Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data

Abstract

BackgroundA large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation.Methods and findingsWe identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses.ConclusionsPublished RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels.

Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections

“…Observational studies report an association between low blood concentrations of 25-hydroxyvitamin D (the major vitamin D metabolite) and susceptibility to acute respiratory tract infections [29,30]. Consistent with these findings, several recent meta-analyses have concluded that vitamin D supplementation can reduce the risk of respiratory tract infections in both children and adults [11,[31][32][33][34][35]. In 2017, Martineau and colleagues performed a systematic review and meta-analysis of individual participant data (n = 10,933) from 25 randomized, double blind, placebo controlled trials of vitamin D supplementation with a specified outcome of acute respiratory tract infection (ARI).…”

Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

“…RCTs comparing outcomes for participants treated or given a placebo are preferred to establish causality related to health outcomes. However, most vitamin D RCTs have not reported that vitamin D supplementation reduced the risk of disease [62,63]. Reasons for the lack of agreement between observational studies and RCTs seems to be due to several factors, including enrolling participants with relatively high 25(OH)D concentrations and using low vitamin D doses and not measuring baseline and achieved 25(OH)D concentrations.…”

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

“…A subsequent trial analysis, systematic review and meta-analysis suggest that vitamin D supplementation might protect against fatal and non-fatal CHFs in older, healthy people (HR 0.75, 95% CI 0.58-0.97), but not against MI or stroke [48]. The most recent meta-analysis on non-skeletal effects of vitamin D supplementation demonstrates that most trials have been done in subjects without low 25[OH]D levels limiting the credibility of the argument that vitamin D supplementation has no potential benefit on outcomes in people with 25[OH] D insufficiency [1]. The Vitamin D Assessment study (ViDA) in 5100 healthy subjects, aged > 50 years, recently reported that 100,000 IU oral vitamin D 3 monthly was neutral for the prevention of CV disease [49,50], with a low rate of 25[OH]D deficiency in participants (25%), a lower than expected endpoint rate and monthly doses cited as possible reasons [51].…”

“…Low serum 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with an increased risk of adverse outcomes generally, [1,2] but especially in patients with suspected coronary artery disease, hypertension and chronic heart failure (CHF) [3][4][5][6][7][8][9][10]. However, published data pertaining to CHF are derived from registry data, or somewhat selected cohorts such as patients referred for coronary angiography, on a waiting list for cardiac transplantation or in-patients.…”