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Melatonin Linked to Seasonal Relapses of Multiple Sclerosis

A hormone involved in circadian rhythms could provide treatment for the autoimmune disease

Multiple sclerosis (MS) relapses are known to swing with the seasons. Scientists have attributed these fluctuations to the rise and fall of vitamin D production, which is triggered by exposure to seasonal sunlight. Now a new study suggests that melatonin, a hormone that regulates your internal body clock and sleep cycles, could also play a protective role.

MS is a disease of the central nervous system in which an abnormal immune response attacks the myelin sheath, or fatty protective layer, around neurons. The resulting degradation slows signaling between the brain and the rest of the body, potentially leading to a wide variety of symptoms that include weakness, vision problems and cognitive changes. The condition may affect as many as 2.3 million people worldwide. The cause of the disease remains unknown, although researchers have started to identify genetic risks and environmental factors, including smoking, viral infections and vitamin D levels in the bloodstream.

The latest environmental influence, observed by Mauricio Farez, a neuroscientist at the Raúl Carrea Institute for Neurological Research, and colleagues could involve peak melatonin levels in the body, which occur during the darker months. The researchers assessed a group of 139 multiple sclerosis patients in Buenos Aires and found a 32 percent reduction in the number of relapses in the fall and winter, when people living in the Southern Hemisphere produce more of the hormone, compared with summer and spring. The results are published on the September 10 Cell.

Past research has shown that melatonin can have a protective effect against MS and that shift work, which disturbs melatonin production, can increase the risk of developing the disease. According to the authors, this research is one of the first to bring together epidemiological evidence with results from both human cells and animal models.

To confirm melatonin’s protective effect in the lab, the team gave daily injections of the hormone to mice with autoimmune encephalomyelitis, a widely used animal model of MS. It worked—the animals showed reduced clinical symptoms and a restored balance of T cells, white blood cells that play a central role in a high-functioning immune system. Melatonin reduced the number of harmful T cells, which promote inflammation, whereas it increased regulatory T cells, defensive bodies that keep the immune system in check. The researchers observed comparable effects in a study of melatonin’s influence on human immune cells in a dish. Melatonin regulates pathways central to the immune response, so these results may pertain to other autoimmune diseases, particularly where seasonal flare-ups occur, such as lupus and rheumatoid arthritis, says study co-author Francisco Quintana, an immunologist at Brigham and Women’s Hospital.

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According to the authors, the current study may help to resolve a “seasonal paradox”—MS flare-ups should decrease during warmer, brighter months when people receive more exposure to sunlight and thus produce more vitamin D, which also has anti-inflammatory properties. But some studies, including this one, show that relapses increase in the spring and summer pointing to the possibility that other environmental factors, such as melatonin levels, are involved.

Not everyone has agreed with this hypothesis. Alberto Ascherio, a Harvard University School of Public Health MS epidemiologist who studies MS and was not part of the research, asserts that vitamin D levels are actually still low in the spring, when MS relapses are found to peak. He points to the fact that the authors of the current study observed this dip in their own results. “MS relapses increase during winter and reach a peak in early spring,” Ascherio says, “and then start declining during summer and reaches a nadir in the fall, when they start rising again. There is no paradox as suggested by Farez and colleagues.”

Beyond this conflict, future studies could investigate how vitamin D and melatonin exert their effects and whether they interact. “Our data shows that melatonin might be one factor explaining the seasonal occurrence of relapses, in addition to infection and vitamin D,” Farez says, “and we need to further understand how they work together to fully understand the effect that we’re seeing.” Some researchers, including Jan Lünemann, a neuroscientist studying neuroinflammation at the University of Zürich, who was not involved in the study, caution overinterpretation of the results. “The findings clearly need to be confirmed in additional, independent cohorts of patients and experimental studies,” he says. “And whether the function of melatonin on T cells as observed in mice can be transferred to humans needs to be investigated.”

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Bottom line: No one should take melatonin to mitigate their MS symptoms, and doctors should not prescribe it until researchers determine the mechanism and other details of its effects in patients, Farez says. His group is in the early stages of developing such a clinical trial to understand the effect of melatonin treatment. Until those results come in it is premature to conclude that melatonin will be effective in people with the disease.

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