In an athletic population, HIIT is an essential training component to maximize performance and has been used for decades [ 5 ]. There is a growing body of evidence suggesting that several nutritional interventions may further augment HIIT by enhancing energy metabolism during exercise thereby increasing total work completed, or by enhancing the adaptive response during recovery leading to an increase in maximal oxygen consumption and exercise performance over time ( Table 1 ). Therefore, the purpose of this review is to highlight recent evidence pertaining to the potential synergistic effects of HIIT and creatine monohydrate, caffeine, nitrate, sodium bicarbonate, beta-alanine, protein, and essential amino acids, as well as in combination with fasting or with a low carbohydrate-based diet, on VOmax and exercise performance. Nutrient timing and potential sex-based differences are also discussed. These supplements and dietary strategies for this review were selected based on the potential ergogenic value noted in recent reviews and position stand papers by the International Olympic Committee [ 11 ] and the International Society of Sports Nutrition [ 12 ], as well as other expert opinions [ 13 ].

High-intensity interval training (HIIT) involves repeated bursts of vigorous intense exercise (lasting a few seconds up to several minutes) separated by passive rest or low-intensity exercise [ 1 ]. HIIT is a viable and time-efficient alternative to induce physiological and cardiorespiratory adaptations [ 2 4 ]. The specific physiological adaptations induced by HIIT are likely determined by several parameters including intensity, duration, number of intervals performed, the duration and activity during recovery, mode of exercise [ 5 6 ], and potentially diet. In untrained and recreationally active individuals, short term (~2 weeks) HIIT is a potent stimulus to induce cardiorespiratory and physiological alterations similar to traditional endurance training, despite lower total exercise volume and training time commitment [ 7 ]. Mechanistically, HIIT stimulates peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1-alpha) [ 8 ], mitochondrial biogenesis, and can enhance whole-body oxidative capacity and maximal oxygen consumption (VOmax; [ 2 7 ]). Furthermore, HIIT has been shown to enhance peripheral vascular structure and function [ 9 ], reduce the rate of glycogen utilization and lactate production (i.e., glycogen sparing) at work matched exercise [ 6 ], and enhance lipid oxidation [ 6 ]. HIIT has also been shown to improve phosphocreatine recovery kinetics following moderate-intensity exercise [ 10 ].

While it is difficult to compare results across studies, the inconsistent findings involving different intermittent, high-intensity activities may be related to methodological differences or variables which may influence an individual’s responsiveness to creatine supplementation (for a detailed review, please see [ 47 ]. Briefly, creatine supplementation may be more efficacious in those with lower pre-supplementation intramuscular creatine stores [ 48 ]. The vast majority of dietary creatine is found in animal-based foods (i.e., meat, seafood, and poultry) and those who consume little to no animal-based products (i.e., vegan, vegetarian) would potentially respond more favorably to creatine supplementation [ 49 ]. Furthermore, individuals with the greatest quantity and cross-sectional area of type II muscle fibers appear to respond optimally to creatine supplementation [ 48 ]. Regarding sex, some evidence exists that males (not females) experience a decrease in indices of muscle protein breakdown from creatine supplementation [ 46 50 ], which may influence recovery from repeated bouts of exercise.

Currently, there are only three chronic HIIT studies (>4 weeks), which have examined the potential for creatine to augment training adaptations [ 23 33 ]. Creatine combined with 4 weeks of HIIT increased ventilatory threshold (VT) [ 23 ] and critical power in young males [ 24 ] compared to HIIT and placebo. Despite some favorable adaptive responses, there was no effect on whole-body oxygen uptake and time to exhaustion or total work capacity [ 23 24 ]. Forbes et al. [ 33 ] extended these findings in female participants, demonstrating that 4 weeks of creatine combined with HIIT did not augment improvements in cardiorespiratory fitness, ventilatory threshold, or time trial performance in females when compared to HIIT plus placebo. Potential sex-based differences in response to creatine may explain any differences [ 46 ].

In regards to intermittent, high-intensity swimming performance, two studies have shown improved performance across three 100-m freestyle sprint swims in junior competitive swimmers (each separated by 60-s of rest) and eight 50-yard swim sprints (each separated by 90-s of rest;) in elite swimmers from creatine supplementation (9–21 g/day for 5–9 days) compared to placebo [ 43 44 ]. However, creatine supplementation (20 g/day for 5 days) did not improve swim performance time for either the 25-, 50- or 100-m trial (each separated by a 300 m active recovery swim) or influence blood lactate compared to placebo in highly trained swimmers [ 45 ].

There have been two studies involving creatine supplementation and intermittent, high-intensity skating performance. In elite ice-hockey players, creatine supplementation (20 g/day for 5 days + 5 g/day for 70 days) significantly improved skating performance time across six 80-m skating sprints compared to placebo [ 41 ]. In contrast, Cornish et al. [ 42 ] failed to observe a beneficial effect from creatine supplementation (0.3 g/kg or ~25 g for 5 days) on skating treadmill performance or blood lactate across repeated 10-s sprints until to fatigue (each sprint was separated by 30-s of rest).

Research is mixed regarding the efficacy of creatine supplementation on intermittent, high-intensity cycling performance. The majority of research suggests that creatine supplementation (5–25 g/day for 3–28 days) can improve total work and average/peak power performance and ventilatory threshold (3–6 cycling trials, 6–120 s of exercise/trial; 20–120 s of rest between trials) in young males and females [ 22 31 ]. However, a few studies have failed to observe the same benefits [ 32 35 ]. Three studies have shown an improvement in intermittent, high-intensity sprint (run) performance (five–six sprints, 15–60 m in length, 30–60 s of rest from creatine supplementation (20 g/day for 5–6 days) in young adults [ 36 38 ] compared to two studies that failed to observe the same benefits [ 39 40 ].

It is well established that creatine supplementation increases intramuscular creatine stores (Phosphocreatine [PCr] and free creatine; [ 14 15 ], which may have a beneficial effect on high-energy phosphate metabolism during periods of intermittent, high-intensity exercise. Theoretically, increased PCr from exogenous creatine supplementation should expand the capacity of the phosphagen energy system and delay the contribution from the glycolytic and oxidative energy systems, leading to greater intermittent, high-intensity exercise performance. PCr hydrolysis consumes hydrogen ions and therefore provides a buffering role against acidosis during exercise [ 14 16 ]. Creatine supplementation also increases the shuttling of high-energy phosphate metabolites between the cytosol and mitochondria, leading to increased oxidative recovery [ 17 18 ]. Furthermore, creatine increases calcium reuptake into the sarcoplasmic reticulum, which may augment myofibrillar cross-bridge cycling during exercise resulting in greater force development [ 19 21 ]. Creatine supplementation may likely increase exercise performance and recovery during intermittent bouts of high-intensity exercise. The vast majority of research in this area has focused on cycling performance, with less attention to other exercise modalities such as running, swimming, and skating performance [ 15 ].

It has been hypothesized that combining caffeine and creatine may be counterproductive due to competing mechanistic pathways, particularly at high levels of caffeine (i.e., >5 mg/kg; [ 70 ]). When evaluated around high-intensity sprint exercise, there does not appear to be an ergolytic effect as consumption of caffeine (5–6 mg/kg) following creatine loading, has been shown to augment high-intensity exercise performance [ 71 72 ].

Combinatory effects of caffeine with multi-ingredient supplements have been evaluated prior to participation with high-intensity exercise. Specifically, the majority of pre-workout products on the market include caffeine, along with various doses of other ingredients. To date, there are only a few studies evaluating the effects of these products when used prior to HIIT. Acute ingestion of a multi-ingredient pre-workout containing caffeine, creatine, and amino acids resulted in significant improvements in intermittent running time to exhaustion at 100%, 105%, and 110% of maximal aerobic capacity [ 68 ].When the same multi-ingredient supplement was combined with 3-weeks of HIIT (running), there were significant improvements in maximal aerobic capacity (VOmax) and lean body mass (+1.2 kg) in active men and women, however, these improvements were not different compared to HIIT and placebo [ 69 ].

Contrasting results may be due to responders and non-responders to caffeine supplementation, however, non-responders to caffeine is typically low (~5%) [ 66 ]. Responders and non-responders to caffeine may be associated with the CYP1A2 gene, which is known to impact caffeine metabolism [ 67 ]. Future research is required to examine the importance of the CYP1A2 gene on caffeine supplementation in conjunction with HIIT in both males and females.

Beyond training status, the type of HIIT may influence the effects of caffeine. Caffeine consumption (3–5 mg/kg body weight) prior to sprint interval training resulted in significantly greater total work completed in the first interval, with maintenance, but not an increase in total work completed in later sprints (bouts four and five) [ 60 ]. Similarly, acute and chronic (2 weeks) intake of caffeine (5 mg/kg) prior to sprint interval training yielded no significant improvements in performance or total work but did significantly reduce the appearance of muscle damage markers, supporting the notion that caffeine may reduce exercise-induced muscle damage [ 61 ]. Under carbohydrate-restricted or depleted environments, caffeine + carbohydrate (mouth rinse) significantly augmented exercise capacity more than carbohydrate alone or placebo [ 62 63 ]. Caffeine alone may directly [ 64 ] and indirectly impact HIIT performance. Indirectly, caffeine may support a reduction in muscle damage and inflammation. Acute caffeine (8 mg/kg) may also support a glycogen sparing effect and enhance mitochondrial adaptations and recovery [ 65 ].

Caffeine is one of the most widely studied dietary supplements, with performance benefits dating back to 1978 [ 51 ]. Caffeine has consistently demonstrated ergogenic effects on aerobic performance with primary mechanistic advantages acting as an adenosine antagonist to reduce the perception of pain and exertion [ 52 ], improving muscle relaxation time by optimizing calcium mobilization in the sarcoplasmic reticulum, and enhancing muscle function by altering the sodium-potassium ATPase pump activity, among others [ 53 ]. Mechanistically, there is reasonable support for the use of caffeine in combination with HIIT. Although data describing the effects of caffeine on training is relatively new, collective evidence suggests caffeine may improve sprint performance in trained subjects [ 54 56 ], but may not be as effective in untrained subjects [ 57 59 ].

4. Sodium Bicarbonate

74,+) efflux from the muscle to help maintain muscle acid-base balance by increasing the H+ gradient and monocarboxylate transport activity [+ and lactate out of the working muscles [ Increases in hydrogen ion production and subsequent decrease in blood pH levels, known as acidosis, contribute to the onset of peripheral muscular fatigue during high-intensity exercise [ 73 75 ]. Furthermore, muscle acidosis can inhibit energy production pathways via inhibiting glycolytic enzymatic activity [ 76 ], oxidative phosphorylation [ 76 ], and regeneration of phosphocreatine [ 77 78 ]. Collectively, these mechanisms can impair power output and exercise performance [ 79 80 ]. As such, strategies to buffer the exercise-induced intracellular and extracellular acidosis are warranted. One such dietary extracellular buffer is sodium bicarbonate [ 75 ]. Sodium bicarbonate is known to increase circulating levels of blood bicarbonate, causing a shift towards a more alkaline environment [ 81 ]. This shift in blood pH facilitates an increased rate of hydrogen (H) efflux from the muscle to help maintain muscle acid-base balance by increasing the Hgradient and monocarboxylate transport activity [ 82 83 ]. Hence, the efficacy of sodium bicarbonate supplementation is most effective during high-intensity exercise that is largely glycolytic and heavily reliant on the ability to shuttle Hand lactate out of the working muscles [ 84 ]. A review from McNaughton and others suggested the benefits of sodium bicarbonate supplementation may be relegated to high-intensity exercise lasting between 1-10 min in duration [ 85 86 ].

The overall literature regarding sodium bicarbonate supplementation has shown promise, however, individual studies are mixed. On average, sodium bicarbonate increases performance in acute or repeated bouts of exercise by ~2-3% [ 86 87 ]. Such improvements are seen in activities ranging from power sports [ 88 89 ], to middle distance events [ 90 ], to combat sports [ 91 ]. While 2–3% may appear trivial at the elite level, this could certainly influence competition results. For example, in the 2016 Olympic games in track and field, the men’s 800 m the difference between 1st and 6th place was only 1.98%. Zajac and co-authors reported a 2.6% improvement in completion times in a 4 × 50 m swim protocol [ 92 ]. Seigler and colleagues similarly demonstrated a 2% increase in completion time utilizing an 8 × 25 m swim protocol [ 93 ]. With respect to repeated sprint ability, Bishop et al. [ 94 ] demonstrated a 5.1% increase in total work done when utilizing 5 × 6 sec all-out sprints with 30s rest in between bouts.

With the aforementioned improvements in single training sessions, recent investigations have begun to explore chronic supplementation over the length of a full training cycle. Edge et al. [ 95 ] showed superior increases in lactate threshold (26% vs. 15%) and time to exhaustion (164% vs. 123%) after 8 weeks of 3x/week training (training progressed from six to 12 two minute intervals at 140–170% of the lactate threshold) in trained female participants who received sodium bicarbonate (0.2 mg/kg at 90 and 30 min) before training compared to placebo [ 95 ]. Additionally, Wang et al. [ 96 ] demonstrated increases in relative peak power after 6 weeks of HIIT training three times per week in college-aged males [ 96 ].

However, it must be noted that not all data support an ergogenic effect of sodium bicarbonate supplementation. In a recent meta-analysis [ 84 ], only 18 of the 35 studies reviewed demonstrated improvements in performance. The authors theorized the variance in study outcomes may be partly explained by differences in modalities examined, as well as dosing/loading protocols utilized, and finally, the participant’s circulating bicarbonate response to the supplementation. The majority of previous investigations have used a dosing protocol of 0.2–0.3 g/kg sodium bicarbonate provided 60 to 90 min prior to the exercise bout mixed in 500–2000 mL of water [ 97 98 ]. Carr et al. [ 99 ] proposed a minimum rise of +5 mmol/L in circulating bicarbonate to elicit an ergogenic effect of sodium bicarbonate supplementation. Jones et al. [ 100 ] utilized a dose of 0.1 g/kg and failed to increase any participant’s circulating bicarbonate levels, the requisite 5 mmol/L. In a recent review by Heibel and colleagues [ 75 ], only two of the 19 studies that achieved an increase of ≥5 mmol/L failed to see an increase in performance. Moreover, no reviewed study that achieved an increase of ≥6 mmol/L in circulating bicarbonate failed to note an increase in performance.