Opening Comments

A little over two weeks ago I gave a presentation to the Army ROTC cadets at Rutgers University, wherein I fielded some questions following the presentation. During that time I was asked the question of whether or not I thought creatine monohydrate was better than creatine ethyl ester in terms of its beneficial effects on weight training (increased strength, muscle size, etc.). This was not surprising given the growing popularity of newer versions of creatine that purport greater strength and muscle gains, etc. Due to various factors, creatine has taken many shapes and forms over the years, and in doing so, has become shrouded in controversy, mainly pertaining to the effectiveness and ergogenic (performance enhancing) capabilities between traditional monohydrate and these other alternate forms.

Without going into my answer just yet, I thought this question would be a great topic for my blog, and is indeed the focus of today’s article. First I will discuss what creatine actually is and how’s it made in the body, along with some of the claims and research behind creatine monohydrate’s characteristics. Then I will get into what creatine ethyl ester (CEE) is and the claims surrounding its potential (non-existent?) benefits over regular creatine monohydrate (CM). Many are under the impression that these newer forms of creatine are better… but are they, and in particular, is CEE?

Creatine 101: a Primer on Creatine Metabolism [1]

So, what is creatine? Well, for starters, creatine is not some dangerous steroid that many uneducated individuals make it out to be, if only half joking. Creatine nutrient found naturally in food sources such as fish and meat and is synthesized daily in all humans and other mammals. Its primary role is to help regenerate ATP (the body’s energy currency) from ADP during intense exercise. Unfortunately it’s only used during shorts bouts of physical exertion i.e. sprints and lifting weights (sorry endurance crowd). There has even been some evidence for the use of creatine in clinical settings, specifically for the use of treating various muscle myopathies and cardiac diseases. That however, is way beyond the scope of today’s focus.

Creatine is synthesized every day from three amino acids, namely glycine, arginine, and methionine. The process starts in the kidney with arginine and methionine, wherein the two amino acids react to form guanidino acetic acid (GAA). GAA then moves to the liver where it is then methylated to become creatine. It’s as simple as that. The newly formed creatine then makes it way to skeletal muscle wherein a phosphate (P) is added, making creatine phosphate. It is this phosphate group (P) which gets added back on to ADP (adenosine DI phosphate) to yield ATP (adenosine TRI phosphate) and essentially increase the ability for the muscle to do more work. The more Creatine phosphate one has, the greater the potential to phosphorylate ADP back to ATP and increase work capacity. In fact, supplementing with creatine (~20g/day for 5 days) has been shown to increase muscle creatine stores (both total and creatine phosphate) by anywhere from 15-40% [2-4], thus proving its potential for ergogenic capabilities.

Now, you may also be wondering why we constantly make new creatine? Well, it is for the simple, yet important, fact that creatine is spontaneously degraded to creatinine in muscle tissue and excreted in the urine. Therefore dietary intake and synthesis make up the majority of our creatine stores (and supplementation to some extent for those using it). The more muscle mass you have, the greater your creatine stores can be, as well as the more you excrete in your urine as creatinine (it’s a two way street). Obviously, vegans and vegetarians would have lower creatine stores than omnivores who regularly consume meat and fish. They (vegetarians and vegans) also excrete less. Vegetarians and vegans would be prime candidates for creatine supplementation due to existing low levels.

Creatine in the Market Place

As a supplement, creatine was introduced in the early 1990’s as creatine monohydrate (CM). It has actually been studied as early as the mid-1920’s but didn’t catch on as a dietary supplement until the past 20+years. CM is the form of creatine found in fish and meats. Shortly after its introduction, newer versions of creatine were introduced to the market, trying to appeal to consumers by promoting their better solubility, stability, bioavailability, and performance enhancing capabilities (ergogenic capacity). Who could resist!? Although partially true, these claims are not substantiated by research and are nothing more than playing at every man’s weakness… and that’s the desire to get stronger (ironic).

So what is the research behind creatine monohydrate that has makes it such a popular supplement, and where are the claims for other versions, specifically creating ethyl ester, going wrong? Time to look into the research and start tallying up the points!

The Research

Solubility [5]

It just so turns out that creatine monohydrate is relatively poor at mixing with water (solubilizing). If any of you have ever added a tsp. (~5g) to your shaker, you know well that the powder does not dissolve and that you’re most likely going to get a couple granules left in your mouth. But so what, just a small price to pay for strength, right? That’s my view anyway. In fact, it would take about a liter of cold water (~40°F) just to dissolve that tsp. of creatine, and who in their right mind would chug a liter of cold water half an hour or so before they lift? Probably not many, however, if you just use warmer water (~70°F) you will increase the solubility, reduce the actual amount of water needed, and boom, dissolve your creatine! You can also just lower the pH (put some lemon juice in your water) and this will also increase the solubility. This gave rise to some liquid versions of creatine which are not effective, reasons for which I explain shortly.

Stability

Along a similar vein, stability is a major factor among creatine properties. Interestingly enough, it has been showed that dry CM being stored at temperatures as high as 140°F had no significant signs of creatinine until 3.5 years later! [6] Pretty good shelf life for such harsh conditions. However, unlike its dry form, CM is not very stable in solution (liquid) and therefore degrades to its inactive form (creatinine) more easily [7]. As long as you drink it immediately there is neither harm nor waste. Only after a few days of being mixed will it start to degrade, and the lower the pH of the liquid, the faster the conversion to creatinine [7-9], therefore mixing it with water (pH ~7) won’t degrade it much at all. And even if you use warmer water or drink it with lemon juice in your own home there will be minimal conversion, if any, as long as you consume it immediately thereafter and don’t leave it sitting around for hours or days on end.

So where does CEE fit into all of this? Well, it just so happens that CEE is even LESS stable in acidic environments (like the stomach for instance) than CM due to the added ethyl group. In fact, this added ethyl group actually accelerates the breakdown of CEE to creatinine [10], and moreover, researchers Giese and Lecher (2009) [11] concluded that under normal physiological conditions CEE is primarily broken down to creatinine and that it most likely contains no ergogenic effect when used as a supplement. They actually went as far as to call it a PRO-nutrient for creatinine rather than creatine. This is the total OPPOSITE of what the companies are claiming! So far it’s not looking good for CEE. But perhaps you’re still not yet convinced.

CM – 1, CEE – 0

Bioavailability

Another important factor of creatine supplementation is bioavailability. This simply means how well the body can 1) absorb and 2) use creatine after ingestion. First off, absorption of CM is nearly 100% [12] (Awesome!), and there is even some evidence that taking it with carbohydrate, protein, or both, or other various compounds like beta-alanine and HMB enhance creatine’s uptake into skeletal muscle [13-15]. However, looking directly at CM vs. CEE [16] it was shown that CEE increased serum (bloodstream) creatinine levels significantly in subjects taking the supplement. For those who don’t follow, that means they were just pissing it out instead of taking it up in the muscle. Also, creatine levels in the muscle for the CEE group were not significantly different than those in the PLACEBO group, i.e. the group not receiving ANY creatine AT ALL. This isn’t to say they didn’t have more; they just didn’t have much more. CM, however, WAS significantly different from the placebo and DID NOT show a significant increase in serum creatinine levels. Simply put, they were able to absorb AND use the creatine. Which brings me to a point that drives me absolutely CRAZY when I (seldom) go into GNC, and that is when the sales rep tries to sell me on the fact that some new form of creatine doesn’t cause water retention. Water retention is a side effect (if you will) of CM [1], but it also lets you know that it’s working. Of course there’s no water weight with CEE, you’re pissing most of it out! However, the same study did see that people who were taking CEE still gained some water weight, albeit less than the CM group… Hmmm, I wonder why?

CM – 2, CEE – 0

Creatine Forms

On a more interesting note, creatine ethyl ester actually contains LESS creatine than creatine monohydrate. Here’s a table of some creatine forms and their respective % of creatine in relation to CM [5]. Just something I found interesting. Companies try to sell a product that is inherently less creatine, for more money. It makes no sense.

CM – 3, CEE – 0

Creatine and Performance

Again, looking at the aforementioned CEE study by Spillane and co. [16], they also looked at actual performance outcomes during the study, which included indices of strength, training adaptations and fat free mass. To this date, this is the only study to do so (CM vs. CEE in this manner), making it very difficult to generalize. Nonetheless, subjects in the CEE group did not experience any additional gains in strength (1RM for bench press), body mass, muscle mass, or sprint performance (Wingate Test) over the CM group or placebo group. In addition, the CM group scored highest in all of those categories, although it was not statistically significant. I should note, however, that this study was conducted in untrained individuals, so any gains that were seen were most likely due to the training protocol and not the supplementation per se. Further studies in weight trained populations are needed to confirm or deny these findings. Either way, in this untrained population, CEE afforded no additional benefits over CM or the placebo.

CM – 4, CEE – 0

Given the accumulation of data thus far in addition to the findings of this study [16] it’s not looking good for CEE. Conversely, studies looking at CM, as an ergogenic aid, are well established and relatively consistent [17-25]. Without getting into too much detail, CM works, and works consistently well, contributing to the fact of why it’s so widely studied and so widely used. I’ll leave you to do some reading in your spare time. The references are always found below. And even if you don’t believe CM works well, it’s safe to assume it works a hell of a lot better than CEE. And it’s probably safer too (no extra creatinine floating around in the bloodstream).

CM – 5, CEE – 0

Final Score

In the end, after tallying up all the points, creatine monohydrate wins, hands down. Surprised anyone? There were no additional benefits to consuming CEE over CM, and in all actuality, there weren’t ANY noticeable benefits from CEE whatsoever… unless you’re in the business of selling CEE. Then in that case, you’re laughing all the way to the bank.

Moral of the story, save your money, buy something that works (and is cheaper!), and try avoiding sensational claims that promise things that seem too good to be true, because, well, they usually are. Given CM’s outstanding track record and ability to remain stable over long periods of time, I would buy CM in bulk, keep it proper stored at temperatures under 140°F (that’s sarcasm), and reap the benefits of CM for years to come. I know I do!

 

References

1. Wyss M, Kaddurrah-Daouk R. Creatine and creatinine metabolism. Physiol Rev 2000;80(3):1107-213.

2. Kreider RB. Creatine supplementation in exercise and sport. In: J. Driskell, I. Wolinsky (eds). Energy-yielding Macronutrients and Energy Metabolism in Sports Nutrition. CRC Press LLC, Boca Raton, FL, 1999, pp. 213-242.

3. Kreider R. Creatine supplementation: Analysis of ergogenic value, medical safety, and concern. J Exerc Physiol 1998;Online 1:7-18.

4. Williams MH, Kreider R, Branch JD. In: Creatine: The Power Supplement. Human Kinetics Publishers, Champaign, IL, 1999.

5. Jager R, Purpura M, Shao A, Inoue T, Kreider RB. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. Amino Acids 2011;40:1369-1383.

6. Jager R. The use of creatine monohydrate in sports nutrition. 2003, Freising, Germany.

7. Howard AN, Harris RC. Compositions containing creatine. 1999, US Patent.

8. Cannon JG, Orencole SF, Fielding RA, Meydani M, Meydani SN, Fiatarone MA, Blumberg JB, Evans WJ. Acute phase response in exercise: interaction of age and vitamin E on neutrophils and muscle enzyme release. 1990 Am J Physiol 259 (6 Pt 2):R1214-R1219.

9. Dash AK, Mo Y, Pyne A. Solid-state properties of creatine monohydrate. J Pharm Sci 2002;91(3):708-718.

10. Child R, Tallon MJ. Creatine ethyl ester rapidly degrades to creatinine in stomach acid. Paper presented at the ISSN 4^th Annual Meeting, Las Vegas, Nevada, June 12, 2007.

11. Giese MW, Lecher CS. Non-enzymatic cyclization of creatine ethyl ester to creatinine. Biochem Biophys Res Commun 2009;388(2):252-5.

12. Deldicque L, Decombaz J, Zbinden Foncea H, Vuichoud J, Poortmans JR, Francaux M. Kinetics of creatine ingested as a food ingredient. Eur J Appl Physiol 2008;102(2):133-143.

13. Cribb PJ, Williams AD, Hayes A. A creatine-protein-carbohydrate supplement enhances responses to resistance training. Med Sci Sports Exerc 2007;39(11):1960-1968.

14. Hoffman J, Ratamess N, Kang J, Mangine G, Faigenbaum A, Stout J. Effect of creatine and beta-alanine supplementation on performance and endocrine responses in strength/power athletes. J Sport Nutri Exerc Metab 2006;16(4):430-446.

15. Jowko E, Ostaszewski P, Jank M, Sacharuk J, Zieniewicz A, Wilczak J, Nissen S. Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight training program. Nutrition 2001;17(7-8):558-566.

16. Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, Willoughby DS. The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. J Int Soc Sports Nutr 2009;6:6 (14 pages).

17. Greenhaff P. Creatine supplementation and implications for exercise performance. In: Jeudendrop A, Brouns M, Brouns F (eds) Advances in training in nutrition for endurance sports. Novartis Nutrition Research Unit, Maasticht.

18. Kraemer WJ, Volek JS. Creatine supplementation. Its role in human performance. 1999 Clin Sports Med 1999;18(3):651-666.

19. Kreider RB. Effects of creatine supplementation on performance and training adaptations. Mol Cell Biochem 2003;244(1-2):89-94.

20. Cribb PJ, Hayes A. Effects of supplement timing and resistance exercise on skeletal muscle hypertrophy. Med Sci Sports Exerc 2006;38(11):1918-1925.

21. Kreider RB, Ferreira M, Wilson M, Grindstaff P, Plisk S, Reinardy J, Cantler E, Almada AL. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc 1998;30(1):73-82.

22. Volek JS, Kraemer WJ, Bush JA, Boetes M, Incledon T, Clark KL, Lynch JM. Creatine supplementation enhances muscular performance during high-intensity resistance exercise. J Am Diet Assoc 1997;97(7):765-770.

23. Volek JS, Duncan ND, et al. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 1999;31(8)1147-1156.

24. Willoughby DS, Rosene J. Effects of oral creatine and resistance training on myosin heavy chain expression. Med Sci Sports Exerc 33(10):1674-1681.

25. Willoughby DS, Rosene J. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc 35(6):923-929.