Wednesday, 30 August 2017

#ClinicSpeak & #ResearchSpeak: what dose of vitamin D?

What dose of vitamin D supplementation do I recommend? #ResearchSpeak #ClinicSpeak

Summary: This blog post makes the case for using an initial dose of vD supplementation (5,000U/day) and then to test blood levels of vD after approximately 6 weeks to adjust the dose accordingly. I use evolutionary medicine to define a treatment target of blood vD levels.

The study below has 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 produce 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. I 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. I never tell my 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, or maintain, your 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 thin bones (osteopenia or 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 am I giving? We tend to favour the Vitamin D Council's advice regarding the 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. Using a reference population gets around the likely problem that modern societies are vD deficient and hence you can use population mean vD levels to establish a normal range of plasma vD levels.

The problem I have 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.


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.

12 comments:

  1. Is there less incidence of MS in people who work outside and are exposed to the sun daily. Such as gardeners, lifeguards, builders and roofers, farm labourers, fishermen and sailors?

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  2. Re: adherence to supplements,I am lucky enough to have a GP who agreed to prescribe vitD (5,000iu) in accordance with my neurologist's advice. It's not just that this saves me money and bother, it's the fact that - at least in theory - it's being monitored and is a recognised part of MS treatment that everyone, including me, takes seriously. In the circs, why would I default?

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  3. The RDA for new born babies is the same as 120kg adults. How can this possibly be correct?

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  4. You never talk of how vital vitamin K is, though. MSers need this.

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    1. We all need vK. It is an abundant fat soluble vitamin. Provided you eat a reasonable diet and don't have fat malabsorption you don't need to take vK supplements.

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  5. Could you please shed some light on VitK while taking VitD(3)?

    It seems to me, from papers I have read, that this would be a recommended additional supplementation to increase the effect and decrease the side effects of high dose VitD(3).
    Thanks! :D

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    Replies
    1. Vitamin K1 and K2. K1 is in vegetables. K2 is in meat including fish eggs, dairy, eggs and some fermented foods.

      Some of the diets people take for MS rule out meat and dairy, so perhaps they might need to think how they would get their K2?

      Please correct me if I am wrong. thanks.

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    2. You are correct. However, vitamin k affects blood clotting in those on Warfarin. Vitamin k is needed to form some of the blood clotting factors and Warfarin blocks this. So if you take Warfarin it is important to consume a consistent amount of vitamin k and be careful if you are going to increase vitamin k intake as your Warfarin dose must also rise.

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  6. This efect is on the T cell brigade

    Where are the B cell?

    Could you get me Doctor Mouse? ....Please

    Obrigado

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  7. I take 10,400 IU of Viatmina D3 every day since the first and only outbreak I've had so far.

    I'm going to the fourth year of MS since my diagnosis. No new lesions, no evolution, EDSS 0 for now.

    I take vitamin D3 during lunch; lettuce is rich in Vitamin K and is inhibitor of vascular calcification.

    So vitamin K in adequate amount will help ensure that calcium goes to the bones where it belongs instead of calcifying various soft tissues.
    For this I invest in foods rich in Vitamin K, and when possible I take vitamin D3 with K, and with Magnesium as well.

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  8. Can you please provide some more information on how evolutionary medicine is used to determine appropriate blood vD levels? Thanks.

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    Replies
    1. Yes, I can but this will need to be done as a separate post. The field is an interesting and expanding one.

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