Vitamins & Supplements · Amino acid
Tryptophan
L-tryptophan (Trp) · also called L-tryptophan, Trp, triptófano
Tryptophan is an essential amino acid: the body cannot make it, so it comes from protein foods. The body uses it to make serotonin. Trials of supplements show mixed, low-certainty results for sleep and mood, and the evidence for depression is too thin to rely on. Cautions include serotonin syndrome with antidepressants and a 1989 contamination outbreak.
General information, not medical advice. Last substantive update · Not medically reviewed. A named clinician has not signed off on this page. How this page is made
About Tryptophan
Tryptophan is an essential amino acid found in all protein foods. The body uses it to make serotonin. Supplement trials are small and mixed, and product quality and medicine interactions are the main cautions.
What tryptophan is
Tryptophan is one of nine essential amino acids. MedlinePlus says the body cannot make these, so they must come from food, and that a balance across the whole day matters more than eating every one at every meal.
Reviews describe tryptophan as the sole starting material for serotonin, a chemical messenger in the brain and gut. It is also turned into kynurenine, tryptamine and indole compounds, partly by gut microbes. The supplement form is L-tryptophan. 5-HTP is a related compound with its own page.
Where tryptophan comes from in food
Every protein food has some. USDA data (per 3 oz or 85 g portion): roasted chicken breast about 308 mg, roasted turkey breast about 244 mg, farmed salmon about 211 mg, light tuna about 178 mg. Per ounce: pumpkin seeds about 163 mg, cheddar about 155 mg, sunflower seeds about 99 mg. A large hard-boiled egg has about 77 mg and a cup of whole milk about 98 mg.
Plant foods carry it too: half a cup of firm tofu about 296 mg, a cup of cooked soybeans about 416 mg, a cup of dry oats about 147 mg and a cup of cooked lentils about 160 mg. A banana has very little. Turkey is a good source, but in these tables it is not higher than chicken, pumpkin seeds or cheese.
What the research shows
For sleep, a 2022 review pooled 4 small studies and found less time awake after falling asleep, but no change in other sleep measures. For mood in healthy adults, 4 of 11 trials in a 2021 review found a benefit. These ratings are low certainty.
For depression, a 2001 Cochrane review found only 2 small good-enough trials and called the evidence insufficient. One 1999 trial found lower mood symptoms in women with PMDD. A small trial found that, added to fluoxetine, tryptophan helped depression scores only in week 1. Exercise trials disagree. None of this shows tryptophan treats a condition.
Food versus pills
Foods supply tryptophan inside whole proteins together with many other amino acids. Almost all trials above used purified L-tryptophan as a supplement. No trial compared food tryptophan with pills. This page gives no amounts to take; if you wonder about your own needs, ask a doctor, pharmacist or dietitian.
At a glance
Traditional uses history, not proof
- An essential amino acid from protein foods
- Sold as supplements for sleep and mood
Studied for research
- Essential nutrient and serotonin building block, high certainty
- Sleep (time awake at night), low certainty
- Mood in healthy adults, low certainty
- Premenstrual dysphoric disorder, low certainty
- Depression, very low certainty
- Exercise performance, low certainty
- Fibromyalgia (combination product), insufficient
Main compounds
- L-tryptophan
- Serotonin
- Kynurenine
- 5-HTP (related)
Common forms
- Food sources (poultry, fish, cheese, seeds, soy, oats)
- L-tryptophan supplements
Research links: 2022 review: tryptophan and sleep quality · 2021 review: tryptophan and mood in healthy adults · 2001 Cochrane review: tryptophan and 5-HTP for depression · 2023 review: impurities and eosinophilia-myalgia syndrome · 2019 review: serotonin syndrome · Research Library · Genes & Biomarkers Library
What it is and its history
- Accepted scientific name
- L-tryptophan (amino acid, abbreviated Trp)
- Common names
- Tryptophan (English); L-tryptophan (English); Trp (English (abbreviation)); Triptófano (Spanish)
- Family or group
- Essential amino acid. MedlinePlus lists it among the nine essential amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine) that the body cannot make.
- Harvest and processing
- A 2023 review says L-tryptophan is used as an animal feed additive and in supplements. The 1989 outbreak was tied in one study to one company's fermentation process and a purification step; details of current manufacture were not read.
- Look-alikes and adulterants
- Name: 5-HTP (5-hydroxytryptophan); Note: A related compound one step closer to serotonin. It has its own page and its own safety questions.; Name: Kynurenine and indole compounds; Note: Other breakdown products of tryptophan, made partly by gut microbes (reviews).; Name: Melatonin and niacin; Note: Not tryptophan itself. They are different molecules; this page does not make claims about them.
- Sustainability and conservation
- Not assessed.
What is inside, and how it may work
What it contains and how those compounds act in cells and animals. Laboratory and animal mechanisms are not proven effects in people.
Main compounds
| Compound | Family | Where it is concentrated | Activity studied | Level of evidence |
|---|---|---|---|---|
| L-tryptophan PubChem 6305 | amino acid | Not read from a source. | An essential amino acid and the sole precursor of serotonin (review). The form sold as a supplement. 21 5 | Human data |
| Serotonin PubChem 5202 | monoamine (made from tryptophan) | Not read from a source. | A chemical messenger the body makes from tryptophan. 5 13 | Human data |
| Kynurenine PubChem 161166 | tryptophan breakdown product | Not read from a source. | Another main route for tryptophan; in rats, high tryptophan raised kynurenine and related metabolites alongside kidney injury. 1 6 | Animal research |
| 5-Hydroxytryptophan (5-HTP) PubChem 144 | related amino acid | Not read from a source. | The immediate step between tryptophan and serotonin; tested together with tryptophan in the depression review. 14 | Human data |
Mechanisms, receptors and pathways
| Target or pathway | Gene or receptor | What was found | Level |
|---|---|---|---|
| Serotonin synthesis | Not specified in the abstracts read | A 2020 review says tryptophan is the sole precursor of serotonin, a messenger that acts on the brain and gut. Whether extra tryptophan raises brain serotonin in people was not shown in the sources read. 5 | Human data |
| Kynurenine and indole routes | Aryl hydrocarbon receptor (AhR) in rats | Tryptophan is also converted to kynurenine, tryptamine and indole, partly by gut microbes (two reviews). In rats, a high-tryptophan diet activated the AhR pathway alongside kidney injury (animal only). 1 5 6 | Animal research |
| Mood after temporary tryptophan lowering | Not applicable | A meta-analysis of depletion studies found mood fell in some vulnerable groups but not in healthy people, and the authors say this does not prove a causal link between serotonin and depression. 12 | Human data |
Absorption, metabolism and elimination
- Absorption
- Not described in the abstracts read.
- Distribution
- Not described in the abstracts read.
- Metabolism
- Reviews say tryptophan goes mainly to serotonin, kynurenine, tryptamine and indole routes, with gut microbes shaping some of them.
- Elimination
- Not described in the abstracts read.
- Bioavailability
- Not compared between foods and supplements in the sources read.
Isolated compounds versus whole extracts
Foods supply tryptophan inside whole proteins together with other amino acids. Trials on this page use purified L-tryptophan as a supplement, sometimes added to meals. No trial compared food tryptophan with pills for health results. MedlinePlus says a balance of amino acids across the day matters rather than any single one.
Nutritional composition
Tryptophan content of foods is from USDA FoodData Central SR Legacy (April 2018 release), nutrient 1210, read 2026-10-26 from a saved local copy; values are per 100 g and per household portion. See the Food sources item and the USDA source note for the full list (for example roasted turkey breast about 244 mg and roasted chicken breast about 308 mg per 3 oz).
2 high certainty1 moderate certainty4 low certainty3 very low certainty1 not enough evidence
What was looked at
The 11 benefits and uses checked for Tryptophan, each with how strong the evidence is. Tap one to open it.
- Essential amino acid and serotonin building blockHigh certainty
- Food sources of tryptophanHigh certainty
- Sleep: time awake after falling asleepLow certainty
- Mood and anxiety in healthy adultsLow certainty
- Depression (treatment trials)Very low certainty
- Premenstrual dysphoric disorder (PMDD)Low certainty
- Added to fluoxetine at the start of depression treatmentVery low certainty
- Exercise performance and tirednessLow certainty
- What happens when tryptophan is temporarily lowered (research tool)Moderate certainty
- Low-tryptophan diet in diarrhoea-type IBSVery low certainty
- Fibromyalgia (in a combination with CoQ10 and magnesium)Not enough evidence
Lab markers tracked in the studies
Time awake after falling asleep (minutes)Premenstrual mood symptom scoreDepression rating score (HDRS-29)Distance covered in the last 20 minutes of exerciseBlood serotoninUrinary 5-HIAA
What is Tryptophan good for?
The main studied uses and how strong the human evidence is for each. Most results are for supplements in small trials, often in healthy people.
Benefits, one by one
Each card is a research question, not a promise. Tap a goal to filter. Open a card to see the studies, doses and limits.
Essential amino acid and serotonin building block
High certaintyTryptophan is one of nine essential amino acids: the body cannot make it, so it has to come from food. MedlinePlus says a balance of amino acids over the whole day matters. The body also uses tryptophan to make serotonin, a chemical messenger. Reviews describe it as the only starting material for serotonin.
3 studiesTryptophan from food proteins, and as an L-tryptophan supplement; for…
Studies, doses and limits
What the trials found
MedlinePlus (review date 2025-01-21) lists tryptophan among the nine essential amino acids that must come from food and says you do not need to eat every amino acid at every meal, but a balance across the whole day is important. Two 2018 and 2020 reviews describe how tryptophan is the only route to serotonin and how gut microbes shape its other routes. No source read says that eating or taking extra tryptophan raises serotonin in the brain of a well-fed person.
Results
Tryptophan is essential and the body uses it to make serotonin. That is a normal role, not proof that extra tryptophan in a pill changes mood or health.
Effect sizes as reported
No effect sizes apply: these are nutrient roles, not trial results.
Why this rating
High that tryptophan is essential and is the starting material for serotonin (MedlinePlus, two reviews). Not a trial result for any supplement.
Form and dose studied
Tryptophan from food proteins, and as an L-tryptophan supplement; forms are not compared here.
Who was studied
General population.
Limits
Role statements come from a health page and two narrative reviews read as abstracts. Gut-brain links come mostly from lab and animal work.
Why researchers looked
People ask whether they get enough tryptophan and what it does in the body.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Established nutrition
Reviews of tryptophan metabolism say it is the sole precursor of serotonin and can also be turned into kynurenine, tryptamine and indole, partly by gut microbes. This is established physiology, not a trial result.
A proposed mechanism does not show that the effect happens in people.
Too much of anything is not always better; see the Safety tab.
Food sources of tryptophan
High certaintyAll protein foods carry tryptophan. By USDA data, 3 oz (85 g) of roasted turkey breast has about 244 mg, roasted chicken breast about 308 mg, farmed salmon about 211 mg. An ounce of pumpkin seeds has about 163 mg, an ounce of cheddar about 155 mg, a large hard-boiled egg about 77 mg, and a cup of whole milk about 98 mg. Soy foods, oats and lentils also supply it.
2 studiesFoods only; this is not a recommendation to eat any food or to take t…
Studies, doses and limits
What the trials found
No trial was read that compares food tryptophan with pills for health results. USDA SR Legacy values (2018 release), tryptophan per 100 g and per portion: chicken breast roasted 0.362 g and about 308 mg per 3 oz; turkey breast roasted (meat only) 0.287 g and about 244 mg per 3 oz; salmon (farmed, cooked) 0.248 g and about 211 mg per 3 oz; tuna (light, canned in water, drained) 0.209 g and about 178 mg per 3 oz; pumpkin seeds 0.576 g and about 163 mg per ounce; cheddar 0.547 g and about 155 mg per ounce; sunflower seeds 0.348 g and about 99 mg per ounce; firm tofu (with calcium sulfate) 0.235 g and about 296 mg per half cup; cooked soybeans 0.242 g and about 416 mg per cup; dry oats 0.182 g and about 147 mg per cup; cooked lentils 0.081 g and about 160 mg per cup; hard-boiled egg 0.153 g and about 77 mg per large egg; whole milk 0.040 g and about 98 mg per cup; banana 0.009 g and about 14 mg per cup sliced.
Results
Chicken, turkey, fish, cheese, eggs, seeds, soy and oats all contain tryptophan. Turkey is a good source but is not unusually high compared with chicken, pumpkin seeds or cheese in these tables. Fruit such as banana has very little.
Effect sizes as reported
USDA tryptophan per 100 g: pumpkin seeds 0.576 g; cheddar 0.547 g; chicken breast 0.362 g; sunflower seeds 0.348 g; turkey breast 0.287 g; salmon 0.248 g; soybeans cooked 0.242 g; tofu 0.235 g; tuna 0.209 g; oats dry 0.182 g; egg 0.153 g; lentils cooked 0.081 g; milk 0.040 g; banana 0.009 g.
Why this rating
High that foods contain these amounts (USDA tables). How much reaches the brain, or how a meal affects mood or sleep, was not measured in the sources read.
Form and dose studied
Foods only; this is not a recommendation to eat any food or to take tryptophan.
Who was studied
General adult diet.
Limits
SR Legacy values are from a 2018 release and vary with cut, cooking and brand. Absorption and what happens after a meal were not measured.
Why researchers looked
Many people want to know which foods contain tryptophan, and whether turkey really stands out.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Nutrient database
These are nutrient amounts in foods taken from USDA tables.
A proposed mechanism does not show that the effect happens in people.
Eat a varied diet; see the Safety tab for supplements.
Sleep: time awake after falling asleep
Low certaintyA 2022 review pooled four studies of tryptophan supplements and found people spent fewer minutes awake after first falling asleep. Other sleep measures did not change. Most of the studies were small.
1 studiesL-tryptophan supplements; amounts studied are in the studies table on…
Studies, doses and limits
What the trials found
The 2022 meta-analysis (Nutrition Reviews) collected 18 articles but could pool only 4. In the pooled studies, tryptophan shortened wake after sleep onset (SMD -1.08, 95% CI -1.89 to -0.28), and the reviewers report a larger effect in studies using higher amounts. Tryptophan did not change other sleep components.
Results
Mixed and thin. Tryptophan may shorten the time people lie awake during the night, but the pooled result rests on four small studies and no other sleep measure improved.
Effect sizes as reported
WASO SMD -1.08 (-1.89 to -0.28); -81.03 min per g (P = 0.017). No change in other sleep components.
Why this rating
Low: only 4 studies could be pooled, the abstract gives no risk-of-bias rating or participant numbers, and only one sleep measure improved.
Form and dose studied
L-tryptophan supplements; amounts studied are in the studies table only.
Who was studied
Adults in small trials; populations not detailed in the abstract.
Limits
Few small studies; the abstract does not describe who took part. This does not show tryptophan treats insomnia.
Why researchers looked
Tryptophan is sold as a sleep aid because the body uses it to make serotonin, which is linked to the sleep-wake cycle.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Preliminary mechanism
Serotonin takes part in the sleep-wake cycle; whether pills change this in people was not shown by the sources read beyond the trial results.
A proposed mechanism does not show that the effect happens in people.
Daytime drowsiness was reported at higher amounts in a depression trial; see the Safety tab.
Mood and anxiety in healthy adults
Low certaintyA 2021 review of 11 trials in healthy adults found 4 in which tryptophan lifted mood or lowered negative feelings compared with the comparison group. The reviewers say tryptophan may reduce anxious feelings in healthy people. It had no effect on aggressive feelings.
1 studiesL-tryptophan supplements added to usual meals.
Studies, doses and limits
What the trials found
The reviewers searched PubMed, the Cochrane Library and a Japanese database and found 11 randomised trials in healthy adults. Four trials found significant differences from the control group in negative and happy feelings. Seven did not. The reviewers concluded tryptophan may help positive mood and anxiety in healthy people but said the best amount and timing are not known.
Results
Mixed. Fewer than half the trials found a benefit, and none was in people with a mood disorder.
Effect sizes as reported
4 of 11 trials significant; no pooled effect size in the abstract.
Why this rating
Low: the review counts trials rather than pooling them, only 4 of 11 were positive, and no risk-of-bias rating is given in the abstract.
Form and dose studied
L-tryptophan supplements added to usual meals.
Who was studied
Healthy adults.
Limits
No pooled numbers in the abstract. Short mood tests in healthy people do not show treatment of anxiety or depression.
Why researchers looked
Because tryptophan makes serotonin, researchers tested whether extra tryptophan changes mood in healthy people.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Preliminary mechanism
Tryptophan is the starting material for serotonin. Whether extra tryptophan raises brain serotonin in these trials was not shown in the abstract.
A proposed mechanism does not show that the effect happens in people.
See the Safety tab for drowsiness and for medicines that affect serotonin.
Depression (treatment trials)
Very low certaintyA 2001 Cochrane review found only 2 good-enough trials (64 people) of tryptophan or 5-HTP for depression. They favoured the amino acid over placebo, but the reviewers said the evidence was not strong enough to be conclusive. Better antidepressants exist, so they did not recommend tryptophan.
2 studiesTryptophan and 5-HTP results combined; trial amounts are in the studi…
Studies, doses and limits
What the trials found
The Cochrane review and a linked meta-analysis found 108 trials, but only 2 met basic quality standards: one of 5-HTP and one of L-tryptophan, 64 people in total. Peto odds ratio 4.10 (1.28 to 13.15). The reviewers say studies were small, publication bias is possible and the question needs larger, better trials.
Results
Insufficient. The little good evidence leans toward benefit but is too small and too old to rely on. Tryptophan is not a proven treatment for depression.
Effect sizes as reported
Peto OR 4.10 (95% CI 1.28 to 13.15); NNT 2.78. Only one tryptophan trial.
Why this rating
Very low: two small trials, one of which was 5-HTP, 25-year-old searches, and the authors themselves call the evidence insufficient.
Form and dose studied
Tryptophan and 5-HTP results combined; trial amounts are in the studies table.
Who was studied
Adults with unipolar depression or dysthymia.
Limits
Searches ended in 2000. No newer systematic review of tryptophan alone for depression was read.
Why researchers looked
People ask whether tryptophan can treat depression the way antidepressants do.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Preliminary mechanism
Tryptophan is a serotonin precursor, which is why it was tested; the trials do not prove that route.
A proposed mechanism does not show that the effect happens in people.
Do not stop or replace a prescribed antidepressant; see the Safety tab on serotonin syndrome.
Premenstrual dysphoric disorder (PMDD)
Low certaintyOne 1999 trial gave 71 women with PMDD either tryptophan or placebo for part of each cycle over three cycles. Mood symptoms (low mood, mood swings, tension, irritability) fell more with tryptophan: about 35% against 10% with placebo. It is a single trial.
1 studiesL-tryptophan, used late in the menstrual cycle in the trial.
Studies, doses and limits
What the trials found
In this double-blind randomised trial, 37 women took L-tryptophan and 34 took placebo from ovulation to day 3 of menstruation over three cycles. Mood scores on visual analogue scales dropped 34.5% with tryptophan and 10.4% with placebo (p = .004).
Results
Possible benefit for mood symptoms in one small trial; not confirmed by other trials in the sources read.
Effect sizes as reported
Mood symptom reduction 34.5% vs 10.4% (p = .004).
Why this rating
Low: one randomised trial of 71 women from 1999 with self-rated scores, and no repeat trial was read.
Form and dose studied
L-tryptophan, used late in the menstrual cycle in the trial.
Who was studied
Women with PMDD.
Limits
Single study. The amount used in the trial was high. The abstract does not describe side effects.
Why researchers looked
Serotonin-acting antidepressants help PMDD, so researchers tested a serotonin starting material.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Preliminary mechanism
Authors suggest raising serotonin synthesis late in the cycle; not shown in the abstract.
A proposed mechanism does not show that the effect happens in people.
See the Safety tab for drowsiness and serotonin-related cautions.
Added to fluoxetine at the start of depression treatment
Very low certaintyIn a small 2000 trial of 30 people with major depression starting fluoxetine, adding tryptophan lowered depression scores more in week 1 only. There was no difference later. No serotonin syndrome occurred in this trial, but the higher amount caused daytime drowsiness.
2 studiesL-tryptophan added to fluoxetine; amounts in the studies table.
Studies, doses and limits
What the trials found
Thirty people with major depressive disorder took fluoxetine plus tryptophan or placebo for 8 weeks. Depression scores (HDRS-29) fell more with tryptophan in week 1 only. Slow-wave sleep fell in the placebo group at week 4 but not in the tryptophan group.
Results
A short-lived early effect in a very small trial. It does not show that adding tryptophan helps people on antidepressants, and combining the two should only be done under medical supervision.
Effect sizes as reported
Greater HDRS-29 fall in week 1; no significant difference at later time points.
Why this rating
Very low: 30 people, benefit only in week 1, preliminary design, and the authors call for larger studies.
Form and dose studied
L-tryptophan added to fluoxetine; amounts in the studies table.
Who was studied
Adults with major depressive disorder.
Limits
Preliminary trial. An erratum is listed (not read).
Why researchers looked
Antidepressants can take weeks to work and can disturb sleep, so researchers tested adding tryptophan at the start.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Preliminary mechanism
The idea was that more serotonin building material could speed up the effect; this was not shown beyond the week-1 scores.
A proposed mechanism does not show that the effect happens in people.
Serotonin syndrome is a known risk when serotonin-raising medicines are combined; see the Safety tab.
Exercise performance and tiredness
Low certaintyTwo small trials gave different answers. In 49 trained male runners, tryptophan before a run to exhaustion made no difference to running performance. In 20 healthy young sportsmen, tryptophan raised cycling power and the distance covered in the last 20 minutes (about 12,526 m against 11,959 m).
2 studiesL-tryptophan, short-term; amounts are in the studies table.
Studies, doses and limits
What the trials found
Stensrud 1992: 49 well-trained male runners, double-blind; a short course over 24 hours before a run at 100% of maximal oxygen uptake; no significant difference in improvement between groups. Javierre 2010: 20 healthy young sportsmen in a double-blind crossover; power outputs and last-20-minute distance were higher with tryptophan (p < .05). The runners' trial was done to check an earlier 49.4% claim by other researchers.
Results
Mixed. One larger trial found nothing; one small crossover trial found a gain. This is not enough to say tryptophan improves sport performance.
Effect sizes as reported
Running: no significant difference. Cycling: 12,526 +/- 1,617 m vs 11,959 +/- 1,753 m in the last 20 minutes (p < .05).
Why this rating
Low: two small trials with opposite results, different exercise tests, and the abstracts give little detail.
Form and dose studied
L-tryptophan, short-term; amounts are in the studies table.
Who was studied
Healthy young men, trained or active.
Limits
Men only. Very short exposure. No long-term sport data.
Why researchers looked
Researchers wondered whether more tryptophan could delay tiredness by changing serotonin activity in the brain.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Preliminary mechanism
The cycling trial authors suggest the serotonin system affects how hard the brain drives muscles; this was not measured in the abstract.
A proposed mechanism does not show that the effect happens in people.
Drowsiness is a possible effect at higher amounts; see the Safety tab.
What happens when tryptophan is temporarily lowered (research tool)
Moderate certaintyScientists sometimes give a drink with no tryptophan to lower serotonin for a day. A 2007 meta-analysis found this did not lower mood in healthy people. It lowered mood a little in people with a family history of depression, moderately in people with past depression off medicine, and brought back depression in people on serotonin-type antidepressants.
1 studiesAmino-acid drinks that lack tryptophan, not supplements.
Studies, doses and limits
What the trials found
Seventy-three depletion studies were found and 45 were meta-analysed. Mood did not fall in healthy people, but it slightly fell in healthy people with a family history of depression, moderately fell in drug-free people with past depression, and relapse occurred in people with past depression who were using serotonergic antidepressants. The authors say this points to a vulnerability trait rather than a simple cause.
Results
This is evidence about LOWERING tryptophan. It does not show that taking extra tryptophan prevents or treats low mood.
Effect sizes as reported
No numeric effect sizes in the abstract.
Why this rating
Moderate that depletion lowers mood in people with a history of depression (meta-analysis of randomised studies); our own rating, as the authors give no GRADE. It says nothing about supplements.
Form and dose studied
Amino-acid drinks that lack tryptophan, not supplements.
Who was studied
Healthy people, people with a family history of depression, people with remitted depression.
Limits
Studies differed in design. A research method rather than a health treatment.
Why researchers looked
Depletion studies help show how much serotonin matters for mood.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Human mechanistic
A temporary dip in the tryptophan supply lowers serotonin; the authors say these studies do not prove that low serotonin causes depression.
A proposed mechanism does not show that the effect happens in people.
Not a supplement trial; safety of supplements is on the Safety tab.
Low-tryptophan diet in diarrhoea-type IBS
Very low certaintyA 2022 study of 40 people with diarrhoea-type irritable bowel syndrome found they had higher blood serotonin than healthy people. After 12 weeks of eating less tryptophan, serotonin fell and abdominal symptoms and anxiety improved. There was no comparison group, so the cause is not clear.
2 studiesDiet restricted in tryptophan; not a supplement.
Studies, doses and limits
What the trials found
Forty adults with IBS-D and 40 healthy people took part. Baseline serum serotonin was higher in IBS-D (198.2 vs 142.3 ng/mL, p < 0.001) and urinary 5-HIAA (a serotonin breakdown product) was higher too. After 12 weeks on a diet limited to a set amount of tryptophan, serotonin and 5-HIAA fell significantly, abdominal symptoms and anxiety scores improved, and depression and insomnia scores did not change.
Results
Very early. This is about eating less tryptophan, not taking more, and it was not a controlled trial.
Effect sizes as reported
Serotonin 198.2 vs 142.3 ng/mL at baseline; fell significantly after the diet (p < 0.001).
Why this rating
Very low: no control group on the diet, a small group, and symptom scores are self-reported.
Form and dose studied
Diet restricted in tryptophan; not a supplement.
Who was studied
Adults with IBS-D.
Limits
Healthy people were only a baseline. Placebo effects could explain symptom changes.
Why researchers looked
The researchers found higher serotonin in people with IBS-D, so they tested a diet with less tryptophan.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Human mechanistic
A review says tryptophan is the sole precursor of serotonin, which also acts in the gut. The study measured serotonin but not why symptoms changed.
A proposed mechanism does not show that the effect happens in people.
Do not cut protein or try restrictive diets without medical advice; tryptophan is an essential nutrient.
Fibromyalgia (in a combination with CoQ10 and magnesium)
Not enough evidenceA 2025 crossover trial of 89 people with fibromyalgia tested a product containing coenzyme Q10, tryptophan and magnesium. The main fatigue result was not met. Pain, sleep quality and overall impact improved with the product, but any result cannot be credited to tryptophan alone.
1 studiesCombination of coenzyme Q10, tryptophan and magnesium.
Studies, doses and limits
What the trials found
One hundred and ten adults with fibromyalgia started and 89 finished a double-blind crossover trial (two 3-month periods). Fatigue improved significantly with placebo and not significantly with the supplement. Pain fell in both groups; sleep quality, functional impact and the total score improved significantly with the supplement. Side effects were mild and similar in both groups.
Results
Insufficient for tryptophan. A three-ingredient product cannot show what one ingredient does, and its main target was missed.
Effect sizes as reported
No numbers in the abstract.
Why this rating
Insufficient: combination product, primary outcome not met, abstract only.
Form and dose studied
Combination of coenzyme Q10, tryptophan and magnesium.
Who was studied
Adults with fibromyalgia, mostly women, most on medicines.
Limits
An erratum is listed for this paper and was not read.
Why researchers looked
Researchers tested a combined supplement in people with fibromyalgia.
Traditional use
Tryptophan is an essential amino acid. Its roles in the body are well established; that is different from showing that extra tryptophan pills treat a condition.
Proposed mechanism Unknown
Not examined for tryptophan alone.
A proposed mechanism does not show that the effect happens in people.
Side effects were mild in this trial.
Connections to the rest of health
How Tryptophan connects to the rest of our health knowledge graph. Every link says what kind of connection it is. A safety link (for example to the liver) is a warning, not a benefit. A study that merely mentions a topic never creates a benefit link.
Explore every connection: goals, body systems, organs, symptoms, genes
A. Wellness goals
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Balanced Nutrition | High certainty | Essential amino acid and serotonin building block: Tryptophan is one of nine essential amino acids: the body cannot make it, so it has to come from food. MedlinePlus says a balance of amino acids over the whole day matters. The body also uses tryptophan to make serotonin, a chemical messenger. Reviews describe it as the only starting material for serotonin. | 21 5 1 | |
| Balanced Nutrition | High certainty | Food sources of tryptophan: All protein foods carry tryptophan. By USDA data, 3 oz (85 g) of roasted turkey breast has about 244 mg, roasted chicken breast about 308 mg, farmed salmon about 211 mg. An ounce of pumpkin seeds has about 163 mg, an ounce of cheddar about 155 mg, a large hard-boiled egg about 77 mg, and a cup of whole milk about 98 mg. Soy foods, oats and lentils also supply it. | 23 21 | |
| Better Sleep | Low certainty | Sleep: time awake after falling asleep: A 2022 review pooled four studies of tryptophan supplements and found people spent fewer minutes awake after first falling asleep. Other sleep measures did not change. Most of the studies were small. | 19 | |
| Mood Balance | Low certainty | Mood and anxiety in healthy adults: A 2021 review of 11 trials in healthy adults found 4 in which tryptophan lifted mood or lowered negative feelings compared with the comparison group. The reviewers say tryptophan may reduce anxious feelings in healthy people. It had no effect on aggressive feelings. | 8 | |
| Anxiety Support | Low certainty | Mood and anxiety in healthy adults: A 2021 review of 11 trials in healthy adults found 4 in which tryptophan lifted mood or lowered negative feelings compared with the comparison group. The reviewers say tryptophan may reduce anxious feelings in healthy people. It had no effect on aggressive feelings. | 8 | |
| Mood Balance | Very low certainty | Depression (treatment trials): A 2001 Cochrane review found only 2 good-enough trials (64 people) of tryptophan or 5-HTP for depression. They favoured the amino acid over placebo, but the reviewers said the evidence was not strong enough to be conclusive. Better antidepressants exist, so they did not recommend tryptophan. | 14 15 | |
| Womens Wellness | Low certainty | Premenstrual dysphoric disorder (PMDD): One 1999 trial gave 71 women with PMDD either tryptophan or placebo for part of each cycle over three cycles. Mood symptoms (low mood, mood swings, tension, irritability) fell more with tryptophan: about 35% against 10% with placebo. It is a single trial. | 17 | |
| Mood Balance | Low certainty | Premenstrual dysphoric disorder (PMDD): One 1999 trial gave 71 women with PMDD either tryptophan or placebo for part of each cycle over three cycles. Mood symptoms (low mood, mood swings, tension, irritability) fell more with tryptophan: about 35% against 10% with placebo. It is a single trial. Added to fluoxetine at the start of depression treatment: In a small 2000 trial of 30 people with major depression starting fluoxetine, adding tryptophan lowered depression scores more in week 1 only. There was no difference later. No serotonin syndrome occurred in this trial, but the higher amount caused daytime drowsiness. | 17 10 13 | |
| Energy Vitality | Low certainty | Exercise performance and tiredness: Two small trials gave different answers. In 49 trained male runners, tryptophan before a run to exhaustion made no difference to running performance. In 20 healthy young sportsmen, tryptophan raised cycling power and the distance covered in the last 20 minutes (about 12,526 m against 11,959 m). | 18 7 | |
| Sports Performance | Low certainty | Exercise performance and tiredness: Two small trials gave different answers. In 49 trained male runners, tryptophan before a run to exhaustion made no difference to running performance. In 20 healthy young sportsmen, tryptophan raised cycling power and the distance covered in the last 20 minutes (about 12,526 m against 11,959 m). | 18 7 | |
| Mood Balance | Moderate certainty | What happens when tryptophan is temporarily lowered (research tool): Scientists sometimes give a drink with no tryptophan to lower serotonin for a day. A 2007 meta-analysis found this did not lower mood in healthy people. It lowered mood a little in people with a family history of depression, moderately in people with past depression off medicine, and brought back depression in people on serotonin-type antidepressants. | 12 | |
| Gut Digestive Health | Very low certainty | Low-tryptophan diet in diarrhoea-type IBS: A 2022 study of 40 people with diarrhoea-type irritable bowel syndrome found they had higher blood serotonin than healthy people. After 12 weeks of eating less tryptophan, serotonin fell and abdominal symptoms and anxiety improved. There was no comparison group, so the cause is not clear. | 3 5 | |
| Pain Comfort | Not enough evidence | Fibromyalgia (in a combination with CoQ10 and magnesium): A 2025 crossover trial of 89 people with fibromyalgia tested a product containing coenzyme Q10, tryptophan and magnesium. The main fatigue result was not met. Pain, sleep quality and overall impact improved with the product, but any result cannot be credited to tryptophan alone. | 11 | |
| Energy Vitality | Not enough evidence | Fibromyalgia (in a combination with CoQ10 and magnesium): A 2025 crossover trial of 89 people with fibromyalgia tested a product containing coenzyme Q10, tryptophan and magnesium. The main fatigue result was not met. Pain, sleep quality and overall impact improved with the product, but any result cannot be credited to tryptophan alone. | 11 |
B. Body systems
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Whole Body | Biological association | High certainty | Studied for: Essential amino acid and serotonin building block | 21 5 1 |
| Nervous System | Biological association | High certainty | Studied for: Essential amino acid and serotonin building block Studied for: Sleep: time awake after falling asleep | 21 5 1 19 8 14 15 17 10 13 18 7 12 11 |
| Nutrition | Biological association | High certainty | Studied for: Food sources of tryptophan | 23 21 |
| Digestive System | Biological association | High certainty | Studied for: Food sources of tryptophan Studied for: Low-tryptophan diet in diarrhoea-type IBS | 23 21 3 5 |
| Sleep And Recovery | Biological association | Low certainty | Studied for: Sleep: time awake after falling asleep | 19 |
| Reproductive System | Biological association | Low certainty | Studied for: Premenstrual dysphoric disorder (PMDD) | 17 |
| Muscles | Biological association | Low certainty | Studied for: Exercise performance and tiredness Studied for: Fibromyalgia (in a combination with CoQ10 and magnesium) | 18 7 11 |
E. Health conditions
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Eosinophilia-myalgia syndrome | Adverse effect or risk | Documented outbreak, 1989 | Linked to one manufacturer's tryptophan; the cause is unresolved. Preparation or compound: Contaminated L-tryptophan |
4 2 16 9 |
| Premenstrual dysphoric disorder | Single trial | One trial found lower mood symptoms with tryptophan than placebo. Preparation or compound: L-tryptophan |
17 |
I. Biomarkers
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Time awake after falling asleep (minutes) | Biological association | Low certainty | Measured in trials: shorter in pooled studies. A lab change is not the same as a health benefit. | 19 |
| Premenstrual mood symptom score | Biological association | Low certainty | Measured in trials: lower with tryptophan in one trial. A lab change is not the same as a health benefit. | 17 |
| Depression rating score (HDRS-29) | Biological association | Very low certainty | Measured in trials: lower in week 1 only. A lab change is not the same as a health benefit. | 10 |
| Distance covered in the last 20 minutes of exercise | Biological association | Low certainty | Measured in trials: higher with tryptophan in one small trial. A lab change is not the same as a health benefit. | 7 18 |
| Blood serotonin | Biological association | Very low certainty | Measured in trials: lower after a low-tryptophan diet. A lab change is not the same as a health benefit. | 3 |
| Urinary 5-HIAA | Biological association | Very low certainty | Measured in trials: lower after a low-tryptophan diet. A lab change is not the same as a health benefit. | 3 |
K. Biological pathways
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Serotonin | Preliminary mechanism | Human | Made from tryptophan; serotonin-raising medicines can combine dangerously. | 5 13 |
| Kynurenine pathway | Preliminary mechanism | Animal | A second main route for tryptophan; linked to kidney findings in rats. | 1 6 |
L. Active compounds
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| 5-HTP | Related | 5-HTP is one step closer to serotonin than tryptophan. The Cochrane depression review combined trials of both. Preparation or compound: 5-hydroxytryptophan |
14 | |
| L-tryptophan | Biological association | Human | An essential amino acid and the sole precursor of serotonin (review). The form sold as a supplement. | 21 5 |
| Serotonin | Biological association | Human | A chemical messenger the body makes from tryptophan. | 5 13 |
| Kynurenine | Biological association | Animal | Another main route for tryptophan; in rats, high tryptophan raised kynurenine and related metabolites alongside kidney injury. | 1 6 |
| 5-Hydroxytryptophan (5-HTP) | Biological association | Human | The immediate step between tryptophan and serotonin; tested together with tryptophan in the depression review. | 14 |
Each connection is stored with the ingredient, the connected record, the kind of connection, the evidence status, the supporting studies, the preparation or compound involved, and a review date (last reviewed October 26, 2026).
Evidence at a glance: what the research found for 11 outcomes
Each outcome below is one thing researchers measured. Certainty is how far the evidence can be trusted, not how well it works. The full studies are on the next tab.
The evidence
The research centre for Tryptophan. Every record here was checked against PubMed or the publisher's page; we never list a study we have not verified.
Evidence by outcome
Bars show how many studies we found for each outcome, not how well it works. People are added up across trials only (reviews are not added, to avoid double counting).
How we rate evidence
High certainty
Several well-run trials or reviews agree; further research is unlikely to change the picture much.
Moderate certainty
Good trials point the same way, but some doubt remains.
Low certainty
Small, short or inconsistent trials. The finding could change with better research.
Very low certainty
Very little or very weak human data. Treat as a possibility only.
Mixed findings
Trials or reviews disagree with each other.
Not enough evidence
Not enough human research to say either way.
Evidence against
Good research found no benefit, or found harm.
We take the reviewers' own risk-of-bias and GRADE statements where they exist, and otherwise judge from study size, design, consistency, directness and whether a product matches what is sold. Many publications do not make evidence high. Method note: We started from our existing tryptophan summary, read the MedlinePlus amino acids page, checked food values in saved USDA FoodData Central data, and re-read PubMed abstracts for reviews, trials and case-control studies. Only abstracts were read for studies. The NIH Office of Dietary Supplements and FDA pages could not be read and are marked unread.
Study library: every study we checked 23
| Study | Design | People | Product, dose, length | Result |
|---|---|---|---|---|
| Agus 2018 Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe · PMID 29902437 · DOI |
Narrative review |
Review of tryptophan metabolism and gut microbes | Tryptophan (dietary) |
In the gut, the three major tryptophan pathways, to serotonin, kynurenine and indole derivatives, are under direct or indirect control of the gut microbiota. No numbers in the abstract. (Not applicable) Methods, limits and fundingOutcomes: Three major tryptophan pathways in the gut Limitations: A review, read from the abstract only. Funding and conflicts: Not stated in the abstract. Read: abstract |
| Belongia 1990 An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med · PMID 2370887 · DOI |
Case control study |
Minnesota surveillance, a community survey in Minneapolis-St. Paul and a case-control study; 30 cases and 35 controls with a known tryptophan source | L-tryptophan products from different manufacturers Oral supplement 1989 outbreak · vs Controls who took tryptophan or did not |
29 of 30 cases and 21 of 35 controls had used tryptophan from a single company. Lots linked to cases had less powdered carbon in a purification step and used a new strain of the fermenting bacterium. A chemical peak ('peak E') was in 9 of 12 lots used by patients and 3 of 11 used by controls. The authors conclude the outbreak followed a chemical constituent tied to one company's manufacturing conditions. Single-company tryptophan: 97% of cases vs 60% of controls (OR 19.3); reduced carbon OR 9.0; new strain OR 6.0; peak E OR 8.0 (OR 19.3 (2.5 to 844.9); reduced carbon OR 9.0 (1.1 to 84.6); new strain OR 6.0 (0.8 to 51.8); peak E OR 8.0 (0.9 to 76.6)) Methods, limits and fundingOutcomes: Which tryptophan products were used by people with EMS; manufacturing conditions; chemical peaks Limitations: Small case-control study with wide confidence intervals. It points to a contaminant; the chemical identity was not proven in the abstract. Funding and conflicts: Research support listed as US Government and non-US government. Read: abstract |
| Chojnacki 2022 A Reduced Tryptophan Diet in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Improves Their Abdominal Symptoms and Their Quality of Life through Reduction of Serotonin Levels and Its Urinary Metabolites. Int J Mol Sci · PMID 36499643 · DOI |
Uncontrolled before after study |
80 40 adults with diarrhoea-predominant IBS and 40 healthy comparison people |
Diet restricted in tryptophan Diet Tryptophan limited to 10 mg per kg body weight a day 12 weeks · vs Healthy people served only as a baseline; patients had no placebo group |
Before the diet, patients had higher serum serotonin (198.2 vs 142.3 ng/mL) and urinary 5-HIAA than healthy people. After 12 weeks on the low-tryptophan diet, serotonin and 5-HIAA fell, and abdominal symptoms and anxiety scores improved. Depression and insomnia scores did not change. Serotonin 198.2 +/- 38.1 vs 142.3 +/- 36.4 ng/mL at baseline (p < 0.001); both serotonin and urinary 5-HIAA fell significantly after the diet (p < 0.001). (p < 0.001) Methods, limits and fundingOutcomes: Abdominal symptoms (GSRS-IBS), anxiety, depression, insomnia scores; serum serotonin; urinary 5-HIAA Limitations: No placebo or diet control group, so changes may be due to other things. This tests eating LESS tryptophan, not extra. Small study. Funding and conflicts: Authors declare no conflict of interest. Read: abstract |
| Eidson 1990 L-tryptophan and eosinophilia-myalgia syndrome in New Mexico. Lancet · PMID 1969024 · DOI |
Case control study |
33 11 cases of EMS and 22 matched controls in New Mexico |
L-tryptophan-containing products Oral supplement May to October 1989 · vs Matched controls |
All 11 cases used L-tryptophan products compared with 2 of the controls. These findings led to a ban on sales in New Mexico and then a nationwide US recall. 11 of 11 cases vs 2 of 22 controls (Not given) Methods, limits and fundingOutcomes: Use of L-tryptophan products Limitations: Very small case-control study; shows association with L-tryptophan products, not which component. Funding and conflicts: Not stated in the abstract. Read: abstract |
| Gao 2020 Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. Adv Nutr · PMID 31825083 · DOI |
Narrative review |
Review of tryptophan metabolism and the gut-brain axis | Tryptophan (dietary) |
Tryptophan is the sole precursor of serotonin. It can also be turned into kynurenine, tryptamine and indole, and gut microbes influence these routes. No numbers in the abstract. (Not applicable) Methods, limits and fundingOutcomes: Tryptophan pathways to serotonin, kynurenine, tryptamine and indole Limitations: A review, read from the abstract. Mostly lab and animal evidence for the gut-brain links. Funding and conflicts: Not stated in the abstract. Read: abstract |
| Hu 2023 Tryptophan intake, not always the more the better. Front Nutr · PMID 37113297 · DOI |
Animal study rat |
Healthy rats and rats with chemically induced chronic kidney disease | Dietary tryptophan at three levels (healthy rats); tryptophan by gavage (kidney-disease rats) Diet / gavage Rat diet 0.6, 1.2 and 1.8% tryptophan for 12 weeks; kidney-disease rats 100 or 500 mg per kg 12 weeks (healthy rats); 8 weeks (kidney-disease rats) · vs Normal diet or untreated disease rats |
High-tryptophan diets raised blood urea nitrogen and caused focal kidney tissue injury in healthy rats. In rats with kidney disease, high tryptophan raised deaths, creatinine and urea and worsened kidney damage. The authors link this to build-up of kynurenine and indole metabolites. Higher BUN; higher mortality in the high-dose kidney-disease rats; numbers not in the abstract. (Not given) Methods, limits and fundingOutcomes: Blood urea nitrogen, creatinine, kidney tissue changes, kynurenine and indole metabolites, survival Limitations: Animal study only. It cannot be applied to people. No human kidney data were read. Funding and conflicts: Authors declare no commercial or financial conflict. Read: abstract |
| Javierre 2010 L-tryptophan supplementation can decrease fatigue perception during an aerobic exercise with supramaximal intercalated anaerobic bouts in young healthy men. Int J Neurosci · PMID 20402569 · DOI |
Randomised crossover trial |
20 20 healthy young sportsmen (mean age 21.2) |
L-tryptophan Oral Not given in the abstract One exercise session on each condition · vs Placebo, double-blind crossover |
Peak power, average anaerobic power and last-20-minute output were higher with tryptophan. Distance in the last 20 minutes was 12,526 m with tryptophan versus 11,959 m with placebo (p < .05). 12,526 +/- 1,617 m vs 11,959 +/- 1,753 m in the last 20 minutes (p < .05) Methods, limits and fundingOutcomes: Peak power, anaerobic power, and distance covered in the last 20 minutes of a cycling protocol Limitations: Small crossover study; the title mentions reduced fatigue perception, but the abstract reports power and distance. Healthy young men only. Funding and conflicts: Not stated in the abstract. Read: abstract |
| Kikuchi 2021 A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning. J Diet Suppl · PMID 32272859 · DOI |
Systematic review |
11 randomised controlled trials in healthy adults | L-tryptophan Oral supplement, added to usual meals 0.14 to 3 g a day across the 11 trials (as summarised by the reviewers) Varied by trial · vs Placebo or control |
Four of 11 trials found a significant difference from control in negative or happy feelings. The reviewers say tryptophan may lower anxiety and raise positive mood in healthy people. No effect on aggressive feelings was seen. 4 of 11 trials showed a significant difference; no numeric effect size in the abstract. (Not given) Methods, limits and fundingOutcomes: Mood: negative feelings, happy feelings, anxiety, aggressive feelings Limitations: Only 4 of 11 trials were positive. No pooled numbers, risk-of-bias rating or participant total in the abstract. The reviewers say the best amount, length and timing are not yet known. Healthy adults only. Funding and conflicts: Not stated in the abstract. Read: abstract |
| Ko 2023 Safety concerns regarding impurities in L-Tryptophan associated with eosinophilia myalgia syndrome. Food Chem Toxicol · PMID 37453474 · DOI |
Narrative review |
Review of the history of eosinophilia-myalgia syndrome (EMS) and impurities in L-tryptophan | L-tryptophan supplements and manufacturing impurities Oral supplement |
EMS is a rare condition with inflammation in muscles, skin and lungs. Six components made during L-tryptophan production have been suspected, but lab and animal studies have drawn no clear and convincing conclusion. No numbers in the abstract. (Not applicable) Methods, limits and fundingOutcomes: Link between impurities in L-tryptophan and EMS Limitations: A narrative review, read from the abstract only. Four of six authors are employed by a Korean company (CJ CheilJedang); the abstract does not state what the company sells, so independence from the amino acid industry cannot be judged. Funding and conflicts: Declaration of competing interest: four authors employed by CJ CheilJedang (Suwon, South Korea). Read: abstract |
| Levitan 2000 Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. J Psychiatry Neurosci · PMID 11022398 |
Randomised controlled trial |
30 30 people with major depressive disorder starting fluoxetine |
L-tryptophan added to fluoxetine Oral 2 to 4 g a day with fluoxetine 20 mg a day 8 weeks · vs Placebo plus fluoxetine, double-blind |
Depression scores fell more in the tryptophan group in week 1 only. Later weeks showed no significant difference. Slow-wave sleep dropped in the placebo group but not the tryptophan group at week 4. No serotonin syndrome occurred; the higher amount caused daytime drowsiness. Greater HDRS-29 fall in week 1 (no numbers in the abstract); no significant differences later. (Not given) Methods, limits and fundingOutcomes: Hamilton Depression Rating Scale (HDRS-29), Beck Depression Inventory, laboratory sleep studies, side effects Limitations: A 30-person preliminary trial. The benefit did not last past week 1. The authors say larger studies are needed. An erratum is listed for this paper and was not read. Funding and conflicts: Support listed as non-US government; no conflict statement in the abstract. Read: abstract |
| Rosselló Aubach 2025 Effects of Coenzyme Q10, Tryptophan, and Magnesium Supplementation on Fatigue in Patients with Fibromyalgia - A Randomized Trial. J Diet Suppl · PMID 40151031 · DOI |
Randomised crossover trial |
110 110 adults with fibromyalgia enrolled, 89 finished (96.6% women); most were on medicines |
Combination of coenzyme Q10, tryptophan and magnesium (tryptophan is not tested alone) Oral supplement Not given in the abstract Two 3-month periods with a 1-month washout · vs Placebo, double-blind crossover |
The main fatigue result was not met: fatigue improved significantly with placebo and not significantly with the supplement. Pain fell in both groups. Sleep quality, functional impact and the total score improved with the supplement. Side effects were mild and similar between groups. Fatigue: improved in placebo, non-significant with supplement; total score improved with supplement. No numbers in the abstract. (Not given) Methods, limits and fundingOutcomes: Fatigue item of the fibromyalgia impact index (primary); pain, sleep quality, total score Limitations: A combination product, so any result cannot be credited to tryptophan. The primary outcome was not met. An erratum is listed for this paper and was not read. Funding not stated in the abstract. Funding and conflicts: Not stated in the abstract. Read: abstract |
| Ruhé 2007 Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry · PMID 17389902 · DOI |
Systematic review meta analysis |
73 acute tryptophan depletion studies found; 45 meta-analysed (healthy people, people with a family history of depression, and people with depression in remission) | Acute tryptophan depletion (a drink lacking tryptophan that temporarily lowers serotonin) compared with a control drink Amino acid drink Acute (single day) · vs Control depletion drink |
Depletion did not lower mood in healthy people. It slightly lowered mood in healthy people with a family history of depression, moderately lowered mood in people with past depression not on drugs, and brought relapse in people with past depression taking serotonergic antidepressants. The authors say depletion studies do not show a causal link between serotonin and depression. No numeric effects in the abstract. (Not given) Methods, limits and fundingOutcomes: Change in mood after depletion Limitations: This studies LOWERING tryptophan, not giving extra. It cannot show that supplements lift mood. Studies differed in design and population. Funding and conflicts: Research support listed as non-US government; no conflict statement in the abstract. Read: abstract |
| Scotton 2019 Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. Int J Tryptophan Res · PMID 31523132 · DOI |
Narrative review |
Review of serotonin syndrome | Serotonergic drugs in general (tryptophan is not named in the abstract) Drugs |
Serotonin syndrome is a potentially life-threatening reaction to too much serotonin activity. Severe cases usually follow starting two or more serotonergic drugs at once, but can follow a single drug in a susceptible person, adding a second drug, or an overdose. Combining a monoamine oxidase inhibitor (MAOI) with other serotonergic drugs is especially dangerous. No numbers in the abstract. (Not applicable) Methods, limits and fundingOutcomes: Causes, features and management of serotonin syndrome Limitations: A review of drugs generally. The abstract does not mention tryptophan supplements, so it supports the general rule, not a rate for tryptophan. Funding and conflicts: No conflicts declared. Read: abstract |
| Shaw 2001 Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev · PMID 11687048 · DOI |
Systematic review |
64 2 randomised trials (64 people) with unipolar depression or dysthymia, out of 108 trials found |
Tryptophan or 5-hydroxytryptophan (5-HTP), results combined Oral Not given in the abstract Not given in the abstract · vs Placebo |
The two trials favoured the amino acid over placebo, but the reviewers say the evidence was not good enough to be conclusive. They add that proven antidepressants exist and that a possible link with eosinophilia-myalgia syndrome had not been explained. Peto odds ratio 4.10; risk difference 0.36; number needed to treat 2.78 (Peto OR 4.10 (1.28 to 13.15)) Methods, limits and fundingOutcomes: Depressive symptoms on rating scales Limitations: Only 2 of 108 trials met quality standards, and they were small. One of the two tested 5-HTP, not tryptophan. A 2001 review that has not been updated in the abstract. Funding and conflicts: No conflict of interest declared. Read: abstract |
| Shaw 2002 Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis. Aust N Z J Psychiatry · PMID 12169147 · DOI |
Systematic review meta analysis |
64 2 studies (one of 5-HTP, one of L-tryptophan), 64 patients, from 108 located |
L-tryptophan and 5-HTP Oral Not given in the abstract Not given in the abstract · vs Placebo |
The two included studies suggested the compounds were better than placebo, but the authors say the small size, publication bias and poor quality of other studies mean they are insufficiently evaluated. Peto OR 4.1 (Peto OR 4.1 (1.3 to 13.2)) Methods, limits and fundingOutcomes: Depressive symptoms Limitations: Only one tryptophan study was included. The authors say the result is doubtful because of small studies and possible publication bias. Search covered 1966 to 2000. Funding and conflicts: Not stated in the abstract. Read: abstract |
| Slutsker 1990 Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer. JAMA · PMID 2355442 |
Case control study |
Oregon: 58 patients with EMS, 30 asymptomatic controls from a random telephone survey and 63 volunteer controls | L-tryptophan products Oral supplement 1989 outbreak · vs Asymptomatic controls |
45 of 46 cases (98%) with known source had taken a product from one manufacturer, compared with 3 of 10 telephone-survey controls (30%) and 15 of 31 volunteer controls (48%). Cases' lots were more likely produced January to June 1989. The authors say the epidemic was caused by a contaminant or alteration in a subset of tryptophan from one company in Japan. 98% of cases vs 30% and 48% of the two control groups (Not given) Methods, limits and fundingOutcomes: Brand, source and manufacturer of tryptophan used Limitations: Case-control design; the contaminant was not identified in the abstract. Funding and conflicts: Not stated in the abstract. Read: abstract |
| Steinberg 1999 A placebo-controlled clinical trial of L-tryptophan in premenstrual dysphoria. Biol Psychiatry · PMID 10023508 · DOI |
Randomised controlled trial |
71 71 women with premenstrual dysphoric disorder (37 tryptophan, 34 placebo) |
L-tryptophan Oral 6 g a day 17 days a month (ovulation to day 3 of menstruation) for 3 cycles · vs Placebo, double-blind |
Mood symptoms fell significantly more with tryptophan than with placebo. Maximum luteal-phase mood score fell 34.5% with tryptophan and 10.4% with placebo (p = .004) (p = .004) Methods, limits and fundingOutcomes: Visual analogue scale scores for dysphoria, mood swings, tension and irritability Limitations: A single trial of 71 women, 1999. Results are self-rated mood scores. The amount used was high and is given here only as what the trial used. Funding not stated in the abstract. Funding and conflicts: Support listed as non-US government; no conflict statement in the abstract. Read: abstract |
| Stensrud 1992 L-tryptophan supplementation does not improve running performance. Int J Sports Med · PMID 1428380 · DOI |
Randomised controlled trial |
49 49 well-trained male runners aged 18 to 44 |
L-tryptophan Oral 1.2 g in total over 24 hours before a run One run to exhaustion after 24 hours of supplement · vs Placebo, double-blind |
No significant difference between the tryptophan and placebo groups. The authors conclude tryptophan did not improve running performance. No significant difference in improvement between groups (no numbers in the abstract). (Not given) Methods, limits and fundingOutcomes: Time to exhaustion running at 100% of maximal oxygen uptake Limitations: Trained men only; one short exposure. The abstract notes the trial was done to repeat an earlier report of a 49.4% gain (not read here). Funding and conflicts: Not stated in the abstract. Read: abstract |
| Sutanto 2022 The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression. Nutr Rev · PMID 33942088 · DOI |
Systematic review meta analysis |
18 articles collected; data from 4 articles were pooled (random-effects meta-analysis and meta-regression) | L-tryptophan supplement Oral supplement Pooled trials used less than 1 g and 1 g or more a day (the abstract gives no single trial dose) Not given in the abstract · vs Control groups (the abstract does not describe them) |
Tryptophan shortened the time spent awake after falling asleep. Doses of 1 g or more a day gave a shorter wake time than doses under 1 g. Other sleep components did not change. WASO -81.03 min per g (P = 0.017); SMD -1.08 (95% CI -1.89 to -0.28). Under 1 g vs 1 g or more: 56.55 vs 28.91 min (P = 0.001). (SMD -1.08 (-1.89 to -0.28)) Methods, limits and fundingOutcomes: Sleep quality, including wake after sleep onset (WASO); other sleep components Limitations: Only 4 of 18 collected articles could be pooled. The abstract does not give participant numbers, the populations studied or the risk of bias. The authors' conclusion that tryptophan 'can help improve sleep quality' rests on one sleep measure. Funding and conflicts: Not stated in the abstract. Read: abstract |
| s-fda-tryptophan US FDA statements on L-tryptophan supplements after the 1989 outbreak (recall and import alert) · Source |
Reference database n/a |
Methods, limits and fundingRead: not-read | ||
| s-medlineplus-amino MedlinePlus Medical Encyclopedia: Amino acids (review date 2025-01-21) · Source |
Reference database n/a |
Methods, limits and fundingRead: full-text | ||
| s-ods-tryptophan NIH Office of Dietary Supplements: fact sheet for tryptophan · Source |
Reference database n/a |
Methods, limits and fundingRead: not-read | ||
| s-usda-sr-legacy-tryptophan USDA FoodData Central, SR Legacy (April 2018 release): tryptophan content of common foods · Source |
Reference database n/a |
Methods, limits and fundingRead: full-text |
What we do not know yet
- No trial was read showing that extra tryptophan helps well-fed adults on a normal diet.
- No official upper intake limit was read (the NIH page was blocked).
- No source on supplements in pregnancy, breastfeeding or children was read.
- Food tryptophan and supplement tryptophan were not compared in trials.
- No current survey of product quality was read.
- Tryptophan for anxiety disorders, ADHD, pain and appetite was not researched here.
How new research is added
New studies are found by a saved PubMed search and placed in a review queue before the page changes.
Lab markers
What changed in blood or saliva tests during trials. A changed number is not the same as feeling or being healthier, and we give no "normal ranges".
Other 6
Time awake after falling asleep (minutes)
Shorter in pooled studies in trials
How many minutes a person is awake during the night after first falling asleep.
Low certaintyResults and what it means
Why it was measured
To see whether tryptophan lets people sleep through the night with fewer wake-ups.
Statistical vs. clinical meaning
Only one sleep measure improved; other sleep components did not change.
Safety implication
Drowsiness has been reported at higher amounts.
| Study | Result | People | Product |
|---|---|---|---|
| 19 | SMD -1.08 (95% CI -1.89 to -0.28); -81.03 min per g (P = 0.017) | 4 pooled studies of tryptophan supplements | L-tryptophan versus control |
Premenstrual mood symptom score
Lower with tryptophan in one trial in trials
A self-rated score for low mood, mood swings, tension and irritability in the late part of the cycle.
Low certaintyResults and what it means
Why it was measured
To see whether tryptophan lowers mood symptoms in women with PMDD.
Statistical vs. clinical meaning
A self-rated score from a single trial.
Safety implication
Side effects not described in the abstract.
| Study | Result | People | Product |
|---|---|---|---|
| 17 | 34.5% fall with tryptophan vs 10.4% with placebo (p = .004) | 71 women with PMDD | L-tryptophan vs placebo, ovulation to day 3 of menstruation |
Depression rating score (HDRS-29)
Lower in week 1 only in trials
A clinician-rated scale of depression symptoms.
Very low certaintyResults and what it means
Why it was measured
To see whether tryptophan added to fluoxetine speeds up improvement.
Statistical vs. clinical meaning
The benefit disappeared after the first week.
Safety implication
Daytime drowsiness at the higher amount used; no serotonin syndrome in 30 people.
| Study | Result | People | Product |
|---|---|---|---|
| 10 | Greater fall in HDRS-29 in the tryptophan/fluoxetine group in week 1; no significant difference later | 30 people with major depressive disorder | Tryptophan plus fluoxetine vs placebo plus fluoxetine |
Distance covered in the last 20 minutes of exercise
Higher with tryptophan in one small trial in trials
How far a person cycles in a fixed time at their best sustained speed after earlier hard efforts.
Low certaintyResults and what it means
Why it was measured
To see whether tryptophan delays tiredness in repeated hard exercise.
Statistical vs. clinical meaning
A separate trial of 49 trained runners found no difference.
Safety implication
Not reported in the abstract.
| Study | Result | People | Product |
|---|---|---|---|
| 7 | 12,526 +/- 1,617 m with tryptophan vs 11,959 +/- 1,753 m with placebo (p < .05) | 20 healthy young sportsmen | L-tryptophan vs placebo, double-blind crossover |
Blood serotonin
Lower after a low-tryptophan diet in trials
The amount of serotonin measured in blood serum.
Very low certaintyResults and what it means
Why it was measured
To see whether a low-tryptophan diet lowers serotonin in IBS-D.
Statistical vs. clinical meaning
Blood serotonin is not the same as brain serotonin.
Safety implication
None reported.
| Study | Result | People | Product |
|---|---|---|---|
| 3 | Baseline 198.2 +/- 38.1 ng/mL in IBS-D vs 142.3 +/- 36.4 in healthy people (p < 0.001); fell significantly after 12 weeks on the diet (p < 0.001) | 40 people with IBS-D and 40 healthy comparison people | Diet restricted in tryptophan for 12 weeks (no control group) |
Urinary 5-HIAA
Lower after a low-tryptophan diet in trials
A breakdown product of serotonin passed in urine.
Very low certaintyResults and what it means
Why it was measured
A marker of how much serotonin the body is turning over.
Statistical vs. clinical meaning
A lab marker only.
Safety implication
None reported.
| Study | Result | People | Product |
|---|---|---|---|
| 3 | Higher in IBS-D (7.7 +/- 1.5 vs 6.0 +/- 1.7 mg/24 h, p < 0.001); fell significantly after the diet | 40 people with IBS-D and 40 healthy people | Low-tryptophan diet, 12 weeks |
Safety
What studies and official sources say about side effects, medicines and who should check first. Each point shows what kind of evidence it comes from.
Main points to know 4
- A past contamination episode caused a serious illness. In 1989, an outbreak of eosinophilia-myalgia syndrome (EMS), a painful inflammatory illness, was linked to L-tryptophan supplements. Case-control studies found almost all cases had used tryptophan from a single manufacturer, and investigators tied it to changes in the manufacturing process. Sales were banned in New Mexico and a US recall followed. A 2023 review says no clear and convincing answer has been reached on which impurity, if any, was responsible. Case control studies and review 4 2 16 9
- Serotonin syndrome is a risk when serotonin-raising medicines are combined. A 2019 review says serotonin syndrome is a potentially life-threatening reaction to too much serotonin activity, and that combining a monoamine oxidase inhibitor (MAOI) with other serotonergic drugs is especially dangerous. Tryptophan is the starting material for serotonin, so the concern is plausible, but the review's abstract does not name tryptophan supplements. In one 30-person trial of tryptophan with fluoxetine, no cases occurred. Review and small trial; tryptophan specific risk not measured 13 10
- Drowsiness. In a small depression trial, the higher amount of tryptophan produced daytime drowsiness. Do not drive or use machinery until you know how it affects you. Randomised trial 10
- Kidney damage in animals only. In rats, high-tryptophan diets raised markers of kidney injury, and rats with kidney disease died more often on high amounts. This is animal evidence only. No human kidney study of tryptophan supplements was read, so people with kidney disease should ask a doctor. Animal study 6
Side effects 3
| Effect | How often | Severity and recovery | Evidence |
|---|---|---|---|
| Daytime drowsiness | Reported at the higher amount used in the fluoxetine trial; no rate in the abstract. | Mild Not described | Randomised trial 10 |
| Eosinophilia-myalgia syndrome (EMS): severe muscle pain with high eosinophil blood counts; inflammation of muscles, skin and lungs Linked to a 1989 outbreak from tryptophan from one manufacturer; the exact cause is unresolved. | Not given in the abstracts read. New Mexico: 11 of 11 cases had used L-tryptophan products vs 2 of 22 controls. | Can be serious and was described as incapacitating (New Mexico case definition) Not described in the abstracts read | Case control and review 4 2 16 9 |
| Side effects in general | The fibromyalgia trial (a three-ingredient product) reported mild side effects evenly spread between groups; the PMDD and runners' trials did not describe side effects in their abstracts. | Mild in the trials that reported them Not described | Randomised trial 11 17 |
Liver
No liver injury from tryptophan was found in the sources read. A liver-safety reference (LiverTox) was not opened for this page.
How often. No frequency was found.
Monitoring. No agency monitoring advice was found.
This is a safety connection. It is not evidence that Tryptophan supports liver health.
Medicines and supplements 3
| With | Why it matters | Importance | Evidence | What to do |
|---|---|---|---|---|
| Antidepressants that raise serotonin (SSRIs, MAOIs and similar medicines) prescription | Tryptophan is the starting material for serotonin, so extra tryptophan could add to the effect of serotonin-raising medicines (a plausible link; a 2019 review warns that combining serotonergic drugs, especially with an MAOI, can cause serotonin syndrome). | In the one 30-person trial with fluoxetine no serotonin syndrome occurred. The review's abstract does not name tryptophan, so the exact risk is not measured. | Review and small trial Low certainty 13 10 | Do not combine with antidepressants or other serotonin-raising medicines without a doctor or pharmacist. |
| Other serotonin-raising supplements or drugs (5-HTP, St. John's wort, certain pain and migraine medicines) supplement or prescription | Several products raise serotonin activity; stacking them can add up (stated generally in the 2019 review as combining serotonergic drugs). | The abstract names combining two or more serotonergic drugs as the usual trigger of severe cases but does not list these products. | Review Low certainty 13 | Ask a pharmacist before combining. |
| Sedatives and sleeping medicines prescription or supplement | Not studied in the sources read. Drowsiness was reported at higher tryptophan amounts, so added sleepiness is possible. | No interaction trial was read. | Inference from a single trial Not enough evidence 10 | Ask a pharmacist. |
Who should check first 4
| Situation | Advice | Evidence |
|---|---|---|
| Anyone taking antidepressants or other serotonin-raising medicines | Ask a doctor or pharmacist before using tryptophan supplements; see the interactions above. | Review and small trial 13 10 |
| Pregnancy and breastfeeding | No source read gave advice on tryptophan supplements in pregnancy or breastfeeding. Ask a doctor or midwife. MedlinePlus covers tryptophan only as an essential amino acid from food. | No source read 21 |
| Children | No source read gave advice on tryptophan supplements for children. Ask a doctor first. | No source read |
| Kidney disease | Animal studies suggest high tryptophan may harm the kidneys, especially in kidney disease. No human data were read. Ask a doctor. | Animal study 6 |
Overdose, product quality and regulators
Summary. Tryptophan from food is part of normal protein intake. Supplements are a different matter: a 1989 contamination episode and animal kidney findings are the main concerns found. No official upper intake limit was read.
Animal. A 2023 rat study found high-tryptophan diets raised blood urea nitrogen and caused focal kidney injury, and rats with kidney disease did worse. Animal evidence only.
High dose or long term signals. Daytime drowsiness at the higher amount in one trial. No long-term human safety study was read.
Overdose response. Not found in the sources read. If someone has taken a large amount, or has symptoms of serotonin syndrome, call emergency services or poison control.
Genotoxicity. Not researched.
Product quality is the central safety issue in the tryptophan story. The 1989 outbreak was linked to one manufacturer's product and to manufacturing changes. Whether today's supplements are free of such impurities was not researched for this page.
1989 EMS outbreak and manufacturing. Investigators found cases were linked to tryptophan from one company that had used less powdered carbon in a purification step and a new strain of fermenting bacteria. A chemical peak ('peak E') was more common in lots used by cases. A 2023 review says six components formed during production were suspected but no clear conclusion has been drawn. 2 16 9
Label accuracy and current product testing. Not researched. No current product survey was read.
| Body | Action | Date |
|---|---|---|
| MedlinePlus (US National Library of Medicine) (United States) | Lists tryptophan as one of nine essential amino acids that must come from food and says a balance across the whole day matters. It gives no supplement advice on this page. source | 2025-01-21 |
When to get medical help
- Severe muscle pain, weakness, shortness of breath, rash or swelling after taking tryptophan: stop and get medical help straight away (symptoms of the 1989 illness involved muscles, skin and lungs).
- New confusion or agitation, sweating, a racing heart, or muscle twitching or stiffness after combining tryptophan with antidepressants or other serotonin-raising medicines: call emergency services (possible serotonin syndrome, which the 2019 review says can be life-threatening).
- Someone has taken a large amount: call poison control or emergency services.
- Thoughts of harming yourself, or worsening mood after changing medicines or supplements: get help now.
Stop using the product and contact a clinician or emergency service. In the US, Poison Control is 1-800-222-1222.
General information only, not medical advice. Ask a clinician or pharmacist before use, especially with medicines, in pregnancy or with a health condition. See the Natural Remedy Safety guide.
Frequently asked questions
What is tryptophan?
Which foods have tryptophan?
All protein foods do. By USDA data, 3 oz of roasted chicken breast has about 308 mg and roasted turkey breast about 244 mg. An ounce of pumpkin seeds has about 163 mg and an ounce of cheddar about 155 mg. Soy foods, oats, eggs and milk also supply it.
Does turkey make you sleepy?
The sources read did not test this. By USDA data turkey is a good source of tryptophan but not unusually high: chicken breast, pumpkin seeds and cheddar have more per 100 g.
Does tryptophan help sleep?
It may shorten the time spent awake during the night. A 2022 review pooled 4 small studies and found that, but no other sleep measure improved. It is not proof that it treats insomnia.
Does tryptophan help mood or anxiety?
In healthy adults the results are mixed: 4 of 11 trials in a 2021 review found better mood or less negative feeling. Those trials do not show it treats depression or an anxiety disorder.
Can tryptophan treat depression?
Is tryptophan safe with antidepressants?
What was the 1989 tryptophan scare?
An outbreak of a painful illness called eosinophilia-myalgia syndrome (EMS) was linked to L-tryptophan supplements. Studies found nearly all cases used tryptophan from one manufacturer, tied to changes in its production process. Sales were banned in New Mexico and a US recall followed. The exact cause has not been settled.
Is tryptophan the same as 5-HTP?
No. 5-HTP is a related compound one step closer to serotonin. It has its own page. The Cochrane depression review combined trials of the two.
Does tryptophan improve sports performance?
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Editorial transparency
- Written by
- AlternativeMed editorial team. Research compiled with AI assistance, then checked against the sources listed.
- Medical review
- None. This page has not been reviewed by a physician or pharmacist.
- First published
- 2026-10-26
- Last substantive update
- 2026-10-26
- How we research
- We started from our existing tryptophan summary, read the MedlinePlus amino acids page, checked food values in saved USDA FoodData Central data, and re-read PubMed abstracts for reviews, trials and case-control studies. Only abstracts were read for studies. The NIH Office of Dietary Supplements and FDA pages could not be read and are marked unread.
- How we rate evidence
- See "How we rate evidence" in the Evidence tab.
- Independence
- No product is promoted on this page. No affiliate links are shown. Four authors of the 2023 safety review are employed by a company; its abstract does not say what the company sells. Trials of tryptophan products may have manufacturer links not stated in abstracts.
Sources 23
Each source was opened and checked. Where we read only the abstract, it says so. The small numbers in the text point here.
- Agus A, Planchais J, Sokol H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease.. Cell Host Microbe. 2018. PMID 29902437. DOI 10.1016/j.chom.2018.05.003. (abstract)
- Belongia EA, Hedberg CW, Gleich GJ, White KE, Mayeno AN, Loegering DA et al.. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use.. N Engl J Med. 1990. PMID 2370887. DOI 10.1056/NEJM199008093230601. (abstract)
- Chojnacki C, Medrek-Socha M, Blonska A, Zajdel R, Chojnacki J, Poplawski T. A Reduced Tryptophan Diet in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Improves Their Abdominal Symptoms and Their Quality of Life through Reduction of Serotonin Levels and Its Urinary Metabolites.. Int J Mol Sci. 2022. PMID 36499643. DOI 10.3390/ijms232315314. (abstract)
- Eidson M, Philen RM, Sewell CM, Voorhees R, Kilbourne EM. L-tryptophan and eosinophilia-myalgia syndrome in New Mexico.. Lancet. 1990. PMID 1969024. DOI 10.1016/0140-6736(90)90421-z. (abstract)
- Gao K, Mu CL, Farzi A, Zhu WY. Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain.. Adv Nutr. 2020. PMID 31825083. DOI 10.1093/advances/nmz127. (abstract)
- Hu D, Liu J, Yu W, Li C, Huang L, Mao W. Tryptophan intake, not always the more the better.. Front Nutr. 2023. PMID 37113297. DOI 10.3389/fnut.2023.1140054. (abstract)
- Javierre C, Segura R, Ventura JL, Suárez A, Rosés JM. L-tryptophan supplementation can decrease fatigue perception during an aerobic exercise with supramaximal intercalated anaerobic bouts in young healthy men.. Int J Neurosci. 2010. PMID 20402569. DOI 10.3109/00207450903389404. (abstract)
- Kikuchi AM, Tanabe A, Iwahori Y. A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning.. J Diet Suppl. 2021. PMID 32272859. DOI 10.1080/19390211.2020.1746725. (abstract)
- Ko SM, Park JE, Heo IK, Shin YU, Kim YH, Son WC. Safety concerns regarding impurities in L-Tryptophan associated with eosinophilia myalgia syndrome.. Food Chem Toxicol. 2023. PMID 37453474. DOI 10.1016/j.fct.2023.113946. (abstract)
- Levitan RD, Shen JH, Jindal R, Driver HS, Kennedy SH, Shapiro CM. Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.. J Psychiatry Neurosci. 2000. PMID 11022398. (abstract)
- Rosselló Aubach L, Fornós Roca X, Fernández Álvarez ME. Effects of Coenzyme Q10, Tryptophan, and Magnesium Supplementation on Fatigue in Patients with Fibromyalgia - A Randomized Trial.. J Diet Suppl. 2025. PMID 40151031. DOI 10.1080/19390211.2025.2483269. (abstract)
- Ruhé HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies.. Mol Psychiatry. 2007. PMID 17389902. DOI 10.1038/sj.mp.4001949. (abstract)
- Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions.. Int J Tryptophan Res. 2019. PMID 31523132. DOI 10.1177/1178646919873925. (abstract)
- Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression.. Cochrane Database Syst Rev. 2001. PMID 11687048. DOI 10.1002/14651858.CD003198. (abstract)
- Shaw K, Turner J, Del Mar C. Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis.. Aust N Z J Psychiatry. 2002. PMID 12169147. DOI 10.1046/j.1440-1614.2002.01046.x. (abstract)
- Slutsker L, Hoesly FC, Miller L, Williams LP, Watson JC, Fleming DW. Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer.. JAMA. 1990. PMID 2355442. (abstract)
- Steinberg S, Annable L, Young SN, Liyanage N. A placebo-controlled clinical trial of L-tryptophan in premenstrual dysphoria.. Biol Psychiatry. 1999. PMID 10023508. DOI 10.1016/s0006-3223(98)00005-5. (abstract)
- Stensrud T, Ingjer F, Holm H, Strømme SB. L-tryptophan supplementation does not improve running performance.. Int J Sports Med. 1992. PMID 1428380. DOI 10.1055/s-2007-1021302. (abstract)
- Sutanto CN, Loh WW, Kim JE. The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression.. Nutr Rev. 2022. PMID 33942088. DOI 10.1093/nutrit/nuab027. (abstract)
- . US FDA statements on L-tryptophan supplements after the 1989 outbreak (recall and import alert). . . (not-read)
- . MedlinePlus Medical Encyclopedia: Amino acids (review date 2025-01-21). . . (full-text)
- . NIH Office of Dietary Supplements: fact sheet for tryptophan. . . (not-read)
- . USDA FoodData Central, SR Legacy (April 2018 release): tryptophan content of common foods. . . (full-text)
Where to buy
Check the label first. Whatever you buy, look for these:
- The amount of the active ingredient per serving, not just the front-label claim
- A third-party testing mark (USP, NSF or ConsumerLab)
- Other ingredients and allergens
- Ask a pharmacist about interactions with your medicines
Talk to a pharmacist or doctor before you start any supplement, especially if you take medicines. See the Safety tab for interactions.
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