Besides playing a key role in maintaining bone health, vitamin D has also been recognised for its antibacterial, antiproliferative, immunomodulatory and anti-inflammatory actions 1,2, whilst its immunomodulatory functions have increasingly become of scientific interest. Indeed, in recent years, both clinical and epidemiological data supporting the link between vitamin D status and the incidence and severity of immunocorrelated conditions, such as multiple sclerosis, psoriasis, diabetes, rheumatoid arthritis, inflammatory bowel disease and infectious diseases, have been published. Whereas the association between these pathological events and vitamin D deficiency has been widely demonstrated, the effect of cholecalciferol supplementation on the same phenomena has not. To complicate the picture, published studies are extremely heterogeneous in terms of the populations considered, the basal 25(OH)D levels, the extent of supplementation and the modality applied to administration (daily rather than boluses).
Attention to the effect of cholecalciferol supplementation on immune cells and inflammatory cytokines was certainly rekindled by publication of the VITAL study last year. In this study, 25,571 subjects were enrolled and randomised to take 2,000 IU of cholecalciferol per day (with or without omega-3 supplementation) versus placebo for five years, demonstrating a 22% reduction in the incidence of autoimmune diseases, including rheumatoid arthritis, polymyalgia rheumatica and psoriasis.
The regulation of inflammation and cytokine expression is also of crucial importance for the recent “inflammaging” hypothesis, which proposes that with increasing age there appears to be a shift towards a proinflammatory state that tends to create and maintain a chronic low-grade inflammation (only partially detectable by serum biomarkers such as C-reactive protein [CRP]) with a subsequent slow accumulation of damage. This acceleration toward ageing, driven by chronic inflammation, is believed to be the basis for progression to several chronic diseases. This has also been confirmed by a recent Anglo-Saxon biobank study of 397,737 subjects, aged between 37 and 73 years. Vitamin D deficiency was found to be associated with increased mortality from several causes, although not with classical serum inflammatory markers. If this is valid in the general population, however, it may be different in patient populations with high levels of inflammation, such as those with cancer, diabetes mellitus or acute cardiovascular disease, where supplementation in deficient subjects showed a reduction in high-sensitivity PCR.