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Htp8.5
5-HTP Research
Likely helpsModerate safety
28 peer-reviewed studies
What the evidence says
Likely helps
5-HTP appears to help in 6 of 7 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality meta-analyses and randomised trials published 2002–2026 with a typical study size of 41 participants.
Based on 28 studies · 1 meta-analysis · 21 RCTs · 6,298 total participants
Confidence
High
What the studies found
6helped1unclear· 21 more without graded effect data
9 studies in the last 5 years · Latest meta-analysis: 2022
200220142026
1Systematic ReviewCited 24×n=2,023 · very large study2022
This review provides uncertain evidence only regarding the use of hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare formula, Oxepa formula, or 5-hydroxytryptophan as universal PTSD prevention strategies.
Bertolini F et al. · The Cochrane database of systematic reviews (2022)
This review provides uncertain evidence only regarding the use of hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare formula, Oxepa formula, or 5-hydroxytryptophan as universal PTSD prevention strategies.
Future research might benefit from larger samples, better reporting of side effects and inclusion of quality of life and functioning measures.
2Systematic ReviewCited 69×n=1,474 · large study2018
There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.
Thorpe J et al. · The Cochrane database of systematic reviews (2018)
Two studies only reported any primary outcomes of interest (patient-reported pain relief of 30%, or 50%, or greater).
There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.
4Alcohol use disorder treatment effectivenessSystematic ReviewCited 8×2018
No significant benefit for the use of combinations over single agents was observed.
Naglich AC et al. · CNS drugs (2018)
Drug combination effect sizes were comparable to those observed in single-agent trials.
No significant benefit for the use of combinations over single agents was observed.
However, benefit may be observed when combined pharmacological interventions address specific symptoms of alcohol use disorder known to be influenced by combination components, or when combinations are used in specific subpopulations in which combination components demonstrate benefit.
8Cognitive function (MoCA score)RCTn=30 · small study2025
However, given the relatively small sample size (n = 30) and short-term (12-week) intervention, these findings should be interpreted cautiously, and further long-term studies with a larger sample size are warranted to confirm these preliminary results.
Li S et al. · Nutrients (2025)
Noticeable benefit
← WorseNo effectBetter →
Borderline
Results: A significant time effect was observed in the MoCA score, which was mainly explained by a significant increase in the 5-HTP group (week 0 vs. week 12: 26.6 ± 1.4 a.u. vs. 27.6 ± 1.4 a.u., p < 0.05).
Moreover, the 5-HTP group showed a significant increase in serum serotonin levels.
Additionally, the GDS score improved in the 5-HTP group (week 0 vs. week 8: 1.2 ± 1.7 a.u. vs. 0.7 ± 1.2 a.u., p < 0.05).
9IBD-related fatigue reductionRCTCited 34×n=166 · medium study2022
Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).
Truyens M et al. · Gastroenterology (2022)
No clear effect
← WorseNo effectBetter →
Could be chance
During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo.
The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P = .830).
10Obsessive-compulsive disorder symptomsRCTCited 12×n=60 · small study2020
The results of this study confirm that 5-hydroxytryptophan may be effective as an augmentative agent in treatment of moderate-to-severe OCD.
Yousefzadeh F et al. · International clinical psychopharmacology (2020)
All patients, regardless of their treatment group, received fluoxetine at 20 mg/day for the initial 4 weeks of the study followed by 60 mg/day of fluoxetine for the rest of the trial course.
Symptoms were assessed using the Y-BOCS at baseline and weeks 4, 8 and 12.
The results of this study confirm that 5-hydroxytryptophan may be effective as an augmentative agent in treatment of moderate-to-severe OCD.
5-HTP supplementation can improve certain sleep quality components in older adults and this benefit was more prominently observed in poor sleepers. 5-HTP was also able to improve the gut microbiota composition in poor sleepers.
Sutanto CN et al. · Clinical nutrition (Edinburgh, Scotland) (2024)
Noticeable benefit
← WorseNo effectBetter →
Likely real
In particular, at week 12, not good sleepers but poor sleepers with 5-HTP supplementation were able to significantly improve subjective GSS (ΔSL5-HTP: -2.80 ± 1.10 min, p-value = 0.005).
5-HTP supplementation can improve certain sleep quality components in older adults and this benefit was more prominently observed in poor sleepers. 5-HTP was also able to improve the gut microbiota composition in poor sleepers.
This study provides evidence that 5-HTP is safe and effective in improving sleep stability in PD, contributing to ameliorate patients' global sleep quality.
Meloni M et al. · Sleep & breathing = Schlaf & Atmung (2022)
5-HTP produced an increase in the total percentage of stage REM sleep without a related increase of RBD episodes, as well as a marginal, non-significant reduction in both arousal index and wake after sleep onset.
The self-reported RBD frequency and clinical global impression (CGI) were improved during 5-HTP and placebo treatment in comparison to baseline. 5-HTP significantly improved our patients' motor experiences of daily living as rated by the Unified Parkinson's Disease Rating Scale (UPDRS) part II.
This study provides evidence that 5-HTP is safe and effective in improving sleep stability in PD, contributing to ameliorate patients' global sleep quality.
It was concluded that the neurotransmitter-precursor-supplement intervention is effective in alleviating the withdrawal and mood symptoms and it may become a supplementary method for patients' recovery from heroin addiction.
Chen D et al. · Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (2012)
The results showed that the insomnia and withdrawal scores were significantly improved over time in participants in the intervention group as compared with those in the control group.
The sleep status and the withdrawal symptoms were observed daily throughout the study, and the mood states were monitored pre- and post-intervention.
A greater reduction in tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and total mood disturbance, and a greater increase in their vigor-activity symptoms were found at day 6 in the intervention group than in the control group (all P<0.05).
Importantly, emotion recognition ability decreased with age which was for positive emotions compensated by TRP.
Since the supramarginal gyrus is associated with empathy, pain and related information integration results could be interpreted as reflecting stricter evaluation of negative behavior due to better integration of information.
Improved recognition of positive emotions with TRP in older participants supports the use of a TRP-rich diet to compensate for age related decline in social-cognitive processes.
This study provides preliminary evidence of clinical benefit of 5-HTP for treating depressive symptoms in PD.
Meloni M et al. · European journal of neurology (2020)
Repeated-measures analysis revealed a significant improvement of depressive symptoms during the 50-mg 5-HTP treatment compared with placebo as assessed by the HDRS.
This study provides preliminary evidence of clinical benefit of 5-HTP for treating depressive symptoms in PD.
Larger studies with a longer treatment duration are needed to corroborate these early findings.
18Cortisol response to 5-HTP challengeRCTCited 1×2020
Pharmacology Research & Perspectives
Guan Z et al. · Pharmacology research & perspectives (2020)
A power function provided a better description than a linear function to relate the saliva and serum cortisol.
In conclusion, a circadian rhythm component was built in the PK/PD model of the 5-HTP challenge test which could better improve the understanding of the stimulating effect on HPA with cortisol change.
After the 5-HTP challenge, saliva cortisol correlated well with serum cortisol and was predictable by a population PK-PD model.