Plant Sterols, Stanols, and Sitosterolemia

Abstract

Phytosterolemia (sitosterolemia) is a rare autosomal recessive sterol storage disease caused by mutations in either of the adenosine triphosphate (ATP) binding cassette transporter genes; (ABC) G5 or ABCG8, leading to impaired elimination of plant sterols and stanols, with their increased accumulation in the blood and tissues. Thus the disease is characterized by substantially elevated serum plant sterols and stanols, with moderate to high plasma cholesterol levels, and increased risk of premature atherosclerosis. Hematologic abnormalities including macrothrombocytopenia, stomatocytosis and hemolysis are frequently observed in sitosterolemia patients. Currently, ezetimibe, a sterol absorption inhibitor, is used as the routine treatment for sitosterolemia, with reported improvement in plant sterol levels and hemolytic parameters. This review summarizes the research related to the health impact of plant sterols and stanols on sitosterolemia.

Figure 1

The mutation in ABCG5/8 in the diseased condition causes plant sterols to be transported from the intestinal lumen back into the blood vessels. Abbreviations: ABCG5/8, adenosine triphosphate (ATP)-binding cassette G5/G8.

Figure 2

Cholesterol and plant sterols biliary and intestinal absorption. The adenosine triphosphate (ATP)- binding cassette ABCG5/8 transporter function is to excrete free cholesterol from the intestinal lumen. Presence of NPC1L1 in the apical membrane of enterocytes and hepatocytes does facilitate intestinal and biliary cholesterol absorption, and uptake of PS from the gut lumen. ABCG5 and ABCG8 that are expressed in hepatocytes also promote the biliary excretion of cholesterol and PS. Abbreviations: ACAT 2, Acylcholesterol acyl transferase; NPC1L1, Niemann-Pick C1-Like 1; ABCG5/8, Adenosine triphosphate (ATP)- binding cassette G5/G8; Chylomicrons(CM); CS, cholesterol; CE, cholesterol ester.