5-HTP

5-HTP (5-hydroxytryptophan) can raise brain serotonin because it’s the immediate biochemical precursor of serotonin and—based on small randomized trials and meta-analyses—appears to reduce depressive symptoms for some people. However the overall evidence base is limited and of mixed quality, and there are important safety issues (notably serotonin syndrome when combined with SSRIs/MAOIs, and rare reports of eosinophilia-myalgia syndrome). If you’re considering it, treat it like a drug: talk with your clinician, check interactions, use a third-party tested product, start at a low dose only under medical supervision, and stop if you develop worrying symptoms.

Biochemistry: serotonin (5-HT) is synthesised from the amino acid tryptophan in two steps. The enzyme tryptophan hydroxylase converts tryptophan → 5-HTP, and then aromatic L-amino-acid decarboxylase (AAAD) converts 5-HTP → serotonin. Orally-administered 5-HTP crosses the blood–brain barrier and can be decarboxylated in the brain to increase central serotonin levels — a plausible mechanism for an antidepressant effect. MDPI

Why this matters clinically: many antidepressants (SSRIs, SNRIs, etc.) act by increasing the synaptic availability of serotonin; supplying more precursor (5-HTP) is an alternative biochemical way to increase serotonin synthesis. That biochemical plausibility is why 5-HTP has been tested as a mood treatment. SAGE Journals

Typical trial doses: published trials of 5-HTP for mood most commonly used roughly 100–300 mg per day (often divided dosing). Some studies have used doses as low as ~50 mg/day or as high as several hundred mg/day; ongoing trials are testing various regimens (for example 100 mg twice daily in recent protocols). Start-low and titrate under clinician supervision is the common approach in the literature. Oxford Academic

How it’s taken: oral capsules/tablets. Some trials used divided doses (e.g., morning + evening) to reduce GI side effects and to maintain more stable levels. Because AAAD (the enzyme that converts 5-HTP → serotonin) requires vitamin B6, some clinicians note the biochemical role of B6 — but routine addition of B6 is not universally standard and should be clinician-guided. Alternative Medicine Review

Practical monitoring and timing:

• Have baseline medication review (important for interactions — see Warnings).
• Start at a low dose (for example 50–100 mg/day) and reassess mood and side effects over 1–2 weeks; increase only with clinician approval up to doses used in trials (commonly up to ~300 mg/day). (Trials vary; discuss target dose with prescriber.)
• Monitor for gastrointestinal effects, agitation, tremor, autonomic signs, or any new/sudden mental status change. If any signs of serotonin excess appear, stop and seek urgent care. WebMD

Duration in trials: many trials are short (2–8 weeks); improvements, when seen, often occur in the first several weeks. Long-term safety and efficacy beyond typical trial periods are less well established. Oxford Academic

• Systematic review & meta-analysis (Nutrition Reviews, 2019): a modern systematic review and meta-analysis concluded 5-HTP may reduce depressive symptoms in some trials, but study quality was variable and sample sizes were small; more, better-designed RCTs are needed. Oxford Academic
• Cochrane review (Tryptophan & 5-HTP for depression): an older Cochrane review concluded that tryptophan and 5-HTP reduced depressive symptoms compared with placebo in some studies, but cautioned that side effects occurred and that the evidence base was limited — more high-quality trials are required before strong conclusions can be drawn. Cochrane
• Individual randomized trials: there are several small RCTs comparing 5-HTP to placebo or to antidepressants. Some older and smaller trials reported effects comparable to antidepressant drugs in the trial populations; others report modest benefits or only benefits when 5-HTP was used as an augmentation. Example: a randomized double-blind comparison versus fluoxetine in an Indian population reported on comparative efficacy; however many such trials are small and single-site. Newer registered trials are ongoing to better define dosing and augmentation roles (see ClinicalTrials records). ScienceDirect

Summary: promising signals exist, but the overall clinical evidence is limited by small sample sizes, heterogeneity of methods, and some older studies of variable quality. Major systematic reviewers (Cochrane, Nutrition Reviews) call for larger, modern randomized trials. Oxford Academic