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Research · Supplements

5-HTP

A 2002 Cochrane review found only 2 of 108 trials of 5-HTP or tryptophan met quality criteria. A 2020 meta-analysis reported large effects on depression scores but found few placebo-controlled studies. Combined with SSRIs, 5-HTP amplified hormone markers of serotonin activity. Contaminants linked to eosinophilia-myalgia syndrome were found in commercial products.

Add to Bio HackChecked 2026-11-09
Status
Dietary supplement in the US.
Also called
5-hydroxytryptophan, L-5-hydroxytryptophan, oxitriptan, Griffonia simplicifolia seed extract
Taken for
depression, mood, sleep, appetite, weight loss, serotonin

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help4

Reported risks2

What people take it for, and what was found

Shown to help4

Moderate

Depression

Shown to improve depression scores over placebo in two small trials of adults with depression, though the review authors judged the evidence too weak to be conclusive.

The numbers and sources
Effect
A Cochrane review located 108 trials of 5-HTP and tryptophan, and only 2 (64 patients) met quality criteria. Combined, they favored the supplements over placebo (Peto OR 4.10, 95% CI 1.28 to 13.15, NNT 2.78), and the authors judged the evidence too weak to be conclusive [1]. A 2020 meta-analysis of 13 studies reported a remission rate of 0.65 (95% CI 0.55 to 0.78) and a large effect on questionnaire scores (Hedges' g 1.11, 95% CI 0.53 to 1.69, I² 76%) [2]. In 60 patients with a first depressive episode, 8 weeks of 5-HTP or fluoxetine gave similar HAM-D reductions, with 73.33% and 80% responding [3]. In a 25-person crossover trial in Parkinson's disease, 50 mg a day improved HDRS depression scores over placebo but not apathy [4].
Population
Adults with unipolar depression or dysthymia [1][2]. First-episode depression in India [3]. Parkinson's disease [4].
Sources
[1], [2], [3], [4]
Caveats
The 2020 review rated studies as relatively weak, and few had placebo groups [2]. The fluoxetine comparison had no placebo arm [3].
Limited

Obsessive-compulsive disorder alongside fluoxetine

One trial found adding 5-HTP to fluoxetine for 12 weeks lowered OCD symptoms more than fluoxetine plus placebo in 60 adults.

The numbers and sources
Effect
In 60 patients with moderate to severe OCD, adding 5-HTP 100 mg twice daily to fluoxetine for 12 weeks gave larger Y-BOCS reductions and higher partial and complete response rates than fluoxetine plus placebo [5].
Population
60 adults with OCD [5].
Sources
[5]
Caveats
One trial. The abstract does not report adverse events [5].
Limited

Appetite and weight

One small trial found obese adults on 900 mg a day lost weight, ate less carbohydrate and felt full sooner than on placebo.

The numbers and sources
Effect
In 20 obese patients given 900 mg a day or placebo for two 6-week periods, those on 5-HTP lost weight in both periods, ate less carbohydrate and reported early satiety [6].
Population
20 obese adults [6].
Sources
[6]
Caveats
One small trial from 1992 [6].
Limited

Sleep

Small trials found 5-HTP improved sleep scores in older adults who slept poorly, raised REM sleep in Parkinson's disease, and cut sleep terrors in children.

The numbers and sources
Effect
In 30 older adults given 100 mg a day or nothing for 12 weeks, poor sleepers on 5-HTP improved their Pittsburgh Sleep Quality Index global score by 2.80 points (p = 0.005), while good sleepers did not change [11]. In 18 people with Parkinson's disease and REM sleep behavior disorder, 50 mg a day for 4 weeks raised the share of REM sleep over placebo, with no rise in episodes and a non-significant fall in arousals and waking after sleep onset [12]. In 45 children with sleep terrors, 29 of 31 (93.5%) given 2 mg/kg at bedtime for 20 days responded at 1 month, against 4 of 14 (28.6%) untreated, and 26 of 31 (83.9%) were free of sleep terrors at 6 months [13].
Population
30 older adults in Singapore, mean age 66 [11]. 18 adults with Parkinson's disease [12]. 45 children aged 3 to 10 [13].
Sources
[11], [12], [13]
Caveats
The older adult trial was single-blinded with an untreated control, not placebo, and the benefit appeared only in the poor sleeper subgroup [11]. The Parkinson's trial was small and short [12]. The sleep terror trial was open label with no placebo [13]. No trial in adults with insomnia was located.

Doses studied

Trials used 50 mg a day in Parkinson's disease [4], 200 mg a day alongside fluoxetine [5], and 900 mg a day for weight [6]. Single 200 mg doses were used in hormone challenge studies with SSRIs [7][8].

Risks

Reported risks2

LimitedHow often is not known

Use with SSRIs and serotonin syndrome

Limited evidence: 5-HTP raised hormone markers of serotonin activity more in people taking fluoxetine. No study counting serotonin syndrome with this combination was found.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In healthy men, a single 200 mg dose of 5-HTP augmented the prolactin and cortisol response to 20 mg of citalopram [7]. In patients with depression or OCD, 5-HTP raised cortisol and prolactin more in those taking fluoxetine than in those on tricyclics or no drug [8]. The study authors used these hormone responses as a marker of increased serotonin-mediated activity [7]. No case series or trial counting serotonin syndrome with 5-HTP and SSRIs was located in Europe PMC searches.
Population
Healthy Asian men [7]. Patients with depression or OCD [8].
Sources
[7], [8]
Caveats
Hormone markers are not clinical outcomes. A 12-week trial combined 5-HTP 200 mg a day with fluoxetine up to 60 mg a day, and its abstract does not report adverse events [5].
LimitedHow often is not known

Eosinophilia-myalgia syndrome and peak X contaminants

Limited evidence: EMS-like symptoms have been linked to 5-HTP, and contaminants called peak X were found in tested products. Sources disagree on whether peak X matters.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Eosinophilia-myalgia syndrome (EMS) was traced in 1989 to contaminated L-tryptophan from one manufacturer [9]. EMS-like symptoms have been associated with 5-HTP, and analysis of EMS-implicated 5-HTP found "peak X," a family of contaminants. All 8 commercial 5-HTP samples tested contained three or more peak X contaminants [10]. A 2004 review reported no definitive toxicity cases in 20 years of use, apart from one unresolved case, and described peak X as a chromatographic artifact at very small concentrations [9].
Population
Product analyses and case reports [9][10].
Sources
[9], [10]
Caveats
The sources disagree on peak X. The Cochrane review states the possible link between these substances and EMS has not been elucidated [1].

Claims tested and not found

  1. That 5-HTP reduces apathy in Parkinson's disease. Apathy Scale scores did not differ from placebo over 4 weeks [4].

Sources

  1. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database of Systematic Reviews. 2002. https://doi.org/10.1002/14651858.CD003198
  2. Javelle F, Lampit A, Bloch W, et al. Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis. Nutrition Reviews. 2020. https://doi.org/10.1093/nutrit/nuz039
  3. Jangid P, Malik P, Singh P, et al. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian Journal of Psychiatry. 2013. https://doi.org/10.1016/j.ajp.2012.05.011
  4. Meloni M, Puligheddu M, Carta M, et al. Efficacy and safety of 5-hydroxytryptophan on depression and apathy in Parkinson's disease: a preliminary finding. European Journal of Neurology. 2020. https://doi.org/10.1111/ene.14179
  5. Yousefzadeh F, Sahebolzamani E, Sadri A, et al. 5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control. International Clinical Psychopharmacology. 2020. https://doi.org/10.1097/YIC.0000000000000321
  6. Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. The American Journal of Clinical Nutrition. 1992. https://doi.org/10.1093/ajcn/56.5.863
  7. Lowe SL, Yeo KP, Teng L, et al. L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology. 2006. https://doi.org/10.1016/j.psyneuen.2005.11.005
  8. Meltzer H, Bastani B, Jayathilake K, Maes M. Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder. Neuropsychopharmacology. 1997. https://doi.org/10.1016/S0893-133X(96)00280-1
  9. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicology Letters. 2004. https://doi.org/10.1016/j.toxlet.2003.12.070
  10. Klarskov K, Johnson KL, Benson LM, et al. Eosinophilia-myalgia syndrome case-associated contaminants in commercially available 5-hydroxytryptophan. Advances in Experimental Medicine and Biology. 1999. https://doi.org/10.1007/978-1-4615-4709-9_58
  11. 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. Clinical Nutrition. 2024. https://doi.org/10.1016/j.clnu.2024.01.010
  12. 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 and Breathing. 2022. https://doi.org/10.1007/s11325-021-02417-w
  13. Bruni O, Ferri R, Miano S, Verrillo E. L-5-Hydroxytryptophan treatment of sleep terrors in children. European Journal of Pediatrics. 2004. https://doi.org/10.1007/s00431-004-1444-7

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