Gylling H, Miettinen T A
Department of Clinical Nutrition, University of Kuopio, Kuopio University Hospital, Kuopio, Finland.
Nutr Metab Cardiovasc Dis. 2002 Feb;12(1):19-23.
Recent large-scale trials have consistently documented the fact that a 25-35% reduction in low-density lipoprotein cholesterol (LDL-C) can delay the progression of atherosclerosis. This raises the question as to how much it is possible to reduce serum cholesterol using feasible therapies. The aim of this study was to investigate the cholesterol-lowering efficacy of a triple therapy combining bile acid malabsorption with the inhibition of cholesterol synthesis and absorption.
Eleven consecutive hypercholesterolemic coronary patients from Lipid Clinics on a low-fat, low-cholesterol baseline diet added simvastatin (20 mg/day) for three months, and then dietary plant stanol ester margarine (2.25 g of stanols/day) for eight weeks; finally, cholestyramine 8 g/day was added for another eight weeks. This was a before-after trial, in which the results of each period were compared with baseline and those of the previous period. Serum lipids were quantitated using commercial kits, and serum sterols by means of gas-liquid chromatography. Simvastatin lowered LDL-C by 39% (p < 0.001), and additional stanol ester margarine by a further 13% (p < 0.05). The triple treatment led to 67% reduction from baseline (p < 0.001), with all LDL-C values being < 2.6 mmol/L, and increased high-density lipoprotein cholesterol (HDL-C) by 15% (p < 0.01). It also increased the serum lathosterol/cholesterol ratio (p < 0.01), thus indicating an upregulation of cholesterol synthesis, and increased the serum sitosterol ratio (p < 0.01) despite the simultaneous consumption of plant stanols.
The massive reduction in LDL and increase in HDL-C obtained using our triple therapy suggests that the combination of stanol ester with only moderate doses of statin and resin makes it possible to control LDL-C levels effectively in hypercholesterolemic subjects.
近期的大规模试验一致证实，低密度脂蛋白胆固醇（LDL-C）降低25% - 35%可延缓动脉粥样硬化进展。这引发了一个问题，即使用可行疗法能将血清胆固醇降低多少。本研究旨在探讨结合胆汁酸吸收不良、抑制胆固醇合成及吸收的三联疗法的降胆固醇疗效。
脂质诊所的11例连续高胆固醇血症冠心病患者，在低脂、低胆固醇基线饮食基础上，先服用辛伐他汀（20毫克/天）三个月，然后食用植物甾醇酯人造黄油（2.25克甾醇/天）八周；最后再添加消胆胺8克/天，持续八周。这是一项前后对照试验，将各阶段结果与基线及上一阶段结果进行比较。使用商用试剂盒定量测定血清脂质，采用气液色谱法测定血清甾醇。辛伐他汀使LDL-C降低39%（p < 0.001），额外添加植物甾醇酯人造黄油后再降低13%（p < 0.05）。三联疗法使LDL-C较基线降低67%（p < 0.001），所有LDL-C值均< 2.6毫摩尔/升，高密度脂蛋白胆固醇（HDL-C）升高15%（p < 0.01）。它还使血清羊毛甾醇/胆固醇比值升高（p < 0.01），表明胆固醇合成上调，尽管同时食用植物甾醇，血清谷甾醇比值仍升高（p < 0.01）。
我们的三联疗法使LDL大幅降低且HDL-C升高，这表明甾醇酯与仅中等剂量的他汀类药物和树脂联合使用，能够有效控制高胆固醇血症患者的LDL-C水平。
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