Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Apr 1;348:g2035.
doi: 10.1136/bmj.g2035.

Vitamin D and Multiple Health Outcomes: Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies and Randomised Trials

Affiliations
Free PMC article
Review

Vitamin D and Multiple Health Outcomes: Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies and Randomised Trials

Evropi Theodoratou et al. BMJ. .
Free PMC article

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

None
Fig 1 Flow chart of eligible studies
None
Fig 2 Map of 137 vitamin D related outcomes: percentage of outcomes per outcome category for all study designs
None
Fig 3 Forest plot of all meta-analyses of observational studies stratified by measured biomarker with relative risk as type of metric
None
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

Comment in

Similar articles

See all similar articles

Cited by 235 articles

See all "Cited by" articles

References

    1. Lips P. Vitamin D physiology. Prog Biophys Mol Biol 2006;92:4-8. - PubMed
    1. Holick MF. McCollum Award Lecture, 1994: vitamin D—new horizons for the 21st century. Am J Clin Nutr 1994;60:619-30. - PubMed
    1. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007;370:657-66. - PubMed
    1. Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, Burckhardt P, Li R, Spiegelman D, et al. Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr 2007;86:1780-90. - PubMed
    1. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 2009;169:551-61. - PubMed
Feedback