RESUMO
OBJECTIVE: To explore the separate and combined effects of simvastatin and a low-saturated diet rich in alpha-linolenic acid on serum fatty acids. METHODS AND RESULTS: 120 hypercholesterolemic men were randomly allocated to a habitual diet or dietary treatment group and to receive, in random order, simvastatin 20 mg/d or placebo, each for 12 weeks, in a double-blind manner. Dietary treatment decreased proportions from total fatty acids of palmitic acid (C16:0) by 3.3% (P<0.05), stearic acid (C18:0) by 3.7% (P<0.05) and increased proportions of oleic acid (C18:1n-9) by 4.2% (P<0.01), and alpha-linolenic acid (C18:3n-3) by 29.8% (P<0.001). Simvastatin decreased proportions from total fatty acids of palmitic acid by 2.0% (P<0.01), linoleic acid (C18:2n-6) by 5.3% (P<0.001), and alpha-linolenic acid by 6.8% (P<0.05), and increased proportions of gamma-linolenic acid (C18:3n-6) by 11.1% (P<0.001), dihomo-gamma-linolenic acid (C20:3n-6) by 4.2% (P<0.01), arachidonic acid (C20:4n-6) by 14.2% (P<0.001), and the sum of long-chain polyunsaturated fatty acids (C20-22) by 9.0% (P<0.001). Simvastatin increased ratios of stearic to palmitic, gamma-linolenic to linoleic, and arachidonic to dihomo-gamma-linolenic acid by 7.6%, 17.0%, and 10.0% (P<0.001 for all), respectively, suggesting increased fatty acid elongase and Delta6- and Delta5-desaturase enzyme activities. CONCLUSIONS: Increased formation of long-chain polyunsaturated fatty acids and their metabolites may contribute a substantial part of the pleiotropic effects of simvastatin.
Assuntos
Anticolesterolemiantes/administração & dosagem , Hipercolesterolemia/dietoterapia , Hipercolesterolemia/tratamento farmacológico , Sinvastatina/administração & dosagem , Ácido alfa-Linolênico/administração & dosagem , Adulto , Terapia Combinada , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/sangue , Ácidos Graxos/sangue , Ácidos Graxos Insaturados/sangue , Comportamento Alimentar , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ácido alfa-Linolênico/sangueRESUMO
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 simvastatin (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 trans-unsaturated 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.