Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions

The aim of the present study was to quantify the incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids after oral administration of n-3 fatty acid ethyl esters, since little is known about the rate and pattern of incorporation into plasma lipid fractions. In addition, we aimed to obtain preliminary information regarding EPA half-life, which is needed to establish an optimal dosing schedule. Five healthy volunteers ingested two 8.5 g doses of n-3 fatty acid ethyl esters daily for 7 d, supplying 6.0 g EPA/d and 5.3 g DHA/d. The fatty acid compositions of plasma phospholipids (PL), cholesteryl esters (CE) and triacylglycerols (TAG) were determined during supplementation and during a washout period of 7 d. Half-lives of EPA and DHA were calculated. The proportion of EPA in PL showed a 15-fold increase after 7 d (P < 0.001), while DHA showed a smaller increase (P < 0.01). In CE, EPA also increased (P < 0.05), while DHA did not increase at all. Remarkably, incorporation of DHA into TAG was even higher than that of EPA. Half-life of EPA in PL ranged from 1.63 to 2.31 d (mean 1.97 (SE 0.15) d), whereas mean half-life of EPA in CE was 3.27 (SE 0.56) d. In three subjects, washout of EPA and DHA from TAG seemed to follow a bi-exponential pattern, with a short half-life (< 1 d) in the initial phase and a half-life of several days in the second phase. In conclusion, EPA ethyl esters are rapidly incorporated into plasma lipids, especially into PL. The relatively long half-life of EPA in plasma would permit a dosing schedule with intervals of > or = 12 h in supplementation studies.     

The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0–4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%–64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology.     

Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*

The capacity for conversion of alpha-linolenic acid (ALNA) to n-3 long-chain polyunsaturated fatty acids was investigated in young men. Emulsified [U-13C]ALNA was administered orally with a mixed meal to six subjects consuming their habitual diet. Approximately 33 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h. [13C]ALNA was mobilised from enterocytes primarily as chylomicron triacylglycerol (TAG), while [13C]ALNA incorporation into plasma phosphatidylcholine (PC) occurred later, probably by the liver. The time scale of conversion of [13C]ALNA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) suggested that the liver was the principal site of ALNA desaturation and elongation, although there was some indication of EPA and DPA synthesis by enterocytes. [13C]EPA and [13C]DPA concentrations were greater in plasma PC than TAG, and were present in the circulation for up to 7 and 14 d, respectively. There was no apparent 13C enrichment of docosahexaenoic acid (DHA) in plasma PC, TAG or non-esterified fatty acids at any time point measured up to 21 d. This pattern of 13C n-3 fatty acid labelling suggests inhibition or restriction of DHA synthesis downstream of DPA. [13C]ALNA, [13C]EPA and [13C]DPA were incorporated into erythrocyte PC, but not phosphatidylethanolamine, suggesting uptake of intact plasma PC molecules from lipoproteins into erythrocyte membranes. Since the capacity of adult males to convert ALNA to DHA was either very low or absent, uptake of pre-formed DHA from the diet may be critical for maintaining adequate membrane DHA concentrations in these individuals.     

Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids

BACKGROUND: Increasing evidence supports n-3 fatty acid (FA) supplementation for patients with psychiatric disorders, such as attention deficit hyperactivity disorder. However, the exact metabolic fate of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on different glyceride carriers remains unclear. OBJECTIVE: We investigated whether conjugation of EPA and DHA to phospholipid (PL-n-3) or to triacylglycerol (fish oil; FO) affects their incorporation in blood compartments and influences executive functioning. DESIGN: Children aged 8-13 y with impaired visual sustained attention performance received placebo, 250 mg/d EPA + DHA esterified to PL-n-3 (300 mg/d phosphatidylserine), or FO for 3 mo in a randomized double-blind manner. Main outcome measures included plasma and erythrocyte FA profile and continuous performance test results (Test of Variables of Attention; TOVA). RESULTS: Sixty of the 83 children enrolled completed the interventions (n = 18-21 per group). There was an enrichment of EPA (1.5-2.2-fold), docosapentaenoic acid (DPA; 1.2-fold), and DHA (1.3-fold) in the PL fraction in the plasma of FO- and PL-n-3-fed children. In erythrocytes, only PL-n-3 resulted in a significant reduction (approximately 30%) of very-long-chain saturated FAs (C20-24) and in an increase (1.2- and 2.2-fold, respectively) in linoleic acid and DPA. Total TOVA scores increased in the PL-n-3 (mean +/- SD: 3.35 +/- 1.86) and FO (1.72 +/- 1.67) groups but not in the placebo group (-0.42 +/- 2.51) (PL-n-3 > FO > placebo; P < 0.001). A significant correlation between the alterations in FAs and increased TOVA scores mainly occurred in the PL-n-3 group. CONCLUSION: Consumption of EPA+DHA esterified to different carriers had different effects on the incorporation of these FAs in blood fractions and on the visual sustained attention performance in children. This trial was registered at clinicaltrials.gov as NCT00382616.     

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.     

Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men

BACKGROUND: Plasma concentrations of long-chain n-3 polyunsaturated fatty acids are lower in vegetarians and in vegans than in omnivores. No data are available on whether these concentrations differ between long- and short-term vegetarians and vegans. OBJECTIVES: We compared plasma fatty acid composition in meat-eaters, vegetarians, and vegans and examined whether the proportions of eicosapentaenoic acid (20:5n-3; EPA), docosapentaenoic acid (22:5n-3; DPA), and docosahexaenoic acid (22:6n-3; DHA) were related to the subjects' duration of adherence to their diets or to the proportions of plasma linoleic acid (18:2n-6; LA) and alpha-linolenic acid (18:3n-3; ALA). DESIGN: The present cross-sectional study included 196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom. Information on anthropometry, diet, and smoking habits was obtained through a questionnaire. Total fatty acid composition in plasma was measured. RESULTS: The proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans than in the meat-eaters, whereas only small differences were seen for DPA. Plasma EPA, DPA, and DHA proportions were not significantly associated with the duration of time since the subjects became vegetarian or vegan, which ranged from <1 y to >20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated with plasma LA. CONCLUSIONS: The proportions of plasma long-chain n-3 fatty acids were not significantly affected by the duration of adherence to a vegetarian or vegan diet. This finding suggests that when animal foods are wholly excluded from the diet, the endogenous production of EPA and DHA results in low but stable plasma concentrations of these fatty acids.     

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.     

Krill oil versus fish oil in modulation of inflammation and lipid metabolism in mice transgenic for TNF-α

Purpose

Biological effects of marine oils, fish oil (FO) and krill oil (KO), are mostly attributed to the high content of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The study was aimed to investigate the influence of FO and KO on lipid homeostasis and inflammation in an animal model of persistent low-grade exposure to human tumor necrosis factor α (hTNF-α) and to evaluate whether these effects depend on the structural forms of EPA and DHA [triacylglycerols (TAG) vs. phospholipids].

Methods

Male C57BL/6 hTNF-α mice were fed for 6 weeks a high-fat control diet (24.50 % total fats, w/w) or high-fat diets containing either FO or KO at similar doses of n-3 PUFAs (EPA: 5.23 vs. 5.39 wt%, DHA: 2.82 vs. 2.36 wt% of total fatty acids).

Results

We found that KO, containing bioactive n-3 PUFAs in the form of phospholipids, was capable of modulating lipid metabolism by lowering plasma levels of TAG and cholesterol and stimulating the mitochondrial and peroxisomal fatty acid β-oxidation, as well as improving the overall carnitine turnover. Though the administration of FO was not as effective as KO in the lowering of plasma TAG, FO significantly improved the levels of all cholesterol classes in plasma. Except from the increase in the levels of IL-17 in FO-fed mice and a trend to decrease in MCP-1 levels in KO-fed animals, the levels of pro-inflammatory cytokines were not substantially different between treatment groups.

Conclusion

Our findings demonstrate that FO and KO are comparable dietary sources of n-3 PUFAs. However, when quantitatively similar doses of n-3 PUFAs are administered, KO seems to have a greater potential to promote lipid catabolism. The effect of dietary oils on the levels of inflammatory markers in hTNF-α transgenic mice fed a high-fat diet needs further investigations.     

Docosahexaenoic acid supplementation decreases remnant-like particle-cholesterol and increases the (n-3) index in hypertriglyceridemic men

Plasma remnant-like particle-cholesterol (RLP-C) and the RBC (n-3) index are novel risk factors for cardiovascular disease. Effects of docosahexaenoic acid (DHA) supplementation on these risk factors in hypertriglyceridemic men have not been studied. We determined effects of DHA supplementation on concentrations of plasma RLP-C, the RBC (n-3) index, and associations between concentrations of plasma RLP-C with those of plasma lipids and fatty acids. Hypertriglyceridemic men aged 39-66 y, participated in a randomized, placebo-controlled, parallel study. They received no supplements for 8 d and then received either 7.5 g/d DHA oil (3 g DHA/d) or olive oil (placebo) for the last 90 d. Fasting blood samples were collected on study d -7, 0 (baseline), 45 (mid-intervention), 84, and 91 (end-intervention). DHA supplementation for 45 d decreased (P < 0.05) fasting RLP-C (36%) and increased plasma eicosapentaenoic acid (EPA):arachidonic acid (AA) (100%) and the RBC (n-3) index (109%). Continued supplementation with DHA between d 45 and 91 further increased the RBC (n-3) index (162%) and plasma EPA:AA (137%) compared with baseline values. RLP-C concentration was positively associated (P < 0.01) with the plasma concentrations of triacylglycerols (Kendall's correlation coefficient or r = 0.46), triacylglycerol:HDL cholesterol (HDL-C) (r = 0.44), total cholesterol:HDL-C (r = 0.26), Apo B (r = 0.22), C III (r = 0.41), and E (r = 0.17), and 18:1(n-9) (r = 0.32); it was negatively associated (P < 0.05) with plasma concentrations of DHA (r = -0.32), EPA (r = -0.25), HDL-C (r = -0.21), LDL cholesterol:Apo B (r = -0.30), and HDL-C:Apo A (r = -0.25). Supplementation with placebo oil did not alter any of the response variables tested. Decreased atherogenic RLP-C and increased cardio-protective (n-3) index may improve cardio-vascular health.     

Conversion of alpha-linolenic acid to eicosapentaenoic,docosapentaenoic and docosahexaenoic acids in young women

The extent to which women of reproductive age are able to convert the n-3 fatty acid alpha-linolenic acid (ALNA) to eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) was investigated in vivo by measuring the concentrations of labelled fatty acids in plasma for 21 d following the ingestion of [U-13C]ALNA (700 mg). [13C]ALNA excursion was greatest in cholesteryl ester (CE) (224 (sem 70) micromol/l over 21 d) compared with triacylglycerol (9-fold), non-esterified fatty acids (37-fold) and phosphatidylcholine (PC, 7-fold). EPA excursion was similar in both PC (42 (sem 8) micromol/l) and CE (42 (sem 9) micromol/l) over 21 d. In contrast both [13C]DPA and [13C]DHA were detected predominately in PC (18 (sem 4) and 27 (sem 7) micromol/l over 21 d, respectively). Estimated net fractional ALNA inter-conversion was EPA 21 %, DPA 6 % and DHA 9 %. Approximately 22 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h of the study. These results suggest differential partitioning of ALNA, EPA and DHA between plasma lipid classes, which may facilitate targeting of individual n-3 fatty acids to specific tissues. Comparison with previous studies suggests that women may possess a greater capacity for ALNA conversion than men. Such metabolic capacity may be important for meeting the demands of the fetus and neonate for DHA during pregnancy and lactation. Differences in DHA status between women both in the non-pregnant state and in pregnancy may reflect variations in metabolic capacity for DHA synthesis.     

Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations - a comparative bioavailability study of fish oil vs. krill oil

Background

Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared.

Methods

In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed.

Results

The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC_{0-72 h}: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC_{0-72 h}: 59.78 ± 36.75%*h) and EE (mean AUC_{0-72 h}: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA.

Conclusion

Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.

     

Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition,conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men

The effect of increased dietary intakes of alpha-linolenic acid (ALNA) or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 2 months upon plasma lipid composition and capacity for conversion of ALNA to longer-chain metabolites was investigated in healthy men (52 (SD 12) years). After a 4-week baseline period when the subjects substituted a control spread, a test meal containing [U-(13)C]ALNA (700 mg) was consumed to measure conversion to EPA, docosapentaenoic acid (DPA) and DHA over 48 h. Subjects were then randomised to one of three groups for 8 weeks before repeating the tracer study: (1) continued on same intake (control, n 5); (2) increased ALNA intake (10 g/d, n 4); (3) increased EPA+DHA intake (1.5 g/d, n 5). At baseline, apparent fractional conversion of labelled ALNA was: EPA 2.80, DPA 1.20 and DHA 0.04 %. After 8 weeks on the control diet, plasma lipid composition and [(13)C]ALNA conversion remained unchanged compared with baseline. The high-ALNA diet resulted in raised plasma triacylglycerol-EPA and -DPA concentrations and phosphatidylcholine-EPA concentration, whilst [(13)C]ALNA conversion was similar to baseline. The high-(EPA+DHA) diet raised plasma phosphatidylcholine-EPA and -DHA concentrations, decreased [(13)C]ALNA conversion to EPA (2-fold) and DPA (4-fold), whilst [(13)C]ALNA conversion to DHA was unchanged. The dietary interventions did not alter partitioning of ALNA towards beta-oxidation. The present results indicate ALNA conversion was down-regulated by increased product (EPA+DHA) availability, but was not up-regulated by increased substrate (ALNA) consumption. This suggests regulation of ALNA conversion may limit the influence of variations in dietary n-3 fatty acid intake on plasma lipid compositions.     

Preterm infant formula supplementation with alpha linolenic acid and docosahexaenoic acid

OBJECTIVES: To investigate if supplementation of preterm infant formula with a high docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio together with alpha-linolenic acid (ALA) was able to maintain plasma and red blood cell DHA levels similar to that obtained with breast milk feeding without altering n-6 fatty acid status. DESIGN AND SUBJECTS: Preterm infants of mothers who elected not to breast feed (n=13) were assigned to ALA- and DHA-enriched formula (DHA group: DHA/EPA=5/l). Infants fed breast milk (n=25) constituted a reference group (BM group). Anthropometric and fatty acid parameters (plasma phospholipids, cholesterol esters, triglycerides and red blood cell phosphatidylethanolamine, PL, CE, TG, RBC-PE, respectively) were obtained after 2 days (D2) and 15 days (D15) of enteral feeding and at the 37th week (W37) of post-conception age and 1 month later (W37+30) in the DHA group. Mean DHA intake ranged between 16.5+/-1.6 and 17.9+/-2.9 mg/kg/day between D2 and W37+30. RESULTS: At W37, infant weights, heights, and head circumferences were similar in DHA and BM groups. PL DHA was maintained in the DHA group at the same level as in the BM group and the same for DHA in PE at W37. In RBC-PE and at W37, AA status was the same in both groups. In PL, AA levels remained very stable throughout the study; however, in the DHA group AA levels in PL remained in the range observed with standard formulas. CONCLUSION: The combined 18:3 n-3 and DHA supplementation of infant formula with DHA/EPA ratio 5/l is compatible with growth and n-3 fatty acid metabolism similar to that of preterm infants fed human milk.     

Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction

BACKGROUND: Whereas dietary intake of long-chain n-3 fatty acids has been associated with risk of nonfatal myocardial infarction (MI), few studies have examined the relation for blood concentrations. OBJECTIVE: We aimed to investigate the effect of long-chain n-3 fatty acids in blood on the risk of nonfatal MI. DESIGN: Baseline blood samples were collected from 32 826 participants of the Nurses' Health Study in 1989-1990, among whom 146 incident cases of nonfatal MI were ascertained during 6 y of follow-up and matched with 288 controls. RESULTS: After multivariate adjustment, the relative risks (95% CI) comparing the highest with the lowest quartiles in plasma were 0.23 (0.09, 0.55; P for trend = 0.001) for eicosapentaenoic acid (EPA), 0.40 (0.20, 0.82; P for trend = 0.004) for docosapentaenoic acid (DPA), and 0.46 (0.18, 1.16; P for trend = 0.07) for docosahexaenoic acid (DHA). The associations for these fatty acids in erythrocytes were generally weaker and nonsignificant. In contrast to EPA and DHA, blood concentrations of DPA were not correlated with dietary consumption of n-3 fatty acids. Higher plasma concentrations of EPA, DPA, and DHA were associated with higher plasma concentrations of HDL cholesterol and lower concentrations of triacylglycerol and inflammatory markers. CONCLUSIONS: Higher plasma concentrations of EPA and DPA are associated with a lower risk of nonfatal MI among women. These findings may partly reflect dietary consumption but, particularly for DPA, may indicate important risk differences based on metabolism of long-chain n-3 fatty acids.     

Adherence to a Mediterranean diet and plasma fatty acids: data from the Bordeaux sample of the Three-City study

Higher adherence to a Mediterranean diet (MeDi) and n-3 PUFA may both contribute to decreased dementia risk, but the association between MeDi adherence and lipid status is unclear. The aim of the present study was to analyse the relationship between plasma fatty acids and MeDi adherence in French elderly community dwellers. The study population (mean age 75·9 years) consisted of 1050 subjects from Bordeaux (France) included in the Three-City cohort. Adherence to the MeDi (scored as 0-9) was computed from a FFQ and 24?h recall. The proportion of each plasma fatty acid was determined. Cross-sectional analysis of the association between plasma fatty acids and MeDi adherence was performed by multi-linear regression. After adjusting for age, sex, energy intake, physical activity, smoking status, BMI, plasma TAG and apoE-?4 genotype, plasma palmitoleic acid was significantly inversely associated with MeDi adherence, whereas plasma DHA, the EPA+DHA index and total n-3 PUFA were positively associated with MeDi adherence. The n-6:n-3 PUFA, arachidonic acid (AA):EPA, AA:DHA and AA:(EPA+DHA) ratios were significantly inversely associated with MeDi adherence. Plasma EPA was positively associated with MeDi adherence only in apoE-?4 non-carriers. There was no association between MeDi adherence and SFA and total MUFA. The present results suggest that the protective effect of the MeDi on cognitive functions might be mediated by higher plasma DHA and lower n-6:n-3 PUFA ratios.     

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.     

(n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary?

Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially for DPA. Nonetheless, the present evidence suggests that EPA and DHA have both shared and complementary benefits. Based on current evidence, increasing consumption of either would be advantageous compared to little or no consumption. Focusing on their combined consumption remains most prudent given the potential for complementary effects and the existing more robust literature on cardiovascular benefits of their combined consumption as fish or fish oil for cardiovascular benefits.     

The effect of feeding structured triacylglycerols enriched in eicosapentaenoic or docosahexaenoic acids on murine splenocyte fatty acid composition and leucocyte phagocytosis

The effects of altering the type of n-3 polyunsaturated fatty acid (PUFA) in the mouse diet on the ability of monocytes and neutrophils to perform phagocytosis were investigated. Male weanling mice were fed for 7 d on one of nine diets which contained 178 g lipid/kg and which differed in the type of n-3 PUFA and in the position of these in dietary triacylglycerol (TAG). The control diet contained 4.4 g alpha-linolenic acid/100 g total fatty acids. In the other diets, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) replaced a proportion (50 or 100 %) of the alpha-linolenic acid, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were significant increases in the content of n-3 PUFA in spleen-cell phospholipids when EPA or DHA was fed. These increases were largely independent of the position of EPA or DHA in dietary TAG except when EPA was fed at the highest level, when the incorporation was greater when it was fed in the sn-2 than in the sn-1(3) position. There was no significant effect of dietary DHA on monocyte or neutrophil phagocytic activity. Dietary EPA dose-dependently decreased the number of monocytes and neutrophils performing phagocytosis. However, when EPA was fed in the sn-2 position, the ability of active monocytes or neutrophils to engulf bacteria was increased in a dose-dependent fashion. This did not occur when EPA was fed in the sn-1(3) position. Thus, there appears to be an influence of the position of EPA, but not of DHA, in dietary TAG on its incorporation into cell phospholipids and on the activity of phagocytic cells.     

Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects

Studies on animal and human subjects have shown that greatly increasing the amount of linseed (also known as flaxseed) 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 a number of markers of immune function. The immunological effects of more modest doses of n-3 PUFA in human subjects are unclear, dose-response relationships between n-3 PUFA supply and immune function have not been established and whether ALNA has the same effects as its long-chain derivatives is not known. Therefore, the objective of the present study was to determine the effect of enriching the diet with different doses of FO or with a modest dose of ALNA on a range of functional responses of human monocytes and lymphocytes. In a randomised, placebo-controlled, double-blind, parallel study, forty healthy males aged 18-39 years were randomised to receive placebo or 3.5 g ALNA/d or 0.44, 0.94 or 1.9 g (EPA+DHA)/d in capsules for 12 weeks. The EPA:DHA ratio in the FO used was 1.0:2.5. ALNA supplementation increased the proportion of EPA but not DHA in plasma phospholipids. FO supplementation decreased the proportions of linoleic acid and arachidonic acid and increased the proportions of EPA and DHA in plasma phospholipids. The interventions did not alter circulating mononuclear cell subsets or the production of tumour necrosis factor-alpha, interleukin (IL) 1beta, IL-2, IL-4, IL-10 or interferon-gamma by stimulated mononuclear cells. There was little effect of the interventions on lymphocyte proliferation. The two higher doses of FO resulted in a significant decrease in IL-6 production by stimulated mononuclear cells. It is concluded that, with the exception of IL-6 production, a modest increase in intake of either ALNA or EPA+DHA does not influence the functional activity of mononuclear cells. The threshold of EPA+DHA intake that results in decreased IL-6 production is between 0.44 and 0.94 g/d.     

Beneficial effects of omega-3 fatty acids on the consequences of a fructose diet are not mediated by PPAR delta or PGC1 alpha

Purpose

To study, in high-fructose-fed rats, the effect of a dietary enrichment in omega-3 polyunsaturated fatty acids (n-3 PUFA) on the expression of genes involved in lipid metabolism and cardiovascular function.

Methods

Twenty-eight male “Wistar Han” rats received for 8 weeks, either a standard chow food or an isocaloric 67 % fructose diet enriched or not in alpha-linolenic acid (ALA) or in docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) mix (DHA/EPA). After sacrifice, blood was withdrawn for biochemical analyses; heart, periepididymal adipose tissue and liver were collected and analyzed for the expression of 22 genes by real-time PCR.

Results

Fructose intake resulted in an increase in liver weight and triglyceride content, plasma triglyceride and cholesterol concentrations, although no difference in glucose and insulin. In the liver, lipogenesis was promoted as illustrated by an increase in stearoyl-CoA desaturase and fatty acid synthase (Fasn) together with a decrease in PPAR gamma, delta and PPAR gamma coactivator 1 alpha (PGC1 alpha) expression. In the heart, Fasn and PPAR delta expression were increased. The addition of ALA or DHA/EPA into the diet resulted in a protection against fructose effects except for the decreased expression of PPARs in the liver that was not counterbalanced by n-3 PUFA suggesting that n-3 PUFA and fructose act independently on the expression of PPARs and PGC1 alpha.

Conclusions

In liver, but not in heart, the fructose-enriched diet induces an early tissue-specific reduction in PPAR gamma and delta expression, which is insensitive to n-3 PUFA intake and dissociated from lipogenesis.