Ultraviolet radiation, vitamin D and multiple sclerosis

There is compelling epidemiological evidence that the risk of developing multiple sclerosis is increased in association with low levels of sun exposure, possibly because this is associated with low vitamin D status. Recent work highlights both vitamin D and non-vitamin D effects on cellular immunity that suggests that higher levels of sun exposure and/or vitamin D status are beneficial for both MS risk and in ameliorating disease progression. Here we review this recent evidence, focusing on regulatory cells, dendritic cells, and chemokines and cytokines released from the skin following exposure to ultraviolet radiation. Practice points There is strong evidence from observational studies that low past sun exposure is associated with an increased risk of developing multiple sclerosis (MS). Lower sun exposure or lower vitamin D status have been linked to more severe MS, that is, more frequent relapses and more rapid progression to disability. Vitamin D supplementation trials for people with MS have shown improvement in immunological and MRI parameters, but with little convincing evidence of clinical benefit. Higher levels of sun exposure may have benefits for MS-related immune parameters through both vitamin D and non-vitamin D pathways. Exposure to ultraviolet radiation may result in immune tolerance that is beneficial for MS through upregulation of T and B regulatory cells, enhanced levels of cis-urocanic acid, alterations in dendritic cell trafficking as well as release of a range of other cytokines and chemokines. Trials of vitamin D supplementation and UVB phototherapy to prevent MS in people with clinically isolated syndrome are now underway. Clues to etiological pathways often lie within the epidemiology of diseases. For multiple sclerosis (MS), the observation that the disease is more common with increasing distance from the equator led, over 50 years ago, to a link being drawn with variation in levels of ultraviolet radiation (UVR) [1]. Ensuing ecological and individual-level studies largely confirmed a link between lower sun exposure and increased risk of MS, and animal studies suggested the protective effect was mediated by vitamin D. However, the vitamin D precursor is not the only chromophore in the skin; a range of other UV-induced products have biological effects likely to be relevant to MS. Here we provide an update on recent vitamin D-related research in MS, and situate this work within a broader consideration of low sun exposure as a risk factor for MS onset and progression