Phytosterols and Cardiovascular Disease

Abstract

Purpose of review: Coronary heart disease is the leading cause of mortality worldwide. Elevated blood cholesterol levels are not only the major but also the best modifiable cardiovascular risk factor. Lifestyle modifications which include a healthy diet are the cornerstone of lipid-lowering therapy. So-called functional foods supplemented with plant sterols lower blood cholesterol levels by about 10-15%.

Recent findings: In the recent revision of the ESC/EAS dyslipidemia guideline 2019, plant sterols are recommended for the first time as an adjunct to lifestyle modification to lower blood cholesterol levels. However, the German Cardiac Society (DGK) is more critical of food supplementation with plant sterols and calls for randomized controlled trials investigating hard cardiovascular outcomes. An increasing body of evidence suggests that plant sterols per se are atherogenic. This review discusses this controversy based on findings from in vitro and in vivo studies, clinical trials, and genetic evidence.

Keywords: ABCG5/G8; Atherosclerosis; Cholesterol metabolism; NPC1L1; Phytosterols.

Fig. 1

Cholesterol and plant sterol metabolism. Cholesterol (C) and plant sterols (PS) from the diet are incorporated into micelles in the small intestine and are transported to the enterocyte mucosa via the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1). Free PS and “excess” C are secreted back into the lumen by the ABCG5/ABCG8 heterodimer tandem transporter. Esterified cholesterol and plant sterols are transported in chylomicrons, secreted into the lymph, converted to chylomicron remnants, and taken up in the liver, whereas small amounts of free C/PS leave the enterocyte via apoA-containing HDL. Chylomicron remnants also contribute to atherosclerotic plaque formation in the arterial wall. Thus, the hepatic pool of sterols consists of endogenously synthesized C and dietary C/PS. Also in the hepatocyte, NPC1L1 absorbs sterols and ABCG5/8 secretes them into the bile. Part of cholesterol is converted into bile acids (BA) which are transported in free and conjugated form by specific BA transporters into the bile. In the liver, very low-density cholesterol (VLDL) is formed from C, lipoproteins (containing mostly apoB100), and tryglycerides. In the bloodstream, VLDL is converted to intermediate-density cholesterol (IDL) and low-density cholesterol (LDL). LDL is the main carrier of cholesterol in the bloodstream. Both C and PS accumulate in the arterial wall and are associated with cardiovascular events