Creatine Content Research Articles

Glutathione s-transferase pi is a marker of loop diuretic resistance in patients with congestive heart failure exacerbation

Abstract Background Loop diuretic resistance (LDR) in patients with heart failure (HF) exacerbation is associated with worse clinical outcomes, greater symptom burden and mortality. Diagnosis and treatment of LDR remains a significant clinical dilemma. Purpose To assess the ability of different urine biomarkers to predict LDR in patients with HF exacerbation. Methods Consecutive patients with congestive HF exacerbation were prospectively included in the study. HF was diagnosed according to ESC 2021 HF Guidelines definition. Congestion was defined as a presence of one or more of the following signs: edema, ascites, pleural effusion. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Urine biomarkers released from different parts of the nephron (Kidney Injury Molecule-1 - KIM-1, N-acetyl-β-D-glucosaminidase - NAG, uromodulin, glutathione S-transferase Pi - pi-GST, aquaporin-2), transthoracic echo, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. Results are presented as mean ±standard deviation or median (interquartile range). Results 40 patients were included in the study with median age 84 (72,8; 86) years, median left ventricle ejection fraction (EF) 35.3 (26,5; 49) %, median NT-proBNP 8967.5 (3024; 15241) pg/ml. LDR was found in 14 (35%) patients. Univariate analysis identified the following risk factors for LDR: urine pi-GST concentration on admission and on the 4th day, right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), presence of mitral regurgitation, serum creatine concentration, serum urea concentration, serum LDL concentration. Logistic regression analysis identified pi-GST concentration as a significant independent risk factor for LDR in this population: odds ratio (OR) 5.75 [95% confidence interval (CI) 1.271–25.990]. Conclusions Urine pi-GST on admission and after 4 days of treatment might be a marker for a development of LDR in patients with congestive HF exacerbation.

Assessing Dietary Creatine Intake in Population Studies: Challenges and Opportunities.

Limited data exist for establishing the dietary requirements for creatine in the general population. This paper delineates the challenges linked to estimating creatine intake from a typical diet, and explores opportunities to improve the assessment of population-wide creatine intake. Conducting additional food chemistry studies with creatine as a standard analyte, labeling the creatine content in common foods, generating more diverse data from population-based studies, and validating new biomarkers could facilitate the establishment of nutrient reference values for this conditionally essential nutrient.

Accuracy of estimating equations for the assessment of glomerular filtration rate in critically ill patients versus outpatients.

Estimating equations for the assessment of glomerular filtration rate (GFR) have been poorly investigated in the critical care setting. We evaluated the agreement between the GFR measured with 51CrEDTA/iohexol (mGFR) and four estimating equations based on serum concentrations of creatine and/or cystatin C (eGFR) in two cohorts: critically ill patients and outpatients with normal-to-moderately reduced GFR. Forty-three patients in the critical care group and 48 patients in the outpatient group were included. GFR was measured (mGFR) by plasma infusion clearance of 51Cr-EDTA/iohexol (critical care group) and the single injection, one-sample plasma 51Cr-EDTA clearance technique (outpatients). The following estimating equations (eGFR) were used: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for creatinine (CKD-EPICr), cystatin C (CKD-EPICys C), creatinine+cystatin C (CKD-EPICr + Cys C) and the Lund-Malmö creatinine+cystatin C equation (LMCr + Cys C). Agreement between mGFR and eGFR was assessed by the Bland-Altman method and accuracy by calculating P30 and P10. In the critically ill group, the bias between the estimating equations and mGFR was -3.6 to 2.8 mL/min/1.73 m2, while the error was 121%-127% and the accuracy (P30) 33%-40%. In the outpatients, the bias between the estimating equations and mGFR was -13.0 to 7.6 mL/min/1.73 m2, while the error was 31%-41% and the accuracy (P30), 67%-96%. All four equations performed poorly in assessing GFR in the critically ill cohort with an unacceptably high error and low accuracy in contrast to the outpatient group. To accurately assess GFR in critically ill patients, GFR must be measured not estimated. For the assessment of glomerular filtration rate (GFR), it can be measured directly, but is frequently estimated using a point measure of serum creatinine concentration. In this study, ICU case GFR estimations, by different adjusted equations, done also for a cohort of outpatients, showed that these serum creatinine-based estimations for ICU cases are not highly precise or reliable.

Decreased mitochondrial creatine kinase 2 impairs skeletal muscle mitochondrial function independently of insulin in type 2 diabetes.

Increased plasma creatine concentrations are associated with the risk of type 2 diabetes, but whether this alteration is associated with or causal for impairments in metabolism remains unexplored. Because skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. In men with type 2 diabetes, plasma creatine concentrations were increased, and intramuscular phosphocreatine content was reduced. These alterations were coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 (CKMT2). In C57BL/6 mice fed a high-fat diet, neither supplementation with creatine for 2 weeks nor treatment with the creatine analog β-GPA for 1 week induced changes in glucose tolerance, suggesting that increased circulating creatine was associated with insulin resistance rather than causing it. In C2C12 myotubes, silencing Ckmt2 using small interfering RNA reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of Ckmt2 in skeletal muscle of high-fat diet-fed male mice increased mitochondrial respiration, independent of creatine availability. Given that overexpression of Ckmt2 improved mitochondrial function, we explored whether exercise regulates CKMT2 expression. Analysis of public data revealed that CKMT2 content was up-regulated by exercise training in both humans and mice. We reveal a previously underappreciated role of CKMT2 in mitochondrial homeostasis beyond its function for creatine phosphorylation, independent of insulin action. Collectively, our data provide functional evidence for how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes.

A-100 Clinical Utility of Measuring Creatine Concentration in Erythrocyte

Abstract Background Shortened erythrocyte lifespan characterizes hemolytic anemia and impacts HbA1c values. Recently, erythrocyte creatine concentration (EC) measurement emerged as a new method to assess erythrocyte lifespan. However, literature reports conflicting findings regarding the association between erythrocyte lifespan and EC concentration. In our study, we noted low EC concentrations in renal diseases, typically linked to short erythrocyte lifespan, while iron deficiency anemia exhibited high EC concentrations. This contradicts established relationships, prompting a reevaluation of EC concentration assessment. The aim is to evaluate the clinical utility of EC concentration measurements by correlating them with various clinical parameters, including hematopoietic status. Methods EC concentrations were measured in 522 subjects (252 females, 270 males) aged 19 to 95 at Kawasaki Medical School Hospital. Medical records and laboratory test results from around one month before and after blood collection were used to create a database. Box-and-whisker plots illustrated EC concentration distribution for each disease, and scatter plots compared EC concentrations with laboratory parameters. Results EC concentrations were lower in renal diseases like Diabetes and Chronic Kidney Disease but higher in iron deficiency anemia (Fig. 1). Moreover, EC concentrations rose as hemoglobin concentrations declined, unaffected by CKD grade (Fig. 2). Conclusions While conventionally, high EC concentrations imply a short erythrocyte lifespan, our study noted the opposite trend. EC concentrations might not indicate erythrocyte lifespan but instead reflect hemoglobin synthesis. Investigating EC concentration's relationship with factors like iron and vitamin B12 involved in hemoglobin synthesis may unveil new clinical applications.

Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic medical condition with no specific pharmacological treatment. Creatine, a nutrient essential for maintaining energy homeostasis in the cells, is a candidate for interventions in ME/CFS. Methods: Fourteen participants with ME/CFS received supplementation with 16 g creatine monohydrate for 6 weeks. Before starting creatine and on the last day of treatment, participants underwent brain magnetic resonance spectroscopy (MRS) scanning of the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC), followed by symptom, cognition, and hand-grip strength assessments. Results: Eleven participants completed the study. Creatine treatment increased creatine concentration in both the pgACC and DLPFC (p = 0.004 and 0.012, respectively), decreased fatigue and reaction time (RT) on congruent and incongruent trials of the Stroop test (p = 0.036 and 0.014, respectively), and increased hand-grip strength (p = 0.0004). There was a positive correlation between increases in pgACC creatine and changes in RT on Stroop congruent and incongruent trials (p = 0.048 and p = 0.022, respectively). Creatine was well tolerated, and none of the participants stopped treatment. Conclusion: Creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition. Despite its methodological limitations, this study encourages placebo-controlled investigations of creatine treatment in ME/CFS.

Establishing Reference Intakes for Creatine in Infants Aged 0 to 12 Months.

Creatine is recognized as a conditionally essential nutrient in certain populations; however, there is a lack of established reference values across different life stages. Infants rely exclusively on dietary creatine from human milk for their first 6 months; evaluating creatine adequacy in this population can be estimated based on preliminary data regarding the intake needed to promote optimal growth. This special article explores creatine requirements for infants aged 0 to 12 months, presents a summary of creatine content in human milk, and proposes reference intakes for creatine in this population.

Cardiac function and energetics in mice with combined genetic augmentation of creatine and creatine kinase activity

Improving energy provision in the failing heart by augmenting the creatine kinase (CK) system is a desirable therapeutic target. However, over-expression of the creatine transporter (CrT-OE) has shown that very high creatine levels result in cardiac hypertrophy and dysfunction. We hypothesise this is due to insufficient endogenous CK activity to maintain thermodynamically favourable metabolite ratios. If correct, then double transgenic mice (dTg) overexpressing both CrT and the muscle isoform of CK (CKM-OE) would rescue the adverse phenotype. In Study 1, overexpressing lines were crossed and cardiac function assessed by invasive haemodynamics and echocardiography. This demonstrated that CKM-OE was safe, but too few hearts had creatine in the toxic range. In Study 2, a novel CrT-OE line was generated with higher, homogeneous, creatine levels and phenotyped as before. Myocardial creatine was 4-fold higher in CrT-OE and dTg hearts compared to wildtype and was associated with hypertrophy and contractile dysfunction. The inability of dTg hearts to rescue this phenotype was attributed to downregulation of CK activity, as occurs in the failing heart. Nevertheless, combining both studies in a linear regression analysis suggests a modest positive effect of CKM over a range of creatine concentrations. In conclusion, we confirm that moderate elevation of creatine is well tolerated, but very high levels are detrimental. Correlation analysis lends support to the theory that this may be a consequence of limited CK activity. Future studies should focus on preventing CKM downregulation to unlock the potential synergy of augmenting both creatine and CK in the heart.

Maternal Supplementation with Dietary Betaine during Late Gestation Increased Ewe Plasma Creatine and Lamb Thermoregulation under Field Conditions.

Twin lamb mortality is a significant economic problem impacting the Australian sheep industry. Maternal betaine supplementation improved lamb vigour and early post-natal survival when ewes and lambs were housed indoors, suggesting that betaine may be beneficial to feed under extensive pasture systems. This study investigated whether maternal betaine supplementation during late gestation would improve Merino twin lamb live weight, thermoregulation, vigour and survival to weaning under field conditions. Ewes received dietary betaine at either 0 g/day (CTL; n = 115) or 4 g/day from day 110 of gestation (dG 110) until ~49 days post-partum (pp) (BET; n = 115). Measures indicative of lamb viability and survival were collected within 4-24 h of birth and at ~49 days pp and ~93 days pp. BET ewes had higher creatine and creatinine concentrations at dG 130 than CTL ewes (p < 0.05). BET lambs had a higher rectal temperature within 4-24 h following birth than CTL lambs (p < 0.05). CTL lambs were heavier at ~49 days pp and grew faster from birth to ~49 days pp than BET lambs (both p < 0.05). The time taken after release from the researcher to first suckling was quicker in the CTL lambs than BET lambs (p < 0.05). This study demonstrated that supplementing betaine increased creatine concentration in twin-bearing ewes and thermoregulatory capacity in neonatal lambs under extensive grazing systems.

Quantification of relevant metabolites in apoptotic bodies from HK-2 cells by targeted metabolomics based on liquid chromatography-tandem mass spectrometry

BackgroundApoptotic bodies play an important role in the cellular communication as a consequence of the great variety of biomolecules they harbor. There is evidence that 1st generation apoptotic bodies from HK-2 cells induced by cisplatin or UV light trigger apoptosis in naïve HK-2 cells whereas 2nd generation apoptotic bodies activate cell proliferation showing an opposite effect. Thus, the development of new analytical strategies to quantify the changes in the involved metabolites is imperative to shed light on the biological mechanisms which trigger apoptosis and cell proliferation. ResultsA LC-(Q-Orbitrap)MS method has been developed to quantify the metabolites unequivocally identified in the apoptotic body fluid from HK-2 cells in our previous works based on untargeted metabolomics. Thus, two different columns and gradients were tested and the HILIC column was selected taking into account the retention times and chromatographic separation. Also, different normal collision energies were tested for each metabolite and the parallel reaction monitoring was chosen to carry out the quantitative analysis. Once the method was optimized, it was evaluated in terms of linearity, limits of detection and quantification, matrix effects, accuracy, and precision, for each metabolite. Limits of detection ranged from 0.02 to 1.4 ng mL−1. A total of 9 relevant metabolites proposed as potential biomarkers to reveal metabolic differences among apoptotic bodies from HK-2 cells were quantified and some insights about the biological relevance were discussed. SignificanceThe first targeted metabolomics methodology enabling the quantification of relevant metabolites in apoptotic bodies from HK-2 cells was developed using LC-(Q-Orbitrap)MS. Pyridoxine, kynurenine, and creatine concentrations were determined in apoptotic bodies from HK-2 cells treated with cisplatin and UV light. Phenylacetylglycine, hippuric acid, butyrylcarnitine, acetylcarnitine, carnitine, and phenylalanine were determined in 1st and 2nd generation apoptotic bodies from HK-2 cells treated with cisplatin. Concentrations determined were useful to establish their biological role in the metabolism.

Myo-inositol and total NAA in the hippocampus are linked to CSF tau pathology in cognitively normal older adults.

Understanding relationships between in vivo neurometabolic changes and Alzheimer's disease (AD) pathology in the hippocampus, a region vulnerable to early changes in AD, will support early diagnosis. Two studies using 1 H-MRS examined concentrations of myo-inositol (MI), total creatine (tCr) and total NAA (tNAA) in the hippocampus. The first study compared hippocampal metabolite concentrations in healthy young and older adults and the second study assessed relationships between hippocampal metabolites and cerebrospinal fluid (CSF) measurements of Aβ42, phosphotau 181 (pTau181), and total tau (t-Tau) while adjusting for demographic covariates and spectral characteristics (linewidth, signal- to-noise ratio) in a separate group of older adults ranging from cognitively normal (CN) to AD-dementia. Hippocampal MI, but not tCr or tNAA, was increased in cognitively normal older versus young adults. Within the second older adult group, MI and tNAA, but not tCr, were linked to increases in CSF pTau181 and t-Tau, but not Aβ42. Tau deposition in cognitively normal individuals is associated with biochemical changes related to glial reactivity and neural integrity in the hippocampus.

Exercise-induced changes in intramuscular total creatine concentration measured with 1H magnetic resonance spectroscopy: A pilot study.

Total amount of creatine (Cr) and phosphocreatine, or total creatine (tCr), may have a significant impact on the performance of skeletal muscles. In sports such as bodybuilding, it is popular to take Cr supplements to maintain tCr level. However, no study has explored the quantitative relationship between exercise intensity and the induced change in muscle's tCr. In this well-controlled study, straight-leg plantar flexion with specific load and duration was performed by 10 healthy subjects inside an MRI scanner, immediately followed by 1H MR spectroscopy (MRS) for measuring tCr concentration in gastrocnemius. For repeatability assessment, the experiment was repeated for each subject on two different days. Across all the subjects, baseline tCr was 46.6 ± 2.4 mM, ranging from 40.6 to 50.1 mM; with exercise, tCr significantly decreased by 10.9% ± 1.0% with 6-lb load and 21.0% ± 1.3% with 12-lb load (p < 0.0001). Between two different days, baseline tCr, percentage decrease induced by exercise with a 6-lb and 12-lb load differed by 2.2% ± 2.3%, 11.7% ± 6.0% and 4.9% ± 3.2%, respectively. In conclusion, the proposed protocol of controlled exercise stimulation and MRS acquisition can reproducibly monitor tCr level and its exercise-induced change in skeletal muscles. The measured tCr level is sensitive to exercise intensity, so can be used to quantitatively assess muscle performance or fatigue.

Decreased Cerebral Creatine and N-Acetyl Aspartate Concentrations after Severe COVID-19 Infection: A Magnetic Resonance Spectroscopy Study.

Background/Objectives: The aim of this study was to evaluate brain metabolism using MR spectroscopy (MRS) after recovery from Coronavirus disease (COVID-19) and to test the impact of disease severity on brain metabolites. Methods: We performed MRS on 81 individuals (45 males, 36 females, aged 40-60), who had normal MRI findings and had recovered from COVID-19, classifying them into mild (17), moderate (36), and severe (28) groups based on disease severity during the acute phase. The study employed two-dimensional spectroscopic imaging above the corpus callosum, focusing on choline (Cho), creatine (Cr), and N-acetylaspartate (NAA). We analyzed Cho/Cr and NAA/Cr ratios as well as absolute concentrations using water as an internal reference. Results: Results indicated that the Cho/Cr ratio was higher with increasing disease severity, while absolute Cho and NAA/Cr ratios showed no significant differences across the groups. Notably, absolute Cr and NAA levels were significantly lower in patients with severe disease. Conclusions: These findings suggest that the severity of COVID-19 during the acute phase is associated with significant changes in brain metabolism, marked by an increase in Cho/Cr ratios and a reduction in Cr and NAA levels, reflecting substantial metabolic alterations post-recovery.

Variation of microbiological and small molecule metabolite profiles of Nuodeng ham during ripening by high-throughput sequencing and GC-TOF-MS

The internal microbial diversity and small molecular metabolites of Nuodeng ham in different processing years (the first, second and third year sample) were analyzed by high-throughput sequencing technology and gas chromatography-time of flight mass spectrography (GC-TOF-MS) to study the effects of microorganisms and small molecular metabolites on the quality of ham in different processing years. The results showed that the dominant bacteria phyla of Nuodeng ham in different processing years were Proteobacteria and Firmicutes, the dominant fungi phyla were Ascomycota and Basidiomycota, while Staphylococcus and Aspergillus were the dominant bacteria and fungi of Nuodeng ham, respectively.Totally, 252 kinds of small molecular metabolites were identified from Nuodeng ham in different processing years, and 12 different metabolites were screened through multivariate statistical analysis. Further metabolic pathway analysis showed that 23 metabolic pathways were related to ham fermentation, of which 8 metabolic pathways had significant effects on ham fermentation (Impact > 0.01, P < 0.05). The content of L-proline, phenyllactic acid, L-lysine, carnosine, taurine, D-proline, betaine and creatine were significantly positively correlated with the relative abundance of Staphylococcus and Serratia, but negatively correlated with the relative abundance of Halomonas, Aspergillus and Yamadazyma.

Dietary guanidinoacetic acid as arginine spare molecule for beef cows at late gestation: Effects on cow’s performance and metabolism, and offspring growth and development

We aimed to assess whether guanidinoacetic acid (GAA) affects the performance, metabolism, and placental vascularization of pregnant beef cows during late gestation as well as its impact on the offspring’s performance. Twenty-eight pregnant Brahman cows, averaging 532±15.1 kg and carrying male (n=15) and female (n=13) fetuses, were used. The basal diet consisted of 688 g/kg corn silage, 147 g/kg sugarcane bagasse, 47.7 g/kg corn, 89.6 g/kg soybean meal, 6.86 g/kg urea, and 21.2 g/kg mineral mixture (DM basis). Cows were fed the experimental diets from 180 to 270 days of gestation. The following treatments were evaluated: control (no addition of GAA) or addition of 0.2 % GAA to the total diet (DM basis). There was no effect (P≥0.37) of GAA on voluntary intake. Similarly, GAA addition did not affect (P≥0.54) cows performance variables, except for ribeye area (REA), which had a lower (P<0.01) variation compared to the initial REA in cows fed dietary GAA compared to the control group. Dietary GAA increased (P≤0.02) both serum nitric oxide and placental vascularization compared to cows fed the control diet. There was no effect (P≥0.43) of GAA on urine and serum creatine concentrations. In contrast, dietary GAA increased (P≤0.03) plasma concentration of arginine, ornithine, citrulline, and tyrosine compared to the control. Conversely, dietary GAA decreased (P<0.02) plasma methionine concentration. Dietary GAA increased AGAT activity (P<0.03) in the liver, with no differences observed (P>0.68) on GAMT activity. There was no effect (P≥0.15) of GAA on performance of the offspring. Addition of GAA in maternal diet did not affect skeletal muscle fiber number (P>0.09) and diameter (P>0.23) of the offspring. Guanidinoacetic acid decreases skeletal muscle mobilization and enhances placental vascularization of beef cows during late gestation. However, providing GAA seems to not affect the performance of the offspring.

Non-invasive mapping of brown adipose tissue activity with magnetic resonance imaging

Thermogenic brown adipose tissue (BAT) has a positive impact on whole-body metabolism. However, in vivo mapping of BAT activity typically relies on techniques involving ionizing radiation, such as [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) and computed tomography (CT). Here we report a noninvasive metabolic magnetic resonance imaging (MRI) approach based on creatine chemical exchange saturation transfer (Cr-CEST) contrast to assess in vivo BAT activity in rodents and humans. In male rats, a single dose of the β3-adrenoceptor agonist (CL 316,243) or norepinephrine, as well as cold exposure, triggered a robust elevation of the Cr-CEST MRI signal, which was consistent with the [18F]FDG PET and CT data and 1H nuclear magnetic resonance measurements of creatine concentration in BAT. We further show that Cr-CEST MRI detects cold-stimulated BAT activation in humans (both males and females) using a 3T clinical scanner, with data-matching results from [18F]FDG PET and CT measurements. This study establishes Cr-CEST MRI as a promising noninvasive and radiation-free approach for in vivo mapping of BAT activity.

Selenium-enriched Lactobacillus plantarum alleviate of high alkalinity-induced microbiota-gut-blood systems affect by improving the gut microbiota

High alkalinity is the most important limiting factor in carbonate-type saline–alkali water aquaculture, and fish growth is slow and survival is low in highly alkaline environments. Selenium-enriched (Se-enriched) Lactobacillus plantarum (L. plantarum) has antioxidant and anti-inflammatory properties and can regulate the balance of the gut flora. However, the physiological regulatory mechanism of Se-enriched L. plantarum on common carp under high alkalinity stress is still unclear. In the present study, 360 common carp were randomly divided into a control group, a high alkalinity group, and a Se-enriched L. plantarum and high alkalinity group and fed for 56 days. High alkalinity stress induced growth inhibition in common carp. Histopathology revealed atrophy of the intestinal villi and damage to the intestinal microvilli and tight junction complexes. Serological parameters showed that the serum ammonia and LPS contents were significantly increased. Gut microbial disruption under high alkalinity stress increased the abundance of Bacteroidota (LPS-producing bacteria), Providencia sp. (ammonia-producing bacteria) and Vibrio (pathogenic bacteria) and significantly decreased the expression of the tight junction proteins Zonula occludens-1 (ZO-1) and Occludin, disrupting the gut barrier. However, Se-enriched L. plantarum decreased the abundance of Bacteroidota Providencia sp. and Vibrio, increased the expression of the tight junction proteins ZO-1 and Occludin, and alleviated intestinal damage caused by high alkalinity while reducing the content of lipopolysaccharides (LPS) and ammonia in the serum. In addition, metabolomic analysis of serum revealed that high alkalinity stress activated autophagy, glucocorticoids and mineralocorticoid receptor agonists/antagonists, ABC transporters, the phosphatidylinositol signalling system, and the Mammalian Target of Rapamycin (mTOR) signalling pathway and significantly increased creatine content and riboflavin. Se-enriched L. plantarum treatment significantly decreased the creatine and D-alanine contents. In summary, this study revealed that Se-enriched L. plantarum can alleviate the harmful effects of high alkalinity on common carp by regulating the balance of the intestinal microbiota, improving intestinal barrier function, reducing the amount of harmful substances entering the bloodstream, and regulating blood metabolites. This study demonstrates the physiological regulatory mechanism of Se-enriched L. plantarum in alleviating high alkalinity stress and provides ideas and a theoretical basis for the protection against high alkalinity poisoning of fish in saline–alkali waters.

Creatine homeostasis and the kidney: comparison between kidney transplant recipients and healthy controls

Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all P > 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, P < 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, P < 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both P < 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both P < 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; P = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; P < 0.001). These associations were fully mediated (93% and 95%; P < 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function.Trial registration ID: NCT02811835.Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT02811835.

Arginine, glycine, and creatine supplementation improves symptoms in a female with creatine transporter deficiency.

X-linked creatine transporter deficiency is caused by hemizygous or heterozygous pathogenic variants in SLC6A8 that cause neuropsychiatric symptoms because of impaired uptake of creatine into tissues throughout the body. Small cohorts have suggested that supplementation of creatine, arginine, and glycine can stop disease progression in males, but only six cases of supplementation in females have been published. Here, we present a female with a de-novo pathogenic SLC6A8 variant who had ongoing weight loss, mild intellectual disability, and neuropsychiatric symptoms. Magnetic resonance spectroscopy of the brain showed reduced creatine on all acquired spectra. The patient was started on creatine-monohydrate, l -arginine, and l -glycine supplementation, and she had significant symptomatic improvement within the following 3 weeks. After 8 months of supplementation, magnetic resonance spectroscopy showed improved creatine concentrations with normalizing semiquantitative ratios with other brain metabolites. Current data supports clinicians trialing creatine, arginine, and glycine supplements for female patients with creatine transporter deficiency.

Leaching of gold ore using creatine monohydrate

Creatine was used as a lixiviant for gold dissolution from gold ore. The effects of creatine concentration, temperature, leach time, and pH were examined for their influence on extent of gold dissolution. The results show that at a temperature of 75°C and pH 11.5, gold dissolution increased from 51% to 88% on increasing creatine concentration from 25 to 50 g/t. Further increase in creatine concentration showed a negative effect on the gold dissolution. Gold dissolution increased from 47% to 87% by increasing the temperature from 25°C to 55°C, and from 61% to 89% by increasing pH from 10 to 11.5. Under the optimum conditions of solids' content of 30%, pH 11.5, creatine concentration of 100 g/t, temperature of 75°C, and hydrogen peroxide addition of 2%, about 90% of the gold could be dissolved from the ore after 24 h. A comparison between creatine and cyanide leaching showed that 90% gold dissolution was achieved at a cyanide concentration of 300 g/t, which is three times higher than the creatine concentration under optimal conditions.