Tryptophan

Tryptophan is an essential amino acid. That means the body cannot make it and has to take it in with food. Both the 2005 US Dietary Reference Intakes report and the 2007 WHO, FAO and UNU report list it among the indispensable amino acids.

The Institute of Medicine (now part of the US National Academies) says the body uses it for more than proteins. From it, the body makes niacin (vitamin B3), the nerve messenger serotonin and the hormone melatonin. The body needs very little of it. WHO puts the adult requirement at 4 mg per kilogram of body weight a day, the lowest of any essential amino acid.

Here is the part most readers do not know. Of the tryptophan the body breaks down, about 95% goes down the kynurenine pathway, which also makes niacin. Only a small share becomes serotonin, and much of the body’s serotonin sits in the gut, not the brain.

Supplements also carry a history. In 1989, contaminated L-tryptophan from one manufacturer caused an outbreak of eosinophilia-myalgia syndrome in the US. It is a severe illness with muscle pain and high levels of certain white blood cells.

Nearly everyone who eats enough protein gets enough tryptophan. US survey data summarized by the Institute of Medicine put the mean intake at 0.9 g a day. That is well above the 0.35 g that the US recommended allowance works out to for a 70 kg adult (our arithmetic).

We found no trial behind the famous link between turkey and sleepiness. The section on how tryptophan works explains why it is not as simple as it sounds.

Health benefits of tryptophan

• ★★Less time awake after falling asleepIn four pooled articles, tryptophan supplements shortened time awake after first falling asleep, though the range was wide; no other sleep measure changed. By dose, time awake was 28.91 minutes at 1 g a day or more, against 56.55 below 1 g.
• ★★Better mood in some healthy adultsSupplements improved mood in 4 of 11 trials in healthy adults, at doses the review puts at 0.14 to 3 g a day. Tryptophan did not reduce aggression.
• ★★Tryptophan depletion lowered mood only in at-risk peopleIn 45 pooled studies that removed tryptophan from the body, mood fell slightly with a family history of depression and moderately in remitted depression. Healthy people with no such history saw no fall, and no supplements were tested.
• ★Too little evidence to judge for depressionA Cochrane review found only 2 trials (64 people) of tryptophan or 5-HTP against placebo that met its criteria in adults with depression. It called the evidence too weak to recommend either, and noted that proven antidepressants exist.
• ★Fewer premenstrual mood symptoms in one trialIn 71 people with a severe form of premenstrual mood symptoms, 6 g of L-tryptophan a day cut symptoms by 34.5%, against 10.4% on placebo. It was taken for 17 days of each cycle, over three cycles.

Foods high in tryptophan

The USDA ranking below changes with how you count. Per serving, soybeans lead: 1 cup (172 g) holds 0.42 g of tryptophan. Next come chicken breast (0.32 g in 4 oz) and a chicken drumstick with skin (0.26 g). Sardines (0.25 g in a can) and a mackerel fillet (0.23 g) follow.

Per 100 g, seeds lead. Pumpkin seeds top the list with 0.58 g, then chia seeds (0.44 g), sesame seeds (0.39 g) and hemp seeds (0.37 g). Sunflower seeds follow, and chicken breast has 0.28 g.

Per 100 kcal, lean fish, chicken and some vegetables rank high. Cod, tuna and chicken breast give 0.24 g each, then shrimp (0.22 g), and spinach and basil (0.17 g each).

Here is what a serving means, by our arithmetic. We use 280 mg a day for a 70 kg adult from WHO and 350 mg from the US allowance. One cup of soybeans gives 420 mg, which is 150% of the WHO value and 120% of the US allowance. A 4 oz chicken breast gives 320 mg (114% and 91%), and a can of sardines 250 mg (89% and 71%).

Plant proteins can be short of tryptophan too. WHO says it is low in cereals, especially maize. In some maize varieties it may be the limiting amino acid, which runs out first. Other cereals are limited by lysine, and legumes by the sulfur amino acids.

In a 90-day trial reported by WHO, stunted children ate a maize variety with 78% more tryptophan than normal maize. It supported their growth about as well as a milk formula. Mixed diets that include beans, seeds or animal foods cover the gaps.

How tryptophan works

Most of the biochemistry below is well established. But the details come from reviews, animal studies and small tests in people rather than from trials of supplements.

Four ideas cover it. Tryptophan is a building block of protein, and most of it is broken down by the kynurenine pathway. A small share becomes serotonin and melatonin, and it competes with other amino acids to enter the brain. The last idea explains why the foods eaten with protein matter.

It is a building block of protein, and the body needs little

Tryptophan is less common in proteins than most amino acids. WHO sets the adult requirement at 4 mg per kilogram a day, based on an average of several approaches that all gave similar values.

Absorption needs a carrier. The SLC6A19 transporter (B⁰AT1) in the intestine and kidney moves tryptophan and other neutral amino acids into cells. People with Hartnup disease carry a faulty version and lose these amino acids in the urine, according to MedlinePlus Genetics.

Most of it is broken down by the kynurenine pathway

After a meal, only a small share of the tryptophan that is broken down becomes serotonin. In one review, the kynurenine pathway accounts for about 95% of dietary tryptophan breakdown. About 90% of that happens in the liver, where the enzyme TDO takes the first step.

The pathway makes nicotinic acid and NAD, so tryptophan can stand in for dietary niacin. In human studies, 1 mg of nicotinamide was produced from 67 mg of tryptophan, although 60 mg is the figure often used. A 2022 review adds that TDO becomes more stable when tryptophan is plentiful. That speeds up the breakdown of dietary tryptophan and keeps the blood level steady.

A small share becomes serotonin and melatonin

The gut holds much of the body’s serotonin. In mice, spore-forming bacteria from the gut microbiota (the gut’s microbes) promote serotonin production by cells in the colon. Melatonin, the hormone of the night, is another product of tryptophan, according to the Institute of Medicine.

A review of tryptophan supplements notes that one pill does several things at once. Taking tryptophan raises brain tryptophan, serotonin production in the gut, serotonin in blood, melatonin and the output of the kynurenine pathway. That is one reason the effects seen in trials are hard to pin on serotonin in the brain alone.

It competes with other amino acids to reach the brain

Tryptophan crosses the blood-brain barrier on a carrier it shares with other large neutral amino acids. Raising blood tryptophan raises its uptake into the brain, while raising branched-chain amino acids lowers it. Brain serotonin synthesis follows these changes, according to a review by Fernstrom. So what predicts brain uptake is the ratio of tryptophan to its competitors in the blood, not tryptophan alone.

What you eat with it changes how much gets in

The protein in a meal matters a lot. In rats, a single meal changed cortex tryptophan 8-fold depending on the protein, with α-lactalbumin raising it and zein lowering it. In six men, 40 g of α-lactalbumin raised the blood tryptophan ratio by 50%, while gluten and zein lowered it.

Ordinary meals work too. Protein-rich meals lower the ratio and carbohydrate-rich ones raise it, whether eaten at breakfast or lunch. In nine adults, the two kinds of breakfast differed by a median of 54%.

This is why the turkey story is shaky. We found no trial that tested turkey, and a protein-rich meal does not simply raise the tryptophan that reaches the brain. What happens depends on the protein and on what is eaten with it. No trial has linked the post-dinner drowsiness to tryptophan.

What has been seen in people

The firmest facts in people are about need and deficiency. Adults need about 4 mg per kilogram a day, and pellagra appears when both niacin and tryptophan run short.

The supplement trials are less firm. A pooled analysis of four studies found less time awake at night at 1 g a day or more. In healthy adults, 4 of 11 trials found a better mood. In depression, only 2 trials in 64 people were good enough for a Cochrane review.

Lowering tryptophan lowers mood only in people who are already vulnerable. The cards above give each result.

How much tryptophan do you need?

Adults need about 4 mg of tryptophan per kilogram of body weight a day, according to the 2007 WHO, FAO and UNU report. That is about 280 mg for a 70 kg adult. The US recommended dietary allowance (RDA, enough for nearly all healthy people) is 5 mg per kilogram, about 350 mg. Neither the FDA nor the EU has set a Daily Value for tryptophan.

Source	Requirement (mg per kg a day)	For a 70 kg adult	Notes
WHO, FAO and UNU, 2007: adults	4	280 mg	Average requirement, set from several approaches including nitrogen balance and amino acid oxidation studies. The 1985 report had 3.5. Also stated as 6 mg per gram of protein. 1
Institute of Medicine, 2005: adults, EAR	4	280 mg	Estimated Average Requirement, the intake that meets the need of half of healthy people. 2
Institute of Medicine, 2005: adults, RDA	5	350 mg	Recommended Dietary Allowance, the EAR raised by 24% to cover nearly all healthy people. 2

Children need more per kilogram because they are growing. WHO gives 9.5 mg per kilogram a day at 6 months, 6.4 at 1 to 2 years and 4.8 at 3 to 14 years. It gives 4.5 at 15 to 18 years and 4.0 from age 18.

The Institute of Medicine sets RDAs of 13 mg per kilogram for ages 7 to 12 months. For ages 1 to 3 years it is 8 mg.

In pregnancy, its EAR is 5 and its RDA 7 mg per kilogram. The EAR (estimated average requirement) is the amount that meets the needs of a typical person. While breastfeeding, the EAR is 7 and the RDA 9. These are scaled from the adult values because there are essentially no direct data.

We found no separate tryptophan value for pregnancy or breastfeeding in the WHO report, which adds protein instead. It adds a safe protein intake of 0.7, 9.6 and 31.2 g a day in the three trimesters. In the first six months of breastfeeding, it adds about 19 g a day.

Intake is usually well above these figures. US survey data from 1988 to 1994 put the mean intake from food and supplements at 0.9 g a day. The 99th percentile, in men aged 51 to 70, was 2.1 g.

Tryptophan deficiency: signs and who is at risk

Pellagra is the classic result of too little tryptophan together with too little niacin. It is a syndrome caused by a deficiency of niacin, its precursor tryptophan, or both. Its cardinal signs are dermatitis, diarrhea and dementia, with death in the worst cases.

Diets built on maize are the historical risk. WHO notes that tryptophan is low in cereals, especially maize, and the history of pellagra in Europe and the US is tied to corn-based diets. Isoniazid, a tuberculosis drug, has also been linked to pellagra. Niacin deficiency has been recognized for decades in people with carcinoid syndrome (a type of hormone-making tumor), although overt pellagra is uncommon there.

Hartnup disease is the inherited form of the problem. It affects about 1 in 30,000 people, and a faulty SLC6A19 gene reduces the absorption of tryptophan and other amino acids. For most people the only sign is extra amino acids in the urine.

Some have episodes of rash, poor coordination and psychiatric symptoms, usually triggered by illness, stress, a poor diet or fever. Researchers think these relate to a lack of tryptophan and niacin. Outside these groups, we found no description of a separate tryptophan deficiency syndrome in people who eat enough protein.

Forms of tryptophan: absorption and effects

Tryptophan is sold as free L-tryptophan, and it comes bound in protein and in enriched foods. It is also sold as 5-HTP, a related compound the body makes on the way to serotonin.

Taking more of any of them raises blood tryptophan. But how much reaches the brain depends on the competing amino acids that arrive with it. So the form and what is eaten with it both matter.

The honest bottom line: we found no trial that compared forms head to head for sleep or mood, apart from one trial of seed protein. The comparisons that exist mostly measure blood levels. The trials in the benefits section used free L-tryptophan, except the enriched cereal, the α-lactalbumin diet and the fluoxetine combination. We found no trial showing that 5-HTP works better or worse than tryptophan.

Form	What it is	What studies show	Source
L-tryptophan (free amino acid)	The free L-form as powder, capsule or tablet	The form used in most supplement trials, at 1 to 6 g a day, for example 6 g in premenstrual dysphoria and 2 to 4 g with fluoxetine. A review says ingesting it raises brain tryptophan and serotonin production. Drowsiness appeared at 4 g a day in one trial. It is the form behind the 1989 outbreak, which came from a contaminant in one manufacturer’s batches.	1, 12, 13, 14
Tryptophan in food protein	Peptide-bound in protein; the tryptophan content differs by protein	In 6 men, 40 g of α-lactalbumin raised blood tryptophan 3-fold, while gluten lowered it by 25% and zein by 50%. An evening α-lactalbumin diet raised the tryptophan ratio by 130% and lowered morning sleepiness in 28 people. Protein also brings competing amino acids, so more tryptophan in a protein does not always mean more in the brain.	2, 4, 11
Tryptophan-enriched foods	Cereal or bars with added tryptophan	Cereal with 60 mg of tryptophan per 30 g portion, eaten at breakfast and dinner, improved sleep measures in 35 older adults in a single-blind trial. We found no trial that compared enriched foods with capsules.	5
Tryptophan-rich seed protein with glucose	Deoiled gourd seed protein taken with glucose	In 49 people who finished a 3-week trial, gourd seed protein with glucose and pharmaceutical-grade tryptophan with glucose both improved measures of insomnia more than glucose alone.	11
5-HTP (5-hydroxytryptophan)	The compound tryptophan becomes on the way to serotonin; not a form of tryptophan itself	A Cochrane review pooled it with tryptophan (2 trials, 64 people). One 12-week trial of 100 mg a day in 30 older adults raised cognitive scores, without a placebo group. Commercial samples contained 4,5-tryptophan-dione, a putative neurotoxin, at 0.5 to 10.3% of the amount in a case-implicated sample. A review by authors at a company laboratory found no definitive cases of toxicity.	6, 7, 8, 9
D- and DL-tryptophan	The mirror-image form, and a mix of both forms	In weanling rats, D-tryptophan worked almost as well as L-tryptophan as a niacin precursor. We found no human trial of D- or DL-tryptophan.	10

Here are the head-to-head and form-specific studies, 3 in all.

Is tryptophan safe? Supplements, dose and interactions

The Institute of Medicine set no tolerable upper intake level (UL) for tryptophan in 2005. A UL is the highest daily intake likely to pose no risk. It gave two reasons: there were no data on the effects of long-term use, and the role of L-tryptophan in eosinophilic fasciitis remained uncertain. We found no upper level from EFSA.

For food, the same report puts the mean US intake from food and supplements at 0.9 g a day. It puts the 99th percentile at 2.1 g and describes no harm at those amounts. The risks below come from supplements.

• Doses and side effects. Many adults take up to 4 to 5 g a day, according to a review. Occasional side effects, mostly at 70 to 200 mg per kilogram, include tremor, nausea and dizziness. In the Institute of Medicine’s summary, 5 g in one sitting caused severe nausea, headache and drowsiness in 10 adults. In 15 people, 2 to 3 g before a meal reduced hunger and increased faintness and dizziness. In the fluoxetine trial, 4 g a day caused daytime drowsiness. The reviewer calls the safety database small and largely anecdotal.
• Antidepressants and serotonin syndrome. In rare cases, tryptophan combined with serotonin-acting drugs such as antidepressants causes serotonin syndrome. Its signs include delirium, muscle jerks, high body temperature and coma. In one trial, 2 g a day with 20 mg of fluoxetine caused no cases in 30 patients. That does not make the combination safe for everyone. Ask a doctor before combining tryptophan with any antidepressant.
• The 1989 outbreak. By July 1990, 1,531 cases of eosinophilia-myalgia syndrome and 27 deaths had been reported in the US, and 36 deaths by August 1991. Investigators in Minnesota and Oregon traced it to tryptophan from one manufacturer. Among patients whose source was known, that was 29 of 30 and 45 of 46. Over-the-counter tryptophan was recalled in November 1989. One review concludes that the cause was a contaminant in certain production batches, not tryptophan. Another says an impurity probably formed when the manufacturing conditions changed, and later chemistry named compounds made from tryptophan and fatty acids. A 2023 review, four of whose authors work for a company, said no clear conclusions on the impurities had been drawn. A pharmacopeial review, from a body that sets drug quality standards, argues for quality specifications in amino acid safety assessments.
• 5-HTP. The same kind of concern was raised for 5-HTP. Commercial samples contained a putative (suspected) neurotoxin, 4,5-tryptophan-dione, at 0.5 to 10.3% of the amount in a sample linked to cases. A review by authors at a company laboratory found no definitive toxicity in 20 years of use.
• Pregnancy and long-term use. We found no trials of tryptophan supplements in pregnancy or breastfeeding, and most trials ran only days to weeks. Ask a doctor before taking tryptophan if you are pregnant, breastfeeding or take regular medicines.

How to get more tryptophan

• Eat enough protein from varied foods. Soybeans (0.42 g per cup), chicken breast (0.32 g in 4 oz), sardines (0.25 g in a can) and beans lead the per-serving ranking above. The mean US intake is 0.9 g a day, against a 0.35 g allowance for a 70 kg adult (our arithmetic).
• If your staple is maize, add beans, seeds or animal foods. WHO says tryptophan can limit the protein in some maize varieties. Seeds top the per-100-gram ranking: pumpkin seeds (0.58 g per 100 g), chia (0.44 g) and sesame (0.39 g).
• Food over pills. The trial doses of 1 to 6 g a day are above the average food intake. They come with side effects and a safety history. A serving of soybeans or chicken covers most or all of a day’s need. If you want to try a supplement for sleep or mood, talk to a doctor first, especially if you take an antidepressant.

History of tryptophan

Frederick Hopkins first reported the isolation of tryptophan in 1901, from casein digested with the enzyme trypsin. The name comes from that digestive enzyme.

Five years later, Edith Willcock and Hopkins published a study on adding tryptophan to a diet in which zein was the only source of nitrogen. Its title stressed the importance of individual amino acids in metabolism. It was an early test of the idea that single amino acids matter in a diet.

The link to niacin came from pellagra. The disease was unknown in Europe before maize arrived from the New World, and there it was linked to poverty and corn-based diets. In the US it became epidemic among poor Southerners in the early 20th century.

From 1914 to 1929, Joseph Goldberger’s studies supported a dietary deficiency explanation. In 1937 Conrad Elvehjem isolated the pellagra-preventive factor and identified it as nicotinic acid. In the 1940s and 1950s, pellagra was recast as a deficiency of both niacin and its amino acid precursor, tryptophan.

Serotonin was found in the gut by Vittorio Erspamer in 1937 and in blood by Maurice Rapport in 1948 and 1949. It was identified as 5-hydroxytryptamine in 1949.

The best-known modern chapter was darker. In 1989 an outbreak of eosinophilia-myalgia syndrome struck the US, and over-the-counter tryptophan was recalled that November. Investigators linked it to tryptophan from one manufacturer. Reviews attribute it to a contaminant in certain batches rather than to tryptophan itself.

Frequently asked questions about tryptophan

Does tryptophan in turkey make you sleepy?

Probably not because of the tryptophan. We found no trial that tested turkey. In human tests, what is eaten with protein matters: protein-rich lunches lowered the tryptophan ratio in blood and carbohydrate-rich ones raised it. Two kinds of breakfast differed by a median of 54%. Protein drinks differed widely too, with α-lactalbumin raising the ratio by 50% and gluten and zein lowering it.

Does tryptophan help you sleep?

A little, at doses of 1 g a day or more, and the evidence is limited. A 2022 meta-analysis of four studies found less time awake after falling asleep. In 15 people with mild insomnia, 1 g shortened the time to fall asleep. A trial of 1 g for 7 nights in 96 people with serious insomnia found no clear gain during treatment. In that trial, tryptophan did not shorten the time to fall asleep until the following week.

How much tryptophan do you need a day?

About 4 mg per kilogram of body weight, or 280 mg for a 70 kg adult, according to WHO. The US recommended allowance is 5 mg per kilogram, about 350 mg. Pregnancy raises the US allowance to 7 mg per kilogram and breastfeeding to 9. Average intake from food is already 0.9 g a day.

Which foods are highest in tryptophan?

Per serving, soybeans lead our USDA ranking, with 0.42 g in 1 cup. Chicken breast (0.32 g in 4 oz), chicken drumstick (0.26 g), sardines (0.25 g) and mackerel (0.23 g) follow. Per 100 g, seeds lead: pumpkin seeds 0.58 g, then chia 0.44 g, sesame 0.39 g and hemp 0.37 g. Turkey is not in our ranking.

Is tryptophan the same as 5-HTP?

No. 5-HTP is the compound the body makes from tryptophan on the way to serotonin. A Cochrane review pooled the two for depression and found only 2 usable trials in 64 people. We found no trial comparing them head to head. Some commercial 5-HTP samples contained 4,5-tryptophan-dione, a suspected neurotoxin, at 0.5 to 10.3% of the amount in a sample linked to cases.

Can you take tryptophan with antidepressants?

Only with a doctor’s advice. Tryptophan combined with serotonin-acting drugs can rarely cause serotonin syndrome, with delirium, muscle jerks, high body temperature and coma. One trial gave 2 g a day with 20 mg of fluoxetine to 30 patients and saw no cases. But it was small, and 4 g a day caused daytime drowsiness.

Is L-tryptophan safe after the 1989 outbreak?

The outbreak was traced to a contaminant in batches from one manufacturer, not to tryptophan itself. Over-the-counter tryptophan was recalled in November 1989, and the outbreak caused 1,531 reported cases and 27 deaths by July 1990. The Institute of Medicine set no upper level, and the main side effects at supplement doses are nausea, drowsiness and dizziness. Ask a doctor before using it, and avoid it if you take antidepressants unless a doctor agrees.

Do vegans get enough tryptophan?

Probably yes with a varied diet, but we found no studies of tryptophan intake in vegans. Soybeans lead our per-serving ranking, with 0.42 g per cup, about 150% of the WHO value for a 70 kg adult. Cranberry beans are also in the top ten, and seeds lead per 100 g. WHO warns that maize can be short of tryptophan, so a diet built on maize needs beans, seeds or other proteins.