Multiple sclerosis and vitamin D: don't (yet) blame it on the sunshine.

Multiple sclerosis and vitamin D: don't (yet) blame it on the sunshine It is all but 50 years since Sir Donald Acheson proposed a relationship between solar radiation and multiple sclerosis (Acheson et al., 1960). The subsequent discovery of the link between sunlight and vitamin D raised the potential for dietary supplementation to prevent or ameliorate the most common chronic neurologic disease of young adults. Research in the field has proceeded down two distinct lines: epidemiological studies aimed at confirming and refining the association; and studies directed towards providing biological plausibility that may advance association to causation or at least justify large-scale clinical trials with an inexpensive agent. If definitive evidence is represented by a completed jigsaw puzzle, many pieces have been added to this story but others are missing and the picture is still indistinct. It is clear that multiple sclerosis results from the interaction of genetic susceptibility with environmental factors. The strongest clue to an environmental candidate is the correlation with lati-tude—prevalence increasing with distance from the equator—for which the clearest data come from Australia where the disease is seven times more prevalent in Tasmania compared with tropical Queensland in populations of similar genetic background (McLeod et al., 1994). Ultraviolet sunlight-dependent metabolism provides the major source of vitamin D 3 (D 3) in humans and at high latitudes solar radiation in winter is too low to produce it in adequate amounts. Replicated evidence now exists for a correlation between the risk of multiple sclerosis and reduced sunlight exposure although interpretation is influenced by uncertain knowledge of the critical period(s) of environmental effects in the pathogenesis of the disease: in utero, in childhood or throughout life. The evidence is significant, although less convincing, for vitamin D deficiency and the risk of multiple sclerosis (Munger et al., 2004, 2006). A major boost to the hypothesis came with the demonstration of the effects of vitamin D on immune function. D 3 is hydroxy-lated to the major circulating form, 25(OH) D 3 and then, through a second hydoxylase, to the biologically active 1,25(OH) 2 D 3 ; catabolism involves a third hydoxylase. 1,25(OH) 2 D 3 exerts its effects through the vitamin D receptor, which acts as a ligand-activated transcription factor by binding to vitamin D response elements in the promoter regions of vitamin D responsive genes. The vitamin D receptor is expressed on antigen-presenting cells and activated lymphocytes and extensive studies …