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The Creatine Roundtable…The World's Authorities Speak 

By By Bob Lefavi, PhD, CSCS, CHES 

What's the scoop on creatine, anyway? Sure, we know it's effective but - once and for all- does creatine have any side effects? While my own research hasn't shown side effects, I decided to go to the world's authorities on creatine for answers. They are Dr. Eric Hultman of Sweden, Drs. Roger Harris and Paul Greenhaff of the United Kingdom, and Drs. William Kraemer and Michael Stone of the U.S. (The latter two are past presidents of the National Strength and Conditioning Association). Here's what they had to say. 

What are your opinions on the effects of creatine on the general health of athletes? Are there side effects of significance?

Hultman: According to my opinion, athletes can take creatine without health risk provided the creatine product is pure and the dosage is within suggested limits. Our experience is from our initial studies with a dose of 20 grams of creatine (or 300mg/kg body weight) per day during three to six days. This supplementation gave no changes in routine biochemical tests including liver and kidney function. The only side effect observed was an increase in body weight varying from 0.5 to 2.5 kilograms, at least partly due to retention of water and in some subjects also to an increase of the muscle glycogen store. A continuation of the creatine administration for one to three months using a dosage of two grams per day after the six days of high dose supplementation showed again unchanged routine biochemistry tests. A proposed side effect of a high dosage of creatine is an overload of creatine to the kidney with adverse effect on kidney function. This was not observed in our initial studies and has recently been confirmed by others showing intact kidney function during short-term creatine supplementation. However, studies of long-term effects in athletes are still lacking. Side effects of long-term creatine intake have been studied in two different patient groups: Patients with gyrate atrophy of the choroid and retina, and children with muscle dystrophies. The gyrate atrophy patients have been treated with creatine in a dosage of 1.5 - 2.0 grams a day for up to five years without changes in routine biochemical tests, including liver and kidney function. Similar results were reported for the children (ages six-12) with different types of muscle dystrophies given a creatine dosage of six to 10 grams per day during a 12-month period. No creatine was given during one day each week. The creatine dosage corresponded to 400 milligrams per kilogram body weight per day, thus higher than the loading dose recommended for a six-day period in athletes. The results in the two patient groups indicate a high tolerance for prolonged creatine intake, also with a dosage far above that necessary in healthy athletes. 

Kraemer: We have studied creatine supplementation from acute loading studies to a three-month training study. In addition, we have studied creatine loading in the heat. All of our subjects have been healthy. To date, we have not been able to replicate the anecdotal observations of side effects (e.g., muscle cramps, nausea) attributed to creatine supplementation. The frequency of any symptoms (e.g., gastric upset), when they do occur, is similar to the placebo groups. A major fear of many is [deals with] the effects of years of use. Such data have not been published in the peer-reviewed literature but concerns would be heightened if inappropriately high amounts were used. Typically, maintenance doses are lower than loading phases which last five to seven days. Education of proper loading of creatine is vital to minimize any theoretical physiological stress. Concerns arise as to the long-term side effects on the kidney, liver and other systems. Others and we have observed slight increases in creatinine and some clinical chemistries, but all are within normal ranges and are consistent with the short-term overflow of creatine disposal after the muscle is loaded during the loading phase. New data indicate lower amounts of creatine over a longer period of time may be as effective in loading the muscle. This would reduce the acute physiological stress on the body's organ systems. Concerns also have been voiced as to the impact loading with creatine has on natural chemical pathways that produce creatine in the body. To date, no data exist to indicate that when supplementation is stopped natural production of creatine does not return to normal. 

Greenhaff: Creatine has been ingested routinely by athletes for nearly ten years now and, at the time of writing, I am aware of only two published reports indicating any significant adverse effect of creatine ingestion. One was in a person who had a previous history of kidney problems and the other was in an apparently healthy individual who had evidently been ingesting 20 grams of creatine per day for one month. It is important to note that this rate of creatine ingestion is way in excess of that required to load muscle creatine stores. We have clearly demonstrated that the ingestion of 20 grams creatine (in four equally spaced five-gram doses) can load muscle creatine stores in five days and that this elevated store can be maintained by ingesting two to three grams per day (in a single dose) thereafter. Ingesting large quantities of creatine on a daily basis may in the long term be detrimental to health; we just don't know, as the data are not available. You can be sure, however, that ingesting large quantities of creatine over prolonged periods will be a waste of money, as the vast majority of it will pass out in the urine. In summary, I can see no obvious health risk- to healthy individuals- of ingesting 20 grams of creatine for five to seven days. Furthermore, we have seen no adverse health effects from maintaining elevated muscle creatine levels by ingesting up to three grams of creatine per day for two months. Studies aimed at investigating the side effects of creatine ingestion over a period of several years are warranted, if only to quell the current media frenzy concerning creatine. 

Stone: There is no evidence that creatine supplementation produces untoward side effects. The only side effects noted in the scientific literature are weight gain and occasional reports of gastro-intestinal upset (which may be related to impurities). Although (at present) there are no long-term longitudinal studies dealing with health aspects, there is observational evidence suggesting that long-term supplementation does not cause adverse effects. For example, there are a number of athletes who have supplemented with creatine for several years. If supplementation caused profound adverse effects, these athletes would be demonstrating symptoms, and they are not. Additionally, my colleagues and I presented a retrospective study at the 1999 NSCA National meeting in Kansas City that dealt with health aspects of creatine supplementation. Using 26 current and former national and international level athletes, we examined a total of 62 variables. These variables included typical clinical blood analyses (i.e. CBC, lipids, liver enzymes etc.), heart rate, blood pressure and answers to a health/injury-related questionnaire. The athletes had been taking creatine for up to four years and displayed no adverse effects. The only reported side effect was occasional gastrointestinal upset during the loading phase. I would also make the observation that it has become apparent that research focusing on health aspects of creatine supplementation appears to have moved from objective science to "creatine has ergogenic properties for strength power athletes so there must be something wrong with it and we're going to find it." I wonder if the same criteria would be imposed on an ergogenic aid that benefited endurance athletes? 

Harris: With the exception of one published case-report, there is no evidence of adverse effects on the well being of clinically healthy athletes taking creatine monohydrate (Cr.H2O) for a week at 20 grams per day to achieve initial "loading" in muscle, followed by the longer use of two to five grams daily. Taking Cr.H2O will, however, increase body weight by one to three kilograms, initially through increased retention of water and later (particularly in athletes engaged in strength training) by an increase in muscle mass. The first effect is comparable to the increase in muscle water seen with dietary carbohydrate loading and needs to be taken into consideration by athletes participating in weight-restricted sports. Athletes should be aware of the dangers of trying to achieve an unrealistic weight target through fluid loss. There are anecdotal reports of gastrointestinal disturbances but this has not been my experience working with a hundred or more athletes and non-athletes where Cr.H2O has been taken as a drink or in solid form. 

Cramping is commonly described as a side effect. Is your experience consistent with this? How common do you think muscle cramping is? What might be the physiological mechanism underlying any cramping and, if it exists, how can athletes avoid it? (There is now some research suggesting shin splints might be a side effect.) 

Greenhaff: I am aware of the anecdotal reports relating creatine ingestion to muscle cramping. However, in nearly ten years of personal and research experience with this compound, I have not observed one incident of muscle cramping. Nor am aware of any published data on this topic. If I had to guess at a physiological mechanism underlying this apparent phenomenon, I would suggest it might be related to a creatine-mediated change in the muscle membrane potential. Creatine transport into muscle is dependent on sodium movement into muscle. However, it just so happens that sodium is also involved in the generation of the muscle membrane electrical potential, the disruption of which may be associated with muscle cramping. Other possible cramping mechanisms might include a creatine-mediated change in body water compartmentation or creatine mediated increases in muscle work output over periods of intense training. 

Stone: While cramping may be a common complaint, there is little evidence that it is caused by creatine supplementation (Krieder et al. 1999). We have performed two longitudinal studies (short-term) with athletes during heavy in-season training (one six-week track and field and one five-week American football). Cramps were not observed in either study, nor did any subject in our retrospective study report cramps, shin splints etc. The mechanism(s) for cramping is poorly understood and may be multi-factorial (Journal of sports Science, 1998). Some evidence indicates adequate fluid replacement may reduce the incidence and severity of cramping. In this context it is interesting to note that factors other than physiological could influence cramping. For example, in American collegiate football, the reports of increased cramping begin about 1995. This was also the same time as two important rule changes. First, fall training could begin with full pads and second, the number of athletes on a squad was cut. This second rule change means that fewer players would be exposed to the same practice time (i.e., complete more drills). These two rule changes may have exposed players to a greater heat stress resulting in greater side effects including cramps. These possibilities should also be examined. 

Hultman: Cramping has been reported to me by a few athletes. I have no idea how common the cramping is among athletes. What's interesting is that I have never heard any complain about cramping in the series of subjects we have used in our creatine studies. These subjects have not been training hard during the supplementation, which probably is an important difference to the athletes taking creatine. I don't know the physiological mechanism responsible for cramping, but it seems to rely on the combination of creatine uptake and repeated hard exercise. 

Harris: Muscle cramping is our most commonly reported side effect, but then mainly in soccer players (at the time of match playing) or cyclists. In soccer there is always some risk of cramping towards the end of a match as players approach a point of muscle glycogen depletion and attempt to try to engage in sprinting beyond this. With creatine "loading," player's show increased sprinting ability and faster between-sprint recovery, and they may play more "aggressively." However, starting with the same "tank of petrol," muscle glycogen depletion will occur much earlier. The remedy is to institute a program maximizing carbohydrate support beginning two days before a match and providing additional supplementation even during breaks in the match itself. Even then, coaches should be aware of the problem and be prepared to pull players off the field if necessary. Early glycogen depletion (and risk of cramping) may be the cost of the increase in performance. 

Kraemer: Muscle cramping has been postured anecdotally as a potential negative side effect. The causes of cramping have been related to losses in water, minerals (i.e., electrolytes), maximal exertion, and other unknown factors. Creatine does hold more water inside the cell to maintain the cell's normal osmotic gradients and thus may make it more difficult for the cell to give water up. This would appear to make it more difficult for the cell to become dehydrated. Typically, muscle cramping is seen in a physiological environment where there is depletion of electrolytes and body water. To date, our observations and those of others have not been able to directly link cramping to the use of creatine under controlled laboratory conditions. There is always the concern for proper water intake behavior in athletes. My observation after working with thousands of athletes over the years is that many athletes are chronically dehydrated. Thus, athletes need to carefully monitor their water intake behavior before, during, and after exercise training sessions, practice and competition. Set amounts of water should be consumed and body weight should be monitored before and after exercise. Remember, "thirst" is not a good marker of an athlete's hydration status. In order for us to understand any causal relationship between creatine and specific side effects like cramping, shin splints etc., we must await the controlled scientific studies. Information coming from the "free living" environment has a great potential for confounding effects of other factors (e.g., dehydration). 

There continue to be questions concerning the safety of creatine for children and teenage athletes. In fact, the state of Texas has placed creatine on a list of substances that should not be consumed by young athletes. Is creatine "safe" for young athletes (in your opinion)? What is the earliest age you'd approve its use? 

Stone: There is currently no evidence that creatine is unsafe for children or teenagers. In my opinion,much of the concern (and reason for bans) stems from "knee jerk" responses to media misinformation. For example, only two months ago I received a phone call from a woman (from Texas) who still believed creatine was the cause of the fluid-related deaths of three wrestlers. She noted that she had read it in the newspaper. She is not an isolated case. Obviously, the media was excellent at misleading the public, but was not so good at correcting misleading statements. In this context, there are several products on the market that have been associated with long- term adverse side effects; for example- acetomenophen. It is also known that a high carbohydrate diet can be associated with adverse changes in blood lipids, especially in the absence of physical training. Yet both acetomenophen and carbohydrates are considered "safe." Asking at what age it is "safe to allow a child or teenager to supplement with creatine" implies that this practice is unsafe. There is no valid rationale (i.e., enhanced growth of specific tissues, etc.) suggesting that supplementation is any unhealthier for children or teenagers than it is for adults. Furthermore, if a child eats meat, he or she is already supplementing with creatine. Additionally, there is little evidence that banning a substance will stop its use; in fact, it may promote it. Children, teenagers and some adults believe that if a substance is banned then it must be fantastic, and they will go out of their way to use it. A more valid approach is to examine all aspects of the child/teenager's sports program. It makes little sense to supplement anything if nutrition/diet, sleep habits or training program are not optimum. I would certainly examine these aspects before suggesting supplementation. 

Greenhaff: From a personal perspective, I cannot see how creatine would pose a danger to the teenage athlete if ingested in appropriate amounts. However, I am also of the opinion that the advantages obtained from creatine ingestion in a young athlete might only be marginal compared to the benefits that could be obtained from correct nutritional intake and a well-designed training program. In the case of a young athlete who insisted on taking creatine, I would suggest that it is best to give him/her sound advice rather than let the youngster approach the issue in an uninformed manner. Thus, I would recommend that he/she be well informed about what creatine is and its reported positive and negative effects. I would suggest that the creatine then be administered on a body mass basis with plenty of fluids, i.e., 0.3 grams per kilogram body mass to load and 0.03 grams per kilogram body mass to maintain muscle levels. 

Harris: Creatine occurs in both present and former human diets, and many of these approach the supplementary levels consumed by athletes. Many young athletes will obtain significant amounts of creatine from their normal diet (steak, fish, etc.) and if supplementation is considered, then my hope is that this is kept to the minimum. However, I know of no physiological or medical dangers to the use of creatine (at circa 60mg/kg body weight for a single dose when "loading"; 30mg/kg bwt for "maintenance" use) but any form of supplementation is against the sporting ethos. So I will set a minimum age of 21 years as marking the end of athletic innocence, after which wider use of creatine might be considered (but I think few will listen). The one concern I have is the taking of synthetic Cr.H2O with high levels of dihydrotriazine and dicyanodiamide by-products. Users should ask for information about these. 

Kraemer: In a recent survey, 80 percent of high school football players are using this supplement. Nevertheless, this is a tough question. As a scientist, one can only speak to the data, as anyone can have an opinion. To date, only one study in young (about 15 years) swimmers has been published in the peer-reviewed literature. The impact of creatine in that study was equivocal for swimming but the sport of swimming also has some very unique performance characteristics (e.g., buoyancy demands) that make interpretation of the data on performance difficult. No negative side effects were reported, suggesting that no novel side effects were present in this population. Based on such data, it is difficult to make statements about creatine's effects on performance. There is an obvious need for more studies. With only one study, statements about any further unique safety aspects are also premature. How side effects might be different for healthy adults has not been articulated in the literature. At present, we need more data to give more factually based recommendations as to its effectiveness and safety in younger athletes. As for my opinion, I can offer only a perspective. As a former junior high school coach, I can tell you that many young athletes need to work on fundamental sports skills, consistent training practices, and proper basic nutrition long before they worry about using creatine to make the difference. The biggest concern of creatine use in younger athletes has been related to its proper use and the "if a little is good then a lot is better" mentality. Here again, education is vital when creatine is used as a nutritional supplement at any age. 

Hultman: The safety of creatine for children and teenage athletes can be divided in two parts. (1) The tolerance for creatine intake seems to be high also in young children; (2) Is the effect of creatine to delay fatigue during intense exercise of importance or eligible in young teenage athletes? It seems reasonable that teenagers should rely on normal food intake, without supplements, during training. To try to increase maximal exercise capacity by supplements in not fully-grown subjects can be harmful. It is thus advisable not to use creatine supplementation before the age of 18-20 years. As far as I know, there are no studies of creatine's effect on young teenage athletes. 

Do you believe there may be any degree of tolerance or negative feedback in the body over time? That is, will creatine lose its effect? Will the body reduce its production during supplementation? 

Hultman: When discussing tolerance or negative feedback, it should be remembered that creatine supplementation only produces an optimum concentration of creatine, not an unphysiological content.Thus, there is no reason to believe that creatine will lose its effect. The uptake of creatine in muscle tissue is dependent on the activity of the creatine transporter. The activity of the transporter is shown to decrease after high creatine loading in the rat. Studies of transporter protein in humans are ongoing. In animal experiments, it has been shown that the endogenous creatine production is decreased during creatine loading, but the production is rapidly restored when creatine supplementation ceases. We measured the decrease in muscle creatine content during a 30-day period after six days of creatine loading. The fall in muscle creatine to preloading concentration could be accounted for by increased urinary excretion of creatinine, indicating an unchanged endogenous creatine production in the postloading period. No measurements of creatine production during creatine supplementation in man have been done. Further studies are needed to understand the creatine transport and metabolism. The suggested use of creatine in athletes would include six days of high- dose supplementation (20g/day) followed by a low maintenance dose during periods of high intensity training. Such periods should be followed by one to two months without creatine supplementation. 

Harris: There is growing evidence to show that the ingestion of large amounts of Cr.H2O will switch off at least one enzyme of synthesis as well as down regulating the transport of creatine into muscle. However, this does not mean creatine will lose its effect. When supplementation is stopped, synthesis and transport will return to pre-supplementation levels. We must bear in mind the high level of creatine that humans have consumed in their diet in the past, as other animals regularly consume today, and that the body is well adjusted to meet these peaks and troughs. What may be of greater concern, because of the ubiquitous role played by creatine in many tissues, is what would happen if biosynthesis fell with aging at a time when dietary creatine intake was also low. We need to move away from regarding creatine as a performance booster for athletes and focus instead on its nutritional importance in other segments of the population. 

Kraemer: Creatine acts to help the body better produce energy under conditions of extreme anaerobic demands in muscle. To date, no data exist to say that this mechanism would change over time. The question of seeing a reduction in natural production of creatine during supplementation has been shown to occur. However, when supplementation is removed, the body reverts back to making its own creatine and normal concentrations are seen in muscle. Therefore, to date, there are no data to suggest that creatine would negatively impact the body's own endogenous chemical pathways for making creatine. 

Greenhaff: Creatine uptake by muscle begins to decline dramatically after only 24 hours of ingestion. This decline occurs as a direct result of the muscle store increasing and is a perfectly normal physiological negative feedback response (you can see therefore that ingesting large quantities of creatine for prolonged periods is pointless). If creatine is ingested for several weeks, it is highly likely that our own production of creatine will stop. Again, this is a negative feedback mechanism. We have been able to demonstrate however, that if supplementation is stopped after one month, the body's production of creatine is initiated once again. Recent animal work suggests that if creatine is ingested chronically in very large quantities, then the amount of the creatine transporter found in the muscle membrane declines. (The creatine transporter is a recently discovered protein that is responsible for the movement of creatine into muscle). Whether a similar response occurs in humans is unknown, as is the consequence of this on creatine metabolism. 

Stone: I have not seen much evidence on this subject. However, it is possible and a good reason to cycle its use (Plisk and Kreider 1999). Supplementation can suppress normal production. However, normal production is re-established post-supplementation.

Dr. Bob Lefavi, Certified Strength and Conditioning Specialist and Certified Health Education Specialist, is a professor in the School of Health Professions, Armstrong Atlantic State University, Savannah, Ga.