Compartmentalization in cardiomyocytes modulates creatine kinase and adenylate kinase activities.

Intracellular molecules are transported by motor proteins or move by diffusion resulting from random molecular motion. Cardiomyocytes are packed with structures that are crucial for function, but also confine the diffusional spaces, providing cells with a means to control diffusion. They form compartments in which local concentrations are different from the overall, average concentrations. For example, calcium and cyclic AMP are highly compartmentalized, allowing these versatile second messengers to send different signals depending on their location. In energetic compartmentalization, the ratios of AMP and ADP to ATP are different from the average ratios. This is important for the performance of ATPases fuelling cardiac excitation-contraction coupling and mechanical work. A recent study suggested that compartmentalization modulates the activity of creatine kinase and adenylate kinase in situ. This could have implications for energetic signaling through, for example, AMP-activated kinase. It highlights the importance of taking compartmentalization into account in our interpretation of cellular physiology and developing methods to assess local concentrations of AMP and ADP to enhance our understanding of compartmentalization in different cell types.

Low serum creatine kinase level is associated with poor prognosis in patients with hepatocellular carcinoma: A retrospective single­center study.

Previous studies have reported low serum creatine kinase (s-CK) levels as a poor prognostic factor in various cancers. However, there have been no reports on its significance in hepatocellular carcinoma. The present study aimed to evaluate the association of the preoperative s-CK levels with clinicopathologic features and their prognostic impact on survival in patients with hepatocellular carcinoma. This retrospective study included 163 patients with hepatocellular carcinoma (127 male and 36 female patients; median age, 69 years) who underwent radical liver resection between January 2004 and December 2021. A cutoff preoperative s-CK level of 91 U/l determined by receiver operating characteristic curve analysis was used to evaluate the significance of s-CK in predicting overall and recurrence-free survival. In addition, the prognostic impact of s-CK was evaluated using univariate and multivariate analysis. s-CK level was not associated with clinicopathologic factors. Overall survival and recurrence-free survival of the low s-CK group were significantly worse compared with the high s-CK group (P=0.043 and P=0.029, respectively). By multivariate analysis, low s-CK was an independent risk factor for poor overall survival and recurrence-free survival (P=0.019 and P=0.014, respectively). This trend was the same for male patients, but no significant difference was observed for female patients. Low preoperative s-CK level might be a poor prognostic biomarker in patients with hepatocellular carcinoma.

Case report: A creatine kinase-borg scale values-based approach to tailor physical training in a central core myopathy patient.

Background: Patients with central core myopathy (CCM) can be at risk of exercise-induced rhabdomyolysis and myalgia. Despite its possible positive effects, physical training has been long avoided in these patients as no population-specific exercise adaption strategies have been developed. Here we present the case of a 17-year-old male CCM patient who underwent a 3-month training program tailored to a preliminary test aimed at assessing his physical exertion tolerance measured via changes in serum creatine kinase (CK). Methods: The preliminary tolerance test consisted of three 25-minute sessions (one session per week) of physical exercise (aerobic, resistance and mixed) at an intensity quantified as level 6 of the Borg Category Ratio (CR) 0-10 scale. A blood sample to assess CK was conducted 36 h following eachsession. The intervention consisted of a training program (three sessions per week) including both resistance and aerobic exercises concomitant with a personalized nutritional plan. Before and after intervention, a battery of metabolic (indirect calorimetry, bioimpedance) and cardiopulmonary (CPET) tests were performed. Results: After training, improvements of the anaerobic threshold (+6.9%), normalized VO2 max (+15%) and body composition (muscle mass, +1.1 kg; fat mass, -1.1 kg were observed without pain, rhabdomyolysis, and blood CK augmentation compared to pretraining values. Conclusion: Our results highlight that a mixed aerobic/resistance training, properly tailored and supported by a specific nutritional plan, may safely improve the physical fitness and body composition in a CCM patient. Dosing exercise-induced CK serum change following Borg CR-10 intensity assessment, may be useful to correctly tailor physical exercise in these patients.

A Case of Legionella Pneumonia with Rhabdomyolysis, with Extremely high Creatinine Kinase without Acute Kidney Injury in an Adult.

Legionella pneumophila is a bacterium that usually causes pulmonary disease but can rarely present with extrapulmonary manifestations, such as rhabdomyolysis. This is a case of Legionella infection with significant rhabdomyolysis but a lack of acute kidney injury. A 38-year-old male with a history of epilepsy presented to the emergency department after a seizure episode with confusion, fever, emesis and bruises. He also complained of a productive cough and scant haemoptysis for the past two months. Chest X-ray showed retrocardiac and left upper lobe opacities; urine was positive for Legionella antigen and myoglobinuria. Creatinine phosphokinase was 242,488 U/l and creatinine was 0.5 mg/dl. The patient was managed with oxygen therapy, aggressive IV hydration and IV azithromycin, and later IV levofloxacin until his symptoms resolved. Rhabdomyolysis may be a sign of Legionella infection. Rapid testing of Legionella antigen, especially in populations at risk, may be crucial for timely diagnosis and treatment. Kidney function may be preserved in the early stages of disease, but early treatment with antibiotics and aggressive hydration are an effective way to prevent deterioration in kidney function. LEARNING POINTS: Legionella pneumonia is difficult to distinguish from bacterial pneumonia, therefore rapid Legionella testing, particularly in areas with high rates of incidence, is important for targeted therapy.Legionella pneumonia with rhabdomyolysis with extremely high CPK levels is usually associated with AKI but preserved kidney function is possible and early diagnosis and treatment can lead to decreased mortality and morbidity in severe cases.

Rhabdomyolysis in Acute HIV Infection.

Rhabdomyolysis is a rare but potentially life-threatening complication of acute HIV infection. We present a case report of a young adult male who presented with fever, myalgia, and elevated creatine phosphokinase levels, ultimately diagnosed with acute HIV infection-associated rhabdomyolysis. This case highlights the importance of considering HIV infection in the differential diagnosis of rhabdomyolysis, particularly in at-risk populations, even in the absence of typical HIV-related symptoms.

Post-marketing surveilance study of creatine-guanidinoacetic acid safety in healthy adults.

A post-marketing surveillance study assessed the adverse events and possible risk of elevated homocysteine levels after the supplementation with creatine-guanidinoacetic acid mixture in apparently healthy adults. The participants were recruited through social media platforms and online discussion boards, with side effects and total plasma homocysteine (T-Hcy) levels evaluated regularly during a supplementation period of 6 months. Thirthy eight individuals (n = 38, 34.2% female) completed the evaluation period and were included in the final analyses. Serious side effects were absent. Two participants (5.3%) reported transitional nausea during the introductory weeks of the supplementation; no participants stopped the treatment. Baseline T-Hcy levels were 11.6 ± 3.1 µmol/L (95% confidence interval [CI], from 10.6 to 12.6). The intervention induced a mild reduction in T-Hcy levels across the monitoring period (p = 0.028), with T-Hcy levels after 1, 2, 3, and 6 months were 10.4 ± 3.0 µmol/L, 10.6 ± 2.9 µmol/L, 10.1 ± 2.7 µmol/L, and 9.3 ± 2.8 µmol/L, respectively. These findings suggest the overall tolerability of creatine-guanidinoacetic mixture in healthy adults, with homocysteine-increasing risk of no concern.

Association of Genetic Profile with Muscle Mass Gain and Muscle Injury Prevention in Professional Football Players after Creatine Supplementation.

BACKGROUND: In recent years, the study of creatine supplementation in professional athletes has been of great interest. However, the genetics involved in response to supplementation is unknown. The aim of this study was to analyse, for the first time, the relationship between muscle performance-related genes and the risk of an increased body mass index (BMI) and muscle mass and a decrease in fat mass in professional football players after creatine supplementation. METHODS: For this longitudinal study, one hundred and sixty-one men's professional football players were recruited. The polymorphisms ACE I/D, ACTN3 c.1729C>T, AMPD1 c.34C>T, CKM c.*800A>G, and MLCK (c.49C>T and c.37885C>A) were genotyped using Single-Nucleotide Primer Extension (SNPE). To assess the combined impact of these six polymorphisms, a total genotype score (TGS) was calculated. The creatine supplementation protocol consisted of 20 g/day of creatine monohydrate for 5 days (loading dose) and 3-5 g/day for 7 weeks (maintenance dose). Anthropometric characteristics (body mass index (BMI), fat, and muscle mass) were recorded before and after the creatine supplementation protocol. Characteristics of non-contact muscle injuries during the 2022/2023 season were classified according to a consensus statement for injury recording. The results showed that the allelic frequencies of ACE and AMPD1 differed between responders and non-responders in muscle mass increase (all p < 0.05). Players with a TGS exceeding 54.16 a.u. had an odds ratio (OR) of 2.985 (95%CI: 1.560-5.711; p = 0.001) for muscle mass increase. By contrast, those with a TGS below 54.16 a.u. had an OR of 9.385 (95%CI: 4.535-19.425; p < 0.001) for suffering non-contact muscle injuries during the season. CONCLUSIONS: The increase in BMI and muscle mass in response to creatine supplementation in professional football players was influenced by a TGS derived from the combination of favourable genotypes linked to muscle performance. The CC genotype and C allele of AMPD1 were particularly associated with a higher likelihood of muscle mass increase under creatine supplementation in this group of professional football players.

Creatine Promotes Endometriosis by Inducing Ferroptosis Resistance via Suppression of PrP.

Endometriosis, a chronic inflammatory disease, significantly impairs the quality of life of women in their reproductive years; however, its pathogenesis remains poorly understood. The accumulation of retrograde menstruation and recurrent bleeding fosters a high-iron environment in ectopic lesions, triggering ferroptosis in ectopic endometrial stromal cells (EESCs), thereby hindering the establishment of endometriosis. However, abnormal EESCs demonstrate resistance to ferroptosis in high-iron environments, promoting the progression of this disease. Here, novel findings on the accumulation of creatine, derived from endogenous synthesis, in both peritoneal fluid and EESCs of patients with endometriosis are presented. Creatine supplementation reduces cellular iron concentrations, mitigating oxidative stress and lipid peroxidation, thereby enhancing cell viability and preventing ferroptosis under high-iron conditions. Utilizing the drug affinity-responsive target stabilization (DARTS) assay, prion protein (PrP) as a potential creatine-sensing protein is identified. Mechanistically, creatine binds to the active site of PrP, inhibits the conversion of trivalent iron to divalent iron, and decreases iron uptake, promoting the tolerance of EESCs to ferroptosis. This interaction contributes to the development of endometriosis. The novel association between creatine and ferroptosis provides valuable insights into the role of creatine in endometriosis progression and highlights its potential as a therapeutic target for endometriosis.

Protective effects of fructose-1,6-bisphosphate postconditioning on myocardial ischemia-reperfusion injury in patients undergoing valve replacement：a randomized, double-blind, placebo-controlled clinical trial.

Legend of Graphical Abstract: The figure describes the serum CK-MB concentrations in the FDP and NS groups at 4, 24, 48, and 72 h postoperatively. OBJECTIVES: Pharmacological postconditioning can protect against myocardial ischaemia-reperfusion injury during cardiac surgery with extracorporeal circulation. The aim of this study was to observe the protective effects of fructose-1, 6-bisphosphate (FDP) postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing cardiac valve replacement with extracorporeal circulation. METHODS: Patients undergoing elective mitral valve replacement and/or aortic valve replacement were divided into normal saline postconditioning group (NS group) and FDP postconditioning group (FDP group). The primary outcome was the plasma concentration of creatine kinase-MB (CK-MB). The secondary outcomes were the plasma concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP), alpha-hydroxybutyrate dehydrogenase (α-HBDH) and cardiac troponin I (cTnI), the spontaneous cardiac rhythm recovery profile, the extracorporeal circulation time and duration of surgery, ICU and postoperative hospitalization. RESULTS: Forty patients were randomly assigned to receive intervention and included in the analysis. The serum concentrations of CK-MB, LDH, CK, cTnI, α-HBDH and hs-CRP at T1∼4 were lower in the FDP group than in the NS group (P < 0.001). Compared with the NS group, the dosage of dopamine administered 1∼90min after cardiac resuscitation, the spontaneous cardiac rhythm recovery time and the incidence of ventricular fibrillation were lower in the FDP group (P < 0.001, P < 0.001 and P = 0.040, respectively). The values of ST- changes were increased more significantly in the NS group than in the FDP group （median [standard deviation] 1.3 [0.3] mm vs 0.7 [0.2] mm）(P < 0.001). Compared with the NS group, the time of recovery of ST-segment deviations was shorter in the FDP group（50.3 [12.3] min vs 34.6 [6.9] min） (P < 0.001). CONCLUSIONS: The fructose-1, 6-bisphosphate postconditioning could improve both myocardial ischaemia-reperfusion injury and the spontaneous cardiac rhythm recovery during cardiac valve surgery with extracorporeal circulation.

SkinCom, a synthetic skin microbial community, enables reproducible investigations of the human skin microbiome.

Existing models of the human skin have aided our understanding of skin health and disease. However, they currently lack a microbial component, despite microbes' demonstrated connections to various skin diseases. Here, we present a robust, standardized model of the skin microbial community (SkinCom) to support in vitro and in vivo investigations. Our methods lead to the formation of an accurate, reproducible, and diverse community of aerobic and anaerobic bacteria. Subsequent testing of SkinCom on the dorsal skin of mice allowed for DNA and RNA recovery from both the applied SkinCom and the dorsal skin, highlighting its practicality for in vivo studies and -omics analyses. Furthermore, 66% of the responses to common cosmetic chemicals in vitro were in agreement with a human trial. Therefore, SkinCom represents a valuable, standardized tool for investigating microbe-metabolite interactions and facilitates the experimental design of in vivo studies targeting host-microbe relationships.

Effects of a Dietary Microalgae (Arthrospira platensis) Supplement on Stress, Well-Being, and Performance in Water Polo Players: A Clinical Case Series.

BACKGROUND: A common tactic used by athletes to improve performance, lessen tiredness, and hasten recovery is dietary supplementation. We aimed to assess the role of a microalgae dietary liquid supplement additivated with Copper 22.5% NRV in water polo players' performance. METHODS: Twenty male water polo players were split into two groups: ten (spirulina group) took a twice-daily nutritional supplement containing 15 mL of spirulina liquid extract (titrated in Phycocyanin 1 mg/mL) and additivated with Copper 22.5% NRV for eight weeks, and ten (the placebo group) did not take the supplement. Subjective evaluations were finished using the Athlete's Subjective Performance Scale (ASPS). Levels of the biomarker creatine phosphokinase (CPK) were also assessed. RESULTS: The spirulina group's mean total ASPS score increased significantly from baseline to follow-up and was significantly better than that of the placebo group (p < 0.001). Conversely, ASPS ratings in the placebo group slightly decreased. A positive correlation between spirulina supplementation and less severe ASPS was found using correlation matrix analysis. However, there was a slight difference in CPK levels from the baseline to the follow-up in the spirulina group. CONCLUSIONS: A dietary supplement comprising spirulina and copper may help water polo players' subjective performance measurements by lowering muscular tension. Larger, randomized controlled trials are yet required.

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.

Phenotype-Genotype Correlation of a Cohort of Patients with Congenital Myopathy: A Single Centre Experience from India.

Background: Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking. Objectives: This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation. Methods: A retrospective chart review of genetically confirmed CMs was evaluated between January 2016 and December 2020 at the neuromuscular clinic. The clinical, genetic, and follow-up data were recorded in a pre-structured proforma as per the medical records, and the data was analyzed. Results: A total of 31(M: F = 14 : 17) unrelated patients were included. The median age at onset and duration of illness are 2.0(IQR:1-8) years and 6.0(IQR:3-10) years respectively. Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology was available in 38.7% of patients, and centronuclear myopathy was the most common histopathology finding. The pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%) genes. Novel mutations were observed in 30.3% of the cohort. Follow-up details were available in 77.4% of children, and the median duration of follow-up and age at last follow-up was 4.5 (Range 0.5-11) years and 13 (Range 3-35) years, respectively. The majority were ambulant with minimal assistance at the last follow-up. Mortality was noted in 8.3% due to respiratory failure in Centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON). Conclusion: This study highlights the various phenotypes and patterns of genetic mutations in a cohort of pediatric patients with congenital myopathy from India. Centronuclear myopathy was the most common histological classification and the mutations in RYR1 followed by DNM2 gene were the common pathogenic variants identified. The majority were independent in their activities of daily living during the last follow-up, highlighting the fact that the disease has slow progression irrespective of the genotype.

Electrophysiological and biochemical effect of zinc oxide nanoparticles on heart functions of male Wistar rats.

Zinc oxide nanoparticles (ZnO NPs) are one of the most abundantly used nanomaterials in cosmetics and topical products, and nowadays, they are explored in drug delivery and tissue engineering. Some recent data evidenced that they are responsible for cardiotoxic effects and systemic toxicity. The present study aimed to investigate the toxic effect of ZnO NPs (39 nm) on the heart of Wistar rats and to perform a dose-response relationship using three different dose levels (25, 50, 100 mg/kg bw) of ZnO NPs on the electrocardiogram (ECG) readings, the levels of biochemical function parameters of heart, and the oxidative stress and antioxidant biomarkers. Furthermore, zinc concentration level and histopathological examination of heart tissues were determined. ZnO NPs showed a dose-dependent effect, as the 100 mg/kg bw ZnO NPs treated group showed the most significant changes in ECGs parameters: R-R distance, P-R interval, R and T amplitudes, and increased levels of heart enzymes Creatine Kinase- MB (CK-MB) and Lactate dehydrogenase (LDH). On the other hand, elevated zinc concentration levels, oxidative stress biomarkers MDA and NO, and decreased GSH levels were found also in a dose-dependent manner, the results were supported by impairment in the histopathological structure of heart tissues. While the dose of 100 mg/kg bw of ZnO bulk group showed no significant effects on heart function. The present study concluded that ZnO NPs could induce cardiac dysfunctions and pathological lesions mainly in the high dose.

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.

Creatine Kinase and Respiratory Decline in Amyotrophic Lateral Sclerosis.

Respiratory dysfunction is an important hallmark of amyotrophic lateral sclerosis (ALS). Elevation of creatine kinase (CK) has been reported in 23-75% of ALS patients, but the underlying mechanisms remain unknown. This work aims to enlighten the role of CK as a prognostic factor of respiratory dysfunction in ALS. A retrospective analysis of demographic and clinical variables, CK, functional decline per month (ΔFS), forced vital capacity (%FVC), and mean amplitude of the phrenic nerve compound motor action potential (pCMAP) in 319 ALS patients was conducted. These measurements were evaluated at study entry, and patients were followed from the moment of first observation until death or last follow-up visit. High CK values were defined as above the 90th percentile (CK ≥ P90) adjusted to sex. We analyzed survival and time to non-invasive ventilation (NIV) as proxies for respiratory impairment. Linear regression analysis revealed that high CK was associated with male sex (p < 0.001), spinal onset (p = 0.018), and FVC ≥ 80% (p = 0.038). CK was 23.4% higher in spinal-onset ALS patients (p < 0.001). High CK levels were not linked with an increased risk of death (p = 0.334) in Cox multivariate regression analysis. CK ≥ P90 (HR = 1.001, p = 0.038), shorter disease duration (HR = 0.937, p < 0.001), lower pCMAP (HR = 0.082, p < 0.001), and higher ΔFS (HR = 1.968, p < 0.001) were risk factors for respiratory failure. The association between high CK levels and poorer respiratory outcomes could derive from cellular metabolic stress or a specific phenotype associated with faster respiratory decline. Our study suggests that CK measurement at diagnosis should be more extensively investigated as a possible marker of poor respiratory outcome in future studies, including a larger population of patients.

Influence of ACTN3 R577X Polymorphism on Blood Creatine Kinase Levels Relative to Number of Sprints in Brazilian Professional Soccer Players.

This study sought to assess how post-game creatine kinase (CK) levels correlate with the number of sprints and the impact of the ACTN3 polymorphism on this response. This research constituted a descriptive/observational, retrospective cross-sectional study. DNA was extracted from blood samples for ACTN3 polymorphism genotyping. CK was measured 48 h after official matches, and the number of sprints (>19 km/h) was tracked using Global Positioning System (GPS) technology. The main cohort included 23 professional soccer players from the top tier of the Brazilian Championship. We analyzed 115 GPS + CK data sets. The replication cohort comprised 18 professional soccer players from the First Division of the Championship, had the same methodology applied, and featured a total of 90 GPS (sprints > 25.2 km/h) + CK data sets. For the main cohort, a significant positive correlation was seen between the number of sprints and the CK levels (p = 0.009). Athletes with the ACTN3 RR genotype had higher CK levels as more sprints were performed during the match (p = 0.017). However, the relationship was not found for X allele carriers (p > 0.05). For the replication cohort, there was a near-significant correlation between CK levels and the number of sprints (p = 0.05), and RR individuals showed a significant association (p = 0.01), whereas X allele carriers did not (p = 0.06). A greater number of sprints during matches is linked to higher CK levels, primarily among players with the ACTN3 RR genotype, which is potentially due to an increased presence of type II muscle fibers. These findings were replicated for both cohorts of elite Brazilian soccer players, emphasizing the importance of genetic factors in injury prevention.

Glycation reactions of methylglyoxal during digestion in a dynamic, in vitro model of the upper gastrointestinal tract (TIM-1).

The 1,2-dicarbonyl compound methylglyoxal (MGO) can react with and thereby impair the function of proteins and DNA, leading to pathophysiological pathways in vivo. However, studies on the bioavailability of dietary MGO and its reactions during digestion have diverging results. Therefore, simulated digestion experiments of MGO, protein, and creatine were performed in the dynamic, in vitro model of the upper gastrointestinal tract (TIM-1). This multicompartment model continuously adjusts pH values and has realistic gastrointestinal transit times while also removing water and metabolites by dialysis. Samples were analyzed with HPLC-UV for MGO and HPLC-MS/MS for creatine and glycated amino compounds. MGO reacted with creatine during simulated digestion in TIM-1 to form the hydroimidazolone MG-HCr in similar amounts as in a human intervention study. 28%-69% of MGO from the meal were passively absorbed in TIM-1, depending on the addition of creatine and protein. Simultaneous digestion of MGO with ovalbumin led to the formation of the lysine adduct N ε -carboxyethyllysine (CEL) and the methylglyoxal-derived hydroimidazolone of arginine (MG-H1). The formation of both compounds decreased with added creatine. Hence, glycation compounds are formed during digestion and significantly contribute to other ingested dietary glycation compounds, whose physiological consequences are critically discussed.

Association between dietary intake of creatine and female reproductive health: Evidence from NHANES 2017-2020.

The hormonal changes in women influence creatine dynamics, emphasizing its potential importance during menstruation, pregnancy, postpartum, menopause, and postmenopause. Yet, limited research explores creatine's impact on female reproductive health at the population level. Our study investigated the relationship between dietary creatine intake and reproductive health indices in US women using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). We extracted a dataset containing females aged 12 years and above who provided details about their reproductive health and dietary habits. Daily creatine intake was quantified as a relative amount (mg per kg body mass) and did not include creatine from dietary supplements and pharmacological agents. A daily requirement for dietary creatine for healthy women was employed to classify respondents into two separate subpopulations: (1) suboptimal intake of creatine (<13 mg per kg body mass per day) or (2) recommended intake (dietary creatine ≥ 13 mg per kg body mass per day). A total of 4522 female participants from the NHANES study (age 44.5 ± 20.5 years) provided data on their reproductive health and dietary intake. The average daily creatine intake for the group was 10.5 ± 10.8 mg per kg body mass. The odds ratio for having irregular periods in women consuming ≥13 mg of creatine per kg body mass daily (recommended intake) compared to those with suboptimal intake was 0.75 (95% CI, from 0.66 to 0.86), indicating a significant association between higher intake of dietary creatine and lower risk of oligomenorrhea (p < .001). Moreover, women consuming less than 13 mg of creatine per kg body mass faced an increased risk of fetal macrosomia (OR 1.26; p = .04), pelvic infection (OR 1.68; p = .01), hysterectomy (OR 1.42; p < .001), oophorectomy (OR 1.54; p < .001), and receiving hormone replacement therapy (OR 1.26; p = .02). Consuming a creatine-rich diet has been linked to lower risks of reproductive issues in US women aged 12 and above. Those consuming ≥13 mg of creatine per kg body mass daily showed notably lower risks of irregular menstrual periods, obstetric conditions, and pelvic pathology. Further studies are needed to confirm these potential benefits.

Effects of acute creatine supplementation on cardiac and vascular responses in older men; a randomized controlled trial.

BACKGROUND AND AIMS: In the recent years creatine has been shown promising results in patients with neurodegenerative diseases, myopathies and dystrophies. Cardiovascular diseases could be another pathology that can benefit from creatine supplementation, considering the influence on the risk factors associated with the development of cardiovascular diseases including reduction in chronic inflammation, and improved control of hyperglycemia and dyslipidemia The aim of the present study was to investigate the impact of short-term creatine supplementation on cardiac and vascular health in older adults. METHODS: Males between the ages of 55-80 were randomly assigned to three groups: creatine, placebo and control. Creatine or placebo was provided for 7-day supplementation, at a dose of 20 g/day. Testing was performed at the same time of the day at baseline and on the eighth day. Vascular responses were assessed using an arterial pulse wave velocity equipment, while cardiac assessment was performed using an impedance cardiography device. RESULTS: The placebo group was older (71.1 ± 8.2 yr) compared to creatine (61.4 ± 5.2 yr) and control (62.5 ± 7.1 yr). Cardio-ankle vascular index improved just in the creatine group (8.7 ± 0.5 to 8.2 ± 0.5, p = 0.03). While the upstroke time of the placebo and control groups did not change after 7 days, the creatine group had a nonsignificant reduction, 178.9 ± 26.5 ms to 158.4 ± 28.6 ms, p = 0.07. Similar tendency was seen with the systolic blood pressures, while the placebo and control did not change, the creatine group showed nonsignificant improvement, especially on the right, 144.0 ± 12.7 mmHg to 136.1 ± 13.4 mmHg, p = 0.08. All three groups had similar responses in stroke volume (p = 0.61), contractility index (p = 0.64) and ejection fraction (p = 0.72). CONCLUSIONS: In older adults, acute creatine supplementation can positively affect vascular parameters of arterial stiffness and atherosclerosis. Creatine supplementation has the potential to serve as a potent adjuvant in the management of CVD for older adults. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov; ID: NCT05329480.