The benefits of flushing with Lemuru fish oil as a source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the performance of reproductive parameters in Garut ewes.

This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp) fish oil on the reproductive performance parameters of Garut ewes. Forty (n = 40) primiparous Garut ewes aged 12-14 months with an average body weight of 28.92 ± 4.94 kg were assigned into four experimental treatment groups. The experimental diets contained roughage: concentrate (30:70%) designated as control concentrate (CNT), flushing concentrate with 6% palm oil (PO), flushing concentrate with 3% palm oil mixed with 3% lemuru oil as DHA and EPA sources (PFO), and flushing concentrate with the addition of 6% lemuru oil (FO). Treatment animals were fed two weeks before and after conception and parturition (8 weeks of total flushing treatment). The addition of fish oil at either 3% (PFO) or 6% (FO) resulted in significantly higher reproductive performance of ewes by increasing the litter size, as reflected by the birth of multiple kids (P < 0.05) compared to CNT and PO. Adding fish oil (PFO and FO) also maintains gestation, resulting in increased lamb yield, especially in the FO treatment, which yields the highest lamb yield (0% single lamb birth). The lamb male ratio was also higher with fish oil supplementation (PFO and PO) (P < 0.05). This research revealed a positive effect of 6% Lemuru oil on decreasing embryo loss and increasing the proportion of twin births. These findings thus support the hypothesis that ration flushing with double the required DHA and EPA from 6% Lemuru fish oil (FO) resulted in significantly higher reproductive performance in Garut sheep.

Impact of fish oil supplementation on plasma levels of highly unsaturated fatty acid-containing lipid classes and molecular species in American football athletes.

BACKGROUND: Previous studies have linked sports-related concussions and repeated subconcussive head impacts in contact sport athletes to elevated brain injury biomarkers. Docosahexaenoic acid (DHA), the primary omega-3 (n-3) highly unsaturated fatty acid (HUFA) in the brain, has shown neuroprotective effects in animal models after brain injury, but clinical research has shown mixed results. METHODS: We conducted a randomized, double-blind, placebo-controlled study on 29 Division 1 collegiate American football players, exploring the impact of DHA (2.5 g) and eicosapentaenoic acid (EPA) (1.0 g) supplied as ethyl esters, on levels of plasma lipids shown to cross the blood-brain barrier. Dietary intake data was collected using food frequency questionnaires (FFQ). Complex lipids and unesterified fatty acids were isolated from plasma, separated via reversed-phase liquid chromatography and analyzed by targeted lipidomics analysis. RESULTS: FFQ results indicated that participants had low dietary n-3 HUFA intake and high omega-6 (n-6):n-3 polyunsaturated fatty acids (PUFA) and HUFA ratios at baseline. After DHA + EPA supplementation, plasma lysophosphatidylcholine (LPC) containing DHA and EPA significantly increased at all timepoints (weeks 17, 21, and 26; p < 0.0001), surpassing placebo at Weeks 17 (p < 0.05) and 21 (p < 0.05). Phosphatidylcholine (PC) molecular species containing DHA or EPA, PC38:6 PC36:6, PC38:7, PC40:6, and PC40:8, increased significantly in the DHA + EPA treatment group at Weeks 17 (and 21. Plasma concentrations of non-esterified DHA and EPA rose post-supplementation in Weeks 17 and 21. CONCLUSIONS: This study demonstrates that n-3 HUFA supplementation, in the form of ethyl esters, increased the DHA and EPA containing plasma lipid pools the have the capacity to enrich brain lipids and the potential to mitigate the effects of sports-related concussions and repeated subconcussive head impacts. TRIAL REGISTRATION: All deidentified data are available at ClinicalTrials.gov #NCT0479207.

Association between fatty acid intake and age-related macular degeneration: a meta-analysis.

Objective: The association of age-related macular degeneration (AMD) with the intake of high and low fatty acids (FAs), respectively, remains controversial. To this end, we performed a comprehensive meta-analysis of all the existing studies on the association of various intake levels of FA subtypes with AMD to determine these associations. Methods: A systematic search of PubMed, Web of Science, Cochrane Library, and EMBASE databases was conducted from inception to September 2023. To compare the highest and lowest groups, odds ratio (OR) with 95% confidence intervals (CIs) was analyzed with a random-effects model/fixed-effects model. Results: A high intake of omega-3 LCPUFAs (OR:0.67; 95%CI:[0.51, 0.88]; p = 0.004), DHA (OR:0.80; 95%CI:[0.70, 0.90]; p < 0.001), EPA (OR:0.91; 95%CI:[0.86, 0.97]; p = 0.004), and simultaneous intake of DHA and EPA (OR:0.79; 95%CI:[0.67, 0.93]; p = 0.035) significantly reduced the risk of overall AMD. Conversely, a high intake of trans-FAs (OR: 2.05; 95%CI: [1.29, 3.25]; p = 0.002) was significantly related to an increased risk of advanced AMD compared to the low-intake group. The subgroup analysis results are shown in the articles. Conclusion: Increasing dietary intake of omega-3 LCPUFAs, specifically DHA, and EPA, or the simultaneous intake of DHA and EPA, is significantly associated with a reduced risk of overall AMD. Various subtypes of omega-3 also have a significant association with a reduced risk of different stages of AMD. The high intake of trans-fatty acids (TFAs) is significantly and positively correlated with the risk of advanced AMD. This could further support the idea that consuming foods rich in omega-3 LCPUFAs and reducing consumption of foods rich in TFAs may prevent AMD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023467227.

Composition and Content of Fatty Acids in Muscle Tissue of the Potanin Altai Osman Oreoleuciscus potanini (Cypriniformes, Actinopterigii) from Mongolian Reservoirs.

The composition of fatty acids in the muscle tissue of the unique Central Asian carp-like fish, Potanin Altai osman Oreoleuciscus potanini, was studied for the first time. The populations of these fish in the reservoirs of the semiarid zone (Durgun and Taishir) during the period of their formation are considered. It was shown that the content of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in O. potanini corresponds to the median of this value in the order Cypriniformes. It was established that the basis of the food web of the herbivorous form of this species consists of microalgae (diatoms, Euglena and, possibly, chrysophytes), as well as bacteria. At the same time, the levels of bacterial biomarkers, 15-17BCFA and 17:0 were significantly higher in fish in the Durgun reservoir, whereas the level of EPA (diatom biomarker) in O. potanini was higher in the Taishir reservoir. The established higher values of the heavy nitrogen isotope content in the muscles of O. potanini from the Taishir reservoir are most likely associated with the yet unformed benthic communities and with the incomplete diversification of the riverine form of the Potanin Altai osman into lacustrine forms.

Eicosapentaenoic Acid Improves Endothelial Nitric Oxide Bioavailability Via Changes in Protein Expression During Inflammation.

BACKGROUND: Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor availability. Loss of endothelial function and NO bioavailability are associated with inflammation, including leukocyte activation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) in relation to on-treatment EPA blood levels. The mechanisms of cardiovascular protection for EPA remain incompletely elucidated but likely involve direct effects on the endothelium. METHODS AND RESULTS: In this study, human ECs were treated with EPA and challenged with the cytokine IL-6 (interleukin-6). Proinflammatory responses in the ECs were confirmed by ELISA capture of sICAM-1 (soluble intercellular adhesion molecule-1) and TNF-α (tumor necrosis factor-α). Global protein expression was determined using liquid chromatography-mass spectrometry tandem mass tag. Release kinetics of NO and peroxynitrite were monitored using porphyrinic nanosensors. IL-6 challenge induced proinflammatory responses from the ECs as evidenced by increased release of sICAM-1 and TNF-α, which correlated with a loss of NO bioavailability. ECs pretreated with EPA modulated expression of 327 proteins by >1-fold (P<0.05), compared with IL-6 alone. EPA augmented expression of proteins involved in NO production, including heme oxygenase-1 and dimethylarginine dimethylaminohydrolase-1, and 34 proteins annotated as associated with neutrophil degranulation. EPA reversed the endothelial NO synthase uncoupling induced by IL-6 as evidenced by an increased [NO]/[peroxynitrite] release ratio (P<0.05). CONCLUSIONS: These direct actions of EPA on EC functions during inflammation may contribute to its distinct cardiovascular benefits.

Production of Omega-3 Fatty Acid Concentrates from Common Kilka Oil: Optimization of the Urea Complexation Process.

There has been an increase in interest in the application of ω-3 PUFAs, especially EPA and DHA, in the development of various food products owing to their myriad health benefits. However, most fish oils do not contain more than 30% combined levels of EPA and DHA. In this study, through the urea complexation procedure, the production of EPA and DHA concentrate in their free fatty acids (FFAs) form was achieved from an enzymatic oil extracted from common kilka (Clupeonella cultriventris caspia). To gain the maximum value of EPA and DHA, the response surface methodology (RSM), which is an effective tool to categorize the level of independent variables onto the responses of an experimental process, was also used. Different variables including the urea-fatty acids (FAs) ratio (in the range of 2-6, w/w), the temperature of crystallization (in the range of -24-8 °C), and the time of crystallization (in the range of 8-40 h) were investigated by response surface methodology (RSM) for maximizing the EPA and DHA contents. Following the model validation, the levels of the variables at which the maximum desirability function (0.907 score) was obtained for response variables were 5:1 (urea-FAs ratio), -9 °C (the temperature of crystallization), and 24 h (the time of crystallization). Under these optimal conditions, increases of 2.2 and 4.4 times in the EPA and DHA concentrations were observed, respectively, and an increase in the concentrations of EPA and DHA from 5.39 and 13.32% in the crude oil to 12.07 and 58.36% in the ω-3 PUFA concentrates were observed, respectively. These findings indicate that the urea complexation process is efficient at optimizated conditions.

Gαz-independent and -dependent Improvements With EPA Supplementation on the Early Type 1 Diabetes Phenotype of NOD Mice.

Prostaglandin E2 (PGE2) is a key mediator of inflammation and is derived from the omega-6 polyunsaturated fatty acid, arachidonic acid (AA). In the ß-cell, the PGE2 receptor, Prostaglandin EP3 receptor (EP3), is coupled to the unique heterotrimeric G protein alpha subunit, Gɑz to reduce the production of cyclic adenosine monophosphate (cAMP), a key signaling molecule that activates ß-cell function, proliferation, and survival pathways. Nonobese diabetic (NOD) mice are a strong model of type 1 diabetes (T1D), and NOD mice lacking Gɑz are protected from hyperglycemia. Therefore, limiting systemic PGE2 production could potentially improve both the inflammatory and ß-cell dysfunction phenotype of T1D. Here, we sought to evaluate the effect of eicosapentaenoic acid (EPA) feeding, which limits PGE2 production, on the early T1D phenotype of NOD mice in the presence and absence of Gαz. Wild-type and Gαz knockout NOD mice were fed a control or EPA-enriched diet for 12 weeks, beginning at age 4 to 5 weeks. Oral glucose tolerance, splenic T-cell populations, islet cytokine/chemokine gene expression, islet insulitis, measurements of ß-cell mass, and measurements of ß-cell function were quantified. EPA diet feeding and Gɑz loss independently improved different aspects of the early NOD T1D phenotype and coordinated to alter the expression of certain cytokine/chemokine genes and enhance incretin-potentiated insulin secretion. Our results shed critical light on the Gαz-dependent and -independent effects of dietary EPA enrichment and provide a rationale for future research into novel pharmacological and dietary adjuvant therapies for T1D.

The value of plasma omega-3 polyunsaturated fatty acids in predicting the response and prognosis of cervical squamous cell carcinoma patients to concurrent chemoradiotherapy.

Background: In recent years, abnormalities in plasma omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been proven to be related to the risk of cancer, but their prognostic value for cancer is unclear. The purpose of this study was to retrospectively evaluate the response and prognostic significance of plasma omega-3 PUFAs in patients with cervical squamous cell carcinoma (CSCC) treated with concurrent chemoradiotherapy (CCRT). Spearman rank correlation analysis was used to analyze the correlation between omega-3 PUFAs and squamous cell carcinoma antigen (SCC-Ag) levels. Methods: A total of 89 patients with CSCC who underwent CCRT were evaluated retrospectively. Binary logistic regression analysis was used to analyze the independent predictors related to complete response (CR) after CCRT. A Cox proportional hazard model and Kaplan-Meier analysis were utilized to perform survival analysis. Results: According to multivariate logistic regression analyses, a high level of plasma EPA was independently correlated with an increased incidence of CR after CCRT (odds ratio (OR), 0.980; 95% confidence interval (CI), 0.962-0.999, p = 0.038). With a median follow-up of 41.3 months, the CSCC patients in the high EPA (≥46.0 nmol/mL) group exhibited longer OS and PFS. According to our multivariate analysis, pretreatment plasma EPA level was an independent prognostic factor for PFS in patients with CSCC who underwent CCRT (hazard ratio (HR), 0.263; 95% CI, 0.089-0.782, p = 0.016). However, it was not an independent prognostic factor of OS. Spearman rank correlation analysis revealed was a negative correlation between pretreatment SCC-Ag (pre SCC-Ag) levels and EPA levels (r = -0.305, p = 0.004), and a weak negative correlation between posttreatment SCC-Ag (post SCC-Ag) levels and EPA levels (r = -0.251, p = 0.018). Conclusion: Plasma omega-3 PUFAs are related to the response and survival outcome of patients with CSCC who underwent CCRT. Pretreatment plasma EPA levels may be a promising biomarker for predicting the response and prognosis of patients with CSCC who undergo CCRT. In addition, the pretreatment plasma EPA levels presented a negative correlation with the SCC-Ag levels.

Eicosapentaenoic Acid Level Predicts Long-Term Survival and Cardiovascular or Limb Event in Peripheral Arterial Disease.

Objectives: We examined the relationship between plasma eicosapentaenoic acid (EPA) level and long-term all-cause death (ACD) and cardiovascular or limb events in patients with peripheral arterial disease (PAD). Method: We performed a prospective cohort study on 637 PAD patients. The endpoints were ACD, major adverse cardiovascular events (MACEs), and lower extremity arterial events (LEAEs). Results: The incidences of ACD, MACEs, and LEAEs had correlation with EPA levels (p <0.05). Plasma EPA level had significant positive correlations with high-density lipoprotein cholesterol, triglyceride, and estimated glomerular filtration rate (eGFR), and negative correlation with C-reactive protein (CRP). In Cox stepwise multivariate analysis, lower EPA (hazard ratio [HR]: 0.996, 95% confidence interval [CI]: 0.993-1.000, p = 0.034), ankle brachial pressure index (ABI), body mass index, serum albumin, eGFR, age, CRP, D-dimer, critical limb ischemia, diabetes, cerebrovascular disease (CVD), and statin were related to ACD (p <0.05); lower EPA (HR: 0.997, 95% CI: 0.994-1.000, p = 0.038), ABI, serum albumin, eGFR, age, diabetes, coronary heart disease, CVD, and statin were related to MACEs (p <0.05); and lower EPA (HR: 0.988, 95% CI: 0.982-0.993, p <0.001), ABI, and low-density lipoprotein cholesterol were related to LEAEs (p <0.05). Conclusions: Low plasma EPA level was a significant risk factor for ACD, MACEs, and LEAEs in patients with PAD.

Effects of omega-3 fatty acids on coronary revascularization and cardiovascular events: a meta-analysis.

AIMS: Benefits of pharmacologic omega-3 fatty acid administration in cardiovascular prevention are controversial. Particularly, effects on coronary revascularization are unclear; also debated are specific benefits of eicosapentaenoic acid (EPA). We investigated incident coronary revascularizations, myocardial infarction (MI), stroke, heart failure (HF), unstable angina, and cardiovascular death, in subjects randomized to receive EPA or EPA + docosahexaenoic acid (EPA + DHA) vs. control. METHODS AND RESULTS: Meta-analysis of randomized controlled trials (RCTs) was conducted after MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library search. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed for abstracting data and assessing data quality and validity. Data were pooled using a random effects model. Eighteen RCTs with 134 144 participants (primary and secondary cardiovascular prevention) receiving DHA + EPA (n = 52 498), EPA alone (n = 14 640), or control/placebo (n = 67 006) were included. Follow-up ranged from 4.5 months to 7.4 years. Overall, compared with controls, omega-3 supplementation reduced the risk of revascularization [0.90, 95% confidence interval (CI) 0.84-0.98; P = 0.001; P-heterogeneity = 0.0002; I2 = 68%], MI (0.89, 95% CI 0.81-0.98; P = 0.02; P-heterogeneity = 0.06; I2 = 41%), and cardiovascular death (0.92, 95% CI 0.85-0.99; P = 0.02; P-heterogeneity = 0.13; I2 = 33%). Lower risk was still observed in trials where most participants (≥60%) were on statin therapy. Compared with DHA + EPA, EPA alone showed a further significant risk reduction of revascularizations (0.76, 95% CI 0.65-0.88; P = 0.0002; P-interaction = 0.005) and all outcomes except HF. CONCLUSION: Omega-3 fatty acid supplementation reduced the risk of cardiovascular events and coronary revascularization, regardless of background statin use. Eicosapentaenoic acid alone produced greater benefits. The role of specific omega-3 molecules in primary vs. secondary prevention and the potential benefits of reduced revascularizations on overall health status and cost savings warrant further research.

It is debated whether pharmacologic administration of omega-3 fatty acids reduces cardiac events. In particular, it is unclear whether benefits are actually restricted to the use of eicosapentaenoic acid (EPA), or whether combined administration of EPA + docosahexaenoic acid (DHA) is needed; furthermore, little is known about possible benefits of omega-3 fatty acids in reducing incidence of coronary revascularization procedures. In this meta-analysis of all published evidence of clinical trials comparing EPA alone or EPA + DHA vs. control (134 144 participants), we demonstrate the following: In the overall analysis of all trials, omega-3 supplementation reduced the risk of myocardial infarction and cardiovascular death, to a modest extent. However, when trials administering EPA alone were separately analysed, a further significant risk reduction for cardiovascular outcomes was demonstrated. Importantly, these benefits were also observed in subjects who were already taking statins as part of their chronic therapy.Administration of omega-3 fatty acids, particularly EPA alone, was also associated with a substantial decrease in the risk for subsequent coronary revascularizations. Reduction of revascularization procedures may induce additional benefits on overall health status and associated cost savings.

Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation.

BACKGROUND: A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels increase the risk of new-onset atrial fibrillation (AF) in older patients. The relationship between the EPA/AA and outcomes post-AF ablation remains unclear. This study investigated the impact of the EPA/AA on AF recurrence and cardiovascular events after AF ablation in older patients. METHODS AND RESULTS: This retrospective cohort study examined consecutive patients with AF aged ≥65 years who underwent a first-time AF ablation. We compared the 3-year AF recurrence and 5-year major adverse cardiovascular event (MACE) rates between patients divided into high and low EPA/AA levels defined as above and below the median EPA/AA value before ablation. MACE was defined as heart failure hospitalizations, strokes, coronary artery disease, major bleeding, and cardiovascular death. Among the 673 included patients, the median EPA/AA value was 0.35. Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log-rank P=0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log-rank P=0.021). A high EPA/AA level was determined as an independent predictor of AF recurrence (hazard ratio [HR], 1.75 95% CI, 1.24-2.49; P=0.002) and MACE (HR, 0.60 [95% CI, 0.36-0.99]; P=0.046). CONCLUSIONS: The EPA/AA was associated with AF recurrence and MACE after ablation in patients with AF aged ≥65 years.

Serum measures of docosahexaenoic acid (DHA) synthesis underestimates whole body DHA synthesis in male and female mice.

Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA synthesis rates are reported to be low, and have not been directly compared between sexes. Here, we apply a new compound specific isotope analysis model to determine n-3 PUFA synthesis rates in male and female mice and assess its potential translation to human populations. Male and female C57BL/6N mice were allocated to one of three 12-week dietary interventions with added ALA, eicosapentaenoic acid (EPA) or DHA. The diets included low carbon-13 (δ13C)-n-3 PUFA for four weeks, followed by high δ13C-n-3 PUFA for eight weeks (n=4 per diet, time point, sex). Following the diet switch, blood and tissues were collected at multiple time points, and fatty acid levels and δ13C were determined and fit to one-phase exponential decay modeling. Hepatic DHA synthesis rates were not different (P>.05) between sexes. However, n-3 docosapentaenoic acid (DPAn-3) synthesis from dietary EPA was 66% higher (P<.05) in males compared to females, suggesting higher synthesis downstream of DPAn-3 in females. Estimates of percent conversion of dietary ALA to serum DHA was 0.2%, in line with previous rodent and human estimates, but severely underestimates percent dietary ALA conversion to whole body DHA of 9.5%. Taken together, our data indicates that reports of low human DHA synthesis rates may be inaccurate, with synthesis being much higher than previously believed. Future animal studies and translation of this model to humans are needed for greater understanding of n-3 PUFA synthesis and metabolism, and whether the higher-than-expected ALA-derived DHA can offset dietary DHA recommendations set by health agencies.

Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: a secondary analysis of the seAFOod polyp prevention trial.

BACKGROUND: A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences the expression of FADS1, which controls the synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for proinflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs. OBJECTIVES: We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2×2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 mo (ISRCTN05926847). METHODS: Participant Indel genotype was determined by polymerase chain reaction (PCR) blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention with its placebo. Presence of ≥1 Indel I allele and an interaction term (I allele × active intervention) were covariates. RESULTS: In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR]: 0.92; 95% confidence interval: 0.74, 1.16), mirroring original seAFOod trial analysis. However, the presence of ≥1 I allele identified EPA users with a significant reduction in colorectal polyp number (IRR: 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR. CONCLUSIONS: The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted. The seAFOod polyp prevention trial and STOP-ADENOMA study were registered at International Standard Randomised Controlled Trial Number registry as ISRCTN05926847.

The Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Coronary Artery Calcium Progression in Subjects With Diabetes and Coronary Artery Disease: A Secondary Analysis of a Randomized Trial.

Higher coronary artery calcium (CAC) scores and progression of CAC are associated with higher mortality. We previously reported that subjects with coronary artery disease randomly allocated to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation or none had similar significant increases in CAC score over 30 months. Whether these findings are influenced by diabetes status is unknown. A total of 242 subjects with coronary artery disease who were on statin therapy were randomly allocated to to 1.86 g EPA and 1.5 g DHA daily or none (control). The CAC score was measured at baseline and 30-month follow-up using noncontrast, cardiac computed tomography. A significant interaction term between diabetes status and treatment arm was noted in the prediction of the CAC score (p <0.001). A total of 176 subjects (85.8% men) had no diabetes and 66 subjects (80.3% men) had diabetes. The mean age was 62.9 ± 7.9 versus 63.2 ± 7.1 years, respectively. The mean low-density lipoprotein cholesterol and median triglyceride levels were not significantly different between those without and with diabetes: 77.7 ± 25.9 versus 77.1 ± 30.2 mg/100 ml, respectively, and 117.0 (78.0 to 158.0) versus 119.0 (84.5 to 201.5) mg/100 ml, respectively. Subjects with diabetes on EPA+DHA had a greater increase in CAC score than subjects with diabetes in the control group (median 380.7 vs 183.5, respectively, p = 0.021). In contrast, no difference occurred between the EPA+DHA and control groups in subjects without diabetes (175.7 vs 201.1, respectively, p = 0.41). In conclusion, EPA+DHA supplementation was associated with greater CAC progression in subjects with diabetes than subjects with diabetes in the control group over a 30-month period; whether this indicates progression of the disease burden or plaque stabilization requires further study.

Omega-3 Long-Chain Polyunsaturated Fatty Acids in Nonseafood and Estimated Intake in the USA: Quantitative Analysis by Covalent Adduct Chemical Ionization Mass Spectrometry.

Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) play critical roles in human development and health. Their intake is often effectively estimated solely based on seafood consumption, though the high intake of terrestrial animal-based foods with minor amounts of LCPUFA may be significant. Covalent adduct chemical ionization (CACI) tandem mass spectrometry is one approach for de novo structural and quantitative analysis of minor unsaturated fatty acids (FA), for which standards are unavailable. Here, CACI-MS and MS/MS are used to identify and quantify minor omega-3 LCPUFA of terrestrial animal foods based on the application of measured response factors (RFs) to various FA. American mean intakes of pork, beef, chicken, and eggs contribute 20, 27, 45, and 71 mg/day of docosahexaenoic acid (DHA), respectively. The estimated intake of omega-3 DHA, eicosapentaenoic acid, and docosapentaenoic acid from nonseafood sources is significant, at 164, 103, and 330 mg/day, greater than most existing estimates of omega-3 LCPUFA intake.

Circulating Omega-3 Polyunsaturated Fatty Acids Levels in Coronary Heart Disease: Pooled Analysis of 36 Observational Studies.

Long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on CHD risk remains a subject of debate. Here, we aimed to investigate the association between n-3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n-3 PUFA. METHODS: Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study. RESULTS: We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools. CONCLUSIONS: n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.

Reversed-Phase Medium-Pressure Liquid Chromatography Purification of Omega-3 Fatty Acid Ethyl Esters Using AQ-C18.

Omega-3 fatty acids are in high demand due to their efficacy in treating hypertriglyceridemia and preventing cardiovascular diseases. However, the growth of the industry is hampered by low purity and insufficient productivity. This study aims to develop an efficient RP-MPLC purification method for omega-3 fatty acid ethyl esters with high purity and capacity. The results indicate that the AQ-C18 featuring polar end-capped silanol groups outperformed C18 and others in retention time and impurity separation. By injecting pure fish oil esters with a volume equivalent to a 1.25% bed volume on an AQ-C18 MPLC column using a binary isocratic methanol-water (90:10, v:v) mobile phase at 30 mL/min, optimal omega-3 fatty acid ethyl esters were obtained, with the notable purity of 90.34% and a recovery rate of 74.30%. The total content of EPA and DHA produced increased from 67.91% to 85.27%, meeting the acceptance criteria of no less than 84% set by the 2020 edition of the Pharmacopoeia of the People's Republic of China. In contrast, RP-MPLC significantly enhanced the production efficiency per unit output compared to RP-HPLC. This study demonstrates a pioneering approach to producing omega-3 fatty acid ethyl esters with high purity and of greater quantity using AQ-C18 RP-MPLC, showing this method's significant potential for use in industrial-scale manufacturing.

Eicosapentaenoic acid: New insights into an oomycete-driven elicitor to enhance grapevine immunity.

The widespread use of pesticides in agriculture remains a matter of major concern, prompting a critical need for alternative and sustainable practices. To address this, the use of lipid-derived molecules as elicitors to induce defence responses in grapevine plants was accessed. A Plasmopara viticola fatty acid (FA), eicosapentaenoic acid (EPA) naturally present in oomycetes, but absent in plants, was applied by foliar spraying to the leaves of the susceptible grapevine cultivar (Vitis vinifera cv. Trincadeira), while a host lipid derived phytohormone, jasmonic acid (JA) was used as a molecule known to trigger host defence. Their potential as defence triggers was assessed by analysing the expression of a set of genes related to grapevine defence and evaluating the FA modulation upon elicitation. JA prompted grapevine immunity, altering lipid metabolism and up-regulating the expression of several defence genes. EPA also induced a myriad of responses to the levels typically observed in tolerant plants. Its application activated the transcription of defence gene's regulators, pathogen-related genes and genes involved in phytoalexins biosynthesis. Moreover, EPA application resulted in the alteration of the leaf FA profile, likely by impacting biosynthetic, unsaturation and turnover processes. Although both molecules were able to trigger grapevine defence mechanisms, EPA induced a more robust and prolonged response. This finding establishes EPA as a promising elicitor for an effectively managing grapevine downy mildew diseases.

Expansion of omega-3 polyunsaturated fatty acid metabolism of the oleaginous diatom Fistulifera solaris by genetic engineering.

Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) are widely used as additives in fish feed in the aquaculture sector. To date, the supply of omega-3 PUFAs have heavily depended upon fish oil production. As the need for omega-3 PUFAs supply for the growing population increases, a more sustainable approach is required to keep up with the demand. The oleaginous diatom Fistulifera solaris is known to synthesize EPA with the highest level among autotrophically cultured microalgae, however, this species does not accumulate significant amounts of DHA, which, in some cases, is required in aquaculture rather than EPA. This is likely due to the lack of expression of essential enzymes namely Δ5 elongase (Δ5ELO) and Δ4 desaturase. In this study, we identified endogenous Δ5ELO genes in F. solaris and introduced recombinant expression cassettes harboring Δ5ELO into F. solaris through bacterial conjugation. As a result, it managed to induce the synthesis of docosapentaenoic acid (DPA; C22:5n-3), a direct precursor of DHA. This study paves the way for expanding our understanding of the omega-3 PUFAs pathway using endogenous genes in the oleaginous diatom.

Docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and neural tube defects in Tunisian population.

OBJECTIVE: To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs). METHODS: ARA, EPA, and DHA composition was assessed using capillary gas chromatography. RESULTS: ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels. CONCLUSIONS: More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.