Effect of carnosine synthesis precursors in the diet on jejunal metabolomic profiling and biochemical compounds in slow-growing Korat chicken.

The slow-growing Korat chicken (KR) has been developed to provide an alternative breed for smallholder farmers in Thailand. Carnosine enrichment in the meat can distinguish KR from other chicken breeds. Therefore, our aim was to investigate the effect of enriched carnosine synthesis, obtained by the ß-alanine and L-histidine precursor supplementation in the diet, on changes to metabolomic profiles and biochemical compounds in slow-growing KR jejunum tissue. Four hundred 21-day-old female KR chickens were divided into 4 experimental groups: a group with a basal diet, a group with a basal diet supplemented with 1.0% ß-alanine, 0.5% L-histidine, and a mix of 1.0% ß-alanine and 0.5% L-histidine. The feeding trial lasted 70 d. Ten randomly selected chickens from each group were slaughtered. Metabolic profiles were analyzed using proton nuclear magnetic resonance spectroscopy. In total, 28 metabolites were identified. Significant changes in the concentrations of these metabolites were detected between the groups. Partial least squares discriminant analysis was used to distinguish the metabolites between the experimental groups. Based on the discovered metabolites, 34 potential metabolic pathways showed differentiation between groups, and 8 pathways (with impact values higher than 0.05, P < 0.05, and FDR < 0.05) were affected by metabolite content. In addition, biochemical changes were monitored using synchrotron radiation-based Fourier transform infrared microspectroscopy. Supplementation of ß-alanine alone in the diet increased the ß-sheets and decreased the α-helix content in the amide I region, and supplementation of L-histidine alone in the diet also increased the ß-sheets. Furthermore, the relationship between metabolite contents and biochemical compounds were confirmed using principal component analysis (PCA). Results from the PCA indicated that ß-alanine and L-histidine precursor group was highly positively correlated with amide I, amide II, creatine, tyrosine, valine, isoleucine, and aspartate. These findings can help to understand the relationships and patterns between the spectral and metabolic processes related to carnosine synthesis.

Effects of ß-alanine and L-histidine supplementation on carnosine contents in and quality and secondary structure of proteins in slow-growing Korat chicken meat.

Carnosine enrichment of slow-growing Korat chicken (KRC) meat helps differentiate KRC from mainstream chicken. We aimed to investigate the effects of ß-alanine and L-histidine supplementation on the carnosine synthesis in and quality and secondary structure of proteins in slow-growing KRC meat. Four hundred 21-day-old female KRC were used, and a completely randomized design was applied. The chickens were divided into 4 experimental groups: basal diet (A), basal diet supplemented with 1.0% ß-alanine (B), 0.5% L-histidine (C), and 1.0% ß-alanine combined with 0.5% L-histidine (D). Each group consisted of 5 replicates (20 chickens per replicate). On d 70, 2 chickens per replicate were slaughtered, and the levels of carnosine, anserine, and thiobarbituric acid reactive substances were analyzed. Biochemical changes were monitored using synchrotron radiation-based Fourier transform infrared microspectroscopy; 5 chickens per replicate were slaughtered, and the meat quality was analyzed. Statistical analysis was performed using ANOVA and principal component analysis (PCA). Group D chickens exhibited the highest carnosine meat content, followed by those in groups B and C. However, amino acid supplementation did not affect anserine content and growth performance. Higher carnosine levels correlated with increasing pH45 min and decreasing drip loss, cooking loss, shear force, and lipid oxidation. PCA revealed that supplementation with only ß-alanine or L-histidine was related to increased content of ß-sheets, ß-turns, and aliphatic bending groups and decreased content of α-helix groups. This study is the first to report such findings in slow-growing chicken. Our findings suggest that KRC can synthesize the highest carnosine levels after both ß-alanine and L-histidine supplementation. Higher carnosine contents do not adversely affect meat quality, improve meat texture, and alter the secondary structures of proteins. The molecular mechanism underlying carnosine synthesis in chickens needs further study to better understand and reveal markers that facilitate the development of nutrient selection programs.

Novel Relationship Between Plasmalogen Lipid Signatures and Carnosine in Humans.

INTRODUCTION: Carnosine is a naturally occurring dipeptide abundant in the skeletal and cardiac muscle and brain, which has been shown to improve glucose metabolism and cardiovascular risk. This study showed that carnosine supplementation had positive changes on plasma lipidome. Here, this study aimed to establish the relationship of muscle carnosine and serum carnosinase-1 with cardiometabolic risk factors and the lipidome. METHODS AND RESULTS: This study profiles >450 lipid species in 65 overweight/obese nondiabetic individuals. Intensive metabolic testing is conducted using direct gold-standard measures of adiposity, insulin sensitivity and secretion, as well as measurement of serum inflammatory cytokines and adipokines. Muscle carnosine is negatively associated with 2-h glucose concentrations, whereas serum carnosinase-1 levels are negatively associated with insulin sensitivity and positively with IL-18. O-PLS and machine learning analyses reveal a strong association of muscle carnosine with ether lipids, particularly arachidonic acid-containing plasmalogens. Carnosinase-1 levels are positively associated with total phosphatidylethanolamines, but negatively with lysoalkylphosphatidylcholines, trihexosylceramides, and gangliosides. In particular, alkylphosphatidylethanolamine species containing arachidonic acid are positively associated with carnosinase-1. CONCLUSION: These associations reinforce the role of muscle carnosine and serum carnosinase-1 in the interplay among low-grade chronic inflammation, glucose homeostasis, and insulin sensitivity.

Space Flight Diet-Induced Deficiency and Response to Gravity-Free Resistive Exercise.

Immune system dysregulation is among the many adverse effects incurred by astronauts during space flights. Omega-3 fatty acids, ß-alanine, and carnosine are among the many nutrients that contribute to immune system health. For space flight, crewmembers are prescribed a diet with a macronutrient composition of 55% carbohydrate, 30% fat, and 15% protein. To quantify omega-3 fatty acid, ß-alanine and carnosine intakes from such a diet, and to examine each nutrient's impact on exercise performance, 21 participants adhered to the aforementioned macronutrient ratio for 14 days which was immediately followed by a workout performed on gravity-independent resistive exercise hardware. Results included daily omega-3 fatty acid intakes below the suggested dietary intake. Daily omega-3 fatty acid, ß-alanine and carnosine intakes each correlated with non-significant amounts of variance from the workout's volume of work. Given the nutritional requirements to maintain immune system function and the demands of in-flight exercise countermeasures for missions of increasingly longer durations current results, in combination with previously published works, imply in-flight supplementation may be a prudent approach to help address the physiological and mental challenges incurred by astronauts on future space flights.

ß-Alanine and l-histidine supplementation associated with combined training increased functional capacity and maximum strength in heart failure rats.

NEW FINDINGS: What is the central question of the study? Does ß-alanine with l-histidine supplementation associated with endurance and strength training improve echocardiographic parameters, functional capacity, and maximum strength in rats with chronic heart failure? What is the main finding and its importance? ß-Alanine with l-histidine supplementation associated with endurance and strength training increased functional capacity and maximum strength through increasing exercise capacity peripherally but did not affect echocardiographic parameters in rats with chronic heart failure. Combined training (CT) has been associated with positive responses in the clinical status of patients with chronic heart failure (CHF). Other non-pharmacological tools, such as amino acid supplementation, may further enhance its adaptation. However, the effects of ß-alanine and l-histidine supplementation in CHF remain unclear. In the present study, the aim was to test whether supplementing carnosine precursors with CT could give improved responses in the functional capacity and echocardiographic variables of rats with CHF. Twenty-four Wistar rats, were submitted to myocardial infarction and allocated to three groups: animals with CHF kept in sedentary conditions (SED, n = 8), animals with CHF submitted to CT in strength and aerobic exercise supplemented with placebo (CT-P, n = 8) and animals with CHF submitted to CT in strength and aerobic exercise supplemented with ß-alanine and l-histidine (CT-S, n = 8). The trained animals were submitted to a strength protocol three times per week with intensity of 65-75% of one repetition maximum test. Aerobic training was conducted two times per week (50 min, 15 m min-1 ). The supplemented group received ß-alanine and l-histidine orally (each 250 mg kg-1  day-1 ). No changes in echocardiographic and morphological parameters were found among the groups (P > 0.05). Functional capacity, Δ V̇O2max and maximum strength were higher in CT-P than in SED and even higher in CT-S than in CT-P (P < 0.01). The CT was able to improve functional capacity, but the supplementation was shown to enhance these parameters even further in the CHF rats. We conclude that the increase in functional capacity and strength gained through CT and supplementation were associated with the improvement in peripheral parameters with no changes in cardiac variables.

Fragmented Dosing of ß-alanine Induces A Body Weight-Independent Pharmacokinetic Response.

Personalised dosing of performance-enhancing food supplements is a hot topic. ß-alanine is currently dosed using a fixed dose; however, evidence suggests that this might favour light compared to heavy subjects. A weight-relative dose seems to reverse this problem. In the present study, a novel dosing strategy was tested. A fragmented dose, composed of a fixed fragment of 800 mg and a weight-relative fragment of 10 mg/kg body weight, was compared to a fixed dose of 1600 mg and a weight-relative dose of 20 mg/kg body weight in a cohort of 20 subjects with a body weight ranging 48-139 kg (79.9 ± 24.4 kg). The results show that, following a fragmented dose, the influence of body weight on the pharmacokinetic response (iAUC) over a 210 min period was absent (r = -0.168; p = 0.478), in contrast to the fixed or weight-relative dose. The pharmacokinetic response also seemed more homogenous (CV% = 26%) following a fragmented dose compared to the fixed (33%) and the weight-relative dose (31%). The primary advantage of the easy-to-calculate fragmented dosing strategy is that it does not systematically favour or impair a certain weight group. Thorough dosage studies are lacking in the current field of sports and food supplements, therefore similar considerations can be made towards other (ergogenic) food supplements.

Development and validation of a HPLC method for the direct separation of carnosine enantiomers and analogues in dietary supplements.

The chiral purity of some molecules such as nutraceuticals is fundamental to ensure their beneficial activities and it must be checked during quality control analysis. Carnosine is a natural histidine dipeptide used as ingredient for food supplements, but only his L-enantiomer is absorbed and active. Despite of this feature, a method for the separation of carnosine enantiomers without derivatization has only recently been published. Herein, we validated a method based on a Chirobiotic T column and an UV detector for the direct quantification of carnosine enantiomers, following ICH guideline. Moreover, we demonstrated that elution with water containing 0.1% formic acid and 20-40% ensures stereo-, chemo- and regio-selectivity for the separation and the identification of carnosine enantiomers and natural analogues. Moreover, the method allows a direct hyphenation with electrospray mass spectrometry to increase detection selectivity and sensitivity. As far as we know, this is the first method allowing the simultaneous identification and quantification of natural analogues of carnosine, which can be important for application such as the identification of enantiomeric impurities or adulteration that can occur during the storage or the preparation of foods or food supplements containing histidine dipeptides.

Effects of dietary supplementation with carnosine on growth performance, meat quality, antioxidant capacity and muscle fiber characteristics in broiler chickens.

BACKGROUND: The effects of dietary carnosine were evaluated on the growth performance, meat quality, antioxidant capacity and muscle fiber characteristics in thigh muscle of 256 one-day-old male broilers assigned to four diets - basal diets supplemented with 0, 100, 200 or 400 mg kg-1 carnosine respectively - during a 42 day experiment. RESULTS: Carnosine concentration and carnosine synthase expression in thigh muscle were linearly increased (P < 0.05) and the feed/gain ratio was decreased (P < 0.05) in the starter period by carnosine addition. Dietary supplementation with carnosine resulted in linear increases in pH45min , redness and cohesiveness and decreases in drip loss, cooking loss, shear force and hardness (P < 0.05). Carnosine addition elevated the activities of antioxidant enzymes and reduced contents of malondialdehyde and carbonyl compounds (P < 0.05). Dietary carnosine linearly decreased diameters and increased densities of muscle fibers (P < 0.01). The ratios of myosin heavy chain (MyHC) I and IIa were increased while that of MyHC IIb was decreased (P < 0.01). The mRNA expressions of genes related to fiber type transformation were linearly up-regulated (P < 0.05). CONCLUSION: These findings indicated that carnosine supplementation was beneficial to improve the growth performance, meat quality, antioxidant capacity and muscle fiber characteristics of broilers. © 2017 Society of Chemical Industry.

Separation of N-derivatized di- and tri-peptide stereoisomers by micro-liquid chromatography using a quinidine-based monolithic column - Analysis of l-carnosine in dietary supplements.

In the present study, a new analytical methodology was developed enabling the enantiomeric determination of N-derivatized di- and tri-peptides in dietary supplements using chiral micro-LC on a monolithic column consisting of poly(O-9-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine-co-2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) (poly(MQD-co-HEMA-co-EDMA)). After optimization of the mobile phase conditions, a baseline resolution of the stereoisomers of 24 out of 53 N-derivatized di- and tri-peptides was obtained. 3,5-Dinitrobenzoyl- and 3,5-dichlorobenzoyl-peptide stereoisomers were separated with exceptionally high selectivity and resolution. The monolithic column was then applied to the quantitative analysis of l-carnosine and its enantiomeric impurity in three different commercial dietary supplements. Method validation demonstrated satisfactory results in terms of linearity, precision, selectivity, accuracy and limits of detection and quantification. The determined amounts of l-carnosine in commercial formulations were in agreement with the labeled content for all analyzed samples, and the enantiomeric impurity was found to be below the limit of detection (LOD), showing the potential of the poly(MQD-co-HEMA-co-EDMA) monolithic column as a reliable tool for the quality control of l-carnosine in dietary supplements by micro-LC.

Effect of dietary histidine on contents of carnosine and anserine in muscles of broilers.

Carnosine (ß-alanyl-L-histidine) and anserine (ß-alanyl-1-methyl-L-histidine) are dipeptides mainly found in skeletal muscle and brain of many vertebrates, and particularly high concentrations are observed in chicken pectoral muscles. It was reported that these peptides have many functions, such as antioxidant activity. In this study, we examined the effect of different levels of dietary histidine on carnosine and anserine contents in broiler muscles. The 14-days-old female Chunky strain broilers were given feeds containing three different levels of histidine; 67% (Low-His), 100% (Control) and 200% (High-His) of histidine requirement according to the NRC (1994). Chicks were fed experimental diets for 10 days. Both dipeptides in muscle were significantly decreased. In particular, carnosine was not detected at all in the Low-His group and was significantly increased in the High-His group. Both dipeptides were not detected in plasma. These results indicated the possibility to produce chicken meat with enhanced amount of these dipeptides by high histidine feeding.

Effects of natural antioxidants on colour stability, lipid oxidation and metmyoglobin reducing activity in raw beef patties.

BACKGROUND: Minced meats undergo oxidative changes and develop rancidity more quickly than intact muscle since grinding exposes more of the muscle surface to air and microbial contamination. Due to concerns about toxicological safety of synthetic antioxidants, recent studies have put more focus on natural antioxidant compounds derived from food components. METHODS: The effects of four natural antioxidants (vitamin E, carnosine, grape seed extract and tea catechins) on oxidative processes and metmyoglobin reducing activity in raw beef patties during refrigerated (4°C) storage were investigated and the results were compared with butylated hydroxyanisole treatment patties. The correlation of lipid oxidation, colour and metmyoglobin reducing activity of beef patties were also studied. RESULTS: Samples treated with carnosine had the highest redness values on the eighth day. Tea catechins, vitamin E and grape seed extract showed higher protective effect against lipid oxidation than carnosine. Metmyoglobin reducing activity increased greatly in all samples during the storage. Significant correlation between redness value and lipid oxidation was demonstrated, while a weak correlation between metmyoglobin reducing activity and any other parameters was shown.

An high-performance liquid chromatographic method for the simultaneous analysis of acetylcarnitine taurinate, carnosine, asparagine and potassium aspartate and for the analysis of phosphoserine in alimentary supplements.

A RP-HPLC method with pre-column derivatization was developed and validated for the simultaneous quantification of carnosine (Carn), acetylcarnitine taurinate (AC-Tau), asparagine (Asn), potassium aspartate (Asp) and for the determination of phosphoserine (p-Ser) in new and commercial alimentary supplements. The effect of complex matrices was evaluated by the study of the amino acid derivatization reaction with 2,4-dinitrofluorobenzene (DNFB) both in standard and placebo solutions. The reaction was carried out for 20 min at 70 °C in alkaline medium (pH10) for p-Ser analysis, whereas for 60 min in the case of Carn, AC-Tau, Asn and Asp analysis. The adducts have been separated on a Discovery RP Amide C16 (250 mm×4.6mm, i.d.) column using a mobile phase consisting of acetonitrile (ACN) and triethylammonium (TEA) phosphate buffer (pH 3, 0.05 M) under gradient elution conditions at a flow-rate of 0.8 mL/min. Detection was set at λ=360 nm. The validation parameters such as linearity, sensitivity, accuracy, precision and specificity were found to be highly satisfactory. Linear responses were observed by placebo solutions (determination coefficient ≤0.9996). Intra-day precision (relative standard deviation, RSD) was ≤1.06% for corrected peak area and ≤0.99% for retention times (tR) without significant differences between intra- and inter-day data. Recovery studies showed good results for all examined compounds (from 97.7% to 101.5%) with RSD ranging from 0.5% to 1.3%). The high stability of derivatized compound solutions at room temperature means an undoubted advantage of the method allowing the simultaneous preparation of a large number of samples and consecutive chromatographic analyses by the use of an autosampler. The developed method can be considered suitable for the quality control of new and commercial products.

Effect of two ß-alanine dosing protocols on muscle carnosine synthesis and washout.

Carnosine (ß-alanyl-L-histidine) is found in high concentrations in skeletal muscle and chronic ß-alanine (BA) supplementation can increase carnosine content. This placebo-controlled, double-blind study compared two different 8-week BA dosing regimens on the time course of muscle carnosine loading and 8-week washout, leading to a BA dose-response study with serial muscle carnosine assessments throughout. Thirty-one young males were randomized into three BA dosing groups: (1) high-low: 3.2 g BA/day for 4 weeks, followed by 1.6 g BA/day for 4 weeks; (2) low-low: 1.6 g BA/day for 8 weeks; and (3) placebo. Muscle carnosine in tibialis-anterior (TA) and gastrocnemius (GA) muscles was measured by 1H-MRS at weeks 0, 2, 4, 8, 12 and 16. Flushing symptoms and blood clinical chemistry were trivial in all three groups and there were no muscle carnosine changes in the placebo group. During the first 4 weeks, the increase for high-low (TA 2.04 mmol/kgww, GA 1.75 mmol/kgww) was ~twofold greater than low-low (TA 1.12 mmol/kgww, GA 0.80 mmol/kgww). 1.6 g BA/day significantly increased muscle carnosine within 2 weeks and induced continual rises in already augmented muscle carnosine stores (week 4-8, high-low regime). The dose-response showed a carnosine increase of 2.01 mmol/kgww per 100 g of consumed BA, which was only dependent upon the total accumulated BA consumed (within a daily intake range of 1.6-3.2 g BA/day). Washout rates were gradual (0.18 mmol/kgww and 0.43 mmol/kgww/week; ~2%/week). In summary, the absolute increase in muscle carnosine is only dependent upon the total BA consumed and is not dependent upon baseline muscle carnosine, the muscle type, or the daily amount of supplemented BA.

The effect of 4 weeks beta-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres.

Seven male students were supplemented with beta-alanine (beta-ALG) for 4 weeks (6.4 g day(-1)) and seven with a matching placebo (PLG). Subjects undertook 4 weeks of isokinetic training with the right leg (T) whilst the left leg was untrained (UT), serving as a control. Each training session consisted of 10 x 10 maximal 90 degrees extension and flexion contractions at 180 degrees /s using a Kin-Com isokinetic dynamometer, with 1 min rest between bouts. Muscle biopsies were taken from the vastus lateralis immediately before and at the end of the supplementation period. Following freeze drying muscle fibres were dissected and characterised by their MHC profile, as type I, IIa, IIx, or as hybrids of these. Carnosine was measured by HPLC. There was a significant increase in carnosine in both T and UT legs of the beta-ALG (9.63 +/- 3.92 mmol kg(-1) dry muscle and 6.55 +/- 2.36 mmol kg(-1) dry muscle respectively). There was a significant increase in the carnosine content of all fibre phentotypes, with no significant difference between types. There were no significant differences in the changes in muscle or in fibres between the T and UT legs. In contrast there was no significant change in the carnosine content in either the T or UT legs with placebo. The results indicate that 4 weeks training has no effect on the muscle carnosine content. Whilst an increase was seen with beta-alanine supplementation, this was not further influenced by training. These findings suggest that beta-alanine availability is the main factor regulating muscle carnosine synthesis.

Creatine supplementation augments skeletal muscle carnosine content in senescence-accelerated mice (SAMP8).

The histidine-containing dipeptides (HCD) carnosine and anserine are found in high concentrations in mammalian skeletal muscle. Given its versatile biologic properties, such as antioxidative, antiglycation, and pH buffering capacity, carnosine has been implicated as a protective factor in the aging process. The present study aimed to systematically explore age-related changes in skeletal muscles HCD content in a murine model of accelerated aging. Additionally, we investigated the effect of lifelong creatine supplementation on muscle HCD content and contractile fatiguability. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 weeks. At week 10, 25, and 60, tibialis anterior muscles were dissected and analysed for HCD and taurine content by HPLC. Soleus and EDL muscles were tested for in vitro contractile fatigue and recovery. From 10 to 60 weeks of age, muscular carnosine (-45%), taurine (-24%), and total creatine (-42%) concentrations gradually and significantly decreased. At 25 but not at 60 weeks, oral creatine supplementation significantly increased carnosine (+88%) and anserine (+40%) content compared to age-matched control-fed animals. Taurine and total creatine content were not affected by creatine supplementation at any age. Creatine-treated mice showed attenuated muscle fatigue (soleus) and enhanced force recovery (m. extensor digitorum longus [EDL]) compared to controls at 25 weeks, but not at 60 weeks. From the present study, we can conclude that skeletal muscle tissue exhibits a significant decline in HCD content at old age. Oral creatine supplementation is able to transiently but potently increase muscle carnosine and anserine content, which coincides with improved resistance to contractile fatigue.

Proton MRS reveals frontal lobe metabolite abnormalities in idiopathic generalized epilepsy.

OBJECTIVE: To assess gamma-aminobutyric acid (GABA) plus homocarnosine (GABA+) and glutamate plus glutamine (GLX) concentrations in the frontal lobes of patients with idiopathic generalized epilepsy (IGE). METHODS: Twenty-one patients and 17 healthy volunteers were studied. A single voxel was prescribed in each frontal lobe for each subject. Point-resolved spectroscopy (PRESS)-localized short echo time MR spectroscopy (MRS) was performed to measure GLX and the metabolites N-acetylaspartate plus N-acetylaspartylglutamate (NAAt), creatine and phosphocreatine (Cr), choline-containing compounds (Cho), and myo-inositol (Ins). A double quantum GABA filter was used to measure GABA+. Segmented T1-weighted images gave the tissue composition of the prescribed voxel. RESULTS: Group comparisons showed elevation of GLX and reduction of NAAt in the patient group (p < 0.05). The metabolite ratios GLX/NAAt and GLX/Ins also showed elevation in IGE (p = 0.01). No group effect was observed for GABA+, Cr, or Cho. Ins concentrations were not significantly reduced in the patient group but were less in the subgroup of patients who were taking sodium valproate. CONCLUSIONS: IGE was associated with bilateral frontal lobe metabolite changes. Elevation in GLX was observed, which may imply increased neuronal excitability, whereas reduction in NAAt suggests reduced overall neuronal numbers or neuronal dysfunction.

High levels of dietary carnosine are associated with increased concentrations of carnosine and histidine in rat soleus muscle.

The aims of this investigation were to: 1) determine the effect of a moderately high dose of carnosine on muscle concentrations of carnosine, histidine and vitamin E at deficient, minimally adequate and sufficient levels of dietary vitamin E and 2) compare the effects of moderately high and pharmacological doses of carnosine on muscle concentrations of carnosine, histidine and vitamin E when dietary vitamin E is minimally adequate. Muscle concentrations of carnosine, histidine and vitamin E were measured in the lateral gastrocnemius and red and white vastus lateralis; carnosine and histidine concentrations were also measured in soleus muscle. Male Sprague-Dawley rats (n = 12/group) were fed a basal vitamin E-deficient diet supplemented with either 0, 0.001 or 0.01% vitamin E and 0, 0.1 or 1.8% carnosine. After 8 wk, 1.8% carnosine resulted in significant fivefold increases in carnosine and twofold increases in histidine in the soleus muscle (P < or = 0.05). Muscle vitamin E concentrations were not significantly affected by dietary carnosine. Thus, very high levels of dietary carnosine are associated with increases in carnosine and histidine concentrations in rat soleus muscle.

Effects of gabapentin on brain GABA, homocarnosine, and pyrrolidinone in epilepsy patients.

PURPOSE: Gabapentin (GBP) was introduced as an antiepileptic drug (AED) and has been used in the management of neuropathic pain. We reported that daily dosing increased brain gamma-aminobutyric acid (GABA) in patients with epilepsy. This study was designed to determine how rapidly brain GABA and the GABA metabolites, homocarnosine and pyrrolidinone, increase in response to the first dose of GBP. METHODS: In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made of a 14-cc volume in the occipital cortex by using a 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Six patients (four women) were studied serially after the first oral dose (1,200 mg) of GBP. Five patients (three women) taking a standard daily dose (range, 1,200-2,000 mg) of GBP were rechallenged with a single high dose (2,400 mg). RESULTS: The first dose of GBP increased median brain GABA by 1.3 mM (range, 0.4-1.8 mM) within 1 h. Homocarnosine and pyrrolidinone did not change significantly by 5 h. Daily GBP therapy increased GABA (0.5 mM; 95% CI, 0.2-0.9), homocarnosine (0.3 mM; 95% CI, 0.2-0.4), and pyrrolidinone (0.10 mM; 95% CI, 0.06-0.14). Rechallenging patients taking GBP daily increased median brain GABA by 0.4 mM (range, 0.3-0.5) within 1 h. CONCLUSIONS: GBP promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the anticonvulsant effects of increased homocarnosine and pyrrolidinone with daily therapy.

Influence of oral beta-alanine and L-histidine supplementation on the carnosine content of the gluteus medius.

The aim of this work was to test the hypothesis that in vivo carnosine biosynthesis is dependent upon endogenous beta-alanine availability, by studying the effect of sustained dietary beta-alanine supplementation in the horse on the carnosine concentration in types I, IIA and IIB skeletal muscle fibres. The diets of 6 Thoroughbred horses were supplemented 3 times/day with beta-alanine (100 mg/kg bwt) and L-histidine (12.5 mg/kg bwt) for a period of 30 days. Percutaneous biopsies of the m. gluteus medius from a depth of 6 cm were taken on the days immediately before and after the supplementation period. Heparinised blood samples were collected at hourly intervals on the first and last days of supplementation, and on every sixth day during the supplementation period, 2 h after each ration. Individual muscle fibres were dissected from freeze-dried biopsies, weighed and characterised histochemically. beta-alanine, histidine and carnosine concentrations were measured in plasma. The areas under the plasma concentration-time curves (AUC) for beta-alanine and histidine were calculated as indicators of the doses absorbed. Carnosine concentrations were measured in types I, IIA and IIB muscle fibres. There was an adaptive response to sustained beta-alanine administration resulting in mean +/- s.d. beta-alanine AUC increasing significantly from 1130 +/- 612 mumol/l h (Day 1) to 2490 +/- 1416 mumol/l h (Day 30) (P < 0.05). This was probably due to increased beta-amino acid transport across the gastrointestinal lumen. There was no consistent increase in histidine AUC between Days 1 and 30, (mean +/- s.d. values being 757 +/- 447 mumol/l h Day 1[ and 1162 +/- 1084 mumol/l h Day 30[ P > 0.05[). Type IIA fibre carnosine concentrations increased from 59.9-102.6 to 76.2-112.2 mmol/kg dry weight (dw). Increases were statistically significant in 2 of the 6 horses (P < 0.05 in both instances). Type IIB fibre carnosine concentrations increased from 101.3-131.2 to 114.3-153.3 mmol/kg dw. Increases were statistically significant in 5 of the 6 horses (P < 0.05 in 3 horses, P < 0.01 in 1 horse, P < 0.005 in 1 horse). Changes in muscle carnosine concentration appeared to be influenced by beta-alanine bioavailability. Individual increases in muscle carnosine concentration were significantly correlated with individual changes in beta-alanine AUC (r2 = 0.973, P < 0.005). Increased muscle carnosine concentrations lead to increased intramuscular hydrogen ion (H+) buffering capacity.

[Taurine and carnosine in tissues of Pacific mollusks]. / Taurin i karnozin v tkaniakh Tikhookeanskikh molliuskov.

The containing of taurine and carnosine (low-molecular biologically active substances) was studied in tissues of molluscs (Gastropodae, Brahiopodae and Cephalopodae) by 38 species. The highest concentration of taurine found in the octopus and 5 species of shells (Gastropodae). The containing of carnosine in mollusks is highly lower than in bovine muscles. Organoleptic quality of lyophilized water-spirit extracts by soft tissues of molluscs allow to use it as a taurine-enriching food addition.