Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men

High linoleic acid (LA) intakes have been suggested to reduce alpha-linolenic acid [ALA, 18:3(n-3)] metabolism to eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)], and favor high arachidonic acid [ARA, 20:4(n-6)]. We used a randomized cross-over study with men (n = 22) to compare the effect of replacing vegetable oils high in LA with oils low in LA in foods, while maintaining constant ALA, for 4 wk each, on plasma (n-3) fatty acids. Nonvegetable sources of fat, except fish and seafoods, were unrestricted. We determined plasma phospholipid fatty acids at wk 0, 2, 4, 6, and 8, and triglycerides, cholesterol, serum CRP, and IL-6, and platelet aggregation at wk 0, 4, and 8. LA and ALA intakes were 3.8 +/- 0.12% and 1.0 +/- 0.05%, and 10.5 +/- 0.53% and 1.1 +/- 0.06% energy with LA:ALA ratios of 4:0 and 10:1 during the low and high LA diets, respectively. The plasma phospholipid LA was higher and EPA was lower during the high than during the low LA diet period (P < 0.001), but DHA declined over the 8-wk period (r = -0.425, P < 0.001). The plasma phospholipid ARA:EPA ratios were (mean +/- SEM) 20.7 +/- 1.52 and 12.9 +/- 1.01 after 4 wk consuming the high or low LA diets, respectively (P < 0.001); LA was inversely associated with EPA (r = -0.729, P < 0.001) but positively associated with ARA:EPA (r = 0.432, P < 0.001). LA intake did not influence ALA, ARA, DPA, DHA, or total, LDL or HDL cholesterol, CRP or IL-6, or platelet aggregation. In conclusion, high LA intakes decrease plasma phospholipid EPA and increase the ARA:EPA ratio, but do not favor higher ARA.     

Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y

BACKGROUND: Animal studies showed that dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid (ALA)], evening primrose oil [rich in the n-6 polyunsaturated fatty acid gamma-linolenic acid (GLA)], and fish oil [rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] can decrease natural killer (NK) cell activity. There have been no studies of the effect on NK cell activity of adding these oils to the diet of humans. OBJECTIVE: Our objective was to determine the effect of dietary supplementation with oil blends rich in ALA, GLA, arachidonic acid (AA), DHA, or EPA plus DHA (fish oil) on the NK cell activity of human peripheral blood mononuclear cells. DESIGN: A randomized, placebo-controlled, double-blind, parallel study was conducted. Healthy subjects aged 55-75 y consumed 9 capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil and oils rich in ALA, GLA, AA, DHA, or EPA plus DHA. Subjects in these groups consumed 2 g ALA, 770 mg GLA, 680 mg AA, 720 mg DHA, or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily, respectively. Total fat intake from the capsules was 4 g/d. RESULTS: The fatty acid composition of plasma phospholipids changed significantly in the GLA, AA, DHA, and fish oil groups. NK cell activity was not significantly affected by the placebo, ALA, GLA, AA, or DHA treatment. Fish oil caused a significant reduction (mean decline: 48%) in NK cell activity that was fully reversed by 4 wk after supplementation had ceased. CONCLUSION: A moderate amount of EPA but not of other n-6 or n-3 polyunsaturated fatty acids can decrease NK cell activity in healthy subjects.     

Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty acid

BACKGROUND: An increase in plasma n-3 fatty acid content, particularly eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA), is observed after consumption of fish oil-enriched supplements. Because alpha-linolenic acid (18:3n-3; ALA) is the direct precursor of EPA and DHA, ALA-enriched supplements such as flax may have a similar effect, although this hypothesis has been challenged because of reported low conversion of ALA into DHA. OBJECTIVE: To address this question, we designed a clinical trial in which flax oil, fish-oil, and sunflower oil (placebo group) capsules were given to firefighters (n = 62), a group traditionally exposed to cardiovascular disease risk factors. DESIGN: Firefighters were randomly divided into 6 experimental groups receiving 1.2, 2.4, or 3.6 g flax oil/d; 0.6 or 1.2 g fish oil/d; or 1 g sunflower oil/d for 12 wk. Blood was drawn every 2 wk, and the total phospholipid fatty acid composition of red blood cells was determined. RESULTS: As expected, fish oil produced a rapid increase in erythrocyte DHA and total n-3 fatty acids. The consumption of either 2.4 or 3.6 g flax oil/d (in capsules) was sufficient to significantly increase erythrocyte total phospholipid ALA, EPA, and docosapentaenoic acid (22:5n-3) fatty acid content. There were no differences among groups in plasma inflammatory markers or lipid profile. CONCLUSIONS: The consumption of ALA-enriched supplements for 12 wk was sufficient to elevate erythrocyte EPA and docosapentaenoic acid content, which shows the effectiveness of ALA conversion and accretion into erythrocytes. The amounts of ALA required to obtain these effects are amounts that are easily achieved in the general population by dietary modification.     

A practical approach to increasing intakes of n-3 polyunsaturated fatty acids: use of novel foods enriched with n-3 fats

OBJECTIVES: To assess the effects of providing a wide range of foodstuffs containing n-3 polyunsaturated fatty acids (PUFA), occurring naturally or from fortification, on intake and blood and tissue proportions of n-3 PUFA. DESIGN: Before/after dietary intervention study. SETTING: Adelaide, Australia. SUBJECTS: 16 healthy males recruited from the community. INTERVENTIONS: Subjects were provided with a range of foodstuffs naturally containing n-3 PUFA (fresh fish, canned fish, flaxseed meal, canola oil) and items fortified with fish oil (margarine spread, milk, sausages, luncheon meat, french onion dip). Food choices were left to the discretion of each subject. Intake was estimated by diet diary. Blood was collected at-2, 0, 2, and 4 weeks for fatty acid analysis. MAIN OUTCOME MEASURES: Dietary intakes; plasma, platelet, and mononuclear cell phospholipid fatty acids. RESULTS: Consumption of n-3 PUFA increased significantly: alpha-linolenic acid (ALA) from 1.4 to 4.1 g/day (P<0.001), eicosapentaenoic acid (EPA) from 0.03 to 0.51 g/day (P<0.001), and docosahexaenoic acid (DHA) from 0.09 to 1.01 g/day (P<0.001). Linoleic acid (LA) intake decreased from 13.1 to 9.2 g/day (P<0.001). The proportions of EPA and DHA increased significantly in all phospholipid pools examined; plasma EPA from 1.13% of total fatty acids to 3.38% (P<0.001) and DHA from 3.76 to 7.23% (P<0.001); mononuclear cell EPA from 0.40 to 1.25% (P<0.001) and DHA from 2.33 to 4.08% (P<0.001); platelet EPA from 0.41 to 1.2% (P<0.001) and DHA from 1.64 to 3.07% (P<0.001). CONCLUSION: Incorporating fish oil into a range of novel commercial foods provides the opportunity for wider public consumption of n-3 PUFA with their associated health benefits. SPONSORSHIP: Dawes Scholarship, Royal Adelaide Hospital.     

Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats

Background

Dietary long-chain polyunsaturated fatty acids (LC-PUFA) are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the neonates.

Methods

Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55%) and eicosapentaenoic acid (EPA, 0.75% of total fatty acids) or α-linolenic acid (ALA, 2.90%). At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA) profile. Data were analyzed by bivariate and multivariate statistics.

Results

In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P < 0.0001) and brain glial cell PE (+18%, P = 0.0001) and PS (+15%, P = 0.0009) were significantly increased compared to the ALA group. The filtered correlation analysis (P < 0.05) underlined that levels of dihomo-γ-linolenic acid (DGLA), DHA and n-3 docosapentaenoic acid (DPA) were negatively correlated with arachidonic acid (ARA) and n-6 DPA in PE of brain glial cells. No significant correlation between n-3 and n-6 LC-PUFA were found in the PS dataset. DMA level in PE was negatively correlated with n-6 DPA. DMA were found to occur in brain glial cell PS fraction; in this class DMA level was correlated negatively with DHA and positively with ARA.

Conclusion

The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.     

Dietary intakes of arachidonic acid and alpha-linolenic acid are associated with reduced risk of hip fracture in older adults

PUFA are hypothesized to influence bone health, but longitudinal studies on hip fracture risk are lacking. We examined associations between intakes of PUFA and fish, and hip fracture risk among older adults (n = 904) in the Framingham Osteoporosis Study. Participants (mean age ~75 y at baseline) were followed for incident hip fracture from the time they completed the baseline exam (1988-1989) until December 31, 2005. HR and 95% CI were estimated for energy-adjusted dietary fatty acid exposure variables [(n-3) fatty acids: α-linolenic acid (ALA), EPA, DHA, EPA+DHA; (n-6) fatty acids: linoleic acid, arachidonic acid (AA); and the (n-6):(n-3) ratio] and fish intake categories, adjusting for potential confounders and covariates. Protective associations were observed between intakes of ALA (P-trend = 0.02) and hip fracture risk in a combined sample of women and men and between intakes of AA (P-trend = 0.05) and hip fracture risk in men only. Participants in the highest quartile of ALA intake had a 54% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.46; 95% CI = 0.26-0.83). Men in the highest quartile of AA intake had an 80% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.20; 95% CI = 0.04-0.96). No significant associations were observed among intakes of EPA, DHA, EPA+DHA, or fish. These findings suggest dietary ALA may reduce hip fracture risk in women and men and dietary AA may reduce hip fracture risk in men.     

Long-term effects of dietary alpha-linolenic acid from perilla oil on serum fatty acids composition and on the risk factors of coronary heart disease in Japanese elderly subjects

Although important roles of dietary n-3 fatty acids in the prevention of coronary heart disease (CHD) have been suggested, long-term effects of dietary alpha-linolenic acid (ALA, 18:3n-3) have not yet been established under controlled conditions. We tested whether a moderate increase of dietary ALA affects fatty acids composition in serum and the risk factors of CHD. Oxidized LDL (OxLDL) was directly measured by ELISA using antibody specific to OxLDL. By merely replacing soybean cooking oil (SO) with perilla oil (PO) (i.e., increasing 3 g/d of ALA), the n-6/n-3 ratio in the diet was changed from 4:1 to 1:1. Twenty Japanese elderly subjects were initially given a SO diet for at least 6 mo (baseline period), a PO diet for 10 mo (intervention period), and then returned to the previous SO diet (washout period). ALA in the total serum lipid increased from 0.8 to 1.6% after 3 mo on the PO diet, but EPA and DHA increased in a later time, at 10 mo after the PO diet, from 2.5 to 3.6% and 5.3 to 6.4%, respectively (p<0.05), and then returned to baseline in the washout period. In spite of increases of serum n-3 fatty acids, the OxLDL concentration did not change significantly when given the PO diet. Body weight, total serum cholesterol, triacylglycerol, glucose, insulin and HbA1c concentrations, platelet count and aggregation function, prothrombin time, partial thromboplastin time, fibrinogen and PAI-1 concentration, and other routine blood analysis did not change significantly when given the PO diet. These data indicate that, even in elderly subjects, a 3 g/d increase of dietary ALA could increase serum EPA and DHA in 10 mo without any major adverse effects.     

Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids

BACKGROUND: For many persons who wish to obtain the health benefits provided by dietary n-3 fatty acids, daily ingestion of fish or fish oil is not a sustainable long-term approach. To increase the number of sustainable dietary options, a land-based source of n-3 fatty acids that is effective in increasing tissue concentrations of the long-chain n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is required. OBJECTIVE: The objective of the study was to examine the ability of dietary stearidonic acid (SDA) to increase tissue concentrations of EPA and DHA in healthy human subjects and to compare the effectiveness of SDA with that of the n-3 fatty acids alpha-linolenic acid (ALA) and EPA. DESIGN: Encapsulated SDA, ALA, or EPA was ingested daily in doses of 0.75 g and then 1.5 g for periods of 3 wk each by healthy male and postmenopausal female subjects (n = 15/group) in a double-blind, parallel-group design. RESULTS: Dietary SDA increased EPA and docosapentaenoic acid concentrations but not DHA concentrations in erythrocyte and in plasma phospholipids. The relative effectiveness of the tested dietary fatty acids in increasing tissue EPA was 1:0.3:0.07 for EPA:SDA:ALA. CONCLUSIONS: Vegetable oils containing SDA could be a dietary source of n-3 fatty acids that would be more effective in increasing tissue EPA concentrations than are current ALA-containing vegetable oils. The use of SDA-containing oils in food manufacture could provide a wide range of dietary alternatives for increasing tissue EPA concentrations.     

Diet (n-3) polyunsaturated fatty acid content and parity interact to alter maternal rat brain phospholipid fatty acid composition

Low tissue levels of (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid [DHA, 22:6(n-3)], are implicated in postpartum depression. The effects of 1-4 sequential reproductive cycles on maternal brain phospholipid fatty acid composition were determined in female rats fed diets containing alpha-linolenic acid (ALA), containing ALA and pre-formed DHA (ALA+DHA), or lacking ALA (low-ALA). Virgin females, fed the diets for commensurate durations served as a control for reproduction. Whole-brain total phospholipid composition was determined at weaning by TLC/GC. A single reproductive cycle on the low-ALA diet decreased brain DHA content by 18% compared to ALA primiparas (P < 0.05), accompanied by incorporation of docosapentaenoic acid ((n-6) DPA, 22:5(n-6)) to 280% of ALA primiparas (P < 0.05). DHA was not further decreased after subsequent cycles; however, there was an additional increase in (n-6) DPA after the second cycle (P < 0.05). Brain DHA of virgin females fed the low-ALA diet for 27 wk decreased 15% (P < 0.05), but was accompanied by a more modest increase in (n-6) DPA than in parous low-ALA dams (P < 0.05). Virgin females and parous dams fed the diet containing ALA+DHA exhibited only minor changes in brain fatty acid composition. These observations demonstrate that brain DHA content of adult animals is vulnerable to depletion under dietary conditions that supply inadequate (n-3) PUFAs, that this effect is augmented by the physiological demands of pregnancy and lactation, and that maternal diet and parity interact to affect maternal brain PUFA status.     

Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses

Fish-oil supplementation can reduce circulating triacylglycerol (TG) levels and cardiovascular risk. This study aimed to assess independent associations between changes in platelet eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and fasting and postprandial (PP) lipoprotein concentrations and LDL oxidation status, following fish-oil intervention. Fifty-five mildly hypertriacylglycerolaemic (TG 1.5-4.0 mmol/l) men completed a double-blind placebo controlled cross over study, where individuals consumed 6 g fish oil (3 g EPA+DHA) or 6 g olive oil (placebo)/d for two 6-week intervention periods, with a 12-week wash-out period in between. Fish-oil intervention resulted in a significant increase in the platelet phospholipid EPA (+491 %, P<0.001) and DHA (+44 %, P<0.001) content and a significant decrease in the arachidonic acid (-10 %, P<0.001) and gamma-linolenic acid (-24 %, P<0.001) levels. A 30 % increase in ex vivo LDL oxidation (P<0.001) was observed. In addition, fish oil resulted in a significant decrease in fasting and PP TG levels (P<0.001), PP non-esterified fatty acid (NEFA) levels, and in the percentage LDL as LDL-3 (P=0.040), and an increase in LDL-cholesterol (P=0.027). In multivariate analysis, changes in platelet phospholipid DHA emerged as being independently associated with the rise in LDL-cholesterol, accounting for 16 % of the variability in this outcome measure (P=0.030). In contrast, increases in platelet EPA were independently associated with the reductions in fasting (P=0.046) and PP TG (P=0.023), and PP NEFA (P=0.015), explaining 15-20 % and 25 % of the variability in response respectively. Increases in platelet EPA+DHA were independently and positively associated with the increase in LDL oxidation (P=0.011). EPA and DHA may have differential effects on plasma lipids in mildly hypertriacylglycerolaemic men.     

Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects

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 (+/- SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 +/- 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 +/- 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.     

Dietary canola oil suppressed growth of implanted MDA-MB 231 human breast tumors in nude mice

Long chain omega 3 (n-3) fatty acids, eicosapentaenoic (EPA) and/or docosahexaenoic acid (DHA), have been shown to suppress growth of most cancer cells. In vivo, alpha linolenic acid (ALA, 18:3n-3) can be converted to EPA or DHA. We hypothesized that substituting canola oil (10% ALA) for the corn oil (1% ALA) in the diet of cancer bearing mice would slow tumor growth by increasing n-3 fatty acids in the diet. Sixty nude mice received MDA-MB 231 human breast cancer cells and were fed a diet containing 8% w/w corn oil until the mean tumor volume was 60 mm3. The dietary fat of half of the tumor bearing mice was then changed to 8% w/w canola oil. Compared to mice that consumed the corn oil containing diet, the mice that consumed the canola oil containing diet had significantly more EPA and DHA in both tumors and livers, and the mean tumor growth rate and cell proliferation in the tumor were significantly slower (P<0.05). About 25 days after diet change, mice that consumed the corn oil diet stopped gaining weight, whereas the mice that consumed the canola oil diet continued normal weight gain. Use of canola oil instead of corn oil in the diet may be a reasonable means to increase consumption of n-3 fatty acids with potential significance for slowing growth of residual cancer cells in cancer survivors.     

Dietary Canola Oil Suppressed Growth of Implanted MDA-MB 231 Human Breast Tumors in Nude Mice

Long chain omega 3 (n-3) fatty acids, eicosapentaenoic (EPA) and/or docosahexaenoic acid (DHA), have been shown to suppress growth of most cancer cells. In vivo, alpha linolenic acid (ALA, 18:3n-3) can be converted to EPA or DHA. We hypothesized that substituting canola oil (10% ALA) for the corn oil (1% ALA) in the diet of cancer bearing mice would slow tumor growth by increasing n-3 fatty acids in the diet. Sixty nude mice received MDA-MB 231 human breast cancer cells and were fed a diet containing 8% w/w corn oil until the mean tumor volume was 60 mm ³ . The dietary fat of half of the tumor bearing mice was then changed to 8% w/w canola oil. Compared to mice that consumed the corn oil containing diet, the mice that consumed the canola oil containing diet had significantly more EPA and DHA in both tumors and livers, and the mean tumor growth rate and cell proliferation in the tumor were significantly slower (P < 0.05). About 25 days after diet change, mice that consumed the corn oil diet stopped gaining weight, whereas the mice that consumed the canola oil diet continued normal weight gain. Use of canola oil instead of corn oil in the diet may be a reasonable means to increase consumption of n-3 fatty acids with potential significance for slowing growth of residual cancer cells in cancer survivors.     

Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans

Alpha-linolenic acid (ALA) is a major dietary (n-3) fatty acid. ALA is converted to longer-chain (n-3) PUFA, such as eicosapentaenoic acid (EPA) and possibly docosahexaenoic acid (DHA). EPA and DHA are fish-based (n-3) fatty acids that have proven cardioprotective properties. We studied the effect of daily supplementation with 3 g of ALA on the plasma concentration of long-chain (n-3) fatty acids in a predominantly African-American population with chronic illness. In a randomized, double-blind trial, 56 participants were given 3 g ALA/d from flaxseed oil capsules (n = 31) or olive oil placebo capsules (n = 25). Plasma EPA levels at 12 wk in the flaxseed oil group increased by 60%, from 24.09 +/- 16.71 to 38.56 +/- 28.92 micromol/L (P = 0.004), whereas no change occurred in the olive oil group. Plasma docosapentaenoic acid (DPA) levels in the flaxseed oil group increased by 25% from 19.94 +/- 9.22 to 27.03 +/- 17.17 micromol/L (P = 0.03) with no change in the olive oil group. Plasma DHA levels did not change in either group. This study demonstrates the efficacy of the conversion of ALA to EPA and DPA in a minority population with chronic disease. ALA may be an alternative to fish oil; however, additional clinical trials with ALA are warranted.     

Effects of alpha-linolenic acid versus those of EPA/DHA on cardiovascular risk markers in healthy elderly subjects

OBJECTIVE: To compare the effects of alpha-linolenic acid (ALA, C18:3n-3) to those of eicosapentaenoic acid (EPA, C20:5n-3) plus docosahexaenoic acid (DHA, C22:6n-3) on cardiovascular risk markers in healthy elderly subjects. DESIGN: A randomized double-blind nutritional intervention study. SETTING: Department of Human Biology, Maastricht University, the Netherlands. SUBJECTS: Thirty-seven mildly hypercholesterolemic subjects, 14 men and 23 women aged between 60 and 78 years. INTERVENTIONS: During a run-in period of 3 weeks, subjects consumed an oleic acid-rich diet. The following 6 weeks, 10 subjects remained on the control diet, 13 subjects consumed an ALA-rich diet (6.8 g/day) and 14 subjects an EPA/DHA-rich diet (1.05 g EPA/day + 0.55 g DHA/day). RESULTS: Both n-3 fatty acid diets did not change concentrations of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerol and apoA-1 when compared with the oleic acid-rich diet. However, after the EPA/DHA-rich diet, LDL-cholesterol increased by 0.39 mmol/l (P = 0.0323, 95% CI (0.030, 0.780 mmol/l)) when compared with the ALA-rich diet. Intake of EPA/DHA also increased apoB concentrations by 14 mg/dl (P = 0.0031, 95% CI (4, 23 mg/dl)) and 12 mg/dl (P = 0.005, 95% CI (3, 21 mg/dl)) versus the oleic acid and ALA-rich diet, respectively. Except for an EPA/DHA-induced increase in tissue factor pathway inhibitor (TFPI) of 14.6% (P = 0.0184 versus ALA diet, 95% CI (1.5, 18.3%)), changes in markers of hemostasis and endothelial integrity did not reach statistical significance following consumption of the two n-3 fatty acid diets. CONCLUSIONS: In healthy elderly subjects, ALA might affect concentrations of LDL-cholesterol and apoB more favorably than EPA/DHA, whereas EPA/DHA seems to affect TFPI more beneficially.     

Validation of a food frequency questionnaire to assess intake of n-3 polyunsaturated fatty acids in subjects with and without major depressive disorder

The role of n-3 polyunsaturated fatty acids (PUFAs) in psychiatric illness is a topic of public health importance. This report describes development and biomarker validation of a 21-item, self-report food frequency questionnaire (FFQ) intended for use in psychiatric research to assess intake of α-linolenic acid (18:3n-3 [ALA]), docosahexaenoic acid (22:6n-3 [DHA]), and eicosapentaenoic acid (20:5n-3 [EPA]). In a cross-sectional study conducted from September 2006 to September 2008, sixty-one ethnically diverse adult participants with (n=34) and without (n=27) major depressive disorder completed this n-3 PUFA FFQ and provided a plasma sample. Plasma levels of n-3 PUFAs EPA and DHA, and n-6 PUFA arachidonic acid (20:4n-6 [AA]) were quantified by gas chromatography. Using Spearman's ρ, FFQ-estimated intake correlated with plasma levels of DHA (r=0.50; P<0.0001) and EPA (r=0.38; P=0.002), but not with ALA levels (r=0.22; P=0.086). Participants were classified into quartiles by FFQ-estimated intake and plasma PUFA concentrations. Efficacy of the FFQ to rank individuals into same or adjacent plasma quartiles was 83% for DHA, 78.1% for EPA, and 70.6% for ALA; misclassification into extreme quartiles was 4.9% for DHA, 6.5% for EPA, and 8.2% for ALA. FFQ-estimated EPA intake and plasma EPA were superior to plasma AA levels as predictors of the plasma AA to EPA ratio. This brief FFQ can provide researchers and clinicians with valuable information concerning dietary intake of DHA and EPA.     

Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition

OBJECTIVE: The aim of this study was to assess the effects of fish oil supplementation in pregnancy on maternal erythrocyte fatty acid composition at different stages of pregnancy and in the post-partum period, and on neonatal erythrocyte fatty acid composition. DESIGN: A double-blind, randomised, placebo-controlled study. SETTING:: Subiaco, Western Australia. SUBJECTS: In all, 98 women booked for delivery at St John of God Hospital, Subiaco, were recruited from private rooms of obstetricians. In total, 83 women and their healthy full-term babies completed the study. INTERVENTION: Women received either 4 g of fish oil (n=52) (56% docosahexaenoic acid (DHA) and 28% eicosapentaenoic acid (EPA) or placebo (olive oil) (n=46) per day from 20 weeks gestation until delivery. MAIN OUTCOME MEASURES: Erythrocyte phospholipid fatty acids were measured in maternal peripheral blood at 20, 30 and 37 weeks of pregnancy and at 6 weeks post partum, and from cord blood collected at birth. RESULTS: Compared to the control group, maternal EPA and DHA were significantly higher in the fish oil group at 30 and 37 weeks gestation, and remained elevated at 6 weeks post partum (P<0.001). The proportions of n-6 polyunsaturated (arachidonic acid, 22:3n-6 and 22:4n-6) were significantly lower in the fish oil supplemented group at the same time periods (P<0.001). Similarly, the proportions of EPA and DHA were significantly higher (P<0.001), and those of n-6 polyunsaturated fatty acids arachidonic acid, 20:3n-6, 22:3n-6 and 22:4n-6 were significantly lower (P<0.001), in erythrocytes from neonates in the fish oil group, compared to those in the control group. CONCLUSION: Fish oil supplementation from 20 weeks of pregnancy until birth is an effective means of enhancing n-3 fatty acid status of both mothers and neonates. Furthermore, the changes in maternal erythrocyte fatty acid composition are retained until at least 6 weeks post partum. It is essential to assess the effects of concomitant decreases in arachidonic acid status before any dietary recommendations can be made. SPONSORSHIP: The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.     

High α-linolenic acid and fish oil ingestion promotes ovulation to the same extent in rats

Prostaglandins (PG) have a regulatory influence on ovulation. α-Linolenic acid (ALA) vs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differently influence PG biosynthesis. Whereas high EPA/DHA reduces PGE₂, enhancing ovulation, we hypothesized that ALA would not affect ovulation. Our objective was to determine the effect of low and high ALA intake vs EPA/DHA on ovarian phospholipids, ovulation, and PG synthesis in rats. Following 27 days on diet and ovulation induction, ovaries were isolated and analyzed in 22 pups per diet. Ovarian phospholipid (n-3) polyunsaturated fatty acid (PUFA) incorporation increased with EPA/DHA ingestion. With significant ovarian (n-3) PUFA or EPA (P < .05) enrichment in the high–n-3 PUFA diets, ova release increased. Although high ALA did not enrich total (n-3), it increased ova release and tissue EPA over low ALA or control. Dietary EPA/DHA more effectively reduced ovarian arachidonic acid levels than dietary ALA. Dietary ALA increased PGF and very high intake reduced PGE, whereas EPA/DHA did not alter PGE or PGF. Enhanced ova release with high (n-3) PUFA intake may be induced via multiple mechanisms including reduced ovarian arachidonic acid. Significant ovarian retention of EPA and DHA enhanced ovulation with unchanged total PGE and PGF. Lack of change in PGE may have resulted from reduced PGE₂ combined with increased PGE₃. When EPA alone was elevated, PGE was reduced, whereas PGF was increased. Results indicate that very high ALA intake enhances ovulation similar to very high EPA/DHA ingestion, an effect potentially mediated via similar patterns of PGF₂α and PGE₂ synthesis.     

Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.     

Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk

BACKGROUND: Flaxseed oil is a rich source of 18:3n-3 (alpha-linolenic acid, or ALA), which is ultimately converted to 22:6n-3 (docosahexaenoic acid, or DHA), a fatty acid important for the development of the infant brain and retina. OBJECTIVE: The objective of this study was to determine the effect of flaxseed oil supplementation on the breast-milk, plasma, and erythrocyte contents of DHA and other n-3 fatty acids in lactating women. DESIGN: Seven women took 20 g flaxseed oil (10.7 g ALA) daily for 4 wk. Breast-milk and blood samples were collected weekly before, during, and after supplementation and were analyzed for fatty acid composition. RESULTS: Breast milk, plasma, and erythrocyte ALA increased significantly over time (P < 0.001) and after 2 and 4 wk of supplementation (P < 0.05). Over time, 20:5n-3 (eicosapentaenoic acid, or EPA) increased significantly in breast milk (P = 0.004) and in plasma (P < 0.001). In addition, plasma EPA increased significantly (P < 0.05) after 2 and 4 wk of supplementation. There were significant increases over time in breast-milk 22:5n-3 (docosapentaenoic acid, or DPA) (P < 0.02), plasma DPA (P < 0.001), and erythrocyte DPA (P < 0.01). No significant changes were observed in breast-milk, plasma, or erythrocyte DHA contents after flaxseed oil supplementation. CONCLUSIONS: Dietary flaxseed oil increased the breast-milk, plasma, and erythrocyte contents of the n-3 fatty acids ALA, EPA, and DPA but had no effect on breast-milk, plasma, or erythrocyte DHA contents.