The possibility that vitamin D could help protect people from developing multiple sclerosis (MS) has been posited by researchers in recent decades, but evidence to support that link has been scant. In the first large-scale, prospective study to investigate the relationship between vitamin D levels and MS, researchers at the Harvard School of Public Health (HSPH) have found an association between higher levels of vitamin D in the body and a lower risk of MS. The study appears in the December 20, 2006, issue of the Journal of the American Medical Association.

“If confirmed, this finding suggests that many cases of MS could be prevented by increasing vitamin D levels. Although these levels could be increased by taking supplements, before any recommendation is made it is important to establish whether we are seeing a true causal association or whether vitamin D levels are only a marker of MS risk,” said Alberto Ascherio, senior author of the study and associate professor of nutrition and epidemiology at HSPH.

MS is a chronic degenerative disease of the central nervous system. It affects some 350,000 people in the U.S. and 2 million worldwide, and occurs most commonly in young adults. Women, who are affected more than men, have a lifetime risk of about 1 in 200 in the U.S. Vitamin D is a hormone manufactured naturally in the body, and its levels can be increased with exposure to sunlight, consumption of foods rich in vitamin D, such as fatty fish, and by taking supplements.

The researchers, led by Ascherio, worked in collaboration with colleagues in the U.S. Army and Navy to determine whether vitamin D levels measured in healthy young adults predict their future risk of developing MS. The investigation relied on a study population of more than 7 million individuals, whose serum samples are stored in the Department of Defense Serum Repository. Between 1992 and 2004, 257 U.S. Army and Navy personnel with at least two serum samples stored in the repository were diagnosed with MS. A control group, consisting of participants who did not develop MS, was randomly selected from the study population. Serum samples were analyzed for levels of 25-hydroxyvitamin D, a good indicator of vitamin D availability to tissues, and individuals were divided into five groups of equal size according to their average levels. Because vitamin D levels are strongly influenced by skin color, separate analyses were conducted among whites, blacks, and Hispanics.

The results showed that, among whites, MS risk declined with increasing vitamin D levels–the risk was 62% lower among individuals in the top fifth of vitamin D concentration (corresponding approximately to levels above 100 nmol/L or 40 ng/mL) than among those in the bottom fifth (approximately below 63 nmol/L or 25 ng/mL). The association was strongest among individuals who were younger than 20 when they first entered the study. No significant association was found among blacks and Hispanics, possibly because of a smaller sample size and the lower levels of vitamin D found in those groups. The average age of onset of MS cases was 28.5 years old; there was no significant difference in the results between men and women.

“The results of this study converge with a growing body of experimental evidence supporting the importance of vitamin D in regulating the immune system and suppressing autoimmune reactions, which are thought by most experts to play a key role in the development of MS,” said Ascherio. Kassandra Munger, first author and a doctoral candidate in nutrition at HSPH, added, “The amount of vitamin D that is needed to reach levels associated with MS protection is largely considered safe, and in fact higher vitamin D levels could be beneficial to prevent osteoporosis and other chronic diseases.”

The researchers note that there could be other possible explanations for the protective role of vitamin D. For example, it’s possible that exposure to UV light from the sun–the major determinant of serum levels of 25-hydroxyvitamin D–could protect people in other ways than increased vitamin D production.

The authors suggest further studies exploring how vitamin D may protect individuals from developing MS. “Although the results of this study are quite encouraging, reasonable certainty of a protective effect of vitamin D supplements requires direct experimental evidence in a large trial. Meanwhile, we are planning to expand our study to obtain more accurate data on the importance of age and of the vitamin D levels that need to be achieved for optimal protection,” said Ascherio.

Living in sunny locations and spending time outdoors may raise the risk for skin cancer, but a new study led by UC San Francisco and the Australian National University shows that in children and young adults, sun exposure may protect against multiple sclerosis. The study follows previous work by other researchers that has demonstrated an association between increased ultraviolet exposure in childhood and lower odds of adult MS.

The study included 332 participants aged between 3 to 22, who had had MS for an average of seven months. Their locations and amount of sun exposure were matched by age and sex to 534 participants without MS, the researchers reported in their study, which publishes in the online issue of Neurology, the journal of the American Academy of Neurology, on Dec. 8, 2021.

In questionnaires filled in by participants with MS or their parents, 19 percent stated that they spent less than 30 minutes daily outdoors during the previous summer, compared to 6 percent of those who did not have MS.  When the researchers adjusted for MS risks, like smoking and female sex, they found that the participants who spent an average of 30 minutes to one hour outdoors daily had a 52 percent lower chance of MS, compared to those who spent an average of less than 30 minutes outdoors daily.

“Sun exposure is known to boost vitamin D levels,” said co-senior author Emmanuelle Waubant, MD, PhD, professor in the UCSF Department of Neurology and of the Weill Institute for Neurosciences. “It also stimulates immune cells in the skin that have a protective role in diseases such as MS. Vitamin D may also change the biological function of the immune cells and, as such, play a role in protecting against autoimmune diseases.”

Progression Slower in Pediatric MS, Despite Inflammatory Onset

While MS usually strikes adults between the ages of 20 to 50, some 3 to 5 percent of the approximately one million patients in the United States with the condition begin experiencing symptoms in childhood. Pediatric-onset MS is initially highly inflammatory, but takes longer than adults to advance, with symptoms of secondary progression, such as moderate to severe weakness, poor coordination and bowel and bladder control, occurring on average 28 years after disease onset, according to experts. However, these disability landmarks are reached approximately 10 years earlier than in adult MS. 

The researchers also found an association with the intensity of sunlight and estimated that residents of Florida would be 21 percent less likely than residents of New York to have MS. They noted that sun exposure was “dose-dependent,” the longer the exposure the lower the risk. And even exposure in the first year of life seemed to protect against MS, they said.

Fortunately, the use of sunscreen does not appear to lessen the therapeutic effects of sunlight in warding off MS, noted Waubant, who is also director of the UCSF Regional Pediatric Multiple Sclerosis Center. Clinical trials are needed to determine if “increasing sun exposure or vitamin D supplementation can prevent the development of MS or alter disease course post-diagnosis,” she said. Meanwhile, “advising regular time in the sun of at least 30 minutes daily especially during summer, using sun protection as needed, especially for first degree relatives of MS patients, may be a worthwhile intervention to reduce the incidence of MS.”

Limited sun exposure and/or low levels of vitamin D have been associated with other conditions. These include Parkinson’s disease, Alzheimer’s and other types of dementia, as well as schizophrenia and other auto-immune diseases like Type 1 diabetes, Crohn’s disease and lupus.