The results of studies investigating the role of selenium with regard to different diseases are inconsistent. The present study should contribute to understanding the effects and the mechanisms (e.g. Nrf2, PTP1B) by which different selenium concentrations influence the metabolism of lipids, homocysteine and xenobiotics. Another main objective of the present study was to examine the influence of methionine, glucoraphanin (GRA) and sulforaphane (SFN) on these pathways as well as the interactions with selenium. It could be shown that feeding a selenium-deficient diet reduced the hepatic cholesterol and triglyceride concentrations and lowered the plasma homocysteine levels. Moreover, it could be shown a synergistic effect for GRA and selenium, because the combination of GRA with slightly supranutritive selenium provided the highest colonic mRNA concentrations of the analyzed Nrf2 target genes. Whereas GRA supplementation had no influence on glutathione and homocysteine, 100 μmol SFN reduced the plasma homocysteine concentrations lightly. Furthermore, the administration of 100 μmol SFN reduced cholesterol and triglyceride levels in the plasma.