Abstract
Background and aimImpaired vasodilatation has been suggested to be caused by inhibition of nitric oxide generation by the recently described asymmetric dimethylarginine (ADMA). In the present study we wanted to explore whether n-3 polyunsaturated fatty acid (PUFA) supplementation and/or diet intervention have beneficial influence on endothelial function assessed as plasma levels of ADMA and L-arginine.MethodsA male population (n = 563, age 70 ± 6 yrs) with long-standing hyperlipidemia, characterized as high risk individuals in 1970–72, was included, randomly allocated to receive placebo n-3 PUFA capsules (corn oil) and no dietary advice (control group), dietary advice (Mediterranean type), n-3 PUFA capsules, or dietary advice and n-3 PUFA combined and followed for 3 years. Fasting blood samples were drawn at baseline and the end of the study.ResultsCompliance with both intervention regimens were demonstrated by changes in serum fatty acids and by recordings from a food frequency questionnaire. No influence of either regimens on ADMA levels were obtained. However, n-3 PUFA supplementation was accompanied by a significant increase in L-arginine levels, different from the decrease observed in the placebo group (p < 0.05). In individuals with low body mass index (<26 kg/m2), the decrease in L-arginine on placebo was strengthened (p = 0.01), and the L-arginine/ADMA ratio was also significantly reduced (p = 0.04).ConclusionIn this rather large randomized intervention study, ADMA levels were not influenced by n-3 PUFA supplementation or dietary counselling. n-3 PUFA did, however, counteract the age-related reduction in L-arginine seen on placebo, especially in lean individuals, which might be discussed as an improvement of endothelial function.
Highlights
Endothelial dysfunction is an early and crucial event in the pathogenesis of atherosclerosis and cardiovascular disease [1]
This is a follow-up study of participants from the Oslo Diet and Anti-smoking study carried out 1972–1977 [32], comprising 1232 men with hypercholesterolemia and at high risk for coronary heart disease. The survivors of this population were 25 years later invited to participate in the Diet and Omega-3 Intervention Trial on Atherosclerosis (DOIT), a 3-year intervention trial aimed to investigate the effect of n-3 polyunsaturated fatty acid (PUFA) supplementation and/or dietary intervention on markers of atherosclerosis [33]
Raised plasma levels of asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide (NO) synthase [9], have been shown to antagonize the endothelium-dependent vasodilatation [9,10,11], and increased levels of ADMA have been shown to be associated with increased risk of coronary events in a selected population [12]
Summary
Endothelial dysfunction is an early and crucial event in the pathogenesis of atherosclerosis and cardiovascular disease [1]. It is reflecting an imbalance between the vasoconstriction and vasodilatation components and is associated with several risk factors such as (page number not for citation purposes). Oral Larginine supplementation has been shown to increase the plasma L-arginine levels with subsequent improvement of endothelial function in healthy elderly individuals [8]. In the present study we wanted to explore whether n-3 polyunsaturated fatty acid (PUFA) supplementation and/or diet intervention have beneficial influence on endothelial function assessed as plasma levels of ADMA and L-arginine
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