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Docosahexaenoic acid (DHA)
(319 References)
Valenzuela, A., R. Von Bernhardi, et al. (2004). "Supplementation of Female Rats with {FC12}a-Linolenic Acid or Docosahexaenoic Acid Leads to the Same Omega-6/Omega-3 LC-PUFA Accretion in Mother Tissues and in Fetal and Newborn Brains." Ann Nutr Metab 48(1): 28-35.
BACKGROUND: Maternal omega-3 fatty acid supplementation has been suggested to provide docosahexaenoic acid (DHA) for the normal brain development during gestation. DHA can be given as such (preformed) or through the omega-3 precursor alpha-linolenic acid (LNA) which is transformed into DHA by elongation and desaturation reactions. Western diet provides low amounts of LNA and DHA; therefore, supplementation with these omega-3 fatty acids has been suggested for pregnant women. However, the bioequivalence of LNA ingestion to DHA supplementation has not been established. METHODS: Recently weaning female Wistar rats were fed a diet containing a small amount of LNA and no DHA. The animals were daily supplemented 40 days before mating, during pregnancy, and until delivery with 60 mg/kg of LNA or 6 mg/kg of DHA dissolved in coconut oil. Fatty acids were given as ethyl ester derivatives. Controls received coconut oil. The fatty acid composition of blood plasma, erythrocytes, liver, visceral adipose tissue, and brain segments (frontal cortex, hippocampus, and cerebellum) was analyzed. Brain segments obtained from 16- and 19-day-old fetuses and from 2- and 21-day-old rats were also analyzed for fatty acid composition. RESULTS: Supplementation with LNA and DHA induced a similar accretion of DHA in plasma, erythrocytes, liver, and brain segments of the mothers. The adipose tissue showed a higher DHA accretion after DHA-supplementation. The DHA accretion in frontal cortex, hippocampus, and cerebellum obtained from the fetuses and the newborn rats was similar when the mothers were supplemented with LNA and DHA. Our results show that under our experimental conditions a similar accretion of DHA in the different tissues of the mothers and in the brain segments of fetuses and newborn rats is obtained after LNA and DHA supplementation. CONCLUSION: LNA and DHA, at the amounts given in this study, show a similar bioequivalence for DHA accretion in different tissues of the mother and in brain segments of fetuses and newborn rats. Copyright 2004 S. Karger AG, Basel
Sijtsma, L. and M. E. De Swaaf (2004). "Biotechnological production and applications of the omega-3 polyunsaturated fatty acid docosahexaenoic acid." Appl Microbiol Biotechnol.
Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid composed of 22 carbon atoms and six double bonds. Because the first double bond, as counted from the methyl terminus, is at position three, DHA belongs to the so-called omega-3 group. In recent years, DHA has attracted much attention because of its beneficial effect on human health. At present, fish oil is the major source of DHA, but alternatively it may be produced by use of microorganisms. Marine microorganisms may contain large quantities of DHA and are considered a potential source of this important fatty acid. Some of these organisms can be grown heterotrophically on organic substrates without light. These processes can be well controlled and DHA with constant quality can be produced all year round. This paper reviews recent advances in the biotechnological production of DHA by marine microorganisms.
Shirai, N. and H. Suzuki (2004). "Effect of Dietary Docosahexaenoic Acid and Catechins on Maze Behavior in Mice." Ann Nutr Metab 48(1): 51-58.
BACKGROUND/AIMS: Docosahexaenoic acid (DHA; 22:6 n-3) and catechins are food components that play an important role in maintaining human health. However, the effect of a simultaneous intake of DHA and catechins on brain function is unknown. The purpose of this study was to investigate the effect of DHA and catechins on maze behavior in mice. METHOD: Adult (5 months old) and old (15 months old) male mice were fed 5% lard diets containing 0 or 1.5% DHA ethyl ester (DHA-EE), either with or without 0.5% catechins, for 3.5 months. Maze behavior was assessed 3 months after the start of the feeding experiment. The time required and distance traveled to reach the maze exit, and the number of times that a mouse strayed into blind alleys in the maze were measured. The fatty acid compositions of plasma and brain lipids were measured after the maze behavior experiment. RESULTS: Adult mice in the catechin, DHA-EE, and DHA-EE + catechin diet groups required less time and traveled a shorter distance to reach the maze exit, and strayed into blind alleys fewer times than those in the corresponding lard groups. Among old mice, the DHA-EE + catechin diet group showed an improvement in maze behavior. No marked differences in the brain fatty acid composition between lard and catechin diet groups were observed; in the DHA-EE intake groups, the brain DHA percentage was raised. CONCLUSION: These results suggest that a simultaneous intake of DHA and catechins may certainly enhance brain function in both adult and old mice. Copyright 2004 S. Karger AG, Basel
Sarkadi-Nagy, E., V. Wijendran, et al. (2004). "Formula feeding potentiates docosahexaenoic and arachidonic acid biosynthesis in term and preterm baboon neonates." J Lipid Res 45(1): 71-80.
Infant formulas supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) are now available in the United States; however, little is known about the factors that affect biosynthesis. Baboon neonates were assigned to one of four treatments: term, breast-fed; term, formula-fed; preterm (155 of 182 days gestation), formula-fed; and preterm, formula+DHA/ARA-fed. Standard formula had no DHA/ARA; supplemented formula had 0.61%wt DHA (0.3% of calories) and 1.21%wt ARA (0.6% of calories), and baboon breast milk contained 0.68 +/- 0.22%wt DHA and 0.62 +/- 0.12%wt ARA. At 14 days adjusted age, neonates received a combined oral dose of [U-(13)C]alpha-linolenic acid (LNA*) and [U-(13)C]linoleic acid (LA*), and tissues were analyzed 14 days after dose. Brain accretion of linolenic acid-derived DHA was approximately 3-fold greater for the formula groups than for the breast-fed group, and dietary DHA partially attenuated excess DHA synthesis among preterms. A similar, significant pattern was found in other organs. Brain linoleic acid-derived ARA accretion was significantly greater in the unsupplemented term group but not in the preterm groups compared with the breast-fed group. These data show that formula potentiates the biosynthesis/accretion of DHA/ARA in term and preterm neonates compared with breast-fed neonates and that the inclusion of DHA/ARA in preterm formula partially restores DHA/ARA biosynthesis to lower, breast-fed levels. Current formula DHA concentrations are inadequate to normalize long-chain polyunsaturated fatty acids synthesis to that of breast-fed levels.
Reinwald, S., Y. Li, et al. (2004). "Repletion with (n-3) Fatty Acids Reverses Bone Structural Deficits in (n-3)-Deficient Rats." J Nutr 134(2): 388-394.
(n-3) PUFA deficiency and repletion effects on bone mechanical properties have not been examined. The primary research aim was to evaluate whether changes in the fatty acid composition of bone tissue compartments previously reported to influence bone formation rates would affect bone modeling and mechanical properties. In this investigation, three groups of rats were studied, second generation (n-3)-deficient, (n-3)-repleted, and a control (n-3)-adequate. The (n-3)-adequate diet contained alpha-linolenic acid [LNA, 18:3(n-3), 2.6% of total fatty acids] and docosahexaenoic acid [DHA, 22:6(n-3), 1.3% of total fatty acids]. Fatty acid composition of the hindlimb tissues (bone and muscle) of chronically (n-3)-deficient rats revealed a marked increase in (n-6) PUFA [20:4(n-6), 22:4(n-6), and 22:5(n-6)] and a corresponding decrease in (n-3) PUFA [18:3(n-3), 20:5(n-3), 22:5(n-3) and 22:6(n-3)]. Measurement of bone mechanical properties (energy to peak load) of tibiae showed that (n-3) deficiency diminished structural integrity. Rats repleted with (n-3) fatty acids demonstrated accelerated bone modeling (cross-sectional geometry) and an improved second moment in tibiae compared with control (n-3)-adequate rats after 28 d of dietary treatment. This study showed that repletion with dietary (n-3) fatty acids restored the ratio of (n-6)/(n-3) PUFA in bone compartments and reversed compromised bone modeling in (n-3)-deficient rats.
Puangkaew, J., V. Kiron, et al. (2004). "Nonspecific immune response of rainbow trout (Oncorhynchus mykiss Walbaum) in relation to different status of vitamin E and highly unsaturated fatty acids." Fish Shellfish Immunol 16(1): 25-39.
This study was designed to examine the effects of dietary vitamin E (VE) on modulation of immune responses when supplied with two levels of n-3 highly unsaturated fatty acids (n-3 HUFA) in rainbow trout, Oncorhynchus mykiss. Six semipurified diets were prepared containing three levels of dietary VE (0, 100 or 1000 mg alpha-tocopheryl acetate kg(-1)diet) and n-3 HUFA either at 20 or 48% of dietary lipid provided from fish oil or docosahexaenoic acid (DHA) concentrated fish oil respectively. The diets were fed to rainbow trout (100 g initial mean weight) for 15 weeks. The VE, vitamin C (VC) content in plasma and tissues and the nonspecific immune responses, both humoral (alternative complement activity, total immunoglobulin) and cellular (phagocytosis, nonspecific cytotoxicity) were examined.VE contents in the kidney reflected the dietary input but were lower in fish fed 48% n-3 HUFA diets, and could have impaired some of immune responses compared to fish fed 20% n-3 HUFA. VC contents in kidney followed the same pattern as VE. Both humoral and cellular immune functions deteriorated in fish fed VE deficient diets whereas improvement in most of the parameters corresponded to its supplementation. However, the higher dose of dietary VE did not substantially enhance the responses assayed compared to the 100 mg dose.Besides clearly indicating the role of VE in maintaining the immune functions in fish in relation to dietary n-3 HUFA, this study has revealed that optimum health benefits could be achieved when VE is maintained slightly above the levels generally recommended for normal growth.
Nilsen, D. W. and W. S. Harris (2004). "n-3 Fatty acids and cardiovascular disease." Am J Clin Nutr 79(1): 166.
Muskiet, F. A., M. R. Fokkema, et al. (2004). "Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized controlled trials." J Nutr 134(1): 183-6.
Musiek, E. S., J. K. Cha, et al. (2004). "Quantification of F-ring isoprostane-like compounds (F(4)-neuroprostanes) derived from docosahexaenoic acid in vivo in humans by a stable isotope dilution mass spectrometric assay." J Chromatogr B Analyt Technol Biomed Life Sci 799(1): 95-102.
Lipid peroxidation has been implicated in the pathophysiological sequelae of human neurodegenerative disorders. It is recognized that quantification of lipid peroxidation is best assessed in vivo by measuring a series of prostaglandin (PG) F(2)-like compounds termed F(2)-isoprostanes (IsoPs) in tissues in which arachidonic acid is abundant. Unlike other organs, the major polyunsaturated fatty acid (PUFA) in the brain is docosahexaenoic acid (DHA, C22:6 omega-6), and this fatty acid is particularly enriched in neurons. We have previously reported that DHA undergoes oxidation in vitro and in vivo resulting in the formation of a series of F(2)-IsoP-like compounds termed F(4)-neuroprostanes (F(4)-NPs). We recently chemically synthesized one F(4)-NP, 17-F(4c)-NP, converted it to an (18)O-labeled derivative, and utilized it as an internal standard to develop an assay to quantify endogenous production of F(4)-NPs by gas chromatography (GC)/negative ion chemical ionization (NICI) mass spectrometry (MS). The assay is highly precise and accurate. The lower limit of sensitivity is approximately 10pg. Levels of F(4)-NPs in brain tissue from rodents were 8.7+/-2.0ng/g wet weight (mean+/-S.D.). Levels of the F(4)-NPs in brains from normal humans were found to be 4.9+/-0.6ng/g (mean+/-S.D.) and were 2.1-fold higher in affected regions of brains from humans with Alzheimer's disease (P=0.02). Thus, this assay provides a sensitive and accurate method to assess oxidation of DHA in animal and human tissues and will allow for the further elucidation of the role of oxidative injury to the central nervous system in association with human neurodegenerative disorders.
Murthy, S., E. Born, et al. (2004). "Liver-X-receptor-mediated increase in ATP-binding cassette transporter A1 expression is attenuated by fatty acids in CaCo-2 cells: effect on cholesterol efflux to high-density lipoprotein." Biochem J 377(Pt 3): 545-52.
The effect of fatty acids on LXR (liver X receptors)-mediated enhancement of ABCA1 (ATP-binding cassette transporter A1) expression and cholesterol efflux was investigated in human intestinal cells CaCo-2. LXR activation by T0901317 increased basolateral cholesterol efflux to lipoprotein particles isolated at a density of 1.21 g/ml or higher. Oleic and arachidonic acids attenuated the amount of cholesterol isolated from these particles. Stearic, linoleic and docosahexaenoic acids also decreased cholesterol efflux from basolateral membranes, with the polyunsaturated fatty acids being the most potent. Although oleic, arachidonic and docosahexaenoic acids modestly decreased ABCA1 mRNA levels in response to LXR activation, stearic and linoleic acids did not. Except for oleic acid, all fatty acids substantially attenuated an increase in ABCA1 mass secondary to LXR activation. Inhibiting acyl-CoA:cholesterol acyltransferase activity prevented the decrease in cholesterol efflux caused by oleic acid. Thus, in response to LXR activation, all fatty acids decreased the efflux of cholesterol from the basolateral membrane of CaCo-2 cells. Although modest suppression of ABCA1 gene expression by oleic, arachidonic and docosahexaenoic acids cannot be completely excluded as a mechanism, the predominant effect of fatty acids on ABCA1 expression and cholesterol efflux is at a post-transcriptional level.
Muller-Navarra, D. C., M. T. Brett, et al. (2004). "Unsaturated fatty acid content in seston and tropho-dynamic coupling in lakes." Nature 427(6969): 69-72.
Determining the factors that control food web interactions is a key issue in ecology. The empirical relationship between nutrient loading (total phosphorus) and phytoplankton standing stock (chlorophyll a) in lakes was described about 30 years ago and is central for managing surface water quality. The efficiency with which biomass and energy are transferred through the food web and sustain the production of higher trophic levels (such as fish) declines with nutrient loading and system productivity, but the underlying mechanisms are poorly understood. Here we show that in seston (fine particles in water) during summer, specific omega3-polyunsaturated fatty acids (omega3-PUFAs), which are important for zooplankton, are significantly correlated to the trophic status of the lake. The omega3-PUFAs octadecatetraenoic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid, but not alpha-linolenic acid, decrease on a double-logarithmic scale with increasing total phosphorus. By combining the empirical relationship between EPA-to-carbon content and total phosphorus with functional models relating EPA-to-carbon content to the growth and egg production of daphnids, we predict secondary production for this key consumer. Thus, the decreasing efficiency in energy transfer with increasing lake productivity can be explained by differences in omega3-PUFA-associated food quality at the plant-animal interface.
Min, Y., K. Ghebremeskel, et al. (2004). "Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes." Diabetologia 47(1): 75-81.
AIMS/HYPOTHESIS. Gestational diabetes is a metabolic disorder affecting 2-5% of women and is a predictor of obesity, Type 2 diabetes mellitus and cardiovascular disease. Insulin resistance, a characteristic of gestational diabetes and obesity, is correlated with the fatty acids profile of the red cell and skeletal muscle membranes. We investigated the plasma and red cell fatty acid status of gestational diabetes. The effect of obesity on membrane fatty acids was also examined. METHODS. Fasting blood obtained at diagnosis was analysed for the fatty acids in plasma choline phosphoglycerides and red cell choline and ethanolamine phosphoglycerides. RESULTS. There were reductions in arachidonic acid (controls 10.74+/-2.35 vs gestational diabetes 8.35+/-3.49, p<0.01) and docosahexaenoic acid (controls 6.31+/-2.67 vs gestational diabetes 3.25+/-2.00, p<0.0001) in the red cell choline phosphoglycerides in gestational diabetes. A similar pattern was found in the ethanolamine phosphoglycerides. Moreover, the arachidonic and docosahexaenoic acids depletion in the red cell choline phosphoglycerides was much greater in overweight/obese gestational diabetes (arachidonic acid=7.49+/-3.37, docosahexaenoic acid=2.98+/-2.18, p<0.01) compared with lean gestational diabetes (arachidonic acid=10.03+/-2.74, docosahexaenoic acid=4.18+/-1.42). CONCLUSION/INTERPRETATION. Apparently normal plasma choline phosphoglycerides fatty acids profile in the gestational diabetic women suggested that membrane lipid abnormality is associated specifically with perturbation in the membrane. The fact that the lipid abnormality is more pronounced in the outer leaflet of the membrane where most of receptor binding and enzyme activities take place might provide an explanation for the increased insulin resistance in gestational diabetes and obesity.
Madani, S., A. Hichami, et al. (2004). "Diacylglycerols containing Omega 3 and Omega 6 fatty acids bind to RasGRP and modulate MAP kinase activation." J Biol Chem 279(2): 1176-83.
We elucidated the effects of different diacylglycerols (DAGs), i.e. 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG), 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDG), and 1-stearoyl-2-eicosapentaenoyl-sn-glycerol (SEG), on [3H]PDBu binding to RasGRP. The competition studies with these DAGs on [3H]PDBu binding to RasGRP revealed different Ki values for these DAG molecular species. Furthermore, we transfected human Jurkat T cells by a plasmid containing RasGRP and assessed the implication of endogenous DAGs on activation of MAP kinases ERK1/ERK2, induced by phorbol-12-myristate-13-acetate (PMA). In control cells, GF109203X, a protein kinase C inhibitor, inhibited ERK1/ERK2 activation. However, this agent curtailed but failed to completely diminish ERK1/ERK2 phosphorylation in RasGRP-overexpressing cells, though calphostin C, a DAG binding inhibitor, suppressed the phosphorylation of MAP kinases in these cells. In cells incubated with arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), PMA induced the production of endogenous DAGs containing these fatty acids, respectively: DAG-AA, DAG-DHA, and DAG-EPA. The inhibition of production of DAG-AA and DAG-DHA significantly inhibited MAP kinase activation in RasGRP overexpressing, but not in control, cells. Our study demonstrates that three DAG molecular species bind to RasGRP, but only DAG-AA and DAG-DHA participate in the modulation of RasGRP-mediated activation of MAP kinases in Jurkat T cells.
MacDonald, I. M., M. Hebert, et al. (2004). "Effect of docosahexaenoic acid supplementation on retinal function in a patient with autosomal dominant Stargardt-like retinal dystrophy." Br J Ophthalmol 88(2): 305-6.
Lauritzen, L., M. H. Jorgensen, et al. (2004). "Test-Retest Reliability of Swept Visual Evoked Potential Measurements of Infant Visual Acuity and Contrast Sensitivity." Pediatr Res.
The aim of the study was to describe variations in swept visual evoked potential (SWEEP-VEP) assessment of visual acuity and contrast sensitivity in infants and to evaluate the best way to estimate visual performance from obtained SWEEP-VEP data. The visual performance of 92 infants (6-40 wk of age) was measured in two separate visits. Results were verified with repeated tests in seven adults. There was a strong association between the two measurements of infant visual acuity (r = 0.91, p < 0.001), with no constant bias and an inter-assay coefficient of variation of 8.4%. The intra-assay coefficient of variation was 17% and in repeated sessions all obtained acuity measures were normally distributed, indicating that the mean and not the maximum threshold best estimates visual acuity. This estimate of visual acuity also had lower test-retest variability than those calculated from the maximum threshold or threshold from the average EEG signals (p = 0.001). Test-retest measures of infant contrast sensitivity had a correlation coefficient of 0.72 (p < 0.001) and an inter-assay coefficient of variation of 23%. With the observed test-retest variability, SWEEP-VEP is less valid for estimating the visual performance of individual subjects, but it can give reliable group means. This method was well suited to describe visual development in the infants, which for acuity as well as contrast sensitivity increased by 0.64 octave per doubling in age. However, the variability of the SWEEP-VEP method can be a limiting factor, for example, in the assessment of the potential effect of dietary docosahexaenoic acid in a homogeneous group of infants.
Kim, H. Y., J. Bigelow, et al. (2004). "Substrate preference in phosphatidylserine biosynthesis for docosahexaenoic Acid containing species." Biochemistry 43(4): 1030-6.
Neuronal membranes contain high levels of phosphatidylserine (PS) and docosahexaenoic acid (22:6n-3, DHA). In this study, substrate preference in PS synthesis was determined to gain insight on the biochemical basis for concentrating PS in neuronal membranes where 22:6n-3 is highly enriched. We first established an in vitro assay method using unilamellar vesicles (LUV) of deuterium-labeled substrates and reversed-phase HPLC/electrospray ionization (ESI) mass spectrometry. The PS production by the incubation of deuterium-labeled substrate and microsomal fractions was monitored. We found that tissue-specific substrate preference exists in PS synthesis. Microsomes from the cerebral cortex synthesized PS from 18:0,22:6-PC most favorably among the PC substrates tested, followed by 18:0,22:5-PC, resulting in the PC substrate preference in the order of 18:0,22:6 > 18:0,22:5 > 18:0,20:4 = 18:0,18:1. Liver microsomes also preferred 18:0,22:6-PC as the substrate in PS synthesis but did not use 18:0,22:5-PC favorably. The 18:0,22:5-PC species was converted to PS at the similar extent as 18:0,20:4- or 18:0,18:1-PC species in the liver. Both brain and liver microsomes showed a preference for 18:0 over 16:0 as the sn-1 fatty acid. From these data it was deduced that preferential conversion of 18:0,22:6-PC to the corresponding PS species is at least partly responsible for concentrating PS in neuronal tissues where 22:6n-3 is particularly abundant. The distinctive preference for 18:0,22:5-PS observed with brain microsomes may help to maintain PS at a high level in the brain when 22:6n-3 is replaced by 22:5n-3 as in the case of n-3 fatty acid deficiency.
Kankaanpaa, P., B. Yang, et al. (2004). "Effects of polyunsaturated fatty acids in growth medium on lipid composition and on physicochemical surface properties of lactobacilli." Appl Environ Microbiol 70(1): 129-36.
Most probiotic lactobacilli adhere to intestinal surfaces, a phenomenon influenced by free polyunsaturated fatty acids (PUFA). The present study investigated whether free linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, or docosahexaenoic acid in the growth medium alters the fatty acid composition of lactobacilli and their physical characteristics. The most abundant bacterial fatty acids identified were oleic, vaccenic, and dihydrosterculic acids. PUFA, especially conjugated linoleic acid (CLA) isomers and gamma-linolenic, eicosapentaenoic, docosahexaenoic, and alpha-linolenic acids, also were identified in lactobacilli. When lactobacilli were cultured in MRS broth supplemented with various free PUFA, the incorporation of a given PUFA into bacterial fatty acids was clearly observed. Moreover, PUFA supplementation also resulted in PUFA-dependent changes in the proportions of other fatty acids; major interconversions were seen in octadecanoic acids (18:1), their methylenated derivatives (19:cyc), and CLA. Intermittent changes in eicosapentaenoic acid proportions also were noted. These results were paralleled by minor changes in the hydrophilic or hydrophobic characteristics of lactobacilli, suggesting that PUFA interfere with microbial adhesion to intestinal surfaces through other mechanisms. In conclusion, we have demonstrated that free PUFA in the growth medium induce changes in bacterial fatty acids in relation to the regulation of the degree of fatty acid unsaturation, cyclization, and proportions of CLA and PUFA containing 20 to 22 carbons. The potential role of lactobacilli as regulators of PUFA absorption may represent another means by which probiotics could redirect the delicate balance of inflammatory mediators derived from PUFA within the inflamed intestine.
Kalmijn, S., M. P. van Boxtel, et al. (2004). "Dietary intake of fatty acids and fish in relation to cognitive performance at middle age." Neurology 62(2): 275-80.
OBJECTIVE: To examine the associations of fatty acid and fish intake with cognitive function. METHODS: Data are from a cross-sectional population-based study among 1,613 subjects ranging from 45 to 70 years old. From 1995 until 2000, an extensive cognitive battery was administered and compound scores were constructed for memory, psychomotor speed, cognitive flexibility (i.e., higher order information processing), and overall cognition. A self-administered food-frequency questionnaire was used to assess habitual food consumption. The risk of impaired cognitive function (lowest 10% of the compound score) according to the energy adjusted intake of fatty acids was assessed with logistic regression, adjusting for age, sex, education, smoking, alcohol consumption, and energy intake. RESULTS: Marine omega-3 polyunsaturated fatty acids (PUFA) (eicosapentaenoic acid and docosahexaenoic acid) were inversely related to the risk of impaired overall cognitive function and speed (per SD increase: OR = 0.81, 95% CI 0.66 to 1.00 and OR = 0.72, 95% CI 0.57 to 0.90). Results for fatty fish consumption were similarly inverse. Higher dietary cholesterol intake was significantly associated with an increased risk of impaired memory and flexibility (per SD increase: OR = 1.27, 95% CI 1.02 to 1.57 and OR = 1.26, 95% CI 1.01 to 1.57). Per SD increase in saturated fat intake, the risk of impaired memory, speed, and flexibility was also increased, although not significantly. CONCLUSIONS: Fatty fish and marine omega-3 PUFA consumption was associated with a reduced risk and intake of cholesterol and saturated fat with an increased risk of impaired cognitive function in this middle-aged population.
Iribarren, C., J. H. Markovitz, et al. (2004). "Dietary intake of n-3, n-6 fatty acids and fish: Relationship with hostility in young adults-the CARDIA study." Eur J Clin Nutr 58(1): 24-31.
BACKGROUND:: Hostility has been shown to predict both the development and manifestation of coronary disease. Examining the inter-relation of dietary intake of fish and of polyunsaturated (n-3 and n-6) essential fatty acids with hostility may provide additional insights into the cardioprotective effect of dietary fish and polyunsaturated fatty acids. OBJECTIVE:: To examine the association of dietary n-3, n-6 fatty acids and fish with level of hostility in a sample of 3581 urban white and black young adults. DESIGN:: Cross-sectional observational study as part of an ongoing cohort study. A dietary assessment in 1992-1993 and measurement of hostility and other covariates in 1990-1991 were used in the analysis. RESULTS:: The multivariate odds ratios of scoring in the upper quartile of hostility (adjusting for age, sex, race, field center, educational attainment, marital status, body mass index, smoking, alcohol consumption and physical activity) associated with one standard deviation increase in docosahexaenoic acid (DHA, 22:6) intake was 0.90 (95% CI=0.82-0.98; P=0.02). Consumption of any fish rich in n-3 fatty acids, compared to no consumption, was also independently associated with lower odds of high hostility (OR=0.82; 95% CI=0.69-0.97; P=0.02). CONCLUSIONS:: These results suggest that high dietary intake of DHA and consumption of fish rich in n-3 fatty acids may be related to lower likelihood of high hostility in young adulthood. The association between dietary n-3 fatty acids and hostile personality merits further research.European Journal of Clinical Nutrition (2004) 58, 24-31. doi:10.1038/sj.ejcn.1601739
Hansen, H. S. and S. F. Olsen (2004). "Sleep patterns, docosahexaenoic acid, and gestational length." Am J Clin Nutr 79(2): 334.
Guichardant, M., B. Chantegrel, et al. (2004). "Specific markers of lipid peroxidation issued from n-3 and n-6 fatty acids." Biochem Soc Trans 32(Pt 1): 139-40.
Several markers of lipid peroxidation are available with different degrees of specificity, from malondialdehyde as a global marker, to F(2)-isoprostane, which is specifically produced from arachidonic acid. Among these, 4-hydroxynonenal is recognized as a breakdown product of fatty acid hydroperoxides, such as 15-hydroperoxy-eicosatetraenoic acid and 13-hydroperoxy-octade cadienoic acid from the n -6 fatty acids. Furthermore, 4-hydroxyhexenal (4-HHE) derives from n -3 fatty acid hydroperoxides. We have recently described the occurrence of 4-hydroxydodecadienal (4-HDDE) from the 12-lipoxygenase product of arachidonic acid 12-hydroperoxy-eicosatetraenoic acid. These three hydroxy-alkenals may be measured in human plasma by GC-MS, but they may partly be generated in the course of sampling, and the relative volatility of 4-HHE makes its measurement quite unreliable. We have successfully characterized and measured the stable oxidized carboxylic acid products from the hydroxy-alkenals 4-HNA, 4-HHA and 4-HDDA in urine. The ratio between 4-HHA and 4-HNA found in the same urinary sample might provide useful information on the location of lipid peroxidation, accounting for the high enrichment of the cerebrovascular system with docosahexaenoic acid, the main n -3 fatty acid in humans.
Ethier, I., G. Beaudry, et al. (2004). "The Transcription Factor NGFI-B (Nur77) and Retinoids Play a Critical Role in Acute Neuroleptic-Induced Extrapyramidal Effect and Striatal Neuropeptide Gene Expression." Neuropsychopharmacology 29(2): 335-46.
Despite extensive investigation, the cellular mechanisms responsible for neuroleptic actions remain elusive. We have previously shown that neuroleptics modulated the expression of some members of the ligand-activated transcription factors (nuclear receptors) including the nerve-growth factor inducible gene B (NGFI-B or Nur77) and retinoid X receptor (RXR) isoforms. Using genetic and pharmacological approaches, we investigated the role of NGFI-B and retinoids in acute behavioral and biochemical responses to dopamine antagonists. NGFI-B knockout (KO) mice display a profound alteration of haloperidol-induced catalepsy and striatal neuropeptide gene expression. Haloperidol-induced increase of striatal enkephalin mRNA is totally abolished in NGFI-B KO mice whereas the increase of neurotensin mRNA expression is reduced by 50%. Interestingly, catalepsy induced by raclopride, a specific dopamine D(2)/D(3) antagonist is completely abolished in NGFI-B-deficient mice whereas the cataleptic response to SCH 23390, a dopamine D(1) agonist, is preserved. Accordingly, the effects of haloperidol on striatal c-fos, Nor-1, and dynorphin mRNA expression are also preserved in NGFI-B-deficient mice. The cataleptic response and the increase of enkephalin mRNA expression induced by haloperidol can also be suppressed by administration of retinoid ligands 9-cis retinoic acid and docosahexaenoic acid. In addition, we demonstrate that haloperidol enhances colocalization of NGFI-B and RXRgamma1 isoform mRNAs, suggesting that both NGFI-B and a RXR isoform are highly coexpressed after haloperidol administration. Our data demonstrate, for the first time, that NGFI-B and retinoids are actively involved in the molecular cascade induced by neuroleptic drugs.Neuropsychopharmacology (2004) 29, 335-346, advance online publication, 5 November 2003; doi:10.1038/sj.npp.1300318
de Groot, R. H., J. Adam, et al. (2004). "Alpha-linolenic acid supplementation during human pregnancy does not effect cognitive functioning." Prostaglandins Leukot Essent Fatty Acids 70(1): 41-7.
Increasing evidence suggests a positive association between docosahexaenoic acid (DHA, 22:6n-3) and cognitive performance. In addition, pregnancy is associated with a reduction of the DHA status and cognitive deficits. In the current study, cognition was assessed in pregnant women receiving a margarine enriched with alpha-linolenic acid (ALA, 18:3n-3, the ultimate dietary precursor of DHA) and some linoleic acid (LA, 18:2n-6, to prevent a possible reduction in n-6 fatty acids). A control group received a margarine enriched with LA only. ALA supplementation hardly affected the maternal DHA status and no significant differences were found in cognitive performance between the two groups. This indicates that ALA supplementation during pregnancy does not affect cognitive performance during and 32 weeks after gestation. At week 14 of pregnancy and 32 weeks after delivery, higher plasma DHA levels were associated with lower cognitive performance as indicated by longer reaction times on the finger precuing task (partial correlation coefficients 0.3705 and 0.4633, respectively, P<0.01). Since this could imply an unexpected adverse association between DHA and certain aspects of cognitive functioning this certainly needs further investigation.
De Groot, R. H., G. Hornstra, et al. (2004). "Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome." Am J Clin Nutr 79(2): 251-260.
BACKGROUND: Maternal essential fatty acid status declines during pregnancy, and as a result, neonatal concentrations of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) may not be optimal. OBJECTIVE: Our objective was to improve maternal and neonatal fatty acid status by supplementing pregnant women with a combination of alpha-linolenic acid (ALA, 18:3n-3) and linoleic acid (LA, 18:2n-6), the ultimate dietary precursors of DHA and AA, respectively. DESIGN: From week 14 of gestation until delivery, pregnant women consumed daily 25 g margarine supplying either 2.8 g ALA + 9.0 g LA (n = 29) or 10.9 g LA (n = 29). Venous blood was collected for plasma phospholipid fatty acid analyses at weeks 14, 26, and 36 of pregnancy, at delivery, and at 32 wk postpartum. Umbilical cord blood and vascular tissue samples were collected to study neonatal fatty acid status also. Pregnancy outcome variables were assessed. RESULTS: ALA+LA supplementation did not prevent decreases in maternal DHA and AA concentrations during pregnancy and, compared with LA supplementation, did not increase maternal and neonatal DHA concentrations but significantly increased eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3) concentrations. In addition, ALA+LA supplementation lowered neonatal AA status. No significant differences in pregnancy outcome variables were found. CONCLUSIONS: Maternal ALA+LA supplementation did not promote neonatal DHA+AA status. The lower concentrations of Osbond acid (22:5n-6) in maternal plasma phospholipids and umbilical arterial wall phospholipids with ALA+LA supplementation than with LA supplementation suggest only that functional DHA status improves with ALA+LA supplementation.
Champeil-Potokar, G., I. Denis, et al. (2004). "Astrocytes in culture require docosahexaenoic acid to restore the n-3/n-6 polyunsaturated fatty acid balance in their membrane phospholipids." J Neurosci Res 75(1): 96-106.
Docosahexaenoic acid (DHA), the main n-3 polyunsaturated fatty acid (PUFA) in membranes, is particularly abundant in brain cells. Decreased cerebral concentrations of DHA, resulting from dietary n-3 deficiency, are associated with impaired cognitive function. Because the cellular causes of this impairment are still unknown, we need in vitro models that mimic the variations in n-3/n-6 PUFA seen in vivo. We have compared the PUFA profiles of hamster astrocytes cultured in medium supplemented with long-chain PUFA [DHA and/or arachidonic acid (AA)] with those of brain tissue from hamsters fed an n-6/n-3 PUFA-balanced diet or one lacking n-3 PUFA. Astrocytes were obtained from the brain cortex of newborn hamsters and cultured in minimum essential medium + 5% fetal calf serum (FCS) supplemented with DHA and/or AA for 10 days. The astrocytes cultured in medium + FCS had low n-3 PUFA contents, comparable to those of brain tissue from hamsters fed an n-3-deficient diet. We have shown that astrocytes grown in medium supplemented with DHA and/or AA, plus alpha-tocopherol to prevent lipid peroxidation, incorporated large amounts of these long-chain PUFA, so that the n-6/n-3 PUFA compositions of the phosphatidylethanolamine and phosphatidylcholine, the two main classes of membrane phospholipids, were greatly altered. Astrocytes cultured in medium plus DHA had a more physiological n-3 status, grew better, and retained their astrocyte phenotype. Thus astrocytes in culture are likely to be physiologically relevant only when provided with adequate DHA. This reliable method of altering membrane phospholipid composition promises to be useful for studying the influence of n-6/n-3 imbalance on astrocyte function.
Buckley, M. S., A. D. Goff, et al. (2004). "Fish oil interaction with warfarin." Ann Pharmacother 38(1): 50-2.
OBJECTIVE: To report a case of elevated international normalized ratio (INR) in a patient taking fish oil and warfarin. CASE SUMMARY: A 67-year-old white woman had been taking warfarin for 1(1/2) years due to recurrent transient ischemic attacks. Her medical history included hypothyroidism, hyperlipidemia, osteopenia, hypertension, and coronary artery disease. She also experienced an inferior myocardial infarction in 1995 requiring angioplasty, surgical repair of her femoral artery in 1995, and hernia repair in 1996. This patient has her INR checked in the anticoagulation clinic and is followed monthly by the clinical pharmacist. Prior to the interaction, her INR was therapeutic for 5 months while she was taking warfarin 1.5 mg/d. The patient admitted to doubling her fish oil dose from 1000 to 2000 mg/d. Without dietary, lifestyle, or medication changes, the INR increased from 2.8 to 4.3 within 1 month. The INR decreased to 1.6 one week after subsequent fish oil reduction, necessitating a return to the original warfarin dosing regimen. DISCUSSION: Fish oil supplementation could have provided additional anticoagulation with warfarin therapy. Fish oil, an omega-3 polyunsaturated fatty acid, consists of eicosapentaenoic acid and docosahexaenoic acid. This fatty acid may affect platelet aggregation and/or vitamin K-dependent coagulation factors. Omega-3 fatty acids may lower thromboxane A(2) supplies within the platelet as well as decrease factor VII levels. Although controversial, this case report illustrates that fish oil can provide additive anticoagulant effects when given with warfarin. CONCLUSIONS: This case reveals a significant rise in INR after the dose of concomitant fish oil was doubled. Patients undergoing anticoagulation therapy with warfarin should be educated about and monitored for possible drug-herb interactions. Pharmacists can play a crucial role in identifying possible drug interactions by asking patients taking warfarin about herbal and other alternative medicine product use.
Blanaru, J. L., J. R. Kohut, et al. (2004). "Dose response of bone mass to dietary arachidonic acid in piglets fed cow milk-based formula." Am J Clin Nutr 79(1): 139-47.
BACKGROUND: The addition of arachidonic acid (AA) and docosahexaenoic acid (DHA) to infant formula was recently approved in North America. In piglets, dietary AA is linked to elevations in bone mass. OBJECTIVE: The objective was to investigate the effects of varied amounts of dietary AA on bone modeling and bone mass with the use of the piglet model for infant nutrition. DESIGN: Male piglets (n = 32) were randomly assigned to receive 1 of 4 formulas supplemented with AA (0.30%, 0.45%, 0.60%, or 0.75% of fat) plus DHA (0.1% of fat) from days 5 to 20 of life. Measurements included biomarkers of bone modeling, fatty acid status, and whole-body and femur bone mineral content; bone area was measured by dual-energy X-ray absorptiometry. Differences among groups were detected with two-factor analysis of variance. Regression analyses were used to determine factors responsible for bone mineral content after dietary AA was accounted for. RESULTS: Proportions of AA in plasma, liver, and adipose were modified by the dietary treatments, but bone modeling was not affected. Liver AA was positively related to plasma insulin-like growth factor 1 and calcitriol and urinary N-telopeptide. Whole-body bone mineral content was elevated in the piglets fed 0.60% and 0.75% AA and was best predicted by dietary AA and bone resorption. CONCLUSIONS: This study confirms that dietary AA alters bone mass and clarifies the best amount of AA to add to the diet of pigs born at term. Because the amount of dietary DHA was held constant, whether other amounts of DHA are related to bone mass requires investigation.
Zhang, C. W. and A. Richmond (2003). "Sustainable, high-yielding outdoor mass cultures of Chaetoceros muelleri var. subsalsum and Isochrysis galbana in vertical plate reactors." Mar Biotechnol (NY) 5(3): 302-10.
Continuous cultures of Chaetoceros muelleri and Isochrysis galbana were grown outdoors in flat plate-glass reactors in which light-path length (LPL) varied from 5 to 30 cm. High daily productivity (13 to 16 g cell mass per square meter of irradiated reactor surface) for long periods of time was obtained in reactors in which the optical path as well as cell density were optimized. 'Twenty centimeters was the optimal LPL, yielding the highest areal productivity of cell mass (g m(-2)d(-1)), eicosapentaenoic acid, and docosahexaenoic acid, which was identical with that previously found for polysaccharide production of Porphyridium and not far from the optimal LPL affecting maximal productivity in Nannochloropsis species. Relating the energy impinging on a given reactor surface area to the appropriate number of cells showed that the most efficient light dose per cell, obtained with the 20-cm LPL reactor, was approximately 2.5 times lower than the light dose available per cell in the 5-cm LPL reactor, in which a significant decline in areal cell density accompanied the lowest areal output of cell mass. The most effective harvesting regimen was in the range of 10% to 15% of culture volume harvested daily and replaced with fresh growth medium, resulting in a sustainable culture density of 24 x 10(6) and 28 x 10(6) cells/ml of C. muelleri and I. galbana, respectively.
Yusufi, A. N., J. Cheng, et al. (2003). "Differential effects of low-dose docosahexaenoic acid and eicosapentaenoic acid on the regulation of mitogenic signaling pathways in mesangial cells." J Lab Clin Med 141(5): 318-29.
Although dietary fish oil supplementation has been used to prevent the progression of kidney disease in patients with IgA nephropathy, relatively few studies provide a mechanistic rationale for its use. Using an antithymocyte (ATS) model of mesangial proliferative glomerulonephritis, we recently demonstrated that fish oil inhibits mesangial cell (MC) activation and proliferation, reduces proteinuria, and decreases histologic evidence of glomerular damage. We therefore sought to define potential mechanisms underlying the antiproliferative effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the predominant omega-3 polyunsaturated fatty acids found in fish oil, in cultured MC. DHA and EPA were administered to MC as bovine serum albumin fatty-acid complexes. Low-dose (10-50 micromol/L) DHA, but not EPA, inhibited basal and epidermal growth factor (EGF)-stimulated [(3)H]-thymidine incorporation in MCs. At higher doses (100 micromol/L), EPA and DHA were equally effective in suppressing basal and EGF-stimulated MC mitogenesis. Low-dose DHA, but not EPA, decreased ERK activation by 30% (P <.01), as assessed with Western-blot analysis using phosphospecific antibodies. JNK activity was increased by low-dose DHA but not by EPA. p38 activity was not significantly altered by DHA or EPA. Cyclin E activity, as assessed with a histone H1 kinase assay, was inhibited by low-dose DHA but not by EPA. DHA increased expression of the cell cycle inhibitor p21 but not p27; EPA had no effect on p21 or p27. We propose that the differential effect of low-dose DHA vs EPA in suppressing MC mitogenesis is related to down-regulation of ERK and cyclin E activity and to induction of p21.
Yuri, T., N. Danbara, et al. (2003). "Dietary docosahexaenoic acid suppresses N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats more effectively than eicosapentaenoic acid." Nutr Cancer 45(2): 211-7.
We compared the effects of identical amounts but different proportions of dietary n-3 polyunsaturated fatty acids (PUFAs) on N-methyl-N-nitrosourea (MNU)-induced mammary cancer in a rat model. The ability of dietary docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to suppress mammary cancer was evaluated. Female Sprague-Dawley rats were randomly assigned to three groups and maintained on diets containing 10% fatty acid consisting of EPA, a 1:1 mixture of EPA-plus-DHA, or DHA. The experimental diet was started after administration of MNU at 49 days of age, and the rats were maintained on the respective diets until the largest mammary tumor reached >1 cm in diameter or until the end of the study period (20 wk after MNU). All histologically detected mammary carcinomas were evaluated, irrespective of size. The DHA diet was associated with significant suppression of the carcinogenic effect of MNU compared with the EPA and EPA-plus-DHA diets: tumor incidence decreased to 23% (3/13) compared with 73% (11/15) and 65% (12/17) (P < 0.01 and P < 0.05, respectively); tumor multiplicity decreased to 0.23 compared with 1.67 and 1.59 (P < 0.01 and P < 0.05, respectively). There was no significant difference in tumor latency among the DHA, EPA, and EPA-plus-DHA groups (119, 105, and 117 days, respectively). Over 20 wk, the fatty acid composition of serum and mammary fat tissue reflected differences in the dietary n-3 PUFAs. Although DHA suppressed MNU-induced mammary carcinogenesis more effectively than EPA, generalized steatosis including mammary fat tissue appeared in all three groups.
Youssef, J. A., L. S. Birnbaum, et al. (2003). "Age-independent, gray matter-localized, brain-enhanced oxidative stress in male fischer 344 rats: brain levels of F(2)-isoprostanes and F(4)-neuroprostanes." Free Radic Biol Med 34(12): 1631-5.
While studies showed that aging is accompanied by increased exposure of the brain to oxidative stress, others have not detected any age-correlated differences in levels of markers of oxidative stress. Use of conventional markers of oxidative damage in vivo, which may be formed ex vivo and/or eliminated by endogenous metabolism, may explain these conflicting results. Recently, F(2)-isoprostanes and F(4)-neuroprostanes, peroxidation products of arachidonic acid and docosahexaenoic acid, respectively, have been identified as sensitive and reliable markers of oxidative injury. Therefore, this study was designed to quantify brain levels of F(2)-isoprostanes and F(4)-neuroprostanes and their precursors in 4, 10, 50, and 100 week old male Fischer 344 rats. Data show that levels of F(2)-isoprostanes and F(4)-neuroprostanes were comparable in all animal age groups. However, levels of F(4)-neuroprostanes were approximately 20-fold higher than those of F(2)-isoprostanes in all age groups, despite the fact that brain levels of docosahexaenoic acid were only twice as high as those of arachidonic acid. Based on our findings, it is concluded that aging is not accompanied by enhanced brain susceptibility to oxidative stress. Furthermore, the metabolically active gray matter of the brain, where docosahexaenoic acid is abundant, appears more susceptible to oxidative stress than the white matter.
Yang, L., Y. Huang, et al. (2003). "Isomeric distribution of conjugated linoleic acids (CLA) in the tissues of layer hens fed a CLA diet." J Agric Food Chem 51(19): 5654-60.
The isomeric distribution of conjugated linoleic acids (CLA) in the tissue lipids of hens in relation to that in the diet was examined. Silver-ion high-performance liquid chromatography was used to quantify individual CLA isomers in total tissue lipids, phospholipids, and triacylglycerols. It was found that the deposition of CLA isomers in hen tissues was selective. All tissues including serum, liver, heart, kidney, abdominal fat, and leg and breast muscles had lesser amounts of total cis/trans isomers ranging from 75.87 to 89.13% of total CLA, which was in contrast to the value of 92% of total CLA in the dietary lipids. Total trans/trans isomers in all tissue lipids ranging from 6.11 to 18.02% of total CLA were greater than that in the diet (4.19%). Among the individual trans/trans isomers, all tissues except for adipose tissue and brain incorporated greater amounts of t-12,t-14-18:2, t-11,t-13-18:2,t-10,t-12-18:2, t-9,t-11-18:2, and t-18,t-10-18:2 compared with the values of the diet. Within the cis/trans group, lesser amounts of c-10,t-12/t-10,c-12-18:2 were found to incorporate into all tissues compared with the value of the diet. Serum and liver had higher percentages of c-9,t-11/t-9,c-11, whereas the other tissues had similar levels of this isomer compared with that of the diet. It was also observed that supplementation of CLA in the diet of layer hens decreased the concentration of docosahexaenoic acid (22:6n-3) in all of the tissue lipids. It is concluded that dietary CLA can transfer to the tissue but that incorporation of CLA isomers into the tissue is selective in hens.
Xi, Z. P. and J. Y. Wang (2003). "Effect of dietary n-3 fatty acids on the composition of long- and very-long-chain polyenoic fatty acid in rat retina." J Nutr Sci Vitaminol (Tokyo) 49(3): 210-3.
The effect of dietary supplementation with n-3 fatty acids, primarily docosahexaenoic acid (DHA) with high purity, on the fatty acid composition, especially very-long-chain fatty acids (VLCFA) longer than DHA, with four or six double bonds, in the rod outer segment (ROS) membranes of young Sprague-Dawley rats was investigated. After several weeks of feeding, diets high in n-3 fatty acids increased the DHA level significantly, while there were decreased levels of most n-6 fatty acids, such as arachidonic acid and 22:5n-6. Six kinds of VLCFA were detected by gas chromatography-mass spectrometry (GC-MS). Feeding a high n-3 fatty acid diet significantly increased the content of some n-3 VLCFAs such as 26:4n-3 and 30:4n-3 in ROS membranes, but not all detected n-3 VLCFAs. This study demonstrates that the dietary level of n-3 fatty acids not only affects the level of DHA, but also the levels of VLCFA in ROS membranes.
Wu, F. C., Y. Y. Ting, et al. (2003). "Dietary docosahexaenoic acid is more optimal than eicosapentaenoic acid affecting the level of cellular defence responses of the juvenile grouper Epinephelus malabaricus." Fish Shellfish Immunol 14(3): 223-38.
The combined effects of dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids on phagocytic, respiratory burst, and leucocyte proliferative activities of the juvenile grouper, Epinephelus malabaricus, were investigated. The test fish were fed for 12wk on test diets containing 1g 100g(-1) diet of DHA and EPA in combinations (DHA/EPA: 3/1, 2/1, 1/1, 0.7/1, 0.3/1). In addition to promoting fish growth, high dietary DHA/EPA ratio significantly enhanced phagocytic and respiratory burst activities of grouper head-kidney leucocytes compared with low ratio. Significant correlations were found between leucocyte phagocytic or respiratory burst activities and concentrations of 20:3(n-3), DHA and EPA in fish liver and muscle tissues. Leucocyte proliferation was significantly higher (P< 0.05) when the diets were high in DHA/EPA ratio than low in DHA/EPA ratio, when stimulated by Con A and PHA-P, but not by LPS. Tissue DHA concentrations and leucocyte proliferation were significantly and positively correlated. Fortification of dietary DHA, thus increased T-cell proliferation and phagocytic function of grouper leucocytes. DHA is the only member in the (n-3) highly unsaturated fatty acid family that stimulated phagocytic functions of leucocytes and T-cell proliferation, and is more optimal than EPA affecting the cellular defence responses of the E. malabaricus juveniles.
Wright, T. C., B. J. Holub, et al. (2003). "Effect of combinations of fish meal and feather meal on milk fatty acid content and nitrogen utilization in dairy cows." J Dairy Sci 86(3): 861-9.
The effect of supplemental fishmeal in combination with feathermeal at two different proportions in the diet on milk docosahexaenoic acid (DHA) content was investigated. Recently, benefits to human health have been attributed to the consumption of this fatty acid, which is normally present in marine lipids. Six Holstein cows past peak lactation were used in a Latin square design with a 2 x 3 factorial arrangement of treatments. Fish- and feathermeals were prepared as pellets at 4:1 and 1:4 combinations and offered at 3.75, 11.75, and 27% of the diet. The supplements were top-dressed onto a basal diet based on corn silage that was progressively replaced by supplement. Nitrogen balance measures were made during the experiment because of the wide range in crude protein content of experimental diets. Milk protein content increased with level of supplementation in the diet reflecting the protein quality of the supplements used. There was overall higher milk DHA content when cows consumed the supplement containing more fishmeal than feather meal. Milk DHA content increased in a quadratic fashion, as more of either supplement was included in the diet. Apparent transfer efficiency of DHA from diet to milk declined with increasing amount of DHA in the diet. Results from this experiment suggest that transfer of docosahexaenoic acid from diet to milk may depend on diet composition and quantity present in the diet.
Wolff, A. C., R. C. Donehower, et al. (2003). "Phase I study of docosahexaenoic acid-paclitaxel: a taxane-fatty acid conjugate with a unique pharmacology and toxicity profile." Clin Cancer Res 9(10 Pt 1): 3589-97.
PURPOSE: Docosahexaenoic acid (DHA)-paclitaxel, a novel conjugate formed by covalently linking the natural fatty acid DHA to paclitaxel, was designed as a prodrug targeting intratumoral activation. This Phase I trial examined its toxicity and pharmacokinetics (PKs). EXPERIMENTAL DESIGN: Patients with advanced refractory solid tumors received a 2-h i.v. infusion of DHA-paclitaxel every 3 weeks. Plasma and urine samples were obtained to characterize the pharmacological profile of DHA-paclitaxel and paclitaxel. RESULTS: Twenty-four patients received 78 cycles of DHA-paclitaxel over five dose levels (200-1100 mg/m(2)). Median number of cycles was 2 (range, 1-8). Myelosuppression was the principal toxicity observed (grade 3/4 neutropenia in 21%/53% of courses at 1100 mg/m(2)); during cycle 1, febrile neutropenia occurred in 1 of 9 patients treated at 1100 mg/m(2). Other grade 3 toxicities were infrequent. No patients developed alopecia, peripheral neuropathy > grade 1, or musculoskeletal toxicity > grade 1. At 1100 mg/m(2), DHA-paclitaxel had a mean (CV%) volume of distribution of 7.5 (64) liters, beta half-life of 112 (56) h, and clearance of 0.11 (30) liters/h. Paclitaxel PK parameters at 1100 mg/m(2) were: C(max), 282 (46) ng/ml; AUC, 10,705 (60) ng/ml x h; and terminal half-life, 85 (101) h. Paclitaxel plasma exposure represented < or =0.06% of DHA-paclitaxel exposure. Paclitaxel AUC was correlated with neutropenia. One partial response was observed. CONCLUSIONS: The starting dose recommended for subsequent studies is 1100 mg/m(2). DHA-paclitaxel dramatically alters the PK profile of derived paclitaxel compared with values observed after a 3-h infusion of paclitaxel (175 mg/m(2)). In addition, its favorable toxicity profile offers potential advantages over existing taxanes.
Wheaton, D. H., D. R. Hoffman, et al. (2003). "Biological safety assessment of docosahexaenoic acid supplementation in a randomized clinical trial for X-linked retinitis pigmentosa." Arch Ophthalmol 121(9): 1269-78.
BACKGROUND: In a 4-year placebo-controlled trial to elevate blood docosahexaenoic acid levels in patients with X-linked retinitis pigmentosa (XLRP), the goal was to assess the potential benefit of docosahexaenoic acid supplementation in altering disease progression. However, docosahexaenoic acid (22:6omega3) is a highly unsaturated fatty acid and considered a target molecule for free-radical oxidative damage. Thus, nutritional provision of docosahexaenoic acid might lead to an increase in antioxidant stress. Additional concerns, such as decreased platelet aggregation, increased bleeding time, and alterations in lipoprotein cholesterol levels, have been reported in supplementation studies with long-chain polyunsaturates. OBJECTIVE: To assess the biological safety of long-term docosahexaenoic acid supplementation. DESIGN: Forty-four male patients (mean age, 16 years) enrolled in a randomized, double-masked, clinical trial and received docosahexaenoic acid, 400 mg/d, or placebo. Blood samples were collected every 6 months. Biological safety analysis included fatty acids, vitamin A and E concentrations, antioxidant capacity, platelet aggregation, alanine aminotransferase activity, and lipoprotein cholesterol and triglyceride profiles. RESULTS: Mean plasma docosahexaenoic acid levels were elevated 2.5-fold by supplementation compared with baseline. Patients receiving placebo capsules exhibited no change (P =.35) in plasma docosahexaenoic acid content. All adverse events reported were minor and equivalently distributed between groups. Plasma vitamin A concentrations remained unchanged during the trial. Mean plasma vitamin E concentrations were correlated with age (P =.005), such that as patients with XLRP matured, plasma vitamin E concentrations increased to approach normal values. There was a trend (P =.10) toward lower mean vitamin E concentrations in the docosahexaenoic acid-supplemented group after 4 years. Docosahexaenoic acid supplementation did not compromise plasma antioxidant capacity, platelet aggregation, liver function enzyme activity, or plasma lipoprotein lipid content in patients with XLRP. CONCLUSION: Long-term docosahexaenoic acid supplementation to patients with XLRP was associated with no identifiable safety risks in this 4-year clinical trial.
Werner, A., R. Havinga, et al. (2003). "Treatment of essential fatty acid deficiency with dietary triglycerides or phospholipids in a murine model of extrahepatic cholestasis." Am J Physiol Gastrointest Liver Physiol.
Background: Essential fatty acid (EFA) deficiency during cholestasis is mainly due to malabsorption of dietary EFA (23). Theoretically, dietary phospholipids (PL) may have a higher bioavailability than dietary triglycerides (TG) during cholestasis. We developed murine models for EFA deficiency with and without extrahepatic cholestasis, and compared the efficacy of oral supplementation of EFA as PL or as TG. Methods: EFA deficiency was induced in mice by feeding a high-fat EFA-deficient (EFAD) diet. After three weeks on this diet, bile duct ligation (BDL) was performed in a subgroup of mice to establish extrahepatic cholestasis. Cholestatic and non-cholestatic EFA-deficient mice continued on the EFAD diet (controls), or were supplemented for three weeks with EFA-rich TG or EFA-rich PL. Fatty acid composition was determined in plasma, erythrocytes, liver and brain. Results: After four weeks of EFAD diet, induction of EFA deficiency was confirmed by a six-fold increased triene/tetraene ratio (T/T-ratio) in erythrocytes of non-cholestatic and cholestatic mice (p<0.001). EFA-rich TG and EFA-rich PL were equally effective in preventing further increase of the erythrocyte T/T-ratio, which was observed in cholestatic and non-cholestatic non-supplemented mice (12- and 16-fold the initial value, respectively). In cholestatic mice, EFA-rich PL was superior to EFA-rich TG in decreasing T/T-ratios of liver triglycerides and phospholipids (each p<0.05), and in increasing brain phospholipid concentrations of the long-chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid and arachidonic acid (each p<0.05). Conclusions: Oral EFA supplementation in the form of PL is more effective than in the form of TG in increasing LCPUFA concentrations in liver and brain of cholestatic EFA-deficient mice.
Watkins, B. A., S. Feng, et al. (2003). "Conjugated linoleic acids alter the fatty acid composition and physical properties of egg yolk and albumen." J Agric Food Chem 51(23): 6870-6.
Effects of dietary conjugated linoleic acids (CLAs) and docosahexaenoic acid (DHA) on the fatty acid composition of different egg compartments after storage were studied. Four dietary treatments [supplemented with safflower oil (SAFF, control group), DHA, CLAs plus DHA (CAD), and CLAs alone] were administered to Single Comb White Leghorn (SCWL) laying hens. Eggs from the different treatment groups were collected and stored for 10 weeks at 4 degrees C before analysis. Fatty acids from the yolk (yolk granules and plasma), egg albumen, and vitelline membrane were analyzed by gas chromatography. The yolk of eggs from hens given CLAs had significantly higher amounts of saturated fatty acids, typically 16:0 and 18:0, but lower amounts of polyunsaturated fatty acids (PUFAs) compared to eggs from the control group (SAFF). CLA content was highest in the yolk and present in both neutral and polar lipids, with the greatest concentrations in neutral lipids. DHA was incorporated mainly into yolk polar lipids. Lipids in yolk plasma and granules contained similar amounts of CLAs. The fatty acid compositions of vitelline membrane and egg albumen mirrored that of the egg yolk. CLA supplementation resulted in hard and rubbery yolks when compared to hard-cooked eggs from the control group. This study showed that feeding CLAs to hens led to accumulation of the isomers in polar and neutral lipids of the egg yolk and that these isomers migrated into egg albumen. Because the sensory properties of hard-cooked eggs were negatively affected by the enrichment of a mixture of CLA isomers in this study, further research should be conducted to evaluate how the different isomers alter the properties of egg yolk and albumen so that the quality of designed eggs containing CLAs and DHA can be improved.
Watkins, S. M., X. Zhu, et al. (2003). "Phosphatidylethanolamine-N-methyltransferase activity and dietary choline regulate liver-plasma lipid flux and essential fatty acid metabolism in mice." J Nutr 133(11): 3386-91.
Phosphatidylethanolamine-N-methyltransferase (PEMT) catalyzes the methylation of phosphatidylethanolamine to form phosphatidylcholine (PC) and represents one of the two major pathways for PC biosynthesis. Mice with a homozygous disruption of the PEMT gene are dependent on the 1,2-diacylglycerol cholinephosphotransferase (CDP-choline) pathway for the synthesis of PC and develop severe liver steatosis when fed a diet deficient in choline. The present study used quantitative lipid metabolite profiling to characterize lipid metabolism in PEMT-deficient mice fed diets containing varying concentrations of choline. Choline supplementation restored liver, but not plasma PC concentrations of PEMT-deficient mice to levels commensurate with control mice. Choline supplementation also restored plasma triglyceride concentrations to normal levels, but did not restore plasma cholesterol ester concentrations in the PEMT-deficient mice to those equal to control mice. PEMT-deficient mice also had substantially diminished concentrations of docosahexaenoic acid [22:6(n-3)] and arachidonic acid [20:4(n-6)] in plasma, independent of choline status. Thus, choline supplementation rescued some but not all of the phenotypes induced by the knockout. These findings indicate that PEMT activity functions beyond its recognized role as a compensatory pathway for PC biosynthesis and that, in contrast, PEMT activity is involved in many physiologic processes including the flux of lipid between liver and plasma and the delivery of essential fatty acids to blood and peripheral tissues via the liver-derived lipoproteins.
Watanabe, S., M. Doshi, et al. (2003). "n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonoylglycerol level in mice." Prostaglandins Leukot Essent Fatty Acids 69(1): 51-9.
2-arachidonoylglycerol (2-AG) is a putative endogenous ligand for cannabinoid receptors and was suggested to play an important role in both physiological and pathological events in the central nervous system (CNS) as well as in peripheral organs. The sequential hydrolysis of arachidonic acid (20:4n-6, AA)-containing phospholipids has been proposed as a major biosynthetic route of 2-AG. On the other hand, the manipulation of the dietary n-3 polyunsaturated fatty acid (PUFA) status changes the AA level in tissue phospholipids. We, therefore, conducted two separate experiments to confirm whether the dietary n-3 PUFA status influences the 2-AG level in the mouse brain. In the first experiment, we fed mice with n-3 PUFA-deficient diet, which resulted in a marked decrease in the docosahexaenoic acid (22:6n-3, DHA) levels without a change in the AA level in brain phospholipids as compared with the mice fed with an n-3 PUFA-sufficient diet. The brain 2-AG level in the n-3 PUFA-deficient group was significantly higher than in the n-3 PUFA sufficient group. In the second experiment, we found that short-term supplementation of DHA-rich fish oil reduced brain 2-AG level as compared with the supplementation with low n-3 PUFA. The decrease in the AA level and the increase in the DHA level in the major phospholipids occurred in the brains of the mice fed the fish oil diet compared with those fed the low n-3 PUFA diet. Our results indicate that the n-3 PUFA deficiency elevates and n-3 PUFA enrichment reduces the brain 2-AG level in mice, suggesting that physiological and pathological events mediated by 2-AG through cannabinoid receptor in the CNS could be modified by the manipulation of the dietary n-3 PUFA status.
Wang, Y., Q. Liu, et al. (2003). "Docosahexaenoic acid inhibits cytokine-induced expression of P-selectin and neutrophil adhesion to endothelial cells." Eur J Pharmacol 459(2-3): 269-73.
Dietary polyunsaturated fatty acids, such as docosahexaenoic acid, may inhibit pathological processes involving endothelial cell activation. Herein, it was found that treatment of endothelial cells with docosahexaenoic acid dose dependently reduced neutrophil adhesion provoked by tumor necrosis factor-alpha (TNF-alpha). In fact, pretreatment with 100 microM of docosahexaenoic acid for 24 h decreased TNF-alpha-induced neutrophil adhesion by 50%. Moreover, this pretreatment with docosahexaenoic acid (100 microM, 24 h) down-regulated TNF-alpha-induced endothelial cell surface expression of P-selection by 75%. Importantly, immunoneutralization of P-selectin reduced neutrophil adhesion to TNF-alpha-activated endothelial cells by more than 50%, indicating a significant role of P-selectin in this model. On the other hand, CXC chemokines, i.e. macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC), are also important regulators of neutrophil activation and adhesion. However, pretreatment with docosahexaenoic acid had no effect on TNF-alpha-provoked production of MIP-2 and KC in endothelial cells. Our study provide evidence that docosahexaenoic acid inhibits expression of P-selectin and subsequent adhesion of neutrophils to endothelial cells in response TNF-alpha, which may help explain the anti-inflammatory effects exerted by docosahexaenoic acid.
Wang, J. Y., S. Sekine, et al. (2003). "Effect of docosahexaenoic acid and ascorbate on peroxidation of retinal membranes of ODS rats." Free Radic Res 37(4): 419-24.
Mutant male osteogenic disorder Shionogi (ODS) rats, unable to synthesize ascorbic acid, were fed diets containing a high content of docosahexaenoic acid (DHA) and different amounts of ascorbic acid, to study the effect of DHA on peroxidative susceptibility of the retina and possible antioxidant action of ascorbic acid. ODS rats were fed from 7 weeks of age with diets containing high DHA (6.4% of total energy). A control group received a diet high in linoleic acid. The diets also contained varying amounts of ascorbic acid. Fatty acid compositions and phospholipid hydroperoxides in rod outer segment (ROS) membranes, and retinal ascorbic acid were analyzed. DHA in ROS membranes was significantly increased in rats fed high DHA, compared with the linoleic acid diet. Levels of phospholipid hydroperoxides in the DHA-fed rats were significantly higher than the linoleic acid-fed rats. Ascorbic acid supplementation did not suppress the phospholipid hydroperoxide levels after a high DHA diet, even when the supplement increased the content of retinal ascorbic acid. In conclusion, high DHA feeding induced a marked increase of phospholipid hydroperoxides in ROS membranes of ODS rats. Supplementation of ascorbic acid did not reverse this increase.
Wang, Y., M. A. Crawford, et al. (2003). "Fish consumption, blood docosahexaenoic acid and chronic diseases in Chinese rural populations." Comp Biochem Physiol A Mol Integr Physiol 136(1): 127-40.
The Chinese traditional diet is low in fat. However, there is regional variability in the amount, type of fat consumed and the pattern of chronic diseases. An epidemiological survey of 65 rural counties in China (6500 subjects) was conducted in the 1980s. We have re-examined the red blood cell fatty acid and antioxidant composition, with fish consumption. Fish consumption correlated significantly with the levels of docosahexaenoic acid (DHA) in red blood cells (RBC) (r=0.640, P<0.001), selenium (r=0.467, P<0.001) and glutathione peroxidase (r=0.333, P<0.01) in plasma. The proportion of DHA in RBC was inversely associated with total plasma triglyceride concentrations. A strong inverse correlation between DHA in RBC and cardiovascular disease (CVD) was found. The strongest correlation was the combination of DHA and oleic acid. RBC docosahexaenoic acid itself also correlated negatively and significantly with most chronic diseases and appeared to be more protective than either eicosapentaenoic or the omega3 docosapenataenoic acids. These results demonstrate the protective nature of fish consumption and DHA, found in high fat Western diets, operates at a low level of fat. This finding suggests the protective effect of fish consumption as validated by red cell DHA is universal. The protective effect is, therefore, most likely to be due to the fundamental properties of docosahexaenoic acid in cell function.
Wang, B., P. McVeagh, et al. (2003). "Brain ganglioside and glycoprotein sialic acid in breastfed compared with formula-fed infants." Am J Clin Nutr 78(5): 1024-9.
BACKGROUND: The concentration of sialic acid in brain gangliosides and glycoproteins has been linked to learning ability in animal studies. Human milk is a rich source of sialic acid-containing oligosaccharides and is a potential source of exogenous sialic acid. OBJECTIVE: The aim of the study was to compare the sialic acid concentration in the brain frontal cortex of breastfed and formula-fed infants. DESIGN: Twenty-five samples of frontal cortex derived from infants who died of sudden infant death syndrome were analyzed. Twelve infants were breastfed, 10 infants were formula-fed, and 1 infant was mixed-fed; the feeding status of the remaining 2 infants was unknown. Ganglioside-bound and protein-bound sialic acid were determined by HPLC. Ganglioside ceramide fatty acids were also analyzed to determine the relation between sialic acid and long-chain polyunsaturated fatty acids. RESULTS: After adjustment for sex with age at death as a covariate, ganglioside-bound and protein-bound sialic acid concentrations were 32% and 22% higher, respectively, in the frontal cortex gray matter of breastfed infants than in that of formula-fed infants (P < 0.01). Protein-bound sialic acid increased with age in both groups (P = 0.02). In breastfed but not in formula-fed infants, ganglioside-bound sialic acid correlated significantly with ganglioside ceramide docosahexaenoic acid and total n-3 fatty acids. CONCLUSIONS: Higher brain ganglioside and glycoprotein sialic acid concentrations in infants fed human milk suggests increased synaptogenesis and differences in neurodevelopment.
Wang, X., X. Zhao, et al. (2003). "Neuroprotective effect of docosahexaenoic acid on glutamate-induced cytotoxicity in rat hippocampal cultures." Neuroreport 14(18): 2457-61.
SUMMARY: The neuroprotective effect of docosahexaenoic acid (DHA) on the glutamate-induced cytotoxicity in rat hippocampal cultures was investigated in the present study. DHA at 5-50 microg/ml successfully protected neurons against the cytotoxicity, markedly increased the cell viability, inhibited both nitric oxide (NO) production and calcium influx, and increased the activities of antioxidant enzymes of glutathione peroxidase (GSH-Px) and glutathione reductase (GR). However, it did not alter the levels of glutathione (GSH) as compared to the control. These results suggest that DHA might be a potent neuroprotector. In addition, they may help to improve our understanding of the effect of DHA on neurodegeneration.
Wallace, F. A., E. A. Miles, et al. (2003). "Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects." Br J Nutr 89(5): 679-89.
Studies on animal and human subjects have shown that greatly increasing the amount of linseed (also known as flaxseed) oil (rich in the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)) or fish oil (FO; rich in the long-chain n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) in the diet can decrease a number of markers of immune function. The immunological effects of more modest doses of n-3 PUFA in human subjects are unclear, dose-response relationships between n-3 PUFA supply and immune function have not been established and whether ALNA has the same effects as its long-chain derivatives is not known. Therefore, the objective of the present study was to determine the effect of enriching the diet with different doses of FO or with a modest dose of ALNA on a range of functional responses of human monocytes and lymphocytes. In a randomised, placebo-controlled, double-blind, parallel study, forty healthy males aged 18-39 years were randomised to receive placebo or 3.5 g ALNA/d or 0.44, 0.94 or 1.9 g (EPA+DHA)/d in capsules for 12 weeks. The EPA:DHA ratio in the FO used was 1.0:2.5. ALNA supplementation increased the proportion of EPA but not DHA in plasma phospholipids. FO supplementation decreased the proportions of linoleic acid and arachidonic acid and increased the proportions of EPA and DHA in plasma phospholipids. The interventions did not alter circulating mononuclear cell subsets or the production of tumour necrosis factor-alpha, interleukin (IL) 1beta, IL-2, IL-4, IL-10 or interferon-gamma by stimulated mononuclear cells. There was little effect of the interventions on lymphocyte proliferation. The two higher doses of FO resulted in a significant decrease in IL-6 production by stimulated mononuclear cells. It is concluded that, with the exception of IL-6 production, a modest increase in intake of either ALNA or EPA+DHA does not influence the functional activity of mononuclear cells. The threshold of EPA+DHA intake that results in decreased IL-6 production is between 0.44 and 0.94 g/d.
von Schacky, C. (2003). "The role of omega-3 fatty acids in cardiovascular disease." Curr Atheroscler Rep 5(2): 139-45.
Plant-derived alpha-linolenic acid has been studied in a limited number of investigations. So far, some epidemiologic and a few mechanistic studies suggest a potential of protection from cardiovascular disease, but this potential remains to be proven in intervention studies. In contrast, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are prevalent in fish and fish oils, have been studied in thousands of investigations. A consistent body of evidence has been elaborated in various types of investigations, ultimately demonstrating reduction in total mortality, cardiovascular mortality, and morbidity by ingestion of roughly 1 g/d of EPA plus DHA. Current guidelines, however, do not discern between the omega-3 fatty acids mentioned; in fact, most even do not differentiate polyunsaturated fatty acids at all. Unfortunately, this complicates efficient implementation of an effective means of prophylaxis of atherosclerosis.
Vogan, C. L., B. H. Maskrey, et al. (2003). "Hepoxilins and trioxilins in barnacles: an analysis of their potential roles in egg hatching and larval settlement." J Exp Biol 206(Pt 18): 3219-26.
The barnacle life cycle has two key stages at which eicosanoids are believed to be involved in cellular communication pathways, namely the hatching of nauplii and the settlement of cypris larvae. Barnacle egg-hatching activity has previously been reported to reside in a variety of eicosanoids, including 8-hydroxyeicosapentaenoic acid and a number of tri-hydroxylated polyunsaturated fatty acid derivatives, the trioxilins. The production of the eicosapentaenoic acid metabolite trioxilin A4 (8,11,12-trihydroxy-5,9,14,17-eicosatetraenoic acid) by the barnacles Balanus amphitrite and Elminius modestus was confirmed using a combination of high-performance liquid chromatography and gas chromatography, both linked to mass spectrometry. In addition, both species also generated trioxilin A3 (8,11,12-trihydroxy-5,9,14-eicosatrienoic acid; an arachidonic acid-derived product), 8,11,12-trihydroxy-9,14,17-eicosatrienoic acid (a omega3 analogue of trioxilin A3; derived from omega3 arachidonic acid) and 10,13,14-trihydroxy-4,7,11,16,19-docosapentaenoic acid (a docosahexaenoic acid-derived product). In contrast to earlier reports, trioxilin A3 had no E. modestus egg-hatching activity at any of the concentrations tested (10(-9)-10(-6) mol l(-1)). The unstable epoxide precursor hepoxilin A3, however, caused significant levels of hatching at 10(-6) mol l(-1). Furthermore, the stable hepoxilin B3 analogue PBT-3 stimulated hatching at 10(-7) mol l(-1). Neither trioxilin A3, hepoxilin A3 or PBT-3 at 0.25-30 micromol l(-1) served as settlement cues for B. amphitrite cypris larvae.
Vericel, E., A. Polette, et al. (2003). "Pro- and antioxidant activities of docosahexaenoic acid on human blood platelets." J Thromb Haemost 1(3): 566-72.
n - 3 polyunsaturated fatty acids may protect against vascular diseases, however, their high accumulation in membranes may increase lipid peroxidation and subsequently induce deleterious effects in patients suffering from oxidative stress. This led us to investigate in vitro the dose-dependent effect of docosahexaenoic acid (DHA) on the redox status of human platelets. We have compared the effect of different DHA concentrations (0.5, 5 and 50 micro mol L(-1)) corresponding to DHA/albumin ratios of 0.01, 0.1 and 1. At the highest concentration, DHA elicited a marked oxidative stress, as evidenced by high malondialdehyde and low vitamin E levels whereas the lowest DHA concentration significantly decreased the malondialdehyde formation, with no change in vitamin E. The proportion of DHA was only increased in plasmalogen phosphatidylethanolamine at low concentration to rise in all phosphatidyl-choline and -ethanolamine subclasses at high concentration. Thus, the results show a biphasic effect of DHA with antioxidant and prooxidant effects at low and high concentrations, respectively, with a possible relationship with the phospholipid subclass in which it accumulates.
Vecera, R., N. Skottova, et al. (2003). "Antioxidant status, lipoprotein profile and liver lipids in rats fed on high-cholesterol diet containing currant oil rich in n-3 and n-6 polyunsaturated fatty acids." Physiol Res 52(2): 177-87.
Plant-based n-3 polyunsaturated fatty acids (PUFA) possess a prospective antiatherogenic potential. Currant oil from Ribes nigrum L. is one of the few plant oils containing PUFAn-3 (15.3 mol%) in addition to PUFAn-6 (60.5 mol%). This study was aimed at comparing the effects of currant oil with those of lard fat, rich in saturated (43.8 mol%) and monounsaturated (47.0 mol%) fatty acids, on antioxidant parameters, the lipoprotein profile and liver lipids in rats fed on 1 % (w/w) cholesterol diets containing either 10 % of currant oil (COD) or lard fat (LFD). After 3 weeks of feeding, the COD induced a significant decrease in blood glutathione (GSH) and an increase in Cu(2+) induced oxidizability of serum lipids, but did not affect liver GSH and t-butyl hydroperoxide-induced lipoperoxidation of liver microsomes. Although the COD did not cause accumulation of liver triacylglycerols as LFD, the lipoprotein profile (VLDL, LDL, HDL) was not significantly improved after COD. The consumption of PUFAn-3 was reflected in LDL as an increase in eicosapentaenoic and docosahexaenoic acid. These results suggest that currant oil affects positively the lipid metabolism in the liver, above all it does not cause the development of a fatty liver. However, adverse effects of currant oil on the antioxidant status in the blood still remain of concern.
VanderJagt, D. J., M. R. Trujillo, et al. (2003). "Phase angle correlates with n-3 fatty acids and cholesterol in red cells of Nigerian children with sickle cell disease." Lipids Health Dis 2(1): 2.
OBJECTIVE: To determine the cholesterol content and fatty acid composition of red cell membrane phospholipids (PL) of children with sickle cell disease (SCD) and to correlate these levels with whole body phase angle that is related to the integrity and function of cell membranes. STUDY DESIGN: Blood samples were obtained from 69 children with SCD and 72 healthy age- and gender-matched controls in Nigeria for the determination of the cholesterol content and proportions of fatty acids in red cell PL. Bioelectrical impedance analysis was used to obtain resistance (R) and reactance (Xc) from which phase angle was calculated as arctan Xc/R. Cholesterol (normalized to lipid phosphorus) and the proportions of individual fatty acids were correlated with phase angle. RESULTS: The proportions of palmitic (p < 0.001), stearic acid (p = 0.003) and cholesterol (p < 0.001) were significantly higher in the red cells of children with SCD, whereas the proportions of arachidonic acid and docosahexaenoic acid were reduced (p = 0.03 and < 0.001, respectively) compared to controls. The phase angle was inversely correlated with the proportions of palmitic acid (p = 0.03) and oleic acid (p < 0.001) and cholesterol (p = 0.003). Three n-3 polyunsaturated fatty acids-eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid- were positively correlated with phase angle (p < 0.001). CONCLUSIONS: The fatty acid composition and cholesterol content of tissue membranes in SCD correlate with the phase shift measured by bioelectrical impedance analysis. Phase angle measurements may provide a non-invasive method for monitoring interventions aimed at altering the lipid composition of membranes.
Usami, M., T. Komurasaki, et al. (2003). "Effect of gamma-linolenic acid or docosahexaenoic acid on tight junction permeability in intestinal monolayer cells and their mechanism by protein kinase C activation and/or eicosanoid formation." Nutrition 19(2): 150-6.
OBJECTIVE: Polyunsaturated fatty acids have been characterized as immunonutrients, but the effect of gamma-linolenic acid (GLA) or docosahexaenoic acid (DHA) on intestinal permeability has rarely been reported. METHODS: Confluent Caco-2 cells on porous filter were used to measure tight junction function by fluorescein sulfonic acid permeability and transepithelial electrical resistance. Treatments with 0, 10, 50, and 100 microM of GLA or DHA during 24 h were compared. Then the effects of butylated hydroxytoluene (antioxidant), 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (protein kinase C antagonist), and inhibitors of enzymatic degradation to the eicosanoids, indomethacin (cyclooxygenase inhibitor) and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone (lipoxygenase inhibitor), on GLA or DHA were examined. RESULTS: GLA and DHA enhanced fluorescein sulfonic acid permeability to 8.7- and 1.4-fold, respectively, and lowered transepithelial electrical resistance to 0.52- and 0.73-fold, respectively, versus the control in a concentration-dependent manner without cell injury (P < 0.001 to 0.05). Indomethacin and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone enhanced the changes mediated by GLA but did not alter the DHA effect. Butylated hydroxytoluene was ineffective. 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine facilitated the changes mediated by GLA, DHA, and eicosapentaenoic acid. The results indicated that the mechanism to change tight junction permeability via protein kinase C regulation is common but that via eicosanoid formation differs among GLA, DHA, and eicosapentaenoic acid. CONCLUSIONS: GLA and DHA affect tight junction permeability in intestinal monolayer cells specifically and in a concentration-dependent manner.
Uauy, R., D. R. Hoffman, et al. (2003). "Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials." J Pediatr 143(4 Suppl): S17-25.
Healthy term infants who are not breast-fed may need long-chain polyunsaturated fatty acids (LCPUFA) in their feeding, based on the changes in plasma and tissue fatty composition. However, consistent functional effects across different studies conducted over the past two decades has been more difficult to document. The interpretation of these data has scientific and public interest with the introduction of LCPUFA supplemented formula. There are 14 controlled trials in term infants that have included formula feeding with or without LCPUFA and functional assessment of visual and other measures of neural development; in addition, 7 have evaluated specific measures related to cognitive development. We chose to examine the effect of DHA dose provided daily on the development of visual acuity to explain the differences in visual acuity responses across randomized studies. A "meta-regression" was performed with the use of a DHA effective dose as the independent variable and visual acuity at 4 months as the dependent variable. Since the two main dietary determinants of DHA status are the LNA provided and the preformed DHA consumed, we defined DHA equivalent dose across studies by assuming a 1%, 5%, and 10% conversion of LNA to DHA. Results indicate a strong and significant effect of DHA equivalent dose on magnitude of the visual acuity response at all conversions tested; greatest significance was found when using a 10% bioequivalency (r(2)=0.68, and P=.001). We conclude that there is a significant relation between the total DHA equivalents provided and effectiveness as defined by visual acuity measurements at 4 months of age.
Turner, N., P. L. Else, et al. (2003). "Docosahexaenoic acid (DHA) content of membranes determines molecular activity of the sodium pump: implications for disease states and metabolism." Naturwissenschaften 90(11): 521-3.
The omega-3 polyunsaturate, docosahexaenoic acid (DHA), plays a number of biologically important roles, particularly in the nervous system, where it is found in very high concentrations in cell membranes. In infants DHA is required for the growth and functional development of the brain, with a deficiency resulting in a variety of learning and cognitive disorders. During adulthood DHA maintains normal brain function and recent evidence suggests that reduced DHA intake in adults is linked with a number of neurological disorders including schizophrenia and depression. Here we report a high positive correlation between the molecular activity (ATP min(-1)) of individual Na(+)K(+)ATPase units and the content of DHA in the surrounding membrane bilayer. This represents a fundamental relationship underlying metabolic activity, but may also represent a link between reduced levels of DHA and neurological dysfunction, as up to 60% of energy consumption in the brain is linked to the Na(+)K(+)ATPase enzyme.
Tully, A. M., H. M. Roche, et al. (2003). "Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study." Br J Nutr 89(4): 483-9.
Low n-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimer's disease, which has been associated with poor dietary fish or n-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case-control study used an established biomarker of n-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determine n-3 PUFA status in patients with Alzheimer's disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76.5 (SD 6.6) years had a clinical dementia rating (CDR) of 1 (SD 0.62) and a mini mental state examination (MMSE) score of 19.5 (SD 4.8). The control subjects (thirty-six females and nine males) aged 70 (SD 6.0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28.9 (SD 1.1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0.05 and P<0.001 respectively) in all MMSE score quartiles of patients with Alzheimer's disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimer's disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer's disease.
Tsuji, M., S. I. Murota, et al. (2003). "Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor." Prostaglandins Leukot Essent Fatty Acids 68(5): 337-42.
It is generally accepted that n-3 polyunsaturated fatty acids have beneficial effects on vascular homeostasis. Among the several functions of endothelial cells, angiogenesis contributes to tumor growth, inflammation, and microangiopathy. We have already demonstrated that eicosapentaenoic acid (EPA, 20:5, n-3) suppressed angiogenesis. In this paper, we examined the effect of docosapentaenoic acid (DPA, 22:5, n-3), an elongated metabolite of EPA, on tube-forming activity in bovine aortic endothelial cells (BAE cells) incubated between type I collagen gels. The pretreatment of BAE cells with DPA suppressed tube-forming activity induced by vascular endothelial growth factor (VEGF). The effect of DPA was stronger than those of EPA and docosahexaenoic acid (22:6, n-3). The migrating activity of endothelial cells stimulated with VEGF was also suppressed by DPA pretreatment. The treatment of BAE cells with DPA caused the suppression of VEGF receptor-2 (VEGFR-2, the kinase insert domain-containing receptor, KDR) expression in both plastic dish and collagen gel cultures. These data indicate that DPA has a potent inhibitory effect on angiogenesis through the suppression of VEGFR-2 expression.
Trebble, T., N. K. Arden, et al. (2003). "Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation." Br J Nutr 90(2): 405-12.
Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20 : 5n-3; EPA) and docosahexaenoic acid (22 : 6n-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function, n-3 PUFA intake and antioxidant co-supplementation is poorly defined. We therefore investigated tumour necrosis factor (TNF)-alpha and interleukin (IL) 6 production by PBMC and phospholipid fatty acid composition in plasma and erythrocytes of healthy male subjects (n 16) receiving supplemental intakes of 0.3, 1.0 and 2.0 g EPA+DHA/d, as consecutive 4-week courses. All subjects were randomised in a double-blind manner to receive a concurrent antioxidant supplement (200 microg Se, 3 mg Mn, 30 mg D-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 microg vitamin A (beta-carotene and retinol)) or placebo. There was a positive dose-dependent relationship between dietary n-3 PUFA intake and EPA and DHA incorporation into plasma phosphatidylcholine and erythrocyte phosphatidylethanolamine, with a tendency towards a plateau at higher levels of intake. Production of TNF-alpha and IL-6 by PBMC decreased with increasing n-3 PUFA intake but tended towards a 'U-shaped' dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary n-3 PUFA intakes. Thus, increased dietary n-3 PUFA consumption resulted in defined but contrasting patterns of modulation of phospholipid fatty acid composition and PBMC function, which were further influenced by antioxidant intake.
Trebble, T. M., S. A. Wootton, et al. (2003). "Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation." Am J Clin Nutr 78(3): 376-82.
BACKGROUND: Prostaglandin E(2) (PGE(2)) inhibits lymphocyte proliferation and the production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells, but the effect of PGE(2) on interleukin 4 (IL-4) production is unclear. Fish oil, which contains eicosapentaenoic and docosahexaenoic acids, inhibits production of PGE(2). The effects of fish oil on lymphocyte proliferation and production of IFN-gamma and IL-4 are unclear and may be influenced by the availability of antioxidants. OBJECTIVE: We investigated the effect of dietary fish oil with and without antioxidant cosupplementation on lymphocyte proliferation and the production of PGE(2), IFN-gamma, and IL-4 by peripheral blood mononuclear cells. DESIGN: Sixteen healthy men received dietary fish-oil supplements providing 0.3, 1, and 2 g eicosapentaenoic acid plus docosahexaenoic acid/d for 4 consecutive weeks each (total of 12 wk). All subjects were randomly assigned to daily cosupplementation with either antioxidants (200 microg Se, 3 mg Mn, 30 mg RRR-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 micro g vitamin A) or placebo. RESULTS: Fish-oil supplementation decreased PGE(2) production and increased IFN-gamma production and lymphocyte proliferation from baseline values. Cosupplementation with antioxidants did not affect cytokine production or lymphocyte proliferation. CONCLUSION: Dietary fish oil modulates production of IFN-gamma and lymphocyte proliferation in a manner consistent with decreased production of PGE(2), but this effect is not modified by antioxidant cosupplementation.
Tonon, T., D. Harvey, et al. (2003). "Identification of a very long chain polyunsaturated fatty acid Delta4-desaturase from the microalga Pavlova lutheri." FEBS Lett 553(3): 440-4.
Pavlova lutheri, a marine microalga, is rich in the very long chain polyunsaturated fatty acids (VLCPUFAs) eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Using an expressed sequence tag approach, we isolated a cDNA designated Pldes1, and encoding an amino acid sequence showing high similarity with polyunsaturated fatty acid front-end desaturases. Heterologous expression in yeast demonstrated that PlDES1 desaturated 22:5n-3 and 22:4n-6 into 22:6n-3 and 22:5n-6 respectively, and was equally active on both substrates. Thus, PlDES1 is a novel VLCPUFA Delta4-desaturase. Pldes1 expression is four-fold higher during the mid-exponential phase of growth compared to late exponential and stationary phases.
Tokudome, Y., K. Kuriki, et al. (2003). "Seasonal variation in consumption and plasma concentrations of fatty acids in Japanese female dietitians." Eur J Epidemiol 18(10): 945-53.
OBJECTIVE: To study seasonal variation in intake and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. SUBJECTS AND METHODS: We assessed consumption of FAs based on four season 7 consecutive day weighed diet records from 71 Japanese female dietitians in 1996-1997. Using overnight fasting venous blood, plasma concentrations of FAs were analyzed by gas chromatography. Seasonal variation in consumption and plasma concentrations was examined by ANOVA for repeated values, followed by Tukey's multiple t-test. We calculated Spearman's partial rank correlation coefficients (CCs) between intake and plasma concentrations of FAs. Furthermore, we computed inter-seasonal Spearman's partial rank CCs for consumption and plasma concentrations of FAs. RESULTS: Statistically significant seasonal diff