The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans

The effect of dietary docosahexaenoic acid (DHA) in the absence of eicosapentaenoic acid (EPA) has been studied infrequently in humans under controlled conditions. This 120-d study followed healthy, adult male volunteers who lived in the metabolic research unit (MRU) of the Western Human Nutrition Research Center for the entire study. The basal (low-DHA) diet consisted of natural foods (30 en% fat, 15 en% protein, and 55 en% carbohydrate), containing <50 mg/d of DHA, and met the recommended daily intake for all essential nutrients. The high-DHA (intervention) diet was similar except that 6 g/d of DHA in the form of a triglyceride containing 40% DHA replaced an equal amount of safflower oil in the basal diet. The subjects (ages 20 to 39) were within −10 to +20% of ideal body weight, nonsmoking, and not allowed alcohol in the MRU. Their exercise level was constant, and their body weights were maintained within 2% of entry level. They were initially fed the low-DHA diet for 30 d. On day 31, six subjects (intervention, group A) were placed on the high-DHA diet; the other four subjects (controls, group B) remained on the low-DHA diet. Platelet aggregation in platelet-rich plasma was determined using ADP, collagen, and arachidonic acid. No statistical differences could be detected between the amount of agonist required to produce 50% aggregation of platelet-rich plasma before and after the subjects consumed the high-DHA diet. The prothrombin time, activated partial thromboplastin time, and the antithrombin-III levels in the subjects were determined, and, again, there were no statistically significant differences in these three parameters when their values were compared before and after the subjects consumed the high-DHA diet. In addition, the in vivo bleeding times did not show any significant difference before and after the subjects consumed the high-DHA diet (9.4 ±3.1 min before and 8.0±3.4 min after). Platelets from the volunteers exhibited more than a threefold increase in their DHA content from 1.54±0.16 to 5.48±1.21 (wt%) during the DHA feeding period. The EPA content of the subjects’ platelets increased from 0.34±0.12 to 2.67±0.91 (wt%) during the high-DHA diet despite the absence of EPA in the subjects’ diets. The results from this study on blood clotting parameters and in vitro platelet aggregation suggest that adding 6 g/d of dietary DHA for 90 d to a typical Western diet containing less than 50 mg/d of DHA produces no observable physiological changes in blood coagulation, platelet function, or thrombotic tendencies in healthy, adult males.     

The effect of conjugated linoleic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans

Despite extensive research on conjugated linoleic acid (CLA) showing multiple beneficial effects in animal models, little is known about the role of dietary CLA in human health. To investigate if the beneficial effects of CLA seen in animal models are relevant to humans, we conducted a study with 17 healthy female volunteers who lived in the Metabolic Research Unit of the Western Human Nutrition Research Center for 93 d. This paper reports only the results from this study that are related to the effects of CLA supplementation on blood coagulation, platelet function, and platelet fatty acid composition. Throughout the study, the subjects were fed a low-fat diet (30 en% fat, 19 en% protein, and 51 en% carbohydrate) consisting of natural foods with the recommended dietary allowances for all known nutrients. After a 30-d stabilization period, subjects were randomly assigned to either an intervention group (n=10) whose diet was supplemented with 3.9 g/d of CLA or a control group (n=7) who received an equivalent amount of sunflower oil consisting of 72.6% linoleic acid with no detectable CLA. Platelet aggregation was measured in platelet-rich plasma using adenosine diphosphate, collagen, and arachidonic acid agonists. No statistical difference was detected between the amount of agonist required to produce 50% aggregation of platelet-rich plasma before and after the subjects consumed the CLA, with the exception of a decrease in response to collagen. This decrease was found in both control and intervention groups with no significant difference between the groups, suggesting that both linoleic acid (sunflower oil) and CLA might have similar effects on platelet function. The prothrombin time, activated partial thromboplastin time, and the antithrombin III levels in the subjects were determined. Again, there was no statistically significant difference in these three parameters when pre-and post-CLA consumption values were compared. The in vivo bleeding times were also unaffected by CLA supplementation (10.4+2.8 min pre- and 10.2+1.6 min postconsumption). Platelet fatty acid composition was not markedly influenced by the consumption of dietary CLA, although there was a small increase in the amount of the 9 cis, 11 trans-18∶2 isomer normally present in platelets after feeding CLA for 63 days. In addition, small amounts of the 8 trans, 10 cis-18∶2 and the 10 trans, 12 cis-18∶2 isomers were detected in the platelets along with traces of some of the other isomers. Thus, when compared to sunflower     

The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans

Normal healthy male volunteers (n=10) were fed diets (high-AA) containing 1.7 g/d of arachidonic acid (AA) for 50 d. The control (low-AA) diet contained 210 mg/d of AA. Dietary AA had no statistically significant effect on the blood cholesterol levels, lipoprotein distribution, or apoprotein levels. Adipose tissue fatty acid composition was not influenced by AA feeding. The plasma total fatty acid composition was markedly enriched in AA after 50 d (P<0.005). The fatty acid composition of plasma lipid fractions, cholesterol esters, triglycerides, free fatty acids, and phospholipid (PL) showed marked differences in the degree of enrichment in AA. The PL plasma fraction from the subjects consuming the low-AA diet contained 10.3% AA while the subjects who consumed the high-AA diet had plasma PL fractions containing 19.0% AA. The level of 22:4n-6 also was different (0.67 to 1.06%) in the plasma PL fraction after 50 d of AA feeding. After consuming the high-AA diet, the total red blood cell fatty acid composition was significantly enriched in AA which mainly replaced linoleic acid. These results indicate that dietary AA is incorporated into tissue lipids, but selectively into different tissues and lipid classes. Perhaps more importantly, the results demonstrate that dietary AA does not alter blood lipids or lipoprotein levels or have obvious adverse health effects at this level and duration of feeding.     

The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans

Normal, healthy male volunteers (n=6) were fed diets [high docosahexaenoic acid-DHA] containing 6 g/d of DHA for 90 d. The stabilization (low-DHA) diet contained less than 50 mg/d of DHA. A control group (n=4) remained on the low-DHA diet for the duration of the study (120 d). Blood samples were drawn on study days 30 (end of the stabilization period), 75 (midpoint of the intervention period), and 120 (end of the intervention period). Adipose tissue (AT) samples were taken on days 30 and 120. The plasma cholesterol (C), low density lipoprotein (LDL)-C and apolipoproteins (apo) [Al, B, and lipoprotein (a)] were unchanged after 90 d, but the triglycerides (TAG) were reduced from a mean value of 76.67±24.32 to 63.83±16.99 mg/dL (n=6, P<0.007 using a paired t-test) and the high density lipoprotein (HDL)-C increased from 34.83±4.38 mg/dL to 37.83±3.32 mg/dL (n=6, P<0.017 using a paired t-test). The control group showed no significant reduction in plasma TAG levels. Apo-E, however, showed a marked increase in the volunteers’ plasma after 90 d on the high-DHA diet, from 7.06±4.47 mg/dL on study day 30 to 12.01±4.96 mg/dL on study day 120 (P<0.002 using a paired t-test). The control subjects showed no significant change in the apo-E in their plasma (8.46±2.90 on day 30 vs. 8.59±2.97 on day 120). The weight percentage of plasma DHA rose from 1.83±0.22 to 8.12±0.76 after 90 d on the high-DHA diet. Although these volunteers were eating a diet free of eicosapentaenoic acid (EPA), plasma EPA levels rose from 0.38±0.05 to 3.39±0.52 (wt%) after consuming the high-DHA diet. The fatty acid composition of plasma lipid fractions—cholesterol esters, TAG, and phospholipid—showed marked similarity in the enrichment of DHA, about 10%, after the subjects consumed the high-DHA diet. The DHA content of these plasma lipid fractions varied from less than 1% (TAG) to 3.5% (phospholipids) at baseline, study day 30. EPA also increased in all plasma lipid fractions after the subjects consumed the high-DHA diet. There were no changes in the plasma DHA or EPA levels in the control group. Consumption of DHA also caused an increase in AT levels of DHA, from 0.10±0.02 to 0.31±0.07 (wt%) (n=6, P<0.001 using a paired t-test), but the amount of EPA in their AT did not change. Thus, dietary DHA will lower plasma TAG without EPA, and DHA is retroconverted to EPA in significant amounts. Dietary DHA appears to enhance apo-E synthesis in the liver. It appears that DHA can be a safe and perhaps beneficial supplement to human diets.     

Effects of dietary marine oils and olive oil on fatty acid composition, platelet membrane fluidity, platelet responses, and serum lipids in healthy humans

The influence of various dietary marine oils and olive oil on fatty acid composition of serum and platelets and effects on platelets and serum lipids were investigated as part of an extensive study of the effects of these oils on parameters associated with cardiovascular/thrombotic diseases. Healthy volunteers (266) consumed 15 mL/d of cod liver oil (CLO); whale blubber oil (refined or unrefined); mixtures of seal blubber oil and CLO; or olive oil/CLO for 12 wk. In the CLO, seal oil/CLO, and whale oil groups, serum levels of eicosapentaenoic acid (EPA) were increased. In platelets, EPA was increased in the CLO, seal/CLO, and olive oil/CLO groups. The localization of n-3 polyunsaturated fatty acids in the triacylglycerols did not seem to influence their absorption. Intake of oleic acid is poorly reflected in serum and platelets. No significant differences in triacylglycerols (IG), total cholesterol, or high density lipoprotein cholesterol were observed, even though TG were reduced in the CLO, CLO/seal oil, and whale oil groups. Mean platelet volume increased significantly in both whale oil groups and the CLO/olive oil group. Platelet count was significantly reduced in the refined whale oil group only. Lipopolysaccharide-stimulated blood tended to generate less thromboxane B₂ in CLO, CLO/seal, and CLO/olive groups. The whale oils tended to reduce in vivo release of β-thromboglobulin. In conclusion, intake of various marine oils causes changes in platelet membranes that are favorably antithrombotic. The combination of CLO and olive oil may produce better effects than these oils given separately. The changes in platelet function are directly associated with alterations of fatty acid composition in platelet membranes.     

Dietary α-linolenic acid alters tissue fatty acid composition,but not blood lipids,lipoproteins or coagulation status in humans

We examined the effect of dietary α-linolenic acid (ALA) on the indices of lipid and coagulation status and on the fatty acid composition of serum and peripheral blood mononuclear cell (PBMNC) lipids in ten healthy men (age 21–37 yr) who consumed all their meals at the Western Human Nutrition Research Center for 126 d. There was a stabilization period of 14 d at the start when all 10 subjects consumed the basal diet (BD) containing 23.4 energy percent (en%) fat and two intervention periods of 56 d each. During the first intervention period, 5 subjects consumed the BD containing 23.4 en% fat, and 5 subjects consumed a diet providing 6.3% calories from α-linolenic acid [flaxseed oil (FSO) diet containing 28.8 en% fat]. Diets were crossed over between the two groups during the second intervention period. Feeding the FSO diet did not nignificantly alter serum triglycerides, cholesterol, highdensity lipoproteins, low-density lipoproteins, apoprotein A-I and apoprotein B when compared to the corresponding values in the subjects fed the BD, nor was there any effect of the FSO diet on the bleeding time, prothrombin time and partial prothrombin time for these subjects. Feeding the ALA-containing diet did cause a significant increase in ALA concentration in serum (P<0.001) and PBMNC lipids (P<0.05). It also caused a significant increase (P<0.05) in the eicosapentaenoic and docosapentaenoic acid contents of PBMNC lipids, and a decrease (P<0.01) in linoleic and eicosatrienoic acid contents of serum lipids. Thus, dietary ALA, fed for 56 d at 6.3% of calories, had no effect on plasma triglyceride or very low density lipoprotein levels or the common risk factors associated with atherosclerosis, although these parameters have been reported by others to be influenced by fatty acids, such as palmitic or linoleic acids, in the diet. Dietary ALA did significantly alter the fatty acid composition of plasma and PBMNC. The views expressed in the paper are those of the authors and do not reflect the official policy or position of the Department of Agriculture or Department of Defense, or the U.S. Government.     

The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans

Conjugated linoleic acid (CLA) has been suggested by some animal studies to possess antiatherogenic properties. To determine, in humans, the effect of dietary CLA on blood lipids, lipoproteins, and tissue fatty acid composition, we conducted a 93-d study with 17 healthy female volunteers at the Metabolic Research Unit of the Western Human Nutrition Research Center. Throughout the study, subjects were fed a low-fat diet [30 energy percent (en%) fat, 19 en% protein, and 51 en% carbohydrate] that consisted of natural foods with the recommended dietary allowances for all known nutrients. After a 30-d stabilization period, subjects were randomly assigned to either an intervention group (n=10) supplemented daily with capsules containing 3.9 g of CLA or a control group (n=7) that received an equivalent amount of sunflower oil. The CIA capsules (CLA 65%) contained four major cis/trans geometric isomers (11.4% 9 cis-,11 trans-18∶2; 10.8% 8 trans-,10 cis-18∶2; 15.3% 11 cis-,13 trans-18∶2; and 14.7% 10 trans-, 12 cis-18∶2) and their corresponding cis/cis (6.74% total) and trans/trans (5.99% total) varieties in smaller amounts. Fasting blood was drawn on study days 30 (end of the stabilization period), 60 (midpoint of the intervention period), and 93 (end of the intervention period). Adipose tissue samples were taken on days 30 and 93. CLA supplementation for 63 d did not change the levels of plasma cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. The weight percentage of CLA in plasma increased from 0.28±0.06 to 1.09±0.31 (n=10, P<0.05) after the supplementation. The 9 cis-,11 trans-isomer was the most prominent variety followed by the 11 cis-,13 trans- and 10 trans-,12 cis-isomers in lesser amounts. CLA in adipose tissue was not influenced by the supplementation (0.79±0.18 to 0.83±0.19 wt%) (n=10) and the 9 cis-,11 trans-variety was the only isomer present. Thus, contrary to findings from some animal studies, CLA does not seem to offer health benefits, in the short term, regarding the prevention of atherosclerosis in humans. CLA supplementation for 2 mon did not alter the blood cholesterol or lipoprotein levels of healthy, normolipidemic subjects. The supplementation did increase CLA in the plasma but only 4.23% of the ingested CLA was present in the plasma at any given time. No adverse effect of CLA supplementation was detected in this study.     

The phospholipid and fatty acid composition of platelets in patients with primary defects of platelet function

Platelet phospholipid and fatty acid composition was determined in nine normal subjects and in 11 patients with primary defects in platelet function. Two of the patients had thrombasthenia (Glanzmann) and nine had various types of abnormalities in platelet aggregation and platelet factor 3 availability attributed to impairment of the platelet release reaction. The values observed for platelet lipids in the normal subjects were similar to those reported by others. Four of the patients with a disturbance in the platelet release reaction were in the same family and showed the same abnormal pattern of platelet lipid composition. Phospholipid analysis showed a decrease in the relative amount of phosphatidyl ethanolamine (PE) and an increase in lecithin. Abnormalities in fatty acids consisted of an increase in the relative amounts of 18∶1ω9, 20∶0 and 20∶1ω9 and a decrease in the 22∶4ω6+24∶1 fraction. Similar changes in PE and 18∶1ω9 were also observed in another patient with a similar defect in platelet function. In this patient the relative amount of platelet sphingomyelin was also increased. The platelet lipid composition in the other six patients and in one normal subject given aspirin was essentially normal.     

The effect of dietary fat on the fatty acid composition of lipids secreted in rats' milk

During pregnancy and lactation, female rats were fed diets containing either 28% partially hydrogenated marine oil (28MO), 2% arachis oil (2AO), or no fat (FF). Milk lipid composition was examined by gas chromatographic analysis of the gastric content of 10-day-old suckling pups. An increase to 45% in the milk content of long chain monoenoic acids, 18∶1, 20∶1 and 22∶1, reflects the fatty acid composition of the marine oil. Milk fatty acids of medium chain length comprised 6%, 31% and 24% of total fatty acids in the (28MO), (2AO) and (FF) groups, respectively, suggesting that a high-fat diet (28MO) inhibits the lipid synthetic activity of mammary glands. The amount of dienoic C₁₈-acids (6%) in the group fed (28MO) containing no essential fatty acids (EFA) was similar to the amount of 18∶2 in the group receiving a low-fat, EFA-rich diet (2AO). However, only half the dienoic acid from the milk of the (28MO)-fed animals was linoleic acid, which was most likely mobilized from fat depots.     

The effect of dietary n−6 and n−3 polyunsaturated fatty acids on blood pressure and tissue fatty acid composition in spontaneously hypertensive rats

Effects of dietary n−6 and n−3 fatty acids (FAs) on blood pressure (BP) and tissue phospholipid (PL) FA composition in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were compared. Male weanling SHR and WKY were fed a fat-free semisynthetic diet supplemented with 10% (w/w) fats containing (a) 78% 18∶2n−6 (LA-rich), (b) 20% LA and 55% 18∶3n−3 (LN-rich), or (c) 11% LA and 3% LN (CON) for seven weeks. Dietary fats did not affect the BP elevation, but significantly altered the FA composition of brain, adrenal gland, renal medulla and cortex PL in SHR. The LA-rich diet increased n−6 FA while it reduced n−3 FA levels. The levels of 20∶4n−6 were not significantly different between animals fed the LA-rich and the CON diets. LN-rich diet increased the levels of n−3 FAs, while it reduced those of n−6 FAs. However, the extent of change was significantly less in SHR than in WKY. In all dietary groups, SHR, as compared to WKY, had a relatively higher level of the 2 series prostaglandin (PG) precursor, 20∶4n−6, and a relatively lower level of the 1 and 3 series PG precursors, 20∶3n−6 and 20∶5n−3. The possibility that the unbalanced eicosanoid FA precursor levels might contribute to the development of hypertension in this animal model is discussed.     

The effect of peroxidized arachidonic acid upon human platelet aggregation

Human platelet aggregation was studied in vitro following exposure to free arachidonic acid and peroxidized arachidonic acid. A slow aggregation response was caused by free arachidonic acid, whereas a rapid, marked response resulted from exposure to peroxidized free arachidonic acid. Aggregation resulting from peroxidized arachidonic acid was not counteracted by adenosine nor by prostaglandin E₁, both in high concentrations. Peroxide-induced platelet aggregation required the presence of added calcium ions in vitro. The aggregation resulting from exposure to peroxidized arachidonic acid was abolished by prior treatment of the lipid peroxide with tocopherol and butylated hydroxy toluenne.     

The effect of dietary supplementation with eicosapentaenoic acid on the phospholipid and fatty acid composition of erythrocytes of marmoset

Adult male marmoset monkeys were fed eicosapentaenoic acid (20∶5n−3) as the ethyl ester in diets containing either 32% (reference diet, no added cholesterol) or 7% (atherogenic diet with 0.2% added cholesterol) linoleic acid (18∶2n−6) for 30 wk. No changes were seen in the level of phosphatidylcholine (PC) or phosphatidylethanolamine (PE) but minor changes were observed in both the sphingomyelin (SPM) and phosphatidylinositol plus phosphatidylserine (PI+PS) fractions of erythrocyte lipids. The extent of total n−3 fatty acid incorporation into membrane lipids was higher in atherogenic diets (polyunsaturated/monounsaturated/saturated (P/M/S) ratio 0.2∶0.6∶1.0) than reference diets (P/M/S ratio 1∶1∶1) and this was true for both PE (33.4±1.0%vs 24.3±1.1%) and PC (9.3±0.5%vs 4.9±0.3%). Although suitable controls for cholesterol effects were not included in the study, earlier results obtained with marmosets lead us to believe such effects were probably small. Regardless of basic diet (atherogenic, reference), 20∶5n−3 was preferentially incorporated into PE (10.8±0.2%, 6.0±0.02%) while smaller amounts were incorporated into PC (6.9±0.4%, 3.2±0.2%). The major n−3 polyunsaturated fatty acid found in PE in response to dietary 20∶5n−3 was the elongation metabolite 22∶5n−3 in both the atherogenic (17.7±0.7%) and reference (14.3±1.0%) dietary groups; 22∶6n−3 levels were less affected by diet (4.7±0.3% and 3.9±0.2%, respectively). The results can be interpreted to indicate an inverse relationship between the amount of dietary 18∶2n−6 and incorporation of 20∶5n−3 into erythrocyte membrane phospholipids regardless of whether the major dietary n−3 fatty acid was α-linolenate (18∶3n−3) or 20∶5n−3. This interpretation is supported by theoretical calculations.     

Effect of maternal dietary arachidonic or linoleic acid on rat pup fatty acid profiles

Rapidly growing neonatal mammals accrete relatively large quantities of long chain (≥C₂₀) polyunsaturated fatty acids (LCP) in membrane phospholipids. We have examined accumulation of ω6 LCP in suckling neonatal rat pups during the first 14 d of life when their dams received essential fatty acids in the form of triglycerides containing linoleic acid or arachidonic acid. Dietary levels of these fatty acids were either 1 or 5% of total dietary fatty acids. The fatty acid profile of pup stomach contents (composed solely of the dams' milk) and plasma lipids, as well as liver and brain phospholipids, were determined. Stomach linoleic and arachidonic acid levels reflected the diet of the dams. Pup plasma and liver arachidonic acid levels increased progressively from the group receiving 1% linoleic acid to 5% linoleic acid and from 1% arachidonic acid to 5% arachidonic acid. Interestingly, brain phosphatidylethanolamine and phosphatidylcholine arachidonic acid levels were more stable than plasma or liver levels. These results suggest that the brain may be capable of either selective transport of ω6 LCP or chain elongation/desaturation of linoleic acid. These data indicate that care must be exercised when adding LCP to infant formula since widely divergent accretion rates of arachidonic acid may occur in various tissues.     

Increased dietary arachidonic acid enhances the synthesis of vasoactive eicosanoids in humans

Data on the effect of dietary arachidonic acid (AA) (20∶4n-6) on the synthesis of thromboxane and prostacyclin (PGI₂) in humans are lacking. We measured the effect of 1.5 g/d (ca. 0.5 en%) of 20∶4n-6 added isocalorically to a stabilization (low-AA) diet on the excretion of 11-dehydrothromboxane B₂ (11-DTXB₂) and 2,3-dinor-6-oxo-PGF_1α (PGI₂-M). In a crossover design, 10 healthy men, living in a metabolic unit, were fed a diet (low-AA) containing 210 mg/d of 20∶4n-6 for 65 d and an identical diet (high-AA) that contained 1.5 g/d of additional 20∶4n-6 for 50 d. Three-day urine pools were collected at the end of each dietary period and analyzed for eicosanoids by gas chromatography-electron capture negative ion-tandem mass spectrometry. Mean excretion of 11-dehydrothromboxane B₂ was 515±76, 493±154, and 696±144 ng/d (SD; n=10) during the acclimation (15 d) low-AA diet and high-AA diet periods, respectively (41% increase from low-AA to high-AA diet, P=0.0037); mean excretion of PGI₂-M was 125±40, 151±36, and 192±55 ng/d (SD; n=10) during acclimation (15 d) low-AA and high-AA diets, respectively (27% increase from low-AA to high-AA diets; P=0.0143). Thus, both the metabolites of thromboxane and PGI₂ increase on the high-AA diet. Furthermore, both indicated changes in metabolite excretion may be associated with measurable effects on several physiologically significant cellular functions, such as platelet aggregation in vivo and inflammation in response to immune challenges.     

Influence of dietary arachidonic acid on metabolism in vivo of 8 cis, 11 cis, 14-eicosatrienoic acid in humans

This study investigated the influence of dietary arachidonic acid (20∶4n-6) on Δ5 desaturation and incorporation of deuterium-labeled 8cis, 11cis, 14-eicosatrienoic acid (20∶3n-6) into human plasma lipids. Adult male subjects (n=4) were fed diets containing either 1.7 g/d (H120∶4 diet) or 0.21 g/d (LO20∶4 diet) of arachidonic acid for 50 d and then dosed with a mixture containing ethyl esters of 20∶3n-6[d4] and 18∶1n-9[d2]. A series of blood samples was sequentially drawn over a 72-h period, and methyl esters of plasma total lipid, triacylglycerol, phospholipids, and cholesteryl ester were analyzed by gas chromatography-mass spectrometry. Based on the concentration of 20∶3n-6[d4] in total plasma lipid, the estimated conversion of 20∶3n-6[d4] to 20∶4n-6[d4] was 17.7.±0.79% (HI20∶4 diet) and 2.13±1.44% (LO20∶4 diet). The concentrations of 20∶4n-6[d4] in total plasma lipids from subjects fed the HI20∶4 and LO20∶4 diets were 2.10±0.6 and 0.29±0.2 μmole/mL plasma/mmole of 20∶3n-6[d4] fed/kg of body weight. These data indicate that conversion of 20∶3n-6[d4] to 20∶4n-6[d4] was stimulated 7-8-fold by the HI20∶4 diet. Phospholipid acyltransferase was 2.5-fold more selective for 20∶3n-6[d4] than 18∶1n-9[d2], and lecithin:cholesterol acyltransferase was 2-fold more selective for 18∶1n-9[d2] than 20∶3n-6[d4]. These differences in selectivity were not significantly influenced by diet. Absorption of ethyl 20∶3n-6[d4] was about 33% less than ethyl 18∶1n-9[d2]. The sum of the n-6 retroconversion products from 20∶3n-6[d4] in total plasma lipids was about 2% of the total deuterated fatty acids. Neither absorption nor retroconversion appears to be influenced by diet.     

The influence of dietary fatty acids and environmental temperature on the fatty acid composition of teleost fish

Marine and fresh water fish were depleted of tissue unsaturated fatty acids to various degrees and subsequently presented with linoleic and linolenic acids at different dietary levels, at different temperatures, with and without other dietary fat. Examination of the tissue fatty acids demonstrated that marine and fresh water fish do not differ between themselves or from other classes of animals in the following basic mechanisms of deposition and interconversions of dietary fatty acids:

1. 1)
   The fish are readily depleted of tissue polyunsaturated fatty acids.     
   
   

The effect of fatty acid composition on biodiesel oxidative stability

Concerning their environmental impact, native based fuels and lubricants show immense potential. In fact, these products are highly exposed to oxidative processes during storage or application [1, 2]. One way to raise oxidative stabilities is the addition of synthetic antioxidants. Another way may be the modification of the fatty acid composition, since polyunsaturated fatty acids show a much higher proneness to autoxidation. In order to decrease the content of polyunsaturated and to raise the content of saturated components, experiments for fractional distillation and crystallisation as well as for hydrogenation of fatty acid methyl esters have been carried out. In distillation experiments with separation columns the methyl esters performed good separation of the lower‐boiling esters with a chain‐length up to 16C‐atoms, from the C‐18 fraction, causing a degree of saturation up to 75 wt‐% in the distillate. In tests with fractional crystallisation, the rate of saturation could be raised up to 92.8 wt‐%. Using the process of catalytic hydrogenation, a rate of saturation up to 100 wt‐% could be achieved, depending on the duration of the hydrogenation process. By partial hydrogenation of the polyunsaturated components, products with high oxidation stability and low pour point could be produced within relatively short hydrogenation time.     

Modulation of adjuvant-induced arthritis by dietary arachidonic acid in essential fatty acid-deficient rats

Controlled feeding of linoleic acid (LA) or arachidonic acid (AA) to essential fatty acid-deficient (EFAD) rats was used to define the relationship between dietary AA and the inflammatory response evoked during adjuvant-induced arthritis. Based on energy percentage, EFAD rats were fed AA at the human daily equivalent (1×; 5.5 mg/day) or 10 times that amount (10×; 55 mg/day) or, alternatively, 0.5× of LA (273 mg/day). Feeding of 0.5×LA restored the plasma level of AA to that in chow-fed controls. In contrast, feeding of 1×AA only partially restored the plasma level of AA; 10×AA was required to fully replete AA. In parallel to the degree of repletion of AA in plasma, there were accompanying decreases in the levels of palmitoleic acid, oleic acid, and Mead acid. Compared to rats fed the standard laboratory chow diet (Control), edema in the primary hind footpads was decreased by 87% in EFAD, 71% in EFAD+1×AA, 45% in EFAD+10×AA, and 30% in EFAD+0.5×LA. The decrease in edema in the footpads of EFAD rats was nearly identical to the decrease in edema in the footpads of Control rats dosed with indomethacin. Hind footpad edema correlated with the final AA plasma level and eicosanoid levels extracted from hind footpad tissue, but not with neutrophil infiltration. The data showed that 0.5×LA and 10×AA, but not 1×AA, could quickly replete AA, accompanied by the synthesis of AA-derived eicosanoids and restoration of edema. These results suggest that in humans consumption of the average daily amount of AA without concurrent ingestion of LA would not alleviate an EFAD state.     

New findings in the fatty acid composition of individual platelet phospholipids in man after dietary fish oil supplementation

Nine healthy male volunteers were given 15 Max EPA fish oil capsules providing 2.67 g of eicosapentaenoic acid (EPA, 20∶5ω3) and 1.72 g of docosahexaenoic acid (DHA, 22∶6ω3) daily for 3 wk. Measurements were taken at baseline, at the end of the fish-oil period, and at 2 and 6 wk postsupplementation. The effect of fish oil on plasma lipids and the fatty acid composition of individual platelet phospholipids was studied. In general, the proportions of 20∶5ω3 and 22∶6ω3 in platelet phosphoglycerides were substantially increased mainly at the expense of arachidonic acid (AA, 20∶4ω6). A large and significant increase in the relative EPA content of phosphatidylcholine (PC) (P<0.001) and phosphatidylethanolamine (PE) (P<0.001) was noted at the end of the 3 wk supplementation. We have also shown for the first time a small but significant (P<0.001) incorporation of EPA in phosphatidylserine (PS). Incorporation of DHA was also detected in PC, PE and PS, whereas the relative AA content of these phospholipids was significantly reduced. Fish oil supplementation led to a significant increase of 22∶5ω3 in PS and decreases of 20∶3ω6 in PC and 22∶4ω6 in PE. Postsupplementation measurements showed a gradual return of all fatty acids to baseline levels. The fatty acid composition of the phosphatidylinositol (PI) fraction remained unchanged throughout the trial period. We conclude that in humans ω3 fatty acids are incorporated into platelet membrane phospholipid subclasses with a high degree of specificity.     

Effect of subacute toxic levels of dietary cyclopropenoid fatty acids upon membrane function and fatty acid composition in the rat

The effect of subacute toxicity levels of dietary cyclopropenoid fatty acids upon several physiological parameters was determined in the rat. Diets containing 2% corn oil, 2%Sterculia foetida oil or 2% hydrogenatedSterculia foetida oil were fed.Sterculia foetida oil (50% cyclopropenoid fatty acids) fed rats exhibited retarded growth, elevated organ to body wt ratios, increased saturation of tissue lipid, and abnormal histopathology when compared to corn oil and hydrogenatedSterculia foetida oil fed rats. Growth was retarded 50%, liver/body wt doubled, and the percentage of saturated fatty acids in adipose tissue increased 2.5-fold forSterculia foetida oil vs. corn oil comparisons. Three membrane systems were examined in corn oil andSterculia foetida oil fed rats. Erythrocyte hemolysis rate in 0.3 M glycerol was increased by 30%; induction of mitochondrial swelling by reduced glutathione was inhibited completely and microsomal codeine demethylase activity was depressed nearly 50% inSterculia foetida oil fed rats. The ability of cyclopropenoid fatty acids to inhibit fatty acyl desaturase and influence tissue and membrane lipid composition is discussed. Most of the detrimental effects observed in cyclopropenoid fatty acids fed rats may be associated with alteration of normal lipid metabolism and membrane function.