Vitamin D Deficiency and Multiple Sclerosis

Hannah - Why are people with low vitamin D levels at risk of multiple sclerosis?  One person who's been studying this extensively and is now urging the government to fortify food in Scotland with vitamin D to protect people is Oxford University Neurologist George Ebers.  Hello, George.  So first of all, can you explain to us what actually is multiple sclerosis?

George -   It's the commonest chronic neurological disease that affects young adults.  We think it's autoimmune and for most people, over time, it leads to progressive disability.

Hannah -   Why would vitamin D levels be linked to the immune system and also the brain as well?

George -   I think what we can say is that the circumstantial evidence has always been in favour of some relationship between MS risk and sunshine.  50 years ago, we knew that if you were from the British Isles and you moved to Australia or you moved to South Africa, your risk of MS plummeted.  It's very clear cut.  So that implicated sunshine even back then, and gradually over time, we've learned that the main biological effects of sunshine are mediated through vitamin D, and evidence has come in which is now directly implicating vitamin D as a main environmental risk factor in the disease.

Hannah -   What kind of evidence has been coming in?  Has it been epidemiological studies, for example, the ones that Elina was talking about and other genetic studies as well?

George -   It comes from several sources.  So just on the epidemiological side, if you look at the fine mapping of the risk of MS in a country like France, where people don't move very much, you can show that the pattern of MS occurrence in the various regions of France fits almost exactly the distribution of ultraviolet radiation.  If you take the end of the winter, say February, the end of the winter for France, then in fact, the UV radiation map - which is generated by the satellites that are orbiting the Earth - maps very, very much onto the prevalence of MS by region.  That was the epidemiological part.

Now the genetics part has been much more recent and several things have happened.  The main gene region that predisposes you to MS turns out to be regulated by vitamin D and then a number of the small genes that make you susceptible turn out to have disproportionate regulation by vitamin D.  I suppose the most recent thing is that we've shown that the enzyme, which is the rate limiting step and really determines how much active vitamin D you've got, turns out to be associated with the risk.  We did this by looking for people who have a deficiency of this enzyme for genetic reasons.  They had a mutation in the gene which markedly reduced the enzyme activity and we found this is very strongly associated with MS.

Hannah -   And in what way was it associated with MS?

George -   The way we did this is that we searched for parents of MS patients who had one normal gene for the enzyme and then one abnormal gene, and then we look to see in the MS offspring which [gene] they inherited.  Now the odds are 50/50 that they would get the normal gene or the abnormal gene.  We found 35 parents with this defective gene on one side of one of their chromosomes and a normal gene on the other side.  When we examined the MS offspring, for them to have inherited the abnormal gene all 35 times would be like flipping a coin 35 times and getting 35 heads, and that's exactly what we found.  We found that invariably, this was transmitted.  So, this is as strong as an association, maybe the strongest association that's ever been reported in one of these complex diseases.  And it's really now making us think in terms of causality rather than association.

Hannah -   And can you tell us what this gene does, the biochemical studies that link the genes and multiple sclerosis, and vitamin D together?

George -   One of the things that's important to point out is that maybe vitamin D shouldn't have really been called a vitamin anyway.  It's really more like a hormone.  So in contrast to something like vitamin E or vitamin A which really fulfils the traditional definition of a vitamin - something you take in small amounts externally and is important in metabolism - Vitamin D is something you can make yourself.  You regulate it very carefully and we've had millions of years of evolution to develop strategies for regulating vitamin D.  The way that it works is that you've got the precursor in your skin, as Elina said, and it's acted on by sunshine - ultraviolet radiation converts it to an active form.  But there is an important additional step which is regulated by the enzyme we were just talking about.  It's called 125-alpha-hydroxylase and it's the one that converts vitamin D to the active form.  And so, we have the ability to control vitamin D and this is going to relevant to a number of questions I think about how much to take and so forth because in fact, the internal system that we have developed over many, many years actually regulates this very tightly.

Hannah -   What do you think then about vitamin D supplements in the food?

George -  I've not come to this quickly, I have to say [I've come to this conclusion] over a large number of years and what I've said to the Scottish government, along with a number of other people who were there to advise them, was that we thought that their solution was probably best reached by administering it to the population.  That's taking into account a number of factors:  The level of deficiency, the likelihood that it's related to a number of diseases, and the very low risk that's involved, the fact that it's dirt cheap and so forth.  All those things, not to mention human nature, telling people to take things doesn't always work as you know.  And so, that was our conclusion.