Medical News

Something Weird Is Going On With Melatonin

In the dark, early days of the coronavirus pandemic, Michael Toce noticed a surprising trend. As a pediatric-emergency-medicine doctor at Boston Children’s Hospital, he was seeing lots of kids who had taken too much medication. The problem wasn’t that they’d overdosed on opioids or painkillers or marijuana. Instead, they’d swallowed too much melatonin, an over-the-counter supplement used as a sleep aid. The ill effects of this mistake seemed mild at the worst—drowsiness, nausea, vomiting—but the number of kids who were affected was going up, up, up.

Other doctors around the country were observing something similar. In 2022, a group in Michigan invited Toce to collaborate on a study of the phenomenon. Their findings, published last June, were striking. Over the prior 10 years, the number of annual calls to poison control for pediatric melatonin overdoses had risen by 530 percent. By 2020, poison control was receiving more calls about pediatric overdoses on melatonin than on any other substance. Just last month, in a broader study based on emergency-room data over a similar period, researchers at the CDC reported a 420 percent increase in visits for pediatric melatonin ingestions. Meanwhile, the overdose numbers for other substances plummeted during the 2010s: Tylenol, down 53 percent; opioids, down 54 percent; many cough and cold medications, down 72 percent. The question is: What sets melatonin apart?

The most obvious answer is its recent surge in popularity. From 2009 to 2018, American melatonin use increased fivefold, and from 2016 to 2020, U.S. sales of the supplement rose from $285 million to $821 million. A pandemic-era surge in diagnosed sleep disorders may have only accelerated this growing popularity. The year before melatonin usage began to rise, the CDC launched an initiative to reduce pediatric overdoses as a whole. It promoted the widespread adoption of flow restrictors and child-resistant packaging, and ran campaigns to educate parents about medication safety and storage. It’s possible that melatonin overdoses are rarer now than they would have been without the CDC’s safety initiative, but are still increasing on account of the supplement’s overall success in the marketplace.

Those changes in demand are “definitely a factor” in the associated surge in overdoses, says Pieter Cohen, a doctor and supplements expert at Cambridge Health Alliance, in Somerville, Massachusetts. Whether they account for all of the surge or most of it or merely some of it remains a mystery. Several other factors would also seem to be involved, Cohen told me. For starters, many melatonin supplements come in an appetizing gummy form. So do all sorts of vitamins and minerals for kids—vitamin A, vitamin C, calcium, zinc—but melatonin is not a vitamin or a mineral. It’s an active hormone, and the body has not developed great mechanisms for coping with its intake in excess, Cohen said.

[Read: Why do we need to sleep?]

Nearly all of the patients Toce saw had eaten gummies, and most of those identified in the CDC’s emergency-room study were 3 to 5 years old. Maribeth Lovegrove, the researcher who led the CDC research, told me that for most medications, pediatric overdoses are concentrated among children under 2 years old. This discrepancy is telling, she said. Babies don’t know what they’re eating and often put random stuff in their mouth; slightly older kids, such as the ones who have been taking too much melatonin, may be more likely to mistake gummies for candy.

Supplements are regulated by the FDA more as foods than as medications. That means that, the CDC’s safety initiative notwithstanding, melatonin’s packaging doesn’t have to be child resistant. The fact that it is marketed as a “natural” supplement may also lead parents to assume that it’s safe, Lovegrove said. And the actual quantity of melatonin contained in each gummy—as well as how that relates to the dosage advertised on the packaging—isn’t strictly regulated either, Cohen told me. Last month, he published a study with researchers from the University of Mississippi showing that many melatonin-gummy brands contain wildly different amounts of the hormone than they claim to. One contained three and a half times more than advertised; another contained no melatonin at all. A Canadian study from 2017 that looked at melatonin supplements more generally, not just at gummies, reached a similar conclusion. In at least one case, these discrepancies have led to a lawsuit.

Although the overwhelming majority of overdoses that the Michigan group identified were as mild as the ones Toce had seen, a small percentage were not. Nearly 300 children required intensive care, five had to be put on ventilators, and two died. Toce found this, too, to be surprising. “When you take too much of anything, you’re always going to have some degree of an upset stomach, some nausea, vomiting,” he told me. But there is no known mechanism by which melatonin could cause more severe complications, and Toce said it’s hard to know whether the supplement really played a role at all. Perhaps some other ingredient in the gummies caused the bad reactions, or maybe it was something else entirely—an unfortunate coincidence of timing.

[Read: The mysterious link between COVID-19 and sleep]

Michael Beuhler, a doctor who co-authored a paper investigating seven children’s deaths in North Carolina potentially related to melatonin, thinks they were most likely caused by melatonin overdoses, paired perhaps with some unusual susceptibility among the victims. “You don’t want to say melatonin definitely, 100 percent caused these deaths,” Beuhler told me, but “this is the type of thing that should be making people hit the pause button, especially when using it in small children.” For the moment, Cohen said, the exact source of deadly outcomes remains “a big mystery.”

A mystery made even harder to solve by the murkiness of the supplement industry. The industry has many well-known problems: a lack of scientific evidence for the benefits of certain products, a habit of misleading marketing, a deep reliance on magical thinking. But the recent spate of pediatric melatonin overdoses represents another big one: the products’ maddening irregularity. If no one knows what’s in the supplements, doctors may never understand whether or how they cause serious harm.