Marine omega-3 fatty acids and coronary heart disease

Purpose of review: To provide an overview of the key earlier intervention studies with marine omega-3 fatty acids and to review and comment on recent studies reporting on mortality outcomes and on selected underlying mechanisms of action. Recent findings: Studies relating marine omega-3 fatty acid status to current or future outcomes continue to indicate benefits, for example, on incident heart failure, congestive heart failure, acute coronary syndrome, and all-cause mortality. New mechanistic insights into the actions of marine omega-3 fatty acids have been gained. Three fairly large secondary prevention trials have not confirmed the previously reported benefit of marine omega-3 fatty acids towards mortality in survivors of myocardial infarction. Studies of marine omega-3 fatty acids in atrial fibrillation and in cardiac surgery-induced atrial fibrillation have produced inconsistent findings and meta-analyses demonstrate no benefit. A study confirmed that marine omega-3 fatty acids reduce the inflammatory burden with advanced atherosclerotic plaques, so inducing greater stability. Summary: Recent studies of marine omega-3 fatty acids on morbidity of, and mortality from, coronary and cardiovascular disease have produced mixed findings. These studies raise new issues to be addressed in future research.

Understanding omega-3 polyunsaturated fatty acids

Current intakes of very long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are low in most individuals living in Western countries. A good natural source of these fatty acids is seafood, especially oily fish. Fish oil capsules contain these fatty acids also. Very long-chain omega-3 fatty acids are readily incorporated from capsules into transport (blood lipids), functional (cell and tissue), and storage (adipose) pools. This incorporation is dose-dependent and follows a kinetic pattern that is characteristic for each pool. At sufficient levels of incorporation, EPA and DHA influence the physical nature of cell membranes and membrane protein-mediated responses, lipid-mediator generation, cell signaling, and gene expression in many different cell types. Through these mechanisms, EPA and DHA influence cell and tissue physiology and the way cells and tissues respond to external signals. In most cases the effects seen are compatible with improvements in disease biomarker profiles or health-related outcomes. As a result, very long-chain omega-3 fatty acids play a role in achieving optimal health and in protection against disease. Long-chain omega-3 fatty acids not only protect against cardiovascular morbidity but also against mortality. In some conditions, for example rheumatoid arthritis, they may be beneficial as therapeutic agents. On the basis of the recognized health improvements brought about by long-chain omega-3 fatty acids, recommendations have been made to increase their intake. The plant omega-3 fatty acid, alpha-linolenic acid (ALA), can be converted to EPA, but conversion to DHA appears to be poor in humans. Effects of ALA on human health-related outcomes appear to be due to conversion to EPA, and since this is limited, moderately increased consumption of ALA may be of little benefit in improving health outcomes compared with increased intake of preformed EPA + DHA.

Effects of omega-3 fatty acids on immune function in broiler chickens

There is interest in the enrichment of poultry meat with long-chain n-3 polyunsaturated fatty acids in order to increase the consumption of these fatty acids by humans. However, there is concern that high levels of n-3 polyunsaturated fatty acids may have detrimental effects on immune function in chickens. The effect of feeding increasing levels of fish oil (FO) on immune function was investigated in broiler chickens. Three-week-old broilers were fed 1 of 4 wheat-soybean basal diets that contained 0, 30, 50, or 60 g/kg of FO until slaughter. At slaughter, samples of blood, bursa of Fabricius, spleen, and thymus were collected from each bird. A range of immune parameters, including immune tissue weight, immuno-phenotyping, phagocytosis, and cell proliferation, were assessed. The pattern of fatty acid incorporation reflected the fatty acid composition of the diet. The FO did not affect the weight of the spleen, but it did increase thymus weight when fed at 50 g/kg (P < 0.001). Fish oil also lowered bursal weights when fed at 50 or 60 g/kg (P < 0.001). There was no significant effect of FO on immune cell phenotypes in the spleen, thymus, bursa, or blood. Feeding 60 g/kg of FO significantly decreased the percentage of monocytes engaged in phagocytosis, but it increased their mean fluorescence intensity relative to that of broilers fed 50 g/kg of FO. Lymphocyte proliferation was significantly decreased after feeding broiler chickens diets rich in FO when expressed as division index or proliferation index, although there was no significant effect of FO on the percentage of divided cells. In conclusion, dietary n-3 polyunsaturated fatty acids decrease phagocytosis and lymphocyte proliferation in broiler chickens, highlighting the need for the poultry industry to consider the health status of poultry when poultry meat is being enriched with FO.

Postprandial enrichment of triacylglycerol-rich lipoproteins with omega-3 fatty acids: lack of an interaction with apolipoprotein E genotype?

Background: We have previously demonstrated that carrying the apolipoprotein (apo) E epsilon 4 (E4+) genotype disrupts omega-3 fatty acids (n − 3 PUFA) metabolism. Here we hypothesise that the postprandial clearance of n − 3 PUFA from the circulation is faster in E4+ compared to non-carriers (E4−). The objective of the study was to investigate the fasted and postprandial fatty acid (FA) profile of triacylglycerol-rich lipoprotein (TRL) fractions: Sf >400 (predominately chylomicron CM), Sf 60 − 400 (VLDL1), and Sf 20 − 60 (VLDL2) according to APOE genotype. Methods: Postprandial TRL fractions were obtained in 11 E4+ (ε3/ε4) and 12 E4− (ε3/ε3) male from the SATgenε study following high saturated fat diet + 3.45 g/d of docosahexaenoic acid (DHA) for 8-wk. Blood samples were taken at fasting and 5-h after consuming a test-meal representative of the dietary intervention. FA were characterized by gas chromatography. Results: At fasting, there was a 2-fold higher ratio of eicosapentaenoic acid (EPA) to arachidonic acid (P = 0.046) as well as a trend towards higher relative% of EPA (P=0.063) in theSf >400 fraction of E4+. Total n − 3 PUFA in the Sf 60 − 400 and Sf 20 − 60 fractions were not APOE genotype dependant. At 5 h, there was a trend towards a time × genotype interaction (P=0.081) for EPA in theSf >400 fraction. When sub-groups were form based on the level of EPA at baseline within the Sf >400 fraction, postprandial EPA (%) was significantly reduced only in the high-EPA group. EPA at baseline significantly predicted the postprandial response in EPA only in E4+ subjects (R2 = 0.816). Conclusion: Despite the DHA supplement contain very low levels of EPA, E4+ subjects with high EPA at fasting potentially have disrupted postprandial n − 3 PUFA metabolism after receiving a high-dose of DHA. Trial registration: Registered at clinicaltrials.gov/show/NCT01544855.

Omega-3 fatty acids, cardiovascular disease and stability of atherosclerotic plaques

Long-chain n-3 polyunsaturated fatty acids are found in oily fish and in fish oils and similar preparations. Substantial evidence from epidemiological and case-control studies indicates that consumption of fish, oily fish and long-chain n-3 fatty acids reduces risk of cardiovascular mortality. Secondary prevention studies using long-chain n-3 fatty acids in patients post-myocardial infarction have shown a reduction in total and cardiovascular mortality with an especially potent effect on sudden death. Long-chain n-3 fatty acids have been shown to beneficially modify a range of cardiovascular risk factors, which may result in primary cardiovascular prevention. However, reduced non-fatal and fatal events and a reduction in sudden death probably involve other mechanisms. Reduced thrombosis following long-chain n-3 fatty acids may play a role. A decrease in arrhythmias is a favoured mechanism of action of long-chain n-3 fatty acids and is supported by cell culture and animal studies. However human trials using implantable cardiac defibrillators have produced inconsistent findings and a recent meta-analysis does not support this mechanism of action. An alternative mechanism of action may be stabilisation of atherosclerotic plaques by long-chain n-3 fatty acids. This is suggested by one published human study which showed that incorporation of long-chain n-3 fatty acids into plaques collected at carotid endarterectomy resulted in fewer macrophages in the plaque and a morphology indicative of increased stability. These findings are supported from observations in an animal model and suggest that the primary effect of long-chain n-3 fatty acids might be on macrophages within the plaque.

n-3 fatty acid enrichment of edible tissue of poultry: A review

There is clear evidence of the nutritional benefits of consuming long-chain n-3 PUFA, which are found predominantly in oily fish. However, oily fish consumption, particularly in the United Kingdom, is declining, as is the consumption of all meats with the exception of poultry, which has increased in consumption by 73% in the last 30 yr. This pattern, if less marked, is reflected throughout Europe, and therefore one means of increasing long-chain n-3 PUFA consumption would be to increase the long-chain n-3 PUFA content in the edible tissues of poultry. This review considers the feasibility of doing this, concentrating particularly on chickens and turkeys. It begins by summarizing the benefits to human health of consuming greater quantities of n-3 FA and the sources of n-3 PUFA in the human diet. The literature on altering the FA composition of poultry meat is then reviewed, and the factors affecting the incorporation of n-3 PUFA into edible tissues of poultry are investigated. The concentration of alpha-linolenic acid (ALA) in the edible tissues of poultry is readily increased by increasing the concentration of ALA in the birds' diet (particularly meat with skin, and dark meat to a greater extent than white meat). The concentration of EPA in both white and dark meat is also increased when the birds' diet is supplemented with EPA, although supplementing the diet with the precursor (ALA) does not result in a noticeable increase in EPA content in the edible tissues. Although supplementing the birds' diets with relatively high concentrations of DHA does result in an increased concentration of DHA in the tissues, the relationship between dietary and tissue concentrations of DHA is much weaker than that observed with ALA and EPA. The impact that altering the FA composition of edible poultry tissue may have on the organoleptic and storage qualities of poultry products is also considered.

UK Food Standards Agency workshop report: the effects of the dietary n-6 : n-3 fatty acid ratio on cardiovascular health

This report summarises a workshop convened by the UK Food Standards Agency (FSA) on 11 September 2006 to review the results of three FSA-funded studies and other recent research on effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. The objective of this workshop was to reach a clear conclusion on whether or not it was worth funding any further research in this area. On the basis of this review of the experimental evidence and on theoretical grounds, it was concluded that the n-6:n-3 fatty acid ratio is not a useful concept and that it distracts attention away from increasing absolute intakes of long-chain n-3 fatty acids which have been shown to have beneficial effects on cardiovascular health. Other markers of fatty acid intake, that more closely relate to physiological function, may be more useful.

Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [C-13]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-C-13]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 DRA 0.04%. After 8 weeks on the control diet, plasma lipid composition and [C-13]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 [C-13]ALNA conversion was similar to baseline. The high-(EPA+DHA) diet raised plasma phosphatidylcholine-EPA and -DHA concentrations, decreased [C-13]ALNA conversion to EPA (2-fold) and DPA (4-fold), whilst [C-13]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.

Omega-3 polyunsaturated fatty acids and human health outcomes

Current intakes of very long chain omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DNA) are low in most individuals living in Western countries. A good natural source of these fatty acids is seafood, especially oily fish. Fish oil capsules contain these fatty acids too. Very long chain w-3 fatty acids are readily incorporated from capsules into transport, functional, and storage pools. This incorporation is dose-dependent and follows a kinetic pattern that is characteristic for each pool. At sufficient levels of incorporation, EPA and DHA influence the physical nature of cell membranes and membrane protein-mediated responses, eicosanoid generation, cell signaling and gene expression in many different cell types. Through these mechanisms, EPA and DHA influence cell and tissue physiology, and the way cells and tissues respond to external signals. In most cases, the effects seen are compatible with improvements in disease biomarker profiles or in health-related outcomes. As a result, very long chain omega-3 fatty acids play a role in achieving optimal health and in protection against disease. Long chain omega-3 fatty acids protect against cardiovascular morbidity and mortality, and might be beneficial in rheumatoid arthritis, inflammatory bowel diseases, childhood learning, and behavior, and adult psychiatric and neurodegenerative illnesses. DHA has an important structural role in the eye and brain, and its supply early in life is known to be of vital importance. On the basis of the recognized health improvements brought about by long chain omega-3 fatty acids, recommendations have been made to increase their intake. (C) 2009 International Union of Biochemistry and Molecular Biology, Inc. Volume 35, Number 3, May/June 2009, Pages 266-272. E-mail: pcc@soton.ac.uk

Improving the fatty acid profile of winter milk from housed cows with contrasting feeding regimes by oilseed supplementation

Many studies show concentrations of nutritionally desirable fatty acids in bovine milk are lower when cows have no access to grazing, leading to seasonal fluctuations in milk quality if cows are housed for part of the year. This study investigated the potential to improve the fatty acid profiles of bovine milk by oilseed supplementation (rolled linseed and rapeseed) during a period of indoor feeding in both organic and conventional production systems. Both linseed and rapeseed increased the concentrations of total monounsaturated fatty acids, vaccenic acid, oleic acid and rumenic acid in milk, but decreased the concentration of the total and certain individual saturated fatty acids. Linseed resulted in greater changes than rapeseed, and also significantly increased the concentrations of α-linolenic acid, total polyunsaturated fatty acids and total omega-3 fatty acids. The response to oilseed supplementation, with respect to increasing concentrations of vaccenic acid and omega-3 fatty acids, appeared more efficient for organic compared with conventional diets.

Effects of n-3 fatty acids on postprandial triacylglycerol and hormone concentrations in normal subjects

The present study reports results from two investigations to determine effects of a 6-week period of moderate n-3 fatty acid supplementation (2.7 g/d) on fasting and on postprandial triacylglycerol and metabolic hormone concentrations in response to standard test meals. In the first study postprandial responses were followed for 210 min after an early morning test meal challenge; in the second study responses to an evening test meal were followed during the evening and overnight for a total period of 12 h. In both studies postprandial triacylglycerol responses to the test meals were significantly reduced after compared with before fish-oil supplementation. In the second study the triacylglycerol peak response seen between 200 and 400 min in subjects studied before supplementation with fish oils was almost completely absent in the same subjects after 6 weeks of n-3 fatty acid supplementation. Analysis of fasting concentrations of metabolites and hormones was carried out on the combined data from the two studies. There were no significant differences in total, low-density-lipoprotein- or high-density-lipoprotein-cholesterol concentrations during fish-oil supplementation, although there was considerable individual variation in cholesterol responses to the supplement. Concentrations of Apo-B and Apo-A1 were unchanged during supplementation with fish oils. Fasting and early morning postprandial GIP concentrations were lower in subjects taking fish oils, possibly due to acute effects of fish-oil capsules taken on the evening before the studies. In both studies fasting insulin and glucose and postprandial insulin concentrations remained unchanged following fish-oil supplementation. The results do not support the view that triacylglycerol-lowering effects of n-3 fatty acids are due to modulation of insulin secretion mediated via the enteroinsular axis. Further studies are required to determine the precise mechanism by which fish oils reduce both fasting and postprandial triacylglycerol concentrations.

NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids

Objective Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene–nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS). Methods Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene–nutrient interactions. Results Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene–nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC + AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes. Conclusions Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations.