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Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering effects and safety of two different plant sterol preparations, an orally administered microcrystalline plant sterol suspension (MPS) in rapeseed oil and a powdered plant sterol supplement, in obese Zucker rats. Dietary plant sterol supplements (0.5%, w/w) were given concurrently with a high cholesterol diet (HCD, 1% cholesterol and 18% fat, w/w). No significant changes in serum triglyceride, blood glucose, serum glutamate oxaloacetic transaminase and glutamic pyruvic transaminase values or body and liver weights were observed. The powdered plant sterol supplement lowered the serum cholesterol by 25% (P < 0.05) and the MPS diet by 35% (P < 0.001) compared with HCD by the end of the 12-week experiment. Interestingly, the plant sterol supplements also produced a marked reduction in serum ubiquinone levels, suggesting a possible effect on isoprene synthesis. Unlike the powdered plant sterol, both MPS and plain rapeseed oil decreased the serum baseline diene conjugation values, suggesting that they protect against oxidative stress-induced lipid peroxidation in rats. This lipid peroxidation diminishing effect is probably due to some antioxidative components in rapeseed oil. These findings indicate that an unesterified plant sterol, such as the microcrystalline suspension in oil, effectively prevents cholesterol absorption in obese Zucker rats.

Ca may interfere with fat and cholesterol metabolism through formation of insoluble soaps with fatty and bile acids in the intestine. In the present study, we examined the effects of different dietary Ca levels on the serum lipid profile and cholesterol metabolism in obese Zucker rats fed a low-fat diet. We also tested whether dietary Ca interfered with the lipid-lowering effects of a pine oil-derived plant sterol mixture. Increase in dietary Ca intake from 0.2 to 0.8%, and further to 2.1% (w/w) dose-dependently decreased serum total cholesterol (r -0.565, P=0.002, n 27), LDL-cholesterol (r -0.538, P=0.006, n 25), and triacylglycerol (r -0.484, P=0.014, n 25) concentrations, and increased HDL-cholesterol (r -0.478, P=0.016, n 25) and HDL: LDL cholesterol (r 0.672, P<0.001, n 25) in rats fed a 1% cholesterol diet. Analysis of serum campesterol: cholesterol and sitosterol: cholesterol suggested that Ca dose-dependently increased intestinal cholesterol absorption (r 0.913, P<0.001, n 18), whereas serum desmosterol: cholesterol and lathosterol: cholesterol indicated that Ca dose-dependently increased endogenous cholesterol synthesis (r 0.691, P=0.003, n 18). Therefore, the decrease of serum LDL-cholesterol appeared to be due to Ca-induced increase in the conversion of cholesterol to bile acids. The increase in Ca intake did not interfere with the beneficial effects of plant sterols on serum total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. The high-Ca diet with plant sterol supplementation further increased the HDL-cholesterol concentration and HDL: LDL cholesterol. The present findings indicate that the beneficial effects of dietary Ca on the serum lipid profile during a low-fat diet are dose-dependent, and resemble those of bile acid sequestrants. Increased dietary Ca did not impede the lipid-lowering effects of natural plant sterols.

In most hypertensive rat models, serum total cholesterol is typically low and the cholesterol is primarily in the HDL rather than the LDL fraction. This difference from humans usually makes these animals unsuitable for experimental atherosclerosis studies. In the present study, we induced severe hypercholesterolemia including a 10-fold increase in serum LDL cholesterol, endothelial dysfunction and hypertension as well as vascular and renal damage in obese Zucker rats by feeding a human-type high fat, high cholesterol and high salt diet (butter 18, cholesterol 1 and NaCl 6 g/100 g dry weight). Supplementation of this atherogenic diet with plant sterols (1 g/100 g) and replacing the NaCl partially by calcium, magnesium and potassium effectively prevented the diet-induced increases in total and LDL cholesterols and 24-h systolic and mean blood pressures, and markedly improved endothelial function. Plant sterols and the minerals also protected against vascular and renal damage and extended the life span of the obese Zucker rats by 60% compared with the rats fed the atherogenic diet. Our findings suggest that human-type cardiovascular disorders can be induced in obese Zucker rats by feeding a human-type atherogenic diet. This seems to be a suitable animal model for experimental studies on atherosclerosis and hypertension as well as for evaluating new dietary approaches to reducing cardiovascular risk.

Background and Aim: Recent clinical studies have demonstrated that plant sterols moderately lower serum cholesterol levels in patients with mild hypercholesterolemia. Furthermore, there is evidence suggesting that mineral nutrients, such as calcium and magnesium, may also decrease serum cholesterol concentrations. In this study, we tested the hypothesis that supplementation with mineral nutrients may enhance the cholesterol-lowering effect of plant sterols in obese Zucker rats. Furthermore, we compared the lipid-lowering effects of monovalent sodium and potassium cations with those of divalent calcium and magnesium cations., Methods and Results: A Western-type high-fat/high-cholesterol diet increased serum cholesterol by 175% and liver cholesterol by 65% in comparison with a low-fat/low-cholesterol control diet. On the contrary, the high-fat/high-cholesterol diet decreased intestinal cholesterol absorption, as assessed by means of serum campesterol-, sitosterol-, and sitostanol-to-cholesterol ratios, thus indicating that it was under negative feedback regulation. Supplementation of the high-fat/high-cholesterol diet with plant sterols or mineral nutrients partially prevented the diet-induced increased in serum cholesterol and, when given concurrently, their cholesterol-lowering effect was enhanced. Their combination also effectively prevented the diet-induced increase in liver cholesterol concentration, and had beneficial effects on liver and myocardial hypertrophy, and the development of obesity. These beneficial effects were at least partially mediated by an enhanced blockade of intestinal cholesterol absorption. Interestingly, only divalent cations enhanced the cholesterol-lowering effect of plant sterols, thus supporting the idea that the lipid-lowering effect of divalent cations is related to the formation of insoluble and inabsorbable calcium and magnesium chelates with fatty acids., Conclusions: Our findings indicate that the cholesterol-lowering effect of plant sterols is enhanced by the co-administration of divalent calcium and magnesium cations but not by monovalent sodium and potassium cations.