Serum Tryptophan Research Articles

Effects of dietary tryptophan supplementation on body temperature, hormone, and cytokine levels in broilers exposed to acute heat stress

The present study was conducted to investigate the effects of tryptophan (Trp) supplementation on rectal temperature, hormone, and cytokine levels in broilers subjected to acute heat stress. A total of 300 18-day-old female Arbor Acres broilers were randomly allocated to five dietary treatment groups with six replicates per treatment group and ten birds per replicate. Broilers were fed a basal diet and in the thermoneutral conditions (TN, 23 ± 1 °C) was considered as the TN group. Broilers were fed a basal diet and exposed to acute heat stress (HS, 34 ± 1 °C) was regarded as the HS group, and other broilers exposed to acute heat stress (34 ± 1°C) were fed a basal diet supplemented with 0.09%, 0.18%, and 0.27% Trp. Results indicated that acute heat stress increased the rectal temperature (P < 0.05), enhanced the concentrations of corticosterone (CORT), dopamine (DA), adrenaline (Adr), adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH) in serum (P < 0.05), and elevated the levels of serum tryptophan hydroxylase (TPH)1, tryptophan 2, 3-dioxygenase (TDO), indoleamine 2, 3-dioxygenase (IDO), and kynurenic acid (P < 0.05), compared with the TN group. Meanwhile, acute heat stress increased the levels of serum Trp, hypothalamic Trp, 5-hydroxytryptophan (5-HT), and interleukin-22 (P < 0.05) relative to the TN group. However, compared with the heat stress group, Trp supplementation decreased the rectal temperature of heat-stressed broilers and dietary 0.09% Trp supplementation decreased the levels of serum CRH and TDO (P < 0.05), increased the levels of serum Trp and IL-22 (P < 0.05) in heat-stressed broilers. In addition, dietary supplemented with 0.18% Trp reduced the levels of serum DA, Adr, noradrenaline (NA), CRH, TDO, IDO, kynurenic acid, IL-1β, and hypothalamic 5-HIAA/5-HT (P < 0.05), increased the levels of serum Trp, 5-HT, and IL-22, and upregulated the concentrations of hypothalamic Trp and 5-HT in heat-stressed broilers (P < 0.05). Moreover, dietary 0.27% Trp supplementation decreased the levels of serum DA, CRH, TDO, and hypothalamic 5-HIAA/5-HT (P < 0.05), and upregulated the levels of serum Trp, 5-HT, IL-22, hypothalamic Trp and 5-HT in heat-stressed broilers (P < 0.05). Taken together, dietary 0.18% Trp supplementation may be the optimal level for broilers reared under acute heat stress.

Kynurenine pathway of tryptophan metabolism in patients with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autoinflammatory syndrome characterized by recurrent episodes of fever and aseptic polyserositis. Subclinical inflammation generates a hidden threat to the development of FMF complications such as amyloidosis in attack-free intervals. The kynurenine pathway (KP) has been considered an important player in inflammation and immune response. The study was aimed to measure serum levels of KP metabolites in patients with FMF in the attack-free period. A total of 161 participants were recruited from the rheumatology department in this single-centre, case-control study. Participants meeting the eligibility criteria were divided into healthy controls (n = 80) and FMF (n = 81). The laboratory data were obtained from the electronic registration database. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid, 3-hydroxykynurenine (3HK), and quinolinic acid (QUIN) concentrations were measured with tandem mass spectrometry. Laboratory findings of FMF patients and healthy controls subjects were compared and evaluated. Serum TRP and KYNA levels were significantly decreased in both FMF groups compared to the control group, while the levels of KYN, QUIN, 3HK, the KYN/TRP ratio, and red cell distribution width were higher. TRP degradation by the KP is increased in patients with FMF. KP metabolites can be useful in demonstrating subclinical inflammation.

Urine neopterin in childhood acute demyelinating diseases: Potential for differential diagnosis

Inflammatory demyelinating diseases of the central nervous system (CNS) in childhood include clinically and radiologically defined diseases such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Differentiation between these phenotypes can be difficult and cases not meeting established diagnostic criteria may remain without any specific diagnosis for months. Laboratory markers can assist in the diagnosis and management of these diseases. Previous studies suggest serum kynurenine-tryptophan pathway products and serum neopterin as biomarkers for CNS autoimmune diseases. Because urine is a reliable and repeatable source for analysis of these products with the additional advantage of easy sampling, we measured neopterin concentrations in serum and urine samples, urinary biopterin and serum kynurenine-tryptophan levels in autoimmune demyelinating diseases of CNS: pediatric multiple sclerosis (pMS, n = 27), MOGAD (n = 10), NMOSD (n = 5) patients and a control group consisting of healthy children or children with non-inflammatory diseases (n = 13), total 55 children. Methods were high performance liquid chromatography (HPLC) for neopterin, biopterin and creatinine in urine and kynurenine and tryptophan in serum; ELISA was used for serum neopterin. Comparison for biomarkers between all diagnostic groups showed urinary neopterin values were significantly higher in the pMS group (p = 0.002). The cut-off point determined by ROC analysis indicated urinary neopterin >167.75 µmol/mol creatinine could distinguish the patients from the controls with a sensitivity of 71% and specificity of 90%. The most significant difference was between the pMS and control groups (p = 0.002) while no difference was observed between pMS patients who were in relapse or stable state. Therefore, urinary neopterin appeared as a potential marker that could differentiate pMS from other demyelinating patient groups MOGAD and NMOSD as well as from controls. The fact that pteridine pathway products had not been studied in urine and serum in children with demyelinating disease before highlights the novelty of this study. If further research in larger samples confirm the present results, these molecules might assist the differential diagnosis of pMS from other demyelinating CNS diseases.

Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine

Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.

The impact of bariatric surgery on serum tryptophan\u2013kynurenine pathway metabolites

This study aims to explore the immediate effects of bariatric surgery on serum tryptophan–kynurenine pathway metabolites in individuals with type 2 diabetes and BMI > 30. With the goal of providing insight into the link between tryptophan pathway metabolites, type 2 diabetes, and chronic obesity-induced inflammation. This longitudinal study included 20 participants. Half were diagnosed with type 2 diabetes. 11 and 9 underwent RYGB and SG respectively. Blood samples were obtained at pre-operative and 3 months post-operative timepoints. Tryptophan and downstream metabolites of the kynurenine pathway were quantified with an ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionisation method. At 3 months post-operation, RYGB led to significant reductions in tryptophan, kynurenic acid and xanthurenic acid levels when compared to baseline. Significant reductions of the same metabolites after surgery were also observed in individuals with T2D irrespective of surgical procedure. These metabolites were significantly correlated with serum HbA1c levels and BMI. Bariatric surgery, in particular RYGB reduces serum levels of tryptophan and its downstream kynurenine metabolites. These metabolites are associated with T2D and thought to be potentially mechanistic in the systemic processes of obesity induced inflammation leading to insulin resistance. Its reduction after surgery is associated with an improvement in glycaemic control (HbA1c).

Simultaneous determination of tryptophan, 5-hydroxytryptophan, tryptamine, serotonin, and 5-HIAA in small volumes of mouse serum using UHPLC-ED

In this paper we report a simple and efficient method for the concurrent analysis of tryptophan, 5-HTP, tryptamine, serotonin, and 5-HIAA in mouse serum using UHPLC-ED after protein precipitation and dilution. These compounds are neuroactive and are of interest in studies of mood and behavior; They are also biomarkers for the presence of neuroendocrine tumors and are used in the diagnosis of these cancers. After a brief series of validation experiments, this method was applied to serum from mouse behaviour experiments.•A convenient UHPLC method with electrochemical detection for concomitant analysis of the serotonin pathway in serum, including, for the first time, tryptamine.•The method met all performance criteria established for use in our lab and was applied in rodent experiments.

Simultaneous Determination of Serum Tryptophan Metabolites in an Elderly Chinese Population

Simultaneous Determination of Serum Tryptophan Metabolites in an Elderly Chinese Population

Simultaneous Determination of Serum Tryptophan Metabolites in an Elderly Chinese Population

Simultaneous Determination of Serum Tryptophan Metabolites in an Elderly Chinese Population

Tryptophan, Kynurenine and Kynurenic Acid Concentrations in Milk and Serum of Dairy Cows with Prototheca Mastitis.

Simple SummaryBovine mastitis continues to be a leading cause of heavy economic losses in the dairy industry worldwide. Among a broad spectrum of infectious agents implicated in this pathology are unicellular, achlorophyllous microalgae of the genus Prototheca. The prevalence of mastitis due to Prototheca algae is currently increasing. The aim of this work was to explore a possible association of the kynurenine pathway of tryptophan metabolism with Prototheca mastitis. The authors were eager to know whether metabolites of tryptophan degradation can be used as markers of the protothecal bovine mastitis. Both tryptophan and its metabolite kynurenine occurred at a significantly lower level in the milk of cows with mastitis compared to healthy animals. Whereas the activity of indoleamine 2,3-dioxygenase, a key enzyme of tryptophan catabolism, was significantly higher in milk of mastitic cows compared to control animals. It was thus concluded that low values of tryptophan and kynurenine concentrations or elevated indoleamine 2,3-dioxygenase activity in milk samples can be used as markers of mastitis due to Prototheca spp.The aim of this work was to investigate serum and milk levels of tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA), as well as the activity of indoleamine 2,3-dioxygenase (IDO) in cows with mastitis due to Prototheca algae. The study was prompted by previous research showing a link between the KYN pathway of TRP metabolism and bovine mastitis of bacterial etiology. The study was carried out over a 2-year period (2018–2019) and included quarter milk and serum samples collected from six dairy herds in Poland. The samples were obtained from healthy cows and cows with Prototheca mastitis of either clinical and subclinical manifestation, as determined upon direct measurement of the somatic cell count or indirectly by performing a California Mastitis Test on suspected quarters. Both TRP and KYN concentrations were significantly lower in milk of mastitic cows compared to healthy animals (0.8 vs. 8.72 µM, p = 0.001; 0.07 vs. 0.32 µM, p = 0.001, respectively). The difference in TRP and KYN concentrations in the sera of the two animal groups was much less pronounced (25.55 vs. 27.57 µM, 3.03 vs. 3.56 nM, respectively). The concentration of KYNA was almost at the same level in milk (1.73 vs. 1.70 nM) and in serum (80.47 vs. 75.48 nM) of both mastitic and healthy cows. The data showed that the level of TRP and its metabolites in serum was conspicuously higher compared to milk in all cows under the study. The activity of IDO was significantly higher in milk of cows with Prototheca mastitis compared to healthy animals (71.4 vs. 40.86, p < 0.05), while in serum it was pretty much the same (135.94 vs. 124.98, p > 0.05). The IDO activity differed significantly between serum and milk both for mastitic (135.94 vs. 71.4, p < 0.05) and healthy cows (124.98 vs. 40.86, p < 0.001). In conclusion, low values of TRP and KYN concentrations or elevated IDO activity in milk samples might be used as markers of mastitis due to infectious causes, including Prototheca spp.

Evaluation of Serum and Urine Amino Acids in Dogs with Chronic Kidney Disease and Healthy Dogs Fed a Renal Diet.

This observational study aimed to evaluate serum and urinary amino acid (AA) concentrations in healthy dogs and dogs with chronic kidney disease (CKD) fed a commercial therapeutic renal diet with reduced protein and phosphorus levels. Ten dogs with CKD stages 3 or 4 composed the study group and received the renal diet for 180 days (RG T180). A control group (CG T30) composed of seven healthy dogs was fed a renal diet for 30 days. When comparing serum AA between RG T180 and CG T30, histidine, isoleucine, leucine, lysine, phenylalanine, tryptophan, cysteine, citrulline, ornithine, taurine, branched-chain amino acids (BCAA), and total essential amino acids (EAA) were higher in RG T180. Meanwhile, arginine, asparagine, aspartate, glutamine, serine, and tyrosine were higher in CG T30. Serum phenylalanine, tryptophan, and hydroxyproline were higher in RG T0 (dogs with CKD before consuming a renal diet) when compared to RG T180. In addition, the serum ratios of arginine/citrulline, tyrosine/phenylalanine, and serine/glycine were higher in CG T30 than in RG T180. Concerning urinary AA concentrations in CKD dogs, isoleucine, phenylalanine, tryptophan, aspartate, cysteine, and BCAA were higher in RG T180. In urine, the total EAA/total non-essential AA ratio in RG T180 was higher than in CG T30 as well as tyrosine/phenylalanine ratio higher in CG T30. In conclusion, the combination of renal diet and conservative treatment over 6 months in dogs with CKD stages 3 or 4 affected the AAs metabolism when compared to healthy adult dogs.

Content of tryptophan and kynurenines in serum and milk of dairy cows with mastitis caused by Streptococcus spp.

The aim of the study was to investigate serum and milk concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA), and activity of indoleamine 2,3-dioxygenase (IDO) in cows suffering from mastitis caused by Streptococcus spp. The blood and milk samples were collected from Holstein-Friesian cows farmed in the Lublin region of Poland. It was found that TRP was lower in cows with mastitis both in serum and milk. KYN was lower in serum but not in milk. KYNA was not significantly altered in diseased cows both in serum and milk. The activity of IDO calculated as KYN to TRP ratio was unchanged in serum but was markedly elevated in milk of cows with mastitis. Our findings may have important implications for diagnosis of mastitis in cows because an increase of activity of IDO and reduction of TRP in milk might be a valuable early marker predicting the occurrence of the disease.

Dietary tryptophan, tyrosine, and phenylalanine depletion induce reduced food intake and behavioral alterations in mice

Important precursors of monoaminergic neurotransmitters, dietary tryptophan (TRP), tyrosine, and phenylalanine (all referred to as TTP), play crucial roles in a wide range of behavioral and emotional functions. In the current study, we investigated whether diets devoid of TTP or diets deficient in TRP alone can affect body weight, behavioral characteristics, and gut microbiota, by comparing mice fed on these amino acids-depleted diets to mice fed on diets containing regular levels of amino acids. Both dietary TTP- and TRP-deprived animals showed a reduction in food intake and body weight. In behavioral analyses, the mice fed TTP-deprived diets were more active than mice fed diets containing regular levels of amino acids. The TRP-deprived group exhibited a reduction in serum TRP levels, concomitant with a decrease in serotonin and 5-hydroxyindoleacetic acid levels in some regions of the brain. The TTP-deprived group showed a reduction in TTP levels in the serum, concomitant with decreases in both phenylalanine and tyrosine levels in the hippocampus, as well as serotonin, norepinephrine, and dopamine concentrations in some regions of the brain. Regarding the effects of TRP or TTP deprivation on gut microbial ecology, the relative abundance of genus Roseburia was significantly reduced in the TTP-deprived group than in the dietary restriction control group. Interestingly, TTP was found even in the feces of mice fed TTP- and TRP-deficient diets, suggesting that TTP is produced by microbial or enzymatic digestion of the host-derived proteins. However, microbe generated TTP did not compensate for the systemic TTP deficiency induced by the lack of dietary TTP intake. Collectively, these results indicate that chronic dietary TTP deprivation induces decreased monoamines and their metabolites in a brain region-specific manner. The altered activities of the monoaminergic systems may contribute to increased locomotor activity.

Quantifying Serum Total Lipids and Tryptophan Concentrations by Raman Spectroscopy During Standardized Obstacle Course in Horses

Raman spectroscopy is an inelastic light-scattering phenomenon that provides vibrational spectrum that contains information relative to chemical bonds and symmetry of a specific molecule, allowing the quali-quantitative simultaneous determination of several components in the biological fluids. Raman spectroscopy measurement returns a spectrum over a wavenumber range constituted by several bands representing biomarkers according to investigated biological matrices. In literature, it has been reported that at the frequencies inside the (1,300–1,360) cm−1 total lipids, and tryptophan have been identified. On the basis of that, the aim of the present study was to compare the serum concentration of total lipids and tryptophan in horses subjected to a standardized obstacle course, in comparison with the data obtained in the (1,300–1,360) cm−1 band. At this purpose, five clinically healthy and regularly trained Italian Saddle horses aged between 8, and 10 years old performed with the same rider an obstacle course of 350 m/min with twelve 1.30 m high jumps preceded by warm-up. Blood samples were collected by means of jugular venipuncture into a vacutainer tubes with clot activator at rest, after the exercise, and 30 minutes after the end of exercise. A high correlation was observed between the area of total lipids and tryptophan in the (1,300–1,360) cm−1 band and their serum concentrations in all experimental conditions. Our preliminary results give a hint to study the exact correspondence between the area that identify these parameters in Raman spectrum and their serum concentration in athletic horses.

Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis

Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy.

Association of serum kynurenine/tryptophan ratio with poor glycemic control in patients with type2 diabetes.

The role of indoleamine 2,3-dioxygenase (IDO) has been shown in insulin resistance and metabolic syndrome. The present study aimed to measure serum IDO activity in patients with type 2 diabetes (T2DM) and to determine its association with glycemic control, oxidative stress, and insulin resistance. Seventy-four patients with T2DM and 74 healthy subjects were selected to participate in this study. Fasting serum biochemical parameters including fasting blood sugar (FBS), HbA1c, insulin, uric acid, albumin, tryptophan, kynurenine, and total antioxidant capacity (TAC) were measured. HOMA-IR, QUICKI, and HOMA-B were calculated using serum FBS and insulin values. IDO activity was estimated using kynurenine/tryptophan ratio (KTR). Data were analyzed using SPSS software (Version 15) and p < 0.05 was considered as a significant difference. The findings showed higher levels of FBS, HbA1c, HOMA-IR, and KTR in the patients compared to the controls. TAC and HOMA-B were significantly lowered in the T2DM patients compared to controls. KTR was significantly correlated with the level of HbA1c, and T2DM patients with poor glycemic control (HbA1c ≤ 8) had significantly higher level of KTR. HOMA-B was significantly correlated with serum tryptophan and inversely correlated with HbA1c. Serum KTR is increased in T2DM patients with poor glycemic control. Potential clinical implications and possible pathogenic roles of IDO in T2DM development should be further elucidated.

The Impact of Cardiovascular Rehabilitation on Psychophysiological Stress, Personality and Tryptophan Metabolism: A Randomized Pilot Feasibility Study.

Multicomponent cardiac rehabilitation (CR) is a secondary prevention strategy for cardiac patients to tackle stress and psychosocial wellbeing. However, there is a lack of data on its psychoneuroimmunological effects and of biomarkers to determine individual risk and to develop treatment strategies. We conducted a pilot randomized controlled trial (RCT) to investigate the feasibility of deriving psychophysiological stress markers in patients with cardiovascular diseases. Thirty individuals with cardiovascular disease (mean age 58.8 years; 23.3% female) were enrolled and randomized into three treatment groups: standard rehabilitation, yoga, or transcendental meditation (TM). Depression, anxiety, sleep, stress perception, personality functioning, hair cortisol, serum tryptophan, kynurenine and neopterin concentrations were estimated at baseline and after a four-week intervention. Hair cortisol levels decreased significantly after rehabilitation in all groups (F = 15.98, p < 0.001). In addition, personality functioning improved in all patients over time. Participants with impairments in personality functioning showed a positive correlation with baseline neopterin that did not remain significant after Bonferroni correction. Concentrations of serum tryptophan and its metabolite kynurenine did not change significantly. This pilot RCT provides preliminary evidence of multicomponent CR leading to stabilization of hair cortisol levels and improved psychophysiological wellbeing and personality functioning. Impairments in personality functioning were correlated with neopterin levels, which may impact the symptomatology and outcome.

Effects of Lactococcus lactis on the Intestinal Functions in Weaning Piglets.

Post-weaning diarrhea of piglets is associated with gut microbiota dysbiosis and intestinal pathogen infection. Recent studies have shown that Lactococcus lactis (L.lactis) could help suppress pathogen infection. This study aimed to investigate the effects of L.lactis on various factors related to growth and immunity in weaning piglets. The results showed that L.lactis improved the growth performance, regulated the amino acid profile (for example, increasing serum tryptophan and ileal mucosal cystine) and the intestinal GABAergic system (including inhibiting ileal gene expression of SLC6A13, GABAAρ1, π, θ, and γ1, and promoting ileal GABAAα5 expression). L.lactis also modulated intestinal immunity by promoting jejunal interleukin 17, 18, 22, ileal toll-like receptor 2, 5, 6, and myeloid differentiation primary response protein 88 gene expression while inhibiting jejunal interferon-γ and ileal interleukin 22 expressions. L.lactis highly affected the intestinal microbiota by improving the beta diversity of gut microbiota and the relative abundance of Halomonas and Shewanella. In conclusion, L.lactis improved the growth performance and regulated amino acid profiles, intestinal immunity and microbiota in weaning piglets.

Prospective study on the association between serum amino acid profiles and depressive symptoms among the Japanese working population

ObjectiveAccumulating evidence suggests that amino acids, particularly tryptophan and glutamate, play an important role in the pathology of depression, but prospective epidemiologic data on this issue is scarce. We examined the association between circulating amino acids and the risk of depressive symptoms in a Japanese working population.MethodsParticipants were 841 workers who were free from depressive symptoms and provided blood at baseline and completed 3-yr follow-up survey. 30 varieties of amino acid concentrations in serum were measured using liquid chromatography/mass spectrometry. Depressive symptoms were defined using the Center for Epidemiologic Studies Depression Scale. Logistic regression was used to calculate the odds ratios of depressive symptoms according to serum amino acids with adjustment for lifestyle factors.ResultsA total of 151 (18.0%) workers were newly identified as having depressive symptoms at the follow-up. Baseline tryptophan and glutamate concentrations in serum were not appreciably associated with the risk of depressive symptoms. Risk of depressive symptoms tended to increase with increasing arginine concentrations; the multivariable-adjusted odds ratio for the highest versus lowest tertile of serum arginine was 1.65 (95% confidence interval: 0.96–2.83; P for trend = 0.07). No clear association was found for other amino acids.ConclusionsResults of the present study do not support a significant role of circulating amino acids in the development of depressive symptoms among Japanese.

Altered kynurenine pathway metabolism in patients with ankylosing spondylitis

BackgroundVarious studies reported that increased proinflammatory cytokines in patients with ankylosing spondylitis (AS). Proinflammatory cytokines can affect the expression of various kynurenine pathway enzymes and therefore lead to metabolic changes that can affect the inflammatory response and immunity. Our aim was to measure serum levels of kynurenine pathway metabolites in patients with AS. MethodsThe study included 85 patients with AS and 50 healthy volunteers. Serum tryptophan, kynurenine, kynurenic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, quinolinic acid concentrations were measured with tandem mass spectrometry. In addition, participants were divided into four groups according to the treatment regimen: TNF-α inhibitor group, conventional therapy group, control group and newly diagnosed AS group. These groups were compared in terms of kynurenine pathways metabolites, interleukin 6 (IL-6), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. ResultsSerum tryptophan, kynurenic acid, 3-hydroxykynurenine levels were significantly decreased (p < 0.05) in both AS groups compared to the control group, while the levels of kynurenine, quinolinic acid, CRP, ESR, and IL-6 were higher (p < 0.05). The Kynurenine/Tryptophan ratio and CRP levels of the conventional therapy and anti-TNF therapy group were significantly lower than the newly diagnosed AS patients (p < 0.05). ConclusionAs a result of our study, we found that altered kynurenine pathway metabolism in patients with AS. Conventional therapy and anti-TNF-α therapy are effective in reducing the Kynurenine/Tryptophan ratio and CRP levels, although the effect of both treatments on other metabolites appears to be limited.

Effects of a Folic Acid 5 Mg Daily Intervention on Markers of Vitamin B Status and Kynurenine Pathway

BackgroundIn Brazil, most folic acid (FA) containing supplements contain 5 mg FA. This dose is usually prescribed for patients with chronic hemolytic anemia and for women planning pregnancy. The effects of high FA doses on vitamin B1, B2 and B6 status including the kynurenine pathway are still unclear.AimsTo assess the effects of a daily intervention with 5 mg FA in healthy subjects on vitamins B1, B2 and B6 serum marker status and serum concentration ok kynurenines.Material and MethodsThirty health subjects participated in a 5 mg/day FA intervention. Blood samples were obtained at baseline (D0) and after 45 (D45) and 90 days (D90) of intervention. We assessed serum concentrations of vitamin B6 (pyridoxal-5'-phosphate (PLP), pyridoxal (PL) and 4-pyridoxic acid (PA)), vitamin B2 (riboflavin and flavin mononucleotide (FMN)) and vitamin B1 vitamers (thiamine and thiamine monophosphate (TMP)), as well as tryptophan, kynurenine and several metabolites of tryptophan catabolism in the kynurenine pathway (3-hydroxykynurenine (HK), kynurenic acid (KA), anthranilic acid (AA), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), picolinic acid (Pic) and quinolinic acid (QA)) using LC-MS/MS. PA ratio (PAr) was calculated by PA/(PLP + PL). All variables were normalized by Box-Cox transformation. Comparisons were performed by repeated-measures ANOVA.ResultsConcentrations of all vitamin B6 vitamers (PLP, PL and PA), as well as PAr, were similar at baseline and D45 and D90 of FA intervention. No differences were found among serum vitamin B2 vitamers (riboflavin and FMN) after FA intervention. However, a trend for a decrease in serum TMP concentrations was observed at D90 (P = 0.054). No changes in serum tryptophan and all serum kynurenine pathway metabolites were observed after intervention with FA compared with baseline, except for AA, which was higher at D45 and D90 than baseline (P < 0.001).ConclusionOur data suggest that daily use of 5 mg FA by healthy subjects may interfere with vitamin B1 status markers. In addition, serum AA increased with FA intervention, which suggest that the use of high dose FA supplements might affect the kynurenine pathway.Financing: FAPESP (2016/18854-4) and CNPq (401586/2014-6) DisclosuresNo relevant conflicts of interest to declare.