Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation

The enzymes encoded by fatty acid desaturase (FADS) 1 and FADS2 are rate-limiting enzymes in the desaturation of linoleic acid [LA; 18:2(n-6)] to arachidonic acid [ARA; 20:4(n-6)], and alpha-linolenic acid [ALA; 18:3(n-3)] to eicosapentaenoic acid [EPA; 20:5(n-3)] and docosahexaenoic acid [DHA; 22:6(n-3)]. ARA, EPA, and DHA play central roles in infant growth, neural development, and immune function. The maternal ARA, EPA, and DHA status in gestation influences maternal-to-infant transfer and breast milk provides fatty acids for infants after birth. We determined if single nucleotide polymorphisms in FADS1 and FADS2 influence plasma phospholipid and erythrocyte ethanolamine phosphoglyceride (EPG) (n-6) and (n-3) fatty acids of women in pregnancy or their breast milk during lactation. We genotyped rs174553, rs99780, rs174575, and rs174583 in the FADS1 FADS2 gene cluster and analyzed plasma and erythrocyte fatty acids and dietary intake for 69 pregnant women and breast milk for a subset of 54 women exclusively breast-feeding at 1 mo postpartum. Minor allele homozygotes of rs174553(GG), rs99780(TT), and rs174583(TT) had lower ARA but higher LA in plasma phospholipids and erythrocyte EPG and decreased (n-6) and (n-3) fatty acid product:precursor ratios at 16 and 36 wk of gestation. Breast milk fatty acids were influenced by genotype, with significantly lower 14:0, ARA, and EPA but higher 20:2(n-6) in the minor allele homozygotes of rs174553(GG), rs99780(TT), and rs174583(TT) and lower ARA, EPA, 22:5(n-3), and DHA in the minor allele homozygotes G/G of rs174575. We showed that genetic variants of FADS1 and FADS2 influence blood lipid and breast milk essential fatty acids in pregnancy and lactation.     

Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio

BACKGROUND: Human in vivo data on dietary determinants of alpha-linolenic acid (ALA; 18:3n-3) metabolism are scarce. OBJECTIVE: We examined whether intakes of ALA or linoleic acid (LA; 18:2n-6) or their ratio influences ALA metabolism. DESIGN: During 4 wk, 29 subjects received a control diet (7% of energy from LA, 0.4% of energy from ALA, ALA-to-LA ratio = 1:19). For the next 6 wk, a control diet, a low-LA diet (3% of energy from LA, 0.4% of energy from ALA, ratio = 1:7), or a high-ALA diet (7% of energy from LA, 1.1% of energy from ALA, ratio = 1:7) was consumed. Ten days before the end of each dietary period, [U-13C]ALA was administered orally for 9 d. ALA oxidation was determined from breath. Conversion was estimated by using compartmental modeling of [13C]- and [12C]n-3 fatty acid concentrations in fasting plasma phospholipids. RESULTS: Compared with the control group, ALA incorporation into phospholipids increased by 3.6% in the low-LA group (P = 0.012) and decreased by 8.0% in the high-ALA group (P < 0.001). In absolute amounts, it increased by 34.3 mg (P = 0.020) in the low-LA group but hardly changed in the high-ALA group. Nearly all ALA from the plasma phospholipid pool was converted into eicosapentaenoic acid. Conversion of eicosapentaenoic acid into docosapentaenoic acid and docosahexaenoic acid hardly changed in the 3 groups and was <0.1% of dietary ALA. In absolute amounts, it was unchanged in the low-LA group, but increased from 0.7 to 1.9 mg (P = 0.001) in the high-ALA group. ALA oxidation was unchanged by the dietary interventions. CONCLUSION: The amounts of ALA and LA in the diet, but not their ratio, determine ALA conversion.     

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.     

Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome

BACKGROUND: Maternal essential fatty acid status declines during pregnancy, and as a result, neonatal concentrations of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) may not be optimal. OBJECTIVE: Our objective was to improve maternal and neonatal fatty acid status by supplementing pregnant women with a combination of alpha-linolenic acid (ALA, 18:3n-3) and linoleic acid (LA, 18:2n-6), the ultimate dietary precursors of DHA and AA, respectively. DESIGN: From week 14 of gestation until delivery, pregnant women consumed daily 25 g margarine supplying either 2.8 g ALA + 9.0 g LA (n = 29) or 10.9 g LA (n = 29). Venous blood was collected for plasma phospholipid fatty acid analyses at weeks 14, 26, and 36 of pregnancy, at delivery, and at 32 wk postpartum. Umbilical cord blood and vascular tissue samples were collected to study neonatal fatty acid status also. Pregnancy outcome variables were assessed. RESULTS: ALA+LA supplementation did not prevent decreases in maternal DHA and AA concentrations during pregnancy and, compared with LA supplementation, did not increase maternal and neonatal DHA concentrations but significantly increased eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3) concentrations. In addition, ALA+LA supplementation lowered neonatal AA status. No significant differences in pregnancy outcome variables were found. CONCLUSIONS: Maternal ALA+LA supplementation did not promote neonatal DHA+AA status. The lower concentrations of Osbond acid (22:5n-6) in maternal plasma phospholipids and umbilical arterial wall phospholipids with ALA+LA supplementation than with LA supplementation suggest only that functional DHA status improves with ALA+LA supplementation.     

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.     

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 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.     

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 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.     

The (n-3) fatty acid dose, independent of the (n-6) to (n-3) fatty acid ratio, affects the plasma fatty acid profile of normal dogs

The purpose of this study was to determine whether the dose of (n-3) fatty acids (FA) administered, independent of the relative ratio of (n-6) to (n-3) FA in the food, influences plasma FA composition in dogs. Healthy female, geriatric beagles (7-10 y old) were fed foods containing (n-6) to (n-3) FA ratios of either 40.0:1 or 1.4:1 for 12 wk (study 1) or 36 wk (study 2). In study 3, beagles were fed food with the same 1:1 ratio of (n-6) to (n-3) FA, but with increasing concentrations of (n-6) and (n-3) FA. Plasma FA concentrations were measured after completing the feeding studies. In studies 1 and 2, dogs fed fish oil-enriched food with a high (n-3) FA concentration had higher plasma total (n-3) FA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) concentrations and lower plasma total (n-6) FA, linoleic acid, and arachidonic acid concentrations than dogs fed corn oil-enriched food with a low (n-3) FA concentration (P < 0.001). Both inclusion of fish oil (P < 0.001) and increased food intake independent of treatment effects increased the plasma DHA (P = 0.05) concentration. Furthermore, constancy of the dose of (n-3) FA administered over long periods of time was necessary to maintain plasma levels of total (n-3) FA, EPA, and DHA. In study 3, up to certain dietary concentrations (6.3 g total (n-3) FA/kg food for DHA and 9.8 g total (n-3) FA/kg food for EPA), the dose of (n-3) FA administered, independent of the (n-6) to (n-3) FA ratio, determined the plasma (n-3) FA composition. Results from our studies indicate that approximately 175 mg DHA/(kg body weight . d) is required to attain maximum plasma levels of DHA.     

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.     

Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer

BACKGROUND: Laboratory studies have shown that n-3 fatty acids inhibit and n-6 fatty acids stimulate prostate tumor growth, but whether the dietary intake of these fatty acids affects prostate cancer risk in humans remains unclear. OBJECTIVE: We prospectively evaluated the association between intakes of alpha-linolenic (ALA; 18:3n-3), eicosapentaenoic (EPA; 20:5n-3), docosahexaenoic (DHA; 22:6n-3), linoleic (LA; 18:2n-6), and arachidonic (AA; 20:4n-6) acids and prostate cancer risk. DESIGN: A cohort of 47 866 US men aged 40-75 y with no cancer history in 1986 was followed for 14 y. RESULTS: During follow-up, 2965 new cases of total prostate cancer were ascertained, 448 of which were advanced prostate cancer. ALA intake was unrelated to the risk of total prostate cancer. In contrast, the multivariate relative risks (RRs) of advanced prostate cancer from comparisons of extreme quintiles of ALA from nonanimal sources and ALA from meat and dairy sources were 2.02 (95% CI: 1.35, 3.03) and 1.53 (0.88, 2.66), respectively. EPA and DHA intakes were related to lower prostate cancer risk. The multivariate RRs of total and advanced prostate cancer from comparisons of extreme quintiles of the combination of EPA and DHA were 0.89 (0.77, 1.04) and 0.74 (0.49, 1.08), respectively. LA and AA intakes were unrelated to the risk of prostate cancer. The multivariate RR of advanced prostate cancer from a comparison of extreme quintiles of the ratio of LA to ALA was 0.62 (0.45, 0.86). CONCLUSIONS: Increased dietary intakes of ALA may increase the risk of advanced prostate cancer. In contrast, EPA and DHA intakes may reduce the risk of total and advanced prostate cancer.     

Moderate fish-oil supplementation reverses low-platelet, long-chain n-3 polyunsaturated fatty acid status and reduces plasma triacylglycerol concentrations in British Indo-Asians

BACKGROUND: The mechanisms involved in the increased mortality from coronary artery disease in British Indo-Asians are not well understood. OBJECTIVES: This study aimed to investigate whether British Indo-Asian Sikhs have higher plasma triacylglycerol concentrations, lower platelet phospholipid levels, and lower dietary intakes of long-chain n-3 polyunsaturated fatty acids (PUFAs) than do age- and weight-matched Europeans and whether moderate dietary fish-oil intake can reverse these differences. DESIGN: A randomized, double-blind, placebo-controlled, parallel, fish-oil intervention study was performed. After a 2-wk run-in period, 44 Europeans and 40 Indo-Asian Sikhs were randomly assigned to receive either 4.0 g fish oil [1.5 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA)] or 4.0 g olive oil (control) daily for 12 wk. RESULTS: At baseline, the Indo-Asians had significantly higher plasma triacylglycerol, small dense LDL, apolipoprotein B, and dietary and platelet phospholipid n-6 PUFA values and significantly lower long-chain n-3 PUFAs (EPA and DHA) than did the Europeans. A significant decrease in plasma triacylglycerol, plasma apolipoprotein B-48, and platelet phospholipid arachidonic acid concentrations and a significant increase in plasma HDL concentrations and platelet phospholipid EPA and DHA levels were observed after fish-oil supplementation. No significant effect of ethnicity on the responses to fish-oil supplementation was observed. CONCLUSIONS: Moderate fish-oil supplementation contributes to a reversal of lipid abnormalities and low n-3 PUFA levels in Indo-Asians and should be considered as an important, yet simple, dietary manipulation to reduce CAD risk in Indo-Asians with an atherogenic lipoprotein phenotype.     

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.     

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.     

Alpha linolenic acid in cholesterol esters: a marker of alphalinolenic acid intake in newborns

OBJECTIVE: To evaluate alpha-linolenic acid (ALA) (18∶3 n-3) and linolenic acid (LA) (18∶2 n-6) in cholesterol esters (CE) as markers of ALA and LA dietary intakes in preterm infants. SUBJECTS: Forty-five preterm infants: two groups fed different formulas, the third fed human milk. DESIGN: ALA and LA dietary intakes were precisely recorded in each infant to accurately determine the cumulative amount of ingested ALA and LA during two intervals: (i) between the second day after the first significant formula intake (D0) and the fifteenth day (D15); and (ii) between D0 and the first day of the 37th week of post-conception age (W37). The corresponding amounts of ingested ALA and LA were related to ALA and LA levels determined by capillary column gas-liquid chromatography in plasma cholesterol esters at D15 and W37, respectively. RESULTS: ALA in CE was very significantly correlated to D0-D15 and D0-W37 ALA intakes (0.66; P=0.0001 and 0.70; P=0.0001), respectively. LA in CE was weakly correlated to D0-D15 LA intakes (0.03; P=0.01) and whatever the group (human milk or enriched formula) the correlation was lost at W37. CONCLUSION: In preterm infants, ALA in CE can be considered as representative of ALA dietary intakes, whereas LA in CE appears as a poor marker of LA intakes.     

Comparison of the effects of fish and fish-oil capsules on the n 3 fatty acid content of blood cells and plasma phospholipids

BACKGROUND: n-3 Fatty acids (FAs) have been shown to be beneficial for cardiovascular health. Whether n-3 FAs from oily fish consumed weekly or from fish-oil capsules taken daily are equally bioavailable is not clear. OBJECTIVE: The purpose of this study was to compare the rate and extent of enrichment of blood cell membranes [ie, red blood cells (RBCs)] and plasma phospholipids with n-3 FAs from these 2 sources. DESIGN: Healthy premenopausal female volunteers were randomly assigned to consume a daily average of 485 mg eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids either from 2 servings of oily fish (ie, salmon and albacore tuna) per week or from 1-2 capsules/d. RESULTS: After 16 wk, EPA+DHA in RBCs in the fish group (n = 11) increased from 4.0 +/- 0.6% of total FAs to 6.2 +/- 1.4%, whereas it rose from 4.3 +/- 1.0% to 6.2 +/- 1.4% in the capsule group (P < 0.0001 for both; NS for group effect). Similar results were observed in plasma phospholipids. EPA+DHA stabilized in the latter after 4 wk but continued to rise through week 16 in RBCs. EPA in RBCs increased significantly (P = 0.01) more rapidly in the fish group than in the capsule group during the first 4 wk, but rates did not differ significantly between groups thereafter. Total FA variances were less in RBCs than in plasma phospholipids (P = 0.04). CONCLUSION: These findings suggest that the consumption of equal amounts of EPA and DHA from oily fish on a weekly basis or from fish-oil capsules on a daily basis is equally effective at enriching blood lipids with n-3 FAs.     

Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans.

Animal and human studies have shown that greatly increasing the amounts of flax seed oil [rich in the (n-3) polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)] or fish oil [FO; rich in the long chain (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease mitogen-stimulated lymphocyte proliferation. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA or FO on the proliferation of mitogen-stimulated human peripheral blood mononuclear cells (PBMC) and on the production of cytokines by those cells. The study was randomized, placebo-controlled, double-blinded and parallel. Healthy subjects ages 55-75 y consumed nine 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 with oils rich in ALNA, GLA, ARA or DHA or FO. Subjects in these groups consumed 2 g of ALNA or 770 mg of GLA or 680 mg of ARA or 720 mg of DHA or 1 g of EPA plus DHA (720 mg of EPA + 280 mg of DHA) daily from the capsules. Total fat intake from the capsules was 4 g/d. The fatty acid composition of PBMC phospholipids was significantly changed in the GLA, ARA, DHA and FO groups. Lymphocyte proliferation was not significantly affected by the placebo, ALNA, ARA or DHA treatments. GLA and FO caused a significant decrease (up to 65%) in lymphocyte proliferation. This decrease was partly reversed by 4 wk after stopping the supplementation. None of the treatments affected the production of interleukin-2 or interferon-gamma by PBMC and none of the treatments affected the number or proportion of T or B lymphocytes, helper or cytotoxic T lymphocytes or memory helper T lymphocytes in the circulation. We conclude that a moderate level GLA or EPA but not of other (n-6) or (n-3) PUFA can decrease lymphocyte proliferation but not production of interleukin-2 or interferon-gamma.     

Vitamin E deficiency decreases long-chain PUFA in zebrafish (Danio rerio)

α-Tocopherol is a required, lipid-soluble antioxidant that protects PUFA. We hypothesized that α-tocopherol deficiency in zebrafish compromises PUFA status. Zebrafish were fed for 1 y either an α-tocopherol-sufficient (E+; 500 mg α-tocopherol/kg) or -deficient (E-; 1.1 mg α-tocopherol/kg) diet containing α-linolenic (ALA) and linoleic (LA) acids but without arachidonic acid (ARA), EPA, or DHA. Vitamin E deficiency in zebrafish decreased by ~20% (n-6) (P < 0.05) and (n-3) (P < 0.05) PUFA and increased the (n-6):(n-3) PUFA ratio (P < 0.05). In E- compared to E+ females, long chain-PUFA status was impaired, as assessed by a ~60% lower DHA:ALA ratio (P < 0.05) and a ~50% lower ARA:LA ratio (P < 0.05). fads2 (P < 0.05) and elovl2 (P < 0.05) mRNA expression was doubled in E- compared to E+ fish. Thus, inadequate vitamin E status led to a depletion of PUFA that may be a result of either or both increased lipid peroxidation and an impaired ability to synthesize sufficient PUFA, especially (n-3) PUFA.     

Plasma concentrations of (n-3) highly unsaturated fatty acids are good biomarkers of relative dietary fatty acid intakes: a cross-sectional study

A cross-sectional study was conducted to clarify the associations of lifestyle factors (habitual exercise, alcohol intake and smoking habit) and plasma fatty acid (FA) concentrations as biomarkers of dietary FA intakes. We collected 7-d weighed diet records, lifestyle information and blood samples from 15 male and 79 female Japanese dietitians, and estimated dietary FA intakes and analyzed plasma FA concentrations. Plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and (n-3) highly unsaturated FA (HUFA) derived from marine foods, but not linoleic and alpha-linolenic acid from plant origins, demonstrated positive correlations with dietary intakes (r = 0.303-0.602, P < 0.05) in both genders. Multiple linear regression analyses adjusted for age, BMI, total energy intake, fat (or respective FA) consumption and lifestyle factors showed that dietary intakes of EPA, DHA and (n-3) HUFA were positively associated with age in men (P < 0.05) and negatively associated with BMI in women [P < 0.01 for DHA and (n-3) HUFA]. The plasma concentrations of EPA, DHA and (n-3) HUFA in women were found to be positively associated with age and marine oil (or respective FA) intake (P < 0.01), and negatively associated with total energy intake [P < 0.05 for EPA and (n-3) HUFA]. Lifestyle factors were not associated with dietary FA intakes and plasma FA concentrations. These findings suggest that the plasma concentrations of EPA, DHA and (n-3) HUFA might be useful biomarkers for the assessment of relative FA intakes without considering associations with habitual exercise, alcohol intake and smoking habit.