Lin X, Racette SB, Lefevre M, et al. Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans. Circulation 2011; doi:10.1161/circulationaha .110.006692.
doi: 10.1161/ CIRCULATIONAHA.110.006692
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Original Article
Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism
A Randomized, Controlled Feeding Study in Humans
Xiaobo Lin, PhD; Susan B. Racette, PhD; Michael Lefevre, PhD; Lina Ma, MS; Catherine Anderson Spearie, MHS, RD; Karen Steger-May, MA; Richard E. Ostlund Jr, MD
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Author Affiliations
. From the Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine (X.L., S.B.R., L.M., R.E.O.), Program in Physical Therapy (S.B.R.), Center for Applied Research Sciences (C.A.S.), and Division of Biostatistics (K.S.-M.), Washington University School of Medicine, St. Louis, MO, and Center for Advanced Nutrition, Utah State University, Logan (M.L.).
Correspondence to Richard E. Ostlund, Jr, MD, Washington University School of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Campus Box 8127, 660 S Euclid Ave, St. Louis, MO 63110. E-mail Rostlund@dom.wustl.edu
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.
Methods and 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).
Conclusion-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.
Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00863265.