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CLINICAL RESEARCH: LIPIDS AND VASCULAR DISEASE

Vascular Effects of Diet Supplementation With Plant Sterols

Oliver Weingärtner, MD^_*, Dieter Lütjohann, PhD, Shengbo Ji^||, Nicole Weisshoff^_*, Franka List^_*, Thomas Sudhop, MD, Klaus von Bergmann, MD, Karen Gertz, MD^||, Jochem König, PhD^¶, Hans-Joachim Schäfers, MD, Matthias Endres, MD^||, Michael Böhm, MD^_* and Ulrich Laufs, MD^_*,_*

^_* Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
Klinik für Thorax- und Herz-Gefäßchirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
Institut für Klinische Chemie und Pharmakologie, Universitätsklinikum Bonn, Germany
Abteilung für Klinische Pharmakologie, Universitätsklinikum Bonn, Germany
^|| Klinik und Poliklinik für Neurologie, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
^¶ Institut für Medizinische Biometrie, Epidemiologie und Informatik, Johannes Gutenberg-Universität Mainz, Germany.

Manuscript received June 22, 2007; revised manuscript received August 29, 2007, accepted September 10, 2007.

^_* Reprint requests and correspondence: Dr. Ulrich Laufs, Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany. (Email: ulrich{at}laufs.com).

Objectives: The purpose of this study was to evaluate vascular effects of diet supplementation with plant sterol esters (PSE).

Background: Plant sterol esters are used as food supplements to reduce cholesterol levels. Their effects on endothelial function, stroke, or atherogenesis are not known.

Methods: In mice, plasma sterol concentrations were correlated with endothelial function, cerebral lesion size, and atherosclerosis. Plasma and tissue sterol concentrations were measured by gas-liquid chromatography-mass spectrometry in 82 consecutive patients with aortic stenosis.

Results: Compared with those fed with normal chow (NC), wild-type mice fed with NC supplemented with 2% PSE showed increased plant sterol but equal cholesterol plasma concentrations. The PSE supplementation impaired endothelium-dependent vasorelaxation and increased cerebral lesion size after middle cerebral artery occlusion. To test the effects of cholesterol-lowering by PSE, apolipoprotein E (ApoE)–/– mice were randomized to Western-type diet (WTD) with the addition of PSE or ezetimibe (EZE). Compared with WTD, both interventions reduced plaque sizes; however, WTD + PSE showed larger plaques compared with WTD + EZE (20.4 ± 2.1% vs. 10.0 ± 1.5%). Plant sterol plasma concentration strongly correlated with increased atherosclerotic lesion formation (r = 0.50). Furthermore, we examined plasma and aortic valve concentrations of plant sterol in 82 consecutive patients with aortic stenosis. Patients eating PSE-supplemented margarine (n = 10) showed increased plasma concentrations and 5-fold higher sterol concentrations in aortic valve tissue.

Conclusions: Food supplementation with PSE impairs endothelial function, aggravates ischemic brain injury, effects atherogenesis in mice, and leads to increased tissue sterol concentrations in humans. Therefore, prospective studies are warranted that evaluate not only effects on cholesterol reduction, but also on clinical endpoints. (Concentration of Plant Sterols in Serum and Aortic Valve Cusps; NCT00222950)

Abbreviations and Acronyms   ApoE = apolipoprotein E   EZE = ezetimibe   LDLR = low-density lipoprotein receptor   NC = normal chow   PSE = plant sterol esters   WTD = Western-type diet

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