Scientific Name(s): Griffonia simplicifolia (Vahl ex DC.) Baill. Family: Caesalpiniaceae/Leguminosae

Common Name(s): 5-HTP , 5-hydroxytryptophan . Extracts of Griffonia simplicifolia are found in commercial preparations such as Relarian and MiniChill .

Uses

Clinical trials of 5-HTP conducted in various conditions have resulted in limited evidence suggesting a place in therapy for anxiety, depression, and neurological conditions in which a serotonin deficiency is a contributory factor. 5-HTP may also be an effective appetite suppressant, but further clinical trials are needed.

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Dosing

Recent clinical trials do not provide adequate dosing guidelines. Studies in depression have used 5-HTP 200 to 300 mg/day given in 3 to 4 divided doses to prevent possible nausea.

Contraindications

The potential for serotonin syndrome exists with concomitant use of selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs).

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

The potential for serotonin syndrome exists with concomitant use of SSRIs or MAOIs. 5-HTP augments the effect of citalopram and clomipramine, while carbidopa increases the bioavailability of 5-HTP.

Adverse Reactions

Nausea and vomiting are the most common dose-related adverse events. Diarrhea, abdominal pain, mild headache, and sleepiness have also been reported.

Toxicology

There is little information on the toxicology of 5-HTP. A possible association with fatal eosinophilia-myalgia syndrome in the 1980s and 1990s has now been attributed to contaminated L-tryptophan.

Botany

Seeds from the woody climbing shrub G. simplicifolia are used as a source of 5-HTP. The plant can grow to 3 m and is found in tropical Africa, most prevalently in Ghana. It has brown-black branches with simple, large, alternate leaves. The flowers are tubular pale green/orange, and the fruit is an oblique cylindrical black pod, approximately 8 cm long and 4 cm wide, containing the seeds. 1

History

The whole plant is used in African traditional medicine. The pulped bark is used topically on syphilitic sores, and a paste made from the leaves is applied to burns. The leaf sap is used for inflamed eyes, while decoctions made from the stem and leaves are used as a purgative, to relieve constipation, and as a topical antiseptic.

Chewing the stems is said to provide an aphrodisiac effect, and the leaves are regarded as a good food source for animals. The plant is an industrial source of 5-HTP, with Ghana exporting raw materials mostly to Germany. 1

Chemistry

The leaves of the plant have a high protein content and contain phosphorus and calcium, as well as a volatile oil, coumarins, and 5-HTP and 5-hydroxytryptamine. The ripe seeds contain as much as 20% 5-HTP and lectins of interest in cancer and neurological research. High-performance liquid chromatography (HPLC) assay methods have been described for the quantification of 5-HTP. 1 , 2

Uses and Pharmacology

Tryptophan, an essential amino acid, is obtained from animal protein in a Western diet. It is enzymatically converted to 5-HTP by tryptophan hydroxylase, which is further converted to serotonin. Factors that may influence the rate-limiting hydroxylase step in 5-HTP production include stress, insulin resistance, vitamin B 6 deficiency, and insufficient magnesium. 3 , 4 Depleted states of serotonin have been implicated in neurological disorders such as autism, epilepsy, depression, and migraine, among other conditions. 4 , 5 , 6 , 7 , 8

5-HTP is used by some researchers as a challenge test to examine central serotonergic function, with cortisol and prolactin release used as a measure of response, as well as excretion of the metabolite 5-hydroxy-indoleacetic acid. 5 , 9 , 10

Anxiety/Sleep terrors
Animal data

Oral administration of an extract of G. simplicifolia seeds exerted an anxiolytic effect on rats subjected to dark-light and open field tests. 11

Clinical data

Studies in healthy volunteers found that oral administration of 5-HTP reduced the incidence of induced panic and associated symptoms when compared with placebo. 12 , 13 A gender difference in panic response was suggested in 1 small study. 13 A study in children with sleep terrors reported a reduction of more than 50% in incidence with 5-HTP 2 mg/kg/day given at bedtime for 20 days. The effect of 5-HTP persisted in the majority of participants at the 6-month end point. 14

Depression
Animal data

Studies in rodents have demonstrated the effect of 5-HTP on circulating serotonin levels and in sleep deprivation. Additionally, serotonin syndrome can be induced in rats given 5-HTP. 4

Clinical data

Approximately 30 clinical trials in depression have been conducted since the 1970s using 5-HTP. Following the occurrence of fatal eosinophilia associated with L-tryptophan and the advent of SSRIs, clinical studies were largely abandoned. 3 , 4 Of the published clinical studies, 11 were conducted in a double-blind manner. However, the trials used small numbers of participants, and the design of the trials, dosages, and duration were heterogeneous, making a meta-analysis impossible. 4 Larger, more robust clinical trials are warranted to determine a place for 5-HTP in the management of depression. 3 , 4 A more recent exploratory study in healthy volunteers suggests a role for 5-HTP in the short-term setting while waiting for the onset of action of an SSRI. 15

Other effects
Aggression

Studies in animals have found both inhibitory effects and heightened aggression with increased serotonin consequent to 5-HTP supplementation. Variables include the animal species used, length of treatment, and type of aggression. Clinical studies are lacking. 16

Appetite suppression

Studies in rats found decreased food intake and loss of weight with administration of G. simplicifolia extract. 17 , 18 A small (N = 20) clinical trial evaluated the effect of the extract on satiety among overweight women. Decreased appetite and a decrease in mean body mass index were demonstrated at 4 weeks. 19 , 20

Headache

Limited clinical studies were conducted in the 1980s. A more recent clinical trial found no effect of 5-HTP 300 mg/day on the number of tension-type (nonmigraine) headaches experienced during the 8-week study. However, in the 2-week period after treatment was stopped, a decrease in number of days with headache was observed. A difference over placebo was found for consumption of analgesics. 21

Menopause

A clinical trial evaluated the efficacy of 5-HTP 150 mg daily in the frequency of hot flashes, finding no difference over placebo. 22

Neurological diseases

Reviews of studies using 5-HTP in degenerative ataxia and pediatric neurotransmitter diseases suggest a potential role in reducing neurological symptoms; however, inconsistent findings have been reported. 7 , 8

Dosage

Studies in depression have used dosages varying from 20 to 3,250 mg daily; however, most commonly 200 to 300 mg/day has been used. 3 , 4 5-HTP has a short half-life, and 3 to 4 divided doses are recommended to reduce the likelihood of nausea. 4 , 9

Studies have been conducted in children (range, 3 to 17 years of age). 5 , 14 , 23 Because 100 mg given twice a day caused agitation in 20% of the participants (behaviorally at-risk children), the dosage was reduced to 100 mg/day. 23

In general, intravenous administration of 5-HTP at 20 mg gave an inadequate response, while at 40 mg caused severe nausea and vomiting, limiting its usefulness. 9

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. 3 5-HTP has been shown to increase luteinizing hormone secretion in women, possibly via an increase in gonadotropin-releasing hormone. 24

Interactions

The potential for serotonin syndrome exists with concomitant use of SSRIs or MAOIs. Reports exist of serotonin syndrome consequent to L-tryptophan and fluoxetine combinations, but no reports to date can be attributed to 5-HTP. 3 Studies have shown 5-HTP to augment the effect of citalopram and clomipramine. 15 Carbidopa increases the bioavailability of 5-HTP. 25

Drug/Lab Test Interactions

5-HTP has been shown to increase the urinary levels of 5-hydroxyindoleacetic acid, a marker for carcinoid tumor, which may lead to misinterpretation of laboratory tests. 26

Adverse Reactions

Nausea and vomiting are the most common dose-related adverse events. Diarrhea, abdominal pain, mild headache, and sleepiness have also been reported. 3 , 15

Laboratory studies in rats have demonstrated a suppressive effect on sexual behavior with short-term doses of G. simplicifolia extract in both males and females; however, no effect was observed with dosing of up to 9 days' duration and clinical importance of this is unclear. 17 , 18

Toxicology

Research reveals little information regarding the toxicology of 5-HTP. A possible association with fatal eosinophilia-myalgia syndrome in the 1980s and 1990s has now been attributed to contaminated L-tryptophan. 3 , 4 , 23 , 27 HPLC identification of the implicated contaminant tryptophan-4,5-dione (referred to in publications as “Peak X”) has also been disputed in a review of the safety of 5-HTP, but remains a requirement of the US Food and Drug Administration for all commercial 5-HTP products. 27 Rats fed 5-HTP for a year showed no toxicological effects, and no reports of human toxicity have been documented since the mid-1990s. 27

Bibliography

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25. Smarius LJ, Jacobs GE, Hoeberechts-Lefrandt DH, et al. Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa. J Psychopharmacol . 2008;22(4):426-433.
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