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5-HTP for Sleep: The Few Trials, the Interactions and the Safety History

By the Sleep Anchors editorial team Published Last reviewed

Unlabeled amber supplement bottles and a dropper beside a printed study and reading glasses on a bedside table, lit by a lamp at night
Illustration

5-hydroxytryptophan, or 5-HTP, is an amino acid the body makes from tryptophan on the way to serotonin and, from serotonin, to melatonin. It is sold as a supplement for sleep and mood. For 5-HTP the sleep evidence is thin and the safety questions weigh heavily, including what it can do alongside other medicines. This guide sets out the few human trials, the safety questions, and what is unknown.

It is not medical advice. If sleep trouble is persistent, talk to a healthcare provider.

The Short Answer

  • We found no placebo-controlled trial of 5-HTP alone in adults with insomnia. The human trials we found are small: one without a placebo in older adults, one in people with Parkinson’s disease, one of a combination formula, and one open trial in children.
  • The safety questions are the main issue. A 2020 toxicology review says 5-HTP may cause nausea and vomiting at doses above 100 mg and that an excess may lead to serotonin syndrome, a potentially life-threatening reaction that occurs most often when two or more medicines that affect serotonin are taken together.
  • There is a manufacturing history to know about. Tryptophan supplements were pulled in 1989 after an outbreak of eosinophilia-myalgia syndrome. A 2003 analysis found a putative neurotoxin, also present in a 5-HTP product implicated in an EMS case, in six over-the-counter samples. A paper from a company laboratory calls that finding not credible.
  • We found no NIH fact sheet on 5-HTP. The MedlinePlus list of herbs and supplements, which links to NIH fact sheets, has no 5-HTP entry.
  • If you take an antidepressant or another medicine that acts on serotonin, ask your prescriber first.

What 5-HTP Is and How It Might Work

5-HTP is an intermediate in the body’s production of serotonin and melatonin from L-tryptophan (Meloni et al., 2022). Some supplements, including the product we review elsewhere, use an extract of Griffonia seed as the source. The idea behind them is that extra 5-HTP raises serotonin, and serotonin is a step toward melatonin. A trial in older adults reported a rise in blood serotonin with 100 mg a day (Sutanto et al., 2024). A rise in serotonin does not by itself show better sleep.

What the Trials Show

  • Sutanto and colleagues, 2024. 30 older adults (average age 66) in Singapore were randomly assigned to take 100 mg of 5-HTP a day or not, for 12 weeks. The comparison group did not take 5-HTP, the abstract mentions no placebo, and the trial was single-blinded. Sleep was measured with the Pittsburgh Sleep Quality Index and a wrist actigraphy device. The authors report a favorable effect on certain sleep components and a rise in blood serotonin. Among people who started as poor sleepers, the subjective global sleep score improved significantly (p = 0.005). The abstract states no funding or conflicts (Sutanto et al., 2024).
  • Meloni and colleagues, 2022. 18 people with Parkinson’s disease and REM sleep behavior disorder took 50 mg a day of 5-HTP or a placebo, each for 4 weeks, in a crossover design. The percentage of REM sleep rose without more REM behavior episodes, and wake after sleep onset and arousals fell by amounts that were not significant. This is a trial in a specific neurological condition, not insomnia. The authors declare no competing interests, and they call for larger studies with higher doses and longer trials (Meloni et al., 2022).
  • Shell and colleagues, 2010. 18 patients with sleep disorders took either a placebo or a formula that combines GABA and 5-HTP. Time to fall asleep fell from 32.3 to 19.1 minutes in the formula group (n = 9), against 34.8 to 33.1 minutes on placebo (n = 9), and reported sleep duration rose from 5.0 to 6.83 hours against no change. Because the formula has two ingredients, the trial cannot separate 5-HTP’s effect. The author is affiliated with Targeted Medical Pharma, and we did not check whether the company sells the formula (Shell et al., 2010).
  • Bruni and colleagues, 2004. An open trial, with no placebo and no blinding, in 45 children aged 3 to 10 with sleep terrors. 31 randomly selected children received 2 mg per kg a day at bedtime for 20 days. After a month, 29 of 31 responded, while in the untreated comparison group the episodes disappeared in 4 of 14. This concerns children and a different disorder from insomnia (Bruni et al., 2004).

Safety

  • Serotonin syndrome. MedlinePlus, from the U.S. National Library of Medicine, describes serotonin syndrome as a potentially life-threatening reaction to certain medicines that causes the body to have too much serotonin. It says it most often occurs when two or more medicines or drugs that affect the body’s serotonin level are taken together. Its examples are SSRI and SNRI antidepressants and triptans for migraine, and it says older antidepressants called MAOIs can cause it when combined with those medicines and with meperidine, fentanyl and dextromethorphan, among others. It says the syndrome is more likely when you first start a medicine or raise the dose, and that you should always tell your providers which medicines you take and not stop a medicine without talking to them first (MedlinePlus, reviewed April 2026). That page does not mention 5-HTP. A 2020 review of 5-HTP toxicology says an excess of 5-HTP may lead to serotonin syndrome (Maffei, 2020).
  • Digestive effects. The same review says 5-HTP may cause dose-dependent gastrointestinal problems, with nausea and vomiting reported at doses above 100 mg. It also says excessive use was associated with severe side effects including behavioral disturbances and abnormal mental function, and that relatively few adverse effects were associated with 5-HTP in early studies in depressed patients (Maffei, 2020). The review is by a single author at the University of Turin.
  • Manufacturing history. Tryptophan supplements were withdrawn in 1989 after an outbreak of eosinophilia-myalgia syndrome (EMS), traced to contaminated synthetic tryptophan from one manufacturer (Maffei, 2020). A 2003 analysis identified a contaminant that had been found in a 5-HTP product implicated in an EMS case, as 4,5-tryptophan-dione, a putative neurotoxin. It was also found in 6 over-the-counter 5-HTP samples, at 0.5% to 10.3% of the amount in the implicated product, and the authors said this gives cause for concern about the safety of such preparations (Klarskov et al., 2003). A 2004 paper from ISSI Laboratories says that no definitive cases of toxicity emerged over 20 years of worldwide use, with the possible exception of one unresolved case, and that the minor “peak X” lacks credibility because of chromatographic artifacts and tiny concentrations (Das et al., 2004). We did not check what ISSI Laboratories does. The two papers disagree, and a label may not say how the 5-HTP was tested.
  • The U.S. National Center for Complementary and Integrative Health says dietary supplements may interact with your medications or pose risks if you have certain medical problems or are going to have surgery, and that many have not been tested in pregnant women, nursing mothers or children. It advises anyone who has side effects to stop taking the supplement and contact a healthcare provider (NCCIH, last updated January 2019).

Who Ran the Research

  • The older-adult trial came from a food science department at the National University of Singapore, and its abstract states no funding.
  • The Parkinson’s trial came from the University of Cagliari, and the authors declare no competing interests.
  • The combination-formula trial was by an author affiliated with Targeted Medical Pharma.
  • The paper that downplays the contaminant finding came from ISSI Laboratories.
  • We did not check the funding of the 2004 open trial, the 2003 analysis or the 2020 review.

Funding does not invalidate a study. It is why we say who is who.

Doses and Forms

  • 50 mg a day for 4 weeks in the Parkinson’s trial.
  • 100 mg a day for 12 weeks in the older-adult trial.
  • 2 mg per kg a day in the children’s trial.
  • Not stated in the abstract: the amount of 5-HTP in the combination formula.
  • No established dose. The review reports nausea and vomiting above 100 mg.

What We Do Not Know

  • Whether 5-HTP alone helps adults with insomnia. We found no placebo-controlled trial.
  • Whether the small trials’ results hold up in larger trials in people without Parkinson’s disease.
  • Which products are free of contaminants. A label may not say how the 5-HTP was tested.
  • How it interacts with the medicines you take. That is a question for a prescriber or pharmacist.
  • Long-term safety. The trials lasted 20 days to 12 weeks.

Questions

Does 5-HTP help you sleep?

We found no placebo-controlled trial of 5-HTP alone in adults with insomnia. The small trials we found were in older adults without a placebo, in Parkinson’s disease, in children with sleep terrors, and of a two-ingredient formula.

Is 5-HTP safe with antidepressants?

Ask your prescriber before combining them. MedlinePlus describes serotonin syndrome as occurring most often when two or more medicines that affect serotonin are taken together, and the 2020 review says an excess of 5-HTP may lead to it.

How much 5-HTP should I take?

We cannot give a dose. The trials used 50 to 100 mg a day in adults, and the toxicology review reports nausea and vomiting above 100 mg. Ask a healthcare provider, especially if you take any medication.

Is 5-HTP the same as tryptophan?

No. Tryptophan is the amino acid the body converts into 5-HTP, and 5-HTP is the step before serotonin. The 1989 outbreak of eosinophilia-myalgia syndrome was linked to tryptophan supplements from one manufacturer.

See Also

5-HTP is one of the ingredients in Yu Sleep. Its label gives no amount for it. If the label follows the ordering rule, the most it can hold is about 127 mg, which is above the 100 mg at which the toxicology review reports nausea and vomiting. It could be much lower. Our side-effects guide explains the arithmetic. That guide contains an affiliate link.

Check current pricing and availability

Sources Cited in This Guide

  1. Sutanto CN, Xia X, Heng CW, et al. “The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial.” Clin Nutr. 2024. Read September 19, 2026 (abstract). PMID 38309227
  2. Meloni M, Figorilli M, Carta M, et al. “Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease.” Sleep Breath. 2022. Read September 19, 2026 (abstract and conflict statement). PMID 34403081
  3. Shell W, Bullias D, Charuvastra E, et al. “A randomized, placebo-controlled trial of an amino acid preparation on timing and quality of sleep.” Am J Ther. 2010. Read September 19, 2026 (abstract and affiliation). PMID 19417589
  4. Bruni O, Ferri R, Miano S, Verrillo E. “L-5-Hydroxytryptophan treatment of sleep terrors in children.” Eur J Pediatr. 2004. Read September 19, 2026 (abstract). PMID 15146330
  5. Maffei ME. “5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology.” Int J Mol Sci. 2020. PMID 33375373
  6. Klarskov K, Johnson KL, Benson LM, et al. “Structural characterization of a case-implicated contaminant, ‘Peak X,’ in commercial preparations of 5-hydroxytryptophan.” J Rheumatol. 2003. Read September 19, 2026 (abstract). PMID 12508395
  7. Das YT, Bagchi M, Bagchi D, Preuss HG. “Safety of 5-hydroxy-L-tryptophan.” Toxicol Lett. 2004. Read September 19, 2026 (abstract and affiliation). PMID 15068828
  8. National Library of Medicine. “Serotonin syndrome.” MedlinePlus Medical Encyclopedia. Review date April 13, 2026. Read September 19, 2026. MedlinePlus
  9. National Library of Medicine. “Herbs and Supplements.” MedlinePlus. Read September 19, 2026 (list checked for a 5-HTP entry). MedlinePlus
  10. National Center for Complementary and Integrative Health, NIH. “Using Dietary Supplements Wisely.” Last updated January 2019. Read September 19, 2026. NCCIH

This guide is for information and is not medical advice. Talk to a healthcare provider about medication, pregnancy, medical conditions and persistent sleep problems.

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