Creatine-Ethyl-Ester and Kre-Alkalyn (Review)

I've seen a lot of hype regarding Kre-Alkalyn and Creatine-Ethyl-Ester (CEE).

Let me give you a quick history lesson before I get into the research.  Creatine Monohydrate  hit the market back in the 90's.  I believe EAS was the first company to mass market this new supplement (it was called Phosphagen).  It was quite expensive at first, but people couldn't get enough of it.  Creatine eventually became more widely available and the price dropped. 

But "new and improved" creatine formulas were soon to follow: supplements promising improved delivery, etc. 

Now to CEE and Kre-Alkalyn.   The product manufacturers often claim "regular" creatine monohydrate rapidly degrades in digestion, making it useless. I find this to be complete nonsense--creatine monohydrate has been backed by multiple studies.  How could it work if it rapidly degrades as some of these supplement ads claim?

Here's some research you might find interesting:

Numerous creatine formulations have been developed primarily to maximize creatine absorption. Creatine ethyl ester is alleged to increase creatine bio-availability. This study examined how a seven-week supplementation regimen combined with resistance training affected body composition, muscle mass, muscle strength and power, serum and muscle creatine levels, and serum creatinine levels in 30 non-resistance-trained males. In a double-blind manner, participants were randomly assigned to a maltodextrose placebo (PLA), creatine monohydrate (CRT), or creatine ethyl ester (CEE) group. The supplements were orally ingested at a dose of 0.30 g/kg fat-free body mass (approximately 20 g/day) for five days followed by ingestion at 0.075 g/kg fat free mass (approximately 5 g/day) for 42 days. Results showed significantly higher serum creatine concentrations in PLA (p = 0.007) and CRT (p = 0.005) compared to CEE. Serum creatinine was greater in CEE compared to the PLA (p = 0.001) and CRT (p = 0.001) and increased at days 6, 27, and 48. Total muscle creatine content was significantly higher in CRT (p = 0.026) and CEE (p = 0.041) compared to PLA, with no differences between CRT and CEE. Significant changes over time were observed for body composition, body water, muscle strength and power variables, but no significant differences were observed between groups. In conclusion, when compared to creatine monohydrate, creatine ethyl ester was not as effective at increasing serum and muscle creatine levels or in improving body composition, muscle mass, strength, and power. Therefore, the improvements in these variables can most likely be attributed to the training protocol itself, rather than the supplementation regimen.

Quoted from the Journal of the International Society of Sports Nutrition (emphasis mine), The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels

So CEE was actually found to be less effective than creatine monohydrate.  

Here's another study:

There are a number of forms of creatine available that attempt to improve the solubility and permeability, with the anticipation this will result in an improved pharmacokinetic profile and ultimately an enhanced ergogenic response. Previous research has shown that the different salt forms can improve solubility resulting in slightly altered pharmacokinetic profiles, however specific data exploring the conversion of esterified derivatives to creatine is lacking. The purpose of this study was to examine the assertion that creatine ethyl ester undergoes enzymatic conversion to creatine in human tissues. The in vitro response of creatine ethyl ester to incubation in human plasma was examined by H-NMR analysis. Lyophilized human plasma was reconstituted in D₂O and phosphate-buffered saline and 1.5 mg of the analyte was added. Following incubation at 37°C for 4h and subsequent protein precipitation, the supernatant was analyzed by NMR, utilizing the diagnostic chemical shift of the methylene signal to determine the species present in solution, i.e. creatine ethyl ester, creatine, or creatinine. Both creatine and creatinine were run in parallel as control experiments and each assay was run in triplicate. As expected both creatine and creatinine remained unchanged. However, conversion of creatine ethyl ester to creatine by the esterases in human plasma was not observed to any detectable extent and the only species detected after the incubation period was creatinine. While not a definitive characterization of the in vivo behavior, these results strongly warrant a complete in vivo pharmacokinetic analysis of creatine ethyl ester since it appears these "pro-nutrients" may actually provide large exogenous sources of pharmacologically inactive creatinine rather than ergogenic creatine. 

From the International Journal of Sports Medicine (emphasis mine), Qualitiative In vitro NMR Analysis of Creatine Ehtyl Ester Pronutrient in Human Plasma.

Same song different verse.

Now let's look at Kre-Alkalyn. 

The problem with this supplement is the lack of independent research.  A Dr. Tallon presented a study to the International Society of Sports Nutrition (ISSN) a few years ago.  This was the punchline:

In contrast to the claims of All American Pharmaceutical and Natural Foods Corp., the rate of creatinine formation from CM was found to be less than 1% of the initial dose, demonstrating that CM is extremely stable under acidic conditions that replicate those of the stomach. This study also showed that KA supplementation actually resulted in 35% greater conversion of creatine to creatinine than CM. In conclusion the conversion of creatine to creatinine is not a limitation in the delivery of creatine from CM and KA is less stable than CM in the acid conditions of the stomach.

Apparently All-American Pharmaceuticals and Natural Foods Corp. filed suite against Dr Tallon.  They claimed Tallon's research was tainted because he was working on another creatine product (if I understand things correctly, Tallon claims he was interested in using kre-alkalyn in his formula but found it to be ineffective). 

Tallon lost because he never responded to the suit.  The above study was pulled from the ISSN website/publications, etc.

There was another study conducted by Royal Knight, Inc.  They tested Kre-Alkalyn degradation in two laboratories under various pH levels and concluded it was "generally stable under physiological temperature, in a wide range of pHs."

Were does that leave us?  I would be interested in seeing more independent research on Kre-Alkalyn (but I'm not holding my breath).

Both studies actually showed Kre-Alkalyn was stable enough to be used as a supplement (even Tallon's). But so far no research has shown it to be more effective than regular creatine monohydrate.     Some of the guys on the forums swear by it, but I'm still just not convinced--I rarely spend money on supplements based on anecdotal evidence.


My Recommendation/Opinion:

So far I'm underwhelmed by any "buffered creatine" formula.  It seems they are trying to fix something that isn't broken. 

I'm sticking with plain 'ole micronized creatine powder (I'm partial to Prolab's product, but any reputable brand would do).