In conclusion, supplementation of vitamin D-replete individuals does not provide demonstrable health benefits. Four Mendelian randomization studies found an increased risk of multiple sclerosis in individuals with genetically lowered serum 25OHD concentrations. 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. Post hoc analysis has suggested some extra-skeletal benefits for individuals with vitamin D deficiency. 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. However, the causal link between vitamin D and many extra-skeletal outcomes remains unclear. There is consensus that severe vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) concentration 50 nmol/l for optimal bone health in older adults. Preclinical and observational data suggest that the vitamin D endocrine system has a wide spectrum of skeletal and extra-skeletal activities. Vitamin D supplementation can prevent and cure nutritional rickets in infants and children.

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