[5][6][7] The initial, acute phase of EMS, which last for three to six months, presents as trouble with breathing and muscle problems, including soreness and spasm, but which may also be intense.
Additional features can include cough, fever, fatigue, joint pain, edema, and numbness or tingling, usually in the limbs, hands and feet.
[8] Subsequent[clarification needed] epidemiological studies suggested that EMS was linked to specific batches of L-tryptophan supplied by a single large Japanese manufacturer, Showa Denko.
[9][10][11][12] It eventually became clear that recent batches of Showa Denko's L-tryptophan were contaminated by trace impurities, which were subsequently thought to be responsible for the 1989 EMS outbreak.
[21][22][23][24][9][19][25][26][27][excessive citations] 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".
[9] Even animal studies have suggested that tryptophan itself "when ingested by susceptible individuals either alone or in combination with some other component in the product, results in the pathological features in EMS".
[9][31] At the time of the outbreak, Showa Denko had recently made alterations to its manufacturing procedures that were thought to be linked to the possible origin of the contaminants detected in the affected lots of tryptophan.
[32] The reduction in the amount of activated carbon used and the introduction of the fifth generation Bacillus amyloliquefaciens strain were both associated with the development of EMS, but due to the high overlap of these changes, the precise independent contribution of each change could not be determined (although the bypass of the reverse-osmosis filtration for certain lots was determined to be not significantly associated with the contaminated lots of tryptophan).
[3] While Showa Denko claimed a purity of 99.6%, it was noted that "the quantities of the known EMS associated contaminants, EBT and PAA, were remarkably small, of the order of 0.01%, and could easily escape detection".