Showing papers on "Fish oil published in 1988"

Cardiovascular effects of n-3 fatty acids

Abstract: A detailed technical overview summarizes and discusses available evidence concerning the effects of fish oil n-3 polyunsaturated fatty acids (PUFA's) on reducing cardiovascular disease risks. Attention is given to: the characteristics and metabolism of n-6 and n-3 PUFA's and the effects of n-3 PUFA's on plasma lipid profiles; the role of n-3 PUFA's in reducing atherosclerosis risk; possible protection of n-3 PUFA's during myocardial infarction; the relative importance of eicosapentaenoic vs. docosahexaneoic acids; and appropriate intakes of n-3 PUFA's. The potential adverse health effects from ingesting fish oils also are discussed.(wz)

Dietary fish oil prevents ventricular fibrillation following coronary artery occlusion and reperfusion

Abstract: Coronary artery occlusion and reperfusion in the anesthetized rat was used as a whole animal model of arrhythmia and sudden cardiac death to examine the influence of long-term dietary lipid modulation of myocardial membrane fatty acids on the development of cardiac arrhythmias. Feeding rats a diet supplemented with tuna fish oil significantly reduced the incidence and severity of arrhythmias, preventing ventricular fibrillation during both occlusion and reperfusion. Dietary sunflower seed oil reduced arrhythmias during occlusion but not in reperfusion. Dietary fat can modify the vulnerability of the myocardium to arrhythmic stimuli. The efficacy of tuna fish oil in reducing vulnerability to both ischemic and reperfusion arrhythmias suggests a potential beneficial effect of dietary n-3 fatty acids in addition to their influence on hemostasis, plasma lipids, and atherosclerosis that may contribute to their proposed role in lowering cardiovascular disease mortality and morbidity.

Fish oils inhibit endothelial cell production of platelet-derived growth factor-like protein

Abstract: Diets rich in fish and fish oils are associated with a reduced risk of cardiovascular disease and atherosclerosis. The interaction of a commercial fish oil extract (MaxEPA) with vascular endothelial cells (ECs) was studied as a possible mechanism for this protective effect. MaxEPA almost completely inhibited EC production of platelet-derived growth factor-like protein (PDGFc) while other lipids had a lesser effect or no effect. Overall protein synthesis was not reduced, nor was the inhibition due to defective secretion or increased degradation of the growth factor. Antioxidants suppressed the inhibitory activity of MaxEPA indicating that free radical oxidative processes were required for the inhibition. These results suggest that fish oils may suppress intimal smooth muscle cell proliferation by decreasing the production of EC-derived paracrine growth factors. This inhibitory process represents a possible molecular mechanism for the antiatherosclerotic action of marine lipids.

Delta 6-desaturase activity in liver microsomes of rats fed diets enriched with cholesterol and/or omega 3 fatty acids.

Abstract: The effect of feeding semipurified diets enriched in linseed (rich in C18:3, omega 3 fatty acid) or fish (rich in C20:5, omega 3 and C22:6, omega 3 fatty acid) oil with and without cholesterol supplementation on the desaturation of linoleic acid (C18:2, omega 6) by rat liver microsomal fractions was investigated. Animals fed diets supplemented with beef tallow were used as equal-energy controls. Both linseed-oil and fish-oil diets, without added cholesterol, decrease conversion of C18:2, omega 6 fatty acid to gamma-linolenic acid (C18:3, omega 6). Reduction in delta 6-desaturation was significantly greater for animals fed the diet containing fish oil than with animals fed the linseed-oil diet. The major effect of cholesterol supplementation was to decrease the rate of desaturation of C18:2, omega 6, when fed in combination with the beef-tallow diet, whereas delta 6-desaturation was unaffected when cholesterol was fed along with diets high in omega 3 fatty acids (linseed oil or fish oil). The activity of the delta 6-desaturase in vitro is consistent with the fatty acid composition observed for the microsomal membranes on which this enzyme is localized. Dietary linseed oil and fish oil lowered the arachidonic (C20:4, omega 6) acid content of rat liver microsomes, with an accompanying increase in membrane eicosapentaenoic (C20:5, omega 3) and docosahexaenoic (C22:6, omega 3) acid content, in comparison with the group fed beef tallow. Inclusion of cholesterol into the beef-tallow or linseed-oil diets resulted in decreased membrane C20:4, omega 6-fatty-acid content, with concomitant increase in C18:2, omega 6-fatty-acid content. However, addition of cholesterol to the fish-oil diet did not alter the microsomal membrane content of C20:4, omega 6 fatty acid. Thus it is suggested that (1) the decrease in prostaglandin E2, thromboxane and prostacyclin levels generally observed after fish-oil consumption may be at least partly due to inhibition of C20:4, omega 6-fatty-acid synthesis from C18:2, omega 6 fatty acid; and (2) consumption of fish oil prevents the further decrease in C20:4, omega 6-fatty-acid levels by dietary cholesterol that is apparent when cholesterol is fed in combination with diets high in saturated fat or C18:3, omega 3 fatty acid.

Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis.

Abstract: In a double blind noncrossover study, dietary supplementation with fish oil (18 g/day), was compared with an olive oil supplement over a 12-week period in patients with rheumatoid arthritis receiving established conventional therapies. An improvement in tender joint score and grip strength was seen at 12 weeks in the fish oil treated group but not in the olive oil treated group. The more subjective measures of mean duration of morning stiffness and analogue pain score improved to a similar extent in both groups, although statistical significance was only achieved in paired analyses in the olive oil treated group. Production of leukotriene B4 by isolated neutrophils stimulated in vitro was reduced by 30% in the fish oil treated group and unchanged in the olive oil treated group.

Effect of Different Levels of Omega-3 and Omega-6 Fatty Acids on Azoxymethane-induced Colon Carcinogenesis in F344 Rats

Abstract: The effect of various levels of dietary Menhaden fish oil containing omega-3 fatty acids plus corn oil containing omega-6 fatty acids fed during the postinitiation phase of colon carcinogenesis was studied in male F344 rats. Starting at 5 weeks of age, groups of animals were fed the 5% corn oil (5% CO) diet. At 7 weeks of age, all animals except the vehicle-treated controls were administered s.c. injections of azoxymethane (15 mg/kg body wt/week for 2 weeks). 4 days after carcinogen or vehicle treatment, groups of animals were transferred to experimental diets containing 4% Menhaden oil + 1% corn oil (4% MO + 1% CO), 23.5% corn oil (23.5% CO), 17.6% corn oil + 5.9% Menhaden oil (17.6% CO + 5.9% MO), 11.8% corn oil + 11.8% Menhaden oil (11.8% CO + 11.8% MO), or 5.9% corn oil + 17.6% Menhaden oil (5.9% CO + 17.6% MO) and fed these diets until termination of the experiment at Week 38 after carcinogen treatment. An additional group consuming a 5% CO diet was continued on these diets. Colon mucosal ornithine decarboxylase activity and microsomal fatty acid composition of colon mucosa were measured in vehicle-treated animals fed experimental diets for 14 weeks. Fatty acids were also analyzed in the microsomal fraction of colon tumors at termination of the experiment. The body weights of animals fed various experimental diets were comparable. Feeding of high fat diets containing 17.6% CO + 5.9% MO, 11.8% CO + 11.8% MO, or 5.9% CO + 17.6% MO significantly inhibited the incidence (percentage of animals with tumors) of colon adenocarcinomas compared to that of 23.5% CO diet. However, the multiplicity (number of tumors/rat) of colon adenocarcinomas was significantly inhibited only in groups fed the 5.9% CO + 17.6% MO compared to those fed the 23.5% CO diet. The incidence and multiplicity of adenocarcinomas were greater in animals fed the 23.5% CO diet compared to those fed the 5% CO diet. Colonic mucosal ornithine decarboxylase activity was lower in animals fed the 11.8% CO + 11.8% MO, 5.9% CO + 17.6% MO, 5% CO, and 4% MO + 1% CO diets compared to the levels in animals fed the 23.5% CO diet. The increasing levels of Menhaden oil in the diet significantly increased the omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid and decreased the omega-6 fatty acids such as linoleic acid, linolenic acid, and arachidonic acid in microsomal fractions from colonic mucosa and tumors.

Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study.

Abstract: In rheumatoid arthritis (RA) benefit from non-steroidal anti-inflammatory drugs (NSAIDs) is mediated through inhibition of the cyclo-oxygenase enzyme, thereby decreasing production of the 2 series prostaglandins (PGs). The lipoxygenase enzyme is intact, however, allowing leucotriene (LT) production, e.g., LTB4 (an inflammatory mediator). Treatment with evening primrose oil (EPO) which contains gamma-linolenic acid (GLA) leads to production of the 1 series PGs, e.g., PGE1, which has less inflammatory effects. Also LT production is inhibited. Eicosapentaenoic acid (EPA, fish oil) treatment provides a substrate for PGs and LTs, which are also less inflammatory. In this study 16 patients with RA were given 540 mg GLA/day (EPO), 15 patients 240 mg EPA and 450 mg GLA/day (EPO/fish oil), and 18 patients an inert oil (placebo). The aim of this study was to determine if EPO or EPO/fish oil could replace NSAID treatment in RA. The initial 12 month treatment period was followed by three months of placebo for all groups. Results at 12 months showed a significant subjective improvement for EPO and EPO/fish oil compared with placebo. In addition, by 12 months the patients receiving EPO and EPO/fish oil had significantly reduced their NSAIDs. After 3 months of placebo those receiving active treatment had relapsed. Despite the decrease in NSAIDs, measures of disease activity did not worsen. It is suggested that EPO and EPO/fish oil produce a subjective improvement and allow some patients to reduce or stop treatment with NSAIDs. There is, however, no evidence that they act as disease modifying agents.

Effect of dietary supplementation with fish oil lipids on mild asthma.

Abstract: Recruitment of inflammatory leucocytes to the airways may play a part in the pathogenesis of asthma. As dietary enrichment with fish oil lipids can suppress leucocyte function, the effect of these lipids on asthma control and neutrophil function was studied in 20 subjects with mild asthma. Twelve subjects received capsules containing 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid daily and eight subjects received placebo capsules containing olive oil for 10 weeks in a double blind fashion. Baseline specific airways conductance, airways responsiveness to histamine and exercise, diurnal peak expiratory flow, symptom scores, and bronchodilator use were measured. Neutrophil fatty acid composition was evaluated by gas chromatography, calcium ionophore induced neutrophil leukotriene (LT)B4 and LTB5 generation were measured by reverse phase high performance liquid chromatography and radioimmunoassay, and neutrophil chemotactic responses to formyl-methionyl-leucyl-phenylalanine (FMLP) and LTB4 were assessed by a microchemotaxis technique. Although the fish oil supplemented diet produced a greater than 10 fold increase in the eicosapentaenoic acid content of neutrophil phospholipids, there was no significant change in airways responsiveness to histamine or any change in any of the clinical measurements. After dietary supplementation with fish oil there was a 50% inhibition of total LTB (LTB4 + LTB5) generation by ionophore stimulated neutrophils and neutrophil chemotaxis was substantially suppressed. Neutrophil function remained unchanged in the placebo group. It is concluded that in subjects with mild asthma a fish oil enriched diet attenuates neutrophil function without changing the severity of asthma.

Mitochondrial function in rats is affected by modification of membrane phospholipids with dietary sardine oil.

Abstract: Phospholipids of heart and liver of rats fed a diet containing sardine oil had more omega 3 polyunsaturated fatty acids and less omega 6 polyunsaturated fatty acids than those of rats fed corn oil, whereas there was little difference in the fatty acid composition of brain phospholipids. The mass of phospholipid classes in rat heart mitochondria was not changed, but their fatty acid compositions were altered. Modification of the fatty acid compositions of mitochondrial phosphatidylcholine and phosphatidylethanolamine reached a plateau after 10 d of feeding, but that of cardiolipin continued for 30 d. The O2 consumption rate of rat heart mitochondria decreased as the fatty acid composition of the phospholipids changed. This may be due to the reduction of the activity of cytochrome c oxidase, which requires cardiolipin for its activity. However, F1F0-ATPase, which also requires cardiolipin, was activated under the same conditions.

Rapid autoxidation of fish oil in diets without added antioxidants.

Abstract: Feeding of purified diets containing fish oil without added antioxidant leads to rapid autoxidation of the oil and the possibility of artifactual results due to the feeding of autoxidation products. Purified diets containing menhaden oil without any added antioxidant deteriorate quickly. Peroxide value of the diet is elevated 5- to 6-fold within 24 h and 12-fold within 48 h when exposed to air at room temperature. Addition of 0.02% t-butylhydroquinone to the fish oil prevents this deterioration for at least 72 h. Determination of fatty acid composition is not a sensitive indicator of diet integrity. Supplementation of fish oil diets with vitamin E to help protect against in vivo peroxidation is discussed.

Dietary linolenic acid and longer-chain n-3 fatty acids: comparison of effects on arachidonic acid metabolism in rats.

Abstract: Rats were fed graded amounts of purified 18:3n-3 or fish oil concentrate in the presence of a constant amount of 18:2n-6 to evaluate the ability of 18:3n-3 compared with longer-chain n-3 fatty acids to inhibit 20:4n-6 metabolism in platelets and lungs. Dietary 18:3n-3 at a ratio of 0.28 (n-3 to n-6 fatty acids) suppressed levels of 20:4n-6 in lung and plasma phospholipids and the capacity of the tissues to synthesize cyclooxygenase-derived products in a dose-dependent fashion. At similar ratios of n-3 to n-6 dietary fatty acids, longer-chain n-3 fatty acids, which are abundant in fish oil, appear to be more effective than 18:3n-3 in suppressing 20:4n-6 levels and the capacity of the tissues to synthesize cyclooxygenase-derived products. Much greater amounts of 12-hydroxyeicosapentaenoic acid (12-HEPE) and 5-HEPE than of 12-hydroxyeicosatetraenoic acid (12-HETE) and 5-HETE appeared to be formed in tissues of the group receiving the highest amount of fish oil. These results suggest that ingestion of fish oil leads to increased formation of lipoxygenase-derived products of longer-chain n-3 fatty acids.

Effect of Fish Oil Concentrate on Lipoprotein Composition in NIDDM

Abstract: Non-insulin-dependent diabetes mellitus (NIDDM) is associated with elevated very-low-density lipoprotein (VLDL) triglyceride concentrations and abnormalities of low-density lipoprotein (LDL) composition. Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects, we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM. Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design. Medications, including antidiabetic therapy, were continued through the study. Compared with safflower oil treatment, fish oil supplementation resulted in a significant reduction of total plasma triglycerides of 24% at the 4-g doseand a larger reduction of 39% at the 7.5-g dose. These decreases were due to similar reductions in VLDL triglycerides. LDL cholesterol levels were mildly elevated, but a larger 20% increase in LDL apolipoprotein B (apoB) concentration was observed. During supplementation with the fish oil concentrate, the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values, but not when compared with safflower oil treatment. Highdensity lipoprotein (HDL) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment. At the 7.5-g dose, fasting glucose and glycohemoglobin levels increased by 20 and 12%, respectively, but were unchanged at the lower level of supplementation. Thus, in NIDDM patients, dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels. However, the observed increase in LDL apoB levels, and the deterioration in glycemic control, indicate thatfurther study will be required to establish whether fish oil has a role in the treatment of NIDDM.

Effect of dietary supplementation with n-3 fatty acids on clinical manifestations of psoriasis

Abstract: In a double-blind, block randomized study we investigated the effect of dietary supplementation with eicosapentaenoic acid in patients with psoriasis. The experimental group received 10 g of fish oil daily containing approximately 1.8 g eicosapentaenoic acid, while the controls were given an isoenergetic amount of olive oil. We found no significant change in the clinical manifestations of psoriasis in either group after 8 weeks of treatment. In the experimental group, the amount of n-3 fatty acids in serum phospholipids was significantly increased at the end of trial as compared to pre-treatment values, whereas the level of n-6 fatty acids was decreased.

Effect of dietary cholesterol and/or omega 3 fatty acids on lipid composition and delta 5-desaturase activity of rat liver microsomes.

Abstract: Male weanling rats were fed for 28 d a purified diet containing 20% (wt/wt) fat providing high levels of either saturated fat or alpha-linolenic acid or eicosapentaenoic and docosahexaenoic acids with or without 2% (wt/wt) cholesterol supplementation. Effect of diet on rate of desaturation of eicosatrienoic acid (20:3 omega 6) and lipid composition of liver microsomal membranes was examined. The desaturation of 20:3 omega 6 to arachidonic acid (20:4 omega 6) was higher in rats fed linseed oil and lower in rats fed fish oil than in control animals fed the beef tallow diet. The desaturation of 20:3 omega 6 was lower in rats fed beef tallow or linseed oil diets supplemented with cholesterol than in the respective unsupplemented diet. Inclusion of 2% (wt/wt) cholesterol in the fish oil diet failed to affect synthesis of 20:4 omega 6 from 20:3 omega 6. These in vitro changes in delta 5-desaturase activity are consistent with the diet-induced alterations observed in the fatty acid composition of microsomal membranes. Both free cholesterol and cholesterol ester in the microsomal membrane were higher in rats fed beef tallow or linseed oil diets supplemented with exogenous cholesterol than in the respective unsupplemented diet, and only free cholesterol was higher in rats fed the fish oil diet supplemented with cholesterol. Feeding fish oil appears to prevent both the inhibition of 20:4 omega 6 biosynthesis and the accumulation of cholesterol ester that were apparent when 2% cholesterol was added to either beef tallow or linseed oil diets.

Enhanced survival to endotoxin in guinea pigs fed IV fish oil emulsion

Abstract: Improved survival to endotoxin has been demonstrated in rats pretreated with cyclooxygenase inhibitors or made essential fatty acid deficient, implying that excessive ω6 fatty acids, possibly through their eicosanoid products, contribute to mortality. Following endotoxin administration, we also have shown improvement in survival with oral diets supplemented with fish oil. This study sought to explore whether parenteral fish oil ameliorates the adverse impact of endotoxin.

Effects of a Low Saturated Fat, Low Cholesterol Fish Oil Supplement in Hypertriglyceridemic Patients: A Placebo-Controlled Trial

Abstract: Study objective To determine the effects of fish oil supplements low in saturated fat and cholesterol on plasma lipid and lipoprotein levels in hypertriglyceridemic patients. Design Single-blind, placebo-controlled (safflower oil), crossover trial with 6-week treatment periods. Setting Outpatient lipid clinic in a university medical center. Patients Eleven adult patients had isolated hypertriglyceridemia (type IV) and seven had concomitant hypercholesterolemia (Type IIb). Intervention Twelve 1-g capsules of either fish oil or placebo (safflower oil) were taken daily during each treatment period. Measurements and main results Blood was drawn at the fifth and sixth week of each period and analyzed for total lipids; cholesterol in very low, low (LDL), and high density (HDL) lipoproteins (mmol/L); and apoprotein B (mg/dL). Compared with the placebo, fish oil lowered plasma triglyceride levels (4.0 +/- 1.8 to 2.5 +/- 1.0), and raised LDL cholesterol levels (3.7 +/- 1.75 to 4.25 +/- 0.85), apolipoprotein B levels (122 +/- 29 to 140 +/- 34), and the ratio of LDL cholesterol to HDL cholesterol (4.0 +/- 0.9 to 4.7 +/- 1.4) (P less than 0.05; mean +/- SD). No significant changes were seen in levels of HDL or HDL cholesterol subfractions. Similar responses were seen in patients with both type IIb and IV lipoprotein phenotypes. Conclusions Because the fish oil supplement contributed negligible amounts of cholesterol and saturated fat to the diet, the n-3 fatty acids most likely caused the observed effects. These findings indicate that relatively small amounts of fish oil can have beneficial effects on plasma triglyceride levels in hypertriglyceridemic patients, but the increase in LDL cholesterol and apoprotein B levels, and in the LDL cholesterol to HDL cholesterol ratio suggests the need for careful monitoring of plasma lipoprotein changes during fish oil supplementation, and for a careful evaluation of their long-term benefits.

Suppression of monosodium urate crystal-induced acute inflammation by diets enriched with gamma-linolenic acid and eicosapentaenoic acid

Abstract: A subcutaneous air pouch formed in Sprague-Dawley rats was used to study the effect of diets enriched in gamma-linolenic acid (GLA) (in plant seed oil) and eicosapentaenoic acid (EPA) (in fish oil) on acute inflammation induced by monosodium urate crystals. The GLA-enriched diet suppressed significantly the cellular phase of inflammation (polymorphonuclear leukocyte accumulation, crystal phagocytosis, and lysosomal enzyme activity), but it had little effect on the fluid phase (exudate volume and protein concentration). In contrast, the EPA-enriched diet suppressed the fluid phase but not the cellular phase of inflammation. The findings indicate that the fluid and cellular phases of acute inflammation can be controlled independently. A combined diet of fish oil and plant seed oil (EPA-enriched and GLA-enriched) reduced both the cellular and fluid phases of inflammation. Thus, dietary provision of alternative substrates for oxidative metabolism (other than arachidonic acid) modifies monosodium urate crystal-induced acute inflammation.

Eicosanoid synthesis in 7,12-dimethylbenz(a) anthracene-induced mammary carcinomas in Sprague-Dawley rats fed primrose oil, menhaden oil or corn oil diet

Abstract: The comparative effects of high-fat diets (20%, w/w) on eicosanoid synthesis during mammary tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats were studied using diets containing 20% primrose oil (PO), 20% menhaden oil (MO) or 20% corn oil (CO). Sprague-Dawley rats fed the PO or MO diet had 21% or 24% fewer adenocarcinomas, respectively, than rats fed the CO diet. Histologically (i.e., mitotic figures, inflammatory cell infiltration and necrosis), the CO-fed rats exhibited the highest frequency of changes within tumors. Plasma fatty acid composition was significantly altered by diet, reflecting the composition of the oils which were being fed. Only the plasma of PO-fed rats contained detectable levels of gamma-linolenic acid (GLA). Arachidonic acid (AA) levels were significantly higher (p<0.05) in PO-fed than in CO- or MO-fed rats. MO-fed rats had significantly higher levels of plasma palmitic acid, while palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were detected only in MO-fed rats. As expected, linoleic acid (LA) and AA levels were lower (p<0.05) in the MO-fed rats than in PO- or CO-fed groups. The plasma of the CO-fed rats contained significantly higher levels of oleic acid. Eicosanoid synthesis in mammary carcinomas of rats fed the 20%-fat diets was 2–10 times higher than in mammary fat pads of control rats. The synthesis of PGE1 and LTB4 was significantly (p<0.05) higher in PO-fed rats than in CO-fed or MO-fed rats, although PGE values were significantly (p<0.05) higher in CO-fed rats than in Mo or PO groups. The synthesis of eicosanoids in both mammary fat pads and mammary carcinomas of MO-fed rats was lower (p<0.05) than in tissues of rats fed either CO or PO diets due to less AA precursor being fed and/or to competition between n−6 and n−3 fatty acids for cyclooxygenase and lipoxygenase. The ratios of monoenoic to dienoic eicosanoids in both mammary fat pads and mammary carcinomas were higher in the PO group than in the MO or CO groups. These results suggest that inclusion of GLA (PO feeding) or EPA and DHA (MO feeding) in the diet may decrease malignancy by altering eicosanoid profiles.

Malondialdehyde excretion by subjects consuming cod liver oil vs a concentrate of n-3 fatty acids.

Abstract: Urinary malondialdehyde (MDA), an indicator of lipid peroxidation in the diat and in the tissues, was determined in human adults consuming a supplement of n-3 fatty acids derived from a pharmaceutical grade of cod liver oil (CLO) without added antioxidants vs a concentrate of n-3 acids containing dodecyl gallate and vitamin E. MDA excretion increased immediately in the subjects consuming CLO but remained unchanged in those ingesting the concentrate for 50 days. The increase in the subjects taking CLO was attributable to MDA in the oil. The results indicate that consuming unstabilized fish oils as a source of n-3 fatty acids may entail exposure to potentially toxic products of lipid peroxidation.

Clinical applications of fish oils.

Abstract: Fish oil supplements are currently being nationally advertised, and many physicians are being queried about their clinical utility. Epidemiologic studies reveal a low incidence of cardiovascular disease in people, such as the Eskimos, who eat large amounts of seafood. Cardiovascular health may be improved because fish and fish oil supplements lower plasma lipid levels (especially triglycerides), inhibit platelet aggregation, and may decrease blood pressure and viscosity and increase high-density lipoprotein (HDL) levels. Preliminary observations also suggest a potential future role for fish oils in the treatment of some autoimmune diseases, such as atopic dermatitis, psoriasis, and rheumatoid arthritis. Patients with serum triglyceride levels greater than 5.64 mmol/L and/or cholesterol levels greater than 7.75 mmol/L refractory to dietary management may benefit from a medically supervised trial of fish oil supplements. Data currently available are insufficient to recommend fish oil supplements for the general public, or for patients with other diseases, and side effects must also be considered. These include occasional adverse lipid changes, potential for bleeding and vitamin E deficiency, and, with some preparations, vitamin A and D toxicity. ( JAMA 1988;260:665-670)

Inhibition of apolipoprotein secretion and phosphatidate phosphohydrolase activity by eicosapentaenoic and docosahexaenoic acids in the perfused rat liver

Abstract: Infusion of albumin-bound eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA), or oleic acid (OA) in perfused rat livers was carried out for two hours at a rate that maintained the perfusate concentration at 1 mmol/L. When compared with fatty acid-poor albumin alone, triacylglycerol (TAG) output was not significantly increased with DHA or EPA, whereas OA infusion resulted in a twofold increase. Incorporation of labeled leucine into VLDL apo B-100, apo B-48, apo E, and apo Cs was decreased by 50% by DHA or EPA compared with OA. The total phosphatidate phosphohydrolase activity was decreased by 35% with DHA or EPA compared to oleic acid or albumin alone. In no case was there a significant change in the distribution of activity between the microsomal and cytosolic factions. Fatty acid infusion did not significantly change the liver TAG content. Total liver lipids, microsomal lipids, and lipids of secreted VLDL were enriched with the infused fatty acids. The degree of enrichment for secreted TAG averaged 24% for OA and 36% for DHA or EPA. The effects of DHA and EPA on PPH activity and on apo B secretion in feeding experiments with marine oils rich in these acids may relate to changes in the fatty acid composition of liver membranes.