Showing papers on "Docosahexaenoic acid published in 1990"

Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects.

Abstract: Forty-nine patients with active rheumatoid arthritis completed a 24-week, prospective, double-blind, randomized study of dietary supplementation with 2 different dosages of fish oil and 1 dosage of olive oil. Clinical evaluations were performed at baseline and every 6 weeks thereafter, and immunologic variables were measured at baseline and after 24 weeks of study. The 3 groups of patients were matched for age, sex, disease severity, and use of disease-modifying antirheumatic drugs (DMARDs). Subjects continued receiving DMARDs and other background medications without change during the study. Twenty patients consumed daily dietary supplements of n3 fatty acids containing 27 mg/kg eicosapentaenoic acid (EPA) and 18 mg/kg docosahexaenoic acid (DHA) (low dose), 17 patients ingested 54 mg/kg EPA and 36 mg/kg DHA (high dose), and 12 patients ingested olive oil capsules containing 6.8 gm of oleic acid. Significant improvements from baseline in the number of tender joints were noted in the low-dose group at week 24 (P = 0.05) and in the high-dose group at week 18 (P = 0.04) and 24 (P = 0.02). Significant decreases from baseline in the number of swollen joints were noted in the low-dose group at weeks 12 (P = 0.003), 18 (P = 0.002), and 24 (P = 0.001) and in the high-dose group at weeks 12 (P = 0.0001), 18 (P = 0.008), and 24 (P = 0.02). A total of 5 of 45 clinical measures were significantly changed from baseline in the olive oil group, 8 of 45 in the low-dose fish oil group, and 21 of 45 in the high-dose fish oil group during the study (P = 0.0002). Neutrophil leukotriene B4 production decreased by 19% from baseline in the low-dose fish oil group (P = 0.0003) and 20% in the high-dose group (P = 0.03), while macrophage interleukin-1 production decreased by 38.5% in the olive oil group (P not significant), 40.6% in the low-dose group (P = 0.06), and 54.7% in the high-dose group (P = 0.0005). Tritiated thymidine incorporation in peripheral blood mononuclear cells after stimulation with concanavalin A increased significantly in all 3 groups after 24 weeks, compared with baseline values. We conclude that the clinical benefits of dietary supplementation with omega-3 fatty acids are more commonly observed in patients consuming higher dosages of fish oil for time intervals that are longer than those previously studied. Dietary supplementation with olive oil is also associated with certain changes in immune function, which require further investigation.

Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromsø study.

Abstract: Studies of whether polyunsaturated fatty acids in fish oil--in particular, eicosapentaenoic and docosahexaenoic acids--lower blood pressure have varied in design and results. We conducted a population-based, randomized, 10-week dietary-supplementation trial in which the effects of 6 g per day of 85 percent eicosapentaenoic and docosahexaenoic acids were compared with those of 6 g per day of corn oil in 156 men and women with previously untreated stable, mild essential hypertension. The mean systolic blood pressure fell by 4.6 mm Hg (P = 0.002), and diastolic pressure by 3.0 mm Hg (P = 0.0002) in the group receiving fish oil; there was no significant change in the group receiving corn oil. The differences between the groups remained significant for both systolic (6.4 mm Hg; P = 0.0025) and diastolic (2.8 mm Hg; P = 0.029) pressure after control for anthropometric, lifestyle, and dietary variables. The decreases in blood pressure were larger as concentrations of plasma phospholipid n-3 fatty acids increased (P = 0.027). Dietary supplementation with fish oil did not change mean blood pressure in the subjects who ate fish three or more times a week as part of their usual diet, or in those who had a base-line concentration of plasma phospholipid n-3 fatty acids above 175.1 mg per liter. We conclude that eicosapentaenoic and docosahexaenoic acids reduce blood pressure in essential hypertension, depending on increases in plasma phospholipid n-3 fatty acids.

reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys'

Abstract: Rhesus monkeys given pre- and postnatal diets defi- cient in n-3 essential fatty acids develop low levels of docosahexa- enoic acid (22:6 n-3, DHA) in the cerebral cortex and retina and impaired visual function. This highly polyunsaturated fatty acid is an important component of retinal photoreceptors and brain synaptic membranes. To study the turnover of polyunsaturated fatty acids in the brain and the reversibility of n-3 fatty acid defi- ciency, we fed five deficient juvenile rhesus monkeys a fish oil diet rich in DHA and other n-3 fatty acids for up to 129 weeks. The results of serial biopsy samples of the cerebral cortex indi- cated that the changes of brain fatty acid composition began as early as 1 week after fish oil feeding and stabilized at 12 weeks. The DHA content of the phosphatidylethanolamine of the fron- tal cortex increased progressively from 3.9 + 1.2 to 28.4 + 1.7 percent of total fatty acids. The n-6 fatty acid, 22:5, abnormally high in the cerebral cortex of n-3 deficient monkeys, decreased reciprocally from 16.2 * 3.1 to 1.6 0.4%. The half-life (tl,*) of DHA in brain phosphatidylethanolamine was estimated to be 21 days. The fatty acids of other phospholipids in the brain (phosphatidylcholine, -serine, and -inositol) showed similar changes. The DHA content of plasma and erythrocyte phospho- lipids also increased greatly, with estimated half-lives of 29 and 21 days, respectively. a We conclude that monkey cerebral cortex with an abnormal fatty acid composition produced by dietary n-3 fatty acid deficiency has a remarkable capacity to change its fatty acid content after dietary fish oil, both to in- crease 22:6 n-3 and to decrease 22:5 n-6 fatty acids. The bio- chemical evidence of n-3 fatty acid deficiency was completely corrected. These data imply a greater lability of the fatty acids of the phospholipids of the cerebral cortex than has been hitherto appreciated. -Connor, W. E., M. Neuringer, and D. S. Lin. Dietary effects on brain fatty acid composition: the reversibility on n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys. J Lipid Res. 1990. 31: 237-247.

Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture.

Abstract: Dietary lipids may influence breast cancer progression and prognosis. The MDA-MB-231 human breast cancer cell line was used to examine the direct effects of the various classes of free fatty acids (FAs) on growth in serum-free medium and the involvement of eicosanoid biosynthesis. Linoleic acid, an ω6 FA, stimulated MDA-MB-231 cell growth with an optimal effect at a concentration of 0.75 µg/ml, whereas oleic acid, an ω9 FA, produced growth stimulation at 0.25 µg/ml but was inhibitory at higher concentrations. Docosahexaenoic acid exhibited a dose-related inhibition of cell growth at concentrations ranging from 0.5 to 2.5 µg/ml; eicosapentaenoic acid, also an ω3 FA, was less effective. Similar inhibitory effects occurred with saturated FAs. Indomethacin, which at high concentrations is an inhibitor of both the cyclooxygenase- and lipoxygenase-catalyzed pathways of eicosanoid synthesis, suppressed cell growth stimulation by an otherwise optimal dose of linoleic acid when present at 40 µg/ml. Experiments with piroxicam, nordihydroguaiaretic acid, and esculetin, other inhibitors of eicosanoid biosynthesis with varying selectivity for enzymes of the prostaglandin and leukotriene pathways, indicated that MDA-MB-231 cell growth was dependent on leukotriene rather than prostaglandin production.

Docosahexaenoic acid is the preferred dietary n-3 fatty acid for the development of the brain and retina.

Abstract: The metabolism of individual dietary n-3 fatty acids was studied in n-3 fatty acid-deficient newly hatched chicks. Laying hens were fed the n-6 fatty acid, ethyl linoleate, as the only source of polyunsaturated fat. Chicks were then fed the n-3-deficient hens' diet, or one of three other diets supplemented with the ethyl ester of 18:3 n-3, 20:5 n-3 [eicosapentaenoic acid (EPA)], or 22:6 n-3 [docosahexaenoic acid (DHA)] at 0.44% of calories. At the end of 0, 1, 2, and 3 wk, the fatty acid composition of the brain, retina, liver, and serum was determined. Dietary EPA and DHA were equally effective at raising levels of DHA in the brain and retina. Dietary 18:3 was relatively ineffective in restoring brain and retina DHA. In the n-3-deficient chicks fed EPA or DHA, levels of DHA recovered to control values in both the brain and retina by 3 wk. Very little EPA accumulated in the brain or retina of chicks fed EPA. Hepatic synthesis of DHA from EPA appeared low, suggesting that the brain and retina synthesized the DHA that accumulated rapidly in these tissues after the feeding of EPA. The delta-4-desaturase enzyme was apparently very active, then, in the brain and retina. Retroconversion of dietary 22:6 to 22:5 and 20:5 was evident in the serum, liver, and retina but not in the brain. Thus, it was possible to study the relative metabolism and especially the interconversion of n-3 fatty acids in a environment uncomplicated by existing stores of these essential fatty acids. This study would suggest that 18:3 as the sole source of n-3 fatty acids in the diets of animals, including the human infant, may not be adequate for the biochemical development of the brain and retina and that dietary DHA is the preferred fatty acid of the n-3 series.

Effects of fish oil supplementation in rheumatoid-arthritis

Abstract: Sixteen patients with rheumatoid arthritis entered a trial to determine the clinical and biochemical effects of dietary supplementation with fractionated fish oil fatty acids. A randomised, double blind, placebo controlled crossover design with 12 week treatment periods was used. Treatment with non-steroidal anti-inflammatory drugs and with disease modifying drugs was continued throughout the study. Placebo consisted of fractionated coconut oil. The following results favoured fish oil rather than placebo: joint swelling index and duration of early morning stiffness. Other clinical indices improved but did not reach statistical significance. During fish oil supplementation relative amounts of eicosapentaenoic acid and docosahexaenoic acid in the plasma cholesterol ester and neutrophil membrane phospholipid fractions increased, mainly at the expense of the omega-6 fatty acids. The mean neutrophil leucotriene B4 production in vitro showed a reduction after 12 weeks of fish oil supplementation. Leucotriene B5 production, which could not be detected either in the control or in the placebo period, rose to substantial quantities during fish oil treatment. This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of rheumatoid arthritis.

Effect of high doses of essential fatty acids on the postviral fatigue syndrome.

Abstract: Sixty-three adults with the diagnosis of the postviral fatigue syndrome were enrolled in a double-blind, placebo-controlled study of essential fatty acid therapy. The patients had been ill for from one to three years after an apparently viral infection, suffering from severe fatigue, myalgia and a variety of psychiatric symptoms. The preparation given contained linoleic, gamma-linolenic, eicosapentaenoic and docosahexaenoic acids and either it, or the placebo, was given as 8 x 500 mg capsules per day over a 3-month period. The trial was parallel in design and patients were evaluated at entry, one month and three months. In consultation with the patient the doctors assessed overall condition, fatigue, myalgia, dizziness, poor concentration and depression on a 3-point scale. The essential fatty acid composition of their red cell membrane phospholipids was analysed at the first and last visits. At 1 month, 74% of patients on active treatment and 23% of those on placebo assessed themselves as improved over the baseline, with the improvement being much greater in the former. At 3 months the corresponding figures were 85% and 17% (p less than 0.0001) since the placebo group had reverted towards the baseline state while those in the active group showed continued improvement. The essential fatty acid levels were abnormal at the baseline and corrected by active treatment. There were no adverse events. We conclude that essential fatty acids provide a rational, safe and effective treatment for patients with the post-viral fatigue syndrome.

Vascular prostacyclin is increased in patients ingesting omega-3 polyunsaturated fatty acids before coronary artery bypass graft surgery.

Abstract: Interest in the antithrombotic potential of diets enriched with fish oil-derived polyunsaturated fatty acids (omega-3 PUFAs) prompted us to examine how these fatty acids, when taken preoperatively, affect hemostasis, plasma lipid levels, and production of prostacyclin (PGI2) by vascular tissues in atherosclerotic patients undergoing coronary artery bypass graft surgery. Fifteen patients with angiographically proven coronary artery disease received 3 g/day eicosapentaenoic acid and 1.3 g/day docosahexaenoic acid as capsules of purified fish oil for 28 days before surgery. Platelet aggregation induced by low concentrations of ADP, collagen, and epinephrine decreased (p less than 0.05) and serum thromboxane B2 decreased 36% (p less than 0.01) from baseline values. Bleeding times increased 40% (p less than 0.01) from baseline. Serum triglycerides decreased 50% (p less than 0.05) without a change in total serum cholesterol. Spontaneous production of PGI2 measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), its stable hydrolytic product, by saphenous vein and aortic and atrial tissues obtained at surgery was greater in tissues from patients receiving omega-3 PUFA supplements than in tissues from matched controls (13.8 +/- 2.2 versus 8.6, 21.0 +/- 3.1 versus 11.5 +/- 2.1, and 166 +/- 13 versus 102 +/- 15 ng/g, respectively, all p less than 0.05). Arachidonate-stimulated production of PGI2, as indicated by increased levels of 6-keto-PGF1 alpha, was increased. Despite changes in platelet function, bleeding time, and vascular PGI2, the perioperative blood loss was not increased in subjects receiving fish oil supplements. Thus, omega-3 PUFAs at moderate dosages may exert antithrombotic effects by increasing prostacyclin production by vessel walls as well as by direct inhibition of platelet activity.

Requirement of juvenile red seabream Pagrus major for eicosapentaenoic and docosahexaenoic acids.

Abstract: A feeding experiment was conducted to compare the EFA value between eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in juvenile red seabream, and to determine their requirements for both fatty acids by feeding them defatted fish meal diets containing different levels of EPA and/or DHA ranging from 0 to 1% in diet. Juvenile red seabream fed a diet without supplemental EFA began to show a high mortality and poor appetite after one week feeding. The cumulative mortality of this group was 46% after 24 days. The growth and feed efficiency were effectively improved by elevating EPA or DHA levels to 1% or 0.5% in the diet, respectively. However, further elevation of the DHA level from 0.5 to 1% and addition of both EPA and DHA in diets at levels of 0.25 and 0.5% each did not result in further improvement of these parameters. The hepatosomatic index was high in the fish fed low levels of EPA or DHA and was reduced by elevating EPA levels to 1% in diets, although DHA was more effective than EPA. Thus, the requirement of EPA and DHA was estimated to be around 1% and 0.5% in diet for juvenile red seabream, respectively. The EFA efficiency of DHA was also found to be about twice as high as that of EPA, and there was no additive effect of EPA and DHA on growth and feed efficiency.

Effect of dietary fish oil on .omega.-3 fatty acid levels in chicken eggs and thigh flesh

Abstract: Incorporation of ω-3 polyunsaturated fatty acids into chicken egg, thigh meat, and adipose tissue was studied by feeding laying hens diets containing up to 3% menhaden oil for 4 weeks. Dietary fish oil increased eicosapentaenoic acid and docosahexaenoic acid in the fatty acid distribution of egg yolk. Organoleptic evaluation showed that eggs and thigh meat remained acceptable with up to a 3% dietary fish oil stabilized with 0.1% ethoxyquin

Omega-3 Fatty Acids in Lake Superior Fish

Abstract: Proximate analysis and fatty acid composition of eight commercially important species of Lake Superior fish were determined. Palmitic acid (C16:0) was the predominant saturated fatty acid, accounting for 68–79% of total saturated acids. Oleic acid (C18:1) was the most abundant monounsaturated fatty acid. Linoleic acid (C18:2), linolenic acid (C18:3), eicosapentaenoic acid (C20:5) and docosahexaenoic acid (C22:6) were the predominant polyunsaturated fatty acids. Brining, smoking and refrigerated storage caused a reduction in total lipid, but only a small loss in n-3 fatty acids. The data revealed that most Lake Superior fish examined were excellent sources of polyunsaturated fatty acids with very high levels of omega-3 (n-3) fatty acids, especially eicosapentaenoic and docosahexaenoic acids.

Placental transfer of essential fatty acids in humans: venous-arterial difference for docosahexaenoic acid in fetal umbilical erythrocytes.

Abstract: Docosahexaenoic acid [22:6(n-3); 22:6(4,-7,10,13,16,19) (DHA)] is required in quantity by the developing nervous system of the fetus. This need could be met through synthesis of DHA from linolenic acid in the fetus or through placental transfer of DHA directly. To study the placental transfer of n-3 fatty acids, we obtained umbilical and maternal blood samples from 26 healthy women and infants at parturition and measured the fatty acid composition and content of both plasma and erythrocytes. A striking finding was a considerable venous-arterial difference for DHA in the umbilical erythrocytes as a proportion of total fatty acids and in absolute concentration. This difference of 2.2 micrograms per billion erythrocytes was 6 times larger than the difference in fetal plasma, when the plasma and erythrocyte concentrations were normalized to whole blood. Most other erythrocyte fatty acids showed a similar trend. In umbilical plasma, significant venous-arterial differences were found for 16:0, 16:1, 18:2, and total saturated fatty acids. There was a similar trend for most other plasma fatty acids. Compared with maternal blood, fetal plasma and erythrocytes had higher levels of 20:4 and DHA and lower levels of 18:2 and 18:3(n - 3) fatty acids as a proportion of total fatty acids. These results suggest that erythrocytes play a major role in the necessary transport of the essential fatty acid DHA into the fetus.

Selective Hydrolysis of Fish Oil by Lipase to Concentrate n-3 Polyunsaturated Fatty Acids

Abstract: Six lipases were examined for concentrating the n-3 polyunsaturated fatty acid (n-3 PUFA) of two kinds of fish oil (cod liver oil and refined sardine oil). Although all lipases could increase the n-3 PUFA content of the remaining glycerides, Candida cylindracea and Aspergillus niger lipases gave glycerides with a more than two-fold increase in n-3 PUFA content over the original fish oils.Candida cylindracea lipase seems the most promising with respect to recovery of triacylglycerol. Aspergillus niger lipase increased not only the docosahexaenoic acid (DHA) content but also eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA), although the absolute value of the latter was quite low. The effects of temperature (15–40 °C) on the concentration of n-3 PUFA were investigated. Lower temperatures did not improve the concentration of n-3 PUFA, but prevented the development of an unpleasant odor in the product.

Severe deficiency of docosahexaenoic acid in peroxisomal disorders: a defect of delta 4 desaturation?

Abstract: In confirmation of previous findings, patients with Zellweger's syndrome had extremely low levels of docosahexaenoic acid (22:6 omega 3) in the brain, liver, and kidneys. The other product of delta 4 desaturation, 22:5 omega 6, was also very significantly decreased, as were the ratios 22:6 omega 3/22:5 omega 3 and 22:5 omega 6/22:4 omega 6, especially in the brain and liver of the Zellweger patients. The infant with pseudo-Zellweger's syndrome also had very low levels of 22:6 omega 3 and of the ratio 22:6 omega 3/22:5 omega 3 in all tissues, especially in the brain, where the index 22:5 omega 6/22:4 omega 6 was also very significantly reduced. The ratio 22:6 omega 3/22:4 omega 6 was markedly decreased in all tissues, in Zellweger's as well as in pseudo-Zellweger's syndrome. The findings reported here strongly reinforce the hypothesis of a new enzymatic defect in peroxisomal disorders involving the desaturation of long polyunsaturated fatty acids, especially of the omega 3 family.

Enzymatic fractionation of fatty acids: Enrichment of γ-linolenic acid and docosahexaenoic acid by selective esterification catalyzed by lipases

Abstract: Immobilized lipase preparations from seedlings of rape (Brassica napus L.) andMucor miehei (lipozyme) used as biocatalysts in esterification and hydrolysis reactions discriminate strongly against γ-linolenic and docosahexaenoic acids/acyl moieties. Utilizing this property, γ-linolenic acid contained in fatty acids of evening primrose oil has been enriched seven to nine-fold, from 9.5 to almost 85% by selective esterification of the other fatty acids with butanol. Similarly, docosahexaenoic acid of cod liver oil has been enriched four to five-fold, from 9.4 to 45% by selective esterification of fatty acids (other than docosahexaenoic acid) with butanol. As long as the reaction is stopped before reaching equilibrium, very little of either γ-linolenic acid or docosahexaenoic acid are converted to butyl esters, which results in high yields of these acids in the unesterified fatty acid fraction.

Effects of dietary n-3 fatty acids on the phospholipid molecular species of monkey brain

Abstract: We examined the changes in the molecular species of brain ethanolamine glycerophospholipids of monkeys fed diets containing widely ranging amounts of n-3 fatty acids. Two groups of rhesus monkeys were fed pre- and postnatally either a control diet (soy oil; containing 8% of fatty acids as 18:3n-3) or a deficient diet (safflower oil; containing less than 0.3% 18:3n-3). The brains of these animals were analyzed at 22 months of age. A third group of monkeys was fed the safflower oil diet to 22 months of age and then switched to a fish oil diet (28% long-chain n-3 fatty acids) for 1-2 years before autopsy. The molecular species of the diacyl, alkylacyl, and alkenylacyl ethanolamine glycerophospholipids from frontal cortex were separated by HPLC. A total of 24 molecular species were identified. Fatty acids in the sn-2 position differed markedly among the diet groups, but the sn-1 position always contained only 16:0, 18:0, or 18:1. In the diacyl subclass of the control brain, the n-3 molecular species represented 41% of total and the n-6 species 45%, whereas in the deficient brain the n-3 molecular species decreased to 9% and n-6 molecular species increased to 77%. The fatty acid 22:5n-6 did not replace 22:6n-3 in a symmetrical fashion in the molecular species of the deficient brain. In the brains of the fish oil-fed monkeys, the n-3 molecular species amounted to 61% and n-6 molecular species were reduced to 25%. The species 18:1-22:6, 16:0-22:6, and 18:0-22:6 generally changed proportionally in response to diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipids in human lipofuscin-enriched subcellular fractions of two age populations. Comparison with rod outer segments and neural retina.

Abstract: The fatty acid composition and content of total phospholipids, free fatty acids (FFA), diacylglycerols (DG), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE) were studied in lipofuscin granules of human donors in two age groups, young (less than 40 yr old) and old (more than 47 yr old), and compared with lipids of the photoreceptor rod outer segments (ROS). Neural retina (NR) and retinal pigment epithelium (RPE) also were studied. In both age groups, the lipid composition of the lipofuscin granules differed from that of the ROS, with a decrease in the proportion of phospholipid and an increase in FFA, suggesting very high phospholipase activity in the lipofuscin granules. In ROS, docosahexaenoic acid (22:6) was the predominant FFA, whereas palmitic acid (16:0), arachidonic acid (20:4) and oleic acid (18:1) were the major fatty acids in the lipofuscin granules. The fatty acid compositions of PC, PE, and PS of lipofuscin granules were different from those of the retina. There was proportionally less 22:6 in lipofuscin, and the amounts of saturated and monounsaturated fatty acyl chains such as 16:0, stearate (18:0), and 18:1 were greater than in retina. Compared to ROS, the lipofuscin granules showed a significant decrease in DG containing 20:4 but not 22:6. With aging, there was a decrease in the amount of total polyunsaturated fatty acyl chains (22:6 and 20:4) in the lipofuscin granules. These results show that the lipid composition of lipofuscin is different from that of ingested ROS, probably because of increased phospholipase and peroxidative activities in lipofuscin, directed toward ingested ROS as well as toward other materials from the RPE and blood.

[Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers].

Abstract: Comparative Bioavailability of Eicosapentaenoic Acid and Docosahexaenoic Acid from Triglycerides, Free Fatty Acids and Ethyl Esters in Volunteers. The bioavailability of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from triglycerides, free fatty acids and ethyl esters was investigated in 8 female volunteers in a randomized triple cross-over trial with baseline control. EPA/DHA was administered in capsules in form of triglycerides (1.68/0.72 g), free fatty acids (1.35/1.065 g) and ethyl esters (1.86/1.27 g). The resulting EPA/DHA plasma levels were determined and evaluated. The mean relative bioavailability of EPA/DHA compared to triglycerides was 186/136% from free fatty acids and 40/48% from ethyl esters. Maximal plasma levels were about 50% higher with free fatty acids and about 50% lower with ethyl esters as compared to triglycerides. The tolerability of the free fatty acids was much worse than that of triglycerides and ethyl esters. The main side effect was eructation.