied Mohammad Ali Caspian journal of internal medicine BACKGROUND:Vitamin D deficiency seems to be associated with pulmonary function deterioration. The present study was designed to investigate the relationship between serum vitamin D and forced expiratory volume in patients with chronic obstructive pulmonary disease (COPD). METHODS:From September 2011 to April 2012 eighty consecutive patients with COPD presented to an outpatient clinic of Babol University- Teaching Hospital entered to the study. Diagnosis of COPD was confirmed according to clinical findings and pulmonary function test. Serum 25-hydroxyvitamin D (25-OHD) was assessed by chemiluminuscence method and postbronchodilator forced expiratory volume in 1s (FEV1) was measured in all patients. The objective of this study was to determine the relationship between serum 25-OHD concentrations and FEV1 value. The patients were classified according to serum 25- OHD concentrations as less 10ng/ml, 10-19.9; 20-29.9; 30-39.9; and 40ng/ml or higher. The mean values of FEV1 for each class of serum 25-OHD were determined and compared. RESULTS:The mean age of patients was 67.4±11.5 years. The mean FEV1 volume in serum 25-OHD deficient COPD was lower than sufficient COPD (1.550±0.55 vs 1.650±-0.58, p=0.45). Mean FEV1 values increased from 1.55±0.55 L in patients with mean serum 25-OHD <20 ng/ml to 1.94±0.74 L in COPD patients with mean serum 25-OHD ±>40 ng/ml. There was a dose-response pattern of relationship between FEV1 and serum 25-OHD. However, the relationship did not reach to a statistically significant level. CONCLUSION:These findings indicated a relationship between serum 25-OHD concentration and FEV1 volume in patients with COPD and suggest optimization of serum vitamin D levels in COPD.
    Effects of vitamin D on immune disorders with special regard to asthma, COPD and autoimmune diseases: a short review. Székely Joseph I,Pataki Ágnes Expert review of respiratory medicine This paper reviews the recent data on the role of vitamin D (VD) in the genesis of various immunological disorders. It inhibits immune reactions in general, but it enhances the transcription of 'endogenous antibiotics' such as cathelicidin and defensins. VD inhibits the genesis of both Th1- and Th2-cell mediated diseases. The pleiotropic character VD-induced effects are due to the altered transcription of hundreds of genes. VD supplementation in most related studies reduced the prevalence of asthma. Th1-dependent autoimmune diseases (e.g., multiple sclerosis, Type 1 diabetes, Crohn's disease, rheumatoid arthritis and so on) are also inhibited by VD due to inhibition of antigen presentation, reduced polarization of Th0 cells to Th1 cells and reduced production of cytokines from the latter cells. VD seems to also be a useful adjunct in the prevention of allograft rejection. Last but not least, VD supplementation may be useful in the prevention or adjunct treatment of chronic obstructive pulmonary disease. 10.1586/ers.12.57
    Vitamin D and skeletal muscle strength and endurance in COPD. Jackson Abigail S,Shrikrishna Dinesh,Kelly Julia L,Kemp Samuel V,Hart Nicholas,Moxham John,Polkey Michael I,Kemp Paul,Hopkinson Nicholas S The European respiratory journal It is not known whether vitamin D levels make a significant contribution to muscle dysfunction in chronic obstructive pulmonary disease (COPD). In 104 COPD patients (mean±sd forced expiratory volume in 1 s 44±22 % predicted) and 100 age- and sex-matched controls, serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and parathyroid hormone (PTH) levels were measured and related to quadriceps strength and endurance. In a subset of 26 patients and 13 controls, quadriceps biopsy was performed and mRNA expression of myogenic regulatory factors (mrf) and fibre-specific myosin heavy chains (MHC) was determined. COPD patients were weaker and less physically active than controls. 25(OH)D levels were similar in both groups (48.5±25.5 nmol·L(-1) COPD versus 55.4±28.3 nmol·L(-1) control, p=0.07) but PTH levels were significantly higher in patients (5.2±2.3 pmol·mL(-1) versus 4.4±2.0 pmol·L(-1), p=0.01). 1,25(OH)D was significantly correlated with strength in controls, but not in COPD patients and not with quadriceps endurance assessed using repetitive magnetic stimulation in COPD (n=35) or control (n=35) subjects. In controls, but not COPD patients, muscle biopsy analysis showed a negative relationship between 25(OH)D and MHCIIa expression (r(2)=0.5, p=0.01) and a positive relationship between mrf4 and MHCIIa expression (r(2)=0.5, p=0.009), and myogenic regulatory factor myf5 and MHCI expression (r(2)=0.72, p=0.004). In contrast with healthy controls, muscle strength is not associated with vitamin D levels in COPD, which may represent vitamin D resistance. 10.1183/09031936.00043112
    Does low vitamin D amplify the association of COPD with total and cardiovascular disease mortality? Lee Hwa Mu,Liu Michael,Lee Katherine,Luo Yanting,Wong Nathan D Clinical cardiology BACKGROUND:Chronic obstructive pulmonary disease (COPD) has been shown to be associated with lower levels of vitamin D, and the latter has been associated with total and cardiovascular disease (CVD) mortality. HYPOTHESIS:We hypothesized that lower vitamin D levels will further enhance the association of COPD and its severity with total and CVD mortality. METHODS:We studied 7746 US adults age ≥40 years without known CVD (mean age, 59.8 years) and followed up through 2006 (8.2 ± 2.5 years) for total and CVD mortality. Serum 25-hydroxyvitamin D levels were categorized as tertiles: first tertile, <50.9 nm/L; second tertile, 50.9 to 73.6 nm/L; and third tertile, >73.6 nm/L. Severity of COPD was classified on the basis of forced expiratory volume per second (FEV1 ): mild COPD (FEV1 ≥80%) and moderate or severe COPD (FEV1 <80%), and requires a FEV1 /forced vital capacity ratio <70%. With Cox regression, we examined the hazard ratio (HR) and 95% confidence interval (CI) for total and CVD mortality according to COPD/vitamin D category, using those with no COPD in the first tertile of vitamin D as the reference group. RESULTS:From Cox regression, unadjusted HRs increased successively with increasing COPD severity and decreasing vitamin D group to 4.5 (95% CI: 3.3-6.1) for total and 3.4 (95% CI: 2.2-5.3) for CVD mortality among those with moderate/severe COPD who were in the first tertile of vitamin D. After adjustment for age, sex, ethnicity, and other risk factors, these associations were attenuated but remained increased. CONCLUSIONS:Lower levels of vitamin D may be associated with further increases in total and CVD mortality associated with COPD; however, age and cardiovascular risk factors appear to explain much of this association. 10.1002/clc.22284
    Effects of Vitamin D Intake on FEV1 and COPD Exacerbation: A Randomized Clinical Trial Study. Zendedel Abolfazl,Gholami Mohammadreza,Anbari Khatereh,Ghanadi Kourosh,Bachari Elham Ceneicel,Azargon Alireza Global journal of health science AIM:This study aimed to evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in the patients with severe and very severe COPD. METHODS:This double blind placebo control randomized clinical trial study was done in the Ashayer university hospital in Khorramabad in 2012. Eighty eight patients with severe and very severe COPD were randomly selected from those who recoursed to the internal medicine clinic of Ashayer hospital. They were randomly allocated to case and placebo group. The patients received routine treatment for COPD. Along with the routine treatment, placebo group received 100,000 IU of oral vitamin D per month, for 6 months. Data was analyzed using SPSS computer software, paired t-test, independent t-test, non parametric t-test and Pearson correlation coefficients. RESULTS:In each group, there were 44 patients. After the intervention, there were significant differences in FEV1 and the number of COPD exacerbation between the case and control group patients. Also, after the study, in the case group, FEV1 was increased and the number of COPD exacerbation was decreased significantly. CONCLUSION:Vitamin D intake decreased COPD exacerbation and improved FEV1 in the patients with severe and very severe COPD. It is suggested that baseline serum vitamin D levels will recorded in similar studies and the effect of vitamin D intake will evaluated regarding the baseline serum vitamin D levels. 10.5539/gjhs.v7n4p243
    Relationship of vitamin D status with lung function and exercise capacity in COPD. Jung Ji Ye,Kim Young Sam,Kim Se Kyu,Kim Ha Yan,Oh Yeon Mok,Lee Sang Min,Seo Joon Beom,Lee Sang-Do, Respirology (Carlton, Vic.) BACKGROUND AND OBJECTIVE:The relationship between blood vitamin D level and clinical parameters in patients with chronic obstructive pulmonary disease (COPD) has been reported with conflicting results. We explored the effects of vitamin D on clinical characteristics of patients with COPD in Korea. METHODS:The study population comprised 193 patients with COPD from Korean Obstructive Lung Disease Cohort. The plasma level of 25-OH vitamin D3 (25-OH-VitD3) was measured every year along with various clinical parameters such as lung function, 6-min walking (6MW) distance, quality of life, exacerbations and emphysema index. Generalized estimating equations and linear mixed model were used for statistical analysis. RESULTS:Of the 193 patients, 12 (6.2%), 28 (14.5%) and 153 (79.3%) were categorized into normal, insufficiency and deficiency groups. Clustered analysis showed that the plasma 25-OH-VitD3 level was associated with the post-bronchodilator ratio of force expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) (estimated = 0.001; P = 0.022). The vitamin D deficiency group showed lower FEV1 (estimated = -0.129, P = 0.043), FEV1 % predicted (estimated = -4.994, P = 0.029) and FEV1 /FVC ratio (estimated = -0.048, P = 0.001) than did the non-deficiency group. The 6MW distance tended to be shorter in deficiency group (estimated = -17.26, P = 0.069) than in non-deficiency group. Quality of life, exacerbation and emphysema index were not associated with plasma 25-OH-VitD3 level. CONCLUSIONS:We demonstrated a high prevalence of vitamin D deficiency in Korean patients with COPD and a significant relationship between vitamin D deficiency and airflow limitation. The exercise capacity tended to be decreased in the vitamin D deficiency group. 10.1111/resp.12538
    Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Jolliffe David A,Greenberg Lauren,Hooper Richard L,Mathyssen Carolien,Rafiq Rachida,de Jongh Renate T,Camargo Carlos A,Griffiths Christopher J,Janssens Wim,Martineau Adrian R Thorax BACKGROUND:Randomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation. METHODS:PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial. RESULTS:Four eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75). CONCLUSIONS:Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels. TRIAL REGISTRATION NUMBER:CRD42014013953. 10.1136/thoraxjnl-2018-212092
    Vitamin D does not improve lung function decline in COPD: a meta-analysis. Chen F-Y,Xiao M,Ling B,Liu L,Chen L European review for medical and pharmacological sciences OBJECTIVE:Vitamin D deficiency plays an important role in chronic obstructive pulmonary disease (COPD). However, the effects of vitamin D supplementation on lung function decline in COPD were inconsistently reported and a meta-analysis is thus needed. MATERIALS AND METHODS:Eligible cohort and randomized controlled trials (RCTs) were searched from databases including PubMed, Embase, and Web of Science. Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated in a random or fixed effects model. RESULTS:Eight studies reaching the inclusion criteria and involving 687 COPD patients were included. Pooled effect size showed vitamin D treatment resulted in no significant improvements in FEV1 (SMD: 0.38, 95% CI: -0.13 to 0.88, p= 0.144), FVC (SMD: 0.55, 95% CI: -0.49 to 1.58, p=0.299), and FEV1/FVC (SMD: 0.00, 95% CI: -0.27-0.27, p=0.995) in COPD patients. Subgroup analysis revealed neither short-term (<6 months) (SMD: 0.10, 95% CI: -0.17 to 0.37, p=0.479) nor long-term (≥6 months) (SMD: 0.52, 95% CI: -0.23 to 1.27, p=0.172) vitamin D exposure could significantly benefit lung function decline in COPD. CONCLUSIONS:This meta-analysis shows neither short-term nor long-term additional supplementation of vitamin D can benefit the lung function decline in COPD. Moreover, large scale RCTs focusing on COPD smokers with low level of vitamin D should be considered. 10.26355/eurrev_201910_19181
    The efficacy of vitamin D therapy for patients with COPD: a meta-analysis of randomized controlled trials. Li Xiaoyan,He Jie,Yu Mi,Sun Jian Annals of palliative medicine BACKGROUND:Many studies have demonstrated that vitamin D has clinical benefits when used to treat patients with chronic obstructive pulmonary disease (COPD). However, most of these studies have insufficient samples or inconsistent results. The aim of this meta-analysis was to evaluate the effects of vitamin D therapy in patients with COPD. METHODS:We performed an electronic literature search of the databases PubMed, China National Knowledge Internet (CNKI), Embase, Web of Science and Wanfang Data. Meta-analysis was carried out by Review Manager Version 5.3 (Revman 5.3), and standardized mean difference (SMD) and mean difference (MD) were used to assess the efficacy of vitamin D therapy in patients with COPD. RESULTS:A total of 25 articles involving 2,670 participants were included in this study. The overall results showed a statistical significance of vitamin D therapy in patients with COPD on forced expiratory volume in 1 second (FEV1) (SMD: 1.21, 95% CI: 0.76-1.66, P<0.01), FEV1/FVC (SMD: 1.07, 95% CI: 0.56-1.58, P<0.01), Exacerbations (SMD: 0.39, 95% CI: 0.23-0.64, P<0.01), Sputum volume (SMD: -6.02, 95% CI: -8.25 to 3.79, P<0.01), 6-minute walk distance (6MWD) (MD: 8.82, 95% CI: 1.67-15.98, P=0.02) and COPD assessment test (CAT) score (SMD: -1.19, 95% CI: -1.74 to 0.63, P<0.01). CONCLUSIONS:Our analysis indicated that vitamin D used in patients with COPD could improve the lung function (FEV1, FEV1/FVC), 6MWD and reduce acute exacerbation, sputum volume and CAT score. 10.21037/apm.2020.02.26
    Vitamin D Deficiency in COPD: Biomarker, Treatable Trait, or Just a Common Comorbidity? Milne Stephen,Sin Don D Chest 10.1016/j.chest.2019.12.007
    Vitamin D deficiency is associated with respiratory symptoms and airway wall thickening in smokers with and without COPD: a prospective cohort study. Ghosh Auyon J,Moll Matthew,Hayden Lystra P,Bon Jessica,Regan Elizabeth,Hersh Craig P, BMC pulmonary medicine BACKGROUND:Previous studies have established a higher prevalence of vitamin D deficiency in patients with COPD, but the relationship between vitamin D levels and COPD exacerbations remains controversial. In addition, the effect of vitamin D levels on imaging characteristics remains mostly unexplored. Using cross-sectional and longitudinal follow up data from the COPDGene Study, we assessed the association between vitamin D levels on respiratory symptoms, exacerbations, and imaging characteristics. We hypothesized that vitamin D deficiency will be associated with worse respiratory-related outcomes. METHODS:Current and former smokers between ages 45-80 were enrolled the COPDGene Study. Subjects completed questionnaires, spirometry, six-minute walk test, and chest computed tomography scans. A subset of subjects had measurement of serum concentration of 25-hydroxyvitamin D (25(OH)D). Vitamin D deficiency was defined as serum concentration less than 20 ng/mL. Longitudinal follow up was conducted via a web-based or telephone questionnaire. RESULTS:Vitamin D levels were measured on 1544 current and former smokers, of which 981 subjects had sufficient vitamin D levels and 563 subjects had vitamin D deficiency. Subjects with vitamin D deficiency were younger with increased likelihood of being African American, being current smokers, having a lower percent predicted FEV, and having COPD. Vitamin D deficiency was associated with worse quality of life, increased dyspnea, decreased exercise tolerance, and increased frequency of severe exacerbations. Vitamin D deficiency was also associated with increased segmental airway wall thickness on chest CT scans. CONCLUSION:Vitamin D deficiency was associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, as well as airway wall thickening on chest CT scans. Further research is needed to determine the potential impact of vitamin D supplementation to improve disease outcomes. 10.1186/s12890-020-1148-4