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5-Hydroxytryptophan

Also indexed as: 5-HTP

Illustration

5-HTP is used by the human body to make serotonin, an important substance for normal nerve and brain function. Serotonin appears to play significant roles in sleep, emotional moods, pain control, inflammation, intestinal peristalsis, and other body functions.1

Where is it found?

5-HTP is not present in significant amounts in a typical diet. The human body manufactures 5-HTP from L-tryptophan, a natural amino acid found in most dietary proteins. However, eating food that contains L-tryptophan does not significantly increase 5-HTP levels. Supplemental 5-HTP is naturally derived from the seeds of Griffonia simplicifolia, a West African medicinal plant.

5-HTP has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings Health Concerns
2Stars

Depression

Fibromyalgia

Insomnia

Migraine headaches

Sleep terrors

Tension headache

Weight loss and obesity

1Star

Bipolar disorder/manic depression

Eating disorders

Parkinson’s disease (with Sinemet®)

Seasonal affective disorder

3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

Disruptions in emotional well-being, including depression and anxiety, have been linked to serotonin imbalances in the brain.2 People with fibromyalgia often have low serotonin levels in their blood.3 4 5 Supplements of 5-HTP may increase serotonin synthesis in these cases. The cause of migraine headaches is related to abnormal serotonin function in blood vessels,6 and 5-HTP may help correct this abnormality. Insomnia has been associated with tryptophan deficiency in the tissues of the brain;7 therefore, 5-HTP may provide a remedy for this condition.

How much is usually taken?

In a controlled trial, 5-HTP (300 mg per day) was shown to be effective in reducing many symptoms of fibromyalgia, including pain, morning stiffness, sleep disturbances, and anxiety.8

For depression, 300 mg per day is often effective, though much of the research used 5-HTP in combination with drugs or was uncontrolled.9 10 11 For insomnia, a single 100-mg nighttime dose of 5-HTP was sufficient to improve the duration and depth of sleep in one placebo-controlled trial.12 For migraine headaches, amounts ranging from 400–600 mg per day have been shown to be effective at reducing the frequency and severity of attacks in most clinical trials.13 14 15 16 17 For tension headaches, 100 mg of 5-HTP taken three times per day led to a significant decrease in consumption of pain-relievers, but no significant change in headache duration or intensity.18

Appetite reduction and weight loss (averaging 11 pounds in 12 weeks) has occurred with amounts of 600–900 mg daily.19 20 In another clinical trial, 750 mg per day has been shown to be effective at decreasing carbohydrate and fat intake, and promoting weight loss.21

Are there any side effects or interactions?

During the clinical trials described above, some people taking large amounts of 5-HTP experienced gastrointestinal upset (e.g. nausea) or, less often, headache, sleepiness, muscle pain, or anxiety.

A substance known as “Peak X” has been found in low concentrations in several over-the-counter 5-HTP preparations. Some researchers think this substance may be linked22 23 24 to toxicity previously reported25 26 27 in a 1989 L-tryptophan contamination incident. However, there is serious question about whether Peak X is actually the toxic agent and it may be unrelated to the problems previously associated with L-tryptophan.28 29 30 31 32 33 34 35 Although two articles reported possible associations between 5-HTP consumption and toxicity symptoms similar to those attributed to contaminated L-tryprophan,36 37 evidence linking 5-HTP or Peak X with any toxicity symptoms remains speculative. Although the structure of Peak X has recently been identified, there is no firm evidence that this substance has caused or contributed to any toxicity or disease.38

Very high intakes of 5-HTP have caused muscle jerks in guinea pigs39 and both muscle jerks40 and diarrhea in mice.41 Injected 5-HTP has also caused kidney damage in rats.42 To date, these problems have not been reported in humans. “Serotonin syndrome,” a serious but uncommon condition caused by excessive amounts of serotonin, has not been reported to result from supplementation with 5-HTP; in theory it could be triggered by the supplement.43 However, the level of intake at which this toxic effect might potentially occur remains unknown.

5-HTP should not be taken with antidepressants, weight-control drugs, other serotonin-modifying agents, or substances known to cause liver damage, because in these cases 5-HTP may have excessive effects. People with liver disease may not be able to regulate 5-HTP adequately and those suffering from autoimmune diseases such as scleroderma may be more sensitive than others, to 5-HTP.44 These people should not take 5-HTP without consulting a knowledgeable healthcare professional. The safety of taking 5-HTP during pregnancy and breast-feeding is not known at this time.

Are there any drug interactions?
Certain medicines may interact with 5-hydroxytryptophan. Refer to drug interactions for a list of those medicines.

References:

1. Guyton AC, Hall JE. Textbook of Medical Physiology, 9th ed. Philadelphia: W. B. Saunders, 1996.

2. van Praag HM, Lemus C. Monoamine precursors in the treatment of psychiatric disorders. Nutrition and the Brain, vol. 7, eds. RJ Wurtman, JJ Wurtman. New York: Raven Press, 1986 [review].

3. Russell IJ, Michalek JE, Vipraio GA, et al. Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol 1992;19:90–4.

4. Yunus MB, Dailey JW, Aldag JC, et al. Platelet 3H-imiprimine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol 1992;19:104–9.

5. Wolfe F, Russell IJ, Vipraio G, et al. Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J Rheumatol 1997;24:555–9.

6. Kimball RW, Friedman AP, Vallejo E. Effect of serotonin in migraine patients. Neurology 1960;10:107–11.

7. Schneider-Helmert D, Spinweber CL. Evaluation of L-tryptophan for treatment of insomnia: A review. Psychopharmacology (Berlin) 1986;89(1):1–7.

8. Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res 1990;18:201–9.

9. Byerley WF, Judd LL, Reimherr FW, Grosser BI. 5-hydroxytryptophan: A review of its antidepressant efficacy and adverse effects . J Clin Psychopharmacol 1987;7:127–37 [review].

10. Zmilacher K, Battegay R, Gastpar M. L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression. Neuropsychobiology 1988;20:28–35.

11. Poldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24(2):53–81.

12. Soulairac A, Lambinet H. Etudes cliniques de líaction du precurseur de la serotonine le L-5-hydroxy-tryptophane, sur les troubles du sommeil. Schweiz Bundschau Med (PRAXIS) 1998;77(34a):19–23 [in French].

13. De Benedittis G, Massei R. 5-HT precursors in migraine prophylaxis: a double-blind cross-over study with L-5-hydroxytryptophan versus placebo. Clin J Pain 1986;3:123–9.

14. Titus F, Davalos A, Alom J, Codina A. 5-hydroxytryptophan versus methysergide in the prophylaxis of migraine. Eur Neurol 1986;25:327–9.

15. Maissen CP, Ludin HP. Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine. Schweizerische Medizinische Wochenschrift /Journal Suisse de Medecine 1991;121:1585–90 [in German].

16. Mathew NT. 5-hydroxytryptophan in the prophylaxis of migraine. Headache 1978;18:111–3.

17. De Giorgis G, Miletto R, Iannuccelli M, et al. Headache in association with sleep disorders in children: a psychodiagnostic evaluation and controlled clinical study ñ L-5-HTP versus placebo. Drugs Exptl Clin Res 1987;13(7):425–33.

18. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache 2000;40:451–6.

19. 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):109–17.

20. 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 1992;56:863–7.

21. Cangiano C, Laviano A, Del Ben M, et al. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Int J Obes Relat Metab Disord 1998;22:648–54.

22. Williamson BL, Benson LM, Tomlinson AJ, et al. On-line HPLC-tandem mass spectrometry analysis of contaminants of L-tryptophan associated with the onset of the eosinophilia-myalgia syndrome. Toxicol Lett 1997;92:139–48.

23. Williamson BL, Klarskov K, Tomlinson AJ, et al. Problems with over-the-counter 5-hydroxy-L-tryptophan. Nat Med 1998;4:983.

24. Williamson BL, Tomlinson AJ, Mishra PK, et al. Structural characterization of contaminants found in commercial preparations of melatonin: similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. Chem Res Toxicol 1998;11:234–40.

25. Belongia EA, Hedberg CW, Gleich GJ, et al. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med 1990;323:357–65.

26. Martin RW, Duffy J, Engel AG, et al. The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of pathophysiology. Ann Intern Med 1990;113:124–34.

27. Mayeno AN, Lin F, Foote CS, et al. Characterization of “peak E,” a novel amino acid associated with eosinophilia-myalgia syndrome. Science 1990;250:1707–8.

28. Belongia EA, Hedberg CW, Gleich GJ, et al. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med 1990;323:357–65.

29. Mayeno AN, Lin F, Foote CS, et al. Characterization of “peak E,” a novel amino acid associated with eosinophilia-myalgia syndrome. Science 1990;250:1707–8.

30. Reinauer S, Plewig G. [Eosinophilia-myalgia syndrome]. Hautarzt 1991;42(3):137–9 [in German].

31. Toyo’oka T, Yamazaki T, Tanimoto T, et al. Characterization of contaminants in EMS-associated L-tryptophan samples by high-performance liquid chromatography. Chem Pharm Bull (Tokyo) 1991;39(3):820–2.

32. Trucksess MW, Thomas FS, Page SW. High-performance liquid chromatographic determination of 1,1’-ethylidenebis(L-tryptophan) in L-tryptophan preparations. J Pharm Sci 1994;83(5):720–2.

33. Trucksess MW. Separation and isolation of trace impurities in L-tryptophan by high-performance liquid chromatography. J Chromatogr 1993;630(1–2):147–50.

34. Ito J, Hosaki Y, Torigoe Y, Sakimoto K. Identification of substances formed by decomposition of peak E substance in tryptophan. Food Chem Toxicol 1992;30(1):71–81.

35. Castot A, Bidault I, Bournerias I, et al. [“Eosinophilia-myalgia” syndrome due to L-tryptophan containing products. Cooperative evaluation of French Regional Centers of Pharmacovigilance. Analysis of 24 cases]. Therapie 1991;46(5):355–65 [in French].

36. Michelson D, Page SW, Casey R, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol 1994;21:2261–5.

37. 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 1980;303(14):782–7.

38. Johnson KL, Klarskov K, Benson LM, et al. Presence of peak X and related compounds: the reported contaminant in case related 5-Hydroxy-L-tryptophan associated with eosinophilia-myalgia syndrome. J Rheumatol 1999;26(12):2714–7.

39. Hagan JJ, Hatcher JP, Slade PD. The role of 5-HT1D and 5-HT1A receptors in mediating 5-hydroxytryptophan induced myoclonic jerks in guinea pigs. Eur J Pharmacol 1995;294:743–51.

40. Green AR, Johnson P, Mountford JA, Nimgaonkar VL. Some anticonvulsant drugs alter monoamine mediated behaviour in mice in ways similar to electroconvulsive shock; implications for antidepressant therapy. Br J Pharmacol 1985;84:337–46.

41. Bourin M, Hascoet M, Deguiral P. 5-HTP induced diarrhea as a carcinoid syndrome model in mice? Fundam Clin Pharmacol 1996;10:450–7.

42. Hirai M, Nakajima T. Biochemical studies on the mechanism of difference in the renal toxicity of 5-hydroxy-L-tryptophan between Sprague Dawley and Wistar rats. J Biochem (Tokyo) 1979;86:907–13.

43. Martin TG. Serotonin syndrome. Ann Emerg Med 1996;28:520–6.

44. 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 1980;303:782–7.

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