Increasing Creatine’s Bioavailability: An Interview of Dr. Ralf Jäger

February 2008

Contents:

1- Featured Article:
Increasing Creatine’s Bioavailability: An Interview of Dr. Ralf Jäger.


Increasing the amount of creatine that is absorbed from the digestive tract into the blood stream is a major focus of many creatine manufacturers as well as prominent creatine researchers. Maximizing creatine absorption will reduce the amount of creatine ingested to notice an improvement in physical performance as well as help mitigate some gastrointestinal complications commonly associated with creatine supplementation.

In this issue of the Creatine Newsletter I have the pleasure of interviewing Dr. Ralf Jäger, one of the authors of a recent manuscript that arose from a scientific collaboration involving two giants in the creatine research field. This study compared the bioavailability of some common forms of commercially available creatine.

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This Month’s Featured Article:

Increasing Creatine’s Bioavailability: An Interview of Dr. Ralf Jäger.

by Alfredo Franco-Obregón, PhD

Today I will be interviewing Dr. Ralf Jäger formerly of SKW/Degussa, one of the leading producers of quality creatine products for human consumption. Dr. Jäger recently joined forces with two renowned creatine researchers, Professor Roger Harris (UK) and Professor Marc Francaux (Belgium) to conduct a scientific study comparing the absorptive capacity of three commercially available forms of creatine, creatine monohydrate, creatine citrate and creatine pyruvate (Ref 1). This study revealed that creatine pyruvate has the highest rate of absorption into the blood stream after ingesting identical amounts of creatine per serving of the agent in question.

The participation of Professors Harris and Francaux in this study greatly increases the credibility of its findings. Professor Harris can be credited with the manuscript that quite literally started the modern day phenomenon of creatine supplementation back in 1992 (Ref 2). Professor Francaux has authored several important manuscripts describing the effects of creatine supplementation over muscle anabolism as well as the possible side effects resulting from creatine supplementation. Professor Francaux recently studied the effects of combining creatine monohydrate with beta-glucan or protein rich foods on creatine retention and could show that creatine monohydrate seemed to be totally absorbed (Ref 3). The contribution of these two scientists to the study is certainly worth noting.

First, tell us a little about the origins of the collaboration that arose between yourself and these two respected creatine researchers.


The article arose from an industrial collaboration between Professor Harris and Degussa. I met Professor Harris in 1999 during a symposium on dietary supplements organized by SKW/Degussa. I have been with Degussa from 1999-2007. During my time with Degussa I tried to stabilize creatine in aqueous solution and all attempts failed. We decided to go with a mechanical solution, keeping creatine separated from the beverage until the time of consumption. Degussa, in cooperation with Ball Corporation, developed the technology FreshCan. A small plastic container swims inside a beverage can and when you open the can the drop in pressure opens the container and releases the creatine into the beverage. Please visit www.fortifyenergy.com to check out an example of a creatine containing beverage utilizing the FreshCan technology. The creatine inside the plastic container has to dissolve quickly and that’s why were interested in creatine salts, which dissolve quicker than creatine monohydrate. We picked creatine pyruvate and creatine citrate and did the bioavailability study with Roger to prove that both forms of creatine are as good as creatine monohydrate. We were surprised by the findings of the study that actually the creatine salts (citrate and pyruvate) resulted in an improved creatine uptake.

Tell us a little something about yourself so that we may gauge your motivation for joining this study.

I am a certified sports nutritionist (CISSN), a Fellow of the International Society of Sports Nutrition (FISSN, www.theissn.org), a member of the National Strength and Conditioning Association (NSCA), and a member of the Editorial Board of the Journal of the International Society of Sports Nutrition (www.jissn.com). I do have a Ph.D. in organic chemistry from the University of Bonn, Germany and was a postdoctoral scholar with the California Institute of Technology (CalTech) in Pasadena, CA, doing basic research in bioorganic chemistry (in the area of breast cancer). In addition, I do have an MBA from the University of Wuerzburg, Germany in cooperation with Boston University and Florida Gulf Coast University. I have been Director of Research and Development for the leading global creatine manufacturer Degussa AG and served as their Vice President Marketing and Sales in the area of functional foods until 2007. Today, I am a managing member of Increnovo LLC, a consulting company for innovative, clinically proven nutritional products (dietary supplements, functional foods). I have been a nutritional consultant to several professional and Olympic athletes and teams during the last 10 years.

You are certainly familiar with the study of Vierck et al. (Ref 4) that showed that creatine pyruvate actually slowed the proliferation of myoblast when administered in tissue culture, suggesting a negative effect of this form on creatine over muscle development. That is, creatine pyruvate appeared to slow the rate at which muscle progenitor cells (myoblasts) multiply when grown outside the animal in plastic dishes. This group also showed that creatine pyruvate made no difference on myoblast differentiation to produce skeletal muscle fibers. You were an author on a recent manuscript, however, that showed that creatine pyruvate is absorbed more readily into the blood stream from the digestive tract of human subjects. Can you place your results within the context of this previous study?

Previous research has shown that plasma creatine levels are influenced by extracellular concentrations of insulin and glucose as well as by the intracellular creatine concentration. However, the form of creatine administered does not appear to have any effect although specific data on this is lacking. Our study examined whether the administration of three different forms of creatine had different effects on plasma creatine concentrations and pharmacokinetics. Each subject was assigned to ingest a single dose of isomolar amounts of creatine (4.4 g) in the form of creatine monohydrate (CrM), tri-creatine citrate (CrC), or creatine pyruvate (CrPyr) using a balanced cross-over design. Mean peak concentrations and area under the curve (AUC) were significantly higher with CrPyr (17 and 14%, respectively) in comparison to CrM and CrC. The findings of our study suggest that different forms of creatine result in slightly altered kinetics of plasma creatine absorption following ingestion of isomolar (with respect to creatine) doses of CrM, CrC and CrPyr. The mechanism by which CrPyr might alter creatine absorption is not yet understood. Vierck et al’s studied the effects of CrM or CrPyr on proliferation or differentiation of myogenic satellite cells. The authors found no increase in proliferation over that of the control cultures, however CrM induced differentiation. The effects seemed to be dose dependent since only one specific concentration showed the desired effect. The difference in creatine concentration of approximate 30% between CrM and CrPyr might explain why CrPyr did not produce detectable fusion. In addition, the author concluded that the CrPyr used in this study might have deteriorated.

View the past issue of the Creatine Newsletter that discussed the results of the study performed by Vierck et al. (2003).

In your opinion, what are the major drawbacks to the modern day practice of creatine supplementation?

Major drawbacks of creatine supplementation are the high daily dose (20 g per day during a loading phase), creatine’s instability in aqueous solution, and its limited solubility in water (1.3% at 20 degrees). This reduces the available delivery forms of commercial creatine and to a certain extent its consumer acceptance.

Where can it be improved?

Delivery forms that improve consumer convenience, including shelf stable beverages and functional foods, to target non-athletes, especially the elderly to make creatine a main stream ingredient for people who could benefit from creatine supplementation such as muscle disuse and improvement in quality of life for the elderly or to prevent mental fatigue in the young.

What do you foresee will be the next big breakthrough in creatine supplementation?

Scientists will continue to try to improve the ergogenic effects of creatine. Improvement in muscle creatine retention, reduction of non-responder rates and the combination of the power of creatine with nutrients those are capable of improving endurance will drive the development in sports nutrition and areas related to muscular strength. Creatine research on brain functions is still in an early stage. I expect the next breakthrough to come from one of those research areas.

Under what circumstances should creatine supplementation be considered doping, if at all?


Creatine should not be considered doping, since there is an upper limit to the amount of creatine that can be stored in the muscles. The amount of increase in muscle storage depends on the levels of creatine in the muscle prior to supplementation. Individuals who have lower muscle creatine stores due to diet low or depleted of meat or fish, are more likely to experience muscle storage increases of 20–40%, whereas subjects with relatively high muscle stores may only increase stores by 10–20% The magnitude of the increase in skeletal muscle creatine content is important because studies have reported performance changes to be correlated to this increase. The increase in skeletal creatine muscle content can also be achieved by choosing a diet rich in creatine (a diet rich in meat or fish) and banning creatine would put individuals choosing a vegetarian or vegan diet at a competitive disadvantage.

Which age group, or social demographic, should not consider creatine supplementation? What precautionary measures should they implement if deciding to supplement?

The only clinically significant side effect reported in scientific literature is weight gain. Many anecdotal claims of side effects including dehydration, cramping, kidney and liver damage, musculoskeletal injury, gastrointestinal distress, and anterior (leg) compartment syndrome still exist in the media and popular literature. While athletes who are taking creatine may experience these symptoms, the scientific literature suggests that these athletes have no greater, and a possibly lower, risk of these symptoms than those not supplementing with creatine. Recent studies confirm the safety in previously controversial areas of renal function (see Gualano et al., Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial. Eur. J. Appl. Physiol. 2008) or muscle cramps and dehydration (see J. Stout et al., Putting the Myth of Creatine Supplementation Leading to Muscle Cramps and Dehydration to Rest. Br. J. Sports Med. 2008). The evidence suggests that creatine supplementation appears to be safe when taken within recommended usage guidelines and might be beneficial in preventing injury. As a precaution, young individuals and pregnant women should consult with their doctor until studies for their specific group are available.

Please visit www.jissn.com/content/4/1/17 to access the original publication. The Journal of the International Society of Sport Nutrition (JISSN) is a peer-reviewed, open access journal solely dedicated to sports nutrition and gives readers interested in sports nutrition research direct access to original articles free of charge.

Finally, are there any other important issues you would like me to bring up to my readers?

Many forms of creatine exist in the marketplace, and these choices can be very confusing for the consumer. We hope that more studies will dare to compare the potential effects of new forms of creatine head-to-head with the golden standard of creatine supplementation, creatine monohydrate.

Scientific References

(Ref. 1) Harris, R. C. et al. (1992) Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Science, Volume 83, pages 367-374.

(Ref. 2) Jäger, R. et al. (2007) Comparison of new forms of creatine in raising plasma creatine levels. Journal of the International Society of Sports Nutrition, Volume 4, pages 17 (www.jissn.com/content/4/1/17).

(Ref. 3) Francaux, M. et al. (2008) Kinetics of creatine ingested as a food ingredient. European Journal of Applied Physiology, Volume 102 (2), pages 133-143.

(Ref. 4) Vierck, J. L. et al. (2003) The effects of ergogenic compounds on myogenic satellite cells. Medicine & Science in Sports & Exercise, Volume 35 (5), pages 769-776.

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