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5-HTP and mood: grade C

Limited evidence. Direction: No effect.

C LimitedSubjective outcome onlyShort-term only

Educational guidance, not medical advice

Why this grade

Rubric condition met: Small, mostly null controlled trials in people without a diagnosis; N needs a meta-analysis or 2 independent adequately sized null RCTs

In healthy undergraduates, a single 100 mg dose did not significantly change mood ratings compared with placebo (n = 46). In 30 healthy older adults, 100 mg a day lowered mood-questionnaire scores within the 5-HTP group at week 8 of a 12-week trial, but the group-by-time comparison with an untreated control was not significant (p = 0.3851) and anxiety scores did not change. A placebo-controlled trial in 166 people with inactive bowel disease found no difference in mood scores (clinical population). Meta-analyses in diagnosed depression are population context only and rest on studies the authors call relatively weak, few with placebo groups.

How we grade evidence

Studies this grade rests on

EffectMixedNo effectSize shows participants (n)2000200520102015202020252030Meta-analysisSystematic reviewRCTCrossover RCTControlled trialTruyens 2022, 2022: crossover RCT, n = 166, result not recordedShaw 2002, 2002: systematic review, n = 64, result not recordedGendle 2010, 2010: controlled trial, n = 46, result not recordedLi 2025, 2025: RCT, n = 30, result not recordedJavelle 2020, 2020: meta-analysis, n not recorded, result not recorded
each study this grade rests on, by publication year and design. Solid: effect versus the comparator; half-filled: mixed; hollow: no effect; dashed: result not recorded yet. Larger marks had more participants.
Show the numbers
StudyYearDesignParticipantsResult
Shaw 20022002systematic review64result not recorded
Gendle 20102010controlled trial46result not recorded
Javelle 20202020meta-analysisnot recordedresult not recorded
Truyens 20222022crossover RCT166result not recorded
Li 20252025RCT30result not recorded

Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial.

Truyens M, Lobatón T, Ferrante M. Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial Gastroenterology, 2022. PMID 35940251

Result not recorded
Design
Multicenter randomized, placebo-controlled crossover trial (two 8-week periods)
Sample
n = 166
Population
Patients with inactive inflammatory bowel disease and fatigue (clinical population)
Funding
BIRD Foundation; Fonds Wetenschappelijk Onderzoek (Crossref funders)

Oral administration of 5-hydroxytryptophan (5-HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task.

Gendle MH, Golding AC. Oral administration of 5-hydroxytryptophan (5-HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task Hum Psychopharmacol, 2010. PMID 20737522

Result not recorded
Design
Placebo-controlled trial, single dose (two 50 mg capsules)
Sample
n = 46
Population
Healthy undergraduates
Funding
not stated in the PubMed or Crossref record; full text not read

The Impact of 5-Hydroxytryptophan Supplementation on Cognitive Function and Mood in Singapore Older Adults: A Randomized Controlled Trial.

Li S, Sutanto CN, Xia X. The Impact of 5-Hydroxytryptophan Supplementation on Cognitive Function and Mood in Singapore Older Adults: A Randomized Controlled Trial Nutrients, 2025. PMID 40944161

Result not recorded
Design
Single-blinded, 12-week parallel randomized controlled trial; control group took nothing (no placebo)
Sample
n = 30
Population
Cognitively healthy older adults in Singapore (66 ± 3 years)
Funding
National University of Singapore iHealthtech Microbiome in Health, Disease and Ageing (PubMed grant)

Tryptophan and 5-hydroxytryptophan for depression.

Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression Cochrane Database Syst Rev, 2002. PMID 11869656

Result not recorded
Design
Cochrane systematic review; 2 of 108 located trials met inclusion criteria
Sample
n = 64
Population
Adults with unipolar depression or dysthymia (clinical population)
Funding
not stated in the PubMed or Crossref record; full text not read

Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis.

Javelle F, Lampit A, Bloch W. Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis Nutr Rev, 2020. PMID 31504850

Result not recorded
Design
Systematic review (13 studies) and meta-analysis (7 studies), preregistered on PROSPERO
Population
People with depression (clinical population)
Funding
not stated in the PubMed or Crossref record; full text not read

Search and history

Search (): (5-hydroxytryptophan[ti] OR 5-HTP[ti]) AND (healthy[tiab]) AND (mood[tiab] OR stress[tiab] OR anxiety[tiab] OR emotion*[tiab])

  • Graded C (proposed): Proposed in the monograph draft
  • C to C (approved): Editor sign-off November 13, 2026: grade matches the editor-approved final page