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1 Journal of Strength and Conditioning Research, 2001, 15(4), National Strength & Conditioning Association Brief Review Is There a Physiologic Basis for Creatine Use in Children and Adolescents? VISWANATH B. UNNITHAN, 1 SUZANNE H.E. VEEHOF, 2 CHANTAL A. VELLA, 3 AND MARIALICE KERN 3 1 Exercise Science, Syracuse University, Syracuse, New York 13244; 2 Exercise and Sport Science, University of San Francisco, San Francisco, California 94117; 3 Department of Kinesiology, San Francisco State University, San Francisco, California ABSTRACT The purported ergogenic benefits of creatine for the adult population have been well documented. In able-bodied children and adolescents, there is a paucity of data on creatine use and the purported ergogenic effects of creatine. Only 1 study to date has investigated the ergogenic properties of creatine in the adolescent population. The purpose of this review was to try to establish a rationale for creatine use in the child and adolescent population. The limited literature available in this area did not provide a strong enough rationale from either a physiologic or performance perspective for creatine supplementation in these populations. However, significantly more research is required before definitive conclusions can be made. Key Words: nutritional ergogenic aid, youth, sports Reference Data: Unnithan, V.B., S.H.E. Veehof, C.A. Vella, and M. Kern. Is there a physiologic basis for creatine use in children and adolescents? J. Strength Cond. Res. 15(4): Introduction The purported ergogenic benefits of creatine for the adult population have been well documented (4, 8, 19, 25). In able-bodied children and adolescents, there is a paucity of data on creatine use and the purported ergogenic effects of creatine. For the purpose of this review, children will be defined as prepubertal in maturational status, and adolescents will be defined as pubertal or postpubertal in maturational status. Only 1 study to date has investigated the ergogenic properties of creatine in the adolescent population (16). The results from this double-blind randomized study indicated that creatine supplementation enhances swim training performance in national- and regional-caliber adolescent swimmers (mean SD age, years). Specifically, the benefits were found with repetitive sprint performance. Adolescents who took creatine monohydrate (21 g per day) for 9 days had faster swim times over a single 100-m race compared with age- and gender-matched adolescents who were ingesting a maltodextrin placebo. The creatine group also sustained their swimming velocity over 2 subsequent 100-m time trials compared with the placebo group. These results indicated that creatine may provide some ergogenic benefit for repetitive sprint performance in an adolescent population. From this study, however, the authors were unable to determine the specific etiology of the improvements in swimming performance. They speculated that the improvements were based on (a) an improved ability to tolerate training, (b) an increased ability to maintain velocity during sprints, and (c) an improved capacity to recover from the sprints. The efficacy of creatine supplementation has also been demonstrated for clinical child and adolescent populations. Two clinical case studies (27, 28) have demonstrated the positive effects of creatine supplementation in children with a deficiency of guanidinoacetate methyltransferase (an enzyme involved in creatine biosynthesis). This condition induces a reduction in creatine and phosphocreatine in muscle and brain. It also manifests itself as retarded motor control development in the children. Long-term creatine supplementation of mg per kg per day and 350 mg per kg per day was demonstrated to be effective in improving cognitive and motor function over a treatment period of months. Creatine supplementation of g per day was also noted to improve muscle power (assessed through cycle ergometry) in 4 adolescents with various mitochondrial encephalomyopathies over a 3-month treatment period (5). With the exception of these 4 studies, as far as we are aware, there are no other published studies addressing the efficacy of creatine supplementation in child and adolescent populations. An anecdotal report (6) suggested that creatine supplementation is wide- 524

2 Creatine in Children and Adolescents 525 spread in athletic child and adolescent populations. There is a lack, however, of data confirming these anecdotal reports. Irrespective of the level of use, the question remains as to whether a physiologic basis exists for creatine supplementation in children and adolescents. The primary aim of this review is to try to identify a physiologic basis for creatine use in the child and adolescent populations. There is a paucity of research dealing directly with creatine supplementation in children and adolescents; therefore, the rationale for use will be addressed by considering (a) the developmental changes in the muscle biochemistry and structure of the growing child, (b) performance models from swimming and track and field, and (c) the trainability of children and adolescents. A secondary aim of this study was to provide preliminary data on the level of creatine use in a trained adolescent population. Developmental Changes in the Biochemistry and Muscle Structure of the Child and Adolescent Scrutiny of the muscle biochemistry and structure of the child and adolescent may help to provide a theoretical basis for creatine use in these populations. It has been established that intramuscular (vastus lateralis) ATP and creatine phosphate concentrations are similar in boys aged years compared with men (10, 12). ATP concentrations of 3 5 mmol per kg muscle (wet weight), and creatine phosphate levels of mmol per kg muscle (wet weight) were obtained (13, 17, 18). The rate of depletion of energy-rich phosphates (ATP and creatine phosphate) was found to be the same when comparing children, adolescents, and adults, all exercising at the same range of relative exercise intensities (percentage of V O2 max) (11, 12). With regard to ATP rephosphorylation, the situation is more complex. Based on a magnetic resonance spectroscopy study, at heavy exercise only, a minimal drop in intramuscular ph was noted in children compared with adults, even after the transition point (at which oxidative metabolism reached its maximum). This finding indicated that even when further energy sources were required during heavy exercise, glycolytic processes played less of a role in the children. Further evidence to support this claim came from the endexercise P i /PCr ratio in the children, which was only 27% of that in adults. Once again, this indicated that soon after the transition point, children were unable to sustain muscle contraction, due to a reduced ability to rephosphorylate ATP at high exercise intensities (30). These data and further evidence suggest that children are far less capable than adults of stimulating ATP rephosphorylation by anaerobic pathways during high-intensity exercise (7, 22). Muscle glycogen stores in children aged years were found to be less than 70% of those in adults (50 60 nmol per kg wet weight of muscle). Some evidence exists to suggest that these levels increase through adolescence, ultimately achieving adult levels (12). Therefore, at the prepubertal level, it does appear that children are not as capable of generating ATP via glycolysis. Children do not perform as well in short-duration, high-intensity events compared with adolescents who, in turn, have a poorer performance than adults (12). This pattern reflects, in part, the reduced ability of children and adolescents to generate mechanical energy from chemical energy sources via anaerobic pathways. One qualitative mechanism that has been suggested to contribute to this process is the lower (8 10 mol per g per minute) activity of the rate-limiting enzyme of glycolysis, phosphofructokinase (PFK), noted in prepubertal children. This concentration represents less than 50% of the value in adults (14, 15). With regard to the adolescent population, no significant differences in PFK activity levels in the vastus lateralis were found between adolescent girls and adults (17). Using animal models, Emmet and Hochachka (9) linked the activity of anaerobic enzymes (glycogen phosphorylase, pyruvate kinase, and lactate dehydrogenase) to an increase in body size. Further work by Berg and Keul (3) demonstrated low levels of lactate dehydrogenase levels in 6-year-old children compared with adolescents of 17 years of age and the highest ratio of fumarase to pyruvate kinase in the youngest age group. This evidence hints at possible increases in the ratio of anaerobic-aerobic power with increasing age in children. There is no clear indication at exactly what stage the enzymatic profile changes from childhood to adulthood. One other possible factor that may limit performance in short-term high-intensity exercise is muscle fiber type. Levels of phosphocreatine in the body are also related to muscle fiber composition; in fact, higher levels of phosphocreatine are related to a higher proportion of Type IIx (formerly known as Type IIb) myosin heavy chain isoforms. As the intrinsic speed of cross-bridge cycling and ATP breakdown increases, so does the buffering capacity of phosphocreatine (26). The percentage of Type II fibers is lower for both sexes in early and mid-childhood compared with adulthood (2). Adult proportions are attained during late adolescence, and this attainment stems from the conversion of undifferentiated Type IIc fibers (15). Performance Models Based on the previous biochemical and muscle data, it would appear that children s anaerobic performance is compromised compared with that of adults. Therefore, one might expect that the performance of children in short-term high-intensity exercise would be relatively inferior compared with that in long-distance events. Bar-Or et al. (1) created a theoretical swimming per-

3 526 Unnithan, Veehof, Vella, and Kern Table 1. Swimming performance minutes for the top 10 child, adolescent, and adult male Canadian swimmers in 1992 (modified from Bar-Or et al., 1994).* Age group Swimming distance, m ,500 Boys y Adolescent boys y Adolescent boys y Men * Values are means SD. Table 2. Difference between child, adolescent, and adult performance times expressed as a percentage of adult time for the top 10 Canadian swimmers in each group in 1992 (modified from Bar-Or et al., 1994). Age group Boys y Adolescent boys y Adolescent boys y Swimming distance, m , formance model to test this theory. These researchers calculated the mean, best 1992 times of the 10 top Canadian male age-group swimmers (11 12 years, years, and years) in the 50-, 200-, and 1,500-m freestyle and compared their times with the corresponding times for the top 10 Canadian male adult swimmers. As expected, the younger children had slower performance times than the older children (Table 1). Table 2 illustrates the difference between the child and adult times relative to the adult time for each distance, also including the 100- and 400-m performance times. These results did not confirm the hypothesis that children s performance would be relatively inferior compared with that of their adult counterparts in the shorter distances. Within each age group, the percentage difference remained virtually constant, independent of the distance under scrutiny. These researchers speculated that during the years of growth, performance depends primarily on mechanical factors and far less on the relative aerobic-anaerobic contribution to performance. Further evidence to support this claim was derived from the comparison of the best performance times of a 10-year-old male U.S. track champion vs. the adult world record times for the 100-, 200-, and 400-m events. The comparison was made for the year Performance differences (with respect to time) across the 3 events between the 2 age groups were 26, 28, and 27%, respectively. Similar trends were also seen for female athletes (29). Therefore, no evidence existed from this comparison to confirm that performance at the shortest distances were preferentially inferior in the child athlete. Trainability of Children and Adolescents in Short-Duration High-Intensity Exercise Very limited research exists in the area of trainability of children and adolescents in short-duration high-intensity exercise. Mero (23) conducted a 2-year training program with a group of male junior athletes (age, years). The training program consisted of strength, speed, and endurance events. Significant improvements in anaerobic capacity were noted in both a 15- and 60-second maximal cycle ergometer test for the training group compared with an age-matched control group. No significant difference in the muscle fiber distribution of the vastus lateralis was noted before and after training. However, relative fast twitch muscle fiber area increased across the training period. Further work by Mero (24) with 58 power athletes, both male and female athletes (sprinters and jumpers) aged years demonstrated significant improvements (3.4%) in maximal sprint speed in male athletes after a 2-year training program. The training program consisted of strength, speed, and event-specific exercises. The only physiologic determinant of the improvement in sprint performance was a significant increase in serum testosterone levels across the 2-year training period in the male athletes only; nonsignificant increases in serum testosterone were noted in the female power athletes over the same time period. As far as we are aware, only 1 documented training study exists that assessed the effects of training on changes in muscle biochemistry of children and adolescents. Biopsy data from Eriksson (10) demonstrated that through high-intensity training, increases in endogenous ATP, creatine phosphate (CP), and glycogen were noted in boys aged years. The data in this area are limited, but the evidence is reasonably compelling; that is, if the training stimulus is sufficient, there is a possibility to improve short-term high-intensity performance in children and adolescents through training alone.

4 Creatine in Children and Adolescents 527 Creatine Use in Children and Adolescents Work undertaken in our laboratory (20) has indicated some interesting trends with regard to creatine use. Trained junior athletes in a Northern California training facility were assessed with regard to patterns of creatine use. Sixty-six out of 200 athletes from a center for young athletes (46 male athletes, 20 female athletes; age, years) completed a nutritional supplement survey and training questionnaire. The training profile revealed a highly trained group: the athletes had been training for years; had participated in competitive sports for years; and were training months per year, times per week, and hours per week. Of the 33% of athletes at the center who completed the survey, 37.9% indicated that they had used or were currently using creatine. Of these 37.9%: 72% indicated that health food stores were the primary source for obtaining creatine, 61.5% reported no limits to obtaining creatine, 100% were male, and 92% indicated that they believed in the ergogenic effects of creatine. These findings provide some of the first empirical data on creatine use and indicate that, despite the fact that neither the ergogenic effect nor the safety of long-term creatine use has truly been established, adolescents are taking the supplement and fully believe in its purported ergogenic effects. Practical Applications The argument for creatine use in a child is that both the rate of use of CP and ATP rephosphorylation via glycolysis appear to be compromised in this population. This subsequently limits a child s ability to regenerate high-energy phosphates during high-intensity exercise. Therefore, the possibility exists that supplementation could offset this metabolic deficit and enhance performance in high-intensity exercise. This theory is based on the assumption that adult levels of the sarcolemma-based creatine transporter protein are present in the child (21). The only piece of compelling evidence to support creatine use in an adolescent population is based on the work by Grindstaff et al. (16); these researchers demonstrated improvements in swimming performance with creatine supplementation, but the etiology of these improvements was not established. There are several arguments against creatine use. (a) The enzymatic profile of the child seems to indicate a greater reliance on aerobic rather than anaerobic metabolism. Therefore, if the goal of creatine supplementation is to enhance anaerobic performance, it would have a limited effect due to the enzymatic profile favoring aerobic metabolism, at least in the child. (b) The muscle fiber structure at the prepubertal stage predisposes the child for preferential aerobic metabolism rather than anaerobic metabolism. (c) The adolescent appears to be adept at both regenerating high energy phosphates during high-intensity exercise and improving performance in short-term high-intensity exercise through training, thereby obviating the need for supplementation. (d) Mechanical factors rather than the relative contribution of the aerobic and anaerobic energy systems seem to influence performance during growth. (e) Perhaps most significantly, neither the efficacy nor the long-term safety of creatine supplementation has been established in the child and adolescent populations. The arguments created for and against creatine supplementation are based on very limited pediatric metabolic data. As pediatric exercise scientists, we are limited from both an ethical and methodologic standpoint in conducting creatine intervention studies and evaluating the metabolic consequences of such studies. Significantly more research is required to fully understand the metabolic changes that accompany growth, irrespective of any issues regarding creatine supplementation. Not until these issues are resolved can we fully hope to examine the long-term safety and efficacy of creatine supplementation in child and adolescent populations. Consequently, based on the literature to date, there does not appear to be a compelling argument for creatine use in the child and adolescent populations. Preliminary data generated from our laboratory indicates that creatine supplementation is occurring, at least in an older adolescent population, even though the rationale for this use is currently unsubstantiated. References 1. BAR-OR, O., V. UNNITHAN, AND C. ILLESCAS. Physiologic considerations in age-group swimming. In: Medicine and Science in Aquatic Sports. M. Myashita, Y. Mutoh, and A.B. Richardson, eds. (volume 39). Basel: Karger, pp BELL, R.D., J.D. MACDOUGALL, R. BILLETER, AND H. HOWALD. Muscle fiber types and morphometric analysis of skeletal muscle in 6-year old children. Med. Sci. Sports Exerc. 12: BERG, A., AND J. KEUL. Biochemical changes during exercise in children. In: Young Athletes. A Biological, Psychological, and Educational Perspective. R.M. Malina, ed. Champaign, IL: Human Kinetics, pp BIRCH, R., D. NOBLE, AND P.L. GREENHAFF. The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. Eur. J. Appl. Physiol. 69: BORCHERT, A., E. WILICHOWSKI, AND F. HANEFELD. Supplementation with creatine monohydrate in children with mitochondrial encephalomyopathies. Muscle Nerve 22: CLARKSON, P.M. Nutritional supplements for adolescent athletes: Myths and realities. Tutorial Lecture, American College of Sports Medicine 46th Annual Meeting; June 2 5, 1999; Seattle. 7. COOPER, D.M., AND T.J. BARSTOW. Magnetic resonance imaging and spectroscopy in studying exercise in children. Exerc. Sports Sci. Rev. 24: EARNEST, C.P., P.G. SNELL, R. RODRIGUEZ, A.L. ALMADA, AND T.L. MITCHELL. The effect of creatine monohydrate ingestion on

5 528 Unnithan, Veehof, Vella, and Kern anaerobic power indices, muscular strength and body composition. Acta Physiol. Scand. 153: EMMET, B., AND P.W. HOCHACHKA. Scaling of oxidative and glycolytic enzymes in mammals. Respir. Physiol. 45: ERIKSSON, B.O. Physical training, oxygen supply and muscle metabolism in year old boys. Acta Physiol. Scand. 384: ERIKSSON, B.O. Physiological analysis of young boys starting intensive training in swimming. In: Physical Activity and Human Well Being. F. Landry and W.A.R. Orban, eds. Miami: Symposia Specialists, pp ERIKSSON, B.O. Muscle metabolism in children A review. Acta Pediatr. Scand. 283: ERIKSSON, B.O., P.D. GOLLNICK, AND B. SALTIN. Muscle metabolism and enzyme activities after training in boys years old. Acta Physiol. Scand. 87: ERIKSSON, B.O., J. KARLSSON, AND B. SALTIN. Muscle metabolites during exercise in pubertal boys. Acta Pediatr. Scand. 217: FOURNIER, M., J. RICCI, A.W. TAYLOR, R. FERGUSON, R. MON- PETIT, AND B. CHAITMAN. Skeletal muscle adaptation in boys: Sprint and endurance training and detraining. Med. Sci. Sports Exerc. 14: GRINDSTAFF, P.D., R. KREIDER, R. BISHOP, M. WILSON, L. WOOD, C. ALEXANDER, AND A. ALMADA. Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers. Int. J. Sports Nutr. 7: HARALAMBIE, G. Enzyme activities in skeletal muscle of year old adolescents. Bull. Eur. Physiopathol. 18: HIRVONEN, J., A. NUMMELA, H. RUSKO, S. REHUNEN, AND M. HARKONEN. Fatigue and changes in ATP, creatine phosphate and lactate during the 400m sprint. Can. J. Sport Sci. 17: KELLEY, V.G., AND D.G. JENKINS. Effect of oral creatine supplementation on near-maximal strength and repeated sets of high intensity bench press exercise. J. Strength Cond. Res. 12: KERN, M., S.H.E. VEEHOF, C.A. VELLA, AND V.B. UNNITHAN. An explorative investigation into creatine usage in trained junior athletes. [Abstract]. Med. Sci. Sports Exerc. 32:S KRAEMER, W.J., AND J.S. VOLEK. Creatine supplementation. Its role in human performance. Clin. Sports Med. 18: KUNO, S., H. TAKAHASHI, K. FUJIMOTO, H. AKIMA, M. MIYA- MARU, I. NEMOTO, Y. ITAI, AND S. KATSUTA. Muscle metabolism during exercise using phosphorous-31 nuclear magnetic resonance spectroscopy in adolescents. Eur. J. Appl. Physiol. 70: MERO, A. Skeletal muscle fiber characteristics and anaerobic work in pubertal boys during training [Abstract]. Med. Sci. Sports Exerc. 24:S MERO, A. Neuromuscular performance and skeletal muscle fibre characteristics in pubertal power athletes during training [Abstract]. Med. Sci. Sports Exerc. 25:S PEARSON, D.R., D.G. HAMBY, W. RUSSEL, AND T. HARRIS. Longterm effects of creatine monohydrate on strength and power. J. Strength Cond. Res. 13: SANT ANA PEREIRA, J.A.A., A.J. SARGENT, A. DE HAAN, A.C.H.J. RADEMAKER, AND W. VAN MECHELEN. Myosin heavy chain isoform expression and high energy phosphate content of human muscle fibres at rest and post-exercise. J. Physiol. (Lond.). 496: SCHULZE, A.,T.HESS, R.WEVERS, E.MAYATEPEK, P.BACHERT, B. MARESCAU, M.V. KNOPP, P.P. DE DEYN, H.J. BREMER, AND D. RATING. Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: Diagnostic tools for a new inborn error of metabolism. J. Pediatr. 131: STOCKLER, S., F. HANEFELD, AND J. FRAHM. Creatine replacement therapy in guanidino acetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet. 348: VAN PRAAGH, E., AND N.M. FRANCA. Measuring maximal short-term power output during growth. In: Pediatric Anaerobic Performance. Champaign, IL: Human Kinetics, pp ZANCONATO, S., S. BUCHTAL, T.J. BARSTOW, AND D.M. COOPER. 31 P-magnetic resonance spectroscopy of leg muscle metabolism during exercise in children and adults. J. Appl. Physiol. 74: Acknowledgments We gratefully acknowledge the undergraduate students in the Department of Exercise and Sport Science at the University of San Francisco who assisted with the data collection; Kate Harding, Dr. Frank Verducci, and Professor Susan Higgins (San Francisco State University) for reviewing the questionnaire and the manuscript; and all of the staff and athletes at the Riekes Center, Menlo Park, CA.

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