5-HTP

5-Hydroxytryptophan is the immediate precursor to serotonin, derived from the seeds of Griffonia simplicifolia. By providing the rate-limiting intermediate in serotonin synthesis, 5-HTP effectively raises brain serotonin levels. Used for mood support, anxiety, sleep, and appetite control. More effective than L-Tryptophan because it bypasses the rate-limiting enzyme step.

Dosage

Standard: 50-200 mg daily. For mood: 50-100 mg 2-3 times daily. For sleep: 100-300 mg 30-60 minutes before bed. Start low — some people are very sensitive. Take with food to reduce nausea.

Dosages shown are for research reference only. Always consult a qualified healthcare provider.

Half-Life

2-5 hours

Administration

Oral (capsules, tablets). Take with food to reduce GI side effects. Evening dosing preferred for sleep benefits.

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Mechanism of Action

5-HTP readily crosses the blood-brain barrier via the large neutral amino acid transporter (LAT1/SLC7A5), unlike serotonin itself which cannot. Once in the brain, aromatic L-amino acid decarboxylase (AADC, also called DOPA decarboxylase) converts 5-HTP to serotonin (5-hydroxytryptamine) using pyridoxal-5-phosphate (active vitamin B6) as a cofactor. This completely bypasses tryptophan hydroxylase (TPH2), the rate-limiting enzyme in the normal serotonin synthesis pathway from dietary L-tryptophan. The result is a reliable, dose-dependent increase in serotonin across multiple brain regions including the dorsal raphe nucleus, hippocampus, and prefrontal cortex. Elevated serotonin activates 5-HT1A autoreceptors (calming), 5-HT2A/2C postsynaptic receptors (mood modulation), and 5-HT3 receptors (gut-brain signaling). In the pineal gland, serotonin is converted by arylalkylamine N-acetyltransferase (AANAT) to N-acetylserotonin, then by hydroxyindole O-methyltransferase (HIOMT) to melatonin — explaining the sleep-promoting effects.

Regulatory Status

Dietary supplement in the US, UK, and most countries. Prescription medication in some European countries.

Risks & Safety

Common

Nausea, diarrhea, stomach cramps.

Serious

Serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, or tramadol — DO NOT combine without medical supervision.

Rare

Eosinophilia-myalgia syndrome (historical concern from contaminated L-tryptophan, not confirmed with modern 5-HTP).

Compare 5-HTP With

Research Papers

10
5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology.

Published: December 25, 2020

AI Summary

In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials.

5-HTP decreases goat mammary epithelial cells apoptosis through MAPK/ERK/Bcl-3 pathway.

Published: February 14, 2021

AI Summary

The Annexin V-FITC/PI staining and western blotting results suggested that 5-HTP decreased GMEC apoptosis through ERK1/2 signaling pathway. And the results of RT-qPCR and western blotting demonstrated that both 5-HTP and ERK1/2 positively regulated Bcl-3 expression.

Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan.

Published: March 13, 2006

AI Summary

This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials.

5-HTP hypothesis of schizophrenia.

Published: January 7, 2014

AI Summary

To pose a new hypothesis of schizophrenia that affirms and unifies conventional hypotheses.

The impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial.

Published: March 16, 2024

AI Summary

Sleep quality is a pivotal part of health and there is growing evidence on the association between gut microbiota composition and sleep quality. 5-Hydroxytryptophan (5-HTP) is known as a precursor of the sleep regulating neurotransmitter and hormone. However, efficacy of 5-HTP supplementation for improving sleep quality in older adults is unclear.

5-Hydroxytryptophan (5-HTP)-induced intracellular syndrome in mouse non-neural embryonic cells is associated with inhibited proliferation and cell death.

Published: August 31, 2021

AI Summary

HPLC analysis found no changes in the intracellular and extracellular levels of 5-HT after 5-HTP treatment, but a significant increase of intracellular 5-HTP levels. Our results suggest that 5-HTP can induce toxic effects through cell cycle arrest and cell death in embryonic stem and somatic cells by enhancing the levels of 5-HT-mediated protein...

The Effects of 5-HTP on Body Composition: An 8-Week Preliminary RCT.

Published: May 17, 2023

AI Summary

Lean body mass, total body water, and % body fat did not change significantly in either group. Moreover, changes in fat mass were significantly different between the 5-HTP and placebo group (p = 0.048).

L-DOPA and 5-HTP modulation of air-stepping in newborn rats.

Published: October 4, 2021

AI Summary

L-DOPA administration increases the spinal content of dopamine in a dose-dependent manner. Injection of 5-HTP increases the spinal serotonin content but does not trigger air-stepping. 5-HTP counteracts the pro-locomotor action of L-DOPA.

PK/PD modeling of 5-hydroxytryptophan (5-HTP) challenge test with cortisol measurement in serum and saliva.

Published: April 22, 2020

AI Summary

The typical value for clearance was 20.40 L h-1 and showed inter-study variability. A power function provided a better description than a linear function to relate the saliva and serum cortisol.

Safety of 5-hydroxy-L-tryptophan.

Published: April 14, 2004

AI Summary

However, no definitive cases of toxicity have emerged despite the worldwide usage of 5-HTP for last 20 years, with the possible exception of one unresolved case of a Canadian woman. Extensive analyses of several sources of 5-HTP have shown no toxic contaminants similar to those associated with L-Trp, nor the presence of any other significant imp...

Frequently Asked Questions

What is 5-HTP used for?

5-Hydroxytryptophan is the immediate precursor to serotonin, derived from the seeds of Griffonia simplicifolia. By providing the rate-limiting intermediate in serotonin synthesis, 5-HTP effectively raises brain serotonin levels. Used for mood support, anxiety, sleep, and appetite control. More effective than L-Tryptophan because it bypasses the rate-limiting enzyme step.

What are the side effects of 5-HTP?

Common: Nausea, diarrhea, stomach cramps. Serious: Serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, or tramadol — DO NOT combine without medical supervision. Rare: Eosinophilia-myalgia syndrome (historical concern from contaminated L-tryptophan, not confirmed with modern 5-HTP).

How is 5-HTP administered?

5-HTP is administered via oral (capsules, tablets). take with food to reduce gi side effects. evening dosing preferred for sleep benefits..

What is the half-life of 5-HTP?

The half-life of 5-HTP is 2-5 hours.

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