Monday, January 20, 2014

Vitamin D status and MS--a Five Year Study

A new study from Harvard School of Public Health followed pwMS for 5 years and found that those with increases of 50-nmol/L in average blood vitamin D levels within the first 12 months after diagnosis showed
57% lower risk of new active brain lesions, 
57% lower risk of relapse, 
25% lower yearly increase in T2 lesion volume and 0.41 percent lower yearly loss in brain volume from months 12 to 60.

http://www.eurekalert.org/pub_releases/2014-01/tjnj-vds011714.php


There were 465 patients enrolled in this study, which was originally designed to measure efficacy of beta interferon.   Fortunately, all had at least one measurement of their serum vitamin D status during the time they were followed with neurological exams and MRIs, up to 5 years in total.  The researchers were not supplementing vitamin D, they were simply measuring it, as part of the blood samples they were collecting.


This study is unique, in that it started out as simply a study of beta interferon--and ended up showing that vitamin D status was a very important factor in disease activity.  The researchers measured vitamin D status in pwMS who were a part of this study during their first year, and then followed these patients with MRI and neurological evaluations to see how their MS progressed.  


What can we learn from this study?  Serum vitamin D levels are obviously important in MS disease progression.  The higher blood levels are, the less disease progression, active lesions, brain atrophy, and relapses.


But does this mean that vitamin D supplementation is the only solution?  I would like to encourage more researchers to look at the work of Dr. Richard Weller, a scientist from the University of Edinburgh.  Dr. Weller is examining how vitamin D status serves as a marker of exposure to UV rays.  His research has shown that vitamin D status is closely related to latitude and exposure to sunshine.  Perhaps we need to consider this factor for pwMS.  UV rays release stores of nitric oxide from our tissues, improving endothelial health and the cardiovascular system.


Here is a wonderful TED talk from Dr. Weller on his research.

http://www.ted.com/talks/richard_weller_could_the_sun_be_good_for_your_heart.html


And also today, the results of a new study from Dr. Weller's team and Dr. Feelisch from the University of Southampton.



During the study, the skin of 24 healthy individuals was exposed to ultraviolet (UVA) light from tanning lamps for two sessions of 20 minutes each. In one session, the volunteers were exposed to both the UVA rays and the heat of the lamps. In another, the UV rays were blocked so that only the heat of the lamps affected the skin.


The results suggest that UVA exposure dilates blood vessels, significantly lowers blood pressure, and alters NO metabolite levels in the circulation. Further experiments indicate that pre-formed stores of NO in the upper skin layers are involved in mediating these effects. The data are consistent with the seasonal variation of blood pressure and cardiovascular risk at temperate latitudes.


Professor Feelisch adds: "These results are significant to the ongoing debate about potential health benefits of sunlight and the role of Vitamin D in this process. It may be an opportune time to reassess the risks and benefits of sunlight for human health and to take a fresh look at current public health advice. Avoiding excess sunlight exposure is critical to prevent skin cancer, but not being exposed to it at all, out of fear or as a result of a certain lifestyle, could increase the risk of cardiovascular disease. Perhaps with the exception of bone health, the effects of oral vitamin D supplementation have been disappointing.


"We believe that NO from the skin is an important, so far overlooked contributor to cardiovascular health. In future studies we intend to test whether the effects hold true in a more chronic setting and identify new nutritional strategies targeted at maximizing the skin's ability to store NO and deliver it to the circulation more efficiently."

http://www.sciencedaily.com/releases/2014/01/140117090139.htm



Here is a recent paper from BNAC which looked at vitamin D, sunlight exposure, and brain volume on MRI in people with MS.

Increased summer sun exposure was associated with increased grey matter volume (GMV, r(p)=0.16, p=0.019) and whole brain volume (WBV, r(p)=0.20, p=0.004) after correcting for Extended Disability Status Scale in the MS group. Inclusion of 25-hydroxy vitamin D3 levels did not substantially affect the positive associations of sun exposure with WBV (r(p)=0.18, p=0.003) and GMV (r(p)=0.14, p=0.026) in the MS group.
CONCLUSIONS:
Sun exposure may have direct effects on MRI measures of neurodegeneration in MS, independently of vitamin D.

http://www.ncbi.nlm.nih.gov/pubmed/23385850


I would suggest that worldwide deficiencies in Vitamin D may well be a biomarker of our modern lifestyle.  We spend less time outdoors, and the time we are in the sun, we are covered up with clothing or sunscreen, limiting the amount of UV rays that can penetrate our skin.  This would also further explain the correlation of latitude and MS rates around the globe.  


I've written to and connected Dr. Weller to the researchers at the ISNVD, and encouraged him to reach out to his colleague, Dr. Jim Wilson, who is currently looking at chronic illness in Scotland.  He replied that he is very interested in looking at UV rays in MS, and is currently writing grant applications to study this.  


Something to ponder,

Joan



6 comments:

  1. Joan, you seem to be suggesting that the link to MS Is solar exposure and the latitude effect rather than to vitamin D levels.

    There are three ways to raise Vitamin D levels: UV-B exposure, diet, or supplements. There is virtually no UV-B radiation available to people who live north of the 34th parallel which runs just a little north of LA, through the middle of North Carolina and in Europe from around Gibraltar through Syria so regardless of lifestyle, you can't get vitamin D from the sun if you live north of this are at this time of the year. The further north, the less annual UV-B. You can get as much as 20,000 IU a day from UV-B but it is virtually impossible to get that from diet. It would take 4.375 pounds of wild salmon to match that.

    While there is no doubt that there are benefits from spending time in the sun beyond vitamin D, that's not to say that it isn't vitamin D levels that are making a difference in MS as the Ascherio study shows. Would the benefits be better if the source of the vitamin D was the sun or diet? I don't know. I don't have a citation, but I believe that Dr. Sunshine, Michael Holick says that there do not appear to be differences in health benefits based on the source of vitamin D, but like so many things, that probably needs more study.

    While there may well be benefits from solar exposure for endothelial health, it is hard to see how these would outweigh the role of vitamin D. Vitamin D directs the formation of blood vessels in utero so there is a direct link between vitamin D deficiency and venous malformations and the birth month effect which is highlighted in higher latitudes. Regulatory hormone vitamin D manages the adaptive immune system so it is responsible for dealing with endothelial injury or infections. Vitamin D also is what initiates the creation of NO in the process identified by Furchgott.

    This is not to say that vitamin D is the only factor in these things or even that it is the most important, but compared with what know from Weller and others, it seems far more likely that it plays a far more critical role in MS than solar exposure.

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  2. Thanks for your very thoughtful response, Edward. I am by no means discounting the importance of vitamin D--I just want to encourage research into how UV rays may figure into the equation. There is much more to learn about what vitamin D status means in MS. It's not just about noting a deficiency and taking a supplement. It's about understanding the mechanisms behind maintaining adequate levels. Here's a recent study from BNAC, which looked at vitamin D status, sunlight exposure and MRIs status--finding that those with higher sunlight exposure, independent of vitamin D staus, had greater gray matter and whole brain volume. I realize we are just at the beginning, but I think it's obvious, we have much to learn about NO, the endothelium, cerebral blood flow and diseases of neurodegeneration.

    http://www.medscape.com/viewarticle/810541_1

    "In conclusion, the results from our cross sectional study suggest that sun exposure could have an effect on brain volume in MS. These effects appear to be dissociated from the increased vitamin D levels that result from increased sun exposure. However, it is necessary to overcome the limitations of the cross sectional study design before definitive conclusions can be established. Further prospective longitudinal studies of the effects of sun exposure on brain volume reserve in controls and on neurodegeneration in MS patients are therefore needed."

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  3. Joan in 'MS', research has shown a dis-regulation of innate immune cells that breach the BBB in lesions of the CNS and in EAE research, they have found dysfunctional innate immune cells have breached the BBB and are damaging the CNS.
    Although the 'cause' of 'MS' breaches is of multiple causes and the EAE is from man made causes is the dysfunction of the innate immune cells the same?
    Would correction or re-booting with calcitriol the innate immune cells that breach the CNS stop them becoming 'immortal' and causing lesions in the CNS, be the same process in 'MS' and EAE? ( results from an EAE study that worked on http://www.news.wisc.edu/22163)
    Or is there a problem because 'MS' has not been defined, yet 'EAE' has been?

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    Replies
    1. Hi Nigel--I really don't think looking at the EAE model in mice--where an ongoing immune system reaction occurs after foreign antigens are injected into mouse brain--is getting us any closer to understanding MS in humans--where immune cells appear to be a secondary reaction to a neurodegenerative process, that continues into progressive MS, when the immune system reaction is silent. So yes, you're right, the problem is that EAE is the model we continue to use, even though it's become obvious it is not the right one.

      As far as calcitrol--the tests you linked from Wisconsin have been in mice, as well. More and more research is finding that simply supplementing vitamin D in humans is not having the same results as it does in mice, and there are doctors coming out and stating that low vitamin D levels appear to be a consequence, not a cause, of ill health.

      UV exposure is a completely different process in humans (mice do not store nitric oxide in the skin, nor do they process the hormone D the same way) This is why Dr. Weller's research is so important.

      I wish it was a simple as taking a supplement....but the research continues to point to a holistic approach. Sunshine and UV ray exposure, whole foods which provide anti-oxidants and phytonutrients, daily exercise, limiting stress, eliminating smoking, and a cardiovascularly healthy life. Hang in there....we're getting there!!!

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  4. Edward, maybe you should try having a teaspoon of fermented cod-liver oil instead of all that salmon! http://www.westonaprice.org/cod-liver-oil/update-on-cod-liver-oil-manufacture

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