Naturally-occurring phytosterols in the usual diet influence cholesterol metabolism in healthy subjects.

BACKGROUND AND AIMS: Modulation of cholesterol absorption is potentially an effective way of lowering blood cholesterol levels and decreasing inherent cardiovascular risk in the general population. It is well established that cholesterol absorption efficiency can be modified by the intake of foods enriched with gram-doses of phytosterols, but little is known about the effects of phytosterols in the usual diet, even though moderate doses have been reported to affect whole-body cholesterol metabolism. A way to indirectly measure cholesterol synthesis and absorption rates is by quantification of serum non-cholesterol sterols. The aim of this study was to investigate the role of naturally occurring phytosterol intake on cholesterol absorption and serum cholesterol concentrations in a Spanish free-living population. METHODS AND RESULTS: A total of 85 healthy volunteers were studied regarding their dietary habits (using a validated food frequency questionnaire), lipid profile and surrogate markers of cholesterol metabolism. Subjects were classified into tertiles of total phytosterol intake, and differences in lipid profile and markers of cholesterol metabolism were assessed by multivariate linear regression models adjusted for various confounders. The estimated daily intake of phytosterols and cholesterol was 489 (median) and 513 (mean) mg, respectively. Both serum low-density lipoprotein (LDL)-cholesterol concentration and sitosterol-to-cholesterol ratio adjusted by sitosterol intake (a surrogate marker of intestinal cholesterol absorption) decreased significantly (p < 0.05, both) across tertiles of phytosterol intake. CONCLUSION: Moderate doses of phytosterols in the habitual diet might have a protective effect on the lipid profile via decreasing cholesterol absorption.

Role of naturally-occurring plant sterols on intestinal cholesterol absorption and plasmatic levels.

Cardiovascular disease is a major health problem in developed countries although its incidence is relatively lower in Mediterranean countries which is partly ascribed to dietary habits. Epidemiologic evidence shows that elevated serum cholesterol, specifically low-density lipoprotein cholesterol (c-LDL), increases cardiovascular disease. Phytosterols are bioactive compounds, found in all vegetable foods, which inhibit intestinal cholesterol absorption and, therefore, have a serum cholesterol-lowering effect. Intestinal cholesterol absorption is a multistep process where plant sterols and stanols may act: a) attenuating the NPC1L1 gene expression, which may result in a lower cholesterol uptake from the lumen; b) lowering the cholesterol esterification rate by the ACAT2 (acyl-CoA cholesterol acyltransferase) and, consequently, the amount of cholesterol secreted via the chylomicrons and c) upregulating the expression of ABC-transporters ABCG5 and ABCG8 in intestinal cells, which may result in an increased excretion of cholesterol by the enterocyte back into the lumen. Many clinical trials proved that commercial products enriched with phytosterols reduce cholesterol levels. Likewise, recent studies show that phytosterols present in natural food matrices are also effective and could be an important component of cardioprotective dietary patterns such as the Mediterranean diet.

A moderate intake of phytosterols from habitual diet affects cholesterol metabolism.

Cholesterol metabolism homeostasis is the result of a balance between synthesis, degradation and intestinal absorption. It is well established that intestinal cholesterol absorption efficiency can be modified by the intake of phytosterol-enriched food and, therefore, have a serum cholesterol-lowering effect. Recent epidemiological and clinical studies have shown that presence of phytosterols at normal diet levels could also be effective on lowering total and LDL serum cholesterol since they affect whole-body cholesterol metabolism even at those moderate doses. The aim of this study was to analyze the effect of the levels of the naturally-occurring phytosterols in the diet on cholesterol metabolism parameters. In order to do that a group of 99 healthy volunteers was studied for their dietary habits and surrogate markers of cholesterol synthesis and absorption. The mean daily dietary intake of phytosterols, measured by a food semiquantitative frequency questionnaire, was found to be 494 mg being beta-sitosterol the major contributor to it. Subjects were classified into tertiles according to their total phytosterol intake and comparisons were done between subgroups. No statistical differences were observed for surrogate markers of intestinal cholesterol absorption, but a significant increase in the cholesterol synthesis surrogate marker lathosterol-to-cholesterol ratio associated to highest dietary phytosterol intake was observed. Regardless of this, only a non significant trend toward a less atherogenic lipid profile was observed in the upper tertile. In conclusion, the intake of moderate amounts of phytosterols naturally present in habitual diet may affect cholesterol metabolism and specially the rate of cholesterol synthesis as estimated by the surrogate marker lathosterol-to-cholesterol ratio in serum.

Papel de los esteroles vegetales de la dieta sobre la absorción intestinal de colesterol y sus niveles plasmáticos / Role of naturally-occurring plant sterols on intestinal cholesterol absorption and plasmatic levels

Cardiovascular disease is a major health problem in developed countries althoughits incidence is relatively lower in Mediterranean countries which is partly ascribedto dietary habits. Epidemiologic evidence shows that elevated serum cholesterol,specifically low-density lipoprotein cholesterol (c-LDL), increases cardiovasculardisease. Phytosterols are bioactive compounds, found in all vegetable foods, whichinhibit intestinal cholesterol absorption and, therefore, have a serum cholesterolloweringeffect. Intestinal cholesterol absorption is a multistep process where plantsterols and stanols may act: a) attenuating the NPC1L1 gene expression, which mayresult in a lower cholesterol uptake from the lumen; b) lowering the cholesterol esterificationrate by the ACAT2 (acyl-CoA cholesterol acyltransferase) and, consequently,the amount of cholesterol secreted via the chylomicrons and c) upregulatingthe expression of ABC-transporters ABCG5 and ABCG8 in intestinal cells, whichmay result in an increased excretion of cholesterol by the enterocyte back into thelumen. Many clinical trials proved that commercial products enriched with phytosterolsreduce cholesterol levels. Likewise, recent studies show that phytosterols presentin natural food matrices are also effective and could be an important componentof cardioprotective dietary patterns such as the Mediterranean diet(AU)

La enfermedad cardiovascular es un problemade salud importante en los países desarrollados,aunque su incidencia es relativamentemenor en los países mediterráneos lo que esparcialmente atribuible a los hábitos dietéticos.Existen evidencias epidemiológicas que muestranque el colesterol sérico elevado, específicamenteel colesterol ligado a las lipoproteínas debaja densidad (c-LDL), incrementa la enfermedadcardiovascular. Los fitosteroles son compuestosbioactivos, presentes en todos los alimentosde origen vegetal, que inhiben la absorciónintestinal de colesterol y, por lo tanto, tienenun efecto reductor en el colesterol sérico.La absorción intestinal de colesterol es un procesomulti-etapa donde los esteroles y estanolesvegetales pueden actuar de diversas formas:a) atenuando la expresión del gen NPC1L1, loque puede suponer una disminución del ingresode colesterol desde el lumen intestinal; b)disminuyendo la tasa de esterificación delcolesterol por la ACAT2 (acil-CoA colesterolaciltransferasa) y, en consecuencia, la cantidadde colesterol excretada vía quilomicrones y c)aumentando la expresión de los ABC-transportadoresABCG5 y ABCG8 en las célulasintestinales, lo que puede derivar en una excreción incrementada de colesterol desde el enterocitohacia el lumen. Diversos ensayos clínicoshan demostrado que los productos comercialesenriquecidos con fitosteroles reducen losniveles de colesterol. Sin embargo, estudiosrecientes muestran que los fitosteroles presentesen matrices alimentarias naturales tambiénpueden ser bioactivos y podrían ser un componenteimportante de los patrones dietéticoscardioprotectores como es la dieta Mediterránea(AU)

A moderate intake of phytosterols from habitual diet affects cholesterol metabolism

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Cholesterol metabolism homeostasis is the result of a balance between synthesis, degradation and intestinal absorption. It is well established that intestinal cholesterol absorption efficiency can be modified by the intake of phytosterol-enriched food and, therefore, have a serum cholesterol-lowering effect. Recent epidemiological and clinical studies have shown that presence of phytosterols at normal diet levels could also be effective on lowering total and LDL serum cholesterol since they affect whole-body cholesterol metabolism even at those moderate doses. The aim of this study was to analyze the effect of the levels of the naturally-occurring phytosterols in the diet on cholesterol metabolism parameters. In order to do that a group of 99 healthy volunteers was studied for their dietary habits and surrogate markers of cholesterol synthesis and absorption. The mean daily dietary intake of phytosterols, measured by a food semiquantitative frequency questionnaire, was found to be 494 mg being beta-sitosterol the major contributor to it. Subjects were classified into tertiles according to their total phytosterol intake and comparisons were done between subgroups. No statistical differences were observed for surrogate markers of intestinal cholesterol absorption, but a significant increase in the cholesterol synthesis surrogate marker lathosterol-to-cholesterol ratio associated to highest dietary phytosterol intake was observed. Regardless of this, only a non significant trend toward a less atherogenic lipid profile was observed in the upper tertile. In conclusion, the intake of moderate amounts of phytosterols naturally present in habitual diet may affect cholesterol metabolism and specially the rate of cholesterol synthesis as estimated by the surrogate marker lathosterol-to-cholesterol ratio in serum (AU)