ARTICLE IN BRIEF
Investigators reported that even at the highest doses of vitamin D, and at levels of vitamin D said to be “toxic” no laboratory or clinical abnormalities were detected, and suggested that the vitamin might be beneficial for patients with multiple sclerosis.
Are high doses of vitamin D safe and potentially therapeutic for patients with multiple sclerosis (MS)?
That was the question for investigators following up on leads from past research that had shown that living close to the equator — where sunlight is a natural and abundant source of vitamin D3 — may be protective, and low vitamin D levels are associated with MS.
Jodie M. Burton, MD, a neurologist and clinical epidemiologist currently at the University of Calgary, became interested in vitamin D as a therapeutic option in MS when a colleague conducted a small pilot study and found it was safe. Dr. Burton and her colleagues set out to conduct a larger study to test the safety of high doses, and as a secondary outcome, to see if there was a clinical benefit.
In the yearlong open-label randomized trial, 25 MS patients received an escalated dose of vitamin D up to 40,000 IU over the first 28 weeks of the study (to assess tolerability) and then the dose was lowered to 10,000 IU for an additional 12 weeks, followed by a further decrease back to 0 by the end of the year. A control group of 24 MS patients took no or low doses (up to 4,000 IUs daily) of vitamin D.
A daily dose of calcium (1,200 mg/d) was given throughout the study, the investigators reported online April 28 in advance of the print edition of Neurology.
Dr. Burton and her colleagues reported that vitamin D levels, even at those high levels, were safe and calcium levels were not abnormally altered. “That is always a concern when you deliver high doses of vitamin D,” she said.
Among the signs of vitamin D toxicity are hypercalcemia, anorexia, nausea, proteinuria, urinary casts, azotemia, and metastatic calcifications (particularly in the kidneys) can develop.
Dr. Burton noted that there was no change in serum calcium at any point in the study. In addition to measuring levels of vitamin D, the investigators also looked for changes in immunological biomarkers and collected information on relapse events and the disability as measured by the Expanded Disability Status Score (EDSS).
Dr. Burton said that although the study “was not powered or blinded to properly address clinical outcomes, clinical outcomes appeared to favor the treatment groups.” Specifically, they reported that T-cell reactivity and proliferation dropped in treated patients. In addition, there was a 41 percent reduction in relapse rates in the treated group compared with a 17 percent reduction in controls who were allowed to take up to 4,000 IUs of vitamin D daily.
Dr. Burton said that enrollment and attention generated by a study like this is likely responsible for the reduction seen in controls. Four patients in the treated group had a relapse in the study year compared to nine of the patients who were taking no or low doses of vitamin D.
“Before we begin studies to test the benefits of treatment we have to know what the right dose is,” said Dr. Burton. The recommended daily allowance, according to Dietary Reference Intakes, is 200 to 600 IUs per day, which is high enough to prevent rickets. Dr. Burton said there is evidence that the tolerable dose is likely much higher, with doses as high as 50,000 IU without any observable toxicity, according to a study in the American Journal of Clinical Nutrition.
“There is a lot of work to be done,” Dr. Burton said. “We need a larger study with a bigger focus on MRI changes and clinical measures.” And investigators are still trying to determine the correct dose. She noted that in a 2003 pilot study of 17 patients who received a much lower dose (1,000 IU a day), there was a hint that it had some benefit to patients.
“I was not surprised that the study found these intakes of vitamin D to be safe,” said Heather Hanwell, a PhD candidate in nutritional sciences at the University of Toronto. That they also found immunological changes, she added, “is compelling.” Ultimately, she said that a double-blind study and even a prevention study could be done to see whether the vitamin should be added to the standard MS treatments.
Hanwell is working with senior investigator Brenda Banwell, MD, assistant professor of pediatrics (neurology) at the Hospital for Sick Children and the University of Toronto, who is leading a prospective study of vitamin D in children who had a first demyelinating attack. One in four of these children will go on to develop MS, Hanwell noted. The investigators will measure vitamin D levels before, during, and after the treatment to see whether vitamin D levels are lower than normal and whether increases in the levels have an impact on the disease process. •
• Burton JM, Kimball S, R. O'Connor P, et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010; E-pub 2010 Apr 28.