Tuesday, 1 September 2015

Handling vitamin D.

Bhargava P, Steele SU, Waubant E, Revirajan NR, Marcus J, Dembele M, Cassard SD, Hollis BW, Crainiceanu C, Mowry EM. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls.Mult Scler. 2015 Aug. pii: 1352458515600248. [Epub ahead of print]

BACKGROUND:Vitamin D insufficiency is a risk factor for multiple sclerosis (MS), and patients do not always show the expected response to vitamin D supplementation.
OBJECTIVE: We aimed to determine if vitamin D supplementation leads to a similar increase in serum 25-hydroxyvitamin-D (25(OH)D) levels in patients with MS and healthy controls (HCs).
METHODS: Participants in this open-label study were female, white, aged 18-60 years, had 25(OH)D levels ⩽ 75 nmol/l at screening, and had relapsing-remitting MS (RRMS) or were HCs. Participants received 5000 IU/day of vitamin D3 for 90 days. Utilizing generalized estimating equations we examined the relationship between the primary outcome (serum 25(OH)D level) and the primary (MS versus HC status) and secondary predictors.
RESULTS: For this study 27 MS patients and 30 HCs were enrolled. There was no significant difference in baseline 25(OH)D level or demographics except for higher body mass index (BMI) in the MS group (25.3 vs. 23.6 kg/m2, p=0.035). In total, 24 MS subjects and 29 HCs completed the study. In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/l (95%CI: 4.2, 29.2, p=0.008) lower increase in 25(OH)D levels compared with HCs.
CONCLUSIONS: Pat
This study suggests that pwMS do handle vitamin D supplementation the same as non-MSers.
ients with MS had a lower increase in 25(OH)D levels with supplementation, even after accounting for putative confounders.

Last week profG posted a paper showing that people with MS may have genes that influence vitamin D levels.

http://multiple-sclerosis research.blogspot.com/2015/08/ researchspeak-vitamin-d-risk-and-ms.html



23 comments:

  1. I started taking 5,000 ui, still outbreak. The vitamin D gave only in me rate below 50 nmol / L. When my neuro increased the daily amount to around 10000-15000 ui then yes the rate reached nearly 80 nmol / L ... The problem is that this issue of Vitamin D does not have a "metric" well defined. What is the ideal dosage / real must be obtained in the body? And after the disease began in what sense it can modify the course of MS? I saw many studies analyzing vitamin D2 and vitamin D3 not, as far as I know the D3 is that it has important role on the immune system ...

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    1. People end up with very different 25(OH)D blood levels for the same supplement intake. There is a graph in a paper, I will try and find the link. What is not know is if this is a difference in absorption/conversion or whether it is a difference in usage/conservation. If a person's immune system uses a lot of vitamin d their levels may be lower for the same supply. If they are poor at using vitamin d they may be higher. So having slightly higher 25(OH)D with a low vitamin d intake may be a bad sign. There may also be ways of turning off certain uses when vitamin d is in short supply, to protect blood calcium levels and this would maintain blood 25(OH)D levels while increasing risk of illness.

      The only solution at the moment for those with MS ( and other illnesses) is to go to the top end of normal. Normal being people who live out doors, with few clothes near the equator, or lifeguards in Florida in the 1950's. The risk appears low (long way from toxicity), the possible gains high and if it does not work you have lost little.

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    2. I wouldn't underestimate the risk of hypervitaminosis D - it can cause kidney damage in the long term - check your calcium levels in addition to Vit D and it can clog your artheries.

      I usually take 1.000 ie daily and get levels of ca. 80 nmol/L - in Germany that's considered sufficient and docs are wary of giving super high doses of VitD due to above-mentioned risks.

      My advice would be not to overdo it as usual.

      I could tell that my relapses healed better when I was in the sun or took Vit D though but I still had relapses so it's no wonder drug.

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    3. The highest recorded 25(OH)D from sunlight alone was 225 nmol/L [Nutrients. 2013 Sep; 5(9): 3605–3616, Vitamin D: Deficiency, Sufficiency and Toxicity, Fahad Alshahrani1 and Naji Aljohani]. Those living a traditional life in East Africa frequently have 25(OH)D levels of 115nmol/L [Br J Nutr. 2012 Nov 14;108(9):1557-61. ,
      Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Luxwolda MF1, Kuipers RS, Kema IP, Dijck-Brouwer DA, Muskiet FA.]. So 80nmol/L is well within the normal range.

      Vitamin d toxicity is much rarer than you would think given the way it is constantly mentioned. Most cases are sensitivity due to lymphomas and sarcoidosis and it is for these that checks on calcium may be needed. The others have been industrial accidents where doses of 1,000,000IU a day have been taken sometimes for weeks or months.

      If your calcium levels are high the symptoms are obvious and debilitating long before permanent damage is done. If the blood calcium is not raised then there is no damage.

      1000IU(ie) is 600IU higher than is recommended for a new born baby and the upper limit for a baby 1 to 18 months. "Guide to Vitamin d in Childhood 2013, Royal College of Paediatrics and Child Health". I would guess you are much bigger than a new born baby.

      Here is a paper considering trials using different doses of vitamin d and they found toxicity very rare. Am J Clin Nutr January 2007 vol. 85 no. 1 6-18, Risk assessment for vitamin D, John N Hathcock, Andrew Shao, Reinhold Vieth, and Robert Heaney

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    4. The figure that shows supplement vs 25(OH)D response is in ANTICANCER RESEARCH 31: 617-622 (2011), Vitamin D Supplement Doses and Serum 25-Hydroxyvitamin D in the Range Associated with Cancer Prevention, CEDRIC F. GARLAND, CHRISTINE B. FRENCH, LEO L. BAGGERLY and ROBERT P. HEANEY.
      A pdf can be found on the Grassrootshealth website at http://www.grassrootshealth.net/media/download/12928garland021811.pdf

      Figure 2 shows how variable serum 25(OH)D is without supplementation and how little change occurs in the distribution when you do, the band moves up, by a small amount. It also shows that the response is not linear and the higher your starting serum 25(OH)D level is the less effect the supplement has on blood levels.

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  2. The point is levels not dosage. Elementary my dear Watson.

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    1. This seems true as I take 1000iu or 2000iu vit D a day and am over 125nmol/L. Tested last month and I'm in the UK.
      I'm not sure I need to take 5000iu a day.


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    2. The graph in the paper I referenced above "Vitamin D Supplement Doses and Serum 25-Hydroxyvitamin D in the Range Associated with Cancer Prevention" shows that if you went from a 1000 or 2000iu a day supplement to 5000iu a day you would still be below 150nmol/L, as the effect of supplementation is not linear.

      When was the test taken? It is probably best to get tested in early spring when levels will be lowest. The low point is where the damage is most likely to be done, assuming there is an effect of vitamin d on MS and this although likely is not proven.

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    3. Had 85 nmol/L in April and around 60 nmol/L in January (not the same year) so it depends really how your ongoing inflammation (not relapse) is doing - I believe inflammation 'eats up' Vit D.

      I'm okay with 1000-2000ie as was recommended by my doc.

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  3. To me the title of article seems a generalist statement. It should read something along the lines of 'The people with MS in the study had diminished response to vitamin D supplementation'.

    I was taking just 400IU of vitamin D for a long time and getting blood test reslts of just under 100 nmol/L. I'm female and have RRMS.

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  4. As far as I'm aware - though I would gladly stand corrected - there is no evidence that vD supplementation makes any difference once you have developed MS. So such news is more important for young people (and pregnant women?) in an effort to lower MS risk.

    I take 800 IU on most days, but I doubt that it's doing anything remarkable for my PPMS. However, vD is important for other things, and the recent articles on here about how pwMS have genetic issues with vD means that I'll probably continue to supplement.

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    1. Sterntaucher: none of the following have large numbers of participants and so are under powered but you may wish to have a look, assuming you have access.

      Multiple Sclerosis 2008; 14: 1220–1224, Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis, J Smolders, P Menheere, A Kessels, J Damoiseaux and R Hupperts

      Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, AustraliaJ Neurol (2007) 254:581–590, I.A.F. van der Mei, A.-L. Ponsonby, T. Dwyer
      L. Blizzard, B.V. Taylor, T. Kilpatrick, H. Butzkueven, A.J. McMichael

      A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis, J.M. Burton, S. Kimball, R. Vieth, A. Bar-Or,H.-M. Dosch, R. Cheung, D. Gagne, C. D’Souza,
      M. Ursell, P. O’Connor, Neurology 74 June 8, 2010 1852-1859

      Vitamin D status is associated with relapse rate in pediatric-onset MS, Ellen M. Mowry, ; Lauren B. Krupp, ; Maria Milazzo, M.S., C.P.N.P. ; Dorothee Chabas, ; Jonathan B. Strober, M.D. ; Anita L. Belman, M.D. ; Jamie C. McDonald, B.S. ; Jorge R. Oksenberg, Ph.D. ; Peter Bacchetti, ; Emmanuelle Waubant, Annals of Neurology Volume 67, Issue 5, pages 618–624, May 2010

      Int J Prev Med. 2013 May; 4(5): 585–591. Vitamin D3 Concentration Correlates with the Severity of Multiple Sclerosis, Saeed Shahbeigi, Hossein Pakdaman, Seyed-Mohammad Fereshtehnejad, Elham Nikravesh, Nazanin Mirabi, and Ghazal Jalilzadeh

      There are many others.




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    2. That's interesting, thank you. My neurologist specifically told me that he does not believe that vD would change anything, but supplementation is probably wise for other reasons anyway.

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    3. I know now that most neurologists mean well. However, they do not know everything about every neurological disease. One consultant neurologist told me raynauds syndrome only involves fingers. I corrected him, it can involve toes, fingers, lips, ears, nose and even nipples.
      My point is it's good to consider a wide range of opinions.

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    4. Sterntaucher; It is fairly certain that raised vitamin d levels will not cure anyone, but it does appear it may be helpful in reducing relapse severity and frequency. The literature shows no toxicity in adults at 10,000IU vitamin d3 a day, so there is little to loose trying. Interestingly there is some evidence that vitamin d2 is not effectively used by the immune system and does not have the same effect, and some early literature does not distinguish.

      I would be worried about a doctor who stated he does not think vitamin d would change anything given the amount of research going on in vitamin d and immune system. The best statement would be we don't know, or unproven.

      Vitamin d appears to affect the reactivation of Epstein Barr virus [The beneficial effects of vitamin D3 on reducing antibody titers against Epstein–Barr virus in multiple sclerosis patients, Adeleh Najafipoora, Rasoul Roghaniana, Sayyed Hamid Zarkesh-Esfahania, Majid Bouzaria, Masoud Etemadifarc, Cellular Immunology, Volume 294, Issue 1, March 2015, Pages 9–12] and it may just be this that is reducing relapses.

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    5. Indeed... Looking also at the information provided by the MS Trust, which usually provides good summaries, the situation is not as black and white as I believed at all: http://www.mstrust.org.uk/atoz/vitamind.jsp

      I feel a missive to my neurologist forming!

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    6. Well, given Prof. Giovannoni's post of April last year, I'll go easy on my poor neurologist:

      http://multiple-sclerosis-research.blogspot.com/2014/04/vitamin-d-and-human-health.html

      "Please note there is no evidence that vD supplements are disease-modifying in MS. The low vD levels in MSers can be due to reverse causation, i.e. MS disease activity results in low vD levels not the other way around. The reverse causation hypothesis, however, is no reason to ignore low vD levels in MSers. The main reason for me recommending vD supplements is for other potential health reasons, in particular bone health."

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    7. The only sin in science is to not change your opinion in the light of the evidence.

      I have watched the science of vitamin d since 2005, when I noticed it alleviated my Epstein Barr induced chronic fatigue if taken in large enough amounts (5000IU to 10000IU a day). The experts in the field have basically stayed in the same place and the rest of the world has largely drifted towards them, apart from those who favour the Marshall Protocol, who scare me.

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  5. Some people may be fine with "lowish" levels of Vit D3 supplementation but some people are also able to get more sun exposure than others. As a fair skinned redhead living in a country with vicious UV rays and a very high skin cancer rate I cannot get much Vit D from sun so I take 5,000 IU a day of D3, but I also take Vit K2 and magnesium to ensure that the Vit D is metabolised properly. The amount of 5,000 IU daily seems to be a fairly common recommendation from many reputable sources. The only problem I had was before I started taking some extra magnesium, once I did that everything was fine.

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  6. I have not had experience with the phenomenon of Uhthoff (with you for as long as I expose to the Sun without too much trouble) but most of the Emerson I know experience worsening of symptoms related to MS (fatigue, dizziness, tingling, etc.) to be exposed to Sun, then see especially for these cases supplementing the D3 as the only alternative ...

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    1. Uhthoff's phenomenon is caused by a rise in body temperature - thus exposure to the sun will sometimes and for some people cause this - so will vigorous exercise or anything else which increases your body's core temperature (such as other illnesses). Vit D3 will not have any effect on Uhthoff's phenomenon.
      http://www.mstrust.org.uk/atoz/uhthoff.jsp

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    2. Yes, I know that D3 does not change the Uthoff phenomenon. What I meant is that many MSers I know try to expose to the sun with the intention of replacing vitamin D in their bodies, but many of these relate expirementarem Uthoff after or during exposure (worsening of symptoms, etc.). So for these perhaps the only way to reset the D3 is via oral supplementation, as exposure to the sun causes this disorder ...

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  7. I had Uhthoff's two years ago when it was hot weather. It was 30 degrees or so. A door slammed and I turned around and it felt like I had severe vertigo for a short time. I was unable to eat hot or warm food.

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