Quick answer

For most healthy adults, L-tryptophan's side effects are mild: drowsiness, nausea, dizziness or tremor, mainly at high doses. Young women took up to 5 g a day for three weeks without adverse effects. The serious risks come from combining it with serotonin medicines and from contaminated batches, as in 1989.^1,2,3

Key facts

Side effects were seen mainly at 70 to 200 mg per kg, far above the dietary need of about 5 mg per kg.¹
NIH's center for complementary health warns that L-tryptophan taken with medicines that affect serotonin may be life-threatening.³
L-tryptophan's use as a supplement stopped in 1989, after contaminated product from one manufacturer caused a rare, serious illness.^3,4
A thorough dose-by-dose safety assessment of tryptophan has not been done.¹

Common side effects

Side effects reported with tryptophan supplements are occasional, mild and short-lived: drowsiness, nausea, dizziness and tremor, mostly at high doses of 70 to 200 mg per kg.¹

Drowsiness is the effect people notice most, and some take tryptophan for exactly that reason. Do not drive or use machinery if it makes you drowsy, and ask before combining it with sleep medicines or sedatives.^1,3

The best direct test of higher amounts gave 17 healthy young women 1, 2, 3, 4 and 5 g a day, three weeks at a time. None of the amounts changed their food intake, weight, routine blood and urine tests or mood scores. It was a small, short study in one group of people, so it cannot rule out rarer problems.²

Serotonin syndrome and medicines

Combined with medicines that raise serotonin, tryptophan can contribute to serotonin syndrome, a rare reaction that can be life-threatening. Warning signs include agitation, confusion, hallucinations, sweating, fever, shivering, a fast heartbeat, muscle twitching or stiffness and loss of coordination.^1,3,5,6

Avoid the combination unless your doctor advises it

The label of phenelzine, an MAOI antidepressant, tells people taking it not to take L-tryptophan: it lists it with compounds that can trigger a dangerous rise in blood pressure with MAOIs, and among the over-the-counter products to avoid. It also says MAOIs combined with tryptophan have been reported to cause disorientation, confusion, agitation, shivering, unsteadiness and other nervous system effects.⁷

On the medicine's label

The sertraline and trazodone labels list tryptophan among serotonergic drugs, together with triptans for migraine, tricyclic antidepressants, tramadol, lithium, buspirone and St. John's wort, that raise the risk of serotonin syndrome when combined with them. If you take any of these, ask before adding tryptophan.^5,8

What happened in 1989

In 1989, contaminated L-tryptophan from a single manufacturer caused an outbreak of eosinophilia-myalgia syndrome in the US, with 1,536 cases and 27 deaths reported by August 1990. The illness brought severe, disabling muscle pain and a very high count of eosinophils, a type of white blood cell, and the use of L-tryptophan as a supplement was stopped.^3,9

Investigators linked the cases to changes in one company's manufacturing, including a new bacterial strain and less purification, rather than to tryptophan itself. Which impurity was responsible has never been settled.^1,4,10

The lesson is about how the supplement is made rather than the amino acid itself. A 2023 review, written mostly by staff of a tryptophan maker, found no clear link to any single impurity. Ask the seller who made the tryptophan and what purity standard it meets.^4,10

Who should not take it, or should ask first

Do not take it if you take an MAOI antidepressant such as phenelzine.⁷
Ask first if you take an SSRI, an SNRI, trazodone or any other medicine that raises serotonin.^5,8
Ask first if you are pregnant or nursing, or under 18: the safety studies here were in adults.²
Ask first if you take a sleep medicine or sedative, because tryptophan can add drowsiness.¹

Questions people ask

Is L-tryptophan safe to take every night?

Long-term nightly use has not been well studied. The best direct test lasted three weeks, and researchers say a thorough dose-by-dose safety assessment has not been done. If you need help sleeping every night, talk to a doctor.^1,2

What are the signs of serotonin syndrome?

MedlinePlus tells people taking sertraline to call a doctor at once for fever, sweating, confusion, a fast heartbeat, shivering, severe muscle stiffness or twitching, agitation, hallucinations, loss of coordination, nausea, vomiting or diarrhea.⁶

Does tryptophan from food carry the same risks?

The warnings on this page are about supplements. In US survey data, food intake averaged about 826 mg a day, and even the highest intakes stayed within normal ranges on most liver and kidney tests.¹¹

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Sources

This page is information, not medical advice. Talk to your doctor or pharmacist about your own situation.