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More Creatine Information1. 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
1. Dempsey RL, Mazzone MF, Meurer LN. Does oral creatine supplementation improve strength? A meta-analysis.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12485548&dopt=Abstract
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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3. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev 2001 Jun;53(2):161-76
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4. Schedel JM, Tanaka H, Kiyonaga A, Shindo M, Schutz Y. Acute creatine ingestion in human: consequences on serum creatine and creatinine concentrations. Life Sci 1999 Oct 29;65(23):2463-70
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5. Saab G, Marsh GD, Casselman MA, Thompson RT. Changes in human muscle transverse relaxation following short-term creatine supplementation. Exp Physiol 2002 May;87(3):383-9
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6. Waldegger S, Busch GL, Kaba NK, Zempel G, Ling H, Heidland A, Haussinger D, Lang F. Effect of cellular hydration on protein metabolism. Miner Electrolyte Metab 1997;23(3-6):201-5 [abstract]
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7. Parise G, Mihic S, MacLennan D, Yarasheski KE, Tarnopolsky MA. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol 2001 Sep;91(3):1041-7
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8. Dangott B, Schultz E, Mozdziak PE. Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int J Sports Med 2000 Jan;21(1):13-6
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9. Lawler JM, Barnes WS, Wu G, Song W, Demaree S. Direct antioxidant properties of creatine. Biochem Biophys Res Commun 2002 Jan 11;290(1):47-52
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10. Sullivan PG, Geiger JD, Mattson MP, Scheff SW. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol 2000 Nov;48(5):723-9 [abstract]
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11. Watanabe A, Kato N, Kato T. Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res 2002 Apr;42(4):279-85 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11985880&dopt=Abstract
12. Rosenshtraukh LV, Anyukhovsky EP, Beloshapko GG, Undrovinas AI, Fleidervish IA, Paju AY, Glukhovtsev EV. Some mechanisms of nonspecific antiarrhythmic action of phosphocreatine in acute myocardial ischemia. Biochem Med Metab Biol 1988 Dec;40(3):225-36 [abstract]
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13. Constantin-Teodosiu D, Greenhaff PL, Gardiner SM, Randall MD, March JE, Bennett T. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase. Br J Pharmacol 1995 Dec;116(8):3288-92 [abstract]
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14. Earnest CP, Almada AL, Mitchell TL. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci (Lond) 1996 Jul;91(1):113-8 [abstract]
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15. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 1999 Aug;31(8):1108-10 [abstract]
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16. Dash AK, Sawhney A. A simple LC method with UV detection for the analysis of creatine and creatinine and its application to several creatine formulations. J Pharm Biomed Anal 2002 Jul 31;29(5):939-45
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17. Burke DG, Smith-Palmer T, Holt LE, Head B, Chilibeck PD. The effect of 7 days of creatine supplementation on 24-hour urinary creatine excretion. J Strength Cond Res 2001 Feb;15(1):59-62
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18. Robinson TM, Sewell DA, Hultman E, Greenhaff PL. Role of submaximal exercise in promoting creatine and glycogen accumulation in human skeletal muscle. J Appl Physiol 1999 Aug;87(2):598-604
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19. Steenge GR, Simpson EJ, Greenhaff PL. Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. J Appl Physiol 2000 Sep;89(3):1165-71
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20. Odoom JE, Kemp GJ, Radda GK. The regulation of total creatine content in a myoblast cell line. Mol Cell Biochem 1996 May 24;158(2):179-88 [abstract]
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21. Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Med 2000 Sep;30(3):155-70 [abstract]
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22. Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med 2000 Aug;34(4):284-8
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