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5-Hydroxytryptophan (5-HTP) 

James Meschino DC, MS, ROHP

General Features

5-HTP is a naturally occurring agent that is extracted from the seed of an African plant, known as the “Griffonia Simplicifolia”.  5-HTP, unlike the amino acid tryptophan, easily crosses the blood-brain barrier.  As a result, while only three percent of an oral dose of tryptophan is converted to serotonin in the brain, studies indicate that over seventy percent of an oral dose of 5-HTP is converted to serotonin. As serotonin is a neurotransmitter that elevates mood and improves sleep quality, 5-HTP has been used in clinical trials to treat depression, insomnia and other conditions where a rise in serotonin levels may be desirable. Some evidence suggests that 5-HTP also increases endorphin and other neurotransmitter levels as well.1

Serotonin and Melatonin Synthesis: In the brain the amino acid tryptophan is converted into 5-hydroxytryptophan (5-HTP). The coenzyme required is tetrahydrobiopterin, which donates two hydrogen atoms to this reaction, thereby becoming dihydrobiopterin. 5-HTP is then converted to serotonin via a decarboxylase enzyme (decarboxylation reactions require vitamin B6). In the pineal gland serotonin can be converted to N-acetylserotonin and then to melatonin. The first reaction requires the B-vitamin Pantothenic acid and the second reaction requires the presence of S-adenosyl methionine (which requires folic acid and vitamin B12 for its formation). Its therefore important to note that certain B-vitamins, such as vitamin B6, Pantothenic acid, folic acid and vitamin B12 play vital roles in optimizing neurotransmitter synthesis throughout our lifetime. Some studies have shown that supplementation with folic acid, vitamin B12 and/or S-adenosyl methionine, can reverse depression and certain aspects of cognitive dysfunction, especially in older subjects.

In the central nervous system serotonin has been shown to affect the control of appetite, sleep, memory, learning, temperature regulation, behavior (including sexual and hallucinogenic) and is well known as a neurotransmitter that elevates mood.

Melatonin is known for it ability to induce sleep, counter the effects of jet lag, stimulate immune function, provide antioxidant protection to the brain and elevate mood.
Supplementation Studies and Clinical Applications

  1. Depression

In several clinical trials 5-Hydroxtryptophan has been tested on its own or against other antidepressant drugs, including selective serotonin re-uptake inhibitor drugs (SSRI) such as fluvoxamine (Luvox).  Fluvoxamine exerts anti-depressant activity comparable to Prozac, Zoloft, and Paxil.

In general, 5-Hydroxytryptophan has been shown to be as effective as other traditional antidepressants and tends to be associated with fewer and less severe side effects.  The usual dosage for this application is 100 mg, three times daily.1-5 However, patients with depression should be under the care of a qualified health professional and combining 5-Hydroxytryptophan supplementation with other anti-depressant drugs or supplements is contraindicated and may result in life-threatening side effects (i.e. serotonin syndrome).6

  1. Insomnia

5-HTP has been shown to improve insomnia and quality of sleep in affected subjects.  For insomnia, a single 100 mg dose of 5-HTP, one hour before bedtime has been shown to improve duration and depth of sleep in one placebo-controlled study.7

  1. Fibromyalgia

Some evidence suggests that 100 mg (5-HTP) taken three times per day may reduce symptoms of fibromyalgia, including pain and insomnia. People with fibromyalgia often have low serotonin levels in their blood. Supplementation with 5-HTP may increase serotonin synthesis in these cases. Both preliminary and double-blind trials have reported that 5-HTP supplementation (100 mg three times per day) relieves some symptoms of fibromyalgia.8

  1. Migraine

Migraine Headache Studies have provided evidence that patients who suffer from migraine headaches may experience a reduction in frequency and severity of attacks with a dosage range of 400-600 mg per day, in divided doses. The cause of migraine headache is believed to be related to abnormal serotonin function in blood vessels, and 5-hydroxytryptophan may therefore affect these levels. In one study, 40 people with recurrent migraines received either 5-HTP (200 mg per day) or methysergide (a drug used to prevent migraines) for 40 days. Both compounds reduced the frequency of migraines by about 50%. Larger amounts of 5-HTP (600 mg per day) were also found to be as effective as medications for reducing migraine headache attacks in adults in two double-blind trials. Migraine attacks were reduced in frequency, severity, and duration in 90% of those taking 400 mg per day of 5-HTP in a double-blind placebo-controlled trial, though not all migraine studies have reported success with 5-HTP.  Children, who suffered from migraines and had problems sleeping, responded well to a daily amount of 5-HTP equal to 20 mg for every 10 pounds of body weight in a controlled trial. However, other studies have failed to show success using 5-HTP for childhood migraines 9-13

Dosage Ranges

  1. Depression: 100 mg, three times daily2
  2. Insomnia: a single dose of 25-100 mg, one hour before bedtime.4
  3. Fibromyalgia: 100 mg, three times daily8
  4. Migraine headaches: 150 mg, three times per day9
  5. Anxiety: 100 mg, three times daily8

Adverse Side Effects

In clinical studies using the above dosages, some patients experience gastrointestinal upset (i.e. nausea) or, less often, headache, sleepiness, muscle pain, or anxiety.1-13

Drug-Nutrient Interactions and Contraindications

5-HTP should not be taken with other antidepressants, weight control drugs, other serotonin-modifying substances, or agents known to cause liver damage.  Individuals with liver disease or scleroderma should also avoid 5-HTP.2,6,14

Herb-Nutrient Interactions

St. John’s Wort
5-HTP may potentiate the effect of St. John’s Wort on brain neurotransmitters and vice versa.  These supplements should not be taken concurrently.17


Animal studies have shown that high doses of 5-HTP can cause muscle jerks in guinea pigs, and when injected has caused kidney damage in rats.  To date, these problems and serotonin syndrome have not been reported in humans, but the potential for serotonin syndrome to develop under certain circumstances (i.e. in combination with antidepressant drugs) is very plausible.6,15,16


 Van Hiele JJ. L-5 hydroxytryptophan in depression: the first substitution therapy in psychiatry?  Neuropsychobiology 1980;6:230-40.

  1. 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].
  2. Van Praaf HM. Management of depression with serotonin precursors.  Biol Psychiatry 1981;16:291-310.
  3. 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.
  4. Praag HM, Lemus C. Monoamine precursors in the treatment of psychiatric disorders.  In: Wurtman RJ, Wurtman JJ editors.  Nutrition and the Brain.  New York: Raven Press: 1986. Vol 7.  89-139
  5. Martin TG. Serotonin syndrome.  Ann Everg Med 1996;28:520-6.
  6. Soulairac A, Lambinet H. Etudes cliniques de liaction du precurseurs de la serotinine le L-5-hydroxy-tryptophane, sur les troubles du sommell. Schweiz Bundaschau Med (Praxis).  1998;77(34a):19-23.
  7. Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V. Double-blind study of 5-hydroxytyptophan versus placebo in the treatment of primary fibromyalgia syndrome.  J Int Med Res 1990;18:201-9.
  8. 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.
  9. Titus F, Davalos A, Alom J, Codina A. 5-hydroxytryptophan versus methysergide in the prophylaxis of migraine.  Eur Neurol 1986;25:327-9.
  10. Maissen CP, Ludin HP. Comparison of the effect of 5-hydroxytryptophan and propranoiol in the interval treatment of migraine.  Med Wochen 1991;121:1585-90.
  11. Matlew WT. 5-hydroxytryptophan in the prophylaxis of magraine.  Headache 1978;18:111-3.
  12. De Giorgis G, Miletto R, Iannuccelli M, Camuffo M, Scerni S. Headache in association with sleep disorders in children.  A Psychodiagnostic evalutation and controlled clinical study with L-5HTP versus placebo.  Drugs Exptl Clin Res 1987;13:425-33.
  13. Sternberg EM, Van Woert MH, Young SN, Magnussen I, Baker H, Gauthier S et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidoba.  New Engl J Med 1980;303:782-7.
  14. Hagan JJ, Hatcher JP, Slade PD. The role of 5-HTID and 5-HTIA receptors in mediating 5-hydroxytryptophan induced myoclonic jerks in guinea pigs.  Eur J Pharmacol 1995;294:743-51.
  15. 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.
  16. Kahn RS, Westenberg HG. L-5-hydroxytryptophan in the treatment of anxiety disorders.  J Affect Disord 1985;8(2):197-200.
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