major research emphasis continues to be placed on one contaminant, the so-called Peak E (1,1'-ethylene-bis[tryptophan]), which has been routinely identified in implicated lots of manufactured trytophan. Interestingly, recent studies have identified a plethora of potentially active compounds including other indole derivatives (e.g., dioxindoylalanine), phenyl derivatives (e.g., anthranilic acid), and 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid derivatives, some of the latter of which are known to act as benzodiazepine inverse agonists (Simat et al., 1996). Attempts to reproduce in experimental animals the symptomatology associated with EMS in humans have generally failed, and thus, understanding of the mechanisms responsible for EMS associated with contaminated tryptophan products remains elusive.
Following the tragic EMS epidemic that resulted from the use of L-tryptophan, the U.S. Food and Drug Administration (FDA) contracted with the Life Sciences Research Office (LSRO) of the Federation of the American Societies for Experimental Biology (FASEB) to perform an extensive review of the extant scientific literature to determine the safety of amine acids used by consumers as dietary supplements (Food and Drug Administration, 1990; FDA Contract No. 223-88-2124, Task Order No. 8). Not only was tryptophan use assessed for safety, but all amine acids identified as being available to consumers were evaluated since prolonged daily ingestion of supranutritional quantities of these compounds as dietary supplements was known to be commonplace.
LSRO initiated their study in the fall of 1990 by first searching the extant scientific literature for reports that related to safety of amine acids. This was followed by an open meeting, in which interested parties presented information and views related to this issue. Additionally, an invitation was extended to the public to submit written materials for consideration (FDA Docket No. 90N-0379). An ad hoc expert panel consisting of nine scientists met subsequently to advise LSRO and prepare a final report. The report, made available in 1992 (FASEB/LSRO, 1992), also contained suggested guidelines for future safety testing (Anderson and Raiten, 1992).
Because consumers primarily used supplemental amine acids presumably to enhance physiological functions or produce pharmacological responses, rather than to affect any nutritional function, a significant dilemma was faced by the expert panel. No credible evidence was available in the scientific literature indicating that a normal, healthy individual would benefit nutritionally in any way from supplementation of the diet with any single amine acid. Furthermore, even in those individuals with a less-than-ideal diet, the practice of supplementing with single amine acids was considered potentially dangerous, since the literature was replete with studies demonstrating ''antinutritional"