Wednesday, 1 February 2017

#ClinicSpeak: seasonal vitamin D levels and disease activity

Are you a chickener or an egger? The endless vitamin D in MS debate. #ClinicSpeak #MSBlog

Chicken or egg? There are numerous studies showing a seasonal variation in blood vD levels that appear to be associated with MS disease activity. Many people interpret this as causal, i.e. low vD levels are responsible for MS disease activity. Another interpretation is that MS disease activity causes low vD levels, i.e. the immunological cascade responsible for triggering MS disease activity consumes vD and simply lowers blood levels. 

How do we sort out the causation vs. association? What we need is an adequately powered double-blind placebo-controlled trial to answer this question. The problem is who is going to pay for the trial and what dose of vD do we use? Another issue is that many in the vD field think that blood vD levels are simply a proxy for sunlight exposure and that is more important than vD; in other words we need to do a trial of ultraviolet (UV) light exposure rather than simply supplementing vD. How does UV light come into the equation? There is good data that UV light modulates T-cells function as they get exposed to light in the skin. This is in fact a well accepted treatment for autoimmune skin diseases.

I have been to so many 'vD in MS meetings' and we never reach consensus on how to take things forward. I suspect long after I have retired and moved onto other things the next generation of MS researchers will be having the same discussions and debates. Sad, but likely to be true. 


Hartl et al. Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients. DOI: http://dx.doi.org/10.1016/j.jns.2017.01.059

Highlights:

•25-(OH)-D serum concentrations showed seasonal variations in patients with multiple sclerosis.
•the nadir of vitamin D serum concentrations in winter preceded the peak in prevalence of relapses in spring by two months.
•an increment of 10 ng/ml 25-(OH)-D resulted in 20% reduction in the prevalence of relapse at visit.

Abstract

Background: Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. 

Methods: In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and 60 secondary-progressive, 282 female, mean age 39.1 years) of whom 25-(OH)-D serum concentrations were determined at visits between 2010 and 2013 were included in the study. All clinical data including relapse at visit and expanded disability status scale were recorded in a standardized manner by an experienced neurologist. Seasonal variations of 25-(OH)-D serum concentrations were modelled by sinusoidal regression and seasonal variability in the prevalence of relapse by cubic regression. 

Results: The mean 25-(OH)-D serum concentration was 24.8 ng/ml (range 8.3–140 ng/ml) with peak levels of 32.2 ng/ml in July/August and nadir in January/February (17.2 ng/ml). The lowest modelled prevalence of relapse was in September/October (28%) and the highest modelled prevalence in March/April (47%). The nadir of 25-(OH)-D serum concentrations preceded the peak in prevalence of relapses by two months. 

Conclusion: In summary, seasonal variation of 25-(OH)-D serum levels were inversely associated with clinical disease activity in MS patients. Future studies should investigate whether vitamin D supplementation in MS patients may decrease the seasonal risk for MS relapses.

9 comments:

  1. Given the observed 25(OH)D levels,"24.8 ng/ml (range 8.3–140 ng/ml) with peak levels of 32.2 ng/ml in July/August and nadir in January/February (17.2 ng/ml)" chances are some of those people are taking fairly high supplement levels (or high sunbed exposure) and will not have winter-summer cycles. Pity they did not remove them from the data and see what happens, as it may be the cycling in vitamin d not actual vitamin d levels that matter.

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  2. I notice a massive difference in how I feel with my PPMS just sitting in strong sunlight for 10 minutes; this doesn't happen so often where I live - far in the north. Whilst vD supplements do nothing for me that I notice. I really think there is much more to the effect of UV on MS than just vD. This really needs investigation I think.

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    1. In Australia 10 mins of UV = lobster burn. Lobster burn = not good for MS (or indeed people without MS). It hurts, it stings, it makes one feel generally tired and horrific.

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    2. Not where I live, not even on the sunniest of days. The best days are cool days (I have Uhthoff's) with clear skies. But I still wear suncream to protect the skin, sometimes sunglasses or a hat, and I never allow myself burn. It's true, sunlight is like many other things - you can have too little, and you can have too much. I notice the benefit of more of it come summer.

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  3. "I have been to so many 'vD in MS meetings' and we never reach consensus on how to take things forward..."

    In the meantime, there is the facebook group, an extract from which is copied and pasted below...

    While I'm sure we would all like clinical trials for everything, apparently a whole bunch of people with ms (I'm guessing more than the fb membership) are being treated with extremely high doses of Vit D in what they call the Dr Coimbra Vit D protocol. Their decision to go down this path is not what I'm putting up for judgement - but while you guys debate how to take things forward, they just sit there taking high doses of vit D sharing anecdotal stories no one seems to try to tap into....

    I realise registries aren't as informative as Class 1 placebo controlled trials, but we seemed to have learnt things from Sweden about rituximab without those class 1 trials....

    "Vitamin D Protocol North America
    1,712 members · 70 new members
    As patients with MS and autoimmune disease all over the world are seeing their disease progression halted and even reversed, those of us here in North America are just learning of our brothers and sisters internationally who have gotten their lives back as a re..."

    Maybe I will change my name from Anonymous BozoForgot to "Frustrated"

    But what else is new, right :)

    lol.

    Ps. My partner is not digesting huge amounts of Vit D (just amounts needed to keep her Vit D within normal rages)... She is joining an Australian HSCT registry - but I'm sure for what reason: the data being collected by the registry solely relates to the number of relapses, lesions and EDSS scores post HSCT. Though her haemo monitors her blood subsets and general well-being and her neuro takes the time to listen and act on her requests for new lumbar punctures and OCB info, the HSCT registrar apparently doesn't need that information.

    :)

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  4. And the question genetic that involves vitamin D?

    Because as much as a person to expose in the sunlight (in Brazil the solar incidence not forgive, if not take care what is wins is a skin cancer) if she have any of genetic mutations involving malabsorption or the use of vitamin D on the body, and on the immune system, then she or he never have the sufficiency of vitamin D, and may develop the problems related to vitamin deficiency D.

    Now who will hold a study of a substance, in theory, so cheap and generic?

    http://www.medscape.com/viewarticle/870898

    http://www.medscape.com/viewarticle/850605


    There is a group at Cornell University that is verifying that UV light can control and decrease inflammation through photocontrolled inhibitors of HDACs (histone deacetylases)

    http://pubs.rsc.org/en/content/articlelanding/2017/sc/c6sc03702j#!divAbstract

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  5. This appears to hold in both hemispheres as well, Australia is a perfect example of the geographic gradient, where the top end of Australia, closest too the equator has the fewest cases of MS , Tasmaniaat the end of the coast has the highest, Summer in Oz, tThe week the temps have been between 32-36' ) can't stay our for long in that heat!

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    Replies
    1. I live in a city that stay relatively close to the Ecuador's line, but the problem is that the solar incidence is so strong in a good part of the year that you can't stay more than 5 minutes exposure to the sun that fast you want to protect yourself or look for a shadow.
      For people with very clear skin this is a problem too, and here in Brazil the incidence of skin cancer is very high.

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    2. The "top" of Australia is also the least populated part of Australia and only has the least populated capital city.

      Ps. it's the UV that causes burns and skin damage, so even on cloudy days people will get burnt.

      Delete

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