- 5-HTP; L-5-Hydroxytryptophan
- L-5-HTP; Oxitriptan (INN)
For Patients & Caregivers
How It Works
5-HTP may be useful for some conditions in which serotonin levels may be low, such as depression, but additional studies are needed.
5-HTP, or 5-Hydroxytryptophan, is generated during the production of melatonin and serotonin from the amino acid tryptophan. Lower levels of serotonin, a neurotransmitter that relays signals to nerve cells, have been associated with disorders such as depression, anxiety, fibromyalgia, insomnia, chronic headaches, and weight gain.
Some studies suggest 5-HTP may be useful for these conditions because it can boost serotonin levels. More studies are needed however, because results were limited or trials were too small to draw definite conclusions. In addition, 5-HTP may interact with medications or herbs that also affect serotonin levels, or cause certain lab test results to be inaccurate. Therefore, patients should consult with their physician before taking this supplement.
To treat anxiety
There is limited evidence to suggest 5-HTP may be helpful for anxiety, but it may also interact with other drugs. Additional studies are needed to confirm safety and effectiveness.
To treat depression
There is limited evidence to suggest 5-HTP may be helpful for some types of depression, but it may also interact with other drugs. Additional studies are needed to confirm safety and effectiveness.
To treat fibromyalgia
Initial findings suggest 5-HTP may benefit patients with fibromyalgia. Additonal studies are needed.
To treat hot flashes
Initial studies suggest 5-HTP is not helpful for hot flashes.
To treat insomnia
Studies evaluating 5-HTP for insomnia are lacking.
To treat migraines
A few studies did not find 5-HTP helpful for migraines or chronic tension headaches.
To treat obesity
Initial findings suggest 5-HTP may help decrease appetite and food intake, and increase weight loss and feelings of fullness. Additonal studies are needed.
Patients taking selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, or other drugs that affect serotonin levels should avoid taking 5-HTP without the supervision of a physician due to the theoretical potential for serotonin syndrome, a serious condition, or other side effects.
Do Not Take If
You are having a 5-HIAA urine test to diagnose/monitor carcinoid tumors: Taking 5-HTP supplements could cause test results to be inaccurate.
You are taking antidepressants or anxiolytics (including tricyclic antidepressants, MAOIs, and SSRIs): Because many of these drugs also affect serotonin levels, there is an increased risk for side effects or toxicities if you also take 5-HTP. Discuss any use of this supplement with your treating physician.
You are taking monamine oxdiase inhibitors: There is a case report of mania following use of an MAOI with 5-HTP in a patient without personal or family history of bipolar disorder.
You are taking linezolid (Zyvox, an antibiotic MAOI): There is a case report of an interaction with 5-HTP causing serotonin syndrome, a serious condition.
You are taking carbidopa (Lodosyn, a dopamine promoter): There is a case report of pain and swelling of the hands and feet, as well as skin rash and weight loss in a patient treated with carbidopa and 5-HTP.
You are taking lorcaserin (Belviq, a weight-loss drug): The package insert warns of specific serious interactions when used with tryptophan because lorcaserin also affects serotonin levels. By extension, 5-HTP may also increase the risk of these side effects and should therefore be avoided when taking this drug.
You are taking St John’s wort: Because SJW may also affect serotonin levels, the use of multiple herbs that do this should be avoided to reduce risks for excess serotonin in the body, a serious condition.
You are taking SAM-e: Because SAME-e may also affect serotonin levels, the use of multiple herbs that do this should be avoided to reduce risks for excess serotonin in the body, a serious condition.
Common: GI disturbances such as nausea, vomiting, or diarrhea
Less common: Headache, insomnia, rapid or irregular heartbeat
Mania: Following combined use of an MAOI and 5-HTP in a patient without history of bipolar disorder.
Serotonin syndrome (Excess serotonin in the body): Caused by an interaction between linezolid and 5-HTP. Symptoms can include rapid or irregular heartbeat, poor coordination, agitation, confusion, headache, shivering, fever, and seizures.
Scleroderma-like illness (Hardening/tightening of skin/tissues): Pain, swelling of hands and feet, skin rash, and weight loss in a 70-year-old patient receiving combination therapy with carbidopa and 5-HTP.
Eosinophiliamyalgia syndrome (EMS; a flu-like neurological condition): Linked to a 5-HTP product that contained impurities which was used by a family. Symptoms resolved after the product was replaced with one that did not have these impurities.
For Healthcare Professionals
5-HTP or L-5-Hydroxytryptophan is a key intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin. It is formed by hydroxylation of the amino acid L-tryptophan. 5-HTP is marketed as a dietary supplement for sleep, to improve mood and well-being, and to suppress appetite. Seeds from the African shrub Griffonia simplicifolia are a major source for these supplements due to their high 5-HTP content (1) (2).
In animal models, anxiolytic and antidyskinetic effects have been demonstrated (3) (4). 5-HTP has also been shown to restore serotonin levels or, at excessive levels, to induce serotonin syndrome (5) (6).
In humans, much of the research on 5-HTP involves small trials with mixed results. A few studies suggest 5-HTP may reduce anxiety (7) (8). Other trials found benefits for depression (2) (9) (10), but not treatment-resistant depression (11) (12). Yet, results from more recent studies suggest antidepressant effects comparable with fluoxetine (13), and potential benefit as part of augmentation therapy for drug-resistant depression (14).
5-HTP has also been evaluated for obesity. Preliminary findings suggest it may help decrease food intake and increase weight loss and early satiety (15) (16). More recently, a sublingual 5-HTP spray increased appetite control in overweight women (17) (18).
Other preliminary studies suggest benefit for patients with fibromyalgia (19), but not for postmenopausal hot flashes (20) or tardive dyskinesia (21). 5-HTP does not appear to reduce chronic tension headaches, although a decrease in analgesic use was noted (22). It was also ineffective as prophylaxis for childhood migraine (23), but may improve pediatric sleep terrors (24).
Larger well-designed studies are needed to determine the populations and conditions for which 5-HTP supplementation may be useful, and to determine safety particularly in conjunction with other serotonergic medications including antidepressants.
Mechanism of Action
5-HTP crosses the blood-brain barrier and increases serotonin synthesis (25). The advantage of 5-HTP over L-tryptophan is its ability to bypass the rate-limiting step that tryptophan must undergo via the enzyme tryptophan hydroxylase to convert to 5-HTP. In addition, this enzyme can be inhibited by various factors including B6 or magnesium deficiencies, stress, or insulin resistance, and make tryptophan unavailable for serotonin production (2).
Relaxation and anxiolytic properties are attributed to the ability of 5-HTP to elevate CNS serotonin levels (2). 5-HTP was shown to augment neuroendocrine response to an SSRI via increased presynaptic 5HT availability, thus enhancing 5HT release into the synapse (26). It was also proposed to potentially reduce hot flashes in menopausal women with breast cancer or with risk of breast cancer by enhancing serotonin levels (27) , but a clinical study in postmenopausal women found it ineffective (20) .
5-HTP can also increase levels of melatonin, dopamine, and norepinephrine (28) (29), compounds involved in mood and sleep regulation and whose mechanistic pathways may also be stimulated (2). As abnormalities in serotonin and epinephrine pathways have been suspected in fibromyalgia and other chronic diseases (5) (30), this may help to explain preliminary benefits seen with 5-HTP supplementation in other disease states.
Additional studies are needed to further identify the mechanisms and conditions under which 5-HTP may exert positive effects or pose concerns when used, especially with other medications due to its modulatory effects on neurotransmitters.
Animal studies have shown that 5-HTP can be toxic at excessive levels (5), and a few cases of toxicity in humans have been reported (see Adverse Reaction Case Reports). The clinical relevance, however, has yet to be determined.
Patients taking selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, or other serotonergic drugs should avoid taking 5-HTP without the supervision of the treating physician due to the theoretical potential for serotonin syndrome or other side effects.
Mania: Following combined use of an MAOI and 5-HTP in a patient without personal or family history of bipolar disorder (34).
Serotonin syndrome: Caused by an interaction between linezolid and 5-HTP (35).
Scleroderma-like illness: Pain, swelling of hands and feet, skin rash, and weight loss in a 70-year-old patient receiving combination therapy with carbidopa and 5-HTP (36).
Eosinophiliamyalgia syndrome (EMS) and eosinophilia: Linked to a 5-HTP product that contained impurities which was used by a family (32). Symptoms resolved after the product was replaced with one that did not have these impurities.
- Antidepressants/anxiolytics (tricyclic antidepressants, MAOIs, and SSRIs): Because 5-HTP can also raise serotonin levels, there is the theoretical potential for increased risk of side effects or toxicities. Larger clinical trials are needed to understand the clinical relevance of these risks.
- Monamine oxdiase inhibitors: Case report of mania following use of an MAOI with 5-HTP in a patient without history of bipolar disorder (34).
- Linezolid (Zyvox, an antibiotic MAOI): Case report of interaction with 5-HTP causing serotonin syndrome (35).
- Carbidopa (Lodosyn, a dopamine promoter): Case of scleroderma-like illness with combination therapy of carbidopa and 5-HTP (36).
- Lorcaserin (Belviq, a weight-loss drug): Locaserin is a serotonergic drug. The package insert warns of specific serious interactions when used with tryptophan (39). By extension, 5-HTP may also increase the risk of these side effects and should therefore be avoided when taking this drug.