Stanol ester margarine alone and with simvastatin lowers serum cholesterolin families with familial hypercholesterolemia caused by the FH-North Karelia mutation

In heterozygous familial hypercholesterolemia (FH), serum low density lipop rotein in (LDL) cholesterol levels are already elevated at birth. Premature coronary heart disease occurs in approximate to 30% of heterozygous untrea ted adult patients. Accordingly, to retard development of atherosclerosis, preventive measures for lowering cholesterol should be started even in chil dhood. To this end, 19 FH families consumed dietary stanol ester for 3 mont hs. 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 cons umed 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 healt hy family members, and a separate group of 12. FH-NK adults who consumed th e 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. Seru m 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 rations 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 s ynthesis was compensatorily upregulated. The FM-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 ret inol concentration and alpha-tocopherol-to-cholesterol ratios were unchange d by stanol ester margarine, but alpha- and beta-carotene concentrations an d ratios were decreased. As assayed in a genetically defined population of FH patients, a dietary regimen with stanol ester margarine proved to be a s afe and effective hypolipidemic treatment for children and adults. In FH-NK adults on simvastatin therapy, serum LDL cholesterol levels could be reduc ed even further by including a stanol ester margarine in the regimen.