POISON PEN

January 1, 1999

Mucking the stalls without the help of creatine

POISON PEN

Mucking the stalls without the help of creatine

In Greek and Roman mythology, the most glorious and powerful hero wasHercules. He was the son of Zeus and a mortal woman.1 The leaderof the gods chose her as a mother for Hercules because of her beauty, virtue,and wisdom. The all-powerful, all-naughty Zeus disguised himself as thelady's husband and lay with her. Hercules grew up to be very strong, buthe was not the sharpest knife in the drawer. Nor was he a good husband orfather. Having been made mentally ill by Zeus's wife, Hera, he slaughteredhis wife and children.

To expiate his sins he submittedhimself to his cousin, King Eurystheus,whoordered him to performtwelve seemingly impossible labors. The fifth laborwas to clean the Augean stables in one day.2 These stalls hadnot been mucked out in years, and they housed thousands of incontinent beasts.Hercules diverted two rivers into the stables and quietly cleaned up themess. He did so without the aid of creatine.

Creatine ingestion is a current fad among would-be Herculean athletes,including many adolescents who want to augment their muscle mass and performance.Because it is classified by the Food and Drug Administration as a nutritionalsupplement, creatine is subject to little or no regulation--and it's bigbusiness in this country. The market for creatine supplements is probablyaround $200 million per year.3,4 In light of its popularity,it seems appropriate to ask the following questions: Does creatine supplementationwork? Is it safe? What should you say when your patients seek your adviceabout using it? And finally, is it ethical to use this substance in competition?

What is creatine?

Creatine is an amino acid, methylguanidine-acetic acid, initially identifiedby the French scientist, Chevreul.5 He named the compound creatine,from the Greek word for flesh.It is technically an ergogenic agent--thatis, it is used to produce energy.6

Creatine is found in nature, primarily in meat and fish. In 1847, anastute observer noted that the meat from foxes killed in the wild containedten times as much creatine as domesticated, relatively inactive, foxes.This scientist concluded that creatine accumulates in muscles as a resultof physical activity.7

The average adult, consuming an unrestricted diet, ingests 1 to 2 g ofcreatine daily. Meat-lovers, especially those who eat large quantities ofred meat, take in much more creatine than vegetarians.8 (In additionto obtaining creatine exogenously from food, the body can synthesize itendogenously from the amino acids glycine and arginine.) Early in this century,it was discovered that not all of the creatine consumed by humans is excretedin the urine; some is stored in the body. In 1912, researchers observedthat ingesting creatine greatly increased the amount of the substance inthe muscles.8 In 1927, creatine phosphate was identified as anessential ingredient in the metabolism of skeletal muscle.5

What does it do?

After ingestion, creatine is absorbed unchanged from the intestinal lumeninto the circulatory system, which carries it to the tissues, primarilyskeletal muscle. Specific protein transporter molecules in the muscle cellscarry creatine directly into muscle tissue. The chemical is actively transportedfrom plasma against a concentration gradient as high as 200 to 1.8Creatine combines with phosphate in skeletal muscle tissue to form creatinephosphate; the phosphate enables adenosine diphosphate (ADP) to regenerateadenosine triphosphate (ATP), the primary fuel for skeletal muscle tissue.

ATP is what we're about here. In 1935, Sir Hans Krebs won the Nobel prizefor his brilliant discovery of the complex chemical reactions that convertall fuel sources to this primary energy compound (memorizing the Krebs cyclehas tortured medical students since that time).9 Ingestion ofcreatine monohydrate, which is the form of creatine sold as a dietary supplement,increases cellular levels of creatine and creatine phosphate.8Creatine phosphate, with its high phosphoryl transport potential, acts asa phosphogen to maintain high levels of ATP.

During exercise, ATP levels do not decrease very much until stores ofcreatine phosphate diminish. True believers in the benefits of creatinetherefore conclude that creatine supplementation can increase intracellularlevels of creatine phosphate, thus maintaining intracellular levels of ATPat optimal levels for longer periods during intense exercise.8This is the reason for creatine's popularity.

To indulge in a bit more biochemical mind bending, remember that energydemand, particularly during short-term, high-intensity exercise, often exceedsthat which oxidative delivery processes can meet. The body must then resynthesizeATP by the anaerobic breakdown of glycogen to lactate and the degradationof phosphocreatine. Because of the high maximum activity of creatine phosphokinaseand the close proximity of the enzyme to its reactants in the cytoplasm,the rate at which ATP can be resynthesized from ADP and phosphocreatineis rapid compared to the rate of glycogenolysis. One of the purposes ofcreatine supplementation is to delay muscle fatigue by elevating phosphocreatinelevels in muscle.

Getting the most out of muscle

According to current thinking, creatine supplementation increases thebioavailability of phosphocreatine in skeletal muscle cells.6Approximately 95% of the total creatine pool in humans is found in skeletalmuscle.7 The remaining 5% is found primarily in the heart, brain,and testes. In skeletal muscle, one third of the total creatine is in thefree form, and the remainder is the phosphorylated form. Supplementationwith creatine increases muscle performance in two ways:6

* Greater availability of phosphocreatine permits faster synthesis ofATP, which provides energy for brief, high-intensity exercise, such as sprinting,weight-lifting, and jumping.

* Phosphocreatine buffers the intracellular hydrogen ions associatedwith lactate production and muscle fatigue during exercise. As creatinephosphate helps to create ATP, it consumes hydrogen ions released by thelactic acid that can build up in muscle cells during intense activity. Sincethe hydrogen ions interfere with muscle contractions, "buffering"them helps to delay fatigue.

In a word, creatine supplementation may provide an ergogenic boost byincreasing the force of muscle contraction and prolonging anaerobic exercise.Many studies have shown that creatine supplementation has ergogenic properties.According to Greenhaff and colleagues, 20 g of creatine per day for fivedays increased muscle creatine availability by 20% and accelerated phosphocreatineregeneration after intense muscle contraction.10 It must be stressed,however, that creatine does not appear to augment either endurance exerciseperformance or maximal oxygen intake.3

Recent data demonstrate that the mean creatine concentration in humanskeletal muscle is 125mmol/kg of dry muscle, and the normal range is 90to160 mmol/kg of dry muscle.6 This rather wide range may help toexplain why some published studies have not demonstrated ergogenic effects.

In one study by Greenhaff, about half the athletes tested had creatineconcentrations less than 125 mmol/kg in dry muscle, with strict vegans showingsignificantly lower concentrations.10 In these athletes, supplementationincreased creatine concentration in muscles and phosphocreatine regenerationand augmented performance. Conversely, and not surprisingly, athletes withhigh presupplementation baseline levels of creatine showed little or noergogenic effect after creatine ingestion.

Another effect of creatine supplementation is "bulking up,"or producing larger, firmer muscles.5 This phenomenon is thoughtto result from an increase in fluid within skeletal muscle cells. As theintracellular fluid in the muscle increases, it pushes against the cellmembrane, augmenting cellular volume. This process can produce muscles thatare bigger and more shapely. Certainly it could avoid getting sand kickedin your face at the beach.

In search of an ergogenic edge

We can now understand the thinking that prompts those who wish to runfaster, jump higher, and lift heavier objects to take creatine supplements.What the users are looking for is an ergogenic edge. In order to achievean ergogenic effect, you need to ingest creatine in loading doses of 20g per day for five days followed by 5 to 10 g per day.3

Creatine was introduced as a potential ergogenic agent in 1993. It isnow used extensively in this country by professional and amateur athletes.Anecdotal evidence suggests that at least 25% of all major league baseballplayers use creatine, probably a similar percentage of professional basketballand hockey players, and possibly 50% of National Football League players.3Needless to say, many Olympic sprinters, cyclists, and weight lifters areusers, as are body builders, boxers, and weekend athletes.

Creatine users also include many high school students. If your adolescentpatients or their parents have not asked you about creatine, you had betterstart asking them. (We did not have any of this stuff when I was a youngathlete. Instead we learned how to run through the streets of Chicago whenwe saw a revolving blue light on the top of a patrol car. Some of our groupbecame quite swift. There is a trophy in one Chicago school that has fourof our names on it for winning a mile relay race.) With this in mind, itis time to try to answer the questions that we posed early in the discussion,beginning with the issue of whether creatine supplementation is effective.

Does creatine supplementation work?

We know that the creatine levels in muscle can be increased by exogenoussupplementation.11 There is evidence that increased levels ofcreatine can increase power output in high-intensity, intermittent, shortduration activities.7 The metabolic explanation for this is notentirely clear as yet, but increased availability of phosphorylated creatine,because of faster resynthesis of this chemical during recovery periods andits probable ability to regulate the rate of muscle glycolysis may be theanswer. Creatine may therefore benefit sprinters and weight lifters butnot necessarily linebackers.

Moreover, creatine phosphate acts as a "buffer" that helpsto control the buildup of lactic acid in the muscles during intense exerciseand delay fatigue.12 Creatine supplementation thus may ease theloneliness of the long-distance runner, although there are no hard datathat creatine improves performance in events such as marathons.

Is it safe?

In our current state of knowledge, the question of whether creatine supplementationis safe is a hard one to answer. In 1997, three collegiate wrestlers whohad taken creatine died, but creatine was not deemed to be the cause, althoughit was considered initially.13 The Centers for Disease Controland Prevention decided that rapid weight-loss methods and dehydration werefactors in the deaths.

The authors of a recent report in The Lancet suggest that creatine supplementationcan adversely affect kidney function, especially in those at risk for renalfailure.14 They report the case of a 25-year-old man with focalsegmental glomerulosclerosis who experienced deteriorating renal functionafter taking creatine supplements (15 g per day for one week followed bya maintenance dose of 2 g per day for seven weeks) to improve his soccertraining regimen. The young man's renal function improved within one monthafter he stopped taking the supplements. The authors allege that strongcircumstantial evidence points to creatine as the cause of the renal deterioration,although, they note, there are no reports of serious side effects at dosesrecommended by the manufacturer--20 g daily for three to seven days, then2 to 5 g daily as a maintenance dose.

The major side effects are dizziness, diarrhea, and muscle cramps. Amild increase in plasma creatinine that is reversible on discontinuationof the product also may occur. The effects and side effects of creatinesupplementation in children and adolescents have not yet been reported inthe scientific literature.11

Because the FDA classifies creatine as a dietary supplement, manufacturersdo not have to prove the safety or efficacy of their products. The qualityof supplements--which are available in powder, liquid, tablet, or gum form--mayvary and cannot be assured.

In June the American College of Sports Medicine advised caution withregard to creatine, stating that "the verdict is still out on the safetyof creatine supplementation."4 The group did not recommendthat athletes avoid using it, however. In a poll of members of the Associationof Professional Team Physicians, 85% of respondents said they would notrecommend that their players take creatine.4

What should you tell patients?

What advice can you offer when patients and their parents ask about creatinesupplementation? The American Academy of Pediatrics Committee on SportsMedicine and Fitness has not yet issued a formal policy statement but wantspediatricians to maintain an open dialogue with patients, share currentknowledge about creatine, and encourage patients to "consider moreproven and safer methods."11 Unresolved issues, in additionto effects and side effects, include the minimal effective dose for differentages and sports, fluid intake requirements during supplementation, and theimpact of supplementation on the body'sabilityto synthesize creatine endogenously.11

When I am asked about creatine supplementation (quite often, I mightadd), I reply, "No." In my opinion, train hard, eat well, sleepwell, but
no extras except eat your Wheaties.

What about ethics?

Is using creatine ethical? I personally do not think so, but I am a puristwhen it comes to athletes competing on a level playing field. Creatine canbe viewed as the "poor man's steroid."

The International Amateur AthleticFederation and the National CollegiateAthletic Association do not list creatine as a prohibited substance.11,12Nor is creatine banned by the International Olympic Committee, possiblybecause of the problems inherent in detecting ingested creatine.7Remember, until recently, the use of marijuana was not banned either.

After finishing his 12 labors, Hercules got into many difficulties, especiallyinvolving women. He married Deianeira but loved Iole, the daughter of aking. Deianeira gave Hercules a shirt that caused our hero to suffer a slow,agonizing death. As the son of Zeus, he was received onto Olympus, marriedHebe, the cupbearer, and lived the life of the gods, all of this withoutcreatine.1

REFERENCES

1. Gordon S: The Encyclopedia of Myths and Legends. London, England,Headline Book Publishing, 1994

2. Weigel J: Mythology. Lincoln, NE, Cliff Notes, 1973

3. Bamberger M: The magic potion. Sports Illustrated, April 20, 1998,p 59

4. Creatine use unsettles physicians. The New York Times, June 14, 1998

5. Sahehan R, Tuttle D: Creatine, Nature's Muscle Builder. Garden CityPark, NY, Avery Publishing Group, 1997

6. Armsey TD, Green GA: Nutrition supplements: Science vs. hype. ThePhysician and SportsMedicine, 1997;25(6):77

7. Balsom PD, Soderlund K, Ekblom B: Creatine in humans with specialreference to creatine supplementation. Sports Med 1994;18(4):269

8. Toler SM: Creatine is an ergogen for anaerobic exercise. Nutr Rev1997;55(1):21

9. Colgan M: Creatine for Muscle and Strength (Progressive Health Series,Colgan Institute). Vancouver, BC, Apple Publishing Co. Ltd., 1997

10. Greenhaff P, Casey A, Short A, et al: Influence of oral creatinesupplementation in muscle torque during repeated bouts of maximal voluntaryexercise in man. Clin Sci 1993;84:565

11. Anderson SJ: Creatine questioned as muscle builder, performance enhancer.AAP News July 1998;14(7)

12. Anderson O: Creatine propels British athletes to Olympic gold medals.Running Research 1993;9(1):1

13. Strauss G, Mihoces G, O'Donnell J: FDA warning out on sports supplement.USA Today, April 23, 1998

14.Pritchard NR, Kalra PA: Renal dysfunction accompanying oral creatinesupplements. Lancet 1998;351:1252

Ronald B. Mack, MD. THE AUTHOR is Professor of Pediatrics,Wake Forest University School of Medicine, Winston-Salem, NC. He is a ContributingEditor for Contemporary Pediatrics.




POISON PEN. Contemporary Pediatrics 1999;0:097.