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Effect of nitrate supplementation on hepatic blood flow and glucose homeostasis: a double-blind, placebo-controlled, randomized control trial.

ABSTRACT: Nitric oxide alters gastric blood flow, improves vascular function, and mediates glucose uptake within the intestines and skeletal muscle. Dietary nitrate, acting as a source of nitric oxide, appears to be a potential low-cost therapy that may help maintain glucose homeostasis. In a randomized, double-blind, placebo-controlled crossover study, 31 young and older adult participants had a standardized breakfast, supplemented with either nitrate-rich beetroot juice (11.91 mmol nitrate) or nitrate-depleted beetroot juice as placebo (0.01 mmol nitrate). MRI was used to assess apparent diffusion coefficient (ADC), portal vein flux, and velocity. Plasma glucose, incretin, and C-peptide concentrations and blood pressure were assessed. Outcome variables were measured at baseline and hourly for 3 h. Compared with a placebo, beetroot juice resulted in a significant elevation in plasma nitrate and plasma nitrite concentration. No differences were seen for the young or older adult cohorts between placebo and beetroot juice for ADC, or portal vein flux. There was an interaction effect in the young adults between visits for portal vein velocity. Nitrate supplementation did not reduce plasma glucose, active GLP-1, total GLP-1, or plasma C-peptide concentrations for the young or older adult cohorts. Despite a significant elevation in plasma nitrite concentration following an acute dose of (11.91 mmol) nitrate, there was no effect on hepatic blood flow, plasma glucose, C-peptide, or incretin concentration in healthy adults.

SUBMITTER: Shepherd AI

PROVIDER: S-EPMC5076007 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Effect of nitrate supplementation on hepatic blood flow and glucose homeostasis: a double-blind, placebo-controlled, randomized control trial.

Shepherd Anthony I AI Wilkerson Daryl P DP Fulford Jon J Winyard Paul G PG Benjamin Nigel N Shore Angela C AC Gilchrist Mark M

American journal of physiology. Gastrointestinal and liver physiology 20160714 3

Nitric oxide alters gastric blood flow, improves vascular function, and mediates glucose uptake within the intestines and skeletal muscle. Dietary nitrate, acting as a source of nitric oxide, appears to be a potential low-cost therapy that may help maintain glucose homeostasis. In a randomized, double-blind, placebo-controlled crossover study, 31 young and older adult participants had a standardized breakfast, supplemented with either nitrate-rich beetroot juice (11.91 mmol nitrate) or nitrate-d ...[more]

PMID: 27418682

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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.

Project description:BACKGROUND:The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. OBJECTIVE:We 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. DESIGN:A 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). RESULTS:Baseline 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. CONCLUSIONS:Sustained 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:Citrulline (CIT) and nitrate-rich beetroot extract (BR) are widely studied ergogenic aids. Nevertheless, both supplements have been studied in short-term trials and separately. To the best of the authors' knowledge, the effects of combining CIT and BR supplementation on recovery status observed by distance covered in the Cooper test, exercise-induced muscle damage (EIMD) and anabolic/catabolic hormone status have not been investigated to date. Therefore, the main purpose of this research was to assess the effect of the long-term (9 weeks) mixture of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates (NO3-)) supplementation on recovery by distance covered in the Cooper test, EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) and anabolic/catabolic hormones (testosterone, cortisol and testosterone/cortisol ratio (T/C)) in male trained triathletes. Thirty-two triathletes were randomized into four different groups of eight triathletes in this double-blind, placebo-controlled trial: placebo group (PLG), CIT group (CITG; 3 g/day of CIT), BR group (BRG; 2.1 g/day of BR (300 mg/day of NO3-)) and CIT-BR group (CIT-BRG; 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3-)). Distance covered in the Cooper test and blood samples were collected from all participants at baseline (T1) and after 9 weeks of supplementation (T2). There were no significant differences in the interaction between group and time in EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) (p > 0.05). However, significant differences were observed in the group-by-time interaction in distance covered in the Cooper test (p = 0.002; η2p = 0.418), cortisol (p = 0.044; η2p = 0.247) and T/C (p = 0.005; η2p = 0.359). Concretely, significant differences were observed in distance covered in the Cooper test percentage of change (p = 0.002; η2p = 0.418) between CIT-BRG and PLG and CITG, in cortisol percentage change (p = 0.049; η2p = 0.257) and in T/C percentage change (p = 0.018; η2p = 0.297) between CIT-BRG and PLG. In conclusion, the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3-) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT + BR improved recovery status by preventing an increase in cortisol and showing an increase in distance covered in the Cooper test and T/C.

Dataset Information

Effect of nitrate supplementation on hepatic blood flow and glucose homeostasis: a double-blind, placebo-controlled, randomized control trial.

Publications

Effect of nitrate supplementation on hepatic blood flow and glucose homeostasis: a double-blind, placebo-controlled, randomized control trial.

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