Creatine

The power of creatine plus resistance training for healthy aging: enhancing physical vitality and cognitive function

Diego A. Bonilla, Jeffrey R. Stout, Darren G. Candow +7 more · Frontiers in Physiology · 2024 · 12 citations

This meta-analysis of 15 randomised controlled trials found that combining creatine supplementation (typically 5 g/day) with resistance training for 8–52 weeks improves lean body mass, upper and lower body strength, and functional performance in adults aged 50+ — with small but measurable benefits for cognitive function, particularly in older adults already experiencing age-related decline.

The effect of protein timing on muscle strength and hypertrophy: a meta-analysis

Brad J. Schöenfeld, Alan A. Aragon, JAMES KRIEGER · Journal of the International Society of Sports Nutrition · 2013 · 193 citations

Consuming protein specifically around your workout (before, during, or immediately after) does not meaningfully increase muscle growth or strength gains compared to eating the same total amount of protein spread across the day — total daily protein intake is what matters most.

Effectiveness of Creatine in Metabolic Performance: A Systematic Review and Meta-Analysis.

Jaramillo AP, Jaramillo L, Castells J +6 more · Cureus · 2023 · 5 citations

This meta-analysis of 10 randomised controlled trials found that creatine monohydrate supplementation (typically 20 g/day for 5–7 days loading, then 3–5 g/day maintenance) significantly improved metabolic performance markers — specifically increased anaerobic power output by ~8% and reduced blood lactate accumulation during high-intensity exercise — but the effects were small-to-moderate and highly dependent on baseline fitness, dosing protocol, and the specific metabolic test used.

Effect of Inorganic Nitrate on Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Payman Zamani, Deepa Rawat, Prithvi Shiva‐Kumar +10 more · Circulation · 2014 · 303 citations

Background— Inorganic nitrate (NO 3 − ), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO 3 − supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise. Methods and Results— Seventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO 3 -rich beetroot juice (NO 3 − , 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak o 2 , total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 μmol/L; P =0.0003), peak o 2 (12.6±3.7 versus 11.6±3.1 mL O 2 ·min −1 ·kg −1 ; P =0.005), and total work performed (55.6±35.3 versus 49.2±28.9 kJ; P =0.04). However, efficiency was unchanged. NO 3 − led to greater reductions in systemic vascular resistance (−42.4±16.6% versus −31.8±20.3%; P =0.03) and increases in cardiac output (121.2±59.9% versus 88.7±53.3%; P =0.006) with exercise. NO 3 − reduced aortic augmentation index (132.2±16.7% versus 141.4±21.9%; P =0.03) and tended to improve mitochondrial oxidative function. Conclusions— NO 3 − increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and o 2. NO 3 − increased exercise vasodilatory and cardiac output reserves. NO 3 − also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling. Clinical Trial Registration— URL: www.clinicaltrials.gov . Unique identifier: NCT01919177.

Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial

Denise Zdzieblik, Steffen Oesser, Manfred W. Baumstark +2 more · British Journal Of Nutrition · 2015 · 261 citations

Adding 15g of collagen peptides daily to a 12-week resistance training programme led to significantly greater gains in fat-free mass (+1.3 kg extra) and muscle strength (+9.2 Nm extra), and greater fat loss (-1.9 kg extra) compared to resistance training alone in elderly men with sarcopenia.

A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: A randomized controlled trial

Kirsten E. Bell, Tim Snijders, Michael A. Zulyniak +4 more · PLoS ONE · 2017 · 110 citations

Protein and other compounds can exert anabolic effects on skeletal muscle, particularly in conjunction with exercise. The objective of this study was to evaluate the efficacy of twice daily consumption of a protein-based, multi-ingredient nutritional supplement to increase strength and lean mass independent of, and in combination with, exercise in healthy older men. Forty-nine healthy older men (age: 73 ± 1 years [mean ± SEM]; BMI: 28.5 ± 1.5 kg/m2) were randomly allocated to 20 weeks of twice daily consumption of either a nutritional supplement (SUPP; n = 25; 30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg calcium, and 1500 mg n-3 PUFA with 700 mg as eicosapentanoic acid and 445 mg as docosahexanoic acid); or a control (n = 24; CON; 22 g of maltodextrin). The study had two phases. Phase 1 was 6 weeks of SUPP or CON alone. Phase 2 was a 12 week continuation of the SUPP/CON but in combination with exercise: SUPP + EX or CON + EX. Isotonic strength (one repetition maximum [1RM]) and lean body mass (LBM) were the primary outcomes. In Phase 1 only the SUPP group gained strength (Σ1RM, SUPP: +14 ± 4 kg, CON: +3 ± 2 kg, P < 0.001) and lean mass (LBM, +1.2 ± 0.3 kg, CON: -0.1 ± 0.2 kg, P < 0.001). Although both groups gained strength during Phase 2, upon completion of the study upper body strength was greater in the SUPP group compared to the CON group (Σ upper body 1RM: 119 ± 4 vs. 109 ± 5 kg, P = 0.039). We conclude that twice daily consumption of a multi-ingredient nutritional supplement increased muscle strength and lean mass in older men. Increases in strength were enhanced further with exercise training. TRIAL REGISTRATION: ClinicalTrials.gov NCT02281331.

The Human Urine Metabolome

Souhaila Bouatra, Farid Aziat, Rupasri Mandal +16 more · PLoS ONE · 2013 · 1,423 citations

Urine has long been a "favored" biofluid among metabolomics researchers. It is sterile, easy-to-obtain in large volumes, largely free from interfering proteins or lipids and chemically complex. However, this chemical complexity has also made urine a particularly difficult substrate to fully understand. As a biological waste material, urine typically contains metabolic breakdown products from a wide range of foods, drinks, drugs, environmental contaminants, endogenous waste metabolites and bacterial by-products. Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine. This involved both computer-aided literature mining and comprehensive, quantitative experimental assessment/validation. The experimental portion employed NMR spectroscopy, gas chromatography mass spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) experiments performed on multiple human urine samples. This multi-platform metabolomic analysis allowed us to identify 445 and quantify 378 unique urine metabolites or metabolite species. The different analytical platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85) by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our use of multiple metabolomics platforms and technologies allowed us to identify several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage. It also allowed us to critically assess the relative strengths and weaknesses of different platforms or technologies. The literature review led to the identification and annotation of another 2206 urinary compounds and was used to help guide the subsequent experimental studies. An online database containing the complete set of 2651 confirmed human urine metabolite species, their structures (3079 in total), concentrations, related literature references and links to their known disease associations are freely available at http://www.urinemetabolome.ca.

IOC consensus statement: dietary supplements and the high-performance athlete

Ronald J. Maughan, Louise M. Burke, Jiří Dvořák +22 more · British Journal of Sports Medicine · 2018 · 933 citations

Nutrition usually makes a small but potentially valuable contribution to successful performance in elite athletes, and dietary supplements can make a minor contribution to this nutrition program. Nonetheless, supplement use is widespread at all levels of sport. Products described as supplements target different issues, including the management of micronutrient deficiencies, supply of convenient forms of energy and macronutrients, and provision of direct benefits to performance or indirect benefits such as supporting intense training regimens. The appropriate use of some supplements can offer benefits to the athlete, but others may be harmful to the athlete's health, performance, and/or livelihood and reputation if an anti-doping rule violation results. A complete nutritional assessment should be undertaken before decisions regarding supplement use are made. Supplements claiming to directly or indirectly enhance performance are typically the largest group of products marketed to athletes, but only a few (including caffeine, creatine, specific buffering agents and nitrate) have good evidence of benefits. However, responses are affected by the scenario of use and may vary widely between individuals because of factors that include genetics, the microbiome, and habitual diet. Supplements intended to enhance performance should be thoroughly trialed in training or simulated competition before implementation in competition. Inadvertent ingestion of substances prohibited under the anti-doping codes that govern elite sport is a known risk of taking some supplements. Protection of the athlete's health and awareness of the potential for harm must be paramount, and expert professional opinion and assistance is strongly advised before embarking on supplement use.

A phase I/IItrial of MYO‐029 in adult subjects with muscular dystrophy

Kathryn R. Wagner, James L. Fleckenstein, Anthony A. Amato +21 more · Annals of Neurology · 2008 · 462 citations

OBJECTIVE: Myostatin is an endogenous negative regulator of muscle growth and a novel target for muscle diseases. We conducted a safety trial of a neutralizing antibody to myostatin, MYO-029, in adult muscular dystrophies (Becker muscular dystrophy, facioscapulohumeral dystrophy, and limb-girdle muscular dystrophy). METHODS: This double-blind, placebo-controlled, multinational, randomized study included 116 subjects divided into sequential dose-escalation cohorts, each receiving MYO-029 or placebo (Cohort 1 at 1 mg/kg; Cohort 2 at 3 mg/kg; Cohort 3 at 10 mg/kg; Cohort 4 at 30 mg/kg). Safety and adverse events were assessed by reported signs and symptoms, as well as by physical examinations, laboratory results, echocardiograms, electrocardiograms, and in subjects with facioscapulohumeral dystrophy, funduscopic and audiometry examinations. Biological activity of MYO-029 was assessed through manual muscle testing, quantitative muscle testing, timed function tests, subject-reported outcomes, magnetic resonance imaging studies, dual-energy radiographic absorptiometry studies, and muscle biopsy. RESULTS: MYO-029 had good safety and tolerability with the exception of cutaneous hypersensitivity at the 10 and 30 mg/kg doses. There were no improvements noted in exploratory end points of muscle strength or function, but the study was not powered to look for efficacy. Importantly, bioactivity of MYO-029 was supported by a trend in a limited number of subjects toward increased muscle size using dual-energy radiographic absorptiometry and muscle histology. INTERPRETATION: This trial supports the hypothesis that systemic administration of myostatin inhibitors provides an adequate safety margin for clinical studies. Further evaluation of more potent myostatin inhibitors for stimulating muscle growth in muscular dystrophy should be considered.

Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease

Daniel Forton, Howard C. Thomas, Christine Murphy +5 more · Hepatology · 2002 · 447 citations

Patients with chronic hepatitis C virus (HCV) infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. Several studies have shown that patients exhibit low quality-of-life scores that are independent of disease severity. We therefore considered whether HCV infection has a direct effect on the central nervous system, resulting in cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV were tested with a computer-based cognitive assessment battery and also completed depression, fatigue, and quality-of-life questionnaires. The HCV-infected patients were impaired on more cognitive tasks than the HCV-cleared group (mean [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P =.02). A factor analysis showed impairments in power of concentration and speed of working memory, independent of a history of intravenous drug usage (IVDU), depression, fatigue, or symptom severity. A subgroup of 17 HCV-infected patients also underwent cerebral proton magnetic resonance spectroscopy (1H MRS). The choline/creatine ratio was elevated in the basal ganglia and white matter in this group. Patients who were impaired on 2 or more tasks in the battery had a higher mean choline/creatine ratio compared with the unimpaired patients. In conclusion, these preliminary results demonstrate cognitive impairment that is unaccounted for by depression, fatigue, or a history of IVDU in patients with histologically mild HCV infection. The findings on MRS suggest that a biological cause underlies this abnormality.

Does oral creatine supplementation improve strength? A meta-analysis.

Rania L. Dempsey, Michael Mazzone, Linda N. Meurer · PubMed · 2002 · 48 citations

Creatine supplementation combined with resistance training increases the maximum weight you can lift for bench press by about 6.9 kg and for squats by about 9.8 kg, but only in young men under 36 — there is no evidence it helps older adults, women, or improves other types of strength like sprint cycling or torque on a machine.

The Effects of Normal as Compared with Low Hematocrit Values in Patients with Cardiac Disease Who Are Receiving Hemodialysis and Epoetin

Anatole Besarab, W. Kline Bolton, Jeffrey K. Browne +5 more · New England Journal of Medicine · 1998 · 1,926 citations

In this randomized, prospective, open-label trial, we studied 1233 patients with congestive heart failure or ischemic heart disease who were undergoing hemodialysis at 51 centers (see the Appendix). The institutional review boards at all centers approved the protocol, and all the patients gave written, informed consent. All the patients had end-stage renal disease and were undergoing longterm hemodialysis, and they had hematocrit values of 27 to 33 percent while receiving epoetin during the four weeks before enrollment. Ninety percent of the patients received epoetin intrave-

Can Creatine Supplementation Improve Body Composition and Objective Physical Function in Rheumatoid Arthritis Patients? A Randomized Controlled Trial

Thomas J. Wilkinson, Andrew Lemmey, Jeremy G. Jones +5 more · Arthritis Care & Research · 2015 · 54 citations

OBJECTIVE: Rheumatoid cachexia (muscle wasting) in rheumatoid arthritis (RA) patients contributes to substantial reductions in strength and impaired physical function. The objective of this randomized controlled trial was to investigate the effectiveness of oral creatine (Cr) supplementation in increasing lean mass and improving strength and physical function in RA patients. METHODS: In a double-blind design, 40 RA patients were randomized to either 12 weeks' supplementation of Cr or placebo. Body composition (dual x-ray absorptiometry and bioelectrical impedance spectroscopy [BIS]), strength, and objectively assessed physical function were measured at baseline, day 6, week 12, and week 24. Data analysis was performed by analysis of covariance. RESULTS: Cr supplementation increased appendicular lean mass (ALM; a surrogate measure of muscle mass) by mean ± SE 0.52 ± 0.13 kg (P = 0.004 versus placebo), and total LM by 0.60 ± 0.37 kg (P = 0.158). The change in LM concurred with the gain in intracellular water (0.64 ± 0.22 liters; P = 0.035) measured by BIS. Despite increasing ALM, Cr supplementation, relative to placebo, failed to improve isometric knee extensor strength (P = 0.408), handgrip strength (P = 0.833), or objectively assessed physical function (P = 0.335-0.764). CONCLUSION: In patients with RA, Cr supplementation increased muscle mass, but not strength or objective physical function. No treatment-related adverse effects were reported, suggesting that Cr supplementation may offer a safe and acceptable adjunct treatment for attenuating muscle loss; this treatment may be beneficial for patients experiencing severe rheumatoid cachexia.

The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level

Wiley Barton, Nicholas Penney, Owen Cronin +6 more · Gut · 2017 · 610 citations

OBJECTIVE: It is evident that the gut microbiota and factors that influence its composition and activity effect human metabolic, immunological and developmental processes. We previously reported that extreme physical activity with associated dietary adaptations, such as that pursued by professional athletes, is associated with changes in faecal microbial diversity and composition relative to that of individuals with a more sedentary lifestyle. Here we address the impact of these factors on the functionality/metabolic activity of the microbiota which reveals even greater separation between exercise and a more sedentary state. DESIGN: Metabolic phenotyping and functional metagenomic analysis of the gut microbiome of professional international rugby union players (n=40) and controls (n=46) was carried out and results were correlated with lifestyle parameters and clinical measurements (eg, dietary habit and serum creatine kinase, respectively). RESULTS: Athletes had relative increases in pathways (eg, amino acid and antibiotic biosynthesis and carbohydrate metabolism) and faecal metabolites (eg, microbial produced short-chain fatty acids (SCFAs) acetate, propionate and butyrate) associated with enhanced muscle turnover (fitness) and overall health when compared with control groups. CONCLUSIONS: Differences in faecal microbiota between athletes and sedentary controls show even greater separation at the metagenomic and metabolomic than at compositional levels and provide added insight into the diet-exercise-gut microbiota paradigm.

Creatine-Kinase- and Exercise-Related Muscle Damage Implications for Muscle Performance and Recovery

Marianne Baird, Scott M. Graham, Julien S. Baker +1 more · Journal of Nutrition and Metabolism · 2012 · 727 citations

The appearance of creatine kinase (CK) in blood has been generally considered to be an indirect marker of muscle damage, particularly for diagnosis of medical conditions such as myocardial infarction, muscular dystrophy, and cerebral diseases. However, there is controversy in the literature concerning its validity in reflecting muscle damage as a consequence of level and intensity of physical exercise. Nonmodifiable factors, for example, ethnicity, age, and gender, can also affect enzyme tissue activity and subsequent CK serum levels. The extent of effect suggests that acceptable upper limits of normal CK levels may need to be reset to recognise the impact of these factors. There is a need for standardisation of protocols and stronger guidelines which would facilitate greater scientific integrity. The purpose of this paper is to examine current evidence and opinion relating to the release of CK from skeletal muscle in response to physical activity and examine if elevated concentrations are a health concern.

ESPEN guideline clinical nutrition in neurology

R. Burgos, Irene Bretón, Emanuele Cereda +13 more · Clinical Nutrition · 2017 · 518 citations

IOC Consensus Statement: Dietary Supplements and the High-Performance Athlete

Ronald J. Maughan, Louise M. Burke, Jiří Dvořák +22 more · International Journal of Sport Nutrition and Exercise Metabolism · 2018 · 506 citations

Nutrition usually makes a small but potentially valuable contribution to successful performance in elite athletes, and dietary supplements can make a minor contribution to this nutrition program. Nonetheless, supplement use is widespread at all levels of sport. Products described as supplements target different issues, including the management of micronutrient deficiencies, supply of convenient forms of energy and macronutrients, and provision of direct benefits to performance or indirect benefits such as supporting intense training regimens. The appropriate use of some supplements can offer benefits to the athlete, but others may be harmful to the athlete’s health, performance, and/or livelihood and reputation if an anti-doping rule violation results. A complete nutritional assessment should be undertaken before decisions regarding supplement use are made. Supplements claiming to directly or indirectly enhance performance are typically the largest group of products marketed to athletes, but only a few (including caffeine, creatine, specific buffering agents and nitrate) have good evidence of benefits. However, responses are affected by the scenario of use and may vary widely between individuals because of factors that include genetics, the microbiome, and habitual diet. Supplements intended to enhance performance should be thoroughly trialed in training or simulated competition before implementation in competition. Inadvertent ingestion of substances prohibited under the anti-doping codes that govern elite sport is a known risk of taking some supplements. Protection of the athlete’s health and awareness of the potential for harm must be paramount, and expert professional opinion and assistance is strongly advised before embarking on supplement use.

MECHANISMS OF MUSCULAR ADAPTATIONS TO CREATINE SUPPLEMENTATION

Eric S. Rawson, Adam M. Persky · International sportmed journal for FIMS · 2007 · 40 citations

Creatine supplementation is a widely used and heavily studied ergogenic aid. Athletes use creatine to increase muscle mass, strength, and muscle endurance. While the performance and muscle-building effects of creatine supplementation have been well documented, the mechanisms responsible for these muscular adaptations have been less studied. Objective: The purpose of this review is to examine studies of the mechanisms underlying muscular adaptations to creatine supplementation. Data sources: PubMed and SPORTDiscus databases were searched from 1992 to 2007 using the terms creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Study selection: Studies of creatine supplementation in healthy adults were included. Data extraction: Due to the small number of studies identified, a meta-analysis was not performed. Data synthesis: Several potential mechanisms underlying muscular adaptations to creatine supplementation were identified, including: metabolic adaptations, changes in protein turnover, hormonal alterations, stabilization of lipid membranes, molecular modifications, or as a general training aid. The mechanisms with the greatest amount of support (metabolic adaptations, molecular modifications, and general training aid) may work in concert rather than independently. Conclusions: Creatine supplementation may alter skeletal muscle directly, by increased muscle glycogen and phosphocreatine, faster phosphocreatine resynthesis, increased expression of endocrine and growth factor mRNA, or indirectly, through increased training volume.

An assessment by the Statin Muscle Safety Task Force: 2014 update

Robert S. Rosenson, Steven K. Baker, Terry A. Jacobson +2 more · Journal of clinical lipidology · 2014 · 478 citations

Strength Training Increases Insulin-Mediated Glucose Uptake, GLUT4 Content, and Insulin Signaling in Skeletal Muscle in Patients With Type 2 Diabetes

Mads Holten, Morten Zacho, Michael Gaster +3 more · Diabetes · 2004 · 595 citations

Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isoglycemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher (P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs (P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-alpha/beta, glycogen synthase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade.

Diagnosis and Monitoring of Hepatic Injury. I. Performance Characteristics of Laboratory Tests

D. Robert Dufour, John Lott, Frederick S. Nolte +3 more · Clinical Chemistry · 2000 · 571 citations

PURPOSE: To review information on performance characteristics for tests that are commonly used to identify acute and chronic hepatic injury. DATA SOURCES AND STUDY SELECTION: A MEDLINE search was performed for key words related to hepatic tests, including quality specifications, aminotransferases, alkaline phosphatase, gamma-glutamyltransferase, bilirubin, albumin, ammonia, and viral markers. Abstracts were reviewed, and articles discussing performance of laboratory tests were selected for review. Additional articles were selected from the references. Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact. The drafts were also reviewed by the Practice Guidelines Committee of the American Association for the Study of Liver Diseases and approved by the committee and the Association's Council. RECOMMENDATIONS: Although many specific recommendations are made in the guidelines, some summary recommendations are discussed here. Alanine aminotransferase is the most important test for recognition of acute and chronic hepatic injury. Performance goals should aim for total error of <10% at the upper reference limit to meet clinical needs in monitoring patients with chronic hepatic injury. Laboratories should have age-adjusted reference limits for enzymes in children, and gender-adjusted reference limits for aminotransferases, gamma-glutamyltransferase, and total bilirubin in adults. The international normalized ratio should not be the sole method for reporting results of prothrombin time in liver disease; additional research is needed to determine the reporting mechanism that best correlates with functional impairment. Harmonization is needed for alanine aminotransferase activity, and improved standardization for hepatitis C viral RNA measurements.

Low-Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More Than High-Load Low Volume Resistance Exercise in Young Men

Nicholas A. Burd, Daniel W. D. West, Aaron W. Staples +8 more · PLoS ONE · 2010 · 518 citations

BACKGROUND: We aimed to determine the effect of resistance exercise intensity (%1 repetition maximum-1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Fifteen men (21+/-1 years; BMI=24.1+/-0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-13C6] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P=0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P=0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P=0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition. CONCLUSIONS/SIGNIFICANCE: These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.

Myocardial Injury and Ventricular Dysfunction Related to Training Levels Among Nonelite Participants in the Boston Marathon

Tomas G. Neilan, James L. Januzzi, Elizabeth Lee-Lewandrowski +10 more · Circulation · 2006 · 516 citations

BACKGROUND: Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. METHODS AND RESULTS: We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler-derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, > 60% of participants had increased cTnT > 99th percentile of normal (> 0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (> or = 0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL (P<0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r=-0.70, P<0.001) and inversely with training mileage (r=-0.71, P<0.001). Compared with athletes training > 45 miles/wk, athletes who trained < or = 35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16+/-5% versus 25+/-4%, P<0.001), myocyte injury (cTnT 0.09 versus < 0.01 ng/mL, P<0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P<0.001). CONCLUSIONS: Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Dietary creatine intake and depression risk among U.S. adults

Amanda V. Bakian, Rebekah S. Huber, Lindsay S. Scholl +2 more · Translational Psychiatry · 2020 · 85 citations

Creatine monohydrate is actively being researched for its antidepressant effects, yet little is known about the link between dietary creatine and depression risk. This study examines the association between dietary creatine and depression in U.S. adults, using data from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). Patient health questionnaire, dietary creatine intake and covariates were obtained on 22,692 NHANES participants ≥20 years of age. Depression prevalence was calculated within quartiles of dietary creatine intake. Adjusted logistic regression models were formulated to determine the relationship between dietary creatine intake and depression risk. Additional covariates included income to poverty ratio, race/ethnicity, sex, age, education level, body mass index, healthcare access, smoking status, physical activity, and antidepressant/anxiolytic medication use. Models were further stratified by sex, age group, and antidepressant/anxiolytic medication use. Depression prevalence was 10.23/100 persons (95% CI: 8.64-11.83) among NHANES participants in the lowest quartile of dietary creatine intake compared with 5.98/100 persons (95% CI: 4.97-6.98) among participants in the highest quartile (p < 0.001). An inverse association was measured between dietary creatine and depression (adjusted odds ratio (AOR) = 0.68, 95% CI: 0.52-0.88). Dietary creatine's negative association with depression was strongest in females (AOR = 0.62, 95% CI: 0.40-0.98), participants aged 20-39 years (AOR = 0.52, 95% CI: 0.34-0.79) and participants not taking antidepressant/anxiolytic medication (AOR = 0.58, 95% CI: 0.43-0.77). Study results indicate a significant negative relationship between dietary creatine and depression in a nationally representative adult cohort. Further research is warranted to investigate the role creatine plays in depression, particularly among women and across the lifespan.

International Association of Athletics Federations Consensus Statement 2019: Nutrition for Athletics

Louise M. Burke, L M Castell, Douglas J. Casa +13 more · International Journal of Sport Nutrition and Exercise Metabolism · 2019 · 233 citations

The International Association of Athletics Federations recognizes the importance of nutritional practices in optimizing an Athlete's well-being and performance. Although Athletics encompasses a diverse range of track-and-field events with different performance determinants, there are common goals around nutritional support for adaptation to training, optimal performance for key events, and reducing the risk of injury and illness. Periodized guidelines can be provided for the appropriate type, amount, and timing of intake of food and fluids to promote optimal health and performance across different scenarios of training and competition. Some Athletes are at risk of relative energy deficiency in sport arising from a mismatch between energy intake and exercise energy expenditure. Competition nutrition strategies may involve pre-event, within-event, and between-event eating to address requirements for carbohydrate and fluid replacement. Although a "food first" policy should underpin an Athlete's nutrition plan, there may be occasions for the judicious use of medical supplements to address nutrient deficiencies or sports foods that help the athlete to meet nutritional goals when it is impractical to eat food. Evidence-based supplements include caffeine, bicarbonate, beta-alanine, nitrate, and creatine; however, their value is specific to the characteristics of the event. Special considerations are needed for travel, challenging environments (e.g., heat and altitude); special populations (e.g., females, young and masters athletes); and restricted dietary choice (e.g., vegetarian). Ideally, each Athlete should develop a personalized, periodized, and practical nutrition plan via collaboration with their coach and accredited sports nutrition experts, to optimize their performance.

Mild dehydration impairs cognitive performance and mood of men

Matthew S. Ganio, Lawrence E. Armstrong, Douglas J. Casa +9 more · British Journal Of Nutrition · 2011 · 298 citations

The present study assessed the effects of mild dehydration on cognitive performance and mood of young males. A total of twenty-six men (age 20·0 (sd 0·3) years) participated in three randomised, single-blind, repeated-measures trials: exercise-induced dehydration plus a diuretic (DD; 40 mg furosemide); exercise-induced dehydration plus placebo containing no diuretic (DN); exercise while maintaining euhydration plus placebo (EU; control condition). Each trial included three 40 min treadmill walks at 5·6 km/h, 5 % grade in a 27·7°C environment. A comprehensive computerised six-task cognitive test battery, the profile of mood states questionnaire and the symptom questionnaire (headache, concentration and task difficulty) were administered during each trial. Paired t tests compared the DD and DN trials resulting in >1 % body mass loss (mean 1·59 (sd 0·42) %) with the volunteer's EU trial (0·01 (sd 0·03) %). Dehydration degraded specific aspects of cognitive performance: errors increased on visual vigilance (P = 0·048) and visual working memory response latency slowed (P = 0·021). Fatigue and tension/anxiety increased due to dehydration at rest (P = 0·040 and 0·029) and fatigue during exercise (P = 0·026). Plasma osmolality increased due to dehydration (P < 0·001) but resting gastrointestinal temperature was not altered (P = 0·238). In conclusion, mild dehydration without hyperthermia in men induced adverse changes in vigilance and working memory, and increased tension/anxiety and fatigue.

Precision nutrition in sports science: an opinion on omics-based personalization and athletic outcomes

Mirza Hapsari Sakti Titis Penggalih, Yosef Stefan Sutanto, Nurpudji Astuti Taslim +4 more · Frontiers in Nutrition · 2025 · 7 citations

This systematic review synthesises evidence that omics-based precision nutrition—using genomics, metabolomics, proteomics, and transcriptomics—can personalise athletic nutrition, but the field lacks large-scale randomised controlled trials, standardised protocols, and actionable tools, meaning athletes cannot yet reliably implement these approaches for performance gains.

Effects of Whey, Soy or Leucine Supplementation with 12 Weeks of Resistance Training on Strength, Body Composition, and Skeletal Muscle and Adipose Tissue Histological Attributes in College-Aged Males

C. Brooks Mobley, Cody T. Haun, Paul A. Roberson +13 more · Nutrients · 2017 · 105 citations

We sought to determine the effects of L-leucine (LEU) or different protein supplements standardized to LEU (~3.0 g/serving) on changes in body composition, strength, and histological attributes in skeletal muscle and adipose tissue. Seventy-five untrained, college-aged males (mean ± standard error of the mean (SE); age = 21 ± 1 years, body mass = 79.2 ± 0.3 kg) were randomly assigned to an isocaloric, lipid-, and organoleptically-matched maltodextrin placebo (PLA, n = 15), LEU (n = 14), whey protein concentrate (WPC, n = 17), whey protein hydrolysate (WPH, n = 14), or soy protein concentrate (SPC, n = 15) group. Participants performed whole-body resistance training three days per week for 12 weeks while consuming supplements twice daily. Skeletal muscle and subcutaneous (SQ) fat biopsies were obtained at baseline (T1) and ~72 h following the last day of training (T39). Tissue samples were analyzed for changes in type I and II fiber cross sectional area (CSA), non-fiber specific satellite cell count, and SQ adipocyte CSA. On average, all supplement groups including PLA exhibited similar training volumes and experienced statistically similar increases in total body skeletal muscle mass determined by dual X-ray absorptiometry (+2.2 kg; time p = 0.024) and type I and II fiber CSA increases (+394 μm2 and +927 μm2; time p &lt; 0.001 and 0.024, respectively). Notably, all groups reported increasing Calorie intakes ~600–800 kcal/day from T1 to T39 (time p &lt; 0.001), and all groups consumed at least 1.1 g/kg/day of protein at T1 and 1.3 g/kg/day at T39. There was a training, but no supplementation, effect regarding the reduction in SQ adipocyte CSA (−210 μm2; time p = 0.001). Interestingly, satellite cell counts within the WPC (p &lt; 0.05) and WPH (p &lt; 0.05) groups were greater at T39 relative to T1. In summary, LEU or protein supplementation (standardized to LEU content) does not provide added benefit in increasing whole-body skeletal muscle mass or strength above PLA following 3 months of training in previously untrained college-aged males that increase Calorie intakes with resistance training and consume above the recommended daily intake of protein throughout training. However, whey protein supplementation increases skeletal muscle satellite cell number in this population, and this phenomena may promote more favorable training adaptations over more prolonged periods.

Lactobacillus plantarum TWK10 Supplementation Improves Exercise Performance and Increases Muscle Mass in Mice

Yi‐Ming Chen, Wei Li, Yen‐Shuo Chiu +4 more · Nutrients · 2016 · 280 citations

Lactobacillus plantarum (L. plantarum) is a well-known probiotic among the ingested-microorganism probiotics (i.e., ingested microorganisms associated with beneficial effects for the host). However, few studies have examined the effects of L. plantarum TWK10 (LP10) supplementation on exercise performance, physical fatigue, and gut microbial profile. Male Institute of Cancer Research (ICR) strain mice were divided into three groups (n = 8 per group) for oral administration of LP10 for six weeks at 0, 2.05 × 10⁸, or 1.03 × 10⁹ colony-forming units/kg/day, designated the vehicle, LP10-1X and LP10-5X groups, respectively. LP10 significantly decreased final body weight and increased relative muscle weight (%). LP10 supplementation dose-dependently increased grip strength (p < 0.0001) and endurance swimming time (p < 0.001) and decreased levels of serum lactate (p < 0.0001), ammonia (p < 0.0001), creatine kinase (p = 0.0118), and glucose (p = 0.0151) after acute exercise challenge. The number of type I fibers (slow muscle) in gastrocnemius muscle significantly increased with LP10 treatment. In addition, serum levels of albumin, blood urea nitrogen, creatinine, and triacylglycerol significantly decreased with LP10 treatment. Long-term supplementation with LP10 may increase muscle mass, enhance energy harvesting, and have health-promotion, performance-improvement, and anti-fatigue effects.

Effects of Supplement Timing and Resistance Exercise on Skeletal Muscle Hypertrophy

Paul J. Cribb, Alan Hayes · Medicine & Science in Sports & Exercise · 2006 · 266 citations

PURPOSE: Some studies report greater muscle hypertrophy during resistance exercise (RE) training from supplement timing (i.e., the strategic consumption of protein and carbohydrate before and/or after each workout). However, no studies have examined whether this strategy provides greater muscle hypertrophy or strength development compared with supplementation at other times during the day. The purpose of this study was to examine the effects of supplement timing compared with supplementation in the hours not close to the workout on muscle-fiber hypertrophy, strength, and body composition during a 10-wk RE program. METHODS: In a single-blind, randomized protocol, resistance-trained males were matched for strength and placed into one of two groups; the PRE-POST group consumed a supplement (1 g x kg(-1) body weight) containing protein/creatine/glucose immediately before and after RE. The MOR-EVE group consumed the same dose of the same supplement in the morning and late evening. All assessments were completed the week before and after 10 wk of structured, supervised RE training. Assessments included strength (1RM, three exercises), body composition (DEXA), and vastus lateralis muscle biopsies for determination of muscle fiber type (I, IIa, IIx), cross-sectional area (CSA), contractile protein, creatine (Cr), and glycogen content. RESULTS: PRE-POST demonstrated a greater (P < 0.05) increase in lean body mass and 1RM strength in two of three assessments. The changes in body composition were supported by a greater (P < 0.05) increase in CSA of the type II fibers and contractile protein content. PRE-POST supplementation also resulted in higher muscle Cr and glycogen values after the training program (P < 0.05). CONCLUSION: Supplement timing represents a simple but effective strategy that enhances the adaptations desired from RE-training.

Effects of Whole-Body Cryotherapy vs. Far-Infrared vs. Passive Modalities on Recovery from Exercise-Induced Muscle Damage in Highly-Trained Runners

Christophe Hausswirth, Julien Louis, François Bieuzen +4 more · PLoS ONE · 2011 · 234 citations

Enhanced recovery following physical activity and exercise-induced muscle damage (EIMD) has become a priority for athletes. Consequently, a number of post-exercise recovery strategies are used, often without scientific evidence of their benefits. Within this framework, the purpose of this study was to test the efficacy of whole body cryotherapy (WBC), far infrared (FIR) or passive (PAS) modalities in hastening muscular recovery within the 48 hours after a simulated trail running race. In 3 non-adjoining weeks, 9 well-trained runners performed 3 repetitions of a simulated trail run on a motorized treadmill, designed to induce muscle damage. Immediately (post), post 24 h, and post 48 h after exercise, all participants tested three different recovery modalities (WBC, FIR, PAS) in a random order over the three separate weeks. Markers of muscle damage (maximal isometric muscle strength, plasma creatine kinase [CK] activity and perceived sensations [i.e. pain, tiredness, well-being]) were recorded before, immediately after (post), post 1 h, post 24 h, and post 48 h after exercise. In all testing sessions, the simulated 48 min trail run induced a similar, significant amount of muscle damage. Maximal muscle strength and perceived sensations were recovered after the first WBC session (post 1 h), while recovery took 24 h with FIR, and was not attained through the PAS recovery modality. No differences in plasma CK activity were recorded between conditions. Three WBC sessions performed within the 48 hours after a damaging running exercise accelerate recovery from EIMD to a greater extent than FIR or PAS modalities.

Creatine supplementation with specific view to exercise/sports performance: an update

Robert G. Cooper, Fernando Naclerio, Judith Allgrove +1 more · Journal of the International Society of Sports Nutrition · 2012 · 298 citations

Creatine is one of the most popular and widely researched natural supplements. The majority of studies have focused on the effects of creatine monohydrate on performance and health; however, many other forms of creatine exist and are commercially available in the sports nutrition/supplement market. Regardless of the form, supplementation with creatine has regularly shown to increase strength, fat free mass, and muscle morphology with concurrent heavy resistance training more than resistance training alone. Creatine may be of benefit in other modes of exercise such as high-intensity sprints or endurance training. However, it appears that the effects of creatine diminish as the length of time spent exercising increases. Even though not all individuals respond similarly to creatine supplementation, it is generally accepted that its supplementation increases creatine storage and promotes a faster regeneration of adenosine triphosphate between high intensity exercises. These improved outcomes will increase performance and promote greater training adaptations. More recent research suggests that creatine supplementation in amounts of 0.1 g/kg of body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Finally, although presently ingesting creatine as an oral supplement is considered safe and ethical, the perception of safety cannot be guaranteed, especially when administered for long period of time to different populations (athletes, sedentary, patient, active, young or elderly).

The Beneficial Effects of Lactobacillus plantarum PS128 on High-Intensity, Exercise-Induced Oxidative Stress, Inflammation, and Performance in Triathletes

Wen-Ching Huang, Chen-Chan Wei, Chi‐Chang Huang +2 more · Nutrients · 2019 · 153 citations

A triathlon, which consists of swimming, bicycling, and running, is a high-intensity and long-term form of exercise that can cause injuries such as muscular damage, inflammation, oxidative stress, and energy imbalance. Probiotics are thought to play an important role in disease incidence, health promotion, and nutrient metabolism, but only a few studies have focused on physiological adaptations to exercise in sports science. Previous studies indicated that Lactobacillus supplementation could improve oxidative stress and inflammatory responses. We investigate the effects of Lactobacillus plantarum PS128 supplementation on triathletes for possible physiological adaptation. The triathletes were assigned to one of two groups with different exercise intensity stimulations with different time-points to investigate the effects of body compositions, inflammation, oxidative stress, performance, fatigue, and injury-related biochemical indices. L. plantarum PS128 supplementation, combined with training, can significantly alleviate oxidative stress (such as creatine kinase, Thioredoxin, and Myeloperoxidase indices) after a triathlon (p < 0.05). This effect is possibly regulated by a 6⁻13% decrease of indicated pro-inflammation (TNF-α, IL-6, and IL-8) cytokines (p < 0.05) and 55% increase of anti-inflammation (IL-10) cytokines (p < 0.05) after intensive exercise stimulation. In addition, L. plantarum PS128 can also substantially increase 24⁻69% of plasma-branched amino acids (p < 0.05) and elevate exercise performance, as compared to the placebo group (p < 0.05). In conclusion, L. plantarum PS128 may be a potential ergogenic aid for better training management, physiological adaptations to exercise, and health promotion.

Cold-water immersion (cryotherapy) for preventing and treating muscle soreness after exercise

Chris Bleakley, Suzanne McDonough, Evie Gardner +3 more · Cochrane Database of Systematic Reviews · 2012 · 183 citations

BACKGROUND: Many strategies are in use with the intention of preventing or minimising delayed onset muscle soreness and fatigue after exercise. Cold-water immersion, in water temperatures of less than 15°C, is currently one of the most popular interventional strategies used after exercise. OBJECTIVES: To determine the effects of cold-water immersion in the management of muscle soreness after exercise. SEARCH METHODS: In February 2010, we searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library (2010, Issue 1), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health (CINAHL), British Nursing Index and archive (BNI), and the Physiotherapy Evidence Database (PEDro). We also searched the reference lists of articles, handsearched journals and conference proceedings and contacted experts.In November 2011, we updated the searches of CENTRAL (2011, Issue 4), MEDLINE (up to November Week 3 2011), EMBASE (to 2011 Week 46) and CINAHL (to 28 November 2011) to check for more recent publications. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing the effect of using cold-water immersion after exercise with: passive intervention (rest/no intervention), contrast immersion, warm-water immersion, active recovery, compression, or a different duration/dosage of cold-water immersion. Primary outcomes were pain (muscle soreness) or tenderness (pain on palpation), and subjective recovery (return to previous activities without signs or symptoms). DATA COLLECTION AND ANALYSIS: Three authors independently evaluated study quality and extracted data. Some of the data were obtained following author correspondence or extracted from graphs in the trial reports. Where possible, data were pooled using the fixed-effect model. MAIN RESULTS: Seventeen small trials were included, involving a total of 366 participants. Study quality was low. The temperature, duration and frequency of cold-water immersion varied between the different trials as did the exercises and settings. The majority of studies failed to report active surveillance of pre-defined adverse events.Fourteen studies compared cold-water immersion with passive intervention. Pooled results for muscle soreness showed statistically significant effects in favour of cold-water immersion after exercise at 24 hour (standardised mean difference (SMD) -0.55, 95% CI -0.84 to -0.27; 10 trials), 48 hour (SMD -0.66, 95% CI -0.97 to -0.35; 8 trials), 72 hour (SMD -0.93; 95% CI -1.36 to -0.51; 4 trials) and 96 hour (SMD -0.58; 95% CI -1.00 to -0.16; 5 trials) follow-ups. These results were heterogeneous. Exploratory subgroup analyses showed that studies using cross-over designs or running based exercises showed significantly larger effects in favour of cold-water immersion. Pooled results from two studies found cold-water immersion groups had significantly lower ratings of fatigue (MD -1.70; 95% CI -2.49 to -0.90; 10 units scale, best to worst), and potentially improved ratings of physical recovery (MD 0.97; 95% CI -0.10 to 2.05; 10 units scale, worst to best) immediately after the end of cold-water immersion.Five studies compared cold-water with contrast immersion. Pooled data for pain showed no evidence of differences between the two groups at four follow-up times (immediately, 24, 48 and 72 hours after treatment). Similar findings for pooled analyses at 24, 48 and 72 hour follow-ups applied to the four studies comparing cold-water with warm-water immersion. Single trials only compared cold-water immersion with respectively active recovery, compression and a second dose of cold-water immersion at 24 hours. AUTHORS' CONCLUSIONS: There was some evidence that cold-water immersion reduces delayed onset muscle soreness after exercise compared with passive interventions involving rest or no intervention. There was insufficient evidence to conclude on other outcomes or for other comparisons. The majority of trials did not undertake active surveillance of pre-defined adverse events. High quality, well reported research in this area is required.

Energy Metabolism during Repeated Sets of Leg Press Exercise Leading to Failure or Not

Esteban M. Gorostiaga, Ion Navarro-Amézqueta, José A. L. Calbet +7 more · PLoS ONE · 2012 · 171 citations

This investigation examined the influence of the number of repetitions per set on power output and muscle metabolism during leg press exercise. Six trained men (age 34 ± 6 yr) randomly performed either 5 sets of 10 repetitions (10REP), or 10 sets of 5 repetitions (5REP) of bilateral leg press exercise, with the same initial load and rest intervals between sets. Muscle biopsies (vastus lateralis) were taken before the first set, and after the first and the final sets. Compared with 5REP, 10REP resulted in a markedly greater decrease (P<0.05) of the power output, muscle PCr and ATP content, and markedly higher (P<0.05) levels of muscle lactate and IMP. Significant correlations (P<0.01) were observed between changes in muscle PCr and muscle lactate (R(2) = 0.46), between changes in muscle PCr and IMP (R(2) = 0.44) as well as between changes in power output and changes in muscle ATP (R(2) = 0.59) and lactate (R(2) = 0.64) levels. Reducing the number of repetitions per set by 50% causes a lower disruption to the energy balance in the muscle. The correlations suggest that the changes in PCr and muscle lactate mainly occur simultaneously during exercise, whereas IMP only accumulates when PCr levels are low. The decrease in ATP stores may contribute to fatigue.

The Effect of a Multi-ingredient Supplement on Resistance Training–induced Adaptations

Mai Wageh, Stephen A. Fortino, Chris McGlory +3 more · Medicine & Science in Sports & Exercise · 2021 · 9 citations

INTRODUCTION: Resistance exercise training (RET) induces muscle hypertrophy that, when combined with co-temporal protein ingestion, is enhanced. However, fewer studies have been conducted when RET is combined with multi-ingredient supplements. PURPOSE: We aimed to determine the effect of a high-quality multi-ingredient nutritional supplement (SUPP) versus an isonitrogenous (lower protein quality), isoenergetic placebo (PL) on RET-induced gains in lean body mass (LBM), muscle thickness, and muscle cross-sectional area (CSA). We hypothesized that RET-induced gains in LBM and muscle CSA would be greater in SUPP versus PL. METHODS: In a double-blind randomized controlled trial, 26 (13 male, 13 female) healthy young adults (mean ± SD, 22 ± 2 yr) were randomized to either the SUPP group (n = 13; 20 g whey protein, 2 g leucine, 2.5 g creatine monohydrate, 300 mg calcium citrate, 1000 IU vitamin D) or the PL group (n = 13; 20 g collagen peptides, 1.4 g alanine, 0.6 g glycine) groups, ingesting their respective supplements twice daily. Measurements were obtained before and after a 10-wk linear progressive RET program. RESULTS: Greater increases in LBM were observed for SUPP versus PL (SUPP: +4.1 ± 1.3 kg, PL: +2.8 ± 1.7 kg, P < 0.05). No additive effect of the supplement could be detected on vastus lateralis muscle CSA, but SUPP did result in increased biceps brachii muscle CSA and thickness (P < 0.05). CONCLUSIONS: We conclude that when combined with RET, the consumption of SUPP increased LBM and upper-body CSA and thickness to a greater extent than to that observed in the PL group of healthy young adults.

Impaired PGC-1α function in muscle in Huntington's disease

Rajnish Kumar Chaturvedi, Peter J. Adhihetty, Shubha Shukla +10 more · Human Molecular Genetics · 2009 · 233 citations

We investigated the role of PPAR gamma coactivator 1alpha (PGC-1alpha) in muscle dysfunction in Huntington's disease (HD). We observed reduced PGC-1alpha and target genes expression in muscle of HD transgenic mice. We produced chronic energy deprivation in HD mice by administering the catabolic stressor beta-guanidinopropionic acid (GPA), a creatine analogue that reduces ATP levels, activates AMP-activated protein kinase (AMPK), which in turn activates PGC-1alpha. Treatment with GPA resulted in increased expression of AMPK, PGC-1alpha target genes, genes for oxidative phosphorylation, electron transport chain and mitochondrial biogenesis, increased oxidative muscle fibers, numbers of mitochondria and motor performance in wild-type, but not in HD mice. In muscle biopsies from HD patients, there was decreased PGC-1alpha, PGC-1beta and oxidative fibers. Oxygen consumption, PGC-1alpha, NRF1 and response to GPA were significantly reduced in myoblasts from HD patients. Knockdown of mutant huntingtin resulted in increased PGC-1alpha expression in HD myoblast. Lastly, adenoviral-mediated delivery of PGC-1alpha resulted increased expression of PGC-1alpha and markers for oxidative muscle fibers and reversal of blunted response for GPA in HD mice. These findings show that impaired function of PGC-1alpha plays a critical role in muscle dysfunction in HD, and that treatment with agents to enhance PGC-1alpha function could exert therapeutic benefits. Furthermore, muscle may provide a readily accessible tissue in which to monitor therapeutic interventions.

Effect of Curcumin Supplementation on Physiological Fatigue and Physical Performance in Mice

Wen-Ching Huang, Wan‐Chun Chiu, Hsiao-Li Chuang +5 more · Nutrients · 2015 · 152 citations

Curcumin (CCM) is a well-known phytocompound and food component found in the spice turmeric and has multifunctional bioactivities. However, few studies have examined its effects on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of CCM supplementation on fatigue and ergogenic function following physical challenge in mice. Male ICR mice were divided into four groups to receive vehicle or CCM (180 μg/mL) by oral gavage at 0, 12.3, 24.6, or 61.5 mL/kg/day for four weeks. Exercise performance and anti-fatigue function were evaluated after physical challenge by forelimb grip strength, exhaustive swimming time, and levels of physical fatigue-associated biomarkers serum lactate, ammonia, blood urea nitrogen (BUN), and glucose and tissue damage markers such as aspartate transaminase (AST), alanine transaminase (ALT), and creatine kinase (CK). CCM supplementation dose-dependently increased grip strength and endurance performance and significantly decreased lactate, ammonia, BUN, AST, ALT, and CK levels after physical challenge. Muscular glycogen content, an important energy source for exercise, was significantly increased. CCM supplementation had few subchronic toxic effects. CCM supplementation may have a wide spectrum of bioactivities for promoting health, improving exercise performance and preventing fatigue.

Distinct Disease Phases in Muscles of Facioscapulohumeral Dystrophy Patients Identified by MR Detected Fat Infiltration

Bárbara Janssen, Nicoline Voet, Christine Nabuurs +6 more · PLoS ONE · 2014 · 147 citations

Facioscapulohumeral muscular dystrophy (FSHD) is an untreatable disease, characterized by asymmetric progressive weakness of skeletal muscle with fatty infiltration. Although the main genetic defect has been uncovered, the downstream mechanisms causing FSHD are not understood. The objective of this study was to determine natural disease state and progression in muscles of FSHD patients and to establish diagnostic biomarkers by quantitative MRI of fat infiltration and phosphorylated metabolites. MRI was performed at 3T with dedicated coils on legs of 41 patients (28 men/13 women, age 34-76 years), of which eleven were re-examined after four months of usual care. Muscular fat fraction was determined with multi spin-echo and T1 weighted MRI, edema by TIRM and phosphorylated metabolites by 3D (31)P MR spectroscopic imaging. Fat fractions were compared to clinical severity, muscle force, age, edema and phosphocreatine (PCr)/ATP. Longitudinal intramuscular fat fraction variation was analyzed by linear regression. Increased intramuscular fat correlated with age (p<0.05), FSHD severity score (p<0.0001), inversely with muscle strength (p<0.0001), and also occurred sub-clinically. Muscles were nearly dichotomously divided in those with high and with low fat fraction, with only 13% having an intermediate fat fraction. The intramuscular fat fraction along the muscle's length, increased from proximal to distal. This fat gradient was the steepest for intermediate fat infiltrated muscles (0.07±0.01/cm, p<0.001). Leg muscles in this intermediate phase showed a decreased PCr/ATP (p<0.05) and the fastest increase in fatty infiltration over time (0.18±0.15/year, p<0.001), which correlated with initial edema (p<0.01), if present. Thus, in the MR assessment of fat infiltration as biomarker for diseased muscles, the intramuscular fat distribution needs to be taken into account. Our results indicate that healthy individual leg muscles become diseased by entering a progressive phase with distal fat infiltration and altered energy metabolite levels. Fat replacement then relatively rapidly spreads over the whole muscle.

Aberrant Mitochondrial Homeostasis in the Skeletal Muscle of Sedentary Older Adults

Adeel Safdar, Mazen J. Hamadeh, Jan Jacek Kaczor +3 more · PLoS ONE · 2010 · 212 citations

The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; female symbol = male symbol). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

Effects of Low-Level Laser Therapy (LLLT) in the Development of Exercise-Induced Skeletal Muscle Fatigue and Changes in Biochemical Markers Related to Postexercise Recovery

Ernesto César Pinto Leal‐Junior, Rodrigo Álvaro Brandão Lopes-Martins, Lúcio Frigo +10 more · Journal of Orthopaedic and Sports Physical Therapy · 2010 · 200 citations

STUDY DESIGN: Randomized crossover double-blinded placebo-controlled trial. OBJECTIVE: To investigate if low-level laser therapy (LLLT) can affect biceps muscle performance, fatigue development, and biochemical markers of postexercise recovery. BACKGROUND: Cell and animal studies have suggested that LLLT can reduce oxidative stress and inflammatory responses in muscle tissue. But it remains uncertain whether these findings can translate into humans in sport and exercise situations. METHODS: Nine healthy male volleyball players participated in the study. They received either active LLLT (cluster probe with 5 laser diodes; lambda = 810 nm; 200 mW power output; 30 seconds of irradiation, applied in 2 locations over the biceps of the nondominant arm; 60 J of total energy) or placebo LLLT using an identical cluster probe. The intervention or placebo were applied 3 minutes before the performance of exercise. All subjects performed voluntary elbow flexion repetitions with a workload of 75% of their maximal voluntary contraction force until exhaustion. RESULTS: Active LLLT increased the number of repetitions by 14.5% (mean +/- SD, 39.6 +/- 4.3 versus 34.6 +/- 5.6; P = .037) and the elapsed time before exhaustion by 8.0% (P = .034), when compared to the placebo treatment. The biochemical markers also indicated that recovery may be positively affected by LLLT, as indicated by postexercise blood lactate levels (P<.01), creatine kinase activity (P = .017), and C-reactive protein levels (P = .047), showing a faster recovery with LLLT application prior to the exercise. CONCLUSION: We conclude that pre-exercise irradiation of the biceps with an LLLT dose of 6 J per application location, applied in 2 locations, increased endurance for repeated elbow flexion against resistance and decreased postexercise levels of blood lactate, creatine kinase, and C-reactiveprotein. LEVEL OF EVIDENCE: Performance enhancement, level 1b.

Improved exercise performance and increased aerobic capacity after endurance training of patients with stable polymyositis and dermatomyositis

Li Alemo Munters, Maryam Dastmalchi, Abram Katz +7 more · Arthritis Research & Therapy · 2013 · 118 citations

Abstract Introduction This randomized, controlled study on patients with polymyositis or dermatomyositis was based on three hypotheses: patients display impaired endurance due to reduced aerobic capacity and muscle weakness, endurance training improves their exercise performance by increasing the aerobic capacity, and endurance training has general beneficial effects on their health status. Methods In the first part of this study, we compared 23 patients with polymyositis or dermatomyositis with 12 age- and gender-matched healthy controls. A subgroup of patients were randomized to perform a 12-week endurance training program (exercise group, n = 9) or to a non-exercising control group ( n = 6). We measured maximal oxygen uptake (VO 2 max) and the associated power output during a progressive cycling test. Endurance was assessed as the cycling time to exhaustion at 65% of VO 2 max. Lactate levels in the vastus lateralis muscle were measured with microdialysis. Mitochondrial function was assessed by measuring citrate synthase (CS) and β-hydroxyacyl-CoA dehydrogenase (β-HAD) activities in muscle biopsies. Clinical improvement was assessed according to the International Myositis Assessment and Clinical Studies Group (IMACS) improvement criteria. All assessors were blinded to the type of intervention (that is, training or control). Results Exercise performance and aerobic capacity were lower in patients than in healthy controls, whereas lactate levels at exhaustion were similar. Patients in the exercise group increased their cycling time, aerobic capacity and CS and β-HAD activities, whereas lactate levels at exhaustion decreased. Six of nine patients in the exercise group met the IMACS improvement criteria. Patients in the control group did not show any consistent changes during the 12-week study. Conclusions Polymyositis and dermatomyositis patients have impaired endurance, which could be improved by 12 weeks of endurance training. The clinical improvement corresponds to increases in aerobic capacity and muscle mitochondrial enzyme activities. The results emphasize the importance of endurance exercise in addition to immunosuppressive treatment of patients with polymyositis or dermatomyositis. Trial registration ClinicalTrials.gov: NCT01184625

Influence of hyperoxia on muscle metabolic responses and the power–duration relationship during severe‐intensity exercise in humans: a³¹P magnetic resonance spectroscopy study

Anni Vanhatalo, Jonathan Fulford, Fred J. DiMenna +1 more · Experimental Physiology · 2009 · 233 citations

Severe-intensity constant-work-rate exercise results in the attainment of maximal oxygen uptake, but the muscle metabolic milieu at the limit of tolerance (T(lim)) for such exercise remains to be elucidated. We hypothesized that T(lim) during severe-intensity exercise would be associated with the attainment of consistently low values of intramuscular phosphocreatine ([PCr]) and pH, as determined using (31)P magnetic resonance spectroscopy, irrespective of the work rate and the inspired O(2) fraction. We also hypothesized that hyperoxia would increase the asymptote of the hyperbolic power-duration relationship (the critical power, CP) without altering the curvature constant (W). Seven subjects (mean +/- s.d., age 30 +/- 9 years) completed four constant-work-rate knee-extension exercise bouts to the limit of tolerance (range, 3-10 min) both in normoxia (N) and in hyperoxia (H; 70% O(2)) inside the bore of 1.5 T superconducting magnet. The [PCr] (approximately 5-10% of resting baseline) and pH (approximately 6.65) at the limit of tolerance during each of the four trials was not significantly different either in normoxia or in hyperoxia. At the same fixed work rate, the overall rate at which [PCr] fell with time was attenuated in hyperoxia (mean response time: N, 59 +/- 20 versus H, 116 +/- 46 s; P < 0.05). The CP was higher (N, 16.1 +/- 2.6 versus H, 18.0 +/- 2.3 W; P < 0.05) and the W was lower (N, 1.92 +/- 0.70 versus H, 1.48 +/- 0.31 kJ; P < 0.05) in hyperoxia compared with normoxia. These data indicate that T(lim) during severe-intensity exercise is associated with the attainment of consistently low values of muscle [PCr] and pH. The CP and W parameters of the power-duration relationship were both sensitive to the inspiration of hyperoxic gas.

Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity.

Michael Sullivan, H J Green, Frederick R. Cobb · Circulation · 1991 · 231 citations

BACKGROUND: Exertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients. METHODS AND RESULTS: We evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p less than 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p greater than 0.25), indicating comparable exercise end points. At rest in patients versus normals, there was a reduction in the activity of hexokinase (p = 0.08), citrate synthetase (p less than 0.02), succinate dehydrogenase (p = 0.0007), and 3-hydroxyacyl CoA dehydrogenase (p = 0.04). In patients, leg blood flow was decreased at rest, submaximal, and maximal exercise when compared to normal subjects (all p less than 0.05), and blood lactate accumulation was accelerated. In patients, during submaximal exercise blood lactate levels were not closely related to leg blood flow but were inversely related to rest citrate synthetase activity in skeletal muscle (r = -0.74, p less than 0.05). At peak exercise there were no intergroup differences in skeletal muscle glycolytic intermediates, adenosine nucleotides, or glycogen, whereas in patients compared to normal subjects less lactate accumulation and phosphocreatine depletion were noted (both p less than 0.05), suggesting that factors other than the magnitude of phosphocreatine depletion or lactate accumulation may influence skeletal muscle fatigue in this disorder. CONCLUSIONS: The results of the present study suggest that in patients with chronic heart failure reduced aerobic activity in skeletal muscle plays an important role in mediating the early onset of anaerobic metabolism during exercise. Our findings are consistent with the concept that reduced aerobic enzyme activity in skeletal muscle is, in part, responsible for determining exercise tolerance and possibly the response to chronic intervention in patients with chronic heart failure.

Reference intervals for serum creatine kinase in athletes

Vassilis Mougios · British Journal of Sports Medicine · 2007 · 307 citations

BACKGROUND: The serum concentration of creatine kinase (CK) is used widely as an index of skeletal muscle fibre damage in sport and exercise. Since athletes have higher CK values than non-athletes, comparing the values of athletes to the normal values established in non-athletes is pointless. The purpose of this study was to introduce reference intervals for CK in athletes. METHOD: CK was assayed in serum samples from 483 male athletes and 245 female athletes, aged 7-44. Samples had been obtained throughout the training and competition period. For comparison, CK was also assayed in a smaller number of non-athletes. Reference intervals (2.5th to 97.5th percentile) were calculated by the non-parametric method. RESULTS: The reference intervals were 82-1083 U/L (37 degrees C) in male and 47-513 U/L in female athletes. The upper reference limits were twice the limits reported for moderately active non-athletes in the literature or calculated in the non-athletes in this study. The upper limits were up to six times higher than the limits reported for inactive individuals in the literature. When reference intervals were calculated specifically in male football (soccer) players and swimmers, a threefold difference in the upper reference limit was found (1492 vs 523 U/L, respectively), probably resulting from the different training and competition demands of the two sports. CONCLUSION: Sport training and competition have profound effects on the reference intervals for serum CK. Introducing sport-specific reference intervals may help to avoid misinterpretation of high values and to optimise training.

Creatine Supplementation Enhances Corticomotor Excitability and Cognitive Performance during Oxygen Deprivation

Clare E. Turner, Winston D. Byblow, Nicholas Gant · Journal of Neuroscience · 2015 · 148 citations

Impairment or interruption of oxygen supply compromises brain function and plays a role in neurological and neurodegenerative conditions. Creatine is a naturally occurring compound involved in the buffering, transport, and regulation of cellular energy, with the potential to replenish cellular adenosine triphosphate without oxygen. Creatine is also neuroprotective in vitro against anoxic/hypoxic damage. Dietary creatine supplementation has been associated with improved symptoms in neurological disorders defined by impaired neural energy provision. Here we investigate, for the first time in humans, the utility of creatine as a dietary supplement to protect against energetic insult. The aim of this study was to assess the influence of oral creatine supplementation on the neurophysiological and neuropsychological function of healthy young adults during acute oxygen deprivation. Fifteen healthy adults were supplemented with creatine and placebo treatments for 7 d, which increased brain creatine on average by 9.2%. A hypoxic gas mixture (10% oxygen) was administered for 90 min, causing global oxygen deficit and impairing a range of neuropsychological processes. Hypoxia-induced decrements in cognitive performance, specifically attentional capacity, were restored when participants were creatine supplemented, and corticomotor excitability increased. A neuromodulatory effect of creatine via increased energy availability is presumed to be a contributing factor of the restoration, perhaps by supporting the maintenance of appropriate neuronal membrane potentials. Dietary creatine monohydrate supplementation augments neural creatine, increases corticomotor excitability, and prevents the decline in attention that occurs during severe oxygen deficit. This is the first demonstration of creatine's utility as a neuroprotective supplement when cellular energy provision is compromised.

Creatine Monohydrate and Conjugated Linoleic Acid Improve Strength and Body Composition Following Resistance Exercise in Older Adults

Mark A. Tarnopolsky, Andrew Zimmer, Jeremy S. Paikin +5 more · PLoS ONE · 2007 · 148 citations

Aging is associated with lower muscle mass and an increase in body fat. We examined whether creatine monohydrate (CrM) and conjugated linoleic acid (CLA) could enhance strength gains and improve body composition (i.e., increase fat-free mass (FFM); decrease body fat) following resistance exercise training in older adults (>65 y). Men (N = 19) and women (N = 20) completed six months of resistance exercise training with CrM (5g/d)+CLA (6g/d) or placebo with randomized, double blind, allocation. Outcomes included: strength and muscular endurance, functional tasks, body composition (DEXA scan), blood tests (lipids, liver function, CK, glucose, systemic inflammation markers (IL-6, C-reactive protein)), urinary markers of compliance (creatine/creatinine), oxidative stress (8-OH-2dG, 8-isoP) and bone resorption (Nu-telopeptides). Exercise training improved all measurements of functional capacity (P<0.05) and strength (P<0.001), with greater improvement for the CrM+CLA group in most measurements of muscular endurance, isokinetic knee extension strength, FFM, and lower fat mass (P<0.05). Plasma creatinine (P<0.05), but not creatinine clearance, increased for CrM+CLA, with no changes in serum CK activity or liver function tests. Together, this data confirms that supervised resistance exercise training is safe and effective for increasing strength in older adults and that a combination of CrM and CLA can enhance some of the beneficial effects of training over a six-month period. Trial Registration. ClinicalTrials.gov NCT00473902.

Nutritional Supplementation Combined with Exercise for Musculoskeletal Health in Women: A Systematic Review and Meta-Analysis Evaluating Proteins, Amino Acids, and Creatine across Reproductive Stages.

Chen KH, Yeh TP, Lin SC +3 more · Int J Med Sci · 2026 · 0 citations

The Creatine Kinase/Creatine Connection to Alzheimer′s Disease: CK Inactivation, APP‐CK Complexes and Focal Creatine Deposits

Tanja S. Bürklen, Uwe Schlattner, Ramin Homayouni +4 more · BioMed Research International · 2006 · 119 citations

Cytosolic brain-type creatine kinase (BB-CK), which is coexpressed with ubiquitous mitochondrial uMtCK, is significantly inactivated by oxidation, in Alzheimer's disease (AD) patients. Since CK has been shown to play a fundamental role in cellular energetics of the brain, any disturbance of this enzyme may exasperate the AD disease process. Mutations in amyloid precursor protein (APP) are associated with early onset AD and result in abnormal processing of APP, and accumulation of A beta peptide, the main constituent of amyloid plaques in AD brain. Recent data on a direct interaction between APP and the precursor of uMtCK support an emerging relationship between AD, cellular energy levels and mitochondrial function. In addition, recently discovered creatine (Cr) deposits in the brain of transgenic AD mice, as well as in the hippocampus from AD patients, indicate a direct link between perturbed energy state, Cr metabolism and AD. Here, we review the roles of Cr and Cr-related enzymes and consider the potential value of supplementation with Cr, a potent neuroprotective substance. As a hypothesis, we consider whether Cr, if given at an early time point of the disease, may prevent or delay the course of AD-related neurodegeneration.

Effects of 4-Week Creatine Supplementation Combined with Complex Training on Muscle Damage and Sport Performance

Chia‐Chi Wang, Chu-Chun Fang, Ying-Hsian Lee +2 more · Nutrients · 2018 · 77 citations

Creatine supplementation has an ergogenic effect in an acute complex training bout, but the benefits of chronic creatine supplementation during long-term complex training remain unknown. The study aimed to evaluate the effects of 4-week complex training combined with creatine supplementation on sport performances and muscle damage biomarkers. Thirty explosive athletes were assigned to the creatine or placebo group, which consumed 20 g of creatine or carboxymethyl cellulose, respectively, per day for 6 days followed by 2 g of the supplements until the end of the study. After 6 days of supplementation, subjects performed tests of one repetition maximum (1-RM) strength of half squat and complex training bouts to determine the optimal individual post-activation potentiation time. Thereafter, all subjects performed a complex training programme consisting of six sets of 5-RM half squats and plyometric jumps 3 times per week for 4 weeks. Body composition, 30-m sprint and jump performances were assessed before and after the training period. Moreover, blood creatine kinase (CK) activity was analysed at the first and the last training bout. After the training, the 1-RM strength in the creatine group was significantly greater than in the placebo group (p &lt; 0.05). CK activity after the complex training bout in the creatine group was significantly reduced compared with the placebo group (p &lt; 0.05). No differences were noted for other variables. This study concluded that creatine supplementation combined with complex training improved maximal muscular strength and reduced muscle damage during training.