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Background: Dietary docosahexaenoic acid (DHA) has triacylglycerol-lowering potential and undergoes in vivo retroconversion to eicosapentaenoic acid (EPA) in humans. Hormone replacement therapy (HRT) influences circulating lipid concentrations and fatty acid metabolism. DHA supplementation has not been studied in postmenopausal women. Objective: We studied the effects of supplementation with DHA (free of EPA) on the resulting elevation in EPA and on selected cardiovascular disease risk factors in postmenopausal women. Design: Women receiving (n = 18) and not receiving (n = 14) HRT completed a randomized, double-blind, placebo-controlled cross-over trial with a DHA supplement (2.8 g DHA/d). A washout period of [greater than or equal to] 6 wk divided the two 28-d intervention periods. Fasting blood samples were collected for analysis. Results: In all women, DHA supplementation was associated with significant changes (P < 0.05), including 20% lower serum triacylglycerol concentrations, 8% higher HDL-cholesterol concentrations, a 28% lower overall ratio of serum triacylglycerol to HDL cholesterol, and a 7% decrease in resting heart rate. DHA supplementation resulted in a 45% lower net increase (P = 0.02) in EPA and a 42% lower (P = 0.0028) estimated percentage retroconversion of DHA to EPA [[DELTA]EPA/([DELTA]EPA + [DELTA]DHA) x 100] in women receiving than in those not receiving HRT. Conclusion: With DHA supplementation, the accumulation of EPA in serum phospholipids is significantly attenuated in postmenopausal women receiving HRT compared with that in women not receiving HRT. DHA supplementation can also favorably influence selected cardiovascular disease risk factors in postmenopausal women. KEY WORDS Fish oil, n-3 fatty acids, docosahexaenoic acid, DHA, total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerol, postmenopausal women, hormone replacement therapy, cardiovascular disease, retroconversion, heart rate, C-reactive protein

Background: Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and [gamma]-linolenic acid (GLA) have lipid-modifying and antiinflammatory properties. The effects of supplement mixtures of these fatty acids on plasma lipids and the fatty acid compositions of serum phospholipids have received little attention. Objective: The objective was to determine the effects of different levels of GLA supplementation together with a constant intake of EPA plus DHA on the triacylglycerol-lowering effect of EPA plus DHA alone and on the fatty acid patterns (eicosanoid precursors) of serum phospholipids. Design: Thirty-one women were assigned to 1 of 4 groups, equalized on the basis of their fasting triacylglycerol concentrations. They received supplements providing 4 g EPA+DHA (4:0, EPA+DHA:GLA; control group), 4 g EPA+DHA plus 1 g GLA (4:1), 2 g GLA (4:2), or 4 g GLA (4:4) daily for 28 d. Plasma lipids and fatty acids of serum phospholipids were measured on days 0 and 28. Results: Plasma triacylglycerol concentrations were significantly lower on day 28 than on day 0 in the 4:0, 4:1, and 4:2 groups. LDL cholesterol decreased significantly (by 11.3%) in the 4:2 group. Dihomo-[gamma]-linolenic acid increased significantly in serum phospholipids only in the 4:2 and 4:4 groups; however, total n-3 fatty acids increased in all 4 groups. Conclusions: A mixture of 4 g EPA+DHA and 2 g GLA favorably altered blood lipid and fatty acid profiles in healthy women. On the basis of calculated PROCAM values, the 4:2 group was estimated to have a 43% reduction in the 10-y risk of myocardial infarction. KEY WORDS Eicosapentaenoic acid, EPA, n-3 fatty acids, docosahexaenoic acid, DHA, arachidonic acid, [gamma]-linolenic acid, dihomo-[gamma]-linolenic acid, triacylglycerols, LDL cholesterol, HDL cholesterol, women

This study examined the effects of garlic and fish-oil supplementation (alone and in combination) on fasting serum lipids and lipoproteins in hypercholesterolemic subjects. After an initial run-in phase, 50 male subjects with moderate hypercholesterolemia were randomly assigned for 12 wk to one of four groups: 1) 900 mg garlic placebo/d + 12 g oil placebo/d; 2) 900 mg garlic/d + 12 g oil placebo/d; 3) 900 mg garlic placebo/d + 12 g fish oil/d, providing 3.6 g n - 3 fatty acids/d; and 4) 900 mg garlic/d + 12 g fish oil/d. In the placebo group, mean serum total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and triacylglycerols were not significantly changed in relation to baseline. Mean group total cholesterol concentrations were significantly lower with garlic + fish oil (-12.2%) and with garlic (-11.5%) after 12 wk but not with fish oil alone. Mean LDL-C concentrations were reduced with garlic + fish oil (-9.5%) and with garlic (-14.2%) but were raised with fish oil (+8.5%). Mean triacylglycerol concentrations were reduced with garlic + fish oil (-34.3%) and fish oil alone (-37.3%). The garlic groups (with and without fish oil) had significantly lower ratios of total cholesterol to high-density-lipoprotein cholesterol (HDL-C) and LDL-C to HDL-C. In summary, garlic supplementation significantly decreased both total cholesterol and LDL-C whereas fish-oil supplementation significantly decreased triacylglycerol concentrations and increased LDL-C concentrations in hypercholesterolemic men. The combination of garlic and fish oil reversed the moderate fish-oil-induced rise in LDL-C. Coadministration of garlic with fish oil was well-tolerated and had a beneficial effect on serum lipid and lipoprotein concentrations by providing a combined lowering of total cholesterol, LDL-C, and triacylglycerol concentrations as well as the ratios of total cholesterol to HDL-C and LDL-C to HDL-C.

This study was undertaken to examine the effects that consumption of eggs from hens fed diets containing flaxseed would have on plasma and platelet lipids of male volunteers. Feeding diets containing 0%, 10%, and 20% ground flaxseed to Leghorn pullets provided a marked progressive increase in n - 3 fatty acid content as [alpha]-linolenic acid ([alpha]-LNA) (28, 261, and 527 mg/egg) and docosahexaenoic acid (DHA) (51, 81, and 87 mg/egg) but no alteration in the cholesterol concentration of the egg yolk. Twenty-eight male volunteers, divided into three groups, were fed four eggs per day for 2 wk according to a cyclic Latin-square design. No statistically significant changes were observed in total cholesterol, high-density-lipoprotein cholesterol, or plasma triglyceride concentrations. Significant increases in total n - 3 fatty acids and in DHA content (which rose from 1.5 to 2.0 % by wt or 33% overall), and a significant decrease in ratio of n - 6 to n - 3 fatty acids were found in platelet phospholipids of subjects consuming eggs from flaxseed-fed hens. Health and Welfare Canada in 1990 set recommended intakes for dietary n - 3 fatty acids and for the ratio of n - 6 to n - 3 fatty acids, which are not being met currently by the overall population. Eggs modified by the inclusion of flaxseed in the laying hens' diet could provide an important nutritional source of n - 3 fatty acid.

The effects of consuming a liquid formula containing either fish oil enriched in [omega]-3 fatty acids or vegetable oil enriched in oleic acid was evaluated in 20 male subjects randomly allocated into two groups over a 42-d period. A decrease in collagen-induced aggregation by using washed platelet suspensions was found in both groups after nutritional supplementation. A considerable rise in [omega]-3 and a decrease in [omega]-6 fatty acids occurred in the platelet phospholipid with fish-oil consumption. The degree of eicosapentaenoic acid (EPA, 20:5n-3) enrichment (fish-oil group) was dramatically greater in the ether-containing plasmenylethanolamine (13.5 mol% of fatty acids; mol% of fatty acids = moles per 100 moles of total fatty acids) than in phosphatidylethanolamine (2.8 mol%) or phosphatidylcholine (2.9 mol%). Neither treatment significantly influenced the agonist-induced accumulation of lysoplasmenylethanolamine as derived via phospholipase [A.sub.2] hydrolysis of plasmenylethanolamine. HPLC measurements of eicosanoid production in A23187-stimulated neutrophils revealed a considerable decrease in the formation of arachidonic acid-derived leukotriene (LTB4), by 41%, and 5-HETE (5-hydroxyeicosatetraenoic acid), by 30%, in the fish-oil group along with the appearance of the corresponding EPA-derived products [LTB5 and 5-HEPE (5-hydroxyeicosapentaenoic acid)]. No such alterations in the formation of lipoxygenase products were found with the vegetable oil treatment. In view of evidence for the involvement of neutrophilderived LTB4 in atherosclerosis/thrombosis and cell injury in early myocardial ischemia, formulated nutritional products enriched in [omega]-3 fatty acids may be of value in the prevention and treatment of cardiovascular risk factors and disease (independent of the lowering of blood cholesterol).

Much research in recent years has focused on the possible beneficial health effects of eating fish or taking fish oil supplements. The omega-3 fatty acids found in fish oil, one of which is eicosapentaenoic acid (EPA), appear to reduce the tendency of blood platelets to clump together and adhere to the inside walls of blood vessels. Consequently, EPA may prevent the formation of blood clots and the narrowing of the coronary arteries, which may lead to heart attack. While EPA is found primarily in fish oil, it is also known that linolenic acid, a component of some vegetable oils, can be converted to EPA. It is not known to what extent this conversion occurs in the human body; this was studied in a group of eight young men. They followed two different diets for 18 days each; one was high in canola oil, which supplies linolenic acid, and the other diet was rich in sunflower oil. Blood samples were taken to analyze the lipid (fat) composition of the platelets. The specific substances in platelets that were studied were the phospholipids, including the alkenylacyl fraction of ethanolamine phosphoglyceride. EPA was found in significantly greater concentrations in platelets after the canola oil diet, compared with levels obtained after the sunflower oil diet and during the pre-experimental period, when subjects followed a mixed-fat diet. It appears that the linolenic acid in the canola oil was converted in the human body into EPA, which was thereby increased in the platelets. In addition to the moderate increases in platelet EPA, there were changes in the amounts of other fatty acids in the platelets. Consumption of canola oil may have a protective effect against formation of blood clots, but a reduction in platelet clumping can also lead to prolonged bleeding times following injury. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background: n-3 Fatty acid supplementation lowered serum triacylglycerol concentrations in studies in which most of the subjects were male. The effects of n-3 fatty acid supplementation in postmenopausal women receiving and not receiving hormone replacement therapy (HRT) have received little attention. Objective: We sought to determine the effects of a fish-oil-derived n-3 fatty acid concentrate on serum lipid and lipoprotein risk factors for cardiovascular disease in postmenopausal women receiving and not receiving HRT, with an emphasis on serum triacylglycerol concentrations and the ratio of triacylglycerol to HDL cholesterol. Design: Postmenopausal women (n = 36) were grouped according to exogenous hormone use and were randomly allocated to receive 8 capsules/d of either placebo oil (control) or n-3 fatty acid-enriched oil (supplement). The supplement provided 2.4 g eicosapentaenoic acid (EPA) plus 1.6 g docosahexaenoic acid (DHA) daily. Serum lipids and the fatty acid composition of serum phospholipids were determined on days 0 and 28. Results: Supplementation with n-3 fatty acids was associated with 26% lower serum triacylglycerol concentrations (P [is less than] 0.0001), a 28% lower overall ratio of serum triacylglycerol to HDL cholesterol (P [is less than] 0.01), and markedly greater EPA and DHA concentrations in serum phospholipids (P [is less than] 0.05). Conclusions: These results show that supplementation with a fish-oil-derived concentrate can favorably influence selected cardiovascular disease risk factors, particularly by achieving marked reductions in serum triacylglycerol concentrations and triacylglycerol:HDL cholesterol in postmenopausal women receiving and not receiving HRT. This approach could potentially reduce the risk of coronary heart disease by 27% in postmenopausal women. Am J Clin Nutr 2000;72:389-94. KEY WORDS Fish oil, n-3 fatty acids, omega-3 fatty acids, total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerol, postmenopausal women, hormone replacement therapy, cardiovascular disease