Creatine Monohydrate

To fully understand the use of creatine as an ergogenic aid, one must appreciate its role in energy metabolism. In this regard, a primary objective for students to understand is that skeletal muscle performs mechanical work through the hydrolysis of adenosine triphosphate (ATP). Commonly referred to as the energy currency of a cell,the quantity of ATP present in skeletal muscle is approximately 3 to 5 µmol/kg or 6 mmol/kg of fresh muscle. The continuation of physical work is based on the maintenance of ATP at a rate equal to the rate of its use. Energy reserves consist of intramuscular phosphagen stores (ATP, phosphocreatine [PCr]) and muscle and liver glycogen and adipose stores. The rate and the extent to which these energy sources are used depends on the intensity and/or duration of exercise. To this end, high-intensity anaerobic exercise is supplied almost exclusively by ATP, PCr, and intramuscular glycogen stores.

In a classic series demonstrating the shift of energy usage in skeletal muscle, Hirvonen et al. examined the changes in the intramuscular concentrations of muscle ATP, PCr, and blood lactic acid concentration in sprinters running distances of 40 to 400 meters lasting approximately 4.5 to 50 seconds . Blood lactic acid is a reflection of muscle glycogen usage or glycolysis. Even on casual observation it is interesting to note that despite the increase in running distance, ATP stores initially decline but appear to reach a minimal or critical level after which no further decrease is observed. In contrast, PCr continually and rapidly decreases while the appearance of blood lactic acid or muscle glycogen usage increases. At this point, the reader should embrace two key points. One is to recognize the immediate contribution of all energy systems simultaneously and cooperatively to facilitate energy needs. These energy contributions do not occur sequentially (i.e., one after the other), but instead are time and intensity dependent as to which system dominates. This continued energy production has been conceptualized as a metabolic flux or energy currency that transforms stored energy into muscle contraction.

The maximum work attainable from any energy source can be characterized as both ATP capacity (amount of ATP produced per mole of available substrate) and ATP power (the rate of ATP produced per substrate storage depot). Despite the low intramuscular stores of ATP and PCr within skeletal muscle, their energy production capabilities are exceptional . A review by Sahlin provides an excellent consensus of research findings elaborating on the available energy capacity (mol ATP), maximal ATP power produced from each source (per mmol ATP/kg of dry muscle), as well as the exercise intensity supported and duration of activity allowed per endogenous energy source. It should become readily apparent that events of shorter duration and higher intensity necessitate physical training and nutritional support aimed toward the enhancement of ATP, PCr, and muscle glycogen as opposed to alternative energy sources such as liver glycogen and adipose stores. These sources serve as less adequate sources of ATP power.

Research has shown an improvement in endogenous energy stores of glycogen, PCr, and ATP following 5 months of heavy resistance training although this correlation has not been universally shown. Although changes in resting PCr concentrations might enhance performance during anaerobic activities (e.g., sprinting, weightlifting, etc.), increases in skeletal muscle glycogen may not confer a similar advantage in these types of activities. Strong evidence shows that the dietary manipulation of glycogen stores does not improve various anaerobic performance indices. Also, oral ATP administration does not appear to be prudent owing to the presence of phosphatase enzymes in the blood and gut. These enzymes readily cleave the phosphate portions of ATP. Thus, it appears that oral ATP does not present itself as a suitable ergogenic aid. The same point may be argued for PCr as well. Thus, it is plausible that creatine ingestion may be the best way of augmenting athletic performance vis-a-vis changes in the phosphagen energy system.

One study that examined PCr supplementation showed a performance benefit, albeit to a smaller degree than creatine supplementation. However, any effect of orally ingested PCr would be expected to be mediated by creatine alone because gut phosphatase enzymes would readily cleave off the phosphate portion of the molecule, liberating free creatine in a smaller quantity than when taking the monohydrate form. To date, no human studies have evaluated PCr’s oral absorption and intramuscular uptake. Additionally, blood serum also possesses high phosphatase activity, leading to rapid breakdown of intravenously administered PCr to creatine and phosphate. A study by Peeters et al. determined that PCr-supplemented subjects exhibited a performance response that was approximately 50% less than than that of a creatine monohydrate group. Given that the creatine portion of the monohydrate form makes up about 92% of the molecule and only 50% of the PCr molecule, these results are not surprising. Similarly, although glycolysis is initiated at muscle contraction, increasing glycogen stores may be more advantageous to longer, high-intensity work efforts (>400 m) because of its lower ATP power. These same objectives do not appear to apply to the use of creatine supplementation because both early and more recent studies involving creatine show that it is readily found in food, is absorbed intact, appears rapidly in the blood, and increases intramuscular stores of total creatine and PCr.

Over the years, numerous nutritional supplements have been purported to affect physiological responses to exercise, enhance training adaptations, and/or improve exercise performance. Although research has generally indicated that many of these nutrients do not affect performance, creatine has consistently proven to be one of the most effective nutritional supplements available to athletes. To date, over 200 research studies have evaluated the safety and effectiveness of short- and/or long-term creatine supplementation in various untrained, trained, and diseased populations. The majority of these studies indicate that short-term creatine supplementation (0.3 g/kg/day for 5 to 7 days) increases muscle creatine and phosphocreatine content by 10-30%, has the ability to improve the ability to maintain high-intensity single effort and/or repetitive sprint performance, and may improve work output during repeated sets of muscle contractions. There is also evidence that creatine supplementation may affect exercise bouts involving anaerobic glycolysis (30 to 150 sec) and high-intensity endurance exercise (150 to 600 see). The improved exercise capacity has been attributed to a creatine­stimulated enhancement of the phosphagen energy system, the buffering of acidity, and the shuttling of mitochondrial ATP by phosphocreatine into the cytoplasm. Additionally, long­term creatine supplementation during training (e.g., 0.3 g/kg/ day for 5-7 days followed by 0.03 to 0.3 g/kg/day) has been reported to increase strength, sprint performance, and training volume, and promote greater gains in fat-free mass and muscle fiber diameter. These findings suggest that creatine supplementation may improve the quality of training, leading to greater training adaptations. Although not all studies report ergogenic benefit, it is my view that, with the exception of carbohydrate, creatine is the most effective nutritional supplement for athletes involved in high-intensity exercise bouts that rely on anaerobic energy systems.

Although creatine has been reported to be an effective ergogenic aid, there have been some concerns regarding the medical safety of creatine supplementation. Some reports, primarily in the popular media, suggest that creatine supplementation may adversely affect renal and liver function, cause long-term suppression of creatine synthesis, alter fluid and electrolyte status-promoting dehydration and muscle cramping, and/or increase the incidence of musculoskeletal injury in athletes. Additionally, some have expressed concern regarding possible side effects of long-term creatine use. Note that there is no evidence from well-controlled short­and/or long-term clinical studies (up to 5 yrs) to support any of these concerns. Furthermore, a number of recent studies that have attempted to evaluate the validity of these concerns have found no adverse effects of short- or long-term creatine supplementation on markers of clinical status.

This said, the question still remains as to whether athletes should take creatine to enhance performance. Adolescent athletes involved in serious training should consider creatine supplementation only with the approval and supervision of parents, trainers, coaches, and qualified health professionals. If the athlete plans to take creatine, quality supplements should be purchased from reputable vendors. Athletic administrators in organized sports who want to establish policies on creatine supplementation for teams should base such policies on the scientific literature. Any formal administration policy should be supervised by a qualified health professional. Although more research is needed, available studies indicate that creatine supplementation does not appear to pose a health risk when taken at recommended doses and may provide therapeutic benefits for various medical populations.