Creatine is one of the most popular supplements available to recreational and high performance athletes alike. In this installment of the Mitochondria Blog, we ask the question: Does it deliver?

What is Creatine?

Creatine represents an organic acid derived from the amino acids arginine and glycine that can carry a high energy phosphate group (forming phosphocreatine). Creatine is found in serum and most tissues. The molecule functions as an energy reserve to provide a source of energy similar to ATP in times of need.

Chemical Structure of Creatine Monohydrate

Creatine represents a widely used supplement and has been available for a number of years. It has also been intensely studied with regard to its potential as an ergogenic substance, aiding endurance, performance and recovery in both human and animal studies.

Supplementation has been shown to be safe (J Am Coll Nutr. 1998 Jun;17(3):216-34) and correlates with increased tissue concentrations (J Sports Sci. 1996 Apr;14(2):175-9), but does creatine it deliver on the promise of improved athletic ability and performance? An examination of published, peer-reviewed, publications follows.

Studies in which Creatine Supplementation Demonstrated Positive Effects

Creatine boosts intracellular phosphocreatine levels and can act as an energy reserve compound improving athletic performance7, 33 when provided at therapeutically significant doses and these claims have been in part substantiated by in vitro muscle cell culture studies (J Int Soc Sports Nutr. 2010 Feb 4;7(1):9. doi: 10.1186/1550-2783-7-9).
A placebo controlled – double blinded - investigation assessing trained male sprinters athletes indicated a meaningful improvement in power output in the athletes (Int J Sport Nutr Exerc Metab. 2015 Jun;25(3):298-306. doi: 10.1123/ijsnem.2014-0146.)
Endurance and recovery has been shown to be improved by supplementing with creatine, and supplementation may increase muscle mass (Essays Biochem. 2008;44:85-98. doi: 10.1042/BSE0440085.)
For runners, improved anaerobic performance, but not aerobic power was documented (Nutr Res. 2010 Sep;30(9):607-14. doi: 10.1016/ j.nutres. 2010.09.004).
Creatine was shown to improve endurance training when used at 10 grams per day (J Strength Cond Res. 2009 Sep;23(6):1663-9. doi: 10.1519/ JSC. 0b013e3181b1fd1f), but no further benefits were achieved in elite cyclists by supplementing at a dosage greater than 100 g per day (J Sports Sci Med. 2003 Sep 1;2(3):88-97. eCollection 2003).
Interestingly muscle hand strength was significantly improved by creatine when provided in the form of creatine pyruvate or creatine citrate, but it would be important to investigate the contribution of the pyruvate and citrate components alone in the strength augmentation effect. (J Int Soc Sports Nutr. 2008 Feb 13;5:4. doi: 10.1186/1550-2783-5-4).
Finally, creatine has been correlated with positive muscular performance and the attainment of lean body mass (J Am Coll Nutr. 1998 Jun;17(3):216-34), but the response if variable and personalized (Eur J Appl Physiol. 2004 May;91(5-6):628-37. Epub 2003 Dec 18; J Am Diet Assoc. 1997 Jul;97(7):765-70).

Studies in which Creatine Supplementation Demonstrated Some Positive Effects

High intensity interval training was not significantly impacted by creatine supplementation, but may influence sub-maximal performance augmentation when used at a concentration of at least 10 grams per day for four weeks.
(J Int Soc Sports Nutr. 2009 Nov 12;6:18. doi: 10.1186/1550-2783-6-18).
Swimmers, benefit when performing some stokes but not others (J Sports Sci Med. 2006 Mar 1;5(1):10-24).
In vitro studies suggest that initial performance improvement may be an indirect effect resulting from the change in ionic balance within muscle fibers (Am J Physiol Cell Physiol. 2004 Dec;287(6):C1589-95. Epub 2004 Jul 28.)
Rowers experienced non-statistically significant improvement in performance (J Sports Sci. 1996 Apr;14(2):175-9)

Studies in which Creatine Supplementation Demonstrated No Effect

Mortelmans et al., 2010 assessed athletic performance in non-athletes who were cardiac patients and was unable to show an improved effect, but no unwanted negative effects were observed indicating the supplement was safe (Clin Rehabil. 2010 Nov;24(11):988-99. doi: 10.1177/0269215510367995. Epub 2010).
In untrained exercised individuals, for example patients with chronic obstructive pulmonary disease, no benefit was observed by oral administration of creatine (Int J Chron Obstruct Pulmon Dis. 2006;1(4):445-53) but in “exercised” Parkinson’s disease patients performance enhancement was observed. (Neurorehabil Neural Repair. 2007 Mar-Apr;21(2):107-15).
An additional study assessing sprinting performance indicated that creatine does not have an ergogenic effect and the supplemented athletes experienced no significant improvement (Eur J Appl Physiol. 2001 Mar;84(3):238-43) while a different study only noted a positive effect with repeated sprinting type activities as seen with well-trained handball players (Jpn J Physiol. 2000 Apr;50(2):273-6)
Quarter horses – oral dosing demonstrated no improvements to any of the performance indicators studied when provided at 28 grams/100 kg doses (J Anim Physiol Anim Nutr (Berl). 2016 Jun;100(3):513-9. doi: 10.1111/jpn.12411).

Studies in which Creatine Supplementation Demonstrated Cautionary or Undesirable Effects

Taekwondo athletes dosed at 50 mg/kg body weight (a relatively moderate dose) showed no improvements in performance but exhibited a fat mass increase without improvement in anaerobic power. The researchers concluded that supplementation was safe, but could increase total body fat indicies (Nutr Hosp. 2013 Mar-Apr;28(2):391-9. doi: 10.3305/nh.2013.28.2.6314)
A creatine dose of 25 g per day given to high intensity athletes were shown to have a significant weight gain, relative to athletes receiving a carbohydrate supplement, although both groups experienced improved performance (J Strength Cond Res. 2008 Jul;22(4):1081-6. doi: 10.1519/JSC.0b013e31816a58c6).

Conclusion: Does Creatine Deliver?

Creatine appears to be a safe, well tolerated, supplement but performance improvement may be dependent on dosing regime and the type of activity the athlete is partaking in. However, there may be negative effects that include increased body fat mass and weight gain in higher doses.

Creatine Supplementation – Does it deliver?