Combination of dietary phytosterols plus niacin or fenofibrate: effects on lipid profile and atherosclerosis in apo E-KO mice.
Patients with mixed dyslipidemias (increased LDL cholesterol and triglyceride as well as low HDL cholesterol levels) benefit from a combination of lipid-modifying drugs such as statins, niacin, fibrates and ezetemibe. However, safety, tolerability and cost are a concern in drug combination therapy. Dietary phytosterols reduce LDL cholesterol, and niacin or fenofibrate primarily reduces triglyceride and increases HDL-cholesterol levels. Thus, we hypothesized that a combination of phytosterols with niacin or fenofibrate will synergistically impact lipoprotein profile and atherogenesis in apo E-KO mice. Phytosterols alone significantly reduced plasma total cholesterol levels (14.1 vs. 16.9 mmol/L, P < .05) and the extent of atherosclerosis (0.42 vs. 0.15 mm(2), P < .05). The addition of fenofibrate to phytosterols increased plasma total cholesterol levels by >50% (14.1 vs. 21.6 mmol/L, P < .05) and decreased HDL-cholesterol concentrations by 50% (0.8 vs. 0.4 mmol/L). These changes were accompanied by slight reductions in the extent of atherosclerosis (0.42 vs. 0.34 mm(2), P > 0.05) as compared to controls, suggesting other potential anti-atherogenic effects of fenofibrate. Unlike fenofibrate, niacin caused an increase of 150% (P < .05) in HDL-cholesterol concentrations and a decrease of 22% (P < .05) in total cholesterol levels which were associated with significant reductions (65%, P < .05) in atherosclerotic lesion size as compared to controls. Neither the addition of niacin nor of fenofibrate reduced plasma triglyceride levels. In conclusion, the addition of niacin to phytosterols synergistically increases HDL-cholesterol levels, while a combination of phytosterols and fenofibrate results in no synergistic effects in apo E-KO mice. Further studies in other animal models are needed to establish synergetic effects between these lipid-modifying dietary and pharmacological agents.
Yeganeh
Behzad
B
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6.
Moshtaghi-Kashanian
Ghollam-Reza
GR
Declercq
Vanessa
V
Moghadasian
Mohammed H
MH
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet; D011345:Fenofibrate / Q000008:administration & dosage / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D010840:Phytosterols / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D010840:Phytosterols; D014280:Triglycerides; D009525:Niacin; D002784:Cholesterol; D011345:Fenofibrate