Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study.

The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate acute inflammation in vivo has not been established in humans. In a double-blinded, placebo-controlled interventional trial, 20 healthy adults were randomized to receive either placebo or a high dose of vitamin D3 (cholecalciferol) one hour after experimental sunburn induced by an erythemogenic dose of UVR. Compared with placebo, participants receiving vitamin D3 (200,000 international units) demonstrated reduced expression of proinflammatory mediators tumor necrosis factor-α (P = 0.04) and inducible nitric oxide synthase (P = 0.02) in skin biopsy specimens 48 hours after experimental sunburn. A blinded, unsupervised hierarchical clustering of participants based on global gene expression profiles revealed that participants with significantly higher serum vitamin D3 levels after treatment (P = 0.007) demonstrated increased skin expression of the anti-inflammatory mediator arginase-1 (P = 0.005), and a sustained reduction in skin redness (P = 0.02), correlating with significant expression of genes related to skin barrier repair. In contrast, participants with lower serum vitamin D3 levels had significant expression of proinflammatory genes. Together the data may have broad implications for the immunotherapeutic properties of vitamin D in skin homeostasis, and implicate arginase-1 upregulation as a previously unreported mechanism by which vitamin D exerts anti-inflammatory effects in humans.

Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data.

IMPORTANCE: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE: To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES: Difference in SBP and DBP measured in an office setting. RESULTS: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

A randomized controlled trial of high dose vitamin D3 in patients with heart failure.

OBJECTIVE: To investigate the effect of Vitamin D3 on physical performance in patients with HF. BACKGROUND: HF is associated with functional decline and frailty. Vitamin D deficiency is associated with loss of muscle strength and poor outcomes in patients with HF. METHODS: Sixty-four patients participated in a 6-month parallel design double blind RCT to test the hypothesis that oral vitamin D3 would improve physical performance. Vitamin D3 50,000 IU or placebo was given weekly; all received daily calcium. Patients were included regardless of EF and 25OHD ≤ 37.5 ng/ml. The primary outcome was peak VO2, and secondary outcomes were the 6MW, TGUG and knee isokinetic muscle strength. Between group comparisons were made using ANCOVA models that adjust for baseline measures. RESULTS: Patients were age 65.9 ± 10.4 years old, 48% women, 64% African American, EF 37.6±13.9, 36% NYHA III, the remainder NYHA II. At baseline the vitamin D group 25OHD was 19.1 ± 9.3 ng/ml and increased to 61.7 ± 20.3 ng/ml; in the placebo group baseline 25OHD was 17.8 ± 9.0 ng/ml and decreased to 17.4 ± 9.8 ng/ml at 6 months (between groups p<0.001). There was no significant change from baseline to 6 months in peak VO2, 6MW, TGUG or isokinetic muscle strength. CONCLUSIONS: Vitamin D3 did not improve physical performance for patients with HF despite a robust increase in serum 25OHD. Vitamin D repletion in patients with HF should conform to standard adult guidelines for vitamin D supplementation.

Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women.

OBJECTIVES: To investigate the effects of dehydroepiandrosterone (DHEA) combined with exercise on bone mass, strength, and physical function in older, frail women. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: A major medical institution. PARTICIPANTS: Ninety-nine women (mean age 76.6 ± 6.0) with low sulfated DHEA (DHEAS) levels, low bone mass, and frailty. INTERVENTION: Participants received 50 mg/d DHEA or placebo for 6 months; all received calcium and cholecalciferol. Women participated in 90-minute twice-weekly exercise regimens. MEASUREMENTS: Hormone levels, bone mineral density (BMD), bone turnover markers, body composition, upper and lower extremity strength, physical performance. RESULTS: Eighty-seven women (88%) completed 6 months. There were no significant changes in BMD or bone turnover markers. DHEA supplementation resulted in gains in lower extremity strength (from 459 ± 121 N to 484 ± 147 N; P=.01). There was also improvement in Short Physical Performance Battery score, a composite score that focuses on lower extremity function, in those taking DHEA (from 10.1 ± 1.8 to 10.7 ± 1.9; P=.02). There were significant changes in all hormone levels, including DHEAS, estradiol, estrone, and testosterone, and a decline in sex hormone-binding globulin levels in those taking DHEA. CONCLUSION: DHEA supplementation improved lower extremity strength and function in older, frail women involved in a gentle exercise program of chair aerobics or yoga. No changes were found in BMD either due to small sample size, short duration of study or no effect. The physical function findings are promising and require further evaluation as frail women are at high risk for falls and fracture.