Is Vitamin D a Ray of Hope for Patients With MS?



ATLANTA—Increasing evidence supports an association between vitamin D deficiency and multiple sclerosis (MS), as researchers have found that high supplemental doses of the vitamin are safe and significantly reduced relapse rates in patients with the disease.

Among patients who received a mean of 14,000 IU/day of vitamin D3—which is more than three times the daily amount recommended by the FDA for many adults and included doses as high as 40,000 IU/day—16% had a relapse, compared with 38% of controls who had taken an average of 1,000 IU/day, reported Jodie Burton, MD, a neurologist at St. Michael’s Hospital, University of Toronto, and colleagues at the 23rd Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

Potential environmental and genetic causes have been a recent focus of MS research. Studies have shown that a higher incidence of MS occurs in regions where sunlight is not as prevalent and that vitamin D levels and ultraviolet radiation exposure early in life may have an impact on the risk of MS.

“If you are unfortunate enough to live at either pole, you basically don’t have sufficient ultraviolet radiation/sun exposure to produce much vitamin D,” said Dr. Burton. “If you live in North America, you have roughly six months or less of ultraviolet radiation to produce a reasonable amount of vitamin D. Closer to the equator, you have the bulk of the year getting good ultraviolet radiation exposure and the potential for vitamin D sufficiency.”

Vitamin D is produced naturally in the skin when ultraviolet radiation is absorbed and is then converted to 25-hydroxyvitamin D [25(OH)D] and the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D] form. Serum concentration of 25(OH)D is regarded as the most reliable indicator of vitamin D status.

Some investigators have hypothesized that vitamin D may act as an immune modulator in decreasing proliferation of proinflammatory T leukocytes and in decreasing production of various cytokines. “We know MS is predominantly an immune-mediated disease, so presumably vitamin D would have to act on the immune system to be biologically valid,” said Dr. Burton.

If Effective, What Is an Appropriate Dose?

The current recommended daily dose of vitamin D is based on the amount believed to prevent rickets in children, “which is great when you are worried about getting rickets, and which is not so great when you are trying to accomplish something else,” said Dr. Burton. “So if you are looking for compelling evidence that that amount of vitamin D has any impact on the immune system, you are not going to find any.” The FDA recommends 200 IU/day for those up to age 50, 400 IU/day for those 51 to 70, and 600 IU/day for those older than 70. “The amounts are pretty low,” said Dr. Burton.

Dr. Burton and colleagues sought to determine whether vitamin D could have a positive impact on patients already diagnosed with MS and what a safe and effective dose would be. The randomized controlled trial included 25 patients on an escalating dose regimen of vitamin D3 and 24 control subjects who took an average of 1,000 IU/day. The dose of vitamin D was escalated for six months to 40,000 IU/day and then was de-escalated down to zero, for a mean of 14,000 IU/day, with about 70% of the year spent at 10,000 IU/day or higher. All participants also received 1,200 mg/day of calcium throughout the trial.

Calcium was used for two reasons, noted Dr. Burton. “People take calcium regularly, so we wanted to make sure you could add vitamin D to calcium without consequences,” she said. “Second, in studies with the animal model of MS—experimental autoimmune encephalitis—as well as cancer prevention studies, vitamin D and calcium appear to work synergistically.”

The primary outcome measures were those of safety, and included mean change in serum calcium in the treatment group for each dose change and mean difference in serum calcium treatment compared with controls. Secondary outcomes were efficacy related and included changes within and between patient groups for relapse activity, Expanded Disability Status Scale (EDSS) score, and ambulation index. A total of 23 treatment patients completed the trial, along with 22 controls. Patients were seen about every six weeks in the treatment group and at four time points in the control group.

Safety and Efficacy of High-Dose Vitamin D

Dr. Burton and colleagues found that serum calcium levels remained steady and within normal limits throughout the dosing regimen, and there were no significant differences between treated patients and control patients at any time point. Mean urine calcium/creatinine levels in the treatment group were also well within normal, increasing slightly at the higher dosing levels, which is to be expected, according to Dr. Burton.

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