Sports Nutrition: Creatine and Athletic Performance: An interview with Dr. Paul Greenhaff
By Richard A. Passwater, Ph.D.
There has been a great deal of excitement among athletes about the dietary supplement creatine. Scientific research has verified that creatine is not just an energy source that powers muscles it is much more. Creatine is becoming one the athletes most important supplements because it:
Creatine is part of the energy storage system used by our bodies to power muscle contractions for bursts of activity. Creatine is naturally made in our bodies. The very basic raw materials needed for our bodies to make creatine are the amino acids arginine, methionine and glycine. We can increase the amount of creatine stored in our muscles by taking creatine supplements, but the variation between individuals can be very large.
This interview begins with a seminal conference held in Bethesda Maryland, June 3 and 4, 1996. This was a great day for the Health Food Industry. Why? Because our highest government scientific institutes were sponsoring the presentation of good scientific evidence concerning the issue whether dietary supplements can help normal, healthy, well-nourished, active people improve their performance. I was more than surprised -- almost startled! The Conference was a National Institutes of Health (NIH) Workshop entitled "The role of dietary supplements for physically active people," and was co-sponsored by eleven divisions of the NIH.
The NIH had invited Dr. Paul Greenhaff from the University of Nottingham in England, along with several other speakers, to brief the newly formed NIH Office of Dietary Supplements. His topic was "Does dietary creatine supplementation have a role to play in exercise metabolism?" British and Swedish researchers had been publishing their scientific studies on the benefits of creatine to athletic performance and athletes had taken notice.
Dr. Paul Greenhaff obtained his Ph. D. in Medical Sciences in 1988, and conducted post-doctoral research in muscle metabolism through 1991, including research with Professor Eric Hultman in Sweden. Since 1991 he has held the position of Lecturer on Research in Muscle Metabolism in the Department of Physiology and Pharmacology of the Faculty of Medicine and Health Sciences at the Medical School of the Queen's Medical Center of the University of Nottingham.
Passwater: I was pleased to see you at the NIH symposium in June 1996. I couldn't help wondering at the time if the organizers were purely interested in science or if the coming Olympics in Atlanta had anything to do with inviting you. Was it a clever effort to pick your brain to help our athletes?
Greenhaff: NIH representatives contacted me and told me they were opening a new office of Dietary Supplements. They were inviting experts from various fields to give them more information about areas that they should perhaps be looking into.
Passwater: You are a recreational athlete and a scientist. What led you to your interest in biochemistry?
Greenhaff: Well, I have always had an interest in exercise both as a participant in some and as a spectator in others. I also had a very big interest in physiology. I am lucky enough to be in a situation where I have been able to marry both these topics. Fortunately, there is a growing interest in the biochemistry and physiology of muscle fatigue which is increasing the need for more research. We have lots of questions for which we need answers.
Passwater: In which sports do you participate?
Greenhaff: I used to compete at cross-country and road running, but knee injuries have changed that. I actively compete in swimming now so I still have an interest in sports. I like to be active in sports because I think sports make you feel better within yourself training and getting completely away from work.
Passwater: I certainly agree with that. You were able to combine your avocation of sports participation with your vocation of biochemistry and physiology. What led your research to creatine?
Greenhaff: That came from the research work being undertaken by Dr. Eric Hultman, Roger Harris and Karen Soderlund when I was working in Sweden with Professor Hultman at the Karolinska Institute. The story that was developing from the research at that time was that phosphocreatine (Creatine phosphate), which is the phosphorylated form of creatine, was very much related to the development of fatigue during very intense muscle contraction. Just as you can load the carbohydrate store of muscle and facilitate performance during sub-maximal exercise, the question was asked if you raise the muscle creatine store, can you improve muscle function? Not only in the sporting context, which is what the press has gotten hold of, but also in pathological conditions where energy production is a limitation.
Passwater: You mentioned carbohydrate loading. That concept was developed about 30 years ago. Doesn't carbo-loading increase endurance performance by increasing the amount of carbohydrate "fuel" (glycogen) stored in muscles.
Greenhaff: Yes, the pioneer there also was Professor Hultman.
Passwater: How long has creatine been used by athletes as an ergogenic aid? I am aware of special creatine supplements for athletic performance being introduced first in the U.K. in 1992 and then in the U. S. in 1993. Is there any truth to the claims that the Soviet block athletes were using creatine decades ago for Olympic training. I haven't seen any verification of that.
Greenhaff: That's anecdotal. There are scientific papers showing that people in the 1930s and 1920s used creatine precursors to try to improve exercise performance. The first reports of positive experiments with using creatine supplements began at around the 1992 Olympics held in Barcelona. British athletes who were taking creatine supplements as a result of the research in Sweden and the UK were having good results.
Passwater: Seems to me like typical British understatement. Wasn't the research done in your laboratory?
Greenhaff: Yes, some of it.
Passwater: You mention some British athletes had "good results." I remember that creatine supplements were credited with powering several of the British athletes to gold medals. The London Times reported (August 7 1992) that Linford Christie, the 100 meter Gold Medalist trained with creatine before the 1992 Olympics, and Bodybuilding Monthly reported that Sally Gunnell, the 400 meter Gold Medalist, also trained with creatine. The London Times also reported that Colin Jackson, the champion British 110-meter hurdler, just began taking creatine right before the Olympics. Although he did not win the gold medal at the Olympics, he soon beat the Olympic Gold Medalist, Mark McCoy, on several occasions.
They were using a technique called "creatine loading" which you have helped perfect. Before I ask you about creatine loading, please review for our readers, what the roles of creatine are in muscle metabolism.
Greenhaff: Well, creatine has two principal roles. One is that it maintains a high cellular ATP/ADP ratio. ATP is required for contraction so creatine acts as a temporal buffer to allow the ATP/ADP ratio to be maintained high during contraction. The other role is that creatine acts as a spatial buffer in that creatine can act to shuttle energy across the cytosol from the mitochondria where ATP is being produced to the myofilaments where contraction is occurring.
Passwater: What degree of increased performance have you measured or observed?
Greenhaff: Creatine certainly can improve athletic performance. There are several papers now that have been published looking at different sports. The point that I would like to make is that you need to get a substantial increase in muscle creatine before you get real substantial improvement in performance. In our hands, 20 to 30 percent of people don't retain sufficient quantities of creatine (when administered alone) to see any effect. Therefore, you need to optimize creatine uptake and in those conditions yes definitely creatine can improve performance.
Passwater: What degree of performance have you measured?
Greenhaff: We've seen anything from between a 5 to a 10 percent improvement in exercise performance. That's during 30 seconds of maximum sprint exercise. Other people have actually measured larger improvements. It's a fairly wide- ranging term "degree of increased performance." For that concept to have real meaning, I think you need to look specifically at the type of exercise that is being performed. Is it a single bench press of a weight or is it a 30-second sprint? These events are physiologically very different.
Passwater: What is creatine loading?
Greenhaff: Creatine loading came out of Professor Hultman's laboratory in the late 1980s although their research was not published until 1992. The idea of a loading phase and then a maintenance phase came out of my laboratory last year, but in collaboration with Professor Hultman.
Passwater: The collaboration between your research groups has really elucidated a lot about improving athletic performance. How did this collaboration come about?
Greenhaff: We first met in 1986 at an exercise conference. I was completing my Ph. D. in Aberdeen at the time, and we spoke of the possibility of my doing post-doctoral research with his research group. One only has to look at the quality of research that has come from his laboratory over the past thirty years to know that there are few, if any, better human muscle research laboratories in the world. I managed to do so during 1989 and 1990. We have worked together ever since, and I consider him a good friend as well as research colleague. I have also had the privilege to do research in the laboratories of Professor Ron Maughan and Dr. Roger Harris, another main figure in creatine research, during my research training.
Passwater: That explains a lot but, I interrupted your answer to my question.
Greenhaff: Well, creatine loading, as the wording implies, is a mechanism of increasing the creatine store of skeletal muscle, which in most people is in the region of 125 millimoles per kilogram of dry muscle (or about 16 milligrams per kilogram). By ingesting creatine in particular quantities, you can increase the muscle creatine uptake by about 25% on average, but I should point out that the variation between individuals is quite large. This is a point which people seem to ignore at the moment. You do find individuals who don't actually respond to creatine ingestion.
Passwater: We'll pick up on how you have found to improve creatine response shortly, but first, please tell us what is happening biochemically to achieve creatine loading?
Greenhaff: The mechanism of creatine transport into muscle is not completely resolved. There are several postulated methods of transport into muscle, but what is clear is once creatine is in the muscle it is trapped there. Creatine doesn't leave the muscle at a very rapid rate, so once you have achieved creatine uptake, your stores remain elevated for quite some time, perhaps having a four-to-six week half-life. They are not degraded during exercise.
Passwater: How can creatine loading be achieved by athletes?
Greenhaff: Our studies show that probably the most effective way to creatine load skeletal muscle is to ingest 20 grams of creatine for 5 days in four 5- gram doses each day, and to ingest that with a carbohydrate solution. We have shown that carbohydrate ingestion facilitates creatine transport such that it reduces the variation between individuals.
Passwater: Can muscle creatine content be optimized using lower doses of creatine?
Greenhaff: Yes, but it takes considerably longer. Lower dose creatine supplementation (e. g., three grams a day for two weeks) is less effective, in the short term, at raising muscle creatine concentration than is a five-day regimen of 20 grams a day. However, following four weeks of supplementation at this lower dose, muscle creatine accumulation is no different when regimens are compared.
Passwater: So you have found that ingesting carbohydrate in solution along with the creatine increases creatine uptake by muscles and enables more people to respond to creatine loading.
Greenhaff: Definitely. The mechanism is not yet clear. Of course it could be related to insulin availability because it's known that insulin has a number of functions, one of which is stimulation of membrane transport. So it could be via that mechanism, but there are other ways. At the moment we don't really know and that's something that needs answered from research.
Passwater: "Cell volumizing" or "cell hydration" is this a real phenomenon or is it a myth?
Greenhaff: Scientifically speaking, I think people may be jumping the gun a little, taking information that has been gained from animal and muscle preparations and applying that directly to exercising humans. What is known is if you increase the volume of a muscle cell in a laboratory situation, the changes in volume can have subsequent physiological responses. For example, it has been shown that an increase in cell volume can stimulate carbohydrate synthesis in muscle. But then to take that and apply it directly to human muscles and even take it a further step and say creatine because it potentially increases muscle water volume then has other affects. It is really speculation and I think again research in this area needs to be undertaken before we can make any more conclusive statements about it.
Passwater: So, this concept has not been fully verified by science at this time, but it does in fact have some basis based on preliminary animal studies.
Passwater: Is creatine supplementation of value to a healthy person other than improving athletic performance. Is there any benefit the average person would have by taking creatine supplements?
Greenhaff: Certainly, I would see a role for creatine supplementation in a vegetarian population where creatine is not present in the diet. Other than that in healthy individuals I can't say there is anything of great value there.
Passwater: What might a vegetarian experience by taking a creatine supplement?
Greenhaff: What we have found is that when you feed creatine to vegetarians they retain enormous quantities of creatine suggesting they are depleted and/or have an upregulated transport into muscle. I don't know anyone yet or haven't seen any published literature showing what happens to their exercise performance but no doubt someone is doing that experiment.
Passwater: Would creatine supplements be of value to persons having illnesses involving muscle wasting? I remember a 1981 paper in the New England Journal of Medicine showing that creatine supplementation partially alleviated gyrate atrophy.
Greenhaff: Yes, creatine supplementation could be of value in several disease states. Certainly in conditions where muscle blood flow is compromised, for example, peripheral vascular disease--there could be a potential there. It has potential in chronic heart failure not only in terms of skeletal muscle creatine uptake but also heart creatine uptake. I know there is clinical research going on in these areas. The point about trying to increase muscle mass is a valid one but at the moment it would appear certainly in the short term the increase in muscle mass probably is just water. During chronic creatine ingestion I don't think there are data at all looking at the effects of what creatine is doing to muscle protein deposition.
Passwater: Does taking creatine supplements shut down endogenous creatine biosynthesis?
Greenhaff: Yes, in the amounts used for increased performance it does. So does, I imagine, eating large amounts of meat which, of course, contains creatine. It's a natural feedback mechanism. But what people should be clear is that once creatine supplementation is stopped and the muscle levels then begin to decline, then endogenous synthesis starts again. You have to remember that we are talking about people ingesting possible 20 grams a day at least initially and dropping to a lower maintenance doses of two grams per day. With normal diets, endogenous synthesis probably contributes one-to-two grams per day. So when you consume more than you normally would have to make, there is no need for the body to synthesize creatine.
Passwater: Yes, our bodies have been designed to conserves our resources and energy usage to do only what is needed. But let me re-state this another way to address the specific concerns raised specifically about taking creatine supplements and the effect on the production of the creatine precursor, guanidine acetic acid (GAA). According to my mail, it seems that someone has published a statement or an advertisement that is causing some concern and confusion.
Essentially, GAA is only needed for creatine production, and if the body is getting all of the creatine it needs from the diet, then GAA production is also halted during the time of adequate creatine intake. GAA and creatine production both are activated again when dietary creatine decreases. As you pointed out, this is natural, normal and of no concern.
Let's address another concern that has been raised. Does creatine supplementation halt creatine transport?
Greenhaff: Well, initially it very much stimulates creatine transport. When the muscles are loaded with creatine additional transport of creatine into the muscles does decline. This is a natural feedback mechanism resulting from the increase in muscle creatine content.
Passwater: Does creatine supplementation affect the production of creatine kinase, the enzyme needed to reconvert creatine back into creatine phosphate?
Greenhaff: I haven't seen any evidence to suggest that anywhere.
Passwater: Does creatine supplementation reduce the number of creatine transporter proteins?
Greenhaff: There is no answer to that question. Researchers have identified a creatine transporter in muscle but no one has measured the number of transporters and whether they change with creatine ingestion.
Passwater: Does creatine supplementation increase creatine excretion?
Greenhaff: Yes, it does increase creatine excretion by virtue of the fact that once you have saturated muscle creatine uptake then the body just naturally excretes any creatine that is available in plasma, in circulation.
Passwater: Does taking creatine supplements increase thirst?
Greenhaff: To be blunt, I don't know. The most effective way to take creatine is in solution, so you already are in fact taking fluids in that way. We haven't seen any individuals that have mentioned they have increased thirst. Certainly in a situation where you are trying to optimize creatine transport you are ingesting further fluids in the form of carbohydrate solution. If you are taking creatine supplements in solution form as our research suggests is the most efficient way, there should be no increase in thirst.
Passwater: Does increased creatine spill into the urine increase the volume of urine?
Greenhaff: No, what we have actually found is during the initial days of supplementation you actually get a decrease in urinary volume but then after two days your urinary volume returns to normal. That's when you are ingesting creatine monohydrate on its own. If you are ingesting a solution of carbohydrates in conjunction with the creatine, then your urinary volume actually increases just by virtue that you are ingesting more fluids.
Passwater: What is your research looking into now?
Greenhaff: We're looking at several areas really and trying to elucidate why some people seem to retain creatine in large quantities when you give it to them while others don't retain any at all. We're interested in looking at the relationship between creatine transport and carbohydrate intake as well.
Passwater: Where do you think your research will be going in the future?
Greenhaff: Our main interests are in human metabolism and the biochemistry of muscle fatigue. We will always have an interest in the biochemistry of muscle and fatigue development in muscle.
Passwater: I know that your research will help a lot of athletes in their efforts to reach their goals. Thank you for sharing your knowledge with us.
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