Effect of vitamin D on health and disease: evidence from Mendelian randomization

Preclinical and epidemiological studies suggest a role of the vitamin D endocrine system in a plethora of health outcomes. However, the causal link between vitamin D and various extraskeletal outcomes remains unclear. Mendelian randomization (MR), a method suited to minimize bias from confounding and allowing for testing putative causal relations, has been widely used to investigate causal effects of vitamin D on human disease in the general population. Most of the MR studies evaluating the consequences of lifelong genetically determined serum levels of 25(OH)D on various outcomes have reported null effects, except for few studies demonstrating a causal effect on multiple sclerosis. Nonlinear MR studies also support causal effects of low serum 25(OH)D (<50nmol/L) on cardiovascular health and all-cause mortality. These findings suggest that vitamin D replacement in the general population is unlikely to be beneficial, expect for people at risk for multiple sclerosis or established vitamin D deficiency.