Whether you're an accomplished athlete or you've just started an exercise program, you need to know about creatine. Many supplements touted over the years as performance enhancers have come and gone, but creatine is here to stay. I predict that it will be one of the most popular muscle-building nutrients ever made available to you. Why? Because it works. Yes, it really works to increase muscle mass.

Note: Over the past two months I have had reports from three individuals (or family members) who have noted increased aggressiveness and irritability from creatine. A study published in the Nov 29 issue of JAMA reports that some creatine products may have been contaminated with small amounts of androstenedione or other anabolic steriods. Could this account for the irritability and aggressiveness? I don't know for sure at this time.

Q. What is Creatine?
A. When we told our friends that we were writing a book on creatine, some of them had quizzical responses. You're writing on creating? Creating what? Is it an herb?

Creatine is not an herb, mineral, vitamin, hormone, or steroid. Creatine is a natural nutrient found in our bodies and the bodies of most animals. Approximately 95% of the body's creatine supply is found in the skeletal muscles. The remaining 5% is scattered throughout the rest of the body, with the highest concentrations in the heart, brain and testes.

The human body gets most of the creatine it needs from food or dietary supplements. Creatine is easily absorbed from the intestinal tract into the bloodstream. When dietary consumption is inadequate to meet the body's needs, a limited supply can be synthesized from the amino acids arginine, glycine and methionine. This creatine production occurs in the liver, pancreas and kidneys.

Q. How Does Creatine Work?
A. Creatine is an essential player in the primary energy source used for muscle contraction. It exists in two different forms within the muscle fiber: as free (chemically-unbound) creatine and as creatine phosphate. This later form of creatine makes up two-thirds of the total creatine supply. When your muscles contract, the initial fuel for this movement is a compound called ATP. ATP provides its energy by releasing one of its phosphate molecules. It then becomes a different compound called ADP. Unfortunately, there is only enough ATP to provide energy for about 10 seconds, so for muscle contraction to continue, more ATP must be produced. Creatine phosphate comes to the rescue by giving up its phosphate molecule to ADP, recreating ATP. This ATP can then be burned again as fuel for more muscle contraction.

The bottom line is that your ability to regenerate ATP depends on your supply of creatine. More creatine, more ATP remade, and more ability to train your muscles to their maximum potential. It's that simple. This greater ATP synthesis also keeps your body from relying on another energy system called glycolysis, which has lactic acid as a byproduct. This lactic acid creates the burning sensation you feel during intense exercise. If the amount of acid becomes too great, muscle movement stops. But if you keep on using ATP because of all the creatine you have, you can minimize the amount of lactic acid produced and actually exercise longer and harder. This helps you gain strength, power and muscle size; and you won't get fatigued as easily.

Creatine has also been shown to enhance your body's ability to make proteins, especially the proteins within the muscle fibers. Two of these proteins, actin and myosin, are essential to all muscle contraction. So when you build up your supply of these contractile proteins, you actually increase your muscle's ability to perform physical work. And the more work you do (whether it's lifting weights or running 100-meter dashes), the stronger you become over time. Creatine can also absorb intracellular water, thus resulting in a higher muscle volume. This could lead to the "pumped up" feeling and look. An additional way creatine increases muscle size is thought to be its fluid retention abilities within muscle tissue.

Q. Who Can Benefit From Creatine?
A. Although the research on creatine and exercise performance is relatively new, so far it appears that the greatest benefits occur in those who wish to put on muscle mass. Athletes in bodybuilding, powerlifting, martial arts, and track and field events such as javelin and shot-put may benefit due to greater strength. So could wrestlers and football players. We doubt that creatine will be of any benefit for people who comfortably cruise on a cart around the golf course and occasionally get up to putt. Other sports where creatine is not likely to be of any significant benefit include skeet shooting, and certainly billiards. Body builders and anyone who wishes to have more muscle build will find creatine extremely helpful.

It is still unclear whether athletes involved in endurance activities such as marathon running or long-distance bicycling will benefit from creatine supplementation. There have been anecdotal reports that people in these sports may benefit (Stroud, 1994), although other studies show that creatine either does not help or may actually hurt. The difficulty in these situations appears to center on the increased muscle mass which creatine provides. While that's great if you're a bodybuilder or wrestler, it can be a detriment if you have to carry all that weight around during a marathon or triathlon. It becomes a tradeoff between the increased strength you get from creatine and the increased muscle mass. Further research will provide us with more definitive answers as to what role creatine supplementation can play in endurance-type sports.

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 (1). 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 (2).

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 (3).

• Increased protein synthesis - Supplementing with creatine has been shown to increase intracellular water retention (5). 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 (3) 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 (9).

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 (3). 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 (10). 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 (11).

• 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 (12), protect cardiac tissue from metabolic stress (13), and reduce plasma cholesterol and triglycerides (14).

5. Are there any side effects?

There are very few side effects associated with creatine use (3, 22). 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 (3, 15, 21, 22). 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 (16).

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) (17). 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 (18), insulin (19, 20), thyroid hormone (T3) (20), and IGF-1 (20) 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 down regulates the creatine transporter, although levels quickly return to normal upon cessation of use (3). 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.

References 

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2. Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL, Pearson DR, Fink WJ, Kraemer WJ. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 1999 Aug;31(8):1147-56 [abstract]
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