title: Pleiotropic benefit of monomeric and oligomeric flavanols on vascular health--a randomized controlled clinical pilot study.
abstract: BACKGROUND
  Cardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man's deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded.
  
  
  METHODS
  In a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets.
  
  
  RESULTS
  In the MOF group serum total cholesterol and LDL decreased significantly (P ≤ 0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05) in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P ≤ 0.05).
  
  
  CONCLUSIONS
  Our integrative multi-biomarker approach unveiled the pleiotropic vascular health benefit of an 8 weeks supplementation with 200 mg/d MOF in humans.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00742287.
authors.affiliation: Department of Toxicology, Maastricht University, Maastricht, The Netherlands. a.weseler@maastrichtuniversity.nl
authors.forename: Antje R
authors.initials: AR
authors.lastname: Weseler
authors.forename: Erik J B
authors.initials: EJ
authors.lastname: Ruijters
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Drittij-Reijnders
authors.forename: Koen D
authors.initials: KD
authors.lastname: Reesink
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D019587:Dietary Supplements; D005340:Fibrinogen / Q000378:metabolism; D044948:Flavonols / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D027843:Vitis / Q000737:chemistry
chemical_list: D000975:Antioxidants; D044948:Flavonols; D008055:Lipids; D005340:Fibrinogen