Epigallocatechin gallate lowers the serum lathosterol to squalene ratio, a novel index of cholesterol synthesis, in the hypercholesterolaemic rabbit model

Background – Epigallocatechin gallate (EGCG) is a major green tea catechin which is related to the reduction of
plasma cholesterol in animal models possibly through inhibition of cholesterol synthesis. Consistent with this, in
vitro studies have shown EGCG to be a non-competitive inhibitor of squalene epoxidase (1). In vivo, inhibition of
squalene epoxidase could be expected to reduce, relative to squalene, the amount of lathosterol produced; lathosterol
is a cholesterol precursor which is produced after squalene in the cholesterol synthetic pathway.
Objective – To determine the effect of EGCG on lathosterol relative to squalene in the hypercholesterolaemic
rabbit.
Design – New Zealand White rabbits (n=12) were fed a rabbit chow with 0.25% (w/w) cholesterol for 2 weeks to
render them hypercholesterolaemic. This was followed by a 4-week treatment period during which the control group
(n=6) remained on the 0.25% (w/w) cholesterol diet while the treatment group (n=6) was fed the same diet plus 2%
(w/w) EGCG added. Serum cholesterol (enzymatic), lathosterol (GC) and squalene (HPLC) were measured.
Outcomes – After the 4-week treatment period, serum lathosterol was significantly reduced in the treatment group
compared to control (P=0.03) but the serum squalene did not differ between the groups (P=0.46). Therefore, the
serum lathosterol to squalene ratio, a novel index of cholesterol synthesis, was significantly lower in the treatment
group compared to control (P=0.03). The EGCG treatment also reduced serum cholesterol by 85% (P=0.02).
Conclusions – These in vivo results support the in vitro observation that EGCG is an inhibitor of sqalene epoxidase.