Omega-3 fatty acids and cognitive function in women.
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ABSTRACT:
SUBMITTER: Robinson JG
PROVIDER: S-EPMC2826215 | biostudies-literature | 2010 Jan
REPOSITORIES: biostudies-literature
Publications
Omega-3 fatty acids and cognitive function in women.
Robinson Jennifer G JG Ijioma Nkechinyere N Harris William W
Women's health (London, England) 20100101 1
Omega-3 fatty acids (FAs) could play an important role in maintaining cognitive function in aging individuals. The omega-3 FA docosahexaenoic acid is a major constituent of neuronal membranes and, along with the other long-chain omega-3 FAs from fish such as eicosapentaentoic acid, has been shown to have a wide variety of beneficial effects on neuronal functioning, inflammation, oxidation and cell death, as well as on the development of the characteristic pathology of Alzheimer's disease. Omega- ...[more]
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Project description:Postmenopausal women are at increased risk for a cardiovascular event due to platelet hyperactivity. There is evidence suggesting that ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have cardioprotective effects in these women. However, a mechanistic understanding of how these fatty acids regulate platelet function is unknown. In this study, we supplemented postmenopausal women with fish oil (ω-3 fatty acids) or evening primrose oil (ω-6 fatty acids) and investigated the effects on their platelet activity. The effects of fatty acid supplementation on platelet aggregation, dense granule secretion, and activation of integrin αIIbβ3 at basal levels and in response to agonist were tested in postmenopausal women following a supplementation and washout period. Supplementation with fish oil or primrose oil attenuated the thrombin receptor PAR4-induced platelet aggregation. Supplementation with ω-3 or ω-6 fatty acids decreased platelet dense granule secretion and attenuated basal levels of integrin αIIbβ3 activation. Interestingly, after the washout period following supplementation with primrose oil, platelet aggregation was similarly attenuated. Additionally, for either treatment, the observed protective effects post-supplementation on platelet dense granule secretion and basal levels of integrin activation were sustained after the washout period, suggesting a long-term shift in platelet reactivity due to fatty acid supplementation. These findings begin to elucidate the underlying mechanistic effects of ω-3 and ω-6 fatty acids on platelet reactivity in postmenopausal women. Hence, this study supports the beneficial effects of fish oil or primrose oil supplementation as a therapeutic intervention to reduce the risk of thrombotic events in postmenopausal women. https://clinicaltrials.gov/ct2/show/NCT02629497.
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Project description:Dietary consumption of ω-3 polyunsaturated fatty acids (PUFAs), present in fish oils, is known to improve the vascular response, but their molecular targets remain largely unknown. Activation of the TRPV4 channel has been implicated in endothelium-dependent vasorelaxation. Here, we studied the contribution of ω-3 PUFAs to TRPV4 function by precisely manipulating the fatty acid content in Caenorhabditis elegans. By genetically depriving the worms of PUFAs, we determined that the metabolism of ω-3 fatty acids is required for TRPV4 activity. Functional, lipid metabolome, and biophysical analyses demonstrated that ω-3 PUFAs enhance TRPV4 function in human endothelial cells and support the hypothesis that lipid metabolism and membrane remodeling regulate cell reactivity. We propose a model whereby the eicosanoid's epoxide group location increases membrane fluidity and influences the endothelial cell response by increasing TRPV4 channel activity. ω-3 PUFA-like molecules might be viable antihypertensive agents for targeting TRPV4 to reduce systemic blood pressure.
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Project description:Background and objectivesKidney function gradually decreases with age, and myocardial infarction accelerates this deterioration. Omega-3 (n-3) fatty acids may slow down the decline of kidney function. The effect of marine and plant-derived n-3 fatty acids on kidney function in patients after myocardial infarction was examined.Design, setting, participants, & measurementsIn the Alpha Omega Trial, 2344 patients with history of myocardial infarction ages 60-80 years old (81% men) were randomized to one of four trial margarines. The patients received an additional targeted amount of 400 mg/d eicosapentaenoic acid and docosahexaenoic acid, 2 g/d α-linolenic acid, eicosapentaenoic acid-docosahexaenoic acid plus α-linolenic acid, or placebo for 40 months. Serum cystatin C and serum creatinine were assessed at baseline and after 40 months. Creatinine-cystatin C-based GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration equation.ResultsPatients consumed 19.9 g margarine/d, providing an additional 239 mg/d eicosapentaenoic acid with 159 mg/d docosahexaenoic acid, 1.99 g/d α-linolenic acid, or both in the active treatment groups. After 40 months, compared with baseline, mean (±SD) creatinine-cystatin C-based GFR was -6.9 (±12.6), -4.8 (±13.4), -6.2 (±12.8), and -6.0 (±13.0) ml/min per 1.73 m(2) in the placebo, eicosapentaenoic acid-docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid-docosahexaenoic acid plus α-linolenic acid groups, respectively. After 40 months, in patients receiving eicosapentaenoic acid-docosahexaenoic acid compared with placebo, the decline in creatinine-cystatin C-based GFR was 2.1 less (95% confidence interval, 0.6 to 3.6; P<0.01) ml/min per 1.73 m(2); other comparisons were not statistical significant. Odds ratios (95% confidence intervals) of incident CKD (<60 ml/min per 1.73 m(2)) and rapid decline of kidney function (≥3 ml/min per year) for eicosapentaenoic acid-docosahexaenoic acid compared with placebo were 0.83 (0.58 to 1.18) and 0.85 (0.67 to 1.08), respectively.ConclusionsLong-term supplementation with 400 mg/d eicosapentaenoic acid-docosahexaenoic acid provides a small beneficial effect on kidney function in patients with a history of myocardial infarction.
| S-EPMC4186521 | biostudies-literature
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Project description:STUDY QUESTION:Are serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (ω3-PUFA) and omega-6 (ω6-PUFA), related to ART outcomes? SUMMARY ANSWER:Serum levels of long-chain ω3-PUFA were positively associated with probability of live birth among women undergoing ART. WHAT IS KNOWN ALREADY:Intake of ω3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ω3-PUFA levels and pregnancy rates after ART. STUDY DESIGN SIZE, AND DURATION:This analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection. PARTICIPANTS/MATERIALS, SETTING, METHODS:Serum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth. MAIN RESULTS AND ROLE OF CHANCE:The median [25th, 75th percentile] serum level of ω3-PUFA was 4.7% [3.8%, 5.8%] of total fatty acids. Higher levels of serum long-chain ω3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8% (4%, 11%) and 8% (95% CI: 1%, 16%), respectively, for every 1% increase in serum long-chain ω3-PUFA levels. Intake of long-chain ω3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95% CI: 1.02, 5.51) when replacing 1% energy of long-chain ω3-PUFA for 1% energy of saturated fatty acids. Serum ω6-PUFA, ratios of ω6 and ω3-PUFA, and total PUFA were not associated with ART outcomes. LIMITATIONS REASONS FOR CAUTION:The generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up. WIDER IMPLICATIONS OF THE FINDINGS:Serum ω3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ω3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART. STUDY FUNDING/COMPETING INTERESTS:NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare.
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| S-EPMC5369607 | biostudies-literature
Project description:More than a dozen epidemiological studies have reported that reduced levels or intake of omega-3 fatty acids or fish consumption is associated with increased risk for age-related cognitive decline or dementia such as Alzheimer's disease (AD). Increased dietary consumption or blood levels of docosahexaenoic acid (DHA) appear protective for AD and other dementia in multiple epidemiological studies; however, three studies suggest that the ApoE4 genotype limits protection. DHA is broadly neuroprotective via multiple mechanisms that include neuroprotective DHA metabolites, reduced arachidonic acid metabolites, and increased trophic factors or downstream trophic signal transduction. DHA is also protective against several risk factors for dementia including head trauma, diabetes, and cardiovascular disease. DHA is specifically protective against AD via additional mechanisms: It limits the production and accumulation of the amyloid beta peptide toxin that is widely believed to drive the disease; and it also suppresses several signal transduction pathways induced by Abeta, including two major kinases that phosphorylate the microtubule-associated protein tau and promote neurofibrillary tangle pathology. Based on the epidemiological and basic research data, expert panels have recommended the need for clinical trials with omega-3 fatty acids, notably DHA, for the prevention or treatment of age-related cognitive decline--with a focus on the most prevalent cause, AD. Clinical trials are underway to prevent and treat AD. Results to-date suggest that DHA may be more effective if it is begun early or used in conjunction with antioxidants.
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Project description:ObjectiveDiabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (?-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ?-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM).DesignMale leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks-26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ?-3 or ?-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet.ResultsThe ?-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ?-6PUFA-rich diet. There was also an enhanced ability of ?-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ?-3PUFAs.ConclusionThis study identifies beneficial effects of dietary ?-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ?-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ?-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM.
| S-EPMC3408641 | biostudies-literature
Project description:ObjectiveTo test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older.MethodsA total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA + EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory.ResultsAfter adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time.ConclusionsWe did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.
| S-EPMC3888166 | biostudies-literature
Project description:RationaleOmega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.ObjectiveTo investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.MethodsAssociations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs.ResultsDPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P2df = 9.4 × 10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, ∼80%) was associated with lower FVC (PSNP = 2.1 × 10-9; βSNP = -161.0 ml), and the association was attenuated by higher DHA levels (PSNP×DHA interaction = 2.1 × 10-7; βSNP×DHA interaction = 36.2 ml).ConclusionsWe corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.
| S-EPMC6396866 | biostudies-literature