Low Eicosapentaenoic Acid Levels Research Articles

Low Levels of Serum n-3 Polyunsaturated Fatty Acids Are Associated With Worse Heart Failure-Free Survival in Patients After Acute Myocardial Infarction

Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. We evaluated whether serum DHA and EPA levels were associated with HF-free survival and HF hospitalization rates after AMI. A total of 712 patients were divided into 3 groups according to their tertile serum levels of DHA and EPA (Low, Middle, and High). Propensity-score-stratified Cox regression analysis revealed that DHA- and EPA-Low groups presented statistically significant worse HF-free survival (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.03-2.72, P=0.0358, and HR 1.69, 95% CI 1.05-2.72, P=0.0280, respectively), with the EPA-Low group having a higher risk of HF hospitalization (HR 2.40, 95% CI 1.21-4.75, P=0.0097) than the DHA-Low group (HR 1.72, 95% CI 0.86-3.45, P=0.1224). The relationship between a low DHA or EPA level and decreased HF-free survival was almost common to all subgroups; however, the effect of low serum EPA on HF hospitalization was prominent in male patients, and those with low levels of high-density lipoprotein cholesterol or without statin therapy. Low levels of circulating n-3 PUFA are associated with decreased HF-free survival in post-AMI patients.

Abstract 18775: Low Levels of Omega-3s In Hispanics Due to Genetic and Dietary Factors Can be Significantly Improved with a Highly Bioavailable Omega-3 Free-fatty Acid Formulation

Background: Hispanic Americans have low fish consumption compared to non-Hispanics. In addition to dietary intake, LC-PUFA plasma levels are affected by FADS1 gene polymorphisms. FADS1 genes code for desaturases that convert MC-PUFAs (linoleic, alpha-linoleic acid) to LC-PUFAs (arachidonic acid (AA), eicosapentaenoic acid (EPA)). The single nucleotide polymorphism (SNP), rs174546 in the FADS1 gene has previously been shown to be associated with variations in plasma EPA and AA and triglycerides levels . The present study evaluated the prevalence of the rs174546 SNP genotypes (CC, CT, TT) and corresponding plasma EPA, DHA and AA levels after treatment with an omega-3 free-fatty acid (FFA) formulation in a population of healthy Hispanic volunteers. Methods: Forty six Hispanic participants in a statin pharmacokinetic study received 40 mg of simvastatin with and without a 4g daily dose of omega-3 FFA (primarily EPA and DHA ) for two weeks in a cross over study. Plasma samples were collected prior to and at the end-of-treatment in the omega-3 FFA arm for analysis of EPA, DHA, and AA. Results: Prior to treatment the Hispanic population had a higher prevalence of TT homozygotes (41%) compared to CC homozygotes (24%) corresponding to significantly different levels of EPA (CC=18 ug/mL; CT=11 ug/mL; TT=7 ug/mL, p <0.0001) and AA (CC=266 ug/mL; CT=202 ug/mL; TT=167 ug/mL, p <0.0001) across genotypes. In response to Omega-3 FFA therapy a substantial increase in EPA was observed, with the largest percent increase in the TT genotype (TT:1054%, CT:573%, CC:253%, p<0.0001). Baseline plasma DHA levels were low suggesting comparable dietary fish intake and changes were similar across genotypes (CC:39%, CT:55%, TT:67%, p=0.2134). Conclusion: In contrast to other ethnicities, the T allele in FADS1 polymorphism, rs174546 is the major allele in Hispanics and the TT genotype is associated with low levels of EPA. This difference in LC-PUFA levels can be exacerbated with low dietary omega-3 intake and may explain the high prevalence of hypertriglyceridemia in Hispanics. Our data suggests that treatment with a highly bioavailable omega-3 FFA may result in significant improvement in omega-3 levels in the Hispanic population.

Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: An integrated backscatter intravascular ultrasound study

ObjectiveTo assess the impact of omega-3 polyunsaturated fatty acids (ω3 PUFAs) on coronary plaque instability. MethodsSerum content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) was measured in 336 of 368 consecutive patients suspected of having coronary artery disease who underwent coronary angiography. Conventional and integrated backscatter intravascular ultrasound (IB-IVUS) parameters were analyzed in 116 patients with 128 coronary plaques, using a 43-MHz (motorized pullback 0.5mm/s) intravascular catheter (View It, Terumo Co., Japan). Lipid-rich plaques were classified into two categories according to their components. ResultsPatients with acute coronary syndrome had significantly lower levels of ω3 PUFAs (especially of EPA and DPA) than those without it. IB-IVUS analyses showed that ω3 PUFAs correlated inversely with % lipid volume and positively with % fibrous volume. Patients with low EPA levels, low DPA levels, and low DHA levels had a significantly higher % lipid volume (p=0.048, p=0.008, and p=0.036, respectively) and a significantly lower % fibrous volume (p=0.035, p=0.008, and p=0.034, respectively) than those with high levels of these fatty acids. Even after adjustment for confounders, the presence of both low EPA and low DPA levels proved to be an independent predictor for lipid-rich plaques in any of the two categories. ConclusionsA lower serum content of ω3 PUFAs (especially of EPA and DPA) was significantly associated with lipid-rich plaques, suggesting the contribution to the incidence of acute coronary syndrome.

Polyunsaturated Fatty Acid Composition of Surgically Removed Hard Exudates in Diabetic Macular Edema.

Three eyes of 2 patients with diabetic macular edema underwent a vitrectomy to remove subfoveal hard exudates. Fatty acid compositions of hard exudates and plasma phospholipids (PL) as an objective estimation of dietary intake were analyzed. Polyunsaturated fatty acids (PUFA) were relatively consistent in hard exudates and PL, but were less abundant in hard exudates. The hard exudates had lower levels of eicosapentaenoic acid (EPA, C20:5 omega3) and docosahexaenoic acid (DHA, C22:6 omega3), which oxidized more readily than other PUFA. Dietary PUFA may be associated with the composition of retinal hard exudates.

Phospholipase A2 and Cyclooxygenase 2 Genes Influence the Risk of Interferon-α–Induced Depression by Regulating Polyunsaturated Fatty Acids Levels

Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an important role in cytokine-induced depression and sickness behavior. Patients with chronic hepatitis C viral infection (n = 132) were assessed to examine the effects of seven single nucleotide polymorphisms in COX2 and PLA2 genes on the development of depression during interferon (IFN)-alpha treatment; a subsample (n = 63) was assessed for the erythrocyte levels of the three main polyunsaturated fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid. An independent "replication" sample of patients with major depression unrelated to cytokine treatment (n = 82) was also examined. Twenty-eight percent of participants developed INF-alpha-induced depression. Participants with the PLA2 BanI GG or the COX2 rs4648308 AG genotypes had a higher risk of IFN-alpha-induced depression (odds ratio = 3.1 and 3.5, respectively). The "at risk" PLA2 genotype was associated with lower EPA levels, and the "at risk" COX2 genotype was associated with lower DHA levels, during IFN-alpha treatment. The PLA2 BanI GG polymorphism was also associated with more somatic symptoms of depression, both in patients with INF-alpha-induced depression and in the replication sample of patients with major depression. Genetic variations in the COX2 and PLA2 genes increase the risk of IFN-alpha-induced depression, possibly by affecting the levels of EPA and DHA. Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our study confirms the role of inflammatory mechanisms in major depression.

Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study

Analyses of brain phospholipid fatty acid profiles reveal a selective deficiency and enrichment in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. In order to account for this difference in brain fatty acid levels, we hypothesized that EPA is more rapidly β-oxidized upon its entry into the brain. Wild-type C57BL/6 mice were perfused with either 14C-EPA or 14C-DHA via in situ cerebral perfusion for 40 s, followed by a bicarbonate buffer to wash out the residual radiolabeled polyunsaturated fatty acid (PUFA) in the capillaries. 14C-PUFA-perfused brains were extracted for chemical analyses of neutral lipid and phospholipid fatty acids. Based on the radioactivity in aqueous, total lipid, neutral lipid and phospholipid fractions, volume of distribution ( V D, μl/g) was calculated. The V D between 14C-EPA- and 14C-DHA-perfused samples was not statistically different for total lipid, neutral lipids or total phospholipids. However, the V D of 14C-EPA in the aqueous fraction was 2.5 times higher than that of 14C-DHA ( p=0.025), suggesting a more extensive β-oxidation than DHA. Furthermore, radiolabeled palmitoleic acid, a fatty acid that can be synthesized de novo, was detected in brain phospholipids from 14C-EPA but not from 14C-DHA-perfused mice suggesting that β-oxidation products of EPA were recycled into endogenous fatty acid biosynthetic pathways. These findings suggest that low levels of EPA in brain phospholipids compared to DHA may be the result of its rapid β-oxidation upon uptake by the brain.

Atlantic salmon ( Salmo salar) muscle structure integrity and lysosomal cathepsins B and L influenced by dietary n-6 and n-3 fatty acids

This study had two main objectives: first, to evaluate the impact of different types and levels of dietary n-6 and n-3 fatty acids (FAs) on Atlantic salmon muscle structure integrity; second, to highlight a possible role of lysosomes and lysosomal degrading enzymes, cathepsins, in fish muscle structure integrity, in relation to dietary fatty acids. Four groups of Atlantic salmon (90 g starting weight) in fresh water tanks were fed one of four diets containing 23% crude lipids, with 100% of the added oils as either fish oil (FO), rapeseed oil (RO), eicosapentaenoic acid (EPA) enriched-oil or docosahexaenoic acid (DHA) enriched-oil. The RO diet was characterised by low levels of EPA + DHA (10% of total FAs), whereas the EPA and DHA diets were characterised by very high levels of EPA + DHA (>50% of total FAs). Fatty acid composition of the muscle crude lysosomal fraction (CLF) generally reflected the diets. Salmon fed the RO diet presented a muscle CLF FA composition close to the one of the FO group, showing moderate PUFA levels, and comparable cathepsin B and cathepsin L activities, relative gene expression of cathepsin B and cathepsin L in the muscle and rate of myofibre–myofibre detachments post-mortem. Salmon fed the EPA and DHA-enriched-oil diets presented a fairly similar muscle CLF FA composition, but different from the FO and RO groups. In the EPA and DHA groups, the percentage of PUFAs in the muscle CLF, the rate of myofibre–myofibre detachments and the relative gene expression of cathepsin B were higher than in the FO and RO groups. Cathepsin B and cathepsin L total activities in the muscle were however lower in the EPA and DHA groups 0 h post-mortem. Dietary lipids influenced the level of lysosomal degrading enzyme activity cathepsin B and cathepsin L as well as the relative gene expression of cathepsin B. Feeding Atlantic salmon with rapeseed oil and extreme levels of EPA + DHA highlighted the impact of fatty acid composition of the diet on salmon muscle integrity and the complexity of the process involving muscle lysosomes and cathepsins in relation to these dietary fatty acids.

P.2.b.006 The influence of L-tryptophan on anxiety behavior in young and old rats with imbalance of thyroid hormones

Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an important role in cytokine-induced depression and sickness behavior.Patients with chronic hepatitis C viral infection (n = 132) were assessed to examine the effects of seven single nucleotide polymorphisms in COX2 and PLA2 genes on the development of depression during interferon (IFN)-α treatment; a subsample (n = 63) was assessed for the erythrocyte levels of the three main polyunsaturated fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid. An independent “replication” sample of patients with major depression unrelated to cytokine treatment (n = 82) was also examined.Twenty-eight percent of participants developed INF-α–induced depression. Participants with the PLA2 BanI GG or the COX2 rs4648308 AG genotypes had a higher risk of IFN-α–induced depression (odds ratio = 3.1 and 3.5, respectively). The “at risk” PLA2 genotype was associated with lower EPA levels, and the “at risk” COX2 genotype was associated with lower DHA levels, during IFN-α treatment. The PLA2 BanI GG polymorphism was also associated with more somatic symptoms of depression, both in patients with INF-α–induced depression and in the replication sample of patients with major depression.Genetic variations in the COX2 and PLA2 genes increase the risk of IFN-α–induced depression, possibly by affecting the levels of EPA and DHA. Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our study confirms the role of inflammatory mechanisms in major depression.

Lipid classes and fatty acids during embryogenesis of captive and wild silverside (Chirostoma estor estor) from Pátzcuaro Lake

Lipid classes and fatty acid levels were analyzed in freshly fertilized eggs, early and late embryo development, and freshly hatched larvae obtained from wild and captive silverside Chirostoma estor estor broodstock, as well as in plankton, Artemia, and pelleted feed. The concentration of triglycerides (TGs) and highly unsaturated fatty acids (HUFAs) in neutral lipid fraction significantly decreased during early development and especially after hatching, whereas phospholipids and HUFA in polar lipid fraction remained constant. These results indicate that TGs rather than PLs are used as energy sources and that all HUFAs [20:4n-6/arachidonic acid (ARA), 20:5n-3/eicosapentaenoic acid (EPA), and 22:6n-3/docosahexaenoic acid (DHA)] of polar lipids are selectively conserved during early development. High levels of DHA (30%, on average, of total fatty acids) and low levels of EPA (4%) were observed in eggs, embryos, and larvae and did not reflect the proportions of these fatty acids in food. Preferential accumulation of DHA from food consumed by broodstock, and then transference to eggs, was probably occurring. The main difference between eggs from both origins was a low level of ARA in eggs from captive fish (4% of total fatty acids) compared to wild fish (9%). This could be associated with a deficiency in the diet that is not compensated for by desaturation/elongation of 18:2n-6 and, possibly, with greater stress in captive fish. In any case, particular requirements of ARA should be determined to optimize the culture of C. estor.

Quality evaluation of Artemia urmiana Günther (Urmia Lake, Iran) with special emphasis on its particular cyst characteristics (International Study on Artemia LXIX)

Artemia urmiana cysts were collected from seven sites in Urmia Lake, Iran. Biometrical analysis revealed that the mean values for the untreated cysts ranged from 262.7 to 286.6 μm, decapsulated cysts from 258.6 to 273.9 μm, and the chorion thickness ranged from 1.2 to 9.3 μm. The cyst samples were tested for their buoyancy at salinities of 35, 50, 100, 150 and 200 g/l. Two cyst batches from Great Salt Lake ( Artemia franciscana) were also tested as reference material. It was found that the majority of Urmia cysts (over 60%) sank after 72 h even at the salinity of 200 g/l, while, GSL cysts reached a much lower figure (less than 10%) after the same time period. Transmission electron microscopy studies of the Urmia cyst chorion revealed a thinner alveolar layer and a thicker fibrous layer in comparison with the respective layers of A. franciscana cysts. A. urmiana instar-I nauplii biometry was also performed (total naupliar length: 466.3–505 μm). Six reproductive and four life span characteristics were investigated at salinities of 35, 50, 100, 140 and 180 g/l in order to evaluate A. urmiana performance at different salinities. A. urmiana individuals showed a preference for high salinity, since high mortality was recorded at 35 and 50 g/l. No significant differences were found between the three highest salinities (100, 140 and 180 g/l) tested ( P > 0.05), with the exception of offspring per brood, reproductive period, and total life span. The analysis of highly unsaturated fatty acid (HUFA) profile of instar-I nauplii hatched from collected cyst batches resulted in low levels of eicosapentaenoic acid (20:5n-3) and high levels of linolenic acid (18:3n-3) ranging from 1.8 to 7.2 and from 32.7 to 54.7 mg/g DW, respectively. Only traces of docosahexaenoic acid (22:6n-3) were found.

Abnormal Fatty Acid Profile of Blood Cell Phospholipids and Dietary Fatty Acid Intake in Patients with Ulcerative Colitis

To elucidate the efficacy of dietary therapy for ulcerative colitis (UC), we analyzed the dietary fatty acid intakes, fatty acid compositions of phospholipids in the plasma and blood cells, and serum cytokines of 12 patients with UC. Correlations among fatty acid compositions in the diet, blood cell phospholipids and serum cytokines were also investigated in UC patients. Although the fat energy ratio was lower in the UC patients than in the controls, no significant difference was observed in their fatty acid intakes. Significantly higher linoleic acid levels were observed in the erythrocyte, mononuclear cell and neutrophil phospholipids of the UC patients compared with the controls. Concerning neutrophil phospholipids, two times higher levels of linoleic acid and arachidonic acid and lower levels of eicosapentaenoic acid (EPA) were observed in the UC patients compared with those in the controls. The serum TNF-α concentration was correlated positively with molar percentage of linoleic acid (r = 0.675, p < 0.02) and negatively with the n-3 polyunsaturated fatty acid (PUFA) (r = -0.584, p < 0.05) in the plasma phospholipids of UC patients. Dietary EPA intake was correlated negatively with the n-6 PUFA molar percentage in the phospholipids of the plasma, mononuclear cells and neutrophils. From these findings, we suggest that a diet high in n-3 PUFA and low in linoleic acid should be recommended for UC patients.

Lower Levels of Eicosapentaenoic Acid and the Ratio of Docosahexaenoic Acid to Arachidonic Acid in Sera of Patients with Multi-Infarct Dementia

To survey the risk factors in multi-infarct dementia (MID), the levels of fatty acids in serum were measured for MID patients and compared with those of healthy individuals. Examined were 40 MID patients aged 57-94 and 152 healthy control subjects aged 50-89. The mean levels of polyunsaturated fatty acid (PUFA), monounsaturated fatty acid and saturated fatty acid of MID were lower than those of the control subjects (p<0.001, respectively). The total amounts of n-3 PUFA and n-6 PUFA in MID were significantly lower than those in control subjects (p<0.01 and p<0.05, respectively) but there were no differences among those of the ratios of n-3/n-6 PUFA. When compared with those of control subjects, low eicosapentaenoic acid (EPA, C20:5n-3) and high arachidonic acid (AA, C20:4n-6) were found in MID (p<0.001, respectively). No significant differences were found in the mean levels of docosahexaenoic acids (DHA, C22:6n-3) between MID and control subjects. The levels of EPA/AA and DHA/AA ratios were lower and the levels of DHA/EPA ratios were higher for the MID than for the control subjects (p<0.001, p<0.01, and p<0.001, respectively). The EPA/AA ratios showed a positive correlation with the DHA/AA ratios in MID patients and control subjects (r=0.65 and r=0.77, p<0.001, respectively). The ratios of DHA/AA showed a positive correlation with the DHA/EPA levels in control subjects (r=0.25, p<0.01), but there was no correlation in the dementia patients. These results suggest that the low EPA and high AA levels and the high DHA/EPA and low DHA/AA ratios might be useful indicators of MID.

Fatty acid composition of five candidate aquaculture species in Central Philippines

Fatty acid composition was determined in five candidate aquaculture species, mangrove red snapper ( Lutjanus argentimaculatus), two rabbitfish ( Siganus guttatus and S. canaliculatus), coral trout ( Plectropomus leopardus) and striped jack ( Caranx fulvoguttatus) sampled in the Central Philippines. Special attention was paid to arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Total lipids of hatchery-produced eggs and newly hatched larvae of mangrove red snapper unexpectedly had equal levels of ARA and EPA. Ovarian polar lipids were subsequently found to have intermediate or high ARA (5.5–10.7%) and DHA (14.4–20.4%) levels but relatively low EPA levels (1.5–1.9%), consequently showing high ARA/EPA (4.4–6.0) and DHA/EPA (7.4–14.9) ratios in wild mangrove red snapper and rabbitfish ( S. guttatus and S. canaliculatus). Similar trends were observed even in hatchery-reared mangrove red snapper, rabbitfish ( S. guttatus) and coral trout. Not only ovary but also liver and muscle contained relatively higher ARA compared with EPA in mangrove red snapper, regardless of the sample source. ARA, EPA and DHA levels in the polar lipids of wild fry (whole body) ranged respectively from 3.2% to 4.0%, from 2.7% to 4.7% and from 23.5% to 27.6% with intermediate or high ARA/EPA (0.8–1.5) and DHA/EPA (5.9–8.8) ratios in mangrove red snapper, rabbitfish ( S. canaliculatus) and striped jack. As overall traits, the five species in the Central Philippines appear to have intermediate or high ARA and DHA levels with low EPA level, consequently having high ARA/EPA and DHA/EPA ratios compared to species in high and temperate northern hemisphere. Thus, the present results indicate that ARA is not a minor component in the tropical species, suggesting that ARA may be nutritionally much more important for egg development and larvae growth in the tropical species than in cold water species. The information of the present study can be used as a guideline for development of appropriate broodstock and/or larval diets in the Philippines.

Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy.

The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S-IgA) levels to food proteins (ovalbumin and beta-lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non-allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme-linked immunosorbent assay (ELISA) was used to measure total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non-allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n-3 (EPA), docosapentaenoic acid C22:5 n-3 (DPA), and docosatetraenoic acid C22:4 n-6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non-allergic children. The total n-6:total n-3 and the arachidonic acid, C20:4 n-6 (AA):EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non-allergic children. The PUFA levels in serum of allergic and non-allergic children were largely similar, except for higher levels of C22:4 n-6 and C22:5 n-6 (p < 0.05 for both) and a higher AA:EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA: EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low alpha-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.

Polyunsaturated fatty acids in school children in relation to allergy and serum IgE levels.

Altered composition of polyunsaturated fatty acids (PUFA) has been observed in allergic individuals and it has been proposed that this is due to an impairment of delta-6-desaturase activity. We have studied the composition of PUFA in serum phospholipids in twenty-two 12-15 year old children with asthma and/or allergic dermatitis and 23 non-atopic controls of similar age. The relative levels of docosahexaenoic acid (DHA, C22:6n-3) and total n-3 long-chain polyunsaturated fatty acids (LCP) were lower (1.46% +/- 0.54 vs. 1.90% +/- 0.58, P = 0.01 for DHA and 2.34% +/- 0.67 vs. 2.80% +/- 0.77, P < 0.05 for total n-3 LCP) and the ratio of total n-6 to n-3 LCP was higher (P < 0.01) in the allergic children than in the controls. In addition to these differences, the relative levels of docosapentaenoic acid (DPA, C22:5n-3) and the ratio of arachidonic acid (AA, C20:4n-6) to dihomo-gamma-linolenic acid (DHGLA, C20:3n-6) were also lower in the 12 allergic children with positive skin prick test, as compared with the SPT negative children (both P < 0.05). In non-allergic children, the levels of total n-3 correlated with n-6 LCP (r = 0.76, p < 0.001). Furthermore, the n-3 LCP, i.e. EPA, DPA and DHA, correlated significantly with each other (r = 0.52-0.78, all p < 0.01) and correlated with n-6 LCP, i.e. C20:2, DHGLA and AA respectively (r = 0.56-0.83, all P < 0.01). Most of these correlations were absent in allergic children. Higher levels of C20:2n-6 and lower levels of eicosapentaenoic acid (EPA, C20:5n-3) were recorded in 11 allergic children with serum IgE above the median level (56 kU/l), as compared to 11 with lower IgE levels (both P < 0.05). Furthermore, the levels of C20:2n-6 correlated with the IgE levels in the children (r = 0.65, P = 0.001). The findings could not confirm an impaired delta-6-desaturase activity in allergic school children and suggest that a disturbance of LCP metabolism is associated with allergic diseases.

Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes

Fish oil is rich in the long chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty acids constitute 20 to 25 g 100 g total fatty acids in fish oil. Feeding rodents diets rich in fish oil has been shown to decrease lymphocyte proliferation and natural killer cell activity. It is not known what level of EPA + DHA is required in the diet to exert these effects. This question was addressed in the current study. Weanling rats were fed on high fat (178 g kg ) diets which contained 4.4 g α-linolenic acid (control) or 4.4 g EPA + DHA (4.4 EPA + DHA) or 6.6 g EPA + DHA ( 6.6 EPA + DHA) 100 g total fatty acids. The n-6 to n-3 polyunsaturated fatty acid ratio was maintained at approximately 7. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Spleen lymphocyte proliferation in response to concanavalin A, spleen natural killer cell activity and PGE 2 production by spleen leukocytes were reduced by feeding the EPA + DHA diets compared with feeding the control diet; the 4.4 and 6.6 EPA + DHA diets caused very similar reductions. The 4.4 EPA + DHA diet reduced popliteal lymph node weight following a localised graft versus host response; this response was not investigated in rats fed the 6.6 EPA + DHA diet. The reductions in lymphocyte functions and in the in vivo graft versus host response caused by the EPA + DHA diets were similar to those previously reported following the feeding of diets rich in fish oil. Thus, this study shows that diets containing relatively low levels of EPA + DHA (20 to 25% of the level found in fish oil) exert immunomodulatory effects. Furthermore, this study suggests that the maximal effect of EPA + DHA is exerted when these fatty acids constitute a level of less than or equal to 4.4 g 100 g total dietary fatty acids.

International study on Artemia. LVI. Characterization of two Artemia populations from Namibia and Madagascar: cytogenetics, biometry, hatching characteristics and fatty acid profiles

Two parthenogenetic Artemia populations from southern Africa, one from Swakopmund saltworks (Namibia) and another from Ankiembe saltworks (Madagascar) have been studied. The population from Namibia is mainly diploid (2n=42) with few tetraploid individuals (4n=84), while the one from Madagascar was found to be triploid (3n=63). No chromocenters have been observed in either of the two populations. The Namibian population has smaller cysts and nauplii compared to those of the Madagascar population. Discriminant analysis revealed significant differences in the biometry of the adults from the two populations. The two populations exhibited very good hatching characteristics. The study of fatty acid methyl esters revealed that the Namibian population belongs to the ‘fresh water’ type of Artemia showing low levels of eicosapentaenoic acid, whereas the population from Madagascar displayed exceptionally high levels of eicosapentaenoic acid, belonging to the ‘marine water’ type.

Requirement of juvenile red seabream Pagrus major for eicosapentaenoic and docosahexaenoic acids.

A feeding experiment was conducted to compare the EFA value between eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in juvenile red seabream, and to determine their requirements for both fatty acids by feeding them defatted fish meal diets containing different levels of EPA and/or DHA ranging from 0 to 1% in diet. Juvenile red seabream fed a diet without supplemental EFA began to show a high mortality and poor appetite after one week feeding. The cumulative mortality of this group was 46% after 24 days. The growth and feed efficiency were effectively improved by elevating EPA or DHA levels to 1% or 0.5% in the diet, respectively. However, further elevation of the DHA level from 0.5 to 1% and addition of both EPA and DHA in diets at levels of 0.25 and 0.5% each did not result in further improvement of these parameters. The hepatosomatic index was high in the fish fed low levels of EPA or DHA and was reduced by elevating EPA levels to 1% in diets, although DHA was more effective than EPA. Thus, the requirement of EPA and DHA was estimated to be around 1% and 0.5% in diet for juvenile red seabream, respectively. The EFA efficiency of DHA was also found to be about twice as high as that of EPA, and there was no additive effect of EPA and DHA on growth and feed efficiency.