Creatine Overview


1. What is creatine?

Creatine is a naturally occurring compound derived from glycine and arginine and found primarily in the heart, brain, and skeletal muscle. It plays a key role in the body's energy system, and has many secondary roles. The average American gets about one gram of creatine per day from their diet, and one gram is produced in the body. Herring, salmon, tuna, and beef are all high in creatine, but you would have to eat very large amounts of these foods to get the benefits achieved through supplementation. Creatine is used primarily to increase athletic performance, but may also be useful in preventing various conditions affecting the brain, heart, and musculature.

2. What application does creatine have?

Creatine supplementation combined with strength training has been shown to cause dramatic improvements in muscle size and strength. A recent meta-analysis at the Medical College of Wisconsin of sixteen placebo-controlled trials on healthy adults showed creatine supplementation to increase the one rep maximum for bench press by an average of 15.07 lbs. (6.85 kg) and squat by an average of 21.47 lbs. (9.76 kg) with a 95% confidence interval. Additionally, creatine supplementation causes a significant increase in hypertrophy. A study that measured muscle fiber hypertrophy with creatine supplementation for 12 weeks found a 35%, 36%, and 35% increase in Type I, IIA, and IIAB muscle fiber cross-sectional areas, respectively, compared to 11%, 15%, and 6% in the placebo group.

3. How does creatine work?

After being ingested, creatine is absorbed into the bloodstream, most likely by the amino acid transporter (3), and usually reaches a maximum plasma concentration in less than two hours (4). While blood levels are elevated, the creatine transporter (CreaT) actively transports creatine into skeletal muscle, cardiac muscle, and the brain (3). At this point, there are a variety of mechanisms by which creatine may exert its ergogenic effects.
Modulation of energy metabolism - Creatine operates as an energy and pH buffer during exercise. Creatine kinase catalyzes a reaction between free creatine and phosphor ions (from the breakdown of ATP to ADP), resulting in phosphocreatine (PCr), which is locked into the muscle cell due to its strong negative charge. The PCr can then react with ADP to form ATP during exercise, and during rest periods more PCr is generated. All of this equates to more energy during sets and faster recovery between sets.
Increased protein synthesis - Supplementing with creatine has been shown to increase intracellular water retention. Not only does this have the benefit of making the muscles appear larger, it may have an anabolic effect as well. Hyperhydration stimulates protein synthesis and inhibits protein breakdown, and cell volume has a correlation with catabolism in a variety of ailments (6). Numerous studies have confirmed that creatine supplementation prevents protein catabolism (3, 7). There is also evidence that creatine increases satellite cell mitotic activity (8).
• Reduced oxidative stress - In addition to direct effects on energy metabolism and protein synthesis, creatine also has indirect effects on them because it protects against tissue damage, thus increasing the body's ability to regenerate ATP and synthesize protein and protecting against a variety of other harms caused by exercise-induced oxidation. Creatine primarily protects against the peroxynitrite and superoxide free radicals.

4. What are some further benefits of creatine use?

Neuroprotection - Creatine is found in high concentrations in the brain, and is being explored in the treatment of a variety of neurodegenerative diseases. Creatine supplementation increases total creatine levels primarily in grey matter, white matter, the cerebellum, and the thalamus. Similar to its action in skeletal muscle, creatine operates through a variety of pathways in the brain, such as reducing oxidative stress and correcting mitochondrial dysfunction. A recent study on mice and rats showed creatine to provide a 36%-50% reduction in cortical damage caused by traumatic brain injury by improving mitochondrial function, decreasing reactive oxygen species, and maintaining ATP levels. This is a new area of research, so few human studies have been done on its neuroprotectant effects at this point. One study found that supplementation of creatine at 5 grams a day for 8 days decreased task-evoked mental fatigue and increased oxygen utilization in the brain.
Cardiac health - Since creatine is also found in high concentrations in the heart, its activity there has been studied as well. It protects the heart in a variety of ways, and has been shown to reduce the occurrence of arrhythmia, protect cardiac tissue from metabolic stress, and reduce plasma cholesterol and triglycerides.

5. Are there any side effects?

There are very few side effects associated with creatine use. Gastrointestinal discomfort is experienced by some, but generally goes away when dosage is lowered. Weight gain is also a common side effect, however this is mostly water weight (from muscle cell volumization). There are two case reports in the literature of creatine exacerbating renal dysfunction, but multiple studies have shown it to have no impact on healthy individuals. You should consult a doctor before using creatine if you have a kidney disorder.

6. What form of creatine is best?

Since creatine is one of the most popular dietary supplements, many companies have released "better" forms of creatine. These generally have no added advantage, and some of them are much less effective.
Creatine monohydrate - This is the most common form of creatine. It is the kind used in most clinical trials and mixes relatively easily.
Anhydrous creatine - This is creatine without the H2O molecule attached, which is about the only difference. It is about the same price per gram of creatine as creatine monohydrate.
Micronized creatine - This is creatine that has been micronized into smaller particles. It is a good alternative for those who experience gastrointestinal discomfort from using regular creatine.
Tricreatine malate - Tricreatine malate may be more bioavailable than other forms of creatine due to increased water solubility. However, it is currently much more expensive than other creatine products, and the low bioavailability of creatine is generally compensated for by the high dosage. Tricreatine malate is about 75% creatine.
Creatine capsules - These are generally much more expensive than creatine in powder form, and the higher price doesn't justify the added convenience, especially since you generally have to take 5-15 capsules daily.
Liquid creatine - Creatine is not stable in solution and quickly breaks down into its waste product creatinine. An analysis of various creatine products showed that a popular liquid creatine product had less than 2% of the creatine that the label claimed.

7. How should I take creatine?

According to a study measuring 24-hour urinary excretion of creatine and creatinine, resistance-trained athletes can generally utilize about 50 mg/kg of creatine per day (about 3.5-6 grams). Since creatine is so inexpensive and effective, it is generally best to overshoot this mark. Most users choose to supplement with 5-15 grams daily, spread out over 2-3 doses. There are also a variety of ways to increase creatine uptake. Exercise, insulin, thyroid hormone (T3), and IGF-1 all increase the amount of creatine uptake into skeletal muscle. This makes pre- and post-workout ideal times to take creatine. Also, because of the effect insulin has on increasing creatine uptake, it is most effective when mixed with a beverage with a high insulin response. Dextrose is ideal, but any non-acidic beverage with a high sugar (non-fructose) content will do. Grape juice is about 50% dextrose.
• Loading - Many creatine users believe it is beneficial to begin use with a "loading" phase in which 20-30 g is taken over 4-6 doses daily for a few days. The literature on loading is conflicting, and the same level of saturation can be achieved with regular, low-dose supplementation, although it may take longer. The decision is ultimately up to the user, as both methods are effective.
• Cycling - This is the idea of taking a week off of creatine every 8-12 weeks to allow natural production of creatine to return to normal levels. This is done because creatine consumption downregulates the creatine transporter, although levels quickly return to normal upon cessation of use. Whether or not cycling is beneficial is still up in the air, but it is definitely not necessary.

8. What are some good products to take along with creatine?

Although insulin increases muscle creatine uptake, one should avoid taking high amounts of high glycemic foods on a chronic basis as this could lead to insulin resistance. Supplements that increase insulin sensitivity can be very beneficial in this regard. Alpha lipoic acid is probably the best choice, as it is even better than many prescription drugs at improving insulin sensitivity and also has many other beneficial effects. The recommended dosage is 100-200 mg of ALA every time creatine is consumed.

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