Plasma Creatine Concentrations Research Articles

SLC6A8 creatine transporter deficiency can be detected by plasma creatine and creatinine concentrations

Creatine transporter deficiency has been described with normal or uninformative levels of creatine and creatinine in plasma, while urine has been the preferred specimen type for biochemical diagnosis. We report a cohort of untreated patients with creatine transporter deficiency and abnormal plasma creatine panel results, characterized mainly by markedly decreased plasma creatinine. We conclude that plasma should be considered a viable specimen type for the biochemical diagnosis of this disorder, and abnormal results should be followed up with further confirmatory testing.

Creatine and creatinine quantified using nuclear magnetic resonance: A method validation study and clinical associations between circulating creatine and fatigue in kidney transplant recipients

BackgroundA potential contributor to fatigue in kidney transplant recipients (KTR) may be impaired creatine homeostasis. We developed and validated a high-throughput NMR assay allowing for simultaneous measurement of circulating creatine and creatinine, and determined plasma creatine and estimated intramuscular creatine concentrations in KTRs, delineated their determinants and explored their associations with self-reported fatigue. MethodsAn NMR assay was developed and validated for measurement of circulating creatinine and creatine concentrations. Plasma creatine and creatinine concentrations were measured in 618 KTR. Fatigue was assessed using the checklist individual strength. Associations of creatine parameters with fatigue was assessed using linear mixed effect models. ResultsThe NMR-based assay had good sensitivity, precision and demonstrated linearity across a large range of values. Among KTR, the mean age was 56 ± 13 years, 62% were men and eGFR was 54 ± 18 ml/min/1.73 m2. Plasma creatine concentration was 27 [19–39] µmol/L. Estimated intramuscular creatine concentration was 27 ± 7 mmol/kg. Higher plasma creatine concentration and higher estimated intramuscular creatine concentration were independently associated with a lower total fatigue score and less motivation problems. ConclusionAn NMR method for measurement of circulating creatine and creatinine which offers the potential for accurate and efficient quantification was developed. The found associations suggest that improving creatine status may play a beneficial role in mitigating fatigue.

Addition of a combination of creatine, carnitine, and choline to a commercial diet increases postprandial plasma creatine and creatinine concentrations in adult dogs.

Creatine is a nitrogenous compound essential for cellular energy homeostasis found in animal protein; however, when heat-processed for pet food, creatine is degraded to creatinine, which is not metabolically active and excreted in urine. The objective of the present investigation was to define the postprandial plasma creatine and creatinine response in dogs fed a commercial diet (CON) formulated for adult dogs, top-dressed with a combination of creatine (9.6 g/kg dry matter, DM), carnitine (2.13 g/kg DM) and choline (0.24 g/kg DM; CCC), methionine (2.6 g/kg DM; MET), or taurine (0.7 g/kg DM; TAU). Eight adult Beagles were fed one of the four diets for 7 days in a Latin Square design with no washout period. On day 7, cephalic catheters were placed and blood samples were collected before being fed (fasted) and up to 6 h post-meal. Creatine and creatinine were analyzed using HPLC and data analyzed using PROC GLIMMIX in SAS. Plasma creatine concentrations were higher in dogs fed CCC (103 ± 10 μmol/L) compared to MET (72 ± 7 μmol/L) at fasted (P < 0.05) and higher compared to all other treatments from 15 to 360 min post-meal (P < 0.05). Plasma creatinine concentrations were higher in dogs fed CCC from 60 to 180 min compared to all other treatments. These data suggest that when creatine, carnitine and choline are top-dressed for 7 days, plasma creatine is rapidly absorbed and remains elevated up to 6 h post-meal. This may have implications for energy metabolism and should be considered when using creatinine as a diagnostic tool in dogs.

124 The Acute Effects of Supplementing a Meat-Based Diet with a Combination of Creatine, Carnitine and Choline, Taurine or Methionine on Post-Prandial Plasma Creatine and Creatinine Concentrations in Dogs

Abstract Creatine is an essential nitrogenous compound for cellular energy homeostasis in vertebrates. It is synthesized from the methylation of guanidinoacetate, a metabolite of arginine and glycine. Creatine is found in animal protein, however, when heat-processed for pet food, the creatine content decreases dramatically and creatinine is formed. Previous data from this study have been presented, however, the current objective was to define the postprandial plasma creatine and creatinine response in dogs fed a commercial meat-based diet (CON), top-dressed with a combination of creatine, carnitine and choline (CCC) or other nutrients involved in methyl metabolism, methionine (MET) or taurine (TAU). The control diet contained 0.195 g/kg creatine and 0.563 g/kg creatinine on an as-fed basis. Eight adult Beagles were fed one of the four diets for 7 days in a Latin Square design. On day 7, dogs had cephalic catheters placed and a series of blood samples were collected at fasted and up to 6 hours post-meal. Creatine and creatinine were analyzed using HPLC and data analyzed using Proc Glimmix in SAS (Version 9.4). Plasma creatine concentrations were greater in dogs fed CCC (103±10 µmol/L) compared with MET (72±7 µmol/L) at fasted (P&amp;lt; 0.05) and greater compared with all other treatments from 15 to 360 minutes post-meal (P&amp;lt; 0.05), with a peak concentration of 735±74 µmol/L at 90 min. Plasma creatinine concentrations were greater in dogs fed CCC from 60 to 180 min post-meal compared to all other treatments (P&amp;lt; 0.05), with a peak concentration of 223±13 µmol/L at 90 min. Both peak concentrations were outside of established reference ranges in dogs. These data suggest that when creatine is top-dressed for 7 days, plasma creatine remains increased at fasted and up to 6 hours post-meal, while plasma creatinine remains increased up to 3 hours post-meal, which has implications for energy production and methyl metabolism.

Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents.

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.

The physiological effects of creatine supplementation in fetal sheep before, during, and after umbilical cord occlusion and global hypoxia.

The aim of this study was to investigate the effects of direct creatine infusion on fetal systemic metabolic and cardiovascular responses to mild acute in utero hypoxia. Pregnant ewes (n = 28) were surgically instrumented at 118 days gestation (dGa). A constant intravenous infusion of creatine (6 mg·kg-1·h-1) or isovolumetric saline (1.5 mL·h-1) began at 121 dGa. After 10 days, fetuses were subjected to 10-min umbilical cord occlusion (UCO) to induce mild global hypoxia (saline-UCO, n = 8; creatine-UCO, n = 7) or sham UCO (saline-control, n = 6; creatine-control, n = 7). Cardiovascular, arterial blood gases and metabolites, and plasma creatine were monitored before, during, and then for 72 h following the UCO. Total creatine content in discrete fetal brain regions was also measured. Fetal creatine infusion increased plasma concentrations fivefold but had no significant effects on any measurement pre-UCO. Creatine did not alter fetal physiology during the UCO or in the early recovery stage, up to 24 h after UCO. During the late recovery stage, 24-72 h after UCO, there was a significant reduction in the arterial oxygen pressure and saturation in creatine fetuses (PUCO × TREATMENT = 0.02 and 0.04, respectively). At 72 h after UCO, significant creatine loading was detected in cortical gray matter, hippocampus, thalamus, and striatum (PTREATMENT = 0.01-0.001). In the striatum, the UCO itself increased total creatine content (PUCO = 0.019). Overall, fetal creatine supplementation may alter oxygen flux following an acute hypoxic insult. Increasing total creatine content in the striatum may also be a fetal adaptation to acute oxygen deprivation.NEW & NOTEWORTHY Direct fetal creatine supplementation increased plasma and cerebral creatine concentrations but did not alter fetal body weight, basal cardiovascular output, or blood chemistry. Creatine-treated fetuses displayed changes to arterial oxygenation 24-72 h after acute global hypoxia. An increase in striatum total creatine levels following UCO was also noted and suggests that increasing creatine tissue availability may be an adaptive response against the effects of hypoxia.

Plasma creatine concentration is associated with incident hypertension in a cohort enriched for the presence of high urinary albumin concentration: the Prevention of Renal and Vascular Endstage Disease study.

Objective: Hypertension is a major risk factor for cardiovascular disease, kidney disease, and premature death. Increased levels of creatine kinase are associated with development of hypertension. However, it is unknown if creatine, a substrate of CK, is associated with the development of hypertension. We therefore, aimed to investigate the association between plasma creatine concentration and incident hypertension.Methods:We measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the population-based PREVEND study. The study outcome was incident hypertension, defined as either a SBP of at least 140 mmHg, a DBP of at least 90 mmHg, or the new usage of antihypertensive drugs. Participants with hypertension at baseline were excluded.Results:We included 3135 participants (46% men) aged 49 ± 10 years. Mean plasma creatine concentrations were 36.2 ± 17.5 μmol/l, with higher concentrations in women than in men (42.2 ± 17.6 versus 29.2 ± 17.6 μmol/l; P < 0.001). During a median of 7.1 [interquartile range: 3.6–7.6] years of follow-up, 927 participants developed incident hypertension. Higher plasma creatine concentrations were associated with an increased risk of incident hypertension [HR per doubling of plasma creatine: 1.21 (95% confidence interval: 1.10–1.34); P < 0.001], which remained significant after adjustment for potential confounders. Sex-stratified analyses demonstrated higher plasma creatine that was independently associated with an increased risk of incident hypertension in men [hazard ratio: 1.26 (95% CI 1.11–1.44); P < 0.001], but not in women (hazard ratio: 1.13 (95% CI 0.96–1.33); P = 0.14]. Causal pathway analyses demonstrate that the association was not explained by sodium or protein intake.Conclusion:Higher plasma creatine is associated with an increased risk of hypertension in men. Future studies are warranted to determine the underlying mechanisms.

Plasma metabolomic profiles as affected by diet and stress in Spanish goats

The effects of high-condensed tannin (CT) diet combined with preslaughter stress have not been studied at the metabolome level in goats. This study was conducted to determine the effects of feeding sericea lespedeza (SL; Lespedeza cuneata), a high-CT legume, and transportation stress on plasma metabolome in goats. Uncastrated male Spanish goats (age = 8 months; BW = 26.0 ± 0.48 kg) were either fed ground ‘Serala’ SL hay (SER), bermudagrass (Cynodon dactylon) hay (BG), or bermudagrass hay-dewormed goats (BG-DW; Control) at 75% of intake, with a corn-based supplementation (25%) for 8 weeks (n = 12/Diet). At the end of the trial, goats were subjected to one of two stress treatments (ST): transported for 90 min to impose stress (TS) or held in pens (NTS) before slaughtering, in two replicates. Live and carcass weights, and blood samples were collected at 0, 30, 60 and 90 min of transportation or holding time (Time). The data were analyzed using MIXED procedures in SAS and metabolomics data were analyzed using the R software. When measured after ST, SER group had the lowest body weight (P < 0.05) among the three diet groups. Carcass weights were high in the BG-DW, low in SER, and intermediate in BG group. Plasma creatine concentrations decreased over Time (P < 0.01) in the TS goats in all diet groups. Meat crude protein percentages were higher (P < 0.05) in SER (22.5 ± 0.22) and BG-DW (22.3 ± 0.22) groups compared to the BG group (21.6 ± 0.22). At the metabolome level, SER group had the lowest (P < 0.05) glycine, alanine, threonine, taurine, trans-hydroxyproline, methionine, and histidine concentrations and highest (P < 0.01) lysine and citrulline concentrations among the Diet groups. Butyric acid, concentration was higher (P < 0.05) in the SER group compared to BG group. Eight medium- and long-chained acylcarnitines were higher (P < 0.05) in the BG-DW group than SER or BG groups. In general, amino acid levels decreased and acylcarnitine increased with Time (P < 0.05) in all groups. Sericea diet can be beneficial in enhancing stress coping abilities in goats due to elevated butyrate, lysine, and citrulline levels; however, SER resulted in lower energy level in goats compared to BG or BG-DW groups. Fatty acid metabolism is the main energy pathway in all groups during prolonged stress. Inclusion of certain varieties of SL in the diet must be carefully controlled to prevent possible negative effect.

Creatine homeostasis and protein energy wasting in hemodialysis patients

Muscle wasting, low protein intake, hypoalbuminemia, low body mass, and chronic fatigue are prevalent in hemodialysis patients. Impaired creatine status may be an often overlooked, potential contributor to these symptoms. However, little is known about creatine homeostasis in hemodialysis patients. We aimed to elucidate creatine homeostasis in hemodialysis patients by assessing intradialytic plasma changes as well as intra- and interdialytic losses of arginine, guanidinoacetate, creatine and creatinine. Additionally, we investigated associations of plasma creatine concentrations with low muscle mass, low protein intake, hypoalbuminemia, low body mass index, and chronic fatigue. Arginine, guanidinoacetate, creatine and creatinine were measured in plasma, dialysate, and urinary samples of 59 hemodialysis patients. Mean age was 65 ± 15 years and 63% were male. During hemodialysis, plasma concentrations of arginine (77 ± 22 to 60 ± 19 μmol/L), guanidinoacetate (1.8 ± 0.6 to 1.0 ± 0.3 μmol/L), creatine (26 [16–41] to 21 [15–30] μmol/L) and creatinine (689 ± 207 to 257 ± 92 μmol/L) decreased (all P < 0.001). During a hemodialysis session, patients lost 1939 ± 871 μmol arginine, 37 ± 20 μmol guanidinoacetate, 719 [399–1070] μmol creatine and 15.5 ± 8.4 mmol creatinine. In sex-adjusted models, lower plasma creatine was associated with a higher odds of low muscle mass (OR per halving: 2.00 [1.05–4.14]; P = 0.04), low protein intake (OR: 2.13 [1.17–4.27]; P = 0.02), hypoalbuminemia (OR: 3.13 [1.46–8.02]; P = 0.008) and severe fatigue (OR: 3.20 [1.52–8.05]; P = 0.006). After adjustment for potential confounders, these associations remained materially unchanged. Creatine is iatrogenically removed during hemodialysis and lower plasma creatine concentrations were associated with higher odds of low muscle mass, low protein intake, hypoalbuminemia, and severe fatigue, indicating a potential role for creatine supplementation.

Plasma creatine and incident type 2 diabetes in a general population-based cohort: The PREVEND study.

BackgroundType 2 diabetes is associated with both impaired insulin action at target tissues and impaired insulin secretion in pancreatic beta cells. Mitochondrial dysfunction may play a role in both insulin resistance and impaired insulin secretion. Plasma creatine has been proposed as a potential marker for mitochondrial dysfunction. We aimed to investigate the association between plasma creatine and incident type 2 diabetes.MethodsWe measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the general population‐based PREVEND study. The study outcome was incident type 2 diabetes, defined as a fasting plasma glucose ≥7.0 mmol/L (126 mg/dl); a random sample plasma glucose ≥11.1 mmol/L (200 mg/dl); self‐report of a physician diagnosis or the use of glucose‐lowering medications based on a central pharmacy registration. Associations of plasma creatine with type 2 diabetes were quantified using Cox proportional hazards models and were adjusted for potential confounders.ResultsWe included 4735 participants aged 52 ± 11 years, of whom 49% were male. Mean plasma creatine concentrations were 36.7 ± 17.6 µmol/L, with lower concentrations in males than in females (30.4 ± 15.1 µmol/L vs. 42.7 ± 17.7 µmol/L; p for difference <.001). During 7.3 [6.2–7.7] years of follow‐up, 235 (5.4%) participants developed type 2 diabetes. Higher plasma creatine concentrations were associated with an increased risk of incident type 2 diabetes (HR per SD change: 1.27 [95% CI: 1.11–1.44]; p < .001), independent of potential confounders. This association was strongly modified by sex (p interaction <.001). Higher plasma creatine was associated with an increased risk of incident type 2 diabetes in males (HR: 1.40 [1.17–1.67]; p < .001), but not in females (HR: 1.10 [0.90–1.34]; p = .37).ConclusionFasting plasma creatine concentrations are lower in males than in females. Higher plasma creatine is associated with an increased risk of type 2 diabetes in males.

208 Effects of supplemental guanidinoacetic acid, creatine, and choline on protein deposition and methyl group metabolites in growing steers

Abstract Methyl group donors (e.g., methionine, choline) can improve performance in transition dairy cows. Our objective was to determine how modulation of methyl group status would affect protein deposition and plasma and urine metabolites associated with methyl group metabolism. Six ruminally cannulated Holstein steers (200 kg) were used in a 6×6 Latin square design with 10-d periods. Factorial treatments, which were continuously infused abomasally, included 3 methyl group modulators (MGM: control; 15 g/d guanidinoacetic acid [GAA]; or 16.8 g/d creatine) and 2 levels of choline (0 or 5 g/d choline ion). Providing GAA or creatine increases body creatine supply; however, GAA consumes methyl groups to synthesize creatine, whereas supplemental creatine directly spares methyl groups that would be used for its synthesis. Steers received 4 kg/d of a corn-based diet. Total collection of urine and feces occurred from d 7 to 9 to measure N retention. Jugular blood was collected on d 10. No interactions between MGM and choline were observed. GAA increased N retention (P = 0.04), whereas creatine did not. Urinary creatine excretion was increased by GAA and creatine supplementation (P &amp;lt; 0.0001). Urinary GAA output was greater for GAA than creatine and control (P &amp;lt; 0.0001). Plasma creatine concentration was increased by GAA and creatine supplementation (P ≤0.01), with GAA leading to a larger increase. Plasma GAA concentration increased with GAA provision (P &amp;lt; 0.0001) but tended to be decreased by creatine (P = 0.09). Plasma urea-N and urinary urea-N output were not affected by MGM (P ≥ 0.25). Choline did not affect N retention (P = 0.69) or urinary GAA or creatine excretions (P ≥ 0.14). Choline increased plasma creatine (P = 0.04), but not plasma GAA. Choline did not affect plasma urea-N or urinary urea-N output (P ≥ 0.68). These data demonstrate that GAA has potential to improve protein deposition in growing cattle. Additionally, choline provision may allow for greater creatine synthesis in the body.

Relative bioavailability of guanidinoacetic acid delivered ruminally or abomasally to cattle.

This study assessed the relative bioavailability of guanidinoacetic acid (GAA) in cattle. Seven ruminally cannulated Holstein steers (initial body weight of 280 kg) were used in an experiment with a 5 × 5 Latin square design; the two additional steers received a treatment sequence identical to two steers in the Latin square. Treatments were: control (no GAA, water infusion), ruminal infusion of 10 or 20 g/d GAA, and abomasal infusion of 10 or 20 g/d GAA, with all infusions delivered continuously. Periods were 7 d in length, and on day 7, blood and urine samples were collected to determine the concentrations of GAA and its associated metabolites. Plasma creatine concentrations increased linearly (P < 0.01) with GAA infusion to the abomasum and tended to increase linearly (P = 0.06) when GAA was infused ruminally. Urinary creatine concentrations increased linearly with increasing amounts of GAA infused in the abomasum (P < 0.01) and the rumen (P < 0.05). There were no significant effects of GAA infusion to either the abomasum or rumen on plasma or urinary concentrations of GAA. Plasma creatinine concentrations were not affected by GAA infusion to the abomasum or rumen. Urinary creatinine concentrations decreased when GAA was infused abomasally (P < 0.05). Because plasma and urinary creatine concentrations yielded the statistically strongest linear responses, they were selected as the primary response criteria for quantifying ruminal escape of GAA. Calculated by slope-ratio methodology, estimates for the ruminal escape of GAA based on plasma creatine and urinary creatine concentrations were 47% and 49%, respectively. Ruminally infused GAA was about half as effective as abomasally infused GAA in elevating plasma and urinary concentrations of creatine.

Evaluation of dietary creatine and guanidinoacetic acid supplementation in juvenile red drumSciaenops ocellatus

Two separate comparative feeding trials were conducted to evaluate if supplemental dietary guanidinoacetic acid (GDA), either singly or in combination with creatine, could enhance growth performance of red drum. The basal diet for both trials was formulated with practical ingredients but was not supplemented with creatine or GDA. For the experimental diets, creatine (0 or 20 g/kg) and GDA (0, 5 or 10 g/kg) were added to the basal diet in a 2 × 3 factorial arrangement for trial 1. Another 2 × 3 experimental design was adopted in trial 2 to further evaluate creatine (0 or 20 g/kg) and GDA (0, 10 or 20 g/kg) supplementation. Each diet was fed to juvenile red drum in either quadruplicate (trial 1) or triplicate (trial 2) aquaria twice daily for a total of 8 weeks. After each feeding trial, fish were sampled for body condition indices and whole‐body composition analysis, as well as determination of plasma, liver and muscle creatine concentrations. In trial 1, dietary creatine supplementation alone significantly (p < .05) improved weight gain and feed efficiency of red drum. An interaction between creatine and GDA was seen in whole‐body protein and lipid in the two trials. In trial 1, the highest levels of whole‐body protein and lipid were observed in fish fed 10 g GDA/kg, and in trial 2, supplementation of the diet with 10 g GDA/kg increased muscle protein and muscle lipid although there was a trending decline in fish fed the 20 g/kg GDA‐supplemented diet. In both trials of the present study, dietary GDA significantly (p < .05) enhanced liver creatine content. Dietary creatine also significantly (p < .05) enhanced plasma and muscle creatine content of red drum. Based on the results of this study, creatine was effective in enhancing weight gain and feed efficiency of red drum as seen in previous studies; however, GDA was not effective in influencing growth performance but limited synthesis of creatine from dietary GDA was apparent.

Urine and plasma concentrations of amino acids and plasma vitamin status differ, and are differently affected by salmon intake, in obese Zucker fa/fa rats with impaired kidney function and in Long-Evans rats with healthy kidneys.

Kidney function affects amino acid metabolism and vitamin status. The aims of the present study were to investigate urine and plasma concentrations of amino acids as well as plasma vitamin status in rats with impaired renal function (Zucker fa/fa rats) and in rats with normal kidney function (Long-Evans rats), and to explore the effects of salmon intake on these parameters and potential biomarkers of salmon intake in both rat strains. Male rats were fed diets with casein as sole protein source (control diet) or 25 % protein from baked salmon and 75 % casein for 4 weeks. Urine concentrations of markers of renal function and most amino acids and plasma concentrations of most vitamins were higher, and plasma concentrations of several amino acids including arginine, total glutathione and most tryptophan metabolites were lower in Zucker fa/fa rats compared with Long-Evans rats fed the control diet. Concentrations of kidney function markers were lower after salmon intake only in Zucker fa/fa rats. A trend towards lower urine concentrations of amino acids was seen in both rat strains fed the salmon diet, but this was more pronounced in Long-Evans rats and did not reflect the dietary amino acid content. Urine 1-methylhistidine, 3-methylhistidine, trimethylamineoxide and creatine concentrations, and plasma 1-methylhistidine and creatine concentrations were higher after salmon intake in both rat strains. To conclude, concentrations of amino acids in urine and plasma as well as vitamin status were different in Zucker fa/fa and Long-Evans rats, and the effects of salmon intake differed by rat strain for some of these parameters.

In ovo feeding of creatine pyruvate modulates growth performance, energy reserves and mRNA expression levels of gluconeogenesis and glycogenesis enzymes in liver of embryos and neonatal broilers.

The effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on the growth performance, energy reserves and mRNA expression levels of gluconeogenesis and glycogenesis enzymes in liver of late-term embryos and neonatal broilers were investigated. After candling on 16 day of incubation, a total of 960 eggs were randomly assigned to three treatments: (i) non-injected control, (ii) saline group injected with 0.6ml of 0.75% physiological saline and (iii) Creatine pyruvate group injected with 0.6 ml of physiological saline containing 12mg CrPyr/egg. After hatching, 120 male chicks with average body weight (BW) were randomly allocated into each treatment group for a 7-day feeding trial. The results showed that broilers subjected to CrPyr treatment had higher BW than those of the control and saline groups on 1, 3 and 7day post-hatch, as well as the yolk sac weight on 19day of incubation (19 E), the day of hatch and 3day post-hatch (p<.05). Compared with the control and saline groups, IOF of CrPyr increased the plasma creatine concentration on the day of hatch, and the plasma pyruvate concentration on the day of hatch and 3day post-hatch (p<.05). Moreover, IOF of CrPyr increased the liver pyruvate and glucose concentrations on 19 E and the day of hatch, and the liver glycogen concentration during the experiment (p<.05). Broilers in the CrPyr group showed increased mRNA expression levels of pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK) and glycogen synthase 2 (GYS2) on 19 E and the day of hatch (p<.05). These results indicated that IOF of CrPyr increased energy reserves in liver of embryos and neonatal broilers possibly through upregulating the mRNA expression levels of PC, PEPCK and GYS2, which could benefit the increase of BW in broilers on 7day post-hatch.

Creatine supplementation to total parenteral nutrition improves creatine status and supports greater liver and kidney protein synthesis in neonatal piglets.

BackgroundCreatine is not included in commercial pediatric parenteral products; the entire creatine requirement must be met by de novo synthesis from arginine during parenteral nutrition (PN). Poor arginine status is common during PN in neonates, which may compromise creatine accretion. We hypothesized that creatine supplementation will improve creatine status and spare arginine in PN-fed piglets.MethodsPiglets (3-5-day (d) old) were provided PN with or without creatine for 14 d. Tissue concentrations of creatine metabolites and activities of creatine-synthesizing enzymes, as well as tissue protein synthesis rates and liver lipid parameters, were measured.ResultsCreatine provision lowered kidney and pancreas L-arginine:glycine amidinotransferase (AGAT, EC number 2.1.4.1) activities and plasma guanidinoacetic acid (GAA) concentration, suggesting the downregulation of de novo creatine synthesis. Creatine increased plasma creatine concentrations to sow-fed reference levels and increased the creatine concentrations in most tissues, but not in the brain. PN creatine resulted in greater protein synthesis in the liver and the kidney, but not in the pancreas, skeletal muscle, or gut. Creatine supplementation also reduced liver cholesterol concentrations, but not triglyceride or total fat.ConclusionThe addition of creatine to PN may optimize the accretion of creatine and reduce the metabolic burden of creatine synthesis in rapidly growing neonates.

Does maternal-fetal transfer of creatine occur in pregnant sheep?

Our aim was to determine the disposition of creatine in ovine pregnancy and whether creatine is transferred across the placenta from mother to fetus. Pregnant ewes received either 1) a continuous intravenous infusion of creatine monohydrate or saline from 122 to 131 days gestation, with maternal and fetal arterial blood and amniotic fluid samples collected daily for creatine analysis and fetal tissues collected at necropsy at 133 days for analysis of creatine content, or 2) a single systemic bolus injection of [13C]creatine monohydrate at 130 days of gestation, with maternal and fetal arterial blood, uterine vein blood, and amniotic fluid samples collected before and for 4 h after injection and analyzed for creatine, creatine isotopic enrichment, and guanidinoacetic acid (GAA; precursor of creatine) concentrations. Presence of the creatine transporter-1 (SLC6A8) and l-arginine:glycine amidinotransferase (AGAT; the enzyme synthesizing GAA) proteins were determined by Western blots of placental cotyledons. The 10-day creatine infusion increased maternal plasma creatine concentration three- to fourfold (P < 0.05) without significantly changing fetal arterial, amniotic fluid, fetal tissues, or placental creatine content. Maternal arterial 13C enrichment was increased (P < 0.05) after bolus [13C]creatine injection without change of fetal arterial 13C enrichment. SLC6A8 and AGAT proteins were identified in placental cotyledons, and GAA concentration was significantly higher in uterine vein than maternal artery plasma. Despite the presence of SLC6A8 protein in cotyledons, these results suggest that creatine is not transferred from mother to fetus in near-term sheep and that the ovine utero-placental unit releases GAA into the maternal circulation.

Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions

ABSTRACTCreatine monohydrate represents one of the largest sports supplement markets. Enhancing creatine (CRE) stability in aqueous solutions, such as with microencapsulation, represents innovation potential. Ten physically active male volunteers were randomly assigned in a double-blind design to either placebo (PLA) (3-g maltodextrin; n = 5) or microencapsulated CRE (3-g creatine monohydrate; n = 5) conditions. Experimental conditions involved ingestion of the samples in a 70-mL ready-to-drink format. CRE was delivered in a novel microencapsulation matrix material consisting entirely of hydrolyzed milk protein. Three hours after ingestion, plasma creatine concentrations were unchanged during PLA, and averaged ∼45 μM. During CRE, plasma creatine concentration peaked after 30 min at 101.6 ± 14.9 μM (p < 0.05), representing a 2.3-fold increase over PLA. Thereafter, plasma creatine concentration gradually trended downwards but remained significantly elevated (∼50% above resting levels) 3 hr after ingestion. These results demonstrate that the microencapsulated form of creatine monohydrate reported herein remains bioavailable when delivered in aqueous conditions, and has potential utility in ready-to-drink formulations for creatine supplementation.

Short-term creatine supplementation does not reduce increased homocysteine concentration induced by acute exercise in humans

The purpose of the study is to evaluate the effects of creatine supplementation on homocysteine (Hcy) plasma levels after acute exercise in humans. Twenty-three young (under-20) soccer players were divided into 2 groups: creatine (Cr)- and placebo (Pla)-supplemented groups. The supplementation was performed in double-blind controlled manner using creatine or placebo tablets with 0.3 g/kg during 7 days. Before and after 7 days of supplementation, the athletes performed an acute high-intensity sprint exercise (two consecutive running-based anaerobic sprint test protocol consisted in 6 × 35 m sprint with 10 s between them). Blood samples were collected before and after 7 days of supplementation as well as 0 and 1 h after exercise protocol. Homocysteine concentration significant increased (P < 0.05) 1 h after acute exercise (18%). Acute exercise also decreased red blood cell S-adenosylmethionine (SAM) 30% with no changes in SAM/SAH ratio. Seven days of creatine supplementation were able to increase (P < 0.05) plasma creatine concentration (Pla 130.1 ± 21.7 vs Cr 1,557.2 ± 220.3 μmol/L) as well as decrease (P < 0.05) plasma guanidinoacetic acid (33%). Controversially, creatine supplementation did not change Hcy plasma level after 7-day supplementation (Pla 6.9 ± 0.2 vs Cr 7.2 ± 0.2 μmol/L) or after acute exercise (Pla 8.2 ± 0.3 vs Cr 8.4 ± 0.3 μmol/L). No changes in plasma vitamin B12 and folate as well as cysteine and methionine were found. Seven days of creatine supplementation does not avoid increased plasma Hcy induced by acute sprint exercise in humans.

Effects of creatine and vitamin E on muscle energetic metabolism, antioxidant stability and meat quality of pigs

The effects of supplementing the diet of pigs with creatine monohydrate (CMH) and vitamin E on blood plasma creatine concentration, vitamin E level in muscle, muscle energy metabolism, antioxidant capacity and meat (musculus longissimus dorsi) quality of pigs (DNA tested and negative on malignant hyperthermia) were investigated. Two treatments were used: supplementation with CMH alone (2 g.kg−1 of feed, 10 days before slaughter); and supplementation with both vitamin E (500 mg α-tocopherol.kg−1 of feed for minimum of 30 days) and CMH (2 g.kg−1 of feed, 10 days before slaughter). Pigs supplemented with CMH alone showed elevated plasma creatine concentration (P ≤ 0.05). Phosphorus nuclear magnetic resonance (31P NMR) measurements on post mortem (15 min.) muscle samples showed the highest phosphocreatine levels and ratio PCr/Pi (P ≤ 0.05) in CMH supplemented pigs alone and in combination with vitamin E. Dietary supplementation with vitamin E significantly (P ≤ 0.05) increased the concentration of α-tocopherol in meat. Supplementation with CMH alone or in combination with vitamin E resulted in higher (P = 0.07) a values of loin chops at 5 days of storage. Antioxidative capacity (measured as MDA production after incubation of longissimus muscle homogenates with Fe2+/ascorbate) was substantially improved by vitamin E and somewhat by CMH supplementation.