EDTA reduces liver cholesterol content in cholesterol-fed rabbits

A study conducted in 1953 by one of the authors (H.S.M. Uhl) reported that orally administered ethylenediamine tetraacetic acid (EDTA) both prevented the accumulation of cholesterol in the liver of cholesterol-fed rabbits and caused the removal of accumulated cholesterol from the liver. These observations were made in rabbits fed high concentrations of cholesterol and have never been confirmed in the literature. The purpose of the present study was to determine if this original observation could be confirmed using lower amounts of dietary cholesterol and more modern and comprehensive methods for analysis of tissue lipids and plasma lipoproteins. New Zealand White rabbits were fed diets containing 0.1% cholesterol with or without EDTA (3 g/day). After 16 weeks, significantly lower concentrations of hepatic cholesterol were found in rabbits fed EDTA (6.95 mg/g wet weight) compared with controls fed the same cholesterol-containing diet without EDTA (16.6 mg/g wet weight). Plasma cholesterol levels in both groups of animals were not significantly different from one another; therefore, the effect of EDTA in reducing liver cholesterol accumulation was independent of changes in plasma cholesterol concentrations. Although the mechanism of this EDTA effect is unknown, it may provide a tool to gain further insight into mechanisms of regulation of hepatic lipoprotein and cholesterol metabolism.