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Nutrients Mar 2021Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting... (Review)
Review
Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting 70-80% lower endogenous creatine stores compared to males. Understanding creatine metabolism pre- and post-menopause yields important implications for creatine supplementation for performance and health among females. Due to the hormone-related changes to creatine kinetics and phosphocreatine resynthesis, supplementation may be particularly important during menses, pregnancy, post-partum, during and post-menopause. Creatine supplementation among pre-menopausal females appears to be effective for improving strength and exercise performance. Post-menopausal females may also experience benefits in skeletal muscle size and function when consuming high doses of creatine (0.3 g·kg·d); and favorable effects on bone when combined with resistance training. Pre-clinical and clinical evidence indicates positive effects from creatine supplementation on mood and cognition, possibly by restoring brain energy levels and homeostasis. Creatine supplementation may be even more effective for females by supporting a pro-energetic environment in the brain. The purpose of this review was to highlight the use of creatine in females across the lifespan with particular emphasis on performance, body composition, mood, and dosing strategies.
Topics: Adult; Affect; Aged; Body Composition; Brain; Creatine; Dietary Supplements; Exercise; Female; Humans; Longevity; Menopause; Middle Aged; Muscle, Skeletal; Phosphocreatine; Resistance Training; Women's Health
PubMed: 33800439
DOI: 10.3390/nu13030877 -
Biomolecules Aug 2019Depressed mood, which can occur in the context of major depressive disorder, bipolar disorder, and other conditions, represents a serious threat to public health and... (Review)
Review
Depressed mood, which can occur in the context of major depressive disorder, bipolar disorder, and other conditions, represents a serious threat to public health and wellness. Conventional treatments are not effective for a significant proportion of patients and interventions that are often beneficial for treatment-refractory depression are not widely available. There is, therefore, an immense need to identify novel antidepressant strategies, particularly strategies that target physiological pathways that are distinct from those addressed by conventional treatments. There is growing evidence from human neuroimaging, genetics, epidemiology, and animal studies that disruptions in brain energy production, storage, and utilization are implicated in the development and maintenance of depression. Creatine, a widely available nutritional supplement, has the potential to improve these disruptions in some patients, and early clinical trials indicate that it may have efficacy as an antidepressant agent.
Topics: Animals; Bipolar Disorder; Brain; Clinical Studies as Topic; Creatine; Depressive Disorder, Major; Energy Metabolism; Humans; Nutritional Support; Phosphocreatine
PubMed: 31450809
DOI: 10.3390/biom9090406 -
Journal of the International Society of... Dec 2023Creatine supplementation is an effective ergogenic aid to augment resistance training and improve intense, short duration, intermittent performance. The effects on... (Review)
Review
Creatine supplementation is an effective ergogenic aid to augment resistance training and improve intense, short duration, intermittent performance. The effects on endurance performance are less known. The purpose of this brief narrative review is to discuss the potential mechanisms of how creatine can affect endurance performance, defined as large muscle mass activities that are cyclical in nature and are >~3 min in duration, and to highlight specific nuances within the literature. Mechanistically, creatine supplementation elevates skeletal muscle phosphocreatine (PCr) stores facilitating a greater capacity to rapidly resynthesize ATP and buffer hydrogen ion accumulation. When co-ingested with carbohydrates, creatine enhances glycogen resynthesis and content, an important fuel to support high-intensity aerobic exercise. In addition, creatine lowers inflammation and oxidative stress and has the potential to increase mitochondrial biogenesis. In contrast, creatine supplementation increases body mass, which may offset the potential positive effects, particularly in weight-bearing activities. Overall, creatine supplementation increases time to exhaustion during high-intensity endurance activities, likely due to increasing anaerobic work capacity. In terms of time trial performances, results are mixed; however, creatine supplementation appears to be more effective at improving performances that require multiple surges in intensity and/or during end spurts, which are often key race-defining moments. Given creatines ability to enhance anaerobic work capacity and performance through repeated surges in intensity, creatine supplementation may be beneficial for sports, such as cross-country skiing, mountain biking, cycling, triathlon, and for short-duration events where end-spurts are critical for performance, such as rowing, kayaking, and track cycling.
Topics: Humans; Creatine; Physical Endurance; Dietary Supplements; Phosphocreatine; Muscle, Skeletal; Glycogen
PubMed: 37096381
DOI: 10.1080/15502783.2023.2204071 -
Circulation Nov 2021Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular...
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM.
METHODS
We performed a comprehensive multiomics profile of the molecular (transcripts, metabolites, and complex lipids), ultrastructural, and functional components of HCM energetics using myocardial samples from 27 HCM patients and 13 normal controls (donor hearts).
RESULTS
Integrated omics analysis revealed alterations in a wide array of biochemical pathways with major dysregulation in fatty acid metabolism, reduction of acylcarnitines, and accumulation of free fatty acids. HCM hearts showed evidence of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and phosphocreatine) and a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Accompanying these metabolic derangements, electron microscopy showed an increased fraction of severely damaged mitochondria with reduced cristae density, coinciding with reduced citrate synthase activity and mitochondrial oxidative respiration. These mitochondrial abnormalities were associated with elevated reactive oxygen species and reduced antioxidant defenses. However, despite significant mitochondrial injury, HCM hearts failed to upregulate mitophagic clearance.
CONCLUSIONS
Overall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM. These results highlight potential new drug targets for attenuation of the clinical disease through improving metabolic function and reducing mitochondrial injury.
Topics: Adult; Aged; Cardiomyopathy, Hypertrophic; Cell Respiration; Computational Biology; Disease Management; Disease Susceptibility; Energy Metabolism; Female; Gene Expression Profiling; Heart Function Tests; Humans; Lipidomics; Male; Metabolome; Metabolomics; Middle Aged; Mitochondria; Mutation; Oxidative Stress; Reactive Oxygen Species; Transcriptome
PubMed: 34672721
DOI: 10.1161/CIRCULATIONAHA.121.053575 -
Nutrients Apr 2021Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will... (Review)
Review
Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in the normal heart, and it is generally safe. In heart failure, creatine and phosphocreatine decrease because of decreased expression of the creatine transporter, and because phosphocreatine degrades to prevent adenosine triphosphate (ATP) exhaustion. This causes decreased contractility reserve of the myocardium and correlates with left ventricular ejection fraction, and it is a predictor of mortality. Thus, there is a strong rationale to supplement with creatine the failing heart. Pending additional trials, creatine supplementation in heart failure may be useful given data showing its effectiveness (1) against specific parameters of heart failure, and (2) against the decrease in muscle strength and endurance of heart failure patients. In heart ischemia, the majority of trials used phosphocreatine, whose mechanism of action is mostly unrelated to changes in the ergogenic creatine-phosphocreatine system. Nevertheless, preliminary data with creatine supplementation are encouraging, and warrant additional studies. Prevention of cardiac toxicity of the chemotherapy compounds anthracyclines is a novel field where creatine supplementation may also be useful. Creatine effectiveness in this case may be because anthracyclines reduce expression of the creatine transporter, and because of the pleiotropic antioxidant properties of creatine. Moreover, creatine may also reduce concomitant muscle damage by anthracyclines.
Topics: Animals; Anthracyclines; Cardiovascular Diseases; Creatine; Dietary Supplements; Disease Models, Animal; Heart; Humans
PubMed: 33917009
DOI: 10.3390/nu13041215 -
International Journal of Environmental... Apr 2020Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore,...
BACKGROUND
Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore, vegetarians have reduced creatine stores and may benefit from supplementation.
OBJECTIVE
to determine the effects of creatine supplementation on vegetarians.
DATA SOURCES
PubMed and SPORTDiscus. Eligibility criteria: Randomized controlled trials (parallel group, cross-over studies) or prospective studies.
PARTICIPANTS
Vegetarians.
INTERVENTION
Creatine supplementation. Study appraisal and synthesis: A total of 64 records were identified, and eleven full-text articles (covering nine studies) were included in this systematic review.
RESULTS
Creatine supplementation in vegetarians increased total creatine, creatine, and phosphocreatine concentrations in vastus lateralis and gastrocnemius muscle, plasma, and red blood cells, often to levels greater than omnivores. Creatine supplementation had no effect on brain levels of phosphocreatine. Creatine supplementation increased lean tissue mass, type II fiber area, insulin-like growth factor-1, muscular strength, muscular endurance, Wingate mean power output, and brain function (memory and intelligence) in vegetarian participants. Studies were mixed on whether creatine supplementation improved exercise performance in vegetarians to a greater extent compared to omnivores.
LIMITATIONS
Studies that were reviewed had moderate-high risk of bias.
CONCLUSIONS
Overall, it appears vegetarian athletes are likely to benefit from creatine supplementation.
Topics: Athletes; Cognition; Creatine; Diet, Vegetarian; Dietary Supplements; Humans; Memory; Physical Fitness; Prospective Studies; Vegetarians
PubMed: 32349356
DOI: 10.3390/ijerph17093041 -
Experimental Physiology Dec 2021What is the topic of this review? The nutritional strategies that athletes use during competition events to optimize performance and the reasons they use them. What... (Review)
Review
NEW FINDINGS
What is the topic of this review? The nutritional strategies that athletes use during competition events to optimize performance and the reasons they use them. What advances does it highlight? A range of nutritional strategies can be used by competitive athletes, alone or in combination, to address various event-specific factors that constrain event performance. Evidence for such practices is constantly evolving but must be combined with understanding of the complexities of real-life sport for optimal implementation.
ABSTRACT
High-performance athletes share a common goal despite the unique nature of their sport: to pace or manage their performance to achieve the highest sustainable outputs over the duration of the event. Periodic or sustained decline in the optimal performance of event tasks, involves an interplay between central and peripheral phenomena that can often be reduced or delayed in onset by nutritional strategies. Contemporary nutrition practices undertaken before, during or between events include strategies to ensure the availability of limited muscle fuel stores. This includes creatine supplementation to increase muscle phosphocreatine content and consideration of the type, amount and timing of dietary carbohydrate intake to optimize muscle and liver glycogen stores or to provide additional exogenous substrate. Although there is interest in ketogenic low-carbohydrate high-fat diets and exogenous ketone supplements to provide alternative fuels to spare muscle carbohydrate use, present evidence suggests a limited utility of these strategies. Mouth sensing of a range of food tastants (e.g., carbohydrate, quinine, menthol, caffeine, fluid, acetic acid) may provide a central nervous system derived boost to sports performance. Finally, despite decades of research on hypohydration and exercise capacity, there is still contention around their effect on sports performance and the best guidance around hydration for sporting events. A unifying model proposes that some scenarios require personalized fluid plans while others might be managed by an ad hoc approach (ad libitum or thirst-driven drinking) to fluid intake.
Topics: Athletes; Athletic Performance; Dietary Carbohydrates; Dietary Supplements; Energy Metabolism; Humans; Nutritional Status
PubMed: 34762329
DOI: 10.1113/EP088188 -
Circulation. Heart Failure Jun 2022Defects in energetics are thought to be central to the pathophysiology of hypertrophic cardiomyopathy (HCM); yet, the determinants of ATP availability are not known. The...
BACKGROUND
Defects in energetics are thought to be central to the pathophysiology of hypertrophic cardiomyopathy (HCM); yet, the determinants of ATP availability are not known. The purpose of this study is to ascertain the nature and extent of metabolic reprogramming in human HCM, and its potential impact on contractile function.
METHODS
We conducted proteomic and targeted, quantitative metabolomic analyses on heart tissue from patients with HCM and from nonfailing control human hearts.
RESULTS
In the proteomic analysis, the greatest differences observed in HCM samples compared with controls were increased abundances of extracellular matrix and intermediate filament proteins and decreased abundances of muscle creatine kinase and mitochondrial proteins involved in fatty acid oxidation. These differences in protein abundance were coupled with marked reductions in acyl carnitines, byproducts of fatty acid oxidation, in HCM samples. Conversely, the ketone body 3-hydroxybutyrate, branched chain amino acids, and their breakdown products, were all significantly increased in HCM hearts. ATP content, phosphocreatine, nicotinamide adenine dinucleotide and its phosphate derivatives, NADP and NADPH, and acetyl CoA were also severely reduced in HCM compared with control hearts. Functional assays performed on human skinned myocardial fibers demonstrated that the magnitude of observed reduction in ATP content in the HCM samples would be expected to decrease the rate of cross-bridge detachment. Moreover, left atrial size, an indicator of diastolic compliance, was inversely correlated with ATP content in hearts from patients with HCM.
CONCLUSIONS
HCM hearts display profound deficits in nucleotide availability with markedly reduced capacity for fatty acid oxidation and increases in ketone bodies and branched chain amino acids. These results have important therapeutic implications for the future design of metabolic modulators to treat HCM.
Topics: Adenosine Triphosphate; Amino Acids, Branched-Chain; Cardiomyopathy, Hypertrophic; Fatty Acids; Heart Failure; Humans; Metabolome; Myocytes, Cardiac; Proteome; Proteomics
PubMed: 35543134
DOI: 10.1161/CIRCHEARTFAILURE.121.009521 -
Nature May 2021Adaptive thermogenesis has attracted much attention because of its ability to increase systemic energy expenditure and to counter obesity and diabetes. Recent data have...
Adaptive thermogenesis has attracted much attention because of its ability to increase systemic energy expenditure and to counter obesity and diabetes. Recent data have indicated that thermogenic fat cells use creatine to stimulate futile substrate cycling, dissipating chemical energy as heat. This model was based on the super-stoichiometric relationship between the amount of creatine added to mitochondria and the quantity of oxygen consumed. Here we provide direct evidence for the molecular basis of this futile creatine cycling activity in mice. Thermogenic fat cells have robust phosphocreatine phosphatase activity, which is attributed to tissue-nonspecific alkaline phosphatase (TNAP). TNAP hydrolyses phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation. Unlike in other cells, TNAP in thermogenic fat cells is localized to the mitochondria, where futile creatine cycling occurs. TNAP expression is powerfully induced when mice are exposed to cold conditions, and its inhibition in isolated mitochondria leads to a loss of futile creatine cycling. In addition, genetic ablation of TNAP in adipocytes reduces whole-body energy expenditure and leads to rapid-onset obesity in mice, with no change in movement or feeding behaviour. These data illustrate the critical role of TNAP as a phosphocreatine phosphatase in the futile creatine cycle.
Topics: Adipocytes; Adipose Tissue, Brown; Alkaline Phosphatase; Animals; Cold Temperature; Energy Metabolism; Hydrolysis; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Mitochondria; Mitochondrial Proteins; Obesity; Phosphocreatine; Thermogenesis
PubMed: 33981039
DOI: 10.1038/s41586-021-03533-z