High intensity interval training exercise-induced physiological changes and their potential influence on metabolic syndrome clinical biomarkers: a meta-analysis

Despite the efforts from national and international bodies to promote healthy behaviours and prevent physical inactivity, global physical inactivity levels have failed to come down over the last decade [1, 2]. In 2016, global physical inactivity prevalence was 27.5%, which means that more than one of every four adults do not meet the minimum recommended physical activity levels [3, 4]. Not meeting the recommended levels of physical activity increases the risk of developing chronic diseases such as obesity, hypertension, type 2 diabetes, osteoporosis, and cancer, and increases the mortality risk [5, 6].

Within these diseases, Metabolic Syndrome (MetS) has one of the highest mortality rates [7]. MetS is defined as a cluster of cardiovascular risk factors that includes elevated blood glucose (BG), low high-density lipoprotein (HDL-C), high triglycerides (TG) levels, high systolic blood pressure (SBP), high diastolic blood pressure (DBP) and increased waist circumference (WC) [8]. It is further agreed that an individual is diagnosed with MetS when three or more of the aforementioned risk factors are present. Even though MetS is responsible for many deaths, it is a condition that is underdiagnosed and therefore undertreated because it is largely asymptomatic [9]. For example, the reported prevalence of MetS in the United States is 35%, however this figure rises to 50% for adults aged 60 and over [10, 11]. In this regard, MetS is a strong predictor of cardiovascular and all-cause mortality. Thus, it is imperative to diagnose and treat individuals with metabolic syndrome effectively [12‐14].

The standard treatment for MetS is to prescribe pharmaceuticals for the treatment of the individual risk factors (i.e. hypertension, diabetes, etc), which also brings potentially adverse side effects, such as gastrointestinal problems, arrhythmias, weight gain, insomnia, dizziness, asthenia, etc. [15, 16]. However, evidence suggests that an appropriate lifestyle can help manage and prevent MetS and its associated factors [17]. More specifically, daily physical activity (PA) has been shown to reduce most of the MetS risk factors, and therefore MetS itself [18, 19]. Thus, exercise prescription should be considered as a non-pharmacological, non-invasive, first-line, low-cost treatment to improve MetS. There is evidence that shows strong links between exercise and reducing the prevalence of MetS [20], likely a result of increased caloric expenditure and structural changes in muscle [21, 22].

Lack of time is often cited as one of the main reasons not to meet the recommended PA levels [23]. Because of the time constraints, there is a growing interest in developing alternative approaches to exercise that require shorter work times and lower training volumes, yet still elicit physiological benefits similar to more traditional exercise bouts.

High Intensity Interval Training (HIIT) on MetS is believed to be one of the most time-efficient training modes that have been recently developed [24]. HIIT consists of bouts of exercise at high intensity interspersed by periods of active/passive recovery. HIIT training combinations, by modifying work and rest ratios, are infinite. With shorter training times, it has been suggested that HIIT training can induce similar benefits as prolonged training on cardiorespiratory fitness and muscle oxidative capacity [25, 26].

Nonetheless the prescription of HIIT to inactive individuals that suffer MetS is not without controversy [27], as HIIT is deemed unsafe by some authors. In the literature, we find that after 24 h after a bout of HIIT in patients with cardiometabolic diseases, the adverse responses (cardiac arrest or myocardial infarction) to HIIT is around 8% (most of them were mild in nature), which is slightly higher than seen after Moderate Intensity Continuous Training (MICT) [28]. Although caution must be taken before high intensity training in people with cardiovascular diseases, recent systematic reviews of randomised controlled trials found that the number of adverse events is low [29, 30] and these percentages are much lower in asymptomatic people [31, 32], so this type of training could classified as safe under supervision. In addition to suggesting that HIIT is potentially less safe than MICT, some authors believe that HIIT will not have a public health impact because it is too demanding, eliciting low enjoyment levels and that current inactive people will not adhere to HIIT on the long term, only active individuals will take up this mode of exercise [27]. On the other hand, those that points out HIIT as a promising opportunity to promote a more active behaviour, say that the traditional forms of exercise, including MICT, have been a failure [27]. In regard to behaviour, several studies have reported that HIIT usually offers more enjoyment and affective responses both during and immediately after exercise [33]. Therefore, HIIT may be an alternative to MICT for inducing positive physiological adaptations [28] and doing so in a more enjoyable way [27].

For these reasons there has been an increase in articles published on the effects HIIT has on populations with various chronic diseases, including MetS. Recent studies seem to find that HIIT elicits big morpho-physiological benefit on MetS treatment. Previous reviews have compared the effects HIIT and MICT have on MetS and in single cardiovascular risk factors, and all are in agreement that HIIT can produce similar health benefits in MetS components compared to MICT, yet in a shorter time frame [34‐36]. However, to date, no review or meta-analysis has compared the effects of HIIT to non-exercising controls in MetS variables.

Therefore, the purpose of this meta-analysis is to review the literature of randomised controlled trials (RCT) in regard to the effectiveness of HIIT interventions on MetS variables (BG, HDL-C, TG, SBP, DBP, and WC) in adults compared to non-exercise controls.

In order to accomplish our objectives, this review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [37]. PRISMA checklist can be found in Appendix 1.

The primary finding of this meta-analysis was that HIIT improved BG, SBP, DBP and WC in individuals with MetS, however HDL-C increase slightly and it did not have any effect on TG.

The reduction observed in BG after HIIT might be explained by increases in skeletal muscle mass, blood flow, and insulin receptors, along with increased disposal of glucose in the skeletal muscle, all as a function of the physical exercise [54]. In addition, there is a known increase in skeletal muscle GLUT-4 expression elicited by training [55] which may be greater following HIIT compared to MICT [56, 57]. HIIT also results in greater recruitment of type II skeletal muscle fibres [58], which may explain the fact that exercise intensity correlates positively with insulin sensitivity [59], an indication that HIIT could potentially be more effective than MICT in managing BG. In the long term, regular exercise, given the acute inflammatory response to exercise partly mediated by IL-6 may protect from low-grade inflammation and thus against insulin resistance [60]. Observed effects of aerobic exercise programs on glucose are similar to those reported in HIIT interventions [61].

The HIIT reduction of SBP and DBP (~ 4 mmHg) has an important clinical impact, since decreases of as little as 2 mmHg reduce the risk of developing coronary artery diseases, myocardial infarction, stroke, and mortality incidence [62‐64]. Mechanisms for these reductions in blood pressure are not entirely clear, although enhanced baroreflex control of the sympathetic nerve activity, reduced circulation of catecholamines (norepinephrine), reduced total peripheral resistance, and changes in vasodilator and vasoconstrictor factors are plausible explanations, as these are all elicited by exercise [65‐67]. While the role intensity plays on reducing SBP and DBP is not fully understood, compared to other modes of training, HIIT appears to be more potent in reducing SBP and DBP [68, 69].

Lastly, HIIT resulted in a significant reduction in WC of − 2.26 cm. It has been previously stated that a reduction of 4 cm might be clinically relevant [70]. Intraabdominal adipose tissue is a major contributor to MetS [71]. Despite not knowing the precise mechanisms, it has been suggested that the WC reductions might be linked to changes in excess post-exercise oxygen consumption (EPOC), greater fat oxidation, and changes in appetite and satiety mechanisms [72]. EPOC is positively correlated with exercise intensity, thus HIIT has a more powerful effect on EPOC than MICT [73]. Gaitanos et al. [74] suggests that HIIT results in greater fatty acids transport because during the latter stages of HIIT sessions anaerobic glycogenolysis is inhibited, resulting in ATP having to be resynthesised mainly from PCr degradation and Triglycerol stores. HIIT has also been reported to improve appetite control by reducing average TNF-Alpha, PYY, and Ghrelin concentrations, and increasing GLP-1 [75]. Another meta-analysis [76] reported a 3 cm reduction in WC induced by MICT in overweight and obese individuals, showing similar decreases in comparison with the HIIT group in that particular meta-analysis and slightly higher than in our study. Nevertheless, the effect of strength training alone on WC has shown to be less potent (− 1.4 cm) [52].

The present meta-analysis showed a slight increase in HDL-C and it did not find any changes in TG, which agrees with a previous meta-analysis [61]. Compared to MICT, HIIT is not superior in altering blood lipids in adults [77], however the mechanisms behind this are not clear and should be addressed in future studies.

The MetS variables that appear to be most sensitive to HIIT are SBP and DBP, thus suggesting that HIIT as a possible first-line treatment for BP. The other MetS variables improved by HIIT improved by the same magnitude as seen with MICT. However, the nature of HIIT is that sessions require less time and often offer greater enjoyment and may therefore be more efficient than MICT.

Despite the mounting evidence that favours using HIIT to improve indices of cardiometabolic health, the potential impact on public health is still subject to debate regarding its safety and adequacy in terms of enjoyment and adherence [27]. Some research in the past has claimed that there is a negative relationship between exercise intensity and affect, thus suggesting this could be detrimental for exercise adherence [78, 79]. However, a recent meta-analysis and systematic review reported that positive affective responses may be obtained from HIIT [33], the rest intervals in HIIT may be responsible for this response by helping reduce discomfort [80]. Recent data show that in healthy non-obese individuals, HIIT is more enjoyable than prolonged continuous exercise due to it being more time-efficient and because of the repeated stimulus changes [81]. On overweight individuals, HIIT is as enjoyable as MICT and with high adherence rates while being performed unsupervised [82]. Also, HIIT appears to become more enjoyable as the training advances, while MICT enjoyment levels remain unchanged as the weeks progress [83], suggesting that in the long term, HIIT appears to be a more suitable mode of exercise. In this meta-analysis there was no drop out difference between control and intervention groups. Data regarding safety of HIIT against MICT shows there are slightly more adverse events following HIIT sessions than MICT sessions [28]. However, a small sample size was employed, thus further research is needed to assess safety of HIIT. Future research should, therefore, focus on optimal training thresholds for HIIT that are effective, enjoyable, and feasible outside to ensure the greatest public health impact.

HIIT interventions showed significant physiological benefits for BG, SBP, DBP and WC reductions, potentially linked with changes in skeletal muscle’s oxidative capacity, arterial peripheral resistance, and EPOC. However, no significant differences were observed between experimental and control groups for TG and HDL-C increased in a non-relevant way. Therefore, HIIT has the potential to have a public health impact on critical components of the metabolic syndrome. In addition, the reduced time commitment of HIIT and equal if not better levels of enjoyment may make HIIT even better than MICT on an individual and population level. There is, however, still a need for additional research to determine the causal mechanism producing the beneficial metabolic changes, and also to assess minimum HIIT thresholds in regard to frequency, rest intervals, etc., to produce optimal outcomes.