Plasma Amino Acid Research Articles

Ingestion of a variety of non-animal-derived dietary protein sources results in diverse postprandial plasma amino acid responses which differ between young and older adults.

Whole-body tissue protein turnover is regulated, in part, by the postprandial rise in plasma amino acid concentrations, although minimal data exist on the amino acid response following non-animal-derived protein consumption. We hypothesised that the ingestion of novel plant- and algae-derived dietary protein sources would elicit divergent plasma amino acid responses when compared with vegan- and animal-derived control proteins. Twelve healthy young (male (m)/female (f): 6/6; age: 22 ± 1 years) and 10 healthy older (m/f: 5/5; age: 69 ± 2 years) adults participated in a randomised, double-blind, cross-over trial. During each visit, volunteers consumed 30 g of protein from milk, mycoprotein, pea, lupin, spirulina or chlorella. Repeated arterialised venous blood samples were collected at baseline and over a 5-h postprandial period to assess circulating amino acid, glucose and insulin concentrations. Protein ingestion increased plasma total and essential amino acid concentrations (P < 0·001), to differing degrees between sources (P < 0·001), and the increase was further modulated by age (P < 0·001). Postprandial maximal plasma total and essential amino acid concentrations were highest for pea (2828 ± 106 and 1480 ± 51 µmol·l-1) and spirulina (2809 ± 99 and 1455 ± 49 µmol·l-1) and lowest for chlorella (2053 ± 83 and 983 ± 35 µmol·l-1) (P < 0·001), but were not affected by age (P > 0·05). Postprandial total and essential amino acid availabilities were highest for pea, spirulina and mycoprotein and lowest for chlorella (all P < 0·05), but no effect of age was observed (P > 0·05). The ingestion of a variety of novel non-animal-derived dietary protein sources elicits divergent plasma amino acid responses, which are further modulated by age.

Crude protein oscillation in diets adequate and deficient in metabolizable protein: Effects on nutrient digestibility, nitrogen balance, plasma amino acids, and greenhouse gas emissions

Reducing dietary CP is a well-established means to improve N use efficiency. Yet, few studies have considered if transient restrictions in dietary CP could reduce the environmental footprint of late-lactation cows. We hypothesized that the effects of CP feeding pattern on digestibility and environmental outputs would be amplified at lower dietary CP. We tested CP levels below and near predicted requirements (low protein [LP], 13.8%; high protein [HP], 15.5%) offered in 2 feeding patterns: where diets alternated ±1.8 percentage units CP every 2 d (oscillating [OF]) or remained static. Our study used a 2 × 2 factorial design with 16 mid- to late-lactation Holsteins (mean = 128, SD = 12 DIM), divided into rumen-cannulated (n = 8) and noncannulated subsets (n = 8). For each 28-d experimental period, we recorded feed intake and milk production and took samples of orts (1×/d) and milk (2×/d) for 4 d. For the cannulated subset, we measured and sampled from the total mass of feces and urine production and collected plasma 2×/d across 4 d. For the noncannulated subset, we sampled carbon dioxide and methane emissions 3×/d for 4 d. For each subset, we fit linear mixed models with fixed effects for CP level, CP feeding pattern, the interaction of CP level and CP feeding pattern, period, and a random effect for cow. For plasma and urinary urea-N, we conducted time series analysis. Contrary to our hypothesis, we found no evidence that dietary CP level and CP feeding pattern interacted to influence N balance, nutrient digestibility, or gas emissions. Results showed HP resulted in similar milk N but increased manure N, reducing N use efficiency (milk true protein N/intake N) relative to LP. For OF, urea-N in urine and plasma peaked 46 to 52 h after the first higher-CP phase feeding. Nutrient digestibility and gas emissions were similar across treatments, except CO2 production was greater for OF-HP. In summary, measured variables were minimally affected by dietary CP alternating ±1.8 percentage units every 48 h, even when average dietary CP was fed below predicted requirements (LP). Although our findings suggest that mid- to late-lactation cows are resilient to oscillation in dietary CP, oscillating CP neither reduced the environmental footprint by improving nutrient use efficiencies nor reduced the potential for direct and indirect greenhouse gas emissions.

Nasogastric bolus administration of a protein-rich drink augments insulinaemia and aminoacidaemia but not whole-body protein turnover or muscle protein synthesis versus oral administration.

Nasogastric feeding of protein-rich liquids is a nutritional support therapy that attenuates muscle mass loss. However, whether administration via a nasogastric tube per se augments whole-body or muscle protein anabolism compared with oral administration is unknown. Healthy participants were administered a protein-rich drink (225 ml containing 21 g protein) orally (ORAL; n=13; age 21 ± 1 year; BMI 22.2 ± 0.6 kg·m-2) or via a nasogastric tube (NG; n=13; age 21 ± 1 yr; BMI 23.9 ± 0.9 kg·m-2) in a parallel group design, balanced for sex. L-[ring-2H5]-phenylalanine and L-[3,3-2H2]-tyrosine were infused to measure postabsorptive and postprandial whole-body protein turnover. Skeletal muscle biopsies were collected at -120, 0, 120 and 300 min relative to drink administration to quantify temporal myofibrillar fractional synthetic rates (myoFSR). Drink administration increased serum insulin and plasma amino acid concentrations, and to a greater extent and duration in NG versus ORAL (all interactions P<0.05). Drink administration increased whole-body protein synthesis (P<0.01), suppressed protein breakdown (P<0.001), and created positive net protein balance (P<0.001), but to a similar degree in ORAL and NG (interactions P>0.05). Drink administration increased myoFSR from the postabsorptive state (P<0.01), regardless of route of administration in ORAL and in NG (interaction P>0.05). Nasogastric bolus administration of a protein-rich drink induces insulinaemia and aminoacidaemia to a greater extent than oral administration, but the postprandial increase in whole-body protein turnover and muscle protein synthesis was equivalent between administration routes. Nasogastric administration is a potent intervention to increase postprandial amino acid availability. Future work should assess its utility in overcoming impaired sensitivity to protein feeding, such as that seen in ageing, disuse, and critical care.

Effects of heating soybeans on postruminal amino acid bioavailability, performance, and ruminal fermentation in lactating cows.

Soybeans can provide ruminally degradable protein, lipid, and metabolizable amino acid (AA) to lactating dairy cows; however, soy-based trypsin inhibitors can limit protein digestion in nonruminants. Eight ruminally cannulated lactating Holstein cows were used to evaluate the impacts of soy-based trypsin inhibitors on nutrient disappearance, lactation, and plasma AA bioavailability. Treatments were abomasal infusion of 0 or 400g/d casein or a crystalline AA analog of casein with unroasted or roasted soybeans fed at 10% dry matter (DM). Data were analyzed using the MIXED procedure of SAS. Measures of digestion were determined from fecal output determined with acid detergent insoluble ash and urine output determined from measures of urine creatinine. Neither soybean processing (P ≥ 0.20) nor the source of abomasal infusion (P ≥ 0.60) impacted nutrient digestibility. Ruminal ammonia, isobutyrate, and isovalerate were increased (P ≤ 0.01) among cattle consuming unroasted soybeans. Source of infusion did not affect (P ≥ 0.38) ruminal volatile fatty acids or nitrogen metabolism. Ruminal N metabolism was largely unaffected by soybean processing although microbial N efficiency was greater (P < 0.01) among cows fed unroasted soybeans. DM intake and energy-corrected milk were greater (P < 0.01) in cows fed roasted compared to unroasted soybeans. The proportion of fat, protein, lactose, and solids not fat (SNF) in milk did not differ between soybean processing or postruminal AA source, but fat, protein, lactose, and SNF yield was greater (P ≤ 0.01) when cows were fed roasted soybeans because milk yields were greater when cows were fed roasted vs. unroasted soybeans. As expected, infusion of casein or its crystalline AA analog increased plasma essential AA and milk urea nitrogen concentration. The rate of increase in essential AA concentration in plasma was 2.9× greater for casein than for crystalline AA. These data seem to indicate that soy-based trypsin inhibitors have no impacts on postruminal AA bioavailability when fed to cows and that metabolizable protein from casein is greater than from crystalline AA.

Plasma amino acids in major depressive disorder: between pathology to pharmacology.

Addressing the formidable challenge posed by the development of effective and personalized interventions for major depressive disorder (MDD) necessitates a comprehensive comprehension of the intricate role that plasma amino acids play and their implications in MDD pathology and pharmacology. Amino acids, owing to their indispensable functions in neurotransmission, metabolism, and immune regulation, emerge as pivotal entities in this intricate disorder. Our primary objective entails unraveling the underlying mechanisms and unveiling tailored treatments through a meticulous investigation into the interplay between plasma amino acids, MDD, and pharmacological strategies. By conducting a thorough and exhaustive review of the existing literature, we have identified pertinent studies on plasma amino acids in MDD, thereby uncovering noteworthy disturbances in the profiles of amino acids among individuals afflicted by MDD when compared to their healthy counterparts. Specifically, disruptions in the metabolism of tryptophan, phenylalanine, and tyrosine, which serve as precursors to essential neurotransmitters, have emerged as prospective biomarkers and critical contributors to the pathophysiology of depression. Amnio acids play an essential role in MDD and could represent an attractive pharmacological target, more studies are further required to fully reveal their underlying mechanisms.

Characteristics of structural changes in the intestine, microbiocenosis and amino acid pool after administration of ertapenem

Аim of the study. To analyze the effect of Ertapenem on the pool of free amino acids, microbiota and intestinal structure. Materials and methods. The study was carried out on 5 animals from the control group and 6 animals from the experimental group. Animals in the control group were intraperitoneally injected with a 0.9% NaCl solution for 10 days; Animals in the experimental group were intraperitoneally administered Invanz (ertapenem) at a dose of 60 mg/kg for 10 days. Immediately after decapitation, the abdominal cavity of the rat was opened, a section of the small intestine was collected, and the samples were fixed in Carnoy's fluid. Determination of free amino acids in plasma and microbial-tissue complex of blood was carried out by reverse-phase HPLC with o-phthalaldehyde and 3-mercaptopropionic acid with isocratic elution and fluorescence detection. Results and discussions. Morphometric analysis of the intestines in the ertapenem group showed a slight decrease in mucosal thickness and crypt depth. In half of the animals, in the apical regions of some villi, a pronounced expansion of blood capillaries with stasis of erythrocytes was observed, in places accompanied by the marginal standing of lymphoid cells. The microbiocenosis was characterized by an increase in the number of aerobes and spore-forming anaerobes, and the absence of lactose-positive bacteria of the Escherichia coli group. The study of the amino acid fund and the spectrum of individual amino acids in the microbial-tissue complex of the small intestine showed a significantly significant increase in aspartate, glycine, as well as a decrease in hypotaurine. Conclusion. The effect of ertapenem led to local mild inflammatory changes in the villous stroma, a moderate decrease in the formation and extrusion of mucus by goblet cells of the villi and crypts. Amino acid changes that occur after the action of ertapenem may be due to both the intestines and changes in the microbiota.

The impact of heat-set milk protein gel textures modified by pH on circulating amino acid appearance and gastric function in healthy female adults: a randomised controlled trial.

Modification of dairy proteins during processing impacts structural assemblies, influencing textural and nutritional properties of dairy products, and release and availability of amino acids during digestion. By modifying only pH, acid heat-set bovine dairy gels with divergent textural properties were developed to alter protein digestion. In vitro assay confirmed faster digestion of protein from a firm gel (pH 5.65) versus a soft gel (pH 6.55). We hypothesised that firm gel (FIRM-G; pH 5.6) would result in greater indispensable amino acid (IAA) appearance in circulation over 5 h and corresponding differences in gastric myoelectrical activity relative to soft gel (SOFT-G; pH 6.2). In a randomised, single-blind cross-over trial, healthy females (n = 20) consumed 150 g of each gel; plasma amino acid appearance was assessed over 5 hours. Iso-nitrogenous, iso-caloric gels were prepared from identical mixtures of bovine milk and whey protein concentrates; providing 17.7 g (FIRM-G) and 18.9 g (SOFT-G) of protein per serving. Secondary outcomes included gastric myoelectrical activity measured by body surface gastric mapping, glycaemic, triglyceridaemic, and subjective appetite and digestive responses. Overall plasma IAA (area under the curve) did not differ between gels. However, plasma IAA concentrations were higher, and increased more rapidly over time after SOFT-G compared with FIRM-G (1455 ± 53 versus 1350 ± 62 μmol L-1 at 30 min, p = 0.024). Similarly, total, branched-chain and dispensable amino acids were higher at 30 min with SOFT-G than FIRM-G (total: 3939 ± 97 versus 3702 ± 127 μmol L-1, p = 0.014; branched-chain: 677 ± 30 versus 619 ± 34 μmol L-1, p = 0.047; dispensable: 2334 ± 53 versus 2210 ± 76 μmol L-1, p = 0.032). All other measured parameters were similar between gels. Peak postprandial aminoacidaemia was higher and faster following ingestion of SOFT-G. Customised plasma amino acid appearance from dairy is achievable by altering gel coagulum structure using pH during processing and may have minimal influence on related postprandial responses, with implications for targeting food design for optimal health. The Clinical Trial Registry number is ACTRN12622001418763 (https://www.anzctr.org.au) registered November 7, 2022.

Correlation between plasma glutamate and adiponectin in patients with type 2 diabetes.

Visceral fat accumulation is a major determinant of type 2 diabetes mellitus and cardiovascular diseases. Recent studies have reported that glutamate is the most elevated amino acid in the plasma amino acid profile in patients with obesity and/or visceral fat accumulation. Here, we show the relationship between plasma glutamate and the clinical features of patients with type 2 diabetes. The study subjects were 62 (28 men and 34 women) Japanese patients with type 2 diabetes. Blood profiles, including glutamate and adiponectin (APN) levels and estimated visceral fat area (eVFA), were measured. We also evaluated the plasma amino acid levels in mice with or without obesity by GC/MS analysis. In patients with type 2 diabetes, plasma glutamate was positively correlated with BMI, eVFA, and fasting insulin but negatively correlated with APN and duration of diabetes. Additionally, multiple regression analysis revealed that plasma glutamate was a significant determinant of APN. The plasma glutamate level was most significantly increased in obese mice compared to control mice, and it was negatively correlated with APN. These results suggest that the level of plasma glutamate could be a strong indicator of adipocyte dysfunction in patients with type 2 diabetes.

Pubertal origin of growth retardation in inborn errors of protein metabolism: A longitudinal cohort study

ObjectivesInherited amino-acid metabolism disorders (IAAMDs) require lifelong protein-restricted diet. We aimed to investigate: 1/ whether IAAMDs was associated with growth, pubertal, bone mineral apparent density (BMAD) or body composition impairments; 2/ associations linking height, amino-acid mixture (AAM), plasma amino-acids and IGF1 concentrations. DesignRetrospective longitudinal study of 213 patients with neonatal-onset urea cycle disorders (UCD,n = 77), organic aciduria (OA,n = 89), maple syrup urine disease (MSUD,n = 34), or tyrosinaemia type 1 (n = 13). MethodsWe collected growth parameters, pubertal status, BMAD, body composition, protein-intake, and IGF1 throughout growth. ResultsOverall final height (n = 69) was below target height (TH): −0.9(1.4) vs. -0.1(0.9) SD, p < 0.001. Final height was ≤ TH-2SD in 12 (21%) patients. Height ≤ − 2SD was more frequent during puberty than during early-infancy and pre-puberty: 23.5% vs. 6.9%, p = 0.002; and vs. 10.7%, p < 0.001. Pubertal delay was frequent (26.7%). Height (SD) was positively associated with isoleucine concentration: β, 0.008; 95%CI, 0.003 to 0.012; p = 0.001. In the pubertal subgroup, height (SD) was lower in patients with vs. without AAM supplementation: −1.22 (1.40) vs. -0.63 (1.46) (p = 0.02). In OA, height and median (IQR) isoleucine and valine concentrations(μmol/L) during puberty were lower in patients with vs. without AAM supplementation: −1.75 (1.30) vs. −0.33 (1.55) SD, p < 0.001; and 40 (23) vs. 60 (25) (p = 0.02) and 138 (92) vs. 191 (63) (p = 0.01), respectively. No correlation was found with IGF1. Lean-mass index was lower than fat-mass index: −2.03 (1.15) vs. -0.44 (0.89), p < 0.001. ConclusionsIn IAAMDs, growth retardation worsened during puberty which was delayed in all disease subgroups. Height seems linked to the disease, AAM composition and lower isoleucine concentration, independently of the GH-IGF1 pathway. We recommend close monitoring of diet during puberty.

Glutamine transporters as effective targets in digestive system malignant tumor treatment.

Glutamine is one of the most abundant non-essential amino acids in human plasma and plays a crucial role in many biological processes of the human body. Tumor cells take up a large amount of glutamine to meet their rapid proliferation requirements, which is supported by the upregulation of glutamine transporters. Targeted inhibition of glutamine transporters effectively inhibits cell growth and proliferation in tumors. Among all cancers, digestive system malignant tumors (DSMTs) have the highest incidence and mortality rates, and the current therapeutic strategies for DSMTs are mainly surgical resection and chemotherapy. Due to the relatively low survival rate and severe side effects associated with DSMTs treatment, new treatment strategies are urgently required. This article summarizes the glutamine transporters involved in DSMTs and describes their role in DSMTs. Additionally, glutamine transporter-target drugs are discussed, providing theoretical guidance for the further development of drugs DSMTs treatment.

Effects of the replacement corn meal by whole mango meal on tambaqui (Colossoma macropomum) diet: Digestibility, growth performance, biochemical, and hematological responses.

This study evaluated the digestibility of whole mango (Mangifera indica) meal (WMM) and determined the growth performance, intestinal enzyme activity, and metabolic and hematologic responses of tambaqui (Colossoma macropomum) juveniles fed diets containing different proportions of corn meal (CM) substitution by WMM. Fish fed with graded levels of WMM (0 (control), 80, 160, 240, and 320 g kg diet-1), replacing part of the dietary CM. The apparent digestibility coefficients of WMM were above 96%. Diets with WMM did not affect growth performance or intestinal enzyme activity. However, they showed a positive linear effect on plasma glucose, amino acids, and albumin levels and a negative linear effect on hepatic aspartate aminotransferase activity and hepatic glycogen, plasma cholesterol, and hemoglobin levels. Increased erythrocyte values and decreased plasma triglyceride levels were verified in fish fed 80 and 160 g WMM kg diet-1. In conclusion, the WMM may be a viable alternative to the tambaqui juveniles' diet, and WMM could replace up to 16% of CM without harming the growth and health of tambaqui juveniles.

Serum amino acid profiles in clinically normal Noma horses.

Plasma or serum amino acids are used to evaluate nutritional status and metabolic disorders. In this study, we aimed to set reference values of serum amino acid concentrations in the Noma horse, a Japanese native horse. Thirty-one horses were classified into six age groups: neonatal foal (0-4 days), foal (0.5-1 years), youth (5 years), middle age (10 years), old (15 years), and extra-old (>20 years). Horses >5 years of age were analyzed together as the adult group. In the adult horses, there were no significant differences among the serum amino acid concentrations of each age group. The foal group had higher concentrations of alanine, aspartic acid, glutamic acid, α-aminoadipic acid, and 3-methyl-histidine than the adult group. The neonatal foal group had higher serum concentrations of phenylalanine, lysine, alanine, proline, aspartic acid, glutamic acid, β-alanine, and β-amino-iso-butyric acid and lower tryptophan concentrations and Fischer's ratios than the adult group. The neonatal foal group had higher β-amino-iso-butyric acid concentrations and lower tryptophan and 3-methyl-histidine concentrations than the foal group. Therefore, reference values might be set separately in neonatal foals, foals, and adult horses. The data for the serum amino acid concentrations can be used for health care through physiological and pathological evaluations in Noma horses.

Frost survival and gene expression in timothy (Phleum pratense L.) cultivars as affected by age and selection in diverse field environments.

The sustainable production of perennial grasses in Northern Norway is at risk due to the ongoing climate change. The predicted increase in temperatures and variable weather patterns are further expected to create challenges for winter survival of timothy (Phleum pratense L.). Knowledge about the molecular mechanisms underlying freezing tolerance is crucial for developing robust cultivars. The current study is aimed at identifying genes involved in freezing stress response of timothy and studying gene expression differentiation due to field selection in contrasting environments using RNAseq. Four timothy cultivars were field tested for three years in Tromsø and Vesterålen, in Northern Norway. The surviving material from the field tests, along with plants raised from the original seed lots, were subjected to freezing tests. LT50 values varied across cultivars and materials. Many genes coding for transcription factors and proteins known to play an important role in freezing tolerance, like dehydrins, c-repeat binding factors, and late embryogenesis abundant proteins were upregulated with decreasing temperatures. Moreover, genes associated with glycolysis/gluconeogenesis, TCA cycle, glutathione metabolism, proteasome pathways and genes encoding autophagy-related proteins, plasma membrane-associated proteins, sugar and amino acid transporters had elevated expression in field survivors compared to plants raised from the original material. The lower freezing stress tolerance of field survivors despite the elevated expression of several stress-responsive genes might be due to a combination of selection in the field and the age effect. Furthermore, differences in freezing stress response between northern and southern adapted cultivars and surviving material from two field trial locations are discussed.

Integrated gut microbiome and metabolomic analyses elucidate the therapeutic mechanisms of Suanzaoren decoction in insomnia and depression models.

Insomnia and depression are psychiatric disorders linked to substantial health burdens. The gut microbiome and metabolomic pathways are increasingly recognized as key contributors to these conditions' pathophysiology. Suanzaoren Decoction (SZRD), a traditional Chinese herbal formulation, has demonstrated significant therapeutic benefits for both insomnia and depression. This study aims to elucidate the mechanistic effects of SZRD on insomnia and depression by integrating gut microbiome and metabolomic analyses and to assess the differential impacts of SZRD dosages. Using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS), we identified 66 chemical constituents within SZRD. Behavioral assays indicated that low-dose SZRD (LSZRD) significantly ameliorated insomnia symptoms in rat models, whereas high-dose SZRD (HSZRD) markedly improved depressive behaviors. 16S rRNA sequencing revealed that SZRD modulated gut microbiome dysbiosis induced by insomnia and depression, characterized by an increased abundance of short-chain fatty acid (SCFA)-producing genera. Metabolomic profiling demonstrated reduced plasma amino acid metabolites and disrupted γ-aminobutyric acid (GABA) and L-glutamic acid metabolism in the hippocampus of affected rats. SZRD administration restored fecal SCFA levels and ameliorated metabolic imbalances in both plasma and hippocampal tissues. These findings underscore the pivotal role of gut microbiome modulation and metabolic regulation in the therapeutic effects of SZRD, providing a scientific basis for its use in treating insomnia and depression.

Genetic associations of plasma amino acid levels with male hypogonadism, erectile dysfunction and infertility

Genetic associations of plasma amino acid levels with male hypogonadism, erectile dysfunction and infertility

The Effect of 8-Week Protein Supplementation with a Simple Exercise Program on Body Composition, Muscle Strength, and Amino Acid OMICS among Healthy Sedentary Indians: A Randomized, Double-Blind, Placebo-Controlled Trial.

Dietary protein plays a crucial role in the modulation of several physiological processes to sustain health and well-being. There is robust evidence of enhanced muscle protein synthesis, improved physical fitness, body composition, and performance contributed by protein supplementation combined with exercise among trained individuals or athletes. Evidence of the efficacy of such intervention on healthy adults having a sedentary lifestyle is limited. The objective of this study was to evaluate the impact of 12 g of additional protein in the form of a protein supplement compared to a placebo combined with a simple exercise program on plasma amino acid level, body composition, and muscle strength among healthy Indian adults having a relatively sedentary lifestyle. This double-blinded, randomized controlled trial was conducted on sedentary healthy adults 20-45 years of age, with a body mass index (BMI) between 18.5 and 27.9 kg/m2. Eighty-two participants were randomized into either the protein (intervention) or placebo (control) group. The exercise regime was the same for both groups. Out of 82 randomized participants, 58 completed the intervention. Blood tests were conducted for the amino acid OMICS measurement followed by dual-energy X-ray absorptiometry (DXA) for body composition and isokinetic dynamometry for muscle strength. A significant improvement was observed in the lean mass (kg) and appendicular muscle mass (AMM) adjusted for weight in the intervention group compared to the control group (p < 0.05). The muscle strength and contractile quality were comparable in the 2 groups. Plasma BCAA showed a significant negative association with body fat % (r = -0.43, p < 0.05 for the intervention group and r = -0.33, p = 0.07 for the control group) and a positive association with lean body mass % (r = 0.56, p < 0.01 in the intervention group vs r = 0.29, p = 0.10 in the control group) in the intervention group compared to control. In conclusion, this study highlighted the value of incorporating a lifestyle intervention including protein supplementation with simple exercises to optimize body composition in sedentary healthy individuals. This trial is registered with CTRI/2018/12/016777.

Effects of increasing dietary arginine supply during the three first weeks after weaning on pig growth performance, plasma amino acid concentrations, and health status.

A total of 425 weaned pigs (Exp. 1: 225 pigs [5.8 ± 0.9 kg]; Exp. 2: 200 pigs [6.1 ± 1.2 kg]) were used to determine the optimal dietary standardized ileal digestible (SID) arginine (Arg) level in early nursery diets based on growth and health responses. The basal diet in Exp.1 was formulated to meet SID Arg recommendation (0.66%; NRC, 2012) and in Exp. 2, SID Arg was set to simulate current industry practices for feeding nursery pigs (1.15 %). Basal diets were supplemented with 0.3%, 0.6%, 0.9%, and 1.2% of l-arginine to provide five levels of dietary SID Arg. Experimental diets were fed during phases I (days 0 to 7) and II (days 8 to 21) with common diets until market. Feed disappearance and body weight (BW) were measured on days 7, 14, 21, and 43. Final BW was recorded at first removal of pigs for market. Pen fecal score was assigned daily from days 0 to 21. Plasma immunoglobulin A (IgA) was determined on days 0, 7, and 14 and amino acids (AAs) concentration and plasma urea nitrogen (PUN) on days 0 and 14. Orthogonal polynomial contrasts were used to determine the linear and quadratic effects of dietary Arg. Optimal SID Arg was determined by fitting the data with piecewise regression, using growth performance as the primary response variable. In Exp. 1, dietary Arg linearly increased (P < 0.1) BW, average daily gain (ADG), and gain to feed ratio (G:F) ratio on day 21, as well as reduced (χ2 = 0.004) the percentage of pigs that lost weight (PLW) in week 1 by 29%. Dietary Arg resulted in linear improvement (P = 0.082) of ADG for the overall nursery period and quadratic improvement (P < 0.1) of final BW at marketing. In Exp. 2, dietary Arg linearly increased (P < 0.05) ADG and average daily feed intake (ADFI) in week 1, BW and ADFI (P < 0.1) on day 14, as well as reduced (χ2 ≤ 0.001) PLW in week 1. From days 0 to 21, G:F was improved quadratically (P < 0.1). Dietary Arg linearly increased (P < 0.1) ADG and BW on day 43. Dietary Arg supplementation decreased the incidence (χ2 < 0.05) of soft and watery feces during the first weeks after weaning and lower concentration of plasma IgA on days 7 and 14. Dietary Arg linearly and/or quadratically influenced plasma AA concentrations (P < 0.05), including an increase in Arg, Leu, Phe, Val, citrulline, ornithine, and PUN concentrations. Overall, weaned pigs exhibit optimal nursery growth performance and health when provided with dietary SID Arg ranging from 1.5% to 1.9%. This dietary range contributes to a reduction in the occurrence of fall-back pigs and improvements in final BW at marketing.

Plasma arginine levels in arginase deficiency in the “real world”

BackgroundDeficiency of arginase-1, the final enzyme in the urea cycle, causes a distinct clinical syndrome and is characterized biochemically by a high level of plasma arginine. While conventional therapy for urea cycle disorders can lower these levels to some extent, it does not normalize them. Until now, research on plasma arginine levels in this disorder has primarily relied on data from specialized tertiary centers, which limits the ability to assess the natural history and treatment efficacy of arginase-1 deficiency due to the small number of patients in each center and technical variations in plasma arginine measurements among different laboratories. MethodIn this study, we reported plasma arginine levels from 51 patients with arginase-1 deficiency in the database of Quest Diagnostics. The samples were collected from different US regions. ResultsThe mean plasma arginine level in these treated patients was 373 μmol/L and the median level was 368.4 μmol/L. Our data set from 30 arginase deficiency patients with plasma amino acid data from five or more collections revealed significant correlations between the levels of arginine and five other amino acids (citrulline, alanine, ornithine, glutamine, and asparagine). ConclusionDespite treatment, the arginine levels remained persistently elevated and did not change significantly with age, suggesting the current treatment regimen is inadequate to control arginine levels and underscoring the need to seek more effective treatments for this disorder.

Plasma amino acids spectrum as an important part of metabolomic pattern in patients with coronary artery disease and atrial fibrillation

The aim of our work was to estimate the plasma amino acid (AA) spectrum peculiarities in coronary artery disease (CAD) patients with atrial fibrillation (AF) and to check their connections with cardiometabolic risk factors and gu, microbiota metabolites. 300 patients were divided into three groups: first – 149 patients with CAD but without arrhythmias, second – 123 patients with CAD and AF paroxysm and control group – 28 patients without CAD and arrhythmias. Plasma AA level was detected by ion exchange liquid column chro­matography method. The plasma AA spectrum changes in CAD patients with AF paroxysm were investigated: some plasma AA (glutamate, glutamine, glycine, alanine, valine, tyrosine) and their combinations (Isoleucine+Leucine/Valine, Glycine+Serine, Glycine/Methionine, Phenylalanine/Tyrosine, Glutamine/Glutamate) had significant changes in second group patients and had correlations with cardiometabolic risk factors (glycine, valine, arginine, glutamate, isoleucine, alanine, methionine (p&lt;0.05)). Plasma AA combinations were revealed, the lattert could be used as an early marker of AF paroxysm in CAD patients by the results of ROC analysis: 2.44 * Isoleucine – Glycine; area under ROC-curve 0.8122 and 3.16 * Phenylalanine – Glycine, area under ROC-curve 0.8061. Plasma AA spectrum evaluation could be a new promising metabolic marker for AF paroxysm in CAD patients. Altered AA levels point to the depth of pathogenetic changes during AF paroxysm formation: disorders of AA metabolism with branched chain (isoleucine, leucine, valine), aromatic AA (phenylalanine, tyrosine), glutamine/glutamate, glycine/serine and glyci­ne/methionine metabolism. A strong reliable connection between plasma AA spectrum and gut microbiota metabolites (trimethylamine, trimethylamine-N-oxide, total amount of fecal short chain fatty acids) was detected.

Administration of Free Amino Acids Improves Exogenous Amino Acid Availability when Compared with Intact Protein in Critically Ill Patients: A Randomized Controlled Study

BackgroundProtein digestion and amino acid absorption appear compromised in critical illness. The provision of enteral feeds with free amino acids rather than intact protein may improve postprandial amino acid availability. ObjectiveOur objective was to quantify the uptake of diet-derived phenylalanine after the enteral administration of intact protein compared with an equivalent amount of free amino acids in critically ill patients. MethodsSixteen patients who were mechanically ventilated in intensive care unit (ICU) at risk of malabsorption received a primed continuous infusion of L-[ring-2H5]-phenylalanine and L-[ring-3,5-2H2]-tyrosine after an overnight fast. Patients were randomly allocated to receive 20 g intrinsically L-[1-13C]-phenylalanine-labeled milk protein or an equivalent amount of amino acids labeled with free L-[1-13C]-phenylalanine via a nasogastric tube over a 2-h period. Protein digestion and amino acid absorption kinetics and whole-body protein net balance were assessed throughout a 6-h period. ResultsAfter enteral nutrient infusion, both plasma phenylalanine and leucine concentrations increased (P-time < 0.001), with a more rapid and greater rise after free amino acid compared with intact protein administration (P-time × treatment = 0.003). Diet-derived phenylalanine released into the circulation was 25% greater after free amino acids compared with intact protein administration [68.7% (confidence interval {CI}: 62.3, 75.1%) compared with 43.8% (CI: 32.4, 55.2%), respectively; P < 0.001]. Whole-body protein net balance became positive after nutrient administration (P-time < 0.001) and tended to be more positive after free amino acid in provision (P-time × treatment = 0.07). ConclusionsThe administration of free amino acids as opposed to intact protein further increases postprandial plasma amino acid availability in critically ill patients, allowing more diet-derived phenylalanine to become available to peripheral tissues.This trial was registered at clinicaltrials.gov as NCT04791774.