title: Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit.
authors.forename: Shanti
authors.initials: S
authors.lastname: Velmurugan
authors.affiliation: William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit.
authors.forename: Jasmine Ming
authors.initials: JM
authors.lastname: Gan
authors.affiliation: William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit.
authors.forename: Krishnaraj S
authors.initials: KS
authors.lastname: Rathod
authors.affiliation: William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit.
authors.forename: Rayomand S
authors.initials: RS
authors.lastname: Khambata
authors.affiliation: William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit.
authors.forename: Suborno M
authors.initials: SM
authors.lastname: Ghosh
authors.affiliation: William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit.
authors.forename: Amy
authors.initials: A
authors.lastname: Hartley
authors.affiliation: William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit.
authors.forename: Sven
authors.initials: S
authors.lastname: Van Eijl
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom; and.
authors.forename: Virag
authors.initials: V
authors.lastname: Sagi-Kiss
authors.affiliation: Barts National Health Service Trust, Department of Diabetes and Metabolic Medicine, The Royal London Hospital, London, United Kingdom.
authors.forename: Tahseen A
authors.initials: TA
authors.lastname: Chowdhury
authors.affiliation: Institute of Dentistry, and.
authors.forename: Mike
authors.initials: M
authors.lastname: Curtis
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom; and.
authors.forename: Gunter G C
authors.initials: GG
authors.lastname: Kuhnle
authors.affiliation: Blizard Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom;
authors.forename: William G
authors.initials: WG
authors.lastname: Wade
authors.affiliation: William Harvey Research Institute, National Institute for Health Research Cardiovascular Biomedical Research Unit, a.ahluwalia@qmul.ac.uk.
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000517:prevention & control; D001419:Bacteria / Q000378:metabolism; D027461:Beta vulgaris / Q000737:chemistry*; D001792:Blood Platelets / Q000378:metabolism; D004032:Diet; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009061:Mouth Mucosa / Q000382:microbiology; D009566:Nitrates / Q000494:pharmacology* / Q000627:therapeutic use; D009573:Nitrites / Q000378:metabolism; D019007:P-Selectin / Q000097:blood; D012463:Saliva / Q000382:microbiology; D014664:Vasodilation / Q000187:drug effects*; D014675:Vegetables / Q000737:chemistry*
chemical_list: D009566:Nitrates; D009573:Nitrites; D019007:P-Selectin; C546937:SELP protein, human
keywords: endothelium; microbiome; nitric oxide; vascular; vegetable