Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials

Evropi Theodoratou, Ioanna Tzoulaki, Lina Zgaga, John P A Ioannidis, Evropi Theodoratou, Ioanna Tzoulaki, Lina Zgaga, John P A Ioannidis

Abstract

Objective: To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes.

Design: Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation.

Data sources: Medline, Embase, and screening of citations and references.

Eligibility criteria: Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D).

Results: 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people.

Conclusions: Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793667/bin/thee017309.f1_default.jpg
Fig 1 Flow chart of eligible studies
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793667/bin/thee017309.f2_default.jpg
Fig 2 Map of 137 vitamin D related outcomes: percentage of outcomes per outcome category for all study designs
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793667/bin/thee017309.f3_default.jpg
Fig 3 Forest plot of all meta-analyses of observational studies stratified by measured biomarker with relative risk as type of metric
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793667/bin/thee017309.f4_default.jpg
Fig 4 Forest plot of all meta-analyses of randomised controlled trials with relative risk as type of metric by compound administered. CKD=chronic kidney disease patients; NRD=not requiring dialysis; RD=requiring dialysis; UV=ultraviolet

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Source: PubMed

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