This is an interesting science story – the fairly recent discovery that there is a potential link between low Vitamin D levels and the risk of multiple sclerosis (MS). It is a good example of how the process of science works to incorporate new ideas.

MS is a complex set of diseases that involve chronic inflammation causing damage to myelin in the central nervous system. There are various types of MS, distinguished by the pattern of outbreaks over time – such as relapsing remitting or chronic progressive. There appears to be meaningful differences between the various types of MS, as they tend to respond differently to treatment.

Ignoring that for now, MS as a disease type is autoimmune in etiology – the immune system is attacking the host itself and causing damage. The trigger for MS is still somewhat mysterious, but there is evidence to suggest that it is a combination of genetic predisposition with an environmental trigger.

So far we have only observational studies of the role of vitamin D in MS. It has been observed for many decades that higher latitude correlates with higher risk of developing MS. Recent, however, it has been suggested that the biological factor at work may be vitamin D levels, and reduced sun exposure leads to lower vitamin D level. Observational studies have now supported this hypothesis.

Further, direct measures of vitamin D levels have been shown to correlate with risk of developing MS. Studies looking at the course of MS have been more variable, but some show a seasonal pattern to MS flares, suggesting that low light seasons have more MS lesions and flares.

Observational studies, however, cannot prove cause and effect. We may be able to infer a cause and effect from observational studies, but this is always difficult. Now we need experimental studies – double blind placebo controlled trials of vitamin D supplementation for the prevention and treatment of MS. These trials have not been done, and are not yet ongoing.

As the evidence for a role of vitamin D in MS mounts, however, so does interest in vitamin D as a potential intervention, and therefore pressure for such experimental trials. I expect that such trials will be done soon.

There is another aspect to the evidence for vitamin D and MS – the role of genes involved with vitamin D metabolism and MS. It is such a study that prompted me to write about this topic today.

Genetic mutations or polymorphisms in genes involved in vitamin D metabolism might explain why some people living in high latitudes get MS and others do not. If such a relationship existed it would be a nice independent line of evidence supporting the vitamin D-MS hypothesis. Up to now studies of a possible link have been mixed, with many finding no association between known genetic variants and MS. (See here also.)

A new study, however, looked for mutations in the CYP27B1 gene, which is involved in vitamin D metabolism. If a person inherits two copies of the abnormal gene variant they will develop rickets – a disease of severely low vitamin D. If they have just one copy of the abnormal variant, and one healthy variant, then they will have low vitamin D levels but not severe enough to develop rickets.

They analyzed this gene in Canadian families with at least one child with MS and unaffected parents. They identified 35 families (out of 3,000 tested) where an unaffected parent had the abnormal variant of the CYP27B1 gene. In every case the child with MS inherited the abnormal variant. Given that the odds in each case is 50/50, the fact that all 35 had the abnormal variant is 2^35, or over 34 billion to one.

This is pretty strong evidence in support of a role for vitamin D metabolism in MS, even if only in a subset of MS patients.

Conclusion

This new study, along with the observation data, strongly suggests that low vitamin D level, in some patients, may increase the risk of developing MS and the severity of the disease. But this is not yet certain, and more specifically it is not clear if taking supplemental vitamin D will reduce the risk of developing MS or reduce its severity.

It’s possible that low vitamin D is a marker for some other metabolic process that is the real culprit. Sun exposure, for example, can modify immune function separate from vitamin D, so perhaps low sun exposure leads to both MS and low vitamin D in some patients.

Before we can make firm recommendations for treatment we need to do large placebo-controlled trials of vitamin D supplementation in the general population and in targeted populations with suspicious gene variants, and separate trials in patients with MS. Only then will we really know what the net effect is of supplementing vitamin D on MS.

The story of vitamin D and MS is a good illustration of how science is supposed to work. A new hypothesis was introduced, which made some sense, and so investigators did preliminary research (observational studies) showing that there was a potential correlation. As the evidence grew, scientific interest grew, and researchers started to look at the question from multiple angles.

So far the hypothesis is holding up under scrutiny, but is far from proven. So researchers are working their way toward large definitive experimental trials. Each step of the way we see that scientists are cautious, thoughtful, skeptical and yet curious and willing to investigate a completely new idea.

Contrast this story to the one of CCSVI – the notion that MS is partially caused by blockages in the veins that drain the brain. Here the plausibility is low, but not zero, warranting some follow up research of the original observation. The follow up research so far is largely negative – the closer we look at this possible phenomenon the more it seems that it probably does not exist.

So scientific interest in CCSVI is rapidly dwindling, but researchers will likely put a few more nails in that coffin before they are done with it, just to be sure. Meanwhile, there is a huge public controversy over CCSVI – not because of the science, but because of unwarranted hype.

Those with more of a conspiracy bent claim that neurologists are just being pig-headed, and perhaps even big Pharma is trying to put it’s thumb on the scale.

Yet – none of this is evident in the vitamin D and MS story. When media hype, fake controversies, and conspiracy theories are not playing a role, the science progresses fine all by itself.