Arachidonic Acid Status Research Articles

Placental F4-Neuroprostanes and F2-Isoprostanes are altered in gestational diabetes mellitus and maternal obesity

We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.

Statin therapy upregulates arachidonic acid status via enhanced endogenous synthesis in patients with plaque psoriasis

Circulating fatty acids (FA) may be important in the psoriatic pro-inflammatory phenotype. FADS1 converts linoleic acid (LA) to arachidonic acid (AA), a precursor to potent signaling molecules. HMG-CoA reductase inhibitors (statins) increase FADS1/2 expression in vitro. Psoriasis patients (42 ± 14 years/age, 47% male) were randomized to 40 mg of atorvastatin (n = 20) or nothing (n = 10) for two weeks and plasma FA measured pre and post treatment. After treatment, LDL-C was 44% lower in the statin compared to the no-treatment group. Statins increased FADS1/2 expression, and lowered LA 12% (33% – > 29%, p<0.001) and raised AA 14% (7.7% – > 9.0%, p<0.01) with no change in the no-treatment group. In psoriasis, statins enhance AA and decrease LA, consistent with the action of enhanced FADS expression in vivo. Therapies intended to blunt the effects of AA on platelet aggregation, such as aspirin or omega-3 fatty acids, may require dose adjustment when co-administered with atorvastatin.NCT: NCT03228017

Statin therapy upregulated arachidonic acid status via enhanced endogenous synthesis in patients with plaque psoriasis

Lead Author's Financial Disclosure: Nothing to disclose.

Supplementing Docosahexaenoic Acid and Arachidonic Acid During Suckling Period Is Beneficial for Developing Tolerance to Egg Protein in Allergy Prone Brown Norway Rats

ObjectivesWe aimed to study the effect of supplementing arachidonic acid (ARA) and docosahexaenoic acid (DHA) during suckling (through Suckling Diet, SD) and weaning (through weaning diet, WD) on oral tolerance (OT) development in allergy susceptible Brown Norway rats. MethodsDams were assigned to consume either ARA+DHA (0.4% ARA, 0.8% DHA w/w total fat) SD or control SD (0% ARA, DHA) for 21d during the pups’ suckling period. At 21d, pups from each SD group were randomized to receive ARA + DHA WD (0.5% ARA, 0.5% DHA w/w total fat) or control WD (0% ARA, DHA) until 8wk. Between 21–25 d, pups from each of the 4 diet groups were randomized to receive ovalbumin (Ova, 3 mg) or a placebo (8% sucrose) for OT induction. At 7 wk, pups received an Ova + alum injection IP to induce systemic immunization. In necropsy, plasma was collected and splenocytes were isolated to determine immune cell types and ex-vivo cytokine production to phorbol myristate acetate + ionomycin (PMAi). ResultsAlthough higher DHA levels in dams’ breastmilk were seen with ARA+DHA SD, this SD effect was not seen in the 8wk pups. At 8wks, ARA+DHA WD resulted in significantly higher DHA level in (1.5x) plasma phospholipids (PL) and (2x) splenocytes. ARA composition in pups’ plasma and splenocytes PL was not different among SD and WD groups. OT development was confirmed by a significantly lower plasma level of Ova-IgG1 and Ova-IgE in Ova OT groups. Further, SD ARA+DHA supplementation also had 30% lower plasma Ova-IgG1 than control SD (P = 0.02) but the SD had no effect on production of IL2, IL4, IL10, IFNg, TNFα and IL13 by PMAi stimulated splenocytes. However, pups from Ova group that received ARA+DHA SD and control WD produced more TGFβ than control for SD and WD (P = 0.05). Pups from sucrose OT groups, when supplemented with ARA+DHA SD had 50% higher T regulatory cells (CD3+CD4+CD25+FoxP3+, Tregs) than controls SD in spleen. In pups that received control SD groups, the Ova group had lower activated T helper (CD3+CD4+CD28+) than sucrose, however, when pups received ARA+DHA SD, OT effect was absent. ConclusionsARA and DHA in WD increased DHA status without affecting ARA status in plasma. ARA and DHA provided in SD was beneficial for OT development shown by lowered ova-IgG1, which may be due to higher Tregs and TGFβ produced by splenocytes in brown Norway offspring. Funding SourcesNSERC, AGES-ALES (Patel).

Brain serotonin transporter binding, plasma arachidonic acid and depression severity: A positron emission tomography study of major depression

BackgroundSerotonin transporter (5-HTT) binding and polyunsaturated fatty acids (PUFAs) are implicated in major depressive disorder (MDD). Links between the two systems in animal models have not been investigated in humans. MethodsUsing positron emission tomography (PET) and [11C]DASB, we studied relationships between 5-HTT binding potential and plasma levels of PUFAs docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) in medication-free MDD patients (n = 21). PUFAs were quantified using transesterification and gas chromatography. Binding potential BPP, and alternative outcome measures BPF and BPND, were determined for [11C]DASB in six a priori brain regions of interest (ROIs) using likelihood estimation in graphical analysis (LEGA) to calculate radioligand total distribution volume (VT), and a validated hybrid deconvolution approach (HYDECA) that estimates radioligand non-displaceable distribution volume (VND) without a reference region. Linear mixed models used PUFA levels as predictors and binding potential measures as outcomes across the specified ROIs; age and sex as fixed effects; and subject as random effect to account for across-region binding correlations. As nonlinear relationships were observed, a quadratic term was added to final models. ResultsAA predicted both 5-HTT BPP and depression severity nonlinearly, described by an inverted U-shaped curve. 5-HTT binding potential mediated the relationship between AA and depression severity. LimitationsGiven the small sample and multiple comparisons, results require replication. ConclusionsOur findings suggest that AA status may impact depression pathophysiology through effects on serotonin transport. Future studies should examine whether these relationships explain therapeutic effects of PUFAs in the treatment of MDD.

Arachidonic acid status negatively associates with forearm bone outcomes and glucose homeostasis in children with an overweight condition or obesity.

Long-chain polyunsaturated fatty acids are implicated in musculoskeletal health in adults. This study examined whether fatty acid status relates to bone health outcomes in children with overweight condition or obesity (body mass index z score, 3.1 ± 0.1; age, 9.0 ± 0.2 years; n = 108). Nondominant forearm bone density (distal one-third), geometry (4% site), and soft tissue composition (66%) were assessed using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Red blood cell (RBC) fatty acid profile and indices of glucose homeostasis were measured. Differences in outcomes among RBC arachidonic acid (AA, C20:4n-6) tertiles were tested using mixed-model ANOVA. Ultra-, mid-, and total-distal forearm bone mineral content, adjusted for sex, age, percentage body fat, race, and forearm length, were 10% to 13% greater in children in the first AA tertile relative to the third. Children in the second tertile had the highest bone cross-sectional area and estimated strength at the 66% radius. Muscle cross-sectional area was 15% lower in the third tertile compared with the first, along with higher fasting insulin concentrations (27%) and homeostasis model of assessment estimate of insulin resistance (31%). Higher RBC AA status aligns with deficits in forearm bone mass, geometry, and muscle mass in children with excess adiposity and early signs of insulin resistance. Novelty Higher arachidonic acid status is associated with lower forearm bone mass in children with overweight condition or obesity. Children with higher arachidonic acid status had increased fasting insulin concentrations and indices of insulin resistance.

Growth, tolerance, and DHA and ARA status of healthy term infants receiving formula with two different ARA concentrations: Double-blind, randomized, controlled trial

Circulating docosahexaenoic acid (DHA) and arachidonic acid (ARA) in total red blood cells (RBC) are considered indicators of fatty acid status. In this study, healthy term infants received study formula through 120 days of age. All study formulas had 17 mg DHA/100 kcal. Investigational formulas had 1) 25 g ARA/100 kcal and no added prebiotic blend (ARA-25; n = 29) or 2) 34 mg ARA/100 kcal and a prebiotic blend (1:1 ratio; 4 g/L) of polydextrose and galactooligosaccharides (PDX/GOS; n = 20). The control formula had 34 mg ARA/100 kcal and no added prebiotic blend (Control: n = 31). Fatty acids in total RBCs and plasma phospholipids (PPLs) at 120 days and buccal epithelial PLs at 14 and 120 days of age were assessed by capillary column gas chromatography. The calculated 90% confidence interval (CI) of each investigational formula relative to the Control for total RBC ARA (ARA-25: 93–105%; PDX/GOS: 96–110%) and total RBC DHA (ARA-25: 95–113%; PDX/GOS: 94–113%) fell within the pre-specified equivalence limit (85–118%), establishing study formula equivalence with respect to ARA and DHA. At day 120, total RBC and buccal epithelia PL ARA (µg/ml) were not significantly correlated (r = 0.041; p = 0.732); correlation in total RBC and buccal epithelia PL DHA was low, albeit significant (r = 0.324; p = 0.006). Consequently, buccal epithelial may not provide a suitable substitute for RBC when assessing fatty acid status and availability. The present RBC data suggest availability of DHA for central nervous system development and function is equivalent among infants receiving formulas that had 34 or 25 mg/100 kcal ARA and 17 mg/100 kcal DHA.

Erythrocyte DHA and AA in infancy is not associated with developmental status and cognitive functioning five years later in Nepalese children

BackgroundLong chain polyunsaturated fatty acids (LCPUFA) especially docosahexaenoic acid (DHA) and arachidonic acid (AA) are crucial for normal brain development in utero and in early infancy. Data on fatty acid status and cognitive development in infants and children from low-income countries are scarce.MethodsWe examined the association between the DHA and AA status in infancy (n = 320) and developmental status and cognitive functioning five years later. At five years of age, we measured development by the Ages and Stages Questionnaire 3rd. ed. (ASQ-3) and cognitive functioning by subtests from the neuropsychological test battery NEPSY II. In addition, infant fatty acid composition in red blood cells (RBC) was analyzed. In multiple linear and logistic regression models, we estimated the associations between DHA and AA status in infancy and scores on the ASQ-3 and the NEPSY II subtests.ResultsThere were no notable associations between infant AA and DHA status, and the scores on the ASQ-3 and the NEPSY II subtests five years later. It should be noted that we found better than expected concentrations of erythrocyte DHA and AA among the infants, and the ASQ scores were left-skewed, which limited the ability to identify associations.ConclusionDHA and AA status in infancy is seemingly not related to neurodevelopment measured 5 years later in this peri-urban population from Nepal.

Erythrocyte fatty acid composition of Nepal breast-fed infants.

Essential fatty acids play a critical role in the growth and development of infants, but little is known about the fatty acid status of populations in low-income countries. The objective was to describe the fatty acid composition of red blood cells (RBC) in breastfeed Nepali infants and a subsample of their mothers and to identify the main sources of fatty acids in the mother's diet, as well as the fatty acid composition of breast milk. RBC fatty acid composition was analyzed in a random sample of 303 infants and 72 mother, along with 68 breastmilk samples. Fatty acid profiles of the most important dietary fat sources were analyzed. Information on mother's diet and intake of fat was collected by three 24-h dietary recalls. In infant RBC's, docosahexaenoic acid (DHA) was the main n-3 fatty acid, and arachidonic acid (AA) was the major n-6 fatty acid. Total n-6 PUFA was three times higher than total n-3 PUFA. Height-for-age (HAZ) was positively associated with DHA status and AA status in multivariable models. The concentration of all fatty acids was higher in children, compared to mothers, except Total n-6 PUFA and Linoleic acid (LA) where no differences were found. The mother's energy intake from fat was 13% and cooking oil (sesame, mustard, soybean or sunflower oil) contributed 52% of the fat intake. RBC-DHA levels in both infants and mother was unexpected high taking into account few dietary DHA sources and the low DHA concentrations in breastmilk.

Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults.

High arachidonic acid (AA; 20:4n-6) status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n-6 polyunsaturated fatty acids (PUFAs) are based on the premise that endogenous conversion from linoleic acid (LA; 18:2n-6) is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25–80 years old) with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44–74 years old) from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy) and food sources of PUFA (fish, red meat, poultry, soy and cooking oils) in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3n-6), alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), and docosahexaenoic acid (DHA; 22:6n-3)) concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05) in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population.

A 22 bp FADS2 Insertion‐Deletion (Indel) Polymorphism Influences Arachidonic Acid Status

IntroductionThe fatty acid desaturase 2 (FADS2) gene product catalyzes a key step in the biosynthesis of biologically active long chain polyunsaturated fatty acids (LCPUFA). The rs66698963 a 22 bp polymorphic insertion‐deletion (Indel) is associated with basal expression of FADS1 which mediates the Δ5‐desaturation of dihomo‐gamma‐linolenic acid to arachidonic acid (20:3n‐6→20:4n‐6), as well as coordinated induction of FADS1 and FADS2 expression in vitro. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage.MethodsA total of 234 individuals of a primarily vegetarian Indian population and 311 individuals from the U.S were genotyped. Evolutionary analysis testing for positive selection on the FADS region was performed using genetic variations data from the 1000 Genomes Project (1000GP). Functional analysis of rs66698963 genotypes and fatty acid levels was evaluated in a subset of the U.S. population.ResultsA much higher I/I genotype frequency was found in Indians (68%) than in the U.S. (18%). Data from 1000 Genomes Project confirmed our observation and revealed a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Evolutionary analyses revealed for the first time signals of positive selection around rs66698963 in only South Asians. Basal plasma phospholipid arachidonic acid status was 8% greater in I/I compared to D/D individuals. The biochemical pathway product‐precursor difference, arachidonic acid minus linoleic acid, was 31% and 13% greater for I/I and I/D compared to D/D, respectively.ConclusionOur study is consistent with previous in vitro data suggesting that the insertion allele enhances n‐6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant‐based diet practice.Support or Funding InformationR01 AT007003

Genetic variation in FADS genes is associated with maternal long-chain PUFA status but not with cognitive development of infants in a high fish-eating observational study

Long-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by Δ-5 (encoded by FADS1) and Δ-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p<0.001) and precursor:product ratios for linoleic acid (LA) (18:2n-6)-to-AA (NC1 p<0.001; NC2 p<0.001) and α-linolenic acid (ALA) (18:3n-3)-to-DHA were increased (NC2 p=0.028). There were no significant associations between maternal FADS genotype and BSID-II scores in either cohort. A trend for improved PDI was found among infants born to mothers with the minor rs3834458 allele.In these high fish-eating cohorts, genetic variability in FADS genes was associated with maternal AA status measured in serum and a subtle association of the FADS genotype was found with neurodevelopment.

Red blood cell long-chain polyunsaturated fatty acid (LC-PUFA) levels in pregnant women predict length of gestation via effects on sleep quality and inflammation

Objective Mechanistic pathways linking maternal long-chain polyunsaturated fatty acid (LC-PUFA) status with gestational length are poorly delineated. Key LC-PUFAs implicated in this association are the antiinflammatory omega-3 docosahexaenoic acid (DHA) and proinflammatory omega-6 arachidonic acid (AA). We hypothesized that (1) lower red blood cell (RBC) DHA:AA ratios would predict shorter gestation and (2) this effect would be mediated by both inflammation and sleep quality. Methods Pregnant women (n = 135) provided blood and completed the Pittsburg Sleep Quality Index at 20–27 weeks gestation. RBC fatty acids were determined by gas chromatography and serum inflammatory markers (IL-6, IL-8, TNF- α , IL-1 β , CRP) were determined by high-sensitivity ELISA. Results Lower DHA:AA ratios predicted higher serum IL-8 (r = −0.20, p = 0.02) and poorer sleep quality (b = −13.8, p = 0.02). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. Mediational analyses demonstrated indirect effects linking lower RBC DHA:AA with shorter gestation via higher IL-8 (95% CI = 0.10, 3.84) and poor sleep (95% CI = 0.35, 3.99). A significant race X DHA:AA interaction in predicting preterm birth (PTB) was observed (p = 0.049); among African Americans only, the odds of PTB decreased significantly as DHA:AA increased (OR for 0.1 unit increase = 0.25 (95% CI = 0.06, 0.99, p = 0.048). Discussion These data support both inflammatory pathways and sleep quality as significant mediators linking maternal DHA:AA status and length of gestation. African Americans may be at greater risk for PTB related to suboptimal DHA levels.

Neonatal fatty acid status and neurodevelopmental outcome at 9 years

BackgroundLong-chain polyunsaturated fatty acids (LCPUFA) are important for prenatal brain development. Previous studies of others assessed outcome until 7years. The associations between neonatal LCPUFA status and long-term developmental outcome are debated. AimTo investigate the relationship between fatty acid status at birth and neurodevelopment at 9years. Age 9 is a unique age after a significant neurodevelopmental transition. Study designCorrelation study. Multivariable analyses were carried out to adjust for potential confounders. Subjects317 children who participated in a trial on effects of postnatal LCPUFA supplementation were eligible. 235 children (74%) were reassessed at age 9. Outcome measuresAt birth, docosahexaenoic acid (DHA) and arachidonic acid (AA) were determined in the wall of the umbilical vein. We primarily studied the correlation between DHA and AA with the complex form of minor neurological dysfunction (cMND). Secondary correlations that were studied were DHA and AA levels with cognitive development in terms of full IQ, and with behavioural development in terms of a total problem score. ResultsBoys with cMND showed lower DHA values in the umbilical vein than children with better neurological condition (p=0.033). A similar association was absent in girls. Neonatal AA values were not associated with neurological outcome. Neither neonatal DHA nor AA values were associated with cognition and behaviour at 9. ConclusionsHigher umbilical DHA levels in boys are associated with better neurological development at 9years. AA status at birth was not associated with neurodevelopment at 9years.

Elevated Arachidonic Acid Intakes Reduce Bone Mineral Content and Trabecular Volume in Growing Obese Rats

Arachidonic acid (AA) is elevated in obesity and in fatty marrow. Whether elevated AA status has implications in bone growth and mineralization in obesogenic states is not clear. The objective was to assess the effect of AA on bone mass acquisition in diet‐induced obesity (DIO) during growth. Male Sprague Dawley rats (n=42, 4 wk, 89.8 ± 1.1g) were randomized to one of the following diets: control, high‐fat (HFD, 16.7% fat w/w), HFD + AA (1% w/w) for 6 wk. Body composition and bone mass were measured by in vivo micro‐computed tomography (μCT) at beginning and end of study. Repeated‐measures two‐way ANOVA with post‐hoc Tukey's HSD was used to test for group differences. Food intake in the control group was significantly greater (8.17%) than HFD groups, but there was no difference in total energy intake between groups. HFD+AA group had significantly greater % body fat (Table 1) and body weight gain (504 ± 12%) than HFD (495 ± 13%) and control (484 ± 11%) beginning from wk 4 of study. Total and trabecular bone mineral content (BMC) in whole body and lumbar spine (LS) 2‐4 were lower in HFD+AA vs HFD and control (Table 1). This was accompanied by reduced bone volume at LS, possibly explaining the higher whole body volumetric bone mineral density (vBMD). These results indicate that short term DIO with excess AA may adversely affect the trabecular bone compartment by decreasing bone mineral accretion and volume during growth. Whether this translates into reduced bone strength remains to be determined. CTRL HFD HFD,AA Whole body Body fat (%) 28.95 ± 0.85a 31.13 ± 0.79ab 31.97 ± 0.85b Total vBMD (g/cm3) 474.78 ± 4.03a 485.86 ± 4.03b 483.30 ± 4.17b BMC (mg) 6828.95 ± 101.80ab 6819.38 ± 101.80a 6671.70 ± 105.64b Trab vBMD (g/cm3) 346.64 ± 4.58a 363.95 ± 4.58b 359.94 ± 4.75ab BMC (mg) 2151.83 ± 49.05ab 2201.17 ± 49.05a 2118.49 ± 50.90b Lumbar spine 2‐4 Total BMC (mg) 331.38 ± 7.13ab 336.58 ± 7.58a 308.55 ± 7.89b Volume (cm3) 0.84 ± 0.02a 0.83 ± 0.02ab 0.77 ± 0.02b Trab BMC (mg) 140.33 ± 4.97ab 144.86 ± 5.31a 124.25 ± 5.36b Volume (cm3) 0.43 ± 0.01a 0.42 ± 0.01ab 0.39 ± 0.01b

Docosahexaenoic acid (DHA) supplementation in pregnancy differentially modulates arachidonic acid and DHA status across FADS genotypes in pregnancy

Some FADS alleles are associated with lower DHA and ARA status assessed by the relative amount of arachidonic acid (ARA) and docosahexaenoic acid (DHA) in plasma and red blood cell (RBC) phospholipids (PL). We determined two FADS single nucleotide polymorphisms (SNPs) in a cohort of pregnant women and examined the relationship of FADS1rs174533 and FADS2rs174575 to DHA and ARA status before and after supplementation with 600mg per day of DHA. The 205 pregnant women studied were randomly assigned to placebo (mixed soy and corn oil) (n=96) or 600mg algal DHA (n=109) in 3 capsules per day for the last two trimesters of pregnancy. Women homozygous for the minor allele of FADS1rs174533 (but not FADS2rs174575) had lower DHA and ARA status at baseline. At delivery, minor allele homozygotes of FADS1rs174533 in the placebo group had lower RBC-DHA compared to major-allele carriers (P=0.031), while in the DHA-supplemented group, all genotypes had higher DHA status compared to baseline (P=0.001) and status did not differ by genotype (P=0.941). Surprisingly, DHA but not the placebo decreased ARA status of minor allele homozygotes of both FADS SNPs but not major allele homozygotes at delivery. Any physiological effects of changing the DHA to ARA ratio by increasing DHA intake appears to be greater in minor allele homozygotes of some FADS SNPs.

Liquid human milk fortifier significantly improves docosahexaenoic and arachidonic acid status in preterm infants

We report the fatty acid composition of mother׳s own human milk from one of the largest US cohorts of lactating mothers of preterm infants. Milk fatty acid data were used as a proxy for intake at enrollment in infants (n=150) who received human milk with a powder human milk fortifier (HMF; Control) or liquid HMF [LHMF; provided additional 12mg docosahexaenoic acid (DHA), 20mg arachidonic acid (ARA)/100mL human milk]. Mothers provided milk samples (n=129) and reported maternal DHA consumption (n=128). Infant blood samples were drawn at study completion (Study Day 28). Human milk and infant PPL fatty acids were analyzed using capillary column gas chromatography.DHA and ARA were within ranges previously published for US term and preterm human milk. Compared to Control HMF (providing no DHA or ARA), human milk fortified with LHMF significantly increased infant PPL DHA and ARA and improved preterm infant DHA and ARA status.

Arachidonic Acid-enriched Triacylglycerol Improves Cognitive Function in Elderly with Low Serum Levels of Arachidonic Acid

Arachidonic acid (ARA) is an n-6 PUFA and is thought to have an important role in various physiological and psychological functions. Recently, supplementation with ARA-enriched TAG was shown to improve age-related decreases in cognitive function in healthy elderly men. To investigate the influence of baseline serum ARA status on cognitive function and its improvement, we analyzed cognitive function stratified by serum ARA level. The stratified analysis was also conducted for the effects of ARA-enriched TAG supplementation on cognitive improvement. Cognitive function was evaluated by measuring event-related potentials (ERPs), including P300 latency and amplitude. When participants were stratified by baseline serum ARA level, P300 latency was significantly longer and P300 amplitude was generally lower in the low-ARA group than in the high-ARA group. No significant difference in P300 components was observed when participants were stratified by serum levels of any other fatty acid. ARA-enriched TAG supplementation significantly shortened P300 latency and increased P300 amplitude in the low-ARA group, although no significant differences were observed in the high-ARA group. These findings suggest that lower serum ARA levels were associated with cognitive function in elderly men and that ARA-enriched TAG supplementation is more effective in improving cognitive function in healthy elderly men with low serum ARA levels than in those with high serum ARA levels.

Supplementation with a powdered blend of PUFAs normalizes DHA and AA levels in patients with PKU

Patients with phenylketonuria (PKU) have a poor LC-PUFA status and require supplementation. The objective of this study was to evaluate the LC-PUFA status of PKU patients supplemented with fish oil or the fatty acid supplement KeyOmega. Plasma and erythrocyte docosahexaenoic acid (DHA) and arachidonic acid (AA) levels were determined in 54 patients (1–18.5years of age) with confirmed PKU. The influence of supplementation with fish oil versus KeyOmega, a powdered blend of DHA and AA, on LC-PUFA status was investigated and compared to the status in samples obtained from unsupplemented patients. Differential effects on LC-PUFA status were observed upon suppletion with fish oil versus KeyOmega. Whereas supplementation with fish oil increased the level of DHA, the AA concentration did not increase to normal values in these patients. In contrast, both DHA and AA levels increased and reached reference values upon supplementation with KeyOmega. In conclusion: these results indicate that KeyOmega offers additional benefit over fish oil since both AA and DHA status are normalized in PKU patients supplemented with KeyOmega.

Heart arachidonic acid is uniquely sensitive to dietary arachidonic acid and docosahexaenoic acid content in domestic piglets

This study determined the sensitivity of heart and brain arachidonic acid (ARA) and docosahexaenoic acid (DHA) to the dietary ARA level in a dose–response design with constant, high DHA in neonatal piglets. On day 3 of age, pigs were assigned to 1 of 6 dietary formulas varying in ARA/DHA as follows (% fatty acid, FA/FA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3–D3) 0.69/1.0; (A4) 1.1/1.0; (D2) 0.67/0.62; and (D1) 0.66/0.33. At necropsy (day 28) higher levels of dietary ARA were associated with increased heart and liver ARA, while brain ARA remained unaffected. Dietary ARA had no effect on tissue DHA accretion. Heart was particularly sensitive, with pigs in the intermediate groups having different ARA (A2, 18.6±0.7%; A3, 19.4±1.0%) and a 0.17% increase in dietary ARA resulted in a 0.84% increase in heart ARA. Further investigations are warranted to determine the clinical significance of heart ARA status in developing neonates.