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Creatine Monohydrate

What does it do? Creatine (creatine monohydrate) is used in muscle tissue for the production of phosphocreatine, an important factor in the formation of ATP, the source of energy for muscle contraction and many other functions in the body.¹ ² Creatine monohydrate supplementation increases phosphocreatine levels in muscle, especially when accompanied by exercise or carbohydrate intake.³ ⁴ It may also increase exercise-related gains in lean body mass,⁵ ⁶ ⁷ though how much of these gains represents more muscle and how much is simply water retention is unclear.⁸

Most, though not all, controlled studies have shown that 20 grams per day of creatine monohydrate for five to six days in sedentary or moderately active people improves performance and delays muscle fatigue during short-duration, high-intensity exercise such as sprinting and weight lifting.⁹ ¹⁰ ¹¹ However, outcomes for trained athletes in competitive situations have not been consistent.¹² ¹³ ¹⁴ Creatine supplementation does not appear to increase endurance performance and may impair it by contributing to weight gain.¹⁵ Improvements in exercise performance after creatine supplementation are strongly dependent on the extent of muscle retention of creatine during supplementation. About 30% of people who take creatine supplements fail to retain significant quantities in the muscle.¹⁶ ¹⁷ Only one controlled study has been done to evaluate the long-term (over one month) effects of creatine monohydrate supplementation;¹⁸ more research is needed.

Creatine supplementation has been reported to improve strength in rare diseases of muscle and energy metabolism.¹⁹ ²⁰ ²¹ For people with congestive heart failure, intravenous creatine has been found to improve heart function, but oral supplementation has not been effective, though skeletal muscle function does improve.²² ²³

A double-blind, placebo-controlled study found that a supplement of 5 grams of creatine plus 1 gram of glucose taken four times per day for five days followed by twice a day for fifty-one days significantly lowered serum total cholesterol and triglycerides, but did not change either LDL or HDL cholesterol, in both men and women.²⁴

Where is it found? Creatine is produced naturally in the human liver, pancreas, and kidneys. It is concentrated primarily in muscle tissues, including the heart. Animal proteins, including fish, are the main source of the 1–2 grams per day of dietary creatine most people consume. Supplements in the form of creatine monohydrate are well absorbed and tolerated by the stomach.

Creatine monohydrate has been used in connection with the following conditions (refer to the individual health concern for complete information):

Ranking

Health Concerns

Secondary

Athletic performance (for high-intensity, short-duration exercise)

Other

Congestive heart failure

High cholesterol

High triglycerides

Who is likely to be deficient? Individuals involved in intense physical activity, especially those limiting their intake of red meat, may have low muscle stores of creatine. Several muscle diseases, as well as rheumatoid arthritis, and chronic circulatory and respiratory diseases, are associated with lowered creatine levels.²⁵

How much is usually taken? Two methods are used for supplementing with creatine. In the loading method, 20 grams of creatine per day (in four divided doses mixed well in warm liquid) are taken for five to six days.²⁶ Muscle creatine levels increase rapidly, which is beneficial if a short-term rise in force is needed, such as during a weight-lifting competition, football game, or sprinting.

In the other method, 3 grams of creatine monohydrate per day are taken over an extended training period of at least four weeks, during which muscle creatine levels rise more slowly, eventually reaching levels similar to those achieved with the loading method.²⁷ Smaller daily amounts of 2–5 grams may be adequate for maintaining elevated muscle creatine concentrations, but whether this is effective for producing long-term improvements in athletic performance is unclear.²⁸ ²⁹ ³⁰ Taking creatine with sugar appears to maximize muscle uptake.³¹ ³²

Caffeine intake should not be excessive, as large amounts may counteract the benefits of creatine supplementation.³³

Are there any side effects or interactions? Little is known about long-term side effects of creatine, but no consistent toxicity appears in most reports of creatine supplementation. In a study of dosing habits and side effects of creatine, diarrhea was the most commonly reported adverse effect of creatine supplementation, followed by muscle cramping.³⁴ Some reports show that kidney, liver, and blood functions are not affected by short-term higher amounts³⁵ ³⁶ or long-term lower amounts (10 grams per day for up to 51 days)³⁷ ³⁸ of creatine supplementation in healthy young adults. In a study of nine people take 5–30 grams per day, no change in kidney function appeared after up to five years of supplementation.³⁹ However, interstitial nephritis, a serious kidney condition, developed in an otherwise healthy young man supplementing with 20 grams of creatine per day.⁴⁰ Improvement in kidney function followed avoidance of creatine. Details of this case strongly suggest that creatine supplementation triggered this case of kidney disease. Creatine supplementation may also be dangerous for people with existing kidney disease; a patient with nephrotic syndrome developed glomerulosclerosis, another serious kidney condition, while taking creatine, which reversed when the supplement was discontinued.⁴¹

Muscle cramping after creatine supplementation has been anecdotally reported in three studies⁴² ⁴³ ⁴⁴

At the time of writing, there were no well-known drug interactions with creatine monohydrate.

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References:

1. Greenhaff PL, Bodin K, Soderlund K, et al. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994;266:E725–30.

2. Greenhaff PL. Creatine and its application as an ergogenic aid. Int J Sport Nutr 1995;5:94–101.

3. Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 1992;83:367–74.

4. Green AL, Simpson EJ, Littlewood JJ, et al. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand 1996;158:195–202.

5. Stone MH, Sanborn K, Smith LL, et al. Effects of in-season (5-weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players. Int J Sport Nutr 1999;9:146–65.

6. Earnest CP, Snell PG, Rodriguez R, et al. The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 1995;153:207–9.

7. Stout JR, Eckerson J, Noonan D, et al. The effects of a supplement designed to augment creatine uptake on exercise performance and fat-free mass in football players. Med Sci Sports Exerc 1997;29:S251.

8. Kreider RB, Ferreira M, Wilson M, et al. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc 1998;30:73–82.

9. Toler SM. Creatine is an ergogen for anaerobic exercise. Nutr Rev 1997;55:21–5 [review].

10. Greenhaff PL. The nutritional biochemistry of creatine. J Nutr Biochem 1997;8:610–8 [review].

11. Greenhaff PL, Casey A, Short AH, et al. Influence of oral creatine supplementation on muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci 1993;84:565–71.

12. Mujika I, Padilla S. Creatine supplementation as an ergogenic aid for sports performance in highly trained athletes: a critical review. Int J Sports Med 1997;18:491–6.

13. Grindstaff PD, Kreider R, Bishop R, et al. Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers. Int J Sports Nutr 1997;7:330–46.

14. Peyrebrune MC, Nevill ME, Donaldson FJ, et al. The effects of oral creatine supplementation on performance in single and repeated sprint swimming. J Sports Sci 1998;16:271–9.

15. PD, Harridge SDR, Soderlund K, et al. Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 1993;149:521–3.

16. Greenhaff PL, Bodin K, Soderlund K, et al. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994;266:E725–30.

17. Casey A, Constantin-Teodosiu D, Howell S, et al. Creatine supplementation favorably affects performance and muscle metabolism during maximal intensity exercise in humans. Am J Physiol 1996;271:E31–E37.

18. Stout JR, Eckerson J, Noonan D, et al. The effects of a supplement designed to augment creatine uptake on exercise performance and fat-free mass in football players. Med Sci Sports Exerc 1997;29:S251.

19. Tarnopolsky MA, Roy BD, MacDonald JR. A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle & Nerve 1997;20:1502–9.

20. Sipila I, Rapola J, Simell O, et al. Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. New Engl J Med 1981;304:867–70.

21. Tarnopolsky M, Martin J. Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology 1999;52:854–7.

22. Andrews R, Greenhaff P, Curtis S, et al. The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure. Eur Heart J 1998;19:617–22.

23. Gordon A, Hultman E, Kaijser L, et al. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 1995;30:413–8.

24. Earnest CP, Almada AL, Mitchell TL. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci 1996;91:113–8.

25. Silber ML. Scientific facts behind creatine monohydrate as a sports nutrition supplement. J Sports Med Phys Fitness 1999;39:179–88 [review].

26. Greenhaff PL. The nutritional biochemistry of creatine. J Nutr Biochem 1997;8:610–8.

27. Hultman E, Soderlund K, Timmons J, et al. Muscle creatine loading in man. J Appl Physiol 1996;81:232–7.

28. Aaserud R, Gramvik P, Olsen SR, Jensen J Creatine supplementation delays onset of fatigue during repeated bouts of sprint running. Scand J Med Sci Sports 1998;8:247–51.

29. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997;83:2055–63.

30. Bermon S, Venembre P, Sachet C, et al. Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults. Acta Physiol Scand 1998;164:147–55.

31. Green AL, Hultman E, Macdonald IA, et al. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in man. Am J Physiol 1996;271:E821–6.

32. Feldman EB. Creatine: a dietary supplement and ergogenic aid. Nutr Rev 1999;57:45–50.

33. Vandenberghe K, Gills N, Van Leemputte M, et al. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996;80:452–7.

34. Juhn MS, O’Kane JW, Vinci DM. Oral creatine supplementation in male collegiate athletes: a survey of dosing habits and side effects. J Am Diet Assoc 1999;99:593–5.

35. Sewell DA, Robinson TM, Casey A, et al. The effect of acute dietary creatine supplementation upon indices of renal, hepatic and haematological function in human subjects. Proc Nutr Soc 1998;57:17A.

36. Poortmans JR, Auquier H. Renaut V, et al. Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol 1997;76:566–7.

37. Earnest C, Almada A, Mitchell T. Influence of chronic creatine supplementation on hepatorenal function. FASEB J 1996;10:4588.

38. Almada A, Mitchell T, Earnest C. Impact of chronic creatine supplementation on serum enzyme concentrations. FASEB J 1996;10:4567.

39. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 1999;31:1108–10.

40. Koshy KM, Griswold E, Schneeberger EE. Interstitial nephritis in a patient taking creatine. N Engl J Med 1999;340:814–5 [letter].

41. Pritchard NR, Kaira PA. Renal dysfunction accompanying oral creatine supplements. Lancet 1998;351:1252–3 [letter].

42. Hultman E, Soderlund K, Timmons J, et al. Muscle creatine loading in man. J Appl Physiol 1996;81:232–7.

43. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997;83:2055–63.

44. Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation: a critical review. Clin J Sport Med 1998;8:298–304 [published erratum appears in Clin J Sport Med 1999;9:62].