The Effects of Creatine Supplementation

John Rendig

Writer’s comment: Unlike many of the papers that I am required to write for classes, my literature review on creatine supplementation as an assignment in English 104E (Scientific Writing) was actually enjoyable. Information about creatine was easy to find and interesting to read. So thorough was my investigation of the subject, I feel like an expert of sorts regarding the pros and cons of creatine supplementation. My paper is something that has not only given me a greater understanding of creatine but, more importantly, also showed me how much fun writing a paper can be.
- John Rendig

Instructor’s comment: I was very pleased by how thoroughly John delved into the topic of creatine supplementation for this literature review. This assignment for English 104E: Scientific Writing only requires a review of six to ten articles, yet John read, digested, and synthesized 16 articles. His initial draft was organized in a way that indicated he had control of the material and was able to put it together logically; often students go astray on this assignment because they just string together summaries of articles. John showed a strong sense of his audience’s needs by grouping the results of the research articles under clear topics.
- Jared Haynes, English Department


The human body uses creatine phosphate to produce ATP, the primary energy supply for working muscles. Creatine phosphate is formed through an enzymatic process from creatine, which is composed of the amino acids arginine, methionine, and glycine. Creatine is produced primarily in the liver, but may also be made in the pancreas and kidneys. Humans both metabolize and synthesize approximately two grams of creatine a day, therefore maintaining homeostasis. Creatine can also be consumed in certain foods. The richest sources are found in animal proteins such as red meat and fish. However, concentrations in these foods are relatively low: one pound of red meat contains about two grams of creatine.
     Researchers have found that supplementing the diet with extra creatine, beyond what the majority of people ingest from their everyday diets, can produce significant effects. Creatine supplementation can have potential benefits on body composition, athletic performance, and disease conditions. However, an optimal protocol for supplementing creatine has not yet been discovered. Creatine supplementation has sound possible short and long term side effects. A greater overall understanding of creatine supplementation will aid individuals and physicians to make better informed decisions about whether or not to use creatine supplements.


     Creatine has dramatic effects on body composition. Subjects who supplemented with creatine increased total body mass and fat-free mass while fat mass remained constant (Kreider et al., 1998; Grindstaff et al., 1997; Volek et al., 1997). Three mechanisms are responsible for this change. First, consuming excess creatine results in greater intramuscular creatine stores (Casey et al., 1996). Water accompanies this excess creatine into muscle cells. Thus, more water can be stored within the muscle. Second, protein synthesis may be enhanced due to the increased muscle cell volume. This enhancement may lead to accumulation of protein within the muscle fiber. Finally, since creatine phosphate produces ATP, the amount of energy stored within the muscle is increased (Casey et al., 1996). This increase may lead to an enhanced capacity for workouts that use ATP as the primary energy source, such as short duration, intense muscle contractions as in weight lifting. Thus, the ability to lift weights may be enhanced. If heavier weights can be lifted, muscle fibers will grow bigger and account for lean tissue gains.
     As a result of its effect on muscle cells, creatine can improve athletic performance. Studies have confirmed that creatine, supplemented in the form of creatine monohydrate, improves performance in high-intensity, intermittent, anaerobic activities (Jones et al., 1999). Sport performances in sprinting, jumping (Bosco et al., 1997), kayaking (McNaughton et al., 1998), ice-skating (Jones et al., 1999) , cycling (Smith et al., 1998), football (Kreider et al., 1998), swimming (Grindstaff et al., 1997), and weight lifting (Tarnopolsky and Martin., 1999; Kreider et al., 1998; Volek et al., 1997) have been enhanced with creatine supplementation. Various mechanisms are responsible for creatine’s effectiveness. Neuromuscular fatigue decreases (Stout et al., 2000), oxygen uptake increases (Rico-Sanz et al., 2000), anaerobic capacity increases, maximum accumulated oxygen deficit increases (Jacobs et al., 1997), and ATP resynthesis increases (Casey et al., 1996). Certainly, creatine supplementation can be beneficial for anyone, athlete or not, participating in high-intensity, intermittent, anaerobic activities.
     Research has shown that in addition to these performance benefits, creatine monohydrate can effectively treat individuals with certain disease and deficiency states. Those with creatine synthesis defects improved dramatically from creatine supplementation. Creatine improved psychomotor retardation, behavioral problems, severe language delays, and mild epilepsy — the presenting symptoms in those with creatine synthesis defects (Van der Knaap et al., 2000; Bianchi et al., 2000). Patients with neuromuscular disease improved as well. Supplementation with creatine increased strength, power, and functionality in neuromuscular disease patients (Tarnopolsky and Martin, 1999). Those with mitochondrial cytopathies also improved with creatine. Supplementation increased performance in both high-intensity anaerobic and aerobic type activities in these individuals (Tarnopolsky et al., 1997). Creatine may even be a future treatment for preventing hyperlipidemia — a common risk factor for heart disease. Research has shown that creatine reduces blood lipids in both men and women (Earnest et al., 1996). Apparently, creatine can be an asset to a wide range of individuals.

Supplementation Protocols

     The amount and duration of optimal creatine supplementation has yet to be discovered. Studies have tried various methods of supplementation, and nearly all have produced excellent results. Most commonly, subjects underwent a ‘loading phase’ of extremely high creatine intake for five days. Subjects ingested 20 grams of creatine per day, in four evenly divided doses of five grams each (Stout et al., 2000; Rico-Sanz et al., 2000; Jones et al., 1999; McNaughton et al., 1998; Smith et al., 1998; Bosco et al., 1997; Poortmans et al., 1997). The rationale for this ‘loading phase’ is to saturate the muscle cell with as much creatine as possible. Ingesting high amounts in the initial five days of supplementation is effective because the enzyme systems that transport creatine into muscle cells are extremely active during this time period. Hence, a greater amount of the ingested creatine is stored in muscle cells. This loading phase is commonly followed by a “maintenance phase” in which five grams of creatine is consumed per day. The purpose of this phase is not to further increase creatine stores, but rather, to maintain the elevated levels already present within the muscle.
     Although most studies follow this protocol, others have used different methods with success. Subjects in some studies ingested glucose with each five gram dose of creatine (Stout et al., 2000; McNaughton et al., 1998; Smith et al., 1998; Kreider et al., 1998; Earnest et al., 1996). The rationale was that glucose stimulates insulin, an anabolic hormone, that shuttles nutrients into muscle cells. Although this method proved effective as well, it is unclear if one method worked more effectively than the other. Though the optimal supplementation protocol has not been discovered, the benefits of creatine are clearly significant regardless of which method is used. Side Effects
     In spite of the extremely high amounts of creatine which are ingested, short-term supplementation does not appear to have any adverse side effects. A recent study tested for detrimental effects on renal responses in men who supplemented with creatine, but no adverse effects occurred (Poortmans et al., 1997). Weight gain due to increased lean body mass, although advantageous in most sports, could be detrimental in some long distance, weight bearing sports such as marathon running. In addition, excess weight, even in the form of lean mass, could be detrimental in sports such as wrestling in which the athlete needs to manage his weight within certain parameters. Anecdotal reports of increased cramping and muscle strains exist, but have not been proven. Although short-term supplementation appears safe and effective, long-term safety has not been thoroughly researched due to the novelty of creatine supplementation.


     Athletes as well as people with creatine synthesis deficiencies may experience excellent results from supplementation. Evidence that creatine may even lower blood lipid levels, however, may be the most beneficial aspect to the general population. By far, heart disease is the greatest cause of mortality in the U.S. Hyperlipidemia is a major risk factor for heart disease. By lowering lipid levels, creatine may help protect individuals from this deadly disease.
     Safety is an important issue when assessing any food or supplement. Although studies suggest that short term supplementation is safe, anecdotal reports of increased cramping and muscle strains are prevalent. It seems logical that creatine supplementation could cause these problems. When muscle cells store extra creatine, more water is drawn into the intercellular space. Too much water inside the cell relative to that which is present in the extracellular space causes cramping. With regard to muscle strains, this also seems like a logical side effect. Creatine allows higher intensity workloads to be performed. The muscles and tendons may be unable to handle this dramatic increase in workload so quickly. More thorough research is necessary to investigate these possible detrimental effects.
     Many questions have yet to be answered regarding creatine supplementation. Does taking creatine with an insulin-releasing carbohydrate such as glucose enable the muscle cell to store more creatine? If so, how much carbohydrate is needed to produce optimal results? What about other nutrients such as chromium, taurine, and lipoic acid, which have been known to enhance insulin release by the pancreas? Would these nutrients enable even greater storage of creatine. Supplementation protocols must be studied to ensure that individuals experience maximum benefits.
     Long term side effects are an unexplored issue that will inevitably be investigated. Presently, creatine supplementation is simply too novel for any long-term effects to be seen. Due to creatine’s popularity and tremendous potential as a supplement, studies of long-term safety should be widespread in the next 20 years. Until then, although creatine has many proven benefits, it should be recognized that the risks have not been fully evaluated.

Literature Cited

Bianchi, M.C., Tosetti, M., Fornai, F., Alessandri, M.G., Cipriani, P., De Vito, G., and Canapicchi, R. (2000), Reversible brain creatine deficiency in two sisters with normal blood creatine level, Ann. Neuro. 47: 511-513.

Bosco, C., Tihanyi, J., Pucspk, J., Kovacs, I., Gabossy A., Colli, R., Pulvirenti, G., Tranquilli, C., Foti, C., Viru, M., and Viru, A. (1997), Effect of oral creatine supplementation on jumping and running performance, Inter. J. Sports Med. 18: 369-372.

Casey, A., Constantin-Teodosiu, D., Howell, S., Hultman, E., and Greenhaff, P.L. (1996), Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans; Amer. J. Physio. 271: 31-37.

Earnest, C.P., Almada, A.L., and Mitchell, T.L. (1996), High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women, Clin. Sci. 91: 113-118.

Grindstaff, P.D., Kreider, R., Bishop, R., Wilson, M., Wood, L., Alexander, C., and Almada, A. (1997), Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers. Inter. J Sport Nutri. 7: 330-346.

Jacobs, I., Bleue, S., and Goodman, J. (1997), Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen deficit, Canadian J. Appl. Phys. 22: 231-243.

Jones, A.M., Atter, T., and Georg, K.P. (1999), Oral creatine supplementation improves multiple sprint performance in elite ice-hockey players. J. Sports Med. and Phys. Fitness 39: 189-196.

Kreider, R.B., Ferreira, M., Wilson, M., Grindstaff, P., Plisk, S., Reinardy, J., Cantler, E., and Almada, A.L. (1998), Effects of creatine supplementation on body composition, strength, and sprint performance. Med. and Sci. in Sports and Exer. 30: 73-82.

McNaughton, L.R., Dalton, B., and Tarr, J. (1998), The effects of creatine supplementation on high-intensity exercise performance in elite performers. Euro. J. Appl. Physio. and Occu. Physio. 78: 236-240.

Poortmans, J.R., Auquier, H., Renaut, V., Durussel, A., Saugy, M., and Brisson, G.R. (1997), Effect of short-term creatine supplementation on renal responses in men, Euro. J. Appl. Physio. 76: 566-567.

Rico-Sanz, J. and Mendez Marco, M.T. (2000), Creatine enhances oxygen uptake and performance during alternative intensity exercise. Med. and Sci. in Sports. and Exer. 32: 379-385.

Smith, J.C., Stephens, D.P., Hall, E.L., Jackson, A.W., and Earnest, C.P. (1998), Effect of oral creatine ingestion on parameters of the work rate-time relationship and time to exhaustion in high-intensity cycling. Euro. I Appl. Physio. and Occu. Physio. 77: 360-365.

Stout, J., Eckerson, J., Ebersole, K., Moore, G., Perry, S., Housh, T., Bull, A., Cramer, J., and Batheja, A. (2000), Effect of creatine loading on neuromuscular fatigue threshold. I Appl. Physio. 88: 109-112.

Tarnopolsky, M. and Martin, J. (1999), Creatine Monohydrate increases strength in patients with neuromuscular disease. Neurology 52: 854-857.

Tarnopolsky, M.A., Roy, B.D., and McDonald, J.R. (1997), A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle and Nerve 20: 1502-1509.

Van der Knaap, M.S., Verhoeven, N.M., Maaswinkel-Mooij, P., Pouwels, P.J., Onkenhout, W., Peeters, E.A., Steockler-1psiroglu, S., and Jacobs, C. (2000), Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect. Ann. Neuro. 47: 540-543.

Volek, J.S., Kraemer, W.J., Bush, J.A., Boetes, M., Incledon, T., Clark, K.L., and Lynch, J.M. (1997), Creatine supplementation enhances muscular performance during high-intensity resistance exercise, J. Amer. Diet. Assoc. 97: 765-770.