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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1952.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men

A Randomized Controlled Trial

Antti Jula; Jukka Marniemi; Tapani Rönnemaa; Arja Virtanen; Risto Huupponen

From the Laboratory for Population Research, Department of Health and Functional Capacity (A.J. J.M.), National Public Health Institute of Finland, Turku; the Research Department (A.V.), Social Insurance Institution, Turku; the Department of Medicine (T.R.), University of Turku; and the Department of Pharmacology and Toxicology (R.H.), University of Kuopio, Finland.

Correspondence to Antti Jula, MD, Laboratory for Population Research, Department of Health and Functional Capacity, National Public Health Institute of Finland, Turku, Finland, Peltolantie 3, FIN-20720 Turku, Finland. E-mail antti.jula{at}ktl.fi

Objective— To explore the separate and combined effects of simvastatin and a low-saturated diet rich in -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 -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 -linolenic acid by 6.8% (P<0.05), and increased proportions of -linolenic acid (C18:3n-6) by 11.1% (P<0.001), dihomo--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, -linolenic to linoleic, and arachidonic to dihomo--linolenic acid by 7.6%, 17.0%, and 10.0% (P<0.001 for all), respectively, suggesting increased fatty acid elongase and 6- and 5-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.

Effects of diet and simvastatin on serum fatty acids in hypercholesterolemic men were studied in a randomized controlled trial. Simvastatin increased the formation of long-chain polyunsaturated fatty acids. Increased formation of long-chain polyunsaturated fatty acids and their metabolites may contribute a substantial part of the pleiotropic effects of simvastatin.

Key Words: fatty acid metabolism • diet • hypercholesterolemia • statins

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