5-HTP

5-HTP (5-hydroxytryptophan) is an intermediate metabolite in the conversion of the essential amino acid tryptophan into the neurotransmitter serotonin. First isolated in the early 20th century, it has been studied for its ability to cross the blood–brain barrier and directly increase central serotonin levels, unlike serotonin itself which cannot cross independently. Commercially, 5-HTP is typically extracted from the seeds of the West African plant Griffonia simplicifolia and is available as an over-the-counter dietary supplement in the United States, Canada, and Europe under various brand names. Clinically, 5-HTP has been investigated for its efficacy in treating depressive symptoms, improving sleep quality, reducing fibromyalgia pain, and promoting satiety for weight management. A 2020 meta-analysis found a large effect size for depression symptom reduction, though methodological heterogeneity tempers confidence in these findings (DOI:10.1093/nutrit/nuz039, PMID:31504850). Small randomized trials have shown improvements in sleep parameters among older adults (https://www.sciencedirect.com/science/article/abs/pii/S0261561424000104) and reductions in fibromyalgia-related pain (PMID:1521674). Typical supplemental doses range from 50 to 300 mg per day, often coadministered with vitamin B6 to support conversion to serotonin. Due to potential serotonin syndrome risk when combined with other serotonergic agents, caution is advised. Overall, 5-HTP remains a popular specialty compound for mood, sleep, and appetite support, but further large-scale, high-quality trials are needed to confirm long-term safety and efficacy.

5-HTP bypasses the rate-limiting enzyme tryptophan hydroxylase by providing the immediate precursor to serotonin. After oral ingestion, 5-HTP is rapidly absorbed and crosses the blood–brain barrier, where it is decarboxylated by aromatic-L-amino-acid decarboxylase—often with vitamin B6 as a cofactor—to form serotonin (5-hydroxytryptamine). Elevated central serotonin levels enhance neurotransmission in mood-regulating pathways, contribute to melatonin synthesis in the pineal gland for sleep regulation, and modulate nociceptive pathways to reduce pain perception. Peripheral conversion of 5-HTP can also produce serotonin in the gastrointestinal tract, influencing gut motility and appetite signals. By increasing the availability of serotonin precursors, 5-HTP supports neurochemical balance without the need for transporter-mediated tryptophan uptake.

5-HTP is naturally found in the seeds of the West African plant Griffonia simplicifolia, which have been the primary source for commercial extraction. Trace amounts are also present in turkey, bananas, and certain other plant-based foods, but dietary intake from these sources is negligible for therapeutic purposes.

There is no established Recommended Daily Intake for 5-HTP. Typical supplemental doses range from 50 to 300 mg per day depending on the indication and individual factors.

5-HTP is available as capsules, tablets, powders, and standardized Griffonia simplicifolia seed extracts. Formulation affects absorption and conversion efficiency to serotonin, often enhanced by coadministration of vitamin B6.