Phospholipid Docosahexaenoic Acid Research Articles

Plasma phospholipid EPA and DHA in relation to atherosclerosis in 61-year-old men

Introduction Increased intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to decrease the risk for cardiovascular death and to reduce CVD risk factors. It has also been suggested that EPA and DHA reduce atherosclerosis progression, but data are inconclusive. Carotid intima-media thickness (IMT) is a well-established surrogate measure for sub-clinical atherosclerosis. Our aim was to examine if plasma phospholipid EPA and DHA are associated with IMT and plaque occurrence and size in the carotid and femoral arteries. Methods IMT and plaque occurrence in carotid and femoral arteries was measured by ultrasound in 487 sixty-one-year-old men in this cross-sectional study. Plasma phospholipid levels of EPA and DHA, serum lipids, cell adhesion molecules, and blood pressure were measured, and occurrence of diabetes and socioeconomic factors were assessed. Results Plasma phospholipid EPA was negatively associated with IMT in carotid and femoral arteries, and with cigarette years and cell adhesion proteins. EPA was positively associated with HDL, total cholesterol, blood pressure, plasma insulin and years of education. The association between EPA and carotid IMT remained after adjustment for blood pressure, but not for other covariates. Plasma phospholipid DHA was negatively associated with cigarette years and several endothelial markers, and positively associated with years of education and systolic blood pressure. In contrast to other studies, EPA content was higher in diabetic patients compared with patients without diabetes. Conclusion Plasma phospholipid EPA, but not DHA, was inversely associated with carotid and femoral IMT, as well as several endothelial markers supporting the concept of an effect of EPA on the vascular wall. This association was independent of blood pressure, but not for other covariates. There was no association between plasma phospholipid EPA or DHA and plaque occurrence in the carotid and femoral arteries.

Frequency and Type of Seafood Consumed Influence Plasma (n-3) Fatty Acid Concentrations

Few studies have adequately considered the type of seafood and background dietary factors when evaluating diet-biomarker and diet-disease associations. The objective of this paper is to evaluate the relationship between different seafood meals and long-chain (n-3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA) with white, Chinese-American, black, and Hispanic participants. Dietary intake from a FFQ and plasma phospholipid fatty acids were assessed in 900 MESA participants who were not taking fish oil supplements. When simultaneously adjusting for all seafood groups, concentrations of EPA and DHA in plasma phospholipids were positively correlated with nonfried fish consumption in all 4 ethnic groups (r = 0.24–0.46; P < 0.01) but not with nonfried shellfish, fried fish, or fish in mixed dishes. The magnitude of this correlation was attenuated by up to 67% when type of seafood was not taken into account. After further adjusting for demographic characteristics and other dietary characteristics in multivariate regression models, the association of nonfried fish consumption remained significant (P-trend < 0.001). Data were suggestive of a plateau effect at a nonfried fish intake of about twice weekly. The association of nonfried fish consumption was not modified by intake of (n-6) PUFA or α-linolenic acid. This study highlights the importance of cooking methods (nonfried vs. fried fish), types of seafood (fish vs. shellfish), and the overall seafood consumption when assessing health effects of long-chain (n-3) fatty acids of seafood consumption.

Effect of Dietary n-3 Polyunsaturated Fatty Acids on Brain Lipid Fatty Acid Composition, Learning Ability, and Memory of Senescence-Accelerated Mouse

Animal studies have shown that a deficiency in brain of the n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with memory loss and diminished cognitive function. The senescence-accelerated prone 8 (SAMP8) mouse develops impairments in learning and memory at 8-12 months of age. The effect of diet supplemented with n-3 PUFA on brain phospholipid DHA status, learning, and memory ability in aged SAMP8 mice was investigated. At the age of 10 months, SAMP8 mice were fed either a low-DHA or a high-DHA diet for 8 weeks. In comparison to SAMP8 mice fed the low-DHA diet, those fed a high-DHA diet had improved acquisition and retention in a T-maze foot shock avoidance test and a higher proportion of DHA in hippocampal and amygdala phospholipids. This study demonstrates that, in mature animals, DHA is incorporated into brain phospholipids and that dietary n-3 PUFA is associated with delay in cognitive decline.

Low Docosahexaenoic Acid in the Diet and Milk of Women in New Mexico

Because docosahexaenoic acid (DHA) is critical for the development of the nervous system, especially during the first year of life, the content of DHA in human milk is important for the well-being of exclusively breastfed infants. The aim of this study was to determine the fatty acid composition, including DHA, of the breast milk fat and serum phospholipids of women in New Mexico, and to correlate these data with dietary fatty acid content. Samples of blood and breast milk, 3-day diet records, and information on dietary supplement use were obtained from 29 women. Eligible subjects were nonsmokers, aged 18 to 40 years, lactating for 1 to 6 months, and not pregnant, taking immunosuppressive drugs, or diagnosed with diabetes. The mean fat content of the breast milk was 3.37±2.34 g/dL. The percentage of DHA in the milk fat was very low (0.11%) relative to international norms (0.2% to 0.4%) and could be explained by the women's low intake of DHA (33 to 58 mg/day). These data can be explained by the fact that the subjects were not taking DHA supplements or consuming foods that are good sources of DHA. Correlations were found between the percentages of DHA in the serum phospholipids and milk fat. The findings underscore the need for educating lactating women about food sources of DHA. Educational opportunities could occur in conjunction with other education postdelivery or during postnatal clinic visits.

Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: Results from the DINO trial

Formula supplemented with docosahexaenoic acid (DHA) improves retinal function of preterm infants but the optimal dose is unknown. In a randomized controlled trial we examined the effect of increasing the DHA concentration of human milk and formula on circulating fatty acids of preterm infants. Infants born <33 weeks gestation were fed high-DHA milk (1% total fat as DHA) or standard-DHA milk (0.2–0.3% DHA) until reaching their estimated due date (EDD). Milk arachidonic acid (AA) concentration was ∼0.5% for both groups. At EDD, erythrocyte membrane phospholipid DHA was elevated in the high-DHA group compared with standard-DHA (mean±SD, high-DHA 6.8±1.2, standard-DHA 5.2±0.7, p<0.0005) but AA was lower (high-DHA 14.9±1.3, standard-DHA 16.0±1.2, p<0.0005). Feeding preterm infants human milk and formula with 1% DHA raises but does not saturate erythrocyte phospholipids with DHA. Milk exceeding 1% DHA may be required to increase DHA status to levels seen in term infants.

Algal-Oil Capsules and Cooked Salmon: Nutritionally Equivalent Sources of Docosahexaenoic Acid

Food and nutrition professionals question whether supplement-sourced nutrients appear to be equivalent to those derived from natural food sources. We compared the nutritional availability of docosahexaenoic acid (DHA) from algal-oil capsules to that from assayed cooked salmon in 32 healthy men and women, ages 20 to 65 years, in a randomized, open-label, parallel-group study. In this 2-week study comparing 600 mg DHA/day from algal-oil capsules to that from assayed portions of cooked salmon, mean change from baseline in plasma phospholipids and erythrocyte DHA levels was analyzed and DHA levels were compared by Student's t tests. In post-hoc analyses to determine bioequivalence, least-squares mean ratios of percent change from baseline in plasma phospholipid and erythrocyte DHA levels were compared. DHA levels increased by ∼80% in plasma phospholipids and by ∼25% in erythrocytes in both groups. Changes in DHA levels in plasma phospholipids and erythrocytes were similar between groups. As measured by delivery of DHA to both plasma and erythrocytes, fish and algal-oil capsules were equivalent. Both regimens were generally well-tolerated. These results indicate that algal-oil DHA capsules and cooked salmon appear to be bioequivalent in providing DHA to plasma and red blood cells and, accordingly, that algal-oil DHA capsules represent a safe and convenient source of non–fish-derived DHA.

Dietary supplementation of salmon roe phospholipid enhances the growth and survival of Pacific bluefin tuna Thunnus orientalis larvae and juveniles

Previous studies have shown that feeding enriched Artemia induces growth failure in Pacific bluefin tuna (PBT) Thunnus orientalis larvae. This growth failure cannot be improved even if the docosahexaenoic acid (DHA) content in enriched Artemia is elevated to the same level as that in yolk-sac larvae, an ideal live feed for PBT larviculture. This might be caused by the differences in the DHA in the live feeds; i.e., yolk-sac larvae of marine fish have a high level of DHA in the larval phospholipids (PLs) but enriched Artemia store DHA in their neutral lipids (NLs). To test this hypothesis two experiments were conducted to evaluate the effect of dietary PL rich in DHA on growth and survival of PBT larvae (Experiment 1) and juveniles (Experiment 2). Three isoproteic and isolipidic artificial test diets (Diets 1, 2 and 3) and two reference live feeds (Diets 4 and 5) were prepared. Diets 1 and 3 were supplemented with NL and PL fractions of commercial salmon Oncorhynchus gorbuscha roe lipid (SRL) as the lipid source, respectively, whereas Diet 2 was supplemented with a mixture of both lipid fractions. Diets 4 and 5 were enriched Artemia and yolk-sac larvae of Japanese parrot fish Oplegnathus fasciatus, respectively. Diets 1, 3, 4 and 5 were given to PBT larvae for 10 days, whereas Diets 1, 2 and 3 were fed to PBT juveniles for 10 days. In Experiment 1, the growth and survival of PBT larvae fed Diet 3 (high PL fraction) were significantly improved when compared with larvae fed Diets 1 and 4, although the best growth and survival were obtained in larvae fed Diet 5. Similar results were obtained in Experiment 2; i.e., growth and survival were significantly improved in PBT juveniles fed Diets 2 and 3. In both experiments, fish fed Diets 2, 3 and/or 5 had higher total lipid contents, TAG levels, n-3 HUFA and/or DHA levels in NL fraction of the body when compared with fish fed Diets 1 or 4, while such a difference was not observed in the PL fraction. In juveniles over 90% of deaths were caused by collisions with the tank walls and the significant difference in mortality between treatments implies diet also affects behavior. SRL PL is concluded to enhance the growth and survival of PBT larvae and juveniles along with the accumulation of storage lipid and DHA in the body.

Bioequivalence of Docosahexaenoic Acid from Different Algal Oils in Capsules and in a DHA‐Fortified Food

Docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for eye and brain development and ongoing visual, cognitive, and cardiovascular health. Unlike fish-sourced oils, the bioavailability of DHA from vegetarian-sourced (algal) oils has not been formally assessed. We assessed bioequivalence of DHA oils in capsules from two different algal strains versus bioavailability from an algal-DHA-fortified food. Our 28-day randomized, placebo-controlled, parallel group study compared bioavailability of (a) two different algal DHA oils in capsules ("DHASCO-T" and "DHASCO-S") at doses of 200, 600, and 1,000 mg DHA per day (n = 12 per group) and of (b) an algal-DHA-fortified food (n = 12). Bioequivalence was based on changes in plasma phospholipid and erythrocyte DHA levels. Effects on arachidonic acid (ARA), docosapentaenoic acid-n-6 (DPAn-6), and eicosapentaenoic acid (EPA) were also determined. Both DHASCO-T and DHASCO-S capsules produced equivalent DHA levels in plasma phospholipids and erythrocytes. DHA response was dose-dependent and linear over the dose range, plasma phospholipid DHA increased by 1.17, 2.28 and 3.03 g per 100 g fatty acid at 200, 600, and 1,000 mg dose, respectively. Snack bars fortified with DHASCO-S oil also delivered equivalent amounts of DHA on a DHA dose basis. Adverse event monitoring revealed an excellent safety and tolerability profile. Two different algal oil capsule supplements and an algal oil-fortified food represent bioequivalent and safe sources of DHA.

N-3 poly-unsaturated fatty Acid (n-3PUFA) and neuroprotection: Is docosahexaenoic acid (DHA) involved in glutamate uptake by astrocytes?

The high amount of DHA (the main n-3PUFA) in brain cell membranes depends on n-3PUFA dietary intake. High n-3PUFA intakes reduce the occurrence of neurodegenerative diseases such as Alzheimer’s disease and have a protective effect on experimentally induced excitotoxicity. A high amount of DHA in cell membranes may thus confer to the brain a better resistance to insults. We recently showed that the amount of DHA in membrane phospholipids infl uences astrocytes physiology. Thus, the neuroprotective effect of n-3PUFA may rely on astrocyte functions involved in neuron protection and synaptic repair. Glutamate scavenging, a major task of astrocytes preventing excitotoxic damage, is under the infl uence of lipid signalling. We thus hypothesized that a high brain DHA content resulting from adequate n-3PUFA intakes may promote the glutamate uptake by astrocytes. We have explored the infl uence of membrane n-3PUFA status on glutamate uptake by astrocytes, on in vivo and in vitro models. In vivo, we compared the amount of astrocytic glutamate transporters GLAST and GLT-1 (western blot), in the cortex and hippocampus from n-3 supplemented or n-3 defi cient rats, from birth to 4 months old. In vitro, we compared GLAST and GLT-1 expression (western blot), 3H-aspartatve uptake and the capture of a bolus of glutamate, on astrocytes cultured in DHA-supplemented or control medium. In vivo and in vitro, n-3 PUFA supplementation induced a strong increase in the amount of DHA in membrane phospholipids (measured in phosphatidylethanolamine and phosphatidylcholine, by Gas Chromatography) as compared to n-3 deprived cells or rats. However, the DHA increase had no major consequences on glutamate transporters or uptake, in basal conditions. We are currently exploring the potential infl uence of DHA in conditions requiring enhanced glutamate c-apture and rapid addressing of the transporters to the membrane.

Platelet phospholipid n−3 PUFA negatively associated with plasma homocysteine in middle-aged and geriatric hyperlipaemia patients

Studies showed that increased dietary intake of n−3 polyunsaturated fatty acids (PUFA) has a cardiovascular beneficial effect. Increased plasma phospholipid (PL) docosahexaenoic acid (22:6 n−3) is associated with decreased plasma homocysteine (Hcy). The aim of this study was to investigate the relationship between platelet PL fatty acid and plasma Hcy in middle-aged and geriatric hyperlipaemia patients (50 males, 31 females) and 65 healthy subjects (43 males, 22 females) in Hangzhou, China. Plasma Hcy demonstrated significant positive correlation with adrenic acid (22:4 n−6) ( r = 0.188 , P = 0.018 ) and negative correlation with 22:6 n−3 ( r = – 0.277 , P = 0.001 ) and the ratio of n−3/ n−6 ( r = – 0.231 , P = 0.003 ) in sex-, age- and BMI-controlled partial correlation analysis. The present results suggest that increased ratio of n−3/ n−6 PUFA in platelet PL is associated with decreased thrombotic risks such as plasma Hcy in middle-aged and geriatric hyperlipaemia patients in Hangzhou.

96 EFFECT OF DIETARY SUPPLEMENTATION WITH TUNA OIL ON THE LIPID COMPOSITION OF BOAR SPERMATOZOA AND CHARACTERISTICS OF SEMEN

In most mammals, docosahexaenoic acid (DHA) is the dominant polyunsaturated fatty acid (PUFA), although, in several species, docosapentaenoic acid is also a major component of the sperm cell membranes. The amount of DHA in spermatozoa is positively correlated with sperm motility. The effect of dietary supplementation with tuna oil (TO) on the lipid and fatty acid composition of boar spermatozoa and the relationship between the changes in composition and boar semen characteristics were studied. Twenty-four boars were distributed in a completely randomized factorial design (2 � 3) with two oil sources (soybean and tuna) and three levels of antioxidant (150, 300, and 450 mg of vitamin E/kg). The diets consisted of a basal diet that was supplemented with 30 g soybean or TO per kg diet. During a period of 10 weeks of feeding the diets, one ejaculate from each boar was collected per week. The sperm was diluted 1:1 with Beltsville thawing solution (BTS) and divided into three portions destined to cooling (5 and 17�C) and freezing. The sperm diluted for cooling at either temperature was stored in plastic bottles for 3 days. After dilution with BTS, the sperm for freezing was centrifuged and rediluted with freezing extender before it was stored in 0.5-mL straws. Thawing was achieved by placing the straws in a water bath (37�C) for 30 s. Motility, vigor, hypoosmotic swelling (host), and morphology were assessed. For determining the fatty acid composition of the spermatozoa and seminal plasma, a sample of 15 mL was taken from each ejaculate shortly after collection and centrifuged for 20 min at 1000g. Sperm motility and vigor were analyzed by placing a sample on a pre-warmed (37�C) microscopic slide, covering with a coverslip, and examining under a light microscope at a magnification of 200�. For host assessment in each case, a volume of 10 µL was mixed with 1 mL hypoosmotic solution (100 mOsm L–1) and incubated for 30 min in a water bath (37�C). After incubation, 50 µL of formol-saline was added to each tube. Sequentially, 20 µL of every sample was smeared on a microscope slide and observed with oil immersion using a phase contrast microscope. A minimum of 200 cells was observed and classified as non-coiled and coiled. Lipid peroxidation was measured using the thiobarbituric acid reaction. Treatment differences for sperm were determined using analysis of variance for means. The proportion of DHA in sperm phospholipid fatty acids increased in semen fatty acid composition after 1 week of feeding TO. The concentrations of the fatty acids were unchanged in the seminal plasma as a result of the diets fed. The proportion of spermatozoa with abnormal morphologies decreased in boars supplemented with TO (P &lt; 0.05). The TO diet showed the lowest level of total antioxidants in the semen (P &lt; 0.05); however, when the diet was supplemented with the higher vitamin E level, an increase in sperm motility and vigor was observed (P &lt; 0.05). Therefore, dietary supplementation with TO alters the lipid composition of the membrane and has a beneficial effect on both cooled and cryopreserved boar spermatozoa by decreasing cold shock during cooling and thus increasing cryosurvival.

Maternal parity and diet (n-3) polyunsaturated fatty acid concentration influence accretion of brain phospholipid docosahexaenoic acid in developing rats.

The long-chain PUFA, docosahexaenoic acid [22:6(n-3), DHA], a major component of neuronal membrane phospholipids, accumulates in brain during late prenatal and early neonatal development and is essential for optimal attentional and cognitive function. Because all nutrition is supplied to the developing fetus/neonate by the mother and maternal DHA status is affected by parity, this study examined the effects of maternal diet and parity on DHA accretion in the developing brain. Whole brain total phospholipid fatty acid composition was determined by TLC and GC in weanling male Long-Evans rats (n = 5) from the 1st, 2nd, 3rd, or 4th litters of dams fed diets containing alpha-linolenic acid (ALA), containing ALA and preformed DHA (ALA + DHA), or lacking ALA (low-ALA). First-litter low-ALA offspring exhibited a decrease in phospholipid fatty acid DHA content to 68% of 1st-litter ALA pups. DHA in 2nd-litter low-ALA pups was further decreased to 55% of 1st-litter ALA pups, but further decreases were not observed in subsequent litters. DHA levels increased 15-20% in 2nd to 4th-litter ALA + DHA pups and 11% in 4th-litter ALA pups compared with 1st-litter ALA pups. These findings demonstrate that maternal diet and parity interact to affect offspring brain DHA status and suggest that maternal multiparity may place offspring at greater risk of decreased accretion of brain DHA if the maternal diet contains insufficient (n-3) PUFA.

Higher plasma docosahexaenoic acid is associated with reduced progression of coronary atherosclerosis in women with CAD

Fish intake, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and in some cases alpha-linolenic acid (ALA) have been associated with reduced risk of cardiovascular events and death. The association between n-3 fatty acids in plasma lipids and the progression of coronary artery atherosclerosis was assessed among women with established coronary artery disease (CAD). A prospective cohort study involved postmenopausal women (n = 228) participating in the Estrogen Replacement and Atherosclerosis Trial. Quantitative coronary angiography was performed at baseline and after 3.2 +/- 0.6 (mean +/- SD) years. Women with plasma phospholipid (PL) DHA levels above the median, compared with below, exhibited less atherosclerosis progression, as expressed by decline in minimum coronary artery diameter (-0.04 +/- 0.02 and -0.10 +/- 0.02 mm, respectively; P = 0.007) or increase in percentage stenosis (1.34 +/- 0.76% and 3.75 +/- 0.74%, respectively; P = 0.006), and had fewer new lesions [2.0% (0.5-3.5%) of measured segments (95% confidence interval) and 4.2% (2.8-5.6%), respectively; P = 0.009] after adjustments for cardiovascular risk factors. Similar results were observed for DHA in the triglycerides (TGs). EPA and ALA in plasma lipids were not significantly associated with atherosclerosis progression. Consistent with higher reported fish intake, higher levels of plasma TG and PL DHA are associated with less progression of coronary atherosclerosis in postmenopausal women with CAD.

Docosahexaenoic acid supply in pregnancy affects placental expression of fatty acid transport proteins

Better understanding of the mechanisms involved in docosahexaenoic acid (DHA) transfer to the neonate may contribute to improve dietary support for infants born prematurely to mothers with placental lipid transport disorders. We studied whether DHA supplements modify the messenger RNA (mRNA) expression of placental lipid transport proteins to allow a selective transfer of DHA to the fetus. Healthy pregnant women (n = 136) received, in a double-blind randomized trial, 500 mg DHA + 150 mg eicosapentaenoic acid, 400 microg 5-methyl-tetrahydrofolic acid, 500 mg DHA + 400 microg 5-methyl-tetrahydrofolic acid, or placebo during the second half of gestation. We analyzed the fatty acid composition of maternal and cord blood phospholipids and of placenta; we quantified placental mRNA expression of fatty acid-transport protein 1 (FATP-1), FATP-4, FATP-6, fatty acid translocase, fatty acid-binding protein (FABP) plasma membrane, heart-FABP, adipocyte-FABP, and brain-FABP. The mRNA expression of the lipid carriers assayed did not differ significantly between the 4 groups. However, the mRNA expression of FATP-1 and FATP-4 in placenta was correlated with DHA in both maternal plasma and placental phospholipids, although only FATP-4 expression was significantly correlated with DHA in cord blood phospholipids. Additionally, the mRNA expression of several membrane lipid carriers was correlated with EPA and DHA in placental triacylglycerols and with EPA in placental free fatty acids. Correlation of the mRNA expression of the membrane placental proteins FATP-1 and especially of FATP-4 with maternal and cord DHA leads us to conclude that these lipid carriers are involved in placental transfer of long-chain polyunsaturated fatty acids.

Efficacy of Omega-3 Fatty Acids in Children and Adults with IgA Nephropathy Is Dosage- and Size-Dependent

Previous studies that have evaluated fish oil preparations in patients with IgA nephropathy (IgAN) have produced a wide range of conclusions. Proposed explanations for these discordant results have not provided a unifying hypothesis. Results from two clinical trials were analyzed to examine whether there is a dosage-dependent effect of Omacor, a purified preparation of omega-3 fatty acids, in patients with IgAN. Whether changes in the level of proteinuria and plasma phospholipid fatty acid profiles were dependent on the dose of Omacor factored by body size was determined. In a post hoc analysis of the first trial results, correlations were found between (1) phospholipid eicosapentaenoic acid (EPA)/arachidonic acid (AA) and docosahexaenoic acid (DHA)/AA ratios and the dosage of Omacor, expressed as milligrams per kilogram of body weight (r = 0.78, P < 0.001 for EPA/AA; r = 0.86, P < 0.001 for DHA/AA), (2) phospholipid EPA/AA and DHA/AA levels and percentage change in urine protein/creatinine ratio after 21 to 24 mo of therapy (r = -0.50, P = 0.02 for EPA/AA; r = -0.52, P = 0.01 for DHA/AA), and (3) dosage of Omacor per kilogram of body weight and change in proteinuria after 21 to 24 mo (r = -0.50, P = 0.02). A similar relationship was observed between urine protein/creatinine ratio and dosage of Omacor per kilogram of body weight in trial 2 (r = -0.38, P < 0.001). It is concluded from these data that the effect of Omacor on proteinuria in patients with IgAN is dosage dependent and is associated with a dosage-dependent effect of Omacor on plasma phospholipid EPA and DHA levels.

Plasma n‐3 fatty acids are inversely associated with n‐6 linoleic acid in men consuming high or low n‐6 linoleic acid and constant n‐3 linolenic acid

The n-3 fatty acids (FA) linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with decreased risk of cardiovascular and inflammatory diseases. High intakes of linoleic acid (LA) may affect conversion of ALA to EPA and DHA, thus compromising the benefit of n-3 FA. However, limited data are available on the effect of LA intakes on n-3 FA status, at constant LNA, in humans. We determined whether lowering LA intake by substituting low for high LA oils with constant LNA in oil blends with a LA:ALA ratio of 2:1 or 8:1 increases plasma phospholipid (PL) EPA or DHA, and decreases the ARA/EPA ratio. Adult men, n=24 consumed fats, oils and baked foods with high or low LA, 4 wks/diet, to replace these foods in their diet in a random cross over design. Fish and seafood were eliminated from 2 wk before and throughout the study. Plasma PL FA, triglyceride (TG), total, HDL, and LDL cholesterol were measured at Wk 0, 4 and 8. The plasma PL LA, and ARA/EPA ratio was significantly higher, and EPA was significantly lower during the high compared to low LA diet period. Plasma PL LA was significantly inversely related to EPA (P<0.001) across all subjects and time points. Total, HDL and LDL cholesterol were not different between the high and low LA diets, but plasma TG was inversely related to PL LA. These studies show that lowering dietary LA improves the ARA/EPA ratio, which may be important in inflammatory diseases.

Docosahexaenoic acid is selectively enriched in plasma phospholipids during pregnancy in Trinidadian women – Results of a pilot study

The fetal demand for docosahexaenoic acid (DHA) has to be satisfied by the mother. We determined the fatty acids in maternal plasma non-esterified fatty acid (NEFA), triacylglycerol (TAG) and phosphatidylcholine (PC), in a cross-sectional study of non-pregnant (n = 10), pregnant (n = 19), and postpartum (n = 9) women. There were lipid class-dependent differences in plasma polyunsaturated fatty acid (PUFA) concentrations between groups. During pregnancy, DHA was most highly enriched in PC, about 230%, with more modest enrichment for linoleic acid (LA) and arachidonic acid (AA), and no enrichment of alpha-linolenic acid (alpha-LNA). There was relative enrichment of LA, AA and alpha-LNA in TAG, but not of DHA. There was no specific enrichment of any PUFA in the NEFA pool. These data accord with the suggestion that the enrichment of alpha-LNA in TAG and of DHA in phospholipids reflects hepatic regulation of n-3 PUFA metabolism which potentially enhances the delivery of DHA to the placenta.

A significant inverse relationship between concentrations of plasma homocysteine and phospholipid docosahexaenoic acid in healthy male subjects

The aim of this study was to investigate the possibility of a relationship between plasma homocysteine (Hcy) and phospholipid FA (PUFA) in healthy Australian males. One hundred thirty six healthy male subjects aged 20-55 yr were recruited from the Melbourne metropolitan area. Each volunteer completed a semiquantitative food frequency questionnaire and gave a blood sample. Plasma Hcy concentrations were determined by an established HPLC method; the plasma phospholipid FA were determined by standard methods. Plasma Hcy concentration was significantly negatively correlated with plasma phospholipid concentration of the PUFA 20:5n-3 (r = -0.226, P = 0.009), 22:5n-3 (r= -0.182, P= 0.036), 22:6n-3 (r= -0.286, P= 0.001), total n-3 (r = -0.270, P = 0.002) and the ratio n-3/n-6 PUFA (r = -0.265, P = 0.002), and significantly positively correlated with 20:4n-6 (r= 0.180, P= 0.037). In the partial correlation analysis, after controlling for serum vitamin B12 and folate concentration, plasma Hcy was significantly negatively correlated with the plasma phospholipid concentration of 22:6n-3 (r = -0.205, P = 0.019), total n-3 (r = -0.182, P= 0.038) and the ratio n-3/n-6 PUFA (r= -0.174, P= 0.048). Evidence indicates that an increased concentration of n-3 PUFA in tissues has a beneficial effect on cardiovascular health. Our findings provide further evidence that increased consumption of dietary n-3 PUFA increases the concentration of n-3 PUFA in plasma phospholipid, which is associated with a protective effect on cardiovascular diseases and lower plasma Hcy levels. The mechanism that might explain the association between plasma 22:6n-3 and Hcy levels is not clear.

The influence of n-3 polyunsaturated fatty acids and very low calorie diet (VLCD) during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women

Polyunsaturated fatty acids of n-3 series (n-3 PUFA) were shown to increase basal fat oxidation in humans. The aim of the study was to compare the effect of n-3 PUFA added to a very low calorie diet (VLCD), with VLCD only during three-week inpatient weight reduction. Twenty severely obese women were randomly assigned to VLCD with n-3 PUFA or with placebo. Fatty acids in serum lipid fractions were quantified by gas chromatography. Differences between the groups were determined using ANOVA. Higher weight (7.55+/-1.77 vs. 6.07+/-2.16 kg, NS), BMI (2.82+/-0.62 vs. 2.22+/-0.74, p&lt;0.05) and hip circumference losses (4.8+/-1.81 vs. 2.5+/-2.51 cm, p&lt;0.05) were found in the n-3 group as compared to the control group. Significantly higher increase in beta-hydroxybutyrate was found in the n-3 group showing higher ketogenesis and possible higher fatty acid oxidation. The increase in beta-hydroxybutyrate significantly correlated with the increase in serum phospholipid arachidonic acid (20:4n-6; r = 0.91, p&lt;0.001). In the n-3 group significantly higher increase was found in n-3 PUFA (eicosapentaenoic acid, 20:5n-3, docosahexaenoic acid, 22:6n-3) in triglycerides and phospholipids. The significant decrease of palmitoleic acid (16:1n-7) and vaccenic acid (18:1n-7) in triglycerides probably reflected lower lipogenesis. A significant negative correlation between BMI change and phospholipid docosahexaenoic acid change was found (r = -0.595, p&lt;0.008). The results suggest that long chain n-3 PUFA enhance weight loss in obese females treated by VLCD. Docosahexaenoate (22:6n-3) seems to be the active component.

Plasma fatty acid composition is associated with the metabolic syndrome and low-grade inflammation in overweight adolescents

Together with adiposity, plasma fatty acid (FA) composition can modulate the development of the metabolic syndrome (MS). Our aim was to investigate the relations of FA composition in plasma phospholipids and cholesterol esters (CEs) with weight status, MS, and inflammation in adolescents. Plasma FA composition was measured by gas-liquid chromatography in 120 (60 normal-weight and 60 overweight) 12-y-old adolescents. We also measured the presence of MS, insulin resistance with the homeostasis model assessment, and interleukin 6 and C-reactive protein concentrations in the adolescents. MS was present in 25% of the overweight adolescents but in none of the normal-weight adolescents. Compared with overweight adolescents, normal-weight adolescents had lower saturated FAs (SFAs) in both phospholipids (P < 0.001) and CEs (P < 0.01) and higher docosahexaenoic acid in phospholipids (P < 0.001). In overweight subjects, FA composition was associated with MS features independent of body fat. The odds ratios of MS for a 0.1 increase in the ratio of polyunsaturated FAs (PUFA) to SFAs (PUFA:SFA) were 0.91 in phospholipids (P = 0.03) and 0.90 in CEs (P = 0.06). In phospholipids, PUFA:SFA and linoleic acid were associated positively with HDL cholesterol (P < 0.01 for both). PUFA:SFA in phospholipids and CEs were associated inversely with interleukin 6 (P < 0.05 for both). Eicosapentaenoic acid in phospholipids (P = 0.06) and CEs (P < 0.05) and linolenic acid in CEs (P < 0.05) were inversely related to C-reactive protein. These relations remained significant after adjustment for the waist-to-hip ratio. No significant relation between FA composition and the homeostasis model assessment was observed. Plasma FA composition is associated with weight status in healthy adolescents. High intake of long-chain PUFAs, especially n-3 PUFAs, may protect obese subjects against MS and low-grade inflammation as early as adolescence.