Eosinophilia-Myalgia Syndrome (L-Tryptophan) Recalls Lawsuit

Eosinophilia-Myalgia Syndrome (L-Tryptophan) Recalls

The product

L-tryptophan is an essential amino acid that was widely sold in the late 1980s as a dietary supplement, promoted for sleep, mood, and other health purposes. In the United States it was marketed by a range of supplement brands, and most of the raw material they purchased came from a small number of bulk manufacturers.

The illness

Eosinophilia-myalgia syndrome (EMS) is a rare and sometimes fatal condition characterized by an abnormally high level of eosinophils, a type of white blood cell, together with severe muscle pain. The acute phase lasts roughly three to six months and presents with breathing difficulties, muscle soreness and spasms, cough, fever, fatigue, joint pain, swelling, and numbness or tingling in the limbs. A chronic phase can follow, marked by eosinophilic fasciitis, neurological signs, and in some cases cardiac or digestive dysfunction. Risk of developing EMS rose with higher doses of tryptophan and with increasing age, and the condition proved fatal in up to five percent of affected patients.

The outbreak

The first cases of EMS were reported to the U.S. Centers for Disease Control and Prevention in November 1989, although some cases had occurred as early as two or three years before that. In all, more than 1,500 cases of EMS were reported to the CDC, along with at least 37 EMS-associated deaths. Preliminary investigations linked the outbreak to intake of L-tryptophan supplements.

Tracing the cause

Epidemiological studies pointed to specific batches of L-tryptophan supplied by a single large Japanese manufacturer, Showa Denko. Around the time of the outbreak the company had altered its manufacturing process, including a reduction in the amount of activated charcoal used to purify each batch and the use of a later-generation genetically engineered bacterial strain to synthesize the amino acid. Analysts eventually identified 63 trace contaminants in the affected batches, six of which could be associated with EMS. One compound, EBT, was the first to be identified, but subsequent mass-spectrometry work characterized additional impurities. No single contaminant was definitively proven to be the cause: only two of the 63 compounds showed a statistically significant association with EMS cases, and the FDA concluded that other brands of L-tryptophan, or the amino acid itself, could not be ruled out as causal or contributing.

Regulatory response and outcome

Following the preliminary findings, the U.S. Food and Drug Administration recalled L-tryptophan supplements in 1989 and banned most public sales in 1990, with other countries following suit. The restriction marked the end of the product's availability as a general supplement in the United States; the FDA loosened its restrictions in 2001 and fully lifted them in 2005. In the interim, 5-hydroxytryptophan, a normal metabolite of the amino acid, became a popular substitute supplement.

The episode is recorded as a products recall and market withdrawal, resolved in 1990, rather than as a litigated case. It remained a notable example of a dietary-supplement safety failure traced to a manufacturing impurity at a single supplier.