Creatine Ethyl Ester

A research article, posted by Lyle McDonald:

Creatine ethyl ester

J Int Soc Sports Nutr. 2009 Feb 19;6(1):6. [Epub ahead of print]

The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels.

Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, Willoughby DS.

ABSTRACT: 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.


Enjoy,

Chillen
 
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Sweet. You just saved me some cash. Everyone is always cheerleading for the ethyl ester, and I've always used the cheaper mono, but was ready to switch over.

Thanks!
 
I'll never go back to mono after trying CEE.

I look like someone pumped me full of air from all the water it puts on me. CEE doesn't bloat me one bit, however the downfall is that it tastes like a shot of rubbing alcohol. If mono works for you though then no need to change, as stated above, it's def cheaper.
 
hahaha, I agree with LV. CRT does make me feel like i am building "fake" muslce b/c of water retention. Now you have confused me chillster. First you take CEE and now you post that CEE is not as effective.. huh? stop being soo up-2-date. :)

Thanks for the post man.
 
hahaha, I agree with LV. CRT does make me feel like i am building "fake" muslce b/c of water retention. Now you have confused me chillster. First you take CEE and now you post that CEE is not as effective.. huh? stop being soo up-2-date. :)

Thanks for the post man.

I continually research, study, and update. There is no greater partner in ones fitness goals. :) :beerchug:

Personally, coming off a no-carb/low-carb diet trend, I like mono's side effect of water entering a high/higher carb phase, because quite simply a no-carb/low-carb dehydrates you. This shouldn't need additional explanation. :)

Besides, If one takes Mono on a low-carb/no-carb diet, water retention is less than optimal (obviously), and likewise, can put Creatine Mono in a less than optimal environment. So (then) I chose CEE, as it didn't require the water intake that mono seems biologically to require.

So, I experimented between the two in different states of diet--primarily due to the efficiencies/deficiencies they bring.

Besides some of the side effects (obviously) of Mono, I personally have seen no difference in the gym. However, between the two (when manipulated), it can effect physical appearance (water retention), which I like to manipulate from time to time.


Best wishes



Chillen
 
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Haha, you're all lucky. I've tried Creatine in many forms in the past and never found it made any difference.

Any chance of a link to the whole study Chillen?
 
The file is too large in PDF format and the site will not allow me to attach it since the allotment is below 500 kilobytes., and the file is only 545 Kilobytes.

So I have to paste it.....bare with me

I will edit it in here.

EDIT: Well, its 121 pages long, LOL. I will see if I can just find a link.

I do have the PDF file, if ones that are interested, want me to e-mail it to them.




Best regards,

Chillen
 
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Here is a link.

The link points to a forum post, at the bottom of the first post, is the the link to the research. It is in PDF format. You can save to your desktop or open it and read it.

It is quite extensive, and 121 pages long.

Enjoy.



Best wishes,

Chillen
 
The Proof is in the Pudding

Research means very little to me if I have tried the product and it works for me.

MRI CE-2 high Def 30 minutes before a workout on an empty give you a great boost for that workout, whether it helps build muscle, etc depends on caloric intake, rest, training ,etc.

I think the proof is always in the pudding, if it doesn't work for 9 people, it may work for 1 and vice versa.

Give it a try!
 
I decided to read that study briefly and a few of the data seems ODD to me:

1) On page 41, he listed the demographics of the subjects. Ten males were in each group (placebo-1, creatine mono-2, and CEE -3)

Group 1(placebo): avg wt = 77.9 kg === mid-range
grp 2 (CR-mono) : avg wt = 89.4 kg === shortest group but weight the most
grp 3 (CEE): avg wt = 73.7 === tallest group but weight the least

Now here comes the interesting part (Average calories consumed) (pg 43):

grp 1: ~ 2000 cal + ~ 100g pro
grp 2 ~ 1600 cal + ~ 115g pro
grp 3 ~ 2700 cal + ~ 115g pro

Now, all three groups gained weight after the 48 days testing. Group 3 gaining weight makes sense but the other 2 group should not have gained weight especially group 2. In fact, group 2 should have lost weight if anything; how can the heaviest group (highest BMR) gain weight while eating the least calories. The participant could possiblily miss record their food log / journal. The +_ SD (standard deviation) puts the macro-caloric intake to not really make to much sense b/c some folks were eating less than 1,000 calore per day.

Another interesting factor is the Bodyfat of each group (pg 51):
grp 1: 19 %
grp 2: 24 %
grp 3: 14 %

If I read properly, this experiment is suppose to be of non-athlete but how many people do you know who do not workout much at all that has about 14% BF. The 10 male sample may not be big enough of a sample population. From the data presented, I am guessing that group 3 kept more detailed log of the intake of food versus group 2. Additionally, the CEE group took more creatine dosage " The creatine monohydrate capsules were 250 mg per capsule, with the creatine ethyl ester (CEE) containing 700 mg per capsule" (pg 33) and this may explain the level of Serum creatinine.

So, this is my take on all those data (I might be wrong) but the CEE group are better athletes (maybe they hike or do more excercise). While all three group gained more fat-free mass after the 7 week period; from my personal experiece, it is easier to gain muscle if we are less athethic (further from our genetic potential) than more athletic (closer to our optinum). Now the amazing thing was that all three group gained muscle strength. If my assestment of group 3 being more athletic than the other 2 groups, then their gains maybe more difficult.

Furthermore, like FT said abvoe; the proof is in the puddling. CEE works for me and a few others on this board (it appears). I am not too sure about this research to be honest. The equipments and protocols seems in place but the test subjects seemed slightly off to me. Would be interesting to see pictures of each of the 30 subjects though; to compare their body composition at the beginning and at the end. Additionally, would been nice for them to do a follow-up 4 weeks afterward without taking any creatine.
 
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Yes, I question the validity of this research.... the numbers does not make sense especially from a body composition make-up of each of the research group. Just my opinion and who am I to question someone's Master's research paper (thesis) which was accepted and approved by 3 phds.

Thanks for the interesting read again, Chillster; nice 90 minutes of reading there.
 
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Yes, I question the validity of this research.... the numbers does not make sense especially from a body composition make-up of each of the research group. Just my opinion and who am I to question someone's Master's research paper (thesis) which was accepted and approved by 3 phds.

Thanks for the interesting read again, Chillster; nice 90 minutes of reading there.

This is the reason I always test something to see how I react to it before I read any studies. Even though someone has a phd, there is always room for human error. At the end of the day, they all bleed red and pee yellow just like you and me.
 
This is the reason I always test something to see how I react to it before I read any studies. Even though someone has a phd, there is always room for human error. At the end of the day, they all bleed red and pee yellow just like you and me.

I pee green. What can I say, I love asparagus.
 
Personally, I don't pee at all. I sweat out my water content. If I pee, it means that I am not working out hard enough. :)-
 
Title: Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training.

Researchers: Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL, Pearson DR, Fink WJ, Kraemer WJ.

Institution: Department of Kinesiology/Center for Sports Medicine, The Pennsylvania State University, University Park 16802, USA. Source: Med Sci Sports Exerc 1999 Aug;31(8):1147-56 Related Articles, Books, LinkOut

Summary: The purpose of this study was to examine the effect of creatine supplementation in conjunction with resistance training on muscle fiber hypertrophy and muscle creatine accumulation.

Methods: Nineteen healthy resistance-trained men were matched and then randomly assigned in a double-blind fashion to either a creatine or placebo group. Periodized heavy resistance training was performed for 12 wk. Creatine or placebo capsules were consumed (25 g x d(-1)) for 1 wk followed by a maintenance dose (5 g x d(-1)) for the remainder of the training period.

Results: After 12 wk, significant increases in body mass and fat-free mass were greater in creatine (6.3% and 6.3%, respectively) than placebo (3.6% and 3.1%, respectively) subjects. After 12 wk, increases in bench press and squat were greater in creatine (24% and 32%, respectively) than placebo (16% and 24%, respectively) subjects. Compared with placebo subjects, creatine subjects demonstrated significantly greater increases in Type I (35% vs 11%), IIA (36% vs 15%), and IIAB (35% vs 6%) muscle fiber cross-sectional areas. Muscle total creatine concentrations were unchanged in placebo subjects. Muscle creatine was significantly elevated after 1 wk in creatine subjects (22%), and values remained significantly greater than placebo subjects after 12 wk. Average volume lifted in the bench press during training was significantly greater in creatine subjects during weeks 5-8. No negative side effects to the supplementation were reported.

Conclusion: Creatine supplementation enhanced fat-free mass, physical performance, and muscle morphology in response to heavy resistance training.

Discussion: Creatine is a naturally occurring compound made within our own bodies. It is also found in many foods we eat, especially meat. Creatine monohydrate has been used as a dietary supplement for at least a decade now, though it was first discovered nearly 170 years ago.

People seem to want to pigeonhole creatine into some sort of hit-or-miss water-retention supplement. Creatine is so much more than that. Creatine is truly one of the greatest supplements there is for building muscle and strength.

There was significant weight gain in this study. The creatine group "loaded" creatine the first 7 days. This was followed by 5 grams per day thereafter. One would expect a significantly greater weight gain the first week over placebo simply because of the well known effect of creatine loading on acute intracellular water retention (cell volumizing). But if this was the only way creatine lead to weight gain, this accelerated weight gain should have tapered off by the end of the first week, then stayed parallel to the placebo group through week 12. Instead, the acceleration of weight gain continued throughout the entire study period reaching nearly 10 pounds of lean mass by week 12! The placebo group gained only 4—in the same period. The creatine group literally doubled their muscle growth by using creatine. This means that creatine continued to effect lean mass gains long after its initial effect on water levels. This increase in body weight was then demonstrated to be true hypertrophy of muscle fibers.

In this study they were able to show, that in trained subjects, creatine supplementation increased muscle mass by nearly twice as much as placebo. Type I muscle fibers increased 35% with creatine but only 11% without it. Likewise, type IIA increased 36% compared to 15%. And finally, Type IIAB fibers increased 35% with creatine supplementation compared to only 6% without it. So on average, creatine supplementation produced 3 times the percentage of muscle fiber growth as placebo. You'd have to be a fool to ignore that!

There's no time to go into the many of other beneficial effects of creatine monohydrate. Suffice it to say, we will be taking a closer look at a lot of research on creatine in the issues to come. Stay tuned!
 
Title: Effects of Long-term Creatine Supplementation on Liver and Kidney Functions in American College Football Players.

Researchers: Mayhew DL, Mayhew JL, Ware JS

Institution: Exercise Science Program at Truman State University, Kirksville, MO 63501 and the Athletic Department at Truman State University, Kirksville, MO.

Summary: The purpose of this study was to determine the effect of long-term Cr supplementation on blood parameters reflecting liver and kidney function.

Methods: Twenty-three members of an NCAA Division II American football team (ages = 19-24 years) with at least 2 years of strength training experience were divided into a Cr monohydrate group (CrM, n = 10) in which they voluntarily and spontaneously ingested creatine, and a control group (n = 13) in which they took no supplements. Individuals in the CrM group averaged regular daily consumption of 5 to 20g for 0.25 to 5.6 years. Venous blood analysis for serum albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, urea, and creatinine produced no significant differences between groups.

Results: Creatinine clearance was estimated from serum creatinine and was not significantly different between groups. Within the CrM group, correlations between all blood parameters and either daily dosage or duration of supplementation were nonsignificant.

Conclusion: Oral supplementation with CrM has no long-term detrimental effects on kidney or liver functions in highly trained college athletes in the absence of other nutritional supplements.

Discussion: Questions about creatine's safety are probably the most frequently brought up by people who don't like (and usually don't understand) supplements. This study by Mayhew and colleagues is a welcome addition to the already growing body of creatine safety research. (1,2,3,4,5,6,7)

Most questions revolve around the effects of creatine supplementation on the liver and kidney. These are the two organs are involved in "processing" creatine once it is ingested. The Liver breaks it down and the kidneys excrete it. From this study, and others before it, we see that long term supplementation with creatine in doses usually taken by bodybuilders (5-20 grams) for extended periods of time do not lead to dysfunction of either organ, nor does it cause abnormalities in the indicators of liver and kidney function.

Considering that fact that creatine supplementation has been shown to enhance anaerobic exercise performance by increasing power output (8), muscular strength and work (9,10,11), and muscle fiber size (12), and to top it off, completely safe even with long term supplementation, its no wonder this is one of my first tier recommendation for effective and safe supplements for putting on muscle size.



Additional References:


1: Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR. Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol. 1997;76(6):566-7.

2: Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999 Aug;31(8):1108-10.

3: Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, Kraemer WJ, Meyer RA, Spriet LL, Tarnopolsky MA, Wagenmakers AJ, Williams MH. American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc. 2000 Mar;32(3):706-17.

4: Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med. 2000 Aug;34(4):284-8.

5: Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Med. 2000 Sep;30(3):155-70.

6: Schilling BK, Stone MH, Utter A, Kearney JT, Johnson M, Coglianese R, Smith L, O'Bryant HS, Fry AC, Starks M, Keith R, Stone ME. Creatine supplementation and health variables: a retrospective study. Med Sci Sports Exerc. 2001 Feb;33(2):183-8.

7: Benzi G, Ceci A. Creatine as nutritional supplementation and medicinal product. J Sports Med Phys Fitness. 2001 Mar;41(1):1-10.

8: Earnest CP, Snell PG, Rodriguez R, Almada AL and Mitchell TL (1995) The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 153: 207-209

9: Casey A, Constantin-Teodosiu D, Howell S, Hultman E and Greenhaff PL (1996) Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 271: E31-E37

10: Vandenberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven L and Hespel P (1997) Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 83: 2055-2063

11: Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL, Pearson DR, Fink WJ and Kraemer WJ (1999) Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 31: 1147-1156

12: Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL, Pearson DR, Fink WJ and Kraemer WJ (1999) Performance and muscle fiber adaptations to
 
Title: Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy.

Researchers: Dangott B, Schultz E, Mozdziak PE.

Institution: Department of Anatomy, University of Wisconsin-Medical School, Madison, USA.

Source: International Journal of Sports Medicine 2000 Jan;21(1):13-6.

Summary: Nutritional status influences muscle growth and athletic performance, but little is known about the effect of nutritional supplements, such as creatine, on satellite cell mitotic activity. The purpose of this study was to examine the effect of oral creatine supplementation on muscle growth, compensatory hypertrophy, and satellite cell mitotic activity.

Methods: Compensatory hypertrophy was induced in the rat plantaris muscle by removing the soleus and gastrocnemius muscles. Immediately following surgery, a group of six rats was provided with elevated levels of creatine monohydrate in their diet. Another group of six rats was maintained as a non-supplemented control group. Twelve days following surgery, all rats were implanted with mini-osmotic pumps containing the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label mitotically active satellite cells. Four weeks after the initial surgery the rats were killed, plantaris muscles were removed and weighed. Subsequently, BrdU-labeled and non-BrdU-labeled nuclei were identified on enzymatically isolated myofiber segments.

Results: Muscle mass and myofiber diameters were larger in the muscles that underwent compensatory hypertrophy compared to the control muscles, but there were no differences between muscles from creatine-supplemented and non-creatine-supplemented rats. Similarly, compensatory hypertrophy resulted in an increased number of BrdU-labeled myofiber nuclei, but creatine supplementation in combination with compensatory hypertrophy resulted in a higher number of BrdU-labeled myofiber nuclei compared to compensatory hypertrophy without creatine supplementation.

Conclusion: Creatine supplementation in combination with an increased functional load results in increased satellite cell mitotic activity compared to increased functional load alone.

Discussion: People seem to want to pigeonhole creatine into some sort of hit-or-miss water-retention supplement. Creatine is so much more than that. Creatine is truly one of the greatest supplements there is for building muscle and strength. Study after study attest to this fact. This is only one of many studies exploring the exciting anabolic properties of creatine monohydrate which we will consider in upcoming issues.

In short, creatine is a naturally occurring compound made within our own bodies. It is also found in many foods we eat, especially meat. Creatine monohydrate has been used as a dietary supplement for at least a decade now, though it was first discovered nearly 170 years ago.

Now in the study we're considering today, the examined the effect of dietary creatine monohydrate on satellite cell activity and subsequent muscle hypertrophy. I won't lie to you and tell you that I have no interest in educating Hypertrophy-Specific readers about creatine. On the contrary, I believe so highly in the effectiveness of creatine that I introduced it into the HSN line of products. Not because people demanded it, but instead because I believe in it. And taking a look at the available research on creatine will make you a believer too. The writing is on the wall with this one folks.

This study looked at the activity of satellite cells. Satellite cells are myogenic stem cells that make hypertrophy of adult skeletal muscle possible. These stem cells are simply generic or non-specific cells that have the ability to transform themselves into new muscle cells when they are instructed to.

Following proliferation (reproduction) and subsequent differentiation (to become a specific type of cell), these satellite cells will fuse with one another or with the adjacent damaged muscle fiber, thereby increasing myonuclei numbers necessary for fiber growth and repair.

In order to better understand what is physically happening between satellite cells and muscle cells, try to picture 2 oil droplets floating on water. The two droplets represent a muscle cell and a satellite cell. Because the lipid bilayer of cells are hydrophobic just like common oil droplets, when brought into proximity to one another in an aqueous environment, they will come into contact for a moment and then fuse together to form one larger oil droplet. Now whatever (i.e. nuclei) was within one droplet will then mix with the contents of the other droplet. This is a simplified model of how satellite cells donate nuclei to existing muscle cells.

The reason this finding about creatine is so exciting is that the process of satellite cells adding nuclei to regenerating muscle cells appears to be critical for hypertrophy. There appears to be a finite limit placed on the cytoplasmic/nuclear ratio (Rosenblatt,1994). This is the ratio of the volume of the muscle cell to the number of nuclei. Whenever a muscle grows in response to functional overload there is a positive correlation between the increase in the number of myonuclei and the increase in fiber cross sectional area (CSA). When satellite cells are prohibited from donating their nuclei, overloaded muscle simply will not grow (Rosenblatt,1992; Phelan,1997).

This study was able to show that creatine supplementation increased the number of myonuclei donated from satellite cells. This increases the potential for growth of those fibers due to the aforementioned cytoplasmic/nuclear ratio. This isncrease in myonuclei probably stems from creatine's ability to increase levels of the myogenic transcription factor MRF4 (Hespel, 2001).

So when it comes to answering the question, "what works and what doesn't" stick to those supplements that have real research behind them. Creatine, proteins, and essential fatty acids top the list of highly researched, highly effective supplements.



References:

1) Phelan JN, Gonyea WJ. Effect of radiation on satellite cell activity and protein expression in overloaded mammalian skeletal muscle. Anat. Rec. 247:179-188, 1997

2)Rosenblatt JD, Parry DJ., Gamma irradiation prevents compensatory hypertrophy of overloaded extensor digitorum longus muscle. J. Appl. Physiol. 73:2538-2543, 1992

3)Rosenblatt JD, Yong D, Parry DJ., Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. Muscle Nerve 17:608-613, 1994

4)Hespel P, Op't Eijnde B, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, Dymarkowski S, Van Hecke P, Richter EA. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol. 2001 Oct 15;536(Pt 2):625-33
 
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