The Role of Vitamin D Deficiency in Cardiovascular, Metabolic and Autoimmune Diseases

Vitamin D deficiency frequently accompanies cardiovascular, metabolic and autoimmune disorders, but the clinical meaning of this association depends on the population, outcome and study design. Evidence from mechanistic studies, observational cohorts, genetic analyses and supplementation trials was assessed to distinguish biological plausibility from demonstrated disease prevention. Vitamin D metabolites regulate transcription through the vitamin D receptor and can modify innate and adaptive immune responses. Low circulating 25-hydroxyvitamin D may nevertheless reflect obesity, reduced outdoor activity, chronic illness or altered metabolism rather than an independent cause of disease. Cardiovascular supplementation trials have generally provided less support for prevention than observational studies. Diabetes and autoimmune outcomes require separate interpretation because baseline risk, deficiency status, dose and follow-up differ across trials. Mechanistic findings support further investigation of selected immune and metabolic pathways but do not establish a universal target concentration for extraskeletal health. Correction of established deficiency and testing of disease-specific hypotheses should be distinguished from indiscriminate supplementation for broad chronic disease prevention. Future studies should prespecify deficiency subgroups, measure adherence and achieved exposure, and prioritize clinically meaningful outcomes.