Demystifying 5-HTP: Benefits, Uses, and More

Demystifying 5-HTP: Benefits, Uses, and More

Aug 31, 2023 | Written by Matthew Lees, PhD | Edited by Scott Sherr, MD

5-hydroxytryptophan, or 5-HTP for short, is the intermediate metabolite of the essential amino acid tryptophan in the process of serotonin biosynthesis [1].

That is to say, it is an immediate precursor to serotonin [1,2].

Its use dates back to the first half of the 20th century, and has applications as a support for serotonin depletion and is considered an interesting alternative to selective serotonin reuptake inhibitors (SSRIs) [3].

The main natural source of 5-HTP is the seeds of the African plant Griffonia simplicifolia, but the seasonal and regional variations of the plant limit their output of 5-HTP, hence biotechnological methods are used to synthesize 5-HTP in an economically and environmentally efficient manner.

Several clinical trials are underway on 5-HTP for the treatment of depression, anxiety, panic attacks, and sleep disorders, with promising but early evidence for its use in other conditions such as obesity and diabetes [3]. For example, 5-HTP can improve blood sugar control [4] and aid weight loss in people who are overweight/obese [5] by increasing satiety (fullness) as one potential mechanism. 5-HTP can also decrease carbohydrate intake which has implications for people with diabetes [4].

There may also be applications for its use in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease [6]. Early research has shown that 5-HTP can improve levodopa-induced dyskinesias (uncontrolled, involuntary movements) in Parkinson’s disease patients [7].

In today’s article, we will examine what 5-HTP is, how it works, the rationale for supplementation, as well as the risks and contraindications associated with it.

5-HTP Biosynthesis and Metabolism

5-HTP is both a drug and a natural component of some dietary supplements. It is produced from tryptophan (an essential amino acid that we must obtain from food) by an enzyme called tryptophan hydroxylase [3]. Tryptophan hydroxylase exists in two isoforms: TPH1 and TPH2.

5-HTP metabolism yields the well-known monoamine neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) that plays roles in emotional regulation, cognition, reward, learning, memory, and other physiological processes [8-10].

Serotonin is further transformed into melatonin (N-acetyl-5-methoxytryptamine), a hormone secreted by the pineal gland that is involved in numerous aspects of the sleep/wake cycle [3,11,12]. You can read more on biological clocks and cycles here.

In terms of absorption, 5-HTP reaches peak concentration rapidly (within 90 minutes) and is also quickly eliminated, with a half-life of 90-120 minutes [13]. Furthermore, 5-HTP is known to cross the blood-brain barrier, whereas serotonin does not [14].

Overall, the metabolism of tryptophan to 5-HTP by TPH1/2 is an essential step in the biosynthesis of two physiologically important molecules, serotonin and melatonin.

Benefits and Potential Uses of 5-HTP

Dysfunction in the serotonergic system, including reduced central serotonin levels, are associated with depression. As a precursor to serotonin, 5-HTP has been used as a non-pharmacological treatment for depression [15,16], with meta-analysis of the evidence showing a large effect [17]. There are, however, weaknesses in the available studies, as many do not include a placebo group, and this is an area that should be addressed.

Supplementation with 5-HTP

In the absence of supplementation with 5-HTP, the amount of 5-HTP available for serotonin synthesis largely depends on the amount of tryptophan available as well as enzymes such as tryptophan hydroxylase [16].

In human supplementation research, participants considered immoral behavior without negative consequences as more reprehensible after consuming 5-HTP (200 mg) [18].

A study of older adults in Singapore observed that daily supplementation with 100 mg of 5-HTP improved sleep quality at 4 and 8 weeks, however these effects did not last beyond this phase (up to 12 weeks) [19]. This potentially suggests that the body acclimatizes to prolonged 5-HTP supplementation, at least in the population in the study.

Beyond these effects on sleep and moral evaluation, there is some promising research suggesting that 5-HTP (750 mg/day) can help overweight non-insulin dependent diabetic patients reduce their daily energy intake and thus their body weight [4]. This is notable given that the brain levels of tryptophan are substantially reduced in diabetic patients, whereas tryptophan metabolites are higher [4,20].

What are the Risks and Contraindications?

Supplementation with 5-HTP may cause unpleasant dose-dependent gastrointestinal problems [21], as well as vomiting and nausea when used at doses in excess of 100 mg [22].

An excess of 5-HTP may be responsible for serotonin syndrome, a potentially life-threatening drug-induced condition of too much serotonin in the synapses of the brain [23,24]. Although cases involving hospitalization and death are rare, and medical intervention is not needed in most instances, it is nevertheless a condition to be mindful of. This is particularly the case when high doses of 5-HTP are used in combination with antidepressants in the SSRI class, which has been shown to cause acute serotonin syndrome in rats [25,26].


In this article, we have discussed 5-HTP and its biosynthesis, metabolism, effects, and the rationale for supplementation. We also looked at the risks and benefits, as well as the contraindications and side effects that might present themselves.

There is evidence that 5-HTP can enhance moral evaluation, sleep, cognition, and help treat major health challenges like obesity and diabetes. However, these findings need to be substantiated by further research.



[1]          T.C. Birdsall, 5-Hydroxytryptophan: a clinically-effective serotonin precursor, Altern Med Rev. 3 (1998) 271–280.

[2]          A. Sharma, R.J. Castellani, M.A. Smith, D.F. Muresanu, P.K. Dey, H.S. Sharma, 5-Hydroxytryptophan: A precursor of serotonin influences regional blood-brain barrier breakdown, cerebral blood flow, brain edema formation, and neuropathology, Int Rev Neurobiol. 146 (2019) 1–44.

[3]          M.E. Maffei, 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology, Int J Mol Sci. 22 (2020) 181.

[4]          C. Cangiano, A. Laviano, M. Del Ben, I. Preziosa, F. Angelico, A. Cascino, F. Rossi-Fanelli, Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients, Int J Obes Relat Metab Disord. 22 (1998) 648–654.

[5]          C. Evans, V. Mekhail, J. Curtis, P. Czartoryski, J. Kaminski, A. Ellerbroek, E. Bustillo, L. Jiannine, J.C. Santana, J. Antonio, The Effects of 5-HTP on Body Composition: An 8-Week Preliminary RCT, J Diet Suppl. 20 (2023) 621–630.

[6]          M. Meloni, M. Figorilli, M. Carta, L. Tamburrino, A. Cannas, F. Sanna, G. Defazio, M. Puligheddu, Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease, Sleep Breath. 26 (2022) 1023–1031.

[7]          M. Meloni, M. Puligheddu, F. Sanna, A. Cannas, R. Farris, E. Tronci, M. Figorilli, G. Defazio, M. Carta, Efficacy and safety of 5-Hydroxytryptophan on levodopa-induced motor complications in Parkinson’s disease: A preliminary finding, J Neurol Sci. 415 (2020) 116869.

[8]          L.A. Jones, E.W. Sun, A.M. Martin, D.J. Keating, The ever-changing roles of serotonin, Int J Biochem Cell Biol. 125 (2020) 105776.

[9]          L.F. Mohammad-Zadeh, L. Moses, S.M. Gwaltney-Brant, Serotonin: a review, J Vet Pharmacol Ther. 31 (2008) 187–199.

[10]        D. Švob Štrac, N. Pivac, D. Mück-Šeler, The serotonergic system and cognitive function, Transl Neurosci. 7 (2016) 35–49.

[11]        C. Ekmekcioglu, Melatonin receptors in humans: biological role and clinical relevance, Biomed Pharmacother. 60 (2006) 97–108.

[12]        L.P.H. Andersen, I. Gögenur, J. Rosenberg, R.J. Reiter, The Safety of Melatonin in Humans, Clin Drug Investig. 36 (2016) 169–175.

[13]        H.J. Gijsman, J.M.A. van Gerven, M.L. de Kam, R.C. Schoemaker, M.S.M. Pieters, M. Weemaes, R. de Rijk, J. van der Post, A.F. Cohen, Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers, J Clin Psychopharmacol. 22 (2002) 183–189.

[14]        Y. Nakatani, I. Sato-Suzuki, N. Tsujino, A. Nakasato, Y. Seki, M. Fumoto, H. Arita, Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat, Eur J Neurosci. 27 (2008) 2466–2472.

[15]        K. Shaw, J. Turner, C. Del Mar, Tryptophan and 5-hydroxytryptophan for depression, Cochrane Database Syst Rev. (2002) CD003198.

[16]        E.H. Turner, J.M. Loftis, A.D. Blackwell, Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan, Pharmacol Ther. 109 (2006) 325–338.

[17]        F. Javelle, A. Lampit, W. Bloch, P. Häussermann, S.L. Johnson, P. Zimmer, Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis, Nutr Rev. 78 (2020) 77–88.

[18]        V. Zamoscik, S.N.L. Schmidt, R. Bravo, L. Ugartemendia, T. Plieger, A.B. Rodríguez, M. Reuter, P. Kirsch, Tryptophan-enriched diet or 5-hydroxytryptophan supplementation given in a randomized controlled trial impacts social cognition on a neural and behavioral level, Sci Rep. 11 (2021) 21637.

[19]        C. Sutanto, C.W. Heng, A.X. Gan, X. Wang, J. Fam, J.E. Kim, The Impact of 5-Hydroxytryptophan Supplementation on Sleep Quality of Older Adults in Singapore: A Randomized Controlled Trial, Current Developments in Nutrition. 5 (2021) 372.

[20]        K. Matsuoka, K. Kato, T. Takao, M. Ogawa, Y. Ishii, F. Shimizu, J. Masuda, A. Takada, Concentrations of various tryptophan metabolites are higher in patients with diabetes mellitus than in healthy aged male adults, Diabetol Int. 8 (2017) 69–75.

[21]        K. Zmilacher, R. Battegay, M. Gastpar, L-5-Hydroxytryptophan Alone and in Combination with a Peripheral Decarboxylase Inhibitor in the Treatment of Depression, Neuropsychobiology. 20 (1988) 28–35.

[22]        L. Smarius, G. Jacobs, D. Hoeberechts-Lefrandt, M. De Kam, J. Van Der Post, R. De Rijk, J. Van Pelt, R. Schoemaker, F. Zitman, J. Van Gerven, H. Gijsman, Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa, J Psychopharmacol. 22 (2008) 426–433.

[23]        E.J.C. Dunkley, G.K. Isbister, D. Sibbritt, A.H. Dawson, I.M. Whyte, The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity, QJM. 96 (2003) 635–642.

[24]        P.K. Gillman, A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action, Biol Psychiatry. 59 (2006) 1046–1051.

[25]        T. Izumi, N. Iwamoto, Y. Kitaichi, A. Kato, T. Inoue, T. Koyama, Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats, Eur J Pharmacol. 532 (2006) 258–264.

[26]        Z. Ma, G. Zhang, C. Jenney, S. Krishnamoorthy, R. Tao, Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats, Eur J Pharmacol. 588 (2008) 198–206.

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