Hormones that have been shown to increase during HIIE include catecholamines, cortisol, and growth hormones. Catecholamine response has been shown to be significantly elevated after Wingate sprints for both men and women [17, 18]. Catecholamine response to HIIE protocols that are less intensive than the Wingate protocol have also been shown to be elevated. For example, Christmass et al. [19] measured catecholamine response to long (24s/36s recovery) and short (6s/9s recovery) bout intermittent treadmill exercise and found that norepinephrine was significantly elevated postexercise. Also Trapp et al. [15] found significantly elevated epinephrine and norepinephrine levels after 20min of HIIE cycle exercise (8s/12s and 12s/24s protocols) in trained and untrained young women. Bracken et al. [16] examined the catecholamine response of 12 males who completed ten 6-second cycle ergometer sprints with a 30-second recovery between each sprint. From baseline, plasma epinephrine increased 6.3-fold, whereas norepinephrine increased 14.5-fold at the end of sprinting (Figure 1). The significant catecholamine response to HIIE is in contrast to moderate, steady state aerobic exercise that results in small increases in epinephrine and norepinephrine [20]. The HIIE catecholamine response is an important feature of this type of exercise as catecholamines, especially epinephrine, have been shown to drive lipolysis and are largely responsible for fat release from both subcutaneous and intramuscular fat stores [21]. Significantly, more β-adrenergic receptors have been found in abdominal compared to subcutaneous fat [22] suggesting that HIIE may have the potential to lower abdominal fat stores. Aerobic endurance training increases β-adrenergic receptor sensitivity in adipose tissue [23]. Interestingly, in endurance trained women, β-adrenergic sensitivity was enhanced, whereas the sensitivity of the anti-lipolytic α₂ receptors was diminished [24]. However, no data are available concerning HIIE training effects on β or α₂ adrenergic receptor sensitivity of human adipocytes.

Nevill et al. [25] examined the growth hormone (GH) response to treadmill sprinting in female and male athletes and showed that there was a marked GH response to only 30s of maximal exercise and the response was similar for men and women but greater for sprint compared to endurance trained athletes. GH concentration was still ten times higher than baseline levels after 1 hour of recovery. Venous blood cortisol levels have also been shown to significantly increase after repeated 100m run sprints in trained males [26], after five 15-second Wingate tests [27], and during and after brief, all-out sprint exercise in type 1 diabetic individuals [28].

Venous blood lactate response to the Wingate test protocols has typically ranged from 6 to 13mmol·L⁻¹. Lactate levels after the Wingate test are typically higher in trained anaerobic athletes and have been shown to be similar [18] and lower for trained women compared to trained men [17]. Lactate levels gradually increase during longer, lower intensity HIIE protocols. Trapp et al. [15] showed that 8s/12s HIIE for 20min increased plasma lactate levels between 2 and 4mmol·L⁻¹ after 5min of HIIE for both trained cyclists and untrained females. Lactate rose to between 4 and 5mmol·L⁻¹after 15min of HIIE. During a 12s/24s HIIE condition lactate levels of the untrained were similar but were significantly higher for the trained female cyclists (between 7 and 8mmol·L⁻¹after 15min). Despite increasing lactate levels during HIIE exercise, it appears that free fatty acid transport is also increased. For example, a 20-minute bout of 8s/12s HIIE produced increased levels of glycerol indicating increased release of fatty acids [15] which peaked for untrained women after 20 min and after 10 min of HIIE for trained women.

HIIE appears to result in significant increases in blood glucose that are still elevated 5min [29] and 30min postexercise [18]. HIIE appears to have a more dramatic effect on blood glucose levels of exercising type 1 diabetic individuals. Bussau et al. [28] examined the ability of one 10-second maximal sprint to prevent the risk of hypoglycemia typically experienced after moderate aerobic exercise in type I diabetics. Twenty minutes of moderate-intensity aerobic exercise resulted in a significant fall in glycemia. However, one 10-second sprint at the end of the 20-minute aerobic exercise bout opposed a further fall in glycemia for 120 minutes, whereas in the absence of a sprint, glycemia decreased further after exercise. The stabilization of glycemia in the sprint trials was associated with elevated levels of catecholamines, growth hormone, and cortisol. In contrast, these hormones remained at near baseline levels after the 20min of aerobic exercise. Thus, one 10-second all out sprint significantly increased glucose, catecholamines, growth hormone, and cortisol of type 1 diabetic individuals for 5min after HIIE. Authors suggest that the addition of one 10-second sprint after moderate intensity aerobic exercise can reduce hypoglycemia risk in physically active individuals who possess type 1 diabetes.

Autonomic function has been analyzed after HIIE by assessing heart rate variability. Parasympathetic activation was found to be significantly impaired in a 10-minute recovery period after repeated sprint exercise [30] and a 1-hour recovery period [31] in trained subjects. Buchhiet et al. [30] have suggested that parasympathetic or vagal impairment is caused by the heightened sympathetic activity that occurs during HIIE exercise and the persistent elevation of adrenergic factors and local metabolites during recovery (e.g., epinephrine, norepinephrine, and venous blood lactate).

With regard to metabolic response, HIIE initially results in decreased adenosine triphosphate (ATP) and phosphocreatine (PCr) stores followed by decreased glycogen stores [32] through anaerobic glycolysis [33]. Gaitanos et al. [29] have suggested that towards the end of an HIIE session, which consists of numerous repeat sprints (e.g., ten 6-second bouts of maximal sprinting), an inhibition of anaerobic glycogenolysis may occur. These authors have further suggested that at the end of the HIIE bout, ATP resynthesis may be mainly derived from PCr degradation and intramuscular triacylglycerol stores. However, this pattern of fuel utilization during HIIE has not been demonstrated in humans. After hard, all-out HIIE exercise, complete phosphagen recovery may take 3-4min but complete restoration of pH and lactate to pre-exercise levels may take hours [33]. The recovery of the exercising muscle after HIIE to its pre-exercise state is undetermined. After a hard bout of aerobic exercise, recovery has typically been found to be biphasic with an initial rapid phase of recovery lasting 10s to a few minutes followed by a slower recovery phase lasting from a few minutes to hours [33]. During recovery, oxygen consumption is elevated to help restore metabolic processes to baseline conditions. The postexercise oxygen uptake in excess of that required at rest has been termed excess postexercise oxygen consumption (EPOC). EPOC during the slow recovery period has been associated with the removal of lactate and H⁺, increased pulmonary and cardiac function, elevated body temperature, catecholamine effects, and glycogen resynthesis [33]. Although EPOC does not appear to have been assessed after HIIE, it is enhanced after split aerobic exercise sessions. For example, magnitude of EPOC was significantly greater when 30-minute [34] and 50-minute [35] aerobic exercise sessions were divided into two parts. Also an exponential relationship between aerobic exercise intensity and EPOC magnitude has been demonstrated [36]. With regard to HIIE, it is feasible that the significant increase in catecholamines (Figure 1) and the accompanying glycogen depletion described earlier could induce significant EPOC. However, aerobic exercise protocols resulting in prolonged EPOC have shown that the EPOC comprises only 6–15% of the net total exercise oxygen cost [36]. Laforgia et al. [36] have concluded that the major impact of exercise on body mass occurs via the energy expenditure accrued during actual exercise. Whether HIIE-induced EPOC is one of the mechanisms whereby this unique form of exercise results in fat loss needs to be determined by future research. In summary, acute responses to a bout of HIIE include significant increases in heart rate, catecholamines, cortisol, growth hormone, plasma lactate and glucose levels, glycerol, and a significant decrease in parasympathetic reactivation after HIIE, and depletion of ATP, PCr, and glycogen stores.

Chronic responses to HIIE training include increased aerobic and anaerobic fitness, skeletal muscle adaptations, and decreased fasting insulin and insulin resistance (Table 1). Surprisingly, aerobic fitness has been shown to significantly increase following minimal bouts of HIIE training. For example, Whyte et al. [45] carried out a 2-week HIIE intervention with three HIIE sessions per week consisting of 4 to 6 Wingate tests with 4min of recovery. Previously, untrained males increased their by 7%. Increases in of 13% for an HIIE program also lasting 2 weeks have been documented [42]. HIIE protocols lasting 6 to 8 weeks have produced increases in of 4% [37] and 6–8% [39]. Longer Wingate-type HIIE programs lasting 12 to 24 weeks have recorded large increases in of 41% [40] and 46% [6] in type 2 diabetic and older cardiac rehabilitation patients. The less intense protocols (8s/12s) coupled with longer duration conducted over 15 and 12 weeks resulted in a 24% [5] and 18% increase [46] in . Collectively, these results indicate that participation in differing forms of HIIE by healthy young adults and older patients, lasting from 2 to 15 weeks, results in significant increases in from between 4% to 46% (Table 1). Mechanisms underlying the aerobic fitness response to HIIE are unclear although a major contributor is phosphocreatine degradation during repeated HIIE. Using thigh cuff occlusion to prevent PCr resynthesis during recovery, Trump et al. [47] showed that PCr contributed approximately 15% of the total ATP provision during a third 30-second bout of maximal isokinetic cycling. Muscle glycogenolysis made a minor contribution to ATP provision during the third 30-second bout indicating that aerobic metabolism was the major source of ATP during repeated sprinting. Similarly, Putman et al. [48] showed that repeated bouts of HIIE resulted in a progressive increase in ATP generation so that by the third out of five 30-second Wingate bouts, the majority of ATP was generated oxidatively.

Other mechanisms underlying the HIIE increase in aerobic power are undetermined but may involve increased stroke volume induced by enhanced cardiac contractility [39], enhanced mitochondrial oxidative capacity, and increased skeletal muscle diffusive capacity [10]. There is also evidence indicating that muscle aerobic capacity is increased following HIIE due to increases in PGC-1a mediated transcription [49] occurring via AMPK activation [50]. Harmer et al. [7] have suggested that these marked oxidative adaptations in the exercising muscle are likely to underlie the significant increases in peak and maximal oxygen uptake documented after regular HIIE.

Anaerobic capacity response to HIIE has typically been assessed by measuring blood lactate levels to a standardized exercise load or anaerobic performance on a Wingate test. A number of studies have demonstrated that HIIE lasting from 2 to 15 weeks results in significant increases in anaerobic capacity from between 5% to 28%. For example, Tabata et al. [51] used a 20s/10s protocol and found that in previously untrained males, anaerobic capacity, measured by maximal accumulated O₂ deficit, was increased by 28%. Whyte et al. [45] carried out a 2-week HIIE intervention and found that previously untrained males increased their anaerobic capacity by 8%, whereas Burgomaster et al. [32] found that Wingate test performance was increased by 5.4% after two weeks of HIIE.

A number of studies have taken muscle biopsies after Wingate test performance in order to examine skeletal muscle adaptations. In a series of studies, Gibala et al. [13, 52] have consistently found increased maximal activity and protein content of mitochondrial enzymes such as citrate synthase and cytochrome oxidase after HIIE training. For example, Talanian et al. [42] carried out an HIIE intervention that consisted of 2 weeks of HIIE exercise performed seven times with each session consisting of ten 4-minute bouts at 90% separated by 2-minute resting intervals. was increased by 13% and plasma epinephrine and heart rate were lower during the final 30min of a 60-minute cycling steady state exercise trial at 60% of pretraining . Exercise whole body fat oxidation also increased by 36%, and net glycogen use was reduced during the steady state cycling trial. HIIE significantly increased muscle β hydroxyacyl coenzyme A dehydrogenase and citrate synthase. Total muscle plasma membrane fatty acid binding protein content also increased significantly after HIIE. Thus, seven sessions of HIIE, over two weeks, induced marked increases in whole body and skeletal muscle capacity for fatty acid oxidation during exercise in moderately active women. Other studies have found similar results with studies reporting large increases in citrate synthase maximal activity after 2 weeks [32] and 6 weeks of HIIE [37]. Similarly, β hydroxyacyl coenzyme A dehydrogenase activity, which catalyzes a key rate-limiting enzyme step in fat oxidation, also significantly increased after HIIE training [38]. Increases in oxidative muscle metabolism (e.g., hexokinase and citrate synthase activity) after 7 weeks of HIIE training with type 1 diabetic individuals have also been documented [7]. Collectively, markers of muscle oxidative capacity have been shown to significantly increase after six sessions of HIIE lasting as little as 2 weeks. Glycolytic enzyme content and activity has also been shown to increase after exposure to HIIE. Tremblay et al. [38] have shown that 16 weeks of HIIE significantly increased phosphofructokinase levels which is a key rate limiting enzyme in glycolysis, whereas Macdougall et al. [53] also showed increases in phosphofructokinase with a Wingate-type protocol carried out for 7 weeks. In summary, Wingate test HIIE protocols of between one and seven weeks have demonstrated marked increases in skeletal muscle capacity for fatty acid oxidation and glycolytic enzyme content and activity.

With regard to abdominal fat, Trapp et al. [5] found that 15 weeks of HIIE led to significantly reduced abdominal fat (.15kg) in untrained young women (Figure 2(b)), whereas Dunn [46] found that 12 weeks of HIIE led to a.12kg decrease in abdominal fat. As women in these studies possessed relatively low abdominal fat levels, it is possible that the greater abdominal fat of men may demonstrate greater reductions after HIIE. For example, Boudou et al. [8], in a study involving older type 2 diabetic males, found that after 8 weeks of HIIE no change in body mass occurred; however, abdominal adiposity was decreased by 44% (Table 1). Mourier et al. [40] found a 48% reduction in visceral fat, measured by MRI, compared to an 18% decrease in subcutaneous fat following an exercise regimen consisting of steady state exercise two days per week and HIIE one day a week for 8 weeks in type 2 diabetic men and women. Tjønna et al. [3] examined 32 middle-aged metabolic syndrome men and women who performed 16 weeks of HIIE three times per week. increased by 26% and body weight was reduced by 2.3kg. Whyte et al. [45] examined ten overweight males aged 32 years after two weeks of HIIE consisting of 6 sessions of a 4–6 repeats of a Wingate test. increased (8%) and significant change in waist circumference was also found (Table 1). Although the effects of HIIE on fat free mass has not been extensively examined, one study using DEXA found that trunk muscle mass was significantly increased after 15 weeks [5], whereas another study using MRI showed a significant 24% increase in thigh muscle cross sectional area after HIIE [8].

A summary of the results of studies examining the effects of HIIE on subcutaneous and abdominal fat, body mass, and waist circumference is illustrated in Table 1. As can be seen studies that carried out relatively brief HIIE interventions (2 to 6 weeks) only resulted in negligible weight loss. However, the majority of subjects in these short-term Wingate test studies have been young adults with normal BMI and body mass. Studies that used longer duration HIIE protocols with individuals possessing moderate elevations in fat mass [5] have resulted in greater weight/fat reduction. Interestingly, the greatest HIIE-induced fat loss was found in two studies that used overweight type 2 diabetic adults (BMI > 29kg/m²) as subjects [8, 40]. Given that greater fat loss to exercise interventions has been found for those individuals possessing larger initial fat mass [54], it is feasible that HIIE will have a greater fat reduction effect on the overweight or obese. Thus, more studies examining the effects of HIIE on obese or overweight individuals are needed.

Possible mechanisms underlying the HIIE-induced fat loss effect include increased exercise and postexercise fat oxidation and decreased postexercise appetite. As mentioned, Gaitanos et al. [29] have suggested that towards the end of an HIIE session that consists of numerous repeat sprints (e.g., ten 6-second bouts of maximal sprinting) an inhibition of anaerobic glycogenolysis occurs and ATP resynthesis is mainly derived from PCr degradation and intramuscular triacylglycerol stores. That increased venous glycerol accompanied HIIE in both trained female cyclists and untrained women [15] supports the notion that acute HIIE progressively results in greater fatty acid transport. Also Burgomaster et al. [55] and Talanian et al. [42] have shown that 6 to 7 sessions of HIIE had marked increases in whole body and skeletal muscle capacity for fatty acid oxidation.

As mentioned previously, the EPOC or postexercise response to HIIE does not appear to have been examined. It is feasible that the catecholamines generated by HIIE (Figure 1) could influence postexercise fat metabolism. Increased fat oxidation after HIIE may also occur as a result of the need to remove lactate and H⁺ and to resynthesize glycogen. The elevated GH levels documented after a bout of HIIE [25] may also contribute to increased energy expenditure and fat oxidation.

Some important issues for future HIIE research include optimization of type and nature of HIIE protocols, individual fat loss response to HIIE, and suitability of HIIE for special populations. The most utilized protocol has been the Wingate test (30s of all-out sprint). This protocol amounts to 3 to 4min of cycle exercise per session with each session being typically performed 3 times a week. This protocol, although remarkably short in duration, is extremely hard and subjects have to tolerate significant discomfiture. Thus, the Wingate protocol is likely to be unsuitable for most overweight, sedentary individuals interested in losing fat. Other less demanding HIIE protocols have included an 8-second cycle sprint followed by 12s of low intensity cycling for a period of 20min [5], a 15-second cycle sprint followed by 15s of low intensity cycling for a period of 20min [45], and a 2-minute cycle sprint followed by 3min of low intensity cycling for a period of 20min [8]. A challenge for future research is to identify the minimal dose of HIIE for the maximum health benefit. As discussed earlier, reducing the length of HIIE training from 15 to 12 weeks still resulted in significant subcutaneous and abdominal fat loss [46]. Thus, more research is needed to identify the optimal length and intensity of the HIIE protocol for achieving varying health outcomes.

With regard to modality, studies have primarily utilized a stationary cycle ergometer, thus, little is known about the effects of other potential HIIE modalities such as rowing, walking, running, stair climbing, and swimming. That insulin resistance has recently been shown to primarily be located in leg muscle [62] suggests that HIIE exercise that focuses on the legs is likely to show the greatest insulin sensitivity increases. How leg muscle adaptations to HIIE impact on subcutaneous and abdominal fat loss and other health markers compared to other regional adaptations is undetermined.

It is unclear if the increase in insulin sensitivity following HIIE training is simply a response to the last exercise session or a result of more permanent skeletal muscle adaptations. Whyte et al. [45] have provided evidence to suggest that for short-term HIIE training of two weeks, the increase in insulin sensitivity was largely a result of the last HIIE session. They assessed insulin resistance 24 hours and 72 hours after the sixth HIIE session in a two-week training program. Insulin sensitivity had increased by 25% at 24 hours after HIIE but had returned to preintervention levels after 72 hours. In contrast to these results, Babraj et al. [4] used a glucose tolerance test to assess insulin sensitivity after a similar intervention and found that insulin sensitivity was improved until at least three days after the last exercise session. Why these similar HIIIE protocols produced differing results differ is not clear and also whether HIIE programs lasting longer than two weeks display a similar effect has not been established.

Individual variability in fat loss to HIIE and other forms of exercise is an important issue for future research. For example, in the intervention previously described [5] there were significant individual differences in the fat loss response to HIIE. Fat response ranged from a loss of 8kg to a gain of .10kg. If fat loss responders alone were examined in this study (women who lost rather than gained fat), then average fat loss was 3.94kg. As there are likely to be responders and nonresponders in every exercise, fat loss trial calculating mean fat loss alone hides the significant fat loss achieved by some individuals. Thus, it is feasible that HIIE fat loss programs are effective for producing a clinical decrease in fat (greater than 6% of fat mass) for some but not all participants. Boutcher and Dunn [63] have highlighted a range of program design factors and individual factors that are behavioral, inherited, and physiological in origin that may affect individual fat loss response to exercise. Therefore, research is needed to identify the major individual factors that both enhance and impede fat loss response to HIIE-based interventions.

A small number of studies have examined the effects of HIIE fat loss and health of special populations and patients. These have included overweight adolescents [3], older adults [6], type 1 [7] and type 2 diabetic individuals [8], paraplegics [9], intermittent claudication [10], chronic obstructive pulmonary disease [11], and cardiac rehabilitation patients [12]. Encouragingly, these studies have shown that HIIE appears to be both safe and beneficial for these patient groups. Future research needs to establish the most beneficial HIIE protocol that is both optimal and sustainable for different types of patients.