Guanidinoacetic Acid Supplementation Research Articles

Guanidinoacetic acid and betaine supplementation have positive effects on growth performance, nutrient digestion and rumen fermentation in Angus bulls

This study evaluated the influences of guanidinoacetic acid (GAA) and betaine (BT) on growth performance, nutrient digestion and ruminal fermentation in bulls. Forty-four Angus bulls were blocked by live body weight and then randomly divided into four groups in a 2 × 2 factorial design. Betaine of 0 or 0.6 g/kg dry matter (DM) was added to diets containing 0 or 0.6 g/kg DM GAA, respectively. The experiment included a 20 day period for adaptation and a 60 day period for data collection. Average daily gain and feed efficiency were increased by GAA or BT but no further increase was observed for supplementing BT and GAA together than for addition with BT or GAA alone. Supplementary GAA or BT did not influence DM intake but increased apparent digestibility of DM, organic matter (OM), crude protein (CP) and acid detergent fibre (ADF). Digestibility of neutral detergent fibre (NDF) was increased by GAA inclusion but was unaltered with BT provision. Ruminal pH reduced but total volatile fatty acids and ammonia nitrogen elevated with dietary inclusion of GAA or BT. Rumen short chain fatty acids percentages and fermentation pattern were not influenced by GAA. Dietary inclusion of BT increased molar proportions of acetate, valerate, isobutyrate and isovalerate as well as the ratio of acetate to propionate. Rumen populations of Ruminococcus flavefaciens and Fibrobacter succinogenes increased with addition of GAA or BT and the increase was greater when BT was added in diets with GAA compared to diets without GAA. Addition of GAA or BT increased activities of cellobiase, xylanase, α-amylase and protease and populations of total bacteria, cellulolytic bacteria and Ruminobacter amylophilus but did not affect Prevotella ruminicola. Addition of BT increased carboxymethyl-cellulase and pectinase activities and total fungi population. Blood creatine content was increased by GAA or BT and was greater for addition of GAA and BT together than for GAA or BT addition alone. Serum contents of glucose, folate, arginine and methionine were unchanged but total protein increased with GAA or BT provision. Blood homocysteine content was unaffected by GAA but decreased with BT supplementation. The data showed that GAA or BT addition improved growth performance and feed efficiency but supplementing GAA and BT together did not further increase the performance of bulls when compared with GAA or BT inclusion alone.

Response of laying hens to l-arginine, l-citrulline and guanidinoacetic acid supplementation in reduced protein diet.

A study was conducted with Hy-Line Brown laying hens to examine the effects of reduced protein diet, deficiency of arginine (Arg), and addition of crystalline Arg, citrulline (Cit) and guanidinoacetic acid (GAA) as substitutes for Arg. Hen performance, egg quality, serum uric acid, liver and reproductive organ weights, and energy and protein digestibility were measured using a completely randomized design with 5 treatments. Treatments were a standard diet (17% protein diet; SP), a reduced diet (13% protein diet deficient in Arg; RP) and RP with added Arg (0.35%, RP-Arg), GAA (0.46% equivalent to 0.35% Arg, RP-GAA) or Cit (0.35%, RP-Cit) to the level of SP. It was hypothesized that performance would decrease with Arg deficient RP diet and the addition of GAA or Cit in RP would allow birds to perform similar or greater than Arg-added RP treatment. The experiment was conducted from 20 to 39 wk of age but the treatment effect was seen only after 29 wk of age. The birds offered RP had reduced egg and albumin weights (P < 0.01), lower yolk color score (P < 0.01), lower protein intake and excretion (P < 0.01) than those offered SP. When Arg or Cit were added to RP to make them equivalent to SP, feed intake (FI) and egg production were not different than those of RP (P > 0.05). The birds offered RP-GAA decreased FI and egg production (P < 0.01) compared to those offered RP. The addition of Arg, Cit or GAA to the RP had no effect on egg quality parameters, protein and energy digestibilities (P > 0.05). However, birds offered the RP-Cit diet tended to have higher Haugh unit (P = 0.095) and lower shell breaking strength (P = 0.088) compared to all other treatments while those offered RP-GAA had higher energy digestibility (P < 0.05) than all other groups but RP. The limited performance response of hens fed RP with added Arg, GAA, or Cit may be due to deficiency of some other nutrients in RP such as phenylalanine, potassium or non-essential amino acids and other components of soybean meal in the diet.

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

BackgroundSuckling 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. ObjectivesTo 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. MethodsYucatan 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. ConclusionsPiglets are capable of synthesizing sufficient creatine from the precursor amino acids arginine and methionine, or from GAA plus methionine.

Guanidino-Acetic Acid: A Scarce Substance in Biomass That Can Regulate Postmortem Meat Glycolysis of Broilers Subjected to Pre-slaughter Transportation.

The different substances in biomass can regulate the metabolism and reproduction of broilers. Guanidino-acetic acid (GAA) is a natural feed additive that showed a potential application in dietary for broilers, while its amount is scarce in biomass. The objective of the present study was to investigate the effects of dietary supplemented with GAA on muscle glycolysis of broilers subjected to pre-slaughter transportation. A total of 160 Qiandongnan Xiaoxiang chickens were randomly assigned into three treatments, including a basal control diet without GAA supplementation (80 birds) or supplemented with 600 mg/kg (40 birds) or 1,200 mg/kg (40 birds) GAA for 14 days. At the end of the experiment, the control group was equally divided into two groups, thus resulting in four groups. All birds in the four groups aforementioned were separately treated according to the following protocols: (1) no transport of birds of the control group fed with the basal diet; (2) a 3-h transport of birds of the control group fed with the basal diet; (3) a 3-h transport of birds fed with diets supplemented with 600 mg/kg GAA; and (4) a 3-h transport of birds fed with diets supplemented with 1,200 mg/kg GAA. The results demonstrated that 3-h pre-slaughter transport stress increased corticosterone contents and lowered glucose contents in plasma (P < 0.05), decreased pH24h (P < 0.05), and resulted in inferior meat quality evidenced by elevating the drip loss, cooking loss, and L∗ value (P < 0.05). Meanwhile, 3-h pre-slaughter transport stress decreased the contents of Cr and ATP in muscle (P < 0.05) and elevated the ratio of AMP:ATP and the glycolytic potential of muscle (P < 0.05). Moreover, 3-h pre-slaughter transport resulted in a significant elevation of mRNA expressions of LKB1 and AMPKα2 (P < 0.05), as well as the increase in protein abundances of LKB1 phosphorylation and AMPKα phosphorylation (P < 0.05). However, 1,200 mg/kg GAA supplementation alleviated negative parameters in plasma, improved meat quality, and ameliorated postmortem glycolysis and energy metabolism through regulating the creatine–phosphocreatine cycle and key factors of AMPK signaling. In conclusion, dietary supplementation with 1,200 mg/kg GAA contributed to improving meat quality via ameliorating muscle energy expenditure and delaying anaerobic glycolysis of broilers subjected to the 3-h pre-slaughter transport.

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

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 600mg kg-1 ) and CA (0 or 150mg kg-1 ). This trial lasted for 18 days. 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. 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.

Supplementation of guanidinoacetic acid and betaine improve growth performance and meat quality of ducks by accelerating energy metabolism

This study was conducted to investigate the effects of guanidinoacetic acid (GAA) and betaine on growth performance, meat quality and metabolism of ducks. A total of 384-one-day-old Cherry Valley meat ducks (55.75 ± 0.55 g) were randomly assigned to four treatments with 6 replicates of 16 ducks. Ducks were fed a basal diet (control) or a test diet supplemented with 0.6 g GAA/kg, 2.0 g betaine/kg, or 0.6 g GAA/kg + 2.0 g betaine/kg. The results showed that compared with the control group, GAA and betaine improved feed conversation ratio from day 1 to 14 and 1 to 35 and body weight at 35 days of age (p < .05). GAA and betaine increased breast muscle percentage while reduced abdominal fat percentage, and drip loss and shear force of breast muscle (p < .05). GAA and betaine lowered free serine, methionine, tryptophan and total amino acid contents in muscles, increased free serine, aspartic acid, phenylalanine and tryptophan contents in plasma (p < .05). There was a synergistic effect on non-esterified fatty acid, lactic acid and uric acid between GAA and betaine. GAA and betaine increased the creatine kinase activity in plasma and creatine and ATP content in breast muscle, decreased the lactate dehydrogenase and L-arginine: glycine amidino transferase activities (p < .05). In conclusion, supplementation of GAA and betaine improved the growth performance and meat quality of ducks by accelerating energy metabolism. There was a synergistic effect on NEFA, LA and UA concentrations in plasma of ducks between GAA and betaine. Highlights Supplementing GAA and betaine improved the growth performance and meat quality of ducks. Adding GAA and betaine accelerated the energy metabolism of ducks. There was a synergistic effect on non-esterified fatty acid, lactic acid and uric acid concentrations in the plasma of ducks between GAA and betaine.

Effects of guanidinoacetic acid supplementation on zootechnical performance and some biometric indices in broilers challenged with T3-Hormone

The objective was to elucidate the effects of dietary guanidinoacetic acid (GAA) supplementation on broiler performance, serum enzymes, oxidative biomarkers, mitochondrial activities, carcase traits, gross lesion of cardiac muscle and liver histopathology in broilers challenged with T3-hormone. A total-of-192 one-day-old mixed sexed broilers were randomly assigned in a two factorial design, including two dietary treatments; control diet supplemented with or without T3-hormone (1.5 ppm) and GAA diet (0.06%) supplemented with or without T3-hormone (1.5 ppm). Each group was subdivided into eight replicates. Results showed interactions between GAAxT3-hormone. GAA diet significantly mitigated the negative effect of T3-hormone on serum total creatine kinase (CK), cardiac muscle (CK-MB), liver malondialdehyde (MDA) and superoxide dismutase (SOD), mitochondrial activities of cardiac muscle and liver histopathological lesion. In conclusion, GAA at a rate of 0.06% may have the potential to mitigate the negative effect of dietary T3-hormone but could not reduce the ascites mortality at such inclusion rate. HIGHLIGHTS GAA protected heart muscle. GAA mitigated the oxidative radicals in T3-hormone challenged birds. GAA modulated the mitochondrial activities in T3-hormone challenged birds.

Effects of dietary supplementation of guanidinoacetic acid on physiological response of broiler chicken exposed to repeated lactic acid injection

Increased blood lactic acid is likely to be involved in the incidence of sudden death syndrome (SDS) in broiler chicken. Guanidinoacetic acid (GAA) with direct or indirect influence on the cardiovascular system may provide, to some degree, protection against lactic acidemia in birds. A total number of 144 male broiler chicks (Ross 308) were used in a complete randomised block design to investigate the effects of dietary supplementation of GAA at 0.6, 1.2, 1.8, 2.4 and 3 g/kg on the physiological response of broiler chicks to an acute lactic acidosis in an 8-days experiment. Birds receiving 1.8 and 3 g/kg GAA exhibited lesser mortality percentage compared with the control birds and those received dietary GAA at 0.6 and 1.2 g/kg (p < .03). Dietary inclusion of 1.2 g/kg GAA to broiler chicks increased serum concentration of uric acid compared to the control birds and those received 2.4 g/kg (p < .02). The mean serum concentration of creatinine was greater in the birds receiving different GAA levels compared with the control birds (p < .0001). The serum concentration of nitric oxide decreased in the birds receiving 1.2 g/kg GAA by 21.05 and 15.57% compared with the control birds and those received 1.8 g/kg of GAA, respectively (p < .04). A lesser frequency for liver colour score 5 was observed in the birds fed on the diet with 0.6 g/k GAA (p < .0001). It was concluded that dietary administration of GAA deteriorates the adaptive physiological responses to an acute lactic acidosis in broiler chicken possibly through liver and kidney dysfunction. HIGHLIGHTS Dietary guanidinoacetic acid decreased mortality but showed an adverse effect on growth performance in chickens exposed to acute lactic acidosis. The adverse effects of guanidinoacetic acid may happen through liver and kidney dysfunction. No firm evidence was found to suggest a significant effect of extra nutritional guanidinoacetic acid on the incidence of sudden death syndrome in chicken.

Effect of guanidinoacetic acid and betaine supplementation in soybean meal-based diets on growth performance, muscle energy metabolism and methionine utilization in the bullfrog Lithobates catesbeianus

This study was carried out to evaluate the impacts and interactions of guanidinoacetic acid (GAA) and betaine (BT) supplementation of soybean-meal-based diets on the growth, meat quality, and methionine utilization in the bullfrog Lithobates catesbeianus. A basal diet was supplemented with 0 or 4 g/kg of BT and/or 0, 0.4, or 4 g/kg GAA to formulate six experimental diets, designated Control (BT/GAA: 0/0), B0G0.4 (0/0.4), B0G4 (0/4), B4G0 (4/0), B4G0.4 (4/0.4) and B4G4 (4/4). Each diet was fed to three individual bullfrogs (initially weighing 51.70 ± 0.33 g) for 8 weeks. As a result, bullfrogs fed diets with GAA showed greater weight gain than the control group (P < 0.05). The addition of GAA or BT to the diets increased whole-body protein deposition and the hind leg index (P < 0.05). Diets supplemented with GAA led to reduced muscle glycolysis, which increased the muscle pH value 24 h after euthanasia (P < 0.05). However, a combination of BT and GAA had an insignificant effect on the expression of betaine homocysteine methyltransferase mRNA compared with the diets supplemented with GAA-only (P > 0.05). The findings of this study suggest that dietary GAA supplementation improves bullfrog growth performance and muscle energy metabolism after slaughter, but GAA combined BT supplementation does not improve methionine utilization for bullfrog.

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.

Effect of dietary sulphur amino acid levels and guanidinoacetic acid supplementation on performance, carcase yield and energetic molecular metabolites in broiler chickens fed wheat-soy diets

The aim of the present study was to evaluate the effects of dietary total sulphur amino acids (TSAA) levels and guanidinoacetic acid (GAA) supplementation on performance, carcase yield and energetic molecular metabolites in heart and breast muscle of broiler chickens fed wheat-soy diet. A total of 450, male one-day-old Ross-308 broiler chicks were assigned in a 3 × 3 factorial arrangement of nine treatments, five replicates and 10 birds each. Dietary treatments included three graded levels of supplementary TSAA (+0.4 g/kg per level) resulting in a deficient, adequate and plus level of recommended by strain, with three levels of GAA (0, 0.6 and 1.2 g/kg) and were fed for 35 days. Dietary TSAA levels only enhanced performance during the starter period (p < .05). At adequate TSAA level, weight gain (WG) and feed conversion ratio (FCR) in the grower phase were positively affected by supplementing GAA at 1.2 g/kg (p < .05). The FCR during the overall experimental period was significantly lower when feeding GAA at 0.6 and 1.2 g/kg compared to non-supplemented (p < .05). Heart and breast muscle ATP/AMP ratio and breast muscle ADP and PCr concentration and PCr/CrN ratio in the birds fed 1.2 g/kg GAA diet were significantly higher than non-supplemented (p < .05). It is concluded, effects of dietary GAA supplementation were influenced by dietary TSAA level, this indicates to need for proper dietary sulphur amino acid formulation by GAA supplementation. Dietary GAA supplementation could improve broiler chicken’s growth performance via regulating some aspects of energy metabolism. HIGHLIGHTS Guanidinoacetic acid plays a critical role in energy homeostasis. The effect of dietary Guanidinoacetic acid supplementation may influenced by the dietary sulphur amino acids.

Dietary guanidinoacetic acid response on digestibility, growth performance, feed utilization and carcass quality in Nile Tilapia ( Oreochromis niloticus )

Creatine plays a vital part in the energy metabolism and physiological roles. It is exclusively found in ingredients of animal origin, so using all-plant protein-based diets increases the risk of creatine deficiency. The objectives of this current study were to determine the optimal level of dietary guanidinoacetic acid (GAA) with regard to the nutrient digestibility, growth performance, feed utilization and carcass quality of Nile tilapia (Oreochromis niloticus). The fish (27.33 ± 0.70 g) were fed with five different isonitrogenous and isoenergetic diets for 60 days: T1 was the positive control diet (HF; 6% fish meal inclusion); T2 was the negative control formulated to contain no GAA (NC, free fish meal); and T3, T4 and T5 were NC supplemented with 0.06%, 0.12% and 0.18% of GAA respectively. At the end of the experiment, it was found that growth performance and feed utilization were not significantly different (p > .05) among the groups. However, fish from the T3 and T4 groups had slightly better weight gain and growth rate, as well as improved digestibility of protein, methionine, lysine and histidine (p < .05). Fish fed the dietary GAA at 0.06 or 0.12% had clearly larger width increment than the other groups. This is important as consumers prefer large dorsal muscles. This result from this study showed no adverse effect on haematological parameters, serum biochemistry parameters, fillet texture quality and histopathological change in the liver of Nile tilapia. Therefore, these results indicate that GAA supplementation at 0.06%–0.12% in Nile tilapia diet can potentially improve fish growth and feed utilization without setback on health.

Guanidinoacetic acid supplementation totally based on vegetable meal diet improved the growth performance, muscle flavor components and sensory characteristics of on-growing grass carp (Ctenopharygodon idella)

This study was conducted to examine the effects of guanidinoacetic acid (GAA) supplementation totally based on vegetable meal diet on growth performance, muscle flavor components and sensory characteristics of on-growing grass carp (Ctenopharygodon idella). Fish were fed with one fishmeal diet and five vegetable meal diets supplemented with graded levels of GAA (0, 150, 300, 450 and 600 mg/kg GAA diet) for 60 days. After the feeding period, we discovered that appropriate GAA supplementation totally based on vegetable meal diet could (1) improve the percentage weight gain (PWG), feed intake (FI) and feed efficiency (FE) of grass carp; (2) increase muscle flavor nucleotide (IMP), flavor-related fatty acid and amino acid contents; (3) improve muscle postmortem pH, water-holding capacity and firmness to enhance sensory characteristics, which were partly related to postmortem glycolysis, density of myofiber and collagen. Furthermore, based on the growth indicator PWG, muscle DHA, pH and firmness, the appropriate levels of GAA supplementation in vegetable meal diet for on-growing grass carp (169.46–600.89 g) were estimated as to be 335.35, 313.75, 321.72 and 314.61 mg/kg, respectively. Summarily, this study is the first to demonstrate that GAA supplementation totally based on vegetable meal diet elevated the growth performance, muscle flavor components and sensory characteristics of grass carp.

The Potential of Guanidino Acetic Acid to Reduce the Occurrence and Severity of Broiler Muscle Myopathies.

Guanidinoacetic acid (GAA) is the biochemical precursor of creatine, which, in its phosphorylated form, is an essential high-energy carrier in the muscle. Although creatine has limited stability in feed processing, GAA is well established as a source of creatine in the animal feed industry. Published data demonstrate beneficial effects of GAA supplementation on muscle creatine, energy compounds, and antioxidant status, leading to improvements in broiler body weight gain, feed conversion ratio, and breast meat yield. Although increases in weight gain and meat yield are often associated with wooden breast (WB) and other myopathies, recent reports have suggested the potential of GAA supplementation to reduce the occurrence and severity of WB while improving breast meat yield. This disorder increases the hardness of the Pectoralis major muscle and has emerged as a current challenge to the broiler industry worldwide by impacting meat quality. Genetic selection, fast-growth rates, and environmental stressors have been identified to be the main factors related to this myopathy, but the actual cause of this disorder is still unknown. Creatine supplementation has been used as a nutritional prescription in the treatment of several muscular myopathies in humans and other animals. Because GAA is a common feed additive in poultry production, the potential of GAA supplementation to reduce broiler myopathies has been investigated in experimental and commercial scenarios. In addition, a few studies have evaluated the potential of creatine in plasma and blood enzymes related to creatine to be used as potential markers for WB. The evidence indicates that GAA could potentially minimize the incidence of WB. More data are warranted to understand the factors affecting the potential efficacy of GAA to reduce the occurrence and severity of myopathies.

Guanidinoacetic acid as a novel food for skeletal muscle health

Abstract Guanidinoacetic acid (GAA) is a direct endogenic precursor of creatine. GAA is also a re-discovered nutraceutical that has been put forward as an energy-facilitating compound by many animal and a few human studies. Recent trials indicated that dietary GAA might have yet another role in muscle growth promotion, acting as an anticatabolic and/or anabolic compound. This opinion paper summarizes the latest findings for advancing (or impeding) dietary GAA in skeletal muscle medicine, discussing open questions that need to be answered before the translation of supplemental GAA use from bench to bedside.

The Effects of Creatine and Related Compounds on Cardiovascular System: From Basic to Applied Studies

Abstract Beneficial effects of creatine were firstly shown in sport, where itself has been recognized as an ergogenic substance, increasing exercise endurancе, muscle strength and lean body mass. Creatine supplementation is very interesting, due to the fact that creatine supplementation have been reported to be beneficial for wide spectrum of diseases and conditions referring neuro-degenerative, rheumatic diseases, myopathies, cancer, type 2 diabetes. Creatine is a principle component of the creatine kinase/phosphagen system. In cardiomyocytes, it plays an important role in the buffering and transport of chemical energy to ensure that supply meets the dynamic demands of the heart. Studies in mice proved that elevated creatine protects the heart from ischemia-reperfusion injury. A natural precursor of creatine, guanidinoacetic acid (GAA), plays an important role as an energy carrier/mediator in the cell. GAA is formed in the first step of creatine synthesis. Supplementation with GAA might be of great significance in some circumstances where biosynthesis of GAA is limited like deficient diet, kidney failure, renal insufficiency, exercise-related GAA depletion. Betaine is a neutral compound in the form of zwitterion. Betaine supplementation is associated with improved cognition, neuroprotection, cardioprotection and exercise physiology. Betaine insufficiency represents increased risk for secondary heart failure and acute myocardial infarction. This mini-review outlines the evidence in support of creatine and creatine related compounds (GAA and betaine) elevation and examines the pharmacological approaches that are currently available. Since data from the available studies, regarding cardioprotection are inconsistent, this review might help clarifying the benefits of creatine, GAA and betaine supplementation on cardiovascular system.

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±2.94kg) 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 450mg/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.

Short-term GAA loading: Responders versus nonresponders analysis.

Dietary guanidinoacetic acid (GAA) has been suggested to be advantageous for favorable changes in tissue bioenergetics in terms of responder versus nonresponder performance, yet no studies so far explored the proportion of two distinct populations following short‐term GAA intervention. A secondary analysis of previously completed guanidinoacetic acid (GAA) trials has been carried out in aim to classify individuals into responders and nonresponders using cut‐off criteria for an increase in intramuscular creatine. A total of 30 individuals (mean age = 34.5 years, women 66.7%) who were supplemented with up to 3 g/day of GAA for at least 28 days with total muscle creatine evaluated using 1.5 T magnetic resonance spectroscopy studies were included in this examination. Pre–post measures included total creatine content (creatine plus phosphocreatine) determined from the quadriceps muscle, with participants were classified by arbitrary cut‐off points in three categories, including responders (>10% increase in total creatine content at follow‐up), quasi‐responders (5%–10% increase), and nonresponders (<5% increase in total intramuscular creatine at postadministration). An average change in total creatine content after GAA supplementation was 22.9%, with 13.3% participants were categorized as nonresponders, 6.6% as quasi‐responders, and 80.0% as responders (p < .001). A fairly high prevalence of individuals sensitive to dietary GAA advances this innovative agent as a rather effective tool to improve muscle creatine levels for at least 10% or more during 28‐day loading.

Guanidinoacetic acid supplementation improves feed conversion in broilers subjected to heat stress associated with muscle creatine loading and arginine sparing

It was hypothesized that dietary guanidinoacetic acid (GAA), the precursor of creatine (Cr), would be beneficial to heat-stressed finisher broilers owing to improved cellular energy status and arginine sparing effects. A total of 720 one-day-old male Ross 308 broilers were allocated to 3 treatments, 0 (control), 0.6, or 1.2 g/kg of GAA added to complete corn–soybean meal diets, and were fed for 39 D, with 12 replicates (20 birds each) per treatment. A chronic cyclic heat stress model (at a temperature of 34°C and 50 to 60% relative humidity for 7 h daily) was applied in the finisher phase (day 25–39). Samples were taken on day 26 and 39 to determine thrombocyte, white blood cell, corticosterone, protein and amino acid levels in blood and Cr, phosphocreatine (PCr), and adenosine triphosphate levels in the breast muscle. Meat quality was assessed on day 40 after overnight fasting. Guanidinoacetic acid at a dose of 1.2 g/kg decreased feed-to-gain ratio compared with the control in the grower phase (1.32 vs. 1.35, respectively; P <0.05). In the finisher period, the supplementation of 1.2 g/kg of GAA reduced feed intake compared with the control (–3.3%, P <0.05), whereas both GAA supplementation levels improved feed efficiency markedly (1.76, 1.66, and 1.67 for 0 [control], 0.6, and 1.2 g/kg of GAA, respectively, P <0.05). Mortality outcomes highlight that GAA feeding improved survival during heat stress, supported by lower panting frequency (linear effect, P <0.05). Plasma arginine was higher with increase in dietary GAA concentration on day 26 (+18.3 and + 30.8% for 0.6 and 1.2 g/kg of GAA, respectively; P <0.05). This suggests enhanced availability of arginine for other metabolic purposes than de novo GAA formation. In the breast muscle, PCr (day 39, P <0.05), free Cr (day 39, P <0.05), total Cr (both days, P <0.05), and PCr-to-adenosine triphosphate ratio (day 39, P <0.05) levels were increased with higher GAA content in diet. Guanidinoacetic acid supplementation improved feed conversion and survival during chronic cyclic heat stress, which may be associated with enhanced breast muscle energy status and arginine sparing effect.

Guanidinoacetic acid supplementation is favourable to broiler diets even containing poultry by-product meal

ABSTRACT 1. Two consecutive trials were conducted to evaluate the effects of guanidinoacetic acid (GAA) supplementation (a creatine precursor) and energy levels in broiler diets based on maize-soybean meal (Trial 1) or that additionally included poultry by-product meal (PBPM; Trial 2) on growth performance, carcass yield and breast meat quality to 41 days of age. 2. A total of 792, one-day-old male Ross 308 broiler chickens were randomly distributed into six treatments – three energy levels (sufficient AMEn or 0.2 and 0.4 MJ/kg reduced AMEn) and two GAA levels (0.00% or 0.06%) with eight replicates for each trial. 3. Reducing dietary energy resulted in poorer body weight gain (BWG) and feed conversion ratios (FCR) for each trial (P < 0.05). However, GAA supplementation improved FCR, BWG and European Production Efficiency Factor (EPEF) (P < 0.05). 4. Dietary energy level and GAA addition had no significant effect on carcass parameters, drip loss, pH and chemical composition of breast meat (P > 0.05), but decreased relative liver weight (P < 0.05). 5. It was concluded that, regardless of dietary energy levels, supplementation of GAA to plant-based diets or those including PBPM has the potential to improve growth performance in broilers.