title: 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.
authors.affiliation: College of Life and Environmental Sciences, Sport and Health Sciences, University of Exeter, Devon, United Kingdom; University of Exeter Medical School and NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital, Exeter, Devon, United Kingdom; Department of Sport and Exercise Science, Portsmouth, United Kingdom ant.shepherd@port.ac.uk.
authors.forename: Anthony I
authors.identifier: 0000-0001-6392-7944
authors.initials: AI
authors.lastname: Shepherd
authors.affiliation: College of Life and Environmental Sciences, Sport and Health Sciences, University of Exeter, Devon, United Kingdom;
authors.forename: Daryl P
authors.initials: DP
authors.lastname: Wilkerson
authors.affiliation: University of Exeter Medical School and NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital, Exeter, Devon, United Kingdom;
authors.forename: Jon
authors.initials: J
authors.lastname: Fulford
authors.affiliation: University of Exeter Medical School and NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital, Exeter, Devon, United Kingdom;
authors.forename: Paul G
authors.initials: PG
authors.lastname: Winyard
authors.affiliation: University of Exeter Medical School and NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital, Exeter, Devon, United Kingdom; Torbay Hospital, Heart and Lung Unit, Torquay, Devon, United Kingdom; and.
authors.forename: Nigel
authors.initials: N
authors.lastname: Benjamin
authors.affiliation: University of Exeter Medical School and NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital, Exeter, Devon, United Kingdom;
authors.forename: Angela C
authors.initials: AC
authors.lastname: Shore
authors.affiliation: University of Exeter Medical School and NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital, Exeter, Devon, United Kingdom;
authors.forename: Mark
authors.identifier: 0000-0002-0284-6048
authors.initials: M
authors.lastname: Gilchrist
mesh_terms: D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008099:Liver / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage* / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D009566:Nitrates; D009569:Nitric Oxide
keywords: C-peptide; glucose; incretin; nitrate; nitric oxide