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Blood pressure and serum lipids from SHR after diets supplemented with evening primrose, sunflowerseed or fish oil.

Spontaneously hypertensive rats (SHR) at 4 weeks of age were fed a diet supplemented with sunflowerseed oil (SO), evening primrose oil (EPO), fish oil (FO) or EPO + FO for 22 weeks. A diet with commercially available pellets served as control. Systolic blood pressure was significantly lower during and after FO, EPO and EPO + FO, whereas the lower level after SO was not significant when compared with the controls. Serum triglycerides and total cholesterol were lowest after EPO followed FO. The combination of both EPO and FO resulted in unexpected high values of triglycerides and cholesterol. HDL-cholesterol was likewise highest after EPO + FO. The results indicate a quantitatively different depression of blood pressure and serum lipids from SHR by individual polyunsaturated fatty acids (PUFA).

Animals↗

Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia.

Dietary fish oils, which are rich in omega-3 fatty acids, have been reported to reduce plasma lipid levels in normolipidemic subjects. We examined the effects of fish oil in 20 hypertriglyceridemic patients: 10 with Type IIb hyperlipidemia and 10 with Type V. These patients were put on three diets differing primarily in fatty acid composition and fat content. The control diet contained a fatty acid mixture typical of a low-fat therapeutic diet (ratio of polyunsaturated to saturated fat, 1.4), the fish-oil diet contained omega-3 fatty acids, and the vegetable-oil diet was rich in the omega-6 fatty acid, linoleic acid. Each diet was followed for four weeks. In the Type IIb group, the fish-oil diet led to decreases in both plasma cholesterol (-27 per cent) and triglyceride (-64 per cent), as compared with the control diet. Very-low-density lipoproteins (VLDLs) were also reduced markedly. The vegetable-oil diet had much less effect. With fish oil, the Type V group had marked decreases in total cholesterol and triglyceride levels (-45 and -79 per cent, respectively). VLDL levels were dramatically lowered, as were apoprotein E levels. The vegetable-oil diet (unlike the fish-oil diet) produced a rapid and significant rise in plasma triglyceride levels. We conclude that fish oils and fish may be useful components of diets for the treatment of hypertriglyceridemia.

Adult↗

N-6 and N-3 PUFA in liver lipids, thromboxane formation and blood pressure from SHR during diets supplemented with evening primrose, sunflowerseed or fish oil.

Spontaneously hypertensive rats (SHR) after weaning (at 4 weeks of age) were fed diets supplemented with either sunflowerseed oil (SO), evening primrose oil (EPO), fish oil (FO) or EPO + FO (50%: 50%, v/v) for 22 weeks. A diet with commercially available pellets served as control. Systolic blood pressure was significantly lower in the dietary groups receiving FO, EPO and FO + EPO, the former being most effective. In liver triglycerides (TG) EPO resulted in a markedly increased percentage of linoleic acid (LA; C 18:2, n-6), alpha-linolenic acid (alpha-LNA; C 18:3, n-6) and especially of arachidonic acid (AA; C 20:4, n-6), whereas the long-chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA; C 20:5, n-3) and docosahexaenoic acid (DHA; C 22:6 n-3), were depressed to undetectable and significantly lower levels, respectively. In liver phosphatidylcholine (PC) and phosphatidylethanolamine (PE) only slight changes of LA and AA were observed. Feeding of FO led to a significant rise of EPA and DHA in liver TG, PC and PE at the expense of n-6 PUFA (except LA in PC and PE). With a combination of both EPO and FO a significant increase of EPA and DHA, but on lower levels as compared to FO alone, was associated with a significant rise of LA, but with a slight decline of AA as compared to the control animals. Nevertheless, the levels of AA in the group fed EPO + FO were still higher than in the FO-group. In the SO-group the increase of LA was even higher when compared with the EPO-group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vitamin E regulates changes in tissue antioxidants induced by fish oil and acute exercise.

PURPOSE: Prooxidant effects of fish oil supplementation could unfavorably affect the cardiovascular benefits of fish oil. We tested the effects of 8 wk vitamin E cosupplementation with fish oil on antioxidant defenses at rest and in response to exhaustive exercise in rats. METHODS: Rats (N = 80) were divided into fish oil, fish oil and vitamin E (FOVE), soy oil, and soy oil and vitamin E (SOVE) supplemented groups. For the vitamin E supplemented rats, corresponding groups (FOVE-Ex and SOVE-Ex) performed an acute bout of exhaustive exercise after the supplementation period. RESULTS: Fish oil supplementation increased the activity of catalase, glutathione peroxidase, and glutathione-S-transferase in the liver and red gastrocnemius (RG) muscle. Fish oil decreased liver total glutathione (TGSH) levels. Vitamin E supplementation decreased antioxidant enzyme activities to levels at or near those in SOVE in a tissue specific pattern. Vitamin E increased TGSH in liver, heart, and RG. Regression analysis showed TGSH to be a negative determinant of protein oxidative damage as measured by protein carbonyl levels in both liver and RG. Catalase activity was associated with liver lipid peroxidation as measured by thiobarbituric acid-reacting substances. The exercise-induced decrease in hepatic TGSH tended to be less in FOVE versus SOVE. Exhaustive exercise also modulated tissue antioxidant enzymes. CONCLUSIONS: Vitamin E supplementation markedly decreased fish oil induced antioxidant enzyme activities in all tissues. Sparing of glutathione may be an important mechanism by which vitamin E decreased tissue protein oxidative damage.

Animals↗

Reduction of hyperlipidemia in hepatoma-bearing rats by dietary fish oil.

The effect of dietary fish oil on serum lipid levels was studied by comparing it with dietary corn oil in Donryu rats subcutaneously implanted with an ascites hepatoma cell line (AH109A). The hepatoma-bearing rats exhibited hyperlipidemia characterized by a rise in both serum cholesterol and triglyceride levels. Increased cholesterogenesis in the host liver and decreased steroid excretion into feces are suggested to be responsible for the hepatoma-induced hypercholesterolemia, and increased fatty acid mobilization from peripheral adipose tissues and decreased triglyceride clearance from the blood circulation are considered causes for the hepatoma-induced hypertriglyceridemia. Dietary fish oil reduced the hyperlipidemia in these animals, suppressed the hepatoma-induced increase in hepatic cholesterogenesis and fatty acid mobilization from adipose tissue. Dietary fish oil also tended to increase fatty acid oxidation in the liver. Such diverse effects of fish oil may lead to the reduction of the hepatoma-induced hyperlipidemia. These results suggest that studies on dietary fish oil may be warranted in patients with cancer-related hyperlipidemia.

Animals↗

Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes.

We have shown that a combination of fish oil (high in n-3 fatty acids) with the butyrate-producing fiber pectin, upregulates apoptosis in colon cells exposed to the carcinogen azoxymethane, protecting against colon tumor development. We now hypothesize that n-3 fatty acids prime the colonocytes such that butyrate can initiate apoptosis. To test this, 30 Sprague-Dawley rats were provided with diets differing in the fatty acid composition (corn oil, fish oil or a purified fatty acid ethyl ester diet). Intact colon crypts were exposed ex vivo to butyrate, and analyzed for reactive oxygen species (ROS), mitochondrial membrane potential (MMP), translocation of cytochrome C to the cytosol, and caspase-3 activity (early events in apoptosis). The fatty acid composition of the three major mitochondrial phospholipids was also determined, and an unsaturation index calculated. The unsaturation index in cardiolipin was correlated with ROS levels (R = 0.99; P = 0.02). When colon crypts from fish oil and FAEE-fed rats were exposed to butyrate, MMP decreased (P = 0.041); and translocation of cytochrome C to the cytosol (P = 0.037) and caspase-3 activation increased (P = 0.032). The data suggest that fish oil may prime the colonocytes for butyrate-induced apoptosis by enhancing the unsaturation of mitochondrial phospholipids, especially cardiolipin, resulting in an increase in ROS and initiating apoptotic cascade.

Animals↗

Altered acyl chain compositions of alkylacyl, alkenylacyl, and diacyl subclasses of choline and ethanolamine glycerophospholipids in rat heart by dietary fish oil.

The effects of dietary fish oil containing n - 3 polyunsaturated fatty acids on the fatty acid compositions of the alkylacyl and alkenylacyl species of choline glycerophospholipids (CGP) and ethanolamine glycerophospholipids (EGP) were studied in rat heart and compared with the corresponding diacylglycerophospholipids. After a 7 week feeding period, all phospholipid classes from the fish oil group exhibited much higher levels of the n - 3 polyunsaturated fatty acids including eicosapentaenoic acid (20:5(n - 30)), docosapentaenoic acid (22:5(n - 3)) and docosahexaenoic acid (22:6(n - 3)), as well as lower levels of the n - 6 series (18:2, 20:4, 22:4 and 22:5), relative to animals given sunflower seed oil-enriched in 18:2(n - 6). However, the docosahexaenoic acid rather than eicosapentaenoic acid provided a much greater contribution to the n - 3 accumulation (fish oil group) in the ether-containing CGP, as indicated by the 20:5(n - 3)/22:6(n - 3) molar ratios of 0.32, 0.26 and 0.56 in the alkylacyl, alkenylacyl and diacyl classes, respectively. In addition to accumulating very high levels of docosahexaenoic acid (e.g., 47.2 mol% of fatty acids in alkenylacylglycerophosphoethanolamine of fish oil group), both ether-linked classes of EGP exhibited significantly higher levels of docosapentaenoic acid than the diacylglycerophosphoethanolamine (GPE) and all classes of CGP. These findings may bear relevance to possible beneficial effects of dietary fish oil on pathophysiological states (including myocardial ischemia) in cardiac tissue and their mediation via platelet-activating factor, 1-alkyl-2-acetylglycerophosphocholine (PAF) and arachidonic acid (20:4(n - 6))-derived eicosanoids.

Animals↗

A biomarker of n-3 compliance in patients taking fish oil for rheumatoid arthritis.

Dietary fish oil supplements have been shown to have benefits in rheumatoid arthritis (RA), other inflammatory diseases, and in cardiovascular disease. As with any medical advice, variability will exist with regard to adherence and consequent biochemical or pharmacophysiologic effects. The aim was to explore the utility of plasma phospholipid EPA as a measure of n-3 PUFA intake and response to standardized therapeutic advice given in an outpatient or office practice setting, to increase dietary n-3 PUFA, including a fish oil supplement. Patients with early RA were given verbal and written advice to alter their dietary n-3 PUFA intake, including ingestion of 20 mL of bottled fish oil on juice daily. The advice included instructions to increase n-3 PUFA and to avoid foods rich in n-6 PUFA. Every 3 mon, blood samples were obtained for analysis of plasma phospholipid FA. Plasma phospholipid EPA was used as the primary index of n-3 PUFA intake. A diverse response was seen, with about one-third of patients achieving a substantial elevation of plasma phospholipid EPA over the 12-mon study period. A third had little change, with the remainder achieving intermediate levels. Data obtained longitudinally from individual patients indicated that substantial elevations of EPA (> 5% total plasma phospholipid FA) could be maintained for more than 3 yr. Plasma phospholipid EPA is a convenient measure of adherence to advice to take a dietary n-3 PUFA-rich fish oil supplement This measure may prove a useful adjunct to intention to treat analyses in determining the effect of dietary fish oil supplements on long-term outcomes in arthritis and other chronic inflammatory diseases. It may also provide a guide to the effectiveness of therapeutic and preventive messages designed to increase n-3 PUFA intake.

Arachidonic Acid↗

Molecular species of ethanolamine plasmalogens and transacylase activity in rat tissues are altered by fish oil diets.

Effects of dietary fish oil ethyl esters and alkyldiacetylglycerols (an ether-linked lipid) on the distribution of subclasses of choline- and ethanolamine-glycerophospholipids as well as effects on highly unsaturated molecular species of ethanolamine plasmalogens from brain, spleen, kidney, lung, and testis of rats were examined. Supplementation of ethyl ester concentrates of n-3 fatty acids had no effect on the distribution of subclasses in any of the tissues. However, the supplements of 1-O-octadec-9'-enyl-2,3-diacetyl-sn-glycerol (diacetates of selachyl alcohol) caused significant increases in the alkylacylglycerophosphocholine and alkylacylglycerophosphoethanolamine subclasses from spleen and lung and in the alkylacylglycerophosphoethanolamine subclass from kidney. Dietary supplements of fish oil ethyl esters reduced the arachidonate-containing species of ethanolamine plasmalogens whereas molecular species having 20:5(n-3), 22:6(n-3), and/or 22:5(n-3) acyl groups were increased in the spleen, lung, and kidneys, but not brain. In testicular tissue from rats fed the fish oil diets, the molecular species of ethanolamine plasmalogens containing 22:5(n-6) acyl groups were reduced. An increase of ethanolamine plasmalogens with 18:1 alk-1-enyl moieties paired with highly unsaturated sn-2 acyl groups were found in the tissues of rats fed the fish oil plus selachyl alcohol diacetate supplements. Rats on the diet containing fish oil ethyl esters had significantly lower [3H]alkyllysoglycerophosphocholine CoA-independent transacylase activity in spleen microsomes than controls. This suggests that supplements of n-3 fatty acids interferes with the transacylation of arachidonate, an event that could seriously impair the release of arachidonate and lysophospholipids (e.g., lyso-PAF) that are precursors of potent bioactive lipid derivatives.

Acyltransferases↗

Dietary fish oils modify adipocyte structure and function.

Dietary fish oils, enriched with omega-3 fatty acids (e.g., MaxEPA fish oil), inhibit lipogenesis and have a marked hypotriglyceridemic effect in man and experimental animals. Dietary omega-3 fatty acids also reduce adipose tissue trophic growth in rats. To understand the metabolic basis for this, we measured the effect of fish oil feeding upon rat plasma triglyceride concentration, fat pad mass, fat cell size, fat cell lipolysis, as well as lipoprotein binding to adipocyte plasma membranes. In adolescent (250 g) male Wistar rats fed 20% (w/w) fish oil supplemented diets for 3 weeks, plasma triglyceride levels and epididymal and perirenal fat pad mass were significantly (P less than 0.005) reduced compared to pair-fed controls given 20% lard diets. These differences in fat pad mass between the diets were greater than differences in whole animal mass or in the mass of livers, testes, kidneys, spleens, or hearts. Isoproterenol-stimulated lipolysis was significantly (P less than 0.005) higher in fish oil fed rats than in pair-fed controls. In young (100 g) rats plasma triglyceride levels were 10 times lower in the fish oil fed group after 5 weeks as compared to the lard-fed controls. This was accompanied by a reduction in epididymal and perirenal fat pad mass as well as a 2-3-fold decrease in adipocyte volumes; there was no significant difference between the two groups in fat cell number in each region. Plasma membranes of epididymal adipocytes from fish oil fed rats bound significantly (P less than 0.001) less HDL1 than the lard-fed rats, possibly as a result of a reduction in fat cell size and/or alteration of plasma membrane structure. Thus in both young and old rats, the reduction in plasma triglyceride concentration in conjunction with increased hormone-stimulated lipolysis may explain in part the selective reduction in adipose tissue trophic growth accompanying fish oil consumption.

Adipose Tissue↗

Dietary fish oil and rheumatic diseases.

Dietary fish oil supplementation can induce several metabolic changes relevant to rheumatic diseases. Both experimental and clinical evidence show that dietary fish oil supplementation modulates inflammatory and immune responses. Many studies have shown beneficial, albeit modest, effects in the treatment of rheumatoid arthritis. Studies in murine models of systemic lupus erythematosus have been encouraging, but few studies have been performed to assess the effects of dietary fish oil in the human disease or in other systemic rheumatic diseases. Further study on the efficacy of dietary fish oil supplementation in the treatment of specific rheumatic diseases is warranted.

Arthritis, Rheumatoid↗

Plasma and tissue lipids of piglets fed formula containing saturated fatty acids from medium-chain triglycerides with or without fish oil.

Addition of fish oil (FO) with carbon chain 20 and 22 (long-chain polyunsaturated fatty acids; LCPs) n-3 fatty acids to formula has been considered as a method to provide 22:6n-3 to preterm infants. These studies determined the effects of including 0.73% n-3 LCPs from FO in formula containing saturated fatty acids as medium-chain triglyceride (MCT) oil on plasma and organ triglyceride (TG), phospholipid (PL), and cholesterol ester (CE) contents and compositions in piglets. Reference piglets were fed their own mother's milk. Piglets fed the formula with FO had significantly lower liver and kidney, but not plasma, TG concentrations; lower liver PL 20:4n-6; and higher plasma, liver, and kidney TG, PL, and CEn-3 LCPs than piglets fed the formula without FO. The increase in liver and kidney lipid n-3 LCPs and the decrease in kidney lipid content shows that inclusion of FO in formula with a high content of MCTs and 18:2n-6 does not promote tissue lipid metabolism similar to natural milk feeding. Piglets fed formula with FO had similar brain 20:4n-6 and 20:5n-3 but higher 22:6n-3 than did piglets fed sow milk. Diet-related differences in plasma and red blood cell PL were not reliable predictors of differences in brain LCP.

Animals↗

Effects of dietary fish oil on renal insufficiency in rats with subtotal nephrectomy.

We studied the effects of fish oil on the progression of renal insufficiency in rats with subtotal nephrectomy. Five weeks after a 1-2/3 nephrectomy, sixteen rats were fed two different diets which differed only in fat composition. Lipid in the control diet was primarily beef tallow; that of the experimental diet, menhaden oil. Fish oil-fed rats had significant increases in plasma creatinines, decreases in urinary PGE2 and accelerated death rates. An additional twelve rats underwent 1-1/3 nephrectomies, and the same dietary manipulations, followed by renal clearance, histologic and biochemical studies after 12 weeks on the diets. Fish oil-fed rats again did worse, with decreased glomerular filtration rates and filtration fractions, more proteinuria and more glomerular sclerosis. Glomeruli and slices of cortex, medulla and papillae from rats fed fish oil produced much less PGE2 and TXB2 than dietary controls. Fish oil-induced suppression of renal PGE2 may be deleterious in this model and may outweigh the beneficial effect derived from TXA2 suppression. In contrast to fish oil's potentially therapeutic role in cardiovascular and immune-mediated renal disease, this diet is detrimental in rat renoprival nephropathy. This illustrates the importance of examining the effects of fatty acid manipulation individually for each disease entity.

Animals↗

Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages.

The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein (LDL) oxidation was examined in 20 treated hypertensive subjects. The randomized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil. Fish oil significantly (-24%, P < 0.01) reduced plasma triglyceride, and increased LDL-cholesterol (+6%, P < 0.01 compared to corn oil). LDL particles were larger (P < 0.01) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride (P < 0.001) both before and after fish oil supplementation, and positively correlated with high density lipoprotein cholesterol (P < 0.01). Fish oil reduced lag time before onset of copper-induced LDL oxidation (-25%, P < 0.001) and significantly increased production of thiobarbituric acid-reactive substances (TBARS) during oxidation, compared with corn oil. Corn oil had no significant effect on lag time and oxidation rate. Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL. Corn oil was without effect. Additionally, macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly (P < 0.001) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids. We conclude that from the standpoint of atherosclerosis, fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable.

Aged↗

Fish oil stabilisation by microencapsulation with modified cellulose.

Fish oil is the richest dietary source of long-chain omega-3 polyunsaturated fatty acids (PUFA). Stabilisation of omega-3 PUFA against oxidation is an important task in food processing. The ability of modified celluloses to act as microencapsulating agents for fish oil was investigated. Fish oil microcapsules were produced by spray-drying of homogenised emulsions containing modified celluloses and maltodextrin as coating materials. The quality of microcapsules was evaluated by scanning electron microscopy, determination of encapsulation efficiency, peroxide value during storage and solubility in water. Methylocellulose (MC) and hydroxypropyl methylocellulose (HPMC) showed good emulsifying properties. Homogenisation of emulsions resulted in creation of high amount of stable foam. More damage occurred in the powders coated with HPMC. The oil retention level was very high, 98.5% (i.e. up to 400.0 g/kg ready powder). Samples with fish oil content of approximately 500.0 g/kg exhibited more structural damage impairing the stabilisation effect. This study indicates that the use of modified cellulose, especially MC, as a coating material for the preparation of spray-dried fish oil microcapsules improves the stability and the concentration of fish oil in the powder.

Cellulose↗

Health benefits and potential risks related to consumption of fish or fish oil.

The nutritional benefits of fish consumption relate to the utilization of proteins of high biological value, as well as certain minerals and vitamins that fish provide. Fish or fish oil contains omega-3 polyunsaturated fatty acids (PUFAs) that appear to play several useful roles for human health. Conversely, some carcinogenic contaminants are also stored in the adipose tissue of fish. The objective of this paper is to evaluate the potential health benefits and risks related to the consumption of fish or fish oil. Health benefits related to the consumption of fish or omega-3 PUFAs were obtained by an extensive literature search. Potential health risks related to carcinogenic contaminants (e.g., dioxin, PCB, etc.) in fish were estimated using the U.S. EPA-approved cancer risk assessment guidelines. Potential health risk estimates were evaluated by comparing them with the acceptable excess risk level of 10(-6)-10(-4). Scientific data indicate that the consumption of fish or fish oil containing omega-3 PUFAs reduces the risk of coronary heart disease, decreases mild hypertension, and prevents certain cardiac arrhythmias and sudden death. Risk estimates in humans for carcinogenic environmental contaminants in fish ranged from an excess risk level of 3x10(-6)-9x10(-4). These risk estimates appeared to meet the acceptable excess risk level criteria. Therefore, consumption of fish in accordance with the State of Michigan Fish Advisory Guidelines is safe and should be encouraged. The top 11 fish species [e.g., sardines, mackerel, herring (Atlantic and Pacific), lake trout, salmon (Chinook, Atlantic, and Sockeye), anchovy (European), sablefish, and bluefish] provide an adequate amount of omega-3 PUFAs (2.7-7.5g/meal) and appear to meet the nutritional recommendation of the American Heart Association.

American Heart Association↗