5-HTP

Purported Benefits, Side Effects & More
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5-HTP

Purported Benefits, Side Effects & More
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5-HTP

Common Names

  • 5-Hydroxytryptophan
  • 5-HTP; L-5-Hydroxytryptophan
  • L-5-HTP; Oxitriptan (INN)
  • 5-OHTrp

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

5-HTP may be useful for some conditions in which serotonin levels may be low, such as depression, but additional studies are needed.

5-HTP, or 5-Hydroxytryptophan, is generated during the production of melatonin and serotonin from the amino acid tryptophan. Lower levels of serotonin, a neurotransmitter that relays signals to nerve cells, have been associated with disorders such as depression, anxiety, fibromyalgia, insomnia, chronic headaches, and weight gain.

Some studies suggest 5-HTP may be useful for these conditions because it can boost serotonin levels. More studies are needed however, because results were limited or trials were too small to draw definite conclusions. In addition, 5-HTP may interact with medications or herbs that also affect serotonin levels, or cause certain lab test results to be inaccurate. Therefore, patients should consult with their physician before taking this supplement.

What are the potential uses and benefits?
  • To treat anxiety

    There is limited evidence to suggest 5-HTP may be helpful for anxiety, but it may also interact with other drugs. Additional studies are needed to confirm safety and effectiveness.
  • To treat depression

    There is limited evidence to suggest 5-HTP may be helpful for some types of depression, but it may also interact with other drugs. Additional studies are needed to confirm safety and effectiveness.
  • To treat fibromyalgia

    Initial findings suggest 5-HTP may benefit patients with fibromyalgia. Additional studies are needed.
  • To treat hot flashes

    Initial studies suggest 5-HTP is not helpful for hot flashes.
  • To treat insomnia

    Studies evaluating 5-HTP for insomnia are lacking.
  • To treat migraines

    A few studies did not find 5-HTP helpful for migraines or chronic tension headaches.
  • To treat obesity

    Initial findings suggest 5-HTP may help decrease appetite and food intake, and increase weight loss and feelings of fullness. Additional studies are needed.
What are the side effects?

Common: GI disturbances such as nausea, vomiting, or diarrhea

Less common: Headache, insomnia, rapid or irregular heartbeat

Case reports

Mania: Following combined use of an MAOI and 5-HTP in a patient without history of bipolar disorder.

Excess serotonin in the body: Caused by an interaction between linezolid and 5-HTP. Symptoms can include rapid or irregular heartbeat, poor coordination, agitation, confusion, headache, shivering, fever, and seizures.

Hardening/tightening of skin/tissues: Pain, swelling of hands and feet, skin rash, and weight loss in a 70-year-old patient receiving combination therapy with carbidopa and 5-HTP.

Flu-like neurological condition: Linked to a 5-HTP product that contained impurities which was used by a family. Symptoms resolved after the product was replaced with one that did not have these impurities.

What else do I need to know?

Patient Warnings:

Patients taking selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, or other drugs that affect serotonin levels should avoid taking 5-HTP without the supervision of a physician due to the theoretical potential for serotonin syndrome, a serious condition, or other side effects.

Use of this supplement should also be avoided if taking other supplements such as St John’s wort or SAM-e because these products may also affect serotonin levels.

Do Not Take if:

You are having a 5-HIAA urine test to diagnose/monitor carcinoid tumors: Taking 5-HTP supplements could cause test results to be inaccurate.

You are taking antidepressants or anxiolytics (including tricyclics, MAOIs, and SSRIs): Because many of these drugs also affect serotonin levels, there is an increased risk for side effects or toxicities if you also take 5-HTP. Discuss any use of this supplement with your treating physician.

You are taking monamine oxdiase inhibitors: There is a case report of mania following use of an MAOI with 5-HTP in a patient without personal or family history of bipolar disorder.

You are taking linezolid (Zyvox, an antibiotic MAOI): There is a case report of an interaction with 5-HTP causing serotonin syndrome, a serious condition.

You are taking carbidopa (Lodosyn, a dopamine promoter): There is a case report of pain and swelling of the hands and feet, as well as skin rash and weight loss in a patient treated with carbidopa and 5-HTP.

You are taking St John’s wort: Because SJW may also affect serotonin levels, the use of multiple herbs that do this should be avoided to reduce risks for excess serotonin in the body, a serious condition.

You are taking SAM-e: Because SAME-e may also affect serotonin levels, the use of multiple herbs that do this should be avoided to reduce risks for excess serotonin in the body, a serious condition.

Special Point:

5-HTP should not be confused with 5-hydroxytryptamine (5-HT), the chemical name for the neurotransmitter serotonin.

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For Healthcare Professionals

Scientific Name
(2S)-2-amino-3-(5-hydroxy-1H-indol-3-yl) propanoic acid; H-Trp(5-OH)-OH
Clinical Summary

5-HTP or L-5-Hydroxytryptophan is a key intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin. It is formed by hydroxylation of the amino acid L-tryptophan. 5-HTP is marketed as a dietary supplement for sleep, to improve mood and well-being, and to suppress appetite. Seeds from the African shrub Griffonia simplicifolia are a major source for these supplements due to their high 5-HTP content (1) (2).

In animal models, anxiolytic and antidyskinetic effects have been demonstrated (3) (4). 5-HTP has also been shown to restore serotonin levels or, at excessive levels, to induce serotonin syndrome (5) (6).

In humans, most research on 5-HTP involves small trials with mixed results. A few studies suggest 5-HTP may reduce anxiety (7) (8) or depression (2) (9) (10), but not treatment-resistant depression (11) (12). Evidence for its use in PTSD prevention is also lacking (40). Other studies suggest antidepressant effects comparable with fluoxetine (13), and potential benefit as part of augmentation therapy for drug-resistant depression (14).

5-HTP has also been evaluated for obesity. Preliminary findings suggest it may help decrease food intake and increase weight loss and early satiety (15) (16). More recently, a sublingual 5-HTP spray increased appetite control in overweight women (17) (18).

Other preliminary studies suggest benefit for patients with fibromyalgia (19), but not for postmenopausal hot flashes (20) or tardive dyskinesia (21). 5-HTP does not appear to reduce chronic tension headaches, although a decrease in analgesic use was noted (22). It was also ineffective as prophylaxis for childhood migraine (23), but may improve pediatric sleep terrors (24).

Larger well-designed studies are needed to determine the populations and conditions for which 5-HTP supplementation may be useful, and to determine safety, particularly in conjunction with other serotonergic medications including antidepressants.

Food Sources

Dietary sources of L-tryptophan, which the body converts to 5-HTP, include turkey, chicken, pumpkin seeds, spinach, milk, and bananas.

Purported Uses and Benefits
  • Anxiety
  • Depression
  • Fibromyalgia
  • Hot Flashes
  • Insomnia
  • Migraines
  • Obesity
Mechanism of Action

5-HTP crosses the blood-brain barrier and increases serotonin synthesis (25). The advantage of 5-HTP over L-tryptophan is its ability to bypass the rate-limiting step that tryptophan must undergo via the enzyme tryptophan hydroxylase to convert to 5-HTP. In addition, this enzyme can be inhibited by various factors including B6 or magnesium deficiencies, stress, or insulin resistance, and make tryptophan unavailable for serotonin production (2).

In a series of preclinical experiments, 5-HTP was metabolized by a wide variety of gut bacteria and converted to 5-hydroxyindole, which can accelerate GI motility, but this conversion depends upon microbial composition and pH (39).

Relaxation and anxiolytic properties of 5-HTP are attributed to its ability to elevate CNS serotonin levels (2). 5-HTP was shown to augment neuroendocrine response to an SSRI via increased presynaptic 5HT availability, thus enhancing 5HT release into the synapse (26). It was also proposed to potentially reduce hot flashes in menopausal women with breast cancer or with risk of breast cancer by enhancing serotonin levels (27) , but a clinical study in postmenopausal women found it ineffective (20) .

5-HTP can also increase levels of melatonin, dopamine, and norepinephrine (28) (29), compounds involved in mood and sleep regulation and whose mechanistic pathways may also be stimulated (2). As abnormalities in serotonin and epinephrine pathways have been suspected in fibromyalgia and other chronic diseases (5) (30), this may help to explain preliminary benefits seen with 5-HTP supplementation in other disease states.

Additional studies are needed to further identify mechanisms and conditions under which 5-HTP may exert positive effects or pose concerns when used, especially with other medications due to its modulatory effects on neurotransmitters.

Warnings

Animal studies have shown that 5-HTP can be toxic at excessive levels (5), and a few cases of toxicity in humans have been reported (see Adverse Reaction Case Reports). The clinical relevance, however, has yet to be determined.

Older reports identified contaminants in some 5-HTP supplements (31) (32) (33).

Contraindications

Patients taking selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, or other serotonergic drugs should avoid taking 5-HTP without the supervision of the treating physician due to the theoretical potential for serotonin syndrome or other side effects.

Use of this supplement should also be avoided if taking other supplements such as St John’s wort or SAM-e because these products may also affect serotonin levels.

Adverse Reactions

Common: GI disturbances such as nausea, vomiting, or diarrhea (5) (13)
Less common: Headache, insomnia, palpitations (2) (5)

Case reports
Mania: Following combined use of an MAOI and 5-HTP in a patient without personal or family history of bipolar disorder (34).
Serotonin syndrome: Caused by an interaction between linezolid and 5-HTP (35).
Scleroderma-like illness: Pain, swelling of hands and feet, skin rash, and weight loss in a 70-year-old patient receiving combination therapy with carbidopa and 5-HTP (36).
Eosinophiliamyalgia syndrome and eosinophilia: Linked to a 5-HTP product that contained impurities which was used by a family (32). Symptoms resolved after the product was replaced with one that did not have these impurities.

Herb-Drug Interactions
  • Antidepressants/anxiolytics (tricyclics, MAOIs, and SSRIs): Because 5-HTP can also raise serotonin levels, there is the theoretical potential for increased risk of side effects or toxicities. Larger clinical trials are needed to understand the clinical relevance of these risks.
  • Monamine oxdiase inhibitors: Case report of mania following use of an MAOI with 5-HTP in a patient without history of bipolar disorder (34).
  • Linezolid (Zyvox, an antibiotic MAOI): Case report of interaction with 5-HTP causing serotonin syndrome (35).
  • Carbidopa (Lodosyn, a dopamine promoter): Case of scleroderma-like illness with combination therapy of carbidopa and 5-HTP (36).
Herb Lab Interactions

5-HIAA urine test used to diagnose/monitor treatment for carcinoid tumors: 5-HTP increases urine 5-HIAA excretion and serum CgA levels, and could lead to misinterpretation of laboratory tests (37) (38).

Dosage (OneMSK Only)
References
  1. Lemaire PA, Adosraku RK. An HPLC method for the direct assay of the serotonin precursor, 5-hydroxytrophan, in seeds of Griffonia simplicifolia. Phytochem Anal. Nov-Dec 2002;13(6):333-337.
  2. Iovieno N, Dalton ED, Fava M, et al. Second-tier natural antidepressants: review and critique. J Affect Disord. May 2011;130(3):343-357.
  3. Carnevale G, Di Viesti V, Zavatti M, et al. Anxiolytic-like effect of Griffonia simplicifolia Baill. seed extract in rats. Phytomedicine. Jul 15 2011;18(10):848-851.
  4. Tronci E, Lisci C, Stancampiano R, et al. 5-Hydroxy-tryptophan for the treatment of L-DOPA-induced dyskinesia in the rat Parkinson’s disease model. Neurobiol Dis. Dec 2013;60:108-114.
  5. Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. Mar 2006;109(3):325-338.
  6. Nisijima K, Yoshino T, Ishiguro T. Risperidone counteracts lethality in an animal model of the serotonin syndrome. Psychopharmacology (Berl). May 2000;150(1):9-14.
  7. Kahn RS, Westenberg HG, Verhoeven WM, et al. Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. Int Clin Psychopharmacol. Jan 1987;2(1):33-45.
  8. Schruers K, van Diest R, Overbeek T, et al. Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Psychiatry Res. Dec 30 2002;113(3):237-243.
  9. Quadbeck H, Lehmann E, Tegeler J. Comparison of the antidepressant action of tryptophan, tryptophan/5-hydroxytryptophan combination and nomifensine. Neuropsychobiology. 1984;11(2):111-115.
  10. van Praag HM, de Haan S. Chemoprophylaxis of depressions. An attempt to compare lithium with 5-hydroxytryptophan. Acta Psychiatr Scand Suppl. 1981;290:191-201.
  11. Nolen WA, van de Putte JJ, Dijken WA, et al. L-5HTP in depression resistant to re-uptake inhibitors. An open comparative study with tranylcypromine. Br J Psychiatry. Jul 1985;147:16-22.
  12. Nolen WA, van de Putte JJ, Dijken WA, et al. Treatment strategy in depression. II. MAO inhibitors in depression resistant to cyclic antidepressants: two controlled crossover studies with tranylcypromine versus L-5-hydroxytryptophan and nomifensine. Acta Psychiatr Scand. Dec 1988;78(6):676-683.
  13. Jangid P, Malik P, Singh P, et al. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr. Feb 2013;6(1):29-34.
  14. Kious BM, Sabic H, Sung YH, et al. An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women. J Clin Psychopharmacol. Oct 2017;37(5):578-583.
  15. Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr. Nov 1992;56(5):863-867.
  16. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm. 1989;76(2):109-117.
  17. Rondanelli M, Klersy C, Iadarola P, et al. Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation. Int J Obes (Lond). Oct 2009;33(10):1174-1182.
  18. Rondanelli M, Opizzi A, Faliva M, et al. Relationship between the absorption of 5-hydroxytryptophan from an integrated diet, by means of Griffonia simplicifolia extract, and the effect on satiety in overweight females after oral spray administration. Eat Weight Disord. Mar 2012;17(1):e22-28.
  19. Caruso I, Sarzi Puttini P, Cazzola M, et al. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. May-Jun 1990;18(3):201-209.
  20. Freedman RR. Treatment of menopausal hot flashes with 5-hydroxytryptophan. Maturitas. Apr 2010;65(4):383-385.
  21. Nasrallah HA, Smith RE, Dunner FJ, et al. Serotonin precursor effects in tardive dyskinesia. Psychopharmacology (Berl). 1982;77(3):234-235.
  22. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. For the Portuguese Head Society. Headache. Jun 2000;40(6):451-456.
  23. Santucci M, Cortelli P, Rossi PG, et al. L-5-hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study. Cephalalgia. Sep 1986;6(3):155-157.
  24. Bruni O, Ferri R, Miano S, et al. L -5-Hydroxytryptophan treatment of sleep terrors in children. Eur J Pediatr. Jul 2004;163(7):402-407.
  25. Jacobsen JPR, Krystal AD, Krishnan KRR, et al. Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression: Clinical and Preclinical Rationale. Trends Pharmacol Sci. Nov 2016;37(11):933-944.
  26. Lowe SL, Yeo KP, Teng L, et al. L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology. May 2006;31(4):473-484.
  27. Curcio JJ, Kim LS, Wollner D, et al. The potential of 5-hydryoxytryptophan for hot flash reduction: a hypothesis. Altern Med Rev. Sep 2005;10(3):216-221.
  28. Dais J, Khosia A, Doulatram G. The Successful Treatment of Opioid Withdrawal-Induced Refractory Muscle Spasms with 5-HTP in a Patient Intolerant to Clonidine. Pain Physician. May-Jun 2015;18(3):E417-420.
  29. National Library of Medicine (NLM). ToxNet Toxicology Data Network: 5-HYDROXYTRYPTOPHAN.
  30. Nihalani ND, Schwartz T, Chlebowski S. Fibromyalgia-: a review for the psychiatrist. Psychiatry (Edgmont). Apr 2006;3(4):44-60.
  31. Klarskov K, Johnson KL, Benson LM, et al. Structural characterization of a case-implicated contaminant, “Peak X,” in commercial preparations of 5-hydroxytryptophan. J Rheumatol. Jan 2003;30(1):89-95.
  32. Michelson D, Page SW, Casey R, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol. Dec 1994;21(12):2261-2265.
  33. Klarskov K, Johnson KL, Benson LM, et al. Eosinophilia-myalgia syndrome case-associated contaminants in commercially available 5-hydroxytryptophan. Adv Exp Med Biol. 1999;467:461-468.
  34. Pardo JV. Mania following addition of hydroxytryptophan to monoamine oxidase inhibitor. Gen Hosp Psychiatry. Jan-Feb 2012;34(1):102.e113-104.
  35. Ostabal Artigas MI. [Serotoninergic syndrome due to interaction between linezolid and 5-hydroxytryptophan]. Med Clin (Barc). Dec 21 2015;145(12):e37-38.
  36. Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med. Oct 2 1980;303(14):782-787.
  37. Joy T, Walsh G, Tokmakejian S, et al. Increase of urinary 5-hydroxyindoleacetic acid excretion but not serum chromogranin A following over-the-counter 5-hydroxytryptophan intake. Can J Gastroenterol. Jan 2008;22(1):49-53.
  38. Hallin ML, Mahmoud K, Viswanath A, et al. ’Sweet Dreams’, ’Happy Days’ and elevated 24-h urine 5-hydroxyindoleacetic acid excretion. Ann Clin Biochem. Jan 2013;50(Pt 1):80-82.
  39. Waclawiková B, Bullock A, Schwalbe M, et al. Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels. PLoS Biol. Jan 2021;19(1):e3001070.
  40. Bertolini F, Robertson L, Bisson JI, et al. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. Feb 10 2022;2(2):Cd013443.
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