***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: Abstract —Single dose administration of dietary inorganic nitrate acutely reduces blood pressure ( BP ) in normotensive healthy volunteers , via bioconversion to the vasodilator nitric oxide . We assessed whether dietary nitrate might provide sustained BP lowering in patients with hypertension . We r and omly assigned 68 patients with hypertension in a double-blind , placebo-controlled clinical trial to receive daily dietary supplementation for 4 weeks with either dietary nitrate ( 250 mL daily , as beetroot juice ) or a placebo ( 250 mL daily , as nitrate-free beetroot juice ) after a 2-week run-in period and followed by a 2-week washout . We performed stratified r and omization of drug-naive ( n=34 ) and treated ( n=34 ) patients with hypertension aged 18 to 85 years . The primary end point was change in clinic , ambulatory , and home BP compared with placebo . Daily supplementation with dietary nitrate was associated with reduction in BP measured by 3 different methods . Mean ( 95 % confidence interval ) reduction in clinic BP was 7.7/2.4 mm Hg ( 3.6–11.8/0.0–4.9 , P<0.001 and P=0.050 ) . Twenty-four-hour ambulatory BP was reduced by 7.7/5.2 mm Hg ( 4.1–11.2/2.7–7.7 , P<0.001 for both ) . Home BP was reduced by 8.1/3.8 mm Hg ( 3.8–12.4/0.7–6.9 , P<0.001 and P<0.01 ) with no evidence of tachyphylaxis over the 4-week intervention period . Endothelial function improved by ≈20 % ( P<0.001 ) , and arterial stiffness was reduced by 0.59 m/s ( 0.24–0.93 ; P<0.01 ) after dietary nitrate consumption with no change after placebo . The intervention was well tolerated . This is the first evidence of durable BP reduction  with dietary nitrate supplementation in a relevant patient group . These findings suggest a role for dietary nitrate as an affordable , readily-available , adjunctive treatment in the management of patients with hypertension ( funded by The British Heart Foundation ) . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01405898 Although inorganic nitrate and beetroot juice supplementation are associated with decreased systolic blood pressure ( BP ) , these results have primarily been obtained from short-term trials that focused on healthy young adults . Therefore , we hypothesized that oral supplementation of beetroot juice concentrate would decrease systolic BP in overweight older participants but that the decline in BP would not be sustained after a 1-week interruption of the beetroot juice supplementation . For 3 weeks , 24 participants were r and omized to either the beetroot juice concentrate or blackcurrant juice group , with a 1-week postsupplementation phase ( week 4 ) . Changes in systolic and diastolic BP were assessed during the supplementation and postsupplementation phases . Blood pressure was measured using 3 different methods : ( 1 ) resting clinic BP , ( 2 ) 24-hour ambulatory BP monitoring , and ( 3 ) home monitoring of daily resting BP . The first 2 methods were applied at baseline and after weeks 3 and 4 . Daily measurements were conducted throughout the study , with 21 subjects completing the study ( beetroot/blackcurrant = 10/11 ; male/female = 12/9 ; age = 62.0 ± 1.4 years ; body mass index = 30.1 ± 1.2 kg/m(2 ) ) . After 3 weeks , beetroot juice supplementation was not associated with significant changes in resting clinic BP or 24-hour ABPM .  Conversely , beetroot juice concentrate  reduced daily systolic BP after 3 weeks ( -7.3 ± 5.9 mm Hg , P = .02 ) ; however , the effect was not maintained after the interruption of the supplementation ( week 4 , 2.8 ± 6.1 mm Hg , P = .09 ) . In overweight older subjects , beetroot juice concentrate supplementation was associated with beneficial effects on daily systolic BP , although the effects were not significant when measured by 24-hour ABPM or resting clinic BP Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 BACKGROUND Dietary nitrate , which is in green leafy vegetables and beetroot , decreases blood pressure through the enterosalivary nitrate-nitrite-nitric oxide pathway in healthy individuals . Whether similar effects would occur in individuals with treated hypertension and , therefore , at increased risk of cardiovascular disease is unclear . OBJECTIVE We assessed whether increased dietary nitrate intake by using beetroot juice for 1 wk lowers blood pressure in treated hypertensive men and women . DESIGN Participants ( n = 27 ) were recruited to a r and omized , placebo-controlled , double-blind crossover trial . The effect of 1-wk intake of nitrate-rich beetroot juice was compared with 1-wk intake of nitrate-depleted beetroot juice ( placebo ) . The primary outcome was blood pressure assessed by measuring home blood pressure during the intervention and 24-h ambulatory blood pressure on day 7 of the intervention . Other outcomes included nitrate metabolism assessed by measuring nitrate and nitrite in plasma , saliva , and urine . RESULTS Relative to the placebo , 1-wk intake of nitrate-rich beetroot juice result ed in a 3-fold increase in plasma nitrite and nitrate , a 7-fold increase in salivary nitrite , an 8-fold higher salivary nitrate , and a 4-fold increase in both urinary nitrite and nitrate ( P < 0.001 ) . However , no differences in home blood pressure and 24-h ambulatory blood pressure were observed with 1-wk intake of nitrate-rich beetroot juice in comparison with the placebo . CONCLUSION An increase in dietary nitrate intake may not be an effective short-term approach to further lower blood pressure in treated hypertensive subjects We tested the hypothesis that inorganic nitrate ( NO3 ( - ) ) supplementation would improve muscle oxygenation , pulmonary oxygen uptake ( V̇o2 ) kinetics , and exercise tolerance ( Tlim ) to a greater extent when cycling at high compared with low pedal rates . In a r and omized , placebo-controlled cross-over study , seven subjects ( mean ± SD , age 21 ± 2 yr , body mass 86 ± 10 kg ) completed severe-intensity step cycle tests at pedal cadences of 35 rpm and 115 rpm during separate nine-day supplementation periods with NO3 (-)-rich beetroot juice ( BR ) ( providing 8.4 mmol NO3 (-)/day ) and placebo ( PLA ) . Compared with PLA , plasma nitrite concentration increased 178 % with BR ( P < 0.01 ) . There were no significant differences in muscle oxyhemoglobin concentration ( [ O2Hb ] ) , phase II V̇o2 kinetics , or Tlim between BR and PLA when cycling at 35 rpm ( P > 0.05 ) . However , when cycling at 115 rpm , muscle [ O2Hb ] was higher at baseline and throughout exercise , phase II V̇o2 kinetics was faster ( 47 ± 16 s vs. 61 ± 25 s ; P < 0.05 ) , and Tlim was greater ( 362 ± 137 s vs. 297 ± 79 s ; P < 0.05 ) with BR compared with PLA . These results suggest that short-term BR supplementation can increase muscle oxygenation , expedite the adjustment of oxidative metabolism , and enhance exercise tolerance when cycling at a high , but not a low , pedal cadence in healthy recreationally active subjects . These findings support recent observations that NO3 ( - ) supplementation may be particularly effective at improving physiological and functional responses in type II muscle fibers Diets rich in green , leafy vegetables have been shown to lower blood pressure ( BP ) and reduce the risk of cardiovascular disease .  Green , leafy vegetables and beetroot are particularly rich in inorganic nitrate . Dietary nitrate supplementation , via sequential reduction to nitrite and NO , has previously been shown to lower BP and improve endothelial function in healthy humans . We sought to determine if supplementing dietary nitrate with beetroot juice , a rich source of nitrate , will lower BP and improve endothelial function and insulin sensitivity in individuals with type 2 diabetes ( T2DM ) . Twenty-seven patients , age 67.2±4.9 years ( 18 male ) , were recruited for a double-blind , r and omized , placebo-controlled crossover trial . Participants were r and omized to begin , in either order , a 2-week period of supplementation with 250ml beetroot juice daily ( active ) or 250ml nitrate-depleted beetroot juice ( placebo ) . At the conclusion of each intervention period 24-h ambulatory blood pressure monitoring , tests of macro- and microvascular endothelial function , and a hyperinsulinemic isoglycemic clamp were performed . After 2 weeks administration of beetroot juice mean ambulatory systolic BP was unchanged : 134.6±8.4mmHg versus 135.1±7.8mmHg ( mean±SD ) , placebo vs active-mean difference of -0.5mmHg ( placebo-active ) , p=0.737 ( 95 % CI -3.9 to 2.8 ) . There were no changes in macrovascular or microvascular endothelial function or insulin sensitivity . Supplementation of the diet with 7.5mmol of nitrate per day for 2 weeks caused an increase in plasma nitrite and nitrate concentration , but did not lower BP , improve endothelial function , or improve insulin sensitivity in individuals with T2DM INTRODUCTION Hypertension is a major contributor to the global burden of cardiovascular diseases and its prevalence increases progressively with ageing . Therefore the identification of effective , age-friendly exercise and nutritional interventions which lower blood pressure ( BP ) is a research priority . OBJECTIVE To undertake a pilot RCT examining the efficacy of isometric h and grip exercise ( IHGE ) and beetroot juice ( a rich source of inorganic nitrate ) consumption in modifying clinic and 24-h ambulatory BP ( 24-h ABP ) , peripheral arterial function and plasma asymmetric dimethylarginine ( ADMA ) in older overweight and obese adults . DESIGN Thirty middle age and older adults ( 62±5 years ) were r and omised to : ( a ) bilateral IHGE at 50 % of maximal voluntary contraction ( 8 min/day ) , ( b ) 140 ml/day of concentrated beetroot juice , or ( c ) no-intervention ( control group ) , for 7 days . All groups followed a st and ardised diet to control nitrate intake . Clinic and 24-h ABP , peripheral arterial function quantified by pulse wave velocity ( PWV ) and arterial volume distensibility were assessed before and after intervention . SETTING Clinical ageing research unit , Newcastle University . RESULTS At baseline , 
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However , the effect was only significant when measured in resting clinical setting s as no significant changes in BP were observed using 24-h ambulatory and daily home BP monitorings .
Conclusion : Positive effects of medium-term dietary nitrate supplementation on BP were only observed in clinical setting s , which were not corroborated by more accurate methods such as 24-h ambulatory and daily home monitorings