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Journal of Lipid Research, Vol 37, 1776-1785, Copyright © 1996 by Lipid Research, Inc.
H Gylling and TA Miettinen
Effectiveness of a simultaneous inhibition of cholesterol absorption and
synthesis, caused by sitostanol ester margarine and pravastatin, was
studied to control mild hypercholesterolemia in men with non-
insulin-dependent diabetes mellitus (NIDDM) (n = 8). Margarine, 24 g daily,
was a basal dietary treatment. Four 7-week intervention periods included
margarine, sitostanol (3 g/day) ester margarine, pravastatin (40 mg/day),
and sitostanol ester margarine plus pravastatin in a random order.
Pravastatin lowered serum total (-32%) and LDL cholesterol (-38%) and
apolipoprotein B (-39%) because of enhanced removal (+20%) and decreased
production (-26%) of LDL apolipoprotein B, and reduced synthesis (-9%) and
turnover (-8%) of cholesterol, which resulted in reduced biliary
cholesterol seretion (-18%). Even though serum triglycerides were lowered
by 28%, VLDL, IDL, and light and dense LDL became triglyceride-enriched.
Despite increasing cholesterol synthesis, sitostanol lowered LDL
cholesterol (-14%) by inhibiting cholesterol absorption (-68%) and LDL
apolipoprotein B production rate (-20%). Combination of pravastatin and
sitostanol ester lowered serum total, VLDL, IDL, and LDL cholesterol and
LDL apolipoprotein B by the highest rate, 35%, 50%, 35%, 44%, and 45% from
the control margarine period, respectively, because of reduced
apolipoprotein B transport rate (but unchanged removal), in both the total
and dense LDL subfractions. HDL cholesterol and apolipoprotein A-I kinetics
were unchanged. In spite of decreased absorption, cholesterol synthesis was
not compensatorily increased. In conclusion, simultaneous inhibition of
cholesterol absorption and synthesis lowers LDL cholesterol and
apolipoprotein B by 44-45% solely through inhibition of LDL apolipoprotein
B production rate in hypercholesterolemic NIDDM patients. A combination of
statin to sitostanol ester margarine- resistant patients offers a safe and
effective measure to normalize abnormally high cholesterol values, probably
with a lowered statin dose.
ARTICLES
Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non- insulin-dependent diabetic men
Department of Medicine, University of Helsinki, Finland.
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