Clinical Briefs: PUFAs and Atherosclerotic Plaques

With Comments from Russell H. Greenfield, MD

Source: Thies F, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: A randomized controlled trial. Lancet 2003;361:477-485.

Goal: To ascertain whether incorporation of n-3 and n-6 polyunsaturated fatty acids (PUFAs) into advanced atherosclerotic plaques increases and decreases, respectively, plaque stability.

Design: Double-blind, randomized controlled study.

Subjects: One hundred eighty-eight patients awaiting carotid endarterectomy (total of 162 patients completed the study).

Methods: Patients were given either control oil (80:20 blend of palm and soybean oils); sunflower oil, or fish oil while continuing on their drug regimens and regular diet. Each patient took six capsules daily (two with each meal) until the date of surgery. Duration of treatment was 7-189 days (median of 42 days). Plaque morphology was evaluated for evidence of stability or instability. The researchers measured concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid in carotid plaques, and tested for the presence of macrophages in plaques via immunohistochemical staining.

Results: Concentrations of EPA and DHA in plaque were highest in patients receiving the fish oil capsules. Plaques from patients treated with fish oil had fewer morphologic signs consistent with inflammation than plaques from those in the sunflower oil or control groups. The number of macrophages found within the plaques of subjects receiving fish oil was less than in the other two groups. Carotid plaque morphology, fatty-acid compositions of plaque lipid fractions, and macrophage infiltration did not differ between control and sunflower oil groups.

Conclusion: n-3 PUFAs from fish oil supplementation are rapidly incorporated into atherosclerotic plaques and limit inflammatory changes, thereby enhancing plaque stability.

Study strength: Adherence to protocol was estimated to be 85-90% in each treatment group.

Study weakness: No group was randomized to a diet high in oily fish.

Of note: Study results suggest that atherosclerotic plaques are relatively dynamic; the fatty acid content of the 80:20 palm and soybean oil blend is stated to closely match that of the average British diet; increased intake of n-6 PUFAs from sunflower oil did not affect the fatty acid composition of plaque, nor plaque stability compared with controls.

Did you know? n-3 PUFAs lower triglyceride levels and have been shown to be very effective in reducing rates of sudden death; the amount of fish oil provided in the capsules can be obtained through regular dietary consumption of oily fish; macrophages contribute to plaque inflammation and instability; vulnerability of plaque to rupture is the primary determinant of acute thrombosis-mediated cardiovascular events.

Clinical import: Although no direct harm was identified with the use of n-6 PUFAs from sunflower oil, there was evidence of benefit from the use of fish oil supplementation. The n-3 PUFAs were incorporated into atherosclerotic plaques and helped stabilize them. This is yet another well-designed study singing the praises of fish oil, whether through dietary intake or supplementation.

What to do with this article: Keep a hard copy in your file and make copies for your peers.