Loughborough University Institutional Repository Metabolism and exercise during youth

Three publications were selected based on the strength of the research questions, but also because they represent different research designs that are used with varying degrees of frequency in the paediatric literature. The first, a prospective, longitudinal cohort observation study from 7 to 16 years with girls and boys reports an intrinsic reduction in absolute resting energy expenditure after adjustment for lean mass, fat mass, and biological maturity. The authors suggest this could be related to evolutionary energy conservation, but may be problematic now that food energy availability is so abundant. The second focuses on the effect of acute exercise on neutrophil reactive oxygen species production and inflammatory markers in independent groups of healthy boys and men. The authors suggested the boys experienced a “sensitized” neutrophil response stimulated by the exercise bout compared with the men; moreover, the findings provided information necessary to design future trials in this important field. In the final study, a dose-response design was used to examine titrated doses of high intensity interval training on cardiometabolic outcomes in adolescent boys. Whilst the authors were unable to identify a recognisable dose-response relationship, there are several design strengths in this study, which was probably underpowered. Citation Mostazir M, Jeffery A, Hosking J, Metcalf B, Voss L, Wilkin T. Evidence for energy conservation during pubertal growth. A 10-year longitudinal study (EarlyBird 71). Int J Obes. 2016; 40(11):1619-1626. DOI: 10.1038/ijo.2016.158 Abstract Background Diabetes is closely linked to obesity, and obesity rates climb during adolescence for reasons that are not clear. Energy efficiency is important to obesity, and we describe a temporary but substantial fall in absolute energy expenditure, compatible with improved energy efficiency, during the rapid growth phase of puberty. Methods In a longitudinal cohort study lasting 10 years, we measured voluntary energy expenditure as physical activity (PA) by accelerometry, involuntary energy expenditure as resting energy expenditure (REE) by oxygen consumption, body mass index (BMI) and body composition by dual energy X-ray absorptiometry annually on 10 occasions from 7 to 16 years in the 347 children of the EarlyBird study. We used mixed effects modelling to analyse the trends in REE and their relationship to BMI, lean mass (LM), fat mass (FM), age, PA and pubertal stage. Results Relative REE and total PA fell during puberty, as previously described, but the longitudinal data and narrow age-range of the cohort (SD ± 4 months) revealed for the first time a substantial fall in absolute REE during the period of maximum growth. The fall became clearer still when adjusted for FM and LM. The fall could not be explained by fasting insulin, adiponectin, leptin, luteinising hormone or follicle stimulating hormone. Conclusions There appears to be a temporary but substantial reduction in energy expenditure during puberty, which is unrelated to changes in body composition. If it means higher energy efficiency, the fall in REE could be advantageous in an evolutionary context to delivering theBackground Diabetes is closely linked to obesity, and obesity rates climb during adolescence for reasons that are not clear. Energy efficiency is important to obesity, and we describe a temporary but substantial fall in absolute energy expenditure, compatible with improved energy efficiency, during the rapid growth phase of puberty. Methods In a longitudinal cohort study lasting 10 years, we measured voluntary energy expenditure as physical activity (PA) by accelerometry, involuntary energy expenditure as resting energy expenditure (REE) by oxygen consumption, body mass index (BMI) and body composition by dual energy X-ray absorptiometry annually on 10 occasions from 7 to 16 years in the 347 children of the EarlyBird study. We used mixed effects modelling to analyse the trends in REE and their relationship to BMI, lean mass (LM), fat mass (FM), age, PA and pubertal stage. Results Relative REE and total PA fell during puberty, as previously described, but the longitudinal data and narrow age-range of the cohort (SD ± 4 months) revealed for the first time a substantial fall in absolute REE during the period of maximum growth. The fall became clearer still when adjusted for FM and LM. The fall could not be explained by fasting insulin, adiponectin, leptin, luteinising hormone or follicle stimulating hormone. Conclusions There appears to be a temporary but substantial reduction in energy expenditure during puberty, which is unrelated to changes in body composition. If it means higher energy efficiency, the fall in REE could be advantageous in an evolutionary context to delivering the extra energy needed for pubertal growth, but unfavourable to weight gain in a contemporary environment. Whilst exercise is not central to this study, the well-known decline in free-living physical activity during adolescence in girls and boys means that the findings are relevant for paediatric exercise scientists concerned with total energy balance and metabolism. Resting energy expenditure (REE), the largest component of total daily energy expenditure, is central to calculations of energy balance and has been linked to obesity. Yanovski (9) proclaimed that identification of sub-populations whose low REE predisposes them to weight gain is one of the “Holy Grails” of obesity research. To date, it is generally agreed that absolute REE rises throughout childhood and adolescence in line with growth in body mass, which is driven by the collective metabolic rates of increasing lean tissue mass (e.g., liver, kidneys, heart, brain and skeletal muscle). Relative REE, scaled to account for changing body size and composition, declines progressively with increasing age in young people, which has been attributed to changes in both cellular oxidative metabolism and a declining proportional contribution from highly metabolically active organs (6). The EarlyBird study, a longitudinal observation of over 300 girls and boys from 5 to 16 years in England has provided many important insights since its inception in 2000, some which have generated considerable debate (1,8). This paper was selected to highlight the author speculation about temporal energy conservation during puberty, which may have farreaching ramifications on strategies to prevent and treat adolescent obesity. Mostazir and colleagues (3) present novel observations from their cohort study to promote an alternative paradigm that programmed reductions in physical activity (PA) and absolute REE during adolescence, conceived originally to save energy important for pubertal growth, may now predispose adolescents to obesity when exposed to the deleterious effects of an obesogenic environment. The methods used to provide the primary variables included in the linear mixed effects models (LMM) suggest that they are unlikely to be the cause of serious bias. Moreover, the data from which the patterns of change in PA, REE, growth velocities and body size/composition are derived use well-established, standardised protocols. The modelled (M1) accelerated decline in PA from 7 to 16 years in girls and boys, and the sex differences, generally mirror the literature. The first of two LMM used to characterise changes in absolute REE (kcal·day) from 7 to 16 years (M2) showed the anticipated rise, but only up to 11 years of age; thereafter it declined unexpectedly until the participants were 15 years old before making a recovery in the final year of measurement – this model was not adjusted for lean or fat mass. In the second absolute REE model (M3), which was adjusted for metabolically active lean and fat mass, an expected plateau in absolute REE from 7 to 10 years was seen. However, the estimated absolute REE values spanning 11 to 15 years declined at a greater rate than seen in M2 and could not be ascribed to body composition during this period of rapid growth or any other variables entered into the model. The measured mean increases in lean mass for girls (9.5 kg) and boys (18.6 kg) from 11 to 15 years resulted in estimated reductions in REE amounting to 284 and 114 kcal·day, respectively. This is a meaningful reduction given it has been estimated that excessive weight gain might be prevented by reducing positive energy balance by 150 kcal·day in children and adolescents (7). The authors went on to suggest that when the fall in REE is considered independently of changes in both lean and fat mass, the real reduction in intrinsic REE is up to 450 kcal·day around 15 years of age. The magnitude of error in these estimations is not clear. Serial measurements of insulin, insulin-like growth factor-1, luteinising hormone, follicle stimulating hormone, leptin and adiponectin did not explain meaningful proportions of the decline in REE independent of body composition, age, sex or maturity. Mostazir et al. (3) speculate that the changes in REE described above are energy efficiency savings that have evolved to “assure the extra energy needed for adolescent growth” and that “systematic change in biological systems implies control, and controlled change infers that there is a survival advantage to be gained” (p. 1623). They also state that using changes in body composition to explain changes in REE, which is commonplace, is incompatible with their longitudinal data. Whilst it appears they are the first to propose this novel paradigm, similar maturity-related reductions in REE were reported first by Sun et al. (5) in a shorter longitudinal study comparing African American and white young people from 7 to 12 years, spanning the full range of biological maturation. There was, however, a considerable imbalance in sample size from Tanner stage 1 to 5, which weaken the findings; hence, the current data provide welcome confirmation. Available evidence increasingly supports population declines in physical activity and high levels of sedentary behaviour (4); add to this an intrinsic reduction in REE across adolescence and ineffective interventions to redress the energy balance through increased activity expenditure (2). Thus, an energy dense nutritional environment places adolescents at increased risk of unhealthy weight gain at a time when intuition might suggest additionalenergy intake is required to fuel puberty. Do we need to revisit nutritional reference intakesfor adolescents? References1. Metcalf BS, Hosking J, Jeffery AN, Voss LD, Henley W, Wilkin TJ. Fatness leads toinactivity, but inactivity does not lead to fatness: a longitudinal study in children(EarlyBird 45). Arch Dis Child. 2011; 96(10):942-947. DOI: 10.1136/adc.2009.1759272. Metcalf B, Henley W, Wilkin T. Effectiveness of intervention on physical activity ofchildren: systematic review and meta-analysis of controlled trials with objectivelymeasured outcomes (EarlyBird 54). BMJ. 2012; 345:e5888. DOI: 10.1136/bmj.e58883. Mostazir M, Jeffery A, Hosking J, Metcalf B, Voss L, Wilkin T. Evidence for energyconservation during pubertal growth. A 10-year longitudinal study (EarlyBird 71). Int JObes. 2016; 40(11):1619-1626. DOI: 10.1038/ijo.2016.1584. Pate RR, Mitchell JA, Byun W, Dowda M. Sedentary behaviour in youth. Brit J Sports Med.2011; 45(11):906-913. DOI: 10.1136/bjsports-2011-0901925. Sun M, Gower BA, Bartolucci AA, Hunter GR, Figueroa-Colon R, Goran MI. A longitudinalstudy of resting energy expenditure relative to body composition during puberty inAfrican American and white children. Am J Clin Nutr. 2001;73(2):308-315.6. Wang Z. High ratio of resting energy expenditure to body mass in childhood andadolescence: a mechanistic model. Am J Hum Biol. 2012; 24(4):460-467. DOI:10.1002/ajhb.222467. Wang YC, Gortmaker SL, Sobol AM, Kuntz KM. Estimating the energy gap among USchildren: a counterfactual approach. Pediatrics 2006; 118(6):e1721–e1733.8. Wilkin TJ, Mallam KM, Metcalf BS, Jeffery AN, Voss LD. Variation in physical activity lieswith the child, not his environment: evidence for an 'activitystat' in young children(EarlyBird 16). Int J Obes. 2006; 30(7):1050-1055.9. Yanovski JA. Resting energy expenditure in African American and white children. Am JClin Nutr. 2001; 73(2):149-150. CitationLiu M, Timmons BW. The effect of acute exercise on neutrophil reactive oxygen speciesproduction and inflammatory markers in healthy prepubertal and adult males. PediatrExerc Sci. 2016;28(1):55-63. DOI: 10.1123/pes.2014-0221. AbstractThe adaptive effects of exercise-induced inflammation and reactive oxygen species (ROS)production has been well studied in adults, but not in children. Characterizing the exerciseThe adaptive effects of exercise-induced inflammation and reactive oxygen species (ROS)production has been well studied in adults, but not in children. Characterizing the exercise responses in children compared with adults will start clarifying the transition from the childphenotype to that of an adult. Ten children aged 8–10 and 12 adults aged 19–21 performed2 × 30-min bouts of continuous cycling, separated by a 6-min rest period, at a target workrate of 60% of their maximum aerobic capacity. Blood samples were collected preandimmediately postexercise, and analyzed for neutrophil count, systemic oxidative andinflammatory markers, and intracellular neutrophil-derived reactive oxygen species.Although postexercise absolute neutrophils increased by approximately twofold in men(2.72 ± 0.49 × 10/L to 4.85 ± 2.05 × 10/L; p = .007), boys showed no such change (3.18 ±0.67 × 10/L to 3.57 ± 0.73 × 10/L; p = .52). Contrary to these findings, boys did show anincrease in overall intracellular neutrophil ROS production, whereas men did not. Boys alsodemonstrated higher overall protein carbonyl levels (0.07 nmol/mg vs 0.04 nmol/mg; boysvs men respectively), whereas men showed higher overall malondialdehyde (0.24 μM vs0.67 μM; boys vs men respectively). The differences observed in the exercise-inducedinflammatory and oxidative stress response may indicate growth-mediated adaptiveresponses to exercise during childhood development. It is well established that research findings based on samples of adults cannot be translateddirectly to children due to a variety of child-adult metabolic and hormonal differences (1).However, exercise science studies rarely include samples of both children and adults toprovide a direct comparison between these populations. Despite the potential for exercise to enhance growth and development in children, it also leads to the production ofinflammatory cytokines that can counteract the anabolic response. Thus, it has recentlybeen proposed that the reduced inflammatory response to exercise in children may be aninherent ‘protective’ mechanism to allow for the anabolic effects of exercise. Although themechanisms underpinning the reduced inflammatory response to exercise in children arepoorly understood, reactive oxygen species (ROS) production from activated neutrophilsmay be involved (5). However, very little is known about neutrophil-generated ROSproduction and the relation with inflammatory markers during acute exercise in eitherchildren or adults; this is partly because the invasive methods associated with studying suchbiological processes often preclude research with children. With this in mind, the publication by Liu and Timmons (3) is highlighted here due to the identification of novelchild-adult differences in circulating inflammatory cytokines and both intracellular andsystemic markers of ROS production in response to exercise. This topic is of furtherrelevance because chronic low grade inflammation can contribute to the development ofcardiovascular diseases, type 2 diabetes and cancer in adulthood (2,8). Thus, the researchfindings not only have implications for growth, but also for maintaining metabolic health inthe transition from childhood to adulthood. Using an acute exercise response study with two groups (i.e., children and adults), Liu andTimmons (3) assessed exercise-induced inflammation and ROS production in response totwo, 30-min bouts of cycling separated by a 6 minute rest in 10 children aged 8 to 10 yearsand 12 adults aged 19 to 21 years. While the low sample size limits statistical power for some of the outcome variables (e.g., the reduction in elastase following exercise and theexercise-induced increase in ROS production), numerous significant age-related differencesin exercise-induced oxidative stress were found. Firstly, the findings on inflammatorymarkers confirmed previous reports, with acute exercise resulting in no change in tumornecrosis factor alpha concentrations ([TNF-α]) in the boys and a small increase in the men,and the boys showing a smaller increase in interleukin-6 (IL-6) compared with the men (4,7).The authors also showed that the men experienced a 1.5-fold increase in post-exerciseabsolute neutrophils, but no change was found in the boys. This finding supports a smallnumber of previous studies (6,7) and may relate to the smaller inflammatory cytokineresponse in the children. The main finding, however, pointed towards the potential for exercise to stimulate a “sensitized” neutrophil response in the boys, which has been shownfor the first time in the study by Liu and Timmons (3). Indeed, the boys showed an increasein overall intracellular neutrophil-stimulated ROS production after exercise, whereas mendid not. This finding is intriguing and opens up avenues for further research to ascertain thereasons for this “sensitized” neutrophil response. It is possible it may be related to the boyseliciting a relatively larger growth hormone response to exercise or recruiting neutrophilsfrom the bone marrow rather than circulating pools in the blood, as suggested by theauthors. With the link between ROS, inflammatory markers, growth and disease, thesechild-adult differences in responses to acute exercise may have meaningful implications for maintaining healthy growth in the exercising child. Ultimately, the reported findings contribute to an evolving understanding of the biologicalprocesses underpinning age and maturational differences in exercise-induced inflammatoryand oxidative stress; highlighting that findings in adults often cannot be translated directlyto children. In terms of exercise promotion, the use of a well-controlled acute exerciseresponse design adds to the current evidence on the benefits of single exercise sessions,which complements the well-documented chronic adaptations. These ‘immediate’ benefits could be used as an important motivator for individuals considering exercise. The acutedesign may also serve as an important start point to assess the effects of accumulatingexercise in the transition from childhood to adulthood. In conjunction with the novelfindings, the study design means that there is much scope to extend this research tofemales, children at different stages of maturation and to ascertain the responses to repeated, chronic exercise. Thus, this study stands to provide an important platform forfurther research in this field to help understand how exercise can maintain healthy growthand development of children. References1. Boisseau N, Delamarche P. Metabolic and hormonal responses to exercise in childrenand adolescents. Sports Med. 2000; 30(6):405-422.2. Jay D, Hitomi H, Griendling KK. Oxidative stress and diabetic cardiovascularcomplications. Free Radic Biol Med. 2006; 40(2):183-192.3. Liu M, Timmons BW. The effect of acute exercise on neutrophil reactive oxygen speciesproduction and inflammatory markers in healthy prepubertal and adult males. PediatrExerc Sci. 2016;28(1):55-63. DOI: 10.1123/pes.2014-0221.4. Nemet D, Oh Y, Kim HS, Hill M, Cooper DM. Effect of intense exercise on inflammatorycytokines and growth mediators in adolescent boys. Pediatrics. 2002; 110(4):681–689.5. Niess AM, Dickhuth HH, Northoff H, Fehrenbach E. Free radicals and oxidative stress inexercise immunological aspects. Exerc Immunol Rev. 1999; 5:22-56.6. Timmons BW, Tarnopolsky MA, Bar-Or O. Immune responses to strenuous exercise andcarbohydrate intake in boys and men. Pediatr Res. 2004; 56(2):227-234.7. Timmons BW. Exercise and the cytokine balance: a paediatric perspective. J Sports Sci.2006; 24(1):1-2.8. Victor VM, Rocha M, Solá E, Bañuls C, Garcia-Malpartida K, Hernández-Mijares A.Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des. 2009;15(26):2988-3002. CitationLogan GRM, Harris N, Duncan S, Plank LD, Merien F, Schofield G. Low-active maleadolescents: a dose response to high-intensity interval training. Med Sci Sports Exerc. 2016;48(3):481–490. DOI: 10.1249/MSS.0000000000000799 AbstractPurpose High-intensity interval training (HIIT) is a potential alternative to traditionallyrecommended steady state exercise for providing health benefits in adolescents, yet itsdose–response relationship in this cohort remains unclear, as does its translatability to real-world, nonclinical settings. The present study adopts a novel dose–response design toinvestigate the effects of undertaking 8 wk of HIIT on the cardiometabolic health of low-active male adolescents. Methods Twenty-six male adolescents (age 16 ± 1 yr), identified aslow active by nonparticipation in structured sport and physical education classes, wererandomly assigned to one of five treatment groups. Corresponding with their groupPurpose High-intensity interval training (HIIT) is a potential alternative to traditionallyrecommended steady state exercise for providing health benefits in adolescents, yet itsdose–response relationship in this cohort remains unclear, as does its translatability to real-world, nonclinical settings. The present study adopts a novel dose–response design toinvestigate the effects of undertaking 8 wk of HIIT on the cardiometabolic health of low-active male adolescents. Methods Twenty-six male adolescents (age 16 ± 1 yr), identified aslow active by nonparticipation in structured sport and physical education classes, wererandomly assigned to one of five treatment groups. Corresponding with their group numbers (1–5), participants completed a number of HIIT ‘‘sets,’’ which consisted of 4repeated bouts of 20-s near-maximal exertion interspersed with 10-s passive recovery.Participants performed two HIIT sessions and one resistance training session each week for8 wk. Baseline and follow-up health measures consisted of peak oxygen uptake (OV 2 peak)with an incremental ramp test to volitional exhaustion; body composition (including visceralfat mass, body fat, and lean tissue mass) with dual-energy x-ray absorptiometry; and lipidprofile, glucose, insulin, and interleukin-6 from blood analysis. All health outcomes wereanalyzed as percentage changes, and data were modelled using a quadratic function toexplore dose-response relationships. Results Significant improvements were observed forOV 2 peak (~6%), body fat percentage (~4%), visceral fat mass (~10%), and waistcircumference-to-height ratio (~3%), but there was no clear effect of dose across groups.Conclusions Low-active adolescent males performing a single HIIT set twice weekly, inaddition to one resistance training session, gained meaningful improvements in fitness andbody composition. Performing additional HIIT sets provided no additional improvements tothose of the lowest dose in this study. High-intensity interval training (HIIT) has been the focus of much attention in recent yearswith some evidence supporting the efficacy of HIIT to induce physiological adaptationscomparable to those elicited by traditional higher-volume exercise training (4). Much of theallure surrounding HIIT stems from the priority afforded to exercise intensity over durationand, thus, its purported time efficiency (5). Logan and colleagues (7) highlight the relativedearth of research examining the efficacy of this form of exercise training on health-relatedrisk factors in adolescents and the need for this research to be conducted in real-world settings. Both of these issues represent directives for future research that is required ifexperimental findings are to inform exercise recommendations for young people effectively.The rationale for the study by Logan and colleagues (7) centred on the uncertaintysurrounding the issue of dose-response to HIIT; the importance of which is clear, and bestillustrated when considering the ‘optimal dose’ of exercise. Although the relevance of theseresearch questions has long been championed by eminent exercise scientists (6), thereremains the need for experimental studies that are carefully designed to examine the dose-response to exercise in young people. Therefore, the main aim of this study was to examinethe efficacy of incremental doses of HIIT performed over an eight-week period and establishthe dose-response relationship in a low-active adolescent population for the first time. As acknowledged by the authors (7), dose-response research is inherently challenging.Repeated-measures study designs, in which each participant receives all exercise‘treatments’ or doses, are optimal but often impractical due to the burden of undergoing multiple training exposures and the extensive ‘wash-out’ period that must be observedbetween treatments. During childhood and adolescence, these issues are exacerbated bygrowth and maturation that will confound the interpretation of data collected over aninevitably extended period. In an attempt to circumvent these impracticalities, the authorsemployed a novel parallel-groups, dose-response study design (1,8) during which participants received one of five HIIT doses. Individual responses to training were plottedand the dose-response effect was represented as a quadratic function. Twenty-six, 16 yearold low-active, asymptomatic adolescent boys completed the study and were allocatedrandomly to one of five exercise groups. Each exercise group performed two HIIT sessionsper week for eight weeks with the exercise dose being titrated from 1 to 5 sets per sessionto correspond with the group allocation. The HIIT protocol duration per session, includingrecovery, ranged from 1 min 50 s to 9 min 10 s in the lowest and highest dose groups,respectively. The prescribed dose of HIIT was achieved using a combination of common modes of exercise with those participants scheduled to perform more than one set of exerciseallowed to change exercise modality upon completion of each HIIT set. The adoption of amixed-exercise experimental design, performed in the school-setting, resulted in goodexercise fidelity and compliance and facilitated a “translatable approach to HIIT” whichshould be commended. Unfortunately, however, this flexibility did cloud the issue of dose-response as the potential for disparate, exercise-specific training adaptations must not beunderestimated. In future, a fixed exercise modality would be advantageous whenexamining the dose-response to HIIT more closely. The tightly controlled laboratory-based assessments completed before and after eightweeks of HIIT represent a major strength of the study. When the data from all exercisegroups were pooled, small (effect sizes 0.11 to 0.29) post-HIIT changes in a number ofoutcome variables were reported including improvements in cardiorespiratory fitness (+6%),body fat percentage (-4%) and visceral fat mass (-10%). Fasting plasma glucose, insulin andlipid concentrations did not change meaningfully. This is perhaps unsurprising given thetight glycaemic regulation exhibited in the absence of metabolic disorders in asymptomaticadolescents and the equivocal evidence surrounding blood lipid responses to exercise intervention (2,3). The quadratic trend provided limited evidence of a dose response toexercise, with the authors (7) concluding that the performance of a single set of HIITperformed twice weekly resulted in meaningful improvements in fitness and bodycomposition whist performing a greater volume of HIIT did not confer any additional benefit.Unfortunately, however, the heterogeneity of the cohort at baseline, coupled with the very small number of participants assigned to each exercise treatment sub-group (n = 5), greatlyreduced the exploratory power of an otherwise well designed study and limits theconclusions that can be drawn from the data. Although Logan and colleagues (7) reportedlittle evidence in support of a dose-response relationship, it would be difficult, at this stage,to conclude with much confidence that such a relationship does not exist. It remains to beseen whether similar quadratic modelling analyses performed on more extensive data setswould yield evidence of a dose-response to HIIT. Importantly, however, despite itslimitations, this study provides a platform on which similar future studies, conducted on alarger scale, may look to build. Moving forward, the issue of dose-response must beaddressed across the broad exercise spectrum as well as in younger age groups if we are to advance our understanding of how exercise might be optimally prescribed during childhoodand adolescence. References1. Barnes KR, Hopkins WG, McGuigan MR, Kilding AE. Effects of different uphill interval-training programs on running economy and performance. Int J Sports Physiol Perform2013; 8(6):639–467.2. Bond B, Cockcroft EJ, Williams CA, Harris S, Gates PE, Jackman SR, Armstrong N, BarkerAR. Two weeks of high-intensity interval training improves novel but not traditionalcardiovascular disease risk factors in adolescents. Am. J. Physiol. Heart Circ. Physiol. 2015;309(6):H1039-H1047. DOI: 10.1152/ajpheart.00360.20153. Corte de Araujo AC, Roschel H, Picanço AR, do Prado DM, Villares SM, de Sá PintoAL, Gualano B. Similar health benefits of endurance and high-intensity interval training inobese children. PLoS ONE. 2012; 7(8):e42747. DOI: 10.1371/journal.pone.00427474. Gibala, MJ, Little JP, van Essen M, Wilkin GP, Burgomaster KA, Safdar A, RahaS, Tarnopolsky MA. Shortterm sprint interval versus traditional endurance training:similar initial adaptations in human skeletal muscle and exercise performance. J. Physiol.2006; 575:901–911.5. Gibala MJ. Highintensity interval training: a time-efficient strategy for health promotion?Curr Sports Med Rep. 2007; 6:211–213.6. Haskell, W.L. Health consequences of physical activity: Understanding and challengesregarding dose-response. Med Sci Sports Exerc. 1994; 26:649-660. 7. Logan GRM, Harris N, Duncan S, Plank LD, Merien F, Schofield G. Low-active maleadolescents: a dose response to high-intensity interval training. Med Sci Sports Exerc.2016; 48(3):481–490. DOI: 10.1249/MSS.00000000000007998. Stepto NK, Hawley JA, Dennis SC, Hopkins WG. Effects of different interval-trainingprograms on cycling time-trial performance. Med Sci Sports Exerc. 1999; 31(5):736–741.