Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.

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Background Vitamin D insufficiency is associated with suboptimal health. The prevalence of vitamin D insufficiency may be rising, but population-based trends are uncertain. We sought to evaluate US population trends in vitamin D insufficiency. Methods We compared serum 25-hydroxyvitamin D (25[OH]D) levels from the Third National Health and Nutrition Examination Survey (NHANES III), collected during 1988 through 1994, with NHANES data collected from 2001 through 2004 (NHANES 2001–2004). Complete data were available for 18 883 participants in NHANES III and 13 369 participants in NHANES 2001–2004. Results The mean serum 25(OH)D level was 30 (95% confidence interval [CI], 29–30) ng/mL during NHANES III and decreased to 24 (23–25) ng/mL during NHANES 2001–2004. Accordingly, the prevalence of 25(OH)D levels of less than 10 ng/mL increased from 2% (95% CI, 2%–2%) to 6% (5%–8%), and 25(OH)D levels of 30 ng/mL or more decreased from 45% (43%–47%) to 23% (20%–26%). The prevalence of 25(OH)D levels of less than 10 ng/mL in non-Hispanic blacks rose from 9% during NHANES III to 29% during NHANES 2001–2004, with a corresponding decrease in the prevalence of levels of 30 ng/mL or more from 12% to 3%. Differences by age strata (mean serum 25[OH]D levels ranging from 28–32 ng/mL) and sex (28 ng/mL for women and 32 ng/mL for men) during NHANES III equalized during NHANES 2001–2004 (24 vs 24 ng/mL for age and 24 vs 24 ng/mL for sex). Conclusions National data demonstrate a marked decrease in serum 25(OH)D levels from the 1988–1994 to the 2001–2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.

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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 ≥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. Randomized controlled trials are warranted to explore the effects of vitamin D supplementation on RTI.

Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. To investigate the relation between blood levels of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) with hemodialysis outcomes, we measured baseline vitamin D levels in a cross-sectional analysis of 825 consecutive patients from within a prospective cohort of incident US hemodialysis patients. Of these patients, 78% were considered vitamin D deficient with 18% considered severely deficient. Calcium, phosphorus, and parathyroid hormone levels correlated poorly with 25D and 1,25D concentrations. To test the association between baseline vitamin D levels and 90-day mortality, we selected the next 175 consecutive participants who died within 90 days and compared them to the 750 patients who survived in a nested case-control analysis. While low vitamin D levels were associated with increased mortality, significant interaction was noted between vitamin D levels, subsequent active vitamin D therapy, and survival. Compared to patients with the highest 25D or 1,25D levels who received therapy, untreated deficient patients were at significantly increased risk for early mortality. Our study shows that among incident hemodialysis patients, vitamin D deficiency is common, correlates poorly with other components of mineral metabolism and is associated with increased early mortality.

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