Plasma Linoleic Acid Concentration Research Articles

Analysis of omega-3 and omega-6 polyunsaturated fatty acid metabolism by compound-specific isotope analysis in humans

Natural variations in the 13C:12C ratio (carbon-13 isotopic abundance [δ13C]) of the food supply have been used to determine the dietary origin and metabolism of fatty acids, especially in the n-3 PUFA biosynthesis pathway. However, n-6 PUFA metabolism following linoleic acid (LNA) intake remains under investigation. Here, we sought to use natural variations in the δ13C signature of dietary oils and fatty fish to analyze n-3 and n-6 PUFA metabolism following dietary changes in LNA and eicosapentaenoic acid (EPA) + DHA in adult humans. Participants with migraine (aged 38.6 ± 2.3 years, 93% female, body mass index of 27.0 ± 1.1 kg/m2) were randomly assigned to one of three dietary groups for 16 weeks: 1) low omega-3, high omega-6 (H6), 2) high omega-3, high omega-6 (H3H6), or 3) high omega-3, low omega-6 (H3). Blood was collected at baseline, 4, 10, and 16 weeks. Plasma PUFA concentrations and δ13C were determined. The H6 intervention exhibited increases in plasma LNA δ13C signature over time; meanwhile, plasma LNA concentrations were unchanged. No changes in plasma arachidonic acid δ13C or concentration were observed. Participants on the H3H6 and H3 interventions demonstrated increases in plasma EPA and DHA concentration over time. Plasma δ13C-EPA increased in total lipids of the H3 group and phospholipids of the H3H6 group compared with baseline. Compound-specific isotope analysis supports a tracer-free technique that can track metabolism of dietary fatty acids in humans, provided that the isotopic signature of the dietary source is sufficiently different from plasma δ13C.

Some Aspects of Neonatal Essential Fatty Acid Status are Altered by Linoleic Acid Supplementation of Women during Pregnancy

To study the effect of maternal linoleic acid [18:2(n-6), LA] supplementation during pregnancy on neonatal essential fatty acid status, pregnant women with relatively low plasma linoleic acid concentrations before 16 wk of gestation (n = 21) were supplied with foods rich in linoleic acid, resulting in an additional intake of 10 g/d of linoleic acid from the 20th week of gestation until delivery. One of the two control groups consisted of pregnant women with comparably low plasma linoleic acid concentrations at the start of the study (LL-control group, n = 22); the other consisted of women with habitually high plasma linoleic acid concentrations (HL-control group, n = 21). The neonatal essential fatty acid status was assessed by determining the fatty acid composition of phospholipids (PL) isolated from umbilical plasma and umbilical vessel walls. The maternal linoleic acid status in the LA-supplemented group increased to a level comparable to that of the HL-control group, but the neonatal linoleic acid status did not differ from that of either control group. Linoleic acid supplementation did result in slightly, but significantly, higher total amounts of (n-6) long-chain polyenes in umbilical plasma and vein vessel wall phospholipids compared with the LL-control group. This increase was associated with significantly lower total amounts of (n-3) long-chain polyenes. In the HL-control group, the concentration of (n-3) long-chain polyenes in umbilical plasma and vessel walls was significantly lower than in the LA-supplemented and the LL-control group. The results of this study indicate that maternal linoleic acid supplementation can affect some aspects of neonatal essential fatty acid status.

Post–artificial insemination supplementation with calcium salts of soybean oil influences pregnancy establishment factors in Bos indicus beef cows1

The objective of this experiment was to compare hormonal, uterine, and conceptus factors associated with pregnancy establishment in beef cows supplemented or not with Ca salts of soybean oil (CSSO) for 21 d beginning after timed AI. One hundred lactating multiparous Nelore cows were allocated to 20 groups of 5 cows/group and timed inseminated on d 0 of the experiment. After AI, groups were randomly assigned to receive (as-fed basis) 100 g of protein-mineral mix + 100 g of ground corn per cow per day, in addition to 1) 100 g/cow daily of CSSO ( = 10) or 2) 100 g/cow daily of kaolin (CON; rumen-inert indigestible substance; = 10). Groups were maintained in 4 pastures (5 groups from the same treatment within each pasture) with ad libitum access to forage. Groups were segregated daily and individually offered treatments from d 0 to 21. Blood samples were collected and transrectal ultrasonography was performed to verify ovulation and corpus luteum (CL) volume immediately before AI (d 0) and on d 7 and 15. After ultrasonography on d 15, 60 cows (30 cows/treatment and 3 cows/group) diagnosed without the presence of a CL on d 0 but with a CL greater than 0.38 cm3 in volume on d 7 and 15 were assigned to conceptus collection via transcervical flushing with PBS followed by endometrial biopsy in the uterine horn ipsilateral to the CL. Additional blood samples were collected for whole-blood RNA extraction (d 20), and pregnancy status was verified by transrectal ultrasonography (d 30) in cows not assigned to conceptus collection. Cows receiving CSSO had greater ( ≤ 0.04) mean plasma linoleic acid concentration, plasma linoleic:linolenic acid ratio, plasma progesterone (P4) concentration, and CL volume during the experiment compared with CON cows. Moreover, CSSO supplementation increased ( ≤ 0.04) length and mRNA expression of and by the conceptus as well as blood mRNA expression of interferon-stimulated genes on d 20 in gestating cows. No treatment differences were detected ( ≥ 0.30) for endometrial mRNA expression of and . In summary, post-AI CSSO supplementation to B. indicus beef cows increased plasma concentration of linoleic acid and enhanced pregnancy establishment factors, which included CL development and plasma P4 concentration, conceptus growth, and mRNA expression of as well as blood mRNA expression of interferon-stimulated genes.

Effects of Marginal Vitamin B6 Deficiency on Plasma Fatty Acid Profiles in Healthy Men and Women

The interaction between vitamin B6 (VB6) and lipid metabolism is not well understood. Previous studies indicated that linoleic acid (LA) levels increased and arachidonic acid (AA) levels decreased in different tissues of VB6‐deficient rats, suggesting an altered n‐6 pathway of fatty acid (FA) synthesis. Our study aimed to determine the effect of marginal VB6 deficiency on plasma FA in human subjects. Thirteen healthy subjects (7 men and 6 women, aged 20–39 yr) received a 2‐d adequate diet followed by a 28‐d VB6 restricted diet (0.5 mg/d) to reach a marginal VB6 deficiency (plasma pyridoxal‐5′‐phosphate 20–30 nM). Fasting blood samples were collected after 2‐d of adequate diet and after 28‐d of VB6 restricted diet. Plasma total FA profiles were analyzed by gas chromatography/flame ionization detection. After 28‐d of VB6 restriction, AA concentration decreased significantly from (mean ± SD) 533 ± 72 nM to 479 ± 59 nM (p=0.004). The conversion indices of AA/LA also significantly decreased from 0.23 ± 0.04 to 0.20 ± 0.04 (p<0.001). There was a slight but non‐significant increase in plasma LA concentration. However, we did not observe any significant alteration in n‐3 fatty acid concentrations. In conclusion, marginal VB6 deficiency is associated with alterations in the distribution of n‐6 fatty acids in plasma lipids in healthy men and women. Supported by NIH grant DK072398 and GCRC grant M01‐RR00082.

Suppressive effect of a selective increase in plasma linoleic acid concentration and intravascular lipolysis on peripheral T cell activation

Suppressive effect of a selective increase in plasma linoleic acid concentration and intravascular lipolysis on peripheral T cell activation

Acute in vivo elevation of intravascular triacylglycerol lipolysis impairs peripheral T cell activation in humans

Previous studies have shown suppressive effects of polyunsaturated fatty acids (PUFAs) on T cell proliferation, but the precise mechanism for this effect has not been fully investigated in vivo in humans. The objective was to determine whether this effect is the result of altered T cell membrane properties and impaired CD3- and CD28-mediated signaling in vivo in humans. Peripheral T cells were isolated from healthy subjects before and 2 h after an intravenous infusion of heparin plus a PUFA-rich lipid emulsion during a euglycemic hyperinsulinemic clamp to induce a 2.5-fold elevation in plasma linoleic acid concentration without significant change in plasma total free fatty acid concentrations. Intravenous infusion of heparin plus the lipid emulsion reduced peripheral T cell membrane fluidity and altered lipid raft organization, both of which were associated with reduced T cell proliferation after stimulation with CD3 plus CD28. Tyrosine phosphorylation of linker of activated T cells and activation of protein kinase B in T cells were also impaired without a reduction in T cell receptor expression. In addition, acute PUFA elevation was associated with a reduction in T cell membrane cholesterol exchange with the cellular milieu ex vivo. A selective increase in plasma linoleic acid concentration and in intravascular lipolysis has a suppressive effect on peripheral T cell CD28-dependent activation, and this effect is associated with changes in plasma membrane properties. Our results have important implications for nutritional therapy in patients at high risk of septic complications and may also be of relevance to postprandial lipid metabolism disorders such as insulin resistance and type 2 diabetes.

Dietary Linoleic Acid Intake Controls the Arterial Blood Plasma Concentration and the Rates of Growth and Linoleic Acid Uptake and Metabolism in Hepatoma 7288CTC in Buffalo Rats ,

In this study, we tested the hypothesis that dietary linoleic acid intake controls the arterial blood plasma linoleic acid concentration and the rates of tumor growth and linoleic acid metabolism in vivo. Seven groups of young male Buffalo rats (11–21 rats/group) were given free access to semipurified diets containing different amounts of corn and/or olive oils. Four other groups (7–11 rats/group) were 30% energy-restricted. Each experiment included periods for rat growth and plasma lipid stabilization (6 wk), measurement of mean daily arterial blood plasma fatty acid concentrations (3 wk), surgical implantation of a subcutaneous tissue-isolated hepatoma 7288CTC, tumor growth and harvest (2–4 wk). Linoleic + arachidonic acid (P = 0.007) and oleic acid (P = 0.002) concentrations in arterial blood plasma were increased as dietary intake of linoleic and oleic acids was increased, respectively. In rats given free access to food, tumor growth was directly dependent on the plasma concentrations of linoleic (P < 0.001) and arachidonic acids (P = 0.04). Tumor growth in energy-restricted rats was dependent only on the linoleic acid concentration (P = 0.008). Energy restriction itself caused a growth inhibition independent of plasma linoleic acid. The linoleic acid and total fatty acid concentrations of tumor triacylglycerols were directly dependent on the plasma linoleic acid concentration in rats given free access to food (P = 0.009). Hepatoma 7288CTC (both in vivo and during perfusion in situ) supported a dose-dependent conversion (P < 0.001) of plasma linoleic acid to the mitogen, 13-hydroxy-9,11-octadecadienoic acid. We conclude that increased arterial blood plasma linoleic acid concentrations, caused by increased dietary intakes, specifically stimulate growth, lipid storage and linoleic acid metabolism in hepatoma 7288CTC in vivo.

Effect of linoleic acid intake on growth of infants with cystic fibrosis

Essential fatty acid deficiency as a result of inadequate linoleic acid impairs growth in healthy infants and is common in infants with malabsorption due to cystic fibrosis (CF). We investigated the effect of dietary linoleic acid intake on the growth of infants with CF. In this study, predigested formula preparations A and B, with linoleic acid contents of 12% and 7% of energy, respectively, were fed before and after 1989 to infants enrolled in the evaluation and treatment protocol of the Wisconsin CF Neonatal Screening Project. Outcome was assessed from height-for-age (HAZ) and weight-for-age (WAZ) Z scores on follow-up exams during the first year. Baseline characteristics did not differ significantly between groups A (n = 43) and B (n = 33). At diagnosis, 53% of the enrolled infants (n = 76) showed low plasma linoleic acid concentrations and 22% had a high ratio of triene to tetraene. After correcting for the effect of potentially confounding variables, we found that HAZ (by .27, P < 0.05) and WAZ (by 0.26, P = 0.081) were higher in group A than in group B. This occurred despite a significantly higher energy intake in group B. This difference was most pronounced between 6 and 9 mo of age. Our results suggest that a high linoleic acid content in formula benefits infants with CF because it optimizes nutrition, growth, and feeding efficiency.

Plasma fatty acid changes and increased lipid peroxidation in patients with adult respiratory distress syndrome

There is a strong evidence that adult patients with acute respiratory distress syndrome (ARDS) are under severe oxidative stress, which leads to molecular damage. Using gas chromatography-mass spectrometry, our objective was to sequentially monitor changes, in intensive care unit (ICU) patients, characteristic of the oxidative loss of plasma unsaturated fatty acids and formation of the highly specific oxidation product of linoleic acid, 4-hydroxy-2-nonenal. Prospective, nonintervention, descriptive study. Limited statistics were applied to facilitate interpretation of the data. ICU of a postgraduate teaching hospital. Eighteen critically ill patients with an established diagnosis of ARDS requiring high FIO2 administered by mechanical ventilation were compared with ten normal, healthy controls and ten patients pre- and postcardiopulmonary bypass surgery at risk for developing ARDS. None. Sixty percent of the patients with ARDS included in this study survived. Major changes in the plasma concentrations of fatty acids occurred in all patients during their stay in the ICU. Percentage decreases in plasma linoleic acid concentrations were accompanied by increases in plasma oleic and palmitoleic acid concentrations. Circulating linoleic acid concentrations were significantly (p = .0001) lower in patients with ARDS than in the two control groups. The patients with ARDS who did not survive had lower (p = .0056) plasma oleic acid values than normal healthy controls and patients at risk for ARDs as a consequence of undergoing cardiopulmonary bypass surgery. Changes in palmitoleic acid, however, did not reach significance within the different groups studied. Patients with ARDS showed higher plasma concentrations of 4-hydroxy-2-nonenal (0.433 +/- 0.048 vs. 0.523 +/- 0.069 nmol/mL plasma for survivors and nonsurvivors, respectively) when compared with normal healthy controls (0.205 +/- 0.03 nmol/mL, p = 0.0001) and cardiopulmonary bypass patients at risk for developing ARDS (0.279 +/- 0.027 nmol/mL, p = .034 prebypass). During intensive care treatment, patients with ARDS decrease their percentage plasma concentrations of total plasma linoleic acid, but increase their percentage concentrations of oleic and palmitoleic acids. As plasma linoleic acid concentrations decreased, there was usually an increase in plasma 4-hydroxy-2-nonenal values, one of its specific peroxidation products, suggestive of severe oxidative stress leading to molecular damage to lipids.

Butylsoyamide protects soybean oil from ruminal biohydrogenation: effects of butylsoyamide on plasma fatty acids and nutrient digestion in sheep.

Based on previous results showing partial resistance of fatty acyl amides to ruminal biohydrogenation, butylsoyamide was added to sheep diets in an attempt to increase unsaturation of plasma fatty acids. Twelve wethers averaging 34 +/- 3.2 kg BW were randomly assigned to three diets containing either no added fat (control), 5% soybean oil, or 5% butylsoyamide. Dry matter intake was greater (P < .05) for sheep fed butylsoyamide than for sheep fed soybean oil (740 and 581 g/d, respectively), but neither fat supplement differed from the control diet (680 g/d). The soybean oil supplement reduced (P < .05) total VFA concentration (59.0 and 38.7 mM) and acetate:propionate (4.10 and 2.56) in ruminal samples compared with the control diet. Butylsoyamide had no effect (P > .05) on total VFA (54.4 mM) or acetate:propionate (2.96). Total tract ADF digestibility was not affected (P > .05) by either fat supplement. Relative to the control diet, soybean oil increased (P < .05) plasma linoleic acid concentration 22% compared with a 58% increase from feeding butylsoyamide (26.7, 32.6, and 42.1% of total fatty acids, respectively). Linoleic acid concentration in plasma neutral lipids, relative to the control diet, increased 15.8% (P < .05) for soybean oil compared with 64.9% (P < .05) for butylsoyamide (31.6, 36.6, and 52.1% of total fatty acids, respectively). Converting soybean oil triglycerides to fatty acyl amides substantially reduces negative effects of the oil on ruminal fermentation and increases unsaturated fatty acids in plasma. The increase in plasma unsaturated fatty acids demonstrates at least partial resistance of fatty acyl amides to ruminal biohydrogenation and their digestion and absorption postruminally.

Changes in plasma fatty acid profile in Japanese patients with chronic pancreatitis.

The serum zinc, prealbumin, retinol-binding protein and carotene concentrations and the plasma fatty acid composition were determined to assess the nutritional condition of 24 patients with chronic pancreatitis compared with that of 20 healthy controls. The daily food intake and faecal fat excretion of the two groups were also measured. In the chronic pancreatitis group, the calorie and fat intakes were significantly lower than those of the controls. Serum levels of zinc, prealbumin and carotene were also significantly lower than those of the controls. Percentages of plasma linoleic and arachidonic acids were low, while percentages of palmitoleic acid, eicosapentaenoic acid and docosahexaenoic acid were high. Fish oil intake correlated negatively with plasma linoleic acid concentration (P < 0.05). The above results indicate that the relatively high intake of fish oil and the relatively low intake of dietary fat in Japanese patients with chronic pancreatitis with a mild degree of steatorrhoea results in an abnormally low plasma level of linoleic acid.

Comparison of amino acid v peptide based enteral diets in active Crohn's disease: clinical and nutritional outcome.

Elemental diets are considered an effective primary treatment for active Crohn's disease. This study examined the hypothesis that improvement occurs because of the presence of amino acids or the low fat content, or both. A randomised, controlled trial was undertaken in 40 patients with active Crohn's disease to evaluate clinical and nutritional outcomes after an amino acid based diet containing 3% fat was given by a feeding tube compared with a peptide based diet containing 33% fat. After three weeks' treatment, clinical remission occurred in 84% of patients who were given the amino acid diet and 75% of patients who received the peptide diet (p = 0.38). Plasma linoleic acid concentration was reduced after the amino acid but not the peptide diet. An increase in total body nitrogen was associated with the magnitude of nutritional depletion before treatment and at six months' follow up, only patients who showed gains in total body nitrogen after enteral nutrition had a sustained clinical remission. This study shows that peptide based high fat diets are as effective as amino acid low fat diets for achieving clinical remission in active Crohn's disease. Improved total body protein stores but not essential fatty acid depletion may be an important indicator of a sustained remission.

The effect of dietary supplementation with linoleic and gammalinolenic acids on the pressor response to angiotensin II--a possible role in pregnancy-induced hypertension?

Dietary supplementation with 3 g/day linoleic acid, 32 mg/day gammalinolenic acid and co-factors for prostaglandin synthesis was given to 10 pregnant and 10 non-pregnant subjects for a week. Their pressor response to the infusion of three doses of angiotensin II (AII) (pregnant: 4, 8, 16 ng kg-1 min-1: non-pregnant: 1, 2, 4 ng kg-1 min-1) was then compared with that of 40 pregnant and 24 non-pregnant controls who had not been given such supplementation. Dietary supplementation was not associated with changes in basal systolic or diastolic blood pressure or heart rate during the week of treatment in pregnant or non-pregnant subjects. Basal systolic blood pressure, diastolic blood pressure and heart rate values did not differ between the treated and untreated subjects in each group. The diastolic pressor response to AII was significantly less after treatment at all doses; the effect was more marked in the pregnant subjects. The systolic response to AII, normally less than the diastolic, was somewhat blunted in the treated pregnant patients at the two higher infusion doses. No significant effect was found in the non-pregnant group. Evidence from other studies suggests that increasing plasma linoleic acid concentrations leads to increased plasma concentrations of epoprostenol (prostacyclin, PGI2) while increased availability of gammalinolenic acid is associated with a rise in prostaglandin E1 and E2 production. Pregnancy-induced hypertension is associated with a diminished tissue production of both epoprostenol and E series prostaglandins, and with an enhanced pressor response to AII.(ABSTRACT TRUNCATED AT 250 WORDS)