5-HTP

NutraPedia - Evidence-Based Supplement Research

Back to Table of Contents
Health Goals: mood sleep stress

Research Overview

Across the abstracts provided, 5-HTP has been most studied in relation to appetite/weight regulation in obesity and metabolic disease, with additional smaller bodies of work examining psychiatric and neuroendocrine outcomes (e.g., depression, panic-disorder HPA-axis probing) and pediatric parasomnias (sleep terrors). The obesity/diabetes studies are characterized by double-blind, placebo-controlled designs (including crossover and longer follow-up with sequential diet phases) and use behavioral endpoints such as diet diaries, macronutrient selection, early satiety/anorexia symptoms, and weight change. Other areas include a randomized comparison with fluoxetine in first-episode depression (8 weeks), an experimental cortisol-response paradigm after acute 5-HTP administration in panic disorder and controls, and an open-label pediatric trial for sleep terrors; Parkinson’s disease is represented by a small randomized crossover trial (details truncated in the excerpt) targeting apathy/depressive symptoms.

The strongest evidence in these abstracts supports an anorexigenic effect of oral 5-HTP in overweight/obese and overweight type 2 diabetic populations, with consistent findings of reduced energy intake—often with a notable reduction in carbohydrate intake—early satiety/anorexia-related symptoms, and modest weight loss over weeks, even without prescribed dietary restriction and with reported good tolerability in these trials. Evidence also supports that 5-HTP acutely stimulates serotonergic-linked HPA-axis activity as indexed by increased salivary cortisol in both panic disorder patients and healthy controls, suggesting utility as a serotonergic probe rather than a disorder-specific therapeutic signal. For depression, one randomized double-blind study reports symptom improvement on standard rating scales comparable to fluoxetine over 8 weeks, but this conclusion rests on limited replication within the provided set and does not address longer-term outcomes or relapse prevention.

Key areas needing more research include larger, multi-center randomized controlled trials with longer follow-up to establish durability of weight-loss effects, optimal dosing, and comparative effectiveness versus established anti-obesity interventions, as well as more rigorous safety characterization (including adverse-event profiling and interaction risks in serotonergic polypharmacy). The pediatric sleep-terror findings are promising but derive from an open trial with non-blinded comparison; confirmatory placebo-controlled trials are needed to rule out expectancy effects and to define which subgroups benefit. For psychiatric and neurologic indications (depression, Parkinson’s-related apathy/depression), the evidence base in these abstracts is suggestive but limited by small samples and incomplete reporting; future work should clarify patient selection (e.g., “serotonin-shortage” phenotypes), objective biomarkers of serotonergic engagement, and clinically meaningful endpoints beyond short-term symptom scales.

1. What conditions has 5-HTP been studied for?

  • Obesity / weight management (obese women; obese adults in longer trial): studied for effects on appetite, food intake (especially carbohydrates), and weight loss.

  • Type 2 diabetes (non–insulin-dependent) with overweight: studied for effects on energy intake, macronutrient selection, and body weight (and rationale related to reduced tryptophan availability).

  • Sleep terrors (pediatric parasomnia): studied as a bedtime treatment to reduce episodes and improve longer-term outcomes.

  • Depression:

    • Major depressive episode: compared with fluoxetine in an 8-week randomized double-blind study.

    • Depressive symptoms in Parkinson’s disease: studied in a randomized double-blind placebo-controlled cross-over trial.

  • Panic disorder / serotonergic function testing: studied as a serotonergic challenge (200 mg) to assess HPA-axis response (salivary cortisol) in panic disorder patients vs healthy controls (not a treatment trial).

  • Conceptual/psychiatric theory: one abstract discusses “serotonin-shortage syndrome” as a framework, but it is not a clinical trial of 5-HTP.

2. Does it work in treating those conditions? Summarize the evidence.

  • Obesity / weight loss: evidence suggests reduced intake and modest weight loss in short-to-medium term trials.

    • In a double-blind crossover study in 19 obese women given 5-HTP 8 mg/kg/day for 5 weeks with no prescribed diet, 5-HTP produced anorexia-related symptoms, decreased food intake, and weight loss, with no change in mood scales (BDI, SI, STAI-T, STAI-S).

    • In a double-blind randomized study in 20 obese patients given 5-HTP 900 mg/day across two consecutive 6-week periods (first: no diet prescribed; second: recommended 5040 kJ/day), the 5-HTP group had significant weight loss in both periods, plus early satiety and reduced carbohydrate intake.

    • Limitations: small samples; older studies; outcomes rely partly on self-reported diet diaries; duration limited (5–12 weeks).

  • Type 2 diabetes with overweight: evidence suggests reduced energy intake and weight loss over 2 weeks.

    • In a double-blind placebo-controlled study of 25 overweight non–insulin-dependent diabetic outpatients randomized to 5-HTP 750 mg/day vs placebo for 2 weeks (no diet prescribed), 20 completed. The 5-HTP group significantly decreased daily energy intake by reducing carbohydrate and fat intake and reduced body weight.

    • The study also reported that brain tryptophan availability (as predicted by plasma amino acid measures) was reduced in diabetic patients vs healthy controls, supporting the mechanistic rationale.

    • Limitations: short duration (2 weeks); small completer sample; not designed to establish long-term glycemic outcomes.

  • Sleep terrors in children: evidence suggests benefit, but trial design limits certainty.

    • An open pharmacological trial in 45 children (31 treated) used L-5-HTP 2 mg/kg/day at bedtime for 20 days. After 1 month, 29/31 (93.5%) treated children improved vs 4/14 (28.6%) in the comparison group; at 6 months, 26/31 (83.9%) treated were sleep-terror–free vs persistence in 10/14 (71.4%) in the comparison group.

    • Limitations: “open” design (not blinded/placebo-controlled), potential expectancy and selection biases, and unclear randomization/blinding procedures for the comparison group.

  • Depression (major depressive episode): evidence suggests antidepressant effects comparable to fluoxetine in one trial, but replication is needed.

    • A randomized double-blind study in first depressive episode patients (60 completers; 8 weeks) found both L-5-HTP and fluoxetine produced significant HAM-D reductions starting at week 2 through week 8; response rates were 73.33% (L-5-HTP) vs 80% (fluoxetine), interpreted as “nearly equal.”

    • Limitations: dosing details not provided in the abstract; single study; unclear allocation concealment and adverse-event reporting in the abstract.

  • Depressive symptoms in Parkinson’s disease: preliminary evidence of benefit at low dose for depression (not apathy).

    • In a randomized double-blind placebo-controlled cross-over trial (n=25) using 5-HTP 50 mg daily for 4 weeks, repeated-measures analysis showed a significant improvement in depressive symptoms vs placebo on the HDRS, but no effect on apathy (Apathy Scale).

    • Limitations: small sample; single-center; short treatment periods; authors explicitly call for larger, longer studies.

  • Panic disorder: not evidence of treatment efficacy; used as a physiological probe.

    • Ingestion of 200 mg L-5-HTP increased salivary cortisol in both panic disorder patients and healthy volunteers, supporting its use as a serotonergic challenge test; the findings were interpreted as evidence against serotonin receptor hypersensitivity in panic disorder.

3. What health benefits does it have?

  • Appetite and dietary intake modulation (especially reduced carbohydrate intake)

    • Obesity trials reported early satiety, anorexia-related symptoms, and reduced food intake, with a notable pattern of reduced carbohydrate intake.

    • In overweight type 2 diabetes patients, 5-HTP reduced energy intake by lowering carbohydrate and fat intake.

  • Weight loss (short-term)

    • Observed in obese subjects over 5 weeks and over two 6-week periods, and in overweight type 2 diabetes patients over 2 weeks.

  • Potential antidepressant effects

    • Improved depressive symptoms similarly to fluoxetine in one 8-week trial in first-episode depression.

    • Improved depression ratings (HDRS) in Parkinson’s disease in a small cross-over trial.

  • Potential benefit for pediatric sleep terrors

    • Large apparent reduction in episodes and sustained improvement at 6 months in an open trial, though higher-quality trials are needed.

  • Research/diagnostic utility

    • Produces measurable serotonergic stimulation of the HPA axis (increased salivary cortisol) in both healthy controls and panic disorder patients, supporting use as a probe of serotonin function.

4. Does it have any downsides or side effects?

  • Anorexia-related symptoms / early satiety

    • In obese women, 5-HTP promoted “typical anorexia-related symptoms” alongside reduced intake and weight loss.

    • In the 12-week obesity study, early satiety was consistently present in the 5-HTP group.

    • These effects may be desirable for weight loss but can be downsides if they lead to inadequate intake, nausea-like symptoms (not detailed in the abstracts), or poor tolerability in some individuals.

  • Mood effects were not consistent across populations

    • In obese women, mood state measures did not change despite appetite effects.

    • In depression and PD depression, symptom improvement was reported, suggesting effects may depend on baseline condition, dose, or study design.

  • Physiological endocrine effect: increased cortisol after a single dose

    • 200 mg L-5-HTP increased salivary cortisol in both panic disorder patients and controls. This demonstrates a real biological effect; whether this is clinically beneficial or harmful long-term is not addressed in the abstract.

  • Tolerability/safety reporting is limited in these abstracts

    • The 12-week obesity study states “good tolerance” and suggests 5-HTP “may be safely used,” but detailed adverse event rates are not provided in the abstract.

    • Across the provided abstracts, common supplement concerns (e.g., gastrointestinal adverse effects, sedation, interactions with serotonergic drugs) are not reported or evaluated, so conclusions about side effects are constrained to what is described.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

The provided abstracts do not evaluate genetic variants or pharmacogenomic subgroups, so no evidence-based claims can be made from these sources about specific genotypes that benefit or are harmed by 5-HTP.

  • No genotype-stratified outcomes reported: none of the trials mention polymorphisms (e.g., serotonin transporter, serotonin receptors, tryptophan hydroxylase, MAO/COMT) or differential response by genotype.

  • Mechanistic hints are not pharmacogenomics: the diabetes study reports reduced predicted brain tryptophan availability vs controls and clinical response to 5-HTP, but this is a metabolic/physiological observation, not a genetic finding.

  • Practical implication: at present, based on these abstracts alone, there is insufficient evidence to recommend 5-HTP (or avoid it) specifically due to known genetic variations.

References

  1. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects
    F Ceci, C Cangiano, M Cairella, A Cascino, M Del Ben (1989)
  2. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan
    C Cangiano, F Ceci, A Cascino, M Del Ben, A Laviano (1992)
  3. L -5-Hydroxytryptophan treatment of sleep terrors in children
    Oliviero Bruni, Raffaele Ferri, Silvia Miano, Elisabetta Verrillo (2004)
  4. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients
    C Cangiano, A Laviano, M Del Ben, I Preziosa, F Angelico (1998)
  5. L-5-hydroxytryptophan induced increase in salivary cortisol in panic disorder patients and healthy volunteers
    Koen Schruers, Rob van Diest, Nancy Nicolson, Eric Griez (2002)
  6. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode
    Purushottam Jangid, Prerna Malik, Priti Singh, Minakshi Sharma, Anil Kumar D Gulia (2013)
  7. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine
    W Pöldinger, B Calanchini, W Schwarz (1991)
  8. Efficacy and safety of 5-hydroxytryptophan on depression and apathy in Parkinson's disease: a preliminary finding
    M Meloni, M Puligheddu, M Carta, A Cannas, M Figorilli (2020)


Want personalized supplement recommendations based on your genetics?
Upload Whole Genome Sequencing (WGS) raw DNA data today!
Or upload raw DNA data to get started with your free analysis!