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Vitamin D and MS: Burton


Associate Clinical Professor, University of Calgary
Hotchkiss Brain Institute (HBI)
Office: 5th Floor, Room 5A214 
Department of Clinical Neurosciences
Rockyview General Hospital - HCACC
7007 14 Street SW
Calgary, AB T2V 1P9
University of Calgary, Alberta, Canada
T (403) 943-3882

Dr. Jodie Burton is the acting principal investigator (PI) of the dose-escalation trial of oral vitamin D3 with calcium supplementation in patients with multiple sclerosis with Dr. O'Connor. She started the trial as his fellow, while doing an additional 2 years of training in MS specifically after she received her neurology certification. She completed her fellowship training in 2007. Now she is staff doing clinical research and continuing with the vitamin D trial. As of August 2009, she will be Assistant Professor in Neurology in the Department of Clinical Neuroscience in Calgary and at the University of Calgary. She will be part of the MS team there with Dr. Luanne Metz and the MS group.

PubMed: Burton JM

Clinical trial
Start Date: July 2006 - completed
Safety Trial of High Dose Oral Vitamin D3 With Calcium in Multiple Sclerosis (VitD4MS)
>> NCT00644904

Please scroll down for an abstract of the trial:
A Phase I/II dose-escalation trial of oral vitamin D3 with calcium supplementation in patients with multiple sclerosis.

For the latest news go to:
High Doses of Vitamin D Cut MS Relapses
Study Shows Vitamin D May Help Reduce Relapse Rate of Multiple Sclerosis

As Dr. Jodie Burton is trying to find a safe and effective dose of oral vitamin D3 which would benefit patients with MS, I asked her what she is advising her own patients in the meantime pending the outcome of her research.

Dr. Burton has kindly answered my questions concerning the vitamin D level to strive for in MS and the daily amount of vitamin D3 and calcium to take to achieve that level.

In answer to your questions (and this likely applies to most of us in the clinic),
Vitamin D level
- Do you measure the serum 25-hydroxyvitamin D concentration of your patients with MS?
From now on I'll be checking the vitamin D level in all new patients with MS and do a recheck after supplementation at 2-3 months to ensure an adequate response.
- If so, when do you measure their serum 25-hydroxyvitamin D concentration?
I would imagine the best time to measure vitamin D3 levels are at presentation, and would predict they might be low in the midst of an MS attack. I might recheck the value at three months to see if it increased - a subset of patients appear to mount a lesser response to supplementation. In truth, if I had no limitations, I'd check the whole immediate family, and during relapses.
- What level do you strive for?
If I did measure routinely, I would strive for a minimum of 100 nmol/L as that appears to come up in studies looking at the connection such as Munger et al. This cut-point also came up in some of our analysis as well, particularly with respect to T-cell reactivity (patients whose levels were 100 nmol/L at trial's end had greater reduction in T-cell reactivity).

Vitamin D3
- Do you advise your patients with MS to take Vitamin D3?
Yes, I do.
- If so, how much Vitamin D3 do you advise them to take?
We typically recommend 100 mcg (4000 IU)/d of vitamin D3. I also recommend that dose to my CIS patients (as they are probably the highest risk group for MS there is). I have started recommending 100 mcg (4000 IU)/d to first degree adult relatives of my patients (at least who are not long-past the age at which MS could strike).
- and their children
I also recommend to my patients to consider supplementing their children (10 mcg (400 IU)/d for young children, 25 mcg (1000 IU)/d in pre-teen/teen years, and 100 mcg (4000 IU)/d as adults) - this is a little controversial, but as long as I've checked for contraindications and they talk to their pediatricians, I think it is safe and good for a host of reasons.

- Do you advise your patients with MS to take calcium?
I do suggest the patients supplement with calcium as well, we cannot be sure that our results are not related to the effects of both vitamin D and calcium, and Cantorna's animal studies as well as the paper in Am J Clinical Nutrition about reducing risk of cancer seem to
point to a role for both.
- If so, how much calcium do you advise them to take?
I recommend 1000 mg of calcium (in our trial we used 1200 mg).

My dosing ideas come from reviewing the literature and working with our vitamin D biochemistry collaborators (Dr. Reinhold Vieth and his PhD student Samantha Kimball here in Toronto).

P20 - A Phase I/II dose-escalation trial of oral vitamin D3 with calcium supplementation in patients with multiple sclerosis
Jodie M. Burton1, Samantha Kimball2, Reinhold Vieth2, Amit Bar-Or3, Hans-Michael Dosch4, Louise Thibault5, Sally Kilborn5, Cheryl D’Souza6, Roy Cheung4, Melanie Ursell7, Paul O’Connor1
1St. Michael’s Hospital, Toronto, Ontario, Canada; 2Mount Sinai Hospital, Toronto, Ontario, Canada; 3Montreal Neurological Institute, Montreal, Quebec, Canada; 4Hospital for Sick Children, Toronto, Ontario, Canada; 5McGill University, Montreal, Quebec, Canada; 6University of Toronto, Toronto, Ontario, Canada; 7Etobicoke General Hospital, Etobicoke, Ontario, Canada


Increasing distance from the equator, low UV radiation and low serum 25-hydroxyvitamin D [25(OH)D] are associated with increased multiple sclerosis (MS) prevalence and risk. While this relationship provides insight into prevention, it begs the question, ‘Is vitamin D3 (VD3), known to have immunoregulatory properties, beneficial in established MS?’ To answer this, a safe, effective dose must be determined.


To characterize the safety profile of highdose oral VD3 in MS.

A prospective controlled 52-week trial matched MS patients for demographic and disease characteristics, randomizing them to treatment or control groups. Treatment patients started VD3 at 4000 IU/day and escalated over 28 weeks to 40 000 IU/day. This was followed by maintenance with 10 000 IU/day for 12 weeks, 4000 IU/day for 8 weeks and a 4-week wash-out, translating into roughly 14 000 IU/day over 52 weeks.

Calcium (1200mg/day) was given throughout the trial. The primary endpoint was mean change in serum calcium in treatment patients at each VD3 dose, and a comparison of calcium between treatment and control groups. Secondary endpoints included 25(OH)D, urine calcium/creatinine (Ca/Cr) and PTH. Cytokines, lymphocyte response and matrix metalloproteinase-9 were also measured, as were Expanded Disability Status Scale (EDSS) and relapses.

Forty-nine patients were enrolled (25 treatment, 24 control) with mean age 40.5 years (21–54 years), EDSS 1.34 (0–6.0) and 25(OH)D 78nmol/l (38–154). No abnormalities or differences in serum calcium, urine Ca/Cr or PTH occurred, nor were there differences in calcium between groups. Despite a maximum mean 25(OH)D of 413nmol/l (66–729), no significant clinical or biochemical adverse events occurred. A greater proportion of treatment patients had stable/improved EDSS vs. control patients (p=0.018). Treatment patients also had fewer relapses and a greater reduction in relapse rate vs. controls. Immunological data will be presented.

High-dose VD3 (~10 000 IU/day, possibly higher) in MS is safe and tolerable, with evidence of clinical improvement.

Supported by: Direct-MS (non-profit agency), Multiple Sclerosis Society of Canada.

Burton JM, Kimball S, Vieth R, et al. A Phase I/II dose-escalation trial of oral vitamin D3 with calcium supplementation in patients with multiple sclerosis. Mult Scler. 2008;14(Suppl 1):S34.

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