Phospholipid Docosahexaenoic Acid Research Articles

Chronic Carbamazepine Decreases the Incorporation Rate and Turnover of Arachidonic Acid but Not Docosahexaenoic Acid in Brain Phospholipids of the Unanesthetized Rat: Relevance to Bipolar Disorder

The basis for carbamazepine's efficacy in treating bipolar disorder is not agreed on. One hypothesis is that, similar to lithium and valproate (antibipolar drugs), carbamazepine might selectively decrease the kinetics of arachidonic acid (AA) in brain phospholipids. To assess whether it targets brain AA kinetics, we administered carbamazepine (25 mg/kg/day, IP) to rats for 30 days and then determined its effect compared with that of vehicle on incorporation and turnover rates of AA and docosahexaenoic acid (DHA) in brain phospholipids. In unanesthetized rats that had received carbamazepine or vehicle, [1-14C]AA or [1-14C]DHA was infused intravenously, and arterial blood plasma was sampled until the animal was killed at 5 min and its brain, after being microwaved, was used for acyl-coenzyme A (acyl-CoA) and phospholipid fatty acid analysis. Chronic carbamazepine, compared with vehicle, decreased the rate of incorporation of AA-CoA (27%-29%) and turnover of AA (25%-27%) but not of DHA-CoA or DHA in brain phospholipids. The results, which are comparable to published findings after chronic administration of lithium and valproic acid to rats, support the hypothesis that drugs effective against mania in bipolar disorder act by selectively downregulating the incorporation rate of AA-CoA and turnover of AA in brain phospholipids.

Long-Chain (n-3) Polyunsaturated Fatty Acids Are More Efficient than α-Linolenic Acid in Improving Electroretinogram Responses of Puppies Exposed during Gestation, Lactation, and Weaning

Long-chain PUFAs (LCPUFAs) are essential for proper neural and retinal development in many mammalian species. We investigated puppies born to dogs fed diets containing varying amounts of vegetable and marine (n-3) fatty acids during gestation/lactation. The fatty acid compositions of dogs' milk and puppy plasma phospholipids were evaluated, and electroretinographic responses of the young dogs were determined after they were weaned to the same diets. Dogs' milk fatty acid composition reflected the diets fed during gestation/lactation. The milk of dogs fed a high alpha-linolenic acid (ALA) diet was enriched in ALA but not docosahexaenoic acid (DHA). Puppies fed this ALA-enriched milk accumulated more plasma phospholipid DHA than the low (n-3) fatty acid group. However, this accumulation was less than that obtained in puppies fed preformed DHA during development and suckling (P < 0.05). Electroretinograms (ERGs) of 12-wk-old puppies revealed significantly improved visual performance in dogs fed the highest amounts of (n-3) LCPUFAs (P < 0.05). These puppies demonstrated improved rod response (improved amplitude and implicit time of the a-wave, P < 0.05). Puppies from the low (n-3) fatty acid group exhibited the poorest ERG responses compared with the high-marine or high-vegetable (n-3) groups. A novel parameter devised in this study, the initial intensity at which the a-wave was detectable (i.e., threshold intensity), also demonstrated that retinal response of puppies consuming the (n-3) LCPUFA-containing diets occurred at lower light intensity, thereby exhibiting greater rod sensitivity, than the other diet groups. These findings indicate that preformed dietary (n-3) LCPUFA is more effective than ALA in enriching plasma DHA during perinatal development and results in improved visual performance in developing dogs.

Topiramate does not Alter the Kinetics of Arachidonic or Docosahexaenoic Acid in Brain Phospholipids of the Unanesthetized Rat

Interest in the potential therapeutic utility of topiramate for treating bipolar disorder was stimulated by published reports of investigator-initiated open label clinical studies. Because chronic lithium, carbamazepine and valproate decrease the turnover of arachidonic acid (AA) but not docosahexaenoic acid (DHA) in brain phospholipids of the awake rat, we tested if topiramate would produce similar results. Rats received either topiramate (20 mg/kg twice per day) or vehicle for 14 days and then while unanesthetized were infused intravenously with either [1-(14)C] AA or [1-(14)C] DHA for 5 min while blood was collected from the femoral artery at fixed times. Topiramate did not alter the incorporation rate of AA or DHA from their respective brain acyl-CoA pool into brain phospholipids, nor the turnover of AA and DHA in brain phospholipids. The results of our study indicate that topiramate does not possess a pharmacological property that three drugs with proven efficacy in treating bipolar disorder have in common.

Timing of incorporation of docosahexaenoic acid into brain and muscle phospholipids during precocial and altricial modes of avian development

We investigated the possibilities that the proportion of docosahexaenoic acid (DHA) in phospholipids of brain and skeletal muscle at hatch, and the ontogenetic timing of the DHA accretion spurt in these tissues, might serve as indices of neonatal functional maturity that discriminate between precocial and altricial avian developmental modes. Comparison of the fatty acid profiles of the initial and residual yolks of two free-living altricial species, the swallow ( Hirundo rustica) and the sparrow ( Passer domesticus), reveals that, in contrast to precocial birds, there is no preferential uptake of DHA from the yolk during embryonic development. At hatch, the proportions of DHA in brain phospholipid (wt.% of fatty acids) of the swallow and sparrow, at 8.1% and 5.0%, respectively, are far lower than the values (16.9–19.6%) reported for non-altricial species. This reflects a marked difference in the timing of the brain DHA accretion spurt, which occurs during the first half of the embryonic period of precocial birds, but is largely delayed until after hatching in the altricial species. By the time of fledging, the proportion of DHA in the swallow brain phospholipid has increased to 14.3%. For non-altricial birds, the brain DHA concentration at hatch shows little interspecies variation, despite major differences in yolk DHA content. The proportions of DHA in leg muscle phospholipid of the newly hatched swallow and sparrow, at 2.9% and 2.5%, respectively, are far lower than the value (6.7%) for the precocial chicken. Again, this relates to differences in developmental timing, with muscle DHA accretion occurring in the first half of the chicken's embryonic period, whereas, in the swallow, this increase is delayed until after hatching. By the time of fledging in the swallow, DHA forms 9.3% of muscle phospholipid fatty acids, equivalent to the level attained in chicken muscle at the mid-embryo stage. The results indicate a clear distinction between altricial and non-altricial avian species in the timing of tissue DHA accretion during development, presumably reflecting differences in neonatal functional maturity.

Benzene increases the ratio of arachidonic acids to docosahexaenoic acids and inhibits the de novo synthesis of ceramide in the rat liver

The present study investigated the effects of inhalation exposure of benzene at 0, 10, 200 and 600 ppm for 1, 2 and 4 weeks on n-6 and n-3 fatty acids and ceramide levels in the rat liver. No significant difference in the ratio of saturated fatty acid to unsaturated fatty acid was found on increasing benzene exposure levels, but the ratio of saturated fatty acid to unsaturated fatty acid decreased with increasing benzene exposure times, with the exception of the phospholipids of rats exposed to 200 and 600 ppm of benzene. A significant increase in the ratio of arachidonic acid to docosahexaenoic acid was found in the phospholipids of rats exposed to 200 and 600 ppm of benzene for 4 weeks. In our study, no change in the relative amounts of sphingomyelin in phospholipids, due to benzene exposure at 600 ppm for 4 weeks resulted in the lack of sphingomyelin turnover. However, ceramide levels in the livers of rats exposed to 600 ppm of benzene for 4 weeks were significantly reduced upon increasing the benzene concentration. This result shows that the de novo synthesis of ceramide was significantly inhibited at higher levels of benzene and that the ratio of arachidonic acid to docosahexaenoic acid in phospholipids is dose-dependently related to benzene exposure.

Docosahexaenoic Acid Attenuates Mycotoxin-Induced Immunoglobulin A Nephropathy, Interleukin-6 Transcription, and Mitogen-Activated Protein Kinase Phosphorylation in Mice

The purpose of this investigation was to evaluate the dose-dependent effects of docosahexaenoic acid (DHA) on deoxynivalenol (DON)-induced IgA nephropathy in mice and their relation to proinflammatory gene expression and mitogen-activated protein kinase (MAPK) activation. Consumption of a modified AIN-93G diet containing 1, 5, and 30 g/kg DHA resulted in dose-dependent increases of DHA in liver phospholipids with concomitant decreases in arachidonic acid compared with control diets. DHA dose dependently inhibited increases in serum IgA and IgA immune complexes (IC) as well as IgA deposition in the kidney in DON-fed mice; the 30 g/kg DHA diet had the earliest detectable effects and maximal efficacy. Both splenic interleukin-6 (IL-6) mRNA and heterogeneous nuclear RNA (hnRNA), an indicator of IL-6 transcription, were significantly reduced in DON-fed mice that consumed 5 and 30 g/kg DHA; a similar reduction was observed for cyclooxygenase (COX-2) mRNA. In a subsequent study, acute DON exposure (25 mg/kg body weight) induced splenic IL-6 mRNA and hnRNA as well as COX-2 mRNA in mice fed the control diet, whereas induction of both RNA species was significantly inhibited in mice fed 30 g/kg DHA. These latter inhibitory effects corresponded to a reduction in DON-induced phosphorylation of p38, extracellular-signal related kinase 1/2, and c-Jun N-terminal kinase 1/2 MAPKs in the spleen. Taken together, the results indicate that DHA dose-dependently inhibited DON-induced IgA dysregulation and nephropathy, and that impairment of MAPK activation and expression of COX-2 and IL-6 are potential critical upstream mechanisms.

Moderate fish-oil supplementation reverses low-platelet, long-chain n−3 polyunsaturated fatty acid status and reduces plasma triacylglycerol concentrations in British Indo-Asians

The mechanisms involved in the increased mortality from coronary artery disease in British Indo-Asians are not well understood. This study aimed to investigate whether British Indo-Asian Sikhs have higher plasma triacylglycerol concentrations, lower platelet phospholipid levels, and lower dietary intakes of long-chain n-3 polyunsaturated fatty acids (PUFAs) than do age- and weight-matched Europeans and whether moderate dietary fish-oil intake can reverse these differences. A randomized, double-blind, placebo-controlled, parallel, fish-oil intervention study was performed. After a 2-wk run-in period, 44 Europeans and 40 Indo-Asian Sikhs were randomly assigned to receive either 4.0 g fish oil [1.5 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA)] or 4.0 g olive oil (control) daily for 12 wk. At baseline, the Indo-Asians had significantly higher plasma triacylglycerol, small dense LDL, apolipoprotein B, and dietary and platelet phospholipid n-6 PUFA values and significantly lower long-chain n-3 PUFAs (EPA and DHA) than did the Europeans. A significant decrease in plasma triacylglycerol, plasma apolipoprotein B-48, and platelet phospholipid arachidonic acid concentrations and a significant increase in plasma HDL concentrations and platelet phospholipid EPA and DHA levels were observed after fish-oil supplementation. No significant effect of ethnicity on the responses to fish-oil supplementation was observed. Moderate fish-oil supplementation contributes to a reversal of lipid abnormalities and low n-3 PUFA levels in Indo-Asians and should be considered as an important, yet simple, dietary manipulation to reduce CAD risk in Indo-Asians with an atherogenic lipoprotein phenotype.

Role of long-chain polyunsaturated fatty acids in infant nutrition.

To review briefly the influence of dietary long-chain polyunsaturated fatty acids (LC-PUFA) on tissue composition and functionality in early infancy. Moreover, the influences of LC-PUFA sources on plasma composition as well as the effects of these fatty acids on intestinal repair after malnutrition are discussed. Human milk not only supplies essential fatty acids but also contains up to 2% of the total fatty acids as LC-PUFA, of which arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered the most important. Plasma and erythrocyte levels of both AA and DHA are decreased in infants fed artificial standard milk formulae. However, the supplementation of formulae with these fatty acids in amounts close to that of human milk leads to tissue LC-PUFA patterns similar to those of breast-fed infants. However, the bioavailability of LC-PUFA depends on the typical LC-PUFA source; egg phospholipids increases both AA and DHA in plasma phospholipids and HDL more than a mixture of tuna and fungal triglycerides. Dietary LC-PUFA affects positively the growth and development of the infant and ameliorates the visual and cognitive functions, particularly in preterm infants. Likewise, LC-PUFA improves intestinal repair in severe protein-energy malnutrition; therefore, its qualitative and quantitative dietary supply should be considered.

Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects

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) α-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-α, interleukin (IL) 1β, IL-2, IL-4, IL-10 or interferon-γ 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.

Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing

Objective: The purpose of this study was to determine the effect of docosahexaenoic acid supplementation on plasma phospholipid docosahexaenoic acid content and indices of depression and information processing for women who breast-feed. Study Design: Mothers who planned to breast-feed their infants were assigned randomly in a double-masked fashion to receive either docosahexaenoic acid (≈200 mg/d) or placebo for the first 4 months after the delivery. Major outcome variables included plasma phospholipid fatty acid patterns and scores on a self-rating questionnaire of current depression symptoms. A structured clinical interview of depression, scores on another self-rating questionnaire of depression symptoms, and a laboratory measure of information processing were obtained in subgroups of the total population. Results: Plasma phospholipid contents of docosahexaenoic acid at baseline were 3.15 ± 0.78 and 3.31 ± 0.70 (mg/dL of total fatty acids) in the docosahexaenoic acid and placebo groups, respectively. After 4 months, the plasma phospholipid docosahexaenoic acid content of the docosahexaenoic acid group was 8% higher (3.40 ± 0.97 mg/dL), whereas that of the placebo group was 31% lower (2.27 ± 0.87 mg/dL). Despite the higher plasma phospholipid docosahexaenoic acid content of the supplemented group after 4 months, there was no difference between groups in either self-rating or diagnostic measures of depression; information processing scores of the two groups also did not differ. Conclusion: Docosahexaenoic acid supplementation (≈ 200 mg/d) for 4 months after the delivery prevented the usual decline in plasma phospholipid docosahexaenoic acid content of women who breastfeed but did not influence self-ratings of depression, diagnostic measures of depression, or information processing. (Am J Obstet Gynecol 2003;188:1348-53.)

Polyunsaturated fatty acid profiles of whole body phospholipids and triacylglycerols in anadromous and landlocked Atlantic salmon ( Salmo salar L.) fry

We compared the fatty acid compositions and gains of whole body triacylglycerols (TAG) and phospholipids (PL) in anadromous and landlocked Atlantic salmon ( Salmo salar) fry, of the same age, fed the same commercial marine oil-rich diet over a 42-day feeding trial. The landlocked strain exhibited significantly ( P<0.05) higher growth rate and feed efficiency, due principally to a higher fat retention, particularly of monounsaturated and saturated fatty acids (SFA). n-3 and n-6 long-chain polyunsaturated fatty acid (PUFA) gains and retentions were significantly higher ( P<0.05) in the landlocked fry. Great similarities were found in the fatty acid profiles of whole body TAG of both strains. However, marked genotypic differences were observed in the PUFA profiles of whole body PL fractions. The total PUFA, n-3 PUFA and docosahexaenoic acid (DHA) level in PL was significantly higher ( P<0.05) while the SFA level, and the PUFA C18/C20 and eicosapentaenoic acid/arachidonic acid ratios were significantly lower ( P<0.05) in the anadromous fry than in landlocked fry. Our results indicate that the level of DHA in salmon PL is under strong genetic control and that the capacity for incorporation, and possibly for the conversion of dietary n-3 and n-6 PUFA, is higher in the landlocked strain.

Higher maternal plasma docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state patterning

The effect of docosahexaenoic acid (DHA) on the developing fetal central nervous system (CNS) and related functional outcomes in infancy remain unexplored. Sleep and wake states of newborns provide a tool for assessing the functional integrity of the CNS. We investigated whether CNS integrity in newborns, measured with sleep recordings, was associated with maternal concentrations of long-chain polyunsaturated fatty acids, especially DHA. Plasma phospholipid fatty acid concentrations were measured in 17 women at parturition. On postpartum day 1 (P1) and day 2 (P2), a pressure-sensitive pad under the infants' bedding recorded body movements and respiratory patterns to measure sleep and wake states. Maternal plasma phospholipid DHA ranged from 1.91% to 4.5% by wt of total fatty acids. On the basis of previously published data and the median DHA concentration, the women were divided into 2 groups: high DHA (> 3.0% by wt of total fatty acids) and low DHA (</= 3.0% by wt of total fatty acids). Infants of high-DHA mothers had a significantly lower ratio of active sleep (AS) to quiet sleep (QS) and less AS than did infants of low-DHA mothers. Furthermore, the former infants had less sleep-wake transition and more wakefulness on P2. Correlations of maternal DHA status with infant sleep states were consistent with these data. Also, the ratio of maternal n-6 to n-3 fatty acids on P1 was inversely associated with QS and positively associated with arousals in QS. On P2, maternal n-6:n-3 was positively associated with AS, sleep-wake transition, and AS:QS. The sleep patterns of infants born to mothers with higher plasma phospholipid DHA suggest greater CNS maturity.

Red blood cell and plasma phospholipid arachidonic and docosahexaenoic acid levels at birth and cognitive development at 4 years of age.

The long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) have biophysical properties that may mediate behavioral outcome, especially cognitive development. This study examined the relationship between the LCPUFA-status at birth and cognitive development at 4 years of age. Cognitive development of 128 full-term neonates, whose umbilical venous plasma and/or red blood cell phospholipid DHA and AA levels were known, was assessed at 4 years of age. Pearson correlation coefficients were calculated between cognitive development and DHA, AA, maternal intelligence, birth weight, duration of breast-feeding and paternal educational attainment. Multiple linear regressions were employed with cognitive development as the dependent variable and whereby the above-mentioned covariables were entered in step one while each of the four LCPUFAs was entered in step two. In bivariate analysis, maternal intelligence, birth weight, maternal smoking habits during pregnancy, paternal education and duration of breast-feeding showed significant correlations with cognitive development (p<0.01). The association of cognitive development with DHA and AA measured zero in bivariate analysis (plasma levels: r=0.03 and r=-0.03, respectively; erythrocyte levels: r=0.01 and r=0.05) and in multiple regression analysis (plasma DHA r=0.01, p=0.88; plasma AA r=0.02, p=0.80; erythrocyte DHA r=-0.01, p=0.95) except for erythrocyte AA (r=0.15, p=0.09). No evidence was found for an association of the DHA or AA-status at birth with cognitive development at 4 years of age.

Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses

Fish-oil supplementation can reduce circulating triacylglycerol (TG) levels and cardiovascular risk. This study aimed to assess independent associations between changes in platelet eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and fasting and postprandial (PP) lipoprotein concentrations and LDL oxidation status, following fish-oil intervention. Fifty-five mildly hypertriacylglycerolaemic (TG 1·5–4·0 mmol/l) men completed a double-blind placebo controlled cross over study, where individuals consumed 6 g fish oil (3 g EPA+DHA) or 6 g olive oil (placebo)/d for two 6-week intervention periods, with a 12-week wash-out period in between. Fish-oil intervention resulted in a significant increase in the platelet phospholipid EPA (+491 %,P&lt;0·001) and DHA (+44 %,P&lt;0·001) content and a significant decrease in the arachidonic acid (-10 %,P&lt;0·001) and γ-linolenic acid (-24 %,P&lt;0·001) levels. A 30 % increase inex vivoLDL oxidation (P&lt;0·001) was observed. In addition, fish oil resulted in a significant decrease in fasting and PP TG levels (P&lt;0·001), PP non-esterified fatty acid (NEFA) levels, and in the percentage LDL as LDL-3 (P=0·040), and an increase in LDL-cholesterol (P=0·027). In multivariate analysis, changes in platelet phospholipid DHA emerged as being independently associated with the rise in LDL-cholesterol, accounting for 16 % of the variability in this outcome measure (P=0·030). In contrast, increases in platelet EPA were independently associated with the reductions in fasting (P=0·046) and PP TG (P=0·023), and PP NEFA (P=0·015), explaining 15–20 % and 25 % of the variability in response respectively. Increases in platelet EPA+DHA were independently and positively associated with the increase in LDL oxidation (P=0·011). EPA and DHA may have differential effects on plasma lipids in mildly hypertriacylglycerolaemic men.

Birthweight in a fishing community: significance of essential fatty acids and marine food contaminants.

Marine food provides essential fatty acids that are important during pregnancy, but the benefits may be limited at high intakes and by seafood contaminants. In the fishing community of the Faroe Islands, 182 pregnant women with spontaneous singleton births were consecutively recruited for a cohort in 1994- 1995. Concentrations of fatty acids and seafood contaminants in blood samples were analysed as predictors of gestational length and birthweight. Serum concentrations of eicosapentaenoic acid (EPA) increased with maternal marine food intake, while the tendency was less clear for docosahexaenoic acid (DHA). An increase in the relative concentration of DHA in cord serum phospholipids by 1% was associated with an increased duration of gestation by 1.5 days (95% CI : 0.7-2.2). However, birthweight adjusted for gestational length decreased by 246 g (95% CI : 16-476) for each increase by 1% of the EPA concentration in cord serum. Concentrations of the seafood pollutants mercury and polychlorinated biphenyls (PCB) were associated with fatty acids levels, but the contaminants did not appear to affect any of the outcome parameters. An increased intake of marine fats appears to prolong the duration of gestation, but birthweight adjusted for gestational age may decrease at high intake levels. This effect does not seem to be due to increased exposures to seafood contaminants.

Relations between n−3 fatty acid status and cardiovascular disease risk factors among Quebecers

Epidemiologic evidence shows an inverse relation between fish consumption and death from ischemic heart disease. This beneficial effect is attributed to n-3 fatty acids. The purpose of this study was to examine the association between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among Quebecers. The study population consisted of 1460 subjects aged 18-74 y who participated in the 1990 Quebec Heart Health and Nutrition Survey. Data were obtained through home interviews and clinic visits. Expressed as the percentage of total fatty acids in plasma phospholipids, the geometric means of EPA, DHA, and their combination were 0.47%, 1.19%, and 1.70%, respectively. Concentrations of n-3 fatty acids were positively associated with fish intake. We found positive associations between EPA and total cholesterol, LDL cholesterol, HDL cholesterol, plasma glucose, and systolic and diastolic blood pressure. We found positive associations between DHA and total cholesterol, the ratio of total to HDL cholesterol, triacylglycerols, systolic blood pressure, and plasma glucose and insulin. We also found positive associations between the ratio of EPA to arachidonic acid and total cholesterol, HDL cholesterol, and systolic blood pressure and a negative association with the ratio of total to HDL cholesterol. Our results indicate that concentrations of EPA and DHA in plasma phospholipids reflected Quebecer fish consumption. Results also show that EPA and the ratio of EPA to arachidonic acid can positively influence HDL-cholesterol concentrations.

Are human milk long-chain polyunsaturated fatty acids related to visual and neural development in breast-fed term infants?

Objective: To determine whether docosahexaenoic acid (DHA) is related to visual and neural development in term breast-fed infants. Design: A prospective study of 83 infants who were exclusively breast-fed for at least 3 months. We determined red blood cell and plasma fatty acids at 2 months, visual acuity at 2, 4, 6, and 12 months, speech perception and an object search task at 9 months, Bayley’s mental development index and psychomotor development index at 6 and 12 months, and novelty pReference at 6 and 9 months. Results: The infant red blood cell phosphatidylethanolamine DHA was significantly related to visual acuity at 2 months of age (r = 0.32, P = .01) and 12 months of age (r = 0.30, P = .03). The ability to discriminate nonnative retroflex and phonetic contrasts at 9 months of age was related to the plasma phospholipid DHA (r = 0.48, P < .02) and red blood cell phosphatidylethanolamine DHA (r = 0.26, P = .02) at 2 months of age after adjusting for covariates. Conclusion: DHA may influence the development of visual acuity and neural pathways associated with the developmental progression of language acquisition in term breast-fed infants. The extent to which our results can be attributed solely to DHA from maternal sources through breast milk or in gestation or other confounding factors remains to be determined. (J Pediatr 2001;139:532-8)

Inverse association between trans isomeric and long-chain polyunsaturated fatty acids in cord blood lipids of full-term infants

Previous studies showed significant inverse correlations between values of trans isomeric and long-chain polyunsaturated fatty acids in plasma lipids of preterm infants and healthy children aged 1-15 y. We sought to evaluate the same correlations in full-term infants at birth. We studied healthy full-term infants (n = 42) born after normal pregnancies and deliveries. All infants had a family history of atopy (both parents or one of the parents and a sibling had atopic symptoms). The fatty acid composition of venous cord blood lipids was determined by high-resolution capillary gas-liquid chromatography. The mean (+/-SEM) sum of trans fatty acids was 0.49 +/- 0.02% by wt in phospholipids, 2.47 +/- 0.20% by wt in cholesterol esters, 1.73 +/- 0.09% by wt in triacylglycerols, and 1.59 +/- 0.07% by wt in nonesterified fatty acids. Linear correlation analysis showed significant inverse correlations between the sum of trans fatty acids and both arachidonic acid and docosahexaenoic acid in phospholipids (r = -0.56, P < 0.001, and r = -0.48, P = 0.01, respectively), cholesterol esters (r = -0.52, P < 0.001, and r = -0.39, P = 0.018, respectively), and nonesterified fatty acids (r = -0.41, P = 0.007, and r = -0.41, P = 0.006, respectively). Because trans fatty acids in the fetal circulation must originate from the maternal diet, our results indicate that maternal exposure to trans fatty acids may represent a previously neglected variable that inversely influences long-chain polyunsaturated fatty acid status in full-term infants at birth.

Maternal-Fetal N-6 and N-3 Polyunsaturated Fatty Acids Gradient in Plasma and Red Cell Phospholipids

Fatty acid distribution was investigated in ethnically and economically homogenous Korean mothers (n = 40) and neonates. Venous blood, maternal before delivery and cord, was obtained. Choline (CPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SM) were assayed. Mean arachidonic acid (AA) level was higher in plasma CPG and SM (p < 0.0001), and red cell CPG (p < 0.0001), EPG (p < 0.0001) and SM (p = 0.005) of the neonates. Similarly, the neonates had higher proportions of docosahexaenoic acid (DHA) in plasma CPG (p < 0.0001) and red cell CPG (p = 0.001) and EPG (p = 0.036). In contrast, linoleic and alpha-linolenic acids were significantly higher in maternal blood. Mead acid was elevated in plasma CPG (p < 0.0001) and red cell CPG and EPG (p < 0.0001) of the neonates. Consistent with data from high-fat-intake populations, our subjects, whose traditional diet is low in fat, exhibited maternal-fetal gradient in AA and DHA in plasma and red cell phospholipids. This may be due to an imbalance between supply and maternal and fetal requirements, and/or a physiological response to pregnancy. Prenatal nutritional constraint is associated with impaired development and a risk of chronic diseases in adults. AA and DHA are vital nutrients. Hence, there is a need to investigate whether the discrepancy between maternal and neonatal AA and DHA is a manifestation of nutritional insufficiency.

Effects of docosahexaenoic acid on retinal development: Cellular and molecular aspects

We have recently shown that docosahexaenoic acid (DHA) is necessary for survival and differentiation of rat retinal photoreceptors during development in vitro. In cultures lacking DHA, retinal neurons developed normally for 4 d; then photoreceptors selectively started an apoptotic pathway leading to extensive degeneration of these cells by day 11. DHA protected photoreceptors by delaying the onset of apoptosis; in addition, it advanced photoreceptor differentiation, promoting opsin expression and inducing apical differentiation in these neurons. DHA was the only fatty acid having these effects. Mitochondrial damage accompanied photoreceptor apoptosis and was markedly reduced upon DHA supplementation. This suggests that a possible mechanism of DHA-mediated photoreceptor protection might be the preservation of mitochondrial activity; a critical amount of DHA in mitochondrial phospholipids might be required for proper functioning of these organelles, which in turn might be essential to avoid cell death. Müller cells in culture appeared to be involved in DHA processing: they took up DHA, incorporated it into glial phospholipids, and channeled it to photoreceptors in coculture. Both Müller cells, when cocultured with neuronal cells, and the glial-derived neurotrophic factor (GDNF) protected photoreceptors from cell death. These results suggest that glial cells may play a central role in regulating photoreceptor survival during development through the provision of trophic factors. The multiple effects of DHA on photoreceptors suggest that, in addition to its structural role, DHA might be one of the trophic factors required by these cells.