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Mendelian randomization: Genetically low vitamin D levels linked to multiple sclerosis

Posted on: August 28, 2015   by  John Cannell, MD


There is much debate regarding the importance of vitamin D. Some experts believe it plays little to no role in disease. However, now we can say, beyond any reasonable doubt, that it does play a role in disease, at least in multiple sclerosis (MS).

In the past, research has provided extensive evidence supporting the relationship between MS and vitamin D. Several of the most conclusive studies, randomized controlled trials, have found vitamin D has a treatment effect in MS. Yet, skeptics still question these findings.

You may think vitamin D levels entirely depend on how much sunshine you receive or supplements you take, but that is not always the case. Some people inherit genes that result in chronically low vitamin D levels. If they don’t sunbath or supplement, they go through their entire life deficient.

Researchers recently used a new technique, one better than randomized controlled trials (RCT), to evaluate how genetically lower levels of vitamin D relate to the risk of MS.

On August 25, 2015, the first Mendelian randomization study of vitamin D and MS was published. Vitamin D Mendelian randomization studies are simple. Researchers assessed genotypes of about 39,000 people, some with MS and some without, looking for those people who have certain genetic variants that result in low levels of vitamin D.

This Mendelian randomization study evaluated whether people with genetically low vitamin D levels are more likely to have MS compared to those who are not genetically predisposed to low vitamin D levels. The researchers discovered that people with the genetic variants were more likely to have MS and the effect is large. It turns out that if the individual’s vitamin D level is about 6 ng/ml lower than the others in the group, they had twice the risk of developing MS.

Mokry et. al. Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study. PLOS Medicine, 2015. 

Mendelian randomization studies are stronger than randomized controlled trials, because, while randomized, Mendelian randomization studies track the effects of a lifetime of vitamin D deficiency. In order to conduct a randomized controlled trial to determine whether vitamin D prevents MS, researchers would have to administer physiological doses of vitamin D to the participants throughout their entire lifespan. Obviously, such a study can and will never be done.

Also, Mendelian randomization does not assess the optimal 25(OH)D level for the prevention of MS. The average vitamin D level of the 39,000 people was not published, but it was probably around 20 ng/ml (50 nmol/l). So, perhaps having levels anywhere between 30 (75 nmol/l) and 80 ng/ml (200 nmol/l) will further reduce the risk of developing MS. We don’t know.

That is why we recommend that you maintain “natural” vitamin D levels, around 50 ng/ml (125 nmol/l) until we do know. To obtain natural levels, we recommend briefly sunbathing or taking at least 5,000 IU/day on the days you don’t sunbathe. That’s the safe thing to do and now it has been proven to prevent MS.

1 Response to Mendelian randomization: Genetically low vitamin D levels linked to multiple sclerosis

  1. [email protected]

    I liked this study so much that I made a web page for it and renamed several others to have a similar title.
    Genes make Multiple Sclerosis 2X more likely unless get more vitamin D – Aug 2015 http://vitamindwiki.com/tiki-index.php?page_id=6835

    Gene makes Hip Fracture 2.5X more likely unless get more vitamin D – Aug 2015

    Gene makes COPD 2.6X more likely unless get more vitamin D – meta-analysis Dec 2014

    2 Genes make AMD 6X more likely if low vitamin D – Aug 2015 http://vitamindwiki.com/tiki-index.php?page_id=6838

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