Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men -: A randomized controlled trial

Context Limited information exists on the interaction between diet and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and the interaction's effect on serum lipid and lipoprotein levels, insulin sensitivity, and circulating antioxidant vitamin and provitamin levels. Objective To evaluate the separate and combined effects of diet and simvastatin therapy on serum levels of lipids, lipoproteins, antioxidants, and insulin. Design, Setting, and Participants Randomized, controlled crossover trial conducted from August 1997 to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64 years who were recruited from the community in Turku, southwestern Finland. Interventions After a 4- to 6-week placebo run-in period, participants were randomly allocated to a habitual diet (n=60) or dietary treatment group (n=60), and each of these groups was further randomized in a double-blind crossover fashion to receive simivastatin (20 mg/d) or placebo, each for 12 weeks (n=30 in each group). The main goals of the dietary treatment were to reduce energy intake from saturated plus transunsaturated fats to no more than 10% by replacing them partly with monounsaturated and polyunsaturated fats rich in omega-3 fatty acids and to increase intake of fruits, vegetables, and dietary fiber. Main Outcome Measures Changes in levels of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol; triglycerides; apolipoprotein B; insulin; glucose; and antioxidants at week 12 of each treatment period, compared among the 4 groups. Results Dietary treatment decreased levels of total cholesterol by 7.6% (P<.001), LDL cholesterol by 10.8% (P<.001), HDL cholesterol by 4.9% (P=.01), apolipoprotein B by 5.7% (P=.003), serum insulin by 14.0% (P=.02), and alpha-tocopherol by 3.5% (P=.04). Simvastatin decreased levels of total cholesterol by 20.8%, LDL cholesterol by 29.7%, triglycerides by 13.6%, apolipoprotein B by 22.4%, alpha-tocopherol by 16.2%, beta-carotene by 19.5%, and ubiquinol-10 by 22.0% (P<.001 for all) and increased levels of HDL cholesterol by 7.0% (P<.001) and serum insulin by 13.2% (P=.005). Glucose levels remained unchanged in all groups. The effects of dietary treatment and simvastatin were independent and additive. Conclusions A modified Mediterranean-type diet rich in omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of simvastatin, counteracted the fasting insulin-elevating effect of simvastatin, and, unlike simvastatin, did not decrease serum levels of beta-carotene and ubiquinol-10.