LCPUFA Status Research Articles

The Maternal Omega-3 Long-Chain Polyunsaturated Fatty Acid Concentration in Early Pregnancy and Infant Neurodevelopment: The ECLIPSES Study.

Omega-3 Long-Chain Polyunsaturated Fatty Acids (n-3 LCPUFAs) play a key role in early neurodevelopment, but evidence from observational and clinical studies remains inconsistent. This study investigates the association between maternal n-3 LCPUFA, Docosahexaenoic Acid (DHA), and eicosapentaenoic acid (EPA) concentrations during pregnancy and infant development functioning at 40 days. This study includes 348 mother-infant pairs. Maternal serum concentrations were assessed in the first and third trimesters alongside sociodemographic, clinical, nutritional, psychological, and obstetrical data. At 40 days, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was administered. An adjusted analysis revealed that lower first-trimester n-3 LCPUFA and DHA concentrations are associated with better infant motor development. These results underscore the potential significance of the maternal n-3 LCPUFA status in early pregnancy for influencing fetal neurodevelopment. However, the complexity of these associations necessitates further investigation, emphasizing the urgent need for additional studies to comprehensively elucidate the nuanced interplay between the maternal n-3 LCPUFA status and infant neurodevelopment.

A Systematic Review of Omega-3 Consumption and Neuroprotective Cognitive Outcomes.

While a great deal of interest has been accorded to the cognitive effects of n-3 long-chain polyunsaturated fatty acids (LC PUFAs), there is a need for systematic review data that assess this outcome across the lifespan, accounting for population differences and highlighting methodological limitations of extant studies. This systematic review addresses the effects of n-3s on human cognition and provides an overview on the current state of research and recommendations for future efforts. Based on a thorough review of highly powered articles from PubMed (MEDLINE), Web of Science, and ProQuest Central, the authors evaluated articles published between 2000 and 2020 assessing LC PUFA status on cognition as a primary outcome measure. Using the PRISMA guidelines, the researchers' primary aim was to provide a comprehensive overview of the articles. The results indicate inconsistent effects of intervention, with benefits for specific groups on specific outcomes. Although results were rarely definitive across cognitive domains, and the majority of studies indicated the presence of a possible threshold effect in which LC PUFA needs were already being met, and supplementation did not have an additional effect, there is evidence for trends towards benefit in cognitive functions, in those experiencing early cognitive decline.

Investigating N-3 Fatty Acids to prevent Neonatal Tobacco-related outcomeS (INFANTS): study protocol for a double-blind, randomized, placebo-controlled parallel clinical trial of n-3 polyunsaturated fatty acids in pregnant smokers

BackgroundTobacco use during pregnancy is the most important modifiable risk factor associated with adverse pregnancy outcomes, increasing the risk of preterm birth, intrauterine growth restriction and sudden infant death syndrome. Fewer than half of pregnant smokers can quit on their own. Identifying safe and effective therapies to prevent tobacco-related adverse pregnancy outcomes and/or increase smoking cessation in pregnant women would have a substantial public health impact. Cigarette smoking is associated with a relative deficiency in circulating n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) levels. A recent analysis found that smokers taking n-3 LCPUFAs during pregnancy had a reduction in preterm labor risk when compared to non-smokers. Studies have shown that supplemental n-3 LCPUFAs may also reduce nicotine cravings and daily cigarette use. Thus, smokers may benefit from supplemental n-3 LCPUFAs by lowering the risk of preterm labor and/or increased smoking cessation. To address important remaining knowledge gaps, we propose the Investigating N-3 Fatty Acids to prevent Neonatal Tobacco related outcomeS (INFANTS).MethodsThe INFANTS study is a multicenter, randomized, double-blind, placebo-controlled study that will randomize 400 pregnant smokers to either supplemental n-3 LCPUFAs or placebo. Participants will be enrolled between 12 and 24 weeks’ gestation and followed until 6 weeks after delivery. We will recruit from clinical centers throughout Middle Tennessee. We will assess smoking behavior after 12 weeks of supplementation using self-report and validated biomarkers of tobacco exposure. We will measure response to supplementation using biological markers of n-3 LCPUFA status. Our primary endpoint will be preterm labor as reflected by gestational age at delivery. Our secondary endpoint will be change from baseline in cigarettes per day at 12 weeks.DiscussionThis study tests the hypothesis that smoking-induced n-3 LCPUFA deficiencies contribute to tobacco-related adverse pregnancy outcomes and that supplementation of n-3 LCPUFAs in pregnant smokers may prevent these complications. If our study demonstrates that supplemental n-3 LCPUFAs are effective at reducing the risk of tobacco-related adverse neonatal outcomes and/or reducing tobacco use during pregnancy, our results could have an immediate and major impact on pregnancy care and neonatal outcomes.Trial registrationClinicalTrials.gov NCT04417595. Registered on April 21, 2020

Expert Opinion on Benefits of Long-Chain Omega-3 Fatty Acids (DHA and EPA) in Aging and Clinical Nutrition.

Life expectancy is increasing and so is the prevalence of age-related non-communicable diseases (NCDs). Consequently, older people and patients present with multi-morbidities and more complex needs, putting significant pressure on healthcare systems. Effective nutrition interventions could be an important tool to address patient needs, improve clinical outcomes and reduce healthcare costs. Inflammation plays a central role in NCDs, so targeting it is relevant to disease prevention and treatment. The long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to reduce inflammation and promote its resolution, suggesting a beneficial role in various therapeutic areas. An expert group reviewed the data on omega-3 LCPUFAs in specific patient populations and medical conditions. Evidence for benefits in cognitive health, age- and disease-related decline in muscle mass, cancer treatment, surgical patients and critical illness was identified. Use of DHA and EPA in some conditions is already included in some relevant guidelines. However, it is important to note that data on the effects of omega-3 LCPUFAs are still inconsistent in many areas (e.g., cognitive decline) due to a range of factors that vary amongst the trials performed to date; these factors include dose, timing and duration; baseline omega-3 LCPUFA status; and intake of other nutrients. Well-designed intervention studies are required to optimize the effects of DHA and EPA in specific patient populations and to develop more personalized strategies for their use.

Impact of erythrocyte long-chain omega-3 polyunsaturated fatty acid levels in early pregnancy on birth outcomes: findings from a Belgian cohort study.

To examine the association between maternal erythrocyte long-chain omega-3 PUFA (n-3 LCPUFA), measured in early pregnancy, and pregnancy and birth outcomes. One hundred and eight healthy women with a singleton pregnancy were included. Erythrocyte fatty acids were analyzed using gas chromatography. Gestational length, birth anthropometric measures, and pregnancy-associated complications were collected from hospital medical records. We observed significant positive associations between maternal docosahexaenoic acid (DHA) levels (p = 0.024) and omega-3 index values (p = 0.021) and gestational length in adjusted linear regression models. Each point in maternal DHA level was associated with 2.19 days longer gestational duration (β = 2.19; 95% CI 0.29-4.09). No consistent associations were found between n-3 PUFA levels and composite pregnancy outcome. These findings suggest that the gestational length is positively affected by maternal n-3 LCPUFA status as soon as the early stages of pregnancy.

Exploring correlations between neuropsychological measures and domain-specific consistency in associations with n-3 LCPUFA status in 8-9 year-old boys and girls.

Long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) have in some studies been associated with cognitive and socioemotional outcomes in children, but results are inconsistent possibly due to the use of different tests and potential gender-specific effects. The objective of this cross-sectional study was to explore overall patterns in neuropsychological scores as well as correlations between scores within specific domains, and to examine potential gender differences and consistency in associations with n-3 LCPUFA status. In 199 Danish 8–9 year-old children, we performed a large battery of tests and questionnaires on attention, processing speed, executive functions, memory, and socioemotional traits, and measured erythrocyte fatty acid composition. Principal component analyses (PCA) showed that most of the variation in both cognitive performance and socioemotional traits was explained by overall performance, followed by speed-accuracy trade off and externalizing vs. internalizing problems, respectively. Boys had higher speed, lower attention and higher externalizing problem scores than girls. Measures of performance within both processing speed and attention domains correlated moderately, whereas no correlations were found for measures of executive functions apart from some weak correlations for impulsivity. Parent-rated scores for both externalizing and internalizing problems correlated strongly, whereas correlations with child-rated scores were weak. Scores within specific domains did not consistently associate with n-3 LCPUFA, except for processing speed measures which all pointed to faster processing with increased n-3 LCPUFA status. Gender differences in the associations were observed for attention and impulsivity. Child- but not parent-rated internalizing and social problems tended to associate directly with n-3 LCPUFA, supported by increased internalizing problems measured by the PCA component. In conclusion, measures of speed and attention seem to represent these domains in general, whereas single measures of more complex cognitive functions should be interpreted with caution. One approach could be to use multiple tests and create multivariate scores to guide interpretations. Furthermore, the results indicate a need to consider both parent- and child-rated socioemotional scores and gender differences in neuropsychological functions e.g. in investigations of n-3 LCPUFA effects.

A High-Throughput Method for the Analysis of Erythrocyte Fatty Acids and the Omega-3 Index.

Omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) have several health benefits. In particular, low n-3 LCPUFA status is associated with cardiovascular disease (CVD) and led to the development of the omega-3 index that is the proportion of eicosapentaenoic acid and docosahexaenoic acid in the erythrocyte membranes, as a marker of CVD risk. Most methods used to measure the omega-3 index are laborious and time consuming. Therefore, the aim of this study was to develop a high-throughput method for the extraction and measurement of erythrocyte fatty acids and the omega-3 index. For sample extraction and quantification, two methods were used; a single-step extraction, degradation, and derivatization method by Lepage and Roy, followed by gas chromatography flame ionization detection (GC-FID), which is commonly used and a high-throughput method using an automated methyl tert-butyl ether extraction followed by electrospray ionization mass spectrometry. Both methods were first applied to the analysis of known concentrations of synthetic phospholipid (PL) mixtures to determine recovery and precision prior to their application in the analysis of human erythrocytes. The range of recoveries over five synthetic PL mixtures were 86.4-108.9% and the coefficient of variation was <10% (within-run) and ≤15.2% (between-run). Both methods showed high correlation (R = 0.993) for the omega-3 index and there was no systematic bias in the detection of omega-3 index using either method. The new high-throughput method described here offers considerable advantages in terms of simplicity and throughput compared to the GC-FID method and provides additional information on molecular PL concentrations.

Effect of complementary food with small amounts of freshwater fish on whole blood n-3 fatty acids in Cambodian infants age 6–15 months

The impact of freshwater fish consumption on the status of long-chain n-3 fatty acids (n-3 LCPUFA) in infants in landlocked, low-income populations is unknown. We used secondary data from a randomized, single-blinded, controlled trial to evaluate the impact of daily consumption of complementary food products with small amounts of freshwater fish on whole blood n-3 LCPUFA in Cambodian infants. Infants (n = 419), received daily, one of four food products for 9 months. Two products contained freshwater fish: WinFood (10% fish by dry weight) and WinFood-L (12% fish by dry weight), while two products were non-fish-based: corn-soy blends (CSB+ and CSB++). Whole blood fatty acids and breastfeeding status were assessed at baseline and endline of the intervention. The WinFood products contributed to an estimated maximum intake of 86.5 mg/day n-3 LCPUFA. There was no difference in whole blood n-3 LCPUFA among the four intervention groups or between the fish-based and the non-fish-based groups (p ≥ 0.142). At endline, 71% of the children were still breastfed. Interaction analyses indicated a lower ratio of n-6/n-3 PUFA in non-breastfed infants in the WinFood groups compared to the CSB groups (pinteraction = 0.026). Thus, a high intake of n-3 LCPUFA from breastmilk may have blurred a potential impact of small amounts of freshwater fish effect on n-3 LCPUFA status in Cambodian infants.

Effects of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation on Cardiovascular Mortality: The Importance of the Dose of DHA.

Recent evidence on the relationship between omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation and cardiovascular health suggests that n-3 LCPUFA may no longer be efficacious. This review summarises the randomised controlled trials (RCTs) that assess the effect of n-3 LCPUFA supplementation on cardiovascular mortality. It appears that in the RCTs that showed no effect of n-3 LCPUFA on cardiovascular mortality, the dose of n-3 LCPUFA (in particular docosahexaenoic acid (DHA)) and hence the n-3 LCPUFA status, may not have been sufficiently high to demonstrate the efficacy, and/or the baseline n-3 LCPUFA status was already too high. The intention-to-treat analysis (ITT) is the gold standard for analysing RCTs and ITT is used for drug intervention trials where exposure to the drug versus no drug exposure provides two clearly distinct groups to determine the efficacy of the drug being studied. This differs in nutrition trials as often the nutrient of interest being studied is already being consumed by both groups (placebo and active) and therefore a true placebo group with absolutely no intake of the nutrient being studied is highly unlikely. Therefore, in n-3 LCPUFA supplementation trials, as there is no clear distinction between the two groups (placebo and n-3 LCPUFA), a per-protocol analysis (comparison of groups that includes only those participants that fully completed the original intervention allocation) should be conducted in addition to ITT analysis. Furthermore, blood analysis pre- and post-supplementation should be conducted to ensure that: (1) that the baseline n-3 status is not too high, in order to alleviate a potential ceiling effect; and (2) that the dose is high enough and hence the increase in omega-3 status will be high enough in order to assess the efficacy of n-3 LCPUFA supplementation.

Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials.

Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using I2 statistic. Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (−2.14 [95% CI −3.22 to −1.07]; p < 0.0001; I2 = 97%), EPA (−0.72 [95% CI −1.25 to −0.18]; p = 0.008; I2 = 88%), and ARA (−0.83 [95% CI, −1.48 to −0.17]; p = 0.01; I2 = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I2 = 74%). Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (−1.96 [95% CI −3.5 to −0.34]; p = 0.02; I2 = 0) and repetitive and restricted interests and behaviours (−1.08 [95% CI −2.17 to −0.01]; p = 0.05; I2 = 0). Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA.

Neonatal fatty acid status and cardiometabolic health at 9 years

BackgroundLong chain polyunsaturated fatty acid (LCPUFA) status is associated with risk of cardiovascular diseases in adulthood. We previously demonstrated no effect of LCPUFA supplementation after birth on BP and anthropometrics. Little is known about the association between fatty acid status at birth and cardiometabolic health at older ages. AimTo evaluate associations between docosahexaenoic acid (DHA) and arachidonic acid (AA) levels in the umbilical cord and blood pressure (BP) and anthropometrics at 9years. Study designObservational follow-up study. Multivariable analyses were carried out to adjust for potential confounders. Subjects229 children who took part in a randomized controlled trial (RCT) on the effects of LCPUFA formula supplementation. Outcome measuresBP was chosen as primary outcome; heart rate and anthropometrics as secondary outcomes. ResultsAA levels in the wall of the umbilical vein and artery were negatively associated with diastolic BP (B: vein −0.831, 95% CI: −1.578; −0.083, p=0.030; artery: −0.605, 95% CI: −1.200; −0.010, p=0.046). AA was not associated with systolic BP; DHA not with diastolic nor systolic BP. The AA:DHA ratio in the umbilical vein was negatively associated with diastolic BP (B: −1.738, 95% CI: −3.141; −0.335, p=0.015). Heart rate and anthropometrics were not associated with neonatal LCPUFA status. ConclusionsHigher AA levels and a higher AA:DHA ratio at birth are associated with lower diastolic BP at age 9. This suggests that the effect of LCPUFAs at early age is different from that in adults, where DHA is regarded anti-adipogenic and AA as adipogenic.

Genetic Variants of the FADS Gene Cluster Are Associated with Erythrocyte Membrane LC PUFA Levels in Patients with Mild Cognitive Impairment.

Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI). The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes). Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck's depression-inventory). These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient.

Fish oil supplementation from 9 to 18 months of age affects the insulin-like growth factor axis in a sex-specific manner in Danish infants.

Several studies have investigated the effects of fish oil (FO) on infant growth, but little is known about the effects of FO and sex on insulin-like growth factor-1 (IGF-1), the main regulator of growth in childhood. We explored whether FO v. sunflower oil (SO) supplementation from 9 to 18 months of age affected IGF-1 and its binding protein-3 (IGFBP-3) and whether the potential effects were sex specific. Danish infants (n 115) were randomly allocated to 5 ml/d FO (1·2 g/d n-3 long-chain PUFA (n-3 LCPUFA)) or SO. We measured growth, IGF-1, IGFBP-3 and erythrocyte EPA, a biomarker of n-3 LCPUFA intake and status, at 9 and 18 months. Erythrocyte EPA increased strongly with FO compared with SO (P<0·001). There were no effects of FO compared with SO on IGF-1 in the total population, but a sex × group interaction (P=0·02). Baseline-adjusted IGF-1 at 18 months was 11·1 µg/l (95% CI 0·4, 21·8; P=0·04) higher after FO compared with SO supplementation among boys only. The sex × group interaction was borderline significant in the model of IGFBP-3 (P=0·09), with lower IGFBP-3 with FO compared with SO among girls only (P=0·03). The results were supported by sex-specific dose-response associations between changes in erythrocyte EPA and changes in IGF-1 and IGFBP-3 (both P<0·03). Moreover, IGF-1 was sex specifically associated with BMI and length. In conclusion, FO compared with SO resulted in higher IGF-1 among boys and lower IGFBP-3 among girls. The potential long-term implications for growth and body composition should be investigated further.

Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study.

Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: 'school performance' and 'reading comprehension'. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved 'school performance' (P=0·015), 'reading comprehension' (P=0·043) and EPA+DHA status 0·21 (95% CI 0·15, 0·27) w/w % (P<0·001), but it did not affect serum ferritin or Hb. At baseline, having small Fe stores was associated with poorer 'school performance' in girls, but with better 'reading comprehension' in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with 'school performance', suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study.

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.

Fatty acid supply with complementary foods and LC-PUFA status in healthy infants: results of a randomised controlled trial.

Introduction of complementary food usually leads to decreasing intakes of long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFA), compared to full breastfeeding. In the randomised controlled PINGU intervention trial, we tested the effects of complementary foods with different contents of alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on term infant LC-PUFA status. Healthy infants born at term were randomised to receive from the introduction of complementary feeding at the age of 4 to 6months until age of 10months ready-made complementary meals either with ALA-rich rapeseed oil (intervention group (IG)-R), with salmon twice weekly to provide preformed DHA (IG-F), or with linoleic acid-rich corn oil (control group, CG). Fatty acid composition was assessed in erythrocyte (RBC) and plasma glycerophospholipids. Complete data of fatty acids in RBC (plasma) were available from 158 (155) infants. After intervention, infants assigned to IG-F showed higher RBC and plasma percentages of eicosapentaenoic acid (EPA), DHA, and total n-3 LC-PUFA than CG (each p<0.001). In IG-R, levels of ALA and the ratio of ALA to LA in plasma and RBC (all p<0.0001) as well as RBC-EPA (p<0.0001) were higher than in CG, while DHA levels did not differ between IG-R and CG. Regular fish consumption during complementary feeding enhances infant EPA and DHA status. The usage of rapeseed oil in small amounts concordant with EU-law for commercial meals enhances endogenic EPA-synthesis, but does not affect DHA status. Provision of oily fish with complementary feeds is advisable to prevent a decline of DHA status. www.clinicaltrials.gov , identifier: NCT01487889, title: Polyunsaturated fatty acids in child nutrition-a German multimodal optimisation study (PINGU).

Metabolic health benefits of long-chain omega-3 polyunsaturated fatty acids.

Restricting energy intake and increasing physical activity are advocated for reducing obesity, but many individuals have difficulty complying with these recommendations. Consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFA) offers multiple mechanisms to counteract obesity, including appetite suppression; circulatory improvements, which promote nutrient delivery to skeletal muscle and changes in gene expression, which shift metabolism toward increased fat oxidation; increased energy expenditure; and reduced fat deposition. n-3 LCPUFA may also alter gene expression in skeletal muscle to suppress catabolic pathways and upregulate anabolic pathways, resulting in greater lean tissue mass, metabolic rate, and maintenance of physical function. n-3 LCPUFA supplementation has been shown to counteract obesity in rodents, but evidence in humans is limited. Epidemiological associations between n-3 LCPUFA intakes and obesity are inconclusive. Several studies, on the other hand, indicate inverse relationships between biomarkers of n-3 LCPUFA status and obesity, although causality is uncertain. There have been few human intervention trials of omega-3 supplementation for obesity; some have indicated potential benefits, especially when combined with energy-restricted diets or exercise. More trials are needed to confirm these effects and identify mechanisms of action.

A method for long term stabilisation of long chain polyunsaturated fatty acids in dried blood spots and its clinical application

Conventional assays of omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) status in humans involve venous blood collection and expensive, multi-step processes that limit their usefulness as screening tools. This study aimed to develop a capillary dried blood spot (DBS) system capable of protecting n-3 LCPUFA from oxidation for up to 2 months at room temperature (20–25°C). We demonstrated that a DBS system comprising both an antioxidant and chelating agent on silica-gel coated paper prevented any significant change in the n-3 LCPUFA profile after 2 months. Our DBS assay was then tested in fifty subjects, and this demonstrated the presence of strong and significant correlations between the results obtained from the DBS system and those obtained from conventional measures for all fatty acids, in particular the n-3 LCPUFA EPA and DHA (r>0.96, P<0.0001). This study therefore validates our DBS system as a reliable method for the assessment of n-3 LCPUFA status in humans.

Modulation of blood oxylipin levels by long-chain omega-3 fatty acid supplementation in hyper- and normolipidemic men

IntroductionLong chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) such as EPA and DHA have been shown to possess beneficial health effects, and it is believed that many of their effects are mediated by their oxygenated products (oxylipins). Recently, we have shown that serum levels of several hydroxy, epoxy, and dihydroxy FAs are dependent on the individual status of the parent FAs in a cohort of normo- and hyperlipidemic subjects. So far, the effect of an increased dietary LC n-3 PUFA intake on hydroxy, epoxy, and dihydroxy FA levels has not been investigated in subjects with mild combined hyperlipidemia. Subjects and methodsIn the present study, we compared oxylipin patterns of 10 hyperlipidemic (cholesterol >200mg/dl; triglyceride >150mg/ml) and 10 normolipidemic men in response to twelve weeks of LC n-3 PUFA intake (1.14g DHA and 1.56g EPA). Levels of 44 free hydroxy, epoxy and dihydroxy FAs were analyzed in serum by LC-MS. Additionally, oxylipin levels were compared with their parent PUFA levels in erythrocyte membranes; a biomarker for the individual PUFA status. ResultsDifferences in the oxylipin pattern between normo- and hyperlipidemic subjects were minor before and after treatment. In all subjects, levels of EPA-derived oxylipins (170–4800pM) were considerably elevated after LC n-3 PUFA intake (150–1400%), the increase of DHA-derived oxylipins (360–3900pM) was less pronounced (30–130%). The relative change of EPA in erythrocyte membranes is strongly correlated (r≥0.5; p<0.05) with the relative change of corresponding epoxy and dihydroxy FA serum levels. The effect on arachidonic acid (AA)-derived oxylipin levels (140–27,100pM) was inconsistent. Discussion and conclusionsThe dietary LC PUFA composition has a direct influence on the endogenous oxylipin profile, including several highly biological active EPA- and DHA-derived lipid mediators. The shift in oxylipin pattern appears to be dependent on the initial LC PUFA status particularly for EPA. The finding that also levels of other oxylipins derived from ALA, LA or AA are modified by LC n-3 PUFA intake might suggest that at least some of the effects of EPA and DHA could be mediated by a shift in the entire oxylipin profile.

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.