title: Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells.
abstract: OBJECTIVE
  Cranberry juice (CJ) contains a remarkably high concentration of polyphenols, considered to be beneficial for cardiovascular and bone health. The current double-blind, randomized study was designed to test whether daily consumption of double-strength Ocean Spray light CJ (2 × 230 ml) over 4 months has beneficial effects on vascular function and on endothelial progenitor cells (EPCs) carrying the osteoblastic marker osteocalcin in particular.
  
  
  METHODS
  A total of 84 participants (49.5 ± 16.2 years) with peripheral endothelial dysfunction and cardiovascular risk factors were enrolled in this double-blind, randomized, controlled trial (69 completed the 4-month protocol-32 in the CJ group and 37 in the placebo group, respectively). Vascular responses to reactive hyperemia were measured non-invasively by peripheral arterial tonometry (EndoPAT). Peripheral blood mononuclear cells were stained for EPC markers, as well as osteocalcin, and counted by flow cytometry.
  
  
  RESULTS
  Baseline characteristics were similar in both groups. The effect of CJ on peripheral endothelial function and on circulating EPC counts (CD34(+)/CD133(+)/KDR(+)) did not change during the study. A high percentage of EPCs expressed osteocalcin (59.4 ± 35.7%). CJ, as compared to placebo, induced a decrease in the fraction of EPCs expressing osteocalcin (-8.64 ± 48.98 and 19.13 ± 46.11%, respectively, p = 0.019). Systemic levels of the adhesion marker ICAM correlated significantly with the number of EPCs expressing osteocalcin.
  
  
  CONCLUSIONS
  The study demonstrated that long-term supplementation of polyphenol-rich CJ did not improve peripheral endothelial function. However, the decrease in the fraction of osteocalcin+ EPCs suggests a potential beneficial effect of polyphenol-rich CJ.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic and College of Medicine, 200 1st Street SW, Rochester, MN 55905, USA.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Flammer
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Martin
authors.forename: Mario
authors.initials: M
authors.lastname: Gössl
authors.forename: R Jay
authors.initials: RJ
authors.lastname: Widmer
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Lennon
authors.forename: Jasmine A
authors.initials: JA
authors.lastname: Sexton
authors.forename: Darrell
authors.initials: D
authors.lastname: Loeffler
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000328:Adult; D000368:Aged; D001628:Beverages / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism*; D059808:Polyphenols / Q000008:administration & dosage*; D012307:Risk Factors; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D029799:Vaccinium macrocarpon / Q000737:chemistry*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D015675:Osteocalcin; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein