5-Hydroxytryptophan
Supplement Forms/Alternate Names• 5-HTP
Principal Proposed Uses
• Depression; Migraine Headaches; Other Types of Headaches
Other Proposed Uses
• Anxiety; Insomnia; Fibromyalgia; Obesity (Weight Loss)
Many antidepressant drugs work, at least in part, by raising serotonin levels. The supplement 5-hydroxytryptophan (5-HTP) has been tried in cases of depression for a similar reason: the body uses 5-HTP to make serotonin, so providing the body with 5-HTP might, therefore, raise serotonin levels.
As a supplement, 5-HTP has also been proposed for all the same uses as other antidepressants, including aiding weight loss, preventing migraine headaches, decreasing the discomfort of fibromyalgia, improving sleep quality, and reducing anxiety.
Sources
5-HTP is not found in foods to any appreciable extent. For use as a supplement, it is manufactured from the seeds of an African plant (Griffonia simplicifolia).
Therapeutic Dosages
A typical dosage of 5-HTP is 100 to 300 mg 3 times daily. Once 5-HTP starts to work, it may be possible to reduce the dosage significantly and still maintain good results.
Therapeutic Uses
The primary use of 5-HTP is for depression. Several small short-term studies have found that it may be as effective as standard antidepressant drugs.1,2 Since standard antidepressants are also used for insomnia and anxiety, 5-HTP has also been suggested as a treatment for those conditions, but there is only very preliminary evidence as yet that it works.3
Similarly, antidepressant drugs are often used for migraine headaches. Some, but not all, studies suggest that regular use of 5-HTP may help reduce the frequency and severity of migraines, as well as help other types of headaches.4-10 Additionally, preliminary evidence suggests that 5-HTP can reduce symptoms of fibromyalgia11 and perhaps help you lose weight.12-15
What Is the Scientific Evidence for 5-Hydroxytryptophan?
Depression
Several small studies have compared 5-HTP to standard antidepressants.16 The best one was a 6-week study of 63 people given either 5-HTP (100 mg 3 times daily) or an antidepressant in the Prozac family (fluvoxamine, 50 mg 3 times daily).17 Researchers found equal benefit between the supplement and the drug. However, 5-HTP caused fewer and less severe side effects.
Migraine and Other Headaches
There is some evidence that 5-HTP may help prevent migraines when taken at a dosage of 400 to 600 mg daily. Lower doses may not be effective.
In a 6-month trial of 124 people, 5-HTP (600 mg daily) proved equally effective as the standard drug methysergide.18 The most dramatic benefits observed were reductions in the intensity and duration of migraines. Since methysergide has been proven better than placebo for migraine headaches in earlier studies, the study results provide meaningful, although not airtight, evidence that 5-HTP is also effective.
Similarly good results were seen in another comparative study, using a different medication and 5-HTP (at a dose of 400 mg daily).19
However, in one study, 5-HTP (up to 300 mg daily) was less effective than the drug propranolol.20 Also, in a study involving children, 5-HTP failed to demonstrate benefit.21 Other studies that are sometimes quoted as evidence that 5-HTP is effective for migraines actually enrolled adults or children with many different types of headaches (including migraines).22,23,24
Putting all this evidence together, it appears likely that 5-HTP can help people with frequent migraine headaches if taken in sufficient doses, but further research needs to be done. In particular, we need a large double-blind study that compares 5-HTP against placebo over a period of several months.
Finally, an 8-week, double-blind, placebo-controlled trial of 65 individuals (mostly women) with tension headaches found that 5-HTP at a dose of 100 mg 3 times daily did not significantly reduce the number of headaches experienced; however, it did reduce participants' need to use other pain-relieving medications.25
Obesity (Weight Loss)
The drug fenfluramine was one member of the now infamous phen-fen treatment for weight loss. Although very successful, fenfluramine was later associated with damage to the valves of the heart and was removed from the market. Because fenfluramine raises serotonin levels, it seems reasonable to believe that other substances that affect serotonin might also be useful for weight reduction.
Four small double-blind, placebo-controlled clinical trials examined whether 5-HTP can aid weight loss. The first, a double-blind crossover study, found that use of 5-HTP (at a daily dose of 8 mg per kilogram body weight) reduced caloric intake despite the fact that the 19 participants made no conscious effort to eat less.26 Participants given placebo consumed about 2,300 calories per day, while those taking 5-HTP ate only 1,800 calories daily. Use of 5-HTP appeared to lead to a significantly enhanced sense of satiety after eating. Over the course of 5 weeks, women taking 5-HTP effortlessly lost more than 3 lbs.
A follow-up study by the same research group enrolled 20 overweight women who were trying to lose weight.27 Participants received either 5-HTP (900 mg per day) or placebo for two consecutive 6-week periods. During the first period, there was no dietary restriction, while during the second period participants were encouraged to follow a defined diet expected to lead to weight loss.
Participants receiving placebo did not lose weight during either period. However, those receiving 5-HTP lost about 2% of their initial body weight during the no-diet period and an additional 3% while on the diet. Thus, a woman with an initial weight of 170 lbs lost about 3-1/2 lbs after 6 weeks of using 5-HTP without dieting and another 5 lbs while dieting. Once again, participants taking 5-HTP experienced quicker satiety.
Similar benefits were seen in a double-blind study of 14 overweight women given 900 mg of 5-HTP daily.28
Finally, a double-blind, placebo-controlled study of 20 overweight individuals with adult-onset diabetes found that use of 5-HTP (750 mg per day) without intentional dieting resulted in about a 4-1/2 lb weight loss over a 2-week period.29 Use of 5-HTP reduced carbohydrate intake by 75% and fat intake to a lesser extent.
Fibromyalgia
Antidepressants are the primary conventional treatment for fibromyalgia, a little-understood disease characterized by aching, tender muscles, fatigue, and disturbed sleep. One study suggests that 5-HTP may be helpful as well. In this double-blind trial, 50 subjects with fibromyalgia were given either 100 mg of 5-HTP or placebo 3 times daily for a month.30 Those receiving 5-HTP experienced significant improvements in all symptom categories, including pain, stiffness, sleep patterns, anxiety, and fatigue.
Anxiety
An 8-week, double-blind, placebo-controlled study compared 5-HTP and the drug clomipramine in 45 individuals suffering from anxiety disorders.31 The results showed that 5-HTP was effective, but clomipramine was more effective.
Safety Issues
No significant adverse effects have been reported in clinical trials of 5-HTP. Side effects appear to be generally limited to short-term, mild digestive distress and possible allergic reactions.
One potential safety issue with 5-HTP involves an interaction with a medication used for Parkinson's disease: carbidopa. Several reports suggest that the combination can create skin changes similar to those that occur in the disease scleroderma.32,33,34
According to several reports, when dogs have consumed excessive amounts of 5-HTP, they developed signs of excess serotonin.39 In humans, this so-called serotonin syndrome includes such symptoms as confusion, agitation, rapid heart rate, high blood pressure, muscle jerks, loss of coordination, sweating, shivering, and fever; rapid breathing, coma, and death are possible. Serotonin syndrome might also occur if 5-HTP is combined with drugs that raise serotonin levels, such as SSRIs (such as, Prozac), other antidepressants, or the pain medication tramadol.
There are some reasons for concern that 5-HTP could increase the risk of “infantile spasms” (technically, massive myoclonic seizure disorder) in developmentally disabled children.35,40
Although safety in children has not been proven, children have been given 5-HTP in studies without any apparent harmful effects.36,37,38 Safety in pregnant or nursing women and those with liver or kidney disease has not been established.
Peak X
One report in 1998 raised a potential safety concern with 5-HTP. Researchers discovered evidence of an unidentified substance called peak X in a limited number of 5-HTP products.41
Peak X has a frightening history involving a supplement related to 5-HTP: tryptophan. The body turns tryptophan into 5-HTP, and the two supplements have similar effects in the body. Until the late 1980s, tryptophan was widely used as a sleep aid. However, it was taken off the market when thousands of people using tryptophan developed a disabling and sometimes fatal blood disorder called eosinophilia myalgia. Peak X, introduced through a manufacturer's mistake, is thought to have been the cause, although not all experts agree.42-50
Despite this one report, it seems unlikely that 5-HTP could present the same risk as tryptophan.51 It is manufactured completely differently; peak X has not been seen again in 5-HTP samples, and no epidemic of eosinophilia myalgia has occurred with 5-HTP use.
Interactions You Should Know About
If you are taking:
- Prescription antidepressants (including SSRIs, MAO inhibitors, or tricyclics), the pain drug tramadol, or migraine drugs in the triptan family (such as sumatriptan): Do not take 5-HTP in addition, except on a physician's advice.
- The Parkinson's disease medication carbidopa: Taking 5-HTP at the same time might cause skin changes similar to those that develop in the disease scleroderma.
References
1. Byerley WF, Judd LL, Reimherr FW, et al. 5-hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. J Clin Psychopharmacol. 1987;7:127-137.
2. 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;24:53-81.
3. 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. 1987;2:33-45.
4. Titus F, Davalos A, Alom J, et al. 5-hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol. 1986;25:327-329.
5. Bono G, Criscuoli M, Martignoni E, et al. Serotonin precursors in migraine prophylaxis. Adv Neurol. 1982;33:357-363.
6. Maissen CP, Ludin HP. Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine [translated from German]. Schweiz Med Wochenschr. 1991;121:1585-1590.
7. De Giorgis G, Miletto R, Iannuccelli M, et al. Headache in association with sleep disorders in children: a psychodiagnostic evaluation and controlled clinical study—L-5-HTP versus placebo. Drugs Exp Clin Res. 1987;13:425-433.
8. Longo G, Rudoi I, Iannuccelli M, et al. Treatment of essential headache in developmental age with L-5-HTP (cross over double-blind study versus placebo) [in Italian; English abstract]. Pediatr Med Chir. 1984;6:241-246.
9. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-Hydroxytryptophan vs. placebo. J Neurosurg Sci. 1985;29:239-248.
10. Ribeiro CAF. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache. 2000;40:451-456.
11. 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. 1990;18:201-209.
12. 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;76:109-117.
13. Cangiano C, Ceci F, Cairella M, et al. Effects of 5-Hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese adult subjects. Adv Exp Med Biol. 1991;294:591-593.
14. 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;56:863-867.
15. 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;22:648-654.
16. Byerley WF, Judd LL, Reimherr FW, et al. 5-hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. J Clin Psychopharmacol. 1987;7:127-137.
17. 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;24:53-81.
18. Titus F, Davalos A, Alom J, et al. 5-hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol. 1986;25:327-329.
19. Bono G, Criscuoli M, Martignoni E, et al. Serotonin precursors in migraine prophylaxis. Adv Neurol. 1982;33:357-363.
20. Maissen CP, Ludin HP. Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine [translated from German]. Schweiz Med Wochenschr. 1991;121:1585-1590.
21. Santucci M, Cortelli P, Rossi PG, et al. L-5-Hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study. Cephalalgia. 1986;6:155-157.
22. De Giorgis G, Miletto R, Iannuccelli M, et al. Headache in association with sleep disorders in children: a psychodiagnostic evaluation and controlled clinical study-L-5-HTP versus placebo. Drugs Exp Clin Res. 1987;13:425-433.
23. Longo G, Rudoi I, Iannuccelli M, et al. Treatment of essential headache in developmental age with L-5-HTP (cross over double-blind study versus placebo) [in Italian; English abstract]. Pediatr Med Chir. 1984;6:241-246.
24. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-Hydroxytryptophan vs. placebo. J Neurosurg Sci. 1985;29:239-248.
25. Ribeiro CAF. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache. 2000;40:451-456.
26. 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;76:109-117.
27. 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;56:863-867.
28. Cangiano C, Ceci F, Cairella M, et al. Effects of 5-Hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese adult subjects. Adv Exp Med Biol. 1991;294:591-593.
29. 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;22:648-654.
30. 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. 1990;18:201-209.
31. 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. 1987;2:33-45.
32. 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;303:782-787.
33. Joly P, Lampert A, Thomine E, et al. Development of pseudobullous morphea and scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. J Am Acad Dermatol. 1991;25(2 pt 1):332-333.
34. Auffranc JC, Berbis P, Fabre JF, et al. Sclerodermiform and poikilodermal syndrome observed during treatment with carbidopa and 5-hydroxytryptophan [translated from French]. Ann Dermatol Venereol. 1985;112:691-692
35. Coleman M. Myoclonus in the young after 5-hydroxytryptophan [letter]. N Engl J Med. 1977;296:820.
36. De Giorgis G, Miletto R, Iannuccelli M, et al. Headache in association with sleep disorders in children: a psychodiagnostic evaluation and controlled clinical study—L-5-HTP versus placebo. Drugs Exp Clin Res. 1987;13:425-433.
37. Longo G, Rudoi I, Iannuccelli M, et al. Treatment of essential headache in developmental age with L-5-HTP (cross over double-blind study versus placebo) [in Italian; English abstract]. Pediatr Med Chir. 1984;6:241-246.
38. Santucci M, Cortelli P, Rossi PG, et al. L-5-Hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study. Cephalalgia. 1986;6:155-157.
39. Gwaltney-Brant SM, Albretsen JC, Khan SA. 5-Hydroxytryptophan toxicosis in dogs: 21 cases (1989-1999). J Am Vet Med Assoc. 2000;216:1937-1940.
40. 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;294:743-751.
41. Klarskov K, Johnson KL, Benson LM, Gleich GJ, Naylor S. Eosinophilia-myalgia syndrome case-associated contaminants in commercially available 5-hydroxytryptophan. Adv Exp Med Biol. 1999;467:461-468.
42. 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;323:357-365.
43. 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;46:355-365.
44. Ito J, Hosaki Y, Torigoe Y, Sakimoto K. Identification of substances formed by decomposition of peak E substance in tryptophan. Food Chem Toxicol. 1992;30:71-81.
45. 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;113:124-134.
46. Mayeno AN, Lin F, Foote CS, et al. Characterization of “peak E,” a novel amino acid associated with eosinophilia-myalgia syndrome. Science. 1990;250:1707-1708.
47. 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;39:820-822.
48. 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;83:720-722.
49. Trucksess MW. Separation and isolation of trace impurities in L-tryptophan by high-performance liquid chromatography. J Chromatogr. 1993;630:147-150.
50. 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;92:139-148.
51. Das YT, Bagchi M, Bagchi D, et al. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004;150:111-22.
Last reviewed September 2009 by EBSCO CAM Review Board
Last Updated: 09/01/2009
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Article ID: 588
