Gylling H, Miettinen T A
Department of Medicine, University of Helsinki, Finland.
J Lipid Res. 1996 Aug;37(8):1776-85.
Effectiveness of a simultaneous inhibition of cholesterol absorption and synthesis, caused by sitostanol ester margarine and pravastatin, was studied to control mild hypercholesterolemia in men with non-insulin-dependent diabetes mellitus (NIDDM) (n = 8). Margarine, 24 g daily, was a basal dietary treatment. Four 7-week intervention periods included margarine, sitostanol (3 g/day) ester margarine, pravastatin (40 mg/day), and sitostanol ester margarine plus pravastatin in a random order. Pravastatin lowered serum total (-32%) and LDL cholesterol (-38%) and apolipoprotein B (-39%) because of enhanced removal (+20%) and decreased production (-26%) of LDL apolipoprotein B, and reduced synthesis (-9%) and turnover (-8%) of cholesterol, which resulted in reduced biliary cholesterol seretion (-18%). Even though serum triglycerides were lowered by 28%, VLDL, IDL, and light and dense LDL became triglyceride-enriched. Despite increasing cholesterol synthesis, sitostanol lowered LDL cholesterol (-14%) by inhibiting cholesterol absorption (-68%) and LDL apolipoprotein B production rate (-20%). Combination of pravastatin and sitostanol ester lowered serum total, VLDL, IDL, and LDL cholesterol and LDL apolipoprotein B by the highest rate, 35%, 50%, 35%, 44%, and 45% from the control margarine period, respectively, because of reduced apolipoprotein B transport rate (but unchanged removal), in both the total and dense LDL subfractions. HDL cholesterol and apolipoprotein A-I kinetics were unchanged. In spite of decreased absorption, cholesterol synthesis was not compensatorily increased. In conclusion, simultaneous inhibition of cholesterol absorption and synthesis lowers LDL cholesterol and apolipoprotein B by 44-45% solely through inhibition of LDL apolipoprotein B production rate in hypercholesterolemic NIDDM patients. A combination of statin to sitostanol ester margarine-resistant patients offers a safe and effective measure to normalize abnormally high cholesterol values, probably with a lowered statin dose.
研究了由谷甾烷醇酯人造黄油和普伐他汀引起的胆固醇吸收与合成同时抑制对控制非胰岛素依赖型糖尿病（NIDDM）男性（n = 8）轻度高胆固醇血症的有效性。每天24克人造黄油是基础饮食治疗。四个为期7周的干预期包括人造黄油、谷甾烷醇（3克/天）酯人造黄油、普伐他汀（40毫克/天）以及谷甾烷醇酯人造黄油加普伐他汀，顺序随机。普伐他汀降低了血清总胆固醇（-32%）、低密度脂蛋白胆固醇（-38%）和载脂蛋白B（-39%），这是由于低密度脂蛋白载脂蛋白B的清除增加（+20%）和生成减少（-26%），以及胆固醇合成减少（-9%）和周转减少（-8%），从而导致胆汁胆固醇分泌减少（-18%）。尽管血清甘油三酯降低了28%，但极低密度脂蛋白（VLDL）、中间密度脂蛋白（IDL）以及轻、重低密度脂蛋白都富含了甘油三酯。尽管胆固醇合成增加，但谷甾烷醇通过抑制胆固醇吸收（-68%）和低密度脂蛋白载脂蛋白B生成率（-20%）降低了低密度脂蛋白胆固醇（-14%）。普伐他汀与谷甾烷醇酯联合使用使血清总胆固醇、极低密度脂蛋白、中间密度脂蛋白和低密度脂蛋白胆固醇以及低密度脂蛋白载脂蛋白B降低的幅度最大，分别比对照人造黄油期降低了35%、50%、35%、44%和45%，这是因为在总低密度脂蛋白和高密度脂蛋白亚组分中载脂蛋白B转运率降低（但清除不变）。高密度脂蛋白胆固醇和载脂蛋白A-I动力学未改变。尽管吸收减少，但胆固醇合成并未代偿性增加。总之，在高胆固醇血症的非胰岛素依赖型糖尿病患者中，同时抑制胆固醇吸收与合成仅通过抑制低密度脂蛋白载脂蛋白B生成率就能使低密度脂蛋白胆固醇和载脂蛋白B降低44% - 45%。对于对谷甾烷醇酯人造黄油耐药的患者，他汀类药物与之联合使用提供了一种安全有效的措施来使异常升高的胆固醇值恢复正常，可能还需要降低他汀类药物的剂量。
