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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    • "ial respiration for O 2 , an effect that is reproduced in vitro—acutely and pH - dependently—by NO − 2 ( Larsen et al . , 2011 ) . Lowered affinity is attributed to an NO induced rise in the apparent K m of cytochrome c oxidase for O 2 ( Larsen et al . , 2011 ) but , inconsistently , NO − 2 does not affect mitochondrial respiration or efficiency ( Larsen et al . , 2011 ) like NO is expected to ( Brown and Borutaite , 2007 ) . Apparent mitochondrial respiratory affinity for O 2 depends strongly on the extent to which respiration is controlled by the enzyme reacting with O 2 ( Affourtit et al . , 2001 ) —control of cytochrome c oxidase over O 2 consumption may well have been affected by NO"
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    ABSTRACT: Inorganic nitrate is present at high levels in beetroot and celery, and in green leafy vegetables such as spinach and lettuce. Though long believed inert, nitrate can be reduced to nitrite in the human mouth and, further, under hypoxia and/or low pH, to nitric oxide. Dietary nitrate has thus been associated favorably with nitric-oxide-regulated processes including blood flow and energy metabolism. Indeed, the therapeutic potential of dietary nitrate in cardiovascular disease and metabolic syndrome-both aging-related medical disorders-has attracted considerable recent research interest. We and others have shown that dietary nitrate supplementation lowers the oxygen cost of human exercise, as less respiratory activity appears to be required for a set rate of skeletal muscle work. This striking observation predicts that nitrate benefits the energy metabolism of human muscle, increasing the efficiency of either mitochondrial ATP synthesis and/or of cellular ATP-consuming processes. In this mini-review, we evaluate experimental support for the dietary nitrate effects on muscle bioenergetics and we critically discuss the likelihood of nitric oxide as the molecular mediator of such effects.
    Frontiers in Physiology 08/2015; 6:211. DOI:10.3389/fphys.2015.00211 · 3.53 Impact Factor
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    • "Similarly, BJ has been found to improve exercise performance (Bond et al. 2012; Lansley et al. 2011). Using either a chronic (~5–8 mmol per day over 3 days; Bailey et al. 2010) or an acute dose of beetroot juice (~5–8 mmol ingested 2.5 h prior to exercise; Lansley et al. 2011), studies have reported a 3–5 % reduction in submaximal ˙ VO 2 for a given workload, indicating increased efficiency of exercise (Bailey et al. 2009; Larsen et al. 2011; Vanhatalo et al. 2010). Other studies have reported improvement in cycling time-trial performance (Cermak et al. 2012; Lansley et al. 2011) following 5–11.2 "
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    ABSTRACT: Sodium phosphate (SP) and beetroot juice (BJ) supplementation was assessed on repeated-sprint ability (RSA). Thirteen female team-sport participants completed four trials: (1) SP and BJ (SP + BJ), (2) SP and placebo (for BJ), (3) BJ and placebo (for SP) and (4) placebo (for SP + BJ), with ~21 days separating each trial. After each trial, participants performed a simulated team-game circuit (STGC) consisting of four 15 min quarters, with a 6 × 20-m repeated-sprint set performed at the start, half-time and end. Total sprint times were between 0.95-1.30 and 0.83-1.12 s faster for each RSA set and 3.25 and 3.12 s faster overall (~5 % improvement) after SP compared with placebo and BJ, respectively (p = 0.02 for sets 1, 2 and overall; Cohen's effect size: d = -0.51 to -0.90 for all sets and overall). Additionally, total sprint times were 0.48 s faster after SP + BJ compared with placebo (set 2; p = 0.05, ~2 % improvement). Furthermore, best sprints were 0.13-0.23 and 0.15-0.20 s faster (~6 % improvement; p < 0.01) after SP compared with placebo and BJ, respectively, for all sets (d = -0.54 to -0.89). SP improved RSA in team-sport, female athletes when fresh (set 1) and during the later sets of a STGC (sets 2 and 3). Specifically, total and best sprint times were faster after SP compared with placebo and BJ.
    Arbeitsphysiologie 06/2015; 115(10). DOI:10.1007/s00421-015-3201-1 · 2.19 Impact Factor
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    • "A key advantage of the IST is that it permits physical and cognitive challenges to be applied simultaneously in a controlled fashion, although it is acknowledged that the test does not reflect other characteristics of team sports. It has been reported that NO 3 − supplementation can improve the efficiency of muscular work during submaximal exercise by reducing ˙ VO 2 , an effect which may be related to a reduced O 2 cost of mitochondrial ATP resynthesis (Larsen et al. 2011) and/or to a lower ATP cost of muscle contraction (Bailey et al. 2010a). In the present study, ˙ VO 2 in the IST was not different with BR compared to PL. "
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    ABSTRACT: It is possible that dietary nitrate (NO3 (-)) supplementation may improve both physical and cognitive performance via its influence on blood flow and cellular energetics. To investigate the effects of dietary NO3 (-) supplementation on exercise performance and cognitive function during a prolonged intermittent sprint test (IST) protocol, which was designed to reflect typical work patterns during team sports. In a double-blind randomised crossover study, 16 male team-sport players received NO3 (-)-rich (BR; 140 mL day(-1); 12.8 mmol of NO3 (-)), and NO3 (-)-depleted (PL; 140 mL day(-1); 0.08 mmol NO3 (-)) beetroot juice for 7 days. On day 7 of supplementation, subjects completed the IST (two 40-min "halves" of repeated 2-min blocks consisting of a 6-s "all-out" sprint, 100-s active recovery and 20 s of rest), on a cycle ergometer during which cognitive tasks were simultaneously performed. Total work done during the sprints of the IST was greater in BR (123 ± 19 kJ) compared to PL (119 ± 17 kJ; P < 0.05). Reaction time of response to the cognitive tasks in the second half of the IST was improved in BR compared to PL (BR first half: 820 ± 96 vs. second half: 817 ± 86 ms; PL first half: 824 ± 114 vs. second half: 847 ± 118 ms; P < 0.05). There was no difference in response accuracy. These findings suggest that dietary NO3 (-) enhances repeated sprint performance and may attenuate the decline in cognitive function (and specifically reaction time) that may occur during prolonged intermittent exercise.
    Arbeitsphysiologie 04/2015; 115(9). DOI:10.1007/s00421-015-3166-0 · 2.19 Impact Factor
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