Tryptophan

Tryptophan, abbreviated Trp or W, is an alpha-amino acid distinguished by an aromatic indole side chain. It is one of the standard amino acids used to build proteins and is encoded by the codon UGG; like other amino acids it exists in mirror-image L and D forms, with the L-form being the one incorporated into proteins. For humans and many animals it is an essential amino acid, since the body lacks the pathway to make it and must acquire it from food.

The amino acid is present in a wide range of protein-rich foods, including red meat, poultry, fish, eggs, milk and other dairy, along with seeds, nuts, soy and other legumes. Plants and microorganisms, unlike animals, can build tryptophan from precursors such as shikimate or anthranilate using the enzyme tryptophan synthase, and this route is harnessed for industrial production by bacterial fermentation. A popular belief holds that the tryptophan in turkey causes drowsiness after a meal, but turkey's content is similar to that of other meats, and any sleepiness owes more to the effect of a large, carbohydrate-heavy meal on how amino acids are carried into the brain.

Within the body tryptophan is far more than a building block for protein. It is the starting material for serotonin, formed by the enzyme tryptophan hydroxylase, and serotonin is in turn converted to melatonin, the hormone that helps set circadian rhythm. Most tryptophan, however, is routed through the kynurenine pathway, which yields niacin along with a series of metabolites of interest in psychiatry and immunology. The amount of tryptophan in the blood influences how much reaches the brain and thus the rate of serotonin synthesis, a link established in classic studies of precursor control of brain monoamines ^[1].

Because of its role in serotonin production, L-tryptophan is sold over the counter as a supplement promoted for depression, anxiety and sleep. The evidence is modest; a Cochrane review found that tryptophan and the related 5-hydroxytryptophan appeared better than placebo for depression but that few trials were of adequate quality ^[3], sleep-medicine guidelines have advised against using it for insomnia, and reviews note that individual genetic differences in serotonin handling may shape the response ^[4]. Effects and side effects reported at higher intake include drowsiness, nausea and dizziness, and, when it is combined with serotonergic drugs, a risk of serotonin syndrome ^[2].

The supplement carries a notable regulatory history. In 1989 an outbreak of eosinophilia-myalgia syndrome, a serious illness that caused over a thousand cases and dozens of deaths in the United States, was traced to contaminated batches of L-tryptophan from a single manufacturer rather than to the amino acid itself ^[2]. Regulators recalled and then restricted tryptophan supplements for a time before access was later eased. Today it is again available as a dietary supplement as well as a normal component of dietary protein.

Generally safe, with possible drowsiness, GI upset, or headache. It can raise serotonin and should be used cautiously with SSRIs, MAOIs, and other serotonergic drugs due to serotonin syndrome risk. There is a historical note about an EMS outbreak in the late 1980s linked to a contaminated batch, which was a manufacturing issue rather than the amino acid itself.

L-tryptophan combined with monoamine oxidase inhibitors (MAOIs) such as phenelzine or tranylcypromine carries risk of mood elevation and hypomania. A case report documented two patients who developed hypomania following addition of L-tryptophan to an MAOI; one patient experienced marked mood elevation within days of starting the combination ^[5]. The mechanism involves L-tryptophan increasing serotonin availability while the MAOI prevents serotonin degradation, creating excessive serotonergic stimulation. Patients taking classic MAOIs should limit L-tryptophan intake unless specifically prescribed as a therapeutic combination and under close psychiatric monitoring ^[6].

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