phytosterols, ezetimibe, and cholesterol metabolism

Conditions: Hypercholesterolemia; Coronary Heart Disease

Summary: phytosterols and ezetimibe each reduce intestinal cholesterol absorption by 30-55% but appear to have different mechanisms of action. the investigators' hypothesis is that phytosterols and ezetimibe given together will block cholesterol absorption in an additive fashion. in a randomized, placebo-controlled crossover trial the effects of placebo, ezetimibe treatment and ezetimibe plus phytosterol treatment will be measured.

the investigators will perform a randomized, placebo-controlled crossover feeding study in 25 subjects with greater than ideal levels of ldl cholesterol who do not require anti-cholesterol drug treatment. subjects will consume a baseline diet provided by a feeding center that is deficient in phytosterols for three periods of 21 days separated by 7-day washout periods. treatments will be given in random order during period b placebo phytosterols and placebo ezetimibe will be given; during period c placebo phytosterols and active ezetimibe will be given; during period a active phytosterols and active ezetimibe will be given. study endpoints are fecal cholesterol excretion and percent cholesterol absorption determined by gas chromatography/mass spectrometry and circulating ldl cholesterol.

Eligibility criteria:
inclusion criteria: * male or female of any race or ethnicity between 18 to 80 years of age; * body mass index between 20 - 35 kg/m2; * ldl-cholesterol between 130 - 189 mg/dl based on the average of duplicate screening measures. if the two ldl-c levels differ by more than 30 mg/dl, a third test will be scheduled with all three results averaged; * free of chronic disease; * willing to eat only the foods that are provided by the center during the diet periods; * willing to abstain from the consumption of alcohol for 48-hours prior to blood draw days; * willing to drink no more than 5 cups of caffeine-containing beverages a day. exclusion criteria: * age \ 80 years; * based on duplicate screening laboratory values: 1)ldl-c \>=190 mg/dl; 2)tg \>=250 mg/dl;3)blood pressure \>= 160 mm hg systolic or 95 mm hg diastolic; * documented presence of atherosclerotic disease; * diabetes mellitus; * renal, hepatic, endocrine, gastrointestinal, hematological or other systemic disease; * body mass index \> 35; * for women, pregnancy, breast feeding or postpartum \< 6 months; * for women, peri-menopausal; * for women, sexually active but not practicing effective birth control methods; * history of drug or alcohol abuse; * history of depression or mental illness requiring treatment or medication within the last 6 months; * multiple food allergies or significant food preferences or restrictions that would interfere with diet adherence; * chronic use of over-the-counter medication which would interfere with study endpoints including laxatives and antacids; * lifestyle or schedule incompatible with the study protocol; * planned continued use of dietary supplements through the study trial; * taking any lipid-lowering, or other medications known to affect blood cholesterol.

Keywords: phytosterols ezetimibe cholesterol excretion cholesterol absorption diet mass spectrometry deuterium