Tryptophan gets mentioned a lot in conversations about sleep and mood. It’s one of the nine essential amino acids your body cannot make on its own, so you need to get it from food or supplements. Beyond its role in building proteins, tryptophan serves as the raw material for several important compounds, including serotonin (the neurotransmitter linked to mood regulation) and melatonin (the hormone that helps regulate your sleep-wake cycle) [1].

The supplement form is called L-tryptophan because amino acids come in two mirror-image forms, and the L-form is the one your body can actually use. This is the version that can cross the blood-brain barrier and get converted into serotonin.

Where does tryptophan come from?

You can get tryptophan from protein-rich foods. Good sources include:

Turkey and chicken (yes, the turkey-makes-you-sleepy idea has some basis, though the effect is probably overstated)
Fish, particularly salmon and tuna
Eggs
Cheese and milk
Nuts and seeds, especially pumpkin seeds
Oats
Bananas
Dark chocolate

The challenge is that tryptophan competes with other amino acids to cross the blood-brain barrier. Eating a high-protein meal actually floods your bloodstream with amino acids that compete with tryptophan for transport. Paradoxically, eating carbohydrates alongside protein might help more tryptophan reach your brain, because the insulin spike clears competing amino acids from your bloodstream [2].

This is one reason some people take tryptophan supplements rather than trying to get more from food. A supplement delivers tryptophan without the competing amino acids.

How tryptophan works in your body

Once tryptophan enters your brain, it gets converted through a series of steps:

Tryptophan to 5-HTP: The enzyme tryptophan hydroxylase converts tryptophan to 5-hydroxytryptophan (5-HTP).
5-HTP to serotonin: Another enzyme then converts 5-HTP to serotonin.
Serotonin to melatonin: In the pineal gland, serotonin can be further converted to melatonin when darkness signals production.

Tryptophan also feeds into the kynurenine pathway, which produces compounds involved in immune function and niacin (vitamin B3) synthesis. Roughly 95% of dietary tryptophan goes down this pathway rather than towards serotonin production [3].

What the research shows about tryptophan benefits

1. Sleep quality

This is the benefit most people are interested in, and the evidence is reasonably supportive.

A systematic review and meta-analysis published in 2021 looked at four randomised controlled trials examining tryptophan supplementation and sleep [4]. The researchers found that tryptophan supplementation reduced the total time participants spent awake after initially falling asleep (a measure called WASO, or wake after sleep onset). The effect was most pronounced at doses of 1 gram or higher.

The logic is straightforward: more tryptophan means more serotonin, and serotonin is the precursor to melatonin. But the relationship isn’t always that simple in practice. Individual responses vary considerably, and factors like the timing of supplementation, what else you’ve eaten, and your baseline sleep quality all influence results.

One thing worth noting: tryptophan supplements seem to work better for people who have genuine trouble staying asleep rather than those who primarily struggle to fall asleep initially. If your main problem is lying awake for ages before sleep comes, melatonin or other approaches might work better.

For sleep purposes, most studies use doses between 1-5 grams, taken about an hour before bed. Starting lower and adjusting based on response makes sense.

2. Depression

The connection between tryptophan and depression has interested researchers for decades. The reasoning is simple enough: low serotonin is associated with depression, tryptophan makes serotonin, so perhaps boosting tryptophan could help.

A meta-analysis of 24 studies with 1,537 participants found that blood tryptophan levels were significantly lower in people with depression compared to healthy controls [5]. The difference was largest in people who hadn’t yet started antidepressant treatment.

This finding is consistent with the serotonin hypothesis of depression, though it doesn’t prove that taking tryptophan supplements will lift your mood. Correlation isn’t causation. It’s possible that depression causes low tryptophan (perhaps through increased breakdown via the kynurenine pathway) rather than low tryptophan causing depression.

There have been some small studies showing benefits from tryptophan supplementation in depression, but the evidence isn’t strong enough to recommend it as a standalone treatment. If you’re dealing with clinical depression, this isn’t something to self-treat with supplements.

3. Premenstrual dysphoric disorder (PMDD)

PMDD is a severe form of premenstrual syndrome affecting roughly 3-8% of menstruating women. Symptoms include marked irritability, depression, mood swings, and anxiety that show up in the days before menstruation and interfere significantly with daily life.

One randomised controlled trial looked at 71 women with PMDD who took either 6 grams of tryptophan daily or placebo during the luteal phase (from ovulation to day 3 of menstruation) [6]. The tryptophan group showed improvements in irritability, mood swings, tension, and overall quality of life compared to the placebo group.

The proposed mechanism involves serotonin. Fluctuations in oestrogen and progesterone during the menstrual cycle affect serotonin signalling, and women with PMDD may be particularly sensitive to these changes. Boosting serotonin production through tryptophan supplementation might buffer against this sensitivity.

This is interesting but it’s a single study. If you have PMDD, other approaches including selective serotonin reuptake inhibitors (SSRIs), hormonal contraceptives, and cognitive behavioural therapy have more robust evidence behind them. Tryptophan might be worth discussing with your doctor as an adjunct, but probably not as a first-line treatment.

4. Aggressive behaviour and impulse control

Serotonin plays a role in inhibiting aggressive and impulsive behaviours. Low serotonin activity has been linked to increased aggression in both animal and human studies [7].

A double-blind crossover study of 39 people described as having “argumentative personality traits” found that tryptophan supplementation reduced quarrelsome and dominant behaviours while increasing agreeable and affiliative traits [8]. The effects were more pronounced in men.

Another randomised controlled trial in 23 boys with aggressive personalities found that tryptophan reduced impulsive behaviour and improved their ability to recognise facial emotions compared to placebo [9].

These are small studies, and “aggressive personality traits” is a broad description that doesn’t map neatly onto clinical diagnoses. The findings are consistent with what we know about serotonin’s role in behaviour regulation, but they don’t mean tryptophan supplements will transform someone’s personality. If you or someone you know struggles with anger management or impulse control, proper psychological support is more appropriate than supplements.

Side effects and the EMS incident

I should address the elephant in the room. In 1989, an outbreak of a serious condition called eosinophilia-myalgia syndrome (EMS) was linked to tryptophan supplements [10]. Over 1,500 people became ill in the United States, with symptoms including severe muscle pain, fatigue, skin changes, hair loss, and neurological problems. At least 37 deaths were attributed to the outbreak.

Investigation traced the problem to contaminated batches from a single Japanese manufacturer that had changed its production process. The contaminant, not tryptophan itself, caused EMS. After the contaminated products were removed from the market, new cases stopped appearing.

This incident led to tryptophan supplements being banned or restricted in several countries for years. The ban has since been lifted in most places, and properly manufactured tryptophan supplements have not been associated with EMS in the decades since.

Still, this history underlines an important point about supplement quality. Buying from reputable manufacturers who follow good manufacturing practices matters.

Other reported side effects of tryptophan at normal doses include:

Drowsiness (unsurprising given its role in sleep)
Nausea, stomach discomfort, or diarrhoea
Dry mouth
Headache
Dizziness
Blurred vision
Loss of appetite
Sweating
Heartburn or hiccups

Most of these are mild and dose-dependent. Taking tryptophan with food may reduce gastrointestinal side effects.

Contraindications and safety warnings

1. Pregnancy, breastfeeding, and impaired liver or kidney function

There isn’t enough safety data to know whether tryptophan supplements are safe during pregnancy or breastfeeding. The NHS recommends caution with supplements that affect serotonin levels during pregnancy [11]. Similarly, people with significant liver or kidney problems should avoid tryptophan supplements because these organs are involved in tryptophan metabolism.

Here’s a counterintuitive finding: while serotonin-boosting approaches generally help anxiety, one study found that tryptophan supplementation actually worsened symptoms in people with social anxiety disorder [12]. The mechanism isn’t clear, but if you have social anxiety specifically, tryptophan supplements may not be appropriate.

3. Serotonergic medications

This is the big one. Tryptophan should not be combined with medications that also increase serotonin levels, because the combination can cause a dangerous condition called serotonin syndrome.

Medications to avoid combining with tryptophan include:

SSRIs (fluoxetine, sertraline, paroxetine, citalopram, escitalopram)
SNRIs (venlafaxine, duloxetine)
MAOIs (phenelzine, tranylcypromine, selegiline)
Tricyclic antidepressants (amitriptyline, nortriptyline)
Tramadol and other opioids that affect serotonin
Triptans for migraine (sumatriptan, rizatriptan)
Dextromethorphan (found in many cough medicines)
Meperidine (pethidine)

Serotonin syndrome symptoms include agitation, confusion, rapid heart rate, elevated blood pressure, dilated pupils, muscle twitching, diarrhoea, and in severe cases, high fever and seizures. It can be life-threatening.

If you’re taking any medication that affects serotonin, speak with your doctor before considering tryptophan supplements. The same applies to other supplements like 5-HTP, St John’s wort, and SAM-e, all of which can increase serotonin.

Tryptophan versus 5-HTP

You might wonder about the difference between tryptophan and 5-HTP supplements, since 5-HTP is what tryptophan gets converted into.

5-HTP is one step closer to serotonin in the metabolic pathway, so in theory it might be more efficient at boosting serotonin levels. It also doesn’t compete with other amino acids for brain entry the way tryptophan does.

On the other hand, tryptophan is a normal dietary component with a longer safety track record. Some researchers argue that tryptophan allows your body to regulate serotonin production more naturally, while 5-HTP might bypass some regulatory mechanisms.

Neither is clearly superior. Both can cause the same serotonin-related drug interactions and neither should be combined with antidepressants.

Typical dosages

For sleep: 1-5 grams taken 30-60 minutes before bed

For mood: 1-3 grams daily, sometimes divided into multiple doses

For PMDD: The study mentioned used 6 grams daily during the luteal phase

Start at the lower end and see how you respond before increasing. Higher doses aren’t necessarily more effective and may increase side effects.

References

Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009;2:45-60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908021/
Wurtman RJ, Wurtman JJ, Regan MM, McDermott JM, Tsay RH, Breu JJ. Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios. Am J Clin Nutr. 2003;77(1):128-32. https://pubmed.ncbi.nlm.nih.gov/12499331/
Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health. Science. 2017;357(6349):eaaf9794. https://pubmed.ncbi.nlm.nih.gov/28751584/
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;80(2):306-316. https://pubmed.ncbi.nlm.nih.gov/33942088/
Ogawa S, Fujii T, Koga N, et al. Plasma L-tryptophan concentration in major depressive disorder: new data and meta-analysis. J Clin Psychiatry. 2014;75(9):e906-15. https://pubmed.ncbi.nlm.nih.gov/25295433/
Steinberg S, Annable L, Young SN, Liyanage N. A placebo-controlled clinical trial of L-tryptophan in premenstrual dysphoria. Biol Psychiatry. 1999;45(3):313-20. https://pubmed.ncbi.nlm.nih.gov/10023508/
Coccaro EF. Central serotonin and impulsive aggression. Br J Psychiatry. 1989;155(Suppl 8):52-62. https://pubmed.ncbi.nlm.nih.gov/2695141/
Moskowitz DS, Pinard G, Zuroff DC, Annable L, Young SN. The effect of tryptophan on social interaction in everyday life: a placebo-controlled study. Neuropsychopharmacology. 2001;25(2):277-89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488902/
Stadler C, Schmeck K, Nowraty I, Müller WE, Poustka F. Platelet 5-HT uptake in boys with conduct disorder. Eur Arch Psychiatry Clin Neurosci. 2004;254(4):234-40. https://pubmed.ncbi.nlm.nih.gov/21673801/
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;264(2):213-7. https://pubmed.ncbi.nlm.nih.gov/2355442/
NHS. Vitamins, supplements and nutrition in pregnancy. https://www.nhs.uk/pregnancy/keeping-well/vitamins-supplements-and-nutrition/
Hood SD, Bell CJ, Argyropoulos SV. Does tryptophan depletion increase anxiety? Results from the Medication-Free Interval Study (MEFIS). J Psychopharmacol. 2005;19(4):405-13.