What I find most interesting is the function of tryptophan. Has anyone ever tried with success supplementing L-tryptophan to ease IBS related symptoms?
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Meleber
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Hi Meleber no I haven’t but there are some foods containing natural tryptophan like cheese , tuna , full fat milk . Interesting articles tho keep them coming x
i’m looking into this as well as I’m having interrupted sleep. And it’s all due to my gut Microbiome. I have purchased tryptophan. But will try the natural route first from food that contain high levels. Tryptophan
Since prucalopride did have adverse effects on my symptoms I decided to focus on tryptophan instead.
"Mood disorders and constipation are often comorbid, yet their shared etiologies have rarely been explored. The neurotransmitter serotonin (5-HT) regulates central nervous system and enteric nervous system (ENS) development and long-term functions, including gastrointestinal (GI) motility and mood. Therefore, defects in neuron production of 5-HT might result in brain and intestinal dysfunction. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in 5-HT biosynthesis. A variant of TPH2 that encodes the R441H substitution (TPH2-R441H) was identified in individuals with severe depression. We studied mice with an analogous mutation (TPH2-R439H), which results in a 60%–80% decrease in levels of 5-HT in the central nervous system and behaviors associated with depression in humans. Feeding chow that contains 5-HTP slow release (5-HTP SR) to TPH2-R439H mice restores levels of 5-HT in the central nervous system and reduces depressive-like behaviors."
Okay, this study from 2019 has limitations, it concerned mice 😉
"Effects of Serotonin and Slow-Release 5-Hydroxytryptophan on Gastrointestinal Motility in a Mouse Model of Depression"
Although mood disorders and constipation are often comorbid, etiologies that link these conditions have rarely been explored.
New Findings
Studies of TPH2-R439H mice found that reduced release of serotonin (5-HT) from enteric neurons resulted in defects in enteric nervous system development and GI motility. Neuron production of 5-HT links constipation with mood dysfunction.
Limitations
The utility of slow-release (SR) 5-HTP in the concomitant treatment of depression and constipation as well as other medical conditions associated with low neuronal 5-HT in humans requires study.
Impact
These findings reveal an important role for neuronal serotonin in linking constipation and depression.Oral 5-HTP SR simultaneously restores enteric serotonin and thus may be useful in treating gut dysfunction associated with low serotonin."
Submission received: 3 March 2024 / Revised: 19 March 2024 / Accepted: 28 March 2024 / Published: 1 April 2024
(This article belongs to the Topic Bioactive Compounds with Application Potentials in Nutraceuticals and Nutricosmetics: Focus on Mechanism of Action and Application Science)
"In summary, the pathogenesis of functional gastrointestinal diseases is complex, but 5-HT homeostasis disorders play a crucial role. Serotonin levels in the intestinal mucosa and the blood depend on the expression of tryptophan hydroxylase and the activity of selective 5-HT reuptake transporters [71]. The level of their expression is influenced by nutritional and bacterial factors [17]. However, the main condition is consuming an appropriate amount of substrate for their synthesis, i.e., exogenous L-tryptophan. For this reason, diet is still a main element of the treatment of gastrointestinal diseases.
Our study has some limitations. The group of respondents is relatively small. This study was conducted as an open-label clinical trial without a placebo. The severity of FC symptoms is based mainly on patients’ subjective assessment. These criteria apply to all functional diseases of GIT. Nevertheless, the assessment of nutrition quality also depends on patients’ complaints, but good cooperation with professional dietitians ensures the reliability of the results.
5. Conclusions
A low FODMAP diet supplemented with L-tryptophan benefits elderly patients with functional constipation. The changes induced by that diet concern the increase in 5-HT production. The increased intake of TRP may influence its level and the activity and balance of its metabolic pathways involving the gut microbiome. Further research is necessary, especially on the type of bacteria involved in TRP metabolism."
Research: Changes in Tryptophan Metabolism on Serotonin and Kynurenine Pathways in Patients with Irritable Bowel Syndrome
"The aim of our study was to evaluate the urinary excretion of tryptophan metabolites deemed as markers of activity of SER and KYN pathways in patients with two different IBS forms: constipation-predominant and diarrhoea-predominant (IBS-C and IBS-D, respectively), related to somatic and mental symptoms in selected group of IBS patients without SIBO and other signals indicating changes in the bacterial flora."
L-Tryptophan (L-Trp) is metabolized via three pathways: the indole pathway in bacteria and the kynurenine and serotonin pathways in mammalian cells.
Disruptions in L-Trp metabolism are reported in several diseases making L-Trp metabolism a promising therapeutic target.
Manipulating L-Trp metabolism is an attractive therapeutic strategy.
Key enzymes of L-Trp metabolism are targets of inhibitors currently undergoing clinical trials in cancerology, dermatology, and gastroenterology.
Serotonin and aryl hydrocarbon receptor (AhR) receptors are targeted in the treatment of gastrointestinal diseases, inflammation, and many cancers.
Next-generation probiotics producing indoles are being developed for their ability to activate AhR in the gut.
Abstract
L-Tryptophan is an essential amino acid required for protein synthesis.
It undergoes an extensive and complex metabolism along several pathways, resulting in many bioactive molecules acting in various organs through different action mechanisms.
Enzymes involved in its metabolism, metabolites themselves, or their receptors, represent potential therapeutic targets, which are the subject of dynamic research.
Disruptions in L-tryptophan metabolism are reported in several neurological, metabolic, psychiatric, and intestinal disorders, paving the way to develop drugs to target it.
This review will briefly describe L-tryptophan metabolism and present and discuss the most recent pharmacological developments targeting it.
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