Analysis of Creatine Ethyl Ester

TU researchers bust myth on popular nutritional supplement

Researchers at The University of Tulsa have taken some of the guesswork out of the decision many athletes will face when it comes to one popular supplement – creatine.

Open any magazine on bodybuilding or fitness and you will find hundreds of advertisements for dozens of nutritional supplements, and there is one thing all these advertisements have in common. After the claims about how the product will make the athlete bigger, stronger, faster, and/or better there is the disclaimer: “These statements have not been evaluated by the Food and Drug Administration.” 

As a result of the disclaimer, supplement manufacturers are able to make a wide range of health claims – leaving the athlete with only trial and error as a means to determine whether the statements are accurate.

In an article in the journal Biochemical and Biophysical Research Communications, TU researchers have shown that the new popular nutritional supplement, creatine ethyl ester, is likely to be no better than taking the long-standing supplement, creatine monohydrate. The study was led by Gordon Purser, professor of chemistry, and three undergraduate researchers in the department of chemistry and biochemistry.

According to Purser, creatine is one of the most popular nutritional supplements for athletes hoping to add lean muscle mass to their body.

“Almost every athlete training for a sport requiring strength will take creatine as they engage in resistance training, also known as lifting weights,” says Purser.

The reason? Because creatine works. Purser pointed to numerous scientific studies involving non-endurance athletes that have shown unequivocally that appropriate supplementation of their diet with creatine is safe and effective for increasing the rate of adding lean muscle mass and producing strength gains.

Purser said the problem with creatine is that muscle cells absorb it poorly and athletes have to take large doses of the supplement to generate an effective level – which can be hard on the kidneys. It can also cause bloating, and for body builders, the retention of water can result in a loss of muscle definition, something they want to avoid especially during competitions.

In an effort to improve the ability of cells to take up creatine, chemists modified the molecule.

“It had been observed that cellular uptake of many other substances is greatly improved when they were esterified,” Purser said. “Esterification is the chemical process of combining an organic acid, like creatine, with an alcohol to produce a new compound.”

An improved uptake of the new compound would mean smaller doses, which in turn is less taxing on the kidneys and would cause less bloating.

For many substances, esterification works well. As for the ester of creatine, no one knew, but supplement marketers didn’t wait to find out.

“The grapevine within the weightlifting community is amazing,” Purser, a weightlifting enthusiast, said. “Once students in the gym find out that I am a chemist, they frequently ask me about what I know about new supplements and if these supplements might work. Often I will get a question about a new supplement that has only been on the market for a few weeks. Usually there is no scientific literature on the effectiveness of the new supplement at all.”

In 2005, an article appeared in Flex, a magazine for bodybuilders in which the science editor wrote, “Because CEE (creatine ethyl ester) can be absorbed directly into muscle cells, it doesn’t need to rely on insulin and it doesn’t sit outside the muscle cells, which can cause bloating.” After that article appeared, everyone just assumed the supplement worked as described.

But researchers at TU were not convinced.

“David Reading, one of my research students and an amateur body builder, was the first person to bring the question of the stability of creatine ethyl ester to my attention,” says Purser. “So I let David begin the research to determine how stable the supplement was. What we discovered was surprising. The creatine ethyl ester was much less stable than we thought it would be.”

Reading, currently a medical student at the University of Texas Southwestern Medical Center in Dallas, graduated from TU before the project could be finished, so coauthors Luay Shaya, now a medical student at The University of Oklahoma Health Sciences Center, and Nicholas Katseres, who plans to enter medical school in 2010, continued the research. All three of these students were participants in TU’s Tulsa Undergraduate Research Challenge (TURC).

“I’ve been very fortunate to have such talented undergraduate students work with me on this project,” Purser explained. “Without them, the truth about creatine ethyl ester would be a secret still.”

The truth, Purser said, is that creatine ethyl ester is very unstable in the bloodstream. Within a few minutes the ester completely breaks down into creatine and ethanol. The decomposition is most likely much faster than absorption into the muscle cells. As a result, taking creatine ethyl ester is no different from taking creatine.

Does that make it harmful? According to Purser, “No.” The decomposition products of the ester are creatine, like you would get from a traditional creatine supplement, and ethyl alcohol, as you would find in beer.

While not harmful, the myth surrounding creatine ethyl ester can lead to two detrimental effects. First, because athletes are told that it is absorbed better than creatine itself, they can take less of it. This means that they probably are getting less than the optimal amount of creatine to their muscles. Second, creatine ethyl ester costs about twice as much as creatine monohydrate, the traditional source of creatine for athletes.

“Athletes should stick with the tried-and–true form of creatine, and save their money,” Purser suggests.

When asked if someone might become intoxicated from the alcohol produced by the decomposition, Purser laughed.

“Well, you would have to consume about 50 grams (20 times the recommended dose) of creatine ethyl ester to get the same amount of alcohol as in a can of beer,” he said. “If you did that, intoxication might be the least of your problems.”

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