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|Patient UK||Eosinophilia–myalgia syndrome|
Eosinophilia–myalgia syndrome (EMS) is an incurable and sometimes fatal flu-like neurological condition thought to be caused by ingestion of poorly produced L-tryptophan dietary supplements. Similar to regular eosinophilia, there is an increase in the number of eosinophil granulocytes in the blood.
See also tryptophan and EMS.
Eosinophilia–myalgia syndrome was first recognized after the doctors of three American women with mysterious symptoms talked together in 1989. However, at least some cases had occurred as early as 2–3 years before the illness was reported to the Centers for Disease Control and Prevention (CDC) in November 1989. From November 1989 to February 1990, approximately 1500 cases were reported to CDC, and by mid-1990 there had been 27 EMS-associated deaths.
Epidemiological studies traced the cause to consumption of L-tryptophan from a single Japanese manufacturer, Showa Denko. The company supplied the majority of L-tryptophan to the United States under various brand names, and nearly all cases of EMS could be associated with specific batches of Showa Denko tryptophan. At the time, Showa Denko had recently altered its manufacturing procedures. First, the specific bacterial culture used to synthesize this tryptophan had recently been genetically engineered to greatly increase tryptophan production. The increased concentrations of tryptophan in the fermentor may in turn have led to increased production of trace impurities. It is also likely that contaminants were increased because the L-Tryptophan producing bacteria were being grown in an open vat in a fertilizer factory. Second, changes were made in the purification process to reduce costs. For example, a purification step that used charcoal adsorption to remove impurities had been modified to reduce the amount of charcoal used. It is possible that one or more of these modifications and/or the environment for manufacture allowed new or greater impurities through the purification system. More than 60 different impurities were identified in the L-tryptophan lots which had been associated with cases of EMS.
The specific impurity (or impurities) responsible for the toxic effects was never firmly established, however two compounds, EBT (1,1'-ethylidene-bis-L-tryptophan, popularly known as "Peak E") and MTCA (1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid), which are close chemical relatives of L-tryptophan were implicated. Additional impurities were found to be associated with case lots of L-tryptophan and labeled UV-5 (FL-7) and UV-28 (FL-36).
Within weeks of the first reports, the United States Food and Drug Administration banned the sale of dietary supplements containing tryptophan manufactured outside the United States, and the incidence of EMS declined rapidly thereafter. The attribution of the EMS epidemic to some contaminant present in these batches is further supported by the near-absence of tryptophan-associated EMS, and the extreme rarity of EMS of any origin, prior to of availability of these batches of Showa Denko product or after the return of tryptophan supplements to the dietary supplement market in 2005. Tryptophan supplements had been available by prescription and then as a supplement for decades, during which EMS-like syndromes were extremely rare in the U.S. population; once tryptophan was withdrawn from the dietary supplement market in the United States, the incidence rapidly declined, and while tryptophan remained available for under prescription from alternative pharmaceutical sources, no further tryptophan-associated EMS cases emerged until the report of a single case in 2011, in a consumer who was also taking many other dietary supplements.
An alternative explanation for tryptophan associated EMS has recently been proposed. Consumption of large doses of tryptophan leads to production of metabolites, some of which may interfere with normal histamine degradation. Furthermore, excessive histamine activity has been linked with blood eosinophilia and myalgia. However, this hypothesis does not seem to be consistent with the absence or near-absence of tryptophan-associated EMS in the years prior to or following the availability of the implicated batches of Showa Denko tryptophan on the US Market.<Allen2011/>
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- National Eosinophilia Myalgia Syndrome Network
- Eosinophilia-Myalgia Syndrome: Information & Support(link expired)