Quick answer

NIH says L-tryptophan supplements may cause life-threatening serotonin toxicity when used with medicines that affect serotonin. Five medicine labels name tryptophan: the sertraline, escitalopram, fluoxetine and trazodone labels list it among products that raise the risk, and the phenelzine label says not to take it. Ask your pharmacist or doctor before combining.^1,2,3,4,5,6

Key facts

NIH's complementary health center says L-tryptophan supplements may cause life-threatening serotonin toxicity when used with medicines that affect serotonin.¹
MedlinePlus says serotonin syndrome most often occurs when two or more medicines that affect serotonin are taken together, and is more likely when a medicine is first started or its dose is raised.⁷
A 2012 review says the syndrome has occurred in rare cases when tryptophan was combined with drugs that raise serotonin.⁸
In a trial of 17 healthy young women who took 1 to 5 g a day in steps of 21 days, no adverse effects appeared on the measures checked, and researchers say a thorough dose-by-dose assessment has not been done.^8,9
The labels name tryptophan without setting an amount, so no source gives a dose at which the risk starts.^2,3

What NIH says about tryptophan and serotonin

NIH's National Center for Complementary and Integrative Health says in its sleep fact sheet that there are serious safety concerns about L-tryptophan supplements, which may cause life-threatening serotonin toxicity when used with medicines that affect serotonin metabolism. The same fact sheet recalls that use of L-tryptophan as a supplement stopped in 1989 after contaminated product from one manufacturer caused a different illness. That illness is not serotonin syndrome and is outside this page.¹

What serotonin syndrome is and how it starts

MedlinePlus describes serotonin syndrome as a potentially life-threatening reaction in which the body has too much serotonin, a chemical made by some nerve cells. It most often occurs when two or more medicines or drugs that affect the body's serotonin level are taken together. It is more likely when a medicine is first started or its dose is raised, and the symptoms appear within minutes to hours.⁷

Symptoms may include agitation or restlessness, abnormal eye movements, diarrhea, a fast heartbeat and high blood pressure, hallucinations, a raised body temperature, loss of coordination, nausea and vomiting, and overactive reflexes. MedlinePlus says people usually stay in the hospital for at least 24 hours for observation, and that untreated, the syndrome can be deadly.⁷

MedlinePlus says to contact your provider right away if you have symptoms. For people who take SSRIs, SNRIs or triptans, it adds that they should not stop their medicine on their own and should talk to their health care provider about their concerns first.⁷

What the medicine labels say about tryptophan

Five medicine labels read for this site name tryptophan. Each entry below says which label it comes from and how the label words the concern.^2,3,4,5,6

Ask your pharmacist or doctor first

The sertraline label lists tryptophan among the serotonergic drugs that raise the risk of serotonin syndrome when taken with sertraline, and tells prescribers to monitor for it. MedlinePlus names tryptophan among the nonprescription products that may interact with sertraline, and NIH warns that L-tryptophan taken with medicines that affect serotonin may cause life-threatening serotonin toxicity.^1,2,10

On the medicine's label

Avoid the combination unless your doctor advises it

The escitalopram label says using it with tryptophan is not recommended, because the combination raises the risk of serotonin syndrome. MedlinePlus also lists tryptophan among the nonprescription products that may interact with escitalopram.^1,3,11

On the medicine's label

Ask your pharmacist or doctor first

The fluoxetine and trazodone labels carry the same warning: tryptophan is among the serotonergic drugs that raise the risk of serotonin syndrome with them, and MedlinePlus lists tryptophan as a product that may interact with trazodone. Not every antidepressant's label names tryptophan, so ask about yours.^4,5,12

On the medicine's label

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.⁶

On the medicine's label

Does tryptophan alone cause it?

A 2012 review of the non-nutritional use of tryptophan says that in rare cases the serotonin syndrome occurs, as the result of too much serotonin stimulation when tryptophan is combined with drugs that act on serotonin. It lists delirium, myoclonus, hyperthermia and coma among the symptoms. The same review says occasional side effects, seen mainly at higher doses of 70 to 200 mg per kg, include tremor, nausea and dizziness, and may occur when tryptophan is taken alone or with such a drug.⁸

None of the sources we read reports serotonin syndrome from tryptophan alone. The review also says its database is small and largely anecdotal, so the sources cannot rule it out.⁸

We found no official upper limit for tryptophan supplements, and researchers say a thorough dose-by-dose safety assessment has not been done. In one trial, 17 healthy young women took up to 5 g a day for 21 days with no adverse effects on the measures checked.^8,9

Tryptophan in food

The warnings on this page concern tryptophan as a supplement or product. The sources do not discuss tryptophan in food, so this page makes no statement about it. For context, MedlinePlus says tryptophan is an essential amino acid that must come from food, and US adults typically take in about 826 mg a day from food.^13,14

Who should ask a doctor or pharmacist first

Anyone who takes an MAOI antidepressant such as phenelzine. The label tells people taking it not to take L-tryptophan.⁶
Anyone who takes an SSRI, an SNRI, trazodone or another antidepressant. The labels name tryptophan among the products that raise the risk of serotonin syndrome.^2,3,4,5
Anyone who takes a triptan for migraine, tramadol, lithium, buspirone or St. John's wort. The sertraline label lists these with tryptophan as products that raise the risk.²
Anyone who has agitation, confusion, fever, sweating, shivering, a fast heartbeat or muscle twitching after combining these products. MedlinePlus says to contact a provider right away.⁷

This page reports what the sources say. It does not tell any person whether to combine tryptophan with a medicine.

Questions people ask

Can L-tryptophan cause serotonin syndrome on its own?

A 2012 review describes the syndrome as occurring in rare cases when tryptophan is combined with serotonin drugs, and reports milder effects such as tremor, nausea and dizziness at high doses taken alone. It says a full dose-by-dose assessment is still missing.⁸

Can I take L-tryptophan with an SSRI?

Only your doctor or pharmacist can answer that for you. The sertraline, escitalopram and fluoxetine labels name tryptophan among products that raise the risk of serotonin syndrome, and the escitalopram label says using it with tryptophan is not recommended.^2,3,4

How much L-tryptophan causes serotonin syndrome?

No source we read gives an amount. The labels name tryptophan without setting one, and the 2012 review says a thorough dose-related assessment has not been done. Ask your pharmacist about the product and the amount.^2,8

What are the symptoms of serotonin syndrome?

MedlinePlus lists agitation or restlessness, abnormal eye movements, diarrhea, fast heartbeat, high blood pressure, hallucinations, raised body temperature, loss of coordination, nausea and vomiting, and overactive reflexes. It says to contact your provider right away.⁷

Does tryptophan in turkey or other food cause serotonin syndrome?

The sources on this page address tryptophan as a supplement or product and do not discuss food. That is not a finding either way, so ask your doctor or pharmacist if you take medicines that affect serotonin.¹

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Sources

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