5-Hydroxytryptophan

5-Hydroxytryptophan (5-HTP), also known as oxitriptan (INN), is a naturally occurring amino acid and chemical precursor as well as metabolic intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin from tryptophan.

5-HTP is sold over-the-counter in the United Kingdom, United States and Canada as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid, and is also marketed in many European countries for the indication of major depression under trade names like Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. Several double-blind placebo-controlled clinical trials have demonstrated the effectiveness of 5-HTP in the treatment of depression, though a lack of high quality studies has been noted.

Metabolism
5-Hydroxytryptophan is decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) by the enzyme aromatic-L-amino-acid decarboxylase with the help of vitamin B6. This reaction occurs both in nervous tissue and in the liver. 5-HTP crosses the blood-brain barrier, while 5-HT does not. Excess 5-HTP, especially when administered with Vitamin B6, is thought to be metabolized and excreted.

Pharmacology
The psychoactive action of 5-HTP is derived from its effect on the production of serotonin in central nervous system tissue. More specifically, 5-HTP increases the production of serotonin. Thus, it has been used to treat conditions such as depression, for which the lack of serotonin is thought to be a contributing factor.



Research shows that co-administration with carbidopa greatly increases plasma 5-HTP levels. However, several studies have reported that 5-HTP is effective even without a peripheral decarboxylase inhibitor (e.g. carbidopa). Other studies have indicated the risk of a scleroderma-like condition resulting from the combination of 5-HTP and carbidopa.

Dietary sources
Though 5-HTP is found in food only in insignificant quantities, it is a chemical involved intermediately in the metabolism of tryptophan, an amino acid found in turkey, milk, potatoes, pumpkin, and various greens. See also the section Dietary sources of the article on L-tryptophan.

Therapeutic use
5-HTP is sold over-the-counter in the United States, the United Kingdom, and Canada as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid. 5-HTP in supplement form is typically sold in 50 mg or 100 mg gelatin or vegetarian capsules. It is usually sourced from the seeds of Griffonia simplicifolia.

5-HTP has been studied and shown to be of benefit in the following conditions: primary fibromyalgia syndrome, Friedreich's ataxia, depression, anxiety, binge eating associated with obesity, and insomnia. There is no statistically significant difference between 5-HTP and placebo in treating chronic headaches (primary or otherwise).

A 2001 meta-analysis found that of 108 studies on 5-HTP published between 1966 and 2000, only two met the authors' quality standards for inclusion. The two studies that were deemed of sufficient quality did not deal with 5-HTP exclusively, instead combining results for 5-HTP and tryptophan, so the results may not be completely applicable for 5-HTP alone. While the combined analysis of the two 5-HTP and tryptophan studies showed significant effectiveness over placebo in treating depression, the authors state that overall "the evidence was of insufficient quality to be conclusive". They also state that "because alternative antidepressants exist which have been proven to be effective and safe, the clinical usefulness of 5-HTP and tryptophan is limited at present".

Possible risks or side effects
Because 5-HTP has not been thoroughly studied in a clinical setting, possible side effects and interactions with other drugs are not well known.

Administered serotonin has been shown to increase the risk of heart valve disease in animals. 5-HTP has not been subjected to this test. Oral 5-HTP results in an increase in urinary 5-HIAA, a serotonin metabolite, indicating that 5-HTP is peripherally metabolized to serotonin, which is then metabolized. This might cause a false positive test in tests looking for carcinoid syndrome.

5-HTP can cause hypertension by increasing plasma renin activity, when not co-administered with a peripheral aromatic L-amino acid decarboxylase inhibitor, such as carbidopa or benserazide.

Direct and indirect evidence for possible yet unproven risks and side effects associated with 5-HTP when overdosed:

It has been suggested that 5-HTP may cause eosinophilia-myalgia syndrome (EMS), a serious condition which results in extreme muscle tenderness, myalgia, and blood abnormalities. However, there is evidence to show that EMS is caused by a contaminant.
 * Heart valve damage or disease (cardiac fibrosis).
 * When combined with MAOIs or SSRIs, 5-HTP can cause acute serotonin syndrome.
 * When combined with carbidopa (as a treatment for symptoms of Parkinson's disease), 5-HTP causes nausea and vomiting; however this can be alleviated via administration of granisetron. As mentioned above under pharmacology, cases of scleroderma-like illness have been reported in patients using carbidopa and 5-HTP.