Effects of creatine supplementation on oxidative stress profile of athletes

Creatine (Cr) supplementation has been widely used among athletes and physically active individuals. Since the beginning of the 1990s, the estimated Cr consumption in the United States alone has reached approximately 2.5 million kg/year[1], and has been one of the most studied ergogenic resources in recent years[2]. In the last 20 years, many authors have suggested that Cr supplementation may be an effective ergogenic aid for exercise and sports[3].

Although clinical studies of Cr supplementation have speculated the occurrence of side effects[4], extensive literature reviews conducted by the American College of Sports and Medicine[1], and more recently by the International Society of Sports Nutrition[5], concluded that such complications were not actually observed in the analyzed studies and reached a consensus that Cr supplementation is a safe practice when administered within the recommended criteria.

Since the 1980s, accumulating evidence indicates that strenuous exercise or unsystematic physical activity entails an imbalance between free radicals and the antioxidant defense system by significantly rising free radical production, and drastically reducing total antioxidant capacity, leading to oxidative stress as inevitable consequence[6, 7]. Although oxidative stress can manifest itself in different ways, during exercise it often leads to lipid peroxidation, caused mainly by the action of hydroxyl radicals (OH·) on unsaturated lipids[8-11], and to the occurrence of ischemia-reperfusion syndrome.

Indeed, ischemia-reperfusion syndrome is one of the most important problems indentified in the production of free radicals. Resistance training is believed to induce ischemia-reperfusion injury owing to the fact that it combines static and dynamic muscle contraction during the resistance training proportional to the effort required to move the weight. This mechanism promotes a number of important hemodynamic responses, for example, increased systolic and diastolic blood pressure and heart rate with concomitant relative increase in peripheral resistance to blood flow[12]. Since resistance exercises consist of short term and high intensity sessions, their primary energy source is the anaerobic production of ATP. During short-duration, high-intensity exercise, the anaerobic pathways of ATP resynthesis are not always sufficient to meet the energy demands. Therefore, the hydrolysis of ADP to AMP is required, leading to the final hypoxanthine formation.

However, a substantial reperfusion occurs in muscles during the intermediary process, thus creating the appropriate environment for free radical formation from ischemia-reperfusion syndrome[13].

Few studies have been published concerning the relationship between Cr supplementation and free radical-induced oxidative stress. Nevertheless, reported results are controversial and inconclusive. Accordingly, resistance-trained men underwent a 7-day Cr supplementation (20g/day Cr monohydrate) or placebo (PL) supplementation. During supplementation the subjects performed a resistance exercise protocol. Plasma malondialdehyde (MDA) and urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured. Cr supplementation caused a significant increase in athletic performance attenuating the changes observed in the urinary 8-OHdG excretion and plasma MDA, suggesting that Cr supplementation reduced oxidative DNA damage and lipid peroxidation associated to resistance training[14].

On the other hand, adult males performed repeated exhaustive incremental cycling trials and received Cr or placebo supplementation. Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol; blood samples were drawn at resting state 20 minutes after stopping exercises and on the day following the exercise. The results showed that supplementation did not influence lipid peroxidation, resistance of low density lipoprotein to oxidative stress or plasma concentrations of non-enzymatic antioxidants. Heart rate and oxygen uptake responses to exercise were not affected by supplementation, whereby the authors concluded that short-term creatine supplementation does not enhance non-enzymatic antioxidant defenses or protect against lipid peroxidation induced by exhaustive exercise[15].

However, findings about the correlation between Cr supplementation and free radical production could help to understand if increase in intramuscular creatine can reduce the formation of hypoxanthine and prevent ischemia reperfusion syndrome; or if great Cr availability could increase oxidative stress, since more energy is generated. Therefore, the purpose of this study is to verify the effects of Cr supplementation and intense resistance training on muscle strength and oxidative stress of athletes.