Becker M, Staab D, Von Bergmann K
Department of Pediatrics, University of Bonn, Federal Republic of Germany.
J Pediatr. 1993 Feb;122(2):292-6. doi: 10.1016/s0022-3476(06)80136-8.
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.
本研究旨在比较两种植物甾醇降低血脂水平的能力，并比较它们在9名重度家族性高胆固醇血症儿童（总胆固醇和低密度脂蛋白胆固醇浓度平均分别为9.57 mmol/L（370 mg/dl）和7.87 mmol/L（301 mg/dl））中的作用机制。经过3个月严格饮食后，这些儿童服用谷甾醇含片（每日3次，每次2克）3个月，随后服用7个月的谷甾烷醇（每日3次，每次0.5克）。测定了所有9名儿童的血清脂蛋白水平以及菜油甾醇和谷甾醇的血清浓度，并在每个治疗方案结束时测定了7名儿童中性和酸性甾醇的粪便排泄量。谷甾醇使低密度脂蛋白胆固醇水平降低了20%（p<0.01）；谷甾烷醇在3个月后使低密度脂蛋白胆固醇水平降低了33%，7个月后降低了29%（与饮食相比，p<0.01；与谷甾醇相比，p<0.05）。虽然谷甾醇未改变菜油甾醇和谷甾醇的血清浓度，但在谷甾烷醇治疗期间出现了显著降低（分别降低了47%和51%；p<0.01）。中性甾醇的粪便排泄量从对照期的每天6.7 mg/kg增加到服用谷甾醇期间的每天9.7 mg/kg（p<0.05），并在服用谷甾烷醇期间增加到每天12.6 mg/kg（与饮食和谷甾醇期相比，p<0.05），表明肠道胆固醇吸收的抑制作用增强。所有儿童均完成了研究，未出现明显副作用。数据表明，即使谷甾烷醇的剂量比谷甾醇低四倍，其在降低升高的低密度脂蛋白胆固醇水平方面仍显著更有效，且血脂水平的降低幅度与全身性降脂药物观察到的幅度相同。这些结果表明，不可吸收的植物甾醇谷甾烷醇可能是治疗儿童家族性高胆固醇血症的首选药物。
