5-HTP
Evidence Fact Sheet
5-Hydroxytryptophan
5-HTP (5-hydroxytryptophan) is a Griffonia simplicifolia-derived serotonin precursor sold as a dietary supplement. Research literature describes 50-100 mg before bed and 300-900 mg/day in divided doses; legal under DSHEA with structure/function claims only. Human efficacy evidence is sparse and methodologically limited.
Also known as: 5-HTP · 5-Hydroxytryptophan · Oxitriptan · Griffonia simplicifolia seed extract
Overview
5-HTP (5-hydroxytryptophan) is an immediate serotonin (5-HT) precursor extracted from Griffonia simplicifolia seed. It bypasses the rate-limiting tryptophan-hydroxylase step and is decarboxylated directly to serotonin, and is a substrate further along the serotonin-to-melatonin pathway, which is why it is studied in mood, appetite, and sleep-precursor research contexts. Research literature describes 50-100 mg taken before bed in the serotonin-precursor context and 300-900 mg/day in divided doses in older mood and appetite studies; common commercial unit strengths are 50-200 mg. In the United States it is a legal dietary-supplement ingredient under DSHEA 1994, permitting structure/function claims with the mandatory FDA disclaimer only — it is not FDA-approved and carries a historical eosinophilia-myalgia syndrome (EMS) safety association; EU status is fragmented by member state and there is no authorized EU health claim. Co-use with SSRI/SNRI/MAOI/tramadol/St John's Wort is treated as an absolute contraindication (serotonin syndrome risk).
Mechanism of Action
Immediate serotonin (5-HT) precursor that bypasses the tryptophan hydroxylase rate-limiting step and is decarboxylated by aromatic L-amino-acid decarboxylase directly to 5-HT (research model) · Downstream substrate for the 5-HT -> N-acetylserotonin -> melatonin pathway (circadian/sleep mechanistic context) · Crosses the blood-brain barrier without a transport carrier, raising central serotonergic tone in animal models (note: rat data show CNS effect may not require a measurable rise in whole-brain 5-HT)
Body systems: Neurological & Cognitive · Mood & Stress Response · Sleep-Wake System · METABOLISM
Evidence-Based Benefits
Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — 5-HTP is not characterized as a treatment for any disease.
Depression (Mood)
Meta-analysis supported- Peto OR = 4.1vs placebo · 95% CI 1.3-13.2
- 2 of 108studies met quality criteria
- 64 patientspooled across 2 trials
A systematic review and meta-analysis of tryptophan and 5-HTP for unipolar depression located 108 studies but found only two of sufficient quality to pool — one of 5-HTP and one of L-tryptophan, totaling 64 patients. The pooled estimate favored the precursors over placebo, but the authors stressed that the small size and poor quality of the eligible literature make the result insufficient to inform clinical practice. This is the strongest mood-research signal but is explicitly low-confidence.
Reported effect: Peto OR = 4.1, 95% CI = 1.3-13.2; only 2 of 108 located studies (64 patients total) met quality criteria
“One hundred and eight studies were located of which only two studies, one of 5-HT and one of L-tryptophan, with a total of 64 patients met sufficient quality criteria to be included. These studies suggest 5-HT and L-tryptophan are better than placebo at alleviating depression (Peto OR = 4.1, 95% CI = 1.3-13.2). However, the small size of the studies, and the large number of inadmissible, poorly executed studies, casts doubt on the result from potential publication bias, and suggests that they are insufficiently evaluated to assess their effectiveness.”
Source: PMID 12169147 · Shaw 2002 · Aust N Z J Psychiatry
Panic / Anxiety Provocation
Null / no benefit RCT supported- 7 + 7panic patients + controls
- 0 panic attacksacross all 5-HTP doses
In a double-blind crossover challenge, intravenous 5-HTP at three doses was infused into 7 panic-disorder patients and 7 healthy controls to test whether boosting serotonergic tone would provoke panic. No participant in either group had a panic attack or showed increased anxiety or depressive symptoms, and the serotonin-hypersensitivity hypothesis of panic disorder was not confirmed. This is an honest negative result.
Reported effect: 0 panic attacks in 7 panic-disorder patients and 7 controls across IV 5-HTP doses; 5-HT hypersensitivity hypothesis not confirmed
“During and after infusion of placebo or any of the different dosages of 5-HTP, none of the patients or controls experienced a panic attack or showed an increase in anxiety or depressive symptoms.”
Source: PMID 8791035 · van Vliet 1996 · Eur Neuropsychopharmacol
Appetite / Weight (Obesity)
RCT supported- 20 patientsrandomized, double-blind
- 900 mg/d5-HTP dose
Twenty obese adults were randomized double-blind to 5-HTP 900 mg/day or placebo across two consecutive 6-week periods (no diet, then a recommended diet). Significant weight loss was reported in the 5-HTP group in both periods, alongside reduced carbohydrate intake and consistent early satiety. The abstract reports the direction and significance but no kilogram figure, so the magnitude is not extractable here.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“20 obese patients were randomly assigned to receive either 5-HTP (900 mg/d) or a placebo. The study was double-blinded and was for two consecutive 6-wk periods... Significant weight loss was observed in 5-HTP-treated patients during both periods. A reduction in carbohydrate intake and a consistent presence of early satiety were also found.”
Source: PMID 1384305 · Cangiano 1992 · Am J Clin Nutr
Fibromyalgia
RCT supported- 50 patientsdouble-blind, placebo-controlled
A double-blind, placebo-controlled trial in 50 patients with primary fibromyalgia syndrome reported that all clinical parameters studied were significantly improved by 5-HTP, with only mild and transient side-effects. The abstract reports direction and significance but no effect-size numbers or p-values, and the authors themselves called for further controlled studies, so the result is qualitative and low-confidence.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“A double-blind, placebo-controlled study of the efficacy and tolerability of 5-hydroxytryptophan (5-HTP) was conducted in 50 patients with primary fibromyalgia syndrome. All the clinical parameters studied were significantly improved by treatment with 5-HTP and only mild and transient side-effects were reported. Further controlled studies are required to define properly the value of 5-HTP in patients with primary fibromyalgia syndrome.”
Source: PMID 2193835 · Caruso 1990 · J Int Med Res
Dosage (research context · not a recommendation)
Educational reference, not a dosing recommendation. Research literature describes 50-100 mg taken before bed in the sleep/serotonin-precursor context and 300-900 mg/day in divided doses in older mood/appetite studies; common commercial unit strengths are 50-200 mg. Doses are framed by small, methodologically limited or mechanistic studies, not by confirmatory efficacy trials.
Regulatory Status · 4 Markets
- US · FDA
- Legal dietary-supplement ingredient under DSHEA 1994 (sourced from Griffonia simplicifolia seed); structure/function claims only with the mandatory FDA disclaimer; no FDA-approved disease/health claim; FDA has historically issued an eosinophilia-myalgia syndrome (EMS) association warning, so it is never accurate to call it FDA-approved
- EU · EFSA
- No EU-wide position and no authorized Reg 432/2012 health claim; member-state fragmentation — permitted as a food supplement in some states (e.g. historically Germany/UK), restricted or treated as medicinal in others; functional copy is not supported at EU level
- CN · China
- Not a permitted food ingredient in China — not listed as novel/health-food raw material nor on CBEC positive list; no compliant supplement pathway.
- BR · ANVISA
- Regulatory classification unclear in Brazil; not an established listed food-supplement constituent — a functional ingredient would require case-by-case ANVISA assessment; no authorized functional claim. (BR access path uncertain.)
Safety
5-HTP single-monotherapy human EFFICACY RCT count = 0; direct meta-analysis/SR count = 0 -> evidence grade C (reclassified from a prior B framing). All cited sleep PMIDs are animal (Touret 1991 rat / Sallanon 1982 cat) or a Drosophila GABA-5-HTP COMBINATION (Hong 2016, PMID 26921634) and were excluded (non-human + combination studies). Critical safety constraint (verbatim): SSRI/SNRI/MAOI/tramadol/St John's Wort co-use = absolute contraindication (serotonin syndrome). FDA EMS history retained.
Related
Goals: cognitive-support
Lifestyles: high-stress
References
PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.
- PMID 12169147 · Shaw 2002 · Aust N Z J Psychiatry — Depression (Mood)
- PMID 8791035 · van Vliet 1996 · Eur Neuropsychopharmacol — Panic / Anxiety Provocation
- PMID 1384305 · Cangiano 1992 · Am J Clin Nutr — Appetite / Weight (Obesity)
- PMID 2193835 · Caruso 1990 · J Int Med Res — Fibromyalgia
Frequently Asked Questions
1. Is 5-HTP proven to treat depression?
No. The strongest mood evidence is a meta-analysis (Shaw 2002, PMID 12169147) that located 108 studies of 5-HTP and L-tryptophan but found only two (totaling 64 patients) of sufficient quality to pool. Although the pooled estimate favored the precursors over placebo (Peto OR 4.1, 95% CI 1.3-13.2), the authors concluded the eligible literature was of insufficient quality to inform clinical practice. This is a research finding, not a treatment claim.
2. What doses appear in the research literature?
The literature describes 50-100 mg taken before bed in the serotonin-precursor context and 300-900 mg/day in divided doses in older mood and appetite studies; the obesity RCT (Cangiano 1992) used 900 mg/day. Common commercial unit strengths are 50-200 mg. These are descriptions of what studies used, not a dosing recommendation.
3. Does 5-HTP cause panic or anxiety?
In a controlled challenge study (van Vliet 1996, PMID 8791035), intravenous 5-HTP at three doses did not provoke a panic attack or increase anxiety in 7 panic-disorder patients or 7 healthy controls. This was an honest negative result that did not confirm the serotonin-hypersensitivity hypothesis of panic disorder.
4. Is 5-HTP safe to combine with antidepressants?
Because 5-HTP raises serotonin, combining it with serotonergic drugs — SSRIs, SNRIs, MAOIs, tramadol, or St John's Wort — is treated as an absolute contraindication due to serotonin-syndrome risk. 5-HTP also carries a historical eosinophilia-myalgia syndrome (EMS) safety association noted by the FDA. This page reports evidence and safety context only and is not medical advice.
Last evidence review: 2026-06-13