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.

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.

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.

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.

Decreased oxidative stress in patients with ulcerative colitis supplemented with fish oil omega-3 fatty acids

OBJECTIVE: the potential pathogenicity of free radicals may have a pivotal role in ulcerative colitis. Fish oil omega-3 fatty acids exert anti-inflammatory effects on patients with ulcerative colitis (UC), but the precise mechanism of the action of fish oil on oxidative stress is still controversial. The aim of the present work was to verify the blood oxidative stress in patients with UC and determine whether the association of sulfasalazine to fish oil omega-3 fatty acids is more effective than isolated use of sulfasalazine to reduce the oxidative stress.METHODS:, Nine patients (seven female and two male; me. an age = 40 +/- 11 y) with mild or moderate active UC were studied in a randomized crossover design. In addition to their usual medication (2 g/d of sulfasalazine), they received fish oil omega-3 fatty acids (4.5 g/d) or placebo for 2-mo treatment periods that were separated by 2 mo, when they only received sulfasalazine. Nine healthy individuals served as control subjects to study the oxidative stress status. Disease activity was assessed by laboratory indicators (C-reactive protein, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, erythrocyte sedimentation rate, albumin, hemoglobin, and platelet count), sigmoidoscopy, and histology scores. Analysis of oxidative stress was assessed by plasma chemiluminescence and erythrocyte lipid peroxidation, both induced by tert butyl hydroperoxide (t-BuOOH) and by plasma malondialdehyde. Antioxidant status was assayed by total plasma antioxidant capacity (TRAP) and microsomal lipid peroxidation inhibition (LPI). Superoxide dismutase (SOD) and catalase erythrocyte enzymatic activities were also determined.RESULTS: No significant changes were observed in any laboratory indicator or in the sigmoidoscopy or histology scores, with the exception of erythrocyte sedimentation rate, which decreased with both treatments. Oxidative stress was demonstrated by significant decreases in TRAP and LPI levels, increased chemiluminescence induced by t-BuOOH, and higher SOD activity in patients with UC. Treatment with fish oil omega-3 fatty acids reverted the chemiluminescence induced by t-BuOOH and LPI to baseline levels but that did not occur when patients received only sulfasalazine. Levels of plasma malondialdehyde, erythrocyte lipid peroxidation, and catalase were not different from those in the control group.CONCLUSIONS: the results indicated that plasma oxidative stress occurs in patients with UC, and there was a significant decrease when the patients used sulfasalazine plus fish oil omega-3 fatty acids. However, there was no improvement in most laboratory indicators, sigmoidoscopy, and histology scores. The results suggested that omega-3 fatty acids may act as free radical scavengers protecting the patients against the overall effect of oxidative stress. (C)Elsevier B.V. 2003.

Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis

Fish oil omega-3 fatty acids exert antiinflammatory effects on patients with ulcerative colitis. However, a comparative study in patients with mild to moderate ulcerative colitis receiving only sulfasalazine or omega-3 fatty acids has not been performed. We sought to detect changes in the inflammatory disease activity with the use of either fish oil omega-3 fatty acids or sulfasalazine in patients with ulcerative colitis. Ten patients (five male, five female; mean age = 48 +/- 12 y) with mild to moderate active ulcerative colitis were investigated in a randomized cross-over design. They received either sulfasalazine (2 g/d) or omega-3 fatty acids (5.4 g/d) for 2 mo. Disease activity was assessed by clinical and laboratory indicators, sigmoidoscopy, histology, and whole-body protein turnover (with N-15-glycine). Treatment with w-3 fatty acids resulted in greater disease activity as detected by a significant increase in platelet count, erythrocyte sedimentation rate, C-reactive protein, and total fecal nitrogen excretion. No major changes in protein synthesis and breakdown were observed during either treatment. In conclusion, treatment with sulfasalazine is superior to treatment with omega-3 fatty acids in patients with mild to moderate active ulcerative colitis. Nutrition 2000;16:87-901 (C) Elsevier B.V. 2000.

Omega-3 fatty acids supplementation decreases metabolic syndrome prevalence after lifestyle modification program

The additional effect of omega-3 supplementation in association with lifestyle modification program (LSMP) in free living-adults was evaluated.We studied 39 adults (control group with LSMP (G1, n = 16) and LSMP plus supplementation of 3 g of fish oil per day (360 mg of docosahexaenoic acid and 540 mg of eicosapentaenoic acid) (G2, n = 23)) during 20 weeks. The fish oil group showed a significant decrease in waist circumference (1.3%) followed by metabolic syndrome reduction (29%) mainly due to normalization of blood pressure (33.3%) and triacylglycerol (27.3%). Omega-3 supplementation provided additional benefits to LSMP in the resolution of metabolic syndrome

Omega-3 fatty acids and the neurovascular responses to mental stress in humans

Hypertension is the most prevalent form of cardiovascular disease (CVD) in the world, and is known to increase the risk for developing other diseases. Recently, the American Heart Association introduced a new classification of blood pressure, prehypertension (PHT). The criteria for PHT include a systolic of 120-139 mmHg and/or a diastolic blood pressure of 80-89 mmHg. It has been observed that individuals with PHT have a higher risk of developing hypertension later in life. Therefore, it is important to understand the mechanisms contributing to PHT in order to possibly prevent hypertension. Omega-3 fatty acids found in fish oils have been suggested as a means of lowering blood pressure. However, little is known on the effects of fish oil in PHT humans. Therefore we conducted two studies. In Study 1 we investigated PHT and normotensive (NT) individuals during a mental stress task. Mental stress is known to contribute to the development of hypertension. In Study 2 PHT and NT subjects were placed in an eight week double-blind placebo controlled study in which subjects consumed 9g/day of either fish oil or placebo (olive oil) in addition to their regular diets. Subjects were tested during a resting baseline (seated and supine), 5 minutes of a mental stress task, and 5 minutes of recovery both pre and post supplementation. We measured arterial pressure (AP), heart rate (HR), muscle sympathetic nerve activity (MSNA), and forearm and calf vascular responses. In Study 1 PHT demonstrated augmented AP and blunted vasodilation during mental stress, but MSNA did not change. In Study 2, fish oil did not directly influence blood pressure, MSNA or vascular responses to mental stress. However, it became clear that fish oil had an effect on some but not all subjects (both PHT and NT). Specifically, subjects who experienced a reduced blood pressure response to fish oil also demonstrated a decrease in MSNA and HR during mental stress. Collectively, the investigations in this dissertation had several novel findings. First, PHT individuals demonstrate an augmented pressor and blunted vascular response to mental stress, a response that may be contributing to the development of hypertension. Second, fish oil does not consistently lower resting blood pressure, but the interindividual responses may be related to MSNA. Third, fish oil attenuated the heart rate and MSNA responses and to mental stress in both PHT and NT. In conclusion, we found that there are both similarities and differences in the way PHT and NT individuals respond to mental stress and fish oil.