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Abstract Purpose: To evaluate the effects of the nutraceuticals omega-6/3 and omega-9/6 on endometriosis-associated infertility and pain. Methods: Controlled experimental study, with each group composed of eight female rats. Fertility groups: sham-operated control (0.9% saline solution); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); and meloxicam (0.8 mg/kg/day). Pain groups: sham-operated control (0.9% saline); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); medroxyprogesterone acetate (5 mg/kg/every 3 days); and meloxicam (0.8 mg/kg/day). Peritoneal endometriosis was surgically induced. Pain was evaluated with the writhing test. Fertility was evaluated by counting the number of embryos in the left hemi-uterus. Results: The mean number of writhings was as follows: sham-operated, 11.1 ± 2.9; control with endometriosis, 49.3 ± 4.4; omega-6/3, 31.5 ± 2.7; omega-9/6, 34.1 ± 4.5; medroxyprogesterone acetate, 2.1 ± 0.8; meloxicam, 1 ± 0.3. There was a significant difference between both controls and all drugs used for treatment. Regarding fertility, the mean values were as follows: sham-operated, 6.8 ± 0.6; control with endometriosis, 4.2 ± 0.7; omega-6/3, 4.7 ± 1; omega-9/6, 3.8 ± 0.9; and meloxicam, 1.8 ± 0.9. Conclusions: The omega-6/3 and omega-9/6 nutraceuticals decreased pain compared to the controls. There was no improvement in fertility in any of the tested groups.

Marine lipids are recognized for their-health promoting features, mainly for being the primary sources of omega-3 fatty acids, and are therefore critical for human nutrition in an age when the global supply for these nutrients is experiencing an unprecedent pressure due to an ever-increasing demand. The seafood industry originates a considerable yield of co-products worldwide that, while already explored for other purposes, remain mostly undervalued as sustainable sources of healthy lipids, often being explored for low-value oil production. These co-products are especially appealing as lipid sources since, besides the well-known nutritional upside of marine animal fat, which is particularly rich in omega-3 polyunsaturated fatty acids, they also have interesting bioactive properties, which may garner them further interest, not only as food, but also for other high-end applications. Besides the added value that these co-products may represent as valuable lipid sources, there is also the obvious ecological upside of reducing seafood industry waste. In this sense, repurposing these bioresources will contribute to a more sustainable use of marine animal food, reducing the strain on already heavily depleted seafood stocks. Therefore, untapping the potential of marine animal co-products as valuable lipid sources aligns with both health and environmental goals by guaranteeing additional sources of healthy lipids and promoting more eco-conscious practices.

N -3 long-chain PUFA (LC-PUFA) and probiotics are generally considered to induce health benefits. The objective was to investigate (1) the impact of fish oil and/or probiotics on serum fatty acids (sFA), (2) the interaction of sFA with low-grade inflammation and (3) the relation of sFA to the onset of gestational diabetes mellitus (GDM). Pregnant women with overweight/obesity were allocated into intervention groups with fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo in early pregnancy (fish oil: 1·9 g DHA and 0·22 g EPA, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp . lactis 420, 10 10 CFU, each daily). Blood samples were collected in early ( n 431) and late pregnancy ( n 361) for analysis of fatty acids in serum phosphatidylcholine (PC), cholesteryl esters (CE), TAG and NEFA with GC and high-sensitivity C-reactive protein and GlycA by immunoassay and NMR spectroscopy, respectively. GDM was diagnosed according to 2 h 75 g oral glucose tolerance test. EPA in PC, CE and TAG and DHA in PC, CE, TAG and NEFA were higher in fish oil and fish oil + probiotics groups compared with placebo. EPA in serum NEFA was lower in women receiving probiotics compared with women not receiving. Low-grade inflammation was inversely associated with n -3 LC-PUFA, which were related to an increased risk of GDM. Fish oil and fish oil + probiotics consumption increase serum n -3 LC-PUFA in pregnant women with overweight/obesity. Although these fatty acids were inversely related to inflammatory markers, n -3 LC-PUFA were linked with an increased risk for GDM.

Background: Maternal nutrition impacts fetal growth and development. The Food Standards Australia New Zealand (FSANZ) guidelines recommend pregnant women consume 2-3 servings (224-336 g) of fish/seafood per week to support intake of long chain omega 3 fatty acids, given adequate consumption supports numerous health benefits including reduced risk of preterm and early preterm birth. Evidence indicates that pregnant women purposely lower their fish/seafood intake, largely due to fears of methylmercury exposure. The aim of this study was to explore pregnant women's knowledge, attitudes, and behaviours regarding their fish/seafood consumption during the antenatal period., Methods: Semi-structured interviews were conducted between October 2018 and December 2020 among a purposive sample of 12 pregnant women from the Australian Capital Territory (ACT). The interviews were recorded, transcribed verbatim, and analysed using an interpretative phenomenological approach. Themes were developed on the women's lived experience related to fish/seafood knowledge, attitudes, and consumption behaviour., Results: The most prominent finding was widespread non-adherence to fish/seafood consumption guidelines. This was largely owing to a lack of proactive health promotion related to the health benefits of fish/seafood throughout pregnancy, including the health promoting roles of long chain omega 3 fatty acids for fetal growth and development. Three themes were identified: nutrition knowledge; sources of health promotion; and barriers and enablers to fish/seafood consumption., Conclusions: To support adequate maternal consumption of fish/seafood throughout pregnancy, emphasis should be placed on the benefits of consuming this food group regularly. Additionally, pregnant women should receive education about the health promoting role of long chain omega 3 fatty acids. Dietitians are well placed to provide this information., (© 2024. The Author(s).)

Background: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium., Methods: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction., Results: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P =0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions., Conclusions: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD., Competing Interests: Disclosures Dr Murphy reports having worked as a consultant for Pharmavite (until 2021). The remaining authors have reported no relationships relevant to the contents of this article. Dr Psaty serves on the steering committee of the Yale Open Data Access Project, funded by Johnson and Johnson.

Omega-3 fatty acids, which consist of alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), are a type of polyunsaturated fatty acids that are crucial for enhancing human health. These three omega-3s are regarded as vital dietary nutrients because it cannot synthesize them on its own. Therefore, they must be obtained through dietary sources. On the other hands, there are concerns regarding the quality and quantity of omega-3 in dietary sources and supplements. In this study, 1 H NMR spectroscopy and multivariate analysis were harnessed for non-destructive profiling of fatty acids in commercially available omega-3 supplements and plant-based oils. Results disclosed substantial disparities in omega-3 content from 8 to over 50 %, with some revealing unexpected adulteration. Notably, in one fish oil sample DHA could not be detected indicating the possibility of adulteration. Additionally, the research delineated the fatty acid composition of plant-based oils, emphasizing variations in alpha-linolenic acid (ALA) and linoleic acid (LA) content among flaxseed, chia seed, and walnut oils. Chia seeds emerged as a rich source of ALA (57-65 %mol), while walnuts contained considerable LA (44-53 % mol). The findings emphasize the power of metabolomics as a rapid and affordable tool for finding omega-3 fatty acids content and adulteration in commercial dietary products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), characterized by neuroinflammation, demyelination, and neurodegeneration. Considering the increasing prevalence among young adults worldwide and the disabling phenotype of the disease, a deeper understanding of the complexity of the disease pathogenesis is needed to ultimately improve diagnosis and personalize treatment opportunities. Recent findings suggest that bioactive lipid mediators (LM) derived from ω-3/-6 polyunsaturated fatty acids (PUFA), also termed eicosanoids, may contribute to MS pathogenesis. For example, disturbances in LM profiles and especially those derived from the ω-6 PUFA arachidonic acid (AA) have been reported in people with MS (PwMS), where they may contribute to the chronicity of neuroinflammatory processes. Moreover, we have previously shown that certain AA-derived LMs also associated with neurodegenerative processes in PwMS, suggesting that AA-derived LMs are involved in more pathological events than solely neuroinflammation. Yet, to date, a comprehensive overview of the contribution of these LMs to MS-associated pathological processes remains elusive., Main Body: This review summarizes and critically evaluates the current body of literature on the eicosanoid biosynthetic pathway and its contribution to key pathological hallmarks of MS during different disease stages. Various parts of the eicosanoid pathway are highlighted, namely, the prostanoid, leukotriene, and hydroxyeicosatetraenoic acids (HETEs) biochemical routes that include specific enzymes of the cyclooxygenases (COXs) and lipoxygenases (LOX) families. In addition, cellular sources of LMs and their potential target cells based on receptor expression profiles will be discussed in the context of MS. Finally, we propose novel therapeutic approaches based on eicosanoid pathway and/or receptor modulation to ultimately target chronic neuroinflammation, demyelination and neurodegeneration in MS., Short Conclusion: The eicosanoid pathway is intrinsically linked to specific aspects of MS pathogenesis. Therefore, we propose that novel intervention strategies, with the aim of accurately modulating the eicosanoid pathway towards the biosynthesis of beneficial LMs, can potentially contribute to more patient- and MS subtype-specific treatment opportunities to combat MS., (© 2024. The Author(s).)

In the context of the alarming rise of infant obesity and its health implications, the present research aims to uncover disruptions in postprandial lipid metabolism and the composition of triglyceride-rich lipoproteins in obese adolescents. A double-blind, controlled clinical trial in the postprandial phase on 23 adolescents aged 12 to 16 years was carried out. Twelve participants were categorized as obese (BMI > 30 kg/m 2 and percentile > 95) and 11 as normal-weight (BMI = 20-25 kg/m 2 , percentile 5-85). Blood samples were collected after a 12-h overnight fast and postprandially after consumption of a standardized breakfast containing olive oil, tomato, bread, orange juice, and skimmed milk. Obese adolescents exhibited elevated triglyceride concentrations in both fasting and postprandial states and higher TG/apo-B48 ratios, indicating larger postprandial triglyceride-rich lipoprotein (TRL) particle size, which suggests impaired clearance. Obese subjects also exhibited higher n-6 PUFA concentrations, potentially linked to increased TRL hydrolysis and the release of pro-inflammatory adipokines. In contrast, TRL from normal-weight individuals showed higher concentrations of oleic acid and DHA (n-3 PUFA), with possible anti-inflammatory effects. The results indicate an interplay involving postprandial TRL metabolism and adipokines within the context of adolescent obesity, pointing to potential cardiovascular implications in the future.

The relationship between erythrocyte membrane n -3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n -3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case-control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n -3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n -3 PUFA and odds of breast cancer. Erythrocyte membrane α -linolenic acid (ALA), docosapentaenoic acid (DPA) and total n -3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n -3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: OR Q4 v . Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: OR Q4 v . Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n -3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n -3 PUFA and odds of breast cancer.

Omega-3 fatty acids ( n -3 FAs) are associated with a lower risk of ischemic stroke in patients with atrial fibrillation (AF). Antithrombotic mechanisms may in part explain this observation. Therefore, we examined the association of n -3 FAs with D-dimer and beta-thromboglobulin (BTG), markers for activated coagulation and platelets, respectively. The n -3 FAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were determined via gas chromatography in the whole blood of 2373 patients with AF from the Swiss Atrial Fibrillation cohort study (ClinicalTrials.gov Identifier: NCT02105844). In a cross-sectional analysis, we examined the association of total n -3 FAs (EPA + DHA + DPA + ALA) and the association of individual fatty acids with D-dimer in patients with detectable D-dimer values ( n = 1096) as well as with BTG ( n = 2371) using multiple linear regression models adjusted for confounders. Median D-dimer and BTG levels were 0.340 ug/mL and 448 ng/mL, respectively. Higher total n -3 FAs correlated with lower D-dimer levels (coefficient 0.94, 95% confidence interval (Cl) 0.90-0.98, p = 0.004) and lower BTG levels (coefficient 0.97, Cl 0.95-0.99, p = 0.003). Likewise, the individual n -3 FAs EPA, DHA, DPA and ALA showed an inverse association with D-dimer. Higher levels of DHA, DPA and ALA correlated with lower BTG levels, whereas EPA showed a positive association with BTG. In patients with AF, higher levels of n -3 FAs were associated with lower levels of D-dimer and BTG, markers for activated coagulation and platelets, respectively. These findings suggest that n-3 FAs may exert antithrombotic properties in patients with AF.

Microalgae are the main source of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), essential for the healthy development of most marine and terrestrial fauna including humans. Inverse correlations of algal EPA and DHA proportions (% of total fatty acids) with temperature have led to suggestions of a warming-induced decline in the global production of these biomolecules and an enhanced importance of high latitude organisms for their provision. The cold Arctic Ocean is a potential hotspot of EPA and DHA production, but consequences of global warming are unknown. Here, we combine a full-seasonal EPA and DHA dataset from the Central Arctic Ocean (CAO), with results from 13 previous field studies and 32 cultured algal strains to examine five potential climate change effects; ice algae loss, community shifts, increase in light, nutrients, and temperature. The algal EPA and DHA proportions were lower in the ice-covered CAO than in warmer peripheral shelf seas, which indicates that the paradigm of an inverse correlation of EPA and DHA proportions with temperature may not hold in the Arctic. We found no systematic differences in the summed EPA and DHA proportions of sea ice versus pelagic algae, and in diatoms versus non-diatoms. Overall, the algal EPA and DHA proportions varied up to four-fold seasonally and 10-fold regionally, pointing to strong light and nutrient limitations in the CAO. Where these limitations ease in a warming Arctic, EPA and DHA proportions are likely to increase alongside increasing primary production, with nutritional benefits for a non-ice-associated food web., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

The levels of blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are very variable and, in general, low in most of the world population. In this study, the effects of age, sex, COVID-19, and dietary habits on the lipid profile of the erythrocyte membranes were assessed in a sub-cohort of healthy population (N = 203) from a large cohort of individuals from the Basque Country, Spain, (AKRIBEA). Sex did not have an effect on RBC lipid profile. COVID-19 infected participants showed higher levels of DGLA. Oldest participants showed higher oleic acid, EPA and DHA levels. Arachidonic acid in RBC correlated positively with the intake of sunflower oil, butter, eggs, processed and red meat, whereas DHA and EPA correlated positively with oily and lean fish. Basque Country population showed lipid profiles similar to other high fish consuming countries, such as Italy and Japan. Baseline levels of the whole lipidomic profile of the RBC including SFA, MUFA and PUFA should be examined to obtain a better description of the health and nutritional status., Competing Interests: Declaration of Competing Interest C.F. is co-founder and scientific director of the company Lipinutragen srl, born as spin-off recognized officially by the National Council of Research and involved in research and development of the membrane lipidomic analysis. The company had no role in the design of the study; in the collection and interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The rest of the authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

During their life, women are likely to develop uterine diseases, which often compromise their fertile and perimenopausal age. Besides benign lesions like leiomyomas, several malignant neoplasms can occur, such as the uterine leiomyosarcoma, which represents the most frequent malignancy among the rarest uterine cancers. It presents several variants similar to both benign and malignant neoplasms, and sometimes it shares symptoms with the benign counterpart. In this scenario, for a correct diagnosis and a successful prognosis, it is mandatory to detect new reliable markers which strengthen histopathological outcomes and let define a more appropriate and less harmful therapy. Based on this concerning evidence, in the present study, Fourier Transform Infrared Microspectroscopy has been exploited at a cellular level on uterine leiomyoma and leiomyosarcoma cell lines to (1) identify specific spectral biomarkers able to distinguish between benign and malignant lesions, and (2) evaluate the efficacy of eicosapentaenoic and docosahexaenoic acids (respectively EPA and DHA), already successfully tested. Results evidenced reliable differences in the spectral signature of benign and malignant cells, mainly in terms of lipids and nucleic acids composition. Moreover, even if EPA and DHA seemed to exert different effects on the tested cell lines, no cytotoxic and/or anti-apoptotic actions were observed after omega-3 based treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the causal effect of plasma omega-3 polyunsaturated fatty acids (PUFAs) on sarcopenia-related traits (lean mass, grip strength and walking pace) utilizing two-sample Mendelian randomization (MR) approach., Methods: Based on genome-wide association study (GWAS) summary statistics, we performed two-sample MR applying the inverse variance weighted (IVW) as the primary method, supplemented with four additional sensitivity analyses. Furthermore, multivariable MR (MVMR) was applied to assess these associations independent of alcohol drinking, type 2 diabetes (T2D), triglycerides (TG), estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP)., Results: In univariable MR, the IVW analysis suggested no significant causal effect of genetically determined plasma omega-3 PUFAs on fat-free mass (right leg: β = 0.01, 95% CI = -0.02 to 0.05, P = 0.375; left leg: β = 0.01, 95% CI = -0.02 to 0.04, P = 0.446; right arm: β = 0.01, 95% CI = -0.02 to 0.05, P = 0.376; left arm: β = 0.01, 95% CI = -0.02 to 0.04, P = 0.384; trunk:β = 0.02, 95% CI = -0.02 to 0.06, P = 0.283; whole: β = 0.01, 95% CI = -0.03 to 0.04, P = 0.631), grip strength (right hand: β = -0.01, 95% CI = -0.03 to 0.01, P = 0.387; left hand: β = -0.01, 95% CI = -0.02 to 0.01, P = 0.553) and walking pace (β = 0.00, 95% CI = -0.01 to 0.02, P = 0.575), and sensitive analysis generated similar non-significant results. Furthermore, the MVMR revealed no independent causal association., Conclusions: Genetically determined plasma omega-3 PUFAs have no causal effect on sarcopenia-related traits., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: N-3 polyunsaturated fatty acids (n-3 PUFAs), abundant in oily fish, exert anti-inflammatory cardiovascular protective effects. We aimed to investigate the association between fish-derived n-3 PUFAs, lifestyle habits, and neutrophil-to-lymphocyte ratio (NLR), an atherosclerotic cardiovascular disease (ASCVD) marker., Methods: This cross-sectional study included 6,950 participants with no history of ASCVD, who underwent annual health check-ups (average age, 46.3 ± 13.0 years; male:female ratio, 58.8%) between April 2019 and March 2020 at the Health Planning Center, Nihon University Hospital. We calculated n-3 PUFA consumption using a questionnaire and the Japan National Health and Nutrition Survey., Results: The average fish consumption frequency and fish-derived n-3 PUFA consumption were 2.20 ± 1.28 days/week and 5.20 ± 3.11 g/week, respectively. A higher fish-derived n-3 PUFA consumption was associated with a lower NLR. Multiple-stepwise regression analysis revealed that higher fish-derived n-3 PUFA consumption and more aerobic exercise habits were significant independent determinants of lower NLR. Furthermore, higher fish-derived n-3 PUFA consumption was associated with habitual aerobic exercise habits., Conclusion: Thus, higher fish-derived n-3 PUFA consumption and more aerobic exercise habits may be synergistically associated with lower NLR. This association may explain the preventive effects of fish consumption on the ASCVD risk., (© 2023 S. Karger AG, Basel.)

Omega-3 polyunsaturated fatty acids (PUFAs) and vitamins exert multiple beneficial effects on host health, some of which may be mediated through the gut microbiome. We investigated the prebiotic potential of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and lipid-soluble phylloquinone (vitamin K 1 ), each at 0.2x, 1x and 5x using the simulator of the human intestinal microbial ecosystem (SHIME®) to exclude in vivo systemic effects and host-microbe interactions.Microbial community composition and, diversity [shotgun metagenomic sequencing] and microbial activity [pH, gas pressure, and production of short-chain fatty acids (SCFAs)] were measured over a period of 48 h. Fermentations supernatants were used to investigate the effect on gut barrier integrity using a Caco-2/goblet cell co-culture model.We found that EPA, DHA and vitamin K 1 increased alpha-diversity at 24 h when compared with control. Moreover, there was an effect on beta-diversity with changes in gut microbial composition, such as an increase in the Firmicutes/Bacteroidetes (F/B) ratio and a consistent increase in Veillonella and Dialister abundances with all treatments. DHA, EPA, and vitamin K 1 also modulated metabolic activity of the gut microbiome by increasing total SCFAs which was related mainly to an increase in propionate (highest with EPA and vitamin K 1 at 0.2x). Finally, we found that EPA and DHA increased gut barrier integrity with DHA at 1x and EPA at 5x ( p  < 0.05, respectively). In conclusion, our in vitro data further establish a role of PUFAs and vitamin K to modulate the gut microbiome with effects on the production of SCFAs and barrier integrity.

There exists significant heterogeneity in the 'freshness' of consumer marine- and plant-derived omega-3 (Ω3) supplements. Fears of rancidity, or the oxidation of consumer Ω3 supplements, has been debated in the literature with several prior authors reporting contradictory findings. We report the peroxide value (PV), para-anisidine value (p-AV) and total oxidation values (TOTOX) associated with 72 consumer Ω3 supplements sold in the United States sampled from 2014-2020. The effect of flavoring on the oxidation of the supplements was examined in an adjusted fixed effects model controlling for type of delivery system (enteric, liquid, animal- and vegetable-derived gelatin softgel, spray), source (algae, calamari, fish, krill, mussels), and certifications assigned by third-party organizations (e.g. USP). Overall, our results revealed that 68% (23/34) of flavored and 13% (5/38) unflavored consumer Ω3 supplements exceeded the TOTOX upper limit set by the Global Organization for EPA and DHA (GOED) voluntary monograph standard of ≤ 26, with 65% (22/34) flavored supplements and 32% (12/38) unflavored supplements failing the PV upper limit of ≤ 5 and 62% (21/34) flavored supplements exceeding the p-AV upper limit of ≤ 20. To our knowledge, no prior authors have modeled the impact of flavoring on oxidative status in 72 marine- and plant-derived Ω3 products sold in the U.S. We present our findings in this context and discuss the clinical implications related to the consumption of oxidized consumer fish oils and their effects on human health.

Technological improvements in dietary supplements and nutraceuticals have highlighted the significance of bioactive molecules in a healthy lifestyle. Eicosapentaenoic acid and Cervonic acid (DHA), omega-3 polyunsaturated fatty acids seem to be famed for their ability to prevent diverse physiological abnormalities. Selection of appropriate pretreatments and extraction techniques for extraction of lipids from robust microalgae cell wall are very important to retain their stability and bioactivity. Therefore, extraction techniques with optimized extraction parameters offer an excellent approach for obtaining quality oil with a high yield. Oils enriched in omega-3 are particularly imperiled to oxidation which ultimately affects customer acceptance. Bio active encapsulation could be one of the effective approaches to overcome this dilemma. This review paper aims to give insight into the cultivation methods, and downstream processes, various lipid extraction approaches, techniques for retaining oxidative stability, bioavailability and food applications based on extracted or encapsulated omega-3.

Background: The effect of marine omega-3 PUFAs on risk of stroke remains unclear., Methods: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome., Results: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P <0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P <0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P =0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P =0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD., Conclusions: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke., Competing Interests: Disclosures Dr O’Keefe reports major ownership interest in Cardiotabs. Dr Harris reports minor ownership interest in Omegaquant Analytics, LLC. Dr Sala-Vila reports travel and grant support from California Walnut Commission. Dr Mora reports compensation for consultant services from Quest Diagnostics. Dr Murphy reports compensation from Pharmavite for consultant services. Dr Bork reports grants from Karen Elise Jensens Fond. Dr Ärnlöv reports compensation from Astellas Pharma for other services; compensation from Boehringer Ingelheim for consultant services; compensation from AstraZeneca for other services; and compensation from Novartis for other services. Dr Geleijnse reports grants from National Institutes of Health to other; grants from Upfield Europe BV to other; and grants from The Dutch Heart Foundation to other. Dr Manson reports grants from National Institutes of Health and compensation from National Institutes of Health for other services. Dr Mora reports compensation from Pfizer for consultant services; employment by Brigham and Women’s Hospital; grants from National Institute of Diabetes and Digestive and Kidney Diseases; and grants from National Heart, Lung, and Blood Institute. Dr Melo van Lent reports grants from National Institutes of Health and grants from Alzheimer’s Association. Dr Mozaffarian reports grants from Rockefeller Foundation; compensation from Beren Therapeutics for other services; stock holdings in HumanCo; compensation from January Inc. for other services; compensation from Filtricine for other services; compensation from Perfect Day for other services; compensation from Tiny Organics for other services; grants from Bill and Melinda Gates Foundation; compensation from Calibrate for other services; grants from Vail Innovative Global Research; grants from Kaiser Permanente Fund at East Bay Community Foundation; compensation from DayTwo for other services; compensation from Instacart health for other services; compensation from Season Health for other services; grants from National Institutes of Health; compensation from Barilla for consultant services; stock holdings in Calibrate; compensation from Kaiser Permanente Fund for other services; compensation from HumanCo for other services

Background: Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce., Objectives: We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts., Methods: Omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined., Results: In the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y., Conclusion: This study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

The synthesis rates of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in rodents and humans are not agreed upon and depend on substrate availability independently of the capacity for synthesis. Therefore, we aimed to assess the activities of the enzymes for n-3 and n-6 PUFA synthesis pathways in liver, brain, testicle, kidney, heart, and lung, in relation to their protein concentration levels. Eight-week-old Balb/c mice (n = 8) were fed a standard chow diet (6.2% fat, 18.6% protein, and 44.2% carbohydrates) until 14 weeks of age, anesthetized with isoflurane and tissue samples were collected (previously perfused) and stored at -80°C. The protein concentration of the enzymes (Δ-6D, Δ-5D, Elovl2, and Elovl5) were assessed by ELISA kits; their activities were assayed using specific PUFA precursors and measuring the respective PUFA products as fatty acid methyl esters by gas chromatographic analysis. The liver had the highest capacity for PUFA biosynthesis, with limited activity in the brain, testicles, and kidney, while we failed to detect activity in the heart and lung. The protein concentration and activity of the enzymes were significantly correlated. Furthermore, Δ-6D, Δ-5D, and Elovl2 have a higher affinity for n-3 PUFA precursors compared to n-6 PUFA. The capacity for PUFA synthesis in mice mainly resides in the liver, with enzymes having preference for n-3 PUFAs., (© 2023 International Union of Biochemistry and Molecular Biology.)

Background/aim: The prevalence of cognitive impairment (CI) is high in hemodialysis patients. In this study, the relationship between CI and serum carnitine, plasma omega-3, omega-6 and omega-3/omega-6 fatty acid ratio was evaluated in hemodialysis patients., Materials and Methods: Sixty two patients [male: 40 (64.5%), mean age 51±13 years] were included in this cross-sectional study. Serum total and free-carnitine levels were determined by ELISA. Plasma omega-3 [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and omega-6 [arachidonic acid (AA), dihomo gamma linoleic acid (DGLA)] levels were measured using LC-ESI-MS/MS. According to the Montreal Cognitive Assessment (MoCA) scores, ≤24 points were considered as CI. MoCA score ≤24 and >24 were determined as Group 1 and Group 2, respectively., Results: Group 1 had significantly higher AA+DGLA/EPA+DHA ratios and lower free-carnitine, DHA and EPA+DHA levels compared to Group 2 (P=0.008, P=0.040, P=0.032, P=0.032, respectively). Group 1 had a statistically lower education level (P<0.05). Negative correlation was found between MoCA scores and AA+DGLA/EPA+DHA ratios (r s =-0.284, P=0.026). Free-carnitine levels were positively correlated with EPA and EPA+DHA levels (r s =0.278, P=0.030 and r s =0.271, P=0.034, respectively), and negative correlated with AA+DGLA/EPA+DHA ratios (r s =-0.414, P=0.001). In multivariate logistic regression analysis, MoCA scores was associated with AA+DGLA/EPA+DHA ratio (P=0.009) and education level (P<0.001)., Conclusion: It was determined that high AA+DGLA/EPA+DHA ratio and low education level could be independent risk factors of the CI. It has been shown that free-carnitine level can have positive effects on plasma EPA+DHA and AA+DGLA distributions. Low omega-3 fatty acid levels may be associated with CI in hemodialysis patients, and low carnitine level may contribute partially to this process. In addition, cognitive education programs may have an effect on preventing CI in hemodialysis patients with low education levels., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Omega-3 fatty acids have gained attention due to numerous health benefits. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) are long chain omega-3 fatty acids produced from precursor ALA (α-linolenic acid) in humans but their rate of biosynthesis is low, therefore, these must be present in diet or should be taken as supplements. The commercial sources of omega-3 fatty acids are limited to vegetable oils and marine sources. The rising concern about vegan source, fish aquaculture conservation and heavy metal contamination in fish has led to the search for their alternative source. Microalgae have gained importance due to the production of high-value EPA and DHA and can thus serve as a sustainable and promising source of long chain omega-3 fatty acids. Although the bottleneck lies in the optimization for enhanced production that involves strategies viz. strain selection, optimization of cultivation conditions, media, metabolic and genetic engineering approaches; while co-cultivation, use of nanoparticles and strategic blending have emerged as innovative approaches that have made microalgae as potential candidates for EPA and DHA production. This review highlights the possible strategies for the enhancement of EPA and DHA production in microalgae. This will pave the way for their large-scale production for human health benefits.

The fatty acid content and the localization and expression of phospholipase A 2 (PLA 2 ) in the testis of Hu sheep were investigated. A total of 18 six-month-old Hu sheep were divided into small group (S, with left testis weight < 50 g), medium group (M, with left testis weight among 90-110 g), and large group (L, with left testis weight >160 g), which had six individuals each. The expression of PLA 2 in testicular tissues of different sizes was analyzed by immunohistochemistry, RT-qPCR, and Western blot. The fatty acid profile was detected by gas chromatography. Immunohistochemical labeling determined that PLA 2 protein was expressed in the Leydig and Sertoli cells of testis, and the immunohistochemical average optional density in the S group was significantly greater than the L group (P < 0.05). RT-qPCR and Western blot analysis showed that PLA 2 in the S group was greater than that in the L group (P < 0.05). Docosahexaenoic acid, ω-3 polyunsaturated fatty acid (PUFA), and total PUFA content in the testis of the L group were significantly less than those of the S and M groups (P < 0.01). This study showed that PLA 2 content in the S group was greater than that in the L group., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Omega-3 fatty acids (omega-3 FAs) have been widely recognized for their therapeutic advantages, including anti-inflammatory and cardioprotective properties. They have shown promise in enhancing regulatory function, promotingdevelopment and mitigating the progression of diabetes and cancer. The scientific communities, along with industries, are actively endorsing initiatives aimed at increasing the daily intake of lipids rich in omega-3 FAs. Nevertheless, incorporating polyunsaturated FAs (PUFAs) into food products poses several challenges due to their susceptibility to oxidation when exposed to oxygen, high temperatures, and moisture. This oxidative deterioration results in undesirable flavours and a loss of nutritional value. Various methods, including physical blending, interesterification, and encapsulation, have been utilized as ways to enhance the stability of edible oils rich in PUFA against oxidation. Encapsulation has emerged as a proven strategy for enhancing the oxidative stability and functional properties of omega-3 FA-rich oils. Multiple encapsulation methods have been developed to stabilize and improve the delivery of omega-3 FAs in food products. The selection of an appropriate encapsulation method depends on the desired application of the encapsulated oil. In addition, encapsulation enhances the bioavailability of omega-3 FAs by promoting increased absorption of the encapsulated form in the intestinal epithelium. This review discusses the techniques and principles of omega-3 FA-rich oil encapsulation and its role in improving stability and bioavailability. Furthermore, it also investigates the potential health benefits of these encapsulated oils. This review explores the variations in bioavailability based on encapsulation techniques and processing, offering vital insights for nutrition and product development., (© 2023 Institute of Food Technologists®.)

Background & Aims: Few studies have investigated alternations in human milk polyunsaturated fatty acid (PUFA) composition in the context of maternal obesity and its effects on infant growth trajectories. This study explored whether maternal weight status and breastfeeding type influence human milk FA composition and infant anthropometry during the first six months of life., Methods: Mother-infant dyads were enrolled from the Prediction of Allergies in Taiwanese Children birth cohort study. Data concerning maternal pre-pregnancy weight, infants' breastfeeding practices, and anthropometric data were obtained regularly. We identified and compared between the composition of 30 FAs in the colostrum and 2-month milk, respectively, in obese/overweight (OB/OW) and normal-weight (NW) mothers. Multiple linear regression analyses were performed to determine the association between PUFA composition at different lactation stages and infant anthropometric parameter changes and to identify the independent variables for body mass index (BMI) z-scores by six months of age., Results: We included 338 mother-infant dyads (OB/OW mothers, 16.9 %). OB/OW mothers exhibited lower total n-3 PUFAs (P = 0.035), higher ratios of arachidonic acid (C20:4n-6)/eicosapentaenoic acid (C20:5n-3) + docosahexaenoic acid (C22:6n-3), and n-6/n-3 PUFA in colostrum (P = 0.037 and 0.011, respectively), and their offspring had higher body weight and BMI z-scores. Nevertheless, no PUFA composition or n-6/n-3 PUFA ratios in colostrum and 2-month milk were associated with anthropometric parameter changes by age 6 months. Infant birth weight z-scores were independently associated with BMI outcomes at age 6 months (adjusted β = 0.16, 95 % confidence interval (0.05-0.35), P = 0.010) CONCLUSION: Neither n-3 nor n-6 PUFA profiles nor n-6/n-3 PUFA ratios at different lactation stages were found to be associated with anthropometric changes by age 6 months, suggesting that human milk PUFA composition may not be an important determinant of early infant growth trajectories., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In recent years, scientific research has increasingly focused on the cardiovascular benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements. The most promising results emerged from the new trials on a high-dose eicosapentaenoic acid (EPA)-only approach, instead of the previously prescribed therapy with EPA + docosahexaenoic acid (DHA). The evidence of the reduction of cardiovascular events in patients at high cardiovascular risk with EPA is intriguing. However, physicians have expressed concern about the potential high risk of atrial fibrillation (AF) occurrence due to such an approach. This study aims to investigate the current evidence on the cardiovascular benefits of EPA and its association with atrial arrhythmogenesis. Current guidelines consider EPA (as IPE) treatment for selected patients but with no specific indication regarding AF risk evaluation. We propose a flowchart that could be a starting point for the future development of an algorithm to help clinicians to prescribe EPA safely and effectively, especially in patients at high risk of incipient AF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Recent data indicate considerable variability in response to very long chain omega-3 fatty acid supplementation on cardiovascular disease risk. This inconsistency may be due to differential effects of EPA vs DHA and/or sex-specific responses., Methods: Sixteen subjects (eight men and eight women) 50-75 y and with low-grade chronic inflammation participated in a randomized controlled crossover trial comparing 3 g/d EPA, 3 g/d DHA, and placebo (3 g/d high oleic acid sunflower oil). Blood monocytes were isolated at the end of each phase for RNA-sequencing., Results: Sex dimorphism in monocyte gene expression was observed, therefore, data for men and women were analyzed separately. 1088 genes were differentially expressed in men and 997 in women (p < 0.05). In both men and women, EPA and DHA repressed genes involved in protein turnover and mitochondrial energy metabolism, relative to placebo. In men only, EPA and DHA upregulated genes related to wound healing and PPARα activation. In women only, EPA and DHA activated genes related to ER stress response. Relative to DHA, EPA resulted in lower expression of genes involved in inflammatory processes in men, and lower expression of genes involved in ER stress response in women., Conclusions: EPA and DHA supplementation elicited both similar and differential effects on monocyte transcriptome, some of which were sex specific. The observed variability in response to EPA and DHA in men and women could in part explain the conflicting results from previous cardiovascular clinical trials using omega-3 fatty acids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of agents with anti-inflammatory properties in youth DD have not been systematically reviewed. Here, the existing evidence on the use of anti-inflammatory drugs (including polyunsaturated fatty acids, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, pioglitazone, corticosteroids, and minocycline or modafinil) in children and adolescents with DD was synthesized using meta-analysis. The PROSPERO preregistered search yielded 22 records meeting search criteria. Of these, data from 19 primary studies (n = 1366 subjects) were subjected to meta-analysis. A significant but small effect in favor of anti-inflammatory agents in reducing depressive symptoms in youth with DD was found (SMD = -0.29, 95 % CI = -0.514; -0.063, p = 0.01). Post-hoc analyzes of drug subclasses found a significant effect of omega-3 fatty acids in reducing depressive symptoms. Results underline the importance to consider inflammatory pathways in the supplemental treatment of youth with DD. Further research is warranted, to clarify if anti-inflammatory agents are only effective in a subpopulation of patients (inflammatory biotype of depression in youth) and/or to alleviate specific symptom domains of depression (e.g., cognitive symptoms)., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)