Professional Review:

5-Hydroxytryptophan (5-HTP)


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Date of Review: July 2007

Common Name: 5-HTP, (L)-5-hydroxytryptophan

Scientific Name: 2-amino-3-(5-hydroxy)indolylpropionic acid (C11H12N2O3)

Other Names:
Griffonia simplicifolia, 5-hydroxy-L-tryptophan, oxitriptan
 
 
** NOTE: Not to be confused with 5-hydroxytryptamine (5-HT, serotonin) or L-tryptophan.



Chemical Constituents:
 
5-HTP is an aromatic amino acid naturally produced by the body from the essential amino acid tryptophan (1), and is commercially extracted from the seeds of the African plant Griffonia simplicifolia (2). It is the immediate precursor of the neurotransmitter serotonin.
 
5-HTP is known to exist as two isomers, the D (dextratory) and L (levoratory) forms. Only the L-isomer is biologically active, while the D-isomer is mostly excreted unchanged in the urine (3, 4).
 



Uses:

1.Likely Effective:
No evidence available
 



2.Possibly Effective:
Depression, Fibromyalgia, Obesity, Panic and Anxiety Disorders
 
Depression
 
 
Numerous trials have been conducted evaluating the efficacy of 5-HTP as a pharmacological treatment for depression. Reviews have been published in attempts to summarize and make conclusions based on the available evidence, however most agree that more conclusive research is called for due to the heterogeneity of the results and variety of outcome measures assessed (1, 5-7). In the most recent systematic review, Turner et al. identified a total of 27 studies (total n=990), consisting of 11 double-blind, placebo-controlled studies, five active comparator studies, and 11 open-label trials (5). Overall the studies seem to suggest a positive effect of 5-HTP in treating depression, but additional trials of larger sample sizes and higher quality are needed to confirm this. No placebo-controlled, monotherapy trials on 5-HTP on depression have been conducted since the early 1980


3.Further Research Required:
Alcoholism (Abstinence from), Autism, Bulimia Nervosa, Cerebellar Ataxia, Headache (Adults), Headache (Children), Miscellaneous Uses, Myoclonic Disorders, Schizophrenia, Sleep Disorders
 
Alcoholism (Abstinence from)
 
One randomized, double-blind, placebo-controlled trial reported that


4.Possibly Ineffective:
No evidence available
 



5.Likely Ineffective:
Down
 
At least six studies have been published on the use of 5-HTP in children with Down



Adverse Effects:

1.Clinical Trial Evidence:
Behavioral (Children), Drowsiness, Gastrointestinal Discomfort, Nausea and Vomiting, Psychological Disturbances, Taste Alteration
 
Behavioral (Children)
 
Behavioral problems, including aggression, emotional lability, and irritability, were experienced by all of five children treated with 5-HTP (2 to 15mg/kg/day) for symptoms of opsoclonus-myoclonus (162). All children were known to have histories of behavioral problems prior to the study, but during 5-HTP treatment these were reported to be worsened in three children, and


2.Cases Reported In Humans:
Eosinophilia-Myalgia Syndrome, Scleroderma, Seizures
 
Eosinophilia-Myalgia Syndrome (EMS) and Related Disorders
 
From 1989 to 1990, ingestion of L-tryptophan (natural precursor to 5-HTP) was associated with an epidemic of EMS (199). These were eventually discovered to originate from a single source, caused by a new fermentation process coupled with inadequate purification processes (200, 201). Symptoms of EMS, aside from eosinphilia and severe myalgia, also include weakness, abdominal pain, skin rash, increased serum aldolase, leukocytosis, and death in serious cases. Due to the structural similarity of 5-HTP to tryptophan, there had been previous concern that ingestion of 5-HTP would lead to the same risk, despite the fact that commercial production of 5-HTP does not require fermentation as L-tryptophan does. As of August 1998, ten cases of EMS-like illnesses had been linked to 5-HTP use, none of which resulted in death, and none in which a direct causation could be proven (5, 199).
 
In what appeared to be the only report of EMS to be investigated, a 28-year-old mother and her two children (33 and 13 months old) developed EMS-like illnesses that were thought to be related to 5-HTP use (202). The boys had been treated with 5-HTP (5 to 7mg/kg daily), tetrahydrobiopterin (50mg every other day), and L-dopa/carbidopa (50mg/5mg daily) for an enzyme deficiency for approximately 12 months when both developed mild leukocytosis and eosinophilia. Their mother, who regularly prepared and came into contact with her children


3.Theoretical Evidence:
Serotonin Syndrome
 
High levels of serotonin in the body can lead to a condition known as serotonin syndrome, characterized by agitation, confusion, delirium, tachycardia, diaphoresis, and fluctuations in blood pressure (1, 208). It can theoretically be caused by any drug that affects the serotonergic pathway, such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) (5). In animal studies, serotonin syndrome has been experimentally induced in rodents with high dosages of 100 to 200mg/kg (209, 210). In humans, cases of serotonin syndrome have not been reported from 5-HTP use alone, or in combination with any other medications (5, 200). No cases were reported when 5-HTP was taken in conjunction with MAOIs (63), tricyclic antidepressants (211), SSRIs (35, 211, 212), or tryptophan (21).



4.Anecdotal/Historical Evidence:
Nightmares
 
5-HTP has been reported anecdotally to cause nightmares or very vivid dreams when used at high concentrations (1). However, it should be noted that 5-HTP has been found to be effective in decreasing occurrence of sleep terrors in children (185).




Drug Interactions:

1.Clinical Trial Evidence:
Citalopram
 
Following acute dosing of 5-HTP (200mg/day) in conjunction with citalopram, a selective serotonin reuptake inhibitor (20mg/day) in 12 healthy Asian males, six cases of nausea and seven cases of vomiting were reported in individuals who did not experience the same symptoms on citalopram or 5-HTP alone (212). However, it should be noted that nausea and vomiting are side effects commonly associated with 5-HTP use (1, 2).



2.Cases Reported in Humans:
Bromocriptine, Clobazam, Flunitrazepam
 
Cases of scleroderma-like conditions have been reported following therapy with 5-HTP and other medications (205, 206). One case involved a 72-year-old Parkinson


3.Theoretical Evidence:
Antidepressants, Serotonin-Receptor Agonists, Sleeping Aids
 
Antidepressants (SSRIs, MAOIs)
 
Co-administration of 5-HTP with serotonergic antidepressants, such as SSRIs (selective serotonin reuptake inhibitors) and MAOIs (monoamine oxidase inhibitors) can cause high levels of serotonin to accumulate in the body. This can theoretically lead to a condition known as serotonin syndrome, which is characterized by agitation, confusion, delirium, tachycardia, diaphoresis, and fluctuations in blood pressure (1, 208). In humans, cases of serotonin syndrome have not been reported from 5-HTP use alone, or in combination with any other medications (5, 200). No cases were reported when 5-HTP was taken in conjunction with MAOIs (63), tricyclic antidepressants (211), SSRIs (35, 211, 212), or tryptophan (21).
 
Serotonin-Receptor Agonists
 
Since 5-HTP is the immediate precursor of serotonin, and is thought to exert its effects by increasing serotonin levels in the body, it can theoretically have additive effects with serotonin-receptor agonists such as drugs used in the treatment of migraines (e.g. sumatriptan, zolmitriptan, rizatriptan) (2). No instances of drug interactions between 5-HTP and serotonin-receptor agonists have been reported.
 
Sleeping Aids
 
Drowsiness has been reported in clinical trials following ingestion of 5-HTP (4, 125, 134, 137, 152), and can theoretically cause additive effects with sleeping aids. No instances of drug interactions between 5-HTP and sleeping aids have been reported. 



4.Anecdotal/Historical Evidence:
No evidence available
 




Dose, Dosage Forms/Formulations

Adult Dose
 
Oral dosage of 5-HTP in clinical trials have greatly varied, and in many cases were individually titrated and adjusted according to the therapeutic versus side effects observed. Clinical trial doses of 5-HTP have ranged from 20 to 3250mg/day, with the majority being 200 to 300mg/day (5). Older trials have considered a

Children's Dose

 
Oral dosage of 5-HTP in clinical trials have greatly varied, and in many cases were individually titrated and adjusted according to the therapeutic versus side effects observed. 5-HTP has been used in children for the treatment of schizophrenia, opsoclonus-myoclonus, sleep terrors, and Down

Product Quality Issues

Cases of eosinophilia-myalgia syndrome (EMS) have been associated with a batch of L-tryptophan, eventually discovered to be caused by contamination from a new strain of bacteria during fermentation, combined with faulty purification processes (200, 201). Due to the structural similarity of 5-HTP to tryptophan, there had been previous concern that ingestion of 5-HTP would lead to the same risk, despite the fact that commercial production of 5-HTP does not require fermentation as L-tryptophan does. Case reports of EMS-like illnesses associated with 5-HTP use have been identified, but never verified (199, 202, 203). In one case, analysis of the implicated source of 5-HTP revealed an impurity on high-performance liquid chromatography, identified as

Regulatory Status

Canada:
All natural health products in Canada are now regulated by the Natural Health Products Directorate of Health Canada (http://www.hc-sc.gc.ca/dhp-mps/prodnatur/index-eng.php).

Authors: Carmen Li, HonBSc

Reviewers: Heather Boon, BScPhm, PhD, Christy Cuku, BScPharm, and Teresa Tsui, BScHon, ND