Atherosclerosis 193 (2007) 86–93 A green tea extract lowers plasma cholesterol by inhibiting cholesterol synthesis and upregulating the LDL receptor in the cholesterol-fed rabbit Christina A. Bursill a,c,d , Mavis Abbey c , Paul D. Roach b,c,∗ a Wellcome Trust Centre of Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom b University of Newcastle, School of Environmental and Life Sciences, P.O. Box 127, Ourimbah, NSW 2258, Australia c CSIRO, Health Sciences and Nutrition, Adelaide, SA 5000, Australia d University of Adelaide, SA 5000, Australia Received 5 June 2006; received in revised form 2 August 2006; accepted 14 August 2006 Available online 12 September 2006 Abstract Green tea extracts enriched in catechins decrease plasma cholesterol in hamsters, mice and rats. The aims of this study were to determine whether a catechin-enriched extract of green tea could lower plasma cholesterol in the cholesterol-fed rabbit and to determine the mechanism of action. Four groups of six New Zealand White rabbits were initially made hypercholesterolaemic by feeding a 0.25% (w/w) cholesterol diet for 2 weeks before the diet was supplemented with a catechin extract from green tea at 0, 0.5, 1 or 2% (w/w) for 4 weeks. Administration of the crude catechin extract from green tea significantly (p < 0.05) lowered cholesterol in plasma (-60%), VLDL + IDL (-70%), LDL (-80%), liver (total by -25% and unesterified by -15%) and aorta (-25%) compared to control. There was a significant reduction in the cholesterol synthesis index (-60%) and a significant increase in hepatic LDL receptor activity (+80%) and protein (+70%) but there was no change in the intrinsic capacity to absorb cholesterol from the intestines. These results suggest that green tea catechins lowered plasma, liver and aortic cholesterol in the cholesterol-fed rabbit by lowering cholesterol synthesis and upregulating the hepatic LDL receptor. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Green tea; LDL receptor; Cholesterol synthesis; Cholesterol absorption; Lathosterol; Phytosterols; Aorta 1. Introduction Green tea is a widely consumed beverage brewed from the plant species ‘Camellia sinensis (L.) O. Kuntze’. It con- tains an abundance of naturally occurring polyphenols called catechins of which epigallocatechin gallate (EGCG) is the most prevalent. Epidemiological studies [1–3] have found that drinking between 5 and 10 cups of green tea per day is associated with lower plasma cholesterol concentrations. Intervention studies in rats, mice and hamsters have also found that green tea or green tea extracts enriched in cate- chins exhibit hypocholesterolaemic effects [4–8]. In contrast, Tijburg et al. [9] found that a green tea extract, included in ∗ Corresponding author. Tel.: +61 2 4348 4129; fax: +61 2 4348 4145. E-mail address: paul.roach@newcastle.edu.au (P.D. Roach). the drinking water, did not significantly decrease cholesterol concentrations in the cholesterol-fed hypercholesterolaemic rabbit. Inhibition of cholesterol absorption has been proposed as a mechanism to explain the cholesterol lowering effects of green tea. This is because the faecal excretion of total lipids and cholesterol were found to be higher in animals con- suming green tea extracts [4,5,8]. The EGCG has also been observed to inhibit the uptake of 14 C-cholesterol from the intestine [10]. This apparent reduction in intestinal choles- terol absorption has been ascribed to EGCG reducing the solubility of cholesterol into mixed bile salt micelles [11]. It has also been found that hamsters and rats fed green tea extracts had increased faecal excretion of bile acids [7,8]. This apparent decrease in cholesterol absorption and bile acid reabsorption by green tea should lead to a reduction 0021-9150/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2006.08.033