The objective of this research was to examine the effects of sitosterol and sitostanol supplementation on plasma cholesterol levels and cholesterol metabolism in hypercholesterolemic subjects consuming a fixed foods diet in a four-phase crossover design. It was hypothesized that addition of either phytosterols, phytostenols, or a 50:50 mixture of sterols and stanols to butter would reduce circulating cholesterol levels, despite butter's hypercholesterolemic effect, through actions involving cholesterol absorption, synthesis, and turnover rates. The data obtained indicate that in their free, unesterified form, plant sterols and stanols lower plasma LDL cholesterol equivalently in hypercholesterolemic subjects. Results of this study provide new data that phytosterols and stanols function by suppressing cholesterol absorption while increasing cholesterol synthesis, however, the de-suppression in synthesis cannot fully compensate for the decrease in absorption making the treatment effective, thus may assist in the development of a food which offers health-promoting advantages related to the prevention of cardiovascular disease.

Background. A high ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, in addition to increased levels of small low-density lipoprotein (LDL) particles, are important indicators of cardiovascular disease risk. Therefore, interventions that combine the lowering of total cholesterol and raising of HDL cholesterol concentrations that also increase LDL particle size, may be preventive against cardiovascular disease. Plant sterols decrease total cholesterol and LDL cholesterol levels by 10-15%, while exercise increases HDL cholesterol levels by 4-22%. In view of their complementary effects, combining plant sterols with exercise would appear to be an effective lifestyle therapy to decrease the risk of future cardiovascular disease. / Objective. The aim of this study was to examine the independent and combined effects of plant sterols and exercise on blood lipid levels, and LDL particle size in previously sedentary, hypercholesterolemic adults. An additional objective of this trial was to assess the underlying mechanism by which this combination therapy modulates whole body cholesterol metabolism, to in turn improve lipid profiles. / Methods. In an 8-week, parallel-arm trial, 84 subjects were randomized to 1 of 4 interventions: (1) plant sterols and exercise,(2) plant sterols alone, (3) exercise alone, or (4) control. Blood lipid concentrations were measured using enzymatic kits, and LDL particle size was assessed using polyacrylamide gel electrophoresis. Cholesterol absorption and synthesis were determined using the single isotope single tracer technique and the deuterium incorporation approach, respectively. / Results. Plant sterol supplementation decreased (P < 0.01) total cholesterol concentrations by 8.2% when compared to baseline. Exercise increased (P < 0.01) HDL cholesterol levels by 7.5% while decreasing (P < 0.01) triglyceride concentrations by 13.3% when compared to baseline. Exercise reduced (P < 0.05) post-treatment LDL peak particle size from 255 to 253 A, and decreased (P < 0.05) the proportion of large LDL particles by 13.1%. Plant sterols had no effect on particle size distribution. Plant sterol supplementation decreased (P < 0.01) intestinal cholesterol absorption by 18%, while exercise had no effect on cholesterol absorption. Non-significant increases in cholesterol synthesis rates of 63%, 59%, and 57%, were observed in the combination, exercise, and plant sterol groups, respectively, relative to control. / Conclusion. These findings suggest that this combination therapy yields the most favourable alterations in lipid profiles when compared to each intervention alone. This combined intervention exerts its beneficial effects on lipid profiles by suppressing intestinal cholesterol absorption. Therefore, this lifestyle therapy may be an effective means of decreasing the risk of cardiovascular disease in hypercholesterolemic adults.

To evaluate the relative efficacy of plant sterols (PS) esterified with the fatty acids from fish oil (PS-FO), olive oil (PS-OO) and sunflower oil (PS-SO) on blood lipid and PS concentrations, 21 hyperlipidemic subjects were randomly assigned to each of five treatments for 28 days using a cross-over design. The results showed that: (1) in a comparison of olive oil (OO), fish oil (FO), PS-FO and PS-SO subgroup, PS-FO reduced triacylglycerols (TG) relative to PS-SO. Total cholesterol (T-C)/high-density lipoprotein cholesterol (HDL-C) ratio was reduced with PS-FO compared with FO. Plasma PS levels were increased with PS-SO and PS-FO. (2) in a comparison of OO, PS-SO and PS-OO subgroup, PS-OO had a larger decrease in T-C than OO, while PS-SO and OO reduced T-C equally. Both PS-SO and PS-OO elevated plasma PS levels. Overall, PS-FO and PS-OO have a higher potential for decreasing the risk of cardiovascular disease in hyperlipidemic subjects than PS-SO and OO supplementations.

Plant sterols are effective cholesterol-lowering agents; however, recent evidence suggests that this treatment may not be safe and beneficial in all individuals. This study determined whether high and low baseline circulating plasma campesterol and sitosterol are related to subsequent changes in plasma LDL-C, plant sterol or CRP levels, after accounting for plant sterol supplementation in hypercholesterolemic men (n=82). This trial was a 2-phase randomized cross-over design consisting of a controlled diet with and without a dose of 2.0 g/d of plant sterols over 4 weeks. There was no significant difference in plasma LDL-C, in the elevation of plasma plant sterol or in the changes of CRP levels for high and low groups, respectively. In view of these data, a supplement of 2.0 g/d of plant sterols should be viewed as a safe and beneficial cholesterol-lowering therapy for all individuals, with respect to their baseline plasma plant sterol levels.

The National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP II) unequivocally advocates an initial trial of dietary modification in both primary and secondary prevention prior to the institution of pharmacotherapy. Perhaps the rationale for this delay rests in the inherent, yet unsubstantiated, fear among clinicians that lifestyle change will be compromised in the presence of concurrent pharmacotherapy. However, the question of adherence to diet and exercise interventions following the initiation of lipid-lowering drug therapy has seemingly never been addressed scientifically. / It was therefore hypothesized that pharmacologically-treated patients with untreated hypercholesterolemia started on a program of lifestyle modification would achieve relatively less reduction in dietary fat intake and body weight, and participate less often in physical activity, if a pharmacologic agent was simultaneously prescribed. This was tested by a protocol in which these and related variables were assessed in participants who thought they were taking a lipid-lowering medication at diagnosis, compared to conventional initial treatment of diet and exercise alone. (Abstract shortened by UMI.)

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