title: Inorganic Nitrate Supplementation in Young and Old Obese Adults Does Not Affect Acute Glucose and Insulin Responses but Lowers Oxidative Stress.
abstract: BACKGROUND
  Aging and obesity are associated with raised oxidative stress and a reduction of nitric oxide (NO) bioavailability, with subsequent decline in insulin sensitivity and endothelial function. Inorganic nitrate is converted into NO via a 2-step reduction process and may be an effective nutritional intervention to modify vascular and metabolic functions.
  
  
  OBJECTIVE
  This study tested whether inorganic nitrate supplementation improved glucose disposal and attenuated the acute effects of hyperglycemia on oxidative stress, inflammation, and vascular function in young and old obese participants.
  
  
  METHODS
  Ten young (aged 18-44 y) and 10 old (aged 55-70 y) obese participants consumed 75 g glucose followed by either potassium nitrate (7 mg/kg body weight) or potassium chloride (placebo) in a randomized, double-blind crossover design. Resting blood pressure (BP), endothelial function, and blood biomarkers were measured for 3 h postintervention. Biomarkers included plasma nitrate/nitrite (NOx), glucose, insulin, cyclic GMP, interleukin 6, 3-nitrotyrosine, E- and P-selectins, intercellular adhesion molecule 3 (ICAM-3), and thrombomodulin, as well as superoxide in freshly isolated peripheral blood mononuclear cells (PBMCs).
  
  
  RESULTS
  Inorganic nitrate supplementation did not affect plasma glucose (P = 0.18) or insulin (P = 0.26) responses. The increase in plasma NOx concentrations 3 h after the administration of inorganic nitrate was significantly higher in young than in old participants (234% increase compared with 149% increase, respectively, P < 0.001). Plasma 3-nitrotyrosine concentrations declined significantly after inorganic nitrate supplementation compared with placebo (3 h postdose, 46% decrease compared with 27% increase, respectively, P = 0.04), and a similar nonsignificant trend was observed for superoxide concentrations (3 h postdose, 16% decrease compared with 23% increase, respectively, P = 0.06). Plasma cyclic GMP, ICAM-3, and thrombomodulin concentrations differed between young and old participants (P < 0.01). Inorganic nitrate supplementation did not improve BP or endothelial function.
  
  
  CONCLUSIONS
  Oral supplementation with inorganic nitrate did not improve glucose and insulin responses but reduced oxidative stress in old individuals during acute hyperglycemia. This trial was registered at www.controlled-trials.com as ISRCTN42776917.
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine.|Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom; and.|College of Medicine, University of Al-Mustansiriyah, Baghdad, Iraq.
authors.forename: Ammar W
authors.initials: AW
authors.lastname: Ashor
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine.
authors.forename: Shakir
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine.
authors.forename: Clio
authors.initials: C
authors.lastname: Oggioni
authors.affiliation: Human Nutrition Research Centre, School of Agriculture, Food and Rural Development.
authors.forename: Othman
authors.initials: O
authors.lastname: Qadir
authors.affiliation: Human Nutrition Research Centre, School of Agriculture, Food and Rural Development.|Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Brandt
authors.affiliation: Institute for Cell and Molecular Biosciences.|Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
authors.forename: Abbas
authors.initials: A
authors.lastname: Ishaq
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine.|Research Councils UK Centre for Ageing and Vitality, and.|Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
authors.affiliation: Institute for Cell and Molecular Biosciences.|Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Saretzki
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, mario.siervo@ncl.ac.uk.|Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
authors.forename: Mario
authors.initials: M
authors.lastname: Siervo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D015415:Biomarkers; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage / Q000494:pharmacology*; D009765:Obesity / Q000378:metabolism*; D018384:Oxidative Stress; D011189:Potassium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D017680:Potassium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D009566:Nitrates; D017680:Potassium Compounds; D011189:Potassium Chloride; C023844:potassium nitrate
keywords: aging; dietary nitrate; endothelial function; inflammation; nitric oxide; obesity; reactive oxygen species