Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.

To investigate the regulation of serum levels of cholesterol precursor sterols and plant sterols, these noncholesterol sterols, fatty acids, and various parameters of cholesterol metabolism were analyzed in 63 volunteers from a randomly selected Finnish male population sample of 100 subjects, aged 50 years, who had normal dietary habits. Serum levels of cholesterol precursors, desmosterol and lathosterol (in terms of micrograms/mg cholesterol), were negatively related to both the fractional and absolute absorption of dietary cholesterol and serum high density lipoprotein (HDL) cholesterol, and positively related to overall cholesterol synthesis and serum very low density lipoprotein (VLDL) cholesterol. Serum levels of the plant sterols, campesterol and sitosterol, exhibited positive correlations with the polyunsaturated/saturated fatty acid ratio of dietary fat, the linoleic acid contents of plasma and dietary lipids, the amount of dietary plant sterols (as indicated by fecal output), fractional and absolute absorption of dietary cholesterol, and HDL cholesterol, but were inversely related to the overall cholesterol synthesis and VLDL cholesterol. Stepwise multiple regression analysis revealed that the serum level of campesterol was associated with fractional cholesterol absorption, dietary plant sterols, and biliary cholesterol secretion, and that of sitosterol with dietary plant sterols, cholesterol synthesis, fractional cholesterol absorption, and biliary cholesterol secretion. Thus, the serum non-cholesterol sterols are significant indicators of cholesterol absorption and synthesis even under basal conditions and, since gas liquid chromatographic determination of these sterols is quite simple, their measurement may be valuable for monitoring cholesterol metabolism in large-scale epidemiologic studies.

Plant sterols are an essential component of the membranes of all eukaryotic organisms. They are either synthesised de novo or taken up from the environment. Their function appears to be to control membrane¯uidity and permeability, although some plant sterols have a speci®c function in signal transduction. The phytosterols are products of the isoprenoid pathway. The dedicated pathway to sterol synthesis in photosynthetic plants occurs at the squalene stage through the activity of squalene synthetase. Although the activity of 3-hydroxymethyl-3-glutaryl coenzyme A (HGMR) is rate-limiting in the synthesis of cholesterol, this does not appear to be the case with the plant sterols. Up-regulation of HGMR appears to increase the biosynthesis of cycloartenol but not the D 5-sterols. A decline in sterol synthesis is associated with a suppression of squalene synthetase activity, which is probably a critical point in controlling carbon¯ow and end-product formation. The major post-squalene biosynthetic pathway is regulated by critical rate-limiting steps such as the methylation of cycloartenol into cycloeucalenol. Little is known about the factors controlling the biosynthesis of the end-point sterol esters or stanols. The commonly consumed plant sterols are sitosterol, stigmasterol and campesterol which are predominantly supplied by vegetable oils. The oils are a rich source of the steryl esters. Less important sources of sterols are cereals, nuts and vegetables. The nutritional interest derives from the fact that the sterols have a similar structure to cholesterol, and have the capacity to lower plasma cholesterol and LDL cholesterol. Since the morbidity and mortality from cardiovascular disease have been dramatically reduced using cholesterol-lowering drugs (statins), the interest in plant sterols lies in their potential to act as a natural preventive dietary product. Stanols (saturated at C-5) occur in low amounts in the diet and are equally effective in lowering plasma cholesterol and do not cause an increase in plasma levels, unlike the sterols which can be detected in plasma.

Plant Stanols and Sterols for Cholesterol 965Mayo Clin Proc. 2003;78:965-978 965

Substituting sitostanol-ester margarine for part of the daily fat intake in subjects with mild hypercholesterolemia was effective in lowering serum total cholesterol and LDL cholesterol.

Plant sterols are an essential component of the membranes of all eukaryotic organisms. They are either synthesised de novo or taken up from the environment. Their function appears to be to control membrane fluidity and permeability, although some plant sterols have a specific function in signal transduction. The phytosterols are products of the isoprenoid pathway. The dedicated pathway to sterol synthesis in photosynthetic plants occurs at the squalene stage through the activity of squalene synthetase. Although the activity of 3‐hydroxymethyl‐3‐glutaryl coenzyme A (HGMR) is rate‐limiting in the synthesis of cholesterol, this does not appear to be the case with the plant sterols. Up‐regulation of HGMR appears to increase the biosynthesis of cycloartenol but not the Δ5‐sterols. A decline in sterol synthesis is associated with a suppression of squalene synthetase activity, which is probably a critical point in controlling carbon flow and end‐product formation. The major post‐squalene biosynthetic pathway is regulated by critical rate‐limiting steps such as the methylation of cycloartenol into cycloeucalenol. Little is known about the factors controlling the biosynthesis of the end‐point sterol esters or stanols. The commonly consumed plant sterols are sitosterol, stigmasterol and campesterol which are predominantly supplied by vegetable oils. The oils are a rich source of the steryl esters. Less important sources of sterols are cereals, nuts and vegetables. The nutritional interest derives from the fact that the sterols have a similar structure to cholesterol, and have the capacity to lower plasma cholesterol and LDL cholesterol. Since the morbidity and mortality from cardiovascular disease have been dramatically reduced using cholesterol‐lowering drugs (statins), the interest in plant sterols lies in their potential to act as a natural preventive dietary product. Stanols (saturated at C‐5) occur in low amounts in the diet and are equally effective in lowering plasma cholesterol and do not cause an increase in plasma levels, unlike the sterols which can be detected in plasma. © 2000 Society of Chemical Industry

Cholesterol lowering with simvastatin produced similar reductions in relative risk for major coronary events in women compared with men and in elderly (> or = 65 years of age) compared with younger patients. There were too few female deaths to assess the effects on mortality in women. Because mortality rates increased substantially with age, the absolute risk reduction for both all-cause and CHD mortality in simvastatin-treated subjects was approximately twice as great in the older patients.

beta-Sitosterol and campesterol were measured in serum lipoproteins of 17 subjects from two families. The serum levels of the two phytosterols were closely correlated with each other (r = 0.974), less consistently with serum cholesterol (r = 0.489), and not at all with serum triglycerides. As compared to cholesterol, serum free and esterified phytosterols tended to be accumulated in HDL where the phytosterol/cholesterol ratios were almost 40% higher than in VLDL and LDL. The serum phytosterol concentrations, the phytosterol/cholesterol ratios, especially in VLDL and LDL, and the fractional absorption of cholesterol were higher in women than in men. The levels of the phytosterols in whole serum and in each lipoprotein were significantly correlated with the percentage absorption of dietary cholesterol but were independent of the amount of dietary cholesterol and plant sterols. Our findings suggest that, in general, serum levels of noncholesterol sterols are effectively determined by the absorption which in turn is proportionate to the fractional absorption of cholesterol.