You have read that tryptophan is the stuff of good moods and restful sleep. Chemists sell capsules of L-tryptophan, and some people in online forums swear by them. But what does the body actually do with tryptophan, and why does only a small share of it end up as serotonin?
This article explains tryptophan metabolism step by step: which routes exist, what stress and inflammation change at the most important junction, and what is known about L-tryptophan for sleep problems.
At a glance
- What it's about: Tryptophan is seen as a building block for good mood and good sleep. What does the body actually do with it?
- Possible causes: Most tryptophan is broken down via the kynurenine pathway. Cortisol and inflammation can push even more along this route.
- What you can do: Eat a balanced diet with enough protein, stay active and look after your sleep. Do not combine L-tryptophan with antidepressants without medical advice.
- What can be measured: Tryptophan, the kynurenine pathway, serotonin and other messengers in urine, plus cortisol and melatonin in saliva, as building blocks.
What is tryptophan?
Tryptophan is an amino acid, in other words a building block of protein. The body cannot make it itself, so it has to come from food. The body needs it to build its own proteins and as the only starting material for the messenger serotonin (PubMed 20651948). Tryptophan is found in protein-containing foods such as dairy products, eggs, pulses, nuts, grains, fish and meat.
Tryptophan, serotonin, melatonin: the well-known route
The body makes serotonin from tryptophan. Serotonin is a messenger in the brain, but also in the gut. In the brain, serotonin is involved in mood, behaviour and thinking (PubMed 20651948).
In the pineal gland, a small gland in the brain, serotonin is turned into the sleep hormone melatonin. There is an intermediate step in between, N-acetylserotonin. Melatonin is made mainly at night and tells the internal clock: it is dark now. Light slows this production (PubMed 12111543) (PubMed 29318587).
This is the route most people know. But it is not the main route.
The kynurenine pathway: the big junction
About 95 per cent of the tryptophan from food is broken down via a different route, the kynurenine pathway. Most of this takes place in the liver (PubMed 28469468). At the end of this pathway are, among other things, niacin (vitamin B3) and NAD, a substance every cell needs for its energy metabolism. Intermediate products are also formed that can influence the immune system and nerve cells (PubMed 28469468).
How much tryptophan flows into this pathway is controlled mainly by two enzymes:
- TDO in the liver
- IDO in many other tissues, including immune cells
Think of it like a set of points on a railway. If they are switched more towards kynurenine, less tryptophan is left for other routes. In this way, the kynurenine pathway also affects how much tryptophan is available to the brain for making serotonin (PubMed 28469468).
Tryptophan and cortisol: what stress and inflammation change
Stress: The stress hormone cortisol is one of the glucocorticoids. These hormones switch on the liver enzyme TDO (PubMed 28469468). So under stress, more tryptophan can be steered towards kynurenine.
Inflammation: When the immune system is activated, the kynurenine pathway outside the liver plays a bigger role, driven by the enzyme IDO (PubMed 28469468). The enzymes of this pathway respond to signals from nutrition and inflammation, and inflammation in the body can contribute to kynurenine building up in the brain as well (PubMed 28751584).
An example from medicine shows how marked this can be: people treated with the immune messenger interferon-alpha afterwards had less tryptophan and more kynurenine in their blood, and their scores for depressive symptoms rose (PubMed 32853625). This is a special situation with a strong inflammatory trigger, not an everyday state.
Another finding is encouraging: research suggests that trained muscles can process more kynurenine and so slow its build-up (PubMed 28751584).
What this can mean for mood and sleep
Researchers see tryptophan metabolism as a possible link between inflammation, stress and mood. A meta-analysis found that, on average, people with depression had altered levels of individual substances in the kynurenine pathway. However, the studies differed widely, and more research is needed (PubMed 29608993).
As for sleep: melatonin is made from serotonin, and serotonin from tryptophan. Whether altered tryptophan metabolism measurably affects a person's sleep in everyday life cannot be concluded from this alone.
So it is important to keep things in perspective: tryptophan metabolism is one building block among many. Depression is a serious illness that should be treated by a doctor or psychotherapist, and it cannot be read from a lab value.
L-tryptophan for sleep problems: what is known
L-tryptophan is sold as a food supplement. A 2022 meta-analysis was only able to pool four studies. In them, time spent awake after falling asleep was shorter, while other aspects of sleep did not change (PubMed 33942088). So the evidence is limited. No recommendation can be drawn from it.
Safety note: L-tryptophan is not harmless for everyone. Together with medicines that affect serotonin, especially certain antidepressants such as MAO inhibitors, it can trigger serotonin syndrome. Signs include confusion, fever, shivering, heavy sweating and muscle twitching (PubMed 7576268). This is an emergency.
If you take antidepressants or other medication, talk to your doctor before taking any L-tryptophan. Do not stop a prescribed medication without talking to your doctor first.
What you can do yourself
- Eat a balanced diet: Protein-containing foods spread over the day provide tryptophan as a matter of course.
- Stay active: Regular exercise influences the kynurenine pathway in the muscles (PubMed 28751584) and gives your day structure.
- Light and darkness: Daylight in the morning and dimmed lighting in the evening support the melatonin rhythm.
- Keep an eye on stress: Take breaks, keep regular sleep times and get help if the strain becomes too much. Read more about stress and sleep in the article Waking up at 3am every night.
Warning signs: when to see a doctor
- Your mood has been low for more than two weeks, or you hardly enjoy anything any more.
- You have been sleeping badly for weeks and can barely cope during the day.
- You take antidepressants and are thinking about also taking L-tryptophan.
- After taking it, you develop confusion, fever, shivering or muscle twitching.
If you are having thoughts of harming yourself, contact the emergency number 112 straight away, or in Germany the Telefonseelsorge helpline on 0800 111 0 111.
Measuring tryptophan metabolism
- The neurotransmitter tryptophan metabolism test is an at-home urine test. The laboratory measures tryptophan and the kynurenine pathway with kynurenine, kynurenic acid, 3-OH-kynurenine, quinolinic acid and NAD, calculates the activity of the enzymes IDO and KMO and determines neopterin as a marker of immune activation, plus serotonin, dopamine, adrenaline and noradrenaline. A 10-minute results consultation is included.
- The plus version also covers GABA, glutamate, phenylalanine and tyrosine, markers for vitamins B6, B12 and B3, methylation, energy metabolism, and TMA and TMAO, among others.
- The Stress & sleep lab package combines tryptophan metabolism with a cortisol day profile with DHEA, melatonin in night-time saliva, a cell stress profile and the Epigenetics Stress Monitor.
The results show metabolism in the body, not in the brain. They are building blocks for a conversation, not a diagnosis. The ORY team of experts, your doctor or your naturopath can help you interpret them.
In brief
- Tryptophan is an amino acid from food and the only starting material for serotonin.
- At night, the sleep hormone melatonin is made from serotonin.
- About 95 per cent of tryptophan is broken down via the kynurenine pathway.
- Cortisol and inflammation can steer more tryptophan into this pathway.
- L-tryptophan has been studied only a little for sleep problems and can interact dangerously with antidepressants.
Frequently asked questions
Why does tryptophan metabolism matter?
It produces proteins, serotonin and melatonin, and via the kynurenine pathway niacin and NAD (PubMed 28469468). It therefore links nutrition, energy metabolism, the immune system and messengers of the nervous system.
How are serotonin and melatonin made from tryptophan?
The body makes serotonin from tryptophan. In the pineal gland, serotonin is converted at night into melatonin via N-acetylserotonin (PubMed 12111543).
What does cortisol have to do with tryptophan?
Cortisol is one of the glucocorticoids, and these switch on the liver enzyme TDO. As a result, more tryptophan can flow into the kynurenine pathway (PubMed 28469468).
What does L-tryptophan do for sleep problems?
A meta-analysis found shorter waking time after falling asleep in a few studies, but no change in other aspects of sleep (PubMed 33942088). For ongoing sleep problems, talking to a doctor is the better first step.
Can you take L-tryptophan with antidepressants?
Only after talking to your doctor. Together with certain antidepressants, especially MAO inhibitors, it can trigger serotonin syndrome (PubMed 7576268).
Can tryptophan metabolism be measured?
Yes, tryptophan, substances of the kynurenine pathway and messengers such as serotonin can be measured in urine. The results show metabolism in the body, not in the brain, and should be discussed with a qualified professional.
Important note: This article does not replace medical advice, diagnosis or treatment. It is for general information only. If your symptoms are persistent or severe, please contact your doctor.
Sources
- Richard DM et al. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009. PubMed 20651948
- Ganguly S et al. Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation. Cell Tissue Res. 2002. PubMed 12111543
- Zisapel N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol. 2018. PubMed 29318587
- Badawy AA. Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects. Int J Tryptophan Res. 2017. PubMed 28469468
- Cervenka I et al. Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health. Science. 2017. PubMed 28751584
- Hunt C et al. Effect of immune activation on the kynurenine pathway and depression symptoms – A systematic review and meta-analysis. Neurosci Biobehav Rev. 2020. PubMed 32853625
- Ogyu K et al. Kynurenine pathway in depression: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2018. PubMed 29608993
- Sutanto CN et al. The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression. Nutr Rev. 2022. PubMed 33942088
- Sporer KA. The serotonin syndrome. Implicated drugs, pathophysiology and management. Drug Saf. 1995. PubMed 7576268
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