{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:38:49Z","timestamp":1760060329002,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grove City College Exercise Science Department"},{"name":"Keto Brick Inc. (Bryant, AR, USA)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objective: Recent work has challenged the notion that preferred substrate oxidation is a key determinant of exercise performance. This investigation tested middle-distance running performance, in the fed state, to control for glycogen and exercise-induced hypoglycemia (EIH) confounders. Methods: In a randomized crossover fashion, all while controlling dietary intake, activity, and body weight, recreational distance runners completed either a 5K (n = 15; VO2max: 58.3 \u00b1 6.2 mL\/kg\/min) or a 10K (n = 15; VO2max: 54.51 \u00b1 5.9 mL\/kg\/min) middle-distance run after consuming isocaloric low-carbohydrate high-fat (LCHF) and high-carbohydrate low-fat (HCLF) pre-exercise meals. Time trial (TT) performance (sec), carbohydrate\/fat substrate oxidation, blood metabolites, heart rate (HR), ratings of perceived exertion (RPE), and subjective fullness and thirst were measured throughout. Results: LCHF pre-exercise nutrition reliably altered substrate oxidation and metabolite profiles compared to HCLF, evidenced by significant increases in fat oxidation (77% higher) and reductions in RER (5% lower), with corresponding shifts in carbohydrate oxidation. Despite distinct preferred substrate oxidation profiles during exercise, the 5 and 10 km TT performances were similar between conditions (p = 0.646\/p = 0.118). RER was significantly lower (p = 0.002) after the LCHF condition compared to HCLF. Capillary R-\u03b2HB increased modestly after LCHF, while blood glucose increased after HCLF only. The LCHF meal was 35% more filling than the HCLF meal. Preferred substrate oxidation did not significantly modulate middle-distance running performance. Conclusion: This work supports recent findings that substrate oxidation is not a primary determinant of aerobic performance, as previously conceived.<\/jats:p>","DOI":"10.3390\/nu17172771","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T15:49:34Z","timestamp":1756309774000},"page":"2771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Substrate Oxidation Does Not Influence Middle Distance Running Performance: A Randomized Controlled Crossover Trial"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8509-4330","authenticated-orcid":false,"given":"Alex","family":"Buga","sequence":"first","affiliation":[{"name":"Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey D.","family":"Buxton","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Plank","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James D.","family":"Minor","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micah T.","family":"Sterrett","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanner R.","family":"Niemann","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret P.","family":"Troxel","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Bryarly","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary","family":"Furry","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarra","family":"Hannon","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Muench","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Stone","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-181X","authenticated-orcid":false,"given":"Dominic P.","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology & Physiology, University of South Florida, Tampa, FL 33620, USA"},{"name":"Human Healthspan, Resilience and Performance, Florida Institute for Human and Machine Cognition, Pensacola, FL 32502, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-0351","authenticated-orcid":false,"given":"Jeff S.","family":"Volek","sequence":"additional","affiliation":[{"name":"Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew P.","family":"Koutnik","sequence":"additional","affiliation":[{"name":"Human Healthspan, Resilience and Performance, Florida Institute for Human and Machine Cognition, Pensacola, FL 32502, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1761-1129","authenticated-orcid":false,"given":"Philip J.","family":"Prins","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Grove City College, Grove City, PA 16127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"C710","DOI":"10.1152\/ajpcell.00583.2024","article-title":"Carbohydrate Ingestion Eliminates Hypoglycemia and Improves Endurance Exercise Performance in Triathletes Adapted to Very Low- and High-Carbohydrate Isocaloric Diets","volume":"328","author":"Prins","year":"2025","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1080\/02640414.2011.585473","article-title":"Carbohydrates for Training and Competition","volume":"29","author":"Burke","year":"2011","journal-title":"J. Sports Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1152\/jappl.1986.61.1.165","article-title":"Muscle Glycogen Utilization during Prolonged Strenuous Exercise When Fed Carbohydrate","volume":"61","author":"Coyle","year":"1986","journal-title":"J. Appl. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1080\/17461391.2022.2130097","article-title":"The Effect of Acute Manipulation of Carbohydrate Availability on High Intensity Running Performance, Running Economy, Critical Speed, and Substrate Metabolism in Trained Male Runners","volume":"23","author":"Ramonas","year":"2023","journal-title":"Eur. J. Sport Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Prins, P.J., Noakes, T.D., Buga, A., D\u2019Agostino, D.P., Volek, J.S., Buxton, J.D., Heckman, K., Jones, D.W., Tobias, N.E., and Grose, H.M. (2023). Low and High Carbohydrate Isocaloric Diets on Performance, Fat Oxidation, Glucose and Cardiometabolic Health in Middle Age Males. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1084021"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s40279-014-0153-2","article-title":"Gastrointestinal Complaints During Exercise: Prevalence, Etiology, and Nutritional Recommendations","volume":"44","author":"Burini","year":"2014","journal-title":"Sports Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1249\/JSR.0b013e31817ef9cb","article-title":"The Latest on Carbohydrate Loading: A Practical Approach","volume":"7","author":"Sedlock","year":"2008","journal-title":"Curr. Sports Med. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bedra\u010d, L., Deutsch, L., Terzi\u0107, S., \u010cervek, M., \u0160elb, J., A\u0161i\u010d, U., Verstraeten, L.M.G., Ku\u0161\u010der, E., and Cvetko, F. (2024). Towards Precision Sports Nutrition for Endurance Athletes: A Scoping Review of Application of Omics and Wearables Technologies. Nutrients, 16.","DOI":"10.3390\/nu16223943"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nieman, D.C. (2021). Multiomics Approach to Precision Sports Nutrition: Limits, Challenges, and Possibilities. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.796360"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.metabol.2019.05.003","article-title":"Exercising with Low Muscle Glycogen Content Increases Fat Oxidation and Decreases Endogenous, but Not Exogenous Carbohydrate Oxidation","volume":"97","author":"Margolis","year":"2019","journal-title":"Metab. Clin. Exp."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12970-018-0207-1","article-title":"Understanding the Factors That Effect Maximal Fat Oxidation","volume":"15","author":"Purdom","year":"2018","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Noakes, T.D., Prins, P.J., Volek, J.S., D\u2019Agostino, D.P., and Koutnik, A.P. (2023). Low Carbohydrate High Fat Ketogenic Diets on the Exercise Crossover Point and Glucose Homeostasis. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1150265"},{"key":"ref_13","first-page":"738","article-title":"High Rates of Fat Oxidation Induced by a Low-Carbohydrate, High-Fat Diet, Do Not Impair 5-Km Running Performance in Competitive Recreational Athletes","volume":"18","author":"Prins","year":"2019","journal-title":"J. Sports Sci. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"465","DOI":"10.5114\/biolsport.2023.116452","article-title":"High Fat Diet Improves Metabolic Flexibility during Progressive Exercise to Exhaustion (VO2max Testing) and during 5 Km Running Time Trials","volume":"40","author":"Prins","year":"2023","journal-title":"Biol. Sport"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1113\/EP091029","article-title":"Metabolic and Ruck Performance Effects of a Novel, Light-Weight, Energy-Dense Ketogenic Bar","volume":"108","author":"Buga","year":"2023","journal-title":"Exp. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1001\/jama.2019.13771","article-title":"Trends in Dietary Carbohydrate, Protein, and Fat Intake and Diet Quality Among US Adults, 1999\u20132016","volume":"322","author":"Shan","year":"2019","journal-title":"JAMA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1123\/ijspp.8.1.62","article-title":"Factors Affecting Perception of Effort (Session Rating of Perceived Exertion) during Rugby League Training","volume":"8","author":"Lovell","year":"2013","journal-title":"Int. J. Sports Physiol. Perform."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1249\/01.MSS.0000106169.35222.8B","article-title":"Validation of the Adult OMNI Scale of Perceived Exertion for Cycle Ergometer Exercise","volume":"36","author":"Robertson","year":"2004","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_19","first-page":"109","article-title":"A New Approach to Monitoring Exercise Training","volume":"15","author":"Foster","year":"2001","journal-title":"J. Strength Cond. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1136\/amiajnl-2012-001510","article-title":"Comparison of Traditional versus Mobile App Self-Monitoring of Physical Activity and Dietary Intake among Overweight Adults Participating in an mHealth Weight Loss Program","volume":"20","author":"Beets","year":"2013","journal-title":"J. Am. Med. Inform. Assoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1123\/jsep.11.3.304","article-title":"Not What, but How One Feels: The Measurement of Affect during Exercise","volume":"11","author":"Hardy","year":"1989","journal-title":"J. Sport Exerc. Psychol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1519\/JSC.0000000000001391","article-title":"Energy Drinks Improve Five-Kilometer Running Performance in Recreational Endurance Runners","volume":"30","author":"Prins","year":"2016","journal-title":"J. Strength Cond. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0031-9384(87)90212-5","article-title":"Thirst and Fluid Intake Following Graded Hypohydration Levels in Humans","volume":"40","author":"Engell","year":"1987","journal-title":"Physiol. Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.metabol.2015.10.028","article-title":"Metabolic Characteristics of Keto-Adapted Ultra-Endurance Runners","volume":"65","author":"Volek","year":"2016","journal-title":"Metabolism"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1123\/ijsnem.18.3.281","article-title":"Effect of Preexercise Meals with Different Glycemic Indices and Loads on Metabolic Responses and Endurance Running","volume":"18","author":"Chen","year":"2008","journal-title":"Int. J. Sport Nutr. Exerc. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/17461390701819451","article-title":"Effect of the Glycaemic Index of Pre-Exercise Carbohydrate Meals on Running Performance","volume":"8","author":"Wong","year":"2008","journal-title":"Eur. J. Sport Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1123\/ijsnem.16.5.510","article-title":"A Low Glycemic Index Meal before Exercise Improves Endurance Running Capacity in Men","volume":"16","author":"Wu","year":"2006","journal-title":"Int. J. Sport Nutr. Exerc. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s40279-016-0632-8","article-title":"Effect of Glycemic Index of a Pre-Exercise Meal on Endurance Exercise Performance: A Systematic Review and Meta-Analysis","volume":"47","author":"Burdon","year":"2017","journal-title":"Sports Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s40279-019-01246-y","article-title":"Exogenous Ketone Supplementation and Keto-Adaptation for Endurance Performance: Disentangling the Effects of Two Distinct Metabolic States","volume":"50","author":"Shaw","year":"2020","journal-title":"Sports Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.7570\/jomes22028","article-title":"The Effects of Medium-Chain Triglyceride Oil Supplementation on Endurance Performance and Substrate Utilization in Healthy Populations: A Systematic Review","volume":"31","author":"Koh","year":"2022","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Vandenberghe, C., St-Pierre, V., Fortier, M., Castellano, C.-A., Cuenoud, B., and Cunnane, S.C. (2020). Medium Chain Triglycerides Modulate the Ketogenic Effect of a Metabolic Switch. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.00003"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/026404197367326","article-title":"Nutritional Strategies for Promoting Fat Utilization and Delaying the Onset of Fatigue during Prolonged Exercise","volume":"15","author":"Lambert","year":"1997","journal-title":"J. Sports Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2165\/00007256-199825040-00003","article-title":"Strategies to Enhance Fat Utilisation during Exercise","volume":"25","author":"Hawley","year":"1998","journal-title":"Sports Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/ajcn\/67.3.397","article-title":"Effect of Medium-Chain Triacylglycerol and Carbohydrate Ingestion during Exercise on Substrate Utilization and Subsequent Cycling Performance","volume":"67","author":"Jeukendrup","year":"1998","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"772S","DOI":"10.1093\/ajcn\/57.5.772S","article-title":"Dietary Fat and the Control of Energy Intake: Evaluating the Effects of Fat on Meal Size and Postmeal Satiety","volume":"57","author":"Blundell","year":"1993","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/ajcn\/60.4.476","article-title":"Satiety after Preloads with Different Amounts of Fat and Carbohydrate: Implications for Obesity","volume":"60","author":"Rolls","year":"1994","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Best, R., Barwick, B., Best, A., Berger, N., Harrison, C., Wright, M., and Sparrow, J. (2018). Changes in Pain and Nutritional Intake Modulate Ultra-Running Performance: A Case Report. Sports, 6.","DOI":"10.3390\/sports6040111"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3390\/diabetology4010008","article-title":"The Lipids and Volume in Satiation and Satiety (LIVES) Hypothesis: A Proposed Alternative Model for the Pathogenesis of Obesity","volume":"4","author":"Warrilow","year":"2023","journal-title":"Diabetology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nutres.2020.02.010","article-title":"Impact of Ketosis on Appetite Regulation-a Review","volume":"77","author":"Deemer","year":"2020","journal-title":"Nutr. Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/17\/2771\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:38Z","timestamp":1760034818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/17\/2771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":39,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["nu17172771"],"URL":"https:\/\/doi.org\/10.3390\/nu17172771","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2025,8,27]]}}}