However, serum 25(OH)D levels increased with high vitamin D doses. At 40,000 IU/day, the mean 25(OH)D level approached 420 nmol/L, “which would scare most people,” said Dr. Burton, adding that 250 nmol/L is the “so-called” normal acceptable level of toxicity. “Despite these values, nobody had any calcium-related consequences whatsoever. So it makes you question exactly how you define toxicity.”
Among clinical outcomes, the treatment group did significantly better, achieving a 41% reduction in annualized relapse rate, compared with a reduction rate of 17% in the control group. “This is with the caveat that this was not blinded, so the result has to be taken with a grain of salt,” commented Dr. Burton.
However, the researchers found a significant change when comparing disability status at time of study entry to disability status at the end of the trial. About 8% of the treatment group left the trial with a greater EDSS score than when they started, versus 37.5% in the control group. “The caveat is that these were small changes in EDSS, so again the clinical interpretation is open to debate, but certainly this was a very robust outcome.”
Regarding immunologic changes, the treatment group compared with the control group, and participants with 25(OH)D levels of 100 nmol/L or greater had a significant drop in their T-cell reactivity and proliferation, a finding not observed in patients who had taken lower doses of vitamin D.
Dr. Burton offered some other reasons as to why patients with MS have low levels of 25(OH)D, including that they may intentionally avoid sun exposure, they do not engage in enough physical activity, and they use steroids. The only adverse event was mild constipation in four treatment patients, and with a change or discontinuation in the calcium supplement, all had resolution of this symptom. One patient had a benign breast calcification on mammography, but the lesion was later found to have been present before the trial.
“We believe that vitamin D3 intake up to 40,000 IU/day for a brief period of time and 10,000q IU/day for a year appears to demonstrate biochemical safety, evidence of clinical benefit, with a grain of salt, and evidence of decreased T-cell proliferation,” Dr. Burton concluded.
Vitamin D Deficiency Linked to MS Severity
In a second trial presented at the 2009 CMSC, researchers found that vitamin D deficiency was associated with a higher disability score and a faster rate of disease progression in patients with MS.
Allison Drake, Neurology-Psychology Research Coordinator, University at Buffalo, State University of New York, and colleagues included 349 patients with MS from the New York State Multiple Sclerosis Consortium in their retrospective study. They used the EDSS to measure disability and the MS Severity Scale (MSSS) to measure the rate of disease progression. Patients also completed a questionnaire regarding clinical and demographic data and provided a blood sample.
A majority of patients were female and Caucasian, the average age was about 50, and most had relapsing-remitting MS. Levels of vitamin D greater than 32 ng/mL were regarded as sufficient, levels between 20 and 32 were insufficient, and levels less than 20 were deficient. About 37% of participants had sufficient levels of vitamin D, 41% had insufficient levels, and 22% had deficient levels.
Due to seasonal changes in exposure to ultraviolet radiation that occur in Buffalo, the researchers examined fluctuations in mean vitamin D levels collected during different seasons and by disease severity. As expected, vitamin D levels were highest during seasons when sun exposure was at its peak, between July and September. On average, less than sufficient levels were detected in all patients during all other seasons. “Interestingly, patients with severe disability, as noted by EDSS scores greater than 6, did not reach sufficient levels at any time during any month,” said Ms. Drake.
In an ordinal regression analysis, after controlling for age, gender, age of disease onset, season, and MS subtype, the researchers found that serum vitamin D levels were significantly predictive of EDSS score. “Patients who were vitamin D deficient were more likely to have high EDSS scores and high disability,” said Ms. Drake. “Also significant were non–relapsing-remitting diagnoses and increasing age. Logistic regression revealed that patients who were vitamin D deficient were 3.3 times more likely to be severely disabled with EDSS scores of greater than 6, compared with patients who had sufficient levels.”
Linear regression analysis also demonstrated that vitamin D levels and MS disease subtype significantly predicted MSSS score. “Though it wasn’t the strongest predictor, decreasing vitamin D levels did make a statistically significant contribution,” said Ms. Drake.