A 16-year-old male athlete seeking dietary supplementation advice

Creatine is alpha-methyl guanidinoacetic acid and is a derivative of the amino acids arginine, glycine, and methionine. It is synthesized in the liver, kidney, and pancreas and can be obtained from dietary sources, namely meat and fish. Nearly all creatine is stored in the skeletal muscle, of which two-thirds is in the form of phosphocreatine. Creatine and phosphocreatine participate in the cycle of adenosine-triphosphate (ATP) metabolism in the muscle.

To understand the role of creatine supplementation in muscle strength and function, it is useful to review the role creatine plays in muscle metabolism. The power output of muscles occurs in two stages. An initial surge of power that abates by about 10 seconds is followed by longer-term power that is lower in power output but longer in duration. ATP is used as energy for the initial burst of power, but the total stores are depleted in about 3 seconds, and then the ATP must be replenished. The ATP is broken down into a diphosphate form (ADP), with the broken phosphate bond providing energy. Creatine accepts the released phosphate, producing phosphocreatine. Phosphocreatine also serves as an energy source in turn by breaking the phosphate bond, releasing energy, and returning the phosphate to ADP, creating ATP. Adding the phosphate from phosphocrea- tine to ADP allows a rapid recycling of ATP. However, phosphocreatine is also very quickly used up in the first 10 to 15 seconds of maximal muscle effort.

After the initial surge of power, the muscles begin using glycogen as the source of energy to replenish ATP by means of anaerobic or aerobic gycolysis. At that point, the power output of the muscle tissue has decreased, and ATP is generated as quickly as it is used.

Activities that take advantage of the added initial power of the ATP system are rapid, powerful actions, such as jumping, weight-lifting, or an all-out sprint. Activities requiring power output for more than a few moments rely on glycolysis rather than immediate ATP stores.

The skeletal muscle can normally store about 120 mmol/kg of creatine. In persons with low starting muscle-creatine content, oral loading with creatine supplementation results in an increased storage concentration, but the upper limit is about 150 to 160 mmol/kg [1]. With the use of muscle-tissue biopsy after different creatine-loading regimens to determine creatine concentration, it has been found that total skeletal muscle stores are significantly increased (P <0.05) [2]. One study found that regimens using glucose and creatine were more effective in increasing muscle stores than were either creatine alone or creatine plus exercise [2].

The next important question, of course, is whether this increased storage capacity translates to improved athletic performance. A number of studies have examined various aspects of athletic performance during creatine supplementation. Although the use of various protocols and performance measures makes it difficult to make direct comparisons between the studies, analysis of many of the early data suggest some improvement in muscle power for activities of very short duration. However, more recent studies offer a less tidy picture with conflicting results.

In a study examining the effects of creatine phosphate loading on anaerobic working capacity, a nonsignificant increase of 13-15% in anaerobic working capacity was found after supplementation [3]. In a study reviewing effects on aerobic capacity, the submaximal volume of oxygen utilization (VO2) decreased significantly by 4.8-11.4% with creatine supplementation with cycling workloads of 75 W and 150 W [4]. In a study of men aged 48-72 years that evaluated the effects of isokinetic training with creatine and/or protein supplementation, no added benefit of supplementation was found [5]. In a study of swimmers doing 400-m sprints, results of those given creatine supplementation were compared with those of swimmers given placebo. Supplementation appeared to decrease the sprinting time in the last 50 m (P <0.005) [6]. Yet in a study examining performance during six consecutive maximal speed 60-m races, no significant difference in performance was found between supplementation with creatine treatment versus placebo [7]. In another study of anaerobic sport performance, supplemented athletes did not show improved performance but did show a significant decrease in post-performance fatigue [8]. This sampling demonstrates the variability in the studies: they used different methods of supplementation and testing, they tested athletes and nonathletes in widely different activities, and the study groups generally were small. The variety of designs and results demonstrate the difficulty in determining whether supplementation improves athletic performance.

One general message that does appear to be emerging from the data is the benefits of creatine supplementation are limited in duration and scope. It appears, on the basis of the variable results of the available studies, that non-elite athletes and athletes participating in aerobic exercise do not stand to benefit from supplementation. It is not yet entirely clear who does benefit and what regimens are effective, but one study concluded from the meta-analysis of currently available studies that young male weight-lifters appear to benefit from supplementation [9].

The long-term effects of creatine supplementation are not known, because the results of long-term studies are not yet available. However, a few short-term medical problems appear to be associated with its use.

The main concern is the effect that creatine loading might have on renal function and on heat-related illness. These concerns have been raised because creatine is cleared by the kidneys, and the metabolism of creatine in the muscle results in increased intracellular water, potentially leading to cellular electrolyte imbalances that might be exacerbated by exercise in hot, humid conditions.

In a literature review of the effects of creatine on renal function, it was found that creatinine clearance remained essentially unchanged in young, healthy athletes using creatine supplementation [10]. In a study of persons treated with either creatine or placebo over an average period of 310 days, no differences were seen in serum urea, urine creatinine, or microalbuminuria. It was found that in creatine-treated persons, oedema from water retention was more likely to develop, and 3 of 16 subjects had either severe diarrhoea or nausea from the supplementation [11].

Acute creatine supplementation did not alter the thermo-regulatory response, as determined by core body temperature and skin temperature, for athletes exercising in 39°C weather, but this did not address longer-term supplementation [12].

In conclusion, the long-term benefits and adverse effects of creatine have not been determined. Effects on growth and other parameters in young athletes may exist, and long-term effects on the kidneys are unknown. Unfortunately, even determining short-term benefit is complicated by the variety of the supplementation protocols and performance measures used. Even when studies are available, they are of small study groups, which can confound the data. Ultimately, the data are not yet adequate to allow any conclusions on the safety or benefit of the use of creatine supplementation.