On meta-regression analysis, duration of intervention showed significance for HIIT versus CON (R 2 = 53.0%, P = 0.04) but nonsignificant for HIIT versus MCT (R 2 = 5.54%, P = 0.245). For HIIT versus CON, longer duration of interventions led to larger increases in V˙O2peak. Neither HIIT versus CON nor HIIT versus MCT showed significant interaction for age (R 2 = 0%, P = 0.637 and R 2 = 0%, P = 0.529, respectively). On meta-regression analysis of HIIT versus MCT, HIIT was more effective in cardiovascular patients (R 2 = 4.46%, P = 0.057) than respiratory patients.
There was no evidence of publication bias in either analysis (P = 0.16 and P = 0.91). The quality of evidence of V˙O2peak data was regarded as moderate for HIIT versus CON (downgraded owing to concerns over risk of bias) and low for HIIT versus MCT (downgraded owing to concerns over risk of bias and unexplained heterogeneity) using GRADE criteria (65).
A single study reported AT after HIIT versus CON, showing a mean improvement in AT after HIIT versus CON (MD = 1.5 mL·kg−1·min−1, 95% CI = 0.18–2.82). There was no further data available for meta-analysis to be performed in relation to AT for HIIT versus CON.
HIIT provided additional increase in AT compared with MCT of borderline statistical but not clinical significance (MD = 1.26 mL·kg−1·min−1, 95% CI = −0.02 to 2.54, I 2 = 38.3%) in six study groups from five trials, comprising 84 individuals receiving HIIT and 79 MCT. Cardiovascular patients showed the greatest mean improvement in AT after HIIT in comparison with MCT (MD = 1.61 mL·kg−1·min−1, 95% CI = 0.33–2.90, I 2 = 39.8%) (Fig. 4). The quality of evidence of AT data for HIIT versus MCT was regarded as low using GRADE criteria (downgraded owing to concerns over risk of bias and imprecision) (65).
A single study reported 6-MWT outcomes for HIIT versus CON with an effect size of 66 m after HIIT (P = 0.001) (66). For the comparison of HIIT versus MCT, six study groups from 6 trials were analyzed, comprising 151 individuals in the HIIT groups and 149 participants in the MCT group. HIIT delivered an increase in 6-MWT distance compared with MCT (MD = 11.67 m, 95% CI = 1.28–22.06, I 2 = 38.9%). Cardiovascular patients showed a greater, yet clinically insignificant improvement (MD = 16.64 m, 95% CI = 5.22–28.07, I 2 = 31.9%) compared with respiratory patients (MD = 2.05 m, 95% CI = −12.57 to 16.66, I 2 = 0%). The quality of evidence 6-MWT was regarded as low using GRADE criteria (downgraded owing to concerns over risk of bias and imprecision) (65).
When analyzing blood pressure changes in HIIT versus CON, six study groups from six trials reported SBP results, whereas only five trials presented data for analysis of DBP changes due to unreliable data in one study (47). These studies comprised 79 individuals for SBP in the HIIT groups (DBP 66 individuals) and 67 individuals for SBP in the CON groups (DBP 57 individuals). Compared with CON, HIIT provided a nonsignificant reduction in SBP (MD = −4.48 mm Hg, 95% CI = −11.13 to 2.18, I 2 = 58.8%) and a statistically significant reduction in DBP (MD = −3.05 mm Hg, 95% CI = −5.41 to −0.69, I 2 = 0%), which however did not meet our a priori target of clinical significance (DBP, 5 mm Hg).
When analyzing BP changes in HIIT versus MCT, for SBP and DBP, eight study groups from eight trials were included. These studies comprised 116 individuals for both SBP and DBP in the HIIT groups and 113 individuals for SBP and DBP in the CON groups. HIIT provided no additional benefit in either SBP (MD = 0.48 mm Hg, 95% CI = −2.01 to 2.97, I 2 = 0.0%) or DBP (MD = −0.51 mm Hg, 95% CI = −2.53 to 1.50, P = 0.136, I 2 = 36.8%) compared with MCT. The quality of evidence for blood pressure was regarded as moderate to low using GRADE criteria (downgraded owing to concerns over risk of bias and imprecision for some analyses) (65).
There was marked variation in both instrument selection and reporting of QoL qualitative measures, and questionnaire outcomes were equivocal between both HIIT versus CON and HIIT versus MCT (see Tables, Supplemental Digital Content 4, http://links.lww.com/MSS/B259, HIIT versus CON, and Supplemental Digital Content 5, http://links.lww.com/MSS/B260, HIIT vs MCT, which shows QoL questionnaire outcomes). The most commonly reported QoL questionnaire was SF-36 (67). Studies including SF-36 data did so either with a total score (overall scores) or by domains (summary scores) of the full questionnaire (i.e., Physical Health, Perceived Health, Mental Health). Dunne et al. (12) reported that HIIT prehabilitation was associated with improvements in overall SF-36 QoL and SF-36 mental health scores (change of +11 P = 0.028 and +11 P = 0.037, respectively). Gloeckl et al. (43) reported increased overall SF-36 scores after both HIIT and MCT; however, only the physical health summary score in the MCT group (MD = 4.3 P < 0.05) and the mental health summary score in the HIIT group (MD = 9.7 P < 0.05) improved significantly. Freese et al. (41) reported clinically meaningful improvements in role–physical scores, bodily pain, vitality, social functioning, mental health, and total SF-36 score after 6 wk HIIT. Jaureguizar et al. (48) reported significant increases in the role emotional, mental health, self-reported health status, and mental health index after HIIT only. Other QoL questionnaires used in more than one study are summarized in Tables, Supplemental Digital Content 4, http://links.lww.com/MSS/B259, and Supplemental Digital Content 5, http://links.lww.com/MSS/B260 as above.
Questionnaires used for anxiety and mood can be seen in the supplementary tables (see Tables, Supplemental Digital Content 4, http://links.lww.com/MSS/B259, HIIT vs CON and Supplemental Digital Content 5, http://links.lww.com/MSS/B260, HIIT vs MCT, which shows QoL questionnaires used within studies). The most commonly reported questionnaire to determine anxiety and mood was the Hospital Anxiety and Depression Scale. Again due to paucity of studies reporting values, no meta-analysis was performed across HIIT versus CON or HIIT versus MCT. Flemmen et al. (40) showed a significant reduction in anxiety favoring CON (P < 0.05) and a significant reduction in depression after HIIT (P < 0.05), with no significant difference in reported insomnia. For HIIT versus MCT, both studies showed improvements in the Hospital Anxiety and Depression Scale anxiety and depression domains, however, with no significant benefit between intervention arms (42,57).
Because of the widespread lack of reporting and insufficient information included within published papers, we deemed it inappropriate to analyze adherence from the number of dropouts to each intervention, as very few studies reported the direct reason for participants dropping out in HIIT or MCT groups. Disparity in duration of exercise (wk) led to varying numbers of scheduled sessions per study. Overall, adherence to scheduled sessions was high in both groups (see Table, Supplemental Digital Content 6, http://links.lww.com/MSS/B261, which shows reported adherence to HIIT vs MCT protocols).
In this review of the current literature exploring the effectiveness of short duration HIIT in disease cohorts, we found that HIIT elicits clinically important improvements (>1.5 mL·kg−1·min−1) in V˙O2peak within 8 wk or less when compared with nonintervention control subjects.
This is in keeping with previous data in both healthy young and older individuals (>60 yr), where HIIT has been shown to improve aspects of fitness. In healthy young individuals completing sprint interval training (4–6 intervals, 30-s all-out sprints), similar adaptations in human skeletal muscle oxidative capacity and exercise performance to those undertaking MCT (90–120 min continuous cycling at 65% V˙O2peak) were seen in as little as 2 wk, despite a vastly reduced time commitment and training volume (approximately 90% lower vs MCT) (68). Similarly, in healthy older individuals, HIIT has been shown to increase V˙O2peak (+8%) and reduce SBP (−9%) in just 6 wk (69). Moreover, in a separate study of healthy older individuals, HIIT has also recently been shown to elicit clinically significant improvements in CRF within just 31 d (70), a time frame that is compliant with the aforementioned UK National Cancer Action Team policy on time from decision to treat to surgery. In addition to the reduced time frame and training volume required by HIIT to elicit improvements in CRF, HIIT may also have the added advantage of rapid adaptation at the level of skeletal muscle, resulting in fewer negative training symptoms (e.g., delayed onset muscle soreness ), which is postulated to lead to increased adherence.
HIIT is at least as effective as MCT over short periods across all groups. Subgroup analysis showed additional benefit in cardiovascular patients versus other patient groups following HIIT. To exemplify, cardiovascular patients showed additional increases in V˙O2peak and AT after HIIT when compared with MCT. It is likely that the rapid benefit shown in this review is a result of peripheral adaptations such as mitochondrial oxidative enzyme upregulation and increased buffering capacity (68) as it is only in longer-term training programs (≥12 wk) that improvements in cardiac structure and systolic function have been shown (71). In response to HIIT, the contribution of cardiac change may be underestimated because of the research focus primarily being on mitochondrial upregulation, with potential cardiac changes being understudied.
A small number patients with cancer were included in this review, with varying outcomes. Lung, colon, and breast cancer groups all showed improvement in CRF with HIIT when compared with no exercise. There was no added benefit of HIIT over MCT. Blunted adaptation in these cancer groups (shown as a lack of CRF improvement in response to HIIT compared with the overall effect of HIIT vs CON) may be explained by blunted mitochondrial enzyme activity while cancers remain in situ (72). In addition, colorectal cancer patients presenting for resection have lower CRF than age-matched controls while the cancer is still in situ. However, removal the cancer facilitates a return toward normal CRF (73). Taken together, these studies may lead to a suggestion that tumour presence hinders adaptive capacity to exercise training, at least in this cancer type. Adjuvant chemotherapy has negative effects on CRF preoperatively in colorectal cancer patients (74) and have resulted in higher rates of heart failure and cardiomyopathy after breast cancer chemotherapy (75), as such these confounding drug regimens must be considered when interpreting trainability within these groups.
The beneficial psychological effects of exercise per se are well known, but it is unclear whether HIIT is superior to MCT in improving QoL from this review. This lack of clarity is due to the heterogeneity of tools used, small numbers of studies reporting QoL outcomes, and lack of suitable comparisons for many of the questionnaires.
Beyond mechanistic propositions based on small-scale nonrandomized control trials in distinct disease groups, reasons why certain pathological subgroups might not show CRF improvements with HIIT are far from clear. One possible explanation for certain subgroups is that exercise intervention studies mainly report mean improvements in CRF parameters as milliliters per kilogram per minute, rendering obese patients at a relative disadvantage for demonstrating improvement over short periods; as in the authors’ experience, individuals normally remain weight stable during short-term HIIT protocols (often due to increased lean muscle mass and fat mass reductions). A recent meta-analysis in obesity concluded that HIIT was superior to traditional exercise to improve CRF and reduce body fat percentage. Notably, the median duration of training protocol for this meta-analysis was 12 wk, with a wide range of 2–52 wk (76), which is does not comply with clinical time frames for cancer surgery. By contrast, but in agreement with this review, another recently published meta-analysis found no clinical benefit of HIIT versus MCT in reduction of total body fat or fat mass over shorter training duration (<12 wk) (77).
To achieve benefit from HIIT, it is thought that a minimal dose of exercise expenditure or training load is required to significantly disturb intracellular homeostasis and stimulate mitochondrial biogenesis (14). This may explain why the respiratory patients seem to gain less benefit versus other pathological groups as respiratory limitation may result in low maximal exercise scores and therefore lower training loads, given that most protocols prescribe the training load as a percentage of V˙O2peak or maximal wattage achieved at cardiopulmonary exercise testing.
HIIT can represent a time efficient training method by which to improve CRF, potentially removing the commonly cited “lack of time” as a barrier to exercise (10). Time efficiency can be due to two facets, reduced work duration within a session and/or individual session time. For example, one of the most commonly used HIIT protocols within studies in this review used 10 intervals of 1 min with 1-min rest periods in between (32,49,52,58,59,62,66,78) totaling a session duration of ~20 min. However, another frequently used HIIT protocol used four intervals of 4-min high-intensity work with 3-min rest periods in between each bout, which led to sessions typically lasting >30 min (12,31,32,36,40,44,55,79), including a work duration of 16 min (vs 10 min in the aforementioned example). Herein we show that, excluding warm-up and end-of-session recovery periods, median work duration during a HIIT session was half of that for MCT protocols (16 vs 30 min). In addition, several studies in this review (34,41,42,46,48,49,51,53,54,58–63) used low volume HIIT protocols, involving 10 min (or less) total work duration (80). Indeed, CRF improvements have been shown in as little as 10% of the training volume with HIIT when compared with MCT (81). Taken in combination, reductions in regime duration, total volume of training, and weekly time commitment represent important drivers for enhancing adherence and reducing costs associated with patient training. However, further work is required to elucidate the optimal work-to-rest ratios within HIIT protocols, which may further reduce the total time commitment for the individual. It is also worth noting that although the majority (>90%) of studies within this review used a static cycle ergometer for HIIT, other training modalities (e.g., running) maybe viable. However, further work is needed to assess the efficacy and tolerability when compared with cycle ergometry within certain patient groups.
QoL and mood outcomes analyzed in this review were pre- to posttraining program questionnaires, mostly global QoL scores or disease specific questionnaires. These outcomes are not specific enough to draw conclusions as to whether individuals preferred HIIT or MCT. However, as there were no significant differences in the number of noncompliers, adherence to scheduled sessions (see Table, Supplemental Digital Content 6, http://links.lww.com/MSS/B261, which shows reported adherence to HIIT vs MCT protocols) or reported serious adverse events lead us to believe that neither HIIT nor MCT are inferior for enjoyment, acceptability, or safety when compared.
The studies in this review have a high risk of bias, some of which is unavoidable because of the nature of exercise intervention studies and the inability to blind participants (see Figure, Supplemental Digital Content 3, http://links.lww.com/MSS/B258, which shows risk of bias summary chart). There is also a risk of contamination between HIIT and nonintervention controls. In addition, heterogeneity among HIIT protocols, training duration, chronological age, and pathology leads to uncertainty about the true effectiveness of interventions (82) [see Tables, Supplemental Digital Content 1, http://links.lww.com/MSS/B256, Paper Characteristics (HIIT vs CON); Supplemental Digital Content 2, http://links.lww.com/MSS/B257, Paper Characteristics (HIIT vs MCT); Supplemental Digital Content 7, http://links.lww.com/MSS/B262, Training regimes (HIIT vs CON); and Supplemental Digital Content 8, http://links.lww.com/MSS/B263, Training regimes (HIIT vs MCT)].
We have shown that HIIT leads to clinically significant improvements in CRF within 8 wk in patients with disease, when compared with no intervention. HIIT also resulted in statistically significant improvements in CRF compared with MCT, with clinically significant benefit seen in cardiovascular patients. Because of the reduced exercise volume and improved efficacy (vs MCT) in certain clinical groups, HIIT can be promoted as a viable clinical exercise intervention to rapidly improve CRF.
This work was supported by the Medical Research Council (grant no. MR/K00414X/1), the Arthritis Research UK (grant no. 19891) awarded to the MRC-ARUK Centre for Musculoskeletal Ageing Research, and the Dunhill Medical Trust (grant no. R468/0216).
The authors declare no conflicts of interest. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.
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HIIT; V˙O2peak; ANAEROBIC THRESHOLD; CLINICAL; SHORT TERM
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