We examined whether the synthesis of interleukin-1 or tumor necrosis factor, two cytokines with potent inflammatory activities, is influenced by dietary supplementation with n-3 fatty acids. Nine healthy volunteers added 18 g of fish-oil concentrate per day to their normal Western diet for six weeks. We used a radioimmunoassay to measure interleukin-1 (IL-1 beta and IL-1 alpha) and tumor necrosis factor produced in vitro by stimulated peripheral-blood mononuclear cells. With endotoxin as a stimulus, the synthesis of IL-1 beta was suppressed from 7.4 +/- 0.9 ng per milliliter at base line to 4.2 +/- 0.5 ng per milliliter after six weeks of supplementation (43 percent decrease; P = 0.048). Ten weeks after the end of n-3 supplementation, we observed a further decrease to 2.9 +/- 0.5 ng per milliliter (61 percent decrease; P = 0.005). The production of IL-1 alpha and tumor necrosis factor responded in a similar manner. Twenty weeks after the end of supplementation, the production of IL-1 beta, IL-1 alpha, and tumor necrosis factor had returned to the presupplement level. The decreased production of interleukin-1 and tumor necrosis factor was accompanied by a decreased ratio of arachidonic acid to eicosapentaenoic acid in the membrane phospholipids of mononuclear cells. We conclude that the synthesis of IL-1 beta, IL-1 alpha, and tumor necrosis factor can be suppressed by dietary supplementation with long-chain n-3 fatty acids. The reported antiinflammatory effect of these n-3 fatty acids may be mediated in part by their inhibitory effect on the production of interleukin-1 and tumor necrosis factor.

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The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells

https://ir.library.oregonstate.edu/downloads/m326m253d

Importance of n−3 fatty acids in health and disease

Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review.

A detailed technical overview summarizes and discusses available evidence concerning the effects of fish oil n-3 polyunsaturated fatty acids (PUFA's) on reducing cardiovascular disease risks. Attention is given to: the characteristics and metabolism of n-6 and n-3 PUFA's and the effects of n-3 PUFA's on plasma lipid profiles; the role of n-3 PUFA's in reducing atherosclerosis risk; possible protection of n-3 PUFA's during myocardial infarction; the relative importance of eicosapentaenoic vs. docosahexaneoic acids; and appropriate intakes of n-3 PUFA's. The potential adverse health effects from ingesting fish oils also are discussed.(wz)

Cardiovascular effects of n-3 fatty acids

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(03)12468-3.pdf

Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial

The effect of feeding fish oil (Menhaden) on the progression of rhesus monkey atherosclerosis was determined by feeding diets containing 2% cholesterol and either 25% coconut oil (Group I), 25% fish oil/coconut oil (1:1) (Group II), or 25% fish oil/coconut oil (3:1) (Group III) for 12 months (n = 8/group). The average serum cholesterol levels were 875 mg/dl for Group I, 463 mg/dl for Group II, and 405 mg/dl for Group III. HDL cholesterol levels were 49 mg/dl for Group I, 29 mg/dl for Group II, and 20 mg/dl for Group III. An average of 79% of the aortic intima was involved with atherosclerosis in Group I, 48% in Group II, and 36% in Group III. The aortas of both fish-oil groups (II or III) contained significantly less cholesterol (total, free, and esterified), as well as less acid lipase, cholesteryl esterase, and ACAT activities when compared to the coconut-oil group (I) (p less than 0.05). Microscopically, the aortic and carotid artery lesions were smaller in cross-sectional area and in thickness, and contained less macrophages in the fish-oil groups (II and III) when compared to the coconut-oil group (I) (p less than 0.05). This protective effect was not consistently enhanced by increasing the proportion of fish oil to 3:1 (Group III) over 1:1 (Group II). The results indicate that fish oil-containing diets reduce serum cholesterol levels and inhibit atherosclerosis even in the face of lowered HDL cholesterol levels when compared to a pure coconut oil/cholesterol diet in rhesus monkeys. Therefore, fish-oil diets exert effective protective control of progression of atherosclerosis during severe atherogenic stimuli.

Fish oil inhibits development of atherosclerosis in rhesus monkeys.

Diet-induced atherosclerosis in rhesus monkeys was suppressed in the carotid arteries and thoracic aorta by the calcium antagonist nifedipine given orally for a period of 1 year at a dose of 10 mg b.i.d. The extent of atherosclerosis was determined by quantitative micromorphometric studies. No change in serum blood cholesterol or biochemical composition of the major vessels was detected, but the intimal area and thickness of the atherosclerotic plaques in the carotid arteries of the nifedipine group were markedly less than those found with the control group (p less than 0.05). However, no statistically significant differences were seen in the degree of atherosclerotic involvement of the other major arterial vessels. Although the mechanism is not clear, nifedipine may be useful in the treatment of carotid artery disease.

R W Wissler

Papers

Fish oil inhibits development of atherosclerosis in rhesus monkeys.

Suppression of atherogenesis by nifedipine in the cholesterol-fed rhesus monkey.

atherosclerotic lesions. Histochemical detection and quantification of macrophages in rhesus and cynomolgus monkey