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Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial.

ABSTRACT: Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3 (-)) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction.Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3 (-) in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3 (-). Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3 (-) increased (P<0.05-0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3 (-) intake. Calculated maximal velocity of knee extension was also higher after NO3 (-) ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred.In this pilot study, acute dietary NO3 (-) intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

SUBMITTER: Coggan AR

PROVIDER: S-EPMC4573847 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial.

Coggan Andrew R AR Leibowitz Joshua L JL Spearie Catherine Anderson CA Kadkhodayan Ana A Thomas Deepak P DP Ramamurthy Sujata S Mahmood Kiran K Park Soo S Waller Suzanne S Farmer Marsha M Peterson Linda R LR

Circulation. Heart failure 20150715 5

<h4>Background</h4>Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3 (-)) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction.<h ...[more]

PMID: 26179185

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Project description:BackgroundThe beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content.ObjectiveWe sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics.DesignA total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD).ResultsBaseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: -0.4, -0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment.ConclusionsSustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.

Project description:BackgroundIn younger individuals, dietary nitrate supplementation has been shown to improve short-term vascular and muscle function. The role of higher habitual nitrate intake as part of a typical diet on muscle function in ageing has not been investigated. A cross-sectional study of relationships between dietary nitrate and measures of muscle function in older community-dwelling Australian women (n = 1420, ≥70 years) was undertaken.MethodsParticipants completed a semi-quantitative food frequency questionnaire assessing dietary intake over the previous year. Total nitrate from vegetables and non-vegetable sources was calculated from a validated instrument that quantified the nitrate content of food recorded within the food frequency questionnaire. Handgrip strength and timed-up-and-go (TUG) were assessed, representing muscle strength and physical function, respectively. Cut-points for weak grip strength (<22 kg) and slow TUG (>10.2 s) were selected due to their association with adverse outcomes. Linear and logistic regressions were used to examine the relationship between total nitrate intake and muscle function measures.ResultsMean ± standard deviation (SD) total nitrate intake was 79.5 ± 31.2 mg/day, of which 84.5% came from vegetables. Across the unadjusted tertiles of nitrate intake (<64.2 mg/day; 64.2 to <89.0 mg/day; ≥89.0 mg/day), women in the highest tertile had a 4% stronger grip strength and a 5% faster TUG performance compared with the lowest tertile. In multivariable-adjusted models, each SD higher nitrate intake (31.2 mg/day) was associated with stronger grip strength (per kilogram, β 0.31, P = 0.027) and faster TUG (per second, β -0.27, P = 0.001). The proportion of women with weak grip strength (<22 kg) or slow TUG (>10.2 s) was 61.0% and 36.9%, respectively. Each SD higher nitrate intake (31.2 mg/day) was associated with lower odds for weak grip strength (OR 0.84, 95% CI 0.74-0.95, P = 0.005) and slow TUG (OR 0.86, 95% CI 0.76-0.98, P = 0.021). Compared with women in the lowest tertile of nitrate intake, women in the highest nitrate intake tertile had lower odds for weak grip strength (OR 0.65, 95% CI 0.49-0.87, Ptrend= 0.004) and slow TUG (OR 0.72, 95% CI 0.53-0.97, Ptrend = 0.044).ConclusionsThis investigation highlights potential benefits of nitrate-rich diets on muscle strength and physical function in a large cohort of older women. Considering poor muscle strength and physical function is associated with a range of adverse health outcomes such as falling, fractures, cardiovascular disease, and mortality, increasing dietary nitrate, especially though vegetable consumption may be an effective way to limit age-related declines in muscle function.

Project description:In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina.Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P=0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P=0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] ?mol/L, P<0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P=0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation.Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication.URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17.

Dataset Information

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial.

Publications

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial.

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