Introduction
 
In 1832, creatine was discovered by Chevreul, a French scientist. Since its discovery, creatine has fascinated scientists with its integral role in skeletal muscle metabolism. A natural substance found in the body that plays a powerful role in energy production and muscular contractions. Recently, creatine supplementation exploded onto the sports scene, showing up in lockers and gym bags in virtually every major sport and physical activity. Athletes use creatine as a dietary supplement to enhance athletic performance and training programs on a daily basis. Just some of the fantastic benefits being reported by athletes and fitness enthusiasts around the world include: more powerful muscle contractions, increased explosiveness, faster muscle recovery, less fatigue, increased weight gain, and increased muscle size. 
 
But as with other substances that enhance performance, along come concerns and criticisms. Creatine is one of the most extensively researched nutrients in sports performance. But creatine is also one of the most misunderstood. Designed to provide an in depth explanation of creatine monohydrate, this booklet will outline creatine's function, benefit, and effectiveness as a dietary supplement, as well as the differences from one product to another. 
 

 
Creatine Monohydrate-The Early Years:
 
After Chevreul's discovery of creatine in 1832, another scientist - Lieberg - confirmed that creatine was a regular constituent of flesh extracted from mammals. His extensive research in 1847 with wild foxes concluded that muscle work involves an accumulation of creatine. Around this time, Researchers Heintz and Pettenkofer discovered a substance in urine called "creatinine". It was speculated that creatinine was from the creatine stored in muscles. 
 
Early in the 20th century scientists were conducting numerous studies with creatine supplementation. It was observed that not all of the creatine ingested by both animals and humans could be recovered in the urine, which suggested that some of the creatine was retained in the body. Researchers Folin and Denis (1912 and 1914) determined that the supplemental creatine had increased the creatine content of the muscle cells. In cats, the increases in muscle tissue was observed to be up to 70% after creatine ingestion. By 1923, Hahn and Meyer had estimated the total creatine content of a 70 kg (154 lb.) male to be approximately 140 grams. 
 
1n 1927, Researchers Fiske and Subbarow discovered "phosphocreatine" which was creatine and phosphate molecules chemically bound together and stored in the muscle tissue. Free form creatine and phosphorylated phosphocreatine are recognized as key intermediates of skeletal muscle metabolism. 
 
Modern research on creatine supplementation has examined the role of creatine in muscle metabolism, the breakdown and resynthesis of adenosine triphosphate (ATP), and phosphocreatine during exercise in humans. It has been determined that phosphocreatine stores in muscle tissue can be increased by more than 20% following a regimen of creatine supplementation. 
 
 
What is Creatine?
 
Creatine is an essential, natural substance required for energy metabolism, muscular movement and human existence. Creatine is as essential to life as protein, carbohydrates, fats, vitamins and minerals. Creatine deficiencies have been associated with certain physical-muscular disorders that can be fatal in humans and animals. 
 
The human body synthesizes creatine from 3 amino acids: glycine, arginine, and methionine. These amino acids are components of protein. In humans, the enzymes involved in the synthesis of creatine are located in the liver, pancreas and kidneys. Creatine can be produced in any of these organs and then transported into the muscle via the bloodstream. Approximately 95% of the total creatine pool is stored in skeletal muscle tissue. The remaining 5% can be found in the heart, brain and testes. As stated earlier, it is estimated that a 70 kg (154 lbs.) male will have a total creatine pool of approximately 140 grams in his body. 
The total creatine pool in humans refers to the combined amount of creatine in its free form and phosphocreatine form. In skeletal muscle tissue, phosphocreatine accounts for two-thirds of the total creatine pool, with free form creatine making up the balance. In the absence of exogenous (from the diet) creatine, the rate of creatine excreted in the form of creatinine has been estimated to be around 1.6% per day in humans. Thus, with a bodyweight of 70kg (154 lbs.) and a total creatine pool of 140 grams, a human will lose approximately 2 grams of creatine per day from normal everyday activity. This turnover of creatine will increase with greater physical activity and must be replaced by the diet or the body's own natural production. 
 
Dietary creatine is found mostly in meat, fish and other animal products. Plants contain only trace amounts. The average daily diet of meats and vegetables contains an estimated creatine level of 1 gram. As only some of the daily requirement of creatine can be attained from diet, the body must synthesize the rest. A vegetarian's daily requirement for creatine can only be achieved by endogenous (from within the body) synthesis via the enzyme GAMT. 
 
The effect of aging on the level of free form creatine and phosphocreatine has been studied by Moller and colleagues at the Karolinska Institute in Stockholm. Interestingly, there were no differences in the total creatine levels between a group of elderly (aged 52 to 79) and young (aged 18 to 36). But the study did reveal that the younger participants had higher phosphocreatine levels than did the older group. Such differences can be attributed to the greater level of activity in the younger group. 
 
Approximate creatine leels in food (grams of creatine per 1000 grams of food source) 
 

How Does Creatine Work?
 
Creatine plays a very powerful role in energy metabolism as a muscle fuel. The immediate energy source for a skeletal muscle contraction is from a molecule called ATP (adenosine triphosphate). All fuel sources, carbohydrates, fats and protein are first converted through various chemical reactions to ATP which is then available as the only molecule the body uses for energy. Everything must be first converted to ATP before it can be used as fuel. 
 
ATP is a simple chemical consisting of one molecule of adenosine and three molecules of phosphate. When ATP releases its energy to fuel muscle contractions, a phosphate group is split off and a new molecule is formed called ADP (adenosine diphosphate). This reaction is reversible by the energy-rich compound phosphocreatine. Phosphocreatine delivers a phosphate group to ADP resynthesizing it back into an ATP molecule, thus making it ready again to release energy to fuel continued muscle contractions. The remaining free form creatine is accumulated in the active muscles and then rephosphorylated back into phosphocreatine. 
 
During a brief period of high intensity exercise, the ATP demand in the working muscles increases significantly to several hundred times higher versus when at rest. High intensity exercise can totally deplete phosphocreatine stores within 10 seconds. The depleted stores of ATP and phosphocreatine must be steadily replenished in order for muscular contractions to continue at peak levels of frequency and intensity. 
 

 
Creatine supplementation:
 
Oral supplementation of creatine monohydrate has been shown in several studies to increase the total creatine pool. Optimum daily dosages varied widely from individual to individual, but not significantly from trained to untrained subjects. One study using a single dosage of 5 grams showed a rise in plasma creatine levels from 50 to 100 µmol/L to over 500 µmol/L within 1 hour after ingestion. And recent studies have examined the administration of creatine monohydrate in varying dosages over different periods of time. 
An initial loading phase of 4 to 6 dosages of 5 grams each for 3 days showed a significant increase in the total creatine pool. But it also showed that there exists an upper limit of creatine which can be stored in muscle. For most subjects, this upper limit seems to be around 160 mmol/kg (kg dm). One recent study concluded that after 6 days of creatine administration of 0.3 grams per day per kilogram of bodyweight maintained maximum total creatine levels for a subsequent 4-week period, during which time the dosage was reduced to 0.03 grams per day per kilogram of bodyweight. 
 
For example, a 70 kg (154lb.) person loading 0.3 grams per day per kg. (21 grams of creatine monohydrate) for six days, followed by a 4 week maintenance phase of 0.03 grams per day per kg. (2.1 grams of creatine monohydrate) per day, may maintain maximum total creatine levels in muscle tissue. 
 
It is currently unclear the mechanisms influencing creatine uptake by the cells from the bloodstream but several factors have been noted that effect creatine uptake. Creatine uptake in exercised muscle has been found to be higher than in non-exercised muscle. So, it may be concluded that a trained muscle will have a greater potential for creatine uptake than a non-trained muscle. Creatine uptake may also be enhanced when administered with a carbohydrate solution. The rise in blood sugar levels causes an insulin reaction, which increases the uptake of glucose into the muscle tissue. The increased release of insulin may also increase the uptake of creatine into the muscle tissue along with glucose. 
 

 
Creatine supplementation and Athletic Performance
 
Creatine supplementation has been shown to enhance the ability to maintain power output during repeated periods of high intensity exercise. Athletes in virtually every sport have reported improved athletic performance. For instance, greater home run production by baseball players, increased strength and power by football players, faster times by sprinters, and longer lasting energy by basketball players. When used properly, most athletes will experience a significant increase in strength and power. 
  
Creatine supplementation in controlled scientific studies in amounts as high as 20 grams per day have been shown to enhance the body's ability to maintain power output during frequent and intense exercise. Sports involving short bursts of energy - like multiple sprint sports - seem to experience the greatest benefit of improved athletic performance. Another benefit of creatine supplementation for athletes may be when high intensity exercise is combined with lower intensity exercise or rest. Team sports such as baseball, basketball, football, hockey and individual sports like wrestling, tennis, track and field and sprinting all consist of short explosive muscle contractions followed by short periods of rest or recovery periods. ATP stores are depleted and replenished by the utilization of the phosphocreatine and creatine stores in the muscle. The greater the total creatine pool, the greater the efficiency of the ATP/CP energy cycle. 
 
 

Creatine supplementation and Muscle Building
 
Creatine supplementation can help the athlete train harder for a longer period of time. Therefore, increased intensity of muscle training will generate faster muscle growth and strength. An example of increased intensity of muscle training can be found in a study done by Conrad Earnest and co-workers. The study was conducted on weight trainers at Texas Southwestern Medical Center and The Cooper Clinic in Dallas, Texas. Creatine supplementation and maximum strength was measured in experienced athletes who consumed 20 grams of creatine per day for 28 days. The average increase in bench press strength was 18 lbs. The average bench press repetitions each athlete could perform at a weight equaling 70% of their 1-rep. maximum increased from 11 reps to 15 reps. The subjects in this study also increased lean mass an average of 3.5 lbs over the 28 day period. Increases in lean muscle tissue verses water retention was observed and attributed to increased muscle overload and greater muscle tissue growth stimulation. 
 

 
At what age can a person start using creatine monohydrate?
 
Generally, there is no age limitation for safe creatine supplementation. In fact, there are some children who suffer from an inborn gene defect called GAMT deficiency. These children are treated with dietary creatine supplementation. The question of safe creatine supplementation for children should be answered by the parent considering creatine. The question of healthy competition and pressure placed on children to improve their athletic performance needs to remain in healthy balance with the spirit of sport and the self confidence the child achieves. The second consideration is in the physical development of the young individual. It is our recommendation that unless prescribed by a medical doctor, creatine supplementation should only be used by adults. Athletes should understand that creatine supplementation is only a part of a training and diet routine, and not a substitute for proper training and dietary habits. 
 
 

Creatine supplementation-Dosages
 
While there have been many creatine supplementation studies done with various dosage amounts, there has not been an exact amount determined to be optimum. Generally the dosage of creatine monohydrate should be as high as necessary, but as low as possible to be effective. The scientific studies with dosages of 5 to 10 grams per day are effective, but many athletes have taken greater than 10 grams per day with no adverse side effects. The body has an upper limit as to how much creatine can be stored in the muscle tissue. Therefore, an initial loading phase is used to fill the creatine pool, followed by a maintenance phase to replenish the lost creatine. A period of no supplementation would allow the body to readjust to synthesizing creatine again after supplementation. 
 
As for general guidelines we recommend for strength athletes the following: 

• 20 grams per day for 3 days
• 5 grams per day for the next 8 weeks
• followed by 4 weeks off with no supplementation
• then repeat the cycle again 

The above dosage amounts are offered as a guideline to loading and maintenance procedures. Until more scientific research is conducted on the varying dosages pertaining to lean body weight and the specific activity performed by the athlete, we do not recommend exceeding the amounts recommended above. Athletes may start a creatine supplementation program with lower dosages and monitor improvements in performance. Remember, more is not necessarily better. Too much creatine will only be excreted in the urine. 
 
 
Are there Side Effects
 
There have been no indications of adverse side effects from long term creatine usage in existing creatine literature. Currently, long term studies are under way to try and measure the effects of long term chronic use. Until these studies are completed, excessive creatine supplementation should not occur. 
 
Creatine that is not stored in the total creatine pool, as either creatine or phosphocreatine, is processed out of the body by the kidneys as creatinine. Creatinine is a natural by-product of creatine production and considered a waste product by the body. Creatine supplementation in excess of the required amount needed to saturate the creatine pool is processed out of the body through the kidneys in the same manner. 
 
 
What about muscle cramps?
 
There has been a great deal of attention to the issue of muscle cramps and creatine usage. It has been proposed by some athletes and sports professionals that there may exist a possible association of creatine supplementation and the increased incidence of muscle cramps. To date, research has not shown association between pure creatine monohydrate supplementation and muscle cramps. The main cause of muscle cramps is an imbalance of the electrolytes, calcium and magnesium in the blood or the muscle tissue stemming from insufficient fluid intake. Thus, creatine monohydrate users should use only creatine monohydrate free of impurities while also consuming a minimum of 2 liters of water per day up to as much as 5 liters per day depending on the duration and intensity of the exercise. 
 
It is possible to prevent muscle cramping by consuming sufficient amounts of fluids and isotonic electrolyte drinks prior to, during, and after exercise. A balanced diet will also contribute trace elements, vitamins and minerals which are key to efficient metabolism and electrolyte balance. The bottom line is that lack of sufficient fluid intake and/or nutritional deficiencies cause cramping, and not creatine at reasonable doses.


Other Medical Uses for Creatine:
 
Creatine is a critical energy intermediary to the production of ATP and muscular energy. It is essential to life because abnormalities or deficiencies may lead to related health problems. Creatine has been researched in several ways that are not sports orientated. Under medical supervision, creatine monohydrate supplementation has been utilized to treat certain physiological and physical disorders as well as being used to help special populations with special needs. For example: 

• Creatine supplementation has shown a positive effect on the reduction of plasma total cholesterol, triacylglycerois and VLDL. 
• Creatine has been found to possess anti-inflammatory activity on acute inflammation, local irritancy and chronic inflammation conditions (i.e. arthritic conditions). 
• The creatine/phosphocreatine system seems to have a protective effect on the nervous system and central nervous system under ischemic and hypoxic conditions. 
• An inborn birth defect call guanidinoacetate-methyltranferase (GAMT) which leads to a creatine deficiency in the brain and correlated to mental and muscular retardation is treated through oral creatine supplementation. 
• Creatine supplementation is used to treat diseases that involve muscle atrophy, creatine depletion and neuro-muscular disorders. 
• Creatine has been used to improve the symptoms of gyrate atrophy, a hereditary and very complex dystrophic eye disease that causes an enzyme inhibition of the creatine bio-synthesis. 
• Creatine is being researched for its possible benefits in inhibiting the growth of certain types of tumors in mammals. 
• Creatine supplementation has been shown to positively effect athletic performance of vegetarians. 
• During chronic heart failure cardiac creatine levels are depressed. Creatine supplementation to patients with chronic heart failure increases skeletal muscle energy-rich phosphocreatine and performance in regards to strength and endurance. 

 
 
Conclusion:
 
Essential to life, health, and well-being, creatine is a unique and somewhat miraculous substance. Scientific studies support the anecdotal testimonials to the improvements in sports performance and overall energy levels. Proper usage can lead to positive effects. The important considerations for all consumers is the safe and proper dosage of a high quality source of creatine. Creatine is a great addition to an athletes training regime and, as researchers may soon show, beneficial for the non-athletes health as well.