Preferential campesterol incorporation into various tissues in apolipoprotein E*3-Leiden mice consuming plant sterols or stanols Jogchum Plat a, ⁎ , Arienne de Jong a , Oscar L. Volger b , Hans M.G. Princen b , Ronald P. Mensink a a Department of Human Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands b TNO Gaubius, PO Box 2215, 2301 CE Leiden, The Netherlands Received 20 November 2007; accepted 9 April 2008 Abstract Intestinal absorption of plant sterols and stanols is much lower as compared with that of cholesterol; and therefore, serum concentrations are low. Circulating plant sterols and stanols are incorporated into tissues. However, hardly any data are available about tissue distributions of individual plant sterols and stanols, particularly in relation to their serum concentrations. We therefore fed female apolipoprotein E*3-Leiden mice a control diet, a plant sterol–enriched diet (1g/100 g diet), or a plant stanol–enriched diet (1g/100 g diet) for 8 weeks. In the sterol group, serum cholesterol-standardized campesterol and sitosterol concentrations were, respectively, 8 and 7 times higher as compared with those in the control group. Consequently, the serum campesterol-sitosterol ratio remained essentially unchanged. Cholesterol-standardized plant sterol concentrations increased significantly in all analyzed tissues, except brain. However, the campesterol-sitosterol ratio also increased in all tissues (except in liver and spleen), suggesting that campesterol is preferentially incorporated over sitosterol in those tissues. For the stanol group, serum plant stanol concentrations also increased; but the increase was but less pronounced. We conclude that, in apolipoprotein E*3-Leiden mice, campesterol is preferentially incorporated into most tissues over sitosterol, which cannot be deduced from changes in serum concentrations. © 2008 Elsevier Inc. All rights reserved. 1. Introduction Plant sterols and stanols are cholesterol-like compounds that reduce intestinal cholesterol absorption and, as a result, lower serum low-density lipoprotein (LDL) cholesterol concentrations. High-density lipoprotein cholesterol concen- trations are unaffected. At a daily intake of 2 to 2.5 g, these components lower LDL cholesterol concentrations on average by 9% to 10% [1]. This can be regarded as a favorable effect because an elevated serum LDL cholesterol concentration is an independent risk factor for coronary heart disease. Estimates for the intestinal absorption ranges from 0.4% to 3.5% for plant sterols and from 0.02% to 0.3% for plant stanols [2,3]. In contrast, cholesterol absorption is much higher and varies between 40% and 60% [3,4]. Consequently, plant sterol and stanol concentrations in serum are rather low. Because plant sterols and stanols are transported by lipoproteins, concentrations are normally expressed relative to those of cholesterol. Thus, an increase in the plant sterol (or plant stanol) to cholesterol ratio indicates a relatively higher concentration of plant sterols and a changed composition of the lipoprotein particles. Examples of factors that change the plant sterol to cholesterol ratio are single nucleotide polymorphisms in the ABCG5/G8 transporters [5,6] as well as the use of statins (hydroxymethylglutaryl–coenzyme A reductase inhibitors) [7]. Recently, we have summarized these factors based on a systematic review of all published placebo-controlled human intervention trials [8]. The impact of increased plasma plant sterol concentrations on human health, either positive or negative, is unknown. It is known, however, that part of these circulating plant sterols and stanols is incorporated into tissues. However, hardly any data are available about changes in tissue distributions of individual plant sterols and stanols in relation to changes in their serum concentrations. In addition to the scarce amount of data concerning plant sterols, even less data are available on tissue concentrations of plant stanols in relation to their serum concentrations. Of course, such data are difficult to Available online at www.sciencedirect.com Metabolism Clinical and Experimental 57 (2008) 1241 – 1247 www.metabolismjournal.com ⁎ Corresponding author. Tel.: +31 43 3881309; fax: +31 43 3670976. E-mail address: j.plat@hb.unimaas.nl (J. Plat). 0026-0495/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2008.04.018