Analysis of microRNA Expression Profiles in Broiler Muscle Tissues by Feeding Different Levels of Guanidinoacetic Acid.

The aim of this study was to explore the molecular mechanisms through which different levels of GAA affect chicken muscle development by influencing miRNA expression, to lay a theoretical foundation for the identification of key functional small RNAs related to poultry muscle development, and to provide new insights into the regulatory mechanisms of GAA on muscle development and meat quality in broilers. It provides a new theoretical basis for using GAA as a feed additive to improve feed performance. Small RNA sequencing technology was utilized to obtain the expression profiles of miRNA in the broiler pectoral muscle fed with different levels of GAA (0 g/kg, 1.2 g/kg and 3.6 g/kg). An analysis of differentially expressed miRNAs revealed 90 such miRNAs in the three combination comparisons, with gga-miR-130b-5p exhibiting significant differences across all three combinations. Furthermore, three of the differentially expressed miRNAs were performed by RT-qPCR verification, yielding results consistent with those obtained from small RNA sequencing. Target gene prediction, as well as the GO and KEGG enrichment analysis of differentially expressed miRNAs, indicated their involvement in muscle cell differentiation and other processes, particularly those associated with the MAPK signaling pathway. This study has, thus, provided valuable insights and resources for the further exploration of the miRNA molecular mechanism underlying the influence of guanidine acetic acid on broiler muscle development. Combined with previous studies and small RNA sequencing, adding 1.2 g/kg GAA to the diet can better promote the muscle development of broilers.

Embryonic thermal manipulation and post-hatch dietary guanidinoacetic acid supplementation alleviated chronic heat stress impact on broiler chickens.

The study investigated the effects of embryonic thermal manipulation (TM) and post-hatch guanidinoacetic acid (GAA) supplementation on male broiler chickens exposed to chronic heat stress (HS). Ross 308 eggs (n = 710) were randomly assigned to control (37.8 °C, 56% RH) or TM (39.5 °C, 65% RH for 12 h/day from embryonic day 7-16) treatments. After hatching, chicks were further assigned to four dietary treatments (n = 12 birds/pen, 5 replicates/treatment): control, control with 1.2 g/kg GAA supplementation (CS), TM, and TM with 1.2 g/kg GAA supplementation (TMS). All birds were subjected to chronic HS (32-36 °C and 55% RH for 6 h/day) from day 28-42. Embryonic TM treatment decreased hatchability, hatching weight (HW), and facial temperature (FT). During the pre-HS period (days 1-28), no significant differences in feed conversion ratio (FCR) and mortality were observed, although the TM group exhibited the lowest body weight gain (BWG). Following HS exposure (days 29-42), the TMS group displayed significantly higher BWG than the control and CS groups. The TM and TMS groups also demonstrated significantly lower FCR and mortality rates during this period. Across the entire period (days 1-42), BWG was significantly higher in the TMS group compared to other groups. Furthermore, TM and TMS treatments were associated with lower mortality rates, improved FCR, better European Performance Efficiency Index (EPEI), and reduced abdominal fat deposition. The experimental treatments did not significantly affect intestinal morphology or most blood parameters, except triiodothyronine (T3), thyroxine (T4), and uric acid. Plasma concentrations of T3, T4, and uric acid were significantly lower in the TM and TMS groups compared to the control and CS treatments. The findings suggest that a combined strategy of embryonic TM and post-hatch dietary GAA supplementation may not only alleviate the detrimental effects of HS but also promote beneficial physiological responses in broiler chickens.

Effects of guanidinoacetic acid supplementation on lactation performance, nutrient digestion and rumen fermentation in Holstein dairy cows.

BACKGROUND: Considering the high energy demand of lactation and the potential of guanidinoacetic acid (GAA) addition on the increase in creatine supply for cows, the present study investigated the effects of 0, 0.3, 0.6 and 0.9 g kg-1 dry matter (DM) of GAA supplementation on lactation performance, nutrient digestion and ruminal fermentation in dairy cows. The study used 40 mid-lactation multiparous Holstein cows and the study duration was 100 days. RESULTS: DM intake was not affected, but milk and milk component yields and feed efficiency increased linearly with increasing GAA addition. The total-tract digestibility of DM, organic matter, neutral detergent fibre, acid detergent fibre and non-fibre carbohydrates increased linearly and that of crude protein increased quadratically with increasing GAA addition. When the addition level of GAA increased, ruminal pH, molar percentages of butyrate, isobutyrate and isovalerate and the acetate-to-propionate ratio decreased linearly, and the total volatile fatty acids concentration and propionate molar percentage also increased linearly, whereas the acetate molar percentage and ammonia-N concentration were unaltered. The activities of fibrolytic enzymes, α-amylase and protease increased linearly. The populations of total bacteria, fungi, Ruminococcus albus, Fibrobacter succinogenes, Ruminococcus flavefaciens, Ruminobacter amylophilus and Prevotella ruminicola increased linearly, whereas protozoa and methanogens decreased linearly with increasing GAA addition. As for the blood metabolites, concentrations of glucose, urea nitrogen and methionine were unchanged, total protein, albumin, creatine and homocysteine increased linearly, and folate decreased linearly with increasing GAA supply. CONCLUSION: The results of the present study indicate that supplementation of GAA improved milk performance and rumen fermentation in lactating dairy cows. © 2022 Society of Chemical Industry.

Dietary creatine and guanidinoacetic acid supplementation have limited effects on hybrid striped bass.

The effects of dietary supplementation of creatine and guanidinoacetic acid (GDA) have been studied to a limited extent in various fish species including red drum (Sciaenops ocellatus) and hybrid striped bass (HBS) (Morone saxatilis x M. chrysops). However, in HSB, there is a need to better understand the impact of creatine and GDA supplementation at elevated salinity which may be encountered by this euryhaline fish. Therefore, two separate feeding trials were conducted at a salinity ranging from 15 to 20 g/L with juvenile HSB for 9 and 8 weeks to evaluate the effects of dietary creatine and GDA. In each trial, four diets were formulated with either singular additions of creatine at 2% of dry weight, GDA at 1% of dry weight, or a combination of both. Fish grew adequately in both feeding trials but no significant (P > 0.05) effects of supplemental creatine or GDA were observed on weight gain, feed efficiency, survival, hepatosomatic index (HSI), intraperitoneal fat (IPF ratio), or protein conversion efficiency (PCE). However, fish fed diets supplemented with creatine had significantly (P < 0.05) increased ash and reduced lipid deposition in whole-body tissues in the first feeding trial. Supplemental creatine also resulted in significantly higher muscle yield in the second trial, but no other effects on growth performance or body composition were observed. The addition of GDA to the diet had little effect except for significantly increasing the creatine content in the liver of fish in both feeding trials due to its role as a precursor and a catalyst for synthesis of creatine within the body. Based on the results of these two trials, supplemental creatine and GDA had rather limited effects on HSB cultured in moderately saline water.

Serum metabolomics reveals the effects of accompanying treatment on fatigue in patients with multiple myeloma.

PURPOSE: The renewal and iteration of chemotherapy drugs have resulted in more frequent long-term remissions for patients with multiple myeloma (MM). MM has transformed into a chronic illness for many patients, but the cancer-related fatigue (CRF) of many MM convalescent patients experience is frequently overlooked. We investigated whether the accompanying treatment of family members would affect MM patients' CRF and explore their serum metabolomics, so as to provide clinicians with new ideas for identifying and treating CRF of MM patients. METHODS: This was a single-center study, and a total of 30 MM patients were included in the study. Patients were divided into two groups based on whether they have close family members accompanying them through the whole hospitalization treatment. These patients received regular chemotherapy by hematology specialists, and long-term follow-up was done by general practitioners. Patients' CRF assessment for several factors used the Chinese version of the Brief Fatigue Inventory (BFI-C). Face-to-face questionnaires were administered at a time jointly determined by the patient and the investigator. All questionnaires were conducted by a general practitioner. The LC-MS-based metabolomics analysis determined whether the patients' serum metabolites were related to their fatigue severity. A correlation analysis investigated the relationship between serum metabolites and clinical laboratory indicators. RESULTS: The fatigue severity of MM patients whose family members participated in the treatment process (group A) was significantly lower than patients whose family members did not participate in the treatment process (group B). There was a statistically significant difference (fatigue severity composite score: t = - 2.729, p = 0.011; fatigue interference composite score: t = - 3.595, p = 0.001). There were no differences between the two groups of patients' gender, age, regarding clinical staging, tumor burden, blood routine, biochemical, or coagulation indexes. There were 11 metabolites, including guanidine acetic acid (GAA), 1-(Methylthio)-1-hexanethiol, isoeucyl-asparagine, L-agaritine, tryptophyl-tyrosine, and betaine, which significantly distinguished the two groups of MM patients. GAA had the strongest correlation with patient fatigue, and the difference was statistically significant (fatigue severity composite score: r = 0.505, p = 0.0044; fatigue interference composite score: r = 0.576, p = 0.0009). The results showed that GAA negatively correlated with albumin (r = - 0.4151, p = 0.0226) and GGT (r = - 0.3766, p = 0.0402). Meanwhile, GAA positively correlated with PT (r = 0.385, p = 0.0473), and the difference was statistically significant. CONCLUSION: The study is the first to report that family presence throughout the whole hospitalization may alleviate CRF in MM patients. Moreover, the study evaluated serum metabolites linked to CRF in MM patients and found that CRF has a significant positive correlation with GAA. GAA may be a more sensitive biomarker than liver enzymes, PT, and serum albumin in predicting patient fatigue. While our sample may not represent all MM patients, it proposes a new entry point to help clinicians better identify and treat CRF in MM patients.

Guanidinoacetic acid provides superior cardioprotection to its combined use with betaine and (or) creatine in HIIT-trained rats.

This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants ( O 2 - , H2O2, NO 2 - , and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the cross-sectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario.

Cataloguing guanidinoacetic acid content in various foods.

Guanidinoacetic acid (GAA) is a natural amino acid derivative involved in several metabolic pathways across the human body, including creatine biosynthesis, arginine utilization, and neuromodulation. Apart from GAA synthesized internally from glycine and arginine, a total daily exposure to GAA also involves exogenous dietary sources. However, a majority of food databases provide no comprehensive data about the amount of GAA available from various foods. In this report, we summarize information for GAA levels in different food groups, as extracted from the available scientific literature. The content of GAA appears to vary across different foods, with meat-based products contain the highest relative amount of GAA (~50 mg per kg), followed by a dairy group (~0.3 mg per kg), and plant-based foods (~1 µg per kg), with the latter considered to be almost negligible. Although no data are currently available about its requirements in humans, cataloguing GAA amount in various foods could help in more accurate quantification of GAA provision via regular diet in the future.

Feeding guanidinoacetic acid to broiler chickens can compensate for low dietary metabolisable energy formulation.

1. This study compared the responses of broilers to diets supplemented with the same level of guanidinoacetic acid (GAA) but formulated to have different N-corrected apparent metabolisable energy (AMEn) contents. The study involved 1280, one-day-old Ross 308 broilers, in 64 pens comprising 32 pens of males and 32 pens females, (20 birds in each) aged from 0 to 42 d.2. Commercial AME levels of 12.55 MJ/kg, 12.97 MJ/kg and 13.18 MJ/kg in the starter, grower and finisher diets, respectively, were set for the positive control (PC) feed. Four dietary treatments were prepared: PC (as above); negative control 1 (NC; PC - 0.21 MJ ME /kg); NC1 + 0.06% GAA; NC2 (PC - 0.42 MJ ME/kg + 0.06% GAA). Each diet was provided in 16 pens (eight male and eight female), following randomisation.3. Overall, birds fed NC1 had lower feed intakes (FI) compared to birds fed the PC and NC2+ GAA, lower weight gain (WG) compared to all the other diets and lower final body weight than birds fed the GAA diets (P < 0.05). There was a diet x sex interaction (P = 0.039), whereby feeding NC+GAA to female birds improved feed efficiency compared to being fed NC2 and NC1+ GAA, but not in males. Birds fed diets with GAA had a higher poultry efficiency factor (P < 0.001) than those fed NC1.4. There were no effects of treatment or sex on litter moisture, footpad score, white striping, wooden breast, AMEn, dry matter and fat retention (P > 0.05). However, the diet NC1+ GAA had 11.2% higher nitrogen retention coefficient compared to the NC1 diet (P = 0.038).5. Overall, the results implied that lower performance induced by a reduction of dietary AMEn in the range of 0.21 to 0.42 MJ/kg was more than compensated by supplementing 600 g/t GAA to the feed.

Neonatal Piglets Can Synthesize Adequate Creatine, but Only with Sufficient Dietary Arginine and Methionine, or with Guanidinoacetate and Excess Methionine.

BACKGROUND: Suckling piglets synthesize most of their creatine requirement, which consumes substantial amounts of arginine in order to synthesize guanidinoacetic acid (GAA) and methionine in order to transmethylate GAA to creatine. OBJECTIVES: To determine whether supplemental GAA or creatine spare arginine and/or methionine for protein synthesis and, if GAA is supplemented, whether excess methionine is needed for conversion to creatine. METHODS: Yucatan miniature piglets (9-11 days old; both sexes) were fed 1 of 5 elemental diets for 5 days: 1) low arginine (0.3 g·kg-1·d-1) and low methionine (0.20 g·kg-1·d-1; Base); 2) Base plus GAA (0.093 g·kg-1·d-1; +GAA); 3) Base plus GAA plus excess methionine (0.5 g·kg-1·d-1; +GAA/Met); 4) Base plus creatine (0.12 g·kg-1·d-1; +Cre); or 5) excess arginine (1.8 g·kg-1·d-1) and excess methionine (+Arg/Met). Isotope tracers were infused to determine whole-body GAA, creatine, and protein synthesis; tissues were analyzed for creatine synthesis enzymes and metabolite concentrations. Data were analyzed by 1-way ANOVA. RESULTS: : GAA and creatine syntheses were 115% and 32% higher, respectively, with the +Arg/Met diet (P < 0.0001), in spite of 33% lower renal L-arginine: glycine amidinotransferase activity (P < 0.0001) compared to Base, suggesting substrate availability dictates synthesis rather than enzyme capacity. GAA or creatine supplementation reduced arginine conversion to creatine by 46% and 43%, respectively (P < 0.01), but did not spare amino acids for whole-body protein synthesis, suggesting that limited amino acids were diverted to protein at the expense of creatine synthesis. The +GAA/Met diet led to higher creatine concentrations in the kidney (2.6-fold) and liver (7.6-fold) than the +GAA diet (P < 0.01), suggesting excess methionine is needed for GAA conversion to creatine. CONCLUSIONS: Piglets are capable of synthesizing sufficient creatine from the precursor amino acids arginine and methionine, or from GAA plus methionine.

Effects of guanidinoacetic acid and coated folic acid supplementation on growth performance, nutrient digestion and hepatic gene expression in Angus bulls.

To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA-) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA- diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA- diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.

Effects of guanidinoacetic acid and complex antioxidant supplementation on growth performance, meat quality, and antioxidant function of broiler chickens.

BACKGROUND: This study was conducted to evaluate the effects of adding guanidinoacetic acid (GAA), or complex antioxidant (CA), or their combination, in diets on the growth performance, carcass traits, meat quality, and antioxidant capacity of broilers. A total of 192 25-day-old broilers were assigned to a 2 × 2 factorial design including two dietary supplements at two different levels, in which the main effects were the addition of GAA (0 or 600 mg kg-1 ) and CA (0 or 150 mg kg-1 ). This trial lasted for 18 days. RESULTS: Compared with the control group, the GAA group, CA group, and GAA + CA group, decreased feed conversion ratio by 7.02%, 6.58%, and 11.40%, respectively. Guanidinoacetic supplementation increased eviscerated yield, pH24h (P < 0.05). Complex antioxidant supplementation increased the a* values (P < 0.05). The combination of GAA and CA did not affect the carcass traits and meat quality. Guanidinoacetic acid alone and CA alone and combined with GAA and CA decreased the reactive oxygen species (ROS) level and malonaldehyde (MDA) content (P < 0.05), and the GAA + CA group had the lowest ROS level and MDA content of broilers. CONCLUSION: Dietary supplementation of GAA, CA or their combination had beneficial effects on growth performance and breast antioxidant capacity, and the combination of GAA and CA could exert a synergistic effect in improving antioxidant capacity. © 2020 Society of Chemical Industry.

Guanidinoacetic acid deficiency: a new entity in clinical medicine?

Guanidinoacetic acid (GAA, also known as glycocyamine or betacyamine) is a naturally-occurring derivative of glycine and a direct metabolic precursor of creatine, a key player in high-phosphate cellular bioenergetics. GAA is found in human serum and urine, with circulating GAA likely reflects an equilibrium between its endogenous production and utilization/excretion. GAA deficiency (as indicated by low serum GAA) has been reported in various conditions yet this intriguing clinical entity appears to be poorly characterized as yet, either as a primary deficit or a sequel of secondary disease. This minireview article summarizes the inherited and acquired disorders with apparent GAA deficiency and discusses a possible relevance of GAA shortfall in clinical medicine.

Dietary guanidinoacetic acid supplementation improved carcass characteristics, meat quality and muscle fibre traits in growing-finishing gilts.

This study was designed to evaluate the effects of guanidinoacetic acid (GAA) on growth performance, carcass characteristics, meat and muscle fibre traits of growing-finishing gilts. 300 female PIC pigs were randomly divided (30.10 ± 2.94 kg) into 2 treatments with 6 replicates of 25 each for a 100-day trial. Two dietary treatments were comprised of a control diet and a control diet fortified with 450 mg/kg GAA. Growth performance was evaluated for each phase. Carcass characteristics and meat quality were determined at last phase. Gilts had free access to feed and water during the experiment. The result indicated that GAA did not affect growth performance (p > 0.05). GAA not only increased longissimus dorsi (LM) muscle weight but also decreased its shear force, b*value and drip loss (p < 0.05). Mandibular fat index was decreased by GAA (p < 0.05). GAA upregulated myosin heavy chain (MyHC) I mRNA expression with lower myofibre cross-sectional area and fibre diameter in LM muscle (p < .05). In conclusion, GAA can improve carcass characteristics and meat quality by changing muscle fibre characteristics and reducing mandibular fat index in finishing gilts.

Correlation between biomarkers of creatine metabolism and serum indicators of peripheral muscle fatigue during exhaustive exercise in active men.

Exhaustive exercise induces various disturbances of homeostasis, with impaired bioenergetics often associated with strenuous muscular work. However, no study so far validated serum biomarkers of creatine metabolism vs. traditional markers of exhaustive exercise and fatigue. Here, we investigated how well changes in serum guanidinoacetic acid (GAA), creatine and creatinine correlate with responses in blood lactate, creatine kinase, interleukin-6 and cortisol in 11 young active men (age 23.2 ± 3.7 years; VO2max 49.5 ± 5.4 ml/kg/min) exposed to exhaustive exercise. All participants were subjected to running at individual running speed at anaerobic threshold until exhaustion, with venous blood drawn at baseline and during an exercise session at 5-min intervals. Running-to-exhaustion markedly affected serum GAA and creatine levels, with circulating GAA increased for 5.3 ± 8.5%(95% CI, -0.4 to 11.0), and serum creatine elevated by 33.9 ± 21.8% (95% CI, 19.3 to 48.6) compared to baseline levels (P ≤ 0.05). In addition, moderate-to-strong positive linear correlations were found between exhaustive exercise-induced changes in serum cortisol and GAA levels (r = 0.79; P = 0.03), and cortisol and creatine concentrations (r = 0.81; P = 0.03). This suggests a link between cortisol and heavy exercise-induced impaired bioenergetics, with future studies needed to evaluate a cause-and-effect interconnection between cortisol and GAA-creatine axis.

Benefits and drawbacks of guanidinoacetic acid as a possible treatment to replenish cerebral creatine in AGAT deficiency.

Arginine-glycine amidinotransferase (AGAT) deficiency is a rare inherited metabolic disorder that severely affects brain bioenergetics. Characterized by mental retardation, language impairment, and behavioral disorders, AGAT deficiency is a treatable condition, where long-term creatine supplementation usually restores brain creatine levels and improves its clinical features. In some cases of AGAT deficiency, creatine treatment might be somewhat limited due to possible shortcomings in performance and transport of creatine to the brain. Guanidinoacetic acid (GAA), a direct metabolic precursor of creatine, has recently been suggested as a possible alternative to creatine to tackle brain creatine levels in experimental medicine. AGAT patients might benefit from oral GAA due to upgraded bioavailability and convenient utilization of the compound, while possible drawbacks (e.g. brain methylation issues, neurotoxicity, and hyperhomocysteinemia) should be accounted as well.

Effects of methionine and guanidinoacetic acid supplementation on performance and energy metabolites in breast muscle of male broiler chickens fed corn-soybean diets.

1. Guanidinoacetic acid (GAA) is the single endogenous precursor of creatine, which plays a critical role in energy homeostasis of cells. Since GAA is endogenously converted to creatine by methylation, it was hypothesised that the effects of dietary GAA supplementation might determine the methionine (Met) availability in corn-soybean based diets. 2. A total of 540, one-day-old male Ross 308 broilers were allocated to nine dietary treatments with six replicates (10 birds each) in a 3 × 3 factorial arrangement with three graded levels of supplementary Met (+0.4 g/kg per level), whilst cystine was equal across groups, resulting in a low, medium and high level of total sulphur amino acids, and with three levels of GAA (0, 0.6 and 1.2 g/kg). Birds were fed for 42 days. 3. Increasing levels of supplemental Met enhanced performance indices in all rearing periods, although there was no effect on feed conversion ratio in the grower or feed intake in the finisher periods. Final body weight was 8.8% and 14.6% higher in the birds fed medium and high Met diets, respectively, compared to the low Met level. Relative breast weight and protein content in muscle on d 25 linearly increased with higher levels of Met. At low and high Met levels, growth in the finisher phase was negatively affected by supplementing GAA at 1.2 g/kg. It was suggested that disturbances in methylation homeostasis and/or changes in Arg metabolism might explain these findings. At the end of the grower phase, muscle creatine content was higher when feeding GAA at 0.6 and 1.2 g/kg (4464 and 4472, respectively, vs. 4054 mg/kg fresh muscle in the control group). 4. The effects of dietary GAA supplementation were influenced by the dietary Met level only in the finisher period, which indicates the need for proper sulphur amino acid formulation in diets when feeding GAA.

Performance and physiological responses of broiler chickens to supplemental guanidinoacetic acid in arginine-deficient diets.

1. The present experiment was designed to examine arginine (Arg)-sparing effects of guanidinoacetic acid (GAA) on production performance, intestinal morphology and certain blood parameters in broiler chickens. 2. A total of 300 male broiler chicks (Ross 308) were randomly allotted to 5 dietary treatments in a completely randomised design during 1-15 and 15-35 d rearing periods. Experimental treatments consisted of a basal diet with a reduction in Arg content (CON-; starter: 12.1 g/kg and grower: 11.3 g/kg Arg), a CON- diet supplemented with synthetic Arg equal to the required Arg level (CON+; starter: 13.80 g/kg; grower: 12.37 g/kg) and CON- diet supplemented with three levels of GAA (GAA0.6; GAA1.2; and GAA1.8; g/kg). 3. Supplemental GAA at 0.6 and 1.2 g/kg reduced the adverse effects of the CON- diet on weight gain and feed conversion ratio in the starter period, equal to the effect of CON+ diet. During the entire rearing period, such an effect was only seen for broilers fed CON- diet supplemented with 1.2 and 1.8 g/kg GAA (P < 0.05). Proportional weights of liver and abdominal fat were decreased in birds fed diets containing supplemental Arg and 1.8 g/kg GAA compared to the CON- broilers (P < 0.05). Jejunal villus height and villus height to crypt depth ratio were increased in broilers receiving the CON- diet (P < 0.05). Serum concentration of nitric oxide increased when the CON- diet was supplemented with either Arg or 1.8 g/kg GAA (P < 0.05). 4. Dietary inclusion of GAA had an Arg-sparing effect, whereby 1.2 and 1.8 g/kg of supplemental GAA resulted in greater growth performance during the starter and entire rearing periods, respectively. Supplementation with 1.8 g/kg GAA had significant effects on some carcass and physiological parameters.

Effects of guanidinoacetic acid on growth performance, creatine metabolism and plasma amino acid profile in broilers.

The objective of this study was to assess the effects of guanidinoacetic acid (GAA) on growth performance, creatine deposition and blood amino acid (AA) profile on broiler chickens. In Exp. 1, a total of 540 one-day-old Arbor Acres male broilers (average initial body weight, 45.23 ± 0.35 g) were divided randomly into five treatments with six replicates of 18 chicks each. Broilers were fed corn-soybean meal-basal diets supplemented with 0, 600, 800, 1,000 or 1,200 mg/kg GAA for 42 days respectively. Results showed that dietary GAA inclusion increased average daily gain (ADG) and improved gain-to-feed ratio (G:F) from 1 to 42 days (p < 0.01). However, average daily feed intake was unaffected by dietary supplementation of GAA. As GAA inclusion increased, the contents of creatine in plasma and kidney were increased (linear, p < 0.01), while the contents of GAA and creatine in liver were decreased (linear, p < 0.01). Similarly, GAA supplementation was inversely related to concentrations of most essential AA in plasma. In Exp. 2, a total of 432 one-day-old Arbor Acres male broilers (average initial body weight, 39.78 ± 0.58 g) were divided randomly into four treatments with six replicates of 18 chicks each. Birds were fed a corn-soybean meal-basal diet supplemented with 0, 200, 400 or 600 mg/kg GAA for 42 days respectively. Dietary inclusion of 600 mg/kg GAA significantly increased ADG and G:F of broilers (p < 0.05). In conclusion, dietary supplementation of 600-1,200 mg/kg GAA can effectively improve the growth performance in broiler chickens by affecting creatine metabolism and utilization efficiency of essential AA, and 600 mg/kg GAA is the minimum dose for improving performance.

Stability of creatine monohydrate and guanidinoacetic acid during manufacture (retorting and extrusion) and storage of dog foods.

The stability of creatine monohydrate (CrMH), crystallised guanidinoacetic acid (GAA-C) and granulated GAA (GAA-G) in a moist retorted and a dry extruded dog food formulation during production and storage was investigated. Commercial food mixtures were supplemented with CrMH, GAA-C or GAA-G. Uniformity after mixing and retorting or extrusion was determined based on replicate samples (moist n = 8, dry n = 10). Storage stability was evaluated at 25°C/60% relative humidity for 15 months and 40°C/75% for 6 months. Foods with CrMH were analysed for creatine (Cr) and creatinine (Crn), whereas GAA-C and GAA-G foods were analysed for GAA concentrations. Coefficients of variation (CV) for uniformity of the additives after mixing of moist and dry pet food formulations were below 15%, and the CV was lower in processed mixtures. Recoveries after retorting and extrusion were higher for GAA-G (79 and 99%) and GAA-C (89 and 86%) compared to CrMH (36 and 85%) foods. In moist CrMH food, Cr concentrations re-increased by 54% whilst Crn concentrations decreased by 39% after storage at 25°C for 15 months. With total molar Cr + Crn remaining stable throughout storage, Crn and Cr appeared to effectively interconvert. Storage of the extruded CrMH food at 25°C for 15 months resulted in a 63% decrease in Cr and a 39% increase in Crn concentration. The decrease in Cr concentration was larger at 6 months storage at 40°C compared to 15 months storage at 25°C. Both GAA-C and GAA-G moist and dry foods were stable during storage (<10% decrease). This study showed that GAA is highly stable during production and storage of moist and dry canine foods whilst CrMH is relatively unstable, particularly during storage. The latter makes it difficult to establish a guaranteed Cr content in finished moist retorted and dry extruded foods with CrMH.

Serum creatine is not a reliable marker of muscular fitness in young adults.

PURPOSE: Elevated serum creatine and higher handgrip strength are individually associated with better health profiles yet the link between two variables remains unknown. In this cross-sectional study, we evaluated serum creatine levels in relation to handgrip strength in a cohort of 130 young healthy adults (61 women and 69 men; age 23.3 ± 2.6 years), while controlling for age, gender, fat-free mass and biomarkers of creatine metabolism as effect modifiers. MATERIALS AND METHODS: Serum creatine, creatinine and guanidinoacetic acid (GAA) levels were measured with liquid chromatography-tandem mass spectroscopy, while handgrip strength was assessed with a hydraulic hand dynamometer. RESULTS: Hierarchical multiple regression revealed that our model as a whole explained 79.9% of the variance in handgrip strength (p < 0.001). However, the evaluation of the contribution of each independent variable revealed that gender and free-fat mass make significant contributions (45.4 and 31.8%, respectively) to our model (p < 0.05), while neither age (0.9%) nor serum creatine (4.5%) or any other lab markers made significant contributions to the model (p > 0.05). CONCLUSIONS: Having higher blood creatine appears to be unrelated with better physical performance in young healthy adults. Serum creatine was not a reliable marker of muscular fitness in this population.