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Background: Greatly increasing dietary flaxseed oil [rich in the n--3 polyunsaturated fatty acid (PUFA) [alpha]-linolenic acid (ALA)] or fish oil [rich in the long-chain n--3 PUFAs eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] can reduce markers of immune cell function. The effects of more modest doses are unclear, and it is not known whether ALA has the same effects as its long-chain derivatives. Objective: The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes. Design: In a placebo-controlled, double-blind, parallel study, 150 healthy men and women aged 25-72 y were randomly assigned to 1 of 5 interventions: placebo (no additional n--3 PUFAs), 4.5 or 9.5 g ALA/d, and 0.77 or 1.7 g EPA+DHA/d for 6 mo. The n--3 PUFAs were provided in 25 g fat spread plus 3 oil capsules. Blood samples were taken at 0, 3, and 6 mo. Results: The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA. The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity, the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester, the proliferation of lymphocytes in response to a T cell mitogen, the production of numerous cytokines by monocytes and lymphocytes, or the in vivo delayed-type hypersensitivity response. Conclusion: An intake of [less than or equal to] 9.5 g ALA/d or [less than or equal to] 1.7 g EPA+DHA/d does not alter the functional activity of neutrophils, monocytes, or lymphocytes, but it changes the fatty acid composition of mononuclear cells. Am J Clin Nutr 2003:77:1287-95. KEY WORDS Fish oil, [alpha]-linolenic acid, n--3 polyunsaturated fatty acids, immunity, lymphocyte, monocyte, neutrophil, cytokine, phagocytosis, oxidative burst

Background: Dietary [alpha]-linolenic acid (ALA) can be converted to long-chain n-3 polyunsaturated fatty acids (PUFAs) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors. Objective: This study aimed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors. Design: This was a placebo-controlled, parallel study involving 150 moderately hyperlipidemic subjects randomly assigned to 1 of 5 interventions: 0.8 or 1.7 g EPA+DHA/d, 4.5 or 9.5 g ALA/d, or an n-6 PUFA control for 6 mo. Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily. Results: The change in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control. The mean ([+ or -] SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 [+ or-] 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 [+ or -] 4.5%). The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions (P < 0.05). There was no significant change in plasma [alpha]-tocopherol concentrations or in whole plasma antioxidant status in any of the groups. Conclusion: At estimated biologically equivalent intakes, dietary ALA and EPA+DHA have different physiologic effects. KEY WORDS [alpha]-Linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, polyunsaturated fatty acids, n-3 fatty acids, lipids, plasma fatty acid, LDL oxidation, moderately hyperlipidemic subjects, triacylglycerol

Background: The effect of long-term increased intakes of [alpha]-linolenic acid (ALA; 18:3n-3) on cardiovascular risk factors is unknown. Objectives: Our objectives were to assess the effect of increased ALA intakes on cardiovascular risk factors and the estimated risk of ischemic heart disease (IHD) at 2 y and the effect of nutritional education on dietary habits. Design: Subjects with multiple cardiovascular risk factors (124 men and 158 women) were randomly assigned in a double-blind fashion to consume a margarine rich in either ALA [46% linoleic acid (LA; 18:2n-6) and 15% ALA; n = 114] or LA (58% LA and 0.3% ALA; n = 168). An intervention group (n = 110; 50% ALA) obtained group nutritional education, and a control group (n = 172; 34% ALA) received a posted leaflet containing the standard Dutch dietary guidelines. Results: Average ALA intakes were 6.3 and 1.0 g/d in the ALA and LA groups, respectively. After 2 y, the ALA group had a higher ratio of total to HDL cholesterol (+0.34; 95% CI: 0.12, 0.56), lower HDL cholesterol (-0.05 mmol/L; -0.10, 0), higher serum triacylglycerol (+0.24 mmol/L; 0.02, 0.46), and lower plasma fibrinogen (-0.18 g/L; -0.31, -0.04; after 1 y) than did the LA group (adjusted for baseline values, sex, and lipid-lowering drugs). No significant difference existed in 10-y estimated IHD risk. After 2 y, the intervention group had lower saturated fat intakes and higher fish intakes than did the control group. Conclusions: Increased ALA intakes decrease the estimated IHD risk to an extent similar to that found with increased LA intakes. Group nutritional education can effectively increase fish intake. KEY WORDS [alpha]-Linolenic acid, linoleic acid, prevention, ischemic heart disease, nutritional education, cardiovascular risk factors, Netherlands, MARGARIN study

The effects of [Alpha]-linolenic acid (ALA, 18:3n -- 3), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) on hemostatic factors were compared. Healthy subjects (29 women and 17 men aged 20-4 y) received either linseed oil (average ALA intake: 5.9 g/d) or fish oil plus sunflower oil (average EPA + DHA intake: 5.2 g/d) for 4 wk. The supplemented amount of fat was 1.19 mg/kJ (1 g/200 kcal) calculated energy expenditure. Stability of habitual diets was monitored. Blood samples were collected at baseline, at the end of the experimental period, and after a 12-wk follow-up period. Different changes in the study groups were seen only in serum cholesterol and triacylglycerols, platelet fatty acid composition, and ADP-induced platelet aggregation. The treatments did not differ in their effects on collagen-induced platelet aggregation and diromboxane production, aggregation to the thromboxane [A.sub.2] mimic I-BOP, urinary excretion of 11-dehydro-thromboxane [B.sub.2] and [Beta]-thromboglobulin, bleeding time, plasma fibrinogen concentration, antithrombin III activity, factor VII coagulant activity, or activity of plasminogen activator inhibitor 1. The results indicate that supplemented ALA from vegetable oil and EPA and DHA from a marine source have largely parallel effects on hemostatic factors.

Dienoic eicosanoids derived from phospholipid arachidonic acid (AA) in lung and liver macrophages promote leukosequestration, thrombosis, and tissue injury. Current enteral diets (diet A) are enriched with linoleic acid (LA), a precursor of AA. Novel diets low in LA and containing eicosapentaenoic acid (EPA) and y-linolenic acid (GLA) foster formation of less inflammatory eicosanoids. The study objective was to assess the rapidity and extent of LA and AA displacement in vivo from alveolar macrophage (AMO, lung, and liver Kupffer and endothelial (KE) cell phospholipids in rats fed enterally with diets enriched with 5.3% (by wt) EPA and either 1.2% or 4.6% GLA (diets B and C, respectively). After surgical placement of catheters, the rats were fed enterally and co-infused intravenously with either endotoxin or vehicle continuously for 3 or 6 d. Rats given either diet B or C had significantly lower (P < 0.01) relative percentages of AA and LA within the AM[phi], lung, and KE cell phospholipids, and concomitantly higher percentages of EPA compared with rats infused with diet A after 3 d of enteral feeding irrespective of endotoxin co-infusion. Incorporation of dihomo-[gamma]-linolenic acid (DHGLA), the metabolite of GLA, into lung and KE phospholipids was significant in rats given diet C. Most of the changes in fatty acid composition occurred by day 3. The polyunsaturated fatty acid composition of AM[phi], lung, and KE cell phospholipids can be rapidly modified by continuous short-term enteral feeding with EPA- and GLA-enriched diets irrespective of concurrent endotoxemia.

Diets low in [alpha]-linolenic acid may not support normal brain accretion of n-3 fatty acids. An n-3 fatty acid-deficient diet was fed to laying hens and the resulting deficient chicks were fed a low-linolenic acid diet based on corn oil, or the same diet supplemented with docosahexaenoic acid. Control chicks from soybean oil-fed hens were fed a soybean oil-based diet. The fatty acid composition of the chick brains, retinas, livers, and serum was determined after 0-4 wk. The corn oil diet did not reverse the deficiency but the combination of corn oil and docosahexaenoic acid rapidly restored brain and retinal concentrations of docosahexaenoic acid. Supplemented chicks, however, showed a slight lowering of arachidonic acid in the brain and serum. This study demonstrates that a low-linolenic acid diet without docosahexaenoic acid fails to support accretion of n-3 fatty acids in the nervous tissue of chicks.

The influence of sow milk or infant formulas containing 181n-6 and 18:3n-3 (% fatty acids) at 30/1, 16/1, 35/4, or 16/4 on plasma and liver phospholipid (PL) and cholesterol ester (CE) arachidonic acid (20:4n-6) was studied in piglets fed from birth for 15 d. Piglets fed the 35/4, 16/1, and 16/4 formulas had a significantly lower percentage of plasma 20:4n-6 in PL than did piglets fed sow milk or the 30/1 formula. The lowest plasma PL 20:4n-6 was in the 16/4 group, the only group in which liver PL 20:4n-6 was significantly reduced. This suggests competitive inhibition of synthesis or acylation of 20:4n-6 when formula with a high content of 18:3n-3 is fed in conjunction with a low content of 18:2n-6. The percentage of plasma CE 20: 4n-6 was not altered by formula feeding. In contrast, the liver CE 20:4n-6 was significantly lower in all formula-fed animals than it was in sow-milk-fed animals. These studies confirm that 20:4n-6 metabolism is altered in artificially fed neonates. Liver and plasma cholesterol concentrations were also significantly lower in all formula-fed than in milk-fed piglets. The potential relationship of the decrease in cholesterol to n-6 fatty acids in CE is unknown. Am J Clin Nutr 1992;56:106-12.