A Combination Therapy Including Psyllium and Plant Sterols Lowers LDL Cholesterol by Modifying Lipoprotein Metabolism in Hypercholesterolemic Individuals1

2 Department of Nutritional Sciences and 3 Department of Kinesiology, University of Connecticut, Storrs, CT 06269; 4 Medicus Research LLC, Northdrige, CA 91325; and 5 Liposcience Inc., Raleigh, NC 27616

* To whom correspondence should be addressed. E-mail: maria-luz.fernandez@uconn.edu.

We conducted a randomized, double blind, crossover, placebo-controlled study to determine the effects of a combination therapy including plant sterols (PS) and psyllium (PSY), provided via cookies, on plasma lipids and on the size and subfraction distribution of VLDL, LDL, and HDL. Thirty-three healthy free-living individuals (11 males and 22 females), aged 35–65 y, with a BMI between 25 and 35 kg/m2 and initial plasma LDL cholesterol (LDL-C) concentrations between 2.6 and 4.1 mmol/L (100 and 160 mg/dL), were randomly assigned to receive treatment cookies (7.68 g/d PSY and 2.6 g/d PS) or placebo cookies (0 g PSY+PS) for 4 wk. After a 3-wkwashout period, subjects received the other cookies for an additional 4 wk. Plasma total cholesterol concentrations were significantly reduced for all subjects, from 5.65 ± 0.72 mmol/L after the placebo period to 5.28 ± 0.76 mmol/L after the PSY+PS cookie period (P < 0.01). These reductions were primarily in LDL-C, which decreased from 3.48 ± 0.70 to 3.14 ± 0.78 mmol/L after PSY+PS cookie consumption (P < 0.01). Intakeof the PSY+PS cookie decreased the number of intermediate density lipoprotein (IDL), LDL, and HDL particles (P< 0.05) and plasma apo B concentrations (P < 0.01). The decreases in LDL and HDL particles were in the small subfractions. Because smaller LDL particles are associated with an increased risk of heart disease and because smaller HDL particles are indicative of diminished reverse cholesterol transport, we conclude that the combination therapy resulted in a less atherogenic lipoprotein profile. In addition, the evaluation of lipoprotein subfractions resulting from the action of the fiber and plant sterols in the intestinal lumen provides an insight on the secondary mechanisms of plasma LDL-C lowering.

J. Nutr. 136:2492-2497, October 2006

A Combination of Psyllium and Plant Sterols Alters Lipoprotein Metabolism in Hypercholesterolemic Subjects by Modifying the Intravascular Processing of Lipoproteins and Increasing LDL Uptake1,2

Departments of 3 Nutritional Sciences and 4 Kinesiology, University of Connecticut, Storrs, CT 06269

* To whom correspondence should be addressed. E-mail: maria-luz.fernandez@uconn.edu.

We previously demonstrated that a diet therapy involving consumption of 7.28 g psyllium (PSY) and 2 g of plant sterols (PS) per day reduced LDL cholesterol from 3.6 ± 0.7 to 3.1 ± 0.8 mmol/L (P < 0.01) and decreased the number of intermediate density lipoprotein particles and the smaller LDL and HDL subfractions in hypercholesterolemic individuals (n = 33). The study design was a randomized double blind crossover. Subjects consumed either 2 test cookies containing PSY+PS or 2 placebo cookies for 1 mo with a 3-wk wash out between treatments. To explore mechanisms of the lipid-lowering effects of combined PSY+PS, we presentdata related to intravascular and molecular regulation. Intake of PSY+PS decreased the cholesterol concentration in LDL-1 from 2.46 ± 0.66 to 2.26 ± 0.46 mmol/L and in LDL-2 from 0.63 ± 0.24 to 0.54 ± 0.27 mmol/L (P < 0.05) in the test compared with the placebo period. An increase in LDL peak size from 27.3 ± 0.8 to 27.5 ± 0.6 nm (P < 0.05) and a decrease in the prevalence of LDL pattern B from 27 to 18% (P < 0.05) also occurred during the PSY+PS period. Cholesteryl ester transfer protein activity was 11% lower (P < 0.05) during the test period. Notably, the abundance of the LDL receptor in circulating mononuclear cells as measured by real time PCR was 26% higher during the test compared with the placebo period (P < 0.03). These results indicate that the hypocholesterolemic action of PSY and PS can be explained in part by modifications in the intravascular processing oflipoproteins and by increases in LDL receptor-mediated uptake.

J. Nutr. 137:1165-1170, May 2007