title: Combined effects of ezetimibe and phytosterols on cholesterol metabolism: a randomized, controlled feeding study in humans.
abstract: BACKGROUND
  Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that the combination of ezetimibe and phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism.
  
  
  RESULTS
  Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple-crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo+phytosterol placebo, (2) 10 mg/d ezetimibe+phytosterol placebo, and (3) 10 mg/d ezetimibe+2.5 g phytosterols for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and low-density lipoprotein cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/d; 95% confidence interval [CI], 368 to 828) relative to control (2161 mg/d; 95% CI, 1112 to 3209) and ezetimibe alone (1054 mg/d; 95% CI, 546 to 1561; both P<0.0001). Fecal cholesterol excretion was significantly greater (P<0.0001) with combined treatment (962 mg/d; 95% CI, 757 to 1168) relative to control (505 mg/d; 95% CI, 386 to 625) and ezetimibe alone (794 mg/d; 95% CI, 615 to 973). Plasma low-density lipoprotein cholesterol values during treatment with control, ezetimibe alone, and ezetimibe+phytosterols averaged 129 mg/dL (95% CI, 116 to 142), 108 mg/dL (95% CI, 97 to 119), and 101 mg/dL (95% CI, 90 to 112; (P<0.0001 relative to control).
  
  
  CONCLUSIONS
  The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma low-density lipoprotein cholesterol. The large cumulative action of combined dietary and pharmacological treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00863265.
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lin
authors.forename: Susan B
authors.initials: SB
authors.lastname: Racette
authors.forename: Michael
authors.initials: M
authors.lastname: Lefevre
authors.forename: Lina
authors.initials: L
authors.lastname: Ma
authors.forename: Catherine Anderson
authors.initials: CA
authors.lastname: Spearie
authors.forename: Karen
authors.initials: K
authors.lastname: Steger-May
authors.forename: Richard E
authors.initials: RE
authors.lastname: Ostlund
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics*; D008078:Cholesterol, LDL / Q000097:blood; D003131:Combined Modality Therapy; D004357:Drug Synergism; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy*; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D010840:Phytosterols; D000069438:Ezetimibe