Lower Docosahexaenoic Acid Levels Research Articles

New Forms of Neuroactive Phospholipids for DHA Enrichment in Brain.

Low levels of docosahexaenoic acid (DHA) in the brain have been related to neurological disorders, like Alzheimer's disease (AD). After ingestion, dietary DHA must cross the blood-brain barrier, where it is absorbed as lysophosphatidylcholine (LPC), due to its role as a preferential DHA carrier in the brain. This work aimed at the production of LPC-DHA extracts to be used in supplementation/food fortification intended neural enrichment in DHA. As it is rich in DHA, especially its phospholipids (PL), Atlantic mackerel (Scomber scombrus, caught in Spring/2022) was used as a raw material. The polar lipids fraction was separated and hydrolysed with Rhizomucor miehei lipase, to enzymatically convert phosphatidylcholine (PC) into LPC. The fish (muscle and by-products) lipids fraction was used for total lipids (TL) content, lipid classes (LC) and fatty acid (FA) profile evaluation, whilst polar lipids extracts were studied for LC production and FA analysis. Muscle TL ranged between 1.45 and 4.64 g/100 g (WW), while by-products accounted for 7.56-8.96 g/100 g, with the highest contents being found in March. However, PL were more abundant in muscle (22.46-32.20% of TL). For polar lipids extracts, PL represented 50.79% of TL, among which PC corresponded to 57.76% and phosphatidylethanolamine to 42.24%. After hydrolysis, nearly half of this PC was converted into LPC. When compared to the initial PC, DHA relative content (33.6% of total FA) was significantly higher after hydrolysis: 55.6% in PC and 73.6% in LPC. Such extract, obtained from this undervalued species, may represent a promising strategy to increase DHA uptake into brain cells while allowing this species to upgrade.

Fatty acid profiles reveal dietary variability of a large calanoid copepod Limnocalanus macrurus in the northern Baltic Sea

Eutrophication, climate-induced warming, and salinity fluctuations are altering the fatty acid profiles and the availability of essential polyunsaturated fatty acids (PUFAs) in marine zooplankton communities. Limnocalanus macrurus Sars G.O., 1863 is a large calanoid copepod inhabiting the low-salinity areas in the Baltic Sea, where it is a major source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to commercially important fish. L. macrurus is sensitive to warming, eutrophication and hypoxia. As an opportunistic feeder, it is capable of dietary shifts, which affects its fatty acid profiles. Although much studied in boreal lakes, there are only a few studies on the fatty acid profiles of the Baltic Sea populations. This study aimed to compare the fatty acid profiles of L. macrurus in three basins of the Baltic Sea, in relation to the community fatty acids and environmental variables. We collected samples of L. macrurus and filtered plankton community for gas chromatographic fatty acid analyses in August 2021 on R/V Aranda. The nutritional quality of L. macrurus to consumers was lower in the Gulf of Finland (GoF) compared to the Gulf of Bothnia, indicated by the low levels of DHA and EPA, as well as the low n-3/n-6 ratio of PUFAs. The lower ratio of 18:1n-7 to 18:1n-9 implied higher degree of omnivory in GoF. In contrast, a diatom marker 16:1n-7 had high proportion in the Bothnian Bay. High temperatures in GoF may have restricted feeding in the upper water column, possibly forcing a shift towards cyanobacteria or seston-based diet, as interpreted from a high proportion of 18:2n-6 and 18:3n-3. We conclude that the ability of L. macrurus to utilize multiple food sources increases its resilience to environmental change, while the consequences on the nutritional quality may have further cascading effects on the food webs.

Altered Red Blood Cell Fatty Acid and Serum Adipokine Profiles in Subjects with Obesity.

Adipokines, as well as the fatty acid profile of red blood cell (RBC) membranes, are known to play important roles in the development and progression of metabolic complications induced by obesity. Thus, the objective of this study is to compare the serum adipokine profile and the RBC membrane fatty acid profile of normal-weight and obese adults, and to analyze their relationship with serum biochemical parameters. An observational case-control study was performed in 75 normal-weight and obese adult subjects. Biochemical serum parameters, eight serum adipokines and the RBC membrane fatty acid profiles were measured. Associations between parameters were established using regression analysis. Subjects with obesity showed increased levels of leptin, fibroblast growth factor 21 (FGF21) and overexpressed nephroblastoma (NOV/CCN3), decreased adiponectin, and similar levels of vaspin and chemerin compared to normal-weight subjects. Significant positive and negative correlations were found with triglycerides and high-density lipoprotein-cholesterol (HDL-c), respectively. An increase in the total ω-6 fatty acids in the RBC membrane fatty acid profiles in subjects with obesity was observed, because of higher levels of both dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), and decreased total ω-3 fatty acids, mainly due to lower levels of docosahexaenoic acid (DHA). The ω-6/ω-3 ratio in the RBCs was significantly higher, suggesting an inflammatory status, as was also suggested by a reduced adiponectin level. A negative association between DGLA and adiponectin, and a positive association between DHA and serum triglycerides, was observed. Important alterations in serum adipokine and RBC fatty acid profiles are found in subjects with obesity.

Contrasting the phospholipid profiles of two neoplastic cell lines reveal a high PC:PE ratio for SH-SY5Y cells relative to A431 cells

Lipids have been implicated in Parkinson's Disease (PD). We therefore studied the lipid profile of the neuroblastoma SH-SY5Y cell line, which is used extensively in PD research and compared it to that of the A431 epithelial cancer cell line. We have isolated whole cell extracts (WC) and plasma membrane (PM) fractions of both cell lines. The isolates were analyzed with 31P NMR. We observed a significant higher abundance of phosphatidylcholine (PC) for SH-SY5Y cells for both WC (55 ± 4.1%) and PM (63.3 ± 3.1%) compared to WC (40.5 ± 2.2%) and PM (43.4 ± 1.3%) of A431. Moreover, a higher abundance of phosphatidylethanolamine was detected for the WC of A431 compared to the SH-SY5Y. Using LC-MS/MS, we also determined the relative abundance of fatty acid (FA) moieties for each phospholipid class, finding that SH-SY5Y had high polyunsaturated FA levels, including arachidonic acid compared to A431 cells. When comparing our results to reported compositions of brain and neural tissues, we note the much higher PC levels, as well as very low levels of docosahexaenoic acid. However, relative levels of arachidonic acid and other polyunsaturated fatty acids were elevated, in line with what is desirable for a neural model system.

Metabolic Interaction Between Folate, Vitamin B12, and Polyunsaturated Fatty Acids in Pregnancy.

Fetal growth and development are influenced by maternal nutrition and gestational weight gain. Adequate intake of nutrients such as folate, vitamin B12, and docosahexaenoic acid (DHA) is essential for healthy fetal and placental development. Many countries havea national flour fortification program with folic acid (FA), together with pre-pregnancy supplementation of FA (400μg/day) during the first trimester of pregnancy. The latter has been recommended by the WHO and adapted to local requirements by perinatal guidelines. On the other hand, in population studies, many women of childbearing age have vitamin B12 deficiency (<148pmol/L), which can be additionally masked by high FA intake and maternal pregestational obesity. Under these conditions, these patients could be having pregnancies in a folate/vitamin B12 imbalance, which is associated with higher adiposity, insulin resistance, altered lipid metabolism, and low DHA levels in their offspring. However, if these neonatal consequences of maternal pregestational obesityand folate/vitamin B12 imbalance can be reverted by DHA supplementation during pregnancy has not been addressed. This chapter reviews the literature and exposes the current gaps in knowledge and challenges in maternal nutrition with a life-course perspective.

What Is the Evidence for Dietary-Induced DHA Deficiency in Human Brains?

Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by endogenous synthesis from α-linolenic acid (ALA), an essential fatty acid. Low blood levels of DHA in some westernised populations have led to speculations that child development disorders and various neurological conditions are associated with sub-optimal neural DHA levels, a proposition which has been supported by the supplement industry. This review searched for evidence of deficiency of DHA in human populations, based on elevated levels of the biochemical marker of n-3 deficiency, docosapentaenoic acid (22:5n-6). Three scenarios/situations were identified for the insufficient supply of DHA, namely in the brain of new-born infants fed with high-linoleic acid (LA), low-ALA formulas, in cord blood of women at birth who were vegetarians and in the milk of women from North Sudan. Twenty post-mortem brain studies from the developed world from adults with various neurological disorders revealed no evidence of raised levels of 22:5n-6, even in the samples with reduced DHA levels compared with control subjects. Human populations most likely at risk of n-3 deficiency are new-born and weanling infants, children and adolescents in areas of dryland agriculture, in famines, or are refugees, however, these populations have rarely been studied. This is an important topic for future research.

Enrichment of livefeed with very low level of docosahexaenoic acid (DHA) is enough for yellowtail sea bream (Acanthopagrus latus) larvae

The marine fish larvae mostly rely on livefeed, with certain nutritional deficiencies such as poor long chain fatty acids, in spite of recent progress in developing artificial feed. Thus, the present experiment was conducted to evaluate a 30-day dietary effects of enriched rotifer (Brachionus rotundiformis) and Artemia nauplii (Artemia franciscana) with docosahexaenoic acid (DHA) on performance of yellowtail sea bream (Acanthopagrus latus) larvae. For this purpose, 60,000 larvae from wild broodstocks were stocked in 12 tanks (50 larvae/L) supplied with green water (0.5 ×106 cell/ml Nannochloropsis. sp). The rotifer and Artemia were enriched with four experimental emulsions contained four levels of DHA including very low (6 %, DHA-VL), low (12 %, DHA-L), medium (24 %, DHA-M) and high (37.8 %, DHA-H). Larvae were fed with rotifers from day 2–20 post hatch (DPH) and Artemia metanauplii (Instar-II, from 16 to 30 DPH). After the 30-day dietary trial, survival rate and growth performance of larvae were found not affected by different levels of DHA (P > 0.05). The activity of digestive enzymes including total proteases, lipase, amylase, alkaline phosphatase, and leucine-alanine peptidase showed some fluctuations among the experimental groups. However, in the most of the sampling intervals, except for protease activity, the activity of digestive enzymes did not change significantly among the experimental groups. The n–3 polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA) and DHA, were the highest in the whole body of larvae from DHA-M treatment. The DHA/EPA ratio in the whole body of larvae was significantly increased with increasing DHA level (P < 0.05). Based on our findings, very low levels of DHA is enough for supporting normal growth, survival and metamorphosis in developing A. latus larvae up to 30 days post hatching.

A new strategy in rearing of European flounder: using live Enchytraeus albidus to enhance juvenile growth

This study reports the use of the annelid worm Enchytraeus albidus as a live feed for reared juvenile European flounder, Platichthys flesus. We investigated growth, lipid composition and mortality in small scale (hundreds of fish) and large scale (thousands of fish) rearing. Live Enchytraeus had a relatively low content of the essential omega-3 fatty acid, docosahexaenoic acid (DHA), but similar levels of other essential fatty acids and amino acids as the normally used commercial dry feed. Despite low DHA levels in live worms, juvenile flounder fed Enchytraeus grew twice as fast as fish fed commercial dry feed. DHA levels in membrane phospholipids of juvenile flounder became depleted when fed Enchytraeus, but this had no apparent negative consequences for development or health of the fish. Our study suggests that the use of Enchytraeus as a live feed for European flounder is feasible at a large scale.

Association between Sarcopenia and Omega-3 Polyunsaturated Fatty Acid in Patients with Hepatocellular Carcinoma.

Introduction: This study aimed to validate whether preoperative sarcopenia can predict long-term outcomes in patients with hepatocellular carcinoma (HCC) and identify the associations between sarcopenia and polyunsaturated fatty acids (PUFAs). Methods: This large, retrospective study included 353 patients who underwent hepatic resection for HCC and preoperative computed tomography scans. Skeletal muscle mass was measured at the third lumbar vertebrae. The cutoff value for sarcopenia followed the Japan Society of Hepatology’s assessment criteria for sarcopenia. Results: Ninety-three patients (26.3%) with preoperative sarcopenia were enrolled. These patients had a significantly lower body mass index (p < 0.0001) and serum albumin level (p = 0.0070) as well as a higher rate of advanced-stage cancer (p = 0.0062) than those without sarcopenia. Patients with sarcopenia had significantly shorter overall survival than the other patients before (p = 0.0001) and after (p = 0.0415) propensity score matching. The sarcopenia group was significantly associated with low levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which were categorized based on omega-3 PUFAs, compared with those in the non-sarcopenia group (p = 0.0030 and p = 0.0135). Conclusions: We demonstrated an association between sarcopenia and the long-term prognosis in patients with HCC. Low EPA and DHA levels were associated with preoperative sarcopenia. Further prospective studies are needed to investigate whether nutritional support using omega-3 PUFAs can prevent and manage skeletal muscle mass depletion.

Fit and fatty freshwater fish: contrasting polyunsaturated fatty acid phenotypes between hybridizing stickleback lineages

Long‐chain polyunsaturated fatty acids are biologically important lipids that are unevenly distributed between and throughout environments. This heterogeneity can affect the evolution of metabolic processes, as populations adapt to the resource landscape that they encounter. Here, we compare fatty acid phenotypes of stickleback over two time scales of evolutionary divergence: between two lineages with different metabolic capacities for fatty acid synthesis (i.e. different copy number of the fatty acid desaturase gene; FADS2) that independently colonized European freshwaters during the Pleistocene and Holocene; and between two ecotypes within each lineage that have diverged more recently (~150 years) in different habitats (i.e. lake and stream). We measured fatty acid profiles of wild‐caught and lab‐reared fish for each lineage and ecotype combination after rearing lab fish on a diet deficient in omega‐3 long‐chain polyunsaturated fatty acids. Since these lineages hybridize in nature, we also measured profiles of lab‐reared hybrids and backcrosses raised on the same deficient diet. Wild fish showed strong compositional differences in fatty acids between habitats, lineages and sexes. Common garden fish had generally lower polyunsaturated fatty acid levels than wild fish, and females had lower omega‐6:omega‐3 than males. Fish from the lineage with fewer FADS2 copies also had lower levels of docosahexaenoic acid. Overall, we document divergence in fatty acid phenotypes between stickleback lineages with different histories of freshwater colonization, and between ecotypes in the early stages of adaptive population divergence.

Unique Trans-fatty Acid Profile in Children With Attention Deficit Hyperactivity Disorder.

Background: Attention deficit hyperactivity disorder (ADHD) is the most common developmental disorder in children. Studies suggest an association between fatty acids composition and ADHD pathogenesis. We aimed to investigate whether children diagnosed with ADHD present unique fatty acid profiles in red blood cells (RBC), as compared to children without ADHD.Method: We examined 60 children aged 6–14 years, out of which 32 were diagnosed with ADHD, and 28 were not. Blood was collected from all children to quantify an array of 26 fatty acids from RBC membranes. Fatty acid methyl esters were generated by acid transesterification and analyzed by gas chromatography.Results: We found that children with ADHD presented unique fatty acid profiles on RBC membranes with significantly higher levels of most of the trans-fatty acids (Total trans-fatty acids 0.64 ± 0.21 vs. 0.49 ± 0.18 p = 0.003) and lower levels of docosahexaenoic acid (DHA), as compared to controls (4.06 ± 0.79 vs. 4.68 ± 1.37 p = 0.040). Additionally, total trans-fatty acids were higher in children with extremely severe clinical ADHD condition score, as compared to milder ADHD scores and to control children (0.72 ± 0.18, 0.64 ± 0.20, 0.61 ± 0.22, 0.49 ± 0.18, p = 0.010, accordingly).Conclusion: Children with ADHD have higher levels of trans-fatty acids in RBCs, compared to children without ADHD. This study points to a possible link between trans-fatty acids and ADHD. Understanding these findings and the clinical meaning will potentially contribute to a more targeted dietary intervention.

Controversy about the critical role of long-chain polyunsaturated fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), during infancy

Long-chain polyunsaturated fatty acids (LC-PUFAs) are critical for infant growth and development, particularly arachidonic acid (ARA, C20:4n-6) and docosahexaenoic acid (DHA, C22:6n-3). ARA and DHA are components of cell membrane phospholipids and play an important role in cell division, differentiation, and signaling; and DHA is the n-3 fatty acid predominant in the developing brain and retina. During the third trimester of pregnancy, LC-PUFAs increase substantially in fetal circulation, and a "biomagnification" process in the fetal brain is observed. Moreover, LC-PUFAs are precursors of eicosanoids and metabolites, which modulate the intensity and duration of the immune response. LC-PUFA synthesis implies complex desaturation and elongation processes on their principal precursors, linoleic acid (LA) (18:3 n-6) (series n-6) and α-linolenic acid (LNA) (20:3 n-3) (series n-3), where fatty acid desaturases (FADS) and elongases (ELOVL) are competing. It is important to notice that during the first months of life, as a consequence of low enzymatic activity, LC-PUFA synthesis from LA and LNA is reduced, especially in those infants carrying variations in the FADS and ELOVL genes, which are involved in LC-PUFA synthesis, and so they are unable to supply their own DHA and ARA needs. Homozygote infants for FADS haplotype A (97 % of the Latinoamerican population) show low levels of ARA (only 43 %) and DHA (only 24 %) when compared to those carrying haplotype D (more prevalent in Europe, Africa and Asia). Human milk is the only source of LA, LNA, ARA, and DHA for the neonate and infant till complementary feeding (CF) is introduced. Infants fed with infant formulas must receive enough amounts of LA, LNA, ARA, and DHA to cover their nutritional requirements. The new guidelines by the European Food Safety Authority (EFSA) (2016) recommend that infant formulas and follow-on formulas must contain 20-50 mg of DHA/100 kcal (0.5-1 % of total fatty acids, which is higher than in human milk and the majority of infant formulas in the market), and it is not necessary to add ARA. This new regulation, which is already applicable since February 2020, has resulted in profound controversy because there is no scientific evidence about its appropriateness and safety for healthy children. Then, different international expert groups have revised the research already published about the effects of ARA and DHA addition to infant formulas, and discussed different emerging questions from this European directive. The expert group led from the University of Granada (Spain) recommends the addition of ARA in similar or higher concentrations than those of DHA, at least equal to those present in human milk (0.3 % of total fatty acids), although preferably 0.5 % and up to around 0.64 % of total fatty acids, since new studies confirm the optimal intake of ARA and DHA during the different developmental stages. This recommendation could be of particular importance for infants carrying the haplotype A of FADS.

Serum docosahexaenoic acid levels are associated with brain volumes in extremely preterm born infants.

Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for fetal brain growth and development. Our aim was to evaluate the association between serum DHA and AA levels and brain volumes in extremely preterm infants. Infants born at <28 weeks gestational age in 2013-2015, a cohort derived from a randomized controlled trial comparing two types of parenteral lipid emulsions, were included (n = 90). Serum DHA and AA levels were measured at postnatal days 1, 7, 14, and 28, and the area under the curve was calculated. Magnetic resonance (MR) imaging was performed at term-equivalent age (n = 66), and volumes of six brain regions were automatically generated. After MR image quality assessment and area under the curve calculation, 48 infants were included (gestational age mean [SD] 25.5 [1.4] weeks). DHA levels were positively associated with total brain (B = 7.966, p = 0.012), cortical gray matter (B = 3.653, p = 0.036), deep gray matter (B = 0.439, p = 0.014), cerebellar (B = 0.932, p = 0.003), and white matter volume (B = 3.373, p = 0.022). AA levels showed no association with brain volumes. Serum DHA levels during the first 28 postnatal days were positively associated with volumes of several brain structures in extremely preterm infants at term-equivalent age. Higher serum levels of DHA in the first 28 postnatal days are positively associated with brain volumes at term-equivalent age in extremely preterm born infants. Especially the most immature infants suffer from low DHA levels in the first 28 postnatal days, with little increase over time. Future research is needed to explore whether postnatal fatty acid supplementation can improve brain development and may serve as a nutritional preventive and therapeutic treatment option in extremely preterm infants.

DNA Damage, n-3 Long-Chain PUFA Levels and Proteomic Profile in Brazilian Children and Adolescents.

Fatty acids play a significant role in maintaining cellular and DNA protection and we previously found an inverse relationship between blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DNA damage. The aim of this study was to explore differences in proteomic profiles, for 117 pro-inflammatory proteins, in two previously defined groups of individuals with different DNA damage and EPA and DHA levels. Healthy children and adolescents (n = 140) aged 9 to 13 years old in an urban area of Brazil were divided by k-means cluster test into two clusters of DNA damage (tail intensity) using the comet assay (cluster 1 = 5.9% ± 1.2 and cluster 2 = 13.8% ± 3.1) in our previous study. The cluster with higher DNA damage and lower levels of DHA (6.2 ± 1.6 mg/dL; 5.4 ± 1.3 mg/dL, p = 0.003) and EPA (0.6 ± 0.2 mg/dL; 0.5 ± 0.1 mg/dL, p < 0.001) presented increased expression of the proteins CDK8–CCNC, PIK3CA–PIK3R1, KYNU, and PRKCB, which are involved in pro-inflammatory pathways. Our findings support the hypothesis that low levels of n-3 long-chain PUFA may have a less protective role against DNA damage through expression of pro-inflammatory proteins, such as CDK8–CCNC, PIK3CA–PIK3R1, KYNU, and PRKCB.

NMR Metabolite Profiles in Male Meat-Eaters, Fish-Eaters, Vegetarians and Vegans, and Comparison with MS Metabolite Profiles.

Metabolomics may help to elucidate mechanisms underlying diet-disease relationships and identify novel risk factors for disease. To inform the design and interpretation of such research, evidence on diet-metabolite associations and cross-assay comparisons is needed. We aimed to compare nuclear magnetic resonance (NMR) metabolite profiles between meat-eaters, fish-eaters, vegetarians and vegans, and to compare NMR measurements to those from mass spectrometry (MS), clinical chemistry and capillary gas-liquid chromatography (GC). We quantified 207 serum NMR metabolite measures in 286 male participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford cohort. Using univariate and multivariate analyses, we found that metabolite profiles varied by diet group, especially for vegans; the main differences compared to meat-eaters were lower levels of docosahexaenoic acid, total n-3 and saturated fatty acids, cholesterol and triglycerides in very-low-density lipoproteins, various lipid factions in high-density lipoprotein, sphingomyelins, tyrosine and creatinine, and higher levels of linoleic acid, total n-6, polyunsaturated fatty acids and alanine. Levels in fish-eaters and vegetarians differed by metabolite measure. Concentrations of 13 metabolites measured using both NMR and MS, clinical chemistry or GC were mostly similar. In summary, vegans’ metabolite profiles were markedly different to those of men consuming animal products. The studied metabolomics platforms are complementary, with limited overlap between metabolite classes.

High Plasma Docosahexaenoic Acid Associated to Better Prognoses of Patients with Acute Decompensated Heart Failure with Preserved Ejection Fraction.

The clinical relevance of polyunsaturated fatty acids (PUFAs) in heart failure remains unclear. The aim of this study was to investigate the association between PUFA levels and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). This retrospective study included 140 hospitalized patients with acute decompensated HFpEF (median age 84.0 years, 42.9% men). The patients’ nutritional status was assessed, using the geriatric nutritional risk index (GNRI), and their plasma levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) were measured before discharge. The primary outcome was all-cause mortality. During a median follow-up of 23.3 months, the primary outcome occurred in 37 patients (26.4%). A Kaplan–Meier analysis showed that lower DHA and DGLA levels, but not EPA or AA levels, were significantly associated with an increase in all-cause death (log-rank; p < 0.001 and p = 0.040, respectively). A multivariate Cox regression analysis also revealed that DHA levels were significantly associated with the incidence of all-cause death (HR: 0.16, 95% CI: 0.06–0.44, p = 0.001), independent of the GNRI. Our results suggest that low plasma DHA levels may be a useful predictor of all-cause mortality and potential therapeutic target in patients with acute decompensated HFpEF.

Metabolic profiles of socio-economic position: a multi-cohort analysis.

BackgroundLow socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear.MethodsWe examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies.ResultsIn risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids.ConclusionsOur work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.

Impact of omega-3 fatty acid DHA and EPA supplementation in pregnant or breast-feeding women on cognitive performance of children: systematic review and meta-analysis.

The omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are important for brain development and cognitive performance. Because they are semi-essential fatty acids, they must be obtained from food. However, the dietary reference intakes of DHA and EPA have not yet been established. In women, a low DHA and/or EPA serum level during pregnancy or breastfeeding might negatively affect their children. For this study, we conducted a systematic review and meta-analysis of randomized control trials on the association between the consumption of fish oil supplements in pregnant and/or breastfeeding women and the cognitive performance of their children. The PubMed, Embase, and Central literature databases were systematically searched. We included and extracted relevant studies in duplicate and assessed study quality. Cognitive outcomes were grouped according to published criteria and according to time elapsed after the intervention. We performed fixed-effects meta-analyses for each cognitive outcome and for birth weight. We assessed potential confounding with meta-regressions and sensitivity analyses. A total of 11 trials were included. No significant association was found between DHA/EPA supplementation and any of the assessed cognitive parameters or birth weight. Our results confirm previous reviews on the studied topic. Reasons for inconclusive results may be small sample sizes for each assessed category, questionable quality of included studies, and the difficulty of reliably measuring cognitive performance in small children. Blood levels of omega-3 long-chain polyunsaturated fatty acids were mostly not comparable. Furthermore, the influence of genetic and environmental factors could not be assessed. Studies in this field should address such shortcomings.

Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy.

Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. Herein, we intended to identify early blood biomarkers that may be of use during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDM groups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects.

Early-onset coronary atherosclerosis in patients with low levels of omega-3 fatty acids.

Coronary artery calcification (CAC) can reliably predict cardiovascular events. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to inhibit vascular calcification on a cellular level and in animal models, however, the correlation in humans is controversial. In symptomatic patients, CAC was quantified according to Agatstons' method using non-contrast coronary CT. We assessed the association of EPA and DHA with early-onset coronary atherosclerosis, defined as presence of CAC above the 75th Agatston-Score (AS) percentile in sex adjusted age categories. Erythrocyte fatty acid composition was analyzed with a standardized methodology. The percentage of EPA and DHA in relation to all fatty acids present in the erythrocyte membrane is regarded the Omega-3 Index®. Among 71 patients, 51 were below and 20 were above the 75th AS-percentile. No differences were seen in age, gender, cardiovascular risk factors, and relevant medication. In univariable analysis, significantly lower values for EPA (0.77%[0.63; 0.97] vs. 0.93%[0.72; 1.21]; p = 0.045), DHA (4.90%[4.12; 5.57] vs. 5.50%[4.58; 6.52]; p = 0.038) and the Omega-3 Index (5.73%[4.75; 6.35] vs. 6.22%[5.46; 7.71]; p = 0.034) were seen in patients above the 75th AS-percentile. All other fatty acids showed no significant differences. In multivariable analysis, the Omega-3 Index showed a significant inverse association with early onset of CAC (OR: 0.533 (95%CI: 0.303-0.938; p = 0.029)), independent of age, gender, statin use, and creatinine level (all p > 0.05). Low levels of EPA and DHA (Omega-3 Index) are associated with early-onset coronary atherosclerosis. This finding needs to be validated in larger cohorts and might help understand the beneficial cardiovascular effects of omega-3 fatty acids.