Alicia Ault

June 10, 2016

NATIONAL HARBOR, Maryland — Though evidence is mounting that low vitamin D levels may increase risk for the development and perhaps progression of multiple sclerosis, clinicians still do not have definitive safety and efficacy data or guidance on whom to supplement and when, appropriate dosage, or duration of supplementation.

And yet it seems that vitamin D supplementation is being added to the standard MS toolbox.

"I think a lot of people are widely accepting it in the MS community, but I worry that it's because it's easy, not because it's evidence-based," Ellen Mowry, MD, MCR, associate professor of neurology and epidemiology at Johns Hopkins University, Baltimore, Maryland, told Medscape Medical News.

Although she offers vitamin D in her practice, "I tell my patients that we actually don't know if supplementing will help," she said. And supplementation comes with risks in people who have heart disease or a history of kidney stones, for instance. "It's important for people to think about their own risk background," she said.

Dr Mowry, who has conducted a number of vitamin D studies and is the primary investigator in the ongoing VIDAMS (Vitamin D to Ameliorate MS) trial, presented an overview of the current evidence on vitamin D here at the Consortium of Multiple Sclerosis Centers (CMSC) 2016 Annual Meeting. She sounded a note of caution to attendees, reminding them that promising supplementation stories have gone wrong in the past.

βCarotene, for instance, was associated with a lower risk for heart disease, but after study, it was found to be linked to more heart disease deaths and an increased risk for lung cancer.

And, while higher vitamin D levels appear to be associated with a decreased risk for MS development or progression, that association might be masking a different relationship, she said.

"It's really important to make sure that we don't get burned," Dr Mowry told attendees. "We should probably subject vitamin D to same kind of rigorous evidence that we would any therapeutic that we give to our patients," she said.

 
It's really important to make sure that we don't get burned. Dr Ellen Mowry
 

Tantalizing Associations

After years of observational data, two studies helped cement the idea "that lower vitamin D levels preceded the onset of disease," said Dr Mowry.

One, published in 2006 (JAMA. 2006;296:2832-2838), found that military personnel who had serum 25-hydroxyvitamin D25 levels of 100 ng/mL had a 50% lower risk for MS, while those with lower levels were more prone to the disease. Swedish researchers replicated the findings in 2012, showing that people with levels above 75 ng/mL had a reduced risk.

A more recent trial (JAMA Neurol. 2016;73:515-519) showed that women with higher vitamin D levels in pregnancy had children who were less likely to develop MS. "That's pretty interesting," said Dr Mowry, but she pointed out that it's possible other things could be at work — for instance, perhaps the offspring who did not develop MS received more ultraviolent (UV) light exposure during childhood.

UV light may itself have immunomodulatory effects, she said, pointing to an Australian study (Neurology. 2011:76;540-548) that found sun exposure seemed to reduce the risk for MS more than did higher vitamin D levels. If sun exposure is more important, "vitamin D supplementation might not help MS at all," said Dr Mowry.

She has conducted several trials looking at vitamin D status in people who already have MS. In children, "we saw striking association between higher levels of vitamin D and lower risk of subsequent relapse," she said, noting that for every 10-ng/mL increase, relapse risk decreased 34% (Ann Neurol. 2010;67:618-624). Adults with MS in another trial (Ann Neurol. 2012;72:234-240) had a reduced risk for new MRI lesions.

Pilot studies specifically looking at supplementation in people with MS have not provided much evidence, she said. One — with just 23 patients — showed no improvement in patients given 6000 IU of vitamin D daily (Neurology. 2011;77:1611-1618), but that trial was not powered to detect significance, said Dr Mowry.

She said many trials underway may soon provide more answers about supplementation, including the following:

  • SOLAR (Supplementation of VigantOL Oil Versus Placebo as Add-on in Patients With Relapsing Remitting Multiple Sclerosis Receiving Rebif Treatment);

  • CHOLINE (A Multicentre Study of the Efficacy and Safety of Supplementary Treatment With Cholecalciferol in Patients With Relapsing Multiple Sclerosis Treated With Subcutaneous Interferon Beta-1a 44 μg 3 Times Weekly), recently completed;

  • VITADEM;

  • EVIDIMS (Efficacy of vitamin D supplementation in multiple sclerosis);

  • PrevANZ (Preventing the risk of Multiple Sclerosis using Vitamin D in patients with a first demyelinating event in Australia and New Zealand); and

  • D-Lay-MS (Efficacy of Cholecalciferol (Vitamin D3) for Delaying the Diagnosis of MS After a Clinically Isolated Syndrome).

Her study — VIDAMS, which is sponsored by the National Multiple Sclerosis Society — is the only United States–based trial. Patients will receive glatiramer acetate for a month and, if they tolerate it, will be randomly assigned to 5000 IU daily or 600 IU daily. The 15-site study will evaluate the effect of vitamin D on relapses.

How to Supplement?

Many MS clinicians and patients are not waiting for trial results. "Most MS patients we run into now are getting supplements," she said.

It's unclear what dosing frequency should be, but she says that a daily, weekly, or monthly dose is fine and that studies have shown that infrequent, very high doses might be more toxic than lower, routine dose levels.

Many patients she sees are taking vitamin D2, but she prefers D3, which she says is a more natural pathway that gets activated by sun exposure. It's also available over the counter, which makes it easier for patients.

Dr Mowry says that if she has decided to supplement, she first checks serum 25-hydroxyvitamin D25 levels. With supplementation, the goal is to bring vitamin D levels up to a range of 40 to 60 ng/mL. At 40 or above, the evidence suggests a lower risk for MS, whereas 60 is the highest end at which evidence has shown a continued association.

The VIDAMS investigators chose a 5000-IU daily dose because kinetics studies have shown that it gets patients with MS into the 40- to 60-ng/mL range, she said. "In my clinical practice, I find people take 1000 or 2000 international units a day, up to 4000 to 5000, depending on the individual," Dr Mowry said.

At 3 months, she tests 25-hydroxyvitamin D25 levels again, but "I don't check it much more after that as long as they are staying on current dose."

In any patient, "we really need to think carefully about the likely benefits," when weighed against the risks, particularly in those with a history of heart disease, kidney stones, or inflammatory disease, said Dr Mowry.

"I always tell people when they ask me about it — we might be doing the wrong thing."

Dr Mowry disclosed that she has been contracted to do research for Biogen and Sun Pharma.

Consortium of Multiple Sclerosis Centers (CMSC) 2016 Annual Meeting. Presented June 2, 2016.

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