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Application of Stable Isotope Tracers in the Study of Exercise Metabolism in Children: A Primer

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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Amino Acid Mixture Enriched With Arginine, Alanine, and Phenylalanine Stimulates Fat Metabolism During Exercise

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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Ketone Monoester Ingestion Alters Metabolism and Simulated Rugby Performance in Professional Players

Oliver J. Peacock, Javier T. Gonzalez, Simon P. Roberts, Alan Smith, Scott Drawer, and Keith A. Stokes

muscle metabolism. BHB-ME-CHO coingestion has been shown to increase plasma BHB availability and net intramuscular triglyceride utilization, while suppressing plasma nonesterified fatty acid availability, glycolysis, and net intramuscular glycogen utilization during moderate-intensity exercise ( Cox et

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For Flux Sake: Isotopic Tracer Methods of Monitoring Human Carbohydrate Metabolism During Exercise

Javier T. Gonzalez and Andy J. King

In studies of metabolism, tracer methods offer the ability to track the fate of substrates such as carbohydrates, lipids, and proteins. While several tracer methods exist for a variety of applications, for example, dyes for tracking energy into feces ( Jumpertz et al., 2011 ), this review

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Influence of Post-Exercise Carbohydrate-Protein Ingestion on Muscle Glycogen Metabolism in Recovery and Subsequent Running Exercise

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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Exercise-Induced Illness and Inflammation: Can Immunonutrition and Iron Help?

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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Can IGF-1 Serum Levels Really be Changed by Acute Physical Exercise? A Systematic Review and Meta-Analysis

Diego de Alcantara Borba, Eduardo da Silva Alves, João Paulo Pereira Rosa, Lucas Alves Facundo, Carlos Magno Amaral Costa, Aldo Coelho Silva, Fernanda Veruska Narciso, Andressa Silva, and Marco Túlio de Mello

% to 4%, while IGF-1 increases were 7% to 8%. Thus, it seems reasonable to speculate that increased IGF-1 concentration is also attributed to its muscular or hepatic release. Regarding the effects of exercise on IGF-1 metabolism, no increase in this polypeptide indicates that exercise does not

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Does Caffeine Increase Fat Metabolism? A Systematic Review and Meta-Analysis

Scott A. Conger, Lara M. Tuthill, and Mindy L. Millard-Stafford

endurance ( Conger et al., 2011 ; Doherty & Smith, 2004 ; Graham, 2001 ). In general, the mechanism by which CAF appears to reduce fatigue has been ascribed to influence metabolism of substrate (e.g., fat) and/or the central nervous system via adenosine antagonism. Other purported potential neuromuscular

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Impact of Polarized Versus Threshold Training on Fat Metabolism and Neuromuscular Variables in Ultrarunners

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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Exercise, Protein Metabolism, and Muscle Growth

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.