Is fat restriction needed with HMGCoA reductase inhibitor treatment?

Fourteen women and five men participated in a 20-week controlled, cross-over trial of the interaction of simvastatin, an HMGCoA reductase inhibitor, with high and low fat diets. Simvastatin was found to be just as effective at lowering LDL cholesterol whether the subjects were on a 22% fat diet or a 38% fat diet (25% and 29% falls, respectively). Nevertheless, the lowest cholesterol levels were achieved by combining simvastatin with a low fat diet, the latter adding a further 5% reduction in plasma cholesterol. Simvastatin plus a low or high fat diet increased HDL cholesterol by 10.0% and 2.9% respectively (P = 0.003 overall) and reduced triglyceride concentration by 15.9% and 19% respectively (P less than 0.001). Significant diet-drug interactions were seen in LDL and HDL3 cholesterol. Simvastatin blunted the effect of dietary fat change so that the difference in LDL cholesterol, which was 0.71 mmol/l between high and low fat in the absence of simvastatin, was only 0.22 mmol/l with simvastatin. On a high fat diet, simvastatin produced almost no rise in HDL3 cholesterol whereas on a low fat diet HDL3 cholesterol was increased by 8.8% with simvastatin. The cholesterol content of VLDL and LDL were significantly reduced by simvastatin. The effects of diet and drug on apoproteins A-I and B resembles those on HDL and LDL cholesterol. The findings show interactions between simvastatin and dietary fat which have a bearing on the treatment of hypercholesterolemia.