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Study shows melatonin supplements may make standing a hazard for the cardiovascular-challenged

Penn State

For insomniacs and jet-lagged travelers, melatonin supplements may enable a good night's sleep.

However, a study by Chester A. Ray, Ph.D., associate professor of medicine, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center suggests that melatonin supplements may make symptoms worse for the half a million people - many of them women and the elderly - with orthostatic intolerance, a condition in which the cardiovascular system cannot maintain adequate blood pressure and blood flow to the brain when a person stands, causing dizziness and fainting.

"Melatonin supplements can hinder nervous system responses that enable the body to compensate for the drop in blood pressure when a person moves from a seated to standing position," Ray said. The study titled, "Melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans," was published in the Sept. 15 issue of the Journal of Physiology (London).

In addition to its use here on Earth, melatonin also is taken by astronauts in space, two-thirds of whom experience orthostatic intolerance immediately after touchdown on Earth.

"When astronauts return to Earth, there is a chance that, for safety reasons, they will need to make a quick exit from the spacecraft," Ray said. "This study suggests that taking melatonin supplements for sleep could exacerbate orthostatic intolerance, making them unable to evacuate the shuttle and compromising their safety."

Melatonin is a hormone made by the pineal gland in the brain and secreted at night on a circadian, or 24 hour, cycle, to make people feel sleepy. Available in synthetic form, dietary supplements of melatonin have been linked to improved sleep, prevention of jet lag, and more. Studies have shown that melatonin supplementation may reduce blood pressure and decrease blood plasma levels of norepinephrine, a neurotransmitter responsible for raising blood pressure.

For this study, 12 healthy volunteers were given either a three-milligram tablet of melatonin - a dose often used and available at nutrition stores - or a non-medicated placebo pill. Fifty minutes later, each volunteer was asked to lay down and place both legs in a lower body negative pressure (LBNP) chamber, a device that reduces pressure to the legs, mimicking the effect of a person standing up. Ray used microneurography to record the sympathetic nerve activity to the blood vessels of the muscles. Sympathetic nerve activity starts a chain reaction that causes the blood vessels to constrict, increasing blood pressure and ensuring adequate blood flow reaches the entire body. After taking measurements at rest, the pressure in the LBNP was decreased and all measures were again taken.

To see if melatonin had an impact during other forms of physical stress, volunteers underwent a handgrip exercise test and a cold pressor test where a hand is placed into ice water for a short period of time. These tests also were done on two separate occasions, once after taking the melatonin supplement and taking a placebo.

Results showed that nerve activity under orthostatic stress (LBNP) was reduced in those volunteers who had taken melatonin compared to those who had taken placebo. Nerve activity was not affected in volunteers who had taken melatonin who underwent the handgrip or cold pressor tests.

"This finding suggests that melatonin has specific physiological effects, namely, decreasing nerve activity, when someone stands, but not necessarily during other types of physical activities," Ray said.

Additional studies will investigate whether melatonin decreases orthostatic tolerance in women, elderly and astronauts.


This research was supported by grants from the National Institutes of Health, National Aeronautics and Space Administration, National Space and Biomedical Research Institute, and American Heart Association. The study was approved by the Institutional Review Board of the Penn State College of Medicine and conducted at the Medical Center's National Institutes of Health-funded General Clinical Research Center.

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