stigmastanol and Hyperlipoproteinemia-Type-II

In familial hypercholesterolemia (FH) the lowering of serum cholesterol levels should be started in childhood in order to prevent coronary artery disease later in life. However, treatment of children is problematic. We studied the effects of sitostanol (3 g/day) ester dissolved in rapeseed oil margarine as a hypocholesterolemic agent in one homozygous and 14 heterozygous children with FH maintained on a low cholesterol diet for 6 weeks, using a double-blind crossover design. Absorption and synthesis of cholesterol were evaluated by measuring serum plant sterol and cholesterol precursor proportions to cholesterol by gas-liquid chromatography. The compliance was good, and the children could not distinguish by taste the two margarines without and with sitostanol ester. Sitostanol margarine significantly reduced serum total, intermediate density (IDL), and low density lipoprotein (LDL) cholesterol by 11, 26, and 15%, respectively, and increased HDL/LDL cholesterol ratio by 27%. The proportions of serum delta 8-cholestenol, lathosterol, and desmosterol were significantly increased by 36, 19, and 18%, and those of serum cholestanol, campesterol, and sitosterol were significantly decreased by 9, 42 and 29%, respectively, suggesting that cholesterol absorption was decreased and synthesis was compensatorily increased. High basal precursor sterol proportions predicted a high decrease in LDL cholesterol levels. In conclusion, partial replacement of normal dietary fat consumption by sitostanol ester margarine appears to be an effective and safe hypocholesterolemic treatment in children with FH.

Topics: Adolescent; Child; Child, Preschool; Dietary Fats; Esters; Female; Humans; Hyperlipoproteinemia Type II; Lipids; Male; Margarine; Sitosterols

Serum cholesterol values were insufficiently reduced by pravastatin in two different patient populations. Therefore, we studied whether further cholesterol reduction could be achieved by inhibiting both cholesterol synthesis (by pravastatin) and absorption (by neomycin or sitostanol ester). Thus, we measured serum cholesterol, cholesterol precursors (reflecting cholesterol synthesis), cholestanol and plant sterols (reflecting cholesterol absorption and biliary secretion) for up to 6 weeks in pravastatin-treated patients with familial hypercholesterolaemia (FH, n = 13) and with and without ileal bypass during addition of neomycin (1.5 g per day) and in another patient population of non-FH (n = 14) subjects during addition of sitostanol ester (1.5 g per day). Addition of neomycin lowered serum total, LDL and HDL cholesterol by a further 20%, and increased the pravastatin-lowered precursor:cholesterol ratios by 20% (irrespective of ileal bypass). It also reduced by 20% the plant sterol:cholesterol ratio (irrespective of ileal bypass) which was markedly increased by pravastatin alone. Pravastatin and neomycin in combination lowered total, LDL and HDL cholesterol by 45%, 53% and 17%, respectively. This combined regimen reduced the serum lathosterol:cholesterol ratio to about half of the reduction caused by pravastatin, while the elevation of the plant sterols:cholesterol ratio was less with the combination than with pravastatin alone. Changes in serum cholesterol precursor:cholesterol and plant sterol:cholesterol ratios during the combined treatment were smaller in the subgroup with ileal bypass. Addition of sitostanol ester did not lower serum total or LDL cholesterol nor the precursor:cholesterol ratios significantly, while the reduction observed in the plant sterols:cholesterol ratios was similar to that achieved with neomycin addition.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticholesteremic Agents; Cholesterol; Drug Therapy, Combination; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Absorption; Male; Middle Aged; Neomycin; Pravastatin; Sitosterols

This study was undertaken to compare the ability of two plant sterols to reduce serum levels of lipids and to compare their mechanism of action in nine children with severe familial hypercholesterolemia (total and low-density lipoprotein cholesterol concentrations averaged 9.57 mmol/L (370 mg/dl) and 7.87 mmol/L (301 mg/dl)). After a 3-month strict diet, the children were given sitosterol pastils (2 gm three times a day) for 3 months, followed by a 7-month course of sitostanol (0.5 gm three times a day). Serum lipoprotein levels and serum concentrations of campesterol and sitosterol were determined in all nine children, and the fecal excretion of neutral and acidic sterols were determined in seven children at the end of each therapeutic regimen. Sitosterol reduced low-density lipoprotein cholesterol levels by 20% (p < 0.01); sitostanol reduced low-density lipoprotein cholesterol levels by 33% after 3 months and 29% after 7 months (p < 0.01 compared with diet; p < 0.05 compared with sitosterol). Although sitosterol did not alter serum concentrations of campesterol and sitosterol, a significant reduction did occur during sitostanol therapy (-47% and -51%, respectively; p < 0.01). Fecal excretion of neutral sterols increased from 6.7 mg/kg per day during the control period to 9.7 mg/kg per day during sitosterol administration (p < 0.05), and to 12.6 mg/kg per day during sitostanol administration (p < 0.05 compared with diet and sitosterol periods), indicating an increase in the inhibition of intestinal cholesterol absorption. All children completed the study and no obvious side effects occurred. The data indicate that sitostanol, even with a dose four-fold lower than that of sitosterol, was significantly more effective in reducing elevated levels of low-density lipoprotein cholesterol, and the reduction in serum lipid levels was of the same magnitude as that observed with systemic lipid-lowering drugs. These results suggest that sitostanol, a nonabsorbable plant sterol, could be the drug of choice for treating familial hypercholesterolemia in childhood.

Topics: Adolescent; Alanine Transaminase; Alkaline Phosphatase; Apolipoproteins B; Carotenoids; Child; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Feces; Female; Heterozygote; Humans; Hyperlipoproteinemia Type II; Male; Phytosterols; Sitosterols; Sterols