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.
Highlights
In recent years the number of studies exploring effects of vitamin D beyond its well-known effects on the musculo-skeletal system have increased markedly
The fact that most MAs on results from randomized clinical trials (RCTs) did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels
None of the analyses showed effects of vitamin D supplementation on risk of incident cancers, and this was not changed by stratification on whether the supplementation was provided as vitamin D alone or vitamin D in combination with calcium (Table Fa in supplementary file (S1 File))
Summary
In recent years the number of studies exploring effects of vitamin D beyond its well-known effects on the musculo-skeletal system have increased markedly. The vitamin D receptor (VDR) and the enzyme (the 1α-hydroxylase) needed to hydroxylate 25-hydroxyvitamin D (25OHD) to its active form 1,25-dihydroxyvitamin D (1,25(OH)2D) has been identified in a large number of different cells. Within the last few years, an increasingly number of SRs has been published, including meta-analyses (MAs) with summary data on results from RCT on non-skeletal outcomes in response to supplementation with vitamin D [18,19,20]. We report characteristics of the individual trials included in MAs, in order to review the evidence-base providing data for published MAs. A 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
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