title: Role of Vitamin D deficiency in extraskeletal complications: predictor of health outcome or marker of health status?
abstract: The relationship of vitamin D with extraskeletal complications, such as cardiovascular disease, cancer, and autoimmune disease, is of major interest considering its roles in key biological processes and the worldwide high prevalence of vitamin D deficiency. However, the causal relationships between vitamin D and most extraskeletal complications are weak. Currently, a heated debate over vitamin D is being conducted according to two hypotheses. In this review, we first present the different arguments that suggest a major role of vitamin D in a very broad type of extraskeletal complications (hypothesis #1). We then present results from recent meta-analyses of randomized controlled trials indicating a lack of association of vitamin D with major extraskeletal complications (hypothesis #2). We discuss different issues (e.g., causality, confounding, reverse causation, misclassification, and Mendelian randomization) that contribute to the favoring of one hypothesis over the other. While ultimately only one hypothesis is correct, we anticipate that the results from the ongoing randomized controlled trials will be unlikely to reconcile the divided experts.
authors.affiliation: Unit of Population Epidemiology, Department of Community Medicine and Primary Care and Emergency Medicine, Geneva University Hospitals, 1214 Geneva, Switzerland ; Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, 1010 Lausanne, Switzerland ; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 1518, USA.
authors.forename: Idris
authors.identifier: 0000-0002-0491-6089
authors.initials: I
authors.lastname: Guessous
mesh_terms: D001327:Autoimmune Diseases / Q000209:etiology / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism; D006801:Humans; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000150:complications / Q000378:metabolism
chemical_list: D014807:Vitamin D