{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:16:46Z","timestamp":1792167406846,"version":"4.4.0"},"reference-count":87,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,28]],"date-time":"2024-01-28T00:00:00Z","timestamp":1706400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine, Pharmacy, Science, and Technology &quot;George Emil Palade\u201d of T\u00e2rgu Mure\u0219 Research","award":["164\/23\/10.01.2023"],"award-info":[{"award-number":["164\/23\/10.01.2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium\u2019s ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge.<\/jats:p>","DOI":"10.3390\/ijms25031605","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T04:57:07Z","timestamp":1706504227000},"page":"1605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review"],"prefix":"10.3390","volume":"25","author":[{"given":"Amalia","family":"Pu\u0219ca\u0219","sequence":"first","affiliation":[{"name":"Biochemistry and Chemistry of the Environmental Factors Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-3867","authenticated-orcid":false,"given":"Ruxandra","family":"\u0218tef\u0103nescu","sequence":"additional","affiliation":[{"name":"Pharmacognosy and Phytotherapy Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0880-6212","authenticated-orcid":false,"given":"Camil-Eugen","family":"Vari","sequence":"additional","affiliation":[{"name":"Pharmacology and Clinical Pharmacy Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca-Eugenia","family":"\u0150sz","sequence":"additional","affiliation":[{"name":"Pharmacology and Clinical Pharmacy Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Filip","sequence":"additional","affiliation":[{"name":"Biochemistry and Chemistry of the Environmental Factors Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana Karlina","family":"Bitzan","sequence":"additional","affiliation":[{"name":"Medical Chemistry and Biochemistry Department, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, Campus Hamburg\u2014UMCH, 22761 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u0103d\u0103lina-Georgiana","family":"Bu\u021b","sequence":"additional","affiliation":[{"name":"Medical Chemistry and Biochemistry Department, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Tero-Vescan","sequence":"additional","affiliation":[{"name":"Medical Chemistry and Biochemistry Department, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1002\/dta.1680","article-title":"Doping Control Analysis of Trimetazidine and Characterization of Major Metabolites Using Mass Spectrometric Approaches: Analysis of Trimetazidine in Doping Controls","volume":"6","author":"Sigmund","year":"2014","journal-title":"Drug Test. Anal."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dai, Z.-L., Song, Y.-F., Tian, Y., Li, Y., Lin, M., Lin, J., Wang, Q., Wang, P., and Gao, W.-L. (2021). Trimetazidine Offers Myocardial Protection in Elderly Coronary Artery Disease Patients Undergoing Non-Cardiac Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial. BMC Cardiovasc. Disord., 21.","DOI":"10.1186\/s12872-021-02287-w"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.coph.2006.10.008","article-title":"Anti-Anginal Effects of Partial Fatty Acid Oxidation Inhibitors","volume":"7","author":"Lam","year":"2007","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.metabol.2015.10.022","article-title":"The Protective Effect of Trimetazidine on Myocardial Ischemia\/Reperfusion Injury through Activating AMPK and ERK Signaling Pathway","volume":"65","author":"Liu","year":"2016","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2165\/00003495-199958010-00016","article-title":"Trimetazidine: A Review of Its Use in Stable Angina Pectoris and Other Coronary Conditions","volume":"58","author":"McClellan","year":"1999","journal-title":"Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1253\/circj.70.1169","article-title":"Trimetazidine Reduces Oxidative Stress in Cardiac Surgery","volume":"70","author":"Iskesen","year":"2006","journal-title":"Circ. J."},{"key":"ref_7","unstructured":"World Anti Doping Agency (2023, June 15). The Prohibited List. Available online: https:\/\/www.wada-ama.org\/en\/prohibited-list."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1081\/JLC-200054785","article-title":"An HPLC Determination of Trimetazidine in Human Plasma Using Liquid-Liquid Extraction for Sample Clean-Up","volume":"28","author":"Jeoung","year":"2005","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Okano, M., Miyamoto, A., Ota, M., Kageyama, S., and Sato, M. (2022). Doping Control Analysis of Trimetazidine in Dried Blood Spot. Drug Test. Anal.","DOI":"10.1002\/dta.3414"},{"key":"ref_10","first-page":"1525","article-title":"Cardiac Fatty Acid Oxidation in Heart Failure Associated with Obesity and Diabetes","volume":"1861","author":"Fukushima","year":"2016","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Cell Biol. Lipids"},{"key":"ref_11","unstructured":"Terjung, R. (2017). Comprehensive Physiology, Wiley."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1146\/annurev-nutr-071812-161220","article-title":"Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism","volume":"34","author":"Pepino","year":"2014","journal-title":"Annu. Rev. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.mito.2018.02.009","article-title":"Mitochondrial \u03b2-Oxidation of Saturated Fatty Acids in Humans","volume":"46","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/s41574-020-0405-1","article-title":"Tuning Fatty Acid Oxidation in Skeletal Muscle with Dietary Fat and Exercise","volume":"16","author":"Fritzen","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.bbamcr.2016.01.023","article-title":"Carnitine Transport and Fatty Acid Oxidation","volume":"1863","author":"Longo","year":"2016","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1113\/jphysiol.2005.102178","article-title":"Mitochondrial Long Chain Fatty Acid Oxidation, Fatty Acid Translocase\/CD36 Content and Carnitine Palmitoyltransferase I Activity in Human Skeletal Muscle during Aerobic Exercise: Human Skeletal Muscle Mitochondrial Fatty Acid Oxidation","volume":"571","author":"Holloway","year":"2006","journal-title":"J. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.yjmcc.2018.01.017","article-title":"Decreased ATP Production and Myocardial Contractile Reserve in Metabolic Heart Disease","volume":"116","author":"Luptak","year":"2018","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yamamoto, T., and Sano, M. (2022). Deranged Myocardial Fatty Acid Metabolism in Heart Failure. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020996"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1016\/j.jacc.2021.02.057","article-title":"Therapeutic Manipulation of Myocardial Metabolism","volume":"77","author":"Honka","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/1440-1681.12370","article-title":"Myocardial Glycogen Dynamics: New Perspectives on Disease Mechanisms","volume":"42","author":"Chandramouli","year":"2015","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pasqua, T., Rocca, C., Giglio, A., and Angelone, T. (2021). Cardiometabolism as an Interlocking Puzzle between the Healthy and Diseased Heart: New Frontiers in Therapeutic Applications. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040721"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"570421","DOI":"10.3389\/fphys.2020.570421","article-title":"Myocardial Energy Metabolism in Non-Ischemic Cardiomyopathy","volume":"11","author":"Greenwell","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E578","DOI":"10.1152\/ajpendo.00093.2009","article-title":"The Randle Cycle Revisited: A New Head for an Old Hat","volume":"297","author":"Hue","year":"2009","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(63)91500-9","article-title":"The Glucose Fatty-Acid Cycle Its Role In Insulin Sensitivity And The Metabolic Disturbances Of Diabetes Mellitus","volume":"281","author":"Randle","year":"1963","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1093\/cvr\/cvy063","article-title":"Glucose Is Preferentially Utilized for Biomass Synthesis in Pressure-Overloaded Hearts: Evidence from Fatty Acid-Binding Protein-4 and -5 Knockout Mice","volume":"114","author":"Umbarawan","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/nm.4245","article-title":"Dissociation of Muscle Insulin Sensitivity from Exercise Endurance in Mice by HDAC3 Depletion","volume":"23","author":"Hong","year":"2017","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.bbadis.2018.09.025","article-title":"Interplay between NAD+ and acetyl-CoA Metabolism in Ischemia-Induced Mitochondrial Pathophysiology","volume":"1865","author":"Klimova","year":"2019","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Basis Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"29530","DOI":"10.1074\/jbc.273.45.29530","article-title":"Regulation of Energy Metabolism of the Heart during Acute Increase in Heart Work","volume":"273","author":"Goodwin","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_29","unstructured":"Balakrishnan, P., Liebe, T., Amro, E., Dhaka, L., Heinzel, T., and Heller, R. (2019). The Science of Hormesis in Health and Longevity, Elsevier."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1152\/japplphysiol.00533.2021","article-title":"Exercise Effects on \u03933-AMPK Activity, Akt Substrate of 160 kDa Phosphorylation, and Glucose Uptake in Muscle of Normal and Insulin-Resistant Female Rats","volume":"132","author":"Wang","year":"2022","journal-title":"J. Appl. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E949","DOI":"10.1152\/ajpendo.00416.2015","article-title":"Mechanisms for Greater Insulin-Stimulated Glucose Uptake in Normal and Insulin-Resistant Skeletal Muscle after Acute Exercise","volume":"309","author":"Cartee","year":"2015","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"787","DOI":"10.2147\/NDT.S157441","article-title":"Beneficial Effects of Trimetazidine on Expression of Serotonin and Serotonin Transporter in Rats with Myocardial Infarction and Depression","volume":"14","author":"Liu","year":"2018","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s40265-014-0233-5","article-title":"Defining the Role of Trimetazidine in the Treatment of Cardiovascular Disorders: Some Insights on Its Role in Heart Failure and Peripheral Artery Disease","volume":"74","author":"Chrusciel","year":"2014","journal-title":"Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15420\/ecr.2018.15.2","article-title":"Trimetazidine and Other Metabolic Modifiers","volume":"13","author":"Guarini","year":"2018","journal-title":"Eur. Cardiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1006\/jmcc.1994.1116","article-title":"Some Biochemical Aspects of the Protective Effect of Trimetazidine on Rat Cardiomyocytes During Hypoxia and Reoxygenation","volume":"26","author":"Fantini","year":"1994","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"170360","DOI":"10.1098\/rsos.170360","article-title":"Modelling Pyruvate Dehydrogenase under Hypoxia and Its Role in Cancer Metabolism","volume":"4","author":"Eyassu","year":"2017","journal-title":"R. Soc. Open Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1161\/01.RES.86.5.580","article-title":"The Antianginal Drug Trimetazidine Shifts Cardiac Energy Metabolism From Fatty Acid Oxidation to Glucose Oxidation by Inhibiting Mitochondrial Long-Chain 3-Ketoacyl Coenzyme A Thiolase","volume":"86","author":"Kantor","year":"2000","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"707399","DOI":"10.3389\/fphar.2021.707399","article-title":"Trimetazidine Attenuates Heart Failure by Improving Myocardial Metabolism via AMPK","volume":"12","author":"Shu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18069","DOI":"10.1074\/jbc.M610101200","article-title":"Energy Depletion Inhibits Phosphatidylinositol 3-Kinase\/Akt Signaling and Induces Apoptosis via AMP-Activated Protein Kinase-Dependent Phosphorylation of IRS-1 at Ser-794","volume":"282","author":"Tzatsos","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fcvm.2018.00017","article-title":"Cardiac-Specific Deletion of Pyruvate Dehydrogenase Impairs Glucose Oxidation Rates and Induces Diastolic Dysfunction","volume":"5","author":"Gopal","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fcvm.2018.00070","article-title":"The Regulation of Insulin-Stimulated Cardiac Glucose Transport via Protein Acetylation","volume":"5","author":"Renguet","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41419-019-1349-z","article-title":"The Pivotal Role of Protein Acetylation in Linking Glucose and Fatty Acid Metabolism to \u03b2-Cell Function","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"J\u00eetc\u0103, G., \u0150sz, B.E., Tero-Vescan, A., Miklos, A.P., Rusz, C.-M., B\u0103tr\u00eenu, M.-G., and Vari, C.E. (2022). Positive Aspects of Oxidative Stress at Different Levels of the Human Body: A Review. Antioxidants, 11.","DOI":"10.3390\/antiox11030572"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12460","DOI":"10.1111\/1755-5922.12460","article-title":"Trimetazidine Suppresses Oxidative Stress, Inhibits MMP-2 and MMP -9 Expression, and Prevents Cardiac Rupture in Mice with Myocardial Infarction","volume":"36","author":"Gong","year":"2018","journal-title":"Cardiovasc. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3389\/fphar.2019.00175","article-title":"Trimetazidine Attenuates Exhaustive Exercise-Induced Myocardial Injury in Rats via Regulation of the Nrf2\/NF-\u03baB Signaling Pathway","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_46","first-page":"17","article-title":"Trimetazidine Prevents Oxidative Changes Induced in a Rat Model of Sporadic Type of Alzheimer\u2019s Disease","volume":"53","author":"Hassanzadeh","year":"2015","journal-title":"Acta Med. Iran."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"645041","DOI":"10.3389\/fphys.2021.645041","article-title":"Function and Mechanism of Trimetazidine in Myocardial Infarction-Induced Myocardial Energy Metabolism Disorder Through the SIRT1\u2013AMPK Pathway","volume":"12","author":"Luo","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1358\/mf.2008.30.10.1316831","article-title":"The Effects of Trimetazidine on Lipid Peroxidation in Patients Withend-Stage Renal Disease","volume":"30","author":"Aygen","year":"2008","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1177\/147323000503300602","article-title":"Effects of Trimetazidine on Lipid Peroxidation, Antioxidant Enzyme Activities and Plasma Brain Natriuretic Peptide Levels in Patients with Chronic Cor Pulmonale","volume":"33","author":"Bayram","year":"2005","journal-title":"J. Int. Med. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.yjmcc.2005.09.012","article-title":"Trimetazidine Inhibits Mitochondrial Permeability Transition Pore Opening and Prevents Lethal Ischemia\u2013Reperfusion Injury","volume":"39","author":"Argaud","year":"2005","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.cjca.2016.12.013","article-title":"Metabolic Modulators in Heart Disease: Past, Present, and Future","volume":"33","author":"Lopaschuk","year":"2017","journal-title":"Can. J. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ehj.2015.03.004","article-title":"Metabolic Approach to Heart Failure: The Role of Metabolic Modulators","volume":"67","author":"Rosano","year":"2015","journal-title":"Egypt. Heart J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1123\/ijsnem.2018-0241","article-title":"Contemporary Nutrition Interventions to Optimize Performance in Middle-Distance Runners","volume":"29","author":"Stellingwerff","year":"2019","journal-title":"Int. J. Sport Nutr. Exerc. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3389\/fnut.2019.00135","article-title":"Can the Skeletal Muscle Carnosine Response to Beta-Alanine Supplementation Be Optimized?","volume":"6","author":"Perim","year":"2019","journal-title":"Front. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12986-020-00436-0","article-title":"Runners\u2019 Metabolomic Changes Following Marathon","volume":"17","author":"Shi","year":"2020","journal-title":"Nutr. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12970-019-0312-9","article-title":"International Society of Sports Nutrition Position Stand: Nutritional Considerations for Single-Stage Ultra-Marathon Training and Racing","volume":"16","author":"Tiller","year":"2019","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/17461390801919094","article-title":"Optimizing Training Adaptations by Manipulating Glycogen","volume":"8","author":"Baar","year":"2008","journal-title":"Eur. J. Sport Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1123\/ijsnem.2018-0273","article-title":"SPRINTING. Dietary Approaches to Optimize Training Adaptation and Performance","volume":"29","author":"Slater","year":"2019","journal-title":"Int. J. Sport Nutr. Exerc. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s12471-020-01407-z","article-title":"TrimetaziDine as a Performance-enhancING Drug in Heart Failure with Preserved Ejection Fraction (DoPING-HFpEF): Rationale and Design of a Placebo-Controlled Cross-over Intervention Study","volume":"28","author":"Bakermans","year":"2020","journal-title":"Neth. Heart J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1093\/eurheartj\/ehi816","article-title":"Effects of Metabolic Modulation by Trimetazidine on Left Ventricular Function and Phosphocreatine\/Adenosine Triphosphate Ratio in Patients with Heart Failure","volume":"27","author":"Fragasso","year":"2006","journal-title":"Eur. Heart J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/MCO.0000000000000321","article-title":"Potential Harmful Effects of Dietary Supplements in Sports Medicine","volume":"19","author":"Deldicque","year":"2016","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.jshs.2015.12.003","article-title":"Tribulus Terrestris Extracts Alleviate Muscle Damage and Promote Anaerobic Performance of Trained Male Boxers and Its Mechanisms: Roles of Androgen, IGF-1, and IGF Binding Protein-3","volume":"6","author":"Ma","year":"2017","journal-title":"J. Sport Health Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-L\u00e1zaro, D., Fernandez-Lazaro, C., Seco-Calvo, J., Garrosa, E., Adams, D., and Mielgo-Ayuso, J. (2022). Effects of Tribulus terrestris L. on Sport and Health Biomarkers in Physically Active Adult Males: A Systematic Review. Int. J. Environ. Res. Public. Health, 19.","DOI":"10.3390\/ijerph19159533"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12986-019-0421-0","article-title":"Functional Properties of Beetroot (Beta vulgaris) in Management of Cardio-Metabolic Diseases","volume":"17","author":"Mirmiran","year":"2020","journal-title":"Nutr. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s40279-014-0149-y","article-title":"Dietary Nitrate Supplementation and Exercise Performance","volume":"44","author":"Jones","year":"2014","journal-title":"Sports Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bbrc.2010.06.048","article-title":"Naringenin, a Citrus Flavonoid, Increases Muscle Cell Glucose Uptake via AMPK","volume":"398","author":"Zygmunt","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","first-page":"1089","article-title":"Diosgenin Prevents High-Fat Diet-Induced Rat Non-Alcoholic Fatty Liver Disease through the AMPK and LXR Signaling Pathways","volume":"41","author":"Cheng","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1750-1172-9-79","article-title":"Stilbenes and Resveratrol Metabolites Improve Mitochondrial Fatty Acid Oxidation Defects in Human Fibroblasts","volume":"9","author":"Aires","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gimeno-Mallench, L., Mas-Bargues, C., Ingl\u00e9s, M., Olaso, G., Borras, C., Gambini, J., and Vina, J. (2019). Resveratrol Shifts Energy Metabolism to Increase Lipid Oxidation in Healthy Old Mice. Biomed. Pharmacother., 118.","DOI":"10.1016\/j.biopha.2019.109130"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.biocel.2005.12.002","article-title":"Effect of Citrus Flavonoids on Lipid Metabolism and Glucose-Regulating Enzyme mRNA Levels in Type-2 Diabetic Mice","volume":"38","author":"Jung","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"(2000). Position of the American Dietetic Association, Dietitians of Canada, and the American College of Sports Medicine. J. Am. Diet. Assoc., 100, 1543\u20131556.","DOI":"10.1016\/S0002-8223(00)00428-4"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e002699","DOI":"10.1136\/bmjdrc-2021-002699","article-title":"Trimetazidine and Exercise Offer Analogous Improvements to the Skeletal Muscle Insulin Resistance of Mice through Nrf2 Signaling","volume":"10","author":"Zhang","year":"2022","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kaufman, M., Nguyen, C., Shetty, M., Oppezzo, M., Barrack, M., and Fredericson, M. (2023). Popular Dietary Trends\u2019 Impact on Athletic Performance: A Critical Analysis Review. Nutrients, 15.","DOI":"10.3390\/nu15163511"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2147\/OAJSM.S180409","article-title":"Impact of Ketogenic Diet on Athletes: Current Insights","volume":"10","author":"McSwiney","year":"2019","journal-title":"Open Access J. Sports Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Thirupathi, A., Wang, M., Lin, J.K., Fekete, G., Istv\u00e1n, B., Baker, J.S., and Gu, Y. (2021). Effect of Different Exercise Modalities on Oxidative Stress: A Systematic Review. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/1947928"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.3892\/mmr.2020.11309","article-title":"Trimetazidine Improves Hepatic Lipogenesis and Steatosis in Non-alcoholic Fatty Liver Disease via AMPK-ChREBP Pathway","volume":"22","author":"Zhang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1124\/jpet.114.214197","article-title":"Treatment with the 3-Ketoacyl-CoA Thiolase Inhibitor Trimetazidine Does Not Exacerbate Whole-Body Insulin Resistance in Obese Mice","volume":"349","author":"Ussher","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"19116","DOI":"10.1038\/s41598-021-98771-6","article-title":"Trimetazidine and Exercise Provide Comparable Improvements to High Fat Diet-Induced Muscle Dysfunction through Enhancement of Mitochondrial Quality Control","volume":"11","author":"Zhang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1093\/oxfordjournals.bmb.a072564","article-title":"Aerobic Exercise, Anaerobic Exercise and the Lactate Threshold","volume":"48","author":"Spurway","year":"1992","journal-title":"Br. Med. Bull."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"725","DOI":"10.2165\/00007256-200131100-00003","article-title":"Energy System Interaction and Relative Contribution during Maximal Exercise","volume":"31","author":"Gastin","year":"2001","journal-title":"Sports Med."},{"key":"ref_81","unstructured":"Patel, H., Kerndt, C.C., and Bhardwaj, A. (2023). StatPearls, StatPearls Publishing."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"946300","DOI":"10.3389\/fnut.2022.946300","article-title":"Editorial: Metabolic Flexibility","volume":"9","author":"Galgani","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"671161","DOI":"10.3389\/fphys.2021.671161","article-title":"Modulation of Perturbed Cardiac Metabolism in Rats Under High-Altitude Hypoxia by Combination Treatment With L-Carnitine and Trimetazidine","volume":"12","author":"Xie","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.bbamcr.2011.01.015","article-title":"Targeting Fatty Acid and Carbohydrate Oxidation--a Novel Therapeutic Intervention in the Ischemic and Failing Heart","volume":"1813","author":"Jaswal","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"113938","DOI":"10.18632\/oncotarget.23044","article-title":"Modulating the Metabolism by Trimetazidine Enhances Myoblast Differentiation and Promotes Myogenesis in Cachectic Tumor-Bearing C26 Mice","volume":"8","author":"Gatta","year":"2017","journal-title":"Oncotarget"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1002\/jcsm.12226","article-title":"The Mitochondrial Metabolic Reprogramming Agent Trimetazidine as an \u2018Exercise Mimetic\u2019 in Cachectic C26-bearing Mice","volume":"8","author":"Molinari","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"E105","DOI":"10.1152\/ajpendo.00680.2010","article-title":"Human Obesity Is Characterized by Defective Fat Storage and Enhanced Muscle Fatty Acid Oxidation, and Trimetazidine Gradually Counteracts These Abnormalities","volume":"301","author":"Bucci","year":"2011","journal-title":"Am. J. Physiol.-Endocrinol. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:50:32Z","timestamp":1760104232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,28]]},"references-count":87,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031605"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031605","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,28]]}}}