stigmastanol and Cardiovascular-Diseases

Sitosterolemia is a rare, autosomal recessive inherited sterol storage disease associated with high tissue and serum plant sterol concentrations, caused by mutations in the adenosine triphosphate-bind-ing cassette (ABC) transporter ABCG5 or ABCG8 genes. Markedly increased serum concentration of plant sterols. such as sitosterol and campesterol, cause premature atherosclerosis and massive xanthomas. Hitherto known treatments for sitosterolemia, including a low-sterol diet, bile-salt binding resins, ileal bypass surgery and low density lipoprotein (LDL) apheresis have not yielded sufficient reduction of serum plant sterol levels and many patients show a sustained elevation of plant sterol levels, subsequently developing premature atherosclerotic cardiovascular diseases. Ezetimibe, an inhibitor of intestinal cholesterol absorption through its binding to Niemann-Pick C1-like 1 (NPC1L1), has been widely used for decreasing serum LDL-cholesterol levels in patients with hypercholesterolemia. Ezetimibe also reduces the gastrointestinal absorption of plant sterols, thereby also lowering the serum concentrations of plant sterols. This pharmacological property of ezetimibe shows its potential as a novel effective therapy for sitosterolemia. In the current review, we discuss the current therapy for patients with sitosterolemia and present two Japanese adolescent patients with this disease, one of whom underwent percutaneous coronary intervention for accelerated coronary atherosclerosis. Ezetimibe administration in addition to conventional drug therapy successfully reduced serum sitosterol levels by 51.3% and 48.9%, respectively, in the two patients, demonstrating ezetimibe as a novel and potent treatment agent for sitosterolemia that could work additively with conventional drug therapy.

Topics: Adolescent; Anticholesteremic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP-Binding Cassette Transporters; Azetidines; Bile Acids and Salts; Cardiovascular Diseases; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ileum; Ion Exchange Resins; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Models, Biological; Mutation, Missense; Phytosterols; Sitosterols; Young Adult

Functional foods enriched with plant sterols and stanols are on sale in many countries. Due to their structural similarity with cholesterol, these additives lower intestinal absorption of cholesterol, resulting in a 10-15% reduction in LDL-cholesterol when their daily intakes are 2-3 g. They are also effective as part of a cholesterol-lowering diet and in combination with cholesterol-lowering drugs. Estimates for the absorption of plant sterols (sitosterol and campesterol) and of campestanol are around 10%, and for sitostanol less than 5%. Lipid-standardized plasma levels are very low, but increase when statins are used. Extensive toxicological evaluation studies have not revealed any harmful side-effects. In human studies, side-effects were comparable to placebo treatment. However, lipid-standardized levels of the hydrocarbon carotenoids may decrease, without leaving the normal range. Together, these findings indicate that these functional foods have great potential in the prevention of coronary heart disease. However, post-marketing surveillance for example for functional foods in general is necessary to monitor possible adverse effects and describe consumers and consumption patterns.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Diet; Food, Organic; Humans; Intestinal Absorption; Lipid Metabolism; Phytosterols; Risk Factors; Safety; Sitosterols