#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.

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