Polyunsaturated Fatty Acid Status Research Articles

Patterns of perinatal polyunsaturated fatty acid status and associated dietary or candidate-genetic factors

Perinatal exposure to omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can be characterized through biomarkers in maternal or cord blood, or breast milk. Objectives were to describe perinatal PUFA status combining multiple biofluids, and to investigate how it was influenced by dietary intake during pregnancy and maternal FADS and ELOVL gene polymorphisms.This study involved 1,901 mother-child pairs from the EDEN cohort, with PUFA levels measured in maternal and cord erythrocytes, and colostrum. Maternal dietary PUFA intake during the last trimester was derived from a food frequency questionnaire. Twelve single nucleotide polymorphisms in FADS and ELOVL genes were genotyped from maternal DNA. Principal component analysis incorporating PUFA levels from the three biofluids identified patterns of perinatal PUFA status. Spearman’s correlations explored associations between patterns and PUFA dietary intake, and linear regression models examined pattern associations with FADS or ELOVL haplotypes.Five patterns were retained: "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs"; "Omega-6 LC-PUFAs"; "Colostrum LC-PUFAs"; "Omega-6 precursor (LA) and DGLA"; "Omega-6 precursor and colostrum ALA". Maternal omega-3 LC-PUFA intakes were correlated with "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs" (r(DHA) = 0.33) and "Omega-6 LC-PUFAs" (r(DHA) = -0.19) patterns. Strong associations were found between FADS haplotypes and PUFA patterns except for "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs".Lack of genetic association with the "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs" pattern, highly correlated with maternal omega-3 LC-PUFA intake, emphasizes the importance of adequate omega-3 LC-PUFA intake during pregnancy and lactation. This study offers a more comprehensive assessment of perinatal PUFA status and its determinants.

Women with Gestational Diabetes Mellitus do not have compromised polyunsaturated fatty acid status

Pregnant women who develop pre-eclampsia (PE) and/or intra-uterine growth restriction (IUGR) have reduced polyunsaturated fatty acid (PUFA) status compared to healthy pregnancy(1). It is unknown if pregnant women diagnosed with Gestational Diabetes Mellitus (GDM), and their offspring, also have compromised PUFA status. To determine if women with GDM, and their offspring, have altered PUFA status compared to healthy pregnancy. Pregnant women were recruited from Glasgow Scotland, and Brisbane, Australia from antenatal clinics for this cross sectional study. Third trimester maternal blood samples were collected after an overnight fast and cord blood samples were collected at delivery. Plasma fatty acids were analysed using gas chromatography from women with GDM (n = 37) and healthy pregnancies (n = 27) and their respective offspring (n = 31, from women with GDM, and n = 27 from healthy women). T-tests were used to determine significant differences between maternal with GDM and healthy pregnancy, as well as for their offspring and significance was set at p<0.05. Previously, erythrocyte fatty acids were analysed from women with PE (n = 21), IUGR (n = 13) and healthy pregnancies (n = 86)(1). All results were expressed as mol percent of total fatty acids. There were no differences in maternal plasma arachidonic acid (4.51 ± 1.23 vs. 4.72 ± 0.64, p = 0.39) and plasma EPA & DHA (2.33 ± 0.74 vs 2.69 ± 1.04, p = 0.14) in women with GDM and healthy pregnancies, respectively. There were no differences in fetal plasma arachidonic acid (11.58 ± 2.26 vs. 12.63 ± 1.69, p = 0.08) and plasma EPA & DHA (4.44 ± 1.17 vs. 4.44 ± 1.00, p = 0.89) in offspring from women with GDM and healthy pregnancies, respectively. Women with PE and IUGR had approximately 25% lower erythrocyte EPA & DHA and 35% lower erythrocyte arachidonic acid compared to healthy pregnant(1). Offspring from women with PE and IUGR had approximately 25% lower erythrocyte EPA & DHA and 22% lower erythrocyte arachidonic acid compared to healthy pregnancy(1).Women with PE and IUGR had lower PUFA status likely due to reduced PUFA synthesis(1) and offspring from women with PE and IUGR had reduced PUFA status likely due to ectopic fat in placenta tissue(2). Women with GDM do not have compromised PUFA status suggesting there is no reduced synthesis and transport of PUFA. Offspring from women with GDM do not have reduced PUFA status suggesting there is no problem with PUFA transport across the placenta, unlike offspring from women with PE and/or IUGR. Women with GDM, and their offspring, do not have compromised plasma PUFA status compared to healthy pregnancy.

Longitudinal trajectories of plasma polyunsaturated fatty acids and associations with psychosis-spectrum outcomes in early adulthood

Evidence supports associations between polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and psychosis. However, PUFA trajectories in the general population have not been characterised and associations with psychosis-spectrum outcomes in early adulthood are unknown. background METHODS: Plasma omega-6:omega-3 ratio and DHA %total fatty acids were measured by nuclear magnetic spectroscopy at 7,15,17 and 24years in the Avon Longitudinal Study of Parents and Children. Curvilinear growth mixture modelling evaluated BMI-adjusted trajectories of both measures. Outcomes were assessed at 24years. Psychotic experiences (PEs), At-Risk-Mental-State status, psychotic disorder and number of PEs were assessed using the Psychosis-Like Symptoms interview PLIKSi (n=3635, 2247 [61.8%]female). Negative symptoms score was measured using the Community Assessment of Psychic Experiences (n=3484, 2161 [62.0%]female). Associations were adjusted for sex, ethnicity, parental social class, cumulative smoking and alcohol use. Relative to stable average, the persistently high omega-6:omega-3 ratio trajectory was associated with increased odds of PEs and psychotic disorder, but attenuated on adjustment for covariates (PEs adjusted odds ratio[aOR] 1.63, 95% confidence interval[CI] 0.92-2.89; psychotic disorder aOR 1.69, 95%CI 0.71-4.07). This was also the case for persistently low DHA (PEs aOR 1.42, 95%CI 0.84-2.37; psychotic disorder aOR 1.14, 95%CI 0.49-2.67). Following adjustment, persistently high omega-6:omega-3 ratio was associated with increased number of PEs (β0.41, 95%CI 0.05-0.78) and negative symptoms score (β0.43, 95%CI 0.14-0.72), as was persistently low DHA (number of PEs:β 0.45, 95%CI 0.14-0.76; negative symptoms:β 0.35, 95%CI 0.12-0.58). Optimisation of PUFA status during development warrants further investigation in relation to psychotic symptoms in early adulthood.

Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (β = −0.18, 95%CI: −0.29 – −0.07, P = 0.002) and progressive motility (β = −0.27, 95%CI: −0.43 – −0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: β = 0.26, 95%CI: 0.01 – −0.51, Pinteraction = 0.047; progressive motility: β = 0.64, 95%CI: 0.23 – 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

Effect of fatty acid profiles in varying recipes of ready-to-use therapeutic foods on neurodevelopmental and clinical outcomes of children (6-59 months) with severe wasting: a systematic review.

In 2020, 13.6 million children under 5 years suffered from severe acute malnutrition (SAM)/wasting. Standard ready-to-use therapeutic foods (RUTFs) improve polyunsaturated fatty acid (PUFA) status but contain suboptimal amounts of omega-3 (n-3) PUFAs with unbalanced n-6-to-n-3 PUFA ratios. The aim was to compare the effects of RUTFs with different essential fatty acid contents on PUFA status, neurodevelopmental, and clinical outcomes (mortality, comorbidities, and recovery) of children with severe wasting. Twelve databases, trial repositories, and article references with no publication limitations. Ten studies from randomized, quasi, and cluster-randomized controlled trials providing RUTFs as home treatment to children 6-59 months with SAM/wasting were included. Plasma phospholipid eicosapentaenoic acid content was higher in children receiving RUTF with altered essential fatty acid contents compared with standard RUTF (0.20 [0.15-0.25], P < 0.00001). Docosahexaenoic acid (DHA) status only improved in children receiving RUTF with added fish oil (0.33 [0.15-0.50], P = 0.0003). The Malawi Developmental Assessment tool (MDAT) global development and problem-solving assessment scores were higher in global assessment and gross motor domains in children receiving added fish oil compared with standard formulation (0.19 [0.0-0.38] and 0.29 [0.03-0.55], respectively). Children receiving high-oleic-acid RUTF (lowering the n-6:n-3 PUFA ratio of the RUTF) with or without fish oil had significantly higher scores in social domains compared with those receiving the standard formulation (0.16 [0.00-0.31] and 0.24 [0.09-0.40]). Significantly higher mortality risk was found in children receiving a standard formulation compared with RUTF with a lower n-6:n-3 PUFA ratio (0.79 [0.67-0.94], P = 0.008). Although lowering n-6:n-3 PUFA ratios did not increase plasma DHA, it improved specific neurodevelopmental scores and mortality due to lower linoleic acid (high-oleic-acid peanuts), higher alpha-linolenic acid (altered oil), or both. Additional preformed n-3 long-chain PUFAs (fish oil) with RUTF improved the children's DHA status, neurodevelopmental outcomes, and weight-for-height z score. More research is needed regarding cost, availability, stability, acceptability, and the appropriate amount of n-3 long-chain PUFAs required in RUTFs for the best clinical outcomes. PROSPERO registration no. CRD42022303694.

Changes in polyunsaturated fatty acids during treatment of malnourished children may be insufficient to reach required essential fatty acid levels – A randomised controlled trial

Severe acute malnutrition (SAM) is a global concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on polyunsaturated fatty acids (PUFA) are almost non-existent. The aim was to investigate the change in whole-blood PUFA and nutrition and health markers among Cambodian children with SAM after treatment with RUTFs. The trial was an 8-week randomised clinical trial of the effectiveness of locally produced fish-based RUTF (L-RUTF) vs standard milk-based RUFT (S-RUTF). Whole-blood fatty acids were analysed using dried blood spots. Nutrition and health markers were assessed using anthropometric assessment and blood samples for markers of inflammation. The trial was conducted at the National Pediatric Hospital, Phnom Penh, Cambodia, with one hundred and twenty-one 6-59-month-old children in treatment for SAM. L-RUTF had a higher content of n-3 PUFA and a higher content of arachidonic acid (AA) and docosahexaenoic acid (DHA), while S-RUTF had the highest content of n-6 PUFA. At baseline, the children presented with a Mead acid level in whole-blood of around 0.08% of total fatty acids (FA%) and an omega-3 index of ∼0.91±0.44. After eight weeks of S-RUTF treatment, linoleic acid (LA), AA, n-6/n-3 PUFA ratio, and Mead acid levels were increased. The L-RUTF intervention did not change the whole-blood PUFAs from baseline. At discharge, the children in the L-RUTF group had a lower n-6/n-3 PUFA ratio than the children in the S-RUTF group, driven by a lower alpha-linolenic acid (ALA) (0.20 vs 0.27 FA%, p=0.004) and lower LA (15.77 vs 14.21 FA%, p=0.018) with no significant differences in AA or DHA levels. Weight-for-height z-score at discharge was negatively associated with total PUFA (β-1.4 FA%, 95%CI.-2.7;-0.1), n-6 LCPUFA (β-1.3 FA%, 95%CI.-1.3;-0.3), and AA (β-0.6 FA%, 95%CI.-1.0;-0.2). Age-adjusted height was negatively associated with the Mead acid:AA ratio (β-1.2 FA%, 95%CI.-2.2;-0.2). No significant change was seen in inflammation markers within groups or between groups during treatment, and n-3 and n-6 PUFAs were not associated with markers of inflammation or haemoglobin status at discharge. The trial found that whole-blood markers of PUFA status were low in children at admission and discharge from SAM treatment, indicating that the currently recommended composition of RUTFs are not able to correct their compromised essential fatty acid status. The higher content of DHA and AA in L-RUTF did not give rise to any improvement in PUFA status. No changes in health markers or associations between PUFA and health markers were found. ClinicalTrials.gov: NCT02907424.

Effect of a pescetarian and vegan diet on fatty acid composition in blood and spermatozoa in young healthy men

IntroductionThere is a growing interest in vegetarian and vegan diets, but both can potentially affect tissue fatty acids (FA) composition. We aimed to evaluate the effect of vegetarian diets on plasma, erythrocytes, and sperm n-3 polyunsaturated fatty acids (n-3 PUFA) status in healthy young men. MethodsFour groups were studied: i) men consuming a regular omnivore diet (OMV-1, n = 35); ii) men consuming an omnivore diet but excluding fish and seafood (OMV-2, n = 34); iii) men consuming a pescetarian diet (including dairy, eggs, fish, and seafood) (PESC, n = 36); and iv) men following a strict vegan diet (VEG, n = 35). Participants in each group should follow their diet for at least the previous 12 months. Diet evaluation used a structured validated food frequency questionnaire. FA composition was measured in plasma, erythrocyte phospho-lipids, and spermatozoa by gas-liquid chromatography, expressed as a mole percentage of the total FA content. ResultsMain findings showed higher alpha-linolenic fatty acid (ALA) and total n-3 PUFA dietary intake in the VEG group. In plasma, arachidonic and eicosapentaenoic acids were higher in OMV and PESC groups, whereas docosahexaenoic acid (DHA) level was lower in VEG. Higher ALA, but reduced DHA and total n-3 PUFA levels were found in erythrocytes and spermatozoa in the VEG group. ConclusionHigher dietary ALA intake was found in pescetarians and vegan men. However, the higher ALA intake was not reflected in higher DHA content in the evaluated tissues. PUFA assessment, with particular emphasis in DHA, are necessary to improve PUFA status in vegan men.

Associations of n-3 polyunsaturated fatty acid status and intake with paediatric major depressive disorder in Swiss adolescents: A case-control study

BackgroundObservational studies suggest a link between n-3 polyunsaturated fatty acid (PUFA) intake, n-3 PUFA status, and depression in adults, but studies in adolescents are scarce. This study aimed to determine associations of n-3 PUFA status and intake with paediatric major depressive disorder (pMDD) in Swiss adolescents. MethodsWe conducted a matched case-control study in 95 adolescents diagnosed with pMDD and 95 healthy controls aged 13 to <18 years. We analysed red blood cell (RBC) fatty acid (FA) composition (% of total FA). n-3 PUFA intake was assessed using a focused food frequency questionnaire and depression severity was assessed by the Children's Depression Rating Scale-Revised (CDRS-R). ResultsMean RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower in cases than controls (EPA: 0.41 ± 0.11 vs 0.46 ± 0.12, p < 0.001; DHA: 4.07 ± 1.04 vs 4.73 ± 1.04, p < 0.001). Subsequently, the mean RBC n-3 index was lower (4.51 ± 1.10 vs 5.20 ± 1.11, p < 0.001) and the n-6/n-3 PUFA ratio higher (5.51 ± 1.25 vs 4.96 ± 1.08, p < 0.001) in cases than controls. Adolescents with a higher n-3 index had lower odds for depression (OR = 0.49 [95% CI: 0.32–0.71]). In contrast, the n-6/n-3 PUFA ratio was associated with higher odds for depression (OR = 1.58 [95% CI: 1.14–2.25]). Intake of alpha-linolenic acid, EPA and DHA did not differ between cases and controls. ConclusionOur results suggest that a higher RBC n-3 PUFA status during adolescence is associated with a lower risk for pMDD, whereas a higher n-6/n-3 PUFA ratio is associated with a higher risk for pMDD. Differences in n-3 PUFA intake did not explain the observed differences in n-3 PUFA status.

Are dietary intake and nutritional status of specific polyunsaturated fatty acids correlated with sarcopenia outcomes in community-dwelling older adults with sarcopenia? – Exploratory results from ENHANce

AimsTo explore the relationship between dietary polyunsaturated fatty acids (PUFAs) intake, nutritional PUFAs status and sarcopenia outcomes in sarcopenic older adults.MethodsThe Exercise and Nutrition for Healthy AgeiNg (ENHANce) is an ongoing 5-armed triple blinded randomized controlled trial, in sarcopenic older adults (> 65y) aiming to assess the effect of combined anabolic interventions (protein, omega-3 supplement and exercise) on physical performance in these adults, compared to single/placebo interventions. Baseline data were used for a secondary, exploratory, cross-sectional analysis. Dietary PUFAs intake was assessed with 4-day food records, status with RBC membrane fatty acids profiles. Spearman’s rho(ρ) correlation coefficients were calculated to explore associations of PUFAs intake and status with sarcopenia-defining parameters (muscle strength, mass and physical performance), physical activity (step count) and quality of life (SF-36, SarQoL).ResultsIn total, 29 subjects (9♂/20♀, mean age 76.3 ± 5.4y) were included. Total omega-3 intake of participants (1.99 ± 0.99 g/d) was below the recommended intake (♂:2.8–5.6 g/d; ♀:2.2–4.4 g/d). Intake and status of PUFAs were not correlated. Regarding correlations with outcomes, α-linolenic acid status was inversely associated with appendicular lean mass (aLM) (ρ:-0.439; p = 0.017), whereas docosahexaenoic acid status was positively associated with aLM (ρ:0.388; p = 0.038). Some omega-3 PUFAs intake and status markers were positively associated with step count, SF-36 and SarQoL scores, whereas gamma-linolenic acid status was inversely associated with SF-36 physical component summary score (ρ = -0.426; p = 0.024).ConclusionsAlthough intake of omega-3 and omega-6 was low, the present exploratory study generated new hypotheses for potential correlations of PUFAs intake and status with sarcopenia outcomes in older adults with sarcopenia.

Patients with Anorexia Nervosa Demonstrate Deficiencies of Selected Essential Fatty Acids, Compensatory Changes in Nonessential Fatty Acids and Decreased Fluidity of Plasma Lipids

The objective of this study was to assess the essential fatty acid status of patients with anorexia nervosa. Blood was collected from eight fasting female anorexia nervosa patients with a mean of 81% ideal body weight. Fatty acid composition of phospholipids, nonesterified fatty acids, triglycerides and cholesteryl esters of plasma were determined by capillary gas chromatography to indicate polyunsaturated fatty acids status compared with 19 healthy female adults <25 y old. Subjects with anorexia nervosa showed polyunsaturated fatty acid deficiencies in plasma phospholipids different from simple nutritional essential fatty acid deficiency or chronic malnutrition. The phospholipid profile showed significantly lower (n-6) and (n-3) elongation and desaturation products, and elevated short-chain saturated, short-chain monounsaturated, branched-chain and odd-chain fatty acids. These elevations indicate enhancement of biosynthesis of alternative fatty acids that only partially compensated for the loss of polyunsaturated fatty acids in providing membrane “fluidity.” Calculated mean melting point of the fatty acids of phospholipids in patients with anorexia nervosa was elevated 7.7°C above normal values. These results demonstrate that patients with anorexia nervosa have deficiencies of selected essential fatty acids, compensatory changes in nonessential fatty acids and decreased fluidity of plasma lipids.

Effect of FADS1 rs174556 Genotype on Polyunsaturated Fatty Acid Status: A Systematic Review and Meta-Analysis.

PUFA status is highly implicated in cognitive development and metabolic disorder-related diseases. Genetic variants of FADS genes encoding enzymes that catalyze the rate-limiting steps of PUFA biosynthesis appear to be associated with n-3 and n-6 PUFA contents. Therefore, we conducted the first systematic review and meta-analysis to explore the association of the A-allele carriers of the FADS1 rs174556 with PUFA status. The PRISMA guidelines were followed. The literature search was conducted up to November 2022 in PubMed, Web of Science, Embase, Cochrane Library, Airiti Library, and CINAHL. The Joanna Briggs Institute checklists were used to assess the methodological quality. The correlation with 95% CIs was determined by a random-effect meta-analysis. Eleven studies that met the inclusion criteria and acceptable quality were included in this systematic review. The data on PUFA contents were collected when they were mainly analyzed using blood samples and breast milk. Results of the meta-analysis on eight studies (one randomized controlled trial, one cohort study, and six cross-sectional studies) showed that the A-allele carriers of rs174556 were significantly negatively correlated with the concentrations of AA (P = 0.001), EPA (P = 0.004), and DHA (P = 0.025). However, ALA and LA were not associated with the A-allele carriers. To clarify the discrepancy, we further divided the studies into blood samples and breast milk subgroups. The subgroup analysis revealed that the A-allele carriers of rs174556 were significantly positively correlated with LA (P = 0.031) and negatively correlated with AA (P = 0.001), EPA (P = 0.036), and DHA (P < 0.001) in the blood sample group, but not in the breast milk group. The current meta-analysis proved that the A-allele carriers of the FADS1 rs174556 appeared to be highly associated with lower concentrations of AA, EPA, and DHA but higher LA in the blood samples. The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO:CRD42022363978). Adv Nutr 2023;x:xx-xx.

Higher n-3 polyunsaturated fatty acid status during early pregnancy is associated with lower risk for depression at 12 months postpartum: The NuPED study

Perinatal depression can negatively affect the health of the mother and her offspring. N-3 polyunsaturated fatty acids (PUFA) may play a role in the aetiology of depression. Therefore, we investigated the association of n-3 PUFA status during early pregnancy with perinatal depression among women living in urban Johannesburg, South Africa. For this prospective analysis, we analysed red blood cell (RBC) total phospholipid fatty acid (FA) composition (% of total FA) of 242 pregnant women at <18 weeks’ gestation. We used the Edinburgh Postnatal Depression Scale (EPDS) to identify women at risk for depression (EPDS score ≥9) at <18, 22 and 36 weeks’ gestation, and at 6 and 12 months postpartum. RBC EPA status was negatively (β=-0.22, p<0.05), and the AA/EPA ratio positively (β=0.24, p<0.05) associated with EPDS scores at 12 months postpartum. Higher RBC DHA and n-3 index were further associated with lower odds (OR=0.56 [95% CI: 0.32-0.91]; OR=0.63 [95% CI: 0.39-0.94]), while higher n-6/n-3 PUFA and AA/EPA ratios early in pregnancy were associated with higher odds for depression at 12 months postpartum ((OR=2.34 [95% CI: 1.12-4.97]; OR=1.02 [95% CI: 1.00-1.05]). Our results suggest that women with a higher RBC n-3 PUFA status during early pregnancy may be at lower risk for depression at 12 months postpartum.

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.

Maternal obesity: new placental paradigms unfolded.

The prevalence of maternal obesity is increasing at an alarming rate, and is providing a major challenge for obstetric practice. Adverse effects on maternal and fetal health are mediated by complex interactions between metabolic, inflammatory, and oxidative stress signaling in the placenta. Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are common downstream pathways of cell stress, and there is evidence that this conserved homeostatic response may be a key mediator in the pathogenesis of placental dysfunction. We summarize the current literature on the placental cellular and molecular changes that occur in obese women. A special focus is cast onto placental ER stress in obese pregnancy, which may provide a novel link for future investigation.

Association between maternal erythrocyte polyunsaturated fatty acid levels during pregnancy and offspring weight status: A birth cohort study.

BackgroundThe findings of the association between maternal polyunsaturated fatty acid (PUFA) levels during pregnancy and offspring weight status are controversial. Furthermore, few studies have focused on Asian populations or used erythrocyte membranes as biological markers. We aimed to examine the associations between maternal erythrocyte PUFA and offspring weight status within the first 2 years among the Chinese population.Materials and methodsA total of 607 mother-child pairs were recruited from a birth cohort. Maternal erythrocyte n-3 and n-6 PUFA during pregnancy were measured by gas chromatography, and the ratio of PUFA was calculated. Weight- and body mass index (BMI)-for-age z (WAZ and BAZ) scores were calculated for offspring at 1, 3, 6, 8, 12, 18, and 24 months of age. The risk of overweight and obesity was defined by the WHO criterion. The Generalized Estimating Equation (GEE) model was carried out for repeated anthropometric data within 2 years of age.ResultsMaternal erythrocyte docosapentaenoic acid (DPA, n-3) was inversely associated with offspring BAZ score [tertile 2 vs. tertile 1, β: −0.18 (−0.29, −0.00)]. Higher maternal erythrocyte arachidonic acid (AA) was inversely associated with lower offspring WAZ and BAZ [tertile 3 vs. tertile 1, β: −0.18 (−0.35, −0.02), −0.22 (−0.38, −0.06), respectively]. Furthermore, higher maternal erythrocyte AA [tertile 3 vs. tertile 1, odds ratio [OR]: 0.52 (0.36, 0.75), ptrend < 0.001] and total n-6 PUFA [tertile 3 vs. tertile 1, OR: 0.56 (0.39, 0.81), ptrend = 0.002] were associated with decreased risk of overweight and obesity in offspring. Maternal erythrocyte n-6/n-3 PUFA and AA/eicosapentaenoic acid (EPA) ratios were not associated with offspring weight status.ConclusionMaternal erythrocyte PUFA might influence offspring weight status within 2 years of age in the Chinese population. Further Asian studies are still needed.

Polyunsaturated Fatty Acids in Mother, Infant, and Placental Tissue, and Their Relationship With Pre-Pregnancy BMI

ObjectivesMaternal obesity produces inflammation, which may result in adverse pregnancy outcomes such as preterm birth. Polyunsaturated fatty acids (PUFA), including omega-6 (n-6) and omega-3 (n-3) fatty acids, regulate inflammation and may mitigate the negative effects of inflammation. Previous studies report higher n-6 and lower n-3 PUFA concentration in early to mid-pregnancy for individuals with higher pre-pregnancy BMI (pBMI). However, the relationship between PUFA concentration at delivery and pBMI are not well understood. The purpose of this study is to determine the relationship between pBMI and maternal plasma, umbilical cord plasma, and placental PUFA concentrations, as well as PUFA intrauterine transfer percentage (IUTP).MethodsFollowing IRB approval, maternal plasma, umbilical cord plasma, and placental samples were collected at delivery from 55 maternal-infant dyads. IUTPs for each PUFA (linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA)) were calculated as [cord blood]/[maternal blood] × 100. Spearman's correlations assessed relationships between PUFA levels, PUFA IUTP, and pBMI. Linear regression models were adjusted for smoking status. A p-value < 0.05 was considered statistically significant.ResultsThe mean pBMI for our cohort was 28.7 kg/m2. Preceding pregnancy, 21% of mothers were normal or underweight, 36% overweight, and 43% obese. Maternal LA (R = −0.3, p = 0.03), maternal DHA (R = −0.27, p = 0.04), and placental EPA (R = −0.42, p = 0.02) were significantly correlated with maternal pBMI. After adjusting for smoking status, no correlations remained significant. PUFA cord levels and PUFA IUTP were not correlated to pBMI.ConclusionsTo our knowledge, this is the first study exploring relationships between pBMI and PUFA levels at delivery. Our findings contrast with previous research reporting correlations between PUFA levels and pBMI in early to mid-pregnancy. The effects of pBMI on PUFA status may be most prominent early in pregnancy. Future research should explore the relationship between pBMI and PUFA levels across all stages of pregnancy.Funding SourcesUNMC Pediatrics Department; Child Health Research Institute.

Determination of n-3 index and arachidonic acid/eicosapentaenoic acid ratio in dried blood spot by gas chromatography.

Background: Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease risk. We describe a simple, sensitiveand non-invasive method for estimating the n-3 index and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in dried blood spots (DBSs). Experimental: After obtaining DBSs on a spot card, PUFAs were transesterified (direct, acidic transesterification) and subsequently extracted with n-hexane. Gas chromatography withflame ionization detection (GC-FID) was used to analyze the extracted PUFAs, and then n-3 index and AA/EPA ratio were calculated. Method validation showed satisfactory precision and linearity. Conclusion: This analysis is simple and reliable to estimate PUFA status, and it was successfully applied to samples from 20 subjects, demonstrating its applicability.

Decreased Tissue Omega-6/Omega-3 Fatty Acid Ratio Prevents Chemotherapy-Induced Gastrointestinal Toxicity Associated with Alterations of Gut Microbiome.

Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing gut bacterial β-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome. We hypothesized that elevated levels of tissue n-3 PUFA with a decreased n-6/n-3 PUFA ratio would reduce CPT-11-induced GIT and associated changes in the gut microbiome. Using a unique transgenic mouse (FAT-1) model combined with dietary supplementation experiments, we demonstrate that an elevated tissue n-3 PUFA status with a decreased n-6/n-3 PUFA ratio significantly reduces CPT-11-induced weight loss, bloody diarrhea, gut pathological changes, and mortality. Gut microbiome analysis by 16S rRNA gene sequencing and QIIME2 revealed that improvements in GIT were associated with the reduction in the CPT-11-induced increase in both GUSB-producing bacteria (e.g., Enterobacteriaceae) and GUSB enzyme activity, decrease in IMB-maintaining bacteria (e.g., Bifidobacterium), IMB dysfunction and systemic endotoxemia. These results uncover a host–microbiome interaction approach to the management of drug-induced gut toxicity. The prevention of CPT-11-induced gut microbiome changes by decreasing the tissue n-6/n-3 PUFA ratio could be a novel strategy to prevent chemotherapy-induced GIT.

Long-Chain Polyunsaturated Fatty Acid Status at Birth and Development of Childhood Allergy: A Systematic Review.

The associations of fetal fatty acids status to immune-related health parameters later in life are unclear. Our aim is to collect all available information on the relationship between fatty acid status at birth and allergy in childhood. Systematic literature search was performed on Ovid MEDLINE, Cochrane Library, and Embase. The search retrieved 897 articles without duplicates; 14 articles remained after excluding those that did not fit into our inclusion criteria. When the dichotomous parameter of suffering or not from allergic condition in childhood was analyzed, cord blood eicosapentaenoic acid (EPA) values proved to be significantly lower in allergic than non-allergic children in four comparisons from three studies. When the linear parameters of odds ratios and relative risks for allergy were taken into consideration, high cord blood EPA, but also high docosahexaenoic acid (DHA) and high total n-3 long-chain polyunsaturated fatty acid values were associated to clinically relevant reduction (at least 38%) in eight comparisons from five studies. Within the cord blood samples, higher EPA, docosapentaenoic acid, and DHA values were significantly and negatively associated in eight correlation analyses from three studies with laboratory parameters considered to reflect allergic trait. The data reported here may provide information for defining optimal fatty acid intakes for pregnant women.

Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation

Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case–control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini–Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.