ABSTRACT
Phytosterols are plant sterols. The most abundant dietary phytosterols are betasitosterol, campesterol, and stigmasterol (Figure 12.1). These are structurally related to cholesterol, but are not made by humans. In humans, the only source of phytosterols is diet and there is only limited absorption of dietary phytosterols. Whereas approximately 50% of dietary cholesterol is absorbed, less than 20% of dietary campesterol and less than 7% of dietary beta-sitosterol are absorbed. The limited absorption of dietary phytosterols is mediated by the cholesterol transporter in the proximal jejunum localized on the surface of the absorptive enterocytes.1 This common transporter has been identified as Niemann-Pick C1 like 1 protein.1 The transporter is selectively inhibited by ezetimibe, a drug marketed as Zetia for the reduction of cholesterol absorption and for the treatment of sitosterolemia.2 Despite the fact that the bulk of phytosterols is transported by
the same transporter as cholesterol, the normal low net absorption of phytosterols is the result of selective rapid efflux of phytosterols into the bile and intestinal lumen via the ATP binding cassette co-transporters ABCG5 and ABCG8, expressed on the apical surface of enterocytes as well as hepatocytes.3-5 Experimental support for this model comes in part from the observation that ABCG5-null mice have significantly elevated levels of beta-sitosterol (37-fold) and campesterol (7.7-fold) compared to wild-type controls.6 Furthermore, there is clear evidence for a strong founder effect for a novel ABCG8 mutation in dyslipidemic individuals on the Micronesian island of Kosrae.7 Heterozygotes and homozygotes for the mutated ABCG8 allele exhibit increased plasma phytosterol levels.7 However, despite the mechanisms for rapid efflux of absorbed dietary phytosterols, significant levels of phytosterols circulate in the blood of normal, healthy individuals. The concentration of plasma beta-sitosterol in humans ranges from 0.005 to 0.024 mmol/L, depending on diet; whereas in sitosterolemic patients the mean baseline circulating levels of beta-sitosterol and campesterol average 0.50 and 0.27 mmol/L, respectively.2,7
Phytosterols from breads and cereals are bioavailable. In a study of 35 healthy subjects that was designed to measure the effects on serum lipids of diets containing high phytosterol, plasma concentrations of beta-sitosterol and campesterol increased significantly while subjects were on a defined diet.8 The study design monitored sterol levels during a 2-week baseline period during which subjects consumed diets of phytosterol-free foods and then a 12-week period during which subjects consumed phytosterol-enriched foods, averaging 6.6 g phytosterol intake/day. Plasma levels of beta-sitosterol and campesterol were 3.32
± 1.47 and 3.14
± 1.53 mg/L at baseline and increased to 5.00
± 1.86 and 6.62
± 2.48 mg/L, respectively, after 12 weeks of a diet high in phytosterols. In a separate study, Muti et al.9 evaluated whether plant food-based diets might increase serum phytosterol levels in postmenopausal women. In this study, subjects consuming diets high in nuts, seeds, and soy for 11 to 16 weeks, without caloric changes, exhibited increases in serum beta-sitosterol up to 20%, confirming the bioavailability of phytosterols from these dietary sources.
