Our library offers providers with in-depth reviews of ingredients commonly found in supplements. Each review contains information about the ingredient’s clinical applications, formulations, dosing and administration, adverse effects, and pharmacokinetics.
5-Hydroxytryptophan (5-HTP)
5-Hydroxytryptophan (5-HTP) is used as an amino acid precursor to boost serotonin (scientifically known as 5-hydroxytryptamine or 5-HT) levels. (18) Serotonin is a neurotransmitter most commonly associated with the regulation of psychiatric and neurological activity, though it is also hormonally involved in most physiological processes in the body. (5) Until 1995, 5-HTP was previously only available via prescription in the United States, however, it is now regulated as a dietary supplement and available over-the-counter. It is most often sourced from the seeds of the African botanical Griffonia simplicifolia, which are composed of up to 20% 5-HTP, but it can also be synthesized from the amino acid L-tryptophan. (18)(19)(26)
Most trials on the primary use of 5-HTP in depression were conducted during the 1970s with very few being published thereafter. The low rates of new research on 5-HTP may have been linked to an initial association between tryptophan and the fatal eosinophilia-myalgia syndrome in 1989. However, it was later discovered that the cause of the syndrome was actually induced by product defects rather than the physiological response to tryptophan or 5-HTP itself. (21) Regardless, clinical evidence supporting the use of 5-HTP continues to be quite dated. Most work was conducted in the late 1900s and early 2000s with little research published within the last 10 years. This highlights the need for more up to date research, particularly considering 5-HTP’s potential applications in psychiatric and mental health.
Not be confused with: 5-HT (serotonin)
Main uses
- Depression, anxiety, and behavioral disorders
- Neurodevelopmental disorders
- Neurological degeneration
- Pain
- Withdrawal symptoms
Formulations
| Formulation | Comparison | |
|---|---|---|
|
Immediate-release |
May lead to adverse effects (e.g., gastrointestinal distress, depressive moods, headaches, dizziness, or heart palpitations) related to rapid serotonin spikes and troughs due to quick absorption and elimination, respectively
Lower half-life with faster fluctuation in plasma levels may require more frequent administration, possibly leading to reduced relative compliance (19) |
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|
Slow-release
|
May possess fewer adverse events related to serotonin spikes and troughs due to slower absorption
May allow for higher dosing/efficacy and better compliance due to fewer required daily doses (19) |
|
Dosing & administration
| Anxiety | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
|
|
Dosing & administration
|
25-150 mg per day with decarboxylase inhibitors (carbidopa) for eight weeks to Px with anxiety or phobias |
|
|
Outcomes |
anxiety symptomatology on the 90-item symptoms checklist (SCL-90) and the State Scale of the Spielberger State-Trait Anxiety Inventory, but this was not as effective as clomipramine (22) |
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|
Class of evidence
|
C |
|
| Autism spectrum disorder | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
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|
Dosing & administration
|
Single administration of 4 mg/kg bodyweight to male adolescents
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Outcomes |
||
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Class of evidence
|
C |
|
| Degenerative ataxias | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
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|
Dosing & administration
|
10 mg/kg bodyweight per day for 4-12 months to Px with inherited or acquired cerebellar ataxias
|
|
|
Outcomes |
Improves ataxia scores and kinetic/static parameters for standing, feet spread, speed of walking, speaking, & writing with improvements continuing from the 4th to 12th month (38) |
|
|
Class of evidence
|
C |
|
|
Dosing & administration
|
200 mg per day for one month, followed by 600 mg to Px 50 kg for five months in Px with Freiderich’s ataxia |
|
|
Outcomes |
Improves kinetic score (coordination) (39) |
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|
Class of evidence
|
C |
|
| Depression | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
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|
Dosing & administration
|
100-400 mg per day with dihydroergocristine, tricyclic antidepressants (clomipramine), monoamine oxidase inhibitors (nialamide), or decarboxylase inhibitors for up to eight weeks
|
|
|
Outcomes |
Improves depressive scores & neuropsychic test performance in combination with dihydroergocristine compared to placebo, HAM-D scores combined with decarboxylase inhibitors compared with 5-HTP alone, HAM-D scores compared to clomipramine alone, and time to recovery compared with nialamide alone (1)(2)(28)(29)(34) |
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|
Class of evidence
|
B |
|
|
Dosing & administration
|
150-400 mg per day for eight weeks (specifically, doses titrated from 50 mg three times per day for two weeks, followed by 100 mg three times per day for two weeks, followed by 133 mg three times per day for four weeks) to Px with first depressive episode |
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|
Outcomes |
Hamilton rating scale for depression (HAM-D) remission rate achieved in ~73% of Px (~22/30) Improvements were equivalent to Px using fluoxetine (20) |
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|
Class of evidence
|
C |
|
|
Dosing & administration
|
200 mg titrated to 3000 mg per day for three weeks to Px with endogenous depression |
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|
Outcomes |
Hamilton rating scale for depression (HAM-D) remission rate achieved in 60% of Px (3/5) (41) |
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|
Class of evidence
|
C |
|
| Fibromyalgia | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
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|
Dosing & administration
|
100 mg three times per day for one month to adults |
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|
Outcomes |
Improves number of tender points and intensity of pain within the first 15 days, as well as morning stiffness, sleep patterns, anxiety, & fatigue in 30 days (11) |
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|
Class of evidence
|
B |
|
| Intestinal permeability | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
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|
Dosing & administration
|
100 mg (single administration) to healthy subjects
|
|
|
Outcomes |
May reinforce the intestinal barrier as measured by reductions in lactulose/L-rhamnose ratios, & redistributions of zonula occludens-1 |
|
|
Class of evidence
|
C |
|
| Migraine/chronic headaches | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
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|
Dosing & administration
|
200-300 mg per day for eight weeks to Px with chronic primary headaches
|
|
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Outcomes |
||
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Class of evidence
|
B |
|
|
Dosing & administration
|
100 mg (to 6 year olds) per day for three years to children at risk for primary headaches (based on familial/genetic factors) |
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|
Outcomes |
occurrence of primary headaches (30) |
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|
Class of evidence
|
B |
|
|
Dosing & administration
|
600 mg per day in divided doses for six months to Px with migraines
|
|
|
Outcomes |
severity and duration of attacks Considered equally effective to methysergide with fewer adverse effects (e.g., limited to mild and transient nausea) (36) |
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|
Class of evidence
|
C |
|
|
Dosing & administration
|
5 mg/kg body weight per day for three months to children and adolescents with migraine without aura or episodic tension-type headaches |
|
|
Outcomes |
frequency and severity of attacks compared to baseline plasma/mononuclear cell beta-endorphin levels (trend), which were initially lower compared with healthy controls (4) |
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|
Class of evidence
|
C |
|
| Opioid withdrawal | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
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|
Dosing & administration
|
200 mg per day (with 50 mg/kg tyrosine, 210 mg phosphatidylcholine, 50 mg/kg L-glutamine, & 1,200 mg lecithin) for one week to detoxified heroin addicts |
|
|
Outcomes |
Improves insomnia and withdrawal scores, specifically with reductions in tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and total mood disturbance, & increases in vigor-activity symptoms (13) |
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|
Class of evidence
|
C |
|
| Panic disorder | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
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|
Dosing & administration
|
200 mg (single administration 90 minutes prior to a cholecystokinin-4 or carbon dioxide stimulated panic attack) to Px with panic disorder or healthy subjects |
|
|
Outcomes |
||
|
Class of evidence
|
C |
|
| Pediatric behavioral disorders | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
|
|
Dosing & administration
|
200 mg in two divided doses (or half doses if causing agitation), with 50 mg L-theanine for 6-8 weeks to behaviorally at-risk children (adopted from traumatic backgrounds), or with at least one clinical diagnosis of ADHD, mood disorder, attachment disorder, or pervasive developmental disorder |
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|
Outcomes |
serotonin & gamma-aminobutyric acid levels parent reports of behavior issues in children (16) |
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Class of evidence
|
C |
|
| Sleep quality | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
|
|
Dosing & administration
|
200-600 mg per night for one week to healthy subjects |
|
|
Outcomes |
REM sleep and activity with no difference between doses (42) |
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|
Class of evidence
|
C |
|
| Sleep disorders | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
|
|
Dosing & administration
|
2 mg/kg bodyweight per day (administered at bedtime) for three weeks to children with night terrors |
|
|
Outcomes |
sleep terror episodes by more than 50% in ~94% (29/31) of children by one-month follow up compared with no therapy At the end of six-month follow up, 84% (26/31) of children were night terror-free (7) |
|
|
Class of evidence
|
C |
|
|
Dosing & administration
|
600 mg per day for four weeks to Px with narcoleptic cataplexy
|
|
|
Outcomes |
duration of nighttime sleep; duration of daytime sleep (trend) Note: no changes in the number of narcoleptic or cataplexic attacks were noted (3) |
|
|
Class of evidence
|
C |
|
| Weight regulation | ||
|---|---|---|
|
General outcomes from A-level evidence |
No data currently available. |
|
|
Dosing & administration
|
~8 mg (within ~31-40 mg of Griffonia simplicifolia oral spray) five times per day for 4-8 weeks to overweight women |
|
|
Outcomes |
sensation of appetite (Haber score), BMI, suprailiac skinfold thickness, arm circumference, arm muscle/fat areas and circumference, & hip circumference |
|
|
Class of evidence
|
B |
|
|
Dosing & administration
|
750-900 mg (in divided doses) per day for 2-6 weeks to obese or overweight Px with or without type II diabetes |
|
|
Outcomes |
||
|
Class of evidence
|
C |
|
|
Dosing & administration
|
8 mg/kg bodyweight (in three divided doses) per day for five weeks to obese women |
|
|
Outcomes |
caloric intake particularly from carbohydrates & bodyweight Note: increases in anorexic behaviors such as smell alteration, nausea and vomiting more frequently reported with 5-HTP than placebo (12) |
|
|
Class of evidence
|
C |
|
Adverse effects
Overall, 5-HTP monotherapy has a good safety profile and low likelihood to cause severe side effects. However, gastrointestinal distress or other mild events such as depressive moods, headaches, dizziness, or heart palpitations may occur. This may be attributed to the intolerance to rapid rises in serotonin levels, particularly if being used as an adjunct to other therapies such as selective serotonin reuptake inhibitors (SSRI). (19)
Long-term or high doses of 5-HTP may also deplete catecholamines, including dopamine, epinephrine, and norepinephrine. Some research suggests that long-term administration of 5-HTP should involve concomitant use of other serotonin or dopamine amino acid-precursors, such as L-tyrosine or L-dopa, to prevent amino acid or neurotransmitter depletion via competing for rate-limiting enzymes that produce catecholamines. (18)(21)
Practitioners should be aware that preclinical studies using extreme doses in combination with SSRIs have induced serotonin syndrome in rats, however, this has yet to be substantiated in humans. (19) 5-HTP may also induce anorexic effects, such as alteration of smell, nausea, vomiting, or meat aversion. (9)(12)
Pharmacokinetics
Absorption
Distribution
- Passes the blood-brain barrier, unlike serotonin (18)(19)
- Less freely, tryptophan (5-HTP precursor) can also cross the blood-brain barrier, but this depends on L-type amino acid transporters which are competed for by other amino acids (e.g., tyrosine, valine, phenylalanine, leucine, or isoleucine) (23)
- Increases intestinal mucosa 5-HTP and serotonin’s primary metabolite, 5-hydroxyindoleacetic acid (5-HIAA), but not serotonin itself (25)
Metabolism
- Decarboxylated to serotonin by the L-aromatic amino acid decarboxylase (AAAD) enzyme (18)(19)
- Conversion occurs without feedback inhibition, providing the possibility of uninhibited rises in serotonin as solely limited by AAAD (21)
- Serotonin may be in turn metabolized by monoamine oxidases to 5-HIAA (18)