title: The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension and endothelial dysfunction. Thus, dietary antioxidants may beneficially influence blood pressure (BP) and endothelial function by reducing oxidative stress.
  
  
  OBJECTIVE
  To determine if vitamin C and polyphenols, alone or in combination, can lower BP, improve endothelial function and reduce oxidative stress in hypertensive individuals.
  
  
  METHODS
  A total of 69 treated hypertensive individuals with a mean 24-h ambulatory systolic blood pressure > or = 125 mmHg participated in a randomized, double-blind, placebo-controlled, factorial trial. Following a 3-week washout, participants received 500 mg/day vitamin C, 1000 mg/day grape-seed polyphenols, both vitamin C and polyphenols, or neither for 6 weeks. At baseline and post-intervention, 24-h ambulatory BP, ultrasound-assessed endothelium-dependent and -independent vasodilation of the brachial artery, and markers of oxidative damage, (plasma and urinary F2-isoprostanes, oxidized low-density lipoproteins and plasma tocopherols), were measured.
  
  
  RESULTS
  A significant interaction between grape-seed and vitamin C treatments for effects on BP was observed. Vitamin C alone reduced systolic BP versus placebo (-1.8 +/- 0.8 mmHg, P = 0.03), while polyphenols did not (-1.3 +/- 0.8 mmHg, P = 0.12). However, treatment with the combination of vitamin C and polyphenols increased systolic BP (4.8 +/- 0.9 mmHg versus placebo; 6.6 +/- 0.8 mmHg versus vitamin C; 6.1 +/- 0.9 mmHg versus polyphenols mmHg, each P < 0.0001) and diastolic BP (2.7 +/- 0.6 mmHg, P < 0.0001 versus placebo; 1.5 +/- 0.6 mmHg, P = 0.016 versus vitamin C; 3.2 +/- 0.7 mmHg, P < 0.0001 versus polyphenols). Endothelium-dependent and -independent vasodilation, and markers of oxidative damage were not significantly altered.
  
  
  CONCLUSIONS
  Although the mechanism remains to be elucidated, these results suggest caution for hypertensive subjects taking supplements containing combinations of vitamin C and polyphenols.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia and West Australian Institute for Medical Research (WAIMR), Perth, Australia. nward@cyllene.uwa.edu.au
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Ward
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hodgson
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.forename: Valerie
authors.initials: V
authors.lastname: Burke
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Beilin
authors.forename: Ian B
authors.initials: IB
authors.lastname: Puddey
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D001916:Brachial Artery / Q000000981:diagnostic imaging; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000378:metabolism; D028441:F2-Isoprostanes / Q000097:blood / Q000652:urine; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000209:etiology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010636:Phenols / Q000627:therapeutic use*; D059808:Polyphenols; D024505:Tocopherols / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D028441:F2-Isoprostanes; D005419:Flavonoids; D008077:Lipoproteins, LDL; D010636:Phenols; D059808:Polyphenols; D001205:Ascorbic Acid; D024505:Tocopherols