Introduction The research on natural substances affecting cholesterol metabolism for prevention of hypercholesterolemic atherosclerosis has particular therapeutic importance. In particular, the identification of dietary components that can be added to foods to lower or regulate cholesterol levels has gained special interest. 1 2 3 4 5 Materials and methods Animal model ldlr 2 2 Test compounds and diets 1A n n n n Fig. 1 Chemical structure of sesamin epimers (A) sesamin and (B) episesamin (or asarinin)  Rationale for dose selection 6 7 9 Analysis 10 11 Statistics P Results Body weight gain 2 P P Fig. 2 n  Effects of the atherogenic diet and test compounds on serum cholesterol and serum triglyceride concentrations P 3 Fig. 3 P  Effects of the atherogenic diet and test compounds on plasma lignan profile after intervention 1 P Table 1 n Group n a END ENL + END I, Control 8 4.61 ± 0.40 6.11 ± 2.10 9.18 ± 2.14 II, Stanol ester 8 3.01 ± 0.35 10.0 ± 4.69 13.0 ± 4.85 III, Sesamin 8 8.01 ± 0.98 569 ± 54.2** 577 ± 55.0** IV, Stanol ester + sesamin 7 6.54 ± 1.99 388 ± 90.7** 394 ± 91.8** P a Discussion 7 12 4 9 13 15 16 17 26 27 28 3 7 14 5 6 13 29 26 11 11 12 11 30 In conclusion, possible confounding factors have been minimized with the use of a specific animal model and the selection a pure sesamin epimer. It can be therefore stated that sesamin does not seem to affect cholesterol biosynthesis or absorption in mice. The so far contradictory results hinder the extrapolation to humans, and only a clinical trial with separate epimeric forms and the elucidation of the complete metabolic pathway of sesamin in humans will contribute to clarify the possible utilization of sesamin as a hyocholesterolemic agent.