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Anthony D. Mahon and Brian W. Timmons

Exercise metabolism in children has traditionally been assessed using the respiratory exchange ratio (RER) to determine the contributions of fat and carbohydrate to the exercise energy demands. Although easily measured, RER measurements have limitations. Other methods to assess metabolism such as the obtainment of a muscle biopsy and the use of nuclear magnetic resonance spectroscopy carry ethical and feasibility concerns, respectively, which limit their use in studies involving children. Stable isotopes, used routinely in studies involving adults, can also be applied in studies involving children in an ethical and feasible manner. Two common stable isotopes used in metabolic studies involving children include carbon-13 (13C) and nitrogen-15 (15N). 13C-glucose can be used to study carbohydrate metabolism and 15N-glycine can be used to assess protein metabolism. This article reviews the use of 13C-glucose and 15N-glycine to study exercise metabolism in children, considers some of the associated ethical aspects, explains the general methodology involved in administering these isotopes and the resources required, and describes studies involving children utilizing these methods. Finally, suggestions for future research are provided to encourage further use of these techniques.

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Keisuke Ueda, Yutaka Nakamura, Makoto Yamaguchi, Takeshi Mori, Masayuki Uchida and Satoshi Fujita

Although there have been many investigations of the beneficial effects of both exercise and amino acids (AAs), little is known about their combined effects on the single-dose ingestion of AAs for lipid metabolism during exercise. We hypothesize that taking a specific combination of AAs implicated in glucagon secretion during exercise may increase fat metabolism. We recently developed a new mixture, d–AA mixture (D-mix), that contains arginine, alanine, and phenylalanine to investigate fat oxidation. In a double-blind, placebo-controlled crossover study, 10 healthy male volunteers were randomized to ingest either D-mix (3 g/dose) or placebo. Subjects in each condition subsequently performed a physical task that included workload trials on a cycle ergometer at 50% of maximal oxygen consumption for 1 hr. After oral intake of D-mix, maximum serum concentrations of glycerol (9.32 ± 6.29 mg/L and 5.22 ± 2.22 mg/L, respectively; p = .028), free fatty acid level (0.77 ± 0.26 mEq/L and 0.63 ± 0.28 mEq/L, respectively; p = .022), and acetoacetic acid levels (37.9 ± 17.7 μmol/L and 30.3 ± 13.9 μmol/L, respectively; p = .040) were significantly higher than in the placebo groups. The area under the curve for glucagon during recovery was numerically higher than placebo (6.61 ± 1.33 μg/L • min and 6.06 ± 1.23 μg/L • min, respectively; p = .099). These results suggest that preexercise ingestion of D-mix may stimulate fat metabolism. Combined with exercise, the administration of AA mixtures could prove to be a useful nutritional strategy to maximize fat metabolism.

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Abdullah F. Alghannam, Dawid Jedrzejewski, James Bilzon, Dylan Thompson, Kostas Tsintzas and James A. Betts

We examined whether carbohydrate-protein ingestion influences muscle glycogen metabolism during short-term recovery from exhaustive treadmill running and subsequent exercise. Six endurance-trained individuals underwent two trials in a randomized double-blind design, each involving an initial run-to-exhaustion at 70% VO2max (Run-1) followed by 4-h recovery (REC) and subsequent run-to-exhaustion at 70% VO2max (Run-2). Carbohydrate-protein (CHO-P; 0.8 g carbohydrate·kg body mass [BM-1]·h-1 plus 0.4 g protein·kg BM-1·h-1) or isocaloric carbohydrate (CHO; 1.2 g carbohydrate·kg BM-1·h-1) beverages were ingested at 30-min intervals during recovery. Muscle biopsies were taken upon cessation of Run-1, postrecovery and fatigue in Run-2. Time-to-exhaustion in Run-1 was similar with CHO and CHO-P (81 ± 17 and 84 ± 19 min, respectively). Muscle glycogen concentrations were similar between treatments after Run-1 (99 ± 3 mmol·kg dry mass [dm-1]). During REC, muscle glycogen concentrations increased to 252 ± 45 mmol·kg dm-1 in CHO and 266 ± 30 mmol·kg dm-1 in CHO-P (p = .44). Muscle glycogen degradation during Run-2 was similar between trials (3.3 ± 1.4 versus 3.5 ± 1.9 mmol·kg dm-1·min-1 in CHO and CHO-P, respectively) and no differences were observed at the respective points of exhaustion (93 ± 21 versus 100 ± 11 mmol·kg dm-1; CHO and CHO-P, respectively). Similarly, time-to-exhaustion was not different between treatments in Run-2 (51 ± 13 and 49 ± 15 min in CHO and CHO-P, respectively). Carbohydrate-protein ingestion equally accelerates muscle glycogen resynthesis during short-term recovery from exhaustive running as when 1.2 g carbohydrate·kg BM-1·h-1 are ingested. The addition of protein did not alter muscle glycogen utilization or time to fatigue during repeated exhaustive running.

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Andrés Pérez, Domingo J. Ramos-Campo, Cristian Marín-Pagan, Francisco J. Martínez-Noguera, Linda H. Chung and Pedro E. Alcaraz

Interestingly, POL has shown to improve VO 2 peak, anaerobic threshold, aerobic efficiency, time to exhaustion during an incremental test, 14 finishing time in 10-km races, 13 and running economy in ultrarunners. 9 In addition, fat metabolism has a key role in endurance events. 15 The maximal fat oxidation

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Lindy M. Castell, David C. Nieman, Stéphane Bermon and Peter Peeling

that metabolism and immunity are inextricably interwoven. This has led to a new area of research termed immunometabolism ( Nieman et al., 2018a ). Studies on human athletes exercising intensely for >2 hr showed that significant increases in at least 300 identified metabolites can be measured, while

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Kevin D. Tipton and Robert R. Wolfe

Exercise has a profound effect on muscle growth, which can occur only if muscle protein synthesis exceeds muscle protein breakdown; there must be a positive muscle protein balance. Resistance exercise improves muscle protein balance, but, in the absence of food intake, the balance remains negative (i.e., catabolic). The response of muscle protein metabolism to a resistance exercise bout lasts for 24-48 hours; thus, the interaction between protein metabolism and any meals consumed in this period will determine the impact of the diet on muscle hypertrophy. Amino acid availability is an important regulator of muscle protein metabolism. The interaction of postexercise metabolic processes and increased amino acid availability maximizes the stimulation of muscle protein synthesis and results in even greater muscle anabolism than when dietary amino acids are not present. Hormones, especially insulin and testosterone, have important roles as regulators of muscle protein synthesis and muscle hypertrophy. Following exercise, insulin has only a permissive role on muscle protein synthesis, but it appears to inhibit the increase in muscle protein breakdown. Ingestion of only small amounts of amino acids, combined with carbohydrates, can transiently increase muscle protein anabolism, but it has yet to be determined if these transient responses translate into an appreciable increase in muscle mass over a prolonged training period.

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Glen E. Duncan and Edward T. Howley

This review addresses issues related to substrate metabolism in children and how this information compares and contrasts to that of adults. The relative percent of fat and carbohydrate (CHO) utilized by an individual can be estimated from respiratory exchange ratio (RER) values between 0.7 (100% fat, 0% CHO) and 1.0 (100% CHO, 0% fat). The rise in RER towards 1.0 in relation to increased exercise intensity demonstrates the augmented role of CHO as an energy source for muscle; however, fat oxidation also represents a major source of energy during exercise of moderate-to-heavy intensity. Preliminary reports suggest that children demonstrate patterns of fat and CHO use in response to exercise intensity similar to those of adults and also show a reduction in RER at submaximal exercise intensities after training. The use of the “crossover concept" may simplify the presentation of how metabolism is affected by exercise intensity and training.

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Rudolph H. Dressendorfer, Stewart R. Petersen, Shona E. Moss Lovshin and Carl L. Keen

This study examined the effects of intense endurance training on basal plasma and 24-hour urinary calcium (Ca), magnesium (Mg), iron (Fe), zinc (Zn), and copper (Cu) levels in 9 male competitive cyclists. The supervised training program followed a baseline period and included a volume phase (6 weeks, averaging 87% of maximal heart rate [HRmax]), an interval phase (18 days, 100% of HRmax), and a 10-day unloading taper. The primary training outcome measure was 20-km time-trial cycling performance. Subjects ate unrestricted diets and maintained their weight. Compared to baseline, performance improved significantly (p < .05), while mineral metabolism was not significantly different after the volume phase. However, after the interval phase, renal Ca excretion increased (p < .05) and plasma Ca fell slightly below the clinical norm. As compared to the interval phase, urinary Ca decreased (p < .05), plasma Ca increased (p < .05), and performance further improved (p < .05) after the taper. Whereas Mg, Fe, Zn, and Cu metabolism remained unchanged throughout the study, greater renal Ca excretion was associated with very high intensity interval training.

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Martin J. Gibala

The contribution of amino acid oxidation to total energy expenditure is negligible during short-term intense exercise and accounts for 3–6% of the total adenosine triphosphate supplied during prolonged exercise in humans. While not quantitatively important in terms of energy supply, the intermediary metabolism of several amino acids—notably glutamate, alanine, and the branched-chain amino acids—afreets other metabolites .including the intermediates within the tricarboxylic acid (TCA) cycle. Glutamate appears to be a key substrate for the rapid increase in muscle TCA cycle intermediates (TCAI) that occurs at the onset of moderate to intense exercise, due to a rightward shift of the reaction catalyzed by alanine aminotransferase (glutamate + pyruvate <-> alanine + 2-oxoglutarate). The pool of muscle TCAI declines during prolonged exercise, and this has been attributed to an increase in leucine oxidation that relies on one of the TCAI. However, this mechanism does not appear to be quantitatively important due of the relatively low maximal activity of branched-chain oxoacid dehydrogenase, the key enzyme involved. It has been suggested that an increase in TCAI is necessary to attain high rates of aerobic energy production and that a decline in TCAI may be a causative factor in local muscle fatigue. These topics remain controversial, but recent evidence suggests that changes in TCAI during exercise are unrelated to oxidative energy provision in skeletal muscle.

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Keith Tolfrey, Julia Kirstey Zakrzewski-Fruer and Alice Emily Thackray

, Goldfield GS , Colley RC , Kenny GP , Doucet E , Tremblay MS . Prolonged sitting and markers of cardiometabolic disease risk in children and youth: a randomized crossover study . Metabolism . 2013 ; 62 ( 10 ): 1423 – 8 . PubMed doi:10.1016/j.metabol.2013.05.010 10.1016/j.metabol.2013