The health effects of vitamin D supplementation: evidence from human studies

Authors

Roger Bouillon, Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium. Roger.Bouillon@kuleuven.be.
Despoina Manousaki, Research Center of the Sainte-Justine University Hospital, University of Montreal, Montreal, Quebec, Canada.
Cliff Rosen, Maine Medical Center Research Institute, Scarborough, ME, USA.Follow
Katerina Trajanoska, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands.
Fernando Rivadeneira, Translational Skeletal Genomics, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands.
J Brent Richards, Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.

Document Type

Article

Publication Date

2-1-2022

Journal Title

Nature reviews. Endocrinology

MeSH Headings

Aged; Child; Diabetes Mellitus, Type 2 (drug therapy); Dietary Supplements; Humans; Infant; Rickets (chemically induced, drug therapy); Vitamin D (therapeutic use); Vitamin D Deficiency (drug therapy)

Abstract

Vitamin D supplementation can prevent and cure nutritional rickets in infants and children. Preclinical and observational data suggest that the vitamin D endocrine system has a wide spectrum of skeletal and extra-skeletal activities. There is consensus that severe vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) concentration /l) should be corrected, whereas most guidelines recommend serum 25OHD concentrations of >50 nmol/l for optimal bone health in older adults. However, the causal link between vitamin D and many extra-skeletal outcomes remains unclear. The VITAL, ViDA and D2d randomized clinical trials (combined number of participants >30,000) indicated that vitamin D supplementation of vitamin D-replete adults (baseline serum 25OHD >50 nmol/l) does not prevent cancer, cardiovascular events, falls or progression to type 2 diabetes mellitus. Post hoc analysis has suggested some extra-skeletal benefits for individuals with vitamin D deficiency. Over 60 Mendelian randomization studies, designed to minimize bias from confounding, have evaluated the consequences of lifelong genetically lowered serum 25OHD concentrations on various outcomes and most studies have found null effects. Four Mendelian randomization studies found an increased risk of multiple sclerosis in individuals with genetically lowered serum 25OHD concentrations. In conclusion, supplementation of vitamin D-replete individuals does not provide demonstrable health benefits. This conclusion does not contradict older guidelines that severe vitamin D deficiency should be prevented or corrected.

First Page

96

Last Page

110

Recommended Citation

Bouillon R, Manousaki D, Rosen C, Trajanoska K, Rivadeneira F, Richards JB. The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol. 2022;18(2):96-110. doi:10.1038/s41574-021-00593-z