5-HTP

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    Last Updated: June 12, 2024

    5-HTP is the precursor to serotonin, a neurotransmitter involved in regulating many body processes like mood, sleep, and appetite. 5-HTP can increase levels of serotonin in the brain, which may reduce symptoms of depression and reduce appetite.

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    305 participants in 8 trials

    What is 5-HTP?

    5-HTP is an amino acid and a precursor to the neurotransmitter serotonin. It is produced in the body from the essential amino acid tryptophan, and it can be supplemented directly. Plants are a rich source of 5-HTP, and Griffonia simplicifolia seeds are often used for the extraction and the commercial production of 5-HTP.[4]

    What are 5-HTP’s main benefits?

    5-HTP is very reliable for increasing serotonin levels in presynaptic neurons in the brain and is actually used as a test drug to help determine the potency of other serotonin-increasing substances.[5]

    Most of the research has looked at 5-HTP for its potential role in treating depression. This is based on the serotonin theory of depression — the debatable theory that depression is the result of low serotonin in the brain.[6] While some research has been promising, the body of evidence is weak overall. Most of this research was conducted in the 1970s and 1980s with poor methodological quality.[1][7]

    5-HTP may reduce symptoms of depression compared to a placebo when taken alone or in addition to standard treatment.[1] Also, two short-term studies (6 to 8 weeks) reported that 5-HTP reduced symptoms of depression to a similar degree as the SSRI antidepressant medications fluoxetine and fluvoxamine.[8][9] While this is promising, higher quality research is needed to confirm these effects.

    5-HTP may also play a role in appetite regulation. In people with overweight or obesity, researchers have observed weight loss due to reduced calorie intake and increased satiety, or the feeling of fullness, during supplementation with 5-HTP.[2][3][10]

    5-HTP has also been studied for its effects on migraine or tension headache prevention,[11][12][13] fibromyalgia,[14][15] and Parkinson’s disease.[16][17] Currently, research is mixed and largely inconclusive.

    Does 5-HTP affect sleep?

    Is tryptophan supplementation a suitable alternative to 5-HTP?

    What are 5-HTP’s main drawbacks?

    5-HTP can cause mild side effects which may improve over time. These include nausea, abdominal pain, and diarrhea, and less commonly fatigue, insomnia, and headaches. Intravenous administration of 5-HTP has been reported to cause confusion, anxiety, and memory impairment.[18][1]

    At high doses (100–200 mg per kg of body weight), 5-HTP has been associated with serotonin syndrome in lab animals, a severe condition caused by high levels of serotonin in the body.[1] In rodents, the risk of serotonin syndrome was increased when 5-HTP was combined with SSRIs (commonly used antidepressant medications). There are no reported toxicity reports at normal doses, and it should be noted that serotonin syndrome from 5-HTP supplementation has not been observed in humans.[1]

    In 1989 and 1990, there were over 1,500 cases of eosinophilia myalgia syndrome (EMS) (a rare syndrome with symptoms of severe muscle pain and fatigue) leading to over 30 reported deaths in people taking tryptophan supplements, a direct precursor to 5-HTP. Additionally, there were a few cases of EMS reported with 5-HTP supplementation. It was determined that EMS likely occurred due to a toxic contaminant in the supplements, and there have been no confirmed cases in recent years. Regardless, this led to a stark decline in the use of and research on tryptophan and 5-HTP supplements. To avoid the risk of EMS, it is important that 5-HTP supplements are purified and tested for contaminants.[1][19]

    How does 5-HTP work?

    5-HTP acts as a direct precursor for the neurotransmitter serotonin. 5-HTP readily crosses the blood-brain barrier, which can lead to increased serotonin levels in presynaptic neurons in the brain. This may play a role in regulating mood, sleep, appetite, memory, and various other processes.[4]

    However, it’s also important to note that the relationship between serotonin levels and depression is not as clear as many people think. The current body of evidence does not consistently show that lower levels of serotonin are associated with or cause depression.[6]

    What are other names for 5-HTP

    Note that 5-HTP is also known as:
    • 5-hydroxytryptophan
    • L-5-Hydroxytryptophan
    • L-5HTP
    • Oxitriptan
    5-HTP should not be confused with:

    Dosage information

    5-HTP is usually taken orally in capsule form. It can be taken once daily or in divided doses (i.e., the total daily dose is split into two or three doses).
    For depression, most studies have used dosages in the range of 200 mg to 300 mg daily for up to 1 year.[1] For weight loss or appetite regulation, 5-HTP has been used in the range of 750 mg to 900 mg daily for up to 6 weeks.[2][3]

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    Frequently asked questions

    What is 5-HTP?

    5-HTP is an amino acid and a precursor to the neurotransmitter serotonin. It is produced in the body from the essential amino acid tryptophan, and it can be supplemented directly. Plants are a rich source of 5-HTP, and Griffonia simplicifolia seeds are often used for the extraction and the commercial production of 5-HTP.[4]

    What are 5-HTP’s main benefits?

    5-HTP is very reliable for increasing serotonin levels in presynaptic neurons in the brain and is actually used as a test drug to help determine the potency of other serotonin-increasing substances.[5]

    Most of the research has looked at 5-HTP for its potential role in treating depression. This is based on the serotonin theory of depression — the debatable theory that depression is the result of low serotonin in the brain.[6] While some research has been promising, the body of evidence is weak overall. Most of this research was conducted in the 1970s and 1980s with poor methodological quality.[1][7]

    5-HTP may reduce symptoms of depression compared to a placebo when taken alone or in addition to standard treatment.[1] Also, two short-term studies (6 to 8 weeks) reported that 5-HTP reduced symptoms of depression to a similar degree as the SSRI antidepressant medications fluoxetine and fluvoxamine.[8][9] While this is promising, higher quality research is needed to confirm these effects.

    5-HTP may also play a role in appetite regulation. In people with overweight or obesity, researchers have observed weight loss due to reduced calorie intake and increased satiety, or the feeling of fullness, during supplementation with 5-HTP.[2][3][10]

    5-HTP has also been studied for its effects on migraine or tension headache prevention,[11][12][13] fibromyalgia,[14][15] and Parkinson’s disease.[16][17] Currently, research is mixed and largely inconclusive.

    Does 5-HTP affect sleep?

    5-HTP is a precursor for serotonin which can be further processed into melatonin. Despite this theoretical mechanism for promoting sleep, current research is limited and not particularly promising.

    Some early research in the 1970s suggested that 5-HTP might increase REM sleep without affecting total sleep duration, but several participants reported experiencing nightmares.[20][21] Furthermore, a 2022 randomized controlled trial in people with Parkinson’s disease found no effect on REM sleep.[22]

    In children with sleep terrors, 5-HTP was reported to significantly reduce night terror episodes, but the study was not placebo-controlled.[23]

    In a 2024 study (summarized here), 5-HTP taken before bed for 12 weeks did not improve sleep but rather was reported to slightly decrease sleep duration in older adults.[24]

    Is tryptophan supplementation a suitable alternative to 5-HTP?

    Tryptophan is an essential amino acid found in some foods and dietary supplements. Tryptophan can be converted into 5-HTP in the body; however, supplementing with 5-HTP directly is more reliable for increasing serotonin levels.

    The conversion of tryptophan to 5-HTP is the rate-limiting step for the synthesis of both serotonin and melatonin. This means that the speed with which the body can produce serotonin or melatonin relies on how quickly tryptophan can be converted to 5-HTP. When supplementing with 5-HTP, this rate-limiting step is bypassed.[4]

    Several factors can limit the conversion of tryptophan to 5-HTP. For one, tryptophan has many different fates within the body (such as protein synthesis), meaning only a small fraction is converted to 5-HTP and subsequently serotonin. However, 5-HTP has the sole purpose of serotonin synthesis. Furthermore, tryptophan has to compete with other amino acids for entry into the brain, while 5-HTP can passively enter the brain without challenge.[18][25][26]

    What are 5-HTP’s main drawbacks?

    5-HTP can cause mild side effects which may improve over time. These include nausea, abdominal pain, and diarrhea, and less commonly fatigue, insomnia, and headaches. Intravenous administration of 5-HTP has been reported to cause confusion, anxiety, and memory impairment.[18][1]

    At high doses (100–200 mg per kg of body weight), 5-HTP has been associated with serotonin syndrome in lab animals, a severe condition caused by high levels of serotonin in the body.[1] In rodents, the risk of serotonin syndrome was increased when 5-HTP was combined with SSRIs (commonly used antidepressant medications). There are no reported toxicity reports at normal doses, and it should be noted that serotonin syndrome from 5-HTP supplementation has not been observed in humans.[1]

    In 1989 and 1990, there were over 1,500 cases of eosinophilia myalgia syndrome (EMS) (a rare syndrome with symptoms of severe muscle pain and fatigue) leading to over 30 reported deaths in people taking tryptophan supplements, a direct precursor to 5-HTP. Additionally, there were a few cases of EMS reported with 5-HTP supplementation. It was determined that EMS likely occurred due to a toxic contaminant in the supplements, and there have been no confirmed cases in recent years. Regardless, this led to a stark decline in the use of and research on tryptophan and 5-HTP supplements. To avoid the risk of EMS, it is important that 5-HTP supplements are purified and tested for contaminants.[1][19]

    How does 5-HTP work?

    5-HTP acts as a direct precursor for the neurotransmitter serotonin. 5-HTP readily crosses the blood-brain barrier, which can lead to increased serotonin levels in presynaptic neurons in the brain. This may play a role in regulating mood, sleep, appetite, memory, and various other processes.[4]

    However, it’s also important to note that the relationship between serotonin levels and depression is not as clear as many people think. The current body of evidence does not consistently show that lower levels of serotonin are associated with or cause depression.[6]

    Update History

    Full page update

    major

    We updated the following FAQs:

    What are 5-HTP's main benefits?: We added more details on the benefits of 5-HTP, as well as research limitations. Reducing symptoms of depression and promoting weight loss through appetite regulation remain the main potential benefits of 5-HTP. We removed sleep from this section due to unclear evidence of a benefit and potentially negative effects on sleep. Parkinson's disease, headache prevention, and fibromyalgia were added as areas of interest with a currently inconclusive and mixed evidence base.

    What are 5-HTP's main drawbacks?: We added information about possible side effects with 5-HTP, the most common being nausea, abdominal pain, and diarrhea. We discussed the connection between 5-HTP and eosinophilia myalgia syndrome which was likely due to a toxic contaminant in the supplements and has not been observed in recent years.

    Does 5-HTP affect sleep?: We added an FAQ to discuss the research on 5-HTP and sleep. Currently, no consistent benefit on sleep has been observed and some studies have reported increased rates of nightmares or reduced sleep duration.

    Is tryptophan supplementation a suitable alternative to 5-HTP?: We added an FAQ to discuss whether tryptophan can be taken in place of 5-HTP. 5-HTP is a more reliable way of increasing serotonin levels than tryptophan because it crosses the blood-brain barrier more easily, requires less steps for serotonin synthesis, and has less alternative uses in the body.

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    References

    1. ^Erick H Turner, Jennifer M Loftis, Aaron D BlackwellSerotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophanPharmacol Ther.(2006 Mar)
    2. ^Cangiano C, Laviano A, Del Ben M, Preziosa I, Angelico F, Cascino A, Rossi-Fanelli FEffects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patientsInt J Obes Relat Metab Disord.(1998 Jul)
    3. ^Cangiano C, Ceci F, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Antonucci F, Rossi-Fanelli FEating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophanAm J Clin Nutr.(1992 Nov)
    4. ^Maffei ME5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology.Int J Mol Sci.(2020-Dec-26)
    5. ^O'Neil MF, Moore NAAnimal models of depression: are there any?Hum Psychopharmacol.(2003 Jun)
    6. ^Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MAThe serotonin theory of depression: a systematic umbrella review of the evidence.Mol Psychiatry.(2023-Aug)
    7. ^Shaw K, Turner J, Del Mar CAre tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis.Aust N Z J Psychiatry.(2002 Aug)
    8. ^Jangid P, Malik P, Singh P, Sharma M, Gulia AKComparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode.Asian J Psychiatr.(2013-Feb)
    9. ^Pöldinger W, Calanchini B, Schwarz WA functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine.Psychopathology.(1991)
    10. ^Ceci F, Cangiano C, Cairella M, Cascino A, Del Ben M, Muscaritoli M, Sibilia L, Rossi Fanelli FThe effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjectsJ Neural Transm.(1989)
    11. ^Ribeiro CAL-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. For the Portuguese Head Society.Headache.(2000 Jun)
    12. ^De Benedittis G, Massei RSerotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo.J Neurosurg Sci.(1985 Jul-Sep)
    13. ^Titus F, Dávalos A, Alom J, Codina A5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial.Eur Neurol.(1986)
    14. ^Caruso I, Sarzi Puttini P, Cazzola M, Azzolini VDouble-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome.J Int Med Res.(1990 May-Jun)
    15. ^Sarzi Puttini P, Caruso IPrimary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study.J Int Med Res.(1992 Apr)
    16. ^Meloni M, Puligheddu M, Sanna F, Cannas A, Farris R, Tronci E, Figorilli M, Defazio G, Carta MEfficacy and safety of 5-Hydroxytryptophan on levodopa-induced motor complications in Parkinson's disease: A preliminary finding.J Neurol Sci.(2020 Aug 15)
    17. ^Chase TN, Ng LK, Watanabe AMParkinson's disease. Modification by 5-hydroxytryptophan.Neurology.(1972 May)
    18. ^Javelle F, Lampit A, Bloch W, Häussermann P, Johnson SL, Zimmer PEffects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis.Nutr Rev.(2020 Jan 1)
    19. ^Das YT, Bagchi M, Bagchi D, Preuss HGSafety of 5-hydroxy-L-tryptophan.Toxicol Lett.(2004 Apr 15)
    20. ^Wyatt RJ, Zarcone V, Engelman K, Dement WC, Snyder F, Sjoerdsma AEffects of 5-hydroxytryptophan on the sleep of normal human subjects.Electroencephalogr Clin Neurophysiol.(1971 Jun)
    21. ^Zarcone V, Kales A, Scharf M, Tan TL, Simmons JQ, Dement WCRepeated oral ingestion of 5-hydroxytryptophan. The effect on behavior and sleep processes in two schizophrenic children.Arch Gen Psychiatry.(1973 Jun)
    22. ^Meloni M, Figorilli M, Carta M, Tamburrino L, Cannas A, Sanna F, Defazio G, Puligheddu MPreliminary 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.(2022 Sep)
    23. ^Bruni O, Ferri R, Miano S, Verrillo EL -5-Hydroxytryptophan treatment of sleep terrors in childrenEur J Pediatr.(2004 Jul)
    24. ^Sutanto CN, Xia X, Heng CW, Tan YS, Lee DPS, Fam J, Kim JEThe impact of 5-hydroxytryptophan supplementation on sleep quality and gut microbiota composition in older adults: A randomized controlled trial.Clin Nutr.(2024-Mar)
    25. ^Yousefzadeh F, Sahebolzamani E, Sadri A, Mortezaei A, Aqamolaei A, Mortazavi SH, Shalbafan MR, Ghaffari S, Alikhani R, Mousavi SB, Naderi S, Shamabadi A, Jalilevand S, Akhondzadeh S5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control.Int Clin Psychopharmacol.(2020 Sep)
    26. ^Birdsall TC5-Hydroxytryptophan: a clinically-effective serotonin precursor.Altern Med Rev.(1998-Aug)

    Examine Database References

    1. Weight - Ceci F, Cangiano C, Cairella M, Cascino A, Del Ben M, Muscaritoli M, Sibilia L, Rossi Fanelli FThe effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjectsJ Neural Transm.(1989)
    2. Weight - Cangiano C, Ceci F, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Antonucci F, Rossi-Fanelli FEating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophanAm J Clin Nutr.(1992 Nov)
    3. Sleep Terrors - Bruni O, Ferri R, Miano S, Verrillo EL -5-Hydroxytryptophan treatment of sleep terrors in childrenEur J Pediatr.(2004 Jul)
    4. Appetite - Cangiano C, Laviano A, Del Ben M, Preziosa I, Angelico F, Cascino A, Rossi-Fanelli FEffects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patientsInt J Obes Relat Metab Disord.(1998 Jul)
    5. Cortisol - Schruers K, van Diest R, Nicolson N, Griez EL-5-hydroxytryptophan induced increase in salivary cortisol in panic disorder patients and healthy volunteersPsychopharmacology (Berl).(2002 Jun)
    6. Depression Symptoms - Jangid P, Malik P, Singh P, Sharma M, Gulia AKComparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode.Asian J Psychiatr.(2013-Feb)
    7. Depression Symptoms - Pöldinger W, Calanchini B, Schwarz WA functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine.Psychopathology.(1991)
    8. Depression Symptoms - Meloni M, Puligheddu M, Carta M, Cannas A, Figorilli M, Defazio GEfficacy and safety of 5-hydroxytryptophan on depression and apathy in Parkinson's disease: a preliminary finding.Eur J Neurol.(2020 May)