Abstract

Low cardiorespiratory fitness (CRF) is considered as an established risk factor for cardiovascular and metabolic disorders. However, the effectiveness of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) in children and adolescents remained uncertain. Electronic databases of the PubMed, EmBase, and the Cochrane library were searched for randomized controlled trials (RCTs) investigated the role of HIIT versus MICT for children and adolescents throughout December 2019. Sixteen RCTs involving a total of 543 children were selected for final meta-analysis. HIIT versus MICT showed high peak VO2 (weighted mean differences (WMD): 2.68; 95% confidence intervals (CIs): 1.81 to 3.55; ), and no evidence of heterogeneity and publication bias was detected. However, there were no significant differences detected between HIIT and MICT on the levels of peak heart rate (HRmax), fat mass, free fat mass, weight, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, glycemia, insulinemia, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, HOMA-IR, HbA1c, and leptinemia. The findings of this study revealed that HIIT versus MICT showed a significant improvement in peak VO2 in children and adolescents. Further large-scale RCTs should be conducted to compare the long-term effects of HIIT versus MICT in children and adolescents.

1. Introduction

Cardiorespiratory fitness (CRF) is an objective reproducible physiological response that is affected by physical activity habits, genetics, and disease status [1]. Low CRF in subjects is identified as a risk factor of cardiovascular morbidity and mortality [2]. Currently, the gold standard for CRF included maximal oxygen uptake, which is measured directly or indirectly by maximal graded cardiorespiratory test [35]. According to a study, high CRF during childhood and adolescence showed association with reduced risk of subsequent cardiovascular disease [6]. A study involving 25.4 million children and adolescents from 27 countries with CRF showed declination by 3.6% per decade [5]. Regular physical activity could improve CRF [7] and whether different types of physical activity yields differential effects on CRF and other cardiovascular risk factors in children and adolescents remains controversial.

Although the high-intensity interval training (HIIT) was completed within a shorter time, it increased aerobic fitness and mental health in children [810]. Children in schools require effective exercise programs to improve their physical fitness and spend shorter time to exercise in schools [11]. Recently, several studies have already compared the effects of HIIT versus moderate-intensity continuous training (MICT) on the outcomes of body mass index (BMI), hypertension, endothelial function, prediabetes, and type 2 diabetes in adults [1215]. Moreover, the CRF, fat loss, and cardiometabolic health between HIIT and MICT in children and adolescents were compared, and various role of HIIT and MICT could explain by mitochondrial adaptations to short-term training [16, 17]. Numerous studies have already been conducted to compare the effects of HIIT versus MICT in children and adolescents, which can enter into pooled analysis to reevaluate the effectiveness of HIIT versus MICT. Therefore, the current systematic review and meta-analysis was conducted on randomized controlled trials (RCTs) that compared the effects of HIIT versus MICT on the health outcomes of children and adolescents.

2. Materials and Methods

2.1. Data Sources, Search Strategy, and Selection Criteria

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement was applied to guide the reporting of this systematic review [18]. Studies designed as RCT that compared the effects of HIIT versus MICT in children and adolescents were considered eligible in our study, and there is no restriction to publication language and status. The core search terms of (high intensity interval OR high-intensity interval OR high intensity intermittent OR high-intensity intermittent OR sprint interval OR HIIT OR HIIE) AND (children [MeSH] OR adolescent [MeSH] OR boy OR girl OR youth [MeSH] OR kids OR student) AND (randomized controlled trials) were employed to search for potential trials from the PubMed, EmBase, and Cochrane Library electronic databases throughout December 2019. The reference lists from the retrieved studies were also reviewed manually to identify for studies that met the inclusion criteria.

Two authors independently conducted the literature search and study selection processes, and any disagreements were settled by group discussion until a consensus was reached. The details regarding the inclusion criteria are as follows: (1) participants: the mean age of children or adolescents <18.0 years; (2) intervention: HIIT; (3) control: MICT; (4) outcomes: peak oxygen uptake (VO2), HRmax, fat mass, free fat mass, weight, BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), glycemia, insulinemia, total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), HOMA-IR, HbA1c, and leptinemia; and (5) study design: RCT. Study with observational design was excluded owing to confounding variables or bias.

2.2. Data Collection and Quality Assessment

The data abstraction and quality evaluation from the retrieved studies were conducted by 2 authors independently, and any conflicts were resolved by group discussion. The data collected included the first author’s surname, publication year, country, sample size, mean age, percentage male, intervention, control, follow-up duration, and reported outcomes. The Jadad scale was used to assess the quality of included trials, which is based on the following 5 subscales: randomization, concealment of treatment allocation, blinding, completeness of follow-up, and use of intention-to-treat analysis [19]. In this study, the trials that scored 4 or 5 were considered as high quality.

2.3. Statistical Analysis

The effects of HIIT versus MICT on health outcomes in children and adolescents were included as continuous data, and the weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated before data pooling. The random-effects models were used to calculate the pooled effect estimates owing to it considering the underlying varies across included studies [20, 21]. The heterogeneity across included trials were assessed using 2 and statistics, and significant heterogeneity was defined as or [22, 23]. The stability of pooled conclusions was then assessed by a sensitivity analysis [24]. Subgroup analyses of investigated outcomes were conducted based on the mean age of subjects, and the differences between subgroups were assessed by interaction test [25]. Publication biases for investigated outcomes were assessed by using the funnel plots, Egger, and Begg tests [26, 27]. The inspection levels for pooled results are two-sided, and was considered as statistically significant difference between HIIT and MICT. The data in this meta-analysis was analyzed by using the STATA software (version 12.0; Stata Corporation, College Station, TX, USA).

3. Results

3.1. Literature Search

A total of 1,846 articles were identified by initial electronic search, and 1,055 articles of these were excluded owing to duplications. Next, 730 articles were further excluded because of irrelevant topics. Full-text evaluations were done for the remaining 61 studies, and 45 studies were excluded because of the following reasons: no appropriate control (), no desirable outcomes (), and no RCT design (). After this, a total of 16 RCTs were considered eligible and included in the final meta-analysis [2843]. No new eligible trial was identified by manual searching of the reference lists of retrieved studies (Figure 1). The baseline characteristics of the included trials are summarized in Table 1.

3.2. Study Characteristics

A total of 543 children were included in the trials that are published from 2005 to 2019. The follow-up duration ranged from 3.0 to 24.0 weeks, and 13-94 children were included in each individual trial. Thirteen RCTs were conducted in Western countries or Africa, and the remaining 3 were conducted in Asia. The mean age of children and adolescents included in the trials ranged from 8.2 to 17.4 years, and 4 trials included only boys. The Jadad scale was used to assess the study quality, in which 5 trials had a score of 4, 7 trials scored 3, 3 trials scored 2, and the remaining 1 trial scored 1.

3.3. Peak VO2

The data regarding the effect of HIIT versus MICT on peak VO2 were available in 10 trials. The peak VO2 was significantly higher in the HIIT group (WMD: 2.68; 95% CI: 1.81 to 3.55; ; Figure 2), and no heterogeneity was detected across the included trials (; ). The conclusion was robust and unchanged by sequential exclusion of each individual trial (Supplemental 1 and Supplemental 3). Subgroup analysis showed significant differences between HIIT and MICT in peak VO2 in (Table 2). No significant publication bias for peak VO2 was detected ( value for Egger: 0.339; value for Begg: 0.213; Supplemental 2).

3.4. Peak Heart Rate

The data regarding the effect of HIIT versus MICT on HRmax were available in 7 trials. No significant difference between HIIT and MICT for HRmax was detected (WMD: 0.35; 95% CI: -3.90 to 4.60; ; Figure 3), and significant heterogeneity was detected among the included trials (; ). Sensitivity analysis found a stable conclusion and was unaltered by sequential exclusion of individual trial (Supplemental 1 and Supplemental 3). Subgroup analysis suggested that HIIT was associated with lower HRmax if the mean age of children was <12.0 years (Table 2). No significant publication bias was observed for HRmax ( value for Egger: 0.596; value for Begg: 1.000; Supplemental 2).

3.5. Fat Mass

The data regarding the effect of HIIT versus MICT on fat mass were available from 11 trials. There were no significant differences between HIIT and MICT for fat mass (WMD: -0.15; 95% CI: -1.85 to 1.55; ; Figure 4), and similarly, no potential significant heterogeneity across the included trials was observed (; ). The conclusion was robust and unaltered by sequential exclusion of individual trials (Supplemental 1 and Supplemental 3). The results of subgroup analyses were consistent with the overall analysis (Table 2). Although the Begg test indicated no significant publication bias, the Egger test showed potentially significant publication bias for fat mass ( value for Egger: 0.019; value for Begg: 0.350; Supplemental 2). The conclusion was changed when the trim and fill method was used to adjust potential publication bias (Supplemental 2).

3.6. Free Fat Mass

The data regarding the effect of HIIT versus MICT on free fat mass were available in 4 trials. HIIT showed no significant effect on free fat mass when compared with MICT (WMD: 0.38; 95% CI: -2.32 to 3.09; ; Figure 5), and no evidence of heterogeneity was observed (; ). The conclusion remained robust after reviewing the results of sensitivity analysis (Supplemental 1 and Supplemental 3). The conclusions of subgroup analyses were consistent with that of overall analysis (Table 2). There was no significant publication bias for free fat mass ( value for Egger: 0.345; value for Begg: 0.308; Supplemental 2).

3.7. Weight

The data regarding the effect of HIIT versus MICT on weight were available from 11 trials, and no significant differences between HIIT and MICT for weight were observed (WMD: -0.46; 95% CI: -2.29 to 1.37; ; Figure 6). Moreover, unimportant heterogeneity was detected for weight (; ). Sensitivity analysis revealed robust conclusion and showed nonsignificant difference by sequentially excluding each trial (Supplemental 1 and Supplemental 3). Subgroup analyses suggested that the conclusions were consistent with the overall analysis in all subsets (Table 2). No significant publication bias for weight was detected ( value for Egger: 0.600; value for Begg: 0.631; Supplemental 2).

3.8. Body Mass Index

The data regarding the effect of HIIT versus MICT on BMI were available from 13 trials. The pooled results suggested that HIIT demonstrated no significant effect on BMI when compared with MICT (WMD: -0.01; 95% CI: -0.62 to 0.60; ; Figure 7), and unimportant heterogeneity was detected (; ). Sensitivity analysis suggested that the conclusion remained unchanged by sequential exclusion of each trial (Supplemental 1 and Supplemental 3). Moreover, the results of subgroup analyses were consistent with that of the overall analysis in all subsets (Table 2). No significant publication bias was observed for BMI ( value for Egger: 0.775; value for Begg: 0.743; Supplemental 2).

3.9. Waist Circumference

The data regarding the effect of HIIT versus MICT on WC were available in 6 trials. There was no significant difference between HIIT and MICT on WC (WMD: -1.47; 95% CI: -4.67 to 1.73; ; Figure 8), and significant heterogeneity was seen for WC (; ). The conclusion remains stable and unaltered by sequentially excluding each trial (Supplemental 1 and Supplemental 3). No significant difference was observed between HIIT and MICT in subgroup analysis (Table 2). There was no significant publication bias detected for WC ( value for Egger: 0.443; value for Begg: 1.000; Supplemental 2).

3.10. Systolic Blood Pressure

The data regarding the effect of HIIT versus MICT on SBP were available in 7 trials. The results revealed that HIIT has no significant effect on SBP when compared with MICT (WMD: -1.36; 95% CI: -3.99 to 1.27; ; Figure 9), and significant heterogeneity was detected (; ). The results of sensitivity analysis suggested that the conclusion was robust and unaltered by sequentially excluding individual trial (Supplemental 1 and Supplemental 3). The results of subgroup analyses showed no significant differences between HIIT and MICT on SBP in all subsets (Table 2). No significant publication bias was observed for SBP ( value for Egger: 0.266; value for Begg: 1.000; Supplemental 2).

3.11. Diastolic Blood Pressure

The data regarding the effect of HIIT versus MICT on DBP were available in 7 trials. There was no significant difference detected between HIIT and MICT for DBP (WMD: 0.57; 95% CI: -0.55 to 1.69; ; Figure 10), and no evidence of heterogeneity was seen (; ). The conclusion was robust and unaffected by sequential exclusion of individual trial (Supplemental 1 and Supplemental 3) and was stratified by the mean age (Table 2). No significant publication bias for DBP was observed ( value for Egger: 0.165; value for Begg: 0.174; Supplemental 2).

3.12. Glycemia

The data regarding the effect of HIIT versus MICT on glycemia were available in 4 trials. No significant difference between the groups for glycemia was observed (WMD: -2.14; 95% CI: -7.62 to 3.35; ; Figure 11), and potentially significant heterogeneity was detected (; ). The results of sensitivity analysis (Supplemental 1 and Supplemental 3) and subgroup analysis were consistent with that of the overall analysis (Table 2). No significant publication bias for glycemia was observed ( value for Egger: 0.879; value for Begg: 0.734; Supplemental 2).

3.13. Insulinemia

The data regarding the effect of HIIT versus MICT on insulinemia were available in 6 trials. The results showed no significant effect of HIIT on insulinemia when compared with MICT (WMD: -1.72; 95% CI: -4.13 to 0.69; ; Figure 12), and no significant heterogeneity across the included trials was observed (; ). The results of sensitivity analysis (Supplemental 1 and Supplemental 3) and subgroup analysis were consistent with that of the overall analysis (Table 2). There was no significant publication bias for insulinemia ( value for Egger: 0.359; value for Begg: 0.707; Supplemental 2).

3.14. Total Cholesterol

The data regarding the effect of HIIT versus MICT on TC were available in 5 trials. There was no significant difference between HIIT and MICT for TC (WMD: -6.22; 95% CI: -12.87 to 0.42; ; Figure 13), and no evidence of heterogeneity across included trials (; ). The results of sensitivity analysis (Supplemental 1 and Supplemental 3) and subgroup analysis were consistent with that of the overall analysis (Table 2). No significant publication bias was seen for TC ( value for Egger: 0.894; value for Begg: 1.000; Supplemental 2).

3.15. High Density Lipoprotein

The data regarding the effect of HIIT versus MICT on HDL were available in 4 trials. HIIT showed no association with HDL when compared with MICT (WMD: 0.73; 95% CI: -4.49 to 5.94; ; Figure 14), but significant heterogeneity was observed (; ). The results of sensitivity analysis indicated that HIIT might be associated with low HDL (Supplemental 1 and Supplemental 3). Moreover, subgroup analysis found no significant difference between groups on HDL in all subsets (Table 2). There was no significant publication bias for HDL ( value for Egger: 0.162; value for Begg: 0.089; Supplemental 2).

3.16. Low Density Lipoprotein

The data regarding the effect of HIIT versus MICT on LDL were available in 4 trials. There was no significant difference between HIIT and MICT for LDL (WMD: -2.58; 95% CI: -9.87 to 4.70; ; Figure 15), and moderate heterogeneity was detected across the included trials (; ). The results of sensitivity analysis (Supplemental 1 and Supplemental 3) and subgroup analysis were consistent with those of the overall analysis (Table 2). No significant publication bias was detected for LDL ( value for Egger: 0.552; value for Begg: 0.734; Supplemental 2).

3.17. Triglyceride

The data regarding the effect of HIIT versus MICT on TG were available from 5 trials. The results showed no significant differences between HIIT and MICT for TG was detected (WMD: -6.03; 95% CI: -13.83 to 1.77; ; Figure 16), and no evidence of heterogeneity among the included trials (; ). The results of sensitivity analysis (Supplemental 1 and Supplemental 3) and subgroup analysis were consistent with that of the overall analysis (Table 2). There was no significant publication bias for TG ( value for Egger: 0.127; value for Begg: 0.221; Supplemental 2).

3.18. HOMA-IR

The data regarding the effect of HIIT versus MICT on HOMA-IR were available in 5 trials. The results showed no significant effect of HIIT on HOMA-IR as compared with MICT (WMD: -0.31; 95% CI: -0.64 to 0.02; ; Figure 17), and no evidence of heterogeneity was seen (; ). The results of sensitivity analysis (Supplemental 1 and Supplemental 3) and subgroup analysis were consistent with that of the overall analysis (Table 2). No significant publication bias for HOMA-IR was seen ( value for Egger: 0.682; value for Begg: 1.000; Supplemental 2).

3.19. HbA1c

The data regarding the effect of HIIT versus MICT on HbA1c were available in 3 trials. The results showed no significant differences between HIIT and MICT (WMD: 0.08; 95% CI: -0.06 to 0.22; ; Figure 18). Moreover, moderate heterogeneity for HbA1c was detected across the included trials (; ). Sensitivity analysis indicated that HIIT might increase HbA1c when compared with MICT (Supplemental 1 and Supplemental 3). Subgroup analysis suggested that HIIT significantly increased HbA1c when the mean age of children was ≥12.0 years (WMD: 0.18; 95% CI: 0.02 to 0.34; ; Table 2). There was no significant publication bias detected for HbA1c ( value for Egger: 0.625; value for Begg: 1.000; Supplemental 2).

3.20. Leptinemia

The data regarding the effect of HIIT versus MICT on leptinemia were available in 3 trials. There was no significant difference between HIIT and MICT for leptinemia (WMD: -0.77; 95% CI: -9.89 to 8.34; ; Figure 19), and significant heterogeneity was detected among the included trials (; ). The results of sensitivity analysis (Supplemental 1 and Supplemental 3) and subgroup analysis were consistent with that of the overall analysis (Table 2). No significant publication bias was detected for leptinemia ( value for Egger: 0.888; value for Begg: 1.000; Supplemental 2).

4. Discussion

This systematic review and meta-analysis was included RCTs that compared the effectiveness of HIIT and MICT on the health outcomes of children and adolescents. The findings of this meta-analysis found that HIIT could significantly improve peak VO2 when compared with MICT, and HIIT showed association with lower HDL and high HbA1c levels. Our results found that children in the HIIT group had high peak VO2 and HbA1c than those in the MICT group when the mean age of children was ≥12.0 years, and the HRmax in children in the HIIT group was significantly lower than those in the MICT group if the mean age of children was <12.0 years. However, no significant differences were observed between HIIT and MICT on HRmax, fat mass, free fat mass, weight, BMI, WC, SBP, DBP, glycemia, insulinemia, TC, HDL, LDL, TG, HOMA-IR, HbA1c, and leptinemia.

Several systematic reviews and meta-analyses have investigated the effectiveness of HIIT. The meta-analysis conducted by Bacon et al. including 334 subjects aged <45.0 years from 37 studies revealed the association of HIIT with high peak VO2 [44]. A meta-analysis conducted by Costigan et al. suggested that HIIT was regarded as a feasible and time-efficient approach to improve CRF and body composition in adolescents [45]. Milanović et al. conducted in his meta-analysis included 723 healthy adults aged 18-45 years and revealed that both HIIT and endurance training showed significant improvement in peak VO2, and HIIT provided a greater improvement in peak VO2 than those who underwent endurance training [46]. A meta-analysis conducted by García-Hermoso et al. included 9 studies and suggested that HIIT is considered as an effective and time-efficient approach to improve blood pressure and aerobic capacity levels than other forms of training in overweight and obese adolescents [47]. Maillard et al. conducted a meta-analysis by including 39 studies and found that HIIT could reduce fat-mass deposits in normal weight and overweight/obese adults [12]. Thivel et al. reported that HIIT significantly improved the maximal oxygen uptake and reduced body mass, body fat, SBP, DBP, and HOMA-IR in overweight and obese children and adolescents [48]. A meta-analysis conducted by Depiazzi et al. found that aquatic HIIT significantly improved the aerobic performance and lower limb strength in a nonathletic population [49]. A meta-analysis conducted by Cao et al. found that HIIT versus MICT showed significant improvement in CRF in children and adolescents [16]. However, the comprehensive health outcomes between HIIT and MICT in children and adolescents were not reported in prior studies. Therefore, the current meta-analysis was conducted to compare the effectiveness of HIIT with MICT in children and adolescents.

The current study revealed that HIIT significantly improved the peak VO2 than MICT, and the significant difference between the groups was mainly observed if the mean age of children was ≥12.0 years. Although the pooled results were consistent with those in the previous meta-analysis study, irrespective for adults or children [16, 46], they applied standard mean difference as an effect estimate, and no stratification was done by the mean age of the subjects. The potential mechanism for this could be that HIIT versus MICT displayed a greater increase in mitochondrial content, including citrate synthase maximal activity, type II fiber activation, adenosine monophosphate activated protein kinase activity, and mass-specific oxygen flux [50, 51]. Also, HIIT played an important role on central adaptation, including maximal stroke volume, cardiac output, and blood volume [5254]. Finally, the improvement of peak VO2 in the HIIT group was more evident in children aged 12.0 years or more, which could be explained by the intensity and regularity of training.

In this study, no significant differences between HIIT and MICT for HRmax, fat mass, free fat mass, weight, BMI, WC, SBP, DBP, glycemia, insulinemia, TC, HDL, LDL, TG, HOMA-IR, HbA1c, and leptinemia were observed, which was not consistent with that of the previous findings. However, the results of HDL and HbA1c between the groups were not robust. The potential reason for this could be that smaller number of included trials reported these parameters, and the power was not enough to obtain a stable result between the HIIT and the MICT groups. Moreover, HbA1c was increased in the HIIT group if the mean age of children was ≥12.0 years. This result showed correlation with high energy intake after training in older children. Interestingly, HIIT showed association with low HRmax than MICT if the children were < 12.0 years age. However, this result was based on 2 included trials, and so large-scale RCT should be conducted to verify the result.

There are several strengths in this study that should be highlighted: (1) this study provided the comprehensive health results between HIIT and MICT in children and adolescents; (2) the analysis of this study was based on RCTs, which included high evidence level results; (3) the analysis was based on inclusion of large number of trials, and the results were robust than any individual trial, and (4) stratified analyses for investigated outcomes according to the mean age of subjects were also conducted. Although above strengths, the limitations of this study should be acknowledged: (1) a smaller number of children were included in individual study, and the deviation was large that could affect the robustness of pooled conclusions; (2) various training types and intensities were included, which could affect the net effects between HIIT and MICT; (3) the status of subjects varied, and the place of training showed significant correlation with health outcomes; (4) several outcomes stratified by the mean age were restricted owing to only 1 study included; (5) whether the effectiveness between HIIT and MICT are differing based on weight status and sexual maturation were not conducted owing to mostly studies did not reported data stratified by weight status and sexual maturation; (6) the data abstracted was based on pooled results in each trial, restricting us in conducting a more detailed analysis; and (7) this analysis was based on published RCTs, and so publication bias was considered inevitable.

5. Conclusions

In summary, a high peak VO2 in the HIIT group was observed than in the MICT group in children and adolescents. Sensitivity analyses suggested that the levels of HDL and HbA1c might differ between the HIIT and the MICT groups. Finally, the effects of HIIT versus MICT on peak VO2, HRmax, and HbA1c might differ based on the mean age of the subjects. The long-term effects of HIIT versus MICT in children and adolescents require assessment in further large-scale RCTs.

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Authors’ Contributions

Jun Yin and Zhixiong Zhou contributed equally to this work.

Acknowledgments

This work was supported by the support program for High-level Teacher Team Development of Beijing Municipal Institutions (IDHT20170515) and Serving National Special Needs in Doctoral Talents Development Program—Performance Training and Health Promotion for Adolescents.

Supplementary Materials

Supplemental 1 Figure S1: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on peak VO2. Figure S2: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on peak heart rate. Figure S3: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on fat mass. Figure S4: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on free fat mass. Figure S5: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on weight. Figure S6: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on body mass index. Figure S7: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on waist circumference. Figure S8: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on systolic blood pressure. Figure S9: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on diastolic blood pressure. Figure S10: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on glycemia. Figure S11: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on insulinemia. Figure S12: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on total cholesterol. Figure S13: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on high density lipoprotein. Figure S14: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on low density lipoprotein. Figure S15: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on triglycerides. Figure S16: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on HOMA-IR. Figure S17: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on HbA1c. Figure S18: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on leptinemia. Supplemental 2 Figure S1: funnel plot of high-intensity interval training versus moderate-intensity continuous training on peak oxygen uptake (VO2). Figure S2: funnel plot of high-intensity interval training versus moderate-intensity continuous training on peak heart rate. Figure S3: funnel plot of high-intensity interval training versus moderate-intensity continuous training on fat mass. Figure S4: results of Trim and fill method for high-intensity interval training versus moderate-intensity continuous training on fat mass. Figure S5: funnel plot of high-intensity interval training versus moderate-intensity continuous training on free fat mass. Figure S6: funnel plot of high-intensity interval training versus moderate-intensity continuous training on weight. Figure S7: funnel plot of high-intensity interval training versus moderate-intensity continuous training on body mass index. Figure S8: Funnel plot of high-intensity interval training versus moderate-intensity continuous training on waist circumference. Figure S9: funnel plot of high-intensity interval training versus moderate-intensity continuous training on systolic blood pressure. Figure S10: funnel plot of high-intensity interval training versus moderate-intensity continuous training on diastolic blood pressure. Figure S11: funnel plot of high-intensity interval training versus moderate-intensity continuous training on glycemia. Figure S12: funnel plot of high-intensity interval training versus moderate-intensity continuous training on insulinemia. Figure S13: funnel plot of high-intensity interval training versus moderate-intensity continuous training on total cholesterol. Figure S14: funnel plot of high-intensity interval training versus moderate-intensity continuous training on high density lipoprotein. Figure S15: funnel plot of high-intensity interval training versus moderate-intensity continuous training on low density lipoprotein. Figure S16: funnel plot of high-intensity interval training versus moderate-intensity continuous training on triglycerides. Figure S17: funnel plot of high-intensity interval training versus moderate-intensity continuous training on HOMA-IR. Figure S18: funnel plot of high-intensity interval training versus moderate-intensity continuous training on HbA1c. Figure S19: funnel plot of high-intensity interval training versus moderate-intensity continuous training on leptinemia. Supplemental 3 Table S1: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on peak VO2. Table S2: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on peak heart rate. Table S3: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on fat mass. Table S4: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on free fat mass. Table S5: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on weight. Table S6: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on body mass index. Table S7: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on waist circumference. Table S8: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on systolic blood pressure. Table S9: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on diastolic blood pressure. Table S10: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on glycemia. Table S11: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on insulinemia. Table S12: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on total cholesterol. Table S13: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on high density lipoprotein. Table S14: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on low density lipoprotein. Table S15: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on triglycerides. Table S16: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on HOMA-IR. Table S17: sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on HbA1c. Table S18: Sensitivity analysis of high-intensity interval training versus moderate-intensity continuous training on leptinemia (Supplementary Materials)