What is 5-Hydroxytryptophan (5-HTP)?

5-Hydroxytryptophan (5-HTP) is an endogenous amino acid, formed from tryptophan as an intermediate in the production of serotonin. Serotonin levels are important for the regulation of sleep, mood disorders, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation.(1) The amount of synaptic serotonin available largely depends on the availability of substrates essential for serotonin synthesis. 5-HTP acts to increase levels of serotonin within the central nervous system (CNS), but, unlike tryptophan, is not shunted down additional biochemical pathways.

Tryptophan can be metabolised to either serotonin or, in cases of vitamin B3 deficiency, to niacin via the kynurenine pathway. It also plays a role in protein formation, as well as kynurenic and quinolinic acids that can affect neurotransmitters in the brain. The conversion of tryptophan to 5-HTP is an irreversible step and, therefore, 5-HTP cannot be used as a precursor for niacin or other tryptophan metabolites. Thus, supplementation with 5-HTP can be of greater benefit than tryptophan to support serotonin levels.(2) Figure 1: Serotonin Pathway | HealthMasters

Serotonin Pathway

Tryptophan requires a carrier molecule to be transported through the blood brain barrier, and tryptophan itself is difficult to absorb from dietary sources. Conversely, approximately 70% of an oral dose of 5-HTP is absorbed from the blood stream and is easily transported across the blood brain barrier without the need for a carrier protein. Serotonin itself, however, when used by the nervous system, must be produced there, since it cannot cross the blood brain barrier.(2)

May Help to Support Serotonin Levels

One of the most common uses of 5-HTP relates to its effects on mood disorders,(3) thought to be linked with serotonergic mechanisms. It is suggested that the regulation of normal mood largely depends on normal serotonin stores, (4) which can be impacted through the provision of adequate precursor nutrients.

Research Review:

An analysis of 15 separate studies, encompassing a total of 511 patients with different types of mood disorders, showed that 285 (56%) of these patients demonstrated significant improvement of symptoms while taking 5-HTP. (5)

May Help to Support Sleep

Serotonin is involved in both sleep and wakefulness through its actions in different areas of the CNS and on different serotonin receptors. Serotonin has been shown to increase both REM (6) and NREM (7) sleep, stimulate wake promoting neurons, (8) and acts as a precursor to melatonin. In fact, the actions of both serotonin and melatonin help to maintain circadian rhythms and sleep maintenance. (10) Thus, supplementing with 5-HTP to support serotonin levels may be beneficial in supporting circadian rhythms and better quality sleep. (9)

May Help to Support Appetite Control

Up to 90% of the body’s serotonin is found in the gastrointestinal tract (GIT) and stored in enterochromaffin cells. (10) Secretion of serotonin in the GIT stimulates both mucosal secretory and peristaltic reflexes. (11) It has a role in intestinal motility, and is released into the blood postprandially and in response to changes in pressure across the gut wall. As such, supplementation with 5-HTP may be supportive in cases of reduced bowel motility. (12)

In the CNS, serotonin plays a role in satiation – believed to be through regulation of leptin and neuropeptide Y (NPY). The release of NPY, which stimulates hunger and appetite, is decreased by serotonin. Leptin, which is released by adipose tissue, plays a role in end of meal satiation. Serotonin release stimulates leptin release which signals feelings of satiety. Leptin release in turn down regulates serotonin release. (13) In the CNS, serotonin release is increased by consumption of carbohydrates, while carbohydrate or sugar cravings are linked to serotonin deficiency. (14)

Clinical Study:

A study into the effects of 5-HTP on food intake, mood and weight loss in obese subjects (BMI of 30-40) determined that an oral dose of 5-HTP (8 mg/kg/day) was associated with a decrease in food intake and subsequent weight loss after five weeks of treatment. (15)

Serotonin and Pain

Serotonin is involved in both pain recognition and pain control, including chronic pain. The effect of serotonin is dependent on both the area of the body and the receptor subtype. (16) It is released from platelets and mast cells after tissue injury, and after nerve injury serotonin levels in the affective nerve increases. This suggests a role for serotonin in inflammation and pain sensitization. (16)

Clinical Study:

A study into whether serotonin displays a nociceptive or antinociceptive role in experimental pain evaluation in healthy volunteers found a lower pain threshold associated with higher serotonin levels. No association with pain tolerance was found. (17)

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