5-HTP (5-hydroxytryptophan)
5-Hydroxytryptophan (5-HTP) is a naturally occurring compound derived from L-tryptophan, serving as a direct precursor to serotonin, a neurotransmitter that regulates mood, sleep, and appetite. Found in supplements extracted from Griffonia simplicifolia seeds, 5-HTP is used to potentially alleviate depression, improve sleep quality, reduce fibromyalgia symptoms, and support weight loss by enhancing satiety.
Benefits
Depression
5-HTP may alleviate depressive symptoms by increasing serotonin levels in the brain. Some studies, particularly in Parkinson’s disease patients or those with mild depression, show modest improvements in mood, though results are inconsistent and often comparable to placebo effects (30–45% response rate).
Sleep Improvement
By boosting serotonin, which is converted to melatonin, 5-HTP may improve sleep quality, particularly in older adults or poor sleepers. Clinical trials have shown reduced sleep latency and better Pittsburgh Sleep Quality Index (PSQI) scores with doses of 100–200 mg/day.
Fibromyalgia
5-HTP may reduce pain, fatigue, and tender point sensitivity in fibromyalgia patients. A 1990 trial showed significant symptom improvement with 300 mg/day, likely due to enhanced serotonin signaling.
Weight Management
5-HTP may promote weight loss by increasing satiety and reducing appetite. Small studies suggest 750–900 mg/day can reduce body weight and fat mass in overweight individuals, though long-term data is limited.
Migraine Prophylaxis
Limited evidence indicates 5-HTP (up to 300 mg/day) may reduce migraine frequency and severity, potentially by stabilizing serotonin levels, with effects comparable to methysergide but fewer side effects.
Gut Health
Preliminary research suggests 5-HTP may enhance gut microbiota diversity and short-chain fatty acid production, potentially benefiting overall health, though this is a newer area of study.
Mechanism of Action
Neurotransmitter Modulation
Elevated serotonin levels enhance signaling through serotonin receptors (e.g., 5-HT1A, 5-HT2C), which are involved in mood regulation, anxiety reduction, and satiety. This underlies 5-HTP’s potential benefits for depression, fibromyalgia, and weight management.
Serotonin produced from 5-HTP is a precursor to melatonin in the pineal gland, promoting sleep onset and quality by regulating circadian rhythms.
Central and Peripheral Effects
Unlike serotonin, 5-HTP crosses the blood-brain barrier, increasing CNS serotonin synthesis. Peripherally, it may influence gut motility and microbiota by boosting serotonin in enterochromaffin cells, potentially affecting gut health.
Anti-Inflammatory and Pain Modulation
In conditions like fibromyalgia, 5-HTP’s serotonin-boosting effects may modulate pain perception by enhancing descending inhibitory pathways in the CNS, reducing sensitivity to pain signals.
Appetite Suppression
5-HTP may activate serotonin receptors (e.g., 5-HT2C) in the hypothalamus, increasing feelings of fullness and reducing carbohydrate cravings, which supports its use in weight management.
Clinical Trials
Effects of 5-Hydroxytryptophan on Depression and Apathy in Parkinson’s Disease: A Preliminary Finding
Study: A single-center, randomized, double-blind, placebo-controlled crossover trial (2020) involving 25 patients with Parkinson’s disease (PD) and depression or apathy. Participants received 50 mg/day 5-HTP or placebo for 4 weeks, with outcomes assessed via the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory-II (BDI-II), and Apathy Scale (AS) at baseline and weeks 4, 8, 12, and 16.
Findings: 5-HTP significantly improved depressive symptoms compared to placebo (HDRS score reduction, p<0.05), but showed no effect on apathy (AS scores). No serious adverse events were reported, suggesting 5-HTP’s safety at low doses in PD patients. The study provides preliminary evidence of 5-HTP’s benefit for depression in PD but highlights the need for larger trials.
Link: https://pubmed.ncbi.nlm.nih.gov/32077186/
Double-Blind Study of 5-Hydroxytryptophan Versus Placebo in the Treatment of Primary Fibromyalgia Syndrome
Study: A double-blind, placebo-controlled trial (1990) involving 50 patients with primary fibromyalgia syndrome. Participants received 100 mg 5-HTP three times daily (300 mg/day) or placebo for 30 days. Outcomes included pain, sleep quality, fatigue, and tender point count.
Findings: 5-HTP significantly improved pain, sleep quality, fatigue, and tender point scores compared to placebo (p<0.05). Side effects were mild and transient (e.g., nausea, heartburn). The study suggests 5-HTP may benefit fibromyalgia symptoms, but further controlled studies are needed to confirm efficacy.
Link: https://pubmed.ncbi.nlm.nih.gov/2193562/
The Impact of 5-Hydroxytryptophan Supplementation on Sleep Quality and Gut Microbiota Composition in Older Adults: A Randomized Controlled Trial
Study: A single-blinded, 12-week randomized controlled trial (2024) involving 30 older adults (mean age 66 ± 3 years) in Singapore. Participants received 100 mg/day 5-HTP or no supplementation, with sleep quality assessed via the Pittsburgh Sleep Quality Index (PSQI), actigraphy, and biomarkers (serum serotonin, urine melatonin, gut microbiota).
Findings: 5-HTP improved sleep quality (PSQI scores) for up to 8 weeks, particularly in poor sleepers (PSQI >5), and increased serum serotonin levels. It also enhanced gut microbiota diversity and short-chain fatty acid production. No significant adverse events were reported. The study supports 5-HTP’s potential for sleep improvement in older adults but notes effects may vary by baseline sleep status.
Link: https://www.sciencedirect.com/science/article/pii/S2666149723000263
5-Hydroxytryptophan Versus Methysergide in the Prophylaxis of Migraine: Randomized Clinical Trial
Study: A randomized, double-blind trial (1986) involving 40 patients with migraine. Participants received 5-HTP (up to 300 mg/day) or methysergide (up to 6 mg/day) for 12 weeks, with outcomes including migraine frequency, severity, and duration.
Findings: 5-HTP reduced migraine frequency and severity comparably to methysergide, with fewer side effects (e.g., mild nausea vs. methysergide’s drowsiness). The study suggests 5-HTP may be a viable alternative for migraine prophylaxis, but larger trials are needed to confirm efficacy and safety.
Link: https://pubmed.ncbi.nlm.nih.gov/3536521/
Effects of 5-Hydroxytryptophan on Body Composition: An 8-Week Preliminary RCT
Study: A randomized, placebo-controlled trial (2022) involving 20 overweight women. Participants received 5-HTP (750 mg/day) or placebo for 8 weeks, with outcomes including body weight, fat mass, and appetite control.
Findings: 5-HTP significantly reduced body weight and fat mass compared to placebo (p<0.05) and increased feelings of fullness, suggesting appetite suppression. No serious side effects were reported. The study indicates potential for 5-HTP in weight management, but larger, longer-term trials are needed.
Link: https://pubmed.ncbi.nlm.nih.gov/35067746/
Effects of 5-Hydroxytryptophan on Distinct Types of Depression: A Systematic Review and Meta-Analysis
Study: A systematic review and meta-analysis (2019) of 13 studies (including RCTs and open-label trials) assessing 5-HTP for depression. Studies varied in design, dosage (50–600 mg/day), and patient populations (e.g., general depression, treatment-resistant depression, PD-related depression).
Findings: 5-HTP showed modest antidepressant effects, particularly when combined with other therapies (e.g., SSRIs or carbidopa), but results were inconsistent due to small sample sizes and methodological variability. A 2009 meta-analysis cited within noted insufficient evidence to recommend 5-HTP broadly for depression. The review calls for larger, placebo-controlled trials with well-defined depression diagnoses.
Link: https://pubmed.ncbi.nlm.nih.gov/31877510/
Potential Side Effects
Gastrointestinal Issues
Nausea, vomiting, diarrhea, stomach pain, or heartburn. These are often mild and transient, occurring more frequently at doses above 100 mg/day.
Neurological Effects
Drowsiness, dizziness, or headache. Tremors, agitation, or confusion, especially at high doses or with drug interactions.
Serotonin Syndrome
Excessive serotonin accumulation, particularly when 5-HTP is combined with serotonergic drugs (e.g., SSRIs, MAOIs, SNRIs). Symptoms include agitation, rapid heart rate, sweating, muscle rigidity, and, in severe cases, seizures or coma. Risk increases with doses above 300 mg/day or in combination with medications like fluoxetine or tramadol.
Eosinophilia-Myalgia Syndrome (EMS)
Linked to contaminated 5-HTP or L-tryptophan supplements in the 1980s–1990s, causing muscle pain, fatigue, and elevated eosinophil counts. Modern 5-HTP is generally safer, but quality control is critical.
Cardiovascular Effects
Potential heart valve damage or cardiac fibrosis due to excessive serotonin signaling, similar to risks with long-term serotonergic drugs, though evidence is limited and not well-established for 5-HTP.
Psychiatric Effects
Mood swings, anxiety, or worsening depression in some individuals, particularly if serotonin levels are imbalanced or doses are too high.