Diet enrichment with calcium and magnesium enhances the cholesterol-lowering effect of plant sterols in obese Zucker rats.

ABSTRACT

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.