Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

Abstract

This article is available online at http://www.jlr.org heart disease in the prospective Spanish EPIC cohort. J. Lipid Res . 2010. 51: 618-624. Supplementary key words plant sterols • sitosterol • campesterol • lathosterol • cholesterol • European Prospective Investigation intoCancer and Nutrition • nested case-control study • cardiometabolic risk • apolipoprotein E Dietary sterols consist of animal-derived cholesterol and plant-derived noncholesterol sterols or phytosterols. Phytosterols are important components of a vegetable-based diet and are particularly abundant in whole grains, nuts, seeds, and oils derived from them. The principal molecular forms are sitosterol and campesterol ( 1 ). These compounds are structurally related to cholesterol but have bulkier and more hydrophobic molecules, which confer them a higher affi nity for intestinal micelles than has cholesterol. Consequently, cholesterol is displaced from micelles, and the amount available for absorption is limited. The phytosterol content of usual diets is similar to that of cholesterol (150 to 450 mg/day), but their intestinal absorption is much less effi cient (see review in Ref.2 ). Because of low absorption and rapid biliary elimination, physiological plasma concentrations of phytosterols are in the order of 10 Ϫ 3 those of cholesterol. Their ratios to cholesterol are accepted as surrogate markers for the effi ciency of cholesterol absorption, while those of the Abstract Phytosterol intake with natural foods, a measure of healthy dietary choices, increases plasma levels, but increased plasma phytosterols are believed to be a coronary heart disease (CHD) risk factor. To address this paradox, we evaluated baseline risk factors, phytosterol intake, and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10 year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake ( P = 0.026). HDL-cholesterol level increased, and adiposity measures, cholesterol/HDL ratios, and levels of glucose, triglycerides, and lathosterol, a cholesterol synthesis marker, decreased across plasma sitosterol tertiles ( P < 0.02; all). Compared with controls, cases had nonsignifi cantly lower median levels of phytosterol intake and plasma sitosterol. The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 (95% confi dence interval, 0.36-0.97). Associations were weaker for plasma campesterol. The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols. The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort, a population with a high phytosterol intake. -Escurriol,

Serum lipid responses to phytosterol-enriched milk in a moderate hypercholesterolemic population is not affected by apolipoprotein E polymorphism or diameter of low-density lipoprotein particles

“…Previous data suggest that an increase in Apo B-100, Apo B-100/Apo A-I ratio and non-HDLc is an important risk factor for coronary heart disease, proving to be even more relevant than lipid concentration per se (Ridker et al, 2005). In this study, we have observed decreases of 7.4 and 5.9% in the Apo B-100/ Apo A-I ratio and 6.3 and 8.3% in non-HDLc in Apo E3 and E4 patients after PS consumption, respectively, suggesting that there is a reduction in cardiovascular risk following intake of PS by patients with both phenotypes, which is in the line with others (Escurriol et al, 2010).…”

Phytosterols and phytosterolemia: gene–diet interactions

“…To address this apparent paradox, two large clinical transversal studies have shown an inverse relationship between phytosterol intakes on a regular diet and total and LDL-C concentrations, suggesting that moderate increases in phytosterolemia in non-sisterolemic subjects could not be harmful, but beneficial [56]. Escurriol et al [22] evaluated baseline risk factors, phytosterol intake, and plasma non-cholesterol sterol levels in participants of a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10-year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake; HDL-cholesterol levels increased; and adiposity measures, cholesterol/HDL ratios, levels of glucose, triglycerides, and lathosterol decreased across plasma sitosterol tertiles.…”

Do clinical and experimental investigations support an antiatherogenic role for dietary phytosterols/stanols?

“…In this situation, the consequence should be a higher cholesterol synthesis rate, which should be confirmed by increase in plasma cholesterol precursors and decrease in LDL-C concentration. However, in PS supplementation, the level of campesterol and of b-sitosterol in plasma may only be understood as an indication of a healthy diet which is associated with a reduced risk for CHD (56). Although consumption of PS from vegetable sources alone is not sufficient to impair cholesterol absorption, a decrease in cholesterol synthesis was observed by these authors because of a low plasma concentration of lathosterol, a cholesterol synthesis precursor.…”

“…New data from EPIC study conducted in Spain, demonstrated a lower cardiovascular risk among people who had a higher plasma concentration of PS (56). In this and in a previous study (57), a higher PS plasma concentration reflected consumption of healthy foods and nutrients, including fruits and seeds, vegetable protein, fiber, and polyunsaturated fatty acids.…”

“…This made the authors conclude that it is not yet possible to conclude whether PS is neutral, antiatherogenic or proatherogenic, and suggested the need for further investigation. A difficulty in associating the PS plasma concentration with CAD is that several epidemiological studies (39,47,48,54,56,61,(63)(64)(65)67) did not evaluate PS consumption but only assessed plasma PS measurements. Unfortunately, there are no studies on the effect of long-term supplementation on cardiovascular outcomes.…”