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.
Project description:The objective is to investigate, using genome-wide DNA methylation analyses, methylation changes following an n-3 FA supplementation in overweight and obese subjects and to identify specific biological pathways potentially altered by the supplementation.
Project description:BACKGROUND:Schizophrenia is a serious long-term psychotic disorder marked by positive and negative symptoms, severe behavioral problems and cognitive function deficits. The cause of this disorder is not completely clear, but is suggested to be multifactorial, involving both inherited and environmental factors. Since human brain regulates all behaviour, studies have focused on identifying changes in neurobiology and biochemistry of brain in schizophrenia. Brain is the most lipid rich organ (approximately 50% of brain dry weight). Total brain lipids is constituted of more than 60% of phospholipids, in which docosahexaenoic acid (DHA, 22:6n-3) is the most abundant (more than 40%) polyunsaturated fatty acid (PUFA) in brain membrane phospholipids. Results from numerous studies have shown significant decreases of PUFAs, in particular, DHA in peripheral blood (plasma and erythrocyte membranes) as well as brain of schizophrenia patients at different developmental phases of the disorder. PUFA deficiency has been associated to psychotic symptoms and cognitive deficits in schizophrenia. These findings have led to a number of clinical trials examining whether dietary omega-3 fatty acid supplementation could improve the course of illness in patients with schizophrenia. Results are inconsistent. Some report beneficial whereas others show not effective. The discrepancy can be attributed to the heterogeneity of patient population. METHODS:In this review, results from recent experimental and clinical studies, which focus on illustrating the role of PUFAs in the development of schizophrenia were examined. The rationale why omega-3 supplementation was beneficial on symptoms (presented by subscales of the positive and negative symptom scale (PANSS), and cognitive functions in certain patients but not others was reviewed. The potential mechanisms underlying the beneficial effects were discussed. RESULTS:Omega-3 fatty acid supplementation reduced the conversion rate to psychosis and improved both positive and negative symptoms and global functions in adolescents at ultra-high risk for psychosis. Omega-3 fatty acid supplementation could also improve negative symptoms and global functions in the first-episode patients with schizophrenia, but improve mainly total or general PANSS subscales in chronic patients. Patients with low PUFA (particularly DHA) baseline in blood were more responsive to the omega-3 fatty acid intervention. CONCLUSION:Omega-3 supplementation is more effective in reducing psychotic symptom severity in young adults or adolescents in the prodromal phase of schizophrenia who have low omega-3 baseline. Omega-3 supplementation was more effective in patients with low PUFA baseline. It suggests that patients with predefined lipid levels might benefit from lipid treatments, but more controlled clinical trials are warranted.
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:Omega-3 polyunsaturated fatty acids (n-3 FAs) have several beneficial effects on cardiovascular (CV) disease risk factors. These effects on CV risk profile may be mediated by several factors, including epigenetic modifications. Our objective is to investigate, using genome-wide DNA methylation analyses, methylation changes following an n-3 FA supplementation in overweight and obese subjects and to identify specific biological pathways potentially altered by the supplementation.Blood leukocytes genome-wide DNA methylation profiles of 36 overweight and obese subjects before and after a 6-week supplementation with 3 g of n-3 FAs were compared using GenomeStudio software. After supplementation, 308 CpG sites, assigned to 231 genes, were differentially methylated (FDR-corrected Diffscore ??13?~ P???0.05). Using Ingenuity Pathway Analysis system, a total of 55 pathways were significantly overrepresented following supplementation. Among these pathways, 16 were related to inflammatory and immune response, lipid metabolism, type 2 diabetes, and cardiovascular signaling. Changes in methylation levels of CpG sites within AKT3, ATF1, HDAC4, and IGFBP5 were correlated with changes in plasma triglyceride and glucose levels as well as with changes in the ratio of total cholesterol/HDL-cholesterol following the supplementation.These data provide key differences in blood leukocytes DNA methylation profiles of subjects following an n-3 FA supplementation, which brings new, potential insights on metabolic pathways underlying the effects of n-3 FAs on CV health.
Project description:Unsaturated omega-3 fatty acids, especially docosahexaenoic acid (DHA), when fed to dogs improves cognitive and neurological development. Supplementation with omega-3 fatty acids such as DHA and eicosapentaenoic acid (EPA) has also been associated with lipid peroxidation, which in turn has been implicated in reduced body weight and altered bone formation. To assess the impact of omega-3 fatty acid supplementation on skeletal growth, diets containing three levels of DHA and EPA (0.01 and 0.01%, 0.14 and 0.12%, and 0.21 and 0.18%, respectively) were fed to bitches during gestation and lactation with puppies also supplemented through weaning. Thus, the subjects studied were the puppies supplemented with DHA and EPA through gestation and early postnatal life. The hip joint conformation of the puppies (n = 676) was recorded at adulthood using two radiographic, non-invasive evaluations. In this population, females had higher hip distraction indices (DI) than males. Males from the lower two levels of DHA and EPA supplementation had significantly smaller hip DI than all females and males from the highest DHA and EPA supplementation. In contrast, there were no diet effects on anatomical indicators of hip joint conformation and no visible arthritic changes. These data suggest that dietary supplementation of DHA and EPA during gestation and the perinatal period to weaning does not adversely influence hip joint formation of dogs.
Project description:Background and study aims
Oily fish such as mackerel and sardines contain natural omega-3 fatty acids (O3FAs). They are commonly used as nutritional supplements in capsule form, with evidence suggesting numerous health benefits including improved cognitive performance, maintenance of a healthy heart and even possible anti-cancer effects. There is however little known about the amount of O3FA that enter an individual’s large bowel after taking O3FA capsules. This is of particular interest as O3FAs may have numerous effects on the environment within the bowel, including anti-bowel cancer effects and possible changes in the type and balance of bacteria. The aim of our study is to measure the amount of O3FAs present in the stoma fluid after taking daily O3FA capsules for 4 weeks. We will also examine how O3FAs alter the balance of bacteria within the gut.
Who can participate?
Patients aged 50 or over with a temporary ileostomy (An ileostomy is where the bowel is diverted through an opening in the tummy [stoma] to collect waste products in a bag. They are performed to allow the bowel to heal after surgery to treat bowel cancer).
What does the study involve?
Participants are required to take two O3FA gelatin capsules twice a day with meals for 4 weeks. The O3FA capsules contain naturally occurring fatty acids found in oily fish such as mackerel and sardines. They are widely available for people to buy over the counter from pharmacies and supermarkets. The amount of O3FA within the stoma fluid is measured after taking the O3FA capsules for 4 weeks. Participants provide a stoma fluid sample at three separate visits over the 4 week period. At the start and end of the study participants also provide blood samples to measure the levels of O3FAs in the blood.
Project description:ContextThe omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury.ObjectiveTo determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28.Design, setting, and participantsThe OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up.InterventionsTwice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement.Main outcome measureVentilator-free days to study day 28.ResultsThe study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001).ConclusionsTwice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.Trial registrationclinicaltrials.gov Identifier: NCT00609180.
Project description:White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = -1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.
Project description:Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with considerable morbidity and mortality. Available pharmacologic antiarrhythmic therapies are often ineffective in preventing the recurrence of AF, possibly because these drugs target a single pathophysiological mechanism. Given their beneficial effects on ventricular arrhythmias, omega-3 polyunsaturated fatty acids (n-3 PUFAs) have recently been investigated as possible candidates in the treatment of supraventricular arrhythmias. In this review, we explore the current understanding of the antiarrhythmic effects attributed to n-3 PUFAs including direct modulation of ionic channels, improvement of membrane fluidity, anti-inflammatory and antifibrotic effects, and modulation of sympatho-vagal balance. We will then focus on the results of epidemiologic studies exploring the associations between nutritional intake of n3 PUFAs and the incidence of AF, and will review the findings of the clinical trials investigating the effects of n-3 PUFAs supplementation in the prophylaxis of AF and in the prevention of its recurrences.