5-hydroxytryptophan, or 5-HTP for short, is the intermediate metabolite of the essential amino acid tryptophan in the process of serotonin biosynthesis .
That is to say, it is an immediate precursor to serotonin [1,2].
Its use dates back to the first half of the 20th century, and has applications as a support for serotonin depletion and is considered an interesting alternative to selective serotonin reuptake inhibitors (SSRIs) .
The main natural source of 5-HTP is the seeds of the African plant Griffonia simplicifolia, but the seasonal and regional variations of the plant limit their output of 5-HTP, hence biotechnological methods are used to synthesize 5-HTP in an economically and environmentally efficient manner.
Several clinical trials are underway on 5-HTP for the treatment of depression, anxiety, panic attacks, and sleep disorders, with promising but early evidence for its use in other conditions such as obesity and diabetes . For example, 5-HTP can improve blood sugar control  and aid weight loss in people who are overweight/obese  by increasing satiety (fullness) as one potential mechanism. 5-HTP can also decrease carbohydrate intake which has implications for people with diabetes .
There may also be applications for its use in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease . Early research has shown that 5-HTP can improve levodopa-induced dyskinesias (uncontrolled, involuntary movements) in Parkinson’s disease patients .
In today’s article, we will examine what 5-HTP is, how it works, the rationale for supplementation, as well as the risks and contraindications associated with it.
5-HTP Biosynthesis and Metabolism
5-HTP is both a drug and a natural component of some dietary supplements. It is produced from tryptophan (an essential amino acid that we must obtain from food) by an enzyme called tryptophan hydroxylase . Tryptophan hydroxylase exists in two isoforms: TPH1 and TPH2.
5-HTP metabolism yields the well-known monoamine neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) that plays roles in emotional regulation, cognition, reward, learning, memory, and other physiological processes [8-10].
Serotonin is further transformed into melatonin (N-acetyl-5-methoxytryptamine), a hormone secreted by the pineal gland that is involved in numerous aspects of the sleep/wake cycle [3,11,12]. You can read more on biological clocks and cycles here.
In terms of absorption, 5-HTP reaches peak concentration rapidly (within 90 minutes) and is also quickly eliminated, with a half-life of 90-120 minutes . Furthermore, 5-HTP is known to cross the blood-brain barrier, whereas serotonin does not .
Overall, the metabolism of tryptophan to 5-HTP by TPH1/2 is an essential step in the biosynthesis of two physiologically important molecules, serotonin and melatonin.
Benefits and Potential Uses of 5-HTP
Dysfunction in the serotonergic system, including reduced central serotonin levels, are associated with depression. As a precursor to serotonin, 5-HTP has been used as a non-pharmacological treatment for depression [15,16], with meta-analysis of the evidence showing a large effect . There are, however, weaknesses in the available studies, as many do not include a placebo group, and this is an area that should be addressed.
Supplementation with 5-HTP
In the absence of supplementation with 5-HTP, the amount of 5-HTP available for serotonin synthesis largely depends on the amount of tryptophan available as well as enzymes such as tryptophan hydroxylase .
In human supplementation research, participants considered immoral behavior without negative consequences as more reprehensible after consuming 5-HTP (200 mg) .
A study of older adults in Singapore observed that daily supplementation with 100 mg of 5-HTP improved sleep quality at 4 and 8 weeks, however these effects did not last beyond this phase (up to 12 weeks) . This potentially suggests that the body acclimatizes to prolonged 5-HTP supplementation, at least in the population in the study.
Beyond these effects on sleep and moral evaluation, there is some promising research suggesting that 5-HTP (750 mg/day) can help overweight non-insulin dependent diabetic patients reduce their daily energy intake and thus their body weight . This is notable given that the brain levels of tryptophan are substantially reduced in diabetic patients, whereas tryptophan metabolites are higher [4,20].
What are the Risks and Contraindications?
Supplementation with 5-HTP may cause unpleasant dose-dependent gastrointestinal problems , as well as vomiting and nausea when used at doses in excess of 100 mg .
An excess of 5-HTP may be responsible for serotonin syndrome, a potentially life-threatening drug-induced condition of too much serotonin in the synapses of the brain [23,24]. Although cases involving hospitalization and death are rare, and medical intervention is not needed in most instances, it is nevertheless a condition to be mindful of. This is particularly the case when high doses of 5-HTP are used in combination with antidepressants in the SSRI class, which has been shown to cause acute serotonin syndrome in rats [25,26].
In this article, we have discussed 5-HTP and its biosynthesis, metabolism, effects, and the rationale for supplementation. We also looked at the risks and benefits, as well as the contraindications and side effects that might present themselves.
There is evidence that 5-HTP can enhance moral evaluation, sleep, cognition, and help treat major health challenges like obesity and diabetes. However, these findings need to be substantiated by further research.
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