European Journal of Nutrition

, Volume 53, Issue 1, pp 61–71 | Cite as

Contribution of creatine to protein homeostasis in athletes after endurance and sprint running

  • Fu-Chun TangEmail author
  • Chun-Chen Chan
  • Po-Ling Kuo
Original Contribution



Few studies have focused on the metabolic changes induced by creatine supplementation. This study investigated the effects of creatine supplementation on plasma and urinary metabolite changes of athletes after endurance and sprint running.


Twelve male athletes (20.3 ± 1.4 y) performed two identical (65–70 % maximum heart rate reserved) 60 min running exercises (endurance trial) before and after creatine supplementation (12 g creatine monohydrate/day for 15 days), followed by a 5-day washout period. Subsequently, they performed two identical 100 m sprint running exercises (power trial) before and after 15 days of creatine supplementation in accordance with the supplementary protocol of the endurance trial. Body composition measurements were performed during the entire study. Plasma samples were examined for the concentrations of glucose, lactate, branched-chain amino acids (BCAAs), free-tryptophan (f-TRP), glutamine, alanine, hypoxanthine, and uric acid. Urinary samples were examined for the concentrations of hydroxyproline, 3-methylhistidine, urea nitrogen, and creatinine.


Creatine supplementation significantly increased body weights of the athletes of endurance trial. Plasma lactate concentration and ratio of f-TRP/BCAAs after recovery from endurance running were significantly decreased with creatine supplementation. Plasma purine metabolites (the sum of hypoxanthine and uric acid), glutamine, urinary 3-methylhistidine, and urea nitrogen concentrations tended to decrease before running in trials with creatine supplements. After running, urinary hydroxyproline concentration significantly increased in the power trial with creatine supplements.


The findings suggest that creatine supplementation tended to decrease muscle glycogen and protein degradation, especially after endurance exercise. However, creatine supplementation might induce collagen proteolysis in athletes after sprint running.


Purine metabolites Glutamine Alanine Hydroxyproline 3-Methylhistidine Urinary urea nitrogen 



This study would not have been possible without the dedication and cooperation of the volunteer athletes. The authors thank Chih-Yun Lin, M.S., R.D. and Jo-Shui Chao, M.S., R.D. for their technical assistance; Charles V. Morr, Ph.D. and Chi-Tang Ho, Ph.D. for their English language editing. The authors are indebted to the National Taiwan Normal University for support of this research.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


  1. 1.
    Paddon-Jones D, Børsheim E, Wolfe RR (2004) Potential ergogenic effects of arginine and creatine supplementation. J Nutr 134(10):S2888–S2894Google Scholar
  2. 2.
    Murray RK (2012) Muscle and the cytoskeleton. In: Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA (eds) Harper’s illustrated biochemistry, 29th edn. McGraw-Hill, New York, pp 608–628Google Scholar
  3. 3.
    Williams M H (2007) Human energy. In: Nutrition for health, fitness and sport, 8th edn. McGraw-Hill, New York, pp 81–110Google Scholar
  4. 4.
    Mujika I, Padilla S (1997) Creatine supplementation as an ergogenic aid for sports performance in highly trained athletes: a critical review. Int J Sports Med 18(7):491–496CrossRefGoogle Scholar
  5. 5.
    Sahlin K, Tonkonogi M, Söderlund K (1998) Energy supply and muscle fatigue in humans. Acta Physiol Scand 162:261–266CrossRefGoogle Scholar
  6. 6.
    Harris RC, Marlin DJ, Snow DH, Harkness RA (1991) Muscle ATP loss and lactate accumulation at different work intensities in the exercising thoroughbred horse. Eur J Appl Physiol 62:235–244CrossRefGoogle Scholar
  7. 7.
    Gropper SS, Smith JL, Groff JL (2009) Protein. In: Advanced nutrition and human metabolism, 5th edn. Wadsworth Cengage Learning, California, pp 179–249Google Scholar
  8. 8.
    Bemben MG, Lamont HS (2005) Creatine supplementation and exercise performance: recent findings. Sports Med 35(2):107–125CrossRefGoogle Scholar
  9. 9.
    Mesa JL, Ruiz JR, Gonzalez-Gross MM, Gutiérrez Sáinz A, Castillo Garzón MJ (2002) Oral creatine supplementation and skeletal muscle metabolism in physical exercise. Sports Med 32(14):903–944CrossRefGoogle Scholar
  10. 10.
    Tang FC (1996) Plasma branched-chain amino acid changes during energetic stress. Nutr Sci J 21:27–36Google Scholar
  11. 11.
    Tang FC (2006) Influence of branched-chain amino acid supplementation on urinary protein metabolite concentrations after swimming. J Am Coll Nutr 25:188–194CrossRefGoogle Scholar
  12. 12.
    Davis JM (1995) Carbohydrates, branched-chain amino acids, and endurance: the central fatigue hypothesis. Int J Sport Nutr 5:S29–S38Google Scholar
  13. 13.
    Newsholme EA, Blomstrand E, Ekblom B (1992) Physical and mental fatigue: metabolic mechanisms and importance of plasma amino acids. Br Med Bul 48(3):477–495Google Scholar
  14. 14.
    Bender DA, Mayes PA (2012) Gluconeogenesis and the control of blood glucose. In: Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA (eds) Harper’s illustrated biochemistry, 29th edn. McGraw-Hill, New York, pp 187–196Google Scholar
  15. 15.
    Candow DG, Little JP, Chilibeck PD, Abeysekara S, Zello GA, Kazachkov M, Cornish SM, Yu PH (2008) Low-dose creatine combined with protein during resistance training in older men. Med Sci Sports Exerc 40(9):1645–1652CrossRefGoogle Scholar
  16. 16.
    Munro HN, Young VR (1978) Urinary excretion of 3-methylhistidine: a tool to study metabolic responses in relation to nutrient and hormonal status in health and disease of man. Am J Clin Nutr 31:1608–1614Google Scholar
  17. 17.
    Haralambie G, Berg A (1976) Serum urea and amino nitrogen changes with exercise duration. Eur J Appl Physiol 36(1):39–48CrossRefGoogle Scholar
  18. 18.
    Vandebuerie F, Vanden Eynde B, Vandenberghe K, Hespel P (1998) Effects of creatine on endurance capacity and sprint power in cyclists. Int J Sports Med 8:2055–2063Google Scholar
  19. 19.
    Garrel DR, Delmas PD, Welsh C, Arnaud MJ, Hamilton SE, Pugeat MM (1988) Effects of moderate physical training on prednisone-induced protein wasting: a study of whole-body and bone protein metabolism. Meta Clin Experi 37:257–262CrossRefGoogle Scholar
  20. 20.
    Prockop DJ, Kivirikko KI (1967) Relationship of hydroxyproline excretion in the urine to collagen metabolism, biochemistry and clinical application. Ann Intern Med 66(6):1243–1266CrossRefGoogle Scholar
  21. 21.
    Zakaria M, Brown PR, Farnes MP, Barker BE (1982) HPLC analysis of aromatic amino acids, nucleosides, and bases in plasma of acute lymphocytic leukemics on chemotherapy. Clin Chim Acta 126:69–80CrossRefGoogle Scholar
  22. 22.
    Mineo I, Kono N, Shimizu T, Hara N, Yamada Y, Sumi S, Nonaka K, Tarui S (1985) Excess purine degradation in exercising muscles of patients with glycogen storage disease types V and VII. J Clin Invest 76:556–560CrossRefGoogle Scholar
  23. 23.
    Ling Y, Wang XY, Yong W, Yuan JQ, Chu XG (2008) Determination of four purines in meat by high performance liquid chromatography. Chin J Anal Chem 36:724–728Google Scholar
  24. 24.
    Butler AR (1975) The jaffe reaction. Identification of the coloured species. Clin Chim Acta 59(2):227–232CrossRefGoogle Scholar
  25. 25.
    Owen JA, Iggo B, Scandrett FJ, Steward CP (1954) The determination of creatinine in plasma or serum and in urine, a critical examination. Biochem J 58:426–437Google Scholar
  26. 26.
    Hickner RC, Dyck DJ, Sklar J, Hatley H, Byrd P (2010) Effects of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race. J Int Soc Sports Nutr 7:26–31CrossRefGoogle Scholar
  27. 27.
    Izquierdo M, Ibanez J, Gonzalez-Badillo JJ, Gorostiaga EM (2002) Effects of creatine supplementation on muscle power, endurance, and sprint performance. Med Sci Sports Exerc 34:332–343CrossRefGoogle Scholar
  28. 28.
    Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gómez AL, Oearson DR, Fink WJ, Kraemer WJ (1999) Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 31:1147–1156CrossRefGoogle Scholar
  29. 29.
    Kraemer WJ, Volek JS (1999) Creatine supplementation: its role in human performance. Clin Sports Med 18:651–666CrossRefGoogle Scholar
  30. 30.
    Volek JS, Kraemer WJ (1996) Creatine supplementation: its effect on human muscular performance and body composition. J Strength Cond Res 10:200–210Google Scholar
  31. 31.
    Greenhaff PL, Bodin K, Söderlund K, Hultman E (1996) Effects of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Acta Physiol Scand 158:195–202CrossRefGoogle Scholar
  32. 32.
    Tarnopolsky MA, Parise G, Yardley NJ, Ballantyne CS, Olatinji S, Phillips SM (2001) Creatine-dextrose and protein-dextrose induce similar strength gains during training. Med Sci Sports Exerc 33(12):2044–2052CrossRefGoogle Scholar
  33. 33.
    Lehmkuhl M, Malone M, Justice B, Trone G, Pistilli E, Vinci D, Haff EE, Kilgore JL, Haff GG (2003) The effects of 8 weeks of creatine monohydrate and glutamine supplementation on body composition and performance measures. J Strength Cond Res 17(3):425–438Google Scholar
  34. 34.
    Ziegenfuss TM, Lowery LM, Lemon PWR (1998) Acute fluid volume changes in men during three days of creatine supplementation. J Exerc Physiol 1(3):1–9Google Scholar
  35. 35.
    Williams MH (2007) Protein: The tissue builder. In: Nutrition for health, fitness and sport, 8th edn. McGraw-Hill, New York, pp 193–236Google Scholar
  36. 36.
    Balsom PD, Ekblom B, Söderlund K, Sjödin B, Hultman E (1993) Creatine supplementation and dynamic high-intensity intermittent exercise. Scand J Med Sci Sports 3:143–149CrossRefGoogle Scholar
  37. 37.
    Balsom PD, Söderlund K, Sjödin B, Ekblom B (1995) Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand 154:303–310CrossRefGoogle Scholar
  38. 38.
    Kamber M, Koster M, Kreis R, Walker G, Boesch C, Hoppeler H (1999) Creatine supplementation, part I: performance, clinical chemistry, and muscle volume. Med Sci Sports Exerc 31:1763–1769CrossRefGoogle Scholar
  39. 39.
    Faria EW, White MT, Coragan C, Faria IE (2000) Effect of oral creatine supplementation on AOD, AT, and blood lactate in oarswomen (Abstract). Med Sci Sports Exerc 32:S559Google Scholar
  40. 40.
    Engelhardt M, Neumann G, Berbalk A, Reuter I (1998) Creatine supplementation in endurance sports. Med Sci Sports Exerc 30(7):1123–1129CrossRefGoogle Scholar
  41. 41.
    Roschel H, Gualano B, Marquezi M, Costa A, Lancha AH (2010) Creatine supplementation spares muscle glycogen during high intensity intermittent exercise in rats. J Int Soc Sports Nutr 7:6–10CrossRefGoogle Scholar
  42. 42.
    Watanabe A, Kato N, Kato T (2002) Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res 42:279–285CrossRefGoogle Scholar
  43. 43.
    Rae C, Digney AL, McEwan SR, Bates TC (2003) Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc R Soc B 270:2147–2150CrossRefGoogle Scholar
  44. 44.
    Bellinger BM, Bold A, Wilson GR, Noakes TD, Myburgh KH (2000) Oral creatine supplementation decreases plasma markers of adenine nucleotide degradation during a 1 h cycle test. Acta Physiol Scand 170:217–224CrossRefGoogle Scholar
  45. 45.
    Beis LY, Polyviou T, Malkova D, Pitsiladis YP (2011) The effects of creatine and glycerol hyperhydration on running economy in well trained endurance runners. J Int Soc Sports Nutr 8:24–32CrossRefGoogle Scholar
  46. 46.
    Costill DL (1972) Physiology of marathon running. JAMA 221:1024–1029CrossRefGoogle Scholar
  47. 47.
    Fudge BW, Westerterp KR, Kiplamai FK, Onywera VO, Boit MK, Kayser B, Pitsiladis YP (2006) Evidence of negative energy balance using doubly labelled water in elite Kenyan endurance runners prior to competition. Br J Nutr 98:59–66CrossRefGoogle Scholar
  48. 48.
    Banister EW, Cameron BJ (1990) Exercise-induced hyperammonemia: peripheral and central effects. Int J Sports Med 11(2):S129–S142CrossRefGoogle Scholar
  49. 49.
    Barsotti RJ (2001) Measurement of ammonia in blood. J Pediatr 138(1):S11–S20CrossRefGoogle Scholar
  50. 50.
    Jowko E, Ostaszewski P, Jank M, Sacharuk J, Zieniewicz A, Wilczak J, Nissen S (2001) Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition 17(7–8):558–566CrossRefGoogle Scholar
  51. 51.
    Parise G, Mihic S, MacLennan D, Yarasheski KE, Tarnopolsky MA (2001) Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol 91(3):1041–1047Google Scholar
  52. 52.
    Tarnopolsky MA, Safdar A (2008) The potential benefits of creatine and conjugated linoleic acid as adjuncts to resistance training in older adults. Appl Physiol Nutr Meta 33(1):213–227CrossRefGoogle Scholar
  53. 53.
    Oliveria SA, Felson DT, Cirillo PA, Reed JI, Walker AM (1999) Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee. Epidemiology 10:161–166CrossRefGoogle Scholar
  54. 54.
    Kennelly PJ, Rodwell VW (2012) Proteins: higher orders of structure. In: Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA (eds) Harper’s illustrated biochemistry, 29th edn. McGraw-Hill, New York, pp 35–47Google Scholar
  55. 55.
    Buford TW, Kreider RB, Stout JR, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J (2007) International society of sports nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr 4:6–12CrossRefGoogle Scholar
  56. 56.
    Kley RA, Tarnopolsky MA, Vorgerd M (2011) Creatine for treating muscle disorders. Cochrane Database Sys Rev 2: CD004760Google Scholar
  57. 57.
    Tarnopolsky MA (2008) Clinical use of creatine in neuromuscular and neurometabolic disorders. Subcell Biochem 46:183–204CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Graduate Institute of Nutritional Sciences and EducationTaipeiTaiwan, ROC
  2. 2.Department of Physical EducationNational Taiwan Normal UniversityTaipeiTaiwan, ROC

Personalised recommendations