Effect of diet and omega-3 fatty acid intervention on asymmetric dimethylarginine

Impaired 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.

A 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.

Compliance 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).

In 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.