on July 14, 2005
Published online before print July 14, 2005, doi: 10.1161/01.ATV.0000177812.84927.fa
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Submitted on June 30, 2004
Accepted on July 1, 2005
Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men. A Randomized Controlled Trial
Antti Jula *;
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.
* To whom correspondence should be addressed. 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.
Key words: fatty acid metabolism • diet • hypercholesterolemia • statins
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