Cholesterol lowering with sterols/stanols

Only a few clinical studies have been published on the effects of low-dose unesterified sterols or stanols. Miettinen and Vanhanen (1994) reported no effect (versus control) with free sterols. A study by Pelletier et al. (1995), in which free sterols were incorporated into butter, was a crossover study with no wash-out period. It found that plasma LDL cholesterol levels were 15% lower in those with a daily intake of 740 mg soy sterols in 50 g butter than in those consuming a control butter. Unfortunately, however, the control butter contained 18% more cholesterol than the sterol-enriched butter, and the paper reported no baseline values that would have allowed independent calculation of the relative serum cholesterol changes induced by the butter alone and by the butter plus free sterols. 

A similar effect is expected to be tme of sterol esters. The combined effect of adding stanol esters and increasing the ratio of polyunsaturated to saturated fatty acids in the diet was a 19% net reduction in semm LDL cholesterol levels, while adding stanol esters to the usual diet yielded a 12% reduction (Andersson et al., 1999 HaUikainen et al., 2000a). Thus, consumption of a spread with added sterol or stanol esters probably further enhances the cholesterol-lowering efficacy of a diet with an improved fatty acid profile. 

Most of the clinical studies on sterol esters and stanol esters have been carried out with typical doses of about 1-3 g/day. In combination, these data support the notion that an optimal serum LDL cholesterol-lowering effect is achieved at an intake in the region of 2 g/day, and that increasing the dose beyond this... 

Knowledge of the serum cholesterol-lowering ability of plant sterols began in the early 1950s but interest was revived with the paper published in The New England Journal of Medicine by Miettinen et al. in 1995 and the simultaneous launch of the first plant sterol-enriched food, Benecol margarine, in Finland. These events indicated the potential of foods enriched with plant stanol esters from the point of view of both clinical efficacy and commercial potential. 

The serum cholesterol-lowering effect of plant sterols and stanols has been proven in several clinical studies. The hypocholesterolemic effects have been verified in normocholesterolemic individuals, in individuals with mild to moderate hypercholesterolemia or with familial hypercholesterolemia, in women with coronary heart disease, and in men with non-insulin-dependent diabetes -in conjunction with cholesterol-lowering statin therapy and irrespective of the background diet. In addition, studies have been conducted with normocholesterolemic children and with children with slightly elevated cholesterol levels, or with familial hypercholesterolemia. 

A concern has been raised that phytosterol doses that are effective for cholesterol reduction may impair the absorption and lower blood concentrations of fat-soluble vitamins and antioxidants. A number of studies showed that phytosterols had no effect on plasma concentrations of vitamin D, retinol, or plasma-lipid-standardized alpha-tocopherol. Moreover, the reports of the effect of phytosterols on concentrations of blood carotenoids (lutein, lycopene, and alpha-carotene) are controversial. There seems to be general agreement that phytosterol doses >1 g/d significantly decrease LDL-C standardized beta-carotene concentrations however, it remains to be determined whether a reported 15-20% reduction in beta-carotene due to phytosterol supplementation is associated with adverse health effects. Noakes et al. found that consumption of one or more carotenoid-rich vegetable or fruit servings a day was sufficient to prevent lowering of plasma carotenoid concentrations in 46 subjects with hypercholesterolemia treated with 2.3 g of either sterol or stanol esters. 

A typical Western diet contains approximately 100-300 mg and 20-50 mg of plant sterol and plant stanol, respectively. The relationship between total dietary phytosterol content and the fatty acid composition of the diet decreases with increasing saturated fatty acids, whereas the total dietary phytosterol content increases with increasing PUFA (89). Fortification of lipid foods, such as margarine, with plant sterols will dramatically increase the daily intake of phytosterols and significantly lower serum cholesterol (90). The dietary consumption of large amounts of plant sterols will interfere with cholesterol absorption, thereby leading to an increased daily neutral steroid excretion. 

Phytosterols are nonnutrient bioactive substances and act as a structural component in the cell membranes, a role which in mammalian cells is played by cholesterol. The methyl or ethyl group at C-24 location makes them different from cholesterol [58]. They include plant sterols (unsaturated form) and plant stanols (saturated form). Both sterols and stanols are effective in lowering plasma total and LDL cholesterols and inhibit the absorption of cholesterol from the small intestine [59]. A wide spectrum of other biological activities in animals and humans has been reported, including anti-inflammatory [60], antibacterial [61], antioxidative [62], and anticancer activities [63]. P-Sitosterol, campesterol, stigmasterol, A -avenasterol, sitostanol, and campestanol are the most common representative members in this series. P-Sitosterol, campesterol, and stigmasterol are the major identified phytosterols in Brazil nut, with sitostanol, campestanol, and A -avenasterol present in trace amounts. 

It is still a matter of controversy whether plant sterols and stanols are equally efficient in reducing cholesterol levels [28]. Some studies have shown that despite their different bioavailability, there is no clinical relevance with regard to their effect on total cholesterol, LDL-c, HDL-cholesterol, or triglyceride levels [25, 29]. Nevertheless, other authors have suggested that the differences in efficacy between plant sterols and plant stanols remain in the long-term interventions rather than in the shortterm studies [30]. For instance, in a recent meta-analysis of randomized placebo-controlled trials, decreases in LDL-c concentrations were dose-dependent for plant stanols but not for sterols. Similarly, intakes of plant stanols higher than 2 g day have been associated with additional and dose-dependent reductions in LDL-c [26]. Yet, this effect remains questionable [29]. It has been proposed that the difference in efficiency between these two compounds may be explained by the fact that plant stanols may reside longer in the intestine due to their lower absorption [31]. 

These studies show that the combination of sterols or stanols with statins leads to a greater reduction in semm total and LDL cholesterol concentrations than statins alone - or, alternatively, allows a lowering of the statin dose. 

Plant sterols (phytosterols), especially 4-desmethyl sterols, have recently gained much scientific and commercial interest due to the introduction of plant sterol-enriched foods and dietary supplements with marked serum cholesterollowering efficacy. Due to the structural similarity between cholesterol and 4-desmethyl plant sterols, the intake of optimal amounts of plant sterols and stanols (saturated sterols) lowers intestinal cholesterol absorption and results in a 6-15% reduction in semm LDL cholesterol concentrations. 

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