Vitamin D in rheumatoid arthritis: panacea or placebo?

Vitamin D deficiency is highly prevalent in the general population including individuals with rheumatoid arthritis (RA). Autocrine regulation of vitamin D modulates important biologic processes including immune responses. Vitamin D deficiency has been implicated in the pathogenesis of several autoimmune diseases including RA. Vitamin D regulates both the innate and adaptive immune responses. Recent evidence indicates that vitamin D's effects on the innate immune system are predominantly through the toll-like receptors (TLR) and on the adaptive immune system through T cell differentiation, particularly the Th17 response. As Th17 cells are critical in the pathogenesis of RA, this has led to an interest in the effects of vitamin D deficiency in RA. Several studies have looked at the association of vitamin D deficiency with markers of disease activity in RA with somewhat mixed results. Based on these results, although the role of vitamin D in mediating various biological processes is well defined, this has not translated into meaningful clinical associations in RA. Herein, we review the immune-modulatory role of vitamin D and its effects on pathogenesis, disease activity, and cardiovascular risk in RA.