Showing papers on "Docosahexaenoic acid published in 2004"

Dietary n-6 and n-3 fatty acid balance and cardiovascular health.

Abstract: Epidemiological and clinical studies have established that the n-6 fatty acid, linoleic acid (LA), and the n-3 fatty acids, linolenic acid (LNA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) collectively protect against coronary heart disease (CHD). LA is the major dietary fatty acid regulating low-density lipoprotein (LDL)-C metabolism by downregulating LDL-C production and enhancing its clearance. Further, the available mass of LA is a critical factor determining the hyperlipemic effects of other dietary fat components, such as saturated and trans fatty acids, as well as cholesterol. By contrast, n-3 fatty acids, especially EPA and DHA, are potent antiarryhthmic agents. EPA and DHA also improve vascular endothelial function and help lower blood pressure, platelet sensitivity, and the serum triglyceride level. The distinct functions of these two families make the balance between dietary n-6 and n-3 fatty acids an important consideration influencing cardiovascular health. Based on published literature describing practical dietary intakes, we suggest that consumption of ~6% en LA, 0.75% en LNA, and 0.25% en EPA + DHA represents adequate and achievable intakes for most healthy adults. This corresponds to an n-6/n-3 ratio of ~6:1. However, the absolute mass of essential fatty acids consumed, rather than their n-6/n-3 ratio, should be the first consideration when contemplating lifelong dietary habits affecting cardiovascular benefit from their intake.

Dietary intake of fatty acids and fish in relation to cognitive performance at middle age.

Abstract: Objective: To examine the associations of fatty acid and fish intake with cognitive function. Methods: Data are from a cross-sectional population-based study among 1,613 subjects ranging from 45 to 70 years old. From 1995 until 2000, an extensive cognitive battery was administered and compound scores were constructed for memory, psychomotor speed, cognitive flexibility (i.e., higher order information processing), and overall cognition. A self-administered food- frequency questionnaire was used to assess habitual food consumption. The risk of impaired cognitive function (lowest 10% of the compound score) according to the energy adjusted intake of fatty acids was assessed with logistic regression, adjusting for age, sex, education, smoking, alcohol consumption, and energy intake. Results: Marine omega-3 polyunsatu- rated fatty acids (PUFA) (eicosapentaenoic acid and docosahexaenoic acid) were inversely related to the risk of impaired overall cognitive function and speed (per SD increase: OR 0.81, 95% CI 0.66 to 1.00 and OR 0.72, 95% CI 0.57 to 0.90). Results for fatty fish consumption were similarly inverse. Higher dietary cholesterol intake was significantly associated with an increased risk of impaired memory and flexibility (per SD increase: OR 1.27, 95% CI 1.02 to 1.57 and OR 1.26, 95% CI 1.01 to 1.57). Per SD increase in saturated fat intake, the risk of impaired memory, speed, and flexibility was also increased, although not significantly. Conclusions: Fatty fish and marine omega-3 PUFA consumption was associated with a reduced risk and intake of cholesterol and saturated fat with an increased risk of impaired cognitive function in this middle-aged population. NEUROLOGY 2004;62:275-280 The notion that dietary factors influence cognitive function and subsequently the risk of dementia is growing. Besides the observation that antioxidant intake is associated with a lower risk of dementia, 1 saturated fat and cholesterol intake were found to be associated with a higher risk of dementia. 2-4 How- ever, in a recent prospective study no association between the intake of any fatty acid and dementia or its subtypes was observed. 5 The findings on dietary cholesterol and saturated fat are consistent with some recent studies showing a protective effect of cholesterol-lowering drugs on dementia 6 and with the observed influence of cholesterol on amyloid pre- cursor protein (APP) processing. 7 Furthermore, mod- erate fish consumption, as a proxy for omega-3 polyunsaturated fatty acid (PUFA) intake, was re- lated to a reduced risk of dementia, in particular Alzheimer disease (AD). 2,8,9 This association may be

Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats.

Abstract: Omega-3 fatty acids (i.e., docosahexaenoic acid; DHA) regulate signal transduction and gene expression, and protect neurons from death. In this study we examined the capacity of dietary omega- 3 fatty acids supplementation to help the brain to cope with the effects of traumatic injury. Rats were fed a regular diet or an experimental diet supplemented with omega-3 fatty acids, for 4 weeks before a mild fluid percussion injury (FPI) was performed. FPI increased oxidative stress, and impaired learning ability in the Morris water maze. This type of lesion also reduced levels of brainderived neurotrophic factor (BDNF), synapsin I, and cAMP responsive element-binding protein (CREB). It is known that BDNF facilitates synaptic transmission and learning ability by modulating synapsin I and CREB. Supplementation of omega-3 fatty acids in the diet counteracted all of the studied effects of FPI, that is, normalized levels of BDNF and associated synapsin I and CREB, reduced oxidative damage, and counteracted learning ...

Alpha-linolenic acid metabolism in men and women: nutritional and biological implications.

Abstract: Purpose of review: This review critically evaluates current knowledge of [alpha]-linolenic acid metabolism in adult humans based on the findings of studies using stable isotope tracers and on increased dietary [alpha]-linolenic acid intake. The relative roles of [alpha]-linolenic acid and of longer-chain polyunsaturated fatty acids in cell structure and function are discussed together with an overview of the major metabolic fates of [alpha]-linolenic acid. The extent of partitioning towards [beta]-oxidation and carbon recycling in humans is described. The use and limitations of stable isotope tracers to estimate [alpha]-linolenic acid desaturation and elongation are discussed. A consensus view of the extent of [alpha]-linolenic acid conversion to longer-chain fatty acids in humans is presented. The extent to which increasing dietary [alpha]-linolenic acid intake alters the concentrations of longer-chain n-3 fatty acids is described. The biological and nutritional implications of these findings are discussed. Recent findings: Conversion of [alpha]-linolenic acid to eicosapentaenoic acid is limited in men and further transformation to docosahexaenoic acid is very low. A lower proportion of [alpha]-linolenic acid is used as a substrate for [beta]-oxidation in women compared with men, while the fractional conversion to longer-chain fatty acids is greater, possibly due to the regulatory effects of oestrogen. Summary: Overall, [alpha]-linolenic acid appears to be a limited source of longer-chain n-3 fatty acids in man and so adequate intakes of preformed n-3 polyunsaturated fatty acids, in particular docosahexaenoic acid, may be important for maintaining optimal tissue function. Capacity to upregulate [alpha]-linolenic acid transformation in women may be important for meeting the demands of the fetus and neonate for docosahexaenoic acid.

Omega-3 fatty acids and inflammation

Abstract: Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune-modulating effects that may be of relevance to atherosclerosis and its clinical manifestations of myocardial infarction, sudden death, and stroke. The n-3 fatty acids that appear to be most potent in this respect are the long-chain polyunsaturates derived from marine oils, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and this review is restricted to these substances. A variety of biologic effects of EPA and DHA have been demonstrated from feeding studies with fish or fish oil supplements in humans and animals. These include effects on triglycerides, high-density lipoprotein cholesterol, platelet function, endothelial and vascular function, blood pressure, cardiac excitability, measures of oxidative stress, pro- and anti-inflammatory cytokines, and immune function. Epidemiologic studies provide evidence for a beneficial effect of n-3 fatty acids on manifestations of coronary heart disease and ischemic stroke, whereas randomized, controlled, clinical feeding trials support this, particularly with respect to sudden cardiac death in patients with established disease. Clinically important anti-inflammatory effects in man are further suggested by trials demonstrating benefits of n-3 fatty acids in rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders. Given the evidence relating progression of atherosclerosis to chronic inflammation, the n-3 fatty acids may play an important role via modulation of the inflammatory processes.

Docosahexaenoic acid promotes neurite growth in hippocampal neurons.

Abstract: Docosahexanoic acid (22:6n-3; DHA) deficiency during development is associated with impairment in learning and memory, suggesting an important role of DHA in neuronal development. Here we provide evidence that DHA promotes neuronal differentiation in rat embryonic hippocampal primary cultures. DHA deficiency in vitro was spontaneously induced by culturing hippocampal cells in chemically defined medium. DHA supplementation improved DHA levels to values observed in freshly isolated hippocampus. We found that DHA supplementation in culture increased the population of neurons with longer neurite length per neuron and with higher number of branches. However, supplementation with arachidonic, oleic or docosapentaenoic acid did not have any effect, indicating specificity of the DHA action on neurite growth. Furthermore, hippocampal cultures obtained from n-3 fatty acid deficient animals contained a lower DHA level and a neuronal population with shorter neurite length per neuron in comparison to those obtained from animals with adequate n-3 fatty acids. DHA supplementation to the deficient group recovered the neurite length to the level similar to n-3 fatty acid adequate cultures. Our data demonstrates that DHA uniquely promotes neurite growth in hippocampal neurons. Inadequate neurite development due to DHA deficiency may contribute to the cognitive impairment associated with n-3 fatty acid deficiency.

Omega-3 fatty acids.

Abstract: Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease. Fatty fish, such as salmon and tuna, and fish oil are rich sources of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Flaxseed, canola oil, and walnuts also are good dietary sources of omega-3 fatty acids. In addition to being antiarrhythmic, the omega-3 fatty acids are antithrombotic and anti-inflammatory. In contrast, omega-6 fatty acids, which are present in most seeds, vegetable oils, and meat, are prothrombotic and proinflammatory. Omega-3 fatty acids also are used to treat hyperlipidemia, hypertension, and rheumatoid arthritis. There are no significant drug interactions with omega-3 fatty acids. The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease. Approximately 1 g per day of eicosapentaenoic acid plus docosahexaenoic acid is recommended for cardioprotection. Higher dosages of omega-3 fatty acids are required to reduce elevated triglyceride levels (2 to 4 g per day) and to reduce morning stiffness and the number of tender joints in patients with rheumatoid arthritis (at least 3 g per day). Modest decreases in blood pressure occur with significantly higher dosages of omega-3 fatty acids.

Association of cystic fibrosis with abnormalities in fatty acid metabolism.

Abstract: BACKGROUND Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.

Omega-3 Fatty Acids in Cardiac Biopsies From Heart Transplantation Patients Correlation With Erythrocytes and Response to Supplementation

Abstract: Background—Omega-3 fatty acids (FAs) appear to reduce the risk of sudden death from myocardial infarction. This reduction is believed to occur via the incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into the myocardium itself, altering the dynamics of sodium and calcium channel function. The extent of incorporation has not been determined in humans. Methods and Results—We first determined the correlation between red blood cell (RBC) and cardiac omega-3 FA levels in 20 heart transplant recipients. We then examined the effects of 6 months of omega-3 FA supplementation (1 g/d) on the FA composition of human cardiac and buccal tissue, RBCs, and plasma lipids in 25 other patients. Cardiac and RBC EPADHA levels were highly correlated (r0.82, P0.001). Supplementation increased EPADHA levels in cardiac tissue by 110%, in RBCs by 101%, in plasma by 139%, and in cheek cells by 73% (P0.005 versus baseline for all; responses among tissues were not significantly different). Conclusions—Although any of the tissues examined could serve as a surrogate for cardiac omega-3 FA content, RBC EPADHA was highly correlated with cardiac EPADHA; the RBC omega-3 response to supplementation was similar to that of the heart; RBCs are easily collected and analyzed; and they have a less variable FA composition than plasma. Therefore, RBC EPADHA (also called the Omega-3 Index) may be the preferred surrogate for cardiac omega-3 FA status. (Circulation. 2004;110:1645-1649.)

Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function

Abstract: The central nervous system has the second highest concentration of lipids after adipose tissue. Long chain fatty acids, particularly arachidonic acid and docosahexaenoic acid, are integral components of neural membrane phospholipids. Alterations in neural membrane phospholipid components cannot only influence crucial intracellular and intercellular signaling but also alter many membrane physical properties such as fluidity, phase transition temperature, bilayer thickness, and lateral domains. A deficiency of docosahexaenoic acid markedly affects neurotransmission, membrane-bound enzyme and ion channel activities, gene expression, intensity of inflammation, and immunity and synaptic plasticity. Docosahexaenoic acid deficiency is associated with normal aging, Alzheimer disease, hyperactivity, schizophrenia, and peroxisomal disorders. Although the molecular mechanism of docosahexaenoic acid involvement in the disorders remains unknown, the supplementation of docosahexaenoic acid in the diet restores gene expression and modulates neurotransmission. Also, improvements are seen in signal transduction processes associated with behavioral deficits, learning activity, peroxisomal disorders, and psychotic changes in schizophrenia, depression, hyperactivity, stroke, and Alzheimer disease.

Essential fatty acids in the planktonic food web and their ecological role for higher trophic levels

Abstract: We measured concentrations of essential fatty acids (EFAs) in four size categories of planktonic organisms— seston (10‐64 mm), microzooplankton (100‐200 mm), mesozooplankton (200‐500 mm), and macrozooplankton (.500 mm)—and in rainbow trout ( Oncorhynchus mykiss) in coastal lakes. Size-dependent patterns in concentrations of specific fatty acids (FAs) are important for ecosystem function, because planktivorous fish and some invertebrates are size-selective predators. We demonstrate that the retention of individual FAs differs among the four size categories of planktonic organisms in our study systems. Changes in individual EFA concentrations within the planktonic food web were similar in all coastal lakes sampled, which indicates the generality of our findings. Although concentrations of arachidonic acid, eicosapentaenoic acid (EPA), and linoleic acid increased steadily with plankton size, the concentration of a-linolenic acid decreased slightly in larger size fractions of zooplankton. Concentrations of another EFA, docosahexaenoic acid (DHA), declined sharply from mesozooplankton to the cladoceran-dominated macrozooplankton size class. Our results indicate that the retention of EFAs, as a function of plankton size, is related, in part, to the taxonomic composition of planktonic food webs. We suggest that, in general, zooplankton exhibit an EPA-retentive metabolism with increasing body size, whereas different taxonomic groups within the planktonic food web retain DHA differently. Finally, we conclude that EPA is highly retained in zooplankton, whereas in rainbow trout DHA is highly retained.

Biotechnological production and applications of the omega-3 polyunsaturated fatty acid docosahexaenoic acid.

Abstract: Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid composed of 22 carbon atoms and six double bonds. Because the first double bond, as counted from the methyl terminus, is at position three, DHA belongs to the so-called omega-3 group. In recent years, DHA has attracted much attention because of its beneficial effect on human health. At present, fish oil is the major source of DHA, but alternatively it may be produced by use of microorganisms. Marine microorganisms may contain large quantities of DHA and are considered a potential source of this important fatty acid. Some of these organisms can be grown heterotrophically on organic substrates without light. These processes can be well controlled and DHA with constant quality can be produced all year round. This paper reviews recent advances in the biotechnological production of DHA by marine microorganisms.

Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production

Abstract: How ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) lower plasma lipid levels is incompletely understood. We previously showed that marine ω-3 PUFAs (docosahexaenoic acid [DHA] and eicosapentaenoic acid) stimulate a novel pathway, post-ER presecretory proteolysis (PERPP), that degrades apolipoprotein B100 (ApoB100), thereby reducing lipoprotein secretion from liver cells. To identify signals stimulating PERPP, we examined known actions of ω-3 PUFA. In rat hepatoma or primary rodent hepatocytes incubated with ω-3 PUFA, cotreatment with the iron chelator desferrioxamine, an inhibitor of iron-dependent lipid peroxidation, or vitamin E, a lipid antioxidant, suppressed increases in thiobarbituric acid–reactive substances (TBARSs; a measure of lipid peroxidation products) and restored ApoB100 recovery and VLDL secretion. Moreover, ω-6 and nonmarine ω-3 PUFA, also prone to peroxidation, increased ApoB100 degradation via intracellular induction of TBARSs. Even without added fatty acids, degradation of ApoB100 in primary hepatocytes was blocked by desferrioxamine or antioxidant cotreatment. To extend these results in vivo, mice were infused with DHA, which increased hepatic TBARSs and reduced VLDL-ApoB100 secretion. These results establish a novel link between lipid peroxidation and oxidant stress with ApoB100 degradation via PERPP, and may be relevant to the hypolipidemic actions of dietary PUFAs, the basal regulation of ApoB100 secretion, and hyperlipidemias arising from ApoB100 overproduction.

Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life.

Abstract: Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are the major polyunsaturated fatty acids in the membranes of brain and retinal cells. Animals specifically deficient in dietary n-3 fatty acids have low DHA content in their membranes, reduced visual acuity and impaired learning ability. Studies on bottle-fed human infants have shown that adding DHA and AA to milk replacer-formulas can bring their concentrations in the infant blood lipids to values as high as those produced by breast-feeding and significantly improves mental development and maturation of visual function. In older subjects, diverse neuropsychiatric and neurodegenerative diseases have been associated to decreased blood levels of n-3 PUFA. Low intakes of fish or of n-3 PUFA in populations have been associated with increased risks of depression and Alzheimer disease, and n-3 PUFA, especially eicosapentaenoic acid (EPA, 20:5n-3), have shown efficacy as adjunctive treatment - and in some cases as the only treatment - in several psychiatric disorders. The mechanisms by which polyunsaturated fatty acids have an impact on neuronal functions will be reviewed: the modulation of membrane biophysical properties, regulation of neurotransmitter release, synthesis of biologically active oxygenated derivatives, and nuclear receptor-mediated transcription of genes responsive to fatty acids or to their derivatives.

n-3 PUFAs reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE2 induced ERK-1 and -2 and HIF-1alpha induction pathway.

Abstract: n-3 Polyunsaturated fatty acids (PUFAs) inhibit the development of microvessels in mammary tumors growing in mice. Human colorectal tumors produce vascular endothelial growth factor (VEGF) whose expression is up-regulated in tumor cells by both cyclooxygenase-2 (COX-2) and PGE(2) and directly correlated to neoangiogenesis and clinical outcome. The goal of this study was to examine the capability of n-3 PUFAs to regulate VEGF expression in HT-29 human colorectal cells in vitro and in vivo. Constitutive VEGF expression was augmented in cultured HT-29 cells by serum starvation and the effects of eicosapentaenoic (EPA) or docosahexaenoic acid (DHA) on VEGF, COX-2, phosphorylated extracellular signal-regulated kinase (ERK)-1 and -2 and hypoxia-inducible-factor 1-alpha (HIF-1alpha) expression and PGE(2) levels were assessed. Tumor growth, VEGF, COX and PGE(2) analysis were carried out in tumors derived from HT-29 cells transplanted in nude mice fed with either EPA or DHA. Both EPA and DHA reduced VEGF and COX-2 expression and PGE(2) levels in HT-29 cells cultured in vitro. Moreover, they inhibited ERK-1 and -2 phosphorylation and HIF-1alpha protein over-expression, critical steps in the PGE(2)-induced signaling pathway leading to the augmented expression of VEGF in colon cancer cells. EPA always showed higher efficacy than DHA in vitro. Both fatty acids decreased the growth of the tumors obtained by inoculating HT-29 cells in nude mice, microvessel formation and the levels of VEGF, COX-2 and PGE(2) in tumors. The data provide evidence that these n-3 PUFAs are able to inhibit VEGF expression in colon cancer cells and suggest that one possible mechanism involved may be the negative regulation of the COX-2/PGE(2) pathway. Their potential clinical application as anti-angiogenic compounds in colon cancer therapy is proposed.

Dietary Docosahexaenoic Acid Suppresses T Cell Protein Kinase Cθ Lipid Raft Recruitment and IL-2 Production

Abstract: To date, the proximal molecular targets through which dietary n -3 polyunsaturated fatty acids (PUFA) suppress the inflammatory process have not been elucidated. Because cholesterol and sphingolipid-enriched rafts have been proposed as platforms for compartmentalizing dynamically regulated signaling assemblies at the plasma membrane, we determined the in vivo effects of fish oil and highly purified docosahexaenoic acid (DHA; 22:6 n -3) on T cell microdomain lipid composition and the membrane subdomain distribution of signal-transducing molecules (protein kinase C (PKC)θ, linker for activation of T cells, and Fas/CD95), before and after stimulation. Mice were fed diets containing 5 g/100 g corn oil (control), 4 g/100 g fish oil (contains a mixture of n -3 PUFA) plus 1 g/100 g corn oil, or 4 g/100 g corn oil plus 1 g/100 g DHA ethyl ester for 14 days. Dietary n -3 PUFA were incorporated into splenic T cell lipid raft and soluble membrane phospholipids, resulting in a 30% reduction in raft sphingomyelin content. In addition, polyclonal activation-induced colocalization of PKCθ with lipid rafts was reduced by n -3 PUFA feeding. With respect to PKCθ effector pathway signaling, both AP-1 and NF-κB activation, IL-2 secretion, and lymphoproliferation were inhibited by fish oil feeding. Similar results were obtained when purified DHA was fed. These data demonstrate for the first time that dietary DHA alters T cell membrane microdomain composition and suppresses the PKCθ signaling axis.

Is Low Dietary Intake of Omega-3 Fatty Acids Associated With Depression?

Abstract: Omega-3 fatty acids are essential long-chain polyunsaturated fatty acids that are concentrated in the CNS, retina, and testes in humans. Alpha-linolenic acid is present in plants and is needed for the synthesis of eicosapentaenoic and docosahexaenoic acids that are received directly from marine sources. There is some evidence that omega-3 fatty acids are linked to depression (1). Studies have reported reduced levels of omega-3 fatty acids in plasma and cell membranes from depressed patients (2–4). One double-blind, placebo-controlled trial (5) has shown that omega-3 supplements improve the short-term clinical course of patients with bipolar disorder. Our aim was to study the association between the dietary intake of omega-3 fatty acids and low mood, depression, and suicide. Consumption of fish rich in long-chain omega-3 fatty acids, specifically, was assessed.

Omega-3 fatty acids from fish oils and cardiovascular disease.

Abstract: Fish and fish oils contain the omega-3 fatty acids known as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Epidemiological studies have shown an inverse relation between the dietary consumption of fish containing EPA/DHA and mortality from coronary heart disease. These relationships have been substantiated from blood measures of omega-3 fatty acids including DHA as a physiological biomarker for omega-3 fatty acid status. Controlled intervention trials with fish oil supplements enriched in EPA/DHA have shown their potential to reduce mortality in post-myocardial infarction patients with a substantial reduction in the risk of sudden cardiac death. The cardioprotective effects of EPA/DHA are widespread, appear to act independently of blood cholesterol reduction, and are mediated by diverse mechanisms. Their overall effects include anti-arrhythmic, blood triglyceride-lowering, anti-thrombotic, anti-inflammatory, endothelial relaxation, plus others. Current dietary intakes of EPA/DHA in North America and elsewhere are well below those recommended by the American Heart Association for the management of patients with coronary heart disease. (Mol Cell Biochem 263: 217-225, 2004).