Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials.

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.

Physical activity and change in fasting glucose and HbA1c: a quantitative meta-analysis of randomized trials.

AIMS: A systematic review was conducted of randomized trials which evaluated the impact of physical activity on the change in fasting glucose and HbA1c. METHODS: A literature search was conducted in PubMed until December 2015. Studies reporting glucose or HbA1c at baseline and at the end of study were included, and the change and its variance were estimated from studies with complete data. Mixed-effect random models were used to estimate the change of fasting glucose (mg/dl) and HbA1c (%) per additional minutes of physical activity per week. RESULTS: A total of 125 studies were included in the meta-analysis. Based on 105 studies, an increase of 100 min in physical activity per week was associated with an average change of -2.75 mg/dl of fasting glucose (95% CI -3.96; -1.55), although there was a high degree of heterogeneity (83.5%). When restricting the analysis on type 2 diabetes and prediabetes subjects (56 studies), the average change in fasting glucose was -4.71 mg/dl (95% CI -7.42; -2.01). For HbA1c, among 76 studies included, an increase of 100 min in physical activity per week was associated with an average change of -0.14% of HbA1c (95% CI -0.18; -0.09) with heterogeneity (73%). A large degree of publication bias was identified (Egger test p < 0.001). When restricting the analysis on type 2 diabetes and prediabetes subjects (60 studies), the average change in HbA1c was -0.16% (95% CI -0.21; -0.11). CONCLUSIONS: This analysis demonstrates that moderate increases in physical activity are associated with significant reductions in both fasting glucose and HbA1c.

Prognostic Value of 25-hydroxyvitamin D3 Levels at Diagnosis and During Follow-up in Melanoma Patients.

BACKGROUND: A low 25-hydroxyvitamin D3 (25(OH)D3) serum concentration at melanoma diagnosis might be associated with worse survival. We prospectively studied the prognostic value of 25(OH)D3 at diagnosis and during follow-up. METHODS: MelanCohort is a cohort of invasive melanoma patients. Serum 25(OH)D3 was measured by mass spectrometry and standardized on month of blood drawn, age, sex, and body mass index (BMI). Role of 25(OH)D3 levels and risk of relapse was analyzed in a Cox proportional hazards model adjusting for age, sex, BMI, and American Joint Committee on Cancer (AJCC) stage. All statistical tests were two-sided. RESULTS: One thousand one hundred seventy-one patients were included. 25(OH)D3 levels at diagnosis (median = 49.0 nmol/L) were inversely correlated with prognostic factors such as AJCC stage (P < .001 Kruskal-Wallis), Breslow's thickness (P < .001 Spearman correlation), and ulceration (P < .001 Kruskal-Wallis), but not with risk of relapse. Changes in 25(OH)D3 levels during follow-up were associated with worse prognosis: With a third quartile Q3 of average change per year (-0.30 to 4.60 nmol/L/Y) used as reference, hazard ratios for the first, second, and fourth quarters were 1.94 (95% confidence interval [CI] = 1.36 to 2.76), 1.23 (95% CI = 0.85 to 1.78), and 1.61 (95% CI = 1.14 to 2.28), respectively. In sensitivity analyses, no changes were observed either by AJCC stage, number of 25(OH)D3 measures performed, or by 25(OH)D3 level at baseline. No evidence of reverse causation was identified. Analyses performed on overall survival yielded similar results. CONCLUSIONS: We show that 25(OH)D3 variation during follow-up is an independent melanoma prognostic marker, but not its level at diagnosis. Previously reported associations between low 25(OH)D3 level at diagnosis and poor prognosis seem to be due to insufficient adjustment for prognostic factors.