What it is
5-HTP (5-hydroxytryptophan) is the intermediate the body makes from tryptophan before converting it into serotonin, which modulates mood, sleep, appetite and pain. As a supplement, it is extracted from the seed of Griffonia simplicifolia, an African shrub, or produced by fermentation. People buy it for mood, sleep and appetite.
What the label does not say
- The Canadian label carries a contraindication, not a simple caution: "do not use if you are taking antidepressants". Examine writes that combining it with an SSRI is potentially fatal. The symptoms of serotonin syndrome appear among the known effects in the monograph: tremors, agitation or confusion, rapid heartbeat.
- Antidepressants are not the only serotonergic agents. The FDA classes among them tramadol, the dextromethorphan in cough syrups, triptans for migraine, linezolid, St. John's wort and tryptophan. The Canadian monograph also asks you to consult if you take carbidopa (Parkinson's disease).
- The effectiveness is thin. Of 108 trials identified by the Cochrane review on tryptophan and 5-HTP in depression, only 2, totalling 64 patients, were of sufficient quality; the authors conclude that the evidence is insufficient and that effective and safe antidepressants exist. For sleep, Operation Supplement Safety, listed by the NIH, writes that there are not enough reliable data.
- Health Canada nonetheless allows the claim "helps to relieve sleep disturbances associated with mood imbalance" at 100 to 200 mg per day: that is mood-related sleep, not a general sleep aid.
The forms on the shelf
- 5-HTP from Griffonia simplicifolia seed: the usual source. The label reads in milligrams of 5-HTP, not milligrams of seed extract.
- 5-HTP from fermentation (Escherichia coli, Saccharomyces cerevisiae): also accepted by the Canadian monograph.
- Tablets and capsules in various doses: the monograph asks you to start low and work up over 2 weeks, with food.
Published reference values
- No recommended intake. Health Canada: 150 to 300 mg per day for mood, 100 to 200 mg for mood-related sleep disturbances, 300 to 400 mg for fibromyalgia, 200 to 600 mg for migraine prevention, at most 300 mg per dose, with food, working up over 2 weeks and for at least 2 weeks before judging the effect.
- Adverse effects: mostly digestive; a 2021 review reports nausea and vomiting above 100 mg, in a dose-dependent way. The OPSS adds headaches, insomnia and palpitations, and cases of mania in combination with antidepressants.
- Eosinophilia-myalgia syndrome was linked to contaminated lots of L-tryptophan pulled from the market by the FDA; impurities have also been reported in 5-HTP, and Cochrane notes that the link has not been clarified.
When
With food, starting low. The time of day matters less than taking stock of everything serotonergic in your medicine cabinet, cough syrups and triptans included.
Keep apart from
- Antidepressants (SSRIs, SNRIs, tricyclics, MAOIs): a Canadian contraindication. Not a matter of spacing, but of exclusion.
- Tramadol, dextromethorphan, triptans, linezolid, St. John's wort, tryptophan: serotonergic agents according to the FDA, not to be combined without advice.
- Carbidopa: consult before use (Health Canada).
To mention to a professional
- Any antidepressant or serotonergic medication, scleroderma (a Canadian contraindication), psychological disorder, Parkinson's disease, pregnancy and breastfeeding: check with a health care professional. Tremors, agitation, confusion or a rapid heartbeat during use: stop and consult without delay.
What it is sold for, and what the data show
5-HTP is sold as a natural antidepressant and sleep aid. The data come down to 2 quality trials totalling 64 patients for mood and nothing reliable for sleep, while the interaction risk is that of a medication. It is the supplement in this family where reading your medicine cabinet matters more than reading the bottle.
Sources
- Health Canada, natural health product monograph, 5-HTP, 2024
- Cochrane, Shaw et al., Tryptophan and 5-Hydroxytryptophan for depression
- Operation Supplement Safety (Uniformed Services University), 5-HTP for depression and other conditions
- FDA, Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines (list of serotonergic agents)
- Maffei, 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology, International Journal of Molecular Sciences, 2021
- Examine.com, 5-HTP
Educational information, drawn from the sources above. It does not replace the advice of a health professional, who remains the reference for your situation, your medications, pregnancy or breastfeeding.