{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:32:07Z","timestamp":1780079527397,"version":"3.54.0"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006453","name":"Taisho Pharmaceutical Co., Ltd.","doi-asserted-by":"publisher","award":["H11PA22111"],"award-info":[{"award-number":["H11PA22111"]}],"id":[{"id":"10.13039\/501100006453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: In this study, we aimed to examine the effect of creatine monohydrate (CrM) supplementation on recovery from eccentric exercise-induced muscle damage (EIMD) in diverse populations, including different sexes and age groups. EIMD decreases maximal voluntary contraction (MVC), restricts the range of motion (ROM), and increases muscle stiffness and delayed-onset muscle soreness, all of which negatively impact athletic performance. Therefore, developing effective recovery strategies is essential. Methods: A double-blind, randomized, placebo-controlled trial was conducted with 40 healthy male and female participants. After 33 days of supplementation with either CrM or placebo (crystalline cellulose), the participants performed eccentric exercises. Recovery indices, including MVC, muscle stiffness, subjective muscle extensive soreness, fatigue, and upper arm circumference, were measured at baseline, immediately after exercise, 48 h post-exercise, and 96 h post-exercise. Results: The creatine supplementation group (CRE) demonstrated a significantly quicker recovery of MVC than the placebo group (PLA). Furthermore, reductions in shear modulus and muscle fatigue were observed in the CRE group. Notably, females in the CRE group exhibited a significant suppression of post-exercise edema, suggesting a sex-specific response. Conclusions: These findings indicate that CrM supplementation may enhance recovery from EIMD, contributing to the maintenance of muscle function and the reduction of discomfort after exercise. CrM has the potential to serve as a practical nutritional strategy to promote recovery, not only for athletes, but also for a broader population.<\/jats:p>","DOI":"10.3390\/nu17111772","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T09:58:09Z","timestamp":1747994289000},"page":"1772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Effects of Creatine Monohydrate Supplementation on Recovery from Eccentric Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial Considering Sex and Age Differences"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6655-9881","authenticated-orcid":false,"given":"Shota","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Institute of Physical Education, Keio University, Yokohama 223-8521, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7299-170X","authenticated-orcid":false,"given":"Takayuki","family":"Inami","sequence":"additional","affiliation":[{"name":"Institute of Physical Education, Keio University, Yokohama 223-8521, Kanagawa, Japan"},{"name":"The Graduate School of Health Management, Keio University, Yokohama 223-8521, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Nishioka","sequence":"additional","affiliation":[{"name":"Institute of Physical Education, Keio University, Yokohama 223-8521, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-1064","authenticated-orcid":false,"given":"Akihisa","family":"Morito","sequence":"additional","affiliation":[{"name":"Taisho Pharmaceutical Co., Ltd., Saitama 331-9530, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0220-5619","authenticated-orcid":false,"given":"Kaho","family":"Ishiyama","sequence":"additional","affiliation":[{"name":"Taisho Pharmaceutical Co., Ltd., Saitama 331-9530, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-5556","authenticated-orcid":false,"given":"Mitsuyoshi","family":"Murayama","sequence":"additional","affiliation":[{"name":"Institute of Physical Education, Keio University, Yokohama 223-8521, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"ref_1","first-page":"121","article-title":"Changes in Urinary Titin N-Terminal Fragment Concentration after Concentric and Eccentric Exercise","volume":"19","author":"Yamaguchi","year":"2020","journal-title":"J. Sports Sci. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1139\/h99-020","article-title":"Etiology of Exercise-Induced Muscle Damage","volume":"24","author":"Clarkson","year":"1999","journal-title":"Can. J. Appl. Physiol."},{"key":"ref_3","first-page":"197","article-title":"Treatment and Prevention of Delayed Onset Muscle Soreness","volume":"17","author":"Connolly","year":"2003","journal-title":"J. Strength Cond. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"607S","DOI":"10.1093\/ajcn\/72.2.607S","article-title":"Does Dietary Creatine Supplementation Play a Role in Skeletal Muscle Metabolism and Performance?","volume":"72","author":"Casey","year":"2000","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3390\/nutraceuticals3020019","article-title":"Creatine Supplementation Alleviates Fatigue after Exercise through Anti-Inflammatory Action in Skeletal Muscle and Brain","volume":"3","author":"Yokota","year":"2023","journal-title":"Nutraceuticals"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Yamaguchi, S., Inami, T., Ishida, H., Morito, A., Yamada, S., Nagata, N., and Murayama, M. (2024). The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial. Nutrients, 16.","DOI":"10.3390\/nu16060896"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1249\/MSS.0b013e31816212ff","article-title":"Sex Differences in Exercise Metabolism and the Role of 17-Beta Estradiol","volume":"40","author":"Tarnopolsky","year":"2008","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2165\/11319760-000000000-00000","article-title":"The Influence of Estrogen on Skeletal Muscle","volume":"40","author":"Enns","year":"2010","journal-title":"Sports Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"140S","DOI":"10.1080\/07315724.2005.10719455","article-title":"Role of Protein and Amino Acids in the Pathophysiology and Treatment of Sarcopenia","volume":"24","author":"Dreyer","year":"2005","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_10","first-page":"11","article-title":"Human Aging, Muscle Mass, and Fiber Type Composition","volume":"50","author":"Lexell","year":"1995","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_11","first-page":"124","article-title":"Muscle Atrophy and Weakness with Aging: Contraction-Induced Injury as an Underlying Mechanism","volume":"50","author":"Faulkner","year":"1995","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1055\/a-1199-7662","article-title":"The Role of Calpains in Skeletal Muscle Remodeling with Exercise and Inactivity-Induced Atrophy","volume":"41","author":"Hyatt","year":"2020","journal-title":"Int. J. Sports Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1152\/japplphysiol.00971.2016","article-title":"Muscle Damage and Inflammation during Recovery from Exercise","volume":"122","author":"Peake","year":"2017","journal-title":"J. Appl. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1007\/s00421-020-04432-3","article-title":"Nutritional Interventions for Reducing the Signs and Symptoms of Exercise-Induced Muscle Damage and Accelerate Recovery in Athletes: Current Knowledge, Practical Application and Future Perspectives","volume":"120","author":"Bongiovanni","year":"2020","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1113\/jphysiol.2006.115006","article-title":"Creatine as a Compatible Osmolyte in Muscle Cells Exposed to Hypertonic Stress","volume":"576","author":"Alfieri","year":"2006","journal-title":"J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"C697","DOI":"10.1152\/ajpcell.1997.272.2.C697","article-title":"Metabolic Support of Na+ Pump in Apically Permeabilized A6 Kidney Cell Epithelia: Role of Creatine Kinase","volume":"272","author":"Guerrero","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13395-019-0205-2","article-title":"Estrogen Signaling Effects on Muscle-Specific Immune Responses through Controlling the Recruitment and Function of Macrophages and T Cells","volume":"9","author":"Liao","year":"2019","journal-title":"Skelet. Muscle"},{"key":"ref_18","first-page":"117","article-title":"Repeated Eccentric Exercise Bouts Do Not Exacerbate Muscle Damage and Repair","volume":"16","author":"Nosaka","year":"2002","journal-title":"J. Strength Cond. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yamaguchi, S., Inami, T., Ishida, H., Nagata, N., Murayama, M., Morito, A., Yamada, S., and Kohtake, N. (2024). Bioimpedance Analysis for Identifying New Indicators of Exercise-Induced Muscle Damage. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-66089-8"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"536","DOI":"10.52082\/jssm.2022.536","article-title":"Changes in Muscle Shear Modulus and Urinary Titin N-Terminal Fragment after Eccentric Exercise","volume":"21","author":"Inami","year":"2022","journal-title":"J. Sports Sci. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.jsams.2019.12.023","article-title":"Changes in Urinary Titin N-Terminal Fragments as a Biomarker of Exercise-Induced Muscle Damage in the Repeated Bout Effect","volume":"23","author":"Yamaguchi","year":"2020","journal-title":"J. Sci. Med. Sport"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1097\/00005768-199608000-00003","article-title":"Changes in Indicators of Inflammation after Eccentric Exercise of the Elbow Flexors","volume":"28","author":"Nosaka","year":"1996","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1550-2783-6-13","article-title":"Creatine Supplementation Enhances Muscle Force Recovery after Eccentrically-Induced Muscle Damage in Healthy Individuals","volume":"6","author":"Cooke","year":"2009","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1123\/ijsnem.2020-0282","article-title":"The Effect of Creatine Supplementation on Markers of Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis of Human Intervention Trials","volume":"31","author":"Northeast","year":"2021","journal-title":"Int. J. Sport. Nutr. Exerc. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1007\/s40279-022-01640-z","article-title":"The Paradoxical Effect of Creatine Monohydrate on Muscle Damage Markers: A Systematic Review and Meta-Analysis","volume":"52","author":"Doma","year":"2022","journal-title":"Sports Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1034\/j.1600-0838.2002.10178.x","article-title":"Delayed-Onset Muscle Soreness Does Not Reflect the Magnitude of Eccentric Exercise-Induced Muscle Damage","volume":"12","author":"Nosaka","year":"2002","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/j.lfs.2003.11.036","article-title":"The Effect of Creatine Supplementation upon Inflammatory and Muscle Soreness Markers after a 30 km Race","volume":"75","author":"Santos","year":"2004","journal-title":"Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1152\/japplphysiol.00046.2018","article-title":"Microvascular Permeability of Skeletal Muscle after Eccentric Contraction-Induced Muscle Injury: In Vivo Imaging Using Two-Photon Laser Scanning Microscopy","volume":"125","author":"Hotta","year":"2018","journal-title":"J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1006\/bbrc.2001.6164","article-title":"Direct Antioxidant Properties of Creatine","volume":"290","author":"Lawler","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1042\/bst0250050","article-title":"Protection against Muscle Damage Exerted by Oestrogen: Hormonal or Antioxidant Action?","volume":"25","author":"Amelink","year":"1997","journal-title":"Biochem. Soc. Trans."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1097\/GME.0000000000001370","article-title":"The Synergistic Effects of Vitamin D and Estradiol Deficiency on Metabolic Syndrome in Chinese Postmenopausal Women","volume":"26","author":"Huang","year":"2019","journal-title":"Menopause"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cabre, H.E., Gould, L.M., Redman, L.M., and Smith-Ryan, A.E. (2024). Effects of the Menstrual Cycle and Hormonal Contraceptive Use on Metabolic Outcomes, Strength Performance, and Recovery: A Narrative Review. Metabolites, 14.","DOI":"10.3390\/metabo14070347"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, Z., Qiu, B., Li, R., Han, Y., Petersen, C., Liu, S., Zhang, Y., Liu, C., Candow, D.G., and Del Coso, J. (2024). Effects of Creatine Supplementation and Resistance Training on Muscle Strength Gains in Adults <50 Years of Age: A Systematic Review and Meta-Analysis. Nutrients, 16.","DOI":"10.3390\/nu16213665"},{"key":"ref_34","first-page":"E821","article-title":"Carbohydrate Ingestion Augments Skeletal Muscle Creatine Accumulation during Creatine Supplementation in Humans","volume":"271","author":"Green","year":"1996","journal-title":"Am. J. Physiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/11\/1772\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:39:24Z","timestamp":1760031564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/11\/1772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,23]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["nu17111772"],"URL":"https:\/\/doi.org\/10.3390\/nu17111772","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,23]]}}}