5-Hydroxytryptophan
amino-acid · also known as 5-HTP, oxitriptan, griffonia simplicifolia extract
This is general information, not medical advice. Supplements can interact with medicines and health conditions. Always check with your doctor or pharmacist before starting or changing supplements.
What it is
5-Hydroxytryptophan (5-HTP) is an amino acid the body produces as an intermediate step in converting dietary tryptophan into serotonin. It is sold as a supplement, commonly derived from the seeds of Griffonia simplicifolia, on the premise that boosting this precursor raises brain serotonin production. 5-HTP became popular after L-tryptophan supplements were pulled from the US market in 1989 following an outbreak of eosinophilia-myalgia syndrome (EMS) traced to a contaminated manufacturing batch; 5-HTP has not been linked to a comparable outbreak, but that episode has kept researchers and regulators cautious about this class of serotonin-precursor supplements. People take 5-HTP hoping to improve mood, anxiety, and sleep onset. Clinical evidence is limited: a small pool of older, mostly low-quality randomised trials suggests possible benefit for depression, and a newer small trial suggests modest sleep-quality benefits, but neither is well established. The most important safety issue is not efficacy but interaction risk: because 5-HTP directly increases serotonin precursor availability, combining it with serotonergic medications (SSRIs, SNRIs, MAOIs, triptans, tramadol, St John's Wort) can precipitate serotonin syndrome, a potentially severe reaction, which is why this supplement is best used short-term and under medical supervision rather than continuously and unsupervised.
Evidence-based benefits
- Grade B· Limited evidence[1]
Pooled evidence from a small number of quality-screened randomised trials suggests 5-HTP (and tryptophan) may be more effective than placebo for depressive symptoms, but the overall evidence base is very limited and of uncertain quality.
A Cochrane systematic review searched for randomised trials of 5-HTP and tryptophan for depression; of 108 trials identified, only 2 trials (64 patients total) met the review's quality criteria for inclusion. Pooled results favoured 5-HTP/tryptophan over placebo (Peto odds ratio 4.10, 95% CI 1.28-13.15; number needed to treat 2.78), but the reviewers concluded the evidence was of insufficient quality to be conclusive, and noted that because effective, well-evidenced antidepressants already exist, the clinical usefulness of 5-HTP remains limited until larger, higher-quality trials are done.
- Grade C· Preliminary evidence[1]
In a small trial without a placebo arm, 5-HTP supplementation improved several sleep-quality measures in older adults, most consistently in participants who started out as poor sleepers, but the effect was not sustained through the full study period.
A 2024 single-blinded, 12-week randomised controlled trial in 30 older adults (mean age 66) compared 100 mg/day 5-HTP against a no-supplement control group (not placebo-controlled). Sleep quality, assessed by the Pittsburgh Sleep Quality Index and actigraphy, improved with 5-HTP through week 8, particularly in participants classified as poor sleepers at baseline, but improvements were not maintained by week 12. The absence of a placebo arm, single-blind design, and small sample size limit how much can be concluded from this single trial.
Risks & contraindications
Combining 5-HTP with serotonergic drugs (SSRIs, SNRIs, MAOIs, triptans, tramadol, St John's Wort, and other agents that raise serotonin activity) risks serotonin syndrome, a potentially severe or life-threatening reaction; this is a mechanism-based interaction documented mainly through case reports and pharmacological review rather than controlled trials, which cannot ethically be run to test it directly.
A 2005 New England Journal of Medicine review of serotonin syndrome documents, with a table of causative drugs and drug combinations, that the syndrome is a predictable consequence of excess serotonergic agonism and can be precipitated by combining serotonergic agents, explicitly including MAOIs combined with SSRIs, and MAOIs combined with other serotonergic drugs, among other pairings. The same table lists tryptophan, the amino acid 5-HTP is directly synthesised from one metabolic step upstream in serotonin biosynthesis, among the dietary supplements associated with serotonin syndrome; the review does not use the term "5-HTP" itself. Because 5-HTP is the immediate next intermediate after tryptophan in that same pathway (skipping the rate-limiting tryptophan-hydroxylase step the body would otherwise need), the mechanism this review describes for tryptophan applies at least as directly to 5-HTP, and is consistent with case reports of serotonin syndrome specifically involving 5-HTP. One such case, from 2017, described a young man taking prescribed sertraline (and other medications) who developed serotonin syndrome with rhabdomyolysis that progressed to acute compartment syndrome after also taking several dietary supplements, including 5-HTP, on the day of presentation; he had also abruptly stopped his usual daily alcohol intake (2-3 beers/day) shortly beforehand. Because he was taking more than 20 different supplements alongside multiple prescription medications, and had also just stopped drinking, causal attribution to 5-HTP alone in this specific case is confounded by both polypharmacy and possible alcohol withdrawal; it is included here as an illustrative, not conclusive, case consistent with the broader mechanism.
- Grade C· Preliminary evidence[1]
Unlike the L-tryptophan supplements withdrawn in 1989, 5-HTP has not been linked to an eosinophilia-myalgia syndrome outbreak, and analyses of commercial 5-HTP have not found the contaminants implicated in that episode; no safe maximum duration of continuous use has been established either way.
A 2004 toxicology review of 5-HTP safety notes that L-tryptophan was discontinued as a dietary supplement in 1989 after an eosinophilia-myalgia syndrome (EMS) outbreak traced to contaminated synthetic material from a single manufacturer, and that 5-HTP became popular in its place. The review reports that no definitive cases of toxicity had emerged over roughly 20 years of worldwide 5-HTP use, with the possible exception of one unresolved Canadian case, and that extensive analyses of several 5-HTP sources found neither the contaminants associated with L-tryptophan nor other significant impurities; it treats the "peak X" chromatographic finding reported in some samples as an artifact present at insignificant concentrations. This is a narrative review of the contamination question, not a controlled long-term safety study: it tests no dose and no duration, and so establishes neither a safe maximum duration of use nor an unsafe one. The serotonergic interaction risk described above, not contamination, is the hazard that governs how this supplement should be used.
Dosage & how to take it
- 5-Hydroxytryptophan: 50–300 mg/day, in the evening, with or without food. Short-term use only: max 90 days at a time. Start at 50 mg/day and titrate slowly to reduce early GI side effects (nausea is common), taken in the evening given 5-HTP's role in serotonin/melatonin synthesis and its most-studied uses for sleep and mood. On sourcing, plainly: this range is not pinned to a trial. The only 5-HTP dose stated in any study cited on this monograph is 100 mg/day (PMID 38309227, the 12-week sleep trial), and the Cochrane review (PMID 11869656) does not report the doses used in its two includable trials. The 50 mg and 300 mg bounds reflect doses commonly used in practice and the capsule strengths commonly sold, not a studied minimum or maximum. The 90-day ceiling is likewise this monograph's editorial precaution rather than a limit any cited source establishes: no study cited here tested duration, controlled human trials of 5-HTP have run only weeks to a few months, no dedicated long-duration safety trial exists, and the 2004 safety review cited here (PMID 15068828) addresses contamination rather than duration and establishes neither a safe maximum nor an unsafe one. We set it at 90 days because that is roughly where the evidence runs out, and because the serotonergic interaction risk is the real hazard: take a break or consult a clinician before continuing past three months rather than treating 90 days as a tested threshold, and stop immediately and seek medical care if starting or adjusting any serotonergic medication.
Interactions
5-HTP directly raises the amount of serotonin your body makes, and SSRIs like sertraline work by keeping serotonin around longer in the brain. Combining the two stacks these effects and can trigger serotonin syndrome, a potentially severe reaction with symptoms like agitation, high fever, rapid heart rate, and muscle rigidity. A widely cited clinical review of serotonin syndrome lists combinations of serotonergic drugs, including SSRIs with other serotonin-raising agents, as a documented cause, and a published case report describes a man on sertraline who developed serotonin syndrome after also taking 5-HTP (among many other supplements, so that case alone is not conclusive on its own, but it is consistent with the broader mechanism). Do not take 5-HTP if you are on an SSRI; talk to your prescriber before starting either one if you're already on the other.
Our medication coverage is not exhaustive. Absence of a warning here is not evidence of safety. Always confirm with your pharmacist.
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