5-Hydroxytryptophan, extracted from the seeds of Griffonia simplicifolia · supplement
Evidence tier: limited
A direct serotonin building block. Supports mood, sleep onset, and reduces appetite, particularly useful in serotonin related low mood.
5-HTP is the immediate biochemical precursor of serotonin. It crosses the blood brain barrier and is decarboxylated to serotonin, bypassing tryptophan hydroxylase, the rate limiting enzyme. This part of the seed is accurate and is well established biochemistry. The problem is that raising serotonin is a real pharmacological action, so the same mechanism that supplies the benefit hypothesis also supplies the serotonin syndrome risk.
Limited, and the honest headline is safety, not efficacy. The Cochrane review of tryptophan and 5-HTP for depression (Shaw, Turner and Del Mar, PMID 11687048) located 108 trials and found only TWO of sufficient quality to include, together enrolling 64 people. Those two favoured the supplement over placebo (Peto odds ratio 4.10, 95 percent CI 1.28 to 13.15), but Cochrane's own verdict is that the evidence was of insufficient quality to be conclusive, and it closes by saying that because effective and safe antidepressants already exist, the clinical usefulness of 5-HTP is limited at present. Memorial Sloan Kettering agrees: limited evidence for some types of depression, initial findings only for fibromyalgia, and for insomnia it says plainly that studies are lacking. The fibromyalgia literature rests largely on a 90 day OPEN study in 50 people (PMID 1521674), which is not a controlled result. So the seed's three headline uses are, in order, poorly evidenced, uncontrolled, and unstudied. The mechanism, by contrast, is not in doubt: 5-HTP is a direct serotonin precursor and it does raise serotonin. That is exactly why the safety signal matters. Combining 5-HTP with SSRIs, SNRIs, MAOIs, tramadol, triptans or other serotonergic agents carries a risk of serotonin syndrome, a potentially fatal condition, and MSK advises against taking it alongside serotonergic drugs without physician supervision. Separately, the eosinophilia myalgia syndrome question remains open rather than closed: EMS was traced to contaminated L tryptophan in 1989, contaminant peaks have since been found in some 5-HTP products, and the NIH position quoted in the literature is that 5-HTP should be used cautiously because the EMS risk has not been well established. An unresolved contamination question is not a clean bill of health.
No authority establishes one. Supplement practice in the literature runs 50 to 300 mg daily, often 50 to 100 mg before bed, and doses of 150 to 300 mg daily appear in the depression trials. Memorial Sloan Kettering deliberately publishes no dose recommendation, which is itself informative.
50 to 200 mg before bed. Start low, too much can cause nausea or vivid dreams.
CRITICAL interaction with SSRIs, MAOIs, tramadol, serotonin syndrome risk. Always screen medications.
Pregnancy: avoid
Breastfeeding: avoid
Active compounds: 5-hydroxytryptophan
Remedies using 5-HTP · Browse by body system · Check it against what you take
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.