Comprehensive Guide to Creatine

CreatineDr. James Meschino DC, MS, ND
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General Features
It is now widely accepted that Creatine supplementation can increase muscle strength and mass.1,2,3,4 Creatine is an amino acid that is stored in muscle in the form of Creatine phosphate. During explosive or intensive exercise, Creatine phosphate is broken down by a specific enzyme to yield Creatine, plus phosphate, plus free energy. The free energy released from the breakdown of Creatine phosphate is used to regenerate ATP, which is the fuel that powers muscle contraction.
The normal daily requirement for Creatine is about 2 grams for a person weighing 70 kg. Animal protein (especially meats) normally provides at least half that amount, with approximately one gram per day synthesized by the liver. A half-pound of raw meat contains about 1 gram of Creatine, but fish is also a good source.
A number of recent studies have demonstrated that short-term Creatine supplementation increases Creatine phosphate stores in skeletal muscle by 10% to 40%.3 This in turn leads to an increase in muscle mass, which is thought to occur from increased protein synthesis, as the muscle lays down an increased number of contractile myofilaments (protein bands that contract and generate force). Increased muscular fluid retention may also participate in muscle volume gains with Creatine use.5,6,7 Creatine has also been shown to provide antioxidant properties. This may be of some significance as free radicals generated from exercise can affect muscle fatigue and protein turnover.
It also appears that Creatine supplementation may allow athletes to train harder (due to increased available energy for muscle concentration), which promotes strength gains, and increases muscle size due to hypertrophy (larger muscle fiber size).
The established protocol for Creatine supplementation used by athletes involves a loading dosage of 20 to 25 grams per day for the first 5 to 7 days. Typically an athlete will mix a heaping teaspoon of Creatine monohydrate crystals into a glass of juice to obtain about 5 grams of Creatine. During the loading phase the athlete does this on 4 or 5 occasions throughout the day to attain an intake of 20-25 grams. After the loading phase is completed, the maintenance daily dosage is usually 5 to 10 grams per day. Recent reports suggest that taking Creatine with glucose (a simple carbohydrate) may increase the amount of Creatine absorbed by the muscles. As such, some manufacturers combine Creatine with carbohydrates in a premix product to help improve Creatine delivery to muscles.
Supplementation Studies and Clinical Applications
1. Increased Strength and Performance In Athletes
Several studies have shown that Creatine supplementation improves performance in repeated bouts of high intensity strength work and repeated sprints, which are requirements for many sports.8,9,10,11,12,13,14,16,17,18 In short, substantial evidence suggests that Creatine supplementation increases lean body mass, muscular strength, and sprint power.
Significant gains in strength and lean mass often occur in the first 6 weeks of Creatine supplementation, when combined with proper training and diet. In one study, college football players who took Creatine supplements for 28 days during resistance and agility training had significant gains in lean mass when compared to players who took the placebo.
Individuals may vary in their response to Creatine supplementation, but it is not uncommon to see a 5 to 10 lb. increase in weight within the first six weeks.
Approximately 80% of Creatine studies have reported a performance-enhancing effect. This is quite impressive when you consider the fact that Creatine is not structurally or functionally related to anabolic steroids, and that Creatine supplements are not banned by the International Olympic Committee or the National Collegiate Athletic Association. Creatine use is based on the same principle as carbohydrate loading in that an athlete is manipulating their dietary intake to optimize muscle Creatine phosphate stores for more explosive power and enhanced performance.
Athletes requiring repeated bouts of explosive power may also benefit from Creatine supplementation as demonstrated by M. Izquierdo et al. Among other positive benefits revealed in their study of nineteen trained athletes, they showed that short-term Creatine supplementation (20 gms per day for 5 days) enhanced repeated sprint performance and attenuated decline in jumping ability after repetitive high-power-output exercise bouts (MRPB).22 Similar results have been documented by G. Cottrell et al, in subjects performing repeated sprint cycling.23 These studies have important implications for many sports such as hockey, basketball, soccer, volleyball, lacrosse, football, tennis and any sport requiring repeated bouts of all-out lower extremity explosive power and/or jumps.
2. Neuromuscular Diseases
Creatine supplementation in humans has been reported to enhance power and strength both in normal subjects and in patients with various neuromuscular diseases.14 Clinical studies in patients with ALS (amyotrophic lateral sclerosis).14 Huntington's disease, Parkinson's disease, Duchenne muscular dystrophy, McArdles disease 15 and Myasthenia Gravis 16 have shown that Creatine supplementation can produce an increase in strength and thus, provide symptomatic treatment and improved quality of life for many of these patients.

3. Heart Failure
Creatine supplementation has been shown to improve exercise capacity in patients with heart failure in some studies. Along with Coenzyme Q10, hawthorn extract and L-carnitine, Creatine is one of few natural health products that is shown to reverse certain parameters of heart failure. As reported by K. Witte et al, there is evidence for a possible role for micronutrient deficiency in heart failure, of which Creatine may be one of the principle factors.

4. Musculoskeletal Rehabilitation
Creatine was shown to speed recovery of muscular power in a double blind, placebo-controlled study involving 20 male and female students whose right legs were immobilized in casts for a period of two weeks. Those given Creatine supplementation during and after leg immobilization displayed more muscular power and greater muscle size after three to ten weeks of physical rehabilitation than did subjects who took the placebo.

5. Anti-Aging in Older Subjects
Creatine supplementation provided to active subjects over 70 years of age, and subjects 59-72 years of age, have resulted in significant gains in several indices of muscle performance including increased maximal dynamic and isometric strength, lower body mean power, lower extremity functional capacity, increased fat-free mass, increased lean mass and endurance power. These studies suggest that Creatine supplementation may help to forestall or reverse muscular atrophy and progressive weakness that occurs during aging, and that Creatine may be useful as an intervention to improve the ability of certain elderly individuals to perform functional living tasks, decreasing dependency and, enhancing their quality of life.
Other studies have noted that younger individuals respond to Creatine supplementation more efficiently than do older subjects in that muscular phosphocreatine stores were shown to increase on average by 35% in young subjects (~24 years of age) and 7% in older subjects (~70 years of age) after five days of Creatine supplementation (20 gms per day). As such, it may take a longer period to maximize Creatine stores in older subjects with Creatine supplentation.
Absorption and Utilization
Creatine absorption from the intestinal tract is very efficient. Studies show that a 6-8 gm oral load of Creatine results in approximately 50% of the ingested Creatine being excreted in the urine. Thus, researchers are still working to identify the ideal single, daily and cumulative doses of Creatine for various applications.26 Other studies demonstrate that a 5 gm oral load of Creatine, followed by 93 gm oral load of simple carbohydrate in solution ( water ) at 30 minutes post-Creatine intake (4-times per day), resulted in a 60% increase in total muscle Creatine compared to subjects ingesting the same amount of Creatine in the absence of a simple carbohydrate drink. Subjects ingesting Creatine and the simple carbohydrate drink had higher insulin levels and significantly less Creatine lost in their urine, indicating that higher insulin levels are likely a key to greater muscle uptake and utilization of Creatine, and a reduction in urinary loss. Thus, it is accepted that Creatine utilization is enhanced by concurrent ingestion of a simple carbohydrate drink (e.g. fruit juice).
Additionally, concurrent administration of Creatine and glycogen reveal that Creatine supplementation enhances muscle levels of glycogen (glycogen supercompensation) beyond that attainable from glycogen loading alone. As supercompensation of muscle glycogen is also an ergogenic factor in exercise performance, the combination of Creatine and carbohydrate loading appear to improve performance by increasing muscle Creatine and muscle glycogen.

Dosage and Standardized Grade (2:1 powdered extract)
1. Athletic Performance (strength, sprint and repeated sprint power, lean mass etc.) - The usual protocol is 5 gm, 4-5-times per day for five consecutive days during the loading phase, followed by 5 gm, twice daily as the maintenance dose. Many athletes cycle one month on, one month off to prevent any possibility of toxicity and to prevent the body from compensating by reducing its own endogenous synthesis of Creatine in the liver.28,22,23,26,27
2. Neuromuscular Diseases / Amyotrophic Lateral sclerosis - One study used 20 gm per day in 5 gm divided doses for 7 days, followed by 3 gm per day for 3-6 months.14 This dose may be appropriate for all neuromuscular diseases mentioned above in regards to adult supplementation, 34 although one patient with myasthenia gravis demonstrated significant improvement with 5 gm of Creatine per day combined with resistance training, 3 times per week.16 In McArdles disease, a daily dose of Creatine of approximately 10 gm per day, followed by a maintenance dose of approximately 4 gm per day has been used successfully to increase muscular strength. 35
Other researchers have shown that a daily adult dose of 10 gm of Creatine per day, and a daily dose of 5 gm of Creatine for children, have been beneficial for individuals with various muscular dystrophies.39,40
3. Heart Failure - A daily dose of 20 gm of Creatine per day, in 5 gm divided doses, has shown good results over the 5-10 day test period. Participants showed improvement in strength, endurance and improved skeletal function upon exertion.17,36,37
4. Musculoskeletal Rehabilitation During and After Immobilization - Same dose as for athletic performance.18
5. Anti-aging in Older Patients - Same dose as for athletic performance.
Adverse Side Effects, Toxicity and Contraindications
As for the safety of Creatine supplementation, a 1997 study showed that short-term Creatine use (20 grams per day for 5 days) did not increase markers of kidney stress in five healthy men.13 A study comparing Creatine users, for up to five years duration, to control subjects has shown that Creatine users have no remarkable differences in their Creatine,urea, and plasma albumin clearances compared to controls. The researchers conclude that neither short-term, medium-term, nor long-term oral Creatine supplements induce detrimental effects in the kidney of healthy individuals.29,30,31 To date no liver abnormalities have been evident in short-term Creatine challenge studies.30 However, individuals with pre-existing kidney disease should be cautious as evidenced by the development of kidney dysfunction in a 25 year old soccer player taking Creatine who previously had been treated for focal segmental glomerulosclerosis of the kidney. His kidney function returned to normal after discontinuing Creatine supplementation.
Some experts suggest that compulsory regular kidney and liver monitoring should accompany the use of Creatine due to the increased burden placed upon the liver and kidneys.30 As pointed out by other experts, Creatine is normally found in cardiac muscle, brain, and testes, as well as skeletal muscle, and these former tissues have been largely unstudied with respect to the effects of Creatine supplementation.32 The Food and Drug Administration (FDA) has advised athletes to consult a physician or a health care professional before embarking on any scheme of Creatine loading or supplementaion.28 Nevertheless, few reported adverse side effects from Creatine use have been reported despite its widespread use among young athletes, with Creatine sales reaching $200 million in the U.S. in 1998.
Other infrequently reported side effects include gastrointestinal disturbances and muscle cramps.
In regards to children and younger athletes, the safety of Creatine supplementation has not yet been investigated in these individuals. Until all safety issues have been evaluated, experts strongly recommend against use of Creatine among children and adolescent athletes.
Overall, Creatine supplementation appears to be safe for healthy adults. It's a low molecular weight compound that is excreted in the kidneys by simple diffusion. In the maintenance phase, athletes consume only slightly more Creatine (3-5 gm per day) than is generally found in the diet, which is usually about 2 gm per day.
Drug-Nutrient Interactions
There are no well-known drug-nutrient interactions for Creatine at this time.
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the developing fetus and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement. Any supplementation practices beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium and the treatment of preeclampsia.)

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