Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols

University of Manitoba

Status and phase: Completed; Phase 4

Conditions: Hyperlipidemia

Treatments: Dietary Supplement: Plant sterol; Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01131832

B2007:073

Details and patient eligibility

About

The substantial range of individual responsiveness to plant sterols has important ramifications. Marked differences across individuals in particular aspects of the cholesterol metabolic pathway must alter the impact of plant sterol consumption. As such, a pronounced need exists to understand the genetic and metabolic factors that explain the substantial degree of heterogeneity in response of lipid concentrations to plant sterols across individuals. The primary focus of this trial is to delineate the impact of differing cholesterol synthesis levels on response of LDL-C and other plasma lipids to plant sterol consumption. Participants pre-identified as high or low endogenous cholesterol synthesizers, according to their screening level of lathosterol to cholesterol ratios, will be given PS or a placebo containing margarine to consume under supervision for 4 weeks in a crossover design. The trial will characterize the responsiveness of the participants' total, LDL, and HDL cholesterol, as well as triacylglycerol (TG) concentrations, to plant sterol consumption. This research will determine if cholesterol synthesis phenotype predicts the responsiveness of lipids to plant sterol consumption. Variations in candidate genes involved in cholesterol metabolism will also be investigated in order to find associations with both cholesterol metabolism phenotypes and responsiveness of lipids to plant sterols. The output of this research will be to advance the knowledge of which genetic factors influence the degree of cardiovascular benefit derived from plant sterols through lipid lowering.

Enrollment: 71 patients

Sex: All

Ages: 30 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• fasting serum LDL cholesterol >3.0 mmol/L
• high or low lathosterol to cholesterol ratio

Exclusion criteria

• smoking
• use of lipid lowering therapy
• documented cardiovascular/atherosclerotic disease
• inflammatory disease
• diabetes
• uncontrolled hypertension
• kidney disease
• liver disease
• other systemic diseases
• cancer
• chronic alcohol consumption (> 2 servings/day)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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71 participants in 1 patient group

Plant sterol

Experimental group

Description:

Plant sterol supplementation, 2 grams per day of plant sterols in a margarine

Treatment:

Dietary Supplement: Placebo

Dietary Supplement: Plant sterol