Non-technical summary Reduced atmospheric O 2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary supplementation with inorganic nitrate reduces markers of muscle fatigue and improves high-intensity exercise tolerance in healthy adults inhaling air containing 14.5% O 2 . In the body, nitrate can be converted to nitrite and nitric oxide. These molecules can improve muscle efficiency and also dilate blood vessels allowing more O 2 to be delivered to active muscle. These results suggest that dietary nitrate could be beneficial during exercise at moderate to high altitude and in conditions where O 2 delivery to muscle is reduced such as in pulmonary, cardiovascular and sleep disorders.Abstract Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double-blind, randomised crossover study, nine healthy subjects completed knee-extension exercise to the limit of tolerance (T lim ), once in normoxia (20.9% O 2 ; CON) and twice in hypoxia (14.5% O 2 ). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed using calibrated 31 P-MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nM) compared to PL (129 ± 23 nM) and CON (142 ± 37 nM). T lim was reduced in H-PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H-BR (477 ± 200 s). The muscle [PCr], [P i ] and pH changed at a faster rate in H-PL compared to CON and H-BR. The [PCr] recovery time constant was greater (P < 0.01) in H-PL (29 ± 5 s) compared to CON (23 ± 5 s) and H-BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate-nitrite-NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia. Abbreviations BP, blood pressure; MAP, mean arterial pressure; MRS, magnetic resonance spectroscopy; S aO 2 , arterial O 2 saturation; T lim , limit of tolerance;V O 2 , O 2 uptake.

Key points• Ageing has been proposed to be associated with increased levels of reactive oxygen species (ROS) that scavenge nitric oxide (NO), thereby decreasing the bioavailability of this potent vasodilator.• Here we show that NO bioavailability is compromised in the systemic circulation and in skeletal muscle of sedentary older humans as evidenced by an increase in NO metabolites after antioxidant infusion.• Lifelong physical activity opposes this effect within the trained musculature and in the arterial circulation.• The reduced blood flow to contracting leg muscles with ageing does not appear to be related to changes in NO bioavailability.• These findings expand our understanding of the mechanisms underlying the age-related changes in vascular function and highlight the beneficial effect of exercise training throughout the lifespan.Abstract Ageing has been proposed to be associated with increased levels of reactive oxygen species (ROS) that scavenge nitric oxide (NO). In eight young sedentary (23 ± 1 years; Y), eight older lifelong sedentary (66 ± 2 years; OS) and eight older lifelong physically active subjects (62 ± 2 years; OA), we studied the effect of ROS on systemic and skeletal muscle NO bioavailability and leg blood flow by infusion of the antioxidant N -acetylcysteine (NAC). Infusion of NAC increased the bioavailability of NO in OS, as evidenced by an increased concentration of stable metabolites of NO (NOx) in the arterial and venous circulation and in the muscle interstitium. In OA, infusion of NAC only increased NOx concentrations in venous plasma whereas in Y, infusion of NAC did not affect NOx concentrations. Skeletal muscle protein levels of endothelial and neuronal NO synthase were 32% and 24% higher, respectively, in OA than in OS. Exercise at 12 W elicited a lower leg blood flow response that was associated with a lower leg oxygen uptake in OS than in Y. The improved bioavailability of NO in OS did not increase blood flow during exercise. These data demonstrate that NO bioavailability is compromised in the systemic circulation and in the musculature of sedentary ageing humans due to increased oxidative stress. Lifelong physical activity opposes this effect within the trained musculature and in the arterial

PurposeThis study tested the hypothesis that nitrate (NO3−) supplementation would improve performance during high-intensity intermittent exercise featuring different work and recovery intervals. MethodTen male team-sport players completed high-intensity intermittent cycling tests during separate 5-day supplementation periods with NO3−-rich beetroot juice (BR; 8.2 mmol NO3− day−1) and NO3−-depleted beetroot juice (PL; 0.08 mmol NO3− day−1). Subjects completed: twenty-four 6-s all-out sprints interspersed with 24 s of recovery (24 × 6-s); seven 30-s all-out sprints interspersed with 240 s of recovery (7 × 30-s); and six 60-s self-paced maximal efforts interspersed with 60 s of recovery (6 × 60-s); on days 3, 4, and 5 of supplementation, respectively.ResultPlasma [NO2−] was 237 % greater in the BR trials. Mean power output was significantly greater with BR relative to PL in the 24 × 6-s protocol (568 ± 136 vs. 539 ± 136 W; P < 0.05), but not during the 7 × 30-s (558 ± 95 vs. 562 ± 94 W) or 6 × 60-s (374 ± 57 vs. 375 ± 59 W) protocols (P > 0.05). The increase in blood [lactate] across the 24 × 6-s and 7 × 30-s protocols was greater with BR (P < 0.05), but was not different in the 6 × 60-s protocol (P > 0.05).ConclusionBR might be ergogenic during repeated bouts of short-duration maximal-intensity exercise interspersed with short recovery periods, but not necessarily during longer duration intervals or when a longer recovery duration is applied. These findings suggest that BR might have implications for performance enhancement during some types of intermittent exercise.

Interrupting sustained sitting with brief repeated bouts of light-intensity walking but not standing reduced insulin demand and improved glucose uptake during a simulated sedentary working day. The benefits of such minor behavioural changes could inform future workplace health interventions.

Both caffeine and beetroot juice have ergogenic effects on endurance cycling performance. We investigated whether there is an additive effect of these supplements on the performance of a cycling time trial (TT) simulating the 2012 London Olympic Games course. Twelve male and 12 female competitive cyclists each completed 4 experimental trials in a double-blind Latin square design. Trials were undertaken with a caffeinated gum (CAFF) (3 mg·kg(-1) body mass (BM), 40 min prior to the TT), concentrated beetroot juice supplementation (BJ) (8.4 mmol of nitrate (NO3(-)), 2 h prior to the TT), caffeine plus beetroot juice (CAFF+BJ), or a control (CONT). Subjects completed the TT (females: 29.35 km; males: 43.83 km) on a laboratory cycle ergometer under conditions of best practice nutrition: following a carbohydrate-rich pre-event meal, with the ingestion of a carbohydrate-electrolyte drink and regular oral carbohydrate contact during the TT. Compared with CONT, power output was significantly enhanced after CAFF+BJ and CAFF (3.0% and 3.9%, respectively, p < 0.01). There was no effect of BJ supplementation when used alone (-0.4%, p = 0.6 compared with CONT) or when combined with caffeine (-0.9%, p = 0.4 compared with CAFF). We conclude that caffeine (3 mg·kg(-1) BM) administered in the form of a caffeinated gum increased cycling TT performance lasting ∼50-60 min by ∼3%-4% in both males and females. Beetroot juice supplementation was not ergogenic under the conditions of this study.