In spite of uncontrolled daily dosage and long-term administration, none of the research on creatine monohydrate safety or side effects in humans included standardized protocols of clinical pharmacology and toxicology. The documented side effects induced by creatine monohydrate are weight gain, an influence on insulin production and long-term damages on renal function. A major point that related to the quality of creatine monohydrate products is the amount of creatine ingested in relation to the amount of contaminants that might be found in those products. During the industrial production of creatine monohydrate from sarcosine and cyanamide, variable amounts of contaminants (dicyandiamide, dihydrotriazines, creatinine, ions) are generated and, thus, their tolerable concentrations (ppm) should be defined and made known to consumers that use creatine products. Furthermore, because sarcosine could originate from bovine tissues, the risk of contamination with prion of bovine spongiform encephalopathy (BSE or mad-cow disease) can’t be excluded. Thus, French authorities forbade the sale of products that contained creatine.
– Journal of Sports Medicine and Physical Fitness 2001 Mar; 41(1):1-10 — Creatine as nutritional supplementation and medicinal product. — Benzi G, Ceci A.

Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals. Liver and kidney dysfunction have also been suggested on the basis of small changes of organ function and of occasional case reports, but well controlled studies on the adverse effects of creatine supplementation are almost nonexistent. Side effects may occur when large amounts of a substance containing an amino group are consumed, and have an effect on the liver and kidneys. Regular monitoring is suggested to avoid any abnormal reactions during oral creatine supplementation.
– Sports Medicine 2000 Sep; 30(3):155-70 — Adverse effects of creatine supplementation: fact or fiction? — Poortmans JR, Francaux M.

Recent trends in football heatstroke fatalities may, in part, be in part to or due by the use of dietary supplements. Credible scientific evidence has been found that amphetamine derivatives and the ergonomic aid known as creatine may contribute to dehydration and heatstroke in selected individuals. Caution is urged in the education and evaluation of football players who train during the hot summer months.
– Neurosurgery 2002 Aug; 51(2):283-6; discussion 286-8 — The neurosurgeon in sport: awareness of the risks of heatstroke and dietary supplements. — Bailes JE, Cantu RC, Day AL.

Creatine supplementation can result in urinary concentrations that are 90 times greater than normal. The long term effects of this have not been investigated, but there is a possibility for a variety of nephrotoxic, i.e., kidney damaging, events. There is potential for direct toxicity on renal tubules where urine is formed, and for acceleration of kidney stone formation. Recently, a baseball player for the Houston Astros was determined to have suffered from dehydration, kidney stones, and transient kidney damage as the result of creatine supplementation. Additionally, the deaths of 3 collegiate wrestlers this past year are being investigated to determine what role creatine supplementation may have played.



There are impurities present in virtually every manufactured product, and in some cases, even though the product may be considered harmless, the impurity is not. Creatine, and other such supplements, are not regulated by the FDA. No published investigation has been conducted on creatine to determine what impurities might be present in creatine supplements, and what their long term side effects might be.



This review suggests that no one can confidently state that prolonged creatine supplementation is safe, and its use would best be avoided until more data can be compiled. The author also states that taking the supplement for a prolonged period of time is really an uncontrolled toxicity study and one which might yield harmful results.
– http://www.rice.edu/~jenky/sports/creatine.html

This link suggests that taking high doses of creatine might harm the kidneys and if taken with medications that can have an effect on the kidneys, it could increase the chance of kidney damage. Some of these medications include cyclosporine (Neoral, Sandimmune); aminoglycosides including amikacin (Amikin), gentamicin (Garamycin, Gentak, others), and tobramycin (Nebcin, others); nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil, Motrin, Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan, Naprosyn), piroxicam (Feldene); and numerous others.
– http://www.nlm.nih.gov/medlineplus/druginfo/natural/873.html

This study shows that creatine supplementation may result in abnormalities in glucose homeostasis in the absence of changes in insulin secretion.
– Annals of Nutrition and Metabolism 2003; 47(1):11-5 — Creatine supplementation affects glucose homeostasis but not insulin secretion in humans. — Rooney KB, Bryson JM, Digney AL, Rae CD, Thompson CH.

Creatine has become one of the most popular dietary supplements in the sports nutrition market. The form of creatine that has been most extensively studied and commonly used in dietary supplements is creatine monohydrate. Studies have consistently indicated that supplementation increases muscle creatine and phosphocreatine concentrations by approximately 15-40%, enhances anaerobic exercise capacity, and increases training volume leading to greater gains in strength, power, and muscle mass. A number of potential therapeutic benefits have also been suggested in various clinical populations. There is little to no evidence that any of the newer forms of creatine are more effective and/or safer than creatine monohydrate whether ingested alone and/or in combination with other nutrients. In addition, whereas the safety, efficacy, and regulatory status of it is clearly defined in almost all global markets; the safety, efficacy, and regulatory status of other forms of creatine present in today’s marketplace as a dietary or food supplement is less clear.
– Amino Acids. 2011 Mar 22. — Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. — Jäger R, Purpura M, Shao A, Inoue T, Kreider RB.

According to this article, the aerobic and anaerobic ability of highly trained male athletes is unaffected by 6 weeks of oral supplementation with beta-hydroxy-beta-methylbutyrate (HMB) or a combination of HMB and creatine monohydrate.
– Journal of Sports Medicine and Physical Fitness 2003 Mar; 43(1):64-8 — Effects of beta-hydroxy-beta-methylbutyrate and creatine monohydrate supplementation on the aerobic and anaerobic capacity of highly trained athletes. — O’Connor DM, Crowe MJ.

Creatine may have dangerous interactions with caffeine, ephedra and other herbs and supplements. As stated above, creatine may also interact with some prescription medications. Consult with your physician before adding it to your workout routine.

A questionnaire assessing awareness and use of creatine supplementation was completed by 674 athletes from 11 high schools. The answers were analyzed to determine the variation among the groups. Of those surveyed, 75 percent had knowledge of creatine supplements, and 16 percent of them used creatine to enhance athletic performance. The percentage of use increased with age and their grade level. The awareness and use of the supplement were found to be greater among boys than girls. Adverse effects were reported by 26 percent of the subjects and most of the athletes consumed creatine using a method inconsistent with scientific recommendations. The use of creatine by adolescent athletes is significant and inconsistent with optimal dosing. Physicians, athletic trainers, and coaches should provide proper information and advice to these adolescent athletes.
– Southern Medical Journal 2001 Jun; 94(6):608-12 — Use of oral creatine as an ergogenic aid for increased sports performance: perceptions of adolescent athletes. — Ray TR, Eck JC, Covington LA, Murphy RB, Williams R, Knudtson J. — Center for Sports Medicine and Orthopaedics Foundation for Research, Chattanooga, Tenn., USA.

The unrestrained consumption of dietary supplements should be avoided, since, besides the lack of evidence that such practice will lead to improvement of performance, it exposes adolescents to several adverse effects. Balanced nutrition, with intake of essential energy and nutrients is usually enough to achieve good athletic performance. The use of dietary supplements must be allowed only for selected cases in which specific nutritional deficiencies are identified.
– J Pediatrics (Rio J). 2009 Jul 7;85(4). Dietary supplement use by adolescents. Alves C, Lima RV.

The vast amount of data on creatine and exercise performance does not support the dramatic claims of muscle building and power development by manufacturers.
– Tex Med 2002 Feb; 98(2):41-6 — Performance-enhancing substances in adolescent athletes. — Gomez JE.

Supplemental creatine has been promoted for it’s positive health effects and is best known for its use by athletes to increase muscle mass. In addition to its role in physical performance, creatine supplementation has protective effects on the brain in models of neuronal damage and also alters mood state and cognitive performance. Recent work shows that creatine supplementation has the ability to function in a manner similar to antidepressant drugs and can offset negative consequences of stress. These observations are important in relation to addictive behaviors as addiction is influenced by psychological factors such as psychosocial stress and depression. The significance of altered brain levels of creatine in drug-exposed individuals and the role of creatine supplementation in models of drug abuse have yet to be explored and represent gaps in the current understanding of brain energetics and addiction.
– Mol Neurobiol. 2011 Mar 12. — A Potential Role for Creatine in Drug Abuse? — D’Anci KE, Allen PJ, Kanarek RB.