Dietary Inorganic Nitrate Improves Mitochondrial Efficiency in Humans

Department of Physiology and Pharmacology, Karolinska Institutet, 11486 Stockholm, Sweden.
Cell metabolism (Impact Factor: 17.57). 02/2011; 13(2):149-59. DOI: 10.1016/j.cmet.2011.01.004
Source: PubMed


Nitrate, an inorganic anion abundant in vegetables, is converted in vivo to bioactive nitrogen oxides including NO. We recently demonstrated that dietary nitrate reduces oxygen cost during physical exercise, but the mechanism remains unknown. In a double-blind crossover trial we studied the effects of a dietary intervention with inorganic nitrate on basal mitochondrial function and whole-body oxygen consumption in healthy volunteers. Skeletal muscle mitochondria harvested after nitrate supplementation displayed an improvement in oxidative phosphorylation efficiency (P/O ratio) and a decrease in state 4 respiration with and without atractyloside and respiration without adenylates. The improved mitochondrial P/O ratio correlated to the reduction in oxygen cost during exercise. Mechanistically, nitrate reduced the expression of ATP/ADP translocase, a protein involved in proton conductance. We conclude that dietary nitrate has profound effects on basal mitochondrial function. These findings may have implications for exercise physiology- and lifestyle-related disorders that involve dysfunctional mitochondria.

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    • "Previous meta-analyses already showed that dietary NO 3 À significantly decreases systolic blood pressure[56]and may have a therapeutic potential in patients with cardiovascular diseases and significantly improves exercise tolerance in healthy subjects[57]. Mechanistically, there were clear evidences from in vitro studies that NO increases mitochondrial oxidative efficiency[39,58]. The present meta-analysis supports that increasing NO bioavailability through dietary NO 3 À translates into a significantly decreased O 2 cost during exercise performed in the heavy and moderate intensity domains, but not at exercise intensities close to the maximum. "
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    ABSTRACT: Recent randomized controlled trials have suggested that dietary nitrate (NO3-), found in beetroot and other vegetables, and inorganic NO3- salts decrease metabolic rate under resting and exercise conditions.
    Full-text · Article · Jan 2016 · Nitric Oxide
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    • "Following days of altitude exposure, plasma NO3 -and NO2 -are elevated at 3500m. Chronic or prolonged elevation in dietary nitrate may increase mitochondrial efficiency or enhance mitochondrial biogenesis (Larsen et al., 2011; Nair, Irving, & Lanza, 2011; Vaughan et al., 2014) and thereby reduce oxygen cost, improve " Effect of Acute Dietary Nitrate Consumption on Oxygen Consumption During Submaximal Exercise in Hypobaric Hypoxia " by Carriker CR et al. "
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    ABSTRACT: Reduced partial pressure of oxygen impairs exercise performance at altitude. Acute nitrate supplementation, at sea level, may reduce oxygen cost during submaximal exercise in hypobaric hypoxia. Therefore, we investigated the metabolic response during exercise at altitude following acute nitrate consumption. Ten well-trained (61.0±7.4 ml/kg/min) males (age 28±7 yr) completed 3 experimental trials (T1, T2, T3). T1 included baseline demographics, a maximal aerobic capacity test (VO2max) and five submaximal intensity cycling determination bouts at an elevation of 1600m. A 4-day dietary washout, minimizing consumption of nitrate-rich foods, preceded T2 and T3. In a randomized, double-blind, placebo-controlled, crossover fashion, subjects consumed either a nitrate-depleted beetroot juice (PL) or ~12.8 mmol nitrate rich (NR) beverage 2.5 hours prior to T2 and T3. Exercise at 3500m (T2 and T3) via hypobaric hypoxia consisted of a 5-min warm-up (25% of normobaric VO2max) and four 5-min cycling bouts (40, 50, 60, 70% of normobaric VO2max) each separated by a 4-min rest period. Cycling RPM and watts for each submaximal bout during T2 and T3 were determined during T1. Pre-exercise plasma nitrite was elevated following NR consumption compared to PL (1.4±1.2 and 0.7±0.3 uM respectively; p<0.05). There was no difference in oxygen consumption (-0.5±1.8, 0.1±1.7, 0.7±2.1, and 1.0±3.0 ml/kg/min) at any intensity (40, 50, 60, 70% of VO2max; respectively) between NR and PL. Further, respiratory exchange ratio, oxygen saturation, heart rate and rating of perceived exertion were not different at any submaximal intensity between NR and PL either. Blood lactate, however, was reduced following NR consumption compared to PL at 40 and 60% of VO2max (p<.0.05). Our findings suggest that acute nitrate supplementation prior to exercise at 3500m does not reduce oxygen cost but may reduce blood lactate accumulation at lower intensity workloads.
    Full-text · Article · Dec 2015 · International Journal of Sport Nutrition and Exercise Metabolism
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    • "Hypoxia facilitates the reduction of nitrite to NO (Millar et al., 1998; Maher et al., 2008), allowing more NO to be generated in tissues receiving less O 2 or that are more metabolically active (Thomas et al., 2001). Oral and dietary nitrate supplementation has been shown to reduce the O 2 cost of locomotion (Larsen et al., 2007, 2011; Bailey et al., 2009; Cermak et al., 2012a), which has been attributed to either improved efficiency of oxidative metabolic (Clerc et al., 2007; Larsen et al., 2011) or contractile processes (Bailey et al., 2010b). During exercise in moderate hypoxia, nitrate supplementation improves peripheral O 2 efficiency and phosphocreatine recovery kinetics (Vanhatalo et al., 2011; Masschelein et al., 2012). "
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    ABSTRACT: Background: Hypoxia-induced pulmonary vasoconstriction increases pulmonary arterial pressure (PAP) and may impede right heart function and exercise performance. This study examined the effects of oral nitrate supplementation on right heart function and performance during exercise in normoxia and hypoxia. We tested the hypothesis that nitrate supplementation would attenuate the increase in PAP at rest and during exercise in hypoxia, thereby improving exercise performance. Methods: Twelve trained male cyclists [age: 31 ± 7 year (mean ± SD)] performed 15 km time-trial cycling (TT) and steady-state submaximal cycling (50, 100, and 150 W) in normoxia and hypoxia (11% inspired O2) following 3-day oral supplementation with either placebo or sodium nitrate (0.1 mmol/kg/day). We measured TT time-to-completion, muscle tissue oxygenation during TT and systolic right ventricle to right atrium pressure gradient (RV-RA gradient: index of PAP) during steady state cycling. Results: During steady state exercise, hypoxia elevated RV-RA gradient (p > 0.05), while oral nitrate supplementation did not alter RV-RA gradient (p > 0.05). During 15 km TT, hypoxia lowered muscle tissue oxygenation (p < 0.05). Nitrate supplementation further decreased muscle tissue oxygenation during 15 km TT in hypoxia (p < 0.05). Hypoxia impaired time-to-completion during TT (p < 0.05), while no improvements were observed with nitrate supplementation in normoxia or hypoxia (p > 0.05). Conclusion: Our findings indicate that oral nitrate supplementation does not attenuate acute hypoxic pulmonary vasoconstriction nor improve performance during time trial cycling in normoxia and hypoxia.
    Full-text · Article · Nov 2015 · Frontiers in Physiology
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