Changes in EPA and DHA during supplementation with omega-3 fatty acids and incident cardiovascular events: secondary analysis from the OMEMI trial

Abstract Background In the OMEMI trial, elderly post-MI patients did not achieve reduction in cardiovascular events from supplementation of 1.8g n-3 polyunsaturated fatty acids (PUFA). In two recent trials of hypertriglyceridaemic patients the REDUCE-IT trial demonstrated an association between high levels of serum eicosapentaenoic acid (EPA) and reduced risk of CV events with 4 g/day icosapent ethyl supplements while in the STRENGTH trial no such association was present in patients treated with 4 g/day of EPA+ docosahexaenoic acid (DHA). Purpose To assess associations between changes in concentrations of EPA and DHA during two years supplementation with n-3 PUFA and incident cardiovascular events in the OMEMI trial. Methods In the randomized controlled OMEMI trial, 1014 elderly patients with a recent acute myocardial infarction (AMI) were treated with 1.8g/day of EPA and docosahexaenoic acid (DHA) or placebo for two years, and followed for the primary outcome of MACE (AMI, coronary revascularization, stroke or heart failure hospitalization) and secondary outcome of new-onset atrial fibrillation (AF). Serum concentrations of EPA and DHA were measured at inclusion and at study completion by gas chromatography, and reported as % weight of total FA (%wt) in serum phospholipids. Results Serial EPA and DHA measurements at study inclusion and completion were available in 881 patients (92% of survivors). At baseline EPA and DHA concentrations were (mean±SD) 2.84±1.41 and 5.71±1.35%wt, respectively. Higher baseline EPA and DHA concentrations were associated with previous n-3 PUFA supplementation, lower prevalence of current smoking and diabetes, lower levels of triglycerides and higher levels of HDL-cholesterol (all p<0.05). In patients randomized to n-3 PUFA, EPA and DHA increased with 2.32±1.92 and 0.91±1.19%wt, respectively, whereas in the placebo group EPA and DHA decreased with −0.39±1.37 and −0.43±1.13%wt, respectively. Greater increases in EPA and DHA during follow-up were associated with a lowering of triglyceride concentrations, increasing HDL concentrations, and lower baseline concentrations of EPA and DHA (all p<0.001). Among patients treated with n-3 PUFA (n=438), a greater increase in EPA was associated with a lower risk of incident MACE (HR 0.89 [95% CI 0.78–1.00] per %wt, p=0.059) and higher risk of new-onset AF in patients free of AF at inclusion (n=339): HR 1.31 [1.06–1.62] per %wt, p=0.012 (Figure). There were no such associations for changes in DHA: HR 0.86 (95% CI 0.70–1.05), p=0.13 for MACE and HR 1.29 (0.91–1.83), p=0.16 for new-onset AF. Conclusion Patients treated with 1.8 g/day n-3 PUFA for two years experienced a doubling of serum EPA concentrations. Greater increases in EPA were associated with a lower risk of MACE, but also a higher risk of new-onset AF. Changes in DHA concentrations were not associated with outcomes, suggesting that EPA may be the more important n-3 PUFA with respect to risk of cardiovascular events. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Oslo University Hospital, Ullevål Figure 1

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Microalgae n-3 PUFAs Production and Use in Food and Feed Industries

Marine Drugs ◽

10.3390/md19020113 ◽

2021 ◽

Vol 19 (2) ◽

pp. 113

Author(s):

Marine Remize ◽

Yves Brunel ◽

Joana L. Silva ◽

Jean-Yves Berthon ◽

Edith Filaire

Keyword(s):

Fatty Acids ◽

Global Warming ◽

Docosahexaenoic Acid ◽

Polyunsaturated Fatty Acids ◽

Eicosapentaenoic Acid ◽

Human Health ◽

Current Knowledge ◽

Epa And Dha ◽

Anti Cancer ◽

Food And Feed

N-3 polyunsaturated fatty acids (n-3 PUFAs), and especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential compounds for human health. They have been proven to act positively on a panel of diseases and have interesting anti-oxidative, anti-inflammatory or anti-cancer properties. For these reasons, they are receiving more and more attention in recent years, especially future food or feed development. EPA and DHA come mainly from marine sources like fish or seaweed. Unfortunately, due to global warming, these compounds are becoming scarce for humans because of overfishing and stock reduction. Although increasing in recent years, aquaculture appears insufficient to meet the increasing requirements of these healthy molecules for humans. One alternative resides in the cultivation of microalgae, the initial producers of EPA and DHA. They are also rich in biochemicals with interesting properties. After defining macro and microalgae, this review synthesizes the current knowledge on n-3 PUFAs regarding health benefits and the challenges surrounding their supply within the environmental context. Microalgae n-3 PUFA production is examined and its synthesis pathways are discussed. Finally, the use of EPA and DHA in food and feed is investigated. This work aims to define better the issues surrounding n-3 PUFA production and supply and the potential of microalgae as a sustainable source of compounds to enhance the food and feed of the future.

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Relationship between fish oil intake by dairy cows and the yield of eicosapentaenoic acid and docosahexaenoic acid in their milk

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200005810 ◽

2001 ◽

Vol 2001 ◽

pp. 199-199 ◽

Cited By ~ 1

Author(s):

C. Rymer ◽

C. Dyer ◽

D.I. Givens ◽

R. Allison

Keyword(s):

Fatty Acids ◽

Docosahexaenoic Acid ◽

Eicosapentaenoic Acid ◽

Fish Oil ◽

Dairy Cows ◽

Fish Consumption ◽

Essential Fatty Acids ◽

Epa And Dha ◽

The Uk

The dietary essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are predominantly found in fish oil, but fish consumption in the UK is low. Increasing the yield of EPA and DHA in cows’ milk would increase human intakes of EPA and DHA, and this can be achieved by including fish oil in cows’ diets. However, because EPA and DHA are susceptible to rumen biohydrogenation, their transfer efficiency into milk is low.In vitroobservations by Gulatiet al. (1999) suggested that if the concentration of fish oil in the rumen exceeded 1 mg/ml, EPA and DHA were not hydrogenated. The objectives of this study were therefore to determine the relationships between fish oil intake by dairy cows, and the probable concentrations of fish oil in the cows’ rumen, with the yield of EPA and DHA in their milk.

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

Frontiers in Nutrition ◽

10.3389/fnut.2021.723813 ◽

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.

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Dietary manipulation to increase conjugated linoleic acids and other desirable fatty acids in beef: A review

Canadian Journal of Animal Science ◽

10.4141/a03-002 ◽

2003 ◽

Vol 83 (4) ◽

pp. 673-685 ◽

Cited By ~ 32

Author(s):

P. S. Mir ◽

M. Ivan ◽

M. L. He ◽

B. Pink ◽

E. Okine ◽

...

Keyword(s):

Fatty Acids ◽

Docosahexaenoic Acid ◽

Eicosapentaenoic Acid ◽

Human Health ◽

Vaccenic Acid ◽

Essential Fatty Acids ◽

Conjugated Linoleic Acids ◽

Feeding Management ◽

Epa And Dha ◽

Total Fat

The diet is the source of many essential fatty acids such as linoleic and linolenic acids for all mammals. These fatty acids either, as altered isomers or as other elongated products, have been found to provide unique advantages to human health. Currently two conjugated linoleic acids (CLA) isomers (cis-9, trans-11 C18:2; trans-10, cis-12 C18:2) and two elongated products of linolenic acid [eicosapentaenoic acid (EPA, C20:5 n-3), docosahexaenoic acid (DHA, C22:6 n-3)] have been recognized for their roles in maintaining human health. Consumers can obtain these functional fatty acids from beef if the feeding management of beef cattle can be altered to include precursor fatty acids. Diet, breed, and gender are important factors that affect total fat content and/or the fatty acid profile of beef with regard to CLA, EPA, and DHA. Diet provides the precursor fatty acids that are altered and deposited, and breed dictates, the amount of fat that is deposited. These fatty acids can be increased in beef by increasing the forage:concentrate ratio, inclusion of non-fermented forage, and supplementation with various oils or oil seeds. The CLA and vaccenic acid (trans-11 C18:1) concentration in beef was increased by feeding sunflower oil or seeds, linseed, and soybean oil supplemented diets, while cattle fed linseed and fish oil supplemented diets had increased concentrations of EPA and DHA. Although the concentration of these fatty acids can be increased in beef, there is a need to further the understanding of the mechanism by which they exert positive affects on human health. Key words: Cattle, beef, fatty acids, conjugated linoleic acid, eicosapentaenoic acid, docosahexaenoic acid

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Do Eicosapentaenoic Acid and Docosahexaenoic Acid Have the Potential to Compete against Each Other?

Nutrients ◽

10.3390/nu12123718 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3718

Author(s):

Anandita Pal ◽

Adam H. Metherel ◽

Lauren Fiabane ◽

Nicole Buddenbaum ◽

Richard P. Bazinet ◽

...

Keyword(s):

Fatty Acids ◽

Docosahexaenoic Acid ◽

Eicosapentaenoic Acid ◽

Docosapentaenoic Acid ◽

Western Diet ◽

Dietary Recommendations ◽

Membrane Phospholipids ◽

Beneficial Effects ◽

Epa And Dha ◽

Wide Range

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 polyunsaturated fatty acids (PUFAs) consumed in low abundance in the Western diet. Increased consumption of n-3 PUFAs may have beneficial effects for a wide range of physiological outcomes including chronic inflammation. However, considerable mechanistic gaps in knowledge exist about EPA versus DHA, which are often studied as a mixture. We suggest the novel hypothesis that EPA and DHA may compete against each other through overlapping mechanisms. First, EPA and DHA may compete for residency in membrane phospholipids and thereby differentially displace n-6 PUFAs, which are highly prevalent in the Western diet. This would influence biosynthesis of downstream metabolites of inflammation initiation and resolution. Second, EPA and DHA exert different effects on plasma membrane biophysical structure, creating an additional layer of competition between the fatty acids in controlling signaling. Third, DHA regulates membrane EPA levels by lowering its rate of conversion to EPA’s elongation product n-3 docosapentaenoic acid. Collectively, we propose the critical need to investigate molecular competition between EPA and DHA in health and disease, which would ultimately impact dietary recommendations and precision nutrition trials.

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Intake of n-3 polyunsaturated fatty acids in childhood, FADS genotype, and incident asthma

European Respiratory Journal ◽

10.1183/13993003.03633-2020 ◽

2021 ◽

pp. 2003633

Author(s):

Mohammad Talaei ◽

Emmanouela Sdona ◽

Philip C. Calder ◽

Louise R. Jones ◽

Pauline M. Emmett ◽

...

Keyword(s):

Fatty Acids ◽

Confidence Interval ◽

Polyunsaturated Fatty Acids ◽

Odds Ratio ◽

Lower Risk ◽

Inverse Association ◽

Dietary Intakes ◽

Omega 3 ◽

Epa And Dha ◽

Incident Asthma

Longitudinal evidence on the relation between dietary intake of n-3 (omega-3) very long-chain polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mid-childhood and asthma risk is scarce. We aimed to investigate whether a higher intake of EPA and DHA from fish in childhood is associated with a lower risk of incident asthma.In the Avon Longitudinal Study of Parents and Children, dietary intakes of EPA and DHA from fish were estimated by food frequency questionnaire at 7 years of age. We used logistic regression, controlling for confounders, to analyse associations between intake of EPA and DHA (quartiles) and incidence of doctor-diagnosed asthma at age 11 or 14 years, and explored potential effect modification by a fatty acid desaturase (FADS) polymorphism (rs1535). Replication was sought in the Swedish BAMSE birth cohort.There was no evidence of association between intake of EPA plus DHA from fish and incident asthma overall (n=4543). However, when stratified by FADS genotype, the odds ratio (95% confidence interval) comparing top versus bottom quartile amongst the 2025 minor G allele carriers was 0.49 (0.31–0.79) (p-trend 0.006), but no inverse association was observed in the homozygous major A allele group (odds ratio 1.43, 95% confidence interval 0.83–2.46, p-trend 0.19) (p-interaction 0.006). This gene-nutrient interaction on incident asthma was replicated in BAMSE.In children with a common FADS variant, higher intake of EPA and DHA from fish in childhood was strongly associated with a lower risk of incident asthma up to mid-adolescence.

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Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Chylomicron and VLDL Synthesis and Secretion in Caco-2 Cells

BioMed Research International ◽

10.1155/2014/684325 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Yue Wang ◽

Qiaowei Lin ◽

Peipei Zheng ◽

Lulu Li ◽

Zhengxi Bao ◽

...

Keyword(s):

Fatty Acids ◽

Docosahexaenoic Acid ◽

Eicosapentaenoic Acid ◽

De Novo ◽

Epa And Dha ◽

Apolipoprotein B48

The present research was undertaken to determine the effects of EPA (20 : 5 n-3) and DHA (22 : 6 n-3) on chylomicron and VLDL synthesis and secretion by Caco-2 cells. Cells were incubated for 12 to 36 h with 400 μM OA, EPA, and DHA; then 36 h was chosen for further study because EPA and DHA decreased de novo triglycerides synthesis in a longer incubation compared with OA (P<0.01). Neither the uptake nor oxidation was different in response to the respective fatty acids (P>0.05). Compared with OA, intercellular and secreted nascent apolipoprotein B48 and B100 were decreased by EPA and DHA (P<0.01). Both DHA and EPA resulted in a lower secretion of chylomicron and VLDL (P<0.01). In contrast to OA, EPA and DHA were preferentially incorporated into phospholipids instead of triacylglycerols (P<0.01). These discoveries demonstrated that exposure of DHA and EPA reduced the secretion of chylomicron and VLDL partly by regulating the synthesis of TG and apoB.

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Dietary supplements during the COVID-19 pandemic: insights from 1.4M users of the COVID Symptom Study app - a longitudinal app-based community survey

10.1101/2020.11.27.20239087 ◽

2020 ◽

Author(s):

Panayiotis Louca ◽

Benjamin Murray ◽

Kerstin Klaser ◽

Mark S Graham ◽

Mohsen Mazidi ◽

...

Keyword(s):

Fatty Acids ◽

Vitamin D ◽

Vitamin C ◽

Dietary Supplements ◽

Lower Risk ◽

Community Survey ◽

Polymerase Chain Reaction Test ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

New Onset

AbstractObjectivesDietary supplements may provide nutrients of relevance to ameliorate SARS-CoV-2 infection, although scientific evidence to support a role is lacking. We investigate whether the regular use of dietary supplements can reduce the risk of testing positive for SARS-CoV-2 infection in around 1.4M users of the COVID Symptom Study App who completed a supplement use questionnaire.DesignLongitudinal app-based community survey and nested case control study.SettingSubscribers to an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in three countries.Main ExposureSelf-reported regular dietary supplement usage since the beginning of the pandemic.Main Outcome MeasuresSARS-CoV-2 infection confirmed by viral RNA polymerase chain reaction test (RT-PCR) or serology test. A secondary outcome was new-onset anosmia.ResultsIn an analysis including 327,720 UK participants, the use of probiotics, omega-3 fatty acids, multivitamins or vitamin D was associated with a lower risk of SARS-CoV-2 infection by 14%(95%CI: [8%,19%]), 12%(95%CI: [8%,16%]), 13%(95%CI: [10%,16%]) and 9%(95%CI: [6%,12%]), respectively, after adjusting for potential confounders. No effect was observed for vitamin C, zinc or garlic supplements. When analyses were stratified by sex, age and body mass index (BMI), the protective associations for probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts. Results were further confirmed in a sub-analysis of 993,365 regular app users who were not tested for SARS-CoV-2 with cases (n= 126,556) defined as those with new onset anosmia (the strongest COVID-19 predictor).ConclusionWe observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2 in women. No clear benefits for men were observed nor any effect of vitamin C, garlic or zinc for men or women. Randomised controlled trials of selected supplements would be required to confirm these observational findings before any therapeutic recommendations can be made.

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