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Tryptophan: from food to serotonin, roles and sources

Essential amino acid and precursor to serotonin, melatonin and NAD+: requirements, richest foods, what studies show about mood and sleep, and precautions for use.

Tryptophan: from food to serotonin, roles and sources

Tryptophan has a persistent reputation: turkey supposedly makes you sleepy after a festive meal. Reality is more interesting. This essential amino acid is used to make serotonin, melatonin and even some NAD+, but what we eat influences its passage into the brain only indirectly. Here are its roles, the foods richest in it, what studies show about mood and sleep, and precautions to know.

Key takeaways

  • Tryptophan is an essential amino acid: adults need around 4mg per kilogram per day.
  • It is used to make proteins, serotonin, melatonin and, through kynurenine, niacin and NAD+.
  • Poultry, fish, cheese, soy and seeds provide plenty; turkey is nothing exceptional.
  • As a supplement, measured effects on mood and sleep are modest and uncertain; it should be avoided with certain antidepressants and triptans.

What is tryptophan?

Tryptophan is one of the essential amino acids: the body cannot make it, so it must come from food. It is also the least abundant amino acid in the body. Only its L form, found in foods, is used to build proteins and crosses the barrier protecting the brain.

In the blood, 75 to 85% of tryptophan circulates bound to a transport protein, albumin. Unlike taurine, often grouped with amino acids but not incorporated into proteins, tryptophan is first and foremost a building material.

What does tryptophan do in the body?

Beyond proteins, tryptophan follows two major pathways: the much-publicised but minor serotonin pathway, and the kynurenine pathway, which consumes most of it.

Serotonin and melatonin. A first enzyme, tryptophan hydroxylase, converts tryptophan into 5-hydroxytryptophan (5-HTP). This is the rate-limiting step, which sets the pace of production. A second enzyme, using vitamin B6 as a cofactor, then converts 5-HTP into serotonin. At night, the pineal gland converts some serotonin into melatonin, the hormone that signals darkness to the body.

These pathways use only a small fraction of tryptophan: around 3% of dietary tryptophan is used to make serotonin throughout the body, and only 1% in the brain. Nearly 95% of the body's serotonin is in the digestive tract. For the role of the sleep hormone, see our article on sleep and melatonin.

Kynurenine, niacin and NAD+. The kynurenine pathway accounts for around 90% of tryptophan breakdown. It produces several molecules active in the brain and leads, among other things, to quinolinic acid, from which the body can make NAD+, a coenzyme essential to reactions producing cellular energy. Our article on NAD+ and its roles explains this molecule.

This pathway also supplies niacin (vitamin B3), but with low efficiency: according to EFSA, around 60mg of tryptophan is needed to obtain 1mg of niacin.

How much tryptophan do you need each day?

The WHO, FAO and United Nations University expert committee estimates adult requirements at 4mg per kilogram of body weight per day, around 280mg for a 70 kg person. Usual intake is much higher: around 900 to 1,000mg daily according to a reference review. With a varied diet sufficiently rich in protein, requirements are therefore easily met.

Which foods are richest in tryptophan?

Tryptophan accompanies protein: it is found mainly in poultry, fish, mature cheeses, soy, nuts and seeds. Values below come from the US Department of Agriculture nutrition database; serving amounts are rounded.

Food Per 100 g Typical serving Per serving
Dried pumpkin seeds 576mg 30 g 170mg
Parmesan 482mg 20 g 95mg
Roast chicken breast 362mg 120 g 435mg
Roast turkey breast 287 to 364mg 120 g 345 to 435mg
Cooked farmed salmon 248mg 120 g 300mg
Firm tofu 235mg 125 g 295mg
Canned tuna in water, drained 209mg 100 g 210mg
Whole egg 167mg 2 eggs (100 g) 165mg
Cooked lentils 81mg 200 g 160mg
Rolled oats 182mg 40 g 75mg
Whole milk 40mg 250 ml 100mg
Banana 9mg 1 fruit (120 g) 11mg

The turkey myth

Turkey is no richer in tryptophan than chicken: 287 to 364mg per 100 g of roast breast, compared with 362mg for chicken breast. Above all, like any meat, it provides many other amino acids that compete with tryptophan to enter the brain. In a reference review, the ratio of tryptophan to these competitors is 0.043 for turkey versus 0.046 for chicken: nothing sets it apart.

Why do carbohydrates influence its entry into the brain?

To enter the brain, tryptophan uses a transporter shared with other large neutral amino acids, such as leucine, valine and tyrosine. Because this transporter is nearly saturated, it is the ratio of tryptophan to competitors that matters, more than its absolute quantity.

A carbohydrate-rich meal triggers insulin secretion, lowering blood levels of competing amino acids: tryptophan then gains ground. A protein-rich meal does the opposite. In eight adults who tested both options, carbohydrate-rich and protein-rich breakfasts produced a median difference of 54% in this ratio. The study did not measure mood or sleep.

Does tryptophan affect mood?

The link between tryptophan and mood is observed in one direction: when researchers abruptly lower blood tryptophan, mood worsens in some people. The reverse, adding more, gives more modest results. A systematic review of 11 trials in healthy adults included four showing an effect on negative or positive emotions, at doses of 0.14 to 3 g daily, but no effect on aggression.

In people with depression, a Cochrane review identified 108 trials of tryptophan and 5-HTP but judged only two sufficiently rigorous, totalling 64 patients. Their favourable results were of insufficient quality to draw conclusions.

Does tryptophan help with sleep?

A meta-analysis published in 2022 pooled 18 articles, four of which could be analysed together. Tryptophan reduced time awake after sleep onset, particularly from 1 g daily, but did not improve other sleep measures. These doses exceed the amount supplied by an ordinary meal. Melatonin, by contrast, has an authorised claim: it “contributes to the reduction of time taken to fall asleep”, with 1mg taken before bedtime.

Tryptophan or 5-HTP: what is the difference?

5-HTP is the product of the rate-limiting step described above. In supplements, it is extracted from seeds of an African plant, Griffonia simplicifolia. Taking it directly bypasses the natural brake on serotonin production, and 5-HTP does not supply the kynurenine or NAD+ pathways. It is therefore not simply equivalent to tryptophan.

It raises the same interaction questions with medicines acting on serotonin. Analyses have also detected an impurity, 4,5-tryptophan-dione, in some commercial 5-HTP samples, calling for attention to product quality.

Is tryptophan dangerous?

The eosinophilia-myalgia syndrome episode

In 1989, an epidemic of eosinophilia-myalgia syndrome, combining disabling muscle pain and an excess of certain white blood cells, affected the United States. By 10 July 1990, 1,531 cases had been reported, including 27 deaths. An investigation in Minnesota showed that 97% of affected people whose source was known had consumed tryptophan from the same manufacturer, compared with 60% of controls. The implicated batches were associated with manufacturing changes: less purification charcoal and a new bacterial strain.

The data therefore point to a contaminant associated with these production conditions, rather than tryptophan itself. Over-the-counter preparations had been withdrawn from the US market from November 1989.

Serotonin syndrome and interactions

Tryptophan increases serotonin production. Combined with medicines that also act on serotonin, it creates a risk of serotonin syndrome: agitation, sweating, fever, tremor and exaggerated reflexes, including severe forms. The first description of such a syndrome, in 1960, specifically concerned combining L-tryptophan with a monoamine oxidase inhibitor (MAOI) antidepressant. The main implicated products are:

  • antidepressants (MAOIs, SSRIs, SNRIs, tricyclics);
  • triptans, used for migraine;
  • certain opioid painkillers, such as tramadol;
  • St John's wort, a herb.

L-tryptophan is also included in combination formulas such as Hexagon® Zen complex, which combines it with magnesium bisglycinate, passionflower, taurine and vitamin B6: these precautions apply to any formula containing it.

Finally, safety data on tryptophan supplements during pregnancy and breastfeeding are too limited to recommend use: advice from a healthcare professional is necessary. No health claim is authorised for tryptophan in the European Union: a supplement cannot attribute effects on mood or sleep to it.

Frequently asked questions

Is banana rich in tryptophan?

No. A medium banana provides about ten milligrams, around forty times less than a serving of chicken breast. It often appears on lists of tryptophan sources, but its content is very low.

Does a glass of warm milk help you sleep?

A 250 ml glass of whole milk supplies around 100mg tryptophan, far below the doses of at least 1 g used in sleep trials. If this ritual helps some people relax, its tryptophan content alone cannot explain an effect.

Can you be deficient in tryptophan?

This is rare with a varied diet: usual intake is three to four times the estimated requirement. The risk mainly concerns very low-protein diets and malnutrition, which warrant medical care.

Is tryptophan a dopamine precursor?

No. Dopamine and noradrenaline are made from another amino acid, tyrosine. Tryptophan leads instead to serotonin, melatonin and kynurenine derivatives.

Does tryptophan cause weight loss?

No weight-related claim is authorised for tryptophan, and the studies presented here do not address that question. Lasting weight loss rests on balanced eating and physical activity, not an isolated amino acid.

Can tryptophan be given to a child?

The cited trials were conducted in adults. In children and adolescents, a tryptophan supplement should only be considered on medical advice, especially as interactions with serotonin medicines remain possible.

Conclusion

Tryptophan is an essential amino acid with multiple roles: proteins, serotonin, melatonin and, for most of its breakdown, the kynurenine pathway, which can lead to NAD+. A varied diet supplies more than enough, with nothing exceptional about turkey. As a supplement, its measured effects on mood and sleep remain modest and rely on few robust trials, while interaction risks with serotonin medicines are very real. To place it among other approaches, see our article on stress and ingredients studied for it.

Sources

  1. Richard DM et al. (2009). L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. International Journal of Tryptophan Research, 2, 45-60. doi:10.4137/IJTR.S2129
  2. WHO, FAO, UNU (2007). Protein and amino acid requirements in human nutrition: report of a joint WHO/FAO/UNU expert consultation. WHO Technical Report Series, 935. iris.who.int
  3. EFSA NDA Panel (2014). Scientific Opinion on Dietary Reference Values for niacin. EFSA Journal, 12(7), 3759. efsa.europa.eu
  4. U.S. Department of Agriculture, Agricultural Research Service. FoodData Central, SR Legacy (April 2018). fdc.nal.usda.gov
  5. Wurtman RJ et al. (2003). Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios. American Journal of Clinical Nutrition, 77(1), 128-132. doi:10.1093/ajcn/77.1.128
  6. Young SN (2013). Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects. Journal of Psychiatry & Neuroscience, 38(5), 294-305. doi:10.1503/jpn.120209
  7. Kikuchi AM, Tanabe A, Iwahori Y (2021). A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning. Journal of Dietary Supplements, 18(3), 316-333. doi:10.1080/19390211.2020.1746725
  8. Shaw K, Turner J, Del Mar C (2001). Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database of Systematic Reviews, (3), CD003198. doi:10.1002/14651858.CD003198
  9. Sutanto CN, Loh WW, Kim JE (2022). The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression. Nutrition Reviews, 80(2), 306-316. doi:10.1093/nutrit/nuab027
  10. Maffei ME (2020). 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. International Journal of Molecular Sciences, 22(1), 181. doi:10.3390/ijms22010181
  11. Swygert LA et al. (1990). Eosinophilia-myalgia syndrome. Results of national surveillance. JAMA, 264(13), 1698-1703. doi:10.1001/jama.1990.03450130070029
  12. Belongia EA et al. (1990). An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. New England Journal of Medicine, 323(6), 357-365. doi:10.1056/NEJM199008093230601
  13. Scotton WJ et al. (2019). Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. International Journal of Tryptophan Research, 12, 1178646919873925. doi:10.1177/1178646919873925
  14. Commission Regulation (EU) No 432/2012 of 16 May 2012 establishing a list of permitted health claims made on foods. Official Journal of the European Union, L 136, 1-40. eur-lex.europa.eu

Food supplements do not replace a varied, balanced diet or a healthy lifestyle. Ask a healthcare professional for advice if you are taking medication, pregnant or breastfeeding.

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