Redox interventions to increase exercise performance

Abstract

Skeletal muscle continually produces reactive oxygen species (ROS) and nitric oxide (NO) derivatives. Both oxidant cascades have complex effects on muscle contraction, metabolic function and tissue perfusion. Strenuous exercise increases oxidant production by muscle, limiting performance during endurance exercise tasks. Conversely, redox interventions that modulate ROS or NO activity have the potential to improve performance. Antioxidants have long been known to buffer ROS activity and lessen oxidative perturbations during exercise. The capacity to enhance human performance varies among antioxidant categories. Vitamins, provitamins and nutriceuticals often blunt oxidative changes at the biochemical level but do not enhance performance. In contrast, reduced thiol donors have been shown to delay fatigue or increase endurance under a variety of experimental conditions. Dietary nitrate supplementation has recently emerged as a second redox strategy for increasing endurance. Purified nitrate salts and nitrate-rich foods, notably beetroot and beetroot juice, are reported to lessen the oxygen cost of exercise, increase efficiency, and enhance performance during endurance tasks. These findings are exciting but enigmatic since nitrate per se has little bioactivity and cannot be converted to NO by mammalian cells. Overall, the available data suggest exercise endurance can be augmented by redox-active supplements, either reduced thiol donors or dietary nitrates. These findings have clear implications for athletes seeking a competitive edge. More importantly, interventions that increase endurance may benefit individuals whose physical activity is limited by illness, ageing, or frailty.

Figure 1. Reactive oxygen cascade

Diagram depicts interactions among reactive oxygen species (ROS) detected in skeletal muscle and selected mediators of individual reactions. SQ^•−, semiquinone; O₂ ^•−, superoxide anion; ^•NO, nitric oxide; ONOO⁻, peroxynitrite; e⁻, free electron; H₂O₂, hydrogen peroxide; Fe²⁺, ferrous iron; ^•OH, hydroxyl radical; GSH, reduced glutathione; GSSG, oxidized glutathione.

Figure 2. Annual rates of publications on exercise and antioxidants

Bars depict numbers of reports published in individual years; arrow highlights the year exercise was shown to increase free radical content in muscle by Jackson et al. (1985); data obtained from PubMed search using terms ‘exercise’ and ‘antioxidants’ performed in June 2015.

Figure 3. Nitric oxide and dietary nitrate

Left to right: canonical pathway for enzymatic synthesis and redox degradation of nitric oxide (^•NO) to nitrite (NO₂ ⁻) and nitrate (NO₃ ⁻). Right to left: proposed pathway for conversion of dietary NO₃ ⁻ to ^•NO. NOS, NO synthase; Hgb, haemoglobin; Mgb, myoglobin.