Evidence Level
Moderate
2 Clinical Trials
3 Documented Benefits
3/5 Evidence Score

L-tryptophan is an essential amino acid that the body uses to make serotonin and, from serotonin, melatonin, the hormone that helps time sleep. Unlike 5-HTP, which is one step closer to serotonin, tryptophan passes through more enzyme steps, and much of it is used by other routes such as the kynurenine pathway. Most of the research is on sleep and mood. The clearest pooled finding is less time awake during the night at about 1 g a day or more; falling asleep faster, reported in older studies, did not hold up when trials were pooled. Mood trials in healthy adults are small and give mixed results. A 1989 outbreak of eosinophilia-myalgia syndrome was traced to contaminated tryptophan from one manufacturer, so product quality matters, and tryptophan should not be combined with serotonergic antidepressants without medical advice.

Studied Dose Sleep studies: about 1,000 mg or more a day, taken in the evening. Mood trials in healthy adults: about 0.14 to 3 g a day. One premenstrual mood trial used 6 g a day, a research dose taken under supervision.
Active Compound L-tryptophan, a free-form essential amino acid, sold as powder or capsules.

Benefits

Less time awake after sleep onset at about 1 g a day or more

A meta-analysis of tryptophan sleep studies found that supplementation shortened time awake after first falling asleep, with a larger effect at 1 g a day or more, but did not change the other sleep measures, including time to fall asleep. In a later placebo-controlled crossover trial in 98 adults, 1 g a day for a week improved sleep efficiency and time awake measured by wrist actigraphy.

Mood ratings in healthy adults

A review of 11 randomized trials in healthy adults found that 4 showed less negative feeling or more positive mood with tryptophan at 0.14 to 3 g a day, and none showed an effect on aggressive feelings. An older review judged the evidence for low mood to be small, dated and mostly not placebo controlled. Tryptophan is not a treatment for depression.

Premenstrual mood ratings in one placebo-controlled trial

In a randomized trial in 71 women with premenstrual dysphoric disorder, a diagnosed condition, 6 g a day of L-tryptophan taken from ovulation to the third day of menstruation for three cycles reduced a combined rating of dysphoria, mood swings, tension and irritability more than placebo. It is a single older trial at a research dose far above typical supplement amounts.

Mechanism of action

1

Serotonin synthesis via 5-HTP

Tryptophan hydroxylase converts tryptophan to 5-hydroxytryptophan (5-HTP), which is then converted to serotonin. Serotonin has roles in mood, anxiety, sleep, cognitive function and appetite.

2

Melatonin synthesis

In the pineal gland serotonin is converted to melatonin, so the same pathway that makes serotonin also supplies melatonin.

3

Kynurenine pathway competition

Much of the body's tryptophan is metabolized through the kynurenine pathway rather than to serotonin, and about 95 percent of serotonin is made and used outside the brain. It has been proposed that extra tryptophan keeps more substrate available for serotonin, but the studies cited here did not test this.

Clinical trials

1
Tryptophan 1 g a day and sleep in 98 adults (crossover RCT)
PubMed

Randomized, double-blind, placebo-controlled crossover trial: one week of tryptophan 1,000 mg a day and one week of placebo, with sleep measured by diary and wrist actigraphy. (van Dalfsen et al. 2019, J Psychopharmacol)

98 adults aged 20 to 30 (73 women), grouped by serotonin transporter gene variant: 47 with two short alleles and 51 with two long alleles. The authors note the group slept relatively well at baseline.

Tryptophan improved actigraphy-measured sleep efficiency and time awake after sleep onset in both genotype groups. Self-rated sleep quality improved only marginally, and only in the short-allele group. Each treatment period lasted one week.

2
Tryptophan and premenstrual mood ratings (RCT)
PubMed

Randomized, double-blind, placebo-controlled trial of L-tryptophan 6 g a day or placebo, taken for 17 days from ovulation to the third day of menstruation, over three cycles. (Steinberg et al. 1999, Adv Exp Med Biol)

71 women with premenstrual dysphoric disorder (37 tryptophan, 34 placebo), a diagnosed condition rather than everyday premenstrual discomfort.

On visual analog mood scales, tryptophan reduced the combined dysphoria, mood swings, tension and irritability ratings more than placebo (p = 0.004). It is a single older trial at a research dose far above typical supplement amounts.

Side effects and drug interactions

Common Potential side effects

A 1989 outbreak of eosinophilia-myalgia syndrome was traced to tryptophan from a single manufacturer and linked to a contaminant tied to its manufacturing conditions. A new case linked to L-tryptophan was reported in 2011, after US sales restrictions were lifted in 2005, so choose a product whose maker documents purity testing.
Drowsiness; take it at bedtime and do not drive if it makes you sleepy.

Important Drug interactions

Antidepressants and other serotonergic drugs (SSRIs, SNRIs, MAOIs): combining serotonergic agents can trigger serotonin syndrome, and the first described case involved L-tryptophan taken with an MAOI. Do not combine without medical supervision.
Sedatives and other drugs that cause drowsiness: the effects may add up, so use caution.

Frequently asked questions about L-Tryptophan

What is tryptophan used for?

L-tryptophan is an essential amino acid the body uses to make serotonin and melatonin, so it is taken for mood, relaxation, and sleep support. It is the precursor that ultimately becomes these calming and sleep-related compounds.

Does tryptophan help with sleep and mood?

Tryptophan is the raw material for serotonin and melatonin. A meta-analysis found that about 1 g a day or more reduced the time spent awake during the night, but did not change how quickly people fell asleep or the other sleep measures examined. Evidence for mood in healthy adults is smaller and mixed.

How much tryptophan should I take?

Sleep studies used about 1 g a day or more, usually in the evening, and mood trials in healthy adults used about 0.14 to 3 g a day. The related supplement 5-HTP is a step closer to serotonin. Follow product labeling.

Is tryptophan safe?

It is usually well tolerated, though it can cause drowsiness, which is one reason it is taken at bedtime. Choose a product whose maker documents purity testing: a 1989 outbreak of eosinophilia-myalgia syndrome was traced to contaminated tryptophan from one manufacturer, and a later case was reported in 2011. Because it raises serotonin, do not combine it with antidepressants such as SSRIs or MAOIs without medical guidance.

What is L-Tryptophan?

L-tryptophan is an essential amino acid that the body uses to make serotonin and, from serotonin, melatonin, the hormone that helps time sleep. Unlike 5-HTP, which is one step closer to serotonin, tryptophan passes through more enzyme steps, and much of it is used by other routes such as the kynurenine pathway.

What is L-Tryptophan used for?

L-Tryptophan is researched primarily for Sleep Health and Mood & Mental Health. A meta-analysis of tryptophan sleep studies found that supplementation shortened time awake after first falling asleep, with a larger effect at 1 g a day or more, but did not change the other sleep measures, including time to fall asleep.

Does L-Tryptophan interact with any medications?

Possible interactions include: Antidepressants and other serotonergic drugs (SSRIs, SNRIs, MAOIs): combining serotonergic agents can trigger serotonin syndrome, and the first described case involved L-tryptophan taken with an MAOI. Do not combine without medical supervision. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for L-Tryptophan?

NutraSmarts rates the evidence for L-Tryptophan as Moderate (3 out of 5). It is backed by 2 study summaries and 11 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(11 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. 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. doi: 10.1093/nutrit/nuab027.PubMedUsed to support: Meta-analysis that pooled 4 of 18 collected studies: tryptophan shortened wake after sleep onset, with a larger effect at 1 g a day or more, and did not affect the other sleep components. Supports the sleep benefit.
  2. 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;18(3):316-333. doi: 10.1080/19390211.2020.1746725.PubMedUsed to support: Systematic review of 11 randomized trials in healthy adults: 4 showed significant effects on negative or happy feelings, none on aggressive feelings, at 0.14 to 3 g a day. Supports the mood benefit and dose range.
  3. Kałużna-Czaplińska J, Gątarek P, Chirumbolo S, Chartrand MS, Bjørklund G. How important is tryptophan in human health? Crit Rev Food Sci Nutr. 2019;59(1):72-88. doi: 10.1080/10408398.2017.1357534.PubMedUsed to support: Review of tryptophan in human health, including its conversion to serotonin and melatonin and its study in sleep and mood. Supports the mechanism section.
  4. Gibson EL. Tryptophan supplementation and serotonin function: genetic variations in behavioural effects. Proc Nutr Soc. 2018;77(2):174-188. doi: 10.1017/S0029665117004451.PubMedUsed to support: Review: serotonin transporter genotype and sex may shape behavioural responses to tryptophan; in women with the S/S' genotype, tryptophan improved mood and lowered cortisol during stress. Also notes that about 95 percent of serotonin is made in the periphery and that tryptophan is used by the kynurenine pathway.
  5. Parker G, Brotchie H. Mood effects of the amino acids tryptophan and tyrosine: 'Food for Thought' III. Acta Psychiatr Scand. 2011;124(6):417-26. doi: 10.1111/j.1600-0447.2011.01706.x.PubMedUsed to support: Review of tryptophan and mood: a small database supports tryptophan for depressed mood, but most studies are dated, small or not placebo controlled, so evidence for it as a depression treatment is limited.
  6. Hartmann E. Effects of L-tryptophan on sleepiness and on sleep. J Psychiatr Res. 1982;17(2):107-13. doi: 10.1016/0022-3956(82)90012-7.PubMedUsed to support: Review of 40 controlled studies: tryptophan at 1 g or more increased rated sleepiness and shortened time to fall asleep, best in mild insomnia, with weaker data on total wakefulness. A review, not a single trial; the later meta-analysis did not confirm the effect on time to fall asleep.
  7. Steinberg S, Annable L, Young SN, Liyanage N. A placebo-controlled study of the effects of L-tryptophan in patients with premenstrual dysphoria. Adv Exp Med Biol. 1999;467:85-8. doi: 10.1007/978-1-4615-4709-9_11.PubMedUsed to support: Randomized, double-blind trial in 71 women with premenstrual dysphoric disorder: 6 g a day of tryptophan from ovulation to day 3 of menstruation over three cycles reduced dysphoria, mood swings, tension and irritability ratings more than placebo (p = 0.004).
  8. van Dalfsen JH, Markus CR. The serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the sleep-promoting effects of tryptophan: A randomized placebo-controlled crossover study. J Psychopharmacol. 2019;33(8):948-954. doi: 10.1177/0269881119855978.PubMedUsed to support: Randomized, double-blind, placebo-controlled crossover trial in 98 adults (47 S/S, 51 L/L serotonin transporter genotype): 1,000 mg a day for one week improved actigraphy sleep efficiency and wake after sleep onset in both groups; self-rated sleep quality improved only marginally in the S/S group. Backs the sleep trial card.
  9. Belongia EA, Hedberg CW, Gleich GJ, White KE, Mayeno AN, Loegering DA, Dunnette SL, Pirie PL, MacDonald KL, Osterholm MT. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med. 1990;323(6):357-65. doi: 10.1056/NEJM199008093230601.PubMedUsed to support: CDC-led investigation of the 1989 eosinophilia-myalgia outbreak: 29 of 30 cases with a known source had used tryptophan from one company, and the outbreak was linked to a chemical constituent tied to that company's manufacturing conditions. Backs the safety note.
  10. Allen JA, Peterson A, Sufit R, Hinchcliff ME, Mahoney JM, Wood TA, Miller FW, Whitfield ML, Varga J. Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan. Arthritis Rheum. 2011;63(11):3633-9. doi: 10.1002/art.30514.PubMedUsed to support: Case report of eosinophilia-myalgia syndrome linked to L-tryptophan after the FDA lifted its sales ban in 2005. Backs the note that purity still matters.
  11. Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. Int J Tryptophan Res. 2019;12:1178646919873925. doi: 10.1177/1178646919873925.PubMedUsed to support: Review of serotonin syndrome: combining serotonergic drugs, especially with MAOIs, can trigger it, and the first described case involved L-tryptophan with an MAOI. Backs the antidepressant interaction warning.