Sunday, 23 July 2017

EBV and Vitamin D..reducing antibodies

Rolf L, Muris AH, Mathias A, Du Pasquier R, Koneczny I, Disanto G, Kuhle J, Ramagopalan S, Damoiseaux J, Smolders J, Hupperts R. Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis. Mult Scler. 2017:1352458517722646. 

BACKGROUND:Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis(MS).
OBJECTIVES:To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels.
METHODS:This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored.
RESULTS:The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D3 group (526 (368-1683) to 455 (380-1148) U/mL) compared to the placebo group (432 (351-1280) to 429 (297-1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures.
CONCLUSION:High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism.
As ProfG sits on a beach pondering the "meaning of MS", does this study hit the jackpot,?

It has vitamin D and EBV as two things close to his heart as the centre of MS susceptibility. 

What does this study  say? 

It is a trial of vitamin D supplementation and they look at EBV antibody levels and find that if you supplement with vitamin D the levels of of antibodies against parts of the EBV virus go down. 

However, this has no impact on viral load. They then conclude this result does not implicate a promoted immune response against EBV.

Whilst ProfG contemplates whats this means, I ask what is the relevant biology here?

The implication is that vitamin D has an impact in utero (in the womb) and perhaps shapes the immune response in early life. This is what is implicated from studies in type 1 diabetes. EBV is a trigger factor when it infects someone years later. 

Now I can go with the flow that studying the effect of vitamin D supplementation,decades after birth, has impact. This idea has caused a myriad of clinical studies in all sorts of conditions, many outside MS. The charities are shelling out loads of cash investigating this, in response to the interest whipped up by the Docs doing the trials. However,  this study highlights one of the problems I have with the vitamin D brigade and the clinical fraternity.

This is a trial involving 53 people. 

What is this really going to tell us about vitamin D?

It is hopelessly underpowered to tell us much and certainly can't tell us whether vitamin D impacts on MS. A P value = 0.023 so about a 1 in fifty chance that this occurs by chance. It will need repeating...another unpowered trial:-(

It is just like the omega oils...lots of useless small trials giving no answers.

They give a whiff of something but are never big enough to give a useful answer about the benefit or lack of it, and we will be supplementing forever so H& B (vitamin Shop) are happy. 

How many individual trials are being funded on vitamin D?.

I suspect that in MSm vitamin D will not be a very good immune modulator, if it was great you would have all sorts of side effects....you don't... so don't expect the earth. Can it be of benefit, sure it can and you need to ensure good bone health.


20 comments:

  1. As vitamin d is naturally present in the body and naturally occurs at levels seen in both cohorts in this trial, can we stop considering vitamin d a drug, at least at levels below that which disrupts the blood calcium levels.

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  2. I am confused MD. I thought previous studies found Vitamin D higher levels would lead to increased CD8 T-cells and hence a reduction in EBV viral load. Does this study not show just the opposite-no effect of Vitamin D on EBV viral load, no effect of Vitamin D on cytotoxic T-cells and a reduced B-cell response with lower anti-EBNA-1 antibody levels? Are they implying that Vitamin D reduces B-cell response in RRMS?

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    Replies
    1. I would think that if there was a real effect it would be consistent, I guess we will have to wait until there is consensus.

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    2. The inconsistency probably comes from the sample sizes, they are small. It is likely that there is a threshold (that may be different for different people) above which the immune system functions correctly and below which it functions incorrectly, as parts of it shuts down to conserve vitamin d. As vitamin d stored in the blood as 25(OH)D is inert until ultra high levels are reached, it is not going to show a dose dependence after sufficiency, as the body is controlling use.

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  3. I wonder if a study has been carried out to see if there is an in increase in the prevalence of MS in submariners (and ex-submariners). I must declare my interest as an ex-submariner with MS. We weren't known as "sun dodgers" for nothing.

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    Replies
    1. Interesting thought, is there more rickets in Submariners.

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    2. Rickets is normally a disease of children and submariners tend not to be children, so it would be a very under-powered trial.

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    3. Reduced bone density leading to osteoporosis is seen in adults with vitamin D deficiency.

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    4. There was not a study on MS specifically but there was a study about VitD levels in submariners: https://www.ncbi.nlm.nih.gov/pubmed/15945402

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    5. If the submariners sailed between October and April then they would have made no less vitamin d from sunshine than the population that stayed at home in the UK. In the UK sunlight lacks the required UVB between Oct and April to start the chemical reaction that leads to vitamin d. If they sailed in the summer you may see an effect, as they would have the equivalent of three winters in succession.

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  4. "High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients".

    I misunderstood or study concluded that it is as if vitamin D were an immunosuppressant, weak but would it?

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  5. just as good as the charcot project?

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    Replies
    1. Ha Ha..... Touche

      However, I would never have selected raltegrovir...but that was an anecdote and Merck was willing to fund the study.

      If they had used HAART it may have been a different story.

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  6. IS this correct? you said" levels of of antibodies against vitamin D go down"

    They said "antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D3 group"
    What is correct?
    Thanks Luis

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  7. "I suspect that in MSm vitamin D will not be a very good immune modulator"

    Gavin GiovannoniMonday, July 17, 2017 12:41:00 pm

    There is on class 1 evidence that it is a DMT. The dose I recommend is based on the Vitamin D Council recommendations.

    How do we square this circle?
    Luis

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    Replies
    1. There is evidence from some lymphoma and from the disease Sarcoidosis that vitamin d is used by the immune system, and therefore it is very likely that a lack of vitamin d will affect the immune system. What it does and what effect it has is much less certain.

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    2. MD said if vitamin D was an immunomodulator then there would be more side effects. This assumes that immuno modulation inevitably means some form of immunodepletion but you can make the immune system function better without negatively affecting its ability to do its job

      better way to think of it is that a good immunomodulator need only have one side effect: no more MS.

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    3. Having a high enough vitamin d level in the blood may simply allow the immune system function correctly. The amounts stored in the blood of most people in this country are far below that seen in those with constant sun exposure eg life guards.And it is fair to say that the levels seen in life guards are more likely to be correct than say office workers.

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