Project description:Prenatal consumption of omega-3 fatty acids can act as an adjuvant in the development of the immune system and affect the inflammatory response of neonates.We conducted a double-blind, randomized, placebo-controlled trial in Cuernavaca, Mexico. We randomly assigned 1,094 pregnant women (18-35 years of age) to receive 400 mg/d of algal docosahexaenoic acid (DHA) or placebo from 18 to 22 weeks of gestation through delivery. Birth outcomes and respiratory symptoms information until 18 months were available for 869 mother-child pairs. Questionnaires were administered, and maternal blood samples were obtained at baseline. Maternal atopy was based on specific IgE levels. During follow-up, information on infants' respiratory symptoms was collected through questionnaires administered at 1, 3, 6, 9, 12, and 18 months of age. Negative binomial regression models were used to evaluate the effect of supplementation on respiratory symptoms in infants.Among infants of atopic mothers, a statistically significant protective effect of DHA treatment was observed on phlegm with nasal discharge or nasal congestion (0.78; 95% CI, 0.60-1.02) and fever with phlegm and nasal discharge or nasal congestion (0.53; 95% CI, 0.29-0.99), adjusting for potential confounders.Our results support the hypothesis that DHA supplementation during pregnancy may decrease the incidence of respiratory symptoms in children with a history of maternal atopy.ClinicalTrials.gov; No.: NCT00646360; URL: www.clinicaltrials.gov.
Project description:Maternal obesity is associated with adverse offspring outcomes. Inflammation and deficiency of anti-inflammatory nutrients like omega(n)-3 polyunsaturated fatty acids (PUFA) may contribute to these associations. Fetal supply of n-3 PUFA is dependent on maternal levels and studies have suggested that improved offspring outcomes are associated with higher maternal intake. However, little is known about how maternal obesity affects the response to n-3 supplementation during pregnancy. We sought to determine (1) the associations of obesity with PUFA concentrations and (2) if the systemic response to n-3 supplementation differs by body mass index (BMI). This was a secondary analysis of 556 participants (46% lean, 28% obese) in the Maternal-Fetal Medicine Units Network trial of n-3 (Docosahexaenoic acid (DHA) + Eicosapentaenoic acid (EPA)) supplementation, in which participants had 2g/day of n-3 (n = 278) or placebo (n = 278) from 19 to 22 weeks until delivery. At baseline, obese women had higher plasma n-6 arachidonic acid concentrations (?: 0.96% total fatty acids; 95% Confidence Interval (CI): 0.13, 1.79) and n-6/n-3 ratio (?: 0.26 unit; 95% CI: 0.05, 0.48) compared to lean women. In the adjusted analysis, women in all BMI groups had higher n-3 concentrations following supplementation, although obese women had attenuated changes (? = -2.04%, CI: -3.19, -0.90, interaction p = 0.000) compared to lean women, resulting in a 50% difference in the effect size. Similarly, obese women also had an attenuated reduction (? = 0.94 units, CI: 0.40, 1.47, interaction p = 0.046) in the n-6/n-3 ratio (marker of inflammatory status), which was 65% lower compared to lean women. Obesity is associated with higher inflammation and with an attenuated response to n-3 supplementation in pregnancy.
Project description:Oxidative stress is a biological imbalance in reactive oxygen species and antioxidants. Increased oxidative stress during pregnancy has been associated with adverse birth outcomes. Omega-3 fatty acid (n-3 FA) supplementation may decrease oxidative stress; however, this relationship is seldom examined during pregnancy. This study assessed the association between n-3 FA supplement use during pregnancy and urinary oxidative stress biomarker concentrations. Data came from The Infant Development and the Environment Study (TIDES), a prospective cohort study that recruited pregnant women in 4 US cities between 2010-2012. Third trimester n-3 FA intake was self-reported. Third trimester urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) was measured as an oxidative stress biomarker. Additionally, we measured the major metabolite of 8-iso-PGF2α and Prostaglandin F2α (PGF2α) and utilized the 8-iso-PGF2α to PGF2α ratio to calculate the change in 8-iso-PGF2α reflecting oxidative stress versus inflammation. Adjusted linear models were used to determine associations with control for confounding. Of 725 women, 165 reported n-3 FA supplement use in the third trimester. In adjusted linear models, n-3 FA use was associated with 10.2% lower levels of 8-iso-PGF2α (95% Confidence Interval [CI]: -19.6, 0.25) and 10.3% lower levels of the metabolite (95% CI: -17.1, -2.91). No associations were observed with PGF2α. The lower levels of 8-iso-PGF2α appeared to reflect a decrease in oxidative stress (percent change with supplement use: -18.7, 95% CI: -30.1, -5.32) rather than inflammation. Overall, third trimester n-3 FA intake was associated with lower concentrations of 8-iso-PGF2α and its metabolite, suggesting a decrease in maternal oxidative stress during pregnancy.
Project description:This study investigates relations of maternal N-3 and N-6 polyunsaturated fatty acids (PUFA) intake during pregnancy with offspring body mass index (BMI), height z-score and metabolic risk (fasting glucose, C-peptide, leptin, lipid profile) during peripuberty (8-14 years) among 236 mother-child pairs in Mexico. We used food frequency questionnaire data to quantify trimester-specific intake of N-3 alpha-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); N-6 linoleic acid and arachidonic acid (AA); and N-6:N-3 (AA:EPA+DHA), which accounts for the fact that the two PUFA families have opposing effects on physiology. Next, we used multivariable linear regression models that accounted for maternal education and parity, and child's age, sex and pubertal status, to examine associations of PUFA intake with the offspring outcomes. In models where BMI z-score was the outcome, we also adjusted for height z-score. We found that higher second trimester intake of EPA, DHA and AA were associated with lower offspring BMI and height z-score. For example, each 1-s.d. increment in second trimester EPA intake corresponded with 0.25 (95% CI: 0.03, 0.47) z-scores lower BMI and 0.20 (0.05, 0.36) z-scores lower height. Accounting for height z-score in models where BMI z-score was the outcome attenuated estimates [e.g., EPA: -0.16 (-0.37, 0.05)], suggesting that this relationship was driven by slower linear growth rather than excess adiposity. Maternal PUFA intake was not associated with the offspring metabolic biomarkers. Our findings suggest that higher PUFA intake during mid-pregnancy is associated with lower attained height in offspring during peripuberty. Additional research is needed to elucidate mechanisms and to confirm findings in other populations.
Project description:It is unanimously recognized that the maternal nutritional status at the pregnancy onset influence both short-term and long-term health of the mother and offspring. Among several nutrients, LCPUFA, particularly from the omega-3 family, are of utmost importance. This study was carried out to determine fatty acids profile of maternal erythrocyte membranes in early pregnancy and to identify potential determinants impacting on this status.A cohort of 122 healthy women with a singleton pregnancy was included. Fatty acids were analyzed using gas chromatography. Because of the lack of cutoff values, reference ranges were used to determine fatty acids categories.Of concern, our data revealed low monounsaturated and long-chain omega-3 fatty acid status in most participants. More than 75% of Belgian pregnant women exhibited Pal, AO and EPA levels as well as IOM3 values below the laboratory reference ranges. Higher DHA concentrations and IOM3 values were found among foreign-nationality participants, non-smokers and physically active women. With regard to dietary factors, omega-3 supplements and diet seem to be complementary since DHA from supplements (but not from diet) and EPA from diet (but not from supplements) were found to be associated with higher concentrations of DHA and EPA, respectively.Our study presents evidence demonstrating that the fatty acid status of most early pregnant women is far from being optimal based on the admitted general reference values. Clinicians should be advice to carefully evaluate and improve this status to guarantee the best possible outcome for both the mother and the baby.
Project description:Scientific societies recommend increasing intake of docosahexaenoic acid (DHA) by 200 mg/day during pregnancy. However, individually, clinical events correlate quite strongly with levels of eicosapentaenoic acid (EPA) and DHA in blood, but these levels poorly correlate with amounts ingested. EPA and DHA in erythrocytes (Omega-3 Index) have a low biologic variability. If analyzed with a standardized analytical procedure (HS-Omega-3 Index®), analytical variability is low. Thus, the largest database of any fatty acid analytical method was provided. Pregnant women in Germany had a mean Omega-3 Index below the target range suggested for cardiovascular disease of 8-11%, with large interindividual variation, and quite independent of supplementation with EPA and DHA. In Germany, premature birth is a major health issue. Premature birth and other health issues of pregnant women and their offspring correlate with levels of EPA and DHA in blood and can be reduced by increasing intake of EPA and DHA, according to individual trials and pertinent meta-analyses. Very high intake or levels of EPA and DHA may also produce health issues, like bleeding, prolonged gestation, or even premature birth. While direct evidence remains to be generated, evidence from various scientific approaches supports that the target range for the Omega-3 Index of 8-11% might also pertain to pregnancy and lactation.
Project description:Metabolic conditions during brain development may have long-term consequences on brain metabolism, thereby influencing the risk of neurodegenerative disease in later life. To ascertain the long-term consequences of omega-3 (?3) fatty acid deficiency during brain development on oxidative fatty acid degradation in the brain and the development of Alzheimer-like pathology, wild-type (WT) female mice were fed diets that were either replete or deficient in ?3 fatty acids for 5 weeks. These females were then mated with hemizygous 5xFAD male transgenic (TG) mouse models of Alzheimer's disease, and the progeny were continued on diets that were either ?3-replete or ?3-deficient. When the progeny were 6 months of age, they received radiolabeled arachidonic acid (ARA) by intracerebroventricular injection. Five days after these injections, the brains were harvested and oxidative degradation of the radiolabeled ARA was characterized. Among the progeny of female mice on an ?3-replete diet, TG progeny had lower PSD-95 expression and higher oxidative ARA degradation than WT progeny. Progeny on an ?3-deficient diet, however, had no significant differences in PSD-95 expression between TG and WT mice, or in the extent of ARA degradation. In TG mice, an ?3-deficient diet reduced oxidative ARA degradation to a greater extent than in WT mice. The reductions in oxidative ARA degradation occurred even if the progeny of female mice on an ?3-deficient diet resumed an ?3-replete diet immediately on weaning. These results demonstrate that dietary ?3 fatty acid deficiency during development can cause long-term changes in the expression of a synaptic marker and long-term reductions in the rate of ARA degradation in the WT brain, which are not completely alleviated by an ?3-replete diet after weaning. The elimination of differences between TG and WT mice by an ?3-deficient diet suggests that mechanisms regulating PSD-95 expression and the oxidative degradation of ARA are related and that the timing of dietary ?3 intake during development may influence Alzheimer's disease-related pathological changes later in life.
Project description:Prostaglandin E2 (PGE2) has been linked to a higher risk of colorectal cancer. PGE2 in colon tissue can be reduced by increasing dietary eicosapentaenoic acid (EPA). The dose-dependent relationships between dietary EPA, serum EPA:arachidonate (AA) ratio, urinary PGE2 metabolites, and colonic eicosanoids were evaluated to develop biomarkers for prediction of colonic PGE2. Male rats were fed diets containing EPA:?6 fatty acid ratios of 0, 0.1, 0.2, 0.4, or 0.6 for 5 weeks. Increasing the dietary EPA:?6 fatty acid ratio increased EPA:AA ratios in serum and in the proximal, transverse, and distal colon (P < 0.001). The urinary PGE2 metabolite was reduced (P = 0.006). EPA-rich diets reduced colonic tissue PGE2 concentrations by 58% to 66% and increased PGE3 by 19- to 28-fold. Other AA-derived eicosanoids were reduced by 35% to 83%. The changes were not linear, with the largest changes in eicosanoids observed with the lower doses. A mathematical model predicts colonic tissue eicosanoids from the EPA:AA ratio in serum and the EPA dose. Every 10% increase in serum EPA:AA was associated with a 2% decrease in the (geometric) mean of PGE2 in the distal colon. These mathematical relationships can now be applied to individualized EPA dosing in clinical trials.
Project description:Epidemiological studies on Greenland Inuits in the 1970s and subsequent human studies have established an inverse relationship between the ingestion of omega-3 fatty acids [C(20-22) ? 3 polyunsaturated fatty acids (PUFA)], blood levels of C(20-22) ? 3 PUFA, and mortality associated with cardiovascular disease (CVD). C(20-22) ? 3 PUFA have pleiotropic effects on cell function and regulate multiple pathways controlling blood lipids, inflammatory factors, and cellular events in cardiomyocytes and vascular endothelial cells. The hypolipemic, anti-inflammatory, anti-arrhythmic properties of these fatty acids confer cardioprotection. Accordingly, national heart associations and government agencies have recommended increased consumption of fatty fish or ? 3 PUFA supplements to prevent CVD. In addition to fatty fish, sources of ? 3 PUFA are available from plants, algae, and yeast. A key question examined in this review is whether nonfish sources of ? 3 PUFA are as effective as fatty fish-derived C(20-22) ? 3 PUFA at managing risk factors linked to CVD. We focused on ? 3 PUFA metabolism and the capacity of ? 3 PUFA supplements to regulate key cellular events linked to CVD. The outcome of our analysis reveals that nonfish sources of ? 3 PUFA vary in their capacity to regulate blood levels of C(20-22) ? 3 PUFA and CVD risk factors.