Cardiovascular disease (CVD) risk can be lowered by introduction of plant sterols (PS) in the diet, since PS have been shown to reduce low-density lipoprotein cholesterol (LDL-C). Given that the efficacy of PS as cholesterol-lowering agents depends on their appropriate solubilization, the cholesterol-lowering efficacy of PS in non-traditional matrices needs to be determined. The primary aim of this thesis was to examine the consumption of PS (a) in an oil rich in medium chain triglycerides (MCT) or (b) low-fat yogurt with or without a meal, on changes in lipid parameters. Additional objectives were: (1) to assess the effects of MCT with PS on body composition and energetics, (2) to compare the effects of PS in low-fat matrix consumed with or without a meal on cholesterol synthesis, (3) to evaluate the risks of PS in low-fat matrix on blood levels of carotenoids and fat-soluble vitamin, and (4) to investigate the relationship between the response to PS, cholesterol kinetics and genotyping. For this purpose two randomized, controlled, crossover-feeding trials were conducted. First, 23 overweight, hyperlipidemic men consumed PS in MCT or olive oil control for six weeks each. In the second trial, 26 hyperlipidemic subjects consumed a placebo yogurt, a PS-enriched yogurt consumed with a meal, or afternoon PS-enriched yogurt as a snack for four weeks each. PS, mixed within a MCT matrix, lower plasma total cholesterol (TC) and LDL-C without changing the high-density-lipoprotein cholesterol concentrations. However, no changes in body composition or energetics were observed. Secondly, a PS-enriched low-fat yogurt as snack lowered TC, along with a lowering trend in LDL-C, to greater extent compared to when consumed with a meal without any risk of deficiency in fat-soluble antioxidants. An increase in cholesterol biosynthesis was also observed in both PS phases compared to control phase. In addition, three non-responsive subjects to PS intervention who had higher cholesterol absorption rates were observed; however, no recognizable pattern of genetic polymorphisms was detected. Overall, these novel matrices for PS incorporation consumed with or between meals may be an effective way of decreasing the risk of CVD; however, some individuals respond better to PS intervention.

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