More Evidence That Vitamin D May Protect Against MS

Pauline Anderson

November 19, 2012

A new study may help end the debate about what level of vitamin D best protects against multiple sclerosis (MS).

The study found that serum levels of 75 nmol of 25-hydroxyvitamin D (25[OH]D), the major circulating form of vitamin D, per liter were associated with a 61% decreased risk for MS. Some experts believe a level of 50 nmol/L is sufficient, but others have suggested higher levels are required.

"This study certainly suggests that 75 nmol/L should be the cutoff," lead study author Jonatan Salzer, MD, Department of Pharmacology and Clinical Neurosciences, Section of Neurology, Umeå University, Sweden, told Medscape Medical News. "However, we don't know if artificially raising levels to above 75 actually protects against MS as this is an observational study."

The study, published in the November 20 issue of Neurology, also showed that vitamin D levels during early pregnancy did not affect MS risk of offspring.

Biobank Samples

Several recent studies have suggested that poor vitamin D status, along with other environmental factors, and several genetic factors, are associated with an increased risk for MS.

In the current study, researchers accessed a biobank of 124,000 serum samples collected since 1975 from pregnant women, and another biobank with 167,500 blood samples collected since 1985 in population-based health programs. The analysis included cases that fulfilled MS diagnostic criteria, excluding those suggestive of MS before sample collection. It also included controls matched for sex, biobank, sampling date, and age.

Dr. Jonatan Salzer

Researchers estimated risk of MS using 25(OH)D levels above and below median, stratified into tertiles, quartiles, and quintiles and into groups with levels of 75 or greater vs less than 75 nmol/L and 50 or greater vs less than 50 nmol/L.

The analysis uncovered 192 patients with MS, of whom 182 had MS according to medical records. The median time from sampling to MS onset was 9 years, and the majority of patients were female.

Compared with 25(OH)D levels under 75 nmol/L, those 75 or greater nmol/L were associated with a lower risk for MS (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.16 - 0.98). In a post hoc analysis of 182 patients born in Nordic countries, the findings were similar (OR, 0.33).

This analysis found no association between vitamin D levels below 75 nmol/L and the risk for MS, and no other significant associations comparing different vitamin D groupings.

"We only found the decreased risk in levels above 75 nmol/L," said Dr. Salzer. "We didn't find any risk decrease with having levels above 50 nmol/L versus below that level." He added that 50 nmol/L is often a recommended target level.

In patients younger than a median age of 26.4 years, the decrease in MS risk associated with vitamin D levels of 75 nmol/L or greater was more pronounced (OR, 0.16; 95% CI, 0.02 - 1.3) but the difference was not significant. Only 1% of young patients and 6% of young controls had vitamin D levels in this range.

However, Dr. Salzer pointed to another study, by Munger et al published in 2006, showing that the association between vitamin D levels and MS risk was stronger for those under age 20 years (both males and females).

This fits with the prevailing view of how the risk for MS is influenced during the life span, noted Dr. Salzer. "We think that the disease actually starts during young adulthood," he said. Confirmed MS cases "usually already have findings on MRI suggestive of a disease that has been there for a few years but hasn't shown itself in terms of symptoms."

Another group of the study used the database of samples from the women who had donated blood in early pregnancy and medical records of offspring who later developed MS. In that analysis, 32 patients fulfilled diagnostic criteria for MS. There was no association between vitamin D levels during early pregnancy and MS risk in the offspring.

"This suggests that if vitamin D is important during pregnancy regarding risk of MS in offspring, it starts acting at least after the first trimester — somewhere between late pregnancy and young adulthood."

Decreasing Prevalence

The researchers were able to determine that the prevalence of vitamin D levels of 75 nmol/L or greater in pregnant women decreased gradually from 1976 to 2005. This suggests that the recommendations for supplementation during pregnancy may need to be reviewed, said Dr. Salzer. Daily doses of at least 2000 IU of vitamin D are probably needed to reach serum concentrations of 75 nmol/L or greater, he said.

According to Dr. Salzer, although this and other observational studies suggest that 75 nmol/L is an appropriate cutoff for vitamin D levels, the Institute of Medicine has determined that the lack of randomized controlled trials prevents recommendations to change current targets. "There is a great need of a randomized controlled primary preventive trial, but that's a daunting task," he said.

Although vitamin D toxicity is possible, it shouldn't be a concern, at least in the short term. "The levels need to be really high — above 200 or 250 perhaps," said Dr. Salzer. "It's safe in the short term to raise levels to 100 or 120, but in the long term, we don't know because these studies haven't been done."

Approached for her views on this research, Anne-Louise Ponsonby, PhD, professor of environmental and genetic epidemiology research, Murdoch Children's Research Institute, Victoria, Australia, said this study adds to the growing evidence that higher levels of vitamin D may be beneficial for reducing the risk for MS.

She noted that patients with a vitamin D level less than 75 nmol/L had a risk of developing MS that was 2.6 times higher than that of patients with a vitamin D status above this level. "Interestingly, this level is above what is the threshold for vitamin D deficiency (often listed as 25 nmol/L) or sufficiency (often listed as 50 nmol/L)," she told Medscape Medical News.

The study "clearly shows a reduction in vitamin D status of pregnant women," over time, Dr. Ponsonby added. "In 1976-1980, 14% of women had a vitamin D level of 75nmol/L or above; by 1991-2005, that had declined significantly to only 1.6%."

The study design meant that the authors couldn't examine season of birth effects, so further work is required in this area, especially because emerging reports indicate that seasonal effects are important, said Dr. Ponsonby.

The study was supported by Biogen Idec, Merck Serono, the Swedish Association of Persons with Neurological Disabilities, Umeå University, and the Västerbotten County Council. Dr. Salzer has received financial support for this study from Biogen Idec, Merck Serono, and The Swedish Association of Neurologically Disabled, received honoraria from Merck Serono for a lecture, and received support to travel to scientific meetings from Biogen Idec and Merck Serono.

Neurology. 2012;79:2140-2145. Abstract