scholarly journals APOE Genotype Modifies the Plasma Oxylipin Response to Omega-3 Polyunsaturated Fatty Acid Supplementation in Healthy Individuals

2021 ◽  
Vol 8 ◽  
Author(s):  
Rasha N. M. Saleh ◽  
Annette L. West ◽  
Annika I. Ostermann ◽  
Nils Helge Schebb ◽  
Philip C. Calder ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Apoe Genotype ◽  
Dose Effect ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Omega 3 ◽  
Pufa Supplementation ◽  
Epa And Dha ◽  
Total Fatty Acids ◽  
The Difference

The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in response to n-3 PUFA supplementation, which in turn is likely to contribute to the overall heterogeneity in response to n-3 PUFA intervention. Given its known role in inflammation and as a modulator of the physiological response to EPA and DHA, here we explore, for the first time, the differential response of plasma hydroxy-, epoxy- and dihydroxy-arachidonic acid, EPA and DHA oxylipins according to apolipoprotein E (APOE) genotype using samples from a dose-response parallel design RCT. Healthy participants were given doses of EPA+DHA equivalent to intakes of 1, 2, and 4 portions of oily fish per week for 12 months. There was no difference in the plasma levels of EPA, DHA or ARA between the wildtype APOE3/E3 and APOE4 carrier groups after 3 or 12 months of n-3 PUFA supplementation. At 12 months, hydroxy EPAs (HEPEs) and hydroxy-DHAs (HDHAs) were higher in APOE4 carriers, with the difference most evident at the highest EPA+DHA intake. A significant APOE*n-3 PUFA dose effect was observed for the CYP-ω hydroxylase products 19-HEPE (p = 0.027) and 20-HEPE (p = 0.011). 8-HEPE, which, along with several other plasma oxylipins, is an activator of peroxisome proliferator activated receptors (PPARs), showed the highest fold change in APOE4 carriers (14-fold) compared to APOE3/E3 (4-fold) (p = 0.014). Low basal plasma EPA levels (EPA < 0.85% of total fatty acids) were associated with a greater change in 5-HEPE, 9-HEPE, 11-HEPE, and 20-HEPE compared to high basal EPA levels (EPA > 1.22% of total fatty acids). In conclusion, APOE genotype modulated the plasma oxylipin response to increased EPA+DHA intake, with APOE4 carriers presenting with the greatest increases following high dose n-3 PUFA supplementation for 12 months.

scholarly journals Changes in Erythrocyte Omega-3 Fatty Acids in German Employees upon Dietary Advice by Corporate Health

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3267
Author(s):  
Dietrich Rein ◽  
Matthias Claus ◽  
Wolfgang Frosch ◽  
Winfried März ◽  
Stefan Lorkowski ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Dietary Advice ◽  
Omega 3 ◽  
Dietary Recommendations ◽  
Working Population ◽  
Rich Food ◽  
Epa And Dha ◽  
Total Fatty Acids

Background: The erythrocyte ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) over total fatty acids, the omega-3 index (O3I), has been suggested as an overall health marker and to motivate corporate health recommendations. We set out to assess the O3I status in a working population, the differences between normal and rotating shift employees, the consumption of omega-3 rich food and whether recommendations to increase intake of omega-3 rich foods can improve the O3I. Methods: Employees registered for their occupational health check-up were offered to participate in a pre-post study at the Ludwigshafen (Germany) site including an assessment of their O3I at baseline and after 4 months (follow-up) and two subsequent food frequency questionnaires. For those with O3I below 8%, a recommendation was provided to increase the intake of omega-3 fatty acid rich food and to take advantage of the employees’ catering service with its enhanced fatty seafood offer during the study period. Dietary intake of EPA and DHA, erythrocyte fatty acid profiles, clinical and lifestyle parameters were assessed. Results: In 500 employees (26.6% female, 21–64 years, median age: 47 years [IQR: 37–53]), at baseline the overall mean O3I was 4.1 ± 1.1% (99.6% of O3I assessed were below 8%), higher in women, in participants with “normal” body weight, upper employment grade, and non-smokers, but not different between regular and rotating shift workers. The three fifths of the cohort also participating in the follow-up increased their EPA and DHA intake by 0.1 g/d and their O3I by 0.5 percentage points. Conclusion: This study provides essential data on omega-3 erythrocyte concentrations in a clinically healthy German working population and the challenges of increasing the O3I with dietary recommendations even in study participants motivated to follow up on their omega-3 status.

Abstract 16407: Plasma Omega-3 Fatty Acids Predict Cardiovascular Events Stratified by Coronary Artery Calcium

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Abdulhamied Alfaddagh ◽  
Karan Kapoor ◽  
Zeina Dardari ◽  
Deepak L Bhatt ◽  
Matthew J Budoff ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Artery Calcium ◽  
Cox Regression ◽  
High Dose ◽  
Omega 3 ◽  
Cvd Risk ◽  
Supplement Use ◽  
Epa And Dha ◽  
The Difference ◽  
Subclinical Cvd

Background: In REDUCE-IT, high-dose eicosapentaenoic acid (EPA) was beneficial in high-risk patients without clinical CVD independent of triglyceride levels. Whether the benefit of higher plasma EPA extends to those without subclinical CVD is unclear. Hypothesis: In those without clinical CVD, plasma omega-3 fatty acid (O3FA) levels predict long-term CVD events, and subclinical CVD measured by coronary artery calcium (CAC) modifies the effect such that individuals with the highest CAC attain the greatest benefit from higher O3FA. Methods: We examined 6568 MESA participants with plasma EPA and docosahexaenoic acid (DHA) levels measured at baseline and classified them by tertiles of EPA and DHA and by CAC category (0, 1-99, ≥100). Our outcome was time to CVD event (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Cox regression models were used to assess the associations between log-transformed EPA and DHA and CVD events adjusted for demographic factors, CVD risk factors, and medication use. Results: Mean age was 62.1±10.2 and 52.9% were females. Higher log(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.93; P = 0.002) and log(DHA) (aHR = 0.80; 95% CI, 0.66-0.96; P = 0.019) were independently associated with fewer CVD events. The difference in absolute CVD event rates between the lowest and highest EPA tertile increased at higher CAC levels (Figure). The adjusted HR for highest compared to lowest EPA tertile within CAC 0 was 1.02 (95% CI, 0.72-1.45), CAC 1-99 was 0.71 (95% CI, 0.51-0.98), and CAC≥100 was 0.66 (95% CI, 0.52-0.83). A similar association was seen in tertiles of DHA by CAC category. These findings were consistent by sex and race category and after adjusting for O3FA supplement use. Conclusion: In an ethnically diverse population free of clinical CVD at baseline, higher plasma O3FA levels were associated with fewer CVD events. The absolute reduction in CVD events with higher O3FA levels was more apparent at higher CAC scores.

Aspirin and Omega-3 Polyunsaturated Fatty Acid Use and Their Interaction in Cardiovascular Diseases and Colorectal Adenomas

2021 ◽  
pp. 1-34
Author(s):  
Ivan E. Wang ◽  
Shana Yi ◽  
Robert C. Block ◽  
Shaker A. Mousa
Keyword(s):  
Synergistic Effects ◽  
Colorectal Adenomas ◽  
Diabetic Patients ◽  
High Dose ◽  
Low Doses ◽  
Omega 3 ◽  
Pufa Supplementation ◽  
Epa And Dha ◽  
Specific Manner ◽  
N3 Polyunsaturated Fatty Acids

Abstract Aspirin (acetylsalicylic acid, ASA) is inexpensive and is established in preventing cardiovascular disease (CVD) and colorectal adenomas. Omega-3 (n3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have also shown benefit in preventing CVD. The combination could be an effective preventative measure in patients with such diseases. ASA and n3 PUFA reduced the risk of CVD in ASA resistant or diabetic patients. EPA and DHA deficient patients also benefited the most from n3 PUFA supplementation. Synergistic effects between ASA and EPA and DHA are “V-shaped” such that optimal ASA efficacy is dependent on EPA and DHA concentrations in blood. In colorectal adenomas, ASA (300 mg/d) and EPA reduced adenoma burden in a location and subtype specific manner. Low doses of ASA (75-100 mg/d) were used in CVD prevention; however ultra-low doses (30 mg/d) can also reduce thrombosis. EPA to DHA ratio is also important with regards to efficacy. DHA is more effective in reducing blood pressure and modulating systemic inflammation, however high dose EPA can lower CVD events in high-risk individuals. Although current literature has yet to examine ASA and DHA in preventing CVD, such combination warrants further investigation. To increase adherence to ASA and n3 PUFA supplementation, combination dosage form may be required to improve outcomes.

scholarly journals Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites

2020 ◽  
Vol 22 (Supplement_J) ◽  
pp. J3-J20
Author(s):  
Timothy D O’Connell ◽  
Richard Preston Mason ◽  
Matthew J Budoff ◽  
Ann Marie Navar ◽  
Gregory C Shearer
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Cardiovascular Events ◽  
Biological Diversity ◽  
Density Lipoprotein ◽  
Left Ventricular ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Omega 3 ◽  
Increased Risk

Abstract Patients with well-controlled low-density lipoprotein cholesterol levels, but persistent high triglycerides, remain at increased risk for cardiovascular events as evidenced by multiple genetic and epidemiologic studies, as well as recent clinical outcome trials. While many trials of low-dose ω3-polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have shown mixed results to reduce cardiovascular events, recent trials with high-dose ω3-PUFAs have reignited interest in ω3-PUFAs, particularly EPA, in cardiovascular disease (CVD). REDUCE-IT demonstrated that high-dose EPA (4 g/day icosapent-ethyl) reduced a composite of clinical events by 25% in statin-treated patients with established CVD or diabetes and other cardiovascular risk factors. Outcome trials in similar statin-treated patients using DHA-containing high-dose ω3 formulations have not yet shown the benefits of EPA alone. However, there are data to show that high-dose ω3-PUFAs in patients with acute myocardial infarction had reduced left ventricular remodelling, non-infarct myocardial fibrosis, and systemic inflammation. ω3-polyunsaturated fatty acids, along with their metabolites, such as oxylipins and other lipid mediators, have complex effects on the cardiovascular system. Together they target free fatty acid receptors and peroxisome proliferator-activated receptors in various tissues to modulate inflammation and lipid metabolism. Here, we review these multifactorial mechanisms of ω3-PUFAs in view of recent clinical findings. These findings indicate physico-chemical and biological diversity among ω3-PUFAs that influence tissue distributions as well as disparate effects on membrane organization, rates of lipid oxidation, as well as various receptor-mediated signal transduction pathways and effects on gene expression.

Cardioprotective effects of omega 3 fatty acids from fish oil and it enhances autoimmunity in porcine cardiac myosin-induced myocarditis in the rat model

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ling-Yan Li ◽  
Xu Wang ◽  
Ting-Chuan Zhang ◽  
Zong-Jun Liu ◽  
Jun-Qing Gao
Keyword(s):  
Fatty Acids ◽  
Fish Oil ◽  
Inflammatory Cells ◽  
Omega 3 Fatty Acids ◽  
Cardiac Myosin ◽  
Omega 3 ◽  
Autoimmune Myocarditis ◽  
Tuna Fish ◽  
Fame Analysis ◽  
Total Fatty Acids

Abstract This experiment proposed to investigate the efficiency of omega 3 fatty acids from fish that improves autoimmune against myocarditis in the rat. Fish oil was extracted from fresh Tuna fish and performed FAME analysis and mice bioassay. The autoimmune myocarditis was induced by subcutaneous injection of porcine cardiac myosin (PCM) into the footpads of rats on the first and seventh day. Rats were dissected on the 21st day to analyze the histopathological, hemodynamic, echocardiographic factors, and immunohistochemistry expressions. In the study, 73.90% of total fatty acids were recorded. Histological analysis revealed that omega 3 fatty acids administrated groups showed tremendous development in the multifocal myocardia hyaline degeneration and necrosis with inflammatory changes. Moreover, omega 3 fatty acids inhabited the expressions of inflammatory cells (CD4, CD8 and CD11b) and suppressed the level of NF-κB. The echocardiographic factors such as heartbeat, SBP, DBP, levels of LVDs, LVDd, LVPW percentage of LVFS, EF, expression levels of inflammatory cytokines (TNF, IL-1β, IFN-ɤ, IL-2, and IL-6) also significantly suppressed by omega 3 fatty acids. Hence, the present study proved that consuming fatty acid-enriched fish might be a successful therapy for improving the inflammatory profile, regenerates the heart tissues, and controlled the production of inflammatory cells.

Comparative study of tissue deposition of omega-3 fatty acids from polar-lipid rich oil of the microalgae Nannochloropsis oculata with krill oil in rats

2015 ◽  
Vol 6 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Michael L. Kagan ◽  
Aharon Levy ◽  
Alicia Leikin-Frenkel
Keyword(s):  
Fatty Acids ◽  
Comparative Study ◽  
Polar Lipid ◽  
Rat Plasma ◽  
Nannochloropsis Oculata ◽  
Polar Lipids ◽  
Omega 3 Fatty Acids ◽  
Krill Oil ◽  
Omega 3 ◽  
Epa And Dha

An oil from micro-algae rich in EPA with no DHA and consisting of 15% polar lipids (phospholipids and glycolipids) showed equivalent uptake of EPA into rat plasma and organs as omega-3 krill oil consisting of EPA and DHA and 40% phospholipids.

Abstract 134: Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Downstream n-3 Fatty Acid Metabolites in Patients With Peripheral Artery Disease

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Marlene Grenon ◽  
Christopher Owens ◽  
Hugh Alley ◽  
Karen Chong ◽  
Priscilla Yen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fish Oil ◽  
Short Duration ◽  
Peripheral Artery Disease ◽  
High Dose ◽  
Peripheral Artery ◽  
Pufa Supplementation ◽  
Fish Group ◽  
Artery Disease

OBJECTIVES: Patients with peripheral artery disease (PAD) experience significant morbidity and mortality, at least partially related to vascular inflammation and endothelial dysfunction. The OMEGA-PAD I Trial (NCT01310270), a randomized, double-blinded, placebo-controlled trial addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function (EF) and inflammation in subjects with PAD. METHODS: Eighty patients with stable, mild-severe claudication and ABI<0.9 received 4.1gm of fish oil (FISH) vs placebo capsules (CTL) for 1 month. The primary endpoint was EF as measured by brachial artery flow-mediated vasodilation (FMD). Secondary endpoints included biomarkers of inflammation, generation of n-3 fatty acid-derived lipid metabolites, lipid profile and walking impairment questionnaires. RESULTS: The FISH and CTL group were no different with regards to age, baseline EF, inflammation and lipid profiles. Following treatment, there was a significant reduction in triglycerides (-34 ± 46, p=0.0001) and an improvement in HDL (+2 ± 6, p=0.03) in the FISH group. These changes were accompanied by an increase in the omega-3 index of 4 ± 1% (p<0.00001). We observed a significant increase in the production of downstream metabolites of n-3 fatty acids including 18-, 15- and 5-hydroxy eicosapentaenoic acids and 4-hydroxy docosahexaenoic acid in the FISH group. n-3 PUFA led to a significant improvement in FMD in the FISH group (+0.7 ± 4.0%, p=0.04) and a non-significant improvement in the CTL (+0.6 ± 2.5, p=0.18) group. There were no significant differences between groups in pro-inflammatory markers or walking parameters post-treatment. CONCLUSIONS: High-dose, short-duration n-3 PUFA supplementation significantly improves the metabolo-lipidomic profile of patients with PAD. Longer studies are needed to assess the effects of n-3 PUFA on inflammation, vascular function, and clinical endpoints in patients with established PAD and to determine whether generation of n-3 fatty acid-derived bioactive lipid mediators is related to clinical outcomes.

scholarly journals Maternal Pre-Pregnancy Obesity Attenuates Response to Omega-3 Fatty Acids Supplementation During Pregnancy

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1908 ◽  
Author(s):  
Carmen Monthé-Drèze ◽  
Annie Penfield-Cyr ◽  
Marcela Smid ◽  
Sarbattama Sen
Keyword(s):  
Fatty Acids ◽  
Maternal Obesity ◽  
Secondary Analysis ◽  
Systemic Response ◽  
Omega 3 Fatty Acids ◽  
Obese Women ◽  
Omega 3 ◽  
Maternal Fetal Medicine ◽  
Inflammatory Status ◽  
Total Fatty Acids

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 (β: 0.96% total fatty acids; 95% Confidence Interval (CI): 0.13, 1.79) and n-6/n-3 ratio (β: 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 (β = −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 (β = 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.

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