5-hydroxytryptophan (5-HTP) is an amino acid that occurs in the body. It is the immediate precursor of the brain neurotransmitter serotonin. 5-HTP is well-absorbed with approximately 70% of an oral dose reaching the bloodstream. Some orally administered 5-HTP is rapidly decarboxylated to serotonin in the "peripheral vasculature" (before reaching the brain), and some crosses the blood-brain barrier and increases synthesis of serotonin. In the process of serotonin biosynthesis, tryptophan is hydroxylated to 5-HTP and then decarboxylated to serotonin (5-HT). The tryptophan hydroxylase enzyme catalyzes tryptophan's conversion to 5-HTP, and the 5-hydroxytryptophan decarboxylase enzyme catalyzes 5-HTP's conversion to 5-HT. The conversion of tryptophan to 5-HTP is the rate-limiting step in the production of serotonin from tryptophan.

The 5-HTP decarboxylase enzyme is widely distributed in the body with highest activity in the gut wall and liver. Peripheral serotonin does not cross the blood-brain barrier. 5-HTP decarboxylase inhibitors are sometimes given in conjunction with 5-HTP to inhibit peripheral conversion and help insure that adequate levels of serotonin are produced in the brain. However, studies indicate that 5-HTP works as well, if not better, when used without decarboxylase inhibitors.

Griffonia simplicifolia seed

Dietary supplements of 5-HTP should be manufactured to 99% or higher purity levels.

5-HTP is extracted from the seeds of the African Griffonia simplicifolia plant using an alcoholic extraction process that produces an oily solid. The oily extract is then purified into a dry solid. Standard preparations available as 25, 50, and 100 mg capsules or tablets.

Depression: 5-HTP has been shown to be effective in treating mild to moderate depression in 5-HT deficient individuals. Its effects are similar to those observed with the antidepressant drugs imipramine and fluvoxamine. Treatment with 5-HTP (ranging from 150 to 300 mg per day for one to six weeks) improved depressed mood, anxiety, insomnia, and physical symptoms.

Fibromyalgia: Numerous clinical studies suggest that low serotonin levels cause symptoms of fibromyalgia. Treatment with 5-HTP enhances serotonin synthesis, which increases pain tolerance and sleep quality. 5-HTP treatment (300 mg tid for 30 to 90 days) has been shown to improve symptoms of depression, anxiety, insomnia, and somatic pain (number of painful areas and morning stiffness) in patients with fibromylagia.

Insomnia: 5-HTP has been shown to reduce the time required to fall asleep and improve sleep quality in numerous double-blind, clinical trials.

Migraine headache: 5-HTP (200 to 600 mg/day for two to six months), has been shown to reduce the frequency and severity of migraine headaches in several clinical trials. Significantly fewer side effects were observed with 5-HTP compared to other migraine headache drugs.

Obesity: 5-HTP treatment causes decreased carbohydrate intake and may result in weight loss in obese patients. It is hypothesized that 5-HTP may promote weight loss by promoting satiety. In one study, overweight persons were given 300 mg 5-HTP three times daily, for six weeks with no dietary restriction. For the second six weeks of the trial, they were placed on a 1,200 calorie-per-day diet in addition to the 5-HTP treatment. At the end of the 12 weeks, the 5-HTP group had lost an average of 11.63 pounds, while the placebo group had lost only 1.87 pounds. Early satiety was reported by 100% of the participants during the first six-week period, and by 90% of the participants on 5-HTP during the second six-week period. In another study, 5-HTP (750 mg per day for two weeks) administered to 25 overweight NIDDM patients caused a significant reduction in daily energy intake (from fat and carbohydrate) and body weight.

Headaches in children: Children with sleep disorder-related headaches have been shown to respond favorably to 5-HTP treatment.

The therapeutic dose and length of treatment will depend on the condition being treated. In clinical trials, dosages ranged from 150 to 900 mg per day and lasted for two weeks to six months.

Relatively few adverse effects are associated with its use in the treatment of depression. 5-HTP causes mild gastrointestinal disturbances in some people. These side effects include mild nausea, heartburn, flatulence, feelings of fullness, and rumbling sensations. Side effects are reduced after extended treatment (four to six weeks).

Individuals taking antidepressant drugs, such as MAOIs or selective serotonin reuptake inhibitors (SSRIs), or other prescription drugs, should consult with their physician before taking 5-HTP. Excessive 5-HTP stimulation may cause "serotonin syndrome" (excess accumulation of serotonin in the synapses), characterized by altered mental states, autonomic dysfunction, and neuromuscular abnormalities.

A case of scleroderma-like illness has been reported in a patient taking L-5-hydroxytryptophan and carbidopa (Joly et al. 1991). An earlier case reported a similar interaction between carbidopa and 5-HTP (Sternberg et al. 1980). This interaction may be due to an alteration in tryptophan metabolism (Joly et al. 1991).

Concomitant use of sumatriptan, SSRIs, and monoamine oxidase inhibitors (MAOIs) is contraindicated due to increased risk for developing serotonin syndrome (Gardner and Lynd 1998; Hines Burnham et al 2000; Joffe and Sokolov 1997). Serotonin syndrome is characterized by mental status changes, rigidity, hyperthermia, rapidly fluctuating vital signs, and possibly coma. Sumatriptan could theoretically interact with 5-HTP by enhancing serotonergic effects.

Tramadol inhibits serotonin uptake and may interact with 5-HTP supplements. A serotonin-like syndrome has been reported in patients taking tramadol with other medications that increase serotonin levels in the central nervous system (Hernandez et al. 1995; Mason and Blackburn 1997; Spiller et al. 1997).

Antidepressants that inhibit serotonin reuptake may interact with 5-HTP supplements by enhancing serotonergic effects, causing symptoms related to central and peripheral toxicity. A serotonin-like syndrome has been reported in patients taking trazodone with other medications that increase serotonin levels in the central nervous system (Bodner et al. 1995; George and Godleski 1996; Nisijima et al. 1996; Reeves and Bullen 1995). Serotonin syndrome has also been reported in patients taking venlafaxine with other medications that increase serotonin levels (Bhatara et al. 1998; Diamond et al. 1998; Perry 2000).

There are several case reports of patients experiencing prolonged hallucinations while taking zolpidem with SSRIs (Elko et al. 1998; Toner et al. 2000). The mechanism for this interaction is not known. Because 5-HTP increases serotonin levels in the brain, it could interact with zolpidem, although no reports of such an interaction are known to have been identified in the literature to date.

Angst J, et al. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr. 1977;224:175-186.

Bhatara VS, Magnus RD, Paul KL, et al. Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechansims. Ann Pharmacother. 1998;32(4):432-436.

Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3:271-280.

Bodner RA,Lynch T, Lewis L, Kahn D. Serotonin syndrome. Neurol. 1995;45(2):219-223.

Byerley WF, et al. 5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. J Clin Psychopharmacol. 1987;7:127-137.

Cangiano C, 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.

Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. J Clin Nutr. 1992;56:863-867.

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.

Ceci F, Cangiano C, Cairella M, Cascino A, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm. 1989;76:109-117.

DeBenedittis 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.

DeGiorgis G, 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.

Diamond S, Pepper BJ, Diamond MI, et al. Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: four patient reports. Neurol. 1998;51(1):274-276.

Elko CJ, Burgess JL, Robertson WO. Zolpidem--associated hallucinations and serotonin reuptake inhibition: a possible interaction. J Toxicol Clin Toxicol. 1998;36(3):195-203.

Ganong WF. Review of Medical Physiology. 13th ed. San Mateo, Calif: Appleton & Lange; 1987.

Gardner DM, Lynd LD. Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother. 1998;32(1):33-38.

George TP, Godleski LS. Possible serotonin syndrome with trazodone addition to fluoxetine. Biol Psychiatry. 1996 Mar;39(5):384-385.

Hernandez AF, Montero MN, Pla A, Villanueva E, et al. Fatal moclobemide overdose or death caused by serotonin syndrome? J Forensic Sci. 1995;40(1):128-130.

Hines Burnham, et al, eds. Drug Facts and Comparisons 2000. 55th ed. St. Louis, MO:Facts and Comparisons; 2000.

Joffe RT, Sokolov ST. Co-adminstration of fluoxetine and sumatriptan: the Canadian experience. Acta Psychiatr Scand. 1997;95(6):551-552.

Joly P, Lampert A, Thomine E, Lauret P. Development of pseudobullous morphea and sclero-derma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. J Am Acad Dermatol. 1991;25(2):332-333.

Juhl JH. Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study. Altern Med Rev. 1998;3:367-375.

Magnussen I, Nielson-Kudsk F. Bioavailability and related pharmacokinetics in man of orally administered L-5-Hydroxytryptophan in steady state. Acta Pharmacol et Toxicol. 1980;46:257-262.

Martin TG. Serotonin syndrome. Ann Emerg Med. 1996;28:520-526.

Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. Ann Pharmacother. 1997;31(2):175-177.

Murray MT, Pizzorno JE. Encyclopedia of Natural Medicine. 2nd ed. Rocklin, Calif: Prima Publishing; 1998.

Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy. Adv Exp Med Biol. 1996;398:373-379.

Nisijima K, Shimizu M, Abe T, Ishijuro T. A case of serotonin syndrome induced by concomitant treatment with low-dose trazodone and amitriptyline and lithium. Int Clin Psychopharmacol. 1996 Dec;11(4):289-290.

Perry NK. Venlafaxine-induced serotonin syndrome with relapse following amitripyline. Postgrad Med J. 2000;76(894):254.

Puttini PS, Caruso I. Primary fibromyalgia and 5-hydroxy-L-tryptophan: a 90-day open study. J Int Med Res. 1992;20:182-189.

Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosom. 1995 Mar-Apr;36(2):159-160.

Reibring L, Agren H, Hartvig P, et al. Uptake and utilization of [beta-11c] 5-hydroxytryptophan (5-HTP) in human brain studied by positron emission tomography. Psychiatry Research. 1992;45:215-225.

Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease. 8th ed. Media, Pa: Williams & Wilkins; 1994:1.

Spiller HA, Gorman SE, Villalobos D, et al. Prospective multicenter evaluation of tramadol exposure. J Toxicol Clin Toxicol. 1997;35(4):361-364.

Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. New Eng J Med. 1980;303:782-787.

Takahashi S, et al. Measurement of 5-hydroxindole compounds during L-5-HTP treatment in depressed patients. Folia Psychiatr Neurol Jpn. 1976;30:461-473.

Toner LC, Tsambiras BM, Catalano G, et al. Central nervous system side effects associated with zolpidem treatment. Clin Neuropharmacol. 2000;23(1):54-58.

Van Hiele LJ. L-5-hydroxytryptophan in depression: the first substitution therapy in psychiatry? Neuropsychobiology. 1980;6:230-240.

Van Praag HM. Management of depression with serotonin precursors. Biol Psychiatry. 1981;16:291-310.

Zmilacher K, et al. L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression. Neuropsychobiology. 1988;20:28-33.