Looking Deeper into the Safety of Melatonin

by Eli Hendel, M.D. Medical Reviewer

Supplements Have Their Own Regulations

Supplements are regulated differently from food and drugs, which are reviewed by a very strict guidelines process managed by the Food and Drug Aministration. The supplement sector, instead, is regulated according to the Dietary and Supplement Health Act of 1994, (DSHEA). These guidelines are less strict, though they do have certain mandates for supplements and dietary supplement ingredients. Updates to the guidelines in 2010 and 2013 failed. The guidelines allow for a significant number of issues. Melatonin has problems.

Blackboard with the chemical formula for melatonin.

Melatonin is a hormone

Melatonin is a hormone produced in the human brain and it helps to consolidate sleep. It’s secreted when the wakeful hormones are depleted, so levels typically rise in the early evening. Melatonin is suppressed by sunlight, so levels drop as morning comes. The hormone is secreted cyclically, coinciding with the sleep-wake cycle. If this cycle is disrupted — insomnia can occur. Consumers often turn to melatonin supplements as the first “safe” treatment of insomnia. Melatonin can also help to limit jetlag.

Man shopping for supplements.

Melatonin is natural, but natural doesn’t mean safe

Melatonin is available over-the-counter. People view these types of treatments as very safe because they’re “natural” and you don’t need a prescription. Consumers assume they are much safer than prescription sleep aids. Let’s be clear that precisely because it is not regulated like drugs or food, manufacturers can be less accurate in terms of the amount of ingredients, or the purity of ingredients in supplements. They answer to a “lower authority,” even when it comes to dangerous contaminants.

Scientist peering through microscope.

Research finds melatonin highly suspect

A Canadian study examined 31 commercially available melatonin supplements. The supplements were analyzed using ultraperformance liquid chromatography with electrochemical detection, to quantify levels of melatonin and serotonin, a suspected but unreported contaminant. Results showed that manufacturers were not meeting the 10 percent FDA-mandated margin for the primary ingredient, melatonin. In fact, melatonin presence ranged from a low of -83% to a high of +478% of the reported amount on the label.

Blackboard with the chemical formula for serotonin.

Unreported serotonin is a problem

Serotonin “contaminant” was also found in eight of the supplements, meaning 26 percent of the supplements tested had it. Serotonin is actually a controlled substance. It’s a derivative of the naturally occurring amino acid tryptophan and a precursor of melatonin. So it’s not surprising that quantities of serotonin were found in the synthetic manufacturing of melatonin. But there was no mention of serotonin on any of the labels.

Depressed woman looking out a window.


Serotonin is a neurotransmitter that has properties on its own that affect brain function. Despite it being a precursor of melatonin, its presence is still troubling given that it may have undesirable effects in some individuals, especially those with depressive disorders and those taking antidepressants that regulate the amount of available Serotonin in the brain. If someone already taking an antidepressant takes melatonin contaminated with serotonin it could potentially put the person at risk.

Various pills and capsules.

So many melatonin supplements to choose from

A large part of the problem is that commercially available melatonin typically comes in a variety of different potencies and forms to satisfy different consumer preferences. You can find it in flavored liquids, rapid-dissolve tablets and strips, liquid gels, and oral solid tablets. All of these preparations will have a different onset of action as well as other properties. Depending on the manufacturer, it may also have undeclared contaminants including serotonin.

Doctor smiling while talking to patient.

Buying supplements like a detective

The results of this study underline the potential dangers of unregulated over-the- counter supplements, including melatonin. Always check with your doctor before buying melatonin. Look for the USP verified mark which indicates that the product has been tested and the label lists all ingredients and does not contain any contaminants. It verifies other safety information and conforms with FDA practices. You can also sign up with independent testing lab, ConsumerLab to verify a product’s safety profile.

Woman taking pills in bed.

Proper use of melatonin

Data from the National Center for Health Statistics of the National Institutes of Health indicates that the use of melatonin supplements has more than doubled in five years with estimates showing more than three million regular users. Clinical guidelines from the Academy of Sleep Medicine recommend that the use of melatonin be strategically timed to treat some circadian rhythm sleep-wake disorders and should not be routinely used for chronic insomnia.

Woman sleeping peacefully.

The bottom line

According to the National Center for Complementary and Integrative Medicine there have been many studies to look at whether melatonin supplements can help some people, but questions still remain on its usefulness, how much to take, when to take it, and long-term safety. It may help people with jet lag, sleep problems related to shift work, and delayed sleep phase disorder (can’t fall asleep). This supplement should be used for a short term. Adopting proper sleep hygiene may be a safer, long-term option.

Eli Hendel, M.D.
Meet Our Writer
Eli Hendel, M.D.

Eli Hendel, M.D., is a board-certified internist/pulmonary specialist with board certification in Sleep Medicine. An Assistant Clinical Professor of Medicine at Keck-University of Southern California School of Medicine, and Qualified Medical Examiner for the State of California Department of Industrial Relations, his areas include asthma, COPD, sleep disorders, obstructive sleep apnea, and occupational lung diseases. Favorite hobby? Playing jazz music.