5-HTP
Also sold as: 5-hydroxytryptophan · L-5-HTP · Oxitriptan
A serotonin precursor sold for sleep, mood and appetite. Clinical evidence is mostly small, older trials and does not establish equivalence to prescription treatment.
Sleep Anxiety Focus
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Research
- Sleep: Small sleep studies include a 2024 older-adult RCT with a published critical commentary; pediatric and Parkinson disease results cannot be generalized.
- Focus: One 2025 older-adult cognitive and mood RCT is preliminary and requires replication; no established healthy-adult focus benefit.
- Anxiety: A small older controlled trial reported improvement, while acute panic challenge studies are not evidence of long-term treatment.
REALITY CHECK // Small trials suggest sleep and anxiety benefits, but depression reviews found too little high-quality evidence for routine use. Serotonergic drug combinations and product purity are central safety concerns. The supplied IBD-fatigue trial has an unresolved result, so no energy benefit is assigned.
Levels: how we grade evidence. Grey = evidence of no benefit; amber = evidence it makes this goal worse.
Ratings are self-reported by a self-selected group of users: how it felt, not proof that it works.
Check your bottle
Compare what your label says with what was used in trials. This is a trial range, not a personal prescription.
Enter the amount from your label to see the result.
How it was studied
01 // STUDIED_DOSE_RANGE
50–400 mg: supplement context
The source reports a much wider 50–3,000 mg/day research span across indications. The calculator uses common labeled amounts, not a validated therapeutic window.
02 // TIMING_&_MATRIX
No universal timing protocol
Sleep, appetite and psychiatric studies use different regimens. Slow release and sublingual marketing do not establish a superior schedule.
03 // EVALUATION_WINDOW
Weeks in clinical studies
Depression and sleep outcomes were assessed with repeated administration; acute challenge studies address different questions.
04 // SAFETY_&_QUALITY_GATE
Serotonergic interactions and purity
No formal UL is established in the dossier. Review medicines and manufacturing quality; long-term safety is unresolved.
UPPER LIMIT // The dossier identifies no established EFSA or NIH/IOM UL for 5-HTP. Trial doses and common capsule strengths do not establish a safe upper intake; long-term safety remains poorly characterized.
Summary
Small trials suggest sleep and anxiety benefits, but depression reviews found too little high-quality evidence for routine use. Serotonergic drug combinations and product purity are central safety concerns. The supplied IBD-fatigue trial has an unresolved result, so no energy benefit is assigned.
Mechanism
5-HTP is converted to serotonin by aromatic amino acid decarboxylase, a vitamin-B6-dependent enzyme. Increased precursor availability does not establish that low serotonin causes a condition or that supplementation treats it.
Typical studied dose
The dossier reports human study doses spanning 50–3,000 mg/day and common supplement amounts of 50–400 mg/day. These combine different conditions and medical regimens, including carbidopa; they are not one proven sleep-dose range or a self-treatment recommendation.
Upper limit
The dossier identifies no established EFSA or NIH/IOM UL for 5-HTP. Trial doses and common capsule strengths do not establish a safe upper intake; long-term safety remains poorly characterized.
Popular stacks with 5-HTP
Not enough stack data yet. A combination with 5-HTP appears here once 5 people rate the same set.
Forms and label traps
| Form on label | Active content | Studied range / day | Absorption & GI tolerance | Verdict |
|---|---|---|---|---|
| Standard capsule or tablet: declared 5-HTP content Best for: Comparing declared 5-HTP mass. |
Extract weight · ~100% marker | 50–400 mg | Orally absorbed; source reviews discuss precursor pharmacology. Dose-related nausea is common. |
Studied standard [REFERENCE // TRIAL_CONTEXT] 50–400 mg is supplement context, not an indication-specific efficacy threshold. Enter the declared 5-HTP amount, not unassayed Griffonia extract mass. |
| Slow-release 5-HTP Best for: Release-profile label review. |
Extract weight · ~100% marker | 50–400 mg | A smoother concentration profile is theoretical here. Reduced nausea is not established head-to-head. |
Caution [CAUTION // LIMITED_COMPARABILITY] No comparative efficacy RCT is supplied; the same mass does not demonstrate equivalent release kinetics. |
| Sublingual spray or strips Best for: Recognizing route differences. |
Extract weight · ~100% marker | 50–400 mg | First-pass avoidance is a marketing rationale; clinical superiority is unproven. Comparative tolerability is uncertain. |
Caution [CAUTION // LIMITED_COMPARABILITY] One small satiety study does not establish superiority for sleep, mood or safety. |
Common label traps
- TRAP_01 // Natural antidepressant equal to medication
Cochrane reviews found too little high-quality evidence; small comparator trials do not establish equivalence or freedom from adverse effects. - TRAP_02 // B6 guarantees clinical synergy
B6 is an enzyme cofactor, but biochemical plausibility is not proof of a better clinical outcome. - TRAP_03 // More serotonin means a cure
A blood serotonin result does not diagnose a brain serotonin deficiency or establish an indication for 5-HTP.
Other outcomes studied
Outside the five leaderboard goals. Same evidence levels as above.
- DEPRESSION Limited · benefit
Reviews found a signal in small older studies, but only two of 108 studies met Cochrane quality criteria; evidence was insufficient for routine treatment. Small fluoxetine/fluvoxamine comparisons do not prove equivalence.
PMID 11687048 PMID 11869656 PMID 12169147 PMID 31504850 PMID 23380314 PMID 1909444 PMID 6381336 - ANXIETY Limited · benefit
An older small controlled comparison reported benefit; panic challenge data are mixed and cannot define a treatment regimen.
PMID 3312397 PMID 8791035 - SLEEP Limited · benefit
A 2024 older-adult RCT reported better sleep, but a critical commentary challenges interpretation. Older architecture and pediatric night-terror findings are population-specific.
PMID 38309227 PMID 4105646 PMID 15146330 - MIGRAINE PREVENTION Limited · benefit
Older adult and pediatric trials are mixed. A 124-person methysergide comparison is historical and does not establish modern treatment equivalence.
PMID 3536521 PMID 3533271 PMID 3913752 PMID 10721054 - FIBROMYALGIA Limited · benefit
One small older blinded trial reported symptom improvement; modern large replication is absent.
PMID 2193835 PMID 8906292 - APPETITE AND WEIGHT Limited · benefit
Small short-term trials reported reduced intake or earlier satiety in obesity and diabetes; durable weight loss and a safe appetite-suppression protocol are not established.
PMID 1384305 PMID 1722953 PMID 2468734 PMID 9705024 PMID 19752879 - OLDER-ADULT COGNITION Limited · benefit
A single 2025 RCT examined cognition and mood; the source calls the signal preliminary.
PMID 40944161 - PARKINSON DISEASE Limited · benefit
Preliminary trials addressed depression/apathy and REM sleep behavior disorder in Parkinson disease, not general supplementation.
PMID 32067288 PMID 34403081
Reader questions
Can it be combined with an SSRI or SNRI?
A serotonergic combination can cause serotonin syndrome. The medication prescriber must assess this; changing or stopping a prescription to add 5-HTP is not a safe workaround.
Does slow release or sublingual 5-HTP work better?
The dossier has no convincing head-to-head efficacy evidence. A small sublingual satiety study cannot establish superiority for sleep or mood.
What about emotional blunting, hair loss and long-term safety?
Nausea is a recognized dose-related effect. Emotional flattening and libido changes are reader reports, while hair-loss causality is not established here. Long-term EMS and cardiac questions remain unresolved rather than proven absent.
Stack interactions
- Danger Serotonergic medicines and St John's wort [DANGER // MEDICAL_REVIEW]
Additive serotonergic effects can cause serotonin syndrome; this is a medication-review issue, especially with MAOIs.
PMID 16023217 PMID 33375373 - Danger Carbidopa [DANGER // MEDICAL_REVIEW]
Changes peripheral conversion and central exposure. Research combinations are not interchangeable with OTC use; scleroderma-like skin effects are noted in the source review.
PMID 16023217 - Caution Glucose-lowering treatment [CAUTION // CLINICAL_REVIEW]
Reduced food intake may change glucose and medication needs; the cited study addresses intake in diabetes, not a definitive pharmacokinetic interaction.
PMID 9705024
Red flags: interactions and who should avoid it
Interactions
SSRIs, SNRIs, MAOIs, tricyclics, tramadol, triptans, linezolid, dextromethorphan and St John's wort may add serotonergic effects. Carbidopa alters disposition and belongs in medical care. Appetite changes may affect glucose control; B6 and tyrosine stacks have no proven clinical superiority.
Avoid or ask a doctor first if
Avoid unsupervised use in pregnancy, breastfeeding, children, bipolar disorder, eating disorders, liver or connective-tissue disease, and with serotonergic medicines. Agitation, fever, tremor, muscle jerks or rapid heartbeat with a serotonergic combination require urgent assessment. Nausea is dose-related. Historical EMS/Peak X contamination reports do not establish that pure 5-HTP itself causes EMS; chronic cardiac-valve risk remains theoretical.
Sources (PubMed, 28)
- Tryptophan and 5-hydroxytryptophan for depression.
PMID 11687048 · 2001 · Systematic reviewReviews found a signal in small older studies, but only two of 108 studies met Cochrane quality criteria; evidence was insufficient for routine treatment. Small fluoxetine/fluvoxamine comparisons do not prove equivalence.
- Tryptophan and 5-hydroxytryptophan for depression.
PMID 11869656 · 2002 · Systematic reviewReviews found a signal in small older studies, but only two of 108 studies met Cochrane quality criteria; evidence was insufficient for routine treatment. Small fluoxetine/fluvoxamine comparisons do not prove equivalence.
- Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis.
PMID 12169147 · 2002 · Meta-analysisReviews found a signal in small older studies, but only two of 108 studies met Cochrane quality criteria; evidence was insufficient for routine treatment. Small fluoxetine/fluvoxamine comparisons do not prove equivalence.
- Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis.
PMID 31504850 · 2020 · Meta-analysisReviews found a signal in small older studies, but only two of 108 studies met Cochrane quality criteria; evidence was insufficient for routine treatment. Small fluoxetine/fluvoxamine comparisons do not prove equivalence.
- Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode.
PMID 23380314 · 2013 · Randomized controlled trialReviews found a signal in small older studies, but only two of 108 studies met Cochrane quality criteria; evidence was insufficient for routine treatment. Small fluoxetine/fluvoxamine comparisons do not prove equivalence.
- A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine.
PMID 1909444 · 1991 · Randomized controlled trialReviews found a signal in small older studies, but only two of 108 studies met Cochrane quality criteria; evidence was insufficient for routine treatment. Small fluoxetine/fluvoxamine comparisons do not prove equivalence.
- Treatment of depression with L-5-hydroxytryptophan combined with chlorimipramine, a double-blind study.
PMID 6381336 · 1983 · Randomized controlled trialReviews found a signal in small older studies, but only two of 108 studies met Cochrane quality criteria; evidence was insufficient for routine treatment. Small fluoxetine/fluvoxamine comparisons do not prove equivalence.
- Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo.
PMID 3312397 · 1987 · Randomized controlled trialAn older small controlled comparison reported benefit; panic challenge data are mixed and cannot define a treatment regimen.
- Behavioral, neuroendocrine and biochemical effects of different doses of 5-HTP in panic disorder.
PMID 8791035 · 1996 · Randomized controlled trialAn older small controlled comparison reported benefit; panic challenge data are mixed and cannot define a treatment regimen.
- The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial.
PMID 38309227 · 2024 · Randomized controlled trialA 2024 older-adult RCT reported better sleep, but a critical commentary challenges interpretation. Older architecture and pediatric night-terror findings are population-specific.
- Effects of 5-hydroxytryptophan on the sleep of normal human subjects.
PMID 4105646 · 1971 · Clinical or pharmacokinetic reportA 2024 older-adult RCT reported better sleep, but a critical commentary challenges interpretation. Older architecture and pediatric night-terror findings are population-specific.
- L -5-Hydroxytryptophan treatment of sleep terrors in children.
PMID 15146330 · 2004 · Randomized controlled trialA 2024 older-adult RCT reported better sleep, but a critical commentary challenges interpretation. Older architecture and pediatric night-terror findings are population-specific.
- 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial.
PMID 3536521 · 1986 · Randomized controlled trialOlder adult and pediatric trials are mixed. A 124-person methysergide comparison is historical and does not establish modern treatment equivalence.
- L-5-hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study.
PMID 3533271 · 1986 · Clinical or pharmacokinetic reportOlder adult and pediatric trials are mixed. A 124-person methysergide comparison is historical and does not establish modern treatment equivalence.
- Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo.
PMID 3913752 · 1985 · Clinical or pharmacokinetic reportOlder adult and pediatric trials are mixed. A 124-person methysergide comparison is historical and does not establish modern treatment equivalence.
- L-5-hydroxytryptophan can prevent nociceptive disorders in man.
PMID 10721054 · 1999 · Randomized controlled trialOlder adult and pediatric trials are mixed. A 124-person methysergide comparison is historical and does not establish modern treatment equivalence.
- Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome.
PMID 2193835 · 1990 · Randomized controlled trialOne small older blinded trial reported symptom improvement; modern large replication is absent.
- Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy.
PMID 8906292 · 1996 · Randomized controlled trialOne small older blinded trial reported symptom improvement; modern large replication is absent.
- Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan.
PMID 1384305 · 1992 · Randomized controlled trialSmall short-term trials reported reduced intake or earlier satiety in obesity and diabetes; durable weight loss and a safe appetite-suppression protocol are not established.
- Effects of 5-hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese adult subjects.
PMID 1722953 · 1991 · Randomized controlled trialSmall short-term trials reported reduced intake or earlier satiety in obesity and diabetes; durable weight loss and a safe appetite-suppression protocol are not established.
- The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects.
PMID 2468734 · 1989 · Clinical or pharmacokinetic reportSmall short-term trials reported reduced intake or earlier satiety in obesity and diabetes; durable weight loss and a safe appetite-suppression protocol are not established.
- Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients.
PMID 9705024 · 1998 · Randomized controlled trialSmall short-term trials reported reduced intake or earlier satiety in obesity and diabetes; durable weight loss and a safe appetite-suppression protocol are not established. Reduced food intake may change glucose and medication needs; the cited study addresses intake in diabetes, not a definitive pharmacokinetic interaction.
- Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation.
PMID 19752879 · 2009 · Randomized controlled trialSmall short-term trials reported reduced intake or earlier satiety in obesity and diabetes; durable weight loss and a safe appetite-suppression protocol are not established. Form or pharmacokinetic context: One small satiety study does not establish superiority for sleep, mood or safety.
- The Impact of 5-Hydroxytryptophan Supplementation on Cognitive Function and Mood in Singapore Older Adults: A Randomized Controlled Trial.
PMID 40944161 · 2025 · Randomized controlled trialA single 2025 RCT examined cognition and mood; the source calls the signal preliminary.
- Efficacy and safety of 5-hydroxytryptophan on depression and apathy in Parkinson's disease: a preliminary finding.
PMID 32067288 · 2020 · Randomized controlled trialPreliminary trials addressed depression/apathy and REM sleep behavior disorder in Parkinson disease, not general supplementation.
- 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.
PMID 34403081 · 2022 · Randomized controlled trialPreliminary trials addressed depression/apathy and REM sleep behavior disorder in Parkinson disease, not general supplementation.
- Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan.
PMID 16023217 · 2006 · Clinical or pharmacokinetic reportForm or pharmacokinetic context: 50–400 mg is supplement context, not an indication-specific efficacy threshold. Enter the declared 5-HTP amount, not unassayed Griffonia extract mass. Additive serotonergic effects can cause serotonin syndrome; this is a medication-review issue, especially with MAOIs. Changes peripheral conversion and central exposure. Research combinations are not interchangeable with OTC use; scleroderma-like skin effects are noted in the source review.
- 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology.
PMID 33375373 · 2020 · Clinical or pharmacokinetic reportForm or pharmacokinetic context: 50–400 mg is supplement context, not an indication-specific efficacy threshold. Enter the declared 5-HTP amount, not unassayed Griffonia extract mass. Additive serotonergic effects can cause serotonin syndrome; this is a medication-review issue, especially with MAOIs.
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