Creatine Supplement Cancer Scare Unfounded

CRN's Background Evaluation

Recent publicity made the following unfounded allegation: "Creatine, a dietary supplement used by many athletes to increase muscle bulk, could lead to cancer" (Reuters, 24 Jan 2001). The story was based on a report from a French government agency, the French Agency of Medical Security for Food (AFSSA). There are two parts of the report and they may be downloaded as follows:

Advice ( http://www.afssa.fr/ ), and the Report( http://www.afssa.fr/ ). The report is available only in French (an English version of the website is "under construction").

The Reuters article makes an issue of potential adverse effects and the ban of creatine by some athletic associations. The AFSSA discusses possible carcinogenic effects and asserts its opinion that use of creatine supplements is against the spirit of sportsmanship and fair competition.

The AFSSA report assertions of possible carcinogenic risk are based on three theoretical possibilities:

1. The first theoretical possibility is that creatine could be involved in formation of carcinogenic nitrosamines, under conditions of high concentrations of sugars and amino acids. These conditions do not apply to oral intakes of creatine, and thus allegations of "lack of safety" for oral creatine cannot be based on this issue.

2. The second possibility is the formation of carcinogenic heterocyclic amines from creatine during charbroiling (pyrolysis) of meats. This possibility is supported by a large body of scientific data, but is not relevant to oral creatine supplementation. It is directly relevant to the safety of charbroiled meats, but not to the safety of creatine used as a dietary supplement. Allegations of "lack of safety" for oral creatine cannot be based on this issue.

3. The third possibility is that creatine itself might be carcinogenic. The AFSSA report cites no studies of any kind to support such a possibility. In fact, there is no available evidence to support the possibility and there is a considerable body of evidence to the contrary. In opposition to a hypothesis that creatine might cause cancer, a strong body of scientific evidence suggests that creatine and some of its chemical analogs may have cancer inhibitory properties (Markus Wyss and Rima Kaddurah-Daouk, Creatine and Creatinine Metabolism,Physiological Reviews, 2000;80:1108-1213).

Experienced creatine researchers from three separate institutions have provided detailed information to support creatine safety:

1. Mark Tarnopolsky, MD, PhD, of McMaster University Medical Center (tarnopol@mcmaster.ca),
2. Drs. Markus Wyss and Rima Kaddurah-Daouk, of the Avicena Group (rima_daouk@avicenagroup.com), and
3. Prof. Theo Wallimann, of the Swiss Federal Institute of Technology Zurich (theo.wallimann@cell.biol.ethz.chand website http://www1.cell.biol.ethz.ch/).

Each of these groups has informed CRN that no scientific evidence suggests that oral creatine increases the risk of cancer. CRN has performed its own computer searches of the scientific literature (Medline and Toxline) and agrees with these experts.

Also, CRN has searched the Food and Drug Administration's AER website for dietary supplements (http://vm.cfsan.fda.gov/), and found 32 reports of adverse event "associated with" creatine. The reported signs and symptoms are "all over the place" and show no discernable pattern of adverse effects. One report states that the subject has "pituitary tumor," but gave no detail about dose, duration, timing, preexisting conditions, or other substances consumed. As with most or all products mentioned in the FDA reports, there is no basis to even assume, much less conclude, a cause-and-effect relationship.

In contrast with the AFSSA report, the European Commission (EC) has published a much more favorable report on creatine safety (http://europa.eu.int/). This report finds no pattern of adverse effects and makes no mention of possible carcinogenicity. It does conclude, however, that not enough long-term studies have been done on the effects and safety of creatine supplementation. The EC report also asserts that studies in well-conditioned athletes cannot be extrapolated to the general population.

Conclusion

CRN's assessment of the scientific literature is that creatine has an extraordinarily low potential to cause adverse effects. The multiple-gram quantities used in scientific tests on athletes, together with their history of use in dietary supplements, supports a strong safety profile for creatine. The absence of credible adverse effects is consistent with these conclusions.

The recent press reports on creatine safety were wrong and misleading. The AFSSA report that prompted this negative publicity does not contain any scientific evidence to support a contention that oral creatine might cause cancer. The working hypothesis by AFSSA seems to be "it might cause cancer, unless you have proven conclusively that it does not." In contrast to this "the evidence is never enough" view, there are large amounts of scientific data and history of use to support a conclusion of safety for oral creatine. This evidence and history includes clinical trials in athletes, laboratory studies on animals and tumor cells, the high natural creatine concentrations in certain conventional foods, and the considerable history of use for creatine in dietary supplements. Thus, the total body of scientific evidence indicates that creatine is safe at current levels of intake, including common uses of dietary supplements.

John N. Hathcock, Ph.D.
Vice President, Nutritional and Regulatory Science
Council for Responsible Nutrition
Washington, DC 20006