LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Clinical Nutrition, University of Kuopio, Kuopio University Hospital, Kuopio, Finland.
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H
Gylling
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TA
Miettinen
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000096:biosynthesis / Q000097:blood / Q000187:drug effects*; D002792:Cholestyramine Resin / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D018752:Diet, Fat-Restricted; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D019821:Simvastatin / Q000627:therapeutic use; D012855:Sitosterols / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D012855:Sitosterols; C407042:plant stanol ester; D002792:Cholestyramine Resin; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol; D019821:Simvastatin