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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
71
USDA-ARS, Beltsville Human Nutrition Research Center
Beltsville, Maryland, United States
Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
Winnipeg, Manitoba, Canada
Serum Lipids
Total Cholesterol, LDL-C, HDL-C, Triglycerides
Time frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Serum non-cholesterol sterols
Lathosterol,Lanosterol,Desmosterol,Sitosterol,Campesterol,Cholestanol,
Time frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Genotype via single nucleotide polymorphism analysis
SNP genotyping in genes related to cholesterol metabolism
Time frame: Baseline
Cholesterol synthesis measurement by deuterium incorporation
Cholesterol biosynthesis will be determined as the rate of incorporation of deuterium from body water into red blood cell membrane free cholesterol over a 24 hour period (day 27 to day 28 of each period). The change in deuterium enrichment within red blood cell free cholesterol will be determined as an index of synthesis, the fractional synthesis rate (FSR) of cholesterol.
Time frame: Endpoint (Day 27,28) of each experimental period
Change in cholesterol absorption due to plant sterol consumption
Ninety-six hours before the end of each period, participants will ingest 65 mg \[3, 4-13C\]-cholesterol. The 13C-cholesterol will be dissolved in 5 g of warmed margarine, and consumed on a slice of bread. A fasted blood sample will be taken at baseline on day 24 prior to isotope administration, as well as fasting samples on days 25, 26, 27 and 28 to monitor enrichment levels of 13C-cholesterol in plasma total cholesterol. The area under the curve of 13C-cholesterol from 0-96 hours (days 24-28) at the end of the control period will be compared to the same area under the curve at the end of the plant sterol period to determine the change in cholesterol absorption due to plant sterol consumption.
Time frame: Change in cholesterol absorption from control period (measured over days 24-28) to plant sterol period (days 24-28)
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