Assessment of the possible adverse effects of oils enriched with n-3 fatty acids in rats: peroxisomal proliferation, mitochondrial dysfunctions and apoplexy

Possible adverse effects of excess intake of dietary n-3 fatty acids have been reevaluated in rats by measuring peroxisomal proliferation, mitochondrial enzyme activity and incidence of apoplexy. When Sprague-Dawley rats were fed diets containing either fish oil rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or perilla seed oil rich in α-linolenic acid for 4 or 12 weeks, DHA accumulated in phospholipids of liver and heart in the fish oil group, but not in the perilla oil group when compared with safflower and soybean oil groups. Feeding a diet containing 15 weight % of fish oil induced a significant proliferation of peroxisomes compared with safflower oil-diet, but the proliferating activity of perilla oil was much less. The peroxisomal β-oxidation activities were negatively correlated with neutral lipid contents in liver. Heart mitochondrial cytochrome c oxidase activity was not affected significantly by feeding fish oil or perilla oil in the presence of an essential amount of linoleic acid for up to 12 weeks, though the proportion of linoleic acid in heart cardiolipin decreased from >86% in the safflower and soybean oil groups to 81% in the perilla oil group and to 33% in the fish oil group. Feeding n-3-enriched fish oil and perilla oil in 10 weight % of the diets did not accelerate the onset of cerebral bleeding in stroke-prone spontaneously hypertensive rats (SHRSP). Although the proliferating activity of peroxisomes by excess intake of fish oils should be noticed, these results provide evidence that n-3-enriched oils are safe under conditions applicable to human nutrition, considering the levels fed the rats were several fold higher than the anticipated maximal intake in human.