Effects of a novel hydrophilic phytostanol analog on plasma lipid concentrations in gerbils

This study was designed to determine the effects of a novel hydrophilic phy tostanol analog, FM-VP4, on total plasma cholesterol, total plasma triglyce ride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprote in (HDL) cholesterol concentrations after acute oral administration to gerb ils. Gerbils were administered a standard gerbil diet for 4 continuous week s, and daily water and food intake was. monitored and replaced. The diet co ntained either no FM-VP4 (control) or FM-VP4 at the following concentration s: 0.25, 0.50, 1.0, or 2.0% w/w; six gerbils were fed each diet formulation . After 4 weeks of receiving a single diet formulation, blood was obtained from each gerbil by cardiac puncture and the animals were sacrificed humane ly. Plasma obtained from this blood was analyzed for total cholesterol, tot al triglyceride, and HDL cholesterol levels by standard enzymatic and preci pitation techniques. LDL cholesterol levels were calculated using the Fried ewald equation. Administration of dietary FM-VP4 resulted in significant de creases in total plasma cholesterol and LDL cholesterol concentrations comp ared with controls. Dietary FM-VP4 at concentrations of 1% and 2%. (w/w) de creased total plasma cholesterol by 3.4 mmol/L compared with controls. This decrease was entirely due to the loss of cholesterol from the LDL pool bec ause LDL cholesterol was decreased by 3.3 and 3.2 mmol/L after 1% and 2% (w /w) FM-VP4, respectively. There were no significant changes in plasma trigl yceride or HDL cholesterol concentrations after the administration of FM-VP 4. Animals administered 1% or 2% (w/w) FM-VP4 also had significantly lower body weight after 4 weeks of treatment compared with the other groups. Howe ver, no unusual behavior was observed in these animals. No major difference s in daily water or food intake were observed throughout the study. These f indings indicate that FM-VP4 decreases total and LDL cholesterol concentrat ions. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association .