Serum Amino Acid Levels Research Articles

Amino acids-targeted metabolomics reveals novel diagnostic biomarkers for ulcerative colitis and Crohn's disease.

Inflammatory bowel disease (IBD), which mainly comprises ulcerative colitis (UC) and Crohn's disease (CD), is a common chronic intestinal inflammatory disease that affects the ileum, rectum, and colon. Currently, the diagnosis of IBD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in amino acid metabolites in IBD serum and to identify potential predictive biomarkers of IBD diagnosis and progression. Serum samples were collected from 158 UC patients, 130 CD patients and 138 healthy controls (HCs). The 37 amino acids in serum were determined by ultra-high-pressure liquid chromatography coupled to a mass spectrometer. A panel of three-amino-acid metabolites (taurine, homocitrulline and kynurenine) was identified as a specific biomarker panel of IBD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 88.4% with a specificity of 84.6% for discriminating CD patients from UC patients. The biomarkers identified are increased in CD compared to UC. Our approach demonstrated a strong relationship between serum amino acid levels and IBD. We successfully identified serum amino acid biomarkers associated with CD and UC. The biomarker panel has potential in clinical practice for IBD diagnosis and will provide new insights into IBD pathogenesis.

A curious case of confusion

A curious case of confusion

Serum metabolic signatures of schizophrenia patients complicated with hepatitis B virus infection: A 1H NMR-based metabolomics study.

Schizophrenia (SZ) is a severe chronic mental disorder with increased risk of hepatitis B virus (HBV) infection, which is incurable currently and induces various negative emotions and psychological pressures in patients to exacerbate mental disorders. To facilitate the therapeutic design for SZ patients complicated with HBV infection (SZ + HBV), it is helpful to first elucidate the metabolic perturbations in SZ + HBV patients. In this study, metabolic profiles of the serum samples from four groups of participants comprising healthy controls (HC, n = 72), HBV infection (n = 52), SZ patients (n = 37), and SZ + HBV (n = 41) patients were investigated using a high-resolution 1H NMR-based metabolomics approach. Distinguishable metabolic profiles were found in the four groups. In comparison with HC, HBV infection induced increased levels of citrate and succinate to perturbate the tricarboxylic acid cycle and succinate-related pathways. Similar to SZ cases, SZ + HBV patients exhibited decreased glucose but increased citrate, pyruvate, and lactate, suggesting the occurrence of disturbance in glucose metabolism. Moreover, in comparison with HC, several serum amino acid levels in SZ + HBV patients were significantly altered. Our findings suggest that Warburg effect, energy metabolism disorders, neurotransmitter metabolism abnormalities, mitochondrial dysfunction and several disturbed pathways in relation to tyrosine and choline appear to play specific and central roles in the pathophysiology of SZ + HBV. Apart from replicating metabolic alterations induced by SZ and HBV separately (e.g., in energy metabolism and Warburg effect), the specific metabolic abnormalities in the SZ + HBV group (e.g., several tyrosine- and choline-related pathways) highlighted the existence of a synergistic action between SZ and HBV pathologies. Current study revealed the metabolic alterations specific to the interaction between SZ and HBV pathologies, and may open important perspectives for designing precise therapies for SZ + HBV patients beyond the simple combination of two individual treatments.

A prospective real-world study evaluating serum levels of arginine and cysteine in women with chronic telogen effluvium: do we really need blanket prescription of amino acid supplementation?

Amino acids form a major component of hair fibres and are prescribed routinely in the form of nutritional supplements in patients with chronic telogen effluvium (CTE). Such a practice is based on assumption of a nutritional deficiency state in such patients. In this prospective study, we evaluated the serum levels of cysteine and arginine in 30 women with CTE and in healthy controls. We found no significant difference between the two groups in terms of serum arginine levels. Cysteine levels were higher in patients with CTE (P < 0.001). No correlation was found between levels of serum amino acids (cysteine and arginine) and either diet type (vegetarian or not) or body mass index, and no significant correlation between levels of the two amino acids and severity of disease. Our work suggests that arginine and cysteine deficiency is not present in women with CTE. Supplementation is unlikely to be of any benefit in nutrient-replete populations and only adds to the cost of therapy.

Sarcopenia-related gut microbial changes are associated with the risk of complications in people with cirrhosis

Sarcopenia and gut dysbiosis are common in individuals with cirrhosis. However, the association between sarcopenia and microbial alterations, and the subsequent impact on cirrhotic outcomes are poorly understood. This study aimed to identify muscle-dependent microbial changes and related risks of cirrhotic complications. From September 2018 to December 2020, 89 individuals with cirrhosis and 16 healthy volunteers were prospectively enrolled. Muscle and nutritional status, serum amino acids, and fecal microbiota were analyzed. The association between microbial signatures of sarcopenia and cirrhotic complications was investigated. A decline in muscle mass and strength were associated with gut microbial alterations in individuals with cirrhosis. The greatest microbial dissimilarity was observed between those with sarcopenia (both decline in muscle mass and strength) and those with normal-muscle status (p= 0.035). Individuals with sarcopenia had lower serum levels of alanine, valine, leucine, isoleucine, proline, tryptophan and ornithine. Besides, gut microbial functions associated with amino acid biosynthesis were significantly reduced in individuals with sarcopenia and cirrhosis. Depletion of Dialister, Ruminococcus 2, and Anaerostipes were associated with cirrhotic sarcopenia, and significantly correlated with the serum levels of amino acids. Individuals with coexistent depletion of Ruminococcus 2 and Anaerostipes developed more infectious (44.4% vs. 3.0%) and non-infectious (74.1% vs. 3.0%) complications, and more hospitalizations (54 vs. 3) than those with cirrhosis with good microbial signatures (all p <0.001). In contrast, fecal enrichment of Ruminococcus 2 and Anaerostipes independently decreased the risk of 1-year complications. Sarcopenia-related fecal microbial alterations are associated with cirrhotic complications. These findings may facilitate measures to improve the outcomes of individuals with cirrhosis and sarcopenia by modifying gut microbiota. The composition and biosynthetic functions of gut microbiota are significantly changed in individuals with sarcopenic cirrhosis. Those with a sarcopenia-related poor microbial signature, in which Ruminococcus 2 and Anaerostipes were both depleted, had significantly more infectious and non-infectious complications, as well as more hospitalizations. These findings highlight the therapeutic potential of modifying the gut microbiota of individuals with sarcopenic cirrhosis to improve their clinical outcomes.

Serum diamine oxidase activity derived from response to chemotherapy affects adverse events and serum amino acid levels.

The relationship between activity of the small intestinal villi and the effectiveness of chemotherapy remains unclear. This study aimed to investigate how serum diamine oxidase (DAO) activity affects antitumor effects, adverse events, and amino acid absorption. We performed a single-center prospective cohort study that enrolled 50 patients with esophageal cancer (EC) receiving docetaxel, cisplatin, and 5-fluorouracil therapy. We determined the cut-off value of serum DAO activity contributing to a response to chemotherapy using a generalized additive model. Additionally, we compared adverse events, inflammatory markers, blood amino acid levels, and quality of life between the high and low DAO activity groups during chemotherapy. The cut-off value of serum DAO activity at the first visit that contributed to a chemotherapy response was 6.5 units/L. Leukopenia and neutropenia of grade ≥ 3 were significantly higher in the DAO low (< 6.5 units/L) group (p = 0.044, 0.017, respectively). Interleukin-6 was significantly lower in the DAO high (≥ 6.5 units/L) group at the first visit and at 4weeks after the end of chemotherapy (p = 0.039, 0.011, respectively). Glutamine was higher in the DAO high group at all measurement points during chemotherapy. Fatigue was significantly lower in the DAO high group (p = 0.001). Serum DAO activity may be a predictor of the response to chemotherapy in patients with EC. The absorption capacity of amino acids was maintained in the group with high DAO activity, which may have contributed to the anti-inflammatory effect and provided a background for reducing adverse events.

Analysis of serum fatty acid, amino acid, and organic acid profiles in gestational hypertension and gestational diabetes mellitus via targeted metabolomics.

This study aimed to characterize metabolite differences and correlations between hypertensive disorders of pregnancy (HP) and gestational diabetes mellitus (GDM) using univariate, multivariate analyses, RF, and pathway analyses in a cross-sectional study. Dietary surveys were collected and targeted metabolomics was applied to measure levels of serum fatty acids, amino acids, and organic acids in 90 pregnant women at 24–28 weeks gestation at the First Affiliated Hospital of Harbin Medical University. Principal components analysis (PCA) and partial least squares-discriminatory analysis (PLS-DA) models were established to distinguish HP, GDM, and healthy, pregnant control individuals. Univariate and multivariate statistical analyses and Random Forest (RF) were used to identify and map co-metabolites to corresponding pathways in the disease states. Finally, risk factors for the disease were assessed by receiver operating characteristics (ROC) analysis. Dietary survey results showed that HP and GDM patients consumed a high-energy diet and the latter also consumed a high-carbohydrate and high-fat diet. Univariate analysis of clinical indices revealed HP and GDM patients had glycolipid disorders, with the former possessing more severe organ dysfunction. Subsequently, co-areas with significant differences identified by basic discriminant analyses and RF revealed lower levels of pyroglutamic acid and higher levels of 2-hydroxybutyric acid and glutamic acid in the GDM group. The number of metabolites increased in the HP group as compared to the healthy pregnant control group, including pyroglutamic acid, γ-aminobutyric acid (GABA), glutamic acid, oleic acid (C18:1), and palmitic acid (C16:0). ROC curves indicated that area under curve (AUC) for pyroglutamic acid in the GDM group was 0.962 (95% CI, 0.920–1.000), and the AUC of joint indicators, including pyroglutamic acid and GABA, in the HP group was 0.972 (95% CI, 0.938–1.000). Collectively, these results show that both GDM and HP patients at mid-gestation possessed dysregulated glucose and lipid metabolism, which may trigger oxidative stress via glutathione metabolism and biosynthesis of unsaturated fatty acids.

Untargeted Metabolomics Reveals the Function of GPRC6A in Amino Acid and Lipid Metabolism in Mice.

GPRC6A is an amino acid sensor in the cytomembrane. Despite substantial evidence for the role of GPRC6A in metabolism, the specific effects and mechanism by which this gene acts on metabolic processes are still unresolved. In this study, serum biochemical parameters related to liver and kidney function and serum amino acid levels were determined in GPRC6A wild-type (WT) and knockout (KO) mice. An untargeted serum metabolomics analysis was also conducted for the first time, to the best of our knowledge, to decipher the function of GPRC6A in metabolic processes. GPRC6A was involved in lipid and amino acid metabolism, mainly by affecting liver function. A loss of GPRC6A function may perturb bile acid metabolism, thus leading to abnormal unsaturated fatty acid metabolism. GPRC6A KO may lead to excessive protein breakdown under starvation, and the loss of GPRC6A had a significant effect on phenylalanine metabolism-related pathways. Our metabolomics data provide a novel basis for further functional studies of GPRC6A.

A wearable electrochemical biosensor for the monitoring of metabolites and nutrients.

Wearable non-invasive biosensors for the continuous monitoring of metabolites in sweat can detect a few analytes at sufficiently high concentrations, typically during vigorous exercise so as to generate sufficient quantity of the biofluid. Here we report the design and performance of a wearable electrochemical biosensor for the continuous analysis, in sweat during physical exercise and at rest, of trace levels of multiple metabolites and nutrients, including all essential amino acids and vitamins. The biosensor consists of graphene electrodes that can be repeatedly regenerated in situ, functionalized with metabolite-specific antibody-like molecularly imprinted polymers and redox-active reporter nanoparticles, and integrated with modules for iontophoresis-based sweat induction, microfluidic sweat sampling, signal processing and calibration, and wireless communication. In volunteers, the biosensor enabled the real-time monitoring of the intake of amino acids and their levels during physical exercise, as well as the assessment of the risk of metabolic syndrome (by correlating amino acid levels in serum and sweat). The monitoring of metabolites for the early identification of abnormal health conditions could facilitate applications in precision nutrition.

Role of the gut-microbiota-metabolite axis in the rotenone model of early-stage Parkinson's Disease.

Gastrointestinal symptoms are common in the early-stage Parkinson's disease (PD), but its potential pathogenesis remains unclear. Therefore, in the present study, we used the 16S ribosomal RNA gene sequencing and gas chromatography coupled with mass spectrometry-based metabolomics to investigate the alterations of gut microbiome and serum amino acid levels in the early-stage PD mice model induced with rotenone. The results demonstrated that the microbial taxa at phylum, family and genus levels remarkably altered in rotenone-induced mice relative to vehicle-induced mice. The rotenone-induced mice had higher relative abundance of Flavobacteriaceae, Staphylococcaceae, and Prevotellaceae as well as lower relative abundance of Lachnospiraceae_UCG-001, Ruminiclostridium, and Prevotellaceae_NK3B31_group than vehicle-induced mice. The evaluation of serum amino acids revealed the alterations in several classes of amino acids, including L-proline, L-alanine, L-serine, L-asparagine, L-threonine, L-glutamine, L-methionine, and L-4-hydroxyproline. Notably, the altered serum amino acid levels were significantly associated with the abundance of gut microbiota, especially Ruminococcaceae and Ruminiclostridium. Our study explored the possible role of the gut-microbiota-metabolite axis in the early-stage PD and provided the possibility of prevention and treatment of PD by gut-microbiota-metabolite axis in the future.

Characterizing serum amino acids in schizophrenic patients: Correlations with gut microbes

Amino acid abnormalities have been suggested to be a key pathophysiological mechanism in schizophrenia (SZ). Recently, gut microbes were found to be critically involved in mental and metabolic diseases. However, the relationship between serum amino acid levels and gut microbes in SZ is rarely studied. Here, we analyzed serum amino acid levels in 76 untreated SZ patients and 79 healthy controls (HC). Serum levels of 10 amino acids were significantly altered in patients with SZ. We further classified the cut-off values for serum arginine, leucine, glutamine, and methionine levels to distinguish SZ patients from controls. These classifiers were shown to be effective in another validation cohort (49 SZ and 48 HC). The correlation between serum amino acids and clinical symptoms and cognitive functions was also analyzed. Arginine, leucine, glutamine, and methionine levels were significantly correlated with clinical symptoms and cognitive impairments in SZ patients. By metagenome shotgun sequencing of fecal samples, we found that patients with SZ with a low level of serum amino acids have higher richness and evenness of the gut microbiota. At the genus level, the abundances of Mitsuokella and Oscillibacter are significantly abnormal. At the mOTU level, 15 mOTUs in the low-level SZ group were significantly different from the HC group. In addition, Mitsuokella multacida was correlated with glutamine and methionine, respectively. Our research revealed that alterations in serum amino acid levels are critically related to changes in gut microbiota composition in SZ patients. These findings may shed light on new strategies for the diagnosis and treatment of SZ.

Consumption of Different Egg-Based Diets Minimally, yet Differentially, Impacts Markers Insulin Resistance in Young Healthy Adults

ObjectivesPrevious epidemiological studies have reported conflicting associations between egg consumption and type 2 diabetes mellitus (T2DM) risk. However, many observational, survey-based studies do not fully characterize intake of additional egg-based foods or clearly differentiate between type of egg consumed. Thus, we investigated whether daily intake of whole eggs, egg whites, or an egg-free diet differentially altered markers of T2DM risk in young healthy adults. MethodsYoung, healthy men and women (18–35 y, BMI < 30 kg/m2 or <30% body fat for men and < 40% body fat for women, n = 26) participated in a randomized, crossover intervention trial where they followed an egg-free diet for 4 weeks, then were randomized to consume either 3 whole eggs or 3 egg whites per day for 4 weeks. Participants then followed a 4-week egg-free diet washout period, before switching to the alternative whole egg or egg white diet treatment. Additional egg-based foods were restricted. Fasting serum samples were collected at the end of each diet period to measure markers of T2DM risk. ResultsAverage fasting serum glucose was 90.7 mg/dL at baseline, and did not significantly change between the egg-free, egg white, or whole egg diet periods. Similarly, there were no changes in pro-inflammatory N-acetylglucosamine/galactosamine (GlycA), which is an independent predictor of insulin resistance (IR). Serum amino acids levels were further assessed, as elevated branched-chain amino acids and reduced glycine levels are predictors of prediabetes, IR, and future T2DM. Interestingly, isoleucine levels were increased following the egg white and whole egg diet as compared to the egg-free diet, whereas glycine levels were increased in by the whole egg diet only. Despite these differences, lipoprotein IR index (LP-IR) scores, which take into account NMR lipoprotein particle profiles, and diabetes risk index scores, which are calculated from LP-IR and branched-chain amino acid measures, did not change over the course of the intervention. ConclusionsOur findings indicate that eggs minimally impact IR markers in young healthy adults, with egg whites yielding more adverse changes than whole eggs. Funding SourcesThis study was funded by an Agriculture and Food Research Initiative Grant from the USDA National Institute of Food and Agriculture.

Serum Amino Acid Profiles Predict the Development of Hepatocellular Carcinoma in Patients with Chronic HBV Infection.

Background: The study aimed to find out the alterations in serum amino acid (AA) profiles and to detect their relationship with carcinoma formation. Methods: Targeted metabolomics based on ultraperformance liquid chromatography triple quadrupole mass spectrometry to quantitatively analyze serum AA levels in 136 hepatitis B (CHB) patients and 93 hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. Results: It was shown that decreased serum levels of leucine, lysine, threonine, tryptophan, valine, serotonin, and taurine were observed in more HCC patients than CHB patients, but the serum phenylalanine level was increased. Serum valine and serotonin were lower in Class C than Class A and Class B in HCC patients. Accompanied with the higher score of Model for End-Stage Liver Disease, serum phenylalanine was increased not only in CHB patients but also in HCC patients. The serum level of phenylalanine increased in the decompensated stage more than in the compensated stage, while serum leucine and serotonin significantly decreased. Serum serotonin still had significant differences between CHB and HCC both in the HBV desoxyribonucleic acid (HBV-DNA) negative group and in the HBV-DNA positive group. Furthermore, it was shown that the tryptophan ratio, branched-chain amino acids (BCAA)/aromatic amino acids ratio, BCAAs/tyrosine ratio, Fischer’s ratio, and serotonin-to-tryptophan ratio significantly decreased, while the tyrosine ratio and the kynurenine-to-tryptophan ratio increased in HCC patients more than those in CHB. Conclusions: A distinct metabolite signature of some specific serum amino acids was found between CHB and HCC patients, which may help predict the development of HCC at an early stage.

Changes in serum amino acid levels in non-small cell lung cancer: a case-control study in Chinese population.

BackgroundPrevious studies have shown the alteration of amino acid (AA) profile in patients with non-small cell lung cancer (NSCLC). However, there is little data regarding AA profile in NSCLC in Chinese population. The aim of this study was to evaluate AA profile in Chinese NSCLC patients, explore its utility in sample classification and further discuss its related metabolic pathways.MethodsThe concentrations of 22 AAs in serum samples from 200 patients with NSCLC and 202 healthy controls were determined by liquid chromatography-tandem mass spectrometer (LC-MS/MS). AA levels in different tumor stages and histological types were also discussed. The performance of AA panel in classifying the cases and controls was evaluated in the training data set and validation data set based on the receiver operating characteristic (ROC) curve, and the important metabolic pathways were identified.ResultsThe concentrations of tryptophan (Trp), phenylalanine (Phe), isoleucine (Ile), glycine (Gly), serine (Ser), aspartic acid (Asp), asparagine (Asn), cystein (Cys), glutamic acid (Glu), ornithine (Orn) and citrulline (Cit) were significantly altered in NSCLC patients compared with controls (all P-FDR < 0.05). Among these, four AAs including Asp, Cys, Glu and Orn were substantially up-regulated in NSCLC patients (FC ≥ 1.2). AA levels were significantly altered in patients with late-stage NSCLC, but not in those with early-stage when comparing with healthy controls. In terms of histological type, these AAs were altered in both adenocarcinoma and squamous cell carcinoma. For discrimination of NSCLC from controls, the area under the ROC curve (AUC) was 0.80 (95% CI [0.74–0.85]) in the training data set and 0.79 (95%CI [0.71–0.87]) in the validation data set. The AUCs for early-stage and late-stage NSCLC were 0.75 (95% CI [0.68–0.81]) and 0.86 (95% CI [0.82–0.91]), respectively. Moreover, the model showed a better performance in the classification of squamous cell carcinoma (AUC = 0.90, 95% CI [0.85–0.95]) than adenocarcinoma (AUC = 0.77, 95% CI [0.71–0.82]) from controls. Three important metabolic pathways were involved in the alteration of AA profile, including Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism; and Arg biosynthesis.ConclusionsThe levels of several AAs in serum were altered in Chinese NSCLC patients. These altered AAs may be utilized to classify the cases from the controls. Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism and Arg biosynthesis pathways may play roles in metabolism of the NSCLC patient.

Metabolomics research on the effect of dexamethasone‐induced chronic stress in serum of rabbits

Stress is a common factor that reduces production performance. However, the physiology of stress is not fully understood. In this study, 40-day-old rabbits were injected 1.0 mg/kg BW Dexamethasone to induce stress. A metabolomic study on serum of stress-induced rabbits was performed to research the metabolism mechanism of stress by using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC–MS). Clear separations between stress rabbits and control rabbits were observed by principal component analysis (PCA) based on the data obtained using both analytical techniques and 90 significantly changed metabolites were identified as potential biomarkers of stress. Stress rabbits were characterised by altered levels of serum lysophosphatidylcholines, amino acids, phosphatidyl choline, and nucleosides, which were related to multiple perturbed metabolic pathways and contributed to the elucidation of the complex mechanism of stress. These were main linked to three different pathways: pyrimidine metabolism, aminoacyl-tRNA biosynthesis, and biosynthesis of amino acid. In summary, we provided a comprehensive understanding of metabolic alterations in the main stress-targeted tissues, helping to understand the potential mechanisms underlying stress. HIGHLIGHTS Stress alters the metabolic composition of serum in rabbits. In rabbits, dexamethasone‐induced chronic stress alters 90 metabolites in serum.

Procena aminokiselinskog profila u serumu pacijenata sa Covid-19 za obezbeđivanje nove strategije lečenja

Amino acids have an important role in metabolism and may affect COVID-19-related outcomes. In our study, the amino acid serum level of hospitalized COVID19 patients was evaluated to determine a new treatment strategy. The amino acid profile covering 43 amino acids in 68 subjects, comprising 30 (14 men and 16 women) controls and 38 (16 men and 22 women) COVID-19 patients, were examined. The amino acid profiles of the participants were screened by LC-MS/MS. Compared with the control group, serum levels of 27 amino acids increased in the patient group. Alpha-aminopimelic acid, sarcosine, and hydroxyproline amino acids were considerably higher in the control group than in the patient group (p<0.0001). There was no notable difference among control group and the case group for 13 amino acids (p≥0.05). A significant positive correlation was seen among the control and the patient groups in the mean amino acid values (r=0.937; p<0.0001). These results postulated a clear picture on the serum levels of amino acid in the COVID-19 patients. Serum amino acids measured in hospitalized COVID-19 patients can explain the patient's metabolic status during the disease.

Assessment of serum amino acids profile in adult patients with Crohn’s disease

Rationale: Amino acids (AAs) act as the key regulatory factor in controlling metabolic pathways and have important effects on keeping the intestinal health. Different studies described altered serum AAs levels in patients with Crohn’s disease (CD), a chronic inflammatory disorder of the gastrointestinal tract, highlighting a potential link between the concentration of AAs and CD. The aim of this study was to assess serum AAs profile in patients with CD and its correlation with disease severity.

Relationship Between Serum Amino Acid Levels and Bone Mineral Density: A Mendelian Randomization Study.

BackgroundThis study aimed to explore the association between serum amino acids (AAs) levels and bone mineral density (BMD).MethodsWe performed a two-sample Mendelian randomization (MR) analysis to analyze the associations between the levels of eight AAs and BMD values by using summary-level genome-wide association study (GWAS) data. We applied the MR Steiger filtering method and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test to check for and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic. The associations were estimated with the inverse variance weighted (IVW), MR-Egger, weighted median and MR Robust Adjusted Profile Score (MR.RAPS) methods.ResultsOur study found that genetically increased isoleucine (Ile) [IVW: effect = 0.1601, 95% confidence interval (CI) = 0.0604 ~ 0.2597, p = 0.0016] and valine (Val) levels (IVW: effect = 0.0953, 95% CI = 0.0251 ~ 0.1655, p = 0.0078) were positively associated with total body BMD (TB-BMD). The results also revealed that genetically increased tyrosine (Tyr) levels were negatively associated with TB-BMD (IVW: effect = -0.1091, 95% CI = -0.1863 ~ -0.0320, p = 0.0055).ConclusionsIn this study, associations between serum AA levels and BMD were established. These findings underscore the important role that serum AAs play in the development of osteoporosis and provide evidence that osteoporosis can be prevented and treated by the intake of certain AAs.

Serum Amino Acid Levels and Mortality in Patients Undergoing Percutaneous Endoscopic Gastrostomy.

To evaluate the effect of feeding via percutaneous endoscopic gastrostomy tube (PEG) on serum amino acid levels and mortality. Descriptive study. University of Health Sciences, Umraniye Training and Research Hospital, Istanbul, Turkey, from January 2016 to February 2019. Patients over 18 years of age, who were indicated for PEG due to loss of swallowing reflex, were included in the study. The follow-up period of the study was one year. The patients were reevaluated on the 3rd, 6th, and 12th months after inclusion. Anthropometric measurements, and nutritional status were evaluated at each visit, and quantitative amino acid levels were analysed. Statistical significance was accepted as p <0.05. The study was carried out with a total of 53 cases (23 men and 30 women) ranging in the age from 18 to 91 years. While 13 patients were still alive, 40 patients died before completing one year. The levels of glutamine, leucine, taurine, and threonine were significantly different between surviving patients and dead. A statistically significant difference was found between the levels of citrulline (p <0.001), ornithine (p = 0.036) and tyrosine (p = 0.011) during the four different visits of patients who survived. In patients who died, a significant difference was found between the levels of threonine, ornithine, and aspartic acid (p <0.043 for all) between visits. Citrulline and tyrosine levels were found to be significantly increased in surviving patients. The amino acid profiles of malnourished patients vary considerably. Increase in citrulline, ornithine and tyrosine levels are noted in surviving patients. Key Words: Amino acid, Percutaneous endoscopic gastrostomy, Malnutrition, Mortality.

Baseline serum amino acid levels predict treatment response to augmentation with N-acetylcysteine (NAC) in a bipolar disorder randomised trial

N-acetylcysteine (NAC) acts on glutamatergic and redox systems, two systems implicated in the pathophysiology of bipolar disorder (BD). This has led to the investigation of NAC as a potential candidate for the treatment of BD. The aim of this study was to investigate metabolomic markers to identify predictors of NAC response in a cohort of BD participants. This study is a secondary analysis of a 16-week, multi-site, randomized, double-blinded, parallel-group, placebo-controlled trial in BD participants with a current acute depressive episode. This study included trial participants who received either NAC 2000 mg/day, or placebo. Participants (NAC: n = 31, placebo: n = 29) were assessed at baseline and week 16 using the Montgomery Åsberg Depression Rating Scale (MADRS) and were dichotomised into “responders” (MADRS at week 16 < 50% of MADRS at baseline) and “non-responders” (MADRS at week 16 > 50% at baseline). Untargeted gas chromatography–mass spectrometry analysis was performed to analyse baseline levels of 68 serum metabolites. Of the nine metabolites that differentiated placebo and NAC groups, five were amino acids with lower levels in the NAC responder group compared with the NAC non-responders. Further analysis generated a predictive model of MADRS improvement including glycine, norleucine, threonine, proline, phenylalanine, tyrosine, glutamic acid, lysine and leucine (R2 = 0.853; adjusted R2 = 0.733). This prediction model predicted 85% of the variance in MADRS outcome after adjunctive treatment with NAC. BD participants with lower serum levels of free amino acids at baseline may be more likely to respond to adjunctive treatment with NAC.