Dec 09 2011
Vitamin D and Multiple Sclerosis
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.
21 Responses to “Vitamin D and Multiple Sclerosis”
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Well, the CCVI and other issues like it will keep the skeptic movement alive.
I was thinking the other day that skeptics will never “win”. I mean, we will never have an entirely rational population. The population is so diverse, the nature of knowledge acquisition and distribution is chaotic, the variations in education and ability to understand and finally the tendency of humans to look for miraculous, rather than natural causes will always create hype for something apparently miraculous.
There will always be conspiracy theories. There will always be news stories that focus on the controversy and the ridiculous because that’s what human’s enjoy watching.
Skeptics will always be necessary to keep the balance. To keep the hype about the ridiculous, in whatever form, in a reasonable check.
But there will always be some version of anti-logic and bad science that will get too much attention. And skeptics will always need to say out loud – That’s not quite right.
@SARA:
In our lifetime, and probably my grandkids (assuming I have them) lifetime, I agree.
But I reserve the right the believe in a Star Trek sort of future where the exact reverse of Idiocracy has occurred and that the jobs and tasks that would otherwise be filled by the anti-logicians are taken up by robots leaving the entirety of humanity to actually learn and pursue science and skepticism in all areas of life.
That would be my utopia, anyways.
Any bets on how long it will be before we see “Helps Prevent Multiple Sclerosis!” on 1,000-pill bottles of Vitaman D at our local drug stores?
(Side bet: At twice the markup of previous vitaman D supplements.)
And how many people will ignore the simple solution of just spending more time outside in the sunshine because they’ve been conditioned to believe that you can only get vitamins from a pill?
“What, humans can produce their own vitamin D just from exposure to sunshine? What are we, plants? Gimmie my pill!”
Or am I being too pessimistic?
Gallenod, you might be a little too pessimistic.
I can’t speak to if Walgreens or CVS will start marketing that D3 helps prevent MS — the science is promising but still in progress, and Vitamin D isn’t an herbal supplement that can speak in hypotheticals.
But speaking as someone with relapsing-remitting MS, it’s not quite as easy as just going out in the sun. For one thing, a major symptom for a number of people is extreme sensitivity to heat, which makes summers pretty tough. Imagine the energy bar for a character in the video game Street Fighter; after about 10 minutes in the heat, that energy bar can drop from 100% to something like 30%, and going inside doesn’t just make it all better. (Once one symptom occurs, that reaction can trigger other symptoms.)
But as for people living in higher latitudes, ethnicity also comes into play. As I recall, people of Irish and Scottish extraction tend to manifest MS more than other ethnic groups; they also tend to be a lot more pale than others (and that’s me). So if a Celt like me with MS wants to go outside in the sun, we need to cover up or make sure we slather on the sunscreen.
Granted, you don’t need that much exposure outside to get the Vitamin D benefit, but if you’re already primed for the disease, it doesn’t make that much difference. The summer I was diagnosed, I was spending quite a bit of time outside, including 10 miles on a bike a day. I still had to go on megadoses (40,000 IU) of D3 to get my levels up to something reasonable.
It sounds like there is still a lot of work to do before we can say that vitamin D can help prevent relapses. Even if it may only be helpful in a subset of MS patients, would it be prudent to supplement now? Doing the cost benefit analysis seems pretty skewed toward doing so, but I don’t know all the risks of supplementing with vitamin D. I live in Canada and my wife has MS, so this hits close to home. If the pills are as effective, I think it makes sense to avoid the added risks of sun exposure. A problem I see, though, is that the root cause could be that the body can’t work with the vitamin D it already has; in which case we’d just be making expensive urine. Thanks for the great article.
As you get older, the ability to create your own vitamin D decreases. This is not exactly related to MS since MS tends to appear in younger people.
D3 is relatively cheap. About $10 will last a year at my dose. The real risk is what long term damage will be found later, if any, from the supplement.
I wouldn’t take any supplement without your doctor’s suggestion. I say “your doctor” because there is no shortage of MDs with pills to peddle or at least endorse.
Incidentally some high latitude ethnic groups have a lower than average incidence of MS. Norwegian Sami for instance.
mobius,
“would it be prudent to supplement now?”
It seems you have partly answered your own question:
“I don’t know all the risks of supplementing with vitamin D”
Vitamin D is a fat soluble vitamin and therefore it can accumulate and cause toxicity:
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002561/
“If the pills are as effective”
The operative being ‘if’. We don’t know that they are effective.
“I think it makes sense to avoid the added risks of sun exposure.”
Sun exposure might have beneficial effects that vitamin D supplements do not have.
In Summer a five minute exposure to the forearms at midday is sufficient and would increase the risk of melanoma to a negligable extent.
In general it is a bad idea to use something that MIGHT help but has not been proven to help. Because there is no end to the number of things that MIGHT help but have not been proven to help. A good example is Ray Kurzwiel who takes everything that MIGHT help increase his life span, as a result he takes 200 pills a day plus weekly infusions. Also, once a market is established for a product that MIGHT help, it is almost impossible to stop it when the evidence says it is useless. It may also turn out to be harmful (eg like antioxidant supplements)
“my wife has MS, so this hits close to home”
My sister has MS as well, so likewise.
The question of supplementation with vitamin D is largely separate from the question does it reduce MS risk.
There is plenty of evidence that ensuring sufficient vitamin D is essential to many aspects of health.
The toxic level is far above the level of supplementation recommended by relevant authorities.
Government advice in the UK is to consider supplementation in under 5′s, over 65′s, the pregnant, the breastfeeding, those who get very little sunlight, and those with dark skin (something those of (recent) African migration are generally aware of, but I think other immigrant communities are less aware, possibly because the effects are less marked).
So supplementation is safe, widely recommended for many subgroups, and has been widely practised in many countries for many generations. Cod liver oil having been a popular supplement in the UK for a LONG time.
The question is how. Parts of the UK get too little UV to use sunlight as a winter source of vitamin D, so winter supplementation has to be dietary. Oily fish is recommended for other health reason. Eggs are a popular food. Cod liver oil supplements are available at a trivial price. As such I think recommendations probably have to be customized to the individual’s life circumstances.
Since serum Vit D levels are becoming more common related to osteoporosis treatment/prevention, I think more and more people will be placed on Vit D supplementation. Any type of Vit D deficiency will be gone and we shall see the impact on MS.
“Vit D levels are becoming more common related to osteoporosis treatment/prevention”
One of the problems with Vitamin D levels and osteoporosis prevention and treatment is that there are known inaccuracies in measuring vitamin D levels. Blood from the same individual sent to different laboratories often give widely different results. You could send off several samples but the tests are damn expensive. Added to that is the fact that there is no agreed upon level at which vitamin D can be said to be deficient (ie lead to osteoporosis). Obviously an unrecordable vitamin D level in a Sudanese immigrant would suggest a supplement is in order. For most of us, however, a bit of sunlight whilst out doing weight bearing exercise would be the best way to go untill these problems are cleared up.
That is my conclusion at least. I have not had my vitamin D level checked and I don’t intend on doing so. I have a light tan and run a lot. However, that is part of my lifestyle not specifically my stradegy for preventing collapsed spines and hip fractures in my old age.
The thoughts about getting enough sunlight are good – though was not the issue of the gene mutation one of D3 synthesis which may require supplementation of some form. When I was diagnosed with MS in ’08 my levels of vit D were low even with supplementation on low level – it has taken 4000 unit/day to keep levels up. I also had low bone density just at -2 standard deviations before starting treatment – lifelong history of running and also fair amount of outdoor activity. Very interested on where this goes for myself and daughter.
Do you think all the people with ms that have been treating themselves successfully with vitamin d for the last couple of decades are happy they didn’t wait for this trial?
Hm Interesting. Vitamin D (well, lack of) may also be implicated in type 1 diabetes. So maybe less people would get T1DB if they had more vitD, although maybe the public health efforts should be more focused on preventing T2DB…..
BillyJoe7-
Exercise? Sunlight?
How low tech of you.
I have had my Vitamin D level tested and it came back low. (I take metformin, known to interfere with D absorption.)
I’m taking 1000 units of D3 daily. I plan to ask my doc to retest me on my next visit. Now that I know the tests are unreliable, though, I get extra fear! Thanks.
(No, really, I prefer to actually know.)
sonic,
“BillyJoe7-
”
Exercise? Sunlight?
How low tech of you.
You should see my strategy for preventing prostate cancer.
My humble contributions:
1. For those who would prefer to get their Vitamin-D via natural sun exposure…..here is a handy online app that purports (I’m not qualified to evaluate its veracity) to calculate optimal exposure time based on a user’s individual geo-location and weather conditions.
http://nadir.nilu.no/~olaeng/fastrt/VitD-ez_quartMED.html
2. For those who opt to pop da’ pills…..errr, make that pop “D” pills, additional attention should be directed to the apparent substantive differences in bioavailability between Vitamin-D2 (inferior) and Vitamin-D3 (superior). Google will handle the search for the most current research on this comparison.
CHEERS!
David
BillyJoe7-
Turns out that some things really are best left to the imagination.
mxyzptlk: My apologies, I did not intend any insensitivity to anyone who suffers from MS. My comments were aimed at those who would try to turn anything they can get their hands on into a way to make money off of suffering and frustration that there are people who fall for their pitches.
I have friends and students who have MS. It’s heartbreaking. Fooling healthy gullible people with “power bands” is one thing, but even the idea of someone preying on the truly vulnerable makes me very angry.
I will be very interested on any information about this topic. I have MS so what other information you have about Multiple Sclerosis I would be interested in reading. you have a very good post.
Has any one here heard about a theory that says that MS might be a viral issue. Specifically a type of measles. I have read information that indicates that the CSF of MS sufferers contain a measles titer and that the occurrence of MS is somewhat correlated by latitude with a higher incidence at higher latitudes. This might tie in with the idea of Vit D being related to MS too. There are a number of papers in journals from the late 90′s and early 2000′s that dispute the autoimmune hypothesis. Not being a medical professional I do not know, but it is interesting that with the idea of Vit D being associated there might be a plausible reason.