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Individual Responses to Creatine Supplementation on Muscular Power is Modulated by Gene Polymorphisms in Military Recruits
Abstract
PurposeThe aim was to explore five established SNPs (rs1815739, rs1805086, rs2700352, rs28497577, and rs28357094) that are known to modulate skeletal muscle protein kinetics in response to creatine supplementation.MethodsA randomized, placebo-controlled, repeated measures design was used. Participants (n = 152) were randomized divided into one of two groups: CREA (20 g/day creatine monohydrate) or PLAC: (dextrose) for 7 days. SNP were assessed, and participants were classified accordingly. Before and after supplementation, anthropometrics (height and body mass) and performance measures (vertical jump, countermovement vertical jump, squat jump, abdominal crunches, and maximum push-ups) were assessed.ResultsCREA gained more body mass than PLAC (CREA: ∆0.864 ± 0.06 kg; PLAC: ∆0.154 ± 0.07 kg, P < 0.001). In the CREA group, the presence of an A allele for the MYLK1 polymorphism was related to changes in countermovement jump height (P = 0.027; effect size [d] = 0.41) and leg power (P = 0.040, effect size [d] = 0.18). The total number of abdominal crunches after supplementation was influenced by treatments and SPP1 gene (P = 0.041). A higher number of abdominal crunches was associated with the G allele in the CREA group and the TT genotype in the PLAC group (effect size [d] = 0.04).Conclusion
Collectively, short-term creatine supplementation increased body mass but was unable to alter muscle performance. However, following creatine supplementation, participants expressing A alleles in the MYLK1 polymorphism had a greater increase in jump height and leg power and participants expressing G alleles in the SPP1 gene had greater improvements in abdominal crunch performance.
... While strong evidence is available in support of the ergogenic benefits of creatine for a variety of active populations and across a wide array of physical performance parameters, less information is available regarding the benefits of creatine supplementation for occupational performance in firefighters. Specifically, mixed results have been reported regarding the ergogenic benefits of creatine in tactical populations [9,12,13,27]. While some studies have reported improvements in select measures of performance (including performance of occupation-specific tasks) [9,12], others have reported null findings [13,27]. ...
... Specifically, mixed results have been reported regarding the ergogenic benefits of creatine in tactical populations [9,12,13,27]. While some studies have reported improvements in select measures of performance (including performance of occupation-specific tasks) [9,12], others have reported null findings [13,27]. Because of the anaerobic nature of firefighter-specific tasks [5,6,28,29], it is plausible that creatine supplementation could confer ergogenic benefits both when used in isolation and when added to a fitness program. ...
Background:
The purpose of this study was to assess the effects of protein and carbohydrate supplementation, with and without creatine, on occupational performance in firefighters.
Methods:
Using a randomized, double-blind approach, thirty male firefighters (age: 34.4 ± 8.4 yrs., height: 1.82 ± 0.07 m; weight: 88.6 ± 12.5 kg; BF%: 17.2 ± 5.8%) were randomized to receive either (A.) 25 g of whey protein isolate + 25 g of carbohydrate powder (ProCarb group); or (B.) ProCarb + 5 g of creatine (Creatine group) in a double-blind fashion over a period of 21-26 days (depending on shift rotations) to evaluate the impact of supplementation on occupation-specific performance. At baseline and following supplementation, firefighters completed a battery of tests. These tests included an aerobic speed test on an air-braked cycle ergometer followed by the hose carry, body drag, stair climb, and Keiser sled hammer for time.
Results:
No significant differences in measures of performance were observed at baseline (p > 0.05). There was a significant main effect for time observed for rescue, stair climb, total time to completion, and time trial performance (p < 0.05). There was a significant group × time (p < 0.05) interaction for rescue and forcible entry. Independent sample t-tests indicated that the Creatine group experienced a greater reduction (from baseline) in completion time for the rescue (1.78 ± 0.57 s, 95% CI: 0.61, 2.95 s, p = 0.004) and forcible entry (2.66 ± 0.97 s, 95% CI: 0.68, 4.65 s, p = 0.01) tests compared to the ProCarb group. No significant group × time interactions were observed for the hose line advance, stair climb, total time to completion, and time trial performance (p > 0.05).
Conclusions:
The addition of supplemental creatine to a protein and carbohydrate supplement to the diet of career firefighters throughout a three week period improves occupational performance in firefighters in specific areas of high-intensity, repetitive actions.
... Creatine, α-methyl guandino-acetic acid, is a wellknown ergogenic aid used by exercising individuals [11][12][13][14]. Creatine was first isolated and extracted from meat in 1832 by a French philosopher and scientist, Michel Eugene Chevreul. ...
Aging is associated with numerous physiological, musculoskeletal, and neurological impairments including a loss of muscle, strength, function, bone mineral, and cognition. Strength training is an effective intervention to counter these age-associated declines. In addition, creatine supplementation is purported to enhance strength training gains in lean tissue mass, muscular strength, and function. There is emerging evidence that creatine combined with strength training can alter bone geometry and cognitive performance. The purpose of this review is to update previous meta-analyses examining creatine combined with strength training on lean tissue mass and bone density compared to strength training and placebo. A secondary purpose was to explore the effects of creatine and strength training on cognition. Updated meta-analyses revealed that creatine enhances lean tissue mass (mean difference [MD]: 1.18 kg, 95 % CI: 0.70–1.67; p<0.00001) and upper body muscular strength (standard mean difference [SMD]: 0.24, 95 % CI: 0.05–0.43; p=0.02) compared to strength training and placebo. Creatine combined with strength training had no greater effects compared to strength training and placebo on lower body muscular strength (SMD: 0.17, 95 % CI: −0.03–0.38; p=0.09), whole-body (MD: −0.00 g cm⁻²; 95 % CI: −0.01–0.00, p=0.32), femoral neck (MD: −0.00 g cm⁻²; 95 % CI: −0.01–0.00, p=1.00), or lumbar bone mineral density (MD: 0.00 g cm⁻², 95 % CI: −0.01–0.01; p=045). There is preliminary evidence that combining strength training and creatine is an effective strategy to improve bone geometry in postmenopausal females and cognitive function in older adults. Overall, the combination of creatine and strength training has favorable effects on lean tissue mass and upper body strength. In contrast, creatine combined with strength training does not enhance lower-body strength or bone mineral.
... Factors such as genetic variations, baseline creatine levels, training status, and diet may contribute to these individual differences [42]. Future research should aim to identify biomarkers or genetic markers that can help predict an individual's response to creatine supplementation [43]. ...
This review paper investigates the relationship between creatine supplementation and the Akt/mTOR pathway, focusing on their impact on muscle performance. The Akt/mTOR pathway is a crucial signaling pathway that regulates muscle protein synthesis and hypertrophy in response to growth factors, nutrients, and mechanical stimuli. Recent evidence suggests that creatine supplementation can influence anabolic signaling pathways, including the phosphorylation of p70S6K, a downstream target of mTOR, leading to enhanced activation of the Akt/mTOR pathway. Additionally, creatine supplementation has been shown to increase intramuscular creatine and phosphocreatine levels, improving ATP availability during exercise and enhancing high-intensity muscle contractions. Understanding the complex regulatory mechanisms of the Akt/mTOR pathway is vital for optimizing muscle performance, as dysregulated signaling can hinder muscle protein synthesis and hypertrophic responses. This review highlights the potential of creatine supplementation to modulate the Akt/mTOR pathway, offering insights into its mechanisms and implications for muscle performance enhancement. By unraveling this connection, researchers and practitioners can develop targeted strategies to maximize muscle performance and promote adaptive responses in various exercise and athletic contexts.
... Failing to meet these demands can result in fatigue, cognitive dysfunction, weight loss, Creatine is a popular ergogenic aid among athletes, known for enhancing performance and promoting exercise adaptations. It is particularly beneficial for short-duration, highintensity exercises [66][67][68][69][70]. The International Society of Sports Nutrition (ISSN) suggests that healthy individuals can use creatine supplements safely, and recent evidence refutes the notion that they could lead to dehydration or muscle cramping [71,72]. ...
Background:
More than 270 million participants and 128,893 professional players play soccer. Although UEFA recommendations for nutrition in elite football exist, implementing these guidelines among professional and semiprofessional soccer players remains suboptimal, emphasizing the need for targeted and individualized nutritional strategies to improve adherence to established recommendations.
Methods:
We conducted a comprehensive search in PubMed, Scopus, Web of Science, and clinical trial registers. Inclusion criteria focused on professional or semiprofessional soccer players, nutrition or diet interventions, performance improvement outcomes, and randomized clinical trial study types. We assessed quality using the Risk of Bias 2 (RoB 2) tool. We identified 16 eligible articles involving 310 participants. No nutritional interventions during the recovery period effectively improved recovery. However, several performance-based interventions showed positive effects, such as tart cherry supplementation, raw pistachio nut kernels, bicarbonate and mineral ingestion, creatine supplementation, betaine consumption, symbiotic supplements, and a high-carbohydrate diet. These interventions influenced various aspects of soccer performance, including endurance, speed, agility, strength, power, explosiveness, and anaerobic capacity.
Conclusions:
Specific strategies, such as solutions with bicarbonate and minerals, high carbohydrate diets, and supplements like creatine, betaine, and tart cherry, can enhance the performance of professional soccer players. These targeted nutritional interventions may help optimize performance and provide the competitive edge required in professional soccer. We did not find any dietary interventions that could enhance recovery.
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 crosscountry skiing, mountain biking, cycling, triathlon, and for short-duration events where end-spurts are critical for performance , such as rowing, kayaking, and track cycling. ARTICLE HISTORY
Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose–response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms.
Creatine is one of the most studied and popular ergogenic aids for athletes and recreational weightlifters seeking to improve sport and exercise performance, augment exercise training adaptations, and mitigate recovery time. Studies consistently reveal that creatine supplementation exerts positive ergogenic effects on single and multiple bouts of short-duration, high-intensity exercise activities, in addition to potentiating exercise training adaptations. In this respect, supplementation consistently demonstrates the ability to enlarge the pool of intracellular creatine, leading to an amplification of the cell’s ability to resynthesize adenosine triphosphate. This intracellular expansion is associated with several performance outcomes, including increases in maximal strength (low-speed strength), maximal work output, power production (high-speed strength), sprint performance, and fat-free mass. Additionally, creatine supplementation may speed up recovery time between bouts of intense exercise by mitigating muscle damage and promoting the faster recovery of lost force-production potential. Conversely, contradictory findings exist in the literature regarding the potential ergogenic benefits of creatine during intermittent and continuous endurance-type exercise, as well as in those athletic tasks where an increase in body mass may hinder enhanced performance. The purpose of this review was to summarize the existing literature surrounding the efficacy of creatine supplementation on exercise and sports performance, along with recovery factors in healthy populations.
Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this review was to (1) perform updated meta-analyses comparing creatine vs. placebo (independent of dosage and frequency of ingestion) during a resistance training program on measures of lean tissue mass and strength, (2) perform meta-analyses examining the effects of different creatine dosing strategies (lower: ≤5 g/day and higher: >5 g/day), with and without a creatine-loading phase (≥20 g/day for 5–7 days), and (3) perform meta-analyses determining whether creatine supplementation only on resistance training days influences measures of lean tissue mass and strength. Overall, creatine (independent of dosing strategy) augments lean tissue mass and strength increase from RT vs. placebo. Subanalyses showed that creatine-loading followed by lower-dose creatine (≤5 g/day) increased chest press strength vs. placebo. Higher-dose creatine (>5 g/day), with and without a creatine-loading phase, produced significant gains in leg press strength vs. placebo. However, when studies involving a creatine-loading phase were excluded from the analyses, creatine had no greater effect on chest press or leg press strength vs. placebo. Finally, creatine supplementation only on resistance training days significantly increased measures of lean tissue mass and strength vs. placebo.
Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl−-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4−]2− and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3−]−. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.
Sarcopenia, defined as age-related reduction in muscle mass, strength, and physical performance, is associated with other age-related health conditions such as osteoporosis, osteosarcopenia, sarcopenic obesity, physical frailty, and cachexia. From a healthy aging perspective, lifestyle interventions that may help overcome characteristics and associated comorbidities of sarcopenia are clinically important. One possible intervention is creatine supplementation (CR). Accumulating research over the past few decades shows that CR, primarily when combined with resistance training (RT), has favourable effects on aging muscle, bone and fat mass, muscle and bone strength, and tasks of physical performance in healthy older adults. However, research is very limited regarding the efficacy of CR in older adults with sarcopenia or osteoporosis and no research exists in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia. Therefore, the purpose of this narrative review is (1) to evaluate and summarize current research involving CR, with and without RT, on properties of muscle and bone in older adults and (2) to provide a rationale and justification for future research involving CR in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia.
Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine ‘loading-phase’ required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.
Aging is associated with reductions in muscle and bone mass and brain function, which may be counteracted by several lifestyle factors, of which exercise appears to be most beneficial. However, less than 20% of older adults (> 55 years of age) adhere to performing the recommended amount of resistance training (≥ 2 days/week) and less than 12% regularly meet the aerobic exercise guidelines (≥ 150 min/week of moderate to vigorous intensity aerobic exercise) required to achieve significant health benefits. Therefore, from a healthy aging and clinical perspective, it is important to determine whether other lifestyle interventions (independent of exercise) can have beneficial effects on aging muscle quality and quantity, bone strength, and brain function. Creatine, a nitrogen containing organic compound found in all cells of the body, has the potential to have favorable effects on muscle, bone, and brain health (independent of exercise) in older adults. The purpose of this narrative review is to examine and summarize the small body of research investigating the effects of creatine supplementation alone on measures of muscle mass and performance, bone mineral and strength, and indices of brain health in older adults.
Background: Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive muscle disorder characterized by heterogeneous progression and severity. We aimed to study the effects of single nucleotide polymorphisms (SNPs) in SPP1 and LTBP4 on DMD progression in Chinese patients.
Methods: We genotyped LTBP4 haplotypes and the SPP1 promoter SNPs rs28357094, rs11730582, and rs17524488 in 326 patients registered in the neuromuscular database of The First Affiliated Hospital of Sun Yat-sen University. Kaplan-Meier curves and log-rank tests were used to estimate and compare median age at loss of ambulation, while Cox proportional hazard regression models were used as to analyze the effects of glucocorticoids treatments, DMD genotype, and SPP1/LTBP4 SNPs on loss of ambulation.
Results: The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (p = 0.006), with hazard ratio 0.63 (p = 0.008), in patients with truncated DMD genotype and undergoing steroid treatment. On the other hand, rs17524488 in SPP1 and the IAAM/IAAM haplotype in LTBP4 were not associated with time to ambulation loss.
Conclusions: SPP1 rs11730582 is a genetic modifier of the long-term effects of steroid treatment in Chinese DMD patients. Thus, any future clinical study in DMD should adjust for glucocorticoids use, DMD genotype, and SPP1 polymorphisms.
Objective
Respiratory insufficiency is a major complication of Duchenne muscular dystrophy (DMD). Its progression shows considerable interindividual variability, which has been less thoroughly characterized and understood than in skeletal muscle. We collected pulmonary function testing (PFT) data from a large retrospective cohort followed at Centers collaborating in the Italian DMD Network. Furthermore, we analyzed PFT associations with different DMD mutation types, and with genetic variants in SPP1, LTBP4, CD40, and ACTN3, known to modify skeletal muscle weakness in DMD. Genetic association findings were independently validated in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG‐DNHS).
Methods and Results
Generalized estimating equation analysis of 1852 PFTs from 327 Italian DMD patients, over an average follow‐up time of 4.5 years, estimated that forced vital capacity (FVC) declined yearly by −4.2%, forced expiratory volume in 1 sec by −5.0%, and peak expiratory flow (PEF) by −2.9%. Glucocorticoid (GC) treatment was associated with higher values of all PFT measures (approximately + 15% across disease stages). Mutations situated 3’ of DMD intron 44, thus predicted to alter the expression of short dystrophin isoforms, were associated with lower (approximately −6%) PFT values, a finding independently validated in the CINRG‐DNHS. Deletions amenable to skipping of exon 51 and 53 were independently associated with worse PFT outcomes. A meta‐analysis of the two cohorts identified detrimental effects of SPP1 rs28357094 and CD40 rs1883832 minor alleles on both FVC and PEF.
Interpretation
These findings support GC efficacy in delaying respiratory insufficiency, and will be useful for the design and interpretation of clinical trials focused on respiratory endpoints in DMD.
Adaptation to exercise training is a complex trait that may be influenced by genetic variants. We identified 36 single nucleotide polymorphisms (SNPs) that had been previously associated with endurance or strength performance, exercise-related phenotypes or exercise intolerant disorders. A MassARRAY multiplex genotyping assay was designed to identify associations with these SNPs against collected endurance fitness phenotype parameters obtained from two exercise cohorts (Gene SMART study; n = 58 and Hawaiian Ironman Triathlon 2008; n = 115). These parameters included peak power output (PP), a time trial (TT), lactate threshold (LT), maximal oxygen uptake (VO2 max) in recreationally active individuals and a triathlon time-to-completion (Hawaiian Ironman Triathlon cohort only). A nominal significance threshold of α < 0.05 was used to identify 17 variants (11 in the Gene SMART population and six in the Hawaiian Ironman Triathlon cohort) which were significantly associated with performance gains in highly trained individuals. The variant rs1474347 located in Interleukin 6 (IL6) was the only variant with a false discovery rate < 0.05 and was found to be associated with gains in VO2 max (additional 4.016 mL/(kg min) for each G allele inherited) after training in the Gene SMART cohort. In summary, this study found further evidence to suggest that genetic variance can influence training response in a moderately trained cohort and provides an example of the potential application of genomic research in the assessment of exercise trait response.
Sarcopenia is an age-related muscle condition characterized by a reduction in muscle quantity, force generating capacity and physical performance. Sarcopenia occurs in 8–13% of adults ≥ 60 years of age and can lead to disability, frailty, and various other diseases. Over the past few decades, several leading research groups have focused their efforts on developing strategies and recommendations for attenuating sarcopenia. One potential nutritional intervention for sarcopenia is creatine supplementation. However, research is inconsistent regarding the effectiveness of creatine on aging muscle. The purpose of this perspective paper is to: (1) propose possible reasons for the inconsistent responsiveness to creatine in aging adults, (2) discuss the potential mechanistic actions of creatine on muscle biology, (3) determine whether the timing of creatine supplementation influences aging muscle, (4) evaluate the evidence investigating the effects of creatine with other compounds (protein, conjugated linoleic acid) in aging adults, and (5) provide insight regarding the safety of creatine for aging adults.
Sarcopenia, defined as the age-related decrease in muscle mass, strength and physical performance, is associated with reduced bone mass and elevated low-grade inflammation. From a healthy aging perspective, interventions which overcome sarcopenia are clinically relevant. Accumulating evidence suggests that exogenous creatine supplementation has the potential to increase aging muscle mass, muscle performance, and decrease the risk of falls and possibly attenuate inflammation and loss of bone mineral. Therefore, the purpose of this review is to: (1) summarize the effects of creatine supplementation, with and without resistance training, in aging adults and discuss possible mechanisms of action, (2) examine the effects of creatine on bone biology and risk of falls, (3) evaluate the potential anti-inflammatory effects of creatine and (4) determine the safety of creatine supplementation in aging adults.
Introduction: Osteopontin (OPN) polymorphisms are associated with muscle size and modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized that OPN may share a molecular network with myostatin (MSTN). Methods: Studies were conducted in the golden retriever (GRMD) and mdx mouse models of DMD. Follow-up in-vitro studies were employed in myogenic cells and the mdx mouse treated with recombinant mouse (rm) or human (Hu) OPN protein. Results: OPN was increased and MSTN was decreased and levels correlated inversely in GRMD hypertrophied muscle. RM-OPN treatment led to induced AKT1 and FoxO1 phosphorylation, microRNA-486 modulation, and decreased MSTN. An AKT1 inhibitor blocked these effects, whereas an RGD-mutant OPN protein and an RGDS blocking peptide showed similar effects to the AKT inhibitor. RMOPN induced myotube hypertrophy and minimal Feret diameter in mdx muscle. Discussion: OPN may interact with AKT1/MSTN/FoxO1 to modify normal and dystrophic muscle. Muscle Nerve 56: 1119–1127, 2017. © 2017 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.
The loss of muscle mass and strength with aging results in significant functional impairment. Creatine supplementation has been used in combination with resistance training as a strategy for increasing lean tissue mass and muscle strength in older adults, but results across studies are equivocal. We conducted a systematic review and meta-analysis of randomized controlled trials of creatine supplementation during resistance training in older adults with lean tissue mass, chest press strength, and leg press strength as outcomes by searching PubMed and SPORTDiscus databases. Twenty-two studies were included in our meta-analysis with 721 participants (both men and women; with a mean age of 57–70 years across studies) randomized to creatine supplementation or placebo during resistance training 2–3 days/week for 7–52 weeks. Creatine supplementation resulted in greater increases in lean tissue mass (mean difference =1.37 kg [95% CI =0.97–1.76]; p<0.00001), chest press strength (standardized mean difference [SMD] =0.35 [0.16–0.53]; p=0.0002), and leg press strength (SMD =0.24 [0.05–0.43]; p=0.01). A number of mechanisms exist by which creatine may increase lean tissue mass and muscular strength. These are included in a narrative review in the discussion section of this article. In summary, creatine supplementation increases lean tissue mass and upper and lower body muscular strength during resistance training of older adults, but potential mechanisms by which creatine exerts these positive effects have yet to be evaluated extensively.
Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson’s, Huntington’s disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).
Purpose
Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A).
Methods
Using Williams and Folland’s model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK <400 U·L⁻¹) vs. marathoners with a high CK response (n = 31; serum CK ≥400 U·L⁻¹).
Results
At the end of the race, low CK responders had lower serum CK (290±65 vs. 733±405 U·L⁻¹; P<0.01) and myoglobin concentrations (443±328 vs. 1009±971 ng·mL⁻¹, P<0.01) than high CK responders. Although the groups were similar in age, anthropometric characteristics, running experience and training habits, total genotype score was higher in low CK responders than in high CK responders (5.2±1.4 vs. 4.4±1.7 point, P = 0.02).
Conclusion
Marathoners with a lower CK response after the race had a more favorable polygenic profile than runners with high serum CK concentrations. This might suggest a significant role of genetic polymorphisms in the levels of exertional muscle damage and rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.
Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrated macrophages and developmental myosin heavy chain–positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy.
Recent studies demonstrated an association between the K153R polymorphism in the myostatin gene with extreme longevity, lower muscle strength and obesity but the molecular basis of these associations has not been clarified. Here, we show that the K153R mutation significantly increases the rate of proteolysis of promyostatin by furin, but has no effect on the activity of the latent complex or the cleavage of the latent complex by bone morphogenetic protein 1 (BMP-1). The increased rate of activation of K153R mutant promyostatin may explain why this polymorphism is associated with obesity, lower muscle strength and extension of lifespan.
Resistance exercise can result in localized damage to muscle tissue. This damage may be observed in sarcolemma, basal lamina, as well as, in the contractile elements and the cytoskeleton. Usually the damage is accompanied by release of enzymes such as creatine kinase (CK) and lactate dehydrogenase, myoglobin and other proteins into the blood. Serum CK has been proposed as one of the best indirect indicators of muscle damage due to its ease of identification and the relatively low cost of assays to quantify it. Thus, CK has been used as an indicator of the training intensity and a diagnostic marker of overtraining. However, some issues complicate CK's use in this manner. There is great interindividual variability in serum CK, which complicates the assignment of reliable reference values for athletes. Furthermore, factors such as training level, muscle groups involved, and gender can influence CK levels to a greater extent than differences in exercise volume completed. This review will detail the process by which resistance exercise induces a rise in circulating CK, illuminate the various factors that affect the CK response to resistance exercise, and discuss the relative usefulness of CK as a marker of training status, in light of these factors.
Myostatin is a catabolic regulator of skeletal muscle mass. The purpose of this study was to determine the effect of resistance training for 8 weeks in conjunction with creatine supplementation on muscle strength, lean body mass, and serum levels of myostatin and growth and differentiation factor-associated serum protein-1 (GASP-1). In a double-blinded design 27 healthy male subjects (23.42+/-2.2 years) were assigned to control (CON), resistance training+placebo (RT+PL) and resistance training+creatine supplementation (RT+CR) groups. The protocol consisted of 3 days per week of training for 8 weeks, each session including three sets of 8-10 repetitions at 60-70% of 1 RM for whole-body exercise. Blood sampling, muscular strength testing and body composition analysis (full body DEXA) were performed at 0, 4th and 8th weeks. Myostatin and GASP-1 was measured. Resistance training caused significant decrease in serum levels of myostatin and increase in that of GASP-1. Creatine supplementation in conjunction with resistance training lead to greater decreases in serum myostatin (p<0.05), but had not additional effect on GASP-1 (p>0.05). The effects of resistance training on serum levels of myostatin and GASP-1, may explain the increased muscle mass that is amplified by creatine supplementation.
Introdução: A avaliação da força explosiva de membros inferiores através do Jump Test é prática comum no futebol. No entanto, a diversidade de metodologias empregadas para este fim pode conduzir a diferentes resultados. Este estudo objetivou comparar o desempenho do salto vertical obtido simultaneamente por duas diferentes metodologias (Delta entre traçados) e cálculo da altura a partir do tempo de vôo obtido por um Foot Switch. Materiais e Métodos: 14 atletas de futebol (17±1 anos) realizaram testes de contração isométrica voluntária máxima de extensão de joelho e Jump Test, sendo a altura do salto mensurada pelo método clássico (diferença entre traçados em uma parede) e com um Foot Switch. Para comparação entre o desempenho do Jump Test obtido pelos dois métodos utilizou-se o teste �t� de Student e para correlação entre os dados de pico de força isométrico e o pico de potência de membros inferiores utilizou-se a correlação de Pearson. Resultados: A altura do salto obtida pelo método de Delta entre traçados mostrou-se maior do que a altura pelo Foot Switch (p<0,05), havendo o mesmo resultado para a potência de membros inferiores. A medida da potência de membros inferiores mensurado pelo Foot Switch demonstrou melhores coeficientes de correlação com a medida do pico de força de extensão de joelho dos membros dominante (r2=0,67) e não dominante (r2=0,68). Discussão: Os resultados fornecidos pelos testes de força explosiva realizados de forma clássica (Delta entre traçados) tendem a superestimar os valores quando comparados à avaliação utilizando análises do tempo de vôo.
Strenuous exercise results in damage to skeletal muscle that is manifested in delayed muscle pain, prolonged strength loss, and increases in muscle proteins in the blood, especially creatine kinase (CK) and myoglobin (Mb). Some individuals experience profound changes in these variables in response to standard laboratory exercise or recreational activities. We proposed that variations in genes coding for two myofibrillar proteins [alpha-actinin 3 (ACTN3) and myosin light chain kinase (MLCK)] may explain the large variability in the response to muscle-damaging exercise. We hypothesized that subjects with specific single nucleotide polymorphisms (SNPs) in ACTN3 and MLCK would show a greater loss in muscle strength and/or a greater increase in blood CK and Mb in response to eccentric exercise. Blood from 157 subjects who performed a standard elbow flexion eccentric exercise protocol was tested for association between genotypes of ACTN3 (1 SNP tested: R577X) and MLCK (2 SNPs tested: C49T and C37885A) and changes in blood CK and Mb and isometric strength. Subjects possessing the ACTN3-deficient genotype (XX) had lower baseline CK compared with the heterozygotes (P = 0.035). After the eccentric exercise, those subjects homozygous for the MLCK 49T rare allele had a significantly greater increase in CK and Mb (P < 0.01) compared with the heterozygotes, and those heterozygous for MLCK C37885A had a significantly greater increase in CK compared with the homozygous wild type (P < 0.05). There was only one subject homozygous for the rare MLCK 37885A allele. MLCK C37885A was also associated with postexercise strength loss (P < 0.05); the heterozygotes demonstrated greater strength loss compared with the homozygous wild type (CC). These results show that variations in genes coding for specific myofibrillar proteins influence phenotypic responses to muscle damaging exercise.
There is increasing evidence for strong genetic influences on athletic performance and for an evolutionary "trade-off" between performance traits for speed and endurance activities. We have recently demonstrated that the skeletal-muscle actin-binding protein alpha-actinin-3 is absent in 18% of healthy white individuals because of homozygosity for a common stop-codon polymorphism in the ACTN3 gene, R577X. alpha-Actinin-3 is specifically expressed in fast-twitch myofibers responsible for generating force at high velocity. The absence of a disease phenotype secondary to alpha-actinin-3 deficiency is likely due to compensation by the homologous protein, alpha-actinin-2. However, the high degree of evolutionary conservation of ACTN3 suggests function(s) independent of ACTN2. Here, we demonstrate highly significant associations between ACTN3 genotype and athletic performance. Both male and female elite sprint athletes have significantly higher frequencies of the 577R allele than do controls. This suggests that the presence of alpha-actinin-3 has a beneficial effect on the function of skeletal muscle in generating forceful contractions at high velocity, and provides an evolutionary advantage because of increased sprint performance. There is also a genotype effect in female sprint and endurance athletes, with higher than expected numbers of 577RX heterozygotes among sprint athletes and lower than expected numbers among endurance athletes. The lack of a similar effect in males suggests that the ACTN3 genotype affects athletic performance differently in males and females. The differential effects in sprint and endurance athletes suggests that the R577X polymorphism may have been maintained in the human population by balancing natural selection.
Creatine enhances resistance training adaptations and may alter ratings of perceived exertion (RPE). Planned load reduction training (10% reduction in load per set) lowered RPE compared to traditional fixed load resistance training (3 sets at a constant load) with similar muscle adaptations. The purpose was to examine the effects of creatine on performance and RPE during both traditional fixed and planned load reduction training compared to placebo. Forty resistance trained males were randomly assigned to either creatine (20 g•day-1) or placebo for 7 days. Following the loading phase, all participants completed 3 resistance training protocols (3 sets of bench press and smith machine squats) in random order; a constant load (CON), 5% load reduction each set (RED 5), and a 10% load reduction each set (RED 10). Total repetitions and RPE were recorded each set. Creatine supplementation increased bench press repetitions with no significant difference in RPE compared to placebo. There were no other differences between supplements or protocols. Creatine supplementation was able to augment bench press performance compared to placebo without increasing RPE. Creatine did not differentially influence fixed compared to planned load reduction training nor was it able to enhance lower body squat total repetitions. Introduction Resistance training is well known to enhance muscular strength and muscle size over time 1. Combining resistance training and creatine monohydrate, a nitrogen-containing compound found in red meat and seafood 2 , has shown promise for augmenting training volume, muscle mass and strength gains (for reviews see 3-6). Ninety-five percent of creatine is stored in skeletal muscle while the remainder is found in brain, liver, kidneys, and testes 2. Within the muscle, ~two-thirds is stored as phosphocreatine (PCr), the remaining one-third is unbound free creatine 2, 7, 8. Creatine monohydrate supplementation can increase PCr and total creatine content (~20%) enhancing the capacity for ATP re-synthesis during sustained intense muscular work or may enhance PCr recovery between working sets 9, 10 , leading to a greater training volume 11, 12 or enhanced muscular performance 8 .
Creatine, a very popular supplement among athletic populations, is of growing interest for clinical applications. Since over 90% of creatine is stored in skeletal muscle, the effect of creatine supplementation on muscle metabolism is a widely studied area. While numerous studies over the past few decades have shown that creatine supplementation has many favorable effects on skeletal muscle physiology and metabolism, including enhancing muscle mass (growth/hypertrophy); the underlying mechanisms are poorly understood. This report reviews studies addressing the mechanisms of action of creatine supplementation on skeletal muscle growth/hypertrophy. Early research proposed that the osmotic effect of creatine supplementation serves as a cellular stressor (osmosensing) that acts as an anabolic stimulus for protein synthesis signal pathways. Other reports indicated that creatine directly affects muscle protein synthesis via modulations of components in the mammalian target of rapamycin (mTOR) pathway. Creatine may also directly affect the myogenic process (formation of muscle tissue), by altering secretions of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors, resulting in enhanced satellite cells mitotic activities and differentiation into myofiber. Overall, there is still no clear understanding of the mechanisms of action regarding how creatine affects muscle mass/growth, but current evidence suggests it may exert its effects through multiple approaches, with converging impacts on protein synthesis and myogenesis.
Sarcopenia refers to the progressive loss of muscle mass and muscle function and is a contributing factor for cachexia, bone loss, and frailty. Resistance training produces several physiological adaptations which improve aging musculoskeletal health, such as increased muscle and bone mass and strength. The combination of creatine supplementation and resistance training may further lead to greater physiological benefits. We performed meta-analyses which indicate creatine supplementation combined with resistance training has a positive effect on aging muscle mass and upper body strength compared to resistance training alone. Creatine also shows promise for improving bone mineral density and indices of bone biology. The combination of creatine supplementation and resistance training could be an effective intervention to improve aging musculoskeletal health.
Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.
There is compelling evidence that genetic factors influence several phenotype traits related to physical performance and training response as well as to elite athletic status. Previous case-control studies showed that ∼20 genetic variants seem to be associated with elite endurance athletic status. The present review aims to introduce novel methodological approaches in the field of sports genetics research, which can be applied in the near future to analyse the genotype profile associated with elite athletic status. These include genotype-phenotype association studies using gene expression analysis, analysis of post-transcriptional factors, particularly microRNAs, genome-wide scan linkage or genome-wide association studies, and novel algorithm approaches, such as 'genotype scores'. Several gaps in the current body of knowledge have been identified including, among others: small sample size of most athletic cohorts, lack of corroboration with replication cohorts of different ethnic backgrounds (particularly, made up of non-Caucasian athletes), the need of research accounting for the potential role of epigenetics in elite athletic performance, and also the need for future models that take into account the association between athletic status and complex gene-gene and gene-environment interactions. Some recommendations are provided to minimize research limitations in the field of sport genetics.
1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated.
2. Low doses (1 g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5 g resulted in a mean peak after 1 h of 795 (sd 104) μmol/l in three subjects weighing 76–87 kg. Repeated dosing with 5 g every 2 h sustained the plasma concentration at around 1000 μmol/l. A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak.
3. Supplementation with 5 g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%.
4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 × 5 g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content.
5. No side effects of creatine supplementation were noted.
6. One hour of hard exercise per day using one leg augmented the increase in the total creatine content of the exercised leg, but had no effect in the collateral. In these subjects the mean total creatine content increased from 118.1 (sd 3.0) mmol/kg dry muscle before supplementation to 148.5 (sd 5.2) in the control leg, and to 162.2 (sd 12.5) in the exercised leg. Supplementation and exercise resulted in a total creatine content in one subject of 182.8 mmol/kg dry muscle, of which 112.0 mmol/kg dry muscle was in the form of phosphocreatine.
The original Physical Activity Readiness Questionnaire (PAR-Q) offers a safe preliminary screening of candidates for exercise testing and prescription, but it screens out what seems an excessive proportion of apparently healthy older adults. To reduce unnecessary exclusions, an expert committee established by Fitness Canada has now revised the questionnaire wording. The present study compares responses to the original and the revised PAR-Q questionnaire in 399 men and women attending 40 accredited fitness testing centres across Canada. The number of subjects screened out by the revised test decreased significantly (p < .05), from 68 to 48 of the 399 subjects. The change reflects in part the inclusion of individuals who had made an erroneous positive response to the original question regarding high blood pressure. There is no simple gold standard to provide an objective evaluation of the sensitivity and specificity of either questionnaire format, but the revised wording has apparently had the intended effect of reducing positive responses, particularly to the question regarding an elevation of blood pressure.
The effect of dietary creatine and supplementation on skeletal muscle creatine accumulation and subsequent degradation and on urinary creatinine excretion was investigated in 31 male subjects who ingested creatine in different quantities over varying time periods. Muscle total creatine concentration increased by approximately 20% after 6 days of creatine supplementation at a rate of 20 g/day. This elevated concentration was maintained when supplementation was continued at a rate of 2 g/day for a further 30 days. In the absence of 2 g/day supplementation, total creatine concentration gradually declined, such that 30 days after the cessation of supplementation the concentration was no different from the presupplementation value. During this period, urinary creatinine excretion was correspondingly increased. A similar, but more gradual, 20% increase in muscle total creatine concentration was observed over a period of 28 days when supplementation was undertaken at a rate of 3 g/day. In conclusion, a rapid way to "creatine load" human skeletal muscle is to ingest 20 g of creatine for 6 days. This elevated tissue concentration can then be maintained by ingestion of 2 g/day thereafter. The ingestion of 3 g creatine/day is in the long term likely to be as effective at raising tissue levels as this higher dose.
This study investigated the effect of carbohydrate (CHO) ingestion on skeletal muscle creatine (Cr) accumulation during Cr supplementation in humans. Muscle biopsy, urine, and plasma samples were obtained from 24 males before and after ingesting 5 g Cr in solution (group A) or 5 g Cr followed, 30 min later, by 93 g simple CHO in solution (group B) four times each day for 5 days. Supplementation resulted in an increase in muscle phosphocreatine (PCr), Cr, and total creatine (TCr; sum of PCr and Cr) concentration in groups A and B, but the increase in TCr in group B was 60% greater than in group A (P < 0.01). There was also a corresponding decrease in urinary Cr excretion in group B (P < 0.001). Creatine supplementation had no effect on serum insulin concentration, but Cr and CHO ingestion dramatically elevated insulin concentration (P < 0.001). These findings demonstrate that CHO ingestion substantially augments muscle Cr accumulation during Cr feeding in humans, which appears to be insulin mediated.
The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology. Very recently, a series of new discoveries have been made that are bound to have distinguished implications for bioenergetics, physiology, human pathology, and clinical diagnosis and that suggest that deregulation of the creatine kinase (CK) system is associated with a variety of diseases. Disturbances of the CK system have been observed in muscle, brain, cardiac, and renal diseases as well as in cancer. On the other hand, Cr and Cr analogs such as cyclocreatine were found to have antitumor, antiviral, and antidiabetic effects and to protect tissues from hypoxic, ischemic, neurodegenerative, or muscle damage. Oral Cr ingestion is used in sports as an ergogenic aid, and some data suggest that Cr and creatinine may be precursors of food mutagens and uremic toxins. These findings are discussed in depth, the interrelationships are outlined, and all is put into a broader context to provide a more detailed understanding of the biological functions of Cr and of the CK system.
The purpose of this study was to describe the physiological profile of responders (>20 mmol.kg(-1) dry weight [dw] increase in total intramuscular creatine monohydrate [Cr] + phosphorylated creatine [PCr]) versus nonresponders (<10 mmol.kg(-1) dw increase) to a 5-day Cr load (0.3 g.kg(-1).d(-1)) in 11 healthy men (mean age = 22.7 years). Pre-post 5-day cellular measures included total resting Cr content (Cr + PCr), fiber type composition, and fiber type cross-sectional area (CSA) determined from muscle biopsies of the vastus lateralis. Body mass, daily dietary intake, 24-hour urine outputs, urinary Cr and creatinine (CrN), and strength performance measures (1 repetition maximum [1RM] bench and leg press) were also assessed before and after the 5-day loading period. Results indicated that there were 3 levels of response to the 5-day supplementation: responders (R), quasi responders (QR), and nonresponders (NR) with mean changes in resting Cr + PCr of 29.5 mmol.kg(-1) dw (n = 3), 14.9 mmol.kg(-1) dw (n = 5), and 5.1 mmol.kg(-1) dw (n = 3), respectively. The results support a person-by-treatment interaction to acute Cr supplementation with R possessing a biological profile of lowest initial levels of Cr + PCr, greatest percentage of type II fibers, and greatest preload muscle fiber CSA and fat-free mass. Responders also showed improvement in 1RM leg press scores following the 5-day loading period. NR had higher preload levels of Cr + PCr, less type II muscle fibers, small preload muscle CSA, and lower fat-free mass and displayed no improvements in 1RM strength scores. The results suggest that to be considered a responder to acute oral supplementation, a favorable preexisting biological profile may determine the final extent to which an individual responds to supplementation. Physiologic profiles of nonresponders appear to be different and may limit their ability to uptake Cr. This may help partially explain the reported equivocal performance findings in the Cr supplementation literature.
Much of the vast diversity we see in animals and people is governed by genetic loci that have quantitative effects of phenotype (quantitative trait loci; QTLs). Here we review the current knowledge of the genetics of atrophy and hypertrophy in both animal husbandry (meat quantity and quality), and humans (muscle size and performance). The selective breeding of animals for meat has apparently led to a few genetic loci with strong effects, with different loci in different animals. In humans, muscle quantitative trait loci (QTLs) appear to be more complex, with few "major" loci identified to date, although this is likely to change in the near future. We describe how the same phenotypic traits we see as positive, greater lean muscle mass in cattle or a better exercise results in humans, can also have negative "side effects" given specific environmental challenges. We also discuss the strength and limitations of single nucleotide polymorphisms (SNP) association studies; what the reader should look for and expect in a published study. Lastly we discuss the ethical and societal implications of this genetic information. As more and more research into the genetic loci that dictate phenotypic traits become available, the ethical implications of testing for these loci become increasingly important. As a society, most accept testing for genetic diseases or susceptibility, but do we as easily accept testing to determine one's athletic potential to be an Olympic endurance runner, or quarterback on the high school football team.
Creatine kinase: an enzyme with a central role in cellular energy metabolism
- T Wallimann
- M Dolder
- U Schlattner
- M Eder
- T Hornemann
- T Kraft
- M Stolz
Wallimann T, Dolder M, Schlattner U, Eder M, Hornemann T,
Kraft T, Stolz M. Creatine kinase: an enzyme with a central role
in cellular energy metabolism. MAGMA. 1998;6(2-3):116-9.
https:// doi. org/ 10. 1007/ BF026 60927./.