Dietary low linolenic acid compared with docosahexaenoic acid alter synaptic plasma membrane phospholipid fatty acid composition and sodium-potassium ATPase kinetics in developing rats

The objective of this study was to investigate if maternal dietary 20:4n-6 arachidonic acid (AA) and 22:6n-3 compared with adequate or low levels of 18:3n-3 linolenic acid (LNA) increases synaptic plasma membrane (SPM) cholesterol and phospholipid content, phospholipid 20:4n-6 and 22:6n-3 content, and Na,K-ATPase kinetics in rat pups at two and five weeks of age. At parturition, Sprague-Dawley rats were fed semi-purified diets containing either AA + docosahexaenoic acid (DHA), adequate LNA (control; 18:2n-6 : 18:3n-3 ratio of 7.1 : 1) or low LNA (18:2n-6 : 18:3n-39 ratio of 835 : 1). During the first two weeks of life, the rat pups received only their dams' milk. After weaning, pups received the same diet as their respective dams to five weeks of age. No significant difference was observed among rat pups fed the diet treatments for SPM cholesterol or total and individual phospholipid content at two and five weeks of age. Fatty acid analysis revealed that maternal dietary AA + DHA, compared with feeding the dams the control diet or the low LNA diet, increased 20:4n-6 in phosphatidylserine and 22:6n-3 content of SPM phospholipids. Rats fed dietary AA + DHA or the control diet exhibited a significantly increased Vmax for SPM Na,K-ATPase. Diet treatment did not alter the Km (affinity) of SPM Na,K-ATPase in rat pups at two and five weeks of age. It is concluded that dietary AA + DHA does not alter SPM cholesterol and phospholipid content but increases the 22:6n-3 content of SPM phospholipids modulating activity of Na,K-ATPase.     

Comparison of bloodstream fatty acid composition from African-American women at gestation, delivery, and postpartum

Our aim was to examine the docosahexaenoic acid (DHA; 22:6n-3) status of pregnant African-American women reporting to the antenatal clinic at Wayne State University in a longitudinal study design. Fatty acid compositions of plasma and erythrocyte total lipid extracts were determined and food frequency surveys were administered at 24 weeks of gestation, delivery, and 3 months postpartum for participants (n = 157). DHA (mean +/- SD) in the estimated total circulating plasma was similar at gestation (384 +/- 162 mg) and delivery (372 +/- 155 mg) but was significantly lower at 3 months postpartum (178 +/- 81 mg). The relative weight percentage of DHA and docosapentaenoic acid n-6 (DPAn-6; 22:5n-6) decreased postpartum, whereas their respective metabolic precursors, eicosapentaenoic acid (EPA; 20:5n-3) and arachidonic acid (AA; 20:4n-6), increased. Similar results were found in erythrocytes. Dietary intake of DHA throughout the study was estimated at 68 +/- 75 mg/day. The relative amounts of circulating DHA and DPAn-6 were increased during pregnancy compared with 3 months postpartum, possibly via increased synthesis from EPA and AA. The low dietary intake and blood levels of DHA in this population compared with others may not support optimal fetal DHA accretion and subsequent neural development.     

Correlations between blood and tissue omega-3 LCPUFA status following dietary ALA intervention in rats

The aim of this study was to assess relationships between the fatty acid contents of plasma and erythrocyte phospholipids and those in liver, heart, brain, kidney and quadriceps muscle in rats. To obtain a wide range of tissue omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFA) we subjected weanling rats to dietary treatment with the n-3 LCPUFA precursor, alpha linolenic acid (ALA, 18:3 n-3) for 3 weeks. With the exception of the brain, we found strong and consistent correlations between the total n-3 LCPUFA fatty acid content of both plasma and erythrocyte phospholipids with fatty acid levels in all tissues. The relationships between eicosapentaenoic acid (EPA, 20:5 n-3) and docosapentaenoic acid (DPA, 22:5 n-3) content in both blood fractions with levels in liver, kidney, heart and quadriceps muscle phospholipids were stronger than those for docosahexaenoic acid (DHA, 22:6 n-3). The strong correlations between the EPA+DHA (the Omega-3 Index), total n-3 LCPUFA and total n-3 PUFA contents in both plasma and erythrocyte phospholipids and tissues investigated in this study suggest that, under a wide range of n-3 LCPUFA values, plasma and erythrocyte n-3 fatty acid content reflect not only dietary PUFA intakes but also accumulation of endogenously synthesised n-3 LCPUFA, and thus can be used as a reliable surrogate for assessing n-3 status in key peripheral tissues.     

Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys

Rhesus monkeys given pre- and postnatal diets deficient in n-3 essential fatty acids develop low levels of docosahexaenoic acid (22:6 n-3, DHA) in the cerebral cortex and retina and impaired visual function. This highly polyunsaturated fatty acid is an important component of retinal photoreceptors and brain synaptic membranes. To study the turnover of polyunsaturated fatty acids in the brain and the reversibility of n-3 fatty acid deficiency, we fed five deficient juvenile rhesus monkeys a fish oil diet rich in DHA and other n-3 fatty acids for up to 129 weeks. The results of serial biopsy samples of the cerebral cortex indicated that the changes of brain fatty acid composition began as early as 1 week after fish oil feeding and stabilized at 12 weeks. The DHA content of the phosphatidylethanolamine of the frontal cortex increased progressively from 3.9 +/- 1.2 to 28.4 +/- 1.7 percent of total fatty acids. The n-6 fatty acid, 22:5, abnormally high in the cerebral cortex of n-3 deficient monkeys, decreased reciprocally from 16.2 +/- 3.1 to 1.6 +/- 0.4%. The half-life (t 1/2) of DHA in brain phosphatidylethanolamine was estimated to be 21 days. The fatty acids of other phospholipids in the brain (phosphatidylcholine, -serine, and -inositol) showed similar changes. The DHA content of plasma and erythrocyte phospholipids also increased greatly, with estimated half-lives of 29 and 21 days, respectively. We conclude that monkey cerebral cortex with an abnormal fatty acid composition produced by dietary n-3 fatty acid deficiency has a remarkable capacity to change its fatty acid content after dietary fish oil, both to increase 22:6 n-3 and to decrease 22:5 n-6 fatty acids. The biochemical evidence of n-3 fatty acid deficiency was completely corrected. These data imply a greater lability of the fatty acids of the phospholipids of the cerebral cortex than has been hitherto appreciated.     

Regulation of PUFA metabolism: pharmacological and toxicological aspects

Levels of the long-chain polyunsaturated fatty acids (LCP) of the n-6 and n-3 series in animal plasma and cells are directly or indirectly dependent upon the intakes of either their precursors, the short-chain polyunsaturated fatty acids (SCP), linoleic (LA, 18:2 n-6) and alpha linolenic acid (ALA, 18:3 n-3), respectively, and/or of the preformed products (arachidonic, 20:4 n-6) and eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3). We report here that pharmacological agents and cytotoxic compounds significantly affect the production of LCP from SCP in cultured cells. Using labelled substrates and radio HPLC separations, we observed that the potent hypocholesterolemic agent, simvastatin, activates the formation of AA from LA, mainly acting at the delta5 desaturation step, and increases also the mRNA levels, in cultured monocytic cells (THP-1). Elevation of AA occurs also in plasma lipids of hyperlipemic patients treated with statins (but not with fibrates). Conversely, oxysterols (mainly 7-beta-oxysterol), which are detected in circulating lipoproteins of rabbits on a hypercholesterolemic diet, potently inhibit the synthesis of AA from LA in hepatocytic cell lines (Hep-G2). At the same time plasma levels o AA are reduced vs controls, in spite of an identical intake of LA. Finally, on the basis of previous work showing reduced levels of LCP, mainly DHA, in the milk of cigarette-smoking mothers, we have observed that the incubation of human mammary gland cells with sera exposed to cigarette smoke results in marked inhibition of the production of DHA from ALA. The products in smoke responsible for this effect, are being identified through mass spectrometric techniques. In conclusion, pharmacological agents and toxic compounds, such as oxysterols and smoke products affect key steps in the synthesis of the LCP, major bioregulators in mammalian cells.     

Alpha-linolenic acid supplementation during human pregnancy does not effect cognitive functioning

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.     

n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonoylglycerol level in mice

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.     

Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men

We studied the long-chain conversion of [U-13C]alpha-linolenic acid (ALA) and linoleic acid (LA) and responses of erythrocyte phospholipid composition to variation in the dietary ratios of 18:3n-3 (ALA) and 18:2n-6 (LA) for 12 weeks in 38 moderately hyperlipidemic men. Diets were enriched with either flaxseed oil (FXO; 17 g/day ALA, n=21) or sunflower oil (SO; 17 g/day LA, n=17). The FXO diet induced increases in phospholipid ALA (>3-fold), 20:5n-3 [eicosapentaenoic acid (EPA), >2-fold], and 22:5n-3 [docosapentaenoic acid (DPA), 50%] but no change in 22:6n-3 [docosahexanoic acid (DHA)], LA, or 20:4n-6 [arachidonic acid (AA)]. The increases in EPA and DPA but not DHA were similar to those in subjects given the SO diet enriched with 3 g of EPA plus DHA from fish oil (n=19). The SO diet induced a small increase in LA but no change in AA. Long-chain conversion of [U-13C]ALA and [U-13C]LA, calculated from peak plasma 13C concentrations after simple modeling for tracer dilution in subsets from the FXO (n=6) and SO (n=5) diets, was similar but low for the two tracers (i.e., AA, 0.2%; EPA, 0.3%; and DPA, 0.02%) and varied directly with precursor concentrations and inversely with concentrations of fatty acids of the alternative series. [13C]DHA formation was very low (<0.01%) with no dietary influences.     

Brain phospholipid arachidonic acid half-lives are not altered following 15 weeks of N-3 polyunsaturated fatty acid adequate or deprived diet

Previous studies have infused radiolabeled arachidonic acid (AA) into rat brains and followed AA esterification into phospholipids for up to 24 h; however, the half-life of AA in rat brain phospholipids is unknown. Eighteen day old rats were fed either an n-3 PUFA adequate or deprived diet for 15 weeks. Following the 15 weeks, 40 µCi of [³H] AA was injected intracerebroventricularly into the right lateral ventricle using stereotaxic surgery and returned to their dietary treatment. From 4–120 days after [³H] AA administration, brains were collected for chemical analyses. The half-life of AA in rat brain phospholipids was 44 ± 4 days for the n-3 PUFA adequate group and 46 ± 4 days for the n-3 PUFA deprived group, which closely approximates the predicted half-life previously reported, based on the rate of entry from the plasma unesterified pool, suggesting the plasma unesterified pool is a major contributor to brain uptake of AA. Furthermore, unlike a previous report in which the half-life of brain phospholipid docosahexaenoic acid (DHA) was increased in n-3 PUFA deprived rats, n-3 PUFA deprivation did not significantly alter the AA half-life, suggesting different mechanisms exist to maintain brain concentrations of AA and DHA.     

n-6 and n-3 Long-chain polyunsaturated fatty acids in the erythrocyte membrane of Brazilian preterm and term neonates and their mothers at delivery

Placental transfer of the long-chain polyunsaturated fatty acids (LCPUFA) arachidonic (AA) and docosahexaenoic (DHA) acids is selectively high to maintain accretion to fetal tissues, especially the brain. The objectives of the present study were to investigate the essential fatty acid (EFA) and LCPUFA status at birth of preterm and term Brazilian infants and their mothers, from a population of characteristically low intake of n-3 LCPUFA, and to evaluate the association between fetal and maternal status, by the determination of the fatty acid composition of the erythrocyte membrane. Blood samples from umbilical cord of preterm (26-36 weeks of gestation; n = 30) and term (37-42 weeks of gestation; n = 30) infants and the corresponding maternal venous blood were collected at delivery. The LCPUFA composition of the erythrocyte membrane and DHA status were similar for mothers of preterm and term infants. Neonatal AA was higher (P < 0.01) whereas its precursor 18:2n-6 was lower (P < 0.01) than maternal levels, as expected. There was no difference in LCPUFA erythrocyte composition between preterm and term infants, except for DHA. Term infants presented a worse DHA status than preterm infants (P < 0.01) and than their mothers (P < 0.01) at delivery. There was a negative correlation of neonatal DHA with maternal AA and a positive correlation between neonatal AA and maternal AA and 18:2n-6 only at term. These results suggest that the persistent low DHA maternal status, together with the comparatively better AA and 18:2n-6 status, might have affected maternal-fetal transfer of DHA when gestation was completed up to term, and possibly contributed to the worse DHA status of term neonates compared with the preterm neonates.     

Chronic nutritional deprivation of n-3 α-linolenic acid does not affect n-6 arachidonic acid recycling within brain phospholipids of awake rats

Using an in vivo fatty acid model and operational equations, we reported that esterified and unesterified concentrations of docosahexaenoic acid (DHA, 22 : 6 n-3) were markedly reduced in brains of third-generation (F3) rats nutritionally deprived of alpha-linolenic acid (18 : 3 n-3), and that DHA turnover within phospholipids was reduced as well. The concentration of docosapentaenoic acid (DPA, 22 : 5 n-6), an arachidonic acid (AA, 20 : 4 n-6) elongation/desaturation product, was barely detectable in control rats but was elevated in the deprived rats. In the present study, we used the same in vivo model, involving the intravenous infusion of radiolabeled AA to demonstrate that concentrations of unesterified and esterified AA, and turnover of AA within phospholipids, were not altered in brains of awake F3-generation n-3-deficient rats, compared with control concentrations. Brain DPA-CoA could be measured in the deprived but not control rats, and AA-CoA was elevated in the deprived animals. These results indicated that AA and DHA are recycled within brain phospholipids independently of each other, suggesting that recycling is regulated independently by AA- and DHA-selective enzymes, respectively. Competition among n-3 and n-6 fatty acids within brain probably does not occur at the level of recycling, but at levels of elongation and desaturation (hence greater production of DPA during n-3 deprivation), or conversion to bioactive eicosanoids and other metabolites.     

Motor, mental and behavioral developments in infancy are associated with fatty acid pattern in breast milk and plasma of premature infants

The objective of this study was to investigate any association between infants' early development and PUFA concentrations in early breast milk and infants' plasma phospholipids at 44 weeks gestational age. Fifty-one premature infants were included. The quality of general movement was assessed at 3 months, and motor, mental and behavioral development at 3, 6, 10 and 18 months corrected age using Bayley's Scales of Infant Development (BSID-II). Linoleic acid, the major n-6/n-3 FA ratios, Mead acid and the EFA deficiency index in early breast milk were negatively associated with development up to 18 months of age. DHA and AA, respectively, in infants' plasma phospholipids was positively, but the AA/DHA ratio negatively, associated with development from 6 to 18 months of age. Our data suggest that the commonly found high n-6 concentration in breast milk is associated with less favorable motor, mental and behavioral development up to 18 months of age.     

Effect of diazepam on the fatty acid composition of plasma and liver phospholipids in rat.

Male Wistar rats (2 months old) were maintained on a nutritionally adequate diet, and diazepam was administered at a dose of 10 mg/kg/day. After 24 weeks the effects on the fatty acid composition of plasma and liver phospholipids were studied. Increased levels of palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), and oleic (18:1n-9) acids were found in plasma phospholipids. In contrast, the levels of docosapentanoic (22:5n-3) and docosahexanoic (22:6n-3; DHA) acids were drastically decreased by diazepam. A significant decrease produced by diazepam was also found in levels of DHA in liver phospholipids.     

Increased risk of postpartum depressive symptoms is associated with slower normalization after pregnancy of the functional docosahexaenoic acid status

Observational studies suggest an association between a low docosahexaenoic acid (DHA, 22:6n-3) status after pregnancy and the occurrence of postpartum depression. However, a comparison of the actual biochemical plasma DHA status among women with and without postpartum depression has not been reported yet. The contents of DHA and of its status indicator n-6 docosapentaenoic acid (n-6DPA, 22:5n-6) were measured in the plasma phospholipids of 112 women at delivery and 32 weeks postpartum. At this latter time point, the Edinburgh Postnatal Depression Scale (EPDS) questionnaire was completed to measure postpartum depression retrospectively. The EPDS cutoff score of 10 was used to define 'possibly depressed' (EPDS score > or =10) and non-depressed women (EPDS score <10). Odds ratios (OR) were calculated using a multiple logistic regression analysis with the EPDS cutoff score as dependent and fatty acid concentrations and ratio's as explanatory variables, while controlling for different covariables. The results demonstrated that the postpartum increase of the functional DHA status, expressed as the ratio DHA/n-6DPA, was significantly lower in the 'possibly depressed' group compared to the non-depressed group (2.34+/-5.56 versus 4.86+/-5.41, respectively; OR=0.88, P=0.03). Lactating women were not more predisposed than non-lactating women were to develop depressive symptoms. From this observation it seems that the availability of DHA in the postpartum period is less in women developing depressive symptoms. Although further studies are needed for confirmation, increasing the dietary DHA intake during pregnancy and postpartum, seems prudent.     

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

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

The calcium uptake of the rat heart sarcoplasmic reticulum is altered by dietary lipid

Summary Small amounts of dietary n-3 fatty acids can have dramatic physiological effects, including the reduction of plasma triglycerides and an elevation of cellular eicosapentanoic (EPA) and docosahexanoic acids (DHA) at the expense of arachidonic acid (AA). We investigated the effects of alterations in the fatty acid compositions of cardiac sarcoplasmic reticulum (CSR) produced by dietary manipulation on the calcium pump protein that is required for energy dependent calcium transport. CSR was isolated from rats fed menhaden oil, which is rich in n-3 fatty acids, and from control animals that were given corn oil. Relative to control membranes, those isolated from rats fed menhaden oil, had a lower content of saturated phospholipids, an increased DHA/AA ratio, and an increased ratio of n-3 to n-6 fatty acids. These changes were associated with a 30% decrease in oxalate-facilitated, ATP-dependent calcium uptake and concomitant decreased Ca-ATPase activity in the membranes from the animals fed menhaden oil. In contrast, there was no alteration in active pump sites as measured by phosphoenzyme formation. Thus, the CSR Ca-ATPase function can be altered by dietary interventions that change the composition, and possibly structure, of the phospholipid membranes thereby affecting enzyme turnover.     

Plasma fatty acids of neonates born to mothers with and without gestational diabetes

Women with gestational diabetes mellitus (GDM) and their neonates have lower levels of arachidonic (AA) and docosahexaenoic (DHA) acids in red cell membranes. It is not clear if this abnormality is restricted to red cells or is a generalised problem. We have investigated plasma fatty acids of neonates (venous cord) of GDM (n=37), and non-diabetic (n=31) women. The GDMs had lower levels of dihomogamma-linolenic (20:3n-6, DHGLA) acid, summation operator n-6 metabolites, DHA and summation operator n-3 metabolites (p<0.05) in choline phosphoglycerides (CPG). They also had lower levels of AA (-4.5%), adrenic acid (22:4n-6, -13%), osbond acid (22:5n-6, -7%) and summation operator n-6 (-2.5%). There was a similar pattern in triglycerides (TG) and cholesterol esters (CE). Mead acid, a marker of generalised shortage of derived and parent essential fatty acids, was higher in CPG and TG of the GDM group by 73% and 76%. The adrenic/osbond acid (22:4n-6/22:5n-6) ratio, a biochemical marker of DHA insufficiency, was reduced in CPG (-4.5%), TG (-63%) and CE (-75%) of the GDM group. These findings, which are consistent with the previous red cell data, suggest that the neuro-visual and vascular development and function of the offspring of GDM women may be adversely affected if the levels of AA and DHA are compromised further by other factors, pre- or post-natally. Studies are required to elucidate the underlying mechanism for the reduction of the two fatty acids and to evaluate the developmental and health implications.     

Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from day 3 prior to conception till day 15 of pregnancy. We concentrated on DHA, AA, Mead acid, and EFA-index [(omega-3+omega-6)/(omega-7+omega-9)] in maternal erythrocytes, maternal brain, and fetal brain. It was found that erythrocyte EFA/LCP sensitively reflects declining EFA/LCP status in pregnancy, although this decline was not apparent in maternal brain. Differences in erythrocyte EFA/LCP coincided with larger differences in fetal brain EFA/LCP as compared to EFA/LCP in maternal brain. Both maternal and fetal brains were affected by short-term EFA/LCP intake, but the developing fetal brain proved most sensitive. The inverse relationship between fetal brain AA and DHA suggests the need of a maternal dietary DHA/AA balance, at least in mice.     

Biomarkers of DHA status

Docosahexaenoic acid (DHA, 22:6n-3) is a long chain omega-3 fatty acid that is the primary n-3 fatty acid found in the central nervous system where it plays both a structural and functional role in cells. Because the tissues of interest are generally inaccessible for fatty acid analysis in humans and because precise DHA intake is difficult to determine, surrogate biomarkers are important for defining DHA status. Analysis of total lipid extracts or phospholipids from plasma or erythrocytes by gas chromatography meet the criteria for a useful biomarker of DHA status. Furthermore, both plasma and erythrocyte DHA levels have been correlated with brain, cardiac, and other tissue levels. Use of these biomarkers of DHA status will enable future clinical trials and observational studies to define more precisely the DHA levels required for either disease prevention or other functional benefits.     

Effect of randomized supplementation with high dose olive, flax or fish oil on serum phospholipid fatty acid levels in adults with attention deficit hyperactivity disorder

Dietary intake of omega-3 fatty acids has been positively correlated with cardiovascular and neuropsychiatric health in several studies. The high seafood intake by the Japanese and Greenland Inuit has resulted in low ratios of the omega-6 fatty acid arachidonic acid (AA, 20:4n-6) to eicosapentaenoic acid (EPA, 20:5n-3), with the Japanese showing AA:EPA ratios of approximately 1.7 and the Greenland Eskimos showing ratios of approximately 0.14. It was the objective of this study to determine the effect of supplementation with high doses (60 g) of flax and fish oils on the blood phospholipid (PL) fatty acid status, and AA/EPA ratio of individuals with Attention Deficit Hyperactivity Disorder (ADHD), commonly associated with decreased blood omega-3 fatty acid levels. Thirty adults with ADHD were randomized to 12 weeks of supplementation with olive oil (< 1% omega-3 fatty acids), flax oil (source of alpha-linolenic acid; 18:3n-3; alpha-LNA) or fish oil (source of EPA and docosahexaenoic acid; 22:6n-3; DHA). Serum PL fatty acid levels were determined at baseline and at 12 weeks. Flax oil supplementation resulted in an increase in alpha-LNA and a slight decrease in the ratio of AA/EPA, while fish oil supplementation resulted in increases in EPA, DHA and total omega-3 fatty acids and a decrease in the AA/EPA ratio to values seen in the Japanese population. These data suggest that in order to increase levels of EPA and DHA in adults with ADHD, and decrease the AA/EPA ratio to levels seen in high fish consuming populations, high dose fish oil may be preferable to high dose flax oil. Future study is warranted to determine whether correction of low levels of long-chain omega-3 fatty acids is of therapeutic benefit in this population.