Combination of dietary phytosterols plus niacin or fenofibrate: effects on lipid profile and atherosclerosis in apo E-KO mice

J Nutr Biochem. 2005 Apr;16(4):222-8. doi: 10.1016/j.jnutbio.2004.12.003.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Arteriosclerosis / pathology
  • Arteriosclerosis / prevention & control*
  • Body Weight / drug effects
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Diet
  • Fenofibrate / administration & dosage
  • Fenofibrate / pharmacology*
  • Hypolipidemic Agents / pharmacology
  • Lipid Metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Niacin / administration & dosage
  • Niacin / pharmacology*
  • Phytosterols / administration & dosage
  • Phytosterols / pharmacology*
  • Triglycerides / blood

Substances

  • Apolipoproteins E
  • Cholesterol, HDL
  • Hypolipidemic Agents
  • Phytosterols
  • Triglycerides
  • Niacin
  • Cholesterol
  • Fenofibrate