Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses

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.

Efficacy and Safety of Plant Stanols and Sterols in the Management of Blood Cholesterol Levels

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

Plant sterols: biosynthesis, biological function and their importance to human nutrition.

Background— Ezetimibe has been shown to inhibit cholesterol absorption in animal models, but studies on cholesterol absorption in humans have not been performed thus far. Methods and Results— The effect of ezetimibe (10 mg/d) on cholesterol absorption and synthesis, sterol excretion, and plasma concentrations of cholesterol and noncholesterol sterols was investigated in a randomized, double-blind, placebo-controlled, crossover study in 18 patients with mild to moderate hypercholesterolemia. Treatment periods lasted 2 weeks with an intervening 2-week washout period. Fractional cholesterol absorption rates averaged 49.8±13.8% on placebo and 22.7±25.8% on ezetimibe, indicating a reduction of 54% (geometric mean ratio; P< 0.001). Cholesterol synthesis increased by 89% from 931±1027 mg/d on placebo to 1763±1098 mg/d on ezetimibe (P<0.001), while the ratio of lathosterol-to-cholesterol, an indirect marker of cholesterol synthesis, was increased by 72% (P<0.001). Bile acid synthesis was insignificantly increased...

Inhibition of Intestinal Cholesterol Absorption by Ezetimibe in Humans

▪ Abstract Phytosterols are cholesterol-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. They are absorbed only in trace amounts but inhibit the absorption of intestinal cholesterol including recirculating endogenous biliary cholesterol, a key step in cholesterol elimination. Natural dietary intake varies from about 167–437 mg/day. Attempts to measure biological effects in feeding studies have been impeded by limited solubility in both water and fat. Esterification of phytosterols with long-chain fatty acids increases fat solubility by 10-fold and allows delivery of several grams daily in fatty foods such as margarine. A dose of 2 g/day as the ester reduces low density lipoprotein cholesterol by 10%, and little difference is observed between Δ5-sterols and 5α-reduced sterols (stanols). Phytosterols can also be dispersed in water after emulsification with lecithin and reduce cholesterol absorption when added to nonfat foods. In contrast to these suppleme...

Phytosterols in human nutrition

. Intestinal absorption of cholesterol, campes-terol, campestanol, stigmasterol and sitosterol were measured in 10 healthy subjects by an intestinal perfusion technique over a 50 cm segment of the upper jejunum using sitostanol as non-absorbable marker. Cholesterol absorption was highest and averaged 33%, whereas the absorption rate of sitosterol averaged 4.2% and of stigmasterol 4.8%. Higher absorption rates were found for campesterol (9.6%). Canipestanol, the 5a saturated derivative of campesterol, showed the highest absorption rate (12.5%) of all plant sterols. A positive correlation between the absorption rate of cholesterol and campesterol was established. In addition, there was a negative correlation between the ratio of sitosterol to cholesterol and the mass of cholesterol absorption. These results are in agreement with previous observations in animal studies, namely, that increasing the length of the side-chain of cholesterol decreases the absorbability of the sterol. Surprisingly, campestanol, the 5α saturated derivate of campesterol, was shown to have higher absorbability compared with its unsaturated compound. This finding is in contrast to previous assumptions, that hydrogenisa-tion of the nucleus double bond of a sterol causes a decrease of absorbability, as has been demonstrated for cholesterol/cholestanol and sitosterol/sitostanol.

Comparison of intestinal absorption of cholesterol with different plant sterols in man

Abstract The transition to turbulence induced by counter-rotating wall-normal rotating cylindrical roughness pairs immersed within a laminar boundary layer on a flat plate is investigated with direct numerical simulations, dynamic mode decomposition (DMD) and perturbation kinetic energy (PKE) analysis. As long as the cylinder stub is rotating, the wake contains a steady dominating inner vortex (DIV) surrounded by a secondary inner vortex. Its circumferential velocity accelerates the fluid on one side of the cylinder and decelerates it on the other side. With low rotation speed, the perturbation is initiated by a combination of elliptical and centrifugal instabilities in the near wake. At medium rotation speeds, Taylor–Couette-like streamwise vortices are generated on the decelerated side, resulting in a protruding reverse-flow zone. Results from DMD analysis and corresponding PKE analysis reveal the unstable nature of the deceleration region and the wake. At the largest rotation speed investigated, the onset of perturbations is directly located on the decelerated side of the cylinder stubs, where a deceleration mechanism feeds the instability. In the near wake, the mechanism gradually changes to a pure centrifugal instability when the rotation speed increases. In the far wake, both elliptical and centrifugal instabilities fade away, and the streaky flow featuring a vigorous DIV is then only subject to inviscid inflectional instability.

G. Axtmann

Papers

Comparison of intestinal absorption of cholesterol with different plant sterols in man

Transition mechanisms in a boundary layer controlled by rotating wall-normal cylindrical roughness elements