According to reports from clinical trials, most people tolerate L-tryptophan supplements without side effects. Occasionally, dizziness, stomach pain, and diarrhea have been reported.¹²

Until 1989, L-tryptophan was a popular nutritional supplement used for a variety of conditions.¹³ In that year, the US Food and Drug Administration removed L-tryptophan from the over-the-counter supplement market, citing the outbreak of an unusual ailment called eosinophilia-myalgia syndrome (EMS) that was associated with its use.¹⁴ Since then, researchers have determined that the most likely cause of this syndrome was a contaminant produced by a single manufacturer during the process of L-tryptophan production that was not effectively removed.^{15, 16} Contamination errors have long since been corrected, and today L-tryptophan is again available as a supplement.

Two case reports suggested that a supplement containing L-tryptophan might have caused a scleroderma-like syndrome that resembled EMS in some ways.^{17, 18} However, the supplement in one case contained a very small amount of L-tryptophan, and it also contained other ingredients.¹⁹ Larger surveys of people with scleroderma have found no link with L-tryptophan supplementation,^{20, 21} so it is likely that these two cases were either a coincidence or it could be a contamination issue. 

The safety of taking L-tryptophan during pregnancy and breast-feeding is unclear. In a double-blind trial, the breathing activity of fetuses was temporarily altered when pregnant women took one gram of L-tryptophan.²² The relevance of that change to fetal health needs further study. In hamsters, supplementation with L-tryptophan during pregnancy decreased the litter size and increased the mortality of the offspring.²³