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Endurance Training and V˙O2max

Role of Maximal Cardiac Output and Oxygen Extraction


Author Information
Medicine & Science in Sports & Exercise: October 2015 - Volume 47 - Issue 10 - p 2024-2033
doi: 10.1249/MSS.0000000000000640


Endurance training (ET) is commonly associated with increased maximal oxygen consumption (V˙O2max) in healthy subjects (3). Improvement in V˙O2max may result from a myriad of adaptations frequently observed in the cardiovascular, hematological, and metabolic systems (6–8,17,18,25,28,32,35,47,49,57). In conformity with the Fick equation, every adaptation influencing V˙O2max must be reflected by a change in maximal cardiac output (Qmax) and/or arteriovenous oxygen difference (a-V˙O2diff). In particular, central adaptations to ET, such as i) enhanced oxygen-carrying capacity of the blood (8,40) and ii) increased blood volume and improved heart function/structure (4,8), may be accordingly mirrored by a wider a-V˙O2diff and increases in stroke volume (SVmax) and cardiac output (Qmax) at maximal exercise. Such increase in Qmax is entirely the effect of enhanced SVmax, as maximal heart rate (HRmax) is largely unaffected by ET (6–8,17,18,25,32,35,47,49,57). Likewise, peripheral adaptations, including decreased systemic vascular resistance (SVR) leading to enhanced venous return, may increase Qmax (15,35,69), whereas a more efficient blood flow distribution (34) may increase oxygen extraction (i.e., a-V˙O2diff). It is less clear how peripheral adaptations to ET related to skeletal muscle capillarization and mitochondrial content/function (31–33,48) per se might substantially impact on V˙O2max considering that oxygen-diffusing capacity and mitochondrial oxidative capacity exceed oxygen delivery during exercise involving half or more of body muscle mass (9,14). Albeit both central and peripheral adaptations to ET could potentially modify each component of V˙O2max, increases in Qmax and oxygen extraction are taken to primarily reflect central and peripheral adaptations, respectively (18,47).

It has long been questioned whether the increase in V˙O2max following ET is associated with that of Qmax and/or oxygen extraction (22,58). Early reports suggested an increase in Qmax alone or along with oxygen extraction at maximal exercise after ET in eight and five healthy young subjects, respectively (22,58). Subsequent studies have had small sample sizes and have shown variable responses of Qmax and oxygen extraction at maximal exercise to ET (6,8,26,32,35,39,47,62,67,69). In addition, the diverse duration and intensity of training of the aforementioned studies could presumably contribute to their inconsistent results (18,47). Therefore, the purpose of this study was to systematically review and meta-analyze the effects of ET on V˙O2max, Qmax, and a-V˙O2diff at maximal exercise, as well as to determine associations among V˙O2max, Qmax, and a-V˙O2diff at maximal exercise and potential moderating factors. We selected studies of healthy young subjects to limit the influence of disease and/or aging.


The review is reported according to Meta-analysis of Observational Studies in Epidemiology Group guidelines (64).

Data sources and searches

Our systematic search included MEDLINE, Scopus, and Web of Science from their inception until September 2014. We used combinations of the following subject headings: “healthy young,” “training,” “effect,” “adaptation,” “V˙O2max,” “maximal,” “peak,” “oxygen,” and “aerobic” (the search strategy for MEDLINE is shown in Figure, Supplemental Digital Content 1, We also performed a hand search of identified reviews, articles included in meta-analysis, and related citations in MEDLINE and Google.

Article selection

To be included in the analysis, an original research article must have assessed V˙O2max along with Qmax and/or a-V˙O2diff at maximal whole-body exercise with a large muscle mass (e.g., cycling and running) before and after an ET intervention lasting ≥3 wk in healthy young adults (mean age <40 yr). The criteria for attainment of V˙O2max must have been reported in the article. In addition, V˙O2max (and Qmax, if applicable) absolute values (volume/time) had to be available or—if normalized by anthropometrical variables (e.g., weight and body surface area)—the latter must not have been significantly altered by the training intervention. We excluded ET interventions less than 3 wk in duration because Qmax may not be significantly increased by this very short ET period (32,47). In the event of multiple publications pertaining to the same research, the first published report or the more comprehensive report was included. Inclusion of articles in our analysis was not limited by publication status or language. Article selection was performed independently and in duplicate by two investigators (D. Montero) and (C. Diaz-Cañestro).

Data extraction and quality assessment

The following variables were summarized in a preformatted spreadsheet: authors, year of publication, characteristics of study participants (n, age, gender, height, weight, body surface area, body mass index, HRmax, blood volume, red cell volume, hemoglobin concentration, hematocrit, SVmax, Qmax, blood pressure, total peripheral resistance, a-V˙O2diff, fitness status, and health status), features of ET (type, modality, frequency, session length, and years of training), and characteristics of the assessment of V˙O2max, Qmax, and a-V˙O2diff at maximal exercise (technique and test protocol). The Fick equation was used to calculate a-V˙O2diff at maximal exercise in studies reporting only V˙O2max and Qmax values (8,26,39,69). Missing standard deviations (SD) of a-V˙O2diff at maximal exercise in the latter studies were imputed from a linear regression analysis of log(SD of a-V˙O2diff at maximal exercise) on log(mean a-V˙O2diff at maximal exercise) from studies that reported complete data [log(SD of a-V˙O2diff at maximal exercise) = 2.42 log(mean a-V˙O2diff at maximal exercise) − 2.77] (6,35,41,47,62,67). A systematic appraisal of quality for observational research (SAQOR) (55) previously applied in meta-analysis of observational studies evaluating cardiovascular function (44,63) was performed to provide assessment of study quality. The SAQOR was adjusted to assess 1) study sample, 2) quality of V˙O2max assessment, 3) quality of Qmax assessment, 4) quality of maximal a-V˙O2diff assessment, 5) confounding variables, and 6) data. Overall, the SAQOR was scored out of 16, with greater scores indicating better quality. Data extraction and quality assessment were performed independently and in duplicate by two investigators (D. Montero) and (C. Diaz-Cañestro).

Data synthesis and analysis

The meta-analysis and related analyses were performed using Review Manager software (RevMan 5.3; Cochrane Collaboration, Oxford, UK) and Comprehensive Meta-Analysis software (version 2; Biostat, Englewood, New Jersey, USA). The primary outcomes were standardized mean differences (SMD) in V˙O2max, Qmax, and a-V˙O2diff at maximal exercise between post-ET and pre-ET measurements. SMD summary statistics allowed us to standardize values obtained using different methods into a uniform scale to complete the meta-analysis (29). Each SMD was weighted by inverse variance and pooled with a random-effects model (19,29). Heterogeneity among studies was assessed using chi-square test for heterogeneity and I2 statistics. Potential moderating factors influencing SMD in V˙O2max, Qmax, and a-V˙O2diff at maximal exercise were evaluated by subgroup analysis comparing studies grouped by dichotomous or continuous variables. Median values of continuous variables were used as cutoff values for grouping studies. Meta-regression analyses were performed to evaluate associations among SMD in V˙O2max, Qmax, and a-V˙O2diff at maximal exercise and potential moderating factors. In all meta-regression models, studies were weighted by the inverse variance of the dependent variable. Potential moderating factors were entered as independent variables in regressions models, with SMD in V˙O2max, Qmax, or a-V˙O2diff at maximal exercise as dependent variable. Meta-regression analyses were also used to determine the slope between: i) (nonstandardized) mean difference (MD; between post-ET and pre-ET measurements) in V˙O2max and MD in Qmax; ii) MD in Qmax and MD in SVmax; and iii) MD in Qmax and MD in HRmax. Publication bias and/or other biases were evaluated by Begg–Mazumdar’s rank correlation test and Egger’s regression test (21). P < 0.05 was considered statistically significant.


Study selection and characteristics

A flow diagram of the process of article selection, which resulted in the inclusion of nine articles, is shown in Figure 1. Two of the articles presented separate study groups (26,69), each of which was evaluated as an individual study. Table 1 illustrates the main characteristics of the resulting 13 studies comprising a total of 130 healthy young subjects (mean age, 22–28 yr). Eleven studies involved untrained or moderately trained subjects, whereas two studies did not report on fitness status but presented fair to very poor mean group V˙O2max values (6,35), conforming to recent guidelines (1). ET programs consisted in continous and/or interval training [endurance continuous training (ECT) and endurance interval training (EIT), respectively] of variable intensity performed through cycle ergometer and/or treadmill/running exercise, with duration ranging from 1.17 to 4.41 h·wk−1 and from 5 to 12.9 wk (Table 2). The quality of the studies was moderate. The mean ± SD score was 8.8 ± 1.8 out of a possible 16 points (Table, Supplemental Digital Content 2, quality assessment of studies included in the meta-analysis, For evaluation of potential biases, funnel plot (Figure, Supplemental Digital Content 3, funnel plot of the SMD in V˙O2max,, Begg–Mazumdar’s rank correlation test, and Egger’s regression test suggested the presence of publication bias and/or other biases for the SMD in V˙O2max in the studies included in the meta-analysis (P = 0.04 and P = 0.03, respectively). There was no evidence of publication bias and/or other biases when we assessed the SMD in Qmax or the SMD in a-V˙O2diff at maximal exercise in the studies included in the meta-analysis.

Main characteristics of studies included in the meta-analysis.
ET characteristics of studies included in the meta-analysis.
Flow diagram of the process of article selection.

Effects of ET on V˙O2max

V˙O2max was determined in all studies during cycle ergometer or treadmill incremental exercise (Table 1). After data pooling, the meta-analysis revealed an increased V˙O2max after ET [SMD = 0.75, 95% confidence interval (CI) = 0.47 to 1.02, P < 0.0001] (Fig. 2). There was no significant heterogeneity between studies (I2 = 13%, P = 0.32). In subgroup analyses (Table 3), studies that implemented cycling ET and assessed maximal incremental exercise in a cycle ergometer (n = 7) presented an increased effect of ET on V˙O2max compared with studies that carried out running/treadmill ET and assessed maximal incremental exercise in a treadmill (n = 6) (SMD = 1.06 vs 0.43, P = 0.02). Moreover, studies with a methodological quality score above the median value (n = 5) showed a reduced effect of ET on V˙O2max compared with studies with a methodological quality score below the median value (n = 8) (SMD = 0.30 vs 1.02, P = 0.02).

Subgroup analyses of the effects of ET on V˙O2max, Q max, and a-V˙O2diff at maximal exercise.
Forest plots of SMD in V˙O2max, Q max, and a-V˙O2diff at maximal exercise. Squares represent the SMD for each study. Diamonds represents the pooled SMD across studies. df, degrees of freedom; IV, inverse variance; SMD, SMD between post-ET and pre-ET measurements.

Effects of ET on Qmax

Qmax was evaluated via single-breath acetylene (C2H2) (n = 5), open-circuit C2H2 (n = 2), bioreactance (n = 2), C2H2 rebreathing (n = 1), nitrous oxide rebreathing (n = 1), thermodilution (n = 1), and radioactive indicator dilution (n = 1) techniques during cycle ergometer or treadmill upright exercise (Table 1). After data pooling, Qmax was enhanced following ET (SMD = 0.64, 95% CI = 0.37 to 0.91, P < 0.0001) (Fig. 2). Heterogeneity between studies was not detected (I2 = 0%, P = 0.86). For intrinsic determinants of Qmax, SVmax was increased (SMD = 0.66, 95% CI = 0.39 to 0.94, P < 0.0001), whereas HRmax was decreased (MD = −1.8 bpm, 95% CI = −3.29 to −0.30, P = 0.02), after ET. In subgroup analyses, none of the assessed potential moderating factors (type, modality, intensity, duration, and load of training, and methodological quality) significantly altered the SMD in Qmax.

Effects of ET on a-V˙O2diff at maximal exercise

The Fick equation was used to calculate a-V˙O2diff at maximal exercise in most of the studies (Table 1). Two studies directly determined a-V˙O2diff at maximal exercise by means of invasive techniques (6,35). After data pooling, ET did not significantly increase a-V˙O2diff at maximal exercise (SMD = 0.21, 95% CI = −0.13 to 0.55, P = 0.23) (Fig. 2). There was no significant heterogeneity between studies (I2 = 38%, P = 0.08). In subgroup analyses, studies with a duration or load of training above the median value (n = 3 and n = 5, respectively) presented an increased effect of ET on a-V˙O2diff at maximal exercise compared with studies with a duration or load of training below the median value (n = 10 and n = 8, respectively) (SMD = 1.10 vs −0.10, P = 0.0002; and SMD = 0.84 vs −0.20, P = 0.0006, respectively).

Meta-regression analyses

A significant positive association was found between the SMD in V˙O2max and the SMD in Qmax (B = 0.91, 95% CI = 0.25 to 1.56, P = 0.006) (Fig. 3A). In contrast, the SMD in V˙O2max was not associated with the SMD in a-V˙O2diff at maximal exercise (B = 0.20, 95% CI = −0.27 to 0.67, P = 0.40) (Fig. 3B). For effects of potential moderating factors, the SMD in a-V˙O2diff at maximal exercise was positively associated with the duration of the training intervention (B = 0.18, 95% CI = 0.09 to 0.28, P = 0.0002). In addition, the slopes between i) MD in V˙O2max (L·min−1) and MD in Qmax (L·min−1) (Figure, Supplemental Digital Content 4, meta-regression,; ii) MD in Qmax (L·min−1) and MD in SVmax (L) (Figure, Supplemental Digital Content 5, meta-regression,; and iii) MD in Qmax (L·min−1) and MD in HRmax (bpm) (Figure, Supplemental Digital Content 6, meta-regression, were, respectively, B = 0.10, 95% CI = −0.02 to 0.21; B = 163, 95% CI = 30 to 295; and B = 0.17 95% CI = −0.16 to 0.50.

Meta-regression plots of the SMD in V˙O2max according to the SMD in Q max (B = 1.09, P = 0.003) (A) and the SMD in a-V˙O2diff at maximal exercise (B = 0.19, P = 0.51) (B). The size of each circle is proportional to the study’s weight. SMD, SMD between post- and pre-ET measurements.


In this systematic review and meta-analysis, we pooled and analyzed data from 13 studies assessing the effects of ET interventions lasting 5–13 wk on V˙O2max and Qmax alone or along with a-V˙O2diff at maximal exercise in a total of 130 previously untrained or moderately trained healthy young subjects. The main finding of this analysis is that Qmax, but not a-V˙O2diff at maximal exercise, is increased and linearly associated with the increase in V˙O2max as a consequence of ET.

The observation that V˙O2max is improved by ET via an increase in Qmax concurs with evidence on the limiting factors of V˙O2max (24,37,46,57). In this regard, it is generally accepted that V˙O2max is primarily determined by the capacity of the cardiovascular system to deliver oxygen to active muscle during maximal exercise involving a large muscle mass (e.g., cycling and running) (5,46,59). Thus, it follows that Qmax, blood flow distribution, and/or oxygen-carrying capacity of the blood must be improved by ET in order to substantially enhance V˙O2max. Provided that a change in blood flow distribution and/or oxygen-carrying capacity of the blood may be mirrored by a-V˙O2diff (unless confounded or limited by the oxygen transfer factor from microvessel to muscle), our present meta-analysis supports the increase in Qmax as the predominant variable accounting for V˙O2max enhancement, given that ET (for an average of 8.4 wk) did not result in a significant increase in oxygen extraction (Fig. 2). This was strongly implied by preceding experimental work demonstrating a relatively large difference in Qmaxversus maximal oxygen extraction between highly trained (high V˙O2max) and untrained (low V˙O2max) subjects (11–13). Of note, any increase in V˙O2max in accordance with that in Qmax must be accompanied by enhanced muscle oxygen conductance, which in turn does not seem to limit V˙O2max in healthy subjects (14,16). For mechanisms, the main factor underlying the early increase in Qmax was recently proposed to be an increase in blood volume following 6 wk of ET in untrained healthy young subjects (8). Moreover, a decrease in SVR at maximal exercise may contribute, as a peripheral adaptation, to the increase in Qmax after 5 and 8 wk of ET (35,69). Furthermore, enhanced muscle capillarization, vascular endothelial function, and/or smooth-muscle dilator function after ET (30,45) could partly explain the increase in vascular conductance, venous return, and thereby Qmax. Whether longer-term ET could prompt functional or structural cardiac adaptations (other than cardiac growth) playing a significant role in the increase in Qmax in healthy young subjects remains uncertain based on 3-month to-12-month longitudinal and cross-sectional data (2,61,65).

Another finding of this meta-analysis was the positive association between the duration of ET and its effects on oxygen extraction. ET interventions lasting 12–13 wk resulted in a significant increase in a-V˙O2diff at maximal exercise, which was not observed in 5-wk to 8-wk ET interventions (Table 3). On the other hand (outside of the duration criterion of this meta-analysis), 2 wk of ET induced an increase in V˙O2max that was entirely dependent on enhanced oxygen extraction in healthy young subjects (32). Likewise, two thirds of the increase in V˙O2max after 3 wk of ET was determined by an increase in oxygen extraction, whereas the increase in V˙O2max from weeks 3 to 12 of ET was only attributed to the increase in Qmax in healthy young subjects (47). Taken together, oxygen extraction seemed to improve early (2–3 wk) and 12 wk after the initiation of ET in healthy young subjects. This suggests that oxygen extraction returns to pretraining level, whereas Qmax increases, from the early period to the 5- to ∼8-wk period of the ET intervention (47). In this respect, we and others have found an increase in the oxidative capacity of skeletal muscle after 2 wk of ET (32), after 10 wk of ET (51), and in the long term (33)—but not after 6 wk of ET—in healthy young subjects (52,53), which could parallel, but not necessarily cause (9), the hypothetical normalization of oxygen extraction in the presence of increased oxygen delivery within the second month of ET. In contrast, in healthy elderly subjects, Qmax and oxygen extraction seem to be consistently increased throughout 12 wk of ET (47). How the progression of V˙O2max components with training in previously untrained or moderately trained healthy young subjects would compare to that in different populations including highly trained and/or diseased subjects is unknown and requires further attention.

Apart from duration, the ET programs of the included studies varied with respect to type, modality, intensity, and load of training (Table 2). Remarkably, the impact of ET on V˙O2max, Qmax, and a-V˙O2diff at maximal exercise was not significantly heterogeneous among studies (Fig. 2). Nonetheless, subgroup analyses demonstrated a larger increase in V˙O2max in studies in which ET was performed and maximal exercise was assessed by cycle ergometer than when completed with running/treadmill (Table 3). This result agrees with previous research (36) and could be related to the observation that V˙O2max, along with Qmax and SVmax, may be lower during maximal cycling than during running (27). Although speculative, the truly maximal cardiac pumping capacity might be limited to a higher degree by SVR during cycling versus running due to the plausible lower muscle mass engaged in the former (10); consequently, cycling ET may be prone to enhancing cycling V˙O2max, among others, through adaptations in SVR (6,35,69), which could be of lesser magnitude and importance for running ET and running V˙O2max, respectively (62). In addition, it is noteworthy that neither modality (ECT and EIT) nor intensity of training had a significant effect in this meta-analysis (Table 3). The latter suggests that the increased oxygen extraction found in studies with higher load of training was primarily driven by the prolonged duration of training, as discussed above.

The ET interventions herein examined were rather short, lasting up to 13 wk, hence probably assessing incomplete training adaptations (60). In long-term endurance-trained young athletes, Qmax and a-V˙O2diff at maximal exercise may be enhanced by 18%–35% and 1%–29%, respectively, compared with age-matched healthy subjects matched for body size (20,38,42,43,50,54,66). Notwithstanding the limitations of cross-sectional data when addressing the impact of exercise training (23), it seems probable that the high V˙O2max associated with chronic ET results from increased levels of both Qmax and oxygen extraction.


There are some limitations to be considered in this systematic review and meta-analysis. First, findings were derived from a relatively small number of studies mostly comprising men; thus, our conclusions should be taken with caution and limited to male subjects. Second, a-V˙O2diff at maximal exercise was calculated by means of the Fick equation (a-V˙O2diff = V˙O2max/Qmax) in the majority of studies, which could have reduced the power to detect the association between a-V˙O2diff and V˙O2max owing to the combined error in Qmax and V˙O2max measurements (56,68). Indeed, a-V˙O2diff ranged from 130 to 210 mL·L−1 (Fig. 2), the latter being above factually measured values at maximal exercise (6,35). However, such source of confounding may have been attenuated by the use of SMD (between post-ET and pre-ET) as summary statistic, as suggested by the null heterogeneity among studies and the associations between the SMD in Qmax and the SMD in V˙O2max (P = 0.006) and between the SMD in a-V˙O2diff and duration of training (P = 0.0002). Nevertheless, the SD of a-V˙O2diff was imputed in some of the studies included in the meta-analysis (8,26,39,69). Yet, equivalent results were obtained when the MD, instead of the SMD, between post-ET and pre-ET measurements in a-V˙O2diff at maximal exercise was examined in the forest plot (MD = 0.37, P = 0.18) and for its potential association with the SMD in V˙O2max (B = 0.10, P = 0.60). Regardless, future studies aiming to determine a-V˙O2diff should assess this invasively to gain accuracy. Finally, the SMD in V˙O2max could have been overestimated in studies with low methodological quality (Table 3), and the presence of publication bias and/or other biases cannot be discarded (Figure, Supplemental Digital Content 3, funnel plot of the SMD in V˙O2max,


The current meta-analysis demonstrates that the effects of ET lasting 5–13 wk on V˙O2max are linearly associated with an increase in Qmax, but not in a-V˙O2diff, in previously untrained or moderately trained healthy young subjects. Further research is needed to establish the main factors associated with V˙O2max improvement after ET of longer duration or in different populations.

This study did not receive any funding.

The authors declare no conflicts of interest.

The results of the present study do not constitute endorsement by American College of Sports Medicine.


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