Elucidating the Antiglycation Effect of Creatine on Methylglyoxal-Induced Carbonyl Stress In Vitro.

Advanced glycation end products (AGEs) with multiple structures are formed at the sites where carbonyl groups of reducing sugars bind to free amino groups of proteins through the Maillard reaction. In recent years, it has been highlighted that the accumulation of AGEs, which are generated when carbonyl compounds produced in the process of sugar metabolism react with proteins, is involved in various diseases. Creatine is a biocomponent that is homeostatically present throughout the body and is known to react nonenzymatically with α-dicarbonyl compounds. This study evaluated the antiglycation potential of creatine against methylglyoxal (MGO), a glucose metabolite that induces carbonyl stress with formation of AGEs in vitro. Further, to elucidate the mechanism of the cytoprotective action of creatine, its effect on the accumulation of carbonyl proteins in the cells and the MGO-induced cellular damage were investigated using neuroblastoma cells. The results revealed that creatine significantly inhibits protein carbonylation by directly reacting with MGO, and creatine added to the culture medium suppressed MGO-derived carbonylation of intracellular proteins and exerted a protective effect on MGO-induced cytotoxicity. These findings suggest that endogenous and supplemented creatine may contribute to the attenuation of carbonyl stress in vivo.

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 ß-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.

The Top 5 Can't-Miss Sport Supplements.

Background/Objectives: Sports supplements have become popular among fitness enthusiasts for enhancing the adaptive response to exercise. This review analyzes five of the most effective ergogenic aids: creatine, beta-alanine, nitrates, caffeine, and protein. Methods: We conducted a narrative review of the literature with a focus on the sport supplements with the most robust evidence for efficacy and safety. Results: Creatine, one of the most studied ergogenic aids, increases phosphocreatine stores in skeletal muscles, improving ATP production during high-intensity exercises like sprinting and weightlifting. Studies show creatine supplementation enhances skeletal muscle mass, strength/power, and muscular endurance. The typical dosage is 3-5 g per day and is safe for long-term use. Beta-alanine, when combined with the amino acid histidine, elevates intramuscular carnosine, which acts as a buffer in skeletal muscles and delays fatigue during high-intensity exercise by neutralizing hydrogen ions. Individuals usually take 2-6 g daily in divided doses to minimize paresthesia. Research shows significant performance improvements in activities lasting 1-4 min. Nitrates, found in beetroot juice, enhance aerobic performance by increasing oxygen delivery to muscles, enhancing endurance, and reducing oxygen cost during exercise. The recommended dosage is approximately 500 milligrams taken 2-3 h before exercise. Caffeine, a central nervous system stimulant, reduces perceived pain while enhancing focus and alertness. Effective doses range from 3 to 6 milligrams per kilogram of body weight, typically consumed an hour before exercise. Protein supplementation supports muscle repair, growth, and recovery, especially after resistance training. The recommended intake for exercise-trained men and women varies depending on their specific goals. Concluions: In summary, creatine, beta-alanine, nitrates, caffeine, and protein are the best ergogenic aids, with strong evidence supporting their efficacy and safety.

Fueling the Firefighter and Tactical Athlete with Creatine: A Narrative Review of a Key Nutrient for Public Safety.

Background/Objectives: Firefighters, tactical police officers, and warriors often engage in periodic, intermittent, high-intensity physical work in austere environmental conditions and have a heightened risk of premature mortality. In addition, tough decision-making challenges, routine sleep deprivation, and trauma exacerbate this risk. Therefore, identifying strategies to bolster these personnel's health and occupational performance is critical. Creatine monohydrate (CrM) supplementation may offer several benefits to firefighters and tactical athletes (e.g., police, security, and soldiers) due to its efficacy regarding physical performance, muscle, cardiovascular health, mental health, and cognitive performance. Methods: We conducted a narrative review of the literature with a focus on the benefits and application of creatine monohydrate among firefighters. Results: Recent evidence demonstrates that CrM can improve anaerobic exercise capacity and muscular fitness performance outcomes and aid in thermoregulation, decision-making, sleep, recovery from traumatic brain injuries (TBIs), and mental health. Emerging evidence also suggests that CrM may confer an antioxidant/anti-inflammatory effect, which may be particularly important for firefighters and those performing tactical occupations exposed to oxidative and physiological stress, which can elicit systemic inflammation and increase the risk of chronic diseases. Conclusions: This narrative review highlights the potential applications of CrM for related tactical occupations, with a particular focus on firefighters, and calls for further research into these populations.

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.

Changes in the medial prefrontal cortex metabolites after 6 months of medication therapy for patients with bipolar disorder: A 1H-MRS study.

AIMS: The study aimed to assess brain metabolite differences in the medial prefrontal cortex (mPFC) between acute and euthymic episodes of bipolar disorder (BD) with both mania and depression over a 6-month medication treatment period. METHODS: We utilized 1H-MRS technology to assess the metabolite levels in 53 individuals with BD (32 in depressive phase, 21 in manic phase) and 34 healthy controls (HCs) at baseline. After 6 months of medication treatment, 40 subjects underwent a follow-up scan in euthymic state. Metabolite levels, including N-acetyl aspartate (NAA), glutamate (Glu), and Glutamine (Gln), were measured in the mPFC. RESULTS: Patients experiencing depressive and manic episodes exhibited a notable reduction in NAA/Cr + PCr ratios at baseline compared to healthy controls (p = 0.004; p = 0.006) in baseline, compared with HCs. Over the 6-month follow-up period, the manic group displayed a significant decrease in Gln/Cr + PCr compared to the initial acute phase (p = 0.03). No significant alterations were found in depressed group between baseline and follow-up. CONCLUSION: This study suggests that NAA/Cr + PCr ratios and Gln/Cr + PCr ratios in the mPFC may be associated with manic and depressive episodes, implicating that Gln and NAA might be useful biomarkers for distinguishing mood phases in BD and elucidating its mechanisms.

Effect of creatine administration on locomotor activity and stress response in olive flounder (Paralichthys olivaceus).

The creatine kinase system is crucial for maintaining cellular energy homeostasis and plays a role in regulating locomotor behavior in organisms, but its significance in the regulating the motionless behavior in olive flounder is limited. In the first experiment of this study, elevated levels of creatine kinase (CK) activity in the spinal cord were detected in the juvenile group (JG) flounder compared to the adult group (AG) flounder. In the second experiment, to further confirm the involvement of CK in the locomotor behavior, the adult flounder was given an intraperitoneal injection of creatine (150 mg/kg), while the flounder in the control group received a saline solution. After one week post-injection, the behavioral analysis revealed that the flounder in the creatine-treated group displayed higher levels of locomotor activity and a greater number of escape attempts in response to external stimuli when compared to the control group. However, the acute stress response, induced by intraperitoneal injection and characterized by tail beating, was significantly alleviated in the flounder in the creatine-treated group. Additionally, there was an upregulation of the UII and AchR genes in the spinal cord, as well as increased levels of UII and AchR in the muscle tissues of the creatine-treated flounder. However, a reduction in UI mRNA levels was observed in the brain of the flounder. Collectively, our data provide the evidence that the elevated enzyme activity and gene expression of creatine kinase play important roles in off-bottom swimming behavior in the JG flounder. Furthermore, administration of creatine improved the locomotor activity and alleviated the stress response in flounder, which is associated with regulation of the locomotor- and stress-related gene in the brain, spinal cord, and muscle.

Creatine Supplementation Prior to Strength Exercise Training Is Not Superior in Preventing Muscle Mass Loss Compared with Standard Nutritional Recommendations in Females After Bariatric Surgery: A Pilot Study.

BACKGROUND: This study examines whether creatine supplementation combined with strength training mitigates muscle mass loss in women during early rehabilitation post-bariatric surgery, as its effectiveness remains untested in this context. METHODS: Fifteen women (37.8 ± 9.6 years; BMI, 38.8 ± 5.6 kg/m2) completed the intervention (creatine group = 7; placebo group = 8). Both groups followed a strength training program three times a week for 8 weeks. The dosage for both the creatine and placebo was 8 g prior to each exercise session. Body weight, skeletal muscle mass, fat mass, handgrip strength, and physical activity levels were measured before and after the intervention. RESULTS: The creatine group showed a reduction of 9.5 ± 1.5 kg in body weight, with a 0.72 ± 0.6 kg decrease in muscle mass and an 8.64 ± 1.2 kg reduction in fat mass. The placebo group had a reduction of 9.6 ± 3.5 kg in body weight, with a 0.6 ± 1.2 kg decrease in muscle mass and an 8.88 ± 3.2 kg reduction in fat mass, without significant differences between groups (p > 0.05). CONCLUSION: The pre-session strength exercise training creatine supplementation is not superior to placebo regarding body weight and fat mass losses and the attenuation of muscle mass loss during the first weeks of rehabilitation following bariatric surgery.

Integrative analysis revealed novel putative therapeutic targets of ulcerative colitis: Role of creatine.

BACKGROUND: Ulcerative colitis (UC) is becoming a global burden. Previous observational studies have unveiled associations between serum metabolites and UC, but their causal relationship remains unclear. METHODS: Serum samples from patients and mice with UC were utilized for untargeted metabolomics to identify UC-associated metabolites. Then, a two-sample mendelian randomization (MR) analysis was employed to estimate their causal relationship. Finally, mice with chronic colitis induced by dextran sodium sulfate (DSS) and macrophages were used to evaluate the protective role of creatine and underlying mechanism. RESULTS: 16 serum metabolites showed associations with UC after adjusting for confounders and multiple testing. Among them, creatine exhibited a robust protective effect against UC (OR=0.39; 95 % CI=0.27-0.56). Significant reduction of creatine was also observed in mice with acute UC induced by DSS. The inverse variance weighted (IVW) MR analysis further confirmed a causal effect of creatine on UC risk (OR IVW=0.45; 95 % CI: 0.27-0.76). Furthermore, creatine supplementation could significantly suppress weight loss, disease activity index, mucosal damage and the infiltration of macrophages in mice with chronic colitis. Remarkably, creatine promoted the polarization of bone marrow-derived macrophage (BMDM) towards M2 phenotype and upregulated the expression of il-10, il-12 and arg-1. CONCLUSIONS: This study revealed a causal relationship between creatine and UC. Creatine supplementation ameliorated chronic colitis by inhibiting the colonic infiltration of macrophages and promoting its polarization towards M2 phenotype. These results offer new insight into the pathogenesis of UC, emphasizing a potential protective role of creatine for UC.

Diffusion magnetic resonance spectroscopy captures microglial reactivity related to gut-derived systemic lipopolysaccharide: A preliminary study.

Neuroinflammation is a key component underlying multiple neurological disorders, yet non-invasive and cost-effective assessment of in vivo neuroinflammatory processes in the central nervous system remains challenging. Diffusion weighted magnetic resonance spectroscopy (dMRS) has shown promise in addressing these challenges by measuring diffusivity properties of different neurometabolites, which can reflect cell-specific morphologies. Prior work has demonstrated dMRS utility in capturing microglial reactivity in the context of lipopolysaccharide (LPS) challenges and serious neurological disorders, detected as changes of microglial metabolite diffusivity properties. However, the extent to which such dMRS metrics are capable of detecting subtler and more nuanced levels of neuroinflammation in populations without overt neuropathology is unknown. Here we examined the relationship between intrinsic, gut-derived levels of systemic LPS and dMRS-based apparent diffusion coefficients (ADC) of choline, creatine, and N-acetylaspartate (NAA) in two brain regions: the thalamus and the corona radiata. Higher plasma LPS concentrations were significantly associated with increased ADC of choline and NAA in the thalamic region, with no such relationships observed in the corona radiata for any of the metabolites examined. As such, dMRS may have the sensitivity to measure microglial reactivity across populations with highly variable levels of neuroinflammation, and holds promising potential for widespread applications in both research and clinical settings.

Maternal prenatal immune activation associated with brain tissue microstructure and metabolite concentrations in newborn infants.

Few human studies have assessed the association of prenatal maternal immune activation (MIA) with measures of brain development and psychiatric risk in newborn offspring. Our goal was to identify the effects of MIA during the 2nd and 3rd trimesters of pregnancy on newborn measures of brain metabolite concentrations, tissue microstructure, and motor development. This was a prospective longitudinal cohort study conducted with nulliparous pregnant women who were aged 14 to 19 years and recruited in their 2nd trimester, as well as their children who were followed through 14 months of age. MIA was indexed by maternal interleukin-6 (IL-6) and C-reactive protein (CRP) in both trimesters of pregnancy. Primary outcomes included: (1) newborn brain metabolite concentrations as ratios to creatine (N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr) measured using Magnetic Resonance Spectroscopy; (2) newborn fractional anisotropy and mean diffusivity, measured using Diffusion Tensor Imaging; and (3) indices of motor development, assessed prenatally and postnatally at ages 4- and 14-months. Maternal IL-6 and CRP levels associated significantly with both metabolites in the putamen, thalamus, insula, and the internal capsule. Maternal IL-6 associated significantly with fractional anisotropy in the putamen, caudate, thalamus, insula, and precuneus, and with mean diffusivity in the inferior parietal and middle temporal gyrus. CRP associated significantly with fractional anisotropy in the thalamus, insula, and putamen. Significant associations were found in common regions across imaging modalities, though the direction of associations differed by immune marker. In addition, both maternal IL-6 and CRP (in both trimesters) prenatally associated significantly with offspring motor development at 4- and 14-months of age. The left thalamus mediated effects of IL-6 on postnatal motor development. These findings demonstrate that levels of MIA in mid- to late pregnancy in a generally healthy sample associate with tissue characteristics in newborn brain regions that primarily support motor integration and coordination, as well as behavioral regulation. Those brain effects may contribute to differences in motor development.

Pro-atherogenic medical conditions are associated with widespread regional brain metabolite abnormalities in those with alcohol use disorder.

AIMS: Widespread brain metabolite abnormalities in those with alcohol use disorder (AUD) were reported in numerous studies, but the effects of the pro-atherogenic conditions of hypertension, type 2 diabetes mellitus, hepatitis C seropositivity, and hyperlipidemia on metabolite levels were not considered. These conditions were associated with brain metabolite abnormalities in those without AUD. We predicted treatment-seeking individuals with AUD and pro-atherogenic conditions (Atherogenic+) demonstrate lower regional metabolite markers of neuronal viability [N-acetylaspartate (NAA)] and cell membrane turnover/synthesis [choline-containing compounds (Cho)], compared with those with AUD without pro-atherogenic conditions (Atherogenic-) and healthy controls (CON). METHODS: Atherogenic+ (n = 59) and Atherogenic- (n = 51) and CON (n = 49) completed a 1.5 T proton magnetic resonance spectroscopic imaging study. Groups were compared on NAA, Cho, total creatine, and myoinositol in cortical gray matter (GM), white matter (WM), and select subcortical regions. RESULTS: Atherogenic+ had lower frontal GM and temporal WM NAA than CON. Atherogenic+ showed lower parietal GM, frontal, parietal and occipital WM and lenticular nuclei NAA level than Atherogenic- and CON. Atherogenic- showed lower frontal GM and WM NAA than CON. Atherogenic+ had lower Cho level than CON in the frontal GM, parietal WM, and thalamus. Atherogenic+ showed lower frontal WM and cerebellar vermis Cho than Atherogenic- and CON. CONCLUSIONS: Findings suggest proatherogenic conditions in those with AUD were associated with increased compromise of neuronal integrity and cell membrane turnover/synthesis. The greater metabolite abnormalities observed in Atherogenic+ may relate to increased oxidative stress-related compromise of neuronal and glial cell structure and/or impaired arterial vasoreactivity/lumen viability.

Reductions in functional muscle mass and ability to ambulate in Duchenne muscular dystrophy from ages 4 to 24 years.

Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4-25 years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P < 0.0001 and r = 0.764, P < 0.0001 respectively). The age-associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non-ambulant subjects, suggesting a threshold of 18-22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D3Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. KEY POINTS: The non-invasive D3creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non-ambulant patients. The difference in %MM between ambulant and non-ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM. The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability.

Mitigating Traumatic Brain Injury: A Narrative Review of Supplementation and Dietary Protocols.

Traumatic brain injuries (TBIs) constitute a significant public health issue and a major source of disability and death in the United States and worldwide. TBIs are strongly associated with high morbidity and mortality rates, resulting in a host of negative health outcomes and long-term complications and placing a heavy financial burden on healthcare systems. One promising avenue for the prevention and treatment of brain injuries is the design of TBI-specific supplementation and dietary protocols centred around nutraceuticals and biochemical compounds whose mechanisms of action have been shown to interfere with, and potentially alleviate, some of the neurophysiological processes triggered by TBI. For example, evidence suggests that creatine monohydrate and omega-3 fatty acids (DHA and EPA) help decrease inflammation, reduce neural damage and maintain adequate energy supply to the brain following injury. Similarly, melatonin supplementation may improve some of the sleep disturbances often experienced post-TBI. The scope of this narrative review is to summarise the available literature on the neuroprotective effects of selected nutrients in the context of TBI-related outcomes and provide an evidence-based overview of supplementation and dietary protocols that may be considered in individuals affected by-or at high risk for-concussion and more severe head traumas. Prophylactic and/or therapeutic compounds under investigation include creatine monohydrate, omega-3 fatty acids, BCAAs, riboflavin, choline, magnesium, berry anthocyanins, Boswellia serrata, enzogenol, N-Acetylcysteine and melatonin. Results from this analysis are also placed in the context of assessing and addressing important health-related and physiological parameters in the peri-impact period such as premorbid nutrient and metabolic health status, blood glucose regulation and thermoregulation following injury, caffeine consumption and sleep behaviours. As clinical evidence in this research field is rapidly emerging, a comprehensive approach including appropriate nutritional interventions has the potential to mitigate some of the physical, neurological, and emotional damage inflicted by TBIs, promote timely and effective recovery, and inform policymakers in the development of prevention strategies.

Combined Impact of Creatine, Caffeine, and Variable Resistance on Repeated Sprint Ability in Young Soccer Players.

There is evidence that both intra-serial variable resistance (I-sVR), as pre-activation within the post-activation performance enhancement cycle (PAPE), and creatine and caffeine supplementation increase athletic performance in isolation. However, the effect of the three conditioning factors on 30 m repeated sprint ability (RSA) performance in young soccer players is unknown. This study determined the summative and isolation effect of ergogenic aids and pre-activation in half-back squats (HBSs) with I-sVR on performance in an RSA test in young soccer players. Twenty-eight young soccer players were randomly assigned to either EG1 (n = 7, creatine + caffeine + I-sVR), EG2 (n = 7, creatine + placebo2 + I-sVR), EG3 (n = 7, placebo1 + caffeine + I-sVR), or EG4 (n = 7, placebo1 + placebo2 + I-sVR), using a factorial, four-group-matched, double-blind, placebo-controlled design. Creatine supplementation included 0.3 g/kg/day for 14 days, caffeine supplementation included 0.3 mg/kg per day, and pre-activation in HBS with I-sVR (1 × 5 at 30% 1RM [1.0-1.1 m/s] + 1 × 4 at 60% 1RM [0.6-0.7 m/s]). The RSA test and HBS outcomes were evaluated. Three-way ANOVA showed non-significant differences for the RSA test and HBS outcomes (p > 0.05). At the end of this study, it was found that the three ergogenic aids, together, do not generate a summative effect on the physical performance of young soccer players. However, it is important to analyze individual responses to these specific protocols.

Analysis of food supplements and sports foods consumption patterns among a sample of gym-goers in Portugal.

BACKGROUND: Gym-goers usually seek methods to improve performance, muscle gain, and overall health. One of the main strategies is including food supplements (FS) into their routine as aids to enhance their athletic capabilities and satisfy their nutritional needs. Thus, this study aimed to investigate and characterize the main FS and Sports Foods (SF) currently consumed, as well as the main reasons for their use and the source of advice in a group of gym-goers in the Lisbon Metropolitan Area (Portugal). METHODS: A cross-sectional study was conducted, including 303 gym-goers from Lisbon, Portugal, who were 133 women and 170 males (30.8 ± 12.9 years old). Face-to-face interviews were used by qualified researchers to gather data. RESULTS: Most of the interviewed athletes (71.95 %) took FS/SF, being men the main consumers. On average, 1.59 supplements were consumed per athlete. Logistic regression models indicated significant associations between age, gender, and motivations for gym attendance. While men and younger groups attended mainly for hypertrophy, women and older groups were focused on well-being. Protein (59.17 %) was the most used FS/SF, followed by creatine (41.28 %) and multivitamins (27.06 %). Men and younger individuals preferred protein and creatine, while older individuals focused more on specific vitamins and minerals. Women seemed to prefer L-carnitine and protein yogurts. Main sources of information included the internet, friends, and dietitians with notable gender and age-based preferences. Online stores were the main place of purchase. Monthly expenditures on FS/SF were not significantly affected by age or gender, but motivations for use had an influence. CONCLUSION: Most of the athletes interviewed took FS/SF, being men the major consumers. Protein was the principal FS/SF used, with online stores being the main place of purchase and the internet the primary source of information. Age and gender were key factors in adopted training, in the FS/SF chosen, and in the source of information selected. It is crucial that health professionals take primary responsibility for providing this guidance.

Creatine monohydrate use is prospectively associated with muscle dysmorphia symptomatology.

This study aimed to determine the prospective association between creatine monohydrate use and muscle dysmorphia symptomatology among adolescents and young adults in Canada. Data from 912 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors were analyzed. Creatine monohydrate use in the past 12 months was assessed at Wave 1, and muscle dysmorphia symptomatology was measured using the Muscle Dysmorphic Disorder Inventory (MDDI) at Wave 1 and Wave 2. The prospective associations between creatine monohydrate use and the MDDI total score and subscale scores were determined using linear regression analyses. Regression analyses controlled for relevant demographic identifiers, prior substance use, and the corresponding Wave 1 MDDI variable. Creatine monohydrate use at Wave 1 was prospectively associated with both total muscle dysmorphia symptomatology (B 1.34, 95 % CI 0.27, 2.42) and greater Appearance Intolerance (B 0.52, 95 % CI 0.02, 1.03) at Wave 2. Importantly, these findings were independent of prior muscle dysmorphia symptomatology, lifetime anabolic-androgenic steroid use, lifetime cigarette use, and frequency of alcohol use. Creatine monohydrate is commonly used among adolescents and young adults. Findings from this study are among the first to document that creatine monohydrate use may be a risk factor for the development of muscle dysmorphia symptomatology among adolescents and young adults. Health and mental health care professionals may consider assessing for both creatine monohydrate use and muscle dysmorphia symptomatology among adolescents and young adults.

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.

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.

Mitohormesis during advanced stages of Duchenne muscular dystrophy reveals a redox-sensitive creatine pathway that can be enhanced by the mitochondrial-targeting peptide SBT-20.

Mitochondrial creatine kinase (mtCK) regulates the "fast" export of phosphocreatine to support cytoplasmic phosphorylation of ADP to ATP which is more rapid than direct ATP export. Such "creatine-dependent" phosphate shuttling is attenuated in several muscles, including the heart, of the D2.mdx mouse model of Duchenne muscular dystrophy at only 4 weeks of age. However, the degree to which creatine-dependent and -independent systems of phosphate shuttling progressively worsen or potentially adapt in a hormetic manner throughout disease progression remains unknown. Here, we performed a series of proof-of-principle investigations designed to determine how phosphate shuttling pathways worsen or adapt in later disease stages in D2.mdx (12 months of age). We also determined whether changes in creatine-dependent phosphate shuttling are linked to alterations in mtCK thiol redox state. In permeabilized muscle fibres prepared from cardiac left ventricles, we found that 12-month-old male D2.mdx mice have reduced creatine-dependent pyruvate oxidation and elevated complex I-supported H2O2 emission (mH2O2). Surprisingly, creatine-independent ADP-stimulated respiration was increased and mH2O2 was lowered suggesting that impairments in the faster mtCK-mediated phosphocreatine export system resulted in compensation of the alternative slower pathway of ATP export. The apparent impairments in mtCK-dependent bioenergetics occurred independent of mtCK protein content but were related to greater thiol oxidation of mtCK and a more oxidized cellular environment (lower GSH:GSSG). Next, we performed a proof-of-principle study to determine whether creatine-dependent bioenergetics could be enhanced through chronic administration of the mitochondrial-targeting, ROS-lowering tetrapeptide, SBT-20. We found that 12 weeks of daily treatment with SBT-20 (from day 4-∼12 weeks of age) increased respiration and lowered mH2O2 only in the presence of creatine in D2.mdx mice without affecting calcium-induced mitochondrial permeability transition activity. In summary, creatine-dependent mitochondrial bioenergetics are attenuated in older D2.mdx mice in relation to mtCK thiol oxidation that seem to be countered by increased creatine-independent phosphate shuttling as a unique form of mitohormesis. Separate results demonstrate that creatine-dependent bioenergetics can also be enhanced with a ROS-lowering mitochondrial-targeting peptide. These results demonstrate a specific relationship between redox stress and mitochondrial hormetic reprogramming during dystrophin deficiency with proof-of-principle evidence that creatine-dependent bioenergetics could be modified with mitochondrial-targeting small peptide therapeutics.