Winter 2001 Issue — Latest Research Results add muscle to the use of Creatine in Non-sports Applications

Dr. Ralph Jäger

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The use of Creatine, the most popular sports supplement of the nineties (1) expands in the new millennium to other muscle related applications. Creatine supplementation in combination with exercise benefits the elderly as well as people recovering from muscle disuse speeding up rehabilitation, e.g. after having a cast.

Creatine sources and metabolism

Creatine is naturally occurring in the human body and participates in metabolic reactions within cells and eventually being catabolized to Creatinine in a non-enzymatic reaction and excreted by the kidneys. The total Creatinine store in humans is approximate 140g for the average-sized adult male (70 kg)(2) and the daily turnover rate of Creatine to Creatinine has been estimated to be about 1.6% of the total Creatine pool (2-3g per day.(3)

Only half of the daily requirement is supplied by the diet, the rest must be synthesized within the body from different amino acids. Dairy products contain only small quantities of Creatine (0.1g/kg in milk), whereas high concentrations can be found in raw meat (e.g. beef and pork 5g/kg) and fish (e.g. herring 10g/kg) (2). When meat or fish is cooked, the Creatine content increases.(4) In strict vegetarians, or vegans, dietary Creatine intake is virtually zero and consequently Creatine blood plasma levels are lower.(5) Orally ingested Creatine is absorbed intact from the intestinal lumen and then enters the bloodstream. Plasma Creatine is delivered to various body tissues, including the heart, brain and testes; however the vast majority (app. 94%) is found in the skeletal muscle. Creatine is taking up from the blood against a large concentration gradient by sodium dependent Creatine transporters (CreaT) that spans the plasma membrane. Extracellular Creatine is sequestered into the cytosol, where rapid phosphorylation by the enzyme Creatine Kinase (6) takes place. About 60-70% of the muscle total Creatine content is stored in the form of the high-energy molecule Phosphocreatine that is able to pass through membranes, thus trapping Creatine in the cell.

Inborn errors of the human body's Creatine synthesis (guanidinoacetate methyltransferase (GAMT) deficiency (7) and arginine: glycine amidinotransferase (AGAT) deficiency) as well as defects of the Creatine transporters have been described. The resulting Creatine deficiency, especially in the brain, leads to serious physical and mental underdevelopment and even death. The importance of Creatine for the development of the human body is also reflected by the presence of Creatine in mother's milk. (8)

All cells use ATP as the immediate energy source, but since ATP stores are limited they must be regenerated by metabolic pathways, including anaerobic glycolysis and oxidative metabolism, in order to sustain high power output. Energy is liberated as the phosphate from ATP is enzymatically removed leaving adenosine diphosphate (ADP) and inorganic phosphate. Creatine and its phosphorylated form Phosphocreatine are essential to the regeneration of ATP from ADP. During times of high-energy demand the phosphate from the Phosphocreatine is cleaved off to provide energy for the re-synthesis of ATP. An increase in Creatine and Phosphocreatine content in the cells will increase their capability to re-syntheses ATP under conditions of high energy demand directly translating in more available energy.

Creatine loading and sports nutrition

Creatine supplementation is reported to increase the muscle Creatine content, e.g. the Phosphocreatine content by approximately 20%. A high-dose loading phase of 20g Creatine Monohydrate per day for 5 to 7 days followed by a maintenance phase of 3 to 5g per day is common under athletes. However, 3g per day for 28 days will lead to the same increase in Creatine content in the muscle. A stimulation of the sodium dependent Creatine transporters by insulin either thru high amounts of Carbohydrates (90g),(9) or a combination of Carbohydrates (47g) and Protein (50g) or a combination of Carbohydrates (25g) and alpha-Lipoic Acid (250mg)(10) result in greater muscle Creatine accumulation than Creatine intake alone. However, the Creatine uptake in the muscle is limited and can not be increased to an unlimited amount.

Creatine is one of the best studied supplements in the field of sports nutrition and its proven efficacy as an ergogenic substance and safety was reviewed and accepted by different authorities. (11) Many celebrated professional athletes acknowledge Creatine use, including 1992 Olympic champions Linford Christie (100m dash) and Sally Gunnell (400m hurdles), as well as the Cambridge University rowing team which defeated heavily favoured Oxford in 1993. It was estimated that 80% of the athletes at the 1996 Summer Olympics in Atlanta used Creatine. Mark McGwire, one major league baseball's greatest sluggers, used Creatine during the 1998 season and his legendary race to set the single season home run record, making Creatine the most popular sports nutrition in the US. Today Creatine supplementation has become a common practice among professional, elite, collegiate and amateur athletes to enhance exercise performance.

Creatine's proven effects on the energy metabolism and on muscle mass, strength and performance in combination with exercise is now investigated in different non-sports applications.

The use of Creatine in the mature population

With aging there are decreases in muscle mass, strength and exercise performance.(12) This loss in power during aging makes our daily life more difficult, each physical targets of our youth such as climbing stairs become to be real obstacles. Reduced levels of Phosphocreatine and total Creatine in the skeletal muscle reported in the elderly (13, 15) may be in part responsible for these declines. In addition, resynthesis rates of Phosphocreatine after exercise decline with age by - 8% every 10 years after 30 years of age. (14)

Several studies have been conducted to investigate the effects of Creatine in older persons who may benefit from Creatine supplementation. Tarnopolsky et al. (2001) studied in a double-blind, placebo-controlled clinical trial in the elderly the effects of Creatine supplementation on the Phosphocreatine and total Creatine levels, body composition and strength.(15) 14 elderly men (67.8 ± 4.0 years) and 14 women (69.3 ±6.3 years) took either 5g of Creatine Monohydrate or placebo during a 4month supervised strength-training program. Creatine supplementation resulted in a significant increase in muscle Phosphocreatine and total Creatine, fat-free mass and isometric knee extension strength. Smith et al. (1998) studied the age influence on muscle metabolism during exercise in a placebo-controlled clinical trial.(16) 5 young (31 ± 5.2 years) and 4 elderly (58 ± 4.5 years) men and women took either 0.3g Creatine Monohydrate per kg body weight (21g for 1 70kg person) per day for 5 days or placebo. The elderly group had a significant lower Phosphocreatine levels and a lower Phosphocreatine re-synthesis rate during placebo administration. After taking Creatine Monohydrate for 5 days the Phosphocreatine levels as well as the Phosphocreatine re-synthesis rate increased in the elderly group to a level not different from the young group. Performance during a single-leg knee-extension exercise, measured by time to exhaustion, was increased in both groups combined after Creatine supplementation.

Creatine supplementation is able to restore Phosphocreatine and total Creatine levels and is able to speed up the re-synthesis rate of Phosphocreatine in the muscle of elderly people, which are decreased, compared to the younger population. Creatine supplementation may enhance strength gains and fat-free body mass during strength-training in the elderly.

The use of Creatine in Rehabilitation

Muscle disuse leads to muscle atrophy (decreased muscle volume), reduced muscle force, reduced muscle energy stores and reduced maximal power. The most prominent condition of muscle disuse is immobilization, for example when a broken extremity like a leg or an arm is immobilized in a cast for some period of time. The muscle atrophy is usually clearly visible by a slimming of the leg or arm. Increased mechanical loading of the muscle either by muscle rehabilitation training or by resumption of a normal level of physical activity, reverses the muscle atrophy with time. Creatine's important role in energy metabolism of the muscle raised the question whether Creatine supplementation can reduce the effects on the muscle during immobilization and whether Creatine supplementation can speed up the rehabilitation.

Hespel et al. (2001) studied the effects of Creatine supplementation during muscle disuse and subsequent training in a double-blind placebo-controlled trail.(17) The right leg of 22 healthy young volunteers was immobilized using a cast for 2 weeks after which the subjects participated in a 10-week rehabilitation program (heavy resistance training). During immobilization, muscle Phosphocreatine concentration decreased by 15% in the placebo group and returned to baseline within the first 3 weeks of rehabilitation. In contrast Creatine supplementation negated a decrease of Phosphocreatine and offsets the decline in muscle content during immobilization and led to an increase of 12% Phosphocreatine after the first 3 weeks of rehabilitation. Muscle strength, measured by isometric knee-extension torque, decreased in both groups to the same degree during immobilization, but power output increased at a significant faster rate in the Creatine group during rehabilitation compared to baseline was significantly increased in the Creatine group compared to the placebo group.

It can be concluded that oral Creatine intake reduces the biochemical and structural deterioration of skeletal muscle during disuse. In addition, Creatine supplementation can shorten the duration of muscle rehabilitation following disuse atrophy. There is proof that Creatine supplementation in combination with appropriate training decrease recovery time of muscle disuse atrophy due to any cause. (18)

The use of Creatine in non-musculature applications

The increase of "back up" energy cells by Creatine supplementation is likely to be the scientific explanation for recent reports on the neuroprotective effects of Creatine in different conditions. (19) This new discovery will lead to several new applications for the power supplement Creatine in the near future.

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