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BioMed Research International
Volume 2015, Article ID 563403, 13 pages
Review Article

Role of Vitamin D Deficiency in Extraskeletal Complications: Predictor of Health Outcome or Marker of Health Status?

1Unit of Population Epidemiology, Department of Community Medicine and Primary Care and Emergency Medicine, Geneva University Hospitals, 1214 Geneva, Switzerland
2Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, 1010 Lausanne, Switzerland
3Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 1518, USA

Received 30 October 2014; Accepted 9 January 2015

Academic Editor: Domenico Santoro

Copyright © 2015 Idris Guessous. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.