Who Found Melatonin, and How a Pineal Gland Hormone Became a Supplement
Melatonin started as an unexplained pineal gland and became a US dietary supplement. This history covers Aaron Lerner's 1958 isolation, the 1994 supplement law, early jet lag and low-dose trials, and why label doses vary.
The history of melatonin runs from an unexplained gland to a bottle on a shelf in roughly a century, and the dose on that bottle is still the least settled part of the story. In 1958, Aaron B. Lerner at Yale University isolated the hormone the pineal gland produces and named it melatonin, according to the [National Library of Medicine](https://profiles.nlm.nih.gov/spotlight/hh/feature/pineal). For the compound itself, see our [melatonin ingredient page](/ingredients/melatonin). What follows traces the hormone from the lab to the supplement aisle, then looks at what the early trials measured and why labels disagree. ## A gland nobody could explain, and a tadpole clue The pineal gland is a small structure deep in the brain, often called the "third eye" because of where it sits. Until the late 1950s, scientists did not understand what it did or how it worked. A clue came in 1917. Carey Pratt McCord and Floyd Pierpont Allen found that when pineal gland was crushed and added to water, tadpoles in that water lightened markedly, an effect that defied explanation at the time. ## The gland became a clock, and light became its switch Lerner's 1958 work was followed by a 1960 paper from Lerner and two colleagues in the Journal of Biological Chemistry, which reported isolating melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands ([PubMed](https://pubmed.ncbi.nlm.nih.gov/14415935/)). The next step came from Axelrod and Richard J. Wurtman. In 1962 they found that melatonin acts as a neurotransmitter and lets the pineal work as a kind of biological clock. By 1965 they had proposed what they called the "melatonin hypothesis": the hormone is released in response to changes in environmental light, and those changes affect reproductive functions in mammals too. NCCIH describes the same switch today. The brain makes melatonin in response to darkness, and exposure to light at night can block that production ([NCCIH](https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know)). ## How a hormone reached the supplement aisle The supplement story runs through US law. In 1994 the Federal Food, Drug, and Cosmetic Act was amended by the Dietary Supplement Health and Education Act, which defined "dietary supplement" and set the FDA's authority over those products. Under that law the FDA does not approve supplements for safety and effectiveness, or approve their labels, before they are sold ([FDA](https://www.fda.gov/consumers/consumer-updates/fda-101-dietary-supplements)). That is the framework melatonin sells under in the US. NCCIH says melatonin is considered a dietary supplement here, which means it is regulated less strictly than a prescription or over-the-counter drug. In several other countries it is available only by prescription and counts as a drug. Most supplement melatonin is made synthetically. NCCIH cites a 2022 study that found US sales rose about 150 percent between 2016 and 2020. For a side-by-side look at another option, see [5-HTP versus melatonin](/compare/5-htp-vs-melatonin). NCCIH also reports the other side of that growth. Reports to US poison control centers about people 19 and younger who took melatonin rose from 8,337 in 2012 to 52,563 in 2021. ## What the early trials measured, and what they did not According to PubMed, a 2002 Cochrane review by Herxheimer and Petrie covered ten trials that compared melatonin with placebo in airline passengers, airline staff and military personnel ([DOI](https://doi.org/10.1002/14651858.CD001520)). Nine of the ten found that melatonin, taken close to bedtime at the destination, reduced jet lag after flights crossing five or more time zones. The review's dose findings matter for the label debate. Daily doses between 0.5 and 5 mg were similarly effective, though people fell asleep faster and slept better after 5 mg than after 0.5 mg. Doses above 5 mg appeared no more effective. The authors also called 2 mg of slow-release melatonin relatively ineffective, which they read as a sign that a short, higher peak works better. They added that routine pharmaceutical quality control of melatonin products "must be established." Lower doses came later. In 1996, Zhdanova and colleagues gave 12 healthy young volunteers, free of sleep disturbances, either 0.3 mg or 1.0 mg of melatonin, or a placebo, at 9 pm, two to four hours before their usual bedtime ([DOI](https://doi.org/10.1093/sleep/19.5.423)). Time to fall asleep dropped after melatonin, neither dose significantly changed sleep architecture, and the authors reported no hangover effects on next-morning mood or performance tests. The study was small, and it tested healthy volunteers, not people looking for help with sleep. Other uses had thinner evidence. NCCIH summarizes two 2014 reviews of shift workers as generally small or inconclusive. One looked at seven studies with 263 participants and suggested people taking melatonin may sleep about 24 minutes longer during the day, though the evidence was low quality. For chronic insomnia, the American College of Physicians (2016) and the American Academy of Sleep Medicine (2017) found too little strong evidence to recommend melatonin, according to NCCIH. Our [sleep and stress guide](/health/sleep-stress-complete-guide) covers the wider picture. ## Why the number on the label keeps drifting According to PubMed, a 2017 analysis by Erland and Saxena tested 31 supplements. The authors reported that melatonin content ranged from -83% to +478% of the labelled content, and that lot-to-lot variation within one product reached 465%. In more than 71% of the supplements, melatonin did not meet the label within a 10% margin, and serotonin was identified in eight of them ([DOI](https://doi.org/10.5664/jcsm.6462)). The pattern showed up again in 2023. NCCIH summarizes a JAMA study of melatonin gummies sold in the US. It reports that 22 of 25 products were inaccurately labeled, one had no detectable melatonin, and in the remaining products melatonin ranged from 74 to 347 percent of the labeled amount ([DOI](https://doi.org/10.1001/jama.2023.2296)). Mt. Angel Vitamins sells [Sleep Dots Melatonin 1 mg](https://mtangelvitamins.com/products/sleep-dots-melatonin-1mg?utm_source=learn_hub&utm_medium=content&utm_campaign=blog_post&utm_content=history-of-melatonin-from-pineal-gland-to-sleep-supplement): 60 dissolvable dots, each labeled at 1 mg of melatonin, for $15.99 (live price checked October 22, 2026). At one dot a day, the lowest amount on the label, that works out to about 27 cents a day. More than a century after those tadpoles lightened in water with crushed pineal gland, the open question on a melatonin bottle is still the same one: how much is inside? ## Next reads - [Melatonin](/ingredients/melatonin): the ingredient reference this history draws on. - [5-HTP versus melatonin](/compare/5-htp-vs-melatonin): a side-by-side look at the two. ### Related reading - [tryptophan from casein to the 1989 recall](/blog/history/history-of-tryptophan-from-casein-to-the-1989-recall) - [vitamin B6 from pyridoxine to P5P](/blog/history/history-of-vitamin-b6-from-pyridoxine-to-p5p)