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Mouse MS: UVB but not Vitamin D reduced incidence - April 2010

When Vitamin D can’t replace UVB exposure: multiple sclerosis

April 28, 2010 by Colby Vorland http://recomp.com/blogma/2010/04/when-vitamin-d-cant-replace-uvb-exposure-multiple-sclerosis

Vitamin D is a hot topic lately, and many observational studies have linked it positively with a reduction in various disease risks. However, we should be careful not to tout it as a panacea without large controlled studies and a deeper understanding of how it regulates various endogenous processes.

A recent publication studying UV radiation exposure in a model of multiple sclerosis (1) is a prime example of how correlation can lead us astray, as it suggests that UVB, but not vitamin D at concentrations obtained by UVB exposure, can inhibit a model of multiple sclerosis in mice.

Multiple sclerosis (MS) is characterized by inflammatory plaques that destroy the myelin sheath around axons, which leads to a faulty communication between neurons. Both genetic and environmental factors have been identified that influence MS incidence, and among the latter, Vitamin D and UV radiation are strongly implicated. MS incidence generally follows a latitudinal gradient in observational studies, and correlations between residential and occupational sun exposure and MS also exist.

When UV radiation hits photoreceptors in the skin, signals are sent out that can suppress cell immunity, both locally and systemically, through a variety of mechanisms. With skin cancer, this is a negative effect. But for autoimmune diseases like MS, it may be beneficial.

The animal model of MS is called experimental autoimmune encephalomyelitis (EAE). The authors cite a previous mouse study showing a 7-day pretreatment with UV radiation prevents induction of the disease.

Also of note, however, are several animal studies showing that supplementing D to supraphysiological concentrations can also suppress induction and progression of disease in the EAE model. These levels cause hypercalcemia, which may be a major role in the immunosuppressive effects in these studies. Would D at normal concentrations do the same? In this experiment, the authors set out to see.

Mice were subjected each day for 7 days to (2 levels of) UV radiation, then disease induced. However this time EAE was not prevented, though slightly delayed with a higher dose. This may be because of differences in mouse strains or for other reasons. Serum calcium levels did not change, while 25OHD increased slightly versus a control group. Figuring the failed results may be because of a lack of exposure after disease induction, they repeated the experiment, this time continuing UV exposure every other day or everything third day. EAE incidence was not reduced, but severity and onset, among other scores, were. Again serum calcium did not change, and 25OHD concentrations increased, but did not remain elevated throughout treatment, suggesting that the UV exposure, not D, suppresses EAE.

They then determined if the 25OHD concentration reached in the previous study could suppress EAE independent of UV exposure with D supplementation (25OHD3 or 1,25OH2D3). Even at very high doses that cause hypercalcemia, only a modest suppression of EAE occurred. At lowers doses that reached concentrations similar to UV treated mice, there was no effect.

In all, the experiments suggest that UV radiation suppresses EAE independent of vitamin D concentrations that can be obtained through exposure to sunlight, at least in mice.

Major limitations include differences in mouse and human immune systems and between MS and EAE, so this will have to be further explored.

We should be careful not to suggest that vitamin D alone explains all of the benefits in which association studies have found so far, UV radiation itself seems to be beneficial and we need studies to disentangle the relative contributions of each.

Clearly this deserves more study, but it is worth highlighting. Could this be relevant to other autoimmune diseases? I don’t see why not: sunlight exposure and vitamin D are correlated with other autoimmune diseases, and while D certainly has a role in many as elucidated elegantly in studies, it is possible that some of the correlations reflect an influence from UV radiation and not D itself.

Until then, get outside periodically and enjoy the sunlight as we are meant to do, just don’t get burned.
Update: a study was recently published that sequenced the genome, epigenome, and transcriptome of monozygotic (identical) twins, one with multiple sclerosis and one without, and interestingly found no differences to explain the disease, suggesting environmental triggers.

1. Becklund BR, Severson KS, Vang SV, & DeLuca HF (2010). UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production. Proceedings of the National Academy of Sciences of the United States of America, 107 (14), 6418-23 PMID: 20308557

See also VitaminDWiki