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In this study, we compare the distribution of intraperitoneally injected sitosterol, 7beta-hydroxysitosterol or vehicle only (control) for 28days in male ApoE-/- mice. Furthermore we examine its impact on surrogate markers of cholesterol biosynthesis and sterol absorption rate in plasma, brain and liver tissues from these animals. Injection of sitosterol revealed a 32.1% (P=0.013) lower plasma total cholesterol compared with control. Cholesterol corrected plasma and absolute brain and liver levels of sitosterol are 4.1-, 1.7-, and 7.2-fold (P<0.001 for all) higher, respectively. This is in accordance with a reduced plasma campesterol to cholesterol ratio (-16.2%; P=0.018) together with a 24.1% (P=0.047) lower concentration of hepatic lathosterol. After injection of 7beta-hydroxysitosterol the concentrations of 7beta-hydroxysitosterol in plasma, brain and liver are 21.0-, 65.8- and 42.7-fold (P<0.001 for all) higher, respectively, compared with control. Injection of 7beta-hydroxysitosterol revealed significantly lower plasma cholesterol corrected cholestanol and campesterol (-44.2%; P=0.001 and -24.5; P=0.004) as well as lower absolute liver cholestanol levels (-31.9%; P<0.001) compared with control. Intraperitoneally injected sitosterol and 7beta-hydroxysitosterol differently influence cholesterol metabolism in plasma and liver. We conclude that the polar 7beta-hydroxysitosterol compound can pass the blood brain barrier with higher efficacy than its substrate, sitosterol. Though present in higher amounts in the brain, both, sitosterol and 7beta-hydroxysitosterol do not influence cholesterol metabolism in the brain as proven by our surrogate markers.