***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background — Inorganic nitrate ( NO3− ) , abundant in certain vegetables , is converted to nitrite by bacteria in the oral cavity . Nitrite can be converted to nitric oxide in the setting of hypoxia . We tested the hypothesis that NO3− supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise . Methods and Results — Seventeen subjects participated in this r and omized , double-blind , crossover study comparing a single dose of NO3-rich beetroot juice ( NO3− , 12.9 mmol ) with an identical nitrate-depleted placebo . Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests , with measurements of cardiac output and skeletal muscle oxygenation . We also assessed skeletal muscle oxidative function . Study end points included exercise efficiency ( total work/total oxygen consumed ) , peak O2 , total work performed , vasodilatory reserve , forearm mitochondrial oxidative function , and augmentation index ( a marker of arterial wave reflections , measured via radial arterial tonometry ) . Supplementation increased plasma nitric oxide metabolites ( median , 326 versus 10 & mgr;mol/L ; P=0.0003 ) , peak O2 ( 12.6±3.7 versus 11.6±3.1 mL O2·min−1·kg−1 ; P=0.005 ) , and total work performed ( 55.6±35.3 versus 49.2±28.9 kJ ; P=0.04 ) . However , efficiency was unchanged . NO3− led to greater reductions in systemic vascular resistance ( −42.4±16.6 % versus −31.8±20.3 % ; P=0.03 ) and increases in cardiac output ( 121.2±59.9 % versus 88.7±53.3 % ; P=0.006 ) with exercise . NO3− reduced aortic augmentation index ( 132.2±16.7 % versus 141.4±21.9 % ; P=0.03 ) and tended to improve mitochondrial oxidative function . Conclusions — NO3− increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities . Efficiency did not change as a result of parallel increases in total work and O2 . NO3− increased exercise vasodilatory and cardiac output reserves . NO3− also reduced arterial wave reflections , which are linked to left ventricular diastolic dysfunction and remodeling . Clinical Trial Registration — URL : www . clinical trials.gov . Unique identifier : NCT01919177 Recent studies surprisingly show that dietary inorganic nitrate , abundant in vegetables , can be metabolized in vivo to form nitrite and then bioactive nitric oxide . A reduction in blood pressure was recently noted in healthy volunteers after dietary supplementation with nitrate ;  an effect consistent with formation of vasodilatory nitric oxide . Oral bacteria have been suggested to play a role in bioactivation of nitrate by first reducing it to the more reactive anion nitrite . In a cross-over design ed study in seven healthy volunteers we examined the effects of a commercially available chlorhexidine-containing antibacterial mouthwash on salivary and plasma levels of nitrite measured after an oral intake of sodium nitrate ( 10mg/kg dissolved in water ) . In the control situation the salivary and plasma levels of nitrate and nitrite increased greatly after the nitrate load . Rinsing the mouth with the antibacterial mouthwash prior to the nitrate load had no effect on nitrate accumulation in saliva or plasma but abolished its conversion to nitrite in saliva and markedly attenuated the rise in plasma nitrite . We conclude that the acute increase in plasma nitrite seen after a nitrate load is critically dependent on nitrate reduction in the oral cavity by commensal bacteria . The removal of these bacteria with an antibacterial mouthwash will very likely attenuate the NO-dependent biological effects of dietary nitrate The anion nitrate-abundant in our diet-has recently emerged as a major pool of nitric oxide ( NO ) synthase-independent NO production . Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides . This reductive pathway is enhanced during low oxygen tension and acidosis . A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate . We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise . Nine healthy , nonsmoking volunteers ( age 30+/-2.3 years , VO(2max ) 3.72+/-0.33 L/min ) participated in this study , which had a r and omized , double-blind crossover design . Subjects received dietary supplementation with sodium nitrate ( 0.1 mmol/kg/day ) or placebo ( NaCl ) for 2 days before the test . This dose corresponds to the amount found in 100 - 300 g of a nitrate-rich vegetable such as spinach or beetroot . The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers . Dietary nitrate reduced VO(2max ) from 3.72+/-0.33 to 3.62+/-0.31 L/min , P<0.05 . Despite the reduction in VO(2max ) the time to exhaustion trended to an increase after nitrate supplementation ( 524+/-31 vs 563+/-30 s , P=0.13 ) . There was a correlation between the change in time to exhaustion and the change in VO(2max ) ( R(2)=0.47 , P=0.04 ) . A moderate dietary dose of nitrate significantly reduces VO(2max ) during maximal exercise using a large active muscle mass . This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved : one that reduces VO(2max ) and another that improves the energetic function of the working muscles Six days of dietary nitrate supplementation in the form of beetroot juice ( ~0.5 L/d ) has been reported to reduce pulmonary oxygen uptake ( VO₂ ) during submaximal exercise and increase tolerance of high-intensity work rates , suggesting that nitrate can be a potent ergogenic aid . Limited data are available regarding the effect of nitrate ingestion on athletic performance , and no study has investigated the potential ergogenic effects of a small-volume , concentrated dose of beetroot juice . The authors tested the hypothesis that 6 d of nitrate ingestion would improve time-trial performance in trained cyclists . Using a double-blind , repeated- measures crossover design , 12 male cyclists ( 31±3 yr , VO2peak=58±2 ml·kg⁻¹·min⁻¹ , maximal power [Wmax]=342±10 W ) ingested 140 ml/d of concentrated beetroot ( ~8 mmol/d nitrate ) juice ( BEET ) or a placebo ( nitrate-depleted beetroot juice ; PLAC ) for 6 d , separated by a 14-d washout . After supplementation on Day 6 , subjects performed 60 min of submaximal cycling ( 2 × 30 min at 45 % and 65 % Wmax , respectively ) , followed by a 10-km time trial . Time-trial performance ( 953±18 vs. 965±18 s , p<.005 ) and power output ( 294±12 vs. 288±12 W , p<.05 ) improved after BEET compared with PLAC supplementation . Submaximal VO₂ was lower after BEET ( 45 % Wmax=1.92±0.06 vs. 2.02±0.09 L/min , 65 % Wmax 2.94±0.12 vs. 3.11±0.12 L/min ) than with PLAC ( main effect , p<.05 ) . Whole-body fuel selection and plasma lactate , glucose , and insulin concentrations did not differ between treatments . Six days of nitrate supplementation reduced VO₂ during submaximal exercise and improved time-trial performance in trained cyclists PURPOSE Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance . However , it is presently unknown whether it may enhance performance during simulated competition . The present study investigated the effects of acute dietary nitrate supplementation on power output ( PO ) , VO2 , and performance during 4- and 16.1-km cycling time trials ( TT ) . METHODS After familiarization , nine club-level competitive male cyclists were assigned in a r and omized , crossover design to consume 0.5 L of beetroot juice ( BR ; containing ∼ 6.2 mmol of nitrate ) or 0.5 L of nitrate-depleted BR ( placebo , PL ; containing ∼ 0.0047 mmol of nitrate ) , ∼ 2.5 h before the completion of a 4- and a 16.1-km TT . RESULTS BR supplementation elevated plasma [ nitrite ] ( PL = 241 ± 125 vs BR = 575 ± 199 nM , P < 0.05 ) . The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance ( P > 0.05 ) , but BR significantly increased mean PO during the 4-km ( PL = 279 ± 51 vs BR = 292 ± 44 W , P < 0.05 ) and 16.1-km TT ( PL = 233 ± 43 vs BR = 247 ± 44 W , P < 0.01 ) . Consequently , BR improved 4-km performance by 2.8 % ( PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min , P < 0.05 ) and 16.1-km performance by 2.7 % ( PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min , P < 0.01 ) . CONCLUSIONS These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy , as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance Ingestion of dietary ( inorganic ) nitrate elevates circulating and tissue levels of nitrite via bioconversion in the entero-salivary circulation . In addition , nitrite is a potent vasodilator in humans , an effect thought to underlie the blood pressure – lowering effects of dietary nitrate ( in the form of beetroot juice ) ingestion . Whether inorganic nitrate underlies these effects and whether the effects of either naturally occurring dietary nitrate or inorganic nitrate supplementation are dose dependent remain uncertain . Using a r and omized crossover study design , we show that nitrate supplementation ( KNO3 capsules : 4 versus 12 mmol [ n=6 ] or 24 mmol of KNO3 ( 1488 mg of nitrate ) versus 24 mmol of KCl [ n=20 ] ) or vegetable intake ( 250 mL of beetroot juice [ 5.5 mmol nitrate ] versus 250 mL of water [ n=9 ] ) causes dose-dependent elevation in plasma nitrite concentration and elevation of cGMP concentration with a consequent decrease in blood pressure  in healthy volunteers . In addition , post hoc analysis demonstrates a sex difference in sensitivity to nitrate supplementation dependent on resting baseline blood pressure and plasma nitrite concentration , whereby blood pressure is decreased in male volunteers , with higher baseline blood pressure and lower plasma nitrite concentration but not in female volunteers . Our findings demonstrate dose-dependent decreases in blood pressure and vasoprotection after inorganic nitrate ingestion in the form of either supplementation or by dietary elevation . In addition , our post hoc analyses intimate sex differences in nitrate processing involving the entero-salivary circulation that are likely to be major contributing factors to the lower blood pressures and the vasoprotective phenotype of premenopausal women PURPOSE Humans can reduce inorganic nitrate ( NO(3)(- ) ) to nitrite ( NO(2)(- ) ) , nitric oxide ( NO ) , and other bioactive nitrogen oxides . The purpose of this study was to test the hypothesis that a single dose of inorganic nitrate before exercise might enhance the tolerance of endurance athletes to high intensity exercise . METHODS Eleven cyclists ( age = 34.3 ± 4.8 yr , VO(2peak ) = 65.1 ± 6.2 mL·kg(-1)·min(-1 ) ) participated in this r and omized , double-blind , crossover study . Subjects received dietary supplementation with nitrate ( NaNO(3 ) 10 mg·kg(-1 ) of body mass ) or a placebo ( NaCl ) 3 h before exercise . They then performed a cycle ergometer test that consisted of four 6-min submaximal workloads , corresponding to 2.0 , 2.5 , 3.0 , and 3.5 W·kg(-1 ) of body mass , interspersed with 3 min of passive recovery . After a 5-min recovery period , subjects performed one incremental exercise test until exhaustion . RESULTS Plasma nitrate and nitrite were significantly higher ( P < 0.05 ) 3 h after supplementation ( nitrate = 250 
    Output:
    
Dietary NO3(- ) supplementation decreases VO2 during exercise performed in the moderate and heavy intensity domains in healthy subjects .
The present meta- analysis did not show any significant effect of  dietary NO3(- ) supplementation on metabolic rate in subjects with chronic diseases , despite enhanced exercise tolerance