Creatine B.S.

Q: I heard creatine can cause cancer. Is that true?

A: I’m not sure where you heard that comment, but I have seen a news story from the Associated Press that quoted a press release, not a study, that makes the claim. The press release first came to my attention on January 25, 2001. It was released by a French agency, the AFSSA, which was created in 1998 to evaluate food safety. Presumably, it operates under the authority of the French government. I had difficulty with the agency’s Web site, as the English-language option was under construction. Fortunately, I can read French well enough to evaluate the site and the relevance of the release.

I’m going to quote some of the AP story as I received it. ‘French food safety experts have linked the popular training supplement creatine to a potential risk of cancer’ and ‘urged it to be listed as a banned substance’ because ‘potential risks associated with taking creatine were ‘currently insufficiently evaluated’ and ‘the product was of little benefit to athletes hoping to improve their performance.’ The person credited with these statements is Martin Husch’no title or educational degrees noted. He does not support his claim with any references and does not provide a list of the experts who support the statement. Mr. Husch has no publications to his credit listed in PubMed.

Now, I’m going to give you a scientific response to that report: It’s a bunch of bull crap. I have no idea who those French experts are, as they don’t list their credentials on the release or on the Web site. There’s no documentation of the method of analysis they used. They offer no standard as to what would be sufficient evaluation to declare any product safe. Note well: It’s impossible to prove risk does not exist. (Perhaps we should use the FDA’s criteria, which allowed Thalidomide and fenfluramine on the market but pulled phenylpropanolamine despite its impressive 30-year safety record. Remember, PPA was pulled by the pharmaceutical industry.) As for creatine having no benefits for athletes, let’s be serious. Creatine is the most well-validated sports-nutrition supplement on the market. How many of you have experienced a benefit from creatine supplementation? I know a few haven’t, but most do benefit from creatine.

I looked for the report that was supposedly posted on the AFSSA Web site and all that came up was a PDF file of the cover page. Not convincing. I received an e-mail, forwarded to me by a friend, from Mark Tarnopolsky, M.D., Ph.D., of McMaster University Medical Center in Hamilton, Ontario, Canada. Dr. Tarnopolsky offered an excellent critique of the release.

The AFSSA claims that creatine, particularly in the presence of simple sugars and amino acids, could have carcinogenic effects. Dr. Tarnopolsky takes particular offense at the statement ‘with the potential carcinogenic effects.’ He states that the comment is unfounded and the jump to stating that epidemiological studies have shown a link is complete fabrication and misinformation.

The AFSSA statement goes on to comment on digestion, muscular and cardiovascular problems related to creatine use. Oddly, the agency’s comments contradict the literature. There have been two studies of humans with congestive heart failure showing benefits in performance and studies of animals showing cardioprotective effects. Also, it has been shown that creatine does not affect blood pressure.

Dr. Tarnopolsky supports the regulation of the manufacturing of creatine and other nutraceuticals.

This is an irresponsible attempt to grab media attention, and part of the blame should go to the Associated Press. There are enough real problems in this industry. Muddying the waters in an attempt to gain momentary fame benefits no one.

Q: How can creatine be natural if it’s manufactured by chemicals? Aren’t natural products safer than chemicals or drugs?

A: Well, in the first part of your question, you’re referring to synthetic creatine. Creatine (monohydrate), synthesized by companies such as SKW (Bioactives Division), is chemically identical to the creatine formed in the body by enzymatic processes in organs like the liver, kidneys and testes. We all ingest creatine from meat sources or are able to make it endogenously’meaning that it’s created in our bodies as opposed to taking it in from an outside source. Creatine is formed from the amino acid arginine. For those of you into the science of all of this (yes, both of you, so listen up while 150,000 other readers blow this off), arginine and glycine, under the influence of glycine amidino-transferase, an enzyme inhibited by exogenous creatine supplementation, form guanidoacetic acid (GAA). GAA then is methylated in a reaction driven by guanido-acetate methyltransferase, forming creatine. So, instead of sarcosine and cyanamide (the substrates used in chemical synthesis of creatine), amino acids are used as the precursors.

Companies marketing products obtained by extraction techniques from plant or animal tissues are making a big push to avoid any product made by chemical synthesis. Frankly, I think the natural-is-better attitude about bioactives is illogical. The extraction techniques involve the use of solvents and conditions not naturally part of digestion. The purpose is to concentrate the amount of a bioactive ingredient in the final extraction. Thus, the extractions attempt to isolate out the same ingredient found in synthetics. The only difference is that extractions have the ingredient already formed by nature and it has to be chemically filtered to get rid of other unwanted chemicals present in the original so-called natural source, whereas synthetics start with smaller chemicals that form the final product. Extractions typically are less than 50 percent pure, whereas synthesized materials are 98 percent pure or better’with the exception of most pro-hormones.

A perfect example is ephedrine. Everyone wants ephedrine’mothers, teenagers, athletes and the obese. Since it was abused by a number of young kids’the same ones who abuse pot and caffeine and inhale nitrous oxide and poppers’ephedrine has come under attack. Using any ephedrine, caffeine or other stimulant carries risk. Using the product only as and when it’s appropriate may minimize the risk to acceptable levels. There’s a group that promotes ephedra, also known as mahuang, as being safer because it’s a plant extract. Complete baloney. Synthetic ephedrine (minithins, white crosses, etc.) is a regulated over-the-counter drug, ensuring the amount of ephedrine in each capsule. The herbal-blend ephedra products are where the real danger lies, particularly those from small one-product, fly-by-night companies. Botanical sources of ephedra are poorly regulated. Even in the larger companies, ensuring lot-to-lot standards is nearly impossible and poorly tracked (if at all).

Rarely does ephedra or mahuang exceed 8 percent of a botanical extract. That means more than 90 percent is other biochemicals, which may interact with the ephedra alkaloids. Some of those chemicals may increase the potency of the product, others may decrease the potency, while still others may have effects completely unrelated to the purpose of the formula. Who has studied the effects of what’s in the other 90 percent of the extracts?

While we’re on the topic, what’s the difference between ephedrine and ephedra alkaloids? Ephedrine is a specific chemical structure with predictable activity in most humans. Ephedra alkaloids are a number of related chemicals that come through the extraction process due to their physical properties. Does that mean you want the other alkaloids or that they will have the exact same activity in the body? Absolutely not. Estradiol (an estrogen) and testosterone are both steroid molecules, yet I doubt anyone would accept an extract that had steroidal extracts as a testosterone replacement. It’s the chemical soup of extracts that’s the wild card of bioactivity.

The Unite States Food and Drug Administration has listed a number of adverse events linked to the use of ephedra and ephedrine, yet they passed restrictions on ephedrine only. Why is that? Is the ephedrine HCl more dangerous than ephedra? No. It goes back to the 1994 DSHEA law allowing the sale of botanicals in an unregulated manner. The FDA has no jurisdiction over botanicals but can regulate the synthetic chemicals. The over-the-counter drugs are more tightly regulated in terms of manufacturing, labeling and sales.

So, to answer your question, creatine is a naturally occurring chemical that can also be synthesized in a lab or large-scale manufacturing facility. Natural products may be the basis of nutrition, but many of the chemicals found in botanicals would be better controlled if produced synthetically. Consider if the product is to feed your body or to produce a reaction that you would like to be able to control and predict’muscle growth, say, or alertness and fat loss.

Editor’s note: Daniel Gwartney, M.D., is a clinical pathologist and a graduate of the University of Nebraska College of Medicine. He’s been bodybuilding for more than 18 years. The material presented in this column is for general-information purposes only and is not to be construed as medical advice or an individual recommendation. Consult with your physician or health care provider before embarking on any fitness, training, diet or supplementation program. The author and IRONMAN assume no liability for the information contained in this column. IM