An enteral formula containing fish oil, indigestible oligosaccharides, gum arabic and antioxidants affects plasma and colonic phospholipid fatty acid and prostaglandin profiles in pigs

Evidence supports a pathogenic role of arachidonic acid-derived inflammatory mediators within the gastrointestinal tract of patients with inflammatory bowel disease. The purpose of this study was to assess the effects of an ulcerative colitis nutritional formula (UCNF) containing oligosaccharides, fish oil, gum arabic and antioxidants on plasma and colonic phospholipid fatty acid and prostaglandin profiles in pigs. Twenty-four growing barrows in two replications were equally randomized among four killing times (d 0, 7, 14 and 21), and one of two diets, a control and the UCNF. Diets contained comparable levels of protein, fat, and nonstructural carbohydrate and met 100% of the energy requirements of the pig. Intake and body weight were recorded daily while blood, urine and tissue samples were collected at time of kill. Within 1 wk of ingestion of the UCNF, the composition of plasma phospholipid fatty acids showed an increase in 20:5(n-3) and 22:6(n-3) (P < 0.0001) and a decrease in 20:4(n-6) and 18:2(n-6) (P < 0.0001). Similar effects were observed for the phospholipids in the colonic and cecal mucosa. Plasma prostaglandin E was unaffected by treatment, whereas thromboxane B2 and 6-keto-prostaglandin F1 alpha levels were significantly decreased after 7 d of UCNF ingestion. Ingestion of the UCNF resulted in a suppression in the synthesis of proinflammatory prostaglandins by cecal and colonic mucosal cells. Levels of colonic and cecal prostaglandin E, 6-keto-prostaglandin F1 alpha and thromboxane B2 were significantly decreased after 7 d of UCNF ingestion. These changes may have been mediated by rapid increases of (n-3) fatty acids into cellular phospholipids. Dietary supplementation with the UCNF may prove beneficial for patients with ulcerative colitis by modulating colonic prostaglandin synthesis.     

Serum phospholipid fatty acid composition and habitual intake of marine foods registered by a semi-quantitative food frequency questionnaire

OBJECTIVE: To examine the relation between consumption of fish and fish products registered by a comprehensive food frequency questionnaire and the composition of fatty acids in serum phospholipids. DESIGN: Cross-section study. SETTING: Cardiovascular screening centre in Trondheim, Mid-Norway. SUBJECTS: Of 256 eligible women 242 agreed to participate in the present study. Altogether 234 middle-aged women (91.4%) completed the questionnaire and gave a valid blood sample. RESULTS: Total frequency consumption of fish for dinner showed only weak association with serum phospholipid fatty acid composition. In separate analyses of lean and fatty fish, consumption of fatty fish was negatively associated with n-6 and positively associated with n-3 fatty acids in serum phospholipids, while no significant associations were found for lean fish consumption. Cod liver oil consumption was strongly related to the phospholipid fatty acid composition. The associations improved moderately when adding portion size information. Spearman's correlation coefficient between dietary intake of eicosapentaenoic acid (EPA) and serum phospholipid EPA was 0.58, and Spearman's correlation coefficient between intake of docosahexaenoic acid (DHA) and serum phospholipid DHA was 0.53. CONCLUSIONS: This study suggests that in populations with a high consumption of fish and cod liver oil, habitual intake can be reflected in serum phospholipids. However, as the fat content of fish is highly variable, separate registration of lean and fatty fish consumption is needed.     

Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexaenoic acid-rich oil among healthy young men

The effects of n-3 fatty acid supplementation in the form of fresh fish, fish oil, and docosahexaenoic acid (DHA) oil on the fatty acid composition of plasma lipid fractions, and platelets and erythrocyte membranes of young healthy male students were examined. Altogether 59 subjects (aged 19-32 yr, body mass index 16.8-31.3 kg/m2) were randomized into the following diet groups: (i) control group; (ii) fish diet group eating fish meals five times per week [0.38 +/- 0.04 g elcosapentaenoic acid (EPA) and 0.67 +/- 0.09 g DHA per day]; (iii) DHA oil group taking algae-derived DHA oil capsules (1.68 g/d DHA in triglyceride form); and (iv) fish oil group (1.33 g EPA and 0.95 g DHA/d as free fatty acids) for 14 wk. The fatty acid composition of plasma lipids, platelets, and erythrocyte membranes was analyzed by gas chromatography. The subjects kept 4-d food records four times during the study to estimate the intake of nutrients. In the fish diet, in DHA oil, and in fish oil groups, the amounts of n-3 fatty acids increased and those of n-6 fatty acids decreased significantly in plasma lipid fractions and in platelets and erythrocyte membranes. A positive relationship was shown between the total n-3 polyunsaturated fatty acids (PUFA) and EPA and DHA intake and the increase in total n-3 PUFA and EPA and DHA in all lipid fractions analyzed. DHA was preferentially incorporated into phospholipid (PL) and triglyceride (TG) and there was very little uptake in cholesterol ester (CE), while EPA was preferentially incorporated into PL. and CE. The proportion of EPA in plasma lipids and platelets and erythrocyte membranes increased also by DHA supplementation, and the proportion of linoleic acid increased in platelets and erythrocyte membranes in the DHA oil group as well. These results suggest retroconversion of DHA to EPA and that DHA also interferes with linoleic acid metabolism.     

The effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group

OBJECTIVE: To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol. METHODS: The participants were 350 normotensive men and women aged 30-54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention. They were randomly assigned to receive placebo or 6 g purified fish oil once a day, which supplied 3 g n-3 polyunsaturated fatty acids for 6 months. RESULTS: Baseline blood pressure was (mean +/- SD) 123 +/- 9/81 +/- 5 mmHg. The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant. There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressures in the upper versus the lower quartile (132/87 versus 114/75 mmHg), low habitual fish consumption (0.4 versus 2.9 times a week) or low baseline plasma levels of n-3 fatty acids. Fish oil increased HDL2-cholesterol significantly compared with the placebo group. Subgroup analysis showed this effect to be significant in the women but not in the men. Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure. CONCLUSION: Moderate amounts of fish oil (6 g/day) are unlikely to lower blood pressure in normotensive persons, but may increase HDL2-cholesterol, particularly in women.     

Enrichment of hen eggs with n-3 long-chain fatty acids and evaluation of enriched eggs in humans

Eggs enriched with n-3 polyunsaturated fatty acids (PUFAs) were produced by hens fed diets containing fish oil or a combination of fish and vegetable oils. In a sensory evaluation, 78 untrained volunteers could not distinguish between ordinary and enriched eggs. Storage life was also not significantly different between egg types. A food intake survey of 4 groups of 14 subjects each who consumed 7 eggs/wk for 24 wk showed that intakes of the major dietary components were not significantly different for 4 different egg types. Mean (n = 56) plasma cholesterol and triacylglycerol concentrations were not significantly different at the start and finish of the study. Body weight and HDL concentrations increased during the study (P < 0.05). For the last 2 wk of the experiment (weeks 23-24), mean egg consumption was increased from a total of 14 to a total of 21 eggs, resulting in a small increase in plasma triacylglycerols only. There were no significant differences (P > 0.05) in body weight, blood pressure, or plasma lipid components among treatment groups consuming the 4 different egg types. Blood samples taken after 16 and 22 wk from fasted subjects showed significant increases in eicosapentaenoic acid, docosahexaenoic acid, and total n-3 PUFAs in subjects consuming enriched eggs compared with controls. In addition, the ratio of n-6 to n-3 PUFAs in plasma was significantly reduced from 12.2:1 to 6.5-7.7:1 in subjects consuming enriched eggs compared with controls. Consumption of only one enriched egg daily can contribute substantially to the recommended daily intake of n-3 PUFAs.     

Changes in plasma and colonic mucosa fatty acid profiles in rats with ulcerative colitis induced by trinitrobenzene sulfonic acid

Polyunsaturated fatty acids have a key role in the pathogenesis of inflammatory bowel disease since some of the arachidonic acid-derived eicosanoids have been found to be increased in inflamed intestinal mucosa in the acute phase of human disease. The aim of this study was to prospectively assess plasma and colon mucosa fatty acid patterns in rats with experimental ulcerative colitis. Twenty rats were treated with trinitrobenzene sulfonic acid and 20 with NaCl; two groups were killed after one week and two after two weeks to evaluate colon damage. Plasma was obtained by aortic puncture and colonic mucosa was scraped off and the fatty acid pattern was determined by gas-liquid chromatography. Total, saturated, and monounsaturated plasma fatty acids were significantly higher in both periods of ulcerative colitis as compared to controls. Plasma n-6 fatty acids were increased after treatment, but no significant changes were observed concerning to n-3 fatty acids. With regard to colon mucosa, saturated and monounsaturated fatty acids did not change because of the disease; however, n-6 fatty acids decreased in the first week and increased in the second week and n-3 fatty acids were increased. Changes on the fatty acid distribution in plasma did not parallel to those of colonic mucosa except for 22:6(n-3). We have also found that experimental ulcerative colitis induced by trinitrobenzene sulfonic acid reproduces many of the features related to changes in plasma and colon mucosa fatty acids observed in the human disease.     

Loss of substance of the lateral region of the face

The cardiovascular effects of a partially purified extract of fish oil, enriched in the n-3 series fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were studied in stroke-prone spontaneously hypertensive rats (SHR-SP) fed with high- and low-sodium diets during 5 weeks. Addition of salt to the low-salt control diet at a level commonly found in human food items (6% NaCl of the dry weight of the diet) produced a remarkable rise in blood pressure, an increase in left ventricular weight-to-body weight ratio (LVH-index) and an increase in kidney weight-to-body weight ratio (RH-index). Fish oil (20% of the dry weight of the diet) did not significantly influence the blood pressure or LVH-index or RH-index during the low-salt control diet. However, fish oil completely prevented the remarkable rise in blood pressure and clearly antagonized the rise of both LVH- and RH-indices, induced by the high-salt diet. The fish oil supplementation increased the levels of the polyunsaturated fatty acids of the n-3 series and decreased those of the n-6 series in plasma and kidney, irrespective of the salt content of the diet. Fish oil lowered serum thromboxane B2 concentration by approximately 75%. During the high-salt diet, fish oil markedly decreased water intake and urine volume, and increased urinary sodium concentration by about 60%. Our findings show that, in addition to an antihypertensive effect, fish oil also decreases LVH and RH. These effects appear to be due to an improved ability to excrete sodium and could be explained by the observed changes in the fatty acid composition and metabolism.     

Influence of dietary fats upon systolic blood pressure in the rat

Studies were performed to determine whether feeding diets with differing fatty acid content and composition had an influence on systolic blood pressure in the rat. Weanling male rats were fed standard laboratory chow (2.9% fat in total), or synthetic diets (10% fat in total) containing fish oil, butter, coconut oil or corn oil, for 5 weeks. Coconut oil and butter diets were rich in saturated fatty acids, whilst fish oil and corn oil were rich in the n-3 and n-6 unsaturated fatty acids respectively. Systolic blood pressure was measured using an indirect tail-cuff method at the end of the feeding period, and compared to a group of weanling rats. Feeding the different diets did not alter the growth of the rats, so all animals were of similar weights at the time of blood pressure determination. Control (chow fed) animals, at nine weeks of age, had higher systolic blood pressures than the weanling, baseline control group. Fish oil fed rats had similar pressures to the chow fed rats. Corn oil fed rats had significantly lower systolic pressures than the controls. The rats led the diets rich in saturated fatty acids (butter and coconut oil) had significantly higher blood pressures than all other groups. Systolic blood pressure was found to be significantly related to the dietary intakes of saturated and unsaturated fatty acids. The dietary intake of linoleic acid was significantly higher in corn oil fed rats than in other groups. Systolic blood pressure was inversely related to linoleic acid intake. Feeding a diet rich in saturated fatty acids significantly increases blood pressure in the rat. A high intake of n-6 fatty acids, and in particular linoleic acid, appears to have a hypotensive effect. Prenatal exposure of the rats to a maternal low protein diet, abolished the hypertensive effects of the coconut oil diet and the hypotensive effect of the corn oil diet upon young adult females. The intrauterine environment may, therefore, be an important determinant of the effects of these fatty acids on blood pressure in later life.     

Dietary fish oil (4 g daily) and cardiovascular risk markers in healthy men

Some epidemiological observations indicate that 1 to 2 weekly servings of fish prevent ischemic heart disease (IHD). This might be explained by an effect of the very-long-chain n-3 polyunsaturated fatty acids (n-3 VLCPUFA) of fish oil on lipid metabolism and/or the hemostatic system, both involved in IHD development. We studied the effect of incorporating natural fish oil (4 g daily equivalent to 0.91 g n-3 VLCPUFA and corresponding to one to two weekly servings of fatty fish) into the diet in a 4-week parallel, randomized, and double-blind trial of 47 healthy males aged 29 to 60 years. Sunflower oil was used as placebo. The fish oil had no significant effect on plasma lipids, apolipoproteins, lipoprotein(a), blood coagulation FVII, fibrinogen, endogenous fibrinolysis, beta-thromboglobulin, von Willebrand factor, glucose, or insulin in fasting blood samples. In nonfasting samples (n = 19), fish oil was associated with an approximately 30% decline in plasma triglycerides (P < .02) and a 9% decline in FVII protein (P < .05), whereas FVII coagulant activity and fibrinolysis were unaffected. In conclusion, our findings indicate that lowering of postprandial triglycerides is the only n-3 VLCPUFA effect that could contribute to primary prevention of IHD in healthy middle-aged men as assessed by currently measurable lipid and hemostatic risk markers.     

Dietary monounsaturated n-3 and n-6 long-chain polyunsaturated fatty acids affect cellular antioxidant defense system in rats with experimental ulcerative colitis induced by trinitrobenzene sulfonic acid

The intrarectal administration of trinitrobenzene sulfonic acid in rats induces ulcerative colitis, which results in histological alterations of colonic mucosa, severe modification of the cellular antioxidant defense system, and enhanced production of inflammatory eicosanoids. This study evaluated the influence of different dietary fatty acids, i.e., monounsaturated, n-3, and n-3 + n-6 polyunsaturated fatty acids, on the recovery of the colonic mucosa histological pattern, the cellular antioxidant defense system of colon, and PGE2 and LTB4 colonic mucosa contents in a model of ulcerative colitis induced by intrarectal administration of trinitrobenzene sulfonic acid. Administration of dietary n-3 polyunsaturated fatty acids led to a minimum stenosis score, a higher histological recovery, lower colon alkaline phosphatase and gamma-glutamyltranspeptidase activities, and lower mucosal levels of PGE2 and LTB4 compared with the other two experimental groups. However, glutathione transferase, glutathione reductase, glutathione peroxidase, and catalase activities were lower in the group treated with n-3 polyunsaturated fatty acids than in the groups fed with either the monounsaturated or the n-6 + n-3 polyunsaturated enriched diet. We conclude that n-3 polyunsaturated fatty acids can be administered to prevent inflammation in ulcerative colitis, but they cause a decrease in the colonic antioxidant defense system, promoting oxidative injury at the site of inflammation.     

Addition of triglycerides with arachidonic acid or docosahexaenoic acid to infant formula has tissue- and lipid class-specific effects on fatty acids and hepatic desaturase activities in formula-fed piglets

The effects of including triglycerides with arachidonic [20:4(n-6)] or docosahexaenoic acid [22:6(n-3)] in formula on plasma chylomicron, LDL and HDL, liver, heart, kidney and brain (n-6) and (n-3) fatty acids were investigated in formula-fed piglets. Piglets were fed formula with (in % total fatty acids) 20% 18:2(n-6) and 2% 18:3(n-3) without or with 0.8% 20:4(n-6) or 0.3% 22:6(n-3) from birth to 18 d. The effects of adding 20:4(n-6) or 22:6(n-3) to the formula differed among different tissues and lipids, with the brain showing resistance to change. Piglets fed formula with 20:4(n-6) had significantly higher plasma, heart and kidney phospholipid and triglyceride, and liver triglyceride 20:4(n-6), but lower plasma and tissue phospholipid 18:2(n-6) than piglets fed formula without 20:4(n-6). Supplementation with 22:6(n-3), in contrast, had no effect on plasma or tissue 18:2(n-6). Higher 22:6(n-3) in liver phospholipid (30-92% greater) and triglyceride (200% greater) in piglets fed formula with 22:6(n-3) rather than without 22:6(n-3) was accompanied by lower 20:4(n-6) in liver phosphatidylethanolamine (mean +/- SEM, 8.6 +/- 0.4 and 10.5 +/- 0.4% fatty acids, respectively), but higher 20:4(n-6) in triglyceride (5.2 +/- 0.4 and 11.5 +/- 0.5%, respectively), and higher liver, heart and kidney phospholipid 20:5(n-3). These results indicate competitive interaction between dietary 20:4(n-6) and tissue 18:2(n-6), and between dietary 20:4(n-6) and tissue 20:5(n-3), rather than 22:6(n-3). The results also show that even at low intakes, dietary 22:6(n-3) or 20:4(n-6) supplementation alters the tissue phospholipid 20:4(n-6) to 20:5(n-3) balance. Studies on the physiologic effects of dietary 20:4(n-6) and 22:6(n-3) supplementation should consider the different sensitivity among tissues to dietary fatty acids.     

The association of increasing dietary concentrations of fish oil with hepatotoxic effects and a higher degree of aorta atherosclerosis in the ad lib.-fed rabbit

The long-term effects of consumption of marine long-chain n-3 polyunsaturated fatty acids (PUFA) on atherosclerosis in the rabbit were examined. Female Dutch rabbits were fed purified diets, containing 40 energy% total fat, for a period of 2.5 years. To study the dose response relationship between fish oil intake and atherosclerosis, four diets were formulated with fish oil levels being 0, 1, 10 and 20 energy%. A fifth and sixth group were fed an alpha-linolenic acid-(C18:3, n-3) and linoleic acid-(C18:2, n-6) rich diet, respectively. Every 6 weeks, blood samples were taken for determination of clinical chemical parameters, triacylglycerol and total cholesterol levels. Feeding 10 and 20 energy% fish oil containing diets, resulted in an increase of liver enzymes (AST, ALT and ALP). Histological evaluation of the liver also revealed adverse effects of fish oil containing diets. Triacylglycerol blood levels were similar in all groups, and remained constant throughout the study. Total cholesterol levels in blood was significantly lower in the animals fed a linoleic acid-rich diet, as compared with the other five groups. An n-3 long-chain PUFA concentration dependent increase in aorta plaque surface area was observed in the fish oil groups. A significant positive relationship was found between the group mean score for severity of liver pathology and the aorta plaque surface area. These results indicate that the long-chain n-3 polyunsaturated fatty acids in fish oil may be hepatotoxic to the herbivorous rabbit, which may interfere with the outcome of atherosclerosis studies. This finding necessitates the exclusion of liver pathology in experimental studies on atherosclerosis in animal models.     

Intake of very-long-chain n-3 fatty acids related to social status and lifestyle

OBJECTIVES: Little information is available about the intake of very-long-chain n-3 fatty acids in random samples of populations. We examined if the intake of these fatty acids was associated with gender, social status and lifestyle in a similar way as other indicators for a healthy diet in a nationwide survey. DESIGN AND SUBJECTS: Data were obtained from self-administered quantitative food frequency questionnaires filled in by a representative sample of Norwegian men and women, aged 16-79 y. 3144 (63%) of the invited subjects responded with acceptable questionnaires. RESULTS: Daily intake of very-long-chain n-3 fatty acids was on average 0.9 g/d and 0.4% of total energy was derived from these fatty acids. Energy derived from very-long-chain n-3 fatty acids was slightly higher among men than women, and two-fold higher among subjects aged 60-79 vs 16-29 y. White collar workers had higher intake of very-long-chain n-3 fatty acids than blue collar workers. Men and women in the highest quartile of intake of very-long-chain n-3 fatty acids had 2-3 E% higher fat intake (mostly mono- and polyunsaturated fatty acids), as compared to individuals in the lowest quartile. They also had 3-4 fold higher daily intake of retinol and vitamin D, as well as 20-50% higher intake of fruits and vegetables, dietary fibre and vitamin C. CONCLUSIONS: Intake of very-long-chain n-3 fatty acids was correlated to indicators for healthy dietary habits. However, contrary to many other indicators of a healthy diet, energy derived from very-long-chain n-3 fatty acids was not significantly associated with female gender or non-smoking.     

Relationships between serum lipids, platelet membrane fatty acid composition and platelet aggregation in type 2 diabetes mellitus

In order to gain further insight into the mechanism of platelet dysfunction frequently reported in diabetes we investigated circulating fatty acids, lipid composition of platelet membrane and platelet function in Type 2 diabetic patients. In these subjects, percentages of C16 : 1n-7 and C18 : 1n-9 in serum phospholipid fraction and of C16 : 1n-7 in serum cholesterol ester fraction were decreased. Moreover, the content of C20 : 4n-6 in serum cholesterol esters was altered in Type 2 diabetic subjects: C18 : 0 and C20 : 3n-6 were increased but C20 : 4n-6 content was similar to controls. Aggregation in vitro did not differ from controls but aggregation in vivo was increased in Type 2 diabetic subjects. No correlation was observed between metabolic parameters -i.e., HbA1, blood glucose, serum triglycerides and total cholesterol, circulating fatty acids and fatty acid content of platelet membrane. A negative linear correlation was found between aggregation in vivo and C20 : 4n-6 content of platelet membrane. Moreover, a U shaped relationship was observed between platelet aggregation in vitro and C20 : 4n-6 content of platelet membrane suggesting that C20 : 4n-6 level should be tightly controlled otherwise platelet hyperreactivity may occur. These results indicate that despite a normal mean C20 : 4n-6 content in the platelet membrane, regulation of C20 : 4n-6 metabolism is less strictly controlled in Type 2 diabetes mellitus and confirm the importance of arachidonic acid platelet content in the regulation of platelet aggregability.     

Fish oils lower rat plasma and hepatic, but not immune cell alpha-tocopherol concentration

These studies were designed to measure the impact of different fish oil sources of dietary (n-3) polyunsaturated fatty acid on the alpha-tocopherol content of rat immune cells. In the first experiment, rats were fed diets containing either lard, corn oil, menhaden fish oil or cod liver oil. In the second study, sardine fish oil replaced corn oil. Dietary fat source did not significantly influence body weights or the yield of immune cells in either study. In both studies, plasma and liver alpha-tocopherol concentrations were significantly lower in (n-3) polyunsaturated fatty acid-fed rats than in rats fed lard. In the first study, immune cell alpha-tocopherol concentrations followed those observed in the plasma and liver. These concentrations closely paralleled the amount of RRR-alpha-tocopheryl acetate added to diets and not the total vitamin E present, which was the same for all treatment groups. However, in the second study, alpha-tocopherol concentration of immune cells was not significantly different among rats fed lard, menhaden fish oil, and sardine fish oil. In that study both the amount and form of vitamin E were carefully balanced across dietary treatment groups. In conclusion, despite having similar amounts of (n-3) polyunsaturated fatty acids, two out of three fish oils tested did not lower immune cell alpha-tocopherol concentration even in the face of significantly reduced plasma and liver alpha-tocopherol concentrations.     

Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients

Several studies have shown that n-3 polyunsaturated fatty acids (n-3 PUFA) are able to lower blood pressure (BP) in humans, but large doses of fish oils have been often used. Moreover, most of the studies available in the literature were not able to evaluate the specific effects of n-3 PUFA because they employed fish oils which contain, together with n-3 PUFA, many other different components. The aim of this preliminary study was to evaluate if medium-term supplementation with a moderate dose of highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl esters is able to reduce BP in mild hypertensive patients. Sixteen mild essential hypertensive (diastolic BP: 95-104 mm Hg), non-diabetic, normolipidemic male outpatients and 16 normotensive male controls were recruited to participate in the study. Both hypertensive and control subjects were randomly assigned to receive either EPA and DHA ethyl esters (2.04 g EPA and 1.4 g DHA) as active treatment or olive oil (4 g/day) as a placebo for a period of 4 months. These subjects were followed up with 24-hour ambulatory BP monitoring and blood chemistry analyses at 2 and 4 months of treatment and 2 months after its discontinuation. The intake of n-3 PUFA was checked by red blood cell (RBC) phosphatidylcholine (PC) fatty acid composition. The effect of n-3 PUFA on BP in the active group was maximum after 2 months. Both systolic (-6 mm Hg, p<0.05) and diastolic (-5 mm Hg, p<0.05) BP significantly decreased during the n-3 PUFA ethyl ester supplementation. No further effect was observed at 4 months with a return to baseline values during the recovery period. These data indicate that 4 g/day of highly purified EPA + DHA ethyl esters are able to favorably affect BP in mild hypertensives.     

Dietary fish oil does not alter glucose tolerance in conscious rats

We examined the effect of dietary fish oil (MaxEPA) and sunflower seed oil on glucose tolerance in male Wistar rats. Semipurified diets containing 100 g oil/kg diet were administered for 30 d. The fish oil diet contained 26 g (n-3) fatty acids, 16 g eicosapentaenoic acid and 10.4 g docosahexaenoic acid/kg diet. Phospholipids from liver, pancreas, and pancreatic islets were enriched in eicosapentaenoic and docosahexaenoic acids by the fish oil diet. In unfed pentobarbital-anesthetized rats, both basal plasma insulin concentration and insulin responses to intravenous glucose were significantly lower for fish oil-fed rats although glucose responses were similar; however, incremental excursions in plasma insulin over the basal concentrations did not differ. Intravenous glucose tolerance was also examined in conscious unfed rats under minimal restraint. Responses of plasma glucose and insulin were similar for fish oil- and sunflower oil-fed groups. Furthermore, in another experiment, intravenous glucose tolerance tests were similar for conscious rats provided with either 100 g fish oil or corn oil/kg nonpurified diet. Thus, glucose-induced insulin secretion is lower in rats fed fish oil than in rats fed sunflower oil, when tests are conducted in pentobarbital-anesthetized animals but not when tests are performed in conscious rats; there was no effect on plasma glucose in either anesthetized or nonanesthetized rats. Therefore, substitution of (n-3) for (n-6) polyunsaturated fatty acids in tissue phospholipids does not alter plasma glucose or insulin in conscious male Wistar rats.     

Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid intake

OBJECTIVES: The hypothesis tested was that menstrual discomfort, e.g. dysmenorrhoea, known to be prostaglandin-mediated, can be influenced by the dietary ratio of n-3 and n-6 polyunsaturated fatty acids. The prostaglandins derived from marine n-3 fatty acids are normally less aggressive and therefore expected to be associated with milder symptoms. DESIGN: The question was surveyed in an epidemiological study based upon self-administered questionnaires concerning menstrual history, present symptoms, general health, socioeconomic factors, and general dietary habits. Two (prospective) 4-day dietary records were used to estimate average daily nutrient intake. SUBJECTS: The subjects were recruited by advertising (about 220 volunteered); 181 healthy Danish women were selected, aged 20-45 years; they were not pregnant and did not use oral contraceptives. RESULTS: No correlations were found between socioeconomic or anthropometric data and menstrual problems. On the contrary certain dietary habits, e.g. low intake of animal and fish products, and intakes of specific nutrients, were correlated with menstrual pain. The average dietary n-3/n-6 ratio of women with menstrual pain was 0.24. It was significantly higher among those with low intake of B12 coincident with low intake of n-3 (0.42, P < 0.001) (chi-square), with low n-3 intake coincident with low n-3/n-6 ratio (0.42, P < 0.005), and finally with low intake of B12 coincident with low n-3/n-6 ratio (0.47, P < 0.001). CONCLUSION: The results were highly significant and mutually consistent and supported the hypothesis that a higher intake of marine n-3 fatty acids correlates with milder menstrual symptoms.     

Role of the microtubule cytoskeleton in gravisensing Chara rhizoids

Docosahexaenoic acid and arachidonic acid are deposited in large amounts in the developing central nervous system, and concentrations are particularly high in synaptic plasma membrane and retina ethanolamine phospholipids. Arachidonic acid and docosahexaenoic acid are present in human milk. The precursors linoleic [18:2(n-6)] and alpha-linolenic [18:3(n-3)] acid, but not arachidonic acid or docosahexaenoic acid, are present in formulas. Desaturation and elongation of 18:2(n-6) and 18:3(n-3) to arachidonic acid and docosahexaenoic acid, respectively, depend on the dietary content and ratio of 18:2(n-6) and 18:3(n-3), but appropriate levels and ratios of 18:2(n-6) and 18:2(n-3) for formula are not well defined. The effect of formula with 1 or 4% fatty acids 18:3(n-3) and 16, 30 or 35% fatty acids 18:2(n-6) on synaptic plasma membrane and retina ethanolamine phospholipid fatty acids was therefore studied in piglets, with reference to piglets fed milk. Piglets fed 4% fatty acids 18:3(n-3), but not those fed 1% fatty acids 18:3(n-3), had similar central nervous system docosahexaenoic acid levels but had significantly lower brain weights than piglets fed sow milk. Synaptic plasma membrane and retina arachidonic acid were lower in piglets fed the formulas with 4% rather than 1% fatty acids 18:3(n-3). The dietary 18:3(n-3) content, rather than the 18:2(n-6) to 18: 3(n-3) ratio, seemed more important for deposition of docosahexaenoic acid in brain. However, synaptic plasma membrane and retina docosahexaenoic acid levels were further reduced in piglets fed 1% fatty acids 18:3(n-3) (0.4% energy) with 30% rather than with 16% fatty acids 18:2(n-6). The need for further study of upper limits of dietary 18:3(n-3) during development is suggested.     

Changes in dietary fatty acids alter phospholipid fatty acid composition in selected regions of rat brain

1. Eighty rats were randomized into four groups receiving one of the following diets: rat chow containing (1) 6% soybean oil, (2) 6% primrose oil, (3) 6% fish oil, (4) a combination of 4.5% primrose and 1.5% fish oil. 2. Following two months of each regimen, the rats were sacrificed by microwave irradiation and the brain's fatty acid composition was analysed with gas chromatography for each of the following regions: frontal cortex, striatum, occipital cortex, hippocampus, hypothalamus, cerebellum and pituitary. 3. Linoleic acid was decreased by both primrose and fish oil supplementations. The fish oil substitution resulted in a significant elevation of 20:3n-6, a decrease of 22:4n-6 and a non-significant decrease of 20:4n-6, probably reflecting inhibition of delta-5-desaturation. At the same time the fish oil diet significantly elevated 22:5n-3 while 22:5n-6 was decreased. 4. The primrose oil diet lowered the n-3/n-6 ratio in all regions except in the cerebellum. In contrast, the fish oil diet elevated the n-3/n-6 ratio in all regions. 5. The results demonstrate that changes in dietary fat composition can alter the fatty acid composition of the adult rat brain and that these effects are region specific. 6. This is of interest since metabolites of essential fatty acids may be involved in physiological and pathological processes in the brain and it has been hypothesized that dietary intake of fats may influence the outcome of psychiatric disorders such as schizophrenia.