Multiple Sclerosis: blaming the sunshine

Multiple sclerosis (MS) is an unpleasant neurological disease, displaying an unpredictable range of symptoms which manifest themselves with equally unpredictable severity and rapidity. It is an autoimmune condition affecting the nerves: during relapses, an over-enthusiastic immune system attacks and damages the protective coating of nerve cells in the brain and spinal cord. People are often diagnosed in their most productive years— their 20s, 30s and 40s— when they must learn to deal with an uncertain prognosis, often ending with debilitating loss of mobility, speech, and memory at an unforeseeable point in the future.

For many years, the cause of the disease remained a mystery. Then, in 1960, Donald Acheson proposed a link between sun exposure in early life and a later diagnosis of MS. This hypothesis was founded on a growing body of evidence suggesting a north-south gradient of diminishing disease risk, based on research in several different northern hemisphere nations. Early studies demonstrated this relationship in World War 1 veterans living in several US states, and across populations in different regions of Norway. In the next few years similar associations were found in the southern hemisphere, but this time going in a reverse direction— with a higher risk of disease in the south versus the north— and it was discovered that immigrants tended to bring the risk of their original country with them when they moved, suggesting exposure in early life was an important factor. It seemed like Acheson was on to something.

And the evidence continued to accumulate: both within and between countries, the latitude link was robust. While there were a few localised exceptions, the overall pattern has been maintained over the decades— Scotland still has more MS than England, Tasmania still has more than Queensland, and the disease remains almost unknown at the equator, where solar radiation is highest.

The reason for this link defied— and to a large extent, still defies— ready explanation. Perhaps this is the reason for an early reluctance to embrace Acheson’s sunlight idea, and the ongoing search for alternative and/or additional explanations. When the young researcher first presented his idea at a scientific conference, a renowned neurologist named FMR Walshe scoffed: “Sunshine? More likely to be the moonshine, my boy!”

Over the years, a more complex picture has emerged. Genetic studies suggest genetic factors play a role, accounting for some of the variation in disease risk. Studies of smoking and MS suggest smoking increases the risk, independently of any other factors. Studies investigating a possible viral aetiology for MS shows that certain viruses possibly contribute something to disease risk, with Epstein Barr virus (EBV) being found in 100% of people with MS, compared with a 90% prevalence in the general population.

These findings are interesting, but peripheral to Acheson’s original insight. Many diseases involve interplay between genetic and environmental factors, so an element of genetic susceptibility is unsurprising. The viral link is intriguing, and EBV and/or other viruses may occupy a slice of the multi-causal MS pie chart, but a causal infectious agent would need to share the distinctive latitudinal distribution to account for the striking geographical pattern of MS (EBV is well distributed throughout all human populations).

It’s not that the sunlight hypothesis has been ignored: much research has focused on the role of vitamin D in the causal pathway. Vitamin D production in the human body relies on ultraviolet radiation-dependent metabolic pathways, which are insufficient for the body’s needs during winter at higher latitudes, and vitamin D has an increasingly recognised immune-modulating role, with a postulated immune dampening effect mediated through T cells. The vitamin D hypothesis thus provides a plausible link between lack of sunshine and MS, and recent laboratory findings seem to provide some supporting evidence. However in vivo and population level findings— including those examining the effect of oral vitamin D supplementation on MS incidence— have been inconclusive.

Surveying this work from outside the field, it seems a little surprising that there hasn’t been more progress, given the striking nature of Acheson’s observed association, and the fact that he noted it over fifty years ago. Intuitively, the latitude link feels like it should have been a big clue. But perhaps not— maybe it’s the complexity of the immune photobiochemistry involved, or just the highly multi-causal nature of the disease’s aetiology, rather than the fact that researchers have been looking in the wrong places or applying the wrong conceptual frameworks.

Further reading:
Multiple sclerosis and vitamin D: don’t (yet) blame it on the sunshine, Brain commentary 2009 and post title inspiration
Environmental factors and multiple sclerosis, Lancet Neurology review 2008 (paywalled)

Addendum 19/4/2011:
Right now there seems to be quite a flurry of new studies on this topic.
BBC-reported repeated cross-sectional study by Ramagopalan et al in Neurology, using satellite data on UVB radiation and English hospital admission statistics, suggests synergistic effect of EBV and sunlight on MS prevalence… somewhat undermined by recent Canadian cohort study by Banwell et al in Lancet Neurology, which suggests only an additive effect.

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One Response to “Multiple Sclerosis: blaming the sunshine”

  1. NEW Research Explains 61% of Multiple Sclerosis Cases | Find Me A Cure Says:

    […] may click to see : *Harvard study finds high vitamin D intake may cut multiple sclerosis risk *Multiple Sclerosis: blaming the sunshine : *Too Little Sunshine Raises Risk of MS […]

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