Creatine as a Promising Component of Paternal Preconception Diet

Sergej M Ostojic, Tonje Holte Stea, Dagrun Engeset, Sergej M Ostojic, Tonje Holte Stea, Dagrun Engeset

Abstract

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.

Keywords: creatine; creatine kinase; energy metabolism; fertility; nutrition.

Conflict of interest statement

S.M.O. serves as a member of the Scientific Advisory Board on creatine in health and medicine (AlzChem LLC). S.M.O. owns patent “Sports Supplements Based on Liquid Creatine” at European Patent Office (WO2019150323 A1), and active patent application “Synergistic Creatine” at UK Intellectual Property Office (GB2012773.4). S.M.O. has served as a speaker at Abbott Nutrition, a consultant of Allied Beverages Adriatic and IMLEK, and has received research funding related to creatine and/or guanidinoacetic acid from the Serbian Ministry of Education, Science, and Technological Development, Provincial Secretariat for Higher Education and Scientific Research, AlzChem GmbH, KW Pfannenschmidt GmbH, Hueston Hennigan LLP, and ThermoLife International LLC. S.M.O. does not own stocks and shares in any organization. T.H.S. is a member of the Norwegian Scientific Committee for Food Safety and has contributed to a risk assessment of creatine as food supplement (Opinion of the Panel of Nutrition, Dietetic Products, Novel Food and Allergy Report 2016:56). D.E. declares no conflict of interest.

Figures

Figure 1
Figure 1
Creatine–phosphocreatine (PCR) shuttle and high-phospate energy (E) production and utilization in spermatozoa. Abbreviations: ATP, adenosine triphosphate; ADP, adenosine diphosphate; CK, creatine kinase; MiMi-CK, mitochondrial CK isoform confined to the midpiece region rich in mitochondria; BB-CK, tail-specific CK isoform localized within the sperm tail but not in the head portion.

References

    1. GBD 2019 Demographics Collaborators Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: A comprehensive demographic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1160–1203. doi: 10.1016/S0140-6736(20)30977-6.
    1. Mann U., Shiff B., Patel P. Reasons for worldwide decline in male fertility. Curr. Opin. Urol. 2020;30:296–301. doi: 10.1097/MOU.0000000000000745.
    1. Virtanen H.E., Jørgensen N., Toppari J. Semen quality in the 21st century. Nat. Rev. Urol. 2017;14:120–130. doi: 10.1038/nrurol.2016.261.
    1. Nassan F.L., Chavarro J.E., Tanrikut C. Diet and men’s fertility: Does diet affect sperm quality? Fertil. Steril. 2018;110:570–577. doi: 10.1016/j.fertnstert.2018.05.025.
    1. Salas-Huetos A., James E.R., Aston K.I., Jenkins T.G., Carrell D.T. Diet and sperm quality: Nutrients, foods and dietary patterns. Reprod. Biol. 2019;19:219–224. doi: 10.1016/j.repbio.2019.07.005.
    1. Skoracka K., Eder P., Łykowska-Szuber L., Dobrowolska A., Krela-Kaźmierczak I. Diet and nutritional factors in male (in)fertility-underestimated factors. J. Clin. Med. 2020;9:1400. doi: 10.3390/jcm9051400.
    1. Karayiannis D., Kontogianni M.D., Mendorou C., Douka L., Mastrominas M., Yiannakouris N. Association between adherence to the Mediterranean diet and semen quality parameters in male partners of couples attempting fertility. Hum. Reprod. 2017;32:215–222. doi: 10.1093/humrep/dew288.
    1. Braga D.P., Halpern G., Figueira Rde C., Setti A.S., Iaconelli A., Jr., Borges E., Jr. Food intake and social habits in male patients and its relationship to intracytoplasmic sperm injection outcomes. Fertil. Steril. 2012;97:53–59. doi: 10.1016/j.fertnstert.2011.10.011.
    1. Fallah A., Mohammad-Hasani A., Colagar A.H. Zinc is an essential element for male fertility: A review of Zn roles in men’s health, germination, sperm quality, and fertilization. J. Reprod. Infertil. 2018;19:69–81.
    1. Scott R., MacPherson A., Yates R.W., Hussain B., Dixon J. The effect of oral selenium supplementation on human sperm motility. Br. J. Urol. 1998;82:76–80. doi: 10.1046/j.1464-410x.1998.00683.x.
    1. Falsig A.L., Gleerup C.S., Knudsen U.B. The influence of omega-3 fatty acids on semen quality markers: A systematic PRISMA review. Andrology. 2019;7:794–803. doi: 10.1111/andr.12649.
    1. Guzick D.S., Overstreet J.W., Factor-Litvak P., Brazil C.K., Nakajima S.T., Coutifaris C., Carson S.A., Cisneros P., Steinkampf M.P., Hill J.A., et al. Sperm morphology, motility, and concentration in fertile and infertile men. N. Engl. J. Med. 2001;345:1388–1393. doi: 10.1056/NEJMoa003005.
    1. Ostojic S.M., Forbes S.C. Perspective: Creatine, a conditionally essential nutrient: Building the case. Adv. Nutr. 2021;18:nmab111. doi: 10.1093/advances/nmab111.
    1. Visconti P.E. Sperm bioenergetics in a nutshell. Biol. Reprod. 2012;87:72. doi: 10.1095/biolreprod.112.104109.
    1. Wallimann T., Tokarska-Schlattner M., Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids. 2011;40:1271–1296. doi: 10.1007/s00726-011-0877-3.
    1. Nasrallah F., Hammami M.B., Omar S., Aribia H.B., Sanhaji H., Feki M. Semen creatine and creatine kinase activity as an indicator of sperm quality. Clin. Lab. 2020;66 doi: 10.7754/Clin.Lab.2020.191248.
    1. Wallimann T., Moser H., Zurbriggen B., Wegmann G., Eppenberger H.M. Creatine kinase isoenzymes in spermatozoa. J. Muscle Res. Cell Motil. 1986;7:25–34. doi: 10.1007/BF01756199.
    1. Wyss M., Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol. Rev. 2000;80:1107–1213. doi: 10.1152/physrev.2000.80.3.1107.
    1. Banihani S.A., Abu-Alhayjaa R.F. The activity of seminal creatine kinase is increased in the presence of pentoxifylline. Andrologia. 2016;48:603–604. doi: 10.1111/and.12486.
    1. Tombes R.M., Shapiro B.M. Metabolite channeling: A phosphorylcreatine shuttle to mediate high energy phosphate transport between sperm mitochondrion and tail. Cell. 1985;41:325–334. doi: 10.1016/0092-8674(85)90085-6.
    1. Grow D., Oehninger S. Strict criteria for the evaluation of human sperm morphology and its impact on assisted reproduction. Andrologia. 1995;27:325–333. doi: 10.1111/j.1439-0272.1995.tb01367.x.
    1. Patel A.S., Leong J.Y., Ramasamy R. Prediction of male infertility by the World Health Organization laboratory manual for assessment of semen analysis: A systematic review. Arab. J. Urol. 2017;16:96–102. doi: 10.1016/j.aju.2017.10.005.
    1. Lehmann H., Griffiths P.D. Creatine-phosphokinase activity in semen. Lancet. 1963;2:498. doi: 10.1016/S0140-6736(63)90233-2.
    1. Gonzalez Buitrago J.M., Miralles J.M., Muńoz M.H., Meza S., Alonso M.T., Garcia Diez L.C. Seminal plasma creatine kinase activity in fertility studies. Arch. Androl. 1980;5:355–360. doi: 10.3109/01485018008987006.
    1. Asseo P.P., Panidis D.K., Papadimas J.S., Ikkos D.G. Creatine kinase in seminal plasma of infertile men: Activity and isoenzymes. Int. J. Androl. 1981;4:431–439. doi: 10.1111/j.1365-2605.1981.tb00727.x.
    1. Gonzalez Buitrago J.M., Garcia Diez L.C. Enzyme levels in semen of men with different types of azoospermia. Andrologia. 1982;14:77–80. doi: 10.1111/j.1439-0272.1982.tb03099.x.
    1. Srivastava A., Chopra S.K., Dasgupta P.R. Biochemical analysis of human seminal plasma. II. Protein, non-protein nitrogen, urea, uric acid and creatine. Andrologia. 1984;16:265–268. doi: 10.1111/j.1439-0272.1984.tb00281.x.
    1. Huszar G., Corrales M., Vigue L. Correlation between sperm creatine phosphokinase activity and sperm concentrations in normospermic and oligospermic men. Gamete Res. 1988;19:67–75. doi: 10.1002/mrd.1120190107.
    1. Sidhu R.S., Sharma R.K., Agarwal A. Relationship between creatine kinase activity and semen characteristics in subfertile men. Int. J. Fertil. Womens Med. 1998;43:192–197.
    1. Hallak J., Sharma R.K., Pasqualotto F.F., Ranganathan P., Thomas A.J., Jr., Agarwal A. Creatine kinase as an indicator of sperm quality and maturity in men with oligospermia. Urology. 2001;58:446–451. doi: 10.1016/S0090-4295(01)01224-9.
    1. Durutovic O., Lalic N., Milenkovic-Petronic D., Bojanic N., Djordjevic D., Milojevic B., Ladjevic N., Mimic A., Tulic L., Dzamic Z., et al. The correlation of biochemical and morphologic parameters in the assessment of sperm maturity. Urology. 2013;82:1296–1299. doi: 10.1016/j.urology.2013.08.031.
    1. Ghaffari M.A., Rostami M. The effect of cigarette smoking on human sperm creatine kinase activity: As an ATP buffering system in sperm. Int. J. Fertil. Steril. 2013;6:258–265.
    1. Celik-Ozenci C., Tasatargil A., Tekcan M., Sati L., Gungor E., Isbir M., Usta M.F., Akar M.E., Erler F. Effect of abamectin exposure on semen parameters indicative of reduced sperm maturity: A study on farmworkers in Antalya (Turkey) Andrologia. 2012;44:388–395. doi: 10.1111/j.1439-0272.2012.01297.x.
    1. Fakih H., MacLusky N., DeCherney A., Wallimann T., Huszar G. Enhancement of human sperm motility and velocity in vitro: Effects of calcium and creatine phosphate. Fertil. Steril. 1986;46:938–944. doi: 10.1016/S0015-0282(16)49839-0.
    1. Umehara T., Kawai T., Goto M., Richards J.S., Shimada M. Creatine enhances the duration of sperm capacitation: A novel factor for improving in vitro fertilization with small numbers of sperm. Hum. Reprod. 2018;33:1117–1129. doi: 10.1093/humrep/dey081.
    1. Umehara T., Tsujita N., Goto M., Tonai S., Nakanishi T., Yamashita Y., Shimada M. Methyl-beta cyclodextrin and creatine work synergistically under hypoxic conditions to improve the fertilization ability of boar ejaculated sperm. Anim. Sci. J. 2020;91:e13493. doi: 10.1111/asj.13493.
    1. Tapeh R.S., Zhandi M., Zaghari M., Akhlaghi A. Effects of guanidinoacetic acid diet supplementation on semen quality and fertility of broiler breeder roosters. Theriogenology. 2017;89:178–182. doi: 10.1016/j.theriogenology.2016.11.012.
    1. Tøttenborg S.S., Glazer C.H., Hærvig K.K., Høyer B.B., Toft G., Hougaard K.S., Flachs E.M., Deen L., Bonde J.P.E., Ramlau-Hansen C.H. Semen quality among young healthy men taking protein supplements. Fertil. Steril. 2020;114:89–96. doi: 10.1016/j.fertnstert.2020.02.103.
    1. Moore N.P. The distribution, metabolism and function of creatine in the male mammalian reproductive tract: A review. Int. J. Androl. 2000;23:4–12. doi: 10.1046/j.1365-2605.2000.00197.x.
    1. Braissant O., Henry H., Villard A.M., Speer O., Wallimann T., Bachmann C. Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1. BMC Dev. Biol. 2005;5:9. doi: 10.1186/1471-213X-5-9.
    1. 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., Berry M.J., et al. Creatine metabolism in female reproduction, pregnancy and newborn health. Nutrients. 2021;13:490. doi: 10.3390/nu13020490.
    1. Korovljev D., Stajer V., Ostojic S.M. Relationship between dietary creatine and growth indicators in children and adolescents aged 2–19 years: A cross-sectional study. Nutrients. 2021;13:1027. doi: 10.3390/nu13031027.
    1. Korovljev D., Todorovic N., Stajer V., Ostojic S.M. Dietary intake of creatine in children aged 0–24 months. Ann. Nutr. Metab. 2021;77:185–188. doi: 10.1159/000515917.
    1. Dickinson H., Ellery S., Ireland Z., LaRosa D., Snow R., Walker D.W. 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. 2014;14:150. doi: 10.1186/1471-2393-14-150.
    1. Kreider R.B., Kalman D.S., Antonio J., Ziegenfuss T.N., Wildman R., Collins R., Candow D.G., Kleiner S.M., Almada A.L., Lopez H.L. International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. J. Int. Soc. Sports Nutr. 2017;14:18. doi: 10.1186/s12970-017-0173-z.

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