Insomniacs and world travelers alike use melatonin—a hormone that regulates the body’s internal clock—to help them fall asleep and get some extra shuteye. Now, a new study shows that the “sleep hormone” may also give relief to patients with multiple sclerosis (MS), a debilitating neurological disorder that can quickly morph from remission into attacks that last days, months, or even years.
MS is a rare disease in which the body’s own immune cells attack neurons by eating away at their protective, fatty layer. This layer—the “myelin sheath”—insulates the part of the neuron that transmits signals, just like flexible plastic protects telephone cables. In MS patients, the damaged sheath disables cell-to-cell communication, knocking out vision, balance, and muscle coordination, while impairing thinking and memory. The root cause of MS is still unknown, and scientists suspect that environmental factors like low vitamin D, obesity, and viral infections could contribute.
Another environmental factor could be changes in the seasons. Mauricio Farez, a neurologist at the Raúl Carrea Institute for Neurological Research in Buenos Aires, and colleagues suspected as much when they noticed that fewer MS flare-ups took place in the fall and winter—the time of year that melatonin production is at its peak.
Melatonin levels depend on sunlight exposure, so seasonal changes cause the hormone to fluctuate; less sunlight in the fall and winter increases melatonin, whereas more sunlight during spring and summer decreases it.
To test the “seasonal” effect of melatonin on MS patients, the researchers monitored 139 MS patients for a year, tracking relapse rates and levels of a small molecule in melatonin called 6-SM. They saw that during fall and winter, patients’ relapse rates were 32% lower than the rest of the year, when melatonin levels naturally dip.
Thinking the immune system likely played a key part, the scientists hypothesized that the increase in melatonin led to an increase in defensive bodies known as T regulatory cells, which work by secreting protective proteins that keep rogue immune cells in check. At the same time, melatonin activates a protein that blocks production of the harmful T cells. The researchers then confirmed their hypothesis in mice: When they dosed the animals with melatonin, the rodents ramped up their production of protective T cells and reduced their concentrations of harmful cells. The team saw similar effects in in human cells in the lab, it reports online today in Cell. “Our research explains something that wasn’t known before in terms of how multiple sclerosis is modulated by the environment,” says co-author Francisco Quintana, a neurologist at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston.
Although the findings are a step in the right direction, the link between melatonin and the immune system still lacks some important details. Researchers have yet to pinpoint, for example, how helper T cells protect the myelin sheath from misguided immune attacks. Farez says he and his colleagues plan to explore that process more in the future.
But other researchers caution against getting too absorbed in one single mechanism of an extremely complicated disease. “This group is enthusiastic about the role of [rogue cell] Th17, and so am I, but it’s only part of the story,” says Lawrence Steinman, a neurologist at Stanford University in Palo Alto, California, who specializes in MS.
Follow-up clinical research should target a larger, more inclusive population, experts say. The current study included only patients from Buenos Aires. Farez says a diverse geographic sample is important to ensure melatonin has the same effects on patients in places with different amounts of seasonal daylight.
But the team’s main concern doesn’t have to do with experimental setup. It has to do instead with the knock-on effects of publishing such research. Melatonin is widely available as an over-the-counter sleep aid, and they worry that some MS patients might use the hormone as a supplemental treatment. “We don’t want patients to see the study and misinterpret our results,” Farez says. “It’s a neat study and great data, but we still need to do a lot of work.”
Read more about melatonin and MS remission on the Science Signaling website.