Efficacy of low dose of plant sterols
Tables 1 and 2 summarize recent human intervention clinical trials assessing the effects of 4-desmethyl free and esterified plant sterols. Doses of plant sterols reported in literature are often difficult to comprehend, particularly those reported in earlier literature. Herein, all doses refer to free plant sterol equivalent doses. If the contribution of naturally occurring plant sterols in the food vehicle was reported, this is then added to the free plant sterol dose. Ideally, the free plant sterol dose should be calculated experimentally using the average mol% of fatty acids relative to free sterols.
Selected studies 1990–1994
Vanhanen and Miettinen [27] in 1992 found a dose of 0.95 g of sitosterol per day, including the contribution of free sterols present in the canola oil used to prepare the basal spread, probably consumed in 2–3 doses, did not result in reduction in total cholesterol compared to control group. LDL cholesterol typically follows changes in total cholesterol, sometimes being more responsive to plant sterol modulation. Since the control spread contained 0.36 g of rape seed oil derived sterols, a level of consumption by vegetarians, the study is essentially comparing vegetarian levels of consumption of plant sterols to a 3-fold higher level. The conclusion from this study alone would be that a higher dose than 0.95 g of free sterols should be considered to achieve a more consistent and effective lowering of LDL cholesterol levels. In another study with a design similar to that of Vanhanen and Miettinen [27], the absolute reduction in LDL cholesterol was only statistically significant for the sitostanol esters, which showed slightly better efficacy than the free sterols and stanols [28]. The dose of 1.0 g sitosterol reduced cholesterol absorption more effectively than the control spread. This is not surprising because absorption is known to be an extremely sensitive marker that does not necessarily correlate to changes in LDL cholesterol levels [7,29-31]. Even basal levels of consumption of plant sterol are correlated with cholesterol absorption.
Vanhanen et al [32] showed that in mildly hypercholesterolemic men and women of age 33–60, 1.2 g of free tall stanol equivalents in mayonnaise decreased LDL levels by 7.7%. Relative to starting levels for this group, this reduction was statistically significant, but the absolute lowering of LDL was not statistically significant after accounting for reductions in LDL cholesterol observed with the control group. The lack of statistical significance in LDL lowering is not surprising because the total sample size was only 15 persons, and there was appreciable plant sterol, about 0.4 g, in the control mayonnaise, which probably reduced LDL cholesterol as well. The quantity of plant sterols in the control spread complicates interpretation of results and makes comparisons to other scientific studies more difficult.
Selected studies 1995–1999
Pelletier et al. [33] demonstrated that 0.7 g of soy sterols in spreads fed to 12 normocholesterolemic individuals reduced LDL cholesterol by 15.2% relative to the control. In another study [20], a dose of 0.8 g of soy sterols fed to 76 normocholesterolemic individuals reduced LDL cholesterol by 6.1% relative to the control, and more importantly, did not reduce carotenoids or carotenoids normalized to cholesterol, as reported by Hendriks et al. [19] with a similar dose of soy free sterol equivalents, administered as an ester. The LDL reductions reported by Sierksma et al. [20] were less than that seen in the Pelletier et al. [33] study, which used a similar dosage. The reduction in LDL in the Seerksma study was not seen in all subjects because of the well-known within person LDL variation of 10% [34] or solubilization issues. Nevertheless, this 6% reduction in LDL correlates with a 15% reduction in CHD risk at age 40, and a 6% reduction at age 70 [35] or a 10% reduction [36].
Hendriks et al [19] showed that in men and women with a wide range of ages and starting total cholesterol from low/normal to high, 0.83 g of free soy sterol equivalents in spreads decreased LDL cholesterol 6.2%. Interestingly, 0.83 g was less effective than the two higher doses,1.6 and 3.2 g of sterol equivalents, at reducing LDL cholesterol, but the differences amongst the three doses were not statistically significant. This study thus gives strong indication that a 0.8 g free sterol equivalent dose of plant sterols can efficaciously diminish LDL cholesterol. Nevertheless, the authors concluded that the 1.6 g dosage is most desirable because of the lack of effect on lipid normalized carotene, and the quantitatively greater reduction in LDL cholesterol.