{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:11:13Z","timestamp":1783487473756,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Male fertility has been declining globally over the past several decades, advancing from a personal issue to a public health problem. Beyond any doubt, a reduction in fertility (often characterized by low sperm count or motility) can severely threaten reproductive health and lifecourse framework in a long-term fashion. Aside from uncovering the currently unknown etiology of modern-day male infertility, the scientific and medical community faces a double burden: finding an efficient biomarker of impaired fertility and exploring any intervention that can act to enhance fertility. A plethora of nutritional compounds have been recognized as possible modulators of semen quality, and specific dietary patterns and nutrients appear to be accompanied by a lower risk of male infertility. Creatine, a conditionally essential nutrient, has caught attention as a male fertility-promoting candidate due to its role in sperm energy metabolism. This mini-review describes the creatine-related bioenergetics of spermatozoa, explores a connection between creatine levels and sperm quality in men, and critically examines available evidence for interventional studies with creatine to affect sperm viability.<\/jats:p>","DOI":"10.3390\/nu14030586","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T05:26:17Z","timestamp":1643433977000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Creatine as a Promising Component of Paternal Preconception Diet"],"prefix":"10.3390","volume":"14","author":[{"given":"Sergej M.","family":"Ostojic","sequence":"first","affiliation":[{"name":"Department of Nutrition and Public Health, University of Agder, P.O. Box 422, 4604 Kristiansand, Norway"},{"name":"FSPE Applied Bioenergetics Lab, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3349-6706","authenticated-orcid":false,"given":"Tonje Holte","family":"Stea","sequence":"additional","affiliation":[{"name":"Department of Health and Nursing Sciences, University of Agder, P.O. Box 422, 4604 Kristiansand, Norway"},{"name":"Department of Child and Adolescence Mental Health, S\u00f8rlandet Hospital, 4604 Kristiansand, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagrun","family":"Engeset","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Public Health, University of Agder, P.O. Box 422, 4604 Kristiansand, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Demographics Collaborators (2020). Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950\u20132019: A comprehensive demographic analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1160\u20131203."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1097\/MOU.0000000000000745","article-title":"Reasons for worldwide decline in male fertility","volume":"30","author":"Mann","year":"2020","journal-title":"Curr. Opin. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/nrurol.2016.261","article-title":"Semen quality in the 21st century","volume":"14","author":"Virtanen","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.fertnstert.2018.05.025","article-title":"Diet and men\u2019s fertility: Does diet affect sperm quality?","volume":"110","author":"Nassan","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.repbio.2019.07.005","article-title":"Diet and sperm quality: Nutrients, foods and dietary patterns","volume":"19","author":"James","year":"2019","journal-title":"Reprod. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Skoracka, K., Eder, P., \u0141ykowska-Szuber, L., Dobrowolska, A., and Krela-Ka\u017amierczak, I. (2020). Diet and nutritional factors in male (in)fertility-underestimated factors. J. Clin. Med., 9.","DOI":"10.20944\/preprints202004.0365.v1"},{"key":"ref_7","first-page":"215","article-title":"Association between adherence to the Mediterranean diet and semen quality parameters in male partners of couples attempting fertility","volume":"32","author":"Karayiannis","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.fertnstert.2011.10.011","article-title":"Food intake and social habits in male patients and its relationship to intracytoplasmic sperm injection outcomes","volume":"97","author":"Braga","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_9","first-page":"69","article-title":"Zinc is an essential element for male fertility: A review of Zn roles in men\u2019s health, germination, sperm quality, and fertilization","volume":"19","author":"Fallah","year":"2018","journal-title":"J. Reprod. Infertil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1046\/j.1464-410x.1998.00683.x","article-title":"The effect of oral selenium supplementation on human sperm motility","volume":"82","author":"Scott","year":"1998","journal-title":"Br. J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/andr.12649","article-title":"The influence of omega-3 fatty acids on semen quality markers: A systematic PRISMA review","volume":"7","author":"Falsig","year":"2019","journal-title":"Andrology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1056\/NEJMoa003005","article-title":"Sperm morphology, motility, and concentration in fertile and infertile men","volume":"345","author":"Guzick","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_13","first-page":"nmab111","article-title":"Perspective: Creatine, a conditionally essential nutrient: Building the case","volume":"18","author":"Ostojic","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1095\/biolreprod.112.104109","article-title":"Sperm bioenergetics in a nutshell","volume":"87","author":"Visconti","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s00726-011-0877-3","article-title":"The creatine kinase system and pleiotropic effects of creatine","volume":"40","author":"Wallimann","year":"2011","journal-title":"Amino Acids"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nasrallah, F., Hammami, M.B., Omar, S., Aribia, H.B., Sanhaji, H., and Feki, M. (2020). Semen creatine and creatine kinase activity as an indicator of sperm quality. Clin. Lab., 66.","DOI":"10.7754\/Clin.Lab.2020.191248"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF01756199","article-title":"Creatine kinase isoenzymes in spermatozoa","volume":"7","author":"Wallimann","year":"1986","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","article-title":"Creatine and creatinine metabolism","volume":"80","author":"Wyss","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/and.12486","article-title":"The activity of seminal creatine kinase is increased in the presence of pentoxifylline","volume":"48","author":"Banihani","year":"2016","journal-title":"Andrologia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0092-8674(85)90085-6","article-title":"Metabolite channeling: A phosphorylcreatine shuttle to mediate high energy phosphate transport between sperm mitochondrion and tail","volume":"41","author":"Tombes","year":"1985","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1439-0272.1995.tb01367.x","article-title":"Strict criteria for the evaluation of human sperm morphology and its impact on assisted reproduction","volume":"27","author":"Grow","year":"1995","journal-title":"Andrologia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.aju.2017.10.005","article-title":"Prediction of male infertility by the World Health Organization laboratory manual for assessment of semen analysis: A systematic review","volume":"16","author":"Patel","year":"2017","journal-title":"Arab. J. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/S0140-6736(63)90233-2","article-title":"Creatine-phosphokinase activity in semen","volume":"2","author":"Lehmann","year":"1963","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3109\/01485018008987006","article-title":"Seminal plasma creatine kinase activity in fertility studies","volume":"5","author":"Miralles","year":"1980","journal-title":"Arch. Androl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1365-2605.1981.tb00727.x","article-title":"Creatine kinase in seminal plasma of infertile men: Activity and isoenzymes","volume":"4","author":"Asseo","year":"1981","journal-title":"Int. J. Androl."},{"key":"ref_26","first-page":"77","article-title":"Enzyme levels in semen of men with different types of azoospermia","volume":"14","year":"1982","journal-title":"Andrologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1439-0272.1984.tb00281.x","article-title":"Biochemical analysis of human seminal plasma. II. Protein, non-protein nitrogen, urea, uric acid and creatine","volume":"16","author":"Srivastava","year":"1984","journal-title":"Andrologia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/mrd.1120190107","article-title":"Correlation between sperm creatine phosphokinase activity and sperm concentrations in normospermic and oligospermic men","volume":"19","author":"Huszar","year":"1988","journal-title":"Gamete Res."},{"key":"ref_29","first-page":"192","article-title":"Relationship between creatine kinase activity and semen characteristics in subfertile men","volume":"43","author":"Sidhu","year":"1998","journal-title":"Int. J. Fertil. Womens Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/S0090-4295(01)01224-9","article-title":"Creatine kinase as an indicator of sperm quality and maturity in men with oligospermia","volume":"58","author":"Hallak","year":"2001","journal-title":"Urology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.urology.2013.08.031","article-title":"The correlation of biochemical and morphologic parameters in the assessment of sperm maturity","volume":"82","author":"Durutovic","year":"2013","journal-title":"Urology"},{"key":"ref_32","first-page":"258","article-title":"The effect of cigarette smoking on human sperm creatine kinase activity: As an ATP buffering system in sperm","volume":"6","author":"Ghaffari","year":"2013","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/j.1439-0272.2012.01297.x","article-title":"Effect of abamectin exposure on semen parameters indicative of reduced sperm maturity: A study on farmworkers in Antalya (Turkey)","volume":"44","author":"Tasatargil","year":"2012","journal-title":"Andrologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0015-0282(16)49839-0","article-title":"Enhancement of human sperm motility and velocity in vitro: Effects of calcium and creatine phosphate","volume":"46","author":"Fakih","year":"1986","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1093\/humrep\/dey081","article-title":"Creatine enhances the duration of sperm capacitation: A novel factor for improving in vitro fertilization with small numbers of sperm","volume":"33","author":"Umehara","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e13493","DOI":"10.1111\/asj.13493","article-title":"Methyl-beta cyclodextrin and creatine work synergistically under hypoxic conditions to improve the fertilization ability of boar ejaculated sperm","volume":"91","author":"Umehara","year":"2020","journal-title":"Anim. Sci. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.theriogenology.2016.11.012","article-title":"Effects of guanidinoacetic acid diet supplementation on semen quality and fertility of broiler breeder roosters","volume":"89","author":"Tapeh","year":"2017","journal-title":"Theriogenology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.fertnstert.2020.02.103","article-title":"Semen quality among young healthy men taking protein supplements","volume":"114","author":"Glazer","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1046\/j.1365-2605.2000.00197.x","article-title":"The distribution, metabolism and function of creatine in the male mammalian reproductive tract: A review","volume":"23","author":"Moore","year":"2000","journal-title":"Int. J. Androl."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Braissant, O., Henry, H., Villard, A.M., Speer, O., Wallimann, T., and Bachmann, C. (2005). Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1. BMC Dev. Biol., 5.","DOI":"10.1186\/1471-213X-5-9"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Muccini, A.M., Tran, N.T., de Guingand, D.L., Philip, M., Della Gatta, P.A., Galinsky, R., Sherman, L.S., Kelleher, M.A., Palmer, K.R., and Berry, M.J. (2021). Creatine metabolism in female reproduction, pregnancy and newborn health. Nutrients, 13.","DOI":"10.3390\/nu13020490"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Korovljev, D., Stajer, V., and Ostojic, S.M. (2021). Relationship between dietary creatine and growth indicators in children and adolescents aged 2\u201319 years: A cross-sectional study. Nutrients, 13.","DOI":"10.3390\/nu13031027"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000515917","article-title":"Dietary intake of creatine in children aged 0\u201324 months","volume":"77","author":"Korovljev","year":"2021","journal-title":"Ann. Nutr. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dickinson, H., Ellery, S., Ireland, Z., LaRosa, D., Snow, R., and Walker, D.W. (2014). Creatine supplementation during pregnancy: Summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy. BMC Pregnancy Childbirth, 14.","DOI":"10.1186\/1471-2393-14-150"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12970-017-0173-z","article-title":"International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine","volume":"14","author":"Kreider","year":"2017","journal-title":"J. Int. Soc. Sports Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/3\/586\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:10:26Z","timestamp":1760134226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/3\/586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":45,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["nu14030586"],"URL":"https:\/\/doi.org\/10.3390\/nu14030586","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]}}}