While critics of this theory have argued that this hypothesis fails to explain the near-absent reports of EMS prior to and following the EMS outbreak, this fails to take into account the sudden rapid increase in tryptophans usage immediately prior to the 1989 outbreak, and ignores the strong influence of the EMS outbreaks legacy and the extended FDA ban on later usage of tryptophan. Crucially, this also ignores the existence of a number of cases of EMS that developed both prior to and after the primary epidemic, including at least one case where the tryptophan was tested and found to lack the contaminants found in the contaminated lots of Showa Denkos tryptophan, as well as cases with other supplements inducing EMS, and even a case of EMS induced by excessive dietary L-tryptophan intake via overconsumption of cashew nuts. A major Canadian analysis located a number of patients that met the CDC criteria for EMS but had never been exposed to tryptophan, which "brings causal interpretations of earlier studies into question". Other studies have highlighted numerous major flaws in many of the epidemiological studies on the association of tryptophan with EMS, which cast serious doubt on the validity of their results. As the FDA concluded, "other brands of L-tryptophan, or L-tryptophan itself, regardless of the levels or presence of impurities, could not be eliminated as causal or contributing to the development of EMS".
While a total of 63 trace contaminants were eventually identified, only six of them could be associated with EMS. The compound EBT (1,1-ethylidene-bis-L-tryptophan, also known as "Peak E") was the only contaminant identifiable by initial analysis, but further analysis revealed PAA (3-(phenylamino)-L-alanine, also known as "UV-5"), and peak 200 (2[3-indolyl-methyl]-L-tryptophan). Two of the remaining uncharacterized peaks associated with EMS were later determined to be 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]-indole-2-carboxylic acid (peak C) and 2-(2-hydroxy indoline)-tryptophan (peak FF). These were characterized using accurate mass LC–MS, LC–MS/MS and multistage mass spectrometry (MSn). The last of the six contaminants (peak AAA/"UV-28", being "the contaminant most significantly associated with EMS"  has been characterized as two related chain-isomers; peak AAA1 ((S)-2-amino-3-(2-((S,E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid, a condensation product between L-tryptophan and 7-methylnonanoic acid) and peak AAA2 ((S)-2-amino-3-(2-((E)-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid, a condensate between L-tryptophan and decanoic acid). No consistent relationship has ever been firmly established between any specific trace impurity or impurities identified in these batches and the effects of EMS. While EBT in particular has been frequently implicated as the culprit, there is no statistically significant association between EBT levels and EMS. Of the 63 trace contaminants, only the two AAA compounds displayed a statistically significant association with cases of EMS (with a p-value of 0.0014).As most research has focused on attempts to associate individual contaminants with EMS, there is a comparative lack of detailed research on other possible causal or contributing factors. Tryptophan itself has been implicated as a potentially major contributory factor in EMS.