Understanding 5-HTP
5-Hydroxytryptophan (5-HTP) is a naturally occurring amino acid. The body makes it from L-tryptophan and converts it into serotonin (Int J Mol Sci review, 2020). Serotonin is also used to make melatonin. Supplement 5-HTP is typically extracted from the seeds of Griffonia simplicifolia, an African plant (same review).
Whether 5-HTP crosses the blood-brain barrier more easily than L-tryptophan is not settled in the sources we checked.
Takeaway: the human trials are old, small and mixed. 5-HTP is not a proven treatment for mood, sleep, appetite or migraine, and it has a real drug-interaction risk (serotonin syndrome). Talk to a clinician before using it.
What the research found
- Depression. A 2001 Cochrane review found only two trials of sufficient quality (64 patients in total). 5-HTP did better than placebo for depression, but the evidence was too weak to be conclusive (Shaw 2001). A 1991 comparison with fluvoxamine exists (Poldinger 1991); its sample size and results could not be verified from the abstract, so we do not quote them.
- Sleep. In a 12-week trial of 30 older adults, 100 mg a day shortened the time to fall asleep by about 2.8 minutes in poor sleepers (Sutanto 2024). A separate randomized, double-blind, placebo-controlled trial of 18 patients tested a combination product with both GABA and 5-HTP. Time to fall asleep fell from 32.3 to 19.1 minutes, versus no significant change on placebo (Shell 2010). That trial tested the combination, not 5-HTP alone. NCCIH notes there is very limited data on 5-HTP's effects on insomnia (NCCIH).
- Appetite and weight. In a trial with two consecutive 6-week periods (12 weeks in total), 20 obese adults were given 900 mg a day of 5-HTP or placebo. Weight loss was significant in the 5-HTP group in both periods, with lower carbohydrate intake and early fullness. Calorie intake was not reported in the abstract (Cangiano 1992).
- Migraine. Two small trials did not show a statistically significant benefit over placebo. In 31 adults with chronic headache, 400 mg a day for 2 months was not significantly better than placebo (De Benedittis 1985). In 27 children, both 5-HTP and placebo reduced attacks, with no difference between them (Santucci 1986).
Doses listed by Health Canada
Health Canada's 5-HTP monograph lists these daily ranges. They come from its review of the literature; they are not recommendations from NootroWorld (Health Canada monograph):
- Mood balance: 150 to 300 mg a day (it cites the 1991 trial).
- Sleep: 100 to 200 mg a day. The older-adult trial above used 100 mg.
- Migraine prevention: 200 to 600 mg a day, with no more than 300 mg in a single dose.
- Weight management: 750 to 900 mg a day in divided doses of up to 300 mg, taken 30 minutes before meals.
- Use for at least 2 weeks before judging the effect. To limit stomach side effects, start low and increase slowly over 2 weeks. Take with food except for weight management.
Safety
- Side effects. Nausea and vomiting have been reported at doses above 100 mg (review, 2020). Health Canada lists stomach discomfort as a known effect.
- Serotonin syndrome. This is a rare but potentially life-threatening condition caused by too much serotonin (Medsafe). Health Canada says not to use 5-HTP if you take antidepressants. Medsafe names MAOIs, SSRIs, SNRIs and tricyclics as the serotonergic antidepressants of concern, and tramadol, pethidine and dextromethorphan as opioids with a high risk of serotonin syndrome when combined with them. Health Canada also advises asking a doctor before using 5-HTP with a dextromethorphan cough medicine or pain killers, or with carbidopa.
- Stop and seek help for tremors, agitation or confusion, or a racing heart. 5-HTP can cause drowsiness; take care when driving (Health Canada).
- Scleroderma. Health Canada says not to use 5-HTP if you have scleroderma.
- Pregnancy and breastfeeding. Health Canada says to ask a health care practitioner first, and not to use it for weight management if pregnant.
- Contaminants. NCCIH says analyses of several sources of 5-HTP have shown no toxic contaminants like those tied to L-tryptophan. The Cochrane review notes a possible link to eosinophilia-myalgia syndrome that is unresolved.
Sources
- Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2001. PubMed 11687048
- Cangiano C et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992. PubMed 1384305
- De Benedittis G, Massei R. J Neurosurg Sci 1985: 5-HTP in chronic headache. PubMed 3913752
- Santucci M et al. Cephalalgia 1986: L-5-HTP versus placebo in childhood migraine. PubMed 3533271
- Shell W et al. A double-blind, randomized, placebo-controlled trial of an amino acid preparation on timing and quality of sleep. Am J Ther 2010. PubMed 19417589
- Sutanto CN et al. Clin Nutr 2024: 5-HTP and sleep in older adults. PubMed 38309227
- Poldinger W, Calanchini B, Schwarz W. Psychopathology 1991: 5-HTP compared with fluvoxamine. PubMed 1909444
- 5-HTP review. Int J Mol Sci 2020. PubMed 33375373
- Health Canada. Natural Health Products monograph: 5-HTP
- Medsafe (NZ). Opioids and serotonergic medicines: risk of serotonin syndrome, 2022.
- NCCIH. Sleep disorders and complementary health approaches
Related guides
- L-tryptophan: sleep, mood and appetite support
- Melatonin supplement guide
- GABA supplement guide
- St John's wort supplement guide
- Glossary: RCT
This article is general information, not medical advice. Do not combine 5-HTP with antidepressants or other serotonergic medicines without medical supervision.
