In heterozygous
familial hypercholesterolemia (FH), serum
low density lipoprotein (
LDL) cholesterol levels are already elevated at birth. Premature
coronary heart disease occurs in approximately 30% of heterozygous untreated adult patients. Accordingly, to retard development of
atherosclerosis, preventive measures for lowering
cholesterol should be started even in childhood. To this end, 19 FH families consumed dietary stanol
ester for 3 months. Stanol
ester margarine lowers the serum
cholesterol level by inhibiting
cholesterol absorption. Each individual in the study replaced part of his or her daily
dietary fat with 25 g of 80%
rapeseed oil margarine containing stanol
esters (2.24 g/d stanols, mainly
sitostanol). The families who consumed this
margarine for 12 weeks included 24 children, aged 3 to 13 years, with the North Karelia variant of FH (FH-NK), 4 FH-NK parents, and 16 healthy family members, and a separate group of 12 FH-NK adults who consumed the
margarine for 6 weeks and who were on
simvastatin therapy (20 or 40 mg/d). Fat-soluble
vitamins were measured by high-pressure liquid chromatography, and
cholesterol precursor
sterols (indexes of
cholesterol synthesis) and
cholestanol and
plant sterols (indexes of
cholesterol absorption efficiency) were assayed by gas-liquid chromatography. No side effects occurred. Serum
LDL cholesterol levels were reduced by 18% (P<0.001), 11%, 12% (P<0.001), and 20% (P<0.001) in the 4 groups, respectively. The serum
campesterol-to-
cholesterol ratios fell by 31% (P<0.001), 29%, 23% (P<0.001), and 36% (P<0.001), respectively, suggesting that
cholesterol absorption efficiency was inhibited. Serum
lathosterol ratios were elevated by 38% (P<0.001), 11%, 15% (P<0.001), and 19% (P<0.001), respectively, suggesting that
cholesterol synthesis was compensatorily upregulated. The FH-NK children increased their serum
lathosterol ratio more than did the FH-NK adults treated with stanol
ester margarine and
simvastatin (P<0.01). In the FH-NK children, serum
retinol concentration and
alpha-tocopherol-to-
cholesterol ratios were unchanged by stanol
ester margarine, but alpha- and
beta-carotene concentrations and ratios were decreased. As assayed in a genetically defined population of FH patients, a dietary regimen with stanol
ester margarine proved to be a safe and effective hypolipidemic treatment for children and adults. In FH-NK adults on
simvastatin therapy, serum
LDL cholesterol levels could be reduced even further by including a stanol
ester margarine in the regimen.