Atherosclerosis prevention is now a major focus of the scientific community and the pharmaceutical industry. Sugar cane policosanols (SCP) have gained increasing popularity over the last decade as a result of numerous studies conducted in Cuba considering SCP as the natural alternative to statin drugs. However, independent research on policosanols was not able to replicate cholesterol reductions reported by Cuban laboratories. No independent study to date has examined the cholesterol-lowering effect and antioxidant capacity of original SCP in humans. In addition, since independent research was criticized because of the use of alternative policosanol formulations, the source and composition of policosanol mixtures are now at the core of the policosanol controversy.The aim of the present thesis project was first to compare the composition and cholesterol-lowering effects of different SCP preparations in hamsters, and secondly to test the cholesterol-lowering efficacy, mechanism of action and antioxidant capacity of the original Cuban SCP in hypercholesterolemic humans.Study 1: Forty-eight male hamsters were randomly assigned to 4 groups for a period of 4 weeks (i) non-cholesterol control, (ii) cholesterol control, (iii) original SCP and (iv) alternative SCP. Hamsters were sacrificed and blood was collected at the end of the feeding period for lipid measurements.Study 2: Twenty-one hypercholesterolemic volunteers consumed 10 mg/day of SCP or a placebo for a period of 28 days in a crossover trial. Plasma lipid levels and LDL oxidation were measured at the start and end of supplementation phases. Cholesterol absorption and synthesis were assessed using single isotope single tracer technique and deuterium incorporation respectively.There was no significant difference in cholesterol-lowering efficacy between hamsters in the original and alternative SCP groups relative to control. Similarly, in hypercholesterolemic humans, original SCP supplementation did not significantly improve lipid parameters and no change in cholesterol absorption or synthesis was observed relative to control. In vivo assessment of LDL oxidation showed no significant changes in oxidized LDL concentration relative to baseline and control.