title: Pomegranate extract (POMx) decreases the atherogenicity of serum and of human monocyte-derived macrophages (HMDM) in simvastatin-treated hypercholesterolemic patients: a double-blinded, placebo-controlled, randomized, prospective pilot study.
abstract: OBJECTIVE
  To analyze pomegranate extract (POMx) effects on serum and on human HMDM atherogenicity in simvastatin - treated hypercholesterolemic patients.
  
  
  RESULTS
  Patients were randomly assigned to receive either simvastatin (20 mg/day) + vegan placebo pill (n = 11), or simvastatin (20 mg/day) + POMx pill (1g/day, n = 12). Fasting blood samples were collected at baseline and after 1 and 2 months of therapy. HMDM were collected from 3 patients in each group at baseline and after 2 months of therapy, as well as from 3 healthy subjects. After 2 months of therapy, serum LDL-cholesterol levels significantly decreased, by 23%, in the simvastatin + placebo group, and by 26% in the simvastatin + POMx group. Simvastatin + POMx therapy increased serum thiols concentration by 6%. Patients' HMDM reactive oxygen species (ROS) levels were significantly increased, by 69%, vs. healthy subjects HMDM. After 2 months of therapy, HMDM ROS levels decreased by 18% in the simvastatin + placebo group, whereas in the simvastatin + POMx group it decreased by up to 30%. A novel finding was the triglycerides levels in the patients' HMDM at baseline which were significantly higher, by 71%, vs. healthy subjects HMDM. The simvastatin + POMx, but not the simvastatin + placebo therapy, significantly reduced macrophage triglycerides content by 48%, vs. baseline levels. In addition, whereas the simvastatin + placebo therapy significantly decreased the patients' HMDM cholesterol biosynthesis rate by 33%, the simvastatin + POMx therapy further decreased it, by 44%.
  
  
  CONCLUSIONS
  The addition of POMx to simvastatin therapy in hypercholesterolemic patients improved oxidative stress and lipid status in the patient's serum and in their HMDM. These anti-atherogenic effects could reduce the risk for atherosclerosis development.
authors.affiliation: Internal Medicine E Department, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Shadi
authors.initials: S
authors.lastname: Hamoud
authors.affiliation: Internal Medicine E Department, Rambam Health Care Campus, Haifa, Israel; The Lipid Research Laboratory, Rambam Health Care Campus, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Tony
authors.initials: T
authors.lastname: Hayek
authors.affiliation: The Lipid Research Laboratory, Rambam Health Care Campus, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Nina
authors.initials: N
authors.lastname: Volkova
authors.affiliation: Stat Laboratory, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Judith
authors.initials: J
authors.lastname: Attias
authors.affiliation: Internal Medicine E Department, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Danit
authors.initials: D
authors.lastname: Moscoviz
authors.affiliation: The Lipid Research Laboratory, Rambam Health Care Campus, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Mira
authors.initials: M
authors.lastname: Rosenblat
authors.affiliation: The Lipid Research Laboratory, Rambam Health Care Campus, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: aviram@tx.technion.ac.il.
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
mesh_terms: D000328:Adult; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D002460:Cell Line; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004357:Drug Synergism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008055:Lipids / Q000097:blood; D029561:Lythraceae / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010865:Pilot Projects; D010936:Plant Extracts / Q000008:administration & dosage*; D011446:Prospective Studies; D017382:Reactive Oxygen Species; D019821:Simvastatin / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014280:Triglycerides; D019821:Simvastatin; D010100:Oxygen
keywords: Cholesterol; Hypercholesterolemia; Macrophages; Oxidative stress; Pomegranate; Triglyceride