Antiarrhythmic effects of n-3 polyunsaturated fatty acids

The n-3 or omega 3 polyunsaturated fatty acids are a promising dietary preventive therapy for cardiovascular disease. The main dietary source of n-3 polyunsaturated fatty acids comes from sea fish. During recent years, the subject of antiarrhythmic role of n-3 polyunsaturated fatty acids has been investigated extensively. A great deal of evidence has shown that the antiarrhythmic effect of n-3 polyunsaturated fatty acids is exerted by altering the electrophysiology of myocytes. This article is intended to review specifically this role of n-3 polyunsaturated fatty acids as demonstrated by both basic and clinical evidence in animal and human studies, including current concepts on the antiarrhythmic mechanism of this class of polyunsaturated fatty acids.     

Lower ratio of n-3 to n-6 fatty acids in cultured than in wild fish

Fish are the major dietary source of very-long-chain n-3 polyunsaturated fatty acids. We investigated whether cultured fish contain fewer n-3 fatty acids than do wild fish. Fifty-eight trout, 51 eel, and 5 salmon were collected from fishermen and hatcheries throughout Europe, pooled into 23 lots (8 of wild and 15 of cultured fish), and analyzed. The ratio of n-3 to n-6 polyunsaturates was significantly lower in cultured than in wild fish (2 vs 7 in trout, 2 vs 5 in eel, and 6 vs 11 in salmon). Hunted fish are a better source of n-3 polyunsaturates than are cultured fish.     

Effects of four doses of n-3 fatty acids given to hyperlipidemic patients for six months.

The long-term effects of practical amounts of fish oil on plasma lipids and lipoprotein cholesterol levels, bleeding times, erythrocyte deformabilities, and plasma phospholipid fatty acid (FA) composition were investigated in this trial. Twenty-eight hyperlipidemic patients with elevated cholesterol and triglyceride (TG) levels were randomly assigned to take 3, 6, 9, or 12 capsules of fish oil daily for 6 months, providing 1.25-5 g of n-3 FAs per day. Baseline parameters were compared to values after 1 and 6 months of treatment, and after 1 month of washout. There were no statistically significant changes in total cholesterol levels at any dose. Both low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels tended to rise, resulting in an unchanged ratio of LDL-C to HDL-C. The TG and very-low-density-lipoprotein cholesterol (VLDL-C) levels decreased significantly with all but the lowest dose. Bleeding times were unaffected despite a nonsignificant 34% increase detected at the highest dose. Red blood cell deformability tended to increase with the two middle doses only. The EPA level in plasma phospholipids was strongly correlated with n-3 FA (FA) consumption. We conclude that long-term treatment of hyperlipidemic patients with practical intakes of n-3 FAs produced persistent reductions in TG levels and no change in the LDL-C/HDL-C ratio.     

Effects of four doses of n-3 fatty acids given to hyperlipidemic patients for six months.

The long-term effects of practical amounts of fish oil on plasma lipids and lipoprotein cholesterol levels, bleeding times, erythrocyte deformabilities, and plasma phospholipid fatty acid (FA) composition were investigated in this trial. Twenty-eight hyperlipidemic patients with elevated cholesterol and triglyceride (TG) levels were randomly assigned to take 3, 6, 9, or 12 capsules of fish oil daily for 6 months, providing 1.25-5 g of n-3 FAs per day. Baseline parameters were compared to values after 1 and 6 months of treatment, and after 1 month of washout. There were no statistically significant changes in total cholesterol levels at any dose. Both low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels tended to rise, resulting in an unchanged ratio of LDL-C to HDL-C. The TG and very-low-density-lipoprotein cholesterol (VLDL-C) levels decreased significantly with all but the lowest dose. Bleeding times were unaffected despite a nonsignificant 34% increase detected at the highest dose. Red blood cell deformability tended to increase with the two middle doses only. The EPA level in plasma phospholipids was strongly correlated with n-3 FA (FA) consumption. We conclude that long-term treatment of hyperlipidemic patients with practical intakes of n-3 FAs produced persistent reductions in TG levels and no change in the LDL-C/HDL-C ratio.     

n-3 fatty acids in psoriasis

Increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Replacement of arachidonic acid by alternative precursor polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), which can be metabolized via the same enzymatic pathways as AA, might be a therapeutic option in psoriasis. However the results of studies evaluating the therapeutic benefit of dietary fish oil have been conflicting and not clearly dose-dependent. To overcome the slow kinetics and limited availability of oral supplementation, we have performed three studies to assess the efficacy and safety of an intravenously administered fish oil derived lipid emulsion on different forms of psoriasis. Patients received daily infusions of either an n-3 fatty acid-based lipid emulsion (Omegaven) or a conventional n-6 lipid emulsion (Lipoven) in different time and dose regimens. In addition to an overall assessment of the clinical course of psoriasis, EPA- and AA-derived neutrophil 5-lipoxygenase (LO)--products, thromboxane (TX) B2/B3, PAF and plasma free fatty acids were investigated. Treatment with n-3 fatty acids resulted in a considerably higher response rate than infusion of n-6 lipids. A more than 10-fold increase in neutrophil EPA-derived 5-LO product formation was noted in the n-3 group, accompanied by a rapid increase in plasma-free EPA within the first days. In conclusion, intravenous n-3-fatty acid administration causes reduction of psoriasis, which may be related to changes in inflammatory eicosanoid generation. The rapidity of the response to intravenous n-3 lipids exceeds by orders of magnitude the hitherto reported kinetics of improvement of psoriatic lesions upon use of oral supplementation.     

The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women

Fish oils rich in (n-3) long-chain PUFA (LCPUFA) can reduce circulating triglycerides and raise HDL-cholesterol. Phytosterols have been shown to reduce total cholesterol and LDL-cholesterol in normocholesterolemic and hyperlipidemic populations. We investigated the combined effects of phytosterols and (n-3) LCPUFA on plasma lipid profile in hyperlipidemic individuals. This study was a 3-wk randomized, double-blind, placebo-controlled, 2 x 2 factorial trial in 4 parallel groups of 60 hyperlipidemic individuals. Subjects were randomized to receive either sunola oil or 1.4 g/d (n-3) LCPUFA capsules with or without 2 g phytosterols per day while maintaining their habitual diet. The combination of phytosterols and (n-3) LCPUFA reduced plasma total cholesterol by 13.3% (P = 0.001), which differed from (n-3) LCPUFA alone (P < 0.001). LDL-cholesterol concentrations followed the same pattern as that of plasma cholesterol with a 12.5% decrease (P = 0.002) in the combination group. The HDL-cholesterol concentration was increased by (n-3) LCPUFA (7.1%; P = 0.01) alone and in combination with phytosterols (8.6%; P = 0.04), whereas phytosterol treatment alone had no effect. Plasma triglyceride concentration was lowered by (n-3) LCPUFA (22.3%; P = 0.004) alone and in combination with phytosterols (25.9%; P = 0.005), whereas phytosterol treatment alone had no effect. In conclusion, the combined supplementation with phytosterols and (n-3) LCPUFA has both synergistic and complementary lipid-lowering effects in hyperlipidemic men and women.     

Intake of n-6 and n-3 fatty acids and fish and risk of community-acquired pneumonia in US men

BACKGROUND: Essential fatty acids modulate inflammation and glucose metabolism and may alter infection risk. OBJECTIVE: We examined the association between intakes of n-6 and n-3 fatty acids and fish and the risk of community-acquired pneumonia. DESIGN: We prospectively evaluated 38,378 male US health professionals aged 44-79 y at the outset. We updated medical and lifestyle information biennially through questionnaires and diet every 4 y with the use of a validated food-frequency questionnaire. We excluded men who reported pneumonia, myocardial infarction, stroke, other heart disease, arterial surgery, cancer, or asthma before 1990 or those with incomplete dietary data. Community-acquired pneumonia was determined by blinded medical record review of chest radiographs. RESULTS: During 10 y of follow-up, there were 441 new cases of nonfatal community-acquired pneumonia. Pneumonia risk was lower in men in the highest energy-adjusted quintiles of intake than in men in the lowest quintiles of intake of linoleic acid [multivariate relative risk (RR): 0.70; 95% CI: 0.51, 0.96; P for trend = 0.01] and alpha-linolenic acid (multivariate RR: 0.68; 95% CI: 0.50, 0.93; P for trend = 0.01). Pneumonia risk decreased 4% for every 1-g/d increase in linoleic acid intake (multivariate RR: 0.96; 95% CI: 0.93, 0.99). Pneumonia risk was reduced by 31% for every 1-g/d increase in alpha-linolenic acid intake (multivariate RR: 0.69; 95% CI: 0.51, 0.93). Intakes of eicosapentaenoic acid and docosahexaenoic acid were not significantly related to pneumonia risk. CONCLUSION: Higher intakes of alpha-linolenic and linoleic acids and possibly of fish may reduce the risk of pneumonia.     

The effects of dietary n-3 polyunsaturated fatty acids on neutrophils

The studies of dietary fish oil supplementation in healthy volunteers demonstrate a significant increase in neutrophil EPA content, a concomitant reduction in neutrophil AA content, and suppression of neutrophil LTB4 synthesis by supplementation with dietary fish oil containing approximately 3-4 g EPA daily for a minimum of 4 weeks. Suppression of neutrophil chemotactic responsiveness to LTB4 and FMLP was observed after dietary n-3 PUFA supplementation at these levels. Dietary EPA is more active than DHA in eliciting these effects in human neutrophils. Dietary n-3 PUFA supplementation inhibits neutrophil chemotaxis to these ligands through the inhibition of the signal transduction pathway between the receptor and phospholipase C, as demonstrated by the inhibition of chemotaxin-stimulated IP3 formation, in the absence of an effect on the number or affinity of the respective chemotaxin receptors. In patients with RA, dietary supplementation with n-3 PUFA resulted in decreased AA content of cellular lipids, with an augmented EPA content and decreased LTB4 generation by neutrophils. Dietary supplementation with n-3 PUFA also resulted in augmentation of depressed neutrophil chemotaxis to LTB4 and FMLP. Preliminary findings suggest that the decreased responsiveness to chemotaxins of neutrophils from RA patients is due to down-regulation of chemotaxin receptor number, resulting in decreased signaling via chemotaxin receptors. Dietary fish oil PUFA partially reversed the down-regulation of the chemotaxin receptor of neutrophils of RA patients, but had a lesser effect on chemotaxin receptor signaling and function, probably due to a post-receptor inhibition induced by fish oil PUFA, as was previously observed in healthy controls. Several small clinical trials have each suggested that dietary supplementation with n-3 PUFA resulted in modest improvements in disease activity. Meta-analysis of these studies confirms statistically significant improvements in tender joint count and morning stiffness after 3 months of dietary fish oil supplementation in patients with RA. Dietary supplementation with gamma-linolenic acid-rich oils also inhibits neutrophil LTB4 formation, has other anti-inflammatory and immunosuppressive effects, and shows promise of therapeutic efficacy in RA.     

n-3 Polyunsaturated fatty acids, inflammation and obesity-related disease

Obese individuals are at increased risk from a range of metabolic diseases, including insulin resistance, dyslipidaemia and hypertension. Adipose tissue is an important endocrine organ, secreting a range of inflammatory mediators, including tumour necrosis factor alpha and interleukin 6. Circulating concentrations of these cytokines are increased in obesity and may contribute to the pathogenesis of metabolic diseases. The present review considers the evidence linking inflammation and obesity-related disease. The data show that an inflammatory phenotype, measured by serum sialic acid concentration, identifies individuals with insulin resistance, dyslipidaemia and hypertension. Serum sialic acid concentration increases progressively in obese individuals with none, one or multiple features of the metabolic syndrome, independent of BMI. Supplementation with long-chain n-3 polyunsaturated fatty acids has shown anti-inflammatory effects in studies of both healthy populations and in models of chronic inflammatory conditions. The effect on insulin sensitivity has been varied, with both positive and negative effects. This variability may relate to the metabolic characteristics of the study population; individuals with high background inflammation may derive greater benefits from n-3 polyunsaturated fatty acid supplements, suggesting a possible interaction between diet and phenotype. Future research is needed to fully evaluate the role of anti-inflammatory strategies in the dietary management of obesity.     

trans Fatty acids in human milk are inversely associated with concentrations of essential all-cis n-6 and n-3 fatty acids and determine trans, but not n-6 and n-3, fatty acids in plasma lipids of breast-fed infants.

BACKGROUND: Human milk fatty acids vary with maternal dietary fat composition. Hydrogenated dietary oils with trans fatty acids may displace cis n-6 and n-3 unsaturated fatty acids or have adverse effects on their metabolism. The effects of milk trans, n-6, and n-3 fatty acids in breast-fed infants are unclear, although n-6 and n-3 fatty acids are important in infant growth and development. OBJECTIVE: We sought to determine the relations between trans and cis unsaturated fatty acids in milk and plasma phospholipids and triacylglycerols of breast-fed infants, and to identify the major maternal dietary sources of trans fatty acids. DESIGN: We collected milk from 103 mothers with exclusively breast-fed 2-mo-old infants, blood from 62 infants, and 3-d dietary records from 21 mothers. RESULTS: Mean (+/-SEM) percentages of trans fatty acids were as follows: milk, 7.1 +/- 0.32%; infants' triacylglycerols, 6.5 +/- 0. 33%; and infants' phospholipids, 3.7 +/- 0.16%. Milk trans fatty acids, alpha-linolenic acid (18:3n-3), arachidonic acid (20:4n-6), docosahexaenoic acid (22:6n-3) (P < 0.001), and linoleic acid (18:2n-6) (P = 0.007) were each related to the same fatty acid in infant plasma phospholipids. Milk trans fatty acids were inversely related to milk 18:2n-6 and 18:3n-3, but not to milk or infant plasma 20:4n-6 or 22:6n-3. trans Fatty acids represented 7.7% of maternal total fat intake (2.5% of total energy); the major dietary sources were bakery products and breads (32%), snacks (14%), fast foods (11%), and margarines and shortenings (11%). CONCLUSIONS: There were comparable concentrations of trans fatty acids in the maternal diet, breast milk, and plasma triacylglycerols of breast-fed infants. Prepared foods were the major dietary source of trans fatty acids.     

膳食脂肪酸及n-6/n-3比与血脂及脂质过氧化关系的研究进展

膳食脂肪酸及n-6/n-3比对血脂及脂质过氧化的影响是营养学研究的重要课题,首先叙述膳食脂肪酸对血脂和脂质过氧化的影响及作用机制.然后从预防动脉粥样硬化的角度,提出建立合理的n-6/n-3脂肪酸供给比的重要性.     

The neuroprotective effect of fish n-3 fatty acids in the hippocampus of diabetic rats

Abstract

Introduction: Diabetes mellitus may lead to functional and structural changes in the brain. Fish oil is a rich source of n-3 essential fatty acids (EFA) such as eicosapentaenoic and docosahexoenoic acids. We examined the neuroprotective effects of fish n-3 EFA in the hippocampus of diabetic rats.

Materials and methods: Nineteen adult male rats were divided into three groups. Group I (control; n = 6) was fed a normal rat diet. Group II (diabetic; n = 6) was fed a normal rat diet and streptozotocin (STZ) was administered to induce diabetes mellitus. Group III (n-3 + diabetic; n = 7) was fed a normal rat diet and fish n-3 EFA (Marincap^®, 0.4 g/kg/day) for 8 weeks and STZ was administered to induce diabetes mellitus. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in the left hippocampus after the animals were sacrificed. The right hemisphere was completely blocked. The sections were stained with Cresyl Violet and apoptotic neurons were counted in the hippocampus.

Results: The levels of MDA and activities of SOD and CAT increased in diabetic rats compared to control rats. However, the levels of MDA and activities of SOD and CAT decreased in n-3 + diabetic rats compared to diabetic rats. Also, the number of apoptotic neurons increased in diabetic rats compared to control rats and decreased in n-3 + diabetic rats compared to diabetic rats.

Conclusions: Fish n-3 EFA reduces oxidative stress and induces apoptotic changes in the hippocampus of STZ-diabetic rats. The addition of fish n-3 EFA to diets may be useful to prevent functional and structural changes to cerebral centers due to diabetes mellitus.     

n-3 polyunsaturated fatty acids raise low-density lipoproteins, high-density lipoprotein 2, and plasminogen-activator inhibitor in healthy young men

The effects of a moderate supplementation in n-3 polyunsaturated fatty acids (PUFAs) were investigated in 36 young healthy adult males. Factors investigated were lipoprotein (including HDL subfractions and apolipoproteins) and hemostasis indexes, assessed by platelet aggregation and plasminogen-activator-inhibitor (PAI) activity. Fat-controlled diets were prescribed, one with and one without a fish-oil supplement (control diet), successively during 3 wk in random order. Total calorie, fat, and cholesterol intakes were similar in the two diets. Triglycerides in serum and very-low-density lipoproteins were lower and high-density-lipoprotein 2 cholesterol was higher with the n-3 PUFA-supplemented diet. These effects as well as a significant decrease in platelet aggregation can be considered beneficial in terms of cardiovascular risk. However, significant increases in low-density-lipoprotein cholesterol and PAI activity occurred and were correlated. This latter effect could be detrimental.