Docosahexaenoic Acid Supplementation Research Articles

The Role of Fresh Beef Intake and Mediterranean Diet Adherence during Pregnancy in Maternal and Infant Health Outcomes

Beef is an excellent source of nutrients important for maternal health and fetal development. It is also true that the Mediterranean diet is beneficial for the health of both the mother and offspring; however, the relative value of fresh beef intake within Mediterranean diet patterns during pregnancy is unknown. The objective of this project was two-fold: (1) assess the relationship between beef intake and nutrient intake in a pregnant population; (2) assess the relationship between maternal beef consumption among varying degrees of Mediterranean diet adherence with maternal risk of anemia and infant health outcomes. This is a secondary analysis of an existing cohort of pregnant women (n = 1076) who participated in one of two completed clinical trials examining the effect of a docosahexaenoic acid supplementation on birth and offspring outcomes. Women were enrolled between 12 and 20 weeks of gestation and were followed throughout their pregnancies to collect maternal and infant characteristics, food frequency questionnaires [providing beef intake and Mediterranean diet (MedD) adherence], and supplement intake. Women with the highest fresh beef intake had the highest intake of many micronutrients that are commonly deficient among pregnant women. Fresh beef intake alone was not related to any maternal or infant outcomes. There was a reduced risk of anemia among women with medium to high MedD quality and higher fresh beef intake. Women in the medium MedD group had 31% lower odds of anemia, and women in the high MedD group had 38% lower odds of anemia with every one-ounce increase in fresh beef intake, suggesting that diet quality indices may be misrepresenting the role of fresh beef within a healthy diet. These findings show that beef intake increases micronutrient intake and may be protective against maternal anemia when consumed within a healthy Mediterranean diet pattern.

Docosahexaenoic Acid (DHA), Vitamin D3, and Probiotics Supplementation Improve Memory, Glial Reactivity, and Oxidative Stress Biomarkers in an Aluminum-Induced Cognitive Impairment Rat Model

Docosahexaenoic Acid (DHA), Vitamin D3, and Probiotics Supplementation Improve Memory, Glial Reactivity, and Oxidative Stress Biomarkers in an Aluminum-Induced Cognitive Impairment Rat Model

Effects of maternal supplementation with DHA and/or egg yolk powder on monoamine homeostasis in the perinatal piglet brain

ABSTRACT Objectives Reports indicate that children of mothers who received docosahexaenoic acid (DHA) or egg yolk supplements during pregnancy have improved performance on cognitive tasks and brain growth; their combination has recently been demonstrated to modulate functional neuronal network connectivity in the human-relevant piglet brain. To expand upon this functional connectivity analysis, neurochemical evaluation to determine how dietary supplementation with one or both of these nutrients during the last trimester of pregnancy alters monoamine homeostasis in selected brain regions of piglets was done. Methods Beginning gestation days 60–69 through weaning, pregnant sows were fed either control diet or diets supplemented with egg yolk powder, DHA, or both. Brains were then collected, and monoamine neurotransmitters and their metabolites were quantified from various brain regions with HPLC-ECD. Results Relative to controls, egg yolk supplementation increased serotonin metabolite (5-HIAA) levels in the cerebellum, while DHA supplementation decreased serotonin (5-HT) levels in the prefrontal cortex; combined supplementation increased norepinephrine metabolite (MHPG) levels in the prefrontal cortex and cerebellum, but decreased 5-HT levels in the posterior hippocampus. Notably, all diets increased serotonin, dopamine, and their respective metabolite levels in the substantia nigra. Disscussion This suggests both overlapping and specific effects of DHA and components of egg yolk in the context of maternal supplementation during pregnancy and lactation that might facilitate optimal neurodevelopment, with the nigrostriatal pathway being particularly sensitive. Such supplementations might impact brain function and facilitate development later in life through modulating monoamine homeostasis.

Effect of Dietary Eicosapentaenoic and Docosahexaenoic Fatty Acid Supplementation during the Last Month of Gestation on Fatty Acid Metabolism and Oxidative Status in Charolais Cows and Calves.

Fatty acids (FAs) are of utmost importance in the peripartal period for the development of the central nervous and immune systems of the newborn. The transport of polyunsaturated fatty acids (PUFAs) through the placenta is considered to be minimal in ruminants. Nevertheless, the cow's FAs are the main source of FAs for the calf during gestation. This research aimed to investigate the influence of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation during late gestation on the FA metabolism of cows and their calves. A total of 20 Charolais cows during the last month of their gestation were included in the feeding trial and were divided into a control group (CON) and an experimental group (EPA + DHA). The latter received a supplement in the amount of 100 g/day (9.1 and 7.8 g/cow/day of EPA and DHA, respectively). Supplementation of low-dose EPA and DHA alters colostrum and milk fatty acid composition through the elevation of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) without affecting milk fat and protein concentrations and oxidative status. Plasma composition in cows was significantly altered, while the same effect was not detected in calf plasma. No significant change in mRNA expression was detected for the genes fatty acid synthase (FASN) and acetyl-CoA carboxylase alpha (ACACA).

The ω-3 polyunsaturated fatty acid docosahexaenoic acid enhances NK-cell antitumor effector functions.

ω-3 polyunsaturated fatty acids (PUFAs) are known to directly repress tumour development and progression. In this study, we explored whether docosahexaenoic acid (DHA), a type of ω-3 PUFA, had an immunomodulatory role in promoting tumour growth in immunocompetent mice. The number of natural killer (NK) cells but not the number of T or B cells was decreased by DHA supplementation in various tissues under physiological conditions. Although the frequency and number of NK cells were comparable, IFN-γ production by NK cells in both the spleen and lung was increased in DHA-supplemented mice in the mouse B16F10 melanoma tumour model. Single-cell RNA sequencing (scRNA-seq) revealed that DHA promoted effector function and oxidative phosphorylation in NK cells but had no obvious effects on other immune cells. Using Rag2-/- mice and NK-cell depletion by PK136 antibody injection, we demonstrated that the suppression of B16F10 melanoma tumour growth in the lung by DHA supplementation was dependent mainly on NK cells. In vitro experiments showed that DHA directly enhanced IFN-γ production, CD107a expression and mitochondrial oxidative phosphorylation (OXPHOS) activity, and slightly increased proliferator-activated receptor gamma coactivator-1α (PGC-1α) protein expression in NK cells. The PGC-1α inhibitor SR-18292 in vitro and NK cell-specific knockout of PGC-1α in mice reversed the antitumour effects of DHA. In summary, our findings broaden the current knowledge on how DHA supplementation protects against cancer growth from the perspective of immunomodulation by upregulating PGC-1α signalling-mediated mitochondrial OXPHOS activity in NK cells.

The effect of curcumin and high-content eicosapentaenoic acid supplementations in type 2 diabetes mellitus patients: a double-blinded randomized clinical trial.

The present study investigated the effect of curcumin and eicosapentaenoic acid, as one the main components of omega-3 polyunsaturated fatty acids, on anthropometric, glucose homeostasis, and gene expression markers of cardio-metabolic risk in patients with type 2 diabetes mellitus. This clinical trial was conducted at the Endocrinology Clinic of Imam Reza Hospital in Tabriz. It aimed to determine the impact of Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA), and curcumin supplements on various health indicators in patients with Type 2 Diabetes Mellitus (DM2) from 2021.02.01 to 2022.02.01. The study was a randomized double-blinded clinical trial and conducted over 12 weeks with 100 participants randomly divided into four groups. Stratified randomization was used to assign participants to two months of supplementation based on sex and Body Mass Index (BMI). The study comprised four groups: Group 1 received 2 capsules of 500 mg EPA and 200 mg DHA, along with 1 nano-curcumin placebo; Group 2 received 1 capsule of 80 mg nano-curcumin and 2 omega 3 Fatty Acids placebos; Group 3 received 2 capsules of 500 mg EPA and 200 mg DHA, and 1 capsule of 80 mg nano-curcumin; Group 4, the control, received 2 omega 3 Fatty Acids placebos and 1 nano-curcumin placebo. After twelve weeks of taking EPA + Nano-curcumin supplements, the patients experienced a statistically significant reduction in insulin levels in their blood [MD: -1.44 (-2.70, -0.17)]. This decrease was significantly greater than the changes observed in the placebo group [MD: -0.63 (-1.97, 0.69)]. The EPA + Nano-curcumin group also showed a significant decrease in High-Sensitivity C-Reactive Protein (hs-CRP) levels compared to the placebo group (p < 0.05). Additionally, the EPA + Nano-curcumin group had a significant increase in Total Antioxidant Capacity (TAC) levels compared to the placebo group (p < 0.01). However, there were no significant differences in Fasting Blood Sugar (FBS), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index, Quantitative Insulin Sensitivity Check Index (QUICKI), or Hemoglobin A1c (HbA1C) levels between the four groups (all p > 0.05). There were significant differences between the Nano-curcumin and EPA groups [MD: -17.02 (-32.99, -1.05)], and between the Nano-curcumin and control groups [MD: -20.76 (-36.73, -4.79)] in terms of lowering the serum cholesterol level. The difference in Triglycerides (TG) serum levels between the EPA + Nano-curcumin and placebo groups were not statistically significant (p = 0.093). The Nano-curcumin group showed significant decreases in Low-Density Lipoprotein (LDL) levels compared to the EPA group [MD: -20.12 (-36.90, -3.34)] and the control group [MD: -20.79 (-37.57, -4.01)]. There was a near-to-significant difference in High-Density Lipoprotein (HDL) serum levels between the EPA + Nano-curcumin and EPA groups (p = 0.056). Finally, there were significant differences in the decrease of serum Vascular Endothelial Growth Factor (VEGF) levels between the EPA and Nano-curcumin groups [MD: -127.50 (-247.91, -7.09)], the EPA and placebo groups [MD: 126.25 (5.83, 246.66)], the EPA + Nano-curcumin and Nano-curcumin groups [MD: -122.76 (-243.17, -2.35)], and the EPA + Nano- curcumin and placebo groups [MD: 121.50 (1.09, 241.92)]. The findings of the present study suggest that 12-week supplementation with EPA and Nano-curcumin may positively impact inflammation, oxidative stress, and metabolic parameters in patients with diabetes. The supplementation of EPA and Nano-curcumin may be a potential intervention to manage diabetes and reduce the risk of complications associated with diabetes. However, further research is needed to validate the study's findings and establish the long-term effects of EPA and Nano-curcumin supplementation in patients with diabetes.

Astaxanthin and DHA Supplementation Modulates the Maternal Undernutrition-induced Impairment of Cognitive Behavior and Synaptic Plasticity in Adult Life of Offspring's -Exploring the Molecular Mechanism.

Maternal nutrition was recognized as a significant part of brain growth and maturation in most mammalian species. Timely intervention with suitable nutraceuticals would provide long-term health benefits. We aim to unravel the molecular mechanisms of perinatal undernutrition-induced impairments in cognition and synaptic plasticity, employing animal model based on dietary nutraceutical supplementation. We treated undernourished dams at their gestational, lactational, and at both the time point with Astaxanthin (AsX) and Docosahexaenoic acid (DHA), and their pups were used as experimental animals. We evaluated the cognitive function by subjecting the pups to behavioral tests in their adult life. In addition, we assessed the expression of genes in the hippocampus related to cognitive function and synaptic plasticity. Our results showed downregulation of Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), cAMP response-element-binding protein (CREB), and uncoupling protein-2 (UCP2) gene expression in pups born to undernourished dams in their adult life, which AsX and DHA modulated. Maternal AsX and DHA supplementation ameliorated the undernutrition-induced learning impairment in novel object recognition (NOR) tests and partially baited radial arm maze (RAM) tasks in offspring's. The expressions of Synapsin-1 and PSD-95 decreased in perinatally undernourished groups compared to control and AsX-DHA treated groups at CA1, CA2, CA3, and DG. AsX and DHA supplementation upregulated BDNF, NT-3, CREB, and UCP2 gene expressions in perinatally undernourished rats, which are involved in intracellular signaling cascades like Ras, PI3K, and PLC. The results of our study give new insights into neuronal differentiation, survival, and plasticity, indicating that the perinatal period is the critical time for reversing maternal undernutrition-induced cognitive impairment in offspring's.

Effect of docosahexaenoic acid and olive oil supplementation on pup weight in alcohol-exposed pregnant rats.

Low birth weight has been observed in offspring of alcoholic mothers due likely to unresolved inflammation and oxidative injury. Dietary lipids play a role in inflammation and its resolution. The primary objective was to investigate the effect of DHA and olive oil on the birth weight of pups born to alcohol-exposed dams. Pregnant rats were randomized to the control or three treatment (alcohol) groups. From gestational days (GD) 8-19, the control group received daily olive oil and malto/dextrose, whereas groups 2 and 3 received olive oil and low-dose alcohol or high-dose alcohol, respectively. Group 4 received daily DHA and high-dose alcohol. The dam's blood was collected on GD 15 and 20 for cytokine analysis. Dams were sacrificed on GD 20. The mean birth weight of pups was compared by one-way ANOVA with post hoc Duncan's test. There was a significant increase in the pups' mean birth weight in the high-dose alcohol/DHA and high-dose alcohol/olive oil. Higher pro-inflammatory cytokines (IL-1β and IL-12p70) were noted in the alcohol-exposed dams. DHA and olive oil supplementation in alcohol-exposed pregnant rats significantly increased their pups' birth weight despite having high pro-inflammatory cytokines. The mechanism of this effect remains to be determined.

Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells.

Disruption of circadian rhythm during pregnancy produces adverse health outcomes in offspring; however, the role of maternal circadian rhythms in the immune system of infants and their susceptibility to inflammation remains poorly understood. Here we show that disruption of circadian rhythms in pregnant mice profoundly aggravates the severity of neonatal inflammatory disorders in both male and female offspring, such as necrotizing enterocolitis and sepsis. The diminished maternal production of docosahexaenoic acid (DHA) and the impaired immunosuppressive function of neonatal myeloid-derived suppressor cells (MDSCs) contribute to this phenomenon. Mechanistically, DHA enhances the immunosuppressive function of MDSCs via PPARγ-mediated mitochondrial oxidative phosphorylation. Transfer of MDSCs or perinatal supplementation of DHA relieves neonatal inflammation induced by maternal rhythm disruption. These observations collectively demonstrate a previously unrecognized role of maternal circadian rhythms in the control of neonatal inflammation via metabolic reprograming of myeloid cells.

Preventive interventional strategies mitigate age-associated degeneration of dorsal hippocampal neural cells in naturally ageing mice

Objectives: The objective of this study was to investigate the effectiveness and potential protective effects of various intervention strategies, such as choline and docosahexaenoic acid (Ch-DHA) supplementation, Clitoria ternatea root extract (CTR) supplements, human embryonic kidney stem cell conditioned media (HEK-CM) treatment and exposure to enriched environments (EEs), in mitigating neural cell degeneration in dorsal hippocampal subregions of naturally ageing mice brain. Materials and Methods: Twelve–fifteen-month-old CF1 male mice were subdivided (n = 6/group) into normal age-matched control, Ch-DHA supplemented, EE exposed, HEK-CM administered and CTR-supplemented groups. Neuro morphological alterations in the dorsal hippocampus were assessed using cresyl violet staining. Results: Higher neural cell degeneration was observed in the CA1–CA3 dorsal hippocampal subregions in normal ageing mice brains. Notably, interventions such as HEK-CM administration, Ch-DHA supplementation, exposure to an EE and CTR supplementation significantly reduced degeneration, particularly in the CA3 and CA2 regions. Conclusion: Ch-DHA supplementation and HEK-CM treatment are observed to significantly reduce age-dependent degeneration of dorsal hippocampal CA3 and CA2 neurons in naturally ageing mice compared to EE exposure or CTR supplementation.

Protective effects of docosahexaenoic acid supplementation on cognitive dysfunction and hippocampal synaptic plasticity impairment induced by early postnatal PM2.5 exposure in young rats.

PM2.5 exposure is a challenging environmental issue that is closely related to cognitive development impairment; however, currently, relevant means for prevention and treatment remain lacking. Herein, we determined the preventive effect of docosahexaenoic acid (DHA) supplementation on the neurodevelopmental toxicity induced by PM2.5 exposure. Neonatal rats were divided randomly into three groups: control, PM2.5, and DHA + PM2.5 groups. DHA could ameliorate PM2.5-induced learning and memory dysfunction, as well as reverse the impairment of hippocampal synaptic plasticity, evidenced by enhanced long-term potentiation, recovered synaptic ultrastructure, and increased expression of synaptic proteins. Moreover, DHA increased CREB phosphorylation and BDNF levels and attenuated neuroinflammation and oxidative stress, reflected by lower levels of IBA-1, IL-1β, and IL-6 and increased levels of SOD1 and Nrf2. In summary, our findings demonstrated that supplementation of DHA effectively mitigated the cognitive dysfunction and synaptic plasticity impairment induced by early postnatal exposure to PM2.5. These beneficial effects may be attributed to the upregulation of the CREB/BDNF signaling pathway, as well as the reduction of neuroinflammation and oxidative stress.

Docosahexaenoic Acid Modulates Nonalcoholic Fatty Liver Disease by Suppressing Endocannabinoid System.

Endocannabinoid signaling regulates energy homeostasis, and is tightly associated with nonalcoholic fatty liver disease (NAFLD). The study previously finds that supplementation of docosahexaenoic acid (DHA) has superior function to ameliorate NAFLD compared with eicosapentaenoic acid (EPA), however, the underlying mechanism remains elusive. The present study aims to investigate whether DHA intervention alleviates NAFLD via endocannabinoid system. In a case-control study, the serum endocannabinoid ligands in 60 NAFLD and 60 healthy subjects are measured. Meanwhile, NAFLD model is established in mice fed a high-fat and -cholesterol diet (HFD) for 9 weeks. DHA or EPA is administrated for additional 9 weeks. Serum primary endocannabinoid ligands, namely anandamide (AEA) and 2-arachidoniylglycerol (2-AG), are significantly higher in individuals with NAFLD compared with healthy controls. NAFLD model shows that serum 2-AG concentrations and adipocyte cannabinoid receptor 1 expression levels are significantly lower in DHA group compared with HFD group. Lipidomic and targeted ceramide analyses further confirm that endocannabinoid signaling inhibition has exerted deletion of hepatic C16:0-ceramide contents, resulting in down-regulation of de novo fatty acid synthesis and up-regulation of fatty acid β-oxidation related protein expression levels. This work elucidates that DHA has improved NAFLD by suppressing endocannabinoid system.

Maternal and Offspring Fatty Acid Desaturase Variants, Prenatal DHA Supplementation, and Dietary n–6:n–3 Fatty Acid Ratio in Relation to Cardiometabolic Health in Mexican Children

BackgroundSingle-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH). ObjectivesWe evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation. MethodsWe used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n–6 (ω–6):n–3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n–6:n–3 ratio on MetS score. ResultsAssociations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n–6:n–3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n–6:n–3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= –0.23; 95% CI: –0.61, 0.16). ConclusionsThere was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile.

Omega-3 Fatty Acids for Depression in the Elderly and Patients with Dementia: A Systematic Review and Meta-Analysis.

This study aimed to evaluate the efficacy of omega-3 fatty acid supplementation interventions in improving depression in patients with dementia. To achieve this objective, randomized controlled trials (RCTs) were identified from primary electronic databases, focusing on the relationship between omega-3 fatty acids and depression in patients with dementia. The primary outcome was the impact of omega-3 fatty acids on post-intervention depression in patients with dementia, with subgroup analyses conducted based on the type of intervention (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) combination), duration of intervention (3 months, 6 months, 12 months, ≥24 months), cognitive function (ranging from mild cognitive impairment (MCI) to severe dementia), and daily dosage (high, medium, low, applicable to both DHA and EPA). The study has been duly registered with PROSPERO (registration ID: CRD42023408744). A meta-analysis of five studies (n = 517) included in nine systematic reviews showed that omega-3 supplementation had a non-significant trend toward affecting depressive symptoms in patients with dementia (standardized mean difference (SMD): 0.147; 95% confidence interval (CI): -0.324 to 0.049; p = 0.141). Subgroup analyses revealed that DHA supplementation significantly reduced depressive symptoms (SMD: -0.247; p = 0.039). There was no significant effect for high (SMD: -0.169; 95% CI: -0.454 to 0.116; p = 0.246) or medium (SMD: -0.061; 95% CI: -0.228 to 0.105; p = 0.470) doses of EPA. However, low doses of EPA were significantly effective (SMD: -0.953; 95% CI: -1.534 to -0.373; p = 0.001), with notable improvements in patients with MCI (SMD: -0.934; p < 0.001). The study concludes that omega-3 fatty acids, particularly through DHA supplementation, may alleviate depressive symptoms in patients with MCI. Given the limited sample size, further long-term RCTs are recommended to better understand the efficacy and optimal management of omega-3 supplementation in this population using different dosages.

Crystalline silica-induced pulmonary inflammation and autoimmunity in mature adult NZBW/f1 mice: age-related sensitivity and impact of omega-3 fatty acid intervention

Objective Occupational exposure to respirable crystalline silica (cSiO2) has been linked to lupus development. Previous studies in young lupus-prone mice revealed that intranasal cSiO2 exposure triggered autoimmunity, preventable with docosahexaenoic acid (DHA). This study explores cSiO2 and DHA effects in mature lupus-prone adult mice, more representative of cSiO2-exposed worker age. Methods Female NZBWF1 mice (14-week old) were fed control (CON) or DHA-supplemented diets. After two weeks, mice were intranasally instilled saline (VEH) or 1 mg cSiO2 weekly for four weeks. Cohorts were then analyzed 1- and 5-weeks postinstillation for lung inflammation, cell counts, chemokines, histopathology, B- and T-cell infiltration, autoantibodies, and gene signatures, with results correlated to autoimmune glomerulonephritis onset. Results VEH/CON mice showed no pathology. cSiO2/CON mice displayed significant ectopic lymphoid tissue formation in lungs at 1 week, increasing by 5 weeks. cSiO2/CON lungs exhibited elevated cellularity, chemokines, CD3+ T-cells, CD45R + B-cells, IgG + plasma cells, gene expression, IgG autoantibodies, and glomerular hypertrophy. DHA supplementation mitigated all these effects. Discussion The mature adult NZBWF1 mouse used here represents a life-stage coincident with immunological tolerance breach and one that more appropriately represents the age (20–30 yr) of cSiO2-exposed workers. cSiO2-induced robust pulmonary inflammation, autoantibody responses, and glomerulonephritis in mature adult mice, surpassing effects observed previously in young adults. DHA at a human-equivalent dosage effectively countered cSiO2-induced inflammation/autoimmunity in mature mice, mirroring protective effects in young mice. Conclusion These results highlight life-stage significance in this preclinical lupus model and underscore omega-3 fatty acids’ therapeutic potential against toxicant-triggered autoimmune responses.

Dietary docosahexaenoic acid supplementation inhibits acute pulmonary transcriptional and autoantibody responses to a single crystalline silica exposure in lupus-prone mice.

Workplace exposure to respirable crystalline silica (cSiO2) has been epidemiologically linked to lupus. Consistent with this, repeated subchronic intranasal cSiO2 instillation in lupus-prone NZBWF1 mice induces inflammation-/autoimmune-related gene expression, ectopic lymphoid tissue (ELT), autoantibody (AAb) production in the lung within 5 to 13 wk followed systemic AAb increases and accelerated onset and progression of glomerulonephritis within 13 to 17 wk. Interestingly, dietary docosahexaenoic acid (DHA) supplementation suppresses these pathologic effects, but the underlying molecular mechanisms remain unclear. This study aimed to test the hypothesis that dietary DHA supplementation impacts acute transcriptional and autoantibody responses in the lungs of female NZBWF1 mice 1 and 4 wk after a single high-dose cSiO2 challenge. Groups of mice were initially fed a control (Con) diet or a DHA-containing diet (10 g/kg). Cohorts of Con- and DHA-fed were subjected to a single intranasal instillation of 2.5 mg cSiO2 in a saline vehicle (Veh), while a Con-fed cohort was instilled with Veh only. At 1 and 4 wk post-instillation (PI), we compared cSiO2's effects on innate-/autoimmune-related gene expression and autoantibody (AAb) in lavage fluid/lungs of Con- and DHA-fed mice and related these findings to inflammatory cell profiles, histopathology, cell death, and cytokine/chemokine production. DHA partially alleviated cSiO2-induced alterations in total immune cell and lymphocyte counts in lung lavage fluid. cSiO2-triggered dead cell accumulation and levels of inflammation-associated cytokines and IFN-stimulated chemokines were more pronounced in Con-fed mice than DHA-fed mice. Targeted multiplex transcriptome analysis revealed substantial upregulation of genes associated with autoimmune pathways in Con-fed mice in response to cSiO2 that were suppressed in DHA-fed mice. Pathway analysis indicated that DHA inhibited cSiO2 induction of proinflammatory and IFN-regulated gene networks, affecting key upstream regulators (e.g., TNFα, IL-1β, IFNAR, and IFNγ). Finally, cSiO2-triggered AAb responses were suppressed in DHA-fed mice. Taken together, DHA mitigated cSiO2-induced upregulation of pathways associated with proinflammatory and IFN-regulated gene responses within 1 wk and reduced AAb responses by 4 wk. These findings suggest that the acute short-term model employed here holds substantial promise for efficient elucidation of the molecular mechanisms through which omega-3 PUFAs exert protective effects against cSiO2-induced autoimmunity.

Dietary supplement use among lactating mothers following different dietary patterns – an online survey

BackgroundBreastfeeding is important for the healthy growth and development of newborns, and the nutrient composition of human milk can be affected by maternal nutrition and supplementation. In Germany, iodine supplementation is recommended for all lactating mothers, and docosahexaenoic acid (DHA) supplementation is recommended for mothers with inadequate or no fish intake. Vitamin B12 supplementation is required for strict vegans during lactation, and other nutrient supplementation may be necessary depending on the individual's nutritional status. To address the lack of data on dietary supplements used by lactating mothers following a vegetarian or vegan diet, an online survey was conducted in Germany, with a focus on iodine, DHA, and vitamin B12.MethodsStudy participants were asked to report whether they followed specific dietary patterns (omnivorous [OM], vegetarian [VT], vegan [VN]) as well as their use of dietary supplements. Relationships between diets and supplement use were analyzed using chi-square tests.Results2054 lactating women were included (1240 OM, 410 VT, and 404 VN) in this analysis. Within OM, VT and VN, at least one dietary supplement was taken by 67.3%, 84.9% and 98.0% respectively (p < 0.001). Overall, 53.2% OM, 66.8% VT, 88.4% VN reported taking at least one supplement containing iodine (p < 0.001). 54.6% OM, 61.7% VT and 58.2% VN reported supplements containing vitamin B12, while 34.1% OM, 40.2% VT and 38.6% VN mentioned supplements containing DHA (p < 0.05).ConclusionMore than half of the participants reported the use of supplements during lactation with the highest proportion in vegans. However, over one third of the mothers did not report supplementing with iodine, regardless of their dietary pattern and most participants also did not report DHA supplements. It is worrisome that a high number of vegans did not report vitamin B12 supplementation, but this could be partly due to issues with reporting. It is crucial to provide further education to breastfeeding mothers about the importance of taking micronutrient supplements, especially for those following a vegetarian or vegan diet. This will help ensure that mothers and their breastfed infants receive optimal nutrition for a healthy development.

Enteral supplementation with arachidonic and docosahexaenoic acid and pulmonary outcome in extremely preterm infants

Enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) in extremely preterm infants has shown beneficial effects on retinopathy of prematurity and pulmonary outcome whereas exclusive DHA supplementation has been associated with increased pulmonary morbidity. This secondary analysis evaluates pulmonary outcome in 204 extremely preterm infants, randomized to receive AA (100 mg/kg/day) and DHA (50 mg/kg/day) enterally from birth until term age or standard care. Pulmonary morbidity was primarily assessed based on severity of bronchopulmonary dysplasia (BPD). Serum levels of AA and DHA during the first 28 days were analysed in relation to BPD. Supplementation with AA:DHA was not associated with increased BPD severity, adjusted OR 1.48 (95 % CI 0.85–2.61), nor with increased need for respiratory support at post menstrual age 36 weeks or duration of oxygen supplementation. Every 1 % increase in AA was associated with a reduction of BPD severity, adjusted OR 0.73 (95 % CI 0.58–0.92). In conclusion, in this study, with limited statistical power, enteral supplementation with AA:DHA was not associated with an increased risk of pulmonary morbidity, but higher levels of AA were associated with less severe BPD. Whether AA or the combination of AA and DHA have beneficial roles in the immature lung needs further research.

APOEε4 genotype and DHA and EPA supplementation on the outcomes of cognitive decline: A systematic review of randomized clinical trials

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) supplementation has been used to improve cognitive outcomes in diseases associated with cognition. However, the influence of APOEε4 genotype on these relationships remains unclear. Therefore, this systematic review aims to discuss the evidence regarding the effects of DHA and EPA supplementation on cognitive decline variables and relate them to APOEε4 genotype in middle-aged and older adults. The Medline (via PubMed), Scopus, Web of Science, and Bireme/Lilacs databases were searched for studies, retrieving 1863 articles. After the step selection, two randomized clinical trials (RCTs) that evaluated the effects of EPA and DHA supplementation on cognitive variables were included. All the methodological steps were performed by two raters. The results of the RCTs were not congruent, as the non-carriers in the APOEε4 supplemented group performed worse in the quick-choice reaction time cognitive domain, whereas the carriers improved in the reasoning domain. The increase in DHA concentration in the supplemented group was lower in APOEε4 carriers than in individuals with other genotypes. Additionally, a smaller decline in right hippocampal brain volume correlated with higher EPA concentrations after supplementation in APOEε4 non-carriers. The dosage and supplementation time (18 months) were similar between studies. In conclusion, DHA and EPA supplementation showed no pragmatic effects on cognitive variables when considering the presence of the APOEε4 allele.

Maternal supplementation with docosahexaenoic acid does not cause constriction of fetal ductus arteriosus: randomized controlled trial.

Docosahexaenoic acid (DHA) is recommended routinely in pregnancy to promote fetal development. DHA has anti-inflammatory activity, but its effects on the fetal heart and circulation are unknown. This study aimed to investigate whether maternal DHA supplementation in the third trimester affects maternal prostaglandin levels and fetal ductus arteriosus flow dynamics. This was a double-blind randomized controlled trial with parallel groups conducted between 2018 and 2021. Pregnant women aged over 18 years with a normal fetus at 27-28 weeks' gestation showing no cardiac/extracardiac anomalies or ductal constriction were eligible for the trial. Women consuming substances with a known inhibitory effect on prostaglandin metabolism, such as non-steroidal anti-inflammatory drugs and polyphenol-rich foods, were excluded. The intervention group received oral supplementation of omega-3 with 450 mg/day of DHA for 8 weeks and the placebo group received capsules of soy lecithin for 8 weeks. Anthropometric measurements, assessment of polyphenol and omega-3 consumption, fetal morphological ultrasound examination, fetal Doppler echocardiographic examination and blood sample collection were performed at the start of the study and the latter two were repeated at follow-up. Prostaglandin E2 (PGE2) level and echocardiographic parameters were compared between the intervention and placebo groups and between baseline and follow-up. A total of 24 participants were included in each group. After 8 weeks, there were no significant differences between the intervention and placebo groups in maternal serum PGE2 level or Doppler echocardiographic parameters of ductal flow. No case of ductus arteriosus constriction was observed. The expected intragroup changes in cardiac morphology, as a result of advancing gestation, were present. Maternal DHA supplementation in the third trimester at a clinically recommended dose did not result in inhibition of PGE2 or constriction of the ductus arteriosus. These findings should be confirmed in postmarket surveillance studies with larger patient numbers in order to test the full safety profile of DHA and provide robust clinical reassurance. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.