Sunday, 3 January 2016

ResearchSpeak: Moderate dose vitamin D supplementation has immune effects

Moderate dose vD supplementation (10,000U/day) has favourable immune effects in MS #ResearchSpeak #MSBlog #MSResearch

Moderate dose vD supplementation (10,000U/day) is safe #ResearchSpeak #MSBlog #MSResearch

"The study below made the news this week when it was shown that moderate vitamin D (vD) supplementation (10,400 IU/day) was safe in pwMS and had favourable effects on the immune system. The immunological changes on moderate dose vD are congruent with the effects we would want to see if MS was an 'autoimmune disease'; e.g. they found a reduction in the proportion of interleukin-17+ve-CD4+ T cells so-called putative autoreactive T cells in MS."

"Why do I say moderate dose vD supplementation rather than high-dose? This is because 10,400IU per day is physiological vD supplementation. If you go into the mid-summer sunlight with your upper body exposed for ~20-30 minutes your skin will make this sort of dose of vD; therefore 10,400IU is not high-dose. The good news is that this study confirms other studies that moderate dose vD supplementation is safe and not associated with any toxicity or adverse events."

"To remind you it is our policy to advise all our patients to ensure they are vD replete; we aim for a plasma level of 25OH-vD3 of greater than 100 nmol/L and less  than 250 nmol/L. We start by recommending 5,000IU/day and testing blood levels about 12 weeks later. If levels are still low and the patient has been adherent then we increase the dose to 10,000 IU/day and if too high we reduce the dose to between 2,000-4,000IU/day. It is clear that plasma levels of vD are highly variable and are affected by dietary and multiple genetic factors. We never tell our patients that this will improve or help their MS; we say it may do but the real reason for being vD replete is to improve you bone health. Please note we do not recommend calcium supplementation in parallel with vD supplementation. As far as we are concerned there is no reason for pwMS to take calcium supplements unless they have osteoporosis. If you are taking moderate or high-dose vD and calcium supplements together you will need to have your calcium levels monitored (please discuss this with your doctor)."

"Who's advice are we giving? We tend to favour the Vitamin D Council's advice regarding initial dose of supplementation. With regard to our target level of plasma vD levels; I have adopted the evolutionary medicine approach espoused by Reinhold Veith (see old slide show below). This theory is based on what your vD levels would be if you worked outdoors with skin exposed (lifeguards & farm labourers) and what vD levels are in hunter-gatherer societies."

"The problem we are having with vD supplementation is adherence; pwMS simply forget to take their supplements and don't take our advice when it comes to getting their relatives on supplements as well. Maybe you have some ideas to help us improve adherence with supplementation in 2016?"

" I am told that non-compliance or non-adherence with medical advice is a complex issue and we need to get with the programme if we want to improve the outcomes of people living with MS."


Epub: Sotirchos  et al. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology. 2015 Dec 30. pii: 10.1212/WNL.0000000000002316.

OBJECTIVE: To study the safety profile and characterize the immunologic effects of high- vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS).

METHODS: In this double-blind, single-center randomized pilot study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months. 

RESULTS: Mean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0-44.7 ng/mL) than in the low-dose group (6.9 ng/mL; 95% CI 1.0-13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17+CD4+ T cells (p = 0.016), CD161+CD4+ T cells (p = 0.03), and effector memory CD4+ T cells (p = 0.021) with a concomitant increase in the proportion of central memory CD4+ T cells (p = 0.018) and naive CD4+ T cells (p = 0.04). These effects were not observed in the low-dose group. 

CONCLUSIONS: Cholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD4+ T cells and decreased proportion of effector memory CD4+ T cells with concomitant increase in central memory CD4+ T cells and naive CD4+ T cells.

CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects.

22 comments:

  1. So how do we get our medics to adhere to this advice and to adopt this protocol?. My tested level was 49nmol/L for all vD and my GP said no you must not take extra vD as it will "leach calcium from your bones, you need at least to take magnesium with it". My Neuro says don't take more than 2,000iu a day but does not test levels he just tells all pwMS to take that. I currently take 2,500 a day v3 on my own without the support of any medics!

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    1. Re: "leach calcium from your bones, you need at least to take magnesium with it"

      Not sure we you get this information. Vitamin D does the opposite and protects your bones and stops the leaching of calcium from bones. In fact it suppresses the production of the parathyroid hormone, or PTH, which is responsible for activating the bone cells called osteoclasts. These are the cells that mobilise calcium from bones.

      Th reason why vD can cause raised calcium in the presence of oral calcium supplements is that it increases the absorption of calcium from the intestines and kidney. This is very rare side effect and only rarely happens.

      Vitamin D can also raise calcium levels in the presence of other diseases associated that are in themselves associated with raised calcium levels; these include hyperparathyroidism, malignancies with bone metastases, sarcoidosis and other granulomatous conditions. We think vD supplements simply unmasks high calcium levels in these conditions; vD is not the primary cause of the high calcium levels.

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  2. Two years ago my neuro recommended that I should be prescribed a daily dose of 5,000iu daily and luckily my GP was convinced, so it's on my repeat prescription. Should I now ask him to recommend a double dosage?
    Re: adherence. I am sure the key is to get it prescribed. When you are ordering it yourself, in your mind it's an add-on rather than essential medication. I'm glad to have it prescribed, NOT because it's now free but because I know it's on my medical records and that it's being considered as an integral part of my treatment and will be monitored as such.

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    1. Perhaps that's the answer then to get the Vit D on prescription and then it would need to be monitored by the NHS.
      I don't think my GP would agree to Vit D being prescribed and monitored on the NHS but worth a try.

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    2. (I am the above'anonymous') When I asked my GP if she'd prescribe it, she said she'd be happy to prescribe anything on the recommendation of the neuro, so at my next neuro appointment I asked him to write to the GP. I saw his letter - it said that a dosage of 5,000iu daily was 'appropriate for an MS patient'. Perhaps this would be the way to convince your GP?

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  3. I have been taking 2,000 IU a day and am over 130nmol. My MS nurse suggests 5,000 IU day.
    I don't think I would want to take 10,000 IU of vit D daily long term unless I was tested every few months, I know I would need to pay privately for that.

    My GP says many people of the general population in the UK have low vit D levels.

    ReplyDelete
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    1. To get from nmol/L to ng/mL you need to divide by 2.5 so you are at 52 ng/mL. However, 25(OH)D levels do not rise linearly with intake of vitamin d it levels off.

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    2. Anon at 10.24am are you saying that if I did take 10,000IU a day (instead of 2,000IU) for over three months my Vit D level would not rise much above 130nmol? It would level off.

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  4. It is better trust in researches and take 10400 IU day than trust in doctors who do no read scientific research. I take 10000Iu/day om my own. Tomorrow I will take 400iu more.

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  5. I have been taking 5000iu D3 daily and level is 64 nmol. I would take 10,000iu based on this research, but the warning about not taking calcium supplement with this concerns me. I take calcium citrate and magnesium currently. Sometimes it is difficult to know what to do for the best! I fractured neck of femur last Feb & bone scan a few months ago showed osteopenia.

    ReplyDelete
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    1. I think they mean don't take the combined vit D/calcium tablets or don't take vit D and calcium tablets together in a short space of time.
      I take my vit D tablet in the morning and then calcium tablet late afternoon.

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    2. Would you guys confirm that this is in fact what you mean? It's safer to take calcium and Vit D spaced out during the day?

      I've got MS and have just been diagnosed with osteoporosis.

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    3. Re: "It's safer to take calcium and Vit D spaced out during the day?"

      You need to discuss things with your doctor. vD's effect are not short lived and work over weeks to months.

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    4. I take a combined calcium and Vitamin D supplement recommended by my orthopaedic consultant for my osteoporosis. Nowhere near the levels mentioned on this post. However, I have been advised to sit in the sun for 20 minutes, unprotected early morning and late afternoon during the months between May and September. Also, I saw my dietician and found I was already eating the correct diet. My MS hasn't improved or stabilised, but I don't need any more health problems from not listening to the experts when they're trying to help me.

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    5. For jayjill
      At 64 nmol your level is really only just above what here in Australia is considered borderline deficient - and our medicos are mostly a rather conservative lot over here. The bottom end of our reference range in Aus is 50 nmol.
      I'd suggest having a look at the Vit D Council's website on what other bits and pieces go with Vit D3 to make it all "work properly". There is now starting to be quite a bit of newer research around showing that Vit K2 is essential with Vit D3 to help prevent high blood calcium levels (i.e. studies showing that fractures in the elderly were reduced when K2 was included with D3 compared to D3 only).
      http://www.vitamindcouncil.org/about-vitamin-d/vitamin-d-and-other-vitamins-and-minerals/

      I also take magnesium, and where I live the most affordable way of obtaining K2 is in a new product which does contain some calcium along with D3 and K2.

      Delete
    6. The following is interesting about having a high milk intake.
      http://www.bmj.com/content/349/bmj.g6015

      Milk intake and risk of mortality and fractures in women and men: cohort studies
      BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g6015 (Published 28 October 2014)

      " What this study adds
      -A high milk intake in both sexes is associated with higher mortality and fracture rates and with higher levels of oxidative stress and inflammatory biomarkers

      -Such a pattern was not observed with high intake of fermented milk products. "

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  6. Would it be best then to aim for a target of 200 to 250nmol/L as the ultimate ideal? (the upper end of the range).

    I know the suggested range is 100 to 250nmol/L.

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    1. Re: "Would it be best then to aim for a target of 200 to 250nmol/L as the ultimate ideal? (the upper end of the range)."

      I am not a vD expert and therefore defer to the advice of Reinhold Veith; he states >100nmol/L without a seasonal cycle that we typically see in the Northern Hemisphere.

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    2. Re "non-compliance or non-adherence with medical advice is a complex issue"
      Yes - indeed it is, but you can lead a horse to water.....
      Problem sometimes is that the medical advice seems to be crap, as is clear from the advice given by Eyesnlegs' GP about Vit D leaching calcium from the bones, and their neuro clearly has a one size fits all approach to their clinical practice. Glad I'm not a patient of either of them!!! Thankfully I have a questioning mind and also say thank heavens for the internet. My GP said a while back that I've learnt more about MS in the last eighteen months than she has had the chance to learn about it in her many years of clinical practice as a GP. To be fair to her though, she is a GP and has to know about lots of things whereas I'm the one with MS and therefore a vested interest in learning about MS.

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  7. I think the big problem it is not patient adherence to supplementation of vitamin D3 every day, but a resistance Neurologists own on the subject. I, for one, the D3 supplement at a dose of 10,000 UI every day since the outbreak that made me discover the disease (nearly 02 years) and I'm fine. Not hypercalcemia, calcium levels remain normal, and D3 are between 50 and 100 nmol / L of blood (the latter verification: 71 nmol / L). I can not expose myself to the sun continuously for I am very white and the risk of skin cancer is a reality in Brazil, cases of melanoma only increase. So I said to my neuro he or she would supplementing the D3 or I would continue taking without the approval of her, she gave in and monitors every 6 months as are the levels of calcium and D3 own. Oh and even I realized I hardly get sick (besides MS), all contract viruses, colds, etc., for example but not me. Before any patient person leaned on me I quickly got sick too ...

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  8. Hi my D3 5.000 a day for 14 years, value is 155 nmol//L
    Should I take more D3 or stay on 5.000.
    Thank you

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  9. Controversial results from recent Vit D3 study and MS.

    Study based on 20,000 IU vit D3 a week is equal to 2,857 IU a day.

    http://www.ncbi.nlm.nih.gov/pubmed/26429571

    J Neurol. 2015 Dec;262(12):2713-21. doi: 10.1007/s00415-015-7902-5. Epub 2015 Oct 1.

    Vitamin D supplementation and systemic inflammation in relapsing-remitting multiple sclerosis.


    " We conclude that in this study of RRMS patients, high-dose oral vitamin D3 supplementation prominently increased serum 25(OH)D levels without affecting markers of systemic inflammation, while a more anti-inflammatory phenotype was found among patients on immunomodulatory treatment. "

    ReplyDelete

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