Tryptophan Intake Research Articles

Poly-methionine/graphitic carbon nitride modified screen-printed electrodes: A metal-free, bio-interface for tryptophan sensing

Tryptophan (TRP) is an essential amino acid needed for the growth and proper functioning of the human body. A balanced intake of TRP-rich food products is essential to meet the daily requirements. As both low and high levels of TRP are associated with clinical disorders, an optimum amount of TRP intake is critical. Hence, developing a method to efficiently detect TRP in food and nutritional supplements is essential. Accordingly, this study reports the electrochemical detection of TRP using poly-methionine/graphitic carbon nitride modified screen-printed electrode (gCN.Meth|SPE). To our knowledge, this study is the first attempt to decipher the electrodeposition of gCN.Meth on a conducting substrate through a systematic analysis of the electro-functionalized gCN.Meth surface using XRD, FT-IR, HR-SEM, EDX, and AFM. The synergistic benefits of both the gCN and conducting poly(methionine) resulted in augmented electrochemical performance exhibiting a pronounced TRP oxidation peak in both cyclic voltammetry (CV) and square wave voltammetry (SWV). The improved electrochemical response can be ascribed to the specific interactions between the TRP and gCN through π- π interactions and hydrogen bonding and electrostatic interaction between TRP and methionine. This facilitated interaction resulted in the electro-catalytic oxidation of TRP with a negative potential shift of 0.126 V and a 16.6-fold increase in the current response compared to unmodified SPE. The gCN.Meth|SPE exhibited a 25.12 times higher sensitivity compared to bare SPE, with a linear response in the concentration ranges of 1.0–300.0 μM and a low detection limit of 29.9 nM. The interference study further indicated that gCN.Meth-modified SPEs is highly effective for the precise and reliable detection of tryptophan in real samples.

Effect of Tryptophan Restriction in the Therapy of Irritable Bowel Syndrome: a Systematic Review.

The metabolic pathways of tryptophan (TRP) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), positing that the strategic modulation of TRP consumption may exert regulatory effects on serotonin levels, consequently altering the clinical manifestation of IBS. This systematic review was meticulously orchestrated to evaluate the effect of TRP restriction on IBS. A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was conducted. Controlled trials that compared the efficacy of TRP restriction in IBS patients were scrutinized. The primary outcomes were gastrointestinal symptoms, quality of life, and pain, whereas the secondary outcomes included anxiety, mood, and safety. The risk of bias was meticulously assessed according to the guidelines recommended by the Cochrane Collaboration. A total of five trials, enrolling 135 participants, were incorporated into the qualitative synthesis. Low-TRP intake attenuated gastrointestinal discomfort and enhanced psychological well-being in IBS patients, while the effects of acute TRP depletion were controversial. Safety data from one randomized controlled trial reported no occurrence of adverse events. This systematic review suggests that moderating, rather than depleting, TRP intake may potentially be a feasible and safe adjunctive treatment for patients with IBS. Future research incorporating a high-quality study design and consensus on clinical outcome measurements for IBS is warranted.

Sleep Patterns and Tryptophan Consumption among Students at Spanish Universities: The Unihcos Project.

The objective of this cross-sectional study was to explore sleep patterns and the potential relationship between sleep and tryptophan intake among Spanish university students. A total of 11,485 students self-reported their sleep and dietary patterns and habits. Tryptophan intake was calculated using a food intake matrix and results were presented as quartiles of total intake. Short sleep duration prevalence was 51.0%, with males exhibiting a significantly higher frequency. A total of 55.0% of participants presented inadequate sleep efficiency, with males again presenting a higher rate. Median tryptophan intake was 692.16 ± 246.61 mg/day, 731.84 ± 246.86 mg/day in males and 677.24 ± 244.87 mg/day in females (p = 0.001). Dietary tryptophan intake below the first quartile (<526.43 mg/day) was associated with a higher risk of short sleep duration in males (1.26; 95%CI: 1.02-1.55) and females (1.19; 95%CI: 1.05-1.34) and with the Athens Insomnia Scale insomnia in males (2.56; 95%CI: 1.36-4.82) and females (1.47; 95%CI: 1.10-2.05). Regarding academic specializations, females in the humanities field showed a higher risk of Athens Insomnia Scale insomnia due to low tryptophan intake (Q1: 3.15; 95% CI: 1.04-9.55 and Q2: 3.41; 95%CI: 1.01-11.5). In summary, lower tryptophan consumption appears to be associated with poorer sleep quality in Spanish university students; however, other social factors affecting students may also influence sleep quality. These findings have important implications for nutritional recommendations aimed at enhancing tryptophan intake to improve sleep quality.

Protein quality enhancement in temperate corn through introgression of o2o2 using marker assisted backcross and shuttle breeding

Abstract Quality protein maize (QPM) has protein quality of opaque 2 (&gt;0.074% tryptopan) with endosperm modifiers which turn its kernels vitreous that is similar to normal maize. Use of QPM as a cereal can significantly improve daily intake of lysine and tryptophan for humans and livestock. However QPM cultivars have lower yields due to trait compensation. Therefore, a breeding programme was carried out to convert parental lines of Shalimar maize hybrid 5 (SMH-5) viz. IML-187 and BML-6 into QPM versions. Marker polymorphism was worked out in donors and recipients. IML-187 was crossed with DQL-2029-1 and BML-6 was crossed with DQL-779-2-9. The first and second backcross generations involving IML-187 as recurrent parent were marked as BC1F1 (A) and BC2F1 (A) respectively, whereas those involving BML-6 were designated as BC1F1 (B) and BC2F1 (B) respectively. The BC2F2 lines derived from two generation of backcrossing coupled with SSR marker and phenotypic background and foreground selection were advanced to BC2F3. Approximately 80–90% of RPG similarity was observed in BC2F2 lines. Eight lines namely IML-187 × DQL-2029-1- BC2F3:06, 07 and 23: BML-6 × DQl-779-2-9: 02,04,09,20 and 13 were identified from BC2F3 to have tryptophan higher than 0.075% and &lt;25% opaqueness. These lines were used for trait fixing and crosses were made to produce QPM version of SMH-5. Six improved versions of SMH-5 were selected for higher grain yield and tryptophan content and are to be employed in further testing and varietal release in Northern Hill Zone (NHZ) in India.

Excessive Tryptophan and Phenylalanine Induced Pancreatic Injury and Glycometabolism Disorder in Grower-finisher Pigs

BackgroundThe increase in circulating insulin levels is associated with the onset of type 2 diabetes (T2D), and the levels of branched-chain amino acids and aromatic amino acids (AAAs) are altered in T2D, but whether AAAs play a role in insulin secretion and signaling remains unclear. ObjectivesThis study aimed to investigate the effects of different AAAs on pancreatic function and on the use of insulin in finishing pigs. MethodsA total of 18 healthy finishing pigs (Large White) with average body weight of 100 ± 1.15 kg were randomly allocated to 3 dietary treatments: Con, a normal diet supplemented with 0.68% alanine; Phe, a normal diet supplemented with 1.26% phenylalanine; and Trp, a normal diet supplemented with 0.78% tryptophan. The 3 diets were isonitrogenous. There were 6 replicates in each group. ResultsHerein, we investigated the effects of tryptophan and phenylalanine on pancreatic function and the use of insulin in finishing pigs and found that the addition of tryptophan and phenylalanine aggravated pancreatic fat deposition, increased the relative content of saturated fatty acids, especially palmitate (C16:0) and stearate (C18:0), and the resulting lipid toxicity disrupted pancreatic secretory function. We also found that tryptophan and phenylalanine inhibited the growth and secretion of β-cells, downregulated the gene expression of the PI3K/Akt pathway in the pancreas and liver, and reduced glucose utilization in the liver. ConclusionsUsing fattening pigs as a model, multiorgan combined analysis of the insulin-secreting organ pancreas and the main insulin-acting organ liver, excessive intake of tryptophan and phenylalanine will aggravate pancreatic damage leading to glucose metabolism disorders, providing new evidence for the occurrence and development of T2D.

Diet and well-being of 1st year Medical Interns during hospital placement

Hospital placement is essential training for medical interns, involving shift work and high-pressure environments. This can increase physiological and psychological stress, which may be mediated by metabolites of microbial digestion(1). Nutrients of interest include those accessible to microbial digestion and associated with altered signalling within the microbiota-gut-brain axis (MGBA)(1). Fibre is fermented by gut microbes to produce short-chain fatty acids(2) and is associated with improved psychological outcomes(3). Tryptophan, a precursor to gut-derived serotonin(2), has been negatively associated with anxiety(4). Processed foods contain food additives, excess sugars, and saturated fats that may disrupt gut homeostasis(1) and impact psychological well-being(4). Lastly, total energy intake may determine the level of substrate available for microbial fermentation(2). Therefore, this research explores how microbiota-accessible food components interact with physical and psychological well-being in a cohort of medical interns undertaking their first-year of hospital placement. Participants were healthy medical interns, during first-year hospital placement (n = 21) from the Hunter New England Local Health District, NSW, Australia. Participants completed diet and wellbeing surveys at baseline and every 2 months over a 10-month period. 24-hour diet diaries were self-recorded from participants using a mobile application (Easy Diet Diary) and analysed using AusNut and the NOVA classification system of ultra-processed foods (ULP). Wellbeing surveys include depression, anxiety, stress scale (DASS), and PROMIS survey for mental (M), physical (P), and sleep well-being. Current data represents an ‘in-progress’ of the longitudinal data collection. This study utilised Spearman correlation and Tukey’s post hoc test for mixed methods analysis. From baseline to timepoint 3 (T3, 4 months) daily energy intake was consistent with cohort estimated energy requirements (EER). However, consumption ranged from 37% to 167% of EER, indicating a large variation of intakes. Energy consumed from ULP ranged from 30% to 34% (p = 0.6875). Baseline tryptophan intake (x¯ = 1139mg) was within the suggested target, whilst fibre intake (x¯ = 23g) was below the recommended intake. Neither saw significant changes from baseline to T3. Fibre intake was positively correlated with mental and physical well-being at baseline (x¯ = 23.1g, M: r = 0.474, p = 0.04, P: r = 0.608, p = 0.007), and timepoint 2 (x¯ = 31.5g, M: r = 0.647,p = 0.026, P: r = 0.780, p = 0.004) but not at T3. In addition, baseline consumption of sugar (x¯ = 18g) and poly-unsaturated fats (x¯ = 15g) were both negatively correlated with mental and physical well-being. Overall, no significant dietary changes were evident from baseline to mid-year collection in a first-year medical intern cohort during hospital placements. Fibre was significantly associated with mental and physical well-being, building on current understanding of fibre’s role in the MGBA. Planned metabolite analysis will explore the mechanisms of proposed microbiome-accessible nutrients alongside diet, well-being, and microbiota data. Findings from this study will identify how diet-microbiome interactions change under stress, with wider positive implications on intense workplace environments with the aim to preserve individual wellbeing.

How effective is ketogenic diet in sleep disorders ?

IntroductionSleep disorders vary widely and its treatment are based on a combination of life style changes and pharmacological therapy adapted to the primer health issue. Ketogenic diet has shown not only its efficacy in different health conditions, but it is also becoming a popular health trend. Could the therapeutic spectrum of ketogenic diet cover sleep disturbances ?ObjectivesThe aim of our study is to evaluate the effect of ketogenic diet on sleep disordersMethods To identify relevant studies ,our literature review was based on the Pubmed interface and adapted for 2 databases : science direct and google scholar. We used the following key words (ketogenic diet [meSH terms]) and (sleep disorders [meSH terms]).ResultsOur research revealed 14 articles published between 2012 and 2022. We selected 8 which corresponded to the purpose of our review. The ketogenic diet affects sleep hemostasis indirectly. In fact, this diet is associated with weight loss and therefore reduction of metabolic and cardiovascular complications disturbing sleep quality. From a neurobiological perspective, this regimen based on limited carbohydrates is associated with a low Tryptophan intake which is the precursor of melatonin. But on the other hand, Ketone bodies trigger adenosine activity which promotes melatonin liberation, the sleep inducing hormone.Conclusionsketogenic diet modulates melatonin activity therefore affects sleep architecture. Meanwhile, Its impact on sleep disorders is still controversed due to the variation of its pathophysiological mechanisms.Disclosure of InterestNone Declared

How effective is ketogenic diet in sleep disorders ?

IntroductionSleep disorders vary widely and its treatment are based on a combination of life style changes and pharmacological therapy adapted to the primer health issue. Ketogenic diet has shown not only its efficacy in different health conditions, but it is also becoming a popular health trend. Could the therapeutic spectrum of ketogenic diet cover sleep disturbances ?ObjectivesThe aim of our study is to evaluate the effect of ketogenic diet on sleep disordersMethodsTo identify relevant studies ,our literature review was based on the Pubmed interface and adapted for 2 databases : science direct and google scholar. We used the following key words ( ketogenic diet [meSH terms]) and (sleep disorders [meSH terms]).ResultsOur research revealed 14 articles published between 2012 and 2022. We selected 8 which corresponded to the purpose of our review. The ketogenic diet affects sleep hemostasis indirectly. In fact, this diet is associated with weight loss and therefore reduction of metabolic and cardiovascular complications disturbing sleep quality. From a neurobiological perspective, this regimen based on limited carbohydrates is associated with a low Tryptophan intake which is the precursor of melatonin. But on the other hand, Ketone bodies trigger adenosine activity which promotes melatonin liberation, the sleep inducing hormone.ConclusionsKetogenic diet modulates melatonin activity therefore affects sleep architecture. Meanwhile, Its impact on sleep disorders is still controversed due to the variation of its pathophysiological mechanisms.Disclosure of InterestNone Declared

Tryptophan intake and pancreatic cancer: findings from a case-control study.

Pancreatic cancer is a leading cause of cancer-related death worldwide. Tryptophan plays a vital role in cell growth and maintenance as a building block of protein and coordination of organismal responses to environmental and dietary cues. Animal model study showed that dietary tryptophan improved treatment response in those who received chemotherapy or immune checkpoint inhibitors. Limited data are available assessing the association between tryptophan intake and risk of pancreatic cancer. We aimed to evaluate this association in a case-control study in Vietnam. We analyzed data from a case-control study, including 3759 cancer cases and 2995 control subjects of whom 37 with pancreatic cancer cases. Tryptophan intake was derived from food frequency questionnaire. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for different levels of tryptophan intake with pancreatic cancer risk. Overall, tryptophan intake was inversely associated with pancreatic cancer risk in a dose-dependent manner. The ORs and 95% CIs of pancreatic cancer were 0.51 (0.29-0.92) for continuous scale, 0.27 (0.10-0.73) for tertile 2 and 0.34 (0.11-1.06) for tertile 3, compared with tertile 1 (the lowest intake) ( Ptrend = 0.02). In stratified analysis, this inverse association pattern was present among those with BMI < 23 kg/m 2 and ever drinkers. A diet with a higher intake of tryptophan was significantly associated with a lower incidence of pancreatic cancer among Vietnamese population. These suggest that dietary modification may be an effective strategy for primary prevention of pancreatic cancer development.

Dietary Intake of Nutrients Involved in Serotonin and Melatonin Synthesis and Prenatal Maternal Sleep Quality and Affective Symptoms.

Poor sleep quality and psychological distress in pregnancy are important health concerns. Serotonin and melatonin levels may underlie variation in these adverse outcomes. In this study, we examined dietary nutrients involved in serotonin and melatonin synthesis in relation to maternal sleep quality and affective symptoms during pregnancy. Pregnant women at no greater than normal medical risk at enrollment completed 24-hour dietary recalls in mid-late pregnancy. Usual intakes of vitamin B6, vitamin D, eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and tryptophan were estimated from dietary intake of foods and supplements using the National Cancer Institute (NCI) method. Sleep quality, depression, and anxiety were measured using validated questionnaires. Associations between nutrient intakes, sleep quality, and affective symptoms were estimated using generalized estimating equation models adjusting for potential confounding factors. In minimally adjusted models, EPA + DHA and tryptophan intakes were associated with a lower score indicating better sleep quality (b: -1.07, 95% CI: -2.09, -0.05) and (b: -12.40, 95% CI: -24.60, -0.21), respectively. EPA + DHA and tryptophan intakes were also associated with a lower odds of shorter sleep duration and sleep disturbances. In addition, tryptophan was associated with a lower odds of higher sleep latency. However, associations were attenuated and nonsignificant after adjustment for demographic and lifestyle factors. In conclusion, intakes of EPA + DHA and tryptophan were associated with improved sleep quality, but these associations were confounded by maternal demographic and lifestyle characteristics. This study highlights the need to consider dietary intake and pregnancy health in the context of demographic characteristics and lifestyle behaviors.

Tryptophan Metabolism in Postmenopausal Women with Functional Constipation.

Constipation belongs to conditions commonly reported by postmenopausal women, but the mechanism behind this association is not fully known. The aim of the present study was to determine the relationship between some metabolites of tryptophan (TRP) and the occurrence and severity of abdominal symptoms (Rome IV) in postmenopausal women with functional constipation (FC, n = 40) as compared with age-adjusted postmenopausal women without FC. All women controlled their TRP intake in their daily diet. Urinary levels of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and 3-indoxyl sulfate (indican, 3-IS), were determined by liquid chromatography/tandem mass spectrometry. Dysbiosis was assessed by a hydrogen-methane breath test. Women with FC consumed less TRP and had a lower urinary level of 5-HIAA, but higher levels of KYN and 3-IS compared with controls. The severity of symptoms showed a negative correlation with the 5-HIAA level, and a positive correlation with the 3-IS level. In conclusion, changes in TRP metabolism may contribute to FC in postmenopausal women, and dysbiosis may underlie this contribution.

Interplay between diet, circulating indolepropionate concentrations and cardiometabolic health in US populations

ObjectivesTo identify indolepropionate (IPA)-predicting gut microbiota species, investigate potential diet–microbiota interactions, and examine the prospective associations of circulating IPA concentrations with type 2 diabetes (T2D) and coronary heart disease (CHD)...

Determination of ileal digestibility of tryptophan in tryptophan biomass for broilers using the direct and regression methods

A total of 372 Ross 308 male broilers were used in a 2-day trial to determine the ileal digestibility of tryptophan in tryptophan biomass using the direct and regression methods, and to compare the digestibility between the 2 methods. A nitrogen-free diet was prepared to estimate the basal endogenous losses of amino acids of birds. Two semi-purified diets were formulated to contain tryptophan biomass as the sole source of amino acids. Five corn-soybean meal-based diets consisted of a basal diet and 4 assay diets containing either 30 or 60 g/kg of tryptophan biomass A or B (TBA or TBB) at the expense of corn and soybean meal in the basal diet. The ratio of corn and soybean meal remained consistent across the basal and assay diets. Birds received a standard starter diet (193 g/kg crude protein) from day 0–19 post-hatch and 8 experimental diets for 2 days from day 19. On day 21 post-hatch, birds were asphyxiated with carbon dioxide and digesta samples from the distal section of the ileum were collected. The linear regression of tryptophan biomass-associated digested tryptophan against tryptophan biomass-associated tryptophan intake was conducted to determine the ileal tryptophan digestibility in tryptophan biomass. The apparent and standardized ileal digestibility of tryptophan determined by the direct method were 0.993 and 0.993 in TBA, and 0.995 and 0.996 in TBB, respectively. The apparent ileal digestibility of amino acids in corn-soybean meal-based diets quadratically increased (P < 0.05) as dietary levels of tryptophan biomass increased. The ileal digestibility of tryptophan determined by the regression method was 1.013 and 1.009 for TBA and TBB, respectively. The ileal digestibility of tryptophan in TBA derived from the regression method was greater (P = 0.033) than that of determined using the direct method, but no difference (P = 0.193) was observed in TBB. However, the ileal digestibility of tryptophan in the tryptophan biomass was close to 100 % irrespective of the method used.

A meta-analysis of dietary metabolizable amino acids and energy supply on nitrogen retention and nitrogen utilization efficiency in beef cattle

Increasing nitrogen utilization efficiency (NUE) can reduce environmental impact and increase economic benefits to maintain a sustainable development of the beef cattle industry. The objectives of this study were to systemically and quantitatively analyze the effects of dietary metabolizable amino acids and energy supply on nitrogen retention and NUE in beef cattle and to develop prediction models using a meta-regression and a machine learning approach. After literature screening and data collection, a dataset was assembled, which finally included 63 peer-reviewed studies published between 1980 and 2022 with 248 treatments. Following bivariate correlation analyses, univariate and multiple linear regression analyses were conducted to analyze effects of body weight (BW) and intake of metabolizable energy (MEI), crude protein (CPI), metabolizable protein (MPI), and 10 metabolizable essential amino acids (MAAI) on retained protein and NUE. The mixed model procedure with study as random effect was used to remove variations across studies. The random forest regression model was used to identify the importance ranking of predictor variables and to compare prediction adequacy with the multiple linear regression models. The stability of parameter estimates and the validity of the obtained model were evaluated using the Monte Carlo cross-evaluation approach. Both retained protein and NUE were negatively quadratically correlated with BW, MEI, CPI, MPI, and MAAI, suggesting that the marginal return of retained protein and NUE are decreased with increased dietary energy and protein supply. The multiple linear regression analyses indicated that retained protein and NUE were negatively correlated with BW, while positively correlated with MEI and metabolizable Arg intake. However, there was a negative correlation between NUE and metabolizable tryptophan intake. Compared with the multiple regression models, the random forest models had greater RMSPE and lesser CCC, suggesting that the prediction accuracy and precision of the random forest models were less than the multiple regression models. In conclusion, the conversion efficiency of MAAI to net protein is not constant, and the developed response surface models can be a reliable approach to estimate AA requirements and optimize NUE in beef cattle.

Tryptophan intake, not always the more the better.

To investigate the effects of excessive tryptophan intake on the body and the effects of tryptophan metabolism-related aryl hydrocarbon receptor (AhR) pathway in healthy rats and chronic kidney disease rats, to study the adverse effects of excess tryptophan. In Part I Experiment, the healthy rats were fed with diet containing 0.6, 1.2 and 1.8% tryptophan for 12 weeks. After the intervention, the blood and kidney tissues were collected. Serum creatinine and blood urea nitrogen were detected. Hematoxylin-eosin (H&E) staining was used to observe renal pathological changes. Enzyme-linked immunosorbent assay was used to detect serum kynurenic acid and AhR levels. The kidney levels of AhR, CyP1A1 and CyP1B1 were detected by western-blot. In Part II Experiment, the chronic kidney disease (CKD) model was induced by intra-gastric gavage with adenine for 4 weeks. Then the CKD rats were given tryptophan at a dose of 100 mg/kg or 500 mg/kg for eight weeks. Rat survival curve, renal function, renal tissue pathology and serum AhR were detected. Tryptophan-targeted ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS) was employed to quantitatively access the tryptophan-targeted metabolites in two parts experiments. In part I experiment, high tryptophan diet can increase the level of blood urea nitrogen (BUN) in healthy rats and induce focal renal tubulointerstitial injury. Tryptophan-targeted analyzes showed that high tryptophan diet feeding can significantly increase the concentration of kynurenine and indole metabolites. The serum AhR level and kidney AhR, CyP1A1 and CyP1B1 were also significantly increased in high tryptophan diet rats. In part II experiment, high tryptophan intervention induced a significant increase in mortality, serum creatinine, urea nitrogen levels, and renal pathological damage in CKD rats. The levels of tryptophan-targeted metabolites, kynurenine, xanthurenate, picolinic acid, 5-hydroxyindole-3-acetic acid, indole-3-lactic acid, indoleacetate and indoxyl sulfate, showed an upward trend in the high-dose tryptophan group (Ade + Trp-H) compared with the adenine group. The serum AhR of Ade + Trp-H rats was significantly higher than those of adenine rats. Moderate tryptophan intake may be beneficial, but excessive tryptophan can lead to accumulation of kynurenine and indole metabolites, activate AhR pathway and induce kidney injury.

Kynurenine Pathway Regulation at Its Critical Junctions with Fluctuation of Tryptophan.

The kynurenine pathway (KP) is the primary route for the catabolism of the essential amino acid tryptophan. The central KP metabolites are neurologically active molecules or biosynthetic precursors to critical molecules, such as NAD+. Within this pathway are three enzymes of interest, HAO, ACMSD, and AMSDH, whose substrates and/or products can spontaneously cyclize to form side products such as quinolinic acid (QA or QUIN) and picolinic acid. Due to their unstable nature for spontaneous autocyclization, it might be expected that the levels of these side products would be dependent on tryptophan intake; however, this is not the case in healthy individuals. On top of that, the regulatory mechanisms of the KP remain unknown, even after a deeper understanding of the structure and mechanism of the enzymes that handle these unstable KP metabolic intermediates. Thus, the question arises, how do these enzymes compete with the autocyclization of their substrates, especially amidst increased tryptophan levels? Here, we propose the formation of a transient enzyme complex as a regulatory mechanism for metabolite distribution between enzymatic and non-enzymatic routes during periods of increased metabolic intake. Amid high levels of tryptophan, HAO, ACMSD, and AMSDH may bind together, forming a tunnel to shuttle the metabolites through each enzyme, consequently regulating the autocyclization of their products. Though further research is required to establish the formation of transient complexation as a solution to the regulatory mysteries of the KP, our docking model studies support this new hypothesis.

Reduced Intake of Dietary Tryptophan Improves Beneficial Action of Budesonide in Patients with Lymphocytic Colitis and Mood Disorders.

Lymphocytic colitis (LC) is a gastrointestinal (GI) tract disease with poorly known pathogenesis, but some environmental and lifestyle factors, including certain dietary components, may play a role. Tryptophan is an essential amino acid, which plays important structural and functional roles as a component of many proteins. It is important in the development and maintenance of the body, in which it is metabolized in two main pathways: kynurenine (KYN) and serotonin. In this work, we explored the effect of reducing of TRP in the diet of patients with LC with mood disorders. We enrolled 40 LC patients who had a normal diet, 40 LC patients with the 8-week diet with TRP content reduced by 25% and 40 controls. All LC patients received budesonide at 9 mg per day, and the severity of their GI symptoms was evaluated by the Gastrointestinal Symptoms Rating Scale. Mood disorders were evaluated by the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA), in urine were determined. Budesonide improved the GI and mental states of LC patients, and the diet with reduced TRP content further amended these symptoms. Dietary intervention decreased the concentration of 5-HIAA by about 50% (3.4 vs. 6.3) and QA by about 45% (3.97 vs. 7.20). These changes were correlated with a significant improvement in the profitable action of budesonide on gastrointestinal and mental health of LC patients as they displayed significantly lower GSRS, HAM-A and HAM-B scores after than before the intervention-10.5 vs. 32, 11.0 vs. 21 and 12 vs. 18, respectively. In conclusion, a reduction in TRP intake in diet may improve GI and mental symptoms in LC patients treated with budesonide and these changes may be mediated by the products of TRP metabolism.

Genetic risk of depression is different in subgroups of dietary ratio of tryptophan to large neutral amino acids

Manipulation of intake of serotonin precursor tryptophan has been exploited to rapidly induce and alleviate depression symptoms. While studies show that this latter effect is dependent on genetic vulnerability to depression, the effect of habitual tryptophan intake in the context of predisposing genetic factors has not been explored. Our aim was to investigate the effect of habitual tryptophan intake on mood symptoms and to determine the effect of risk variants on depression in those with high and low tryptophan intake in the whole genome and specifically in serotonin and kynurenine pathways. 63,277 individuals in the UK Biobank with data on depressive symptoms and tryptophan intake were included. We compared two subpopulations defined by their habitual diet of a low versus a high ratio of tryptophan to other large amino acids (TLR). A modest protective effect of high dietary TLR against depression was found. NPBWR1 among serotonin genes and POLI in kynurenine pathway genes were significantly associated with depression in the low but not in the high TLR group. Pathway-level analyses identified significant associations for both serotonin and kynurenine pathways only in the low TLR group. In addition, significant association was found in the low TLR group between depressive symptoms and biological process related to adult neurogenesis. Our findings demonstrate a markedly distinct genetic risk profile for depression in groups with low and high dietary TLR, with association with serotonin and kynurenine pathway variants only in case of habitual food intake leading to low TLR. Our results confirm the relevance of the serotonin hypothesis in understanding the neurobiological background of depression and highlight the importance of understanding its differential role in the context of environmental variables such as complexity of diet in influencing mental health, pointing towards emerging possibilities of personalised prevention and intervention in mood disorders in those who are genetically vulnerable.

Increased Fecal Serotonin After Gastric Bypass Is Unrelated To Tryptophan Intake

Increased Fecal Serotonin After Gastric Bypass Is Unrelated To Tryptophan Intake

Higher dietary intake of aromatic amino acids was associated with lower risk of cardiovascular disease mortality in adult participants in NHANES III

Little is known about the associations between dietary aromatic amino acids (AAAs) intake and mortality from all causes and cardiovascular disease (CVD). Accordingly, we evaluated these associations in the adult population of the United States using data from the Third National Health and Nutrition Examination Survey. This was a cohort study. Dietary intake of AAAs (tyrosine, phenylalanine, and tryptophan) was determined from the total nutrient intake document. We hypothesized that higher dietary AAA intake would lower all-cause and CVD mortality in adults in the United States. First, we categorized participants into quintiles based on their dietary intakes of total AAAs, tyrosine, phenylalanine, and tryptophan. Then, we established 4 Cox proportional-hazards models (models 1-4) and calculated hazard ratios and 95% confidence intervals to estimate the associations between dietary intakes of total AAAs, tyrosine, phenylalanine, and tryptophan and all-cause and CVD mortality. Mortality status was primarily obtained from files linked to the National Death Index records up to December 31, 2015. After multivariate adjustment, the hazard ratios (95% confidence intervals) of CVD mortality in the highest quintiles of dietary total AAAs, tyrosine, phenylalanine, and tryptophan intake (reference: the lowest quintiles) were 0.66 (0.52-0.84), 0.65 (0.51-0.83), 0.66 (0.52-0.85) and 0.64 (0.50-0.82), respectively. In a nationally representative cohort, higher dietary intakes of total AAA and the 3 individual AAAs were independently associated with a lower risk of CVD mortality, and these associations were stronger in non-Hispanic White people than in other people.