The Supplement Scandal That Shaped 5-HTP: What Really Happened in 1989
In 1989, people across America were taking a popular supplement from their local health food store to help them sleep and lift their mood. Within months, more than 1,500 of them were seriously ill and at least 37 had died. The supplement was L-tryptophan, not 5-HTP, but it is 5-HTP's closest relative. The story of what went wrong is stranger than most conspiracy theories, it is still not fully settled, and it is the most useful thing you can know before you buy 5-HTP.
A Mystery Illness Appears
In the autumn of 1989, doctors in the United States began seeing a new illness. Patients had extremely high levels of a type of white blood cell called eosinophils, along with severe, often disabling muscle pain. Many also had joint pain, swelling, breathlessness, fever and rashes. Doctors named it eosinophilia-myalgia syndrome, or EMS.
Investigators quickly found a common thread: almost everyone affected had been taking L-tryptophan supplements. L-tryptophan is an amino acid found naturally in food, and it was widely sold for sleep, low mood and premenstrual symptoms.
The US Food and Drug Administration asked for tryptophan supplements to be recalled in November 1989 and restricted their sale the following year. Cases were also reported in the UK, Germany, Canada and elsewhere, and in 1990 tryptophan products were withdrawn from sale in the UK on expert advice. Many people who survived were left with long-term muscle, nerve and skin problems.
The Factory Behind It
When investigators traced the tryptophan back to its source, most of the illness led to batches from a single large Japanese manufacturer, Showa Denko. The company had changed the way it made tryptophan, using bacteria grown in large fermentation vats and a new strain designed to increase output. Because the end product was considered chemically the same as before, no extra safety testing was required.
Laboratory analysis found trace impurities in the suspect batches. Scientists eventually identified dozens of contaminants, and a small number of them were linked to the illness. One became known as "peak E". The company faced a wave of lawsuits from people who had been harmed.
Here is the part the tidy version of the story leaves out. Not everyone who took the contaminated batches became ill, and some EMS cases occurred before and after the 1989 outbreak. Some researchers have argued that very high doses of tryptophan itself may play a role, not just the impurities. More than 35 years later, the exact cause is still debated. What is not in doubt is that a change in manufacturing was followed by a public health disaster.
The tryptophan behind the 1989 outbreak was considered chemically identical to earlier versions, so it needed no new safety testing. The problem was traced largely to how one company made it. Same molecule on the label, very different product in the bottle.
Where 5-HTP Comes In
5-HTP, or 5-hydroxytryptophan, is the step between tryptophan and serotonin. Your body makes it from tryptophan, then turns it into serotonin, a chemical messenger involved in mood, which it later uses to make melatonin. After tryptophan was pulled from shelves, 5-HTP grew in popularity as an alternative. Most supplement-grade 5-HTP is extracted from the seeds of a West African plant, Griffonia simplicifolia.
To be clear, 5-HTP was not the cause of the 1989 outbreak. Its link to this story came later. In 1998, researchers at the Mayo Clinic reported finding a contaminant called "peak X" in commercial 5-HTP products. Days later, the FDA confirmed that impurities, including peak X, were present in some 5-HTP supplements. The FDA said the significance was unknown, but that past experience meant vigilance was warranted. Peak X had earlier been detected in a batch of 5-HTP linked to a reported case of EMS.
A 2003 study went further, identifying one component of peak X as a possible nerve toxin and detecting it in all six over-the-counter samples tested, at widely varying levels. To keep this in proportion, only a handful of EMS cases linked to 5-HTP have been reported in the medical literature. But the lesson from 1989 is that small manufacturing details can have large consequences.
What This Means If You Take 5-HTP
The key question is not whether a molecule is natural or synthetic. It is how well it was made, and whether anyone checked. Before you buy 5-HTP, it is reasonable to ask where it is sourced, whether it is made under Good Manufacturing Practice, and whether the maker tests each batch for impurities and will show you a certificate of analysis.
Interactions matter just as much. Because 5-HTP raises serotonin, combining it with antidepressants such as SSRIs or MAOIs, or with other medicines that affect serotonin, can cause a dangerous condition called serotonin syndrome. Warning signs include agitation, a racing heart, heavy sweating, muscle twitching and a high temperature, and they need urgent medical attention. Always check with your doctor or pharmacist before combining 5-HTP with any medication, and speak to a professional first if you are pregnant or breastfeeding.
Finally, be realistic about the evidence. A Cochrane review of tryptophan and 5-HTP for low mood found only a small number of trials of adequate quality. There were some signs of benefit, but not enough good-quality evidence to be confident. Anyone who tells you 5-HTP is proven to work is getting ahead of the science.
The lesson of 1989 is not that supplements are dangerous, and it is not that regulators overreacted. It is that the same ingredient can be safe or harmful depending on how it is made and who is checking. That puts the power in your hands. Ask questions, ask for proof of testing, and tell your doctor or pharmacist what you take.
- Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT). COT statement on tryptophan and the eosinophilia-myalgia syndrome (amended 2004). UK Food Standards Agency. https://cot.food.gov.uk/sites/default/files/cot/tryptophanamend200401.pdf
- Belongia, E.A., Hedberg, C.W., Gleich, G.J. et al., 1990. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. New England Journal of Medicine, 323, 357–365.
- US Food and Drug Administration, 1998. Impurities confirmed in dietary supplement 5-hydroxy-L-tryptophan. FDA Talk Paper T98-48, 31 August 1998.
- Klarskov, K., Johnson, K.L., Benson, L.M., Cragun, J.D., Gleich, G.J., Wrona, M., Jiang, X.R., Dryhurst, G. and Naylor, S., 2003. Structural characterization of a case-implicated contaminant, "Peak X," in commercial preparations of 5-hydroxytryptophan. Journal of Rheumatology, 30(1), 89–95.
- Shaw, K., Turner, J. and Del Mar, C., 2002. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database of Systematic Reviews, Issue 1, CD003198.
- Williamson, B.L., Klarskov, K., Tomlinson, A.J., Gleich, G.J. and Naylor, S., 1998. Problems with over-the-counter 5-hydroxy-L-tryptophan. Nature Medicine, 4(9), 983.
- Mayeno, A.N., Lin, F., Foote, C.S. et al., 1990. Characterization of "peak E," a novel amino acid associated with eosinophilia-myalgia syndrome. Science, 250, 1707–1708.
- Birdsall, T.C., 1998. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Alternative Medicine Review, 3(4), 271–280.
This article is intended for informational and educational purposes only and is not medical advice. The 1989 eosinophilia-myalgia syndrome outbreak was linked to L-tryptophan supplements, not 5-HTP. If you take antidepressants or any other medication, or are pregnant or breastfeeding, please speak to your doctor or pharmacist before taking 5-HTP.