Vitamin D: A magic bullet or a myth?

The interest in Vitamin D (Vit D) is increased after the finding of Vit D receptors in many different cells. This led to the hypothesis that Vit D may have more impact on human health than its role in bone health. Epidemiological studies found associations between low plasma levels of Vit D and the prevalence of many diseases. However, Large RCTs did not find convincing evidence for a positive effect of Vit D supplementation on cancer, cardiovascular disease, auto-immune disease and inflammatory diseases. In this review, the results are described of a literature search regarding the relationship between Vit D status and different diseases. Pubmed was used to find systematic reviews of observational studies describing the association between Vit D status, diseases (cancer, coronary heart diseases, auto-immune diseases, sepsis) and mortality. Subsequently, a search was performed for RCTs and the results of large RCTs are described. Studies with a positive intervention effect on primary or secondary outcome variables are summarized. No exclusion criteria were used. The metabolism of Vit D is reviewed, its endogenous production and the intake from food, its activation and transport in the body. The article addresses the effects of diseases on the metabolism of Vit D with special focus on the role of Vit D Binding Protein and its effects on assessing Vit D status. Studies addressing the association between vitamin D status and cancer, cardiovascular diseases, auto-immune diseases, inflammation and severe illness are reviewed. A search for RCTs with positive effects of Vit D supplementation on different diseases yielded only a few studies. The vast majority of RCTs showed no significant positive effects. The presumed high prevalence of Vit D deficiency is questioned based on these results and on altered concentrations of Vit D binding protein, leading to low Vit D levels in plasma but not to low active Vit D levels during disease related inflammation In these conditions, plasma levels of Vit D are therefore not a valid reflection of Vit D status. Reversed causality is described as a possible factor interfering with the correct assessment of the Vit D status. It is concluded that further widespread fortification of foods and stimulation of supplement use should be reconsidered.