Dietary omega-3 fatty acids prevent carbohydrate-induced hypertriglyceridemia

Dietary fish oils rich in omega-3 fatty acids are remarkably hypotriglyceridemic in both normal and hypertriglyceridemic subjects. This present study was designed to examine the hypothesis that dietary fish oils could prevent the usual sharp increase in plasma triglyceride and very low-density lipoprotein (VLDL) levels that occur physiologically after the induction by a high-carbohydrate diet. Seven healthy volunteers consumed three experimental liquid formula diets: the baseline diet (45% fat, 10% protein, 45% carbohydrate) and two high-carbohydrate diets (15% fat, 10% protein, 75% carbohydrate), one as a control diet and the other containing fish oil. The baseline and control dietary fats were a mixture of peanut oil and cocoa butter, whereas the fish oil diet contained high levels of omega-3 fatty acids. The plasma triglyceride levels rose from 105 mg/dL during baseline diet to 194 mg/dL during the high-CHO control diet (P less than 0.005). VLDL triglyceride levels increased from 69 to 156 mg/dL (P less than 0.005) and VLDL cholesterol from 18 to 34 mg/dL (P less than 0.005). When fish oil was substituted for the control fats, plasma triglyceride levels fell from 194 to 75 mg/dL (P less than 0.005), VLDL triglyceride and cholesterol levels were reduced from 156 to 34 mg/dL (P less than 0.005) and from 34 to 12 mg/dL (P less than 0.005), respectively. These effects were noted by two to three days after beginning the fish oil diet. Thus, dietary omega-3 fatty acids from fish oil rapidly and markedly reduced VLDL triglyceride levels even in the face of a high-carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drug therapy for hypertriglyceridemia: Fibrates and omega-3 fatty acids

The reduction of low-density lipoprotein cholesterol in patients at risk for acute cardiovascular events is the cornerstone of lipid management in both the primary and secondary prevention settings. Serum triglyceride levels exceeding 150 mg/dL are abnormal and confer increased risk for developing coronary artery disease in both men and women. Serum triglycerides are derived from both dietary and endogenous biosynthetic pathways. Triglyceride metabolism has a complex regulatory circuitry and intimately impacts the production and disposal of multiple lipoprotein species. Hypertriglyceridemia is highly prevalent and is associated with multiple forms of dyslipidemia but tends to be undertreated. Therapeutic intervention with fibric acid derivatives and omega-3 fish oils is associated with significant reductions in both fasting and postprandial serum triglyceride concentrations. A variety of prospective, placebo-controlled clinical trials have also shown that these agents significantly impact risk for multiple cardiovascular end points.     

Supplementation of omega-3 fatty acids in patients with ankylosing spondylitis

OBJECTIVE: To study the effect of supplementation with omega-3 fatty acids on disease variables and drug consumption in patients with ankylosing spondylitis (AS). METHODS: Twenty-four patients were randomized to either a low-dose (1.95 g omega-3/day) or a high-dose (4.55 g omega-3/day) supplement. Disease activity, functional impairment, erythrocyte sedimentation rate (ESR), and drug consumption were assessed during visits at baseline and at weeks 7, 14, and 21. RESULTS: Eighteen patients completed the study, nine patients from each group. The patients in the high-dose group exhibited a significant decrease in disease activity according to the Bath Ankylosing Disease Activity Index (BASDAI; p = 0.038), which was not seen in the low-dose group. Significant differences were not found on drug consumption or in functional capacity in either of the groups. No significant differences were found when comparing the results between the high- and low-dose groups. CONCLUSION: Omega-3 fatty acids in adequate doses may have the capacity to decrease the disease activity of AS. However, larger and better controlled studies are needed before any further conclusions can be made on the extent of this capacity.     

Treatment of primary chylomicronemia due to familial hypertriglyceridemia by omega-3 fatty acids.

Primary familial forms of chylomicronemia can lead to acute life-threatening complications, especially acute pancreatitis. The main aim of therapy is to avoid this so-called chylomicronemia syndrome. In 12 patients with primary chylomicronemia due to familial hypertriglyceridemia, the addition of 2.16 g omega-3 fatty acids over 4 weeks and 4.32 g for 8 weeks resulted in a decrease of serum triglyceride levels from 1,624 +/- 333 to 894 +/- 241 mg/dL after 12 weeks. Cholesterol and triglyceride levels in the chylomicron fraction were reduced concomitantly, the apolipoprotein B-100/B-48 ratio increased, very--low-density lipoprotein (VLDL) triglycerides, VLDL cholesterol, and total cholesterol levels decreased, and low-density lipoprotein (LDL) cholesterol showed a tendency to increase, but this finding did not reach significance. High-density lipoprotein (HDL) cholesterol levels remained unchanged, as did the levels of apolipoproteins A-I, A-II, and E, and lipoprotein(a). Apolipoprotein B levels decreased significantly. The decrease of triglyceride levels to still-elevated concentrations was accompanied by a substantial decrease in plasma and whole-blood viscosity and erythrocyte aggregation, which reached normal values. As in chylomicronemia, complications usually occur at triglyceride levels higher than 1,500 mg/dL; patients can still profit from treatment with omega-3 fatty acids, even though triglyceride levels are still substantially elevated. No clinically relevant side effects occurred, with the exception of the manifestation of diabetes mellitus in one patient, which could be reversed after discontinuation of treatment.     

Anti-obesity effects of long-chain omega-3 polyunsaturated fatty acids

Animal studies suggest that increased consumption of the long-chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, can protect against the development of obesity in animals exposed to an obesogenic diet and reduce body fat when already obese. There is also evidence that increased intakes of these fatty acids can reduce body fat in humans, but human studies are relatively few and have generally been conducted over short time periods with small sample sizes, making it difficult to draw definitive conclusions. Reported reductions in body fat may result from appetite-suppressing effects, adipocyte apoptosis and changes of gene expression in skeletal muscle, heart, liver, intestine and adipose tissues that suppress fat deposition and increase fat oxidation and energy expenditure. We conclude that increased intakes of long-chain omega-3 fatty acids may improve body composition, but longer-term human studies are needed to confirm efficacy and determine whether increasing omega-3 intakes might be an effective strategy to combat obesity.     

Comparative cardiometabolic effects of fibrates and omega-3 fatty acids

Even with the aggressive reduction of low-density lipoprotein cholesterol by statin therapy, a high residual risk of cardiovascular events remains substantially and attracts attention to the need for additional preventive therapies. Therefore, effective reductions of residual risk of cardiovascular disease have emerged as therapeutic targets. Fibrates and omega-3 fatty acids have been introduced to reduce triglycerides and to increase high-density lipoprotein cholesterol and have shown anti-atherosclerotic, vascular and metabolic effects. However, some effects are controversial and very recent randomized clinical trials report different results from the earlier ones. In this review, we address the vascular and metabolic effects and the results of recent clinical trials of fibrates and omega-3 fatty acids. We also compared their effects under modern guideline therapy regarding potential drugs to reduce a residual cardiometabolic risk of cardiovascular disease.     

Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients with coronary heart disease

BACKGROUND AND AIM: There are only little data about the effects of lipid-lowering drugs (LLDs) on the metabolism of essential n-6 and n-3 fatty acids in patients with established coronary heart disease (CHD). METHODS AND RESULTS: Male patients with CHD and high cholesterol levels (>6.2 mmol/L) were randomized (double-blind protocol) to receive either simvastatin 20mg (S) or fenofibrate 200mg daily (F) for 3 months. Dietary habits and plasma fatty acids were not different in the two groups at baseline. After treatment, there were significant changes in both the groups for the main n-6 fatty acids, with an increase in arachidonate (from 6.5+/-1.7% of total fatty acids to 7.5+/-2.1, p<0.001 in S and from 6.2+/-1.4 to 6.8+/-1.4, p<0.005 in F) and a decrease in linoleate (from 26.9+/-3.9 to 24.2+/-3.6, p<0.001, and from 27.8+/-3.4 to 26.1+/-4.2, p<0.05, in S and F, respectively). In addition, there was a decrease in two major n-3 fatty acids (alpha-linolenate and docosahexanoate, both p<0.05), but only in F. CONCLUSIONS: For the first time in a double-blind randomized study in CHD patients, we report that LLDs significantly alter the metabolism of essential fatty acids that are critically important for the pathogenesis and prevention of CHD. Further studies are urgently needed to examine the effects of higher dosages of statins (as currently proposed to reduce more cholesterol) on these essential fatty acids in the clinical setting and the crucial questions of whether specific dietary intervention (combining low intake of n-6 fatty acids and high intake of n-3 fatty acids) may improve the effectiveness of these drugs.     

Immunonutrition in experimental colitis: beneficial effects of omega-3 fatty acids

BACKGROUND: Recent data have given emphasis to the benefits of immunonutrition with omega-3 fatty acids (n-3 FA) in various clinical situations. This work presents the results of parenteral administration of different lipid emulsions in experimental acute colitis and reviews the pertinent literature. METHODS: Seventy-four adult male Wistar rats were randomized in six groups that had 10% acetic acid-induced colitis (except CS). During 7 days, control groups CS (without colitis) and CC (with colitis) received physiological solution and the others received specific lipid emulsion by a central venous catheter (0.5 mL/h). The n-3/n-6 FA ratio and lipidic compositions were: group L--1:7.7 (LCT, n = 12), M--1:7.0 (MCT and LCT, n = 12), LW-3--1:4.5 (LCT plus FO, n = 12) and MW-3--1:3.0 (MCT and LCT plus FO, n = 13). Rats were evaluated to assess abdominal and intestinal alterations, macrophage cellularity and colonic concentrations of LTB4, LTC4, PGE2 and TXB2. RESULTS: N-3 FA treated rats (LW-3 and MW-3) presented less inflammatory abdominal alterations than CC rats. Mucosal ulcer formation in MW-3 group was the only comparable to CS group. Only CS, M and MW-3 rats presented smaller cellularity than CC group. Comparing to CC group, there were found smaller averages of LTB4 in CS, LW-3 and MW-3 groups, of PGE2 in CS, M and MW-3 groups, and of TXB2 in CS and MW-3 groups. LTC4 averages were not different. CONCLUSIONS: 1) LCT-containing lipid emulsion with low n-3/n-6 ratio do not modify inflammatory colitis derived manifestations; 2) the association of MCT/LCT-containing lipid emulsion with fish oil with high n-3/n-6 ratio impels great beneficial impact, attenuating morphological and inflammatory consequences and decreasing colonic concentrations of proinflammatory mediators.     

Cardiovascular benefits of omega-3 fatty acids

Cardiac societies recommend the intake of 1 g/day of the two omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for cardiovascular disease prevention, treatment after a myocardial infarction, prevention of sudden death, and secondary prevention of cardiovascular disease. These recommendations are based on a body of scientific evidence that encompasses literally thousands of publications. Of four large scale intervention studies three also support the recommendations of these cardiac societies. One methodologically questionable study with a negative result led a Cochrane meta-analysis to a null conclusion. This null conclusion, however, has not swayed the recommendations of the cardiac societies mentioned, and has been refuted with good reason by scientific societies. Based on the scientific evidence just mentioned, we propose a new risk factor to be considered for sudden cardiac death, the omega-3 index. It is measured in red blood cells, and is expressed as a percentage of EPA + DHA of total fatty acids. An omega-3 index of >8% is associated with 90% less risk for sudden cardiac death, as compared to an omega-3 index of <4%. The omega-3 index as a risk factor for sudden cardiac death has striking similarities to LDL as a risk factor for coronary artery disease. Moreover, the omega-3 index reflects the omega-3 fatty acid status of a given individual (analogous to HbA1c reflecting glucose homeostasis). The omega-3 index can therefore be used as a goal for treatment with EPA and DHA. As is the case now for LDL, in the future, the cardiac societies might very well recommend treatment with EPA and DHA to become goal oriented (e.g. an omega-3 index>8%).     

Acute effects of monounsaturated fatty acids with and without omega-3 fatty acids on vascular reactivity in individuals with type 2 diabetes

Aims/hypothesis We examined the acute postprandial effects of meals containing unsaturated fatty acids on flow-mediated dilation (FMD) of the brachial artery and triacylglycerols in individuals with type 2 diabetes. We hypothesised that consumption of omega-3 fatty acids would enhance vascular function. Saturated fat reduces FMD for several hours, but there is inconsistent evidence about whether foods containing unsaturated fats impair FMD acutely. Little is known about the acute effects of omega-3 fatty acids on vascular reactivity.Methods We measured FMD before and 4 h after 3 test meals (50 g fat, 2,615 kJ) in 18 healthy adults with type 2 diabetes. The monounsaturated fatty acids (MUFA) meal contained 50 g fat from high oleic safflower and canola oils. Two additional meals were prepared by replacing 7% to 8% of MUFA with docosahexaenoic acid and eicosapentaenoic acid from sardine oil or -linolenic acid from canola oil.Results In the sample as a whole, FMD was increased 17% at 4 h vs. the fasting baseline. After the MUFA meal, subjects with the largest increases in triacylglycerols had the largest FMD decreases. The opposite pattern was observed after meals containing docosahexaenoic acid and eicosapentaenoic acid or -linolenic acid. In subjects with high fasting triacylglycerols, meals containing 3 to 5 g of omega-3 fatty acids increased FMD by 50% to 80% and MUFA alone had no significant effects on FMD.Conclusions/interpretation Endothelium-dependent vasodilation was not impaired 4 h after meals containing predominantly unsaturated fatty acids. The fatty acid composition of the meal and the metabolic status of the individual determine the vascular effects of a high-fat meal.     

Role of omega-3 polyunsaturated fatty acids in diet of patients with rheumatic diseases

The beneficial effects of omega-3 polyunsaturated fatty acids have been widely described in the literature in particular those on cardiovascular system. In the last decade there has been an increased interest in the role of these nutrients in the reduction of articular inflammation as well as in the improvement of clinical symptoms in subjects affected by rheumatic diseases, in particular rheumatoid arthritis (RA). Nutritional supplementation with omega-3 may represent an additional therapy to the traditional pharmacological treatment due to the anti-inflammatory properties which characterize this class of lipids: production of alternative eicosanoids, reduction of inflammatory cytokines, reduction of T-lymphocytes activation, reduction of catabolic enzymes activity. The encouraging results of dietetic therapy based on omega-3 in RA are leading researchers to test their effectiveness on patients with other rheumatic conditions such as systemic lupus erythematosus and ankylosing spondylitis. Nutritional therapy based on food rich in omega-3 or on supplementation with fish oil capsules, proved to be a valid support to he treatment of chronic inflammatory rheumatic diseases.     

New approaches to therapy with omega-3 fatty acids

With greater focus on chronic disease prevention, renewed attention has been directed toward understanding the pathophysiology of various medical conditions and the development of newer medical treatments to prevent and treat complications. There has been immense interest in evaluating societal lifestyles, cultural attitudes toward health, and dietary influences on health conditions. The omega-3 fatty acids have become a focus of interest, and recent research and trial evidence have highlighted their effects, including potential clinical advantages. Despite this progress, the precise mechanisms through which omega-3 fatty acids act remain poorly understood. These agents are now recommended as secondary prevention after acute myocardial infarction, and ongoing large clinical trials should provide insight into the use of omega-3 fatty acids in heart failure and the primary prevention of cardiovascular disease.     

Antiarrhythmic effects of omega-3 fatty acids: from epidemiology to bedside

Omega-3 polyunsaturated fatty acids are emerging as a safe and effective means to reduce sudden death after acute myocardial infarction. This review summarizes the epidemiological background for the use of omega-3 fatty acids with this indication, clinical trials performed so far, and experimental data supporting their antiarrhythmic efficacy.