Exhaustive exercise induces systemic inflammatory responses, which are associated with exercise-induced tissue/organ damage, but the sources and triggers are not fully understood. Herein, the basics of inflammatory mediator cytokines and research findings on the effects of exercise on systemic inflammation are introduced. Subsequently, the association between inflammatory responses and tissue damage is examined in exercised and overloaded skeletal muscle and other internal organs. Furthermore, an overview of the interactions between oxidative stress and inflammatory mediator cytokines is provided. Particularly, the transcriptional regulation of redox signaling and pro-inflammatory cytokines is described, as the activation of the master regulatory factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is involved directly or indirectly in controlling pro-inflammatory genes and antioxidant enzymes expression, whilst nuclear factor-kappa B (NF-κB) regulates the pro-inflammatory gene expression. Additionally, preventive countermeasures against the pathogenesis along with the possibility of interventions such as direct and indirect antioxidants and anti-inflammatory agents are described. The aim of this review is to give an overview of studies on the systematic inflammatory responses to exercise, including our own group as well as others. Moreover, the challenges and future directions in understanding the role of exercise and functional foods in relation to inflammation and oxidative stress are discussed.

Adjusting dietary fat intake is reported to affect mitochondrial biogenesis and fatty acid oxidation (FAO), and thus may enhance exercise capacity. However, a high-fat diet where carbohydrate intake is not limited enough also makes it difficult for athletes to maintain weight, and may fail to force the body to utilize fat. As such, a low-carbohydrate, high-fat, ketogenic diet (KD) may be viable. We have previously reported that an eight-week KD enhances exercise capacity, and suggested the mechanism to be enhanced lipolysis and ketolysis. In the present study, we investigated how an eight-week KD alters mRNA expression during fatty acid mobilization, FAO and ketolysis. We found that an eight-week KD may remodel the lipid metabolism profile, thus contributing to influence exercise capacity. We also found that ketolysis, lipolysis and FAO adaptations may contribute to enhanced exhaustive exercise performance. Along with enhanced FAO capacity during exhaustive exercise, a KD may also alter IL-6 synthesis and secretion profile, thus contribute to fatty acid mobilization, ketolysis, lipolysis and preventing muscle damage. Both the lipid metabolism response and IL-6 secretion appeared to be muscle fiber specific. Taken together, the previous and present results reveal that an eight-week KD may enhance exercise performance by up-regulating ketolysis and FAO ability. Therefore, a KD may have the potential to prevent muscle damage by altering IL-6 secretion profile, indicating that a KD may be a promising dietary approach in endurance athletes, sports, and for injury prevention.

A low-carbohydrate, high-fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. In our previous study, we found that an eight-week ketogenic high-fat, low-carbohydrate diet increased the capacity of endurance exercise in mice without aggravated muscle injury, despite the decrease of absolute muscle volume. The potential mechanism is most possibly to be enhanced capacity to mobilize and utilize fat. In the present study, we investigated whether a ketogenic diet influences post-exercise recovery by measuring blood biomarkers, muscle and liver oxidative state as well as fatigue recovery 24 h post exercise by employing an open-field locomotion test. Several biochemistry markers indicating exercise-induced injury after exhaustive exercise were improved by KD, followed by a 24-h rest with free feed access, including lactate. No aggravated hepatic oxidative damage was observed, whereas muscular oxidative stress was increased by KD. Accelerated recovery induced by exhaustive exercise was also observed from blood biomarkers of injury. For fatigue recovery, lactate concentration, a marker often employed as exhaustion index was lowered by KD, whereas an open field test showed that KD application contributed to increased locomotion after exhaustive exercise, followed by a 24-h rest. These results suggest that KD has the potential to be used as a fatigue-preventing and/or recovery-promoting diet approach in endurance athletes.

Icing is still one of the most common treatments to acute skeletal muscle damage in sports medicine. However, previous studies using rodents reported the detrimental effect of icing on muscle regeneration following injury. This study aimed to elucidate the critical factors governing the impairment of muscle regeneration by icing with a murine model of eccentric contraction-induced muscle damage by electrical stimulation. Because of icing after muscle injury, the infiltration of polynuclear and mononuclear cells into necrotic muscle fibers was retarded and attenuated, leading to the persistent presence of necrotic cellular debris. These phenomena coincided with the delayed emergence and sustained accumulation of Pax7+ myogenic cells within the regenerating area. Additionally, due to icing, delayed and/or sustained infiltration of M1 macrophages was noted in accordance with the perturbed expression patterns of inflammation-related factors, including tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). The key myogenic regulatory factors (i.e., MyoD and myogenin) involved in the activation/proliferation and differentiation of myogenic precursor cells were not altered by icing during the regenerative process. A detailed analysis of regenerating myofibers by size distribution at day 14 after muscle damage showed that the ratio of small regenerating fibers to total regenerating fibers was higher in icing-treated animals than in untreated animals. These findings suggest that icing following muscle damage blunts the efficiency of muscle regeneration by perturbing the removal of necrotic myofibers and phenotypic dynamics of macrophages rather than affecting myogenic factors.