We studied the effects of feeding experimental diets containing (n-6) to (n-3) fatty acid ratios of 31:1, 5.4:1, and 1.4:1 to 20 healthy female geriatric Beagles (9.5-11.5 y) for 8-12 wk on various indices of the immune response. Compared with the 31:1 diet, consumption of the 5.4:1 and 1.4:1 diets significantly increased (n-3) fatty acids in plasma (2.17 +/- 0.64, 9.05 +/- 0.64, 17.46 +/- 0.64 g/100 g fatty acids, respectively, P < 0.0001). Although supplementation with (n-3) fatty acids did not significantly alter the humoral immune response to keyhole limpet hemocyanin (KLH), it significantly suppressed the cell-mediated immune response based on results of a delayed-type hypersensitivity (DTH) skin test. The DTH response after intradermal injection of KLH at 24 h was significantly lower in the group consuming the 1.4:1 diet compared with the group consuming the 5.4:1 (P = 0.02) or the 31:1 diets (P = 0.04), and remained significantly suppressed at 48 h in the group fed 1.4:1 relative to the group fed 31:1. After consumption of the 1.4:1 diet, stimulated mononuclear cells produced 52% less prostaglandin E2 (PGE2) than those from dogs fed the 31:1 diet (224 +/- 74 and 451 +/- 71 pmol/L, respectively, P = 0.04). Plasma concentration of alpha-tocopherol was 20% lower in dogs fed the 1.4:1 diet compared with those fed the 31:1 diet (P = 0.04), and lipid peroxidation was greater in both plasma (P = 0.03) and urine (P = 0.002). These data suggest that although a ratio of dietary (n-6) to (n-3) fatty acids of 1.4:1 depresses the cell-mediated immune response and PGE2 production, it increases lipid peroxidation and lowers vitamin E concentration.

Background: Although the replacement of dietary saturated fat with unsaturated fat has been advocated to reduce the risk of cardiovascular disease, diets high in polyunsaturated fatty acids (PUFAs) could increase lipid peroxidation, potentially contributing to the pathology of atherosclerosis. Objective: The objective of this study was to examine indexes of in vivo lipid peroxidation, including free F 2 -isoprostanes, malondialdehyde (MDA), and thiobarbituric acid reacting substances (TBARS), in the plasma of postmenopausal women taking dietary oil supplements rich in oleate, linoleate, and both eicosapentaenoic acid and docosahexaenoic acid. Results: Plasma free F 2 -isoprostane concentrations were lower after fish-oil supplementation than after sunflower-oil supplementation (P = 0.003). When plasma free F 2 -isoprostane concentrations were normalized to plasma arachidonic acid concentrations, significant differences among the supplements were eliminated. Plasma MDA concentrations were lower after fishoil supplementation than after sunflower-oil supplementation (P = 0.04), whereas plasma TBARS were higher after fish-oil supplementation than after sunflower oil (P = 0.003) and safflower oil (P = 0.001) supplementation. When plasma MDA concentrations were normalized to plasma PUFA concentrations, significant differences were eliminated, but TBARS remained higher after fish-oil supplementation than after sunflower oil (P = 0.01) and safflower-oil (P = 0.0003) supplementation. Conclusions: With fish-oil supplementation, there was no evidence of increased lipid peroxidation when assessed by plasma F 2 -isoprostanes and MDA, although plasma TBARS was higher than with sunflower-oil and safflower-oil supplementation. Am J Clin Nutr 2000;72:714-22.

Although these data show a small but statistically significant increase in oxidative stress on the basis of plasma TBARS concentrations after the consumption of EPA and DHA, the clinical relevance of this change is questionable. In addition, as supplements of alpha-tocopheryl acetate were added to the diet, neither the plasma TBARS concentration nor the protein oxidation changed. Consequently, the results of this study indicate that there is no basis for vitamin E supplementation after consumption of EPA and DHA.

We evaluated the effects of RRR-alpha-tocpheryl acetate (alpha-tocopheryl acetate) and hormone-replacement therapy (HRT) on the oxidative susceptibility of low-density lipoprotein (LDL) in postmenopausal women consuming a fish oil supplement. The independent effect of fish oil was also assessed. Forty-eight women, equally divided between women using and not using HRT, participated in a double-blind crossover trial. Each of the four periods lasted 5 wk and was followed by a 4-wk washout interval. During each period all subjects were given a 15-g supplement of fish oil and either 0 (placebo), 100, 200, or 400 mg alpha-tocopheryl acetate daily. LDL resistance to oxidative modification was assessed by calculating lag time, propagation rate, and maximum production of conjugated dienes. Supplementation with fish oil and placebo shortened lag time and slowed propagation rate in women both using and not using HRT. After subjects consumed fish oil, supplementation with alpha-tocopheryl acetate increased plasma and LDL alpha-tocopherol contents significantly and lengthened lag time (at even the lowest concentration) but had no significant effect on propagation rate or maximum production compared with values measured after consumption of fish oil alone. Women not using HRT had faster propagation rates and higher maximum production than women using HRT; after supplementation with fish oil and alpha-tocopheryl acetate these differences prevailed. Supplements as low as 100 mg alpha-tocopheryl acetate/d increase the resistance of LDL to oxidation when fish oil supplements are used. HRT and fish oil supplements may independently affect LDL oxidative susceptibility.

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Although diets containing fish have been shown to be therapeutically valuable, the vitamin E requirement when large quantities of (n-3) fatty acids are consumed is not known. Additionally, as estrogens may function as an antioxidant, the requirement may be modified in postmenopausal women using hormone replacement therapy (HRT). Consequently, the purpose of this study was to measure the impact of graduated doses of RRR-alpha-tocopheryl acetate (TA) on in vivo indices of lipid peroxidation in postmenopausal women with and without hormone replacement therapy when given a supplement of fish oil. Forty-eight postmenopausal women, half receiving (+HRT) and half not receiving (-HRT) hormone replacement therapy, participated in a four-period, double-blind crossover trial. Each period lasted 5 wk followed by a 4-wk washout interval. During each period, the subjects consumed a 15-g supplement of fish oil and either 0, 100, 200, or 400 mg TA/d in a balanced, single square dosing order. Plasma levels of (n-3) fatty acids were significantly higher after fish oil supplementation; alpha-tocopherol concentration of plasma was significantly higher at each level of supplementation compared with the level without supplementation. Urinary excretion of thiobarbituric acid reactive substances (TBARS) and malondialdehyde, measured as the thiobarbituric-malondialdehyde adduct (TRA-MDA adduct), and the plasma concentration of the adduct were significantly greater after the fish oil supplement. Although urinary TBARS decreased linearly as the dose of TA increases (P < or = 0.05), urinary and plasma concentrations of TBA-MDA adduct did not. This study suggests that the evaluation of highly unsaturated fatty acids as oxidative stressors requires several measures of assessment.