Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia mutation.
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.
Vuorio
A F
AF
Department of Medicine, University of Helsinki, Helsinki, Finland. alpo.vuorio@huch.fi
Gylling
H
H
Turtola
H
H
Kontula
K
K
Ketonen
P
P
Miettinen
T A
TA
D000293:Adolescent; D000328:Adult; D000732:Androstanols / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D004952:Esters / Q000627:therapeutic use*; D005260:Female; D005387:Finland; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000178:diet therapy* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008383:Margarine; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D019821:Simvastatin / Q000627:therapeutic use*; D013261:Sterols / Q000627:therapeutic use*
D000732:Androstanols; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D004952:Esters; D013261:Sterols; D008383:Margarine; D002784:Cholesterol; D019821:Simvastatin