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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.

Abstract A correlation between omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and osteoarthritis (OA) incidence has been established, but research on the long-term outlook of OA patients remains limited. This study investigates the association between omega-3 PUFA intake and the risk of all-cause and cardiovascular (CV) mortality in the U.S. OA population. A cohort of 3,467 OA patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was studied. Cox proportional hazards regression models, Kaplan-Meier curves, and subgroup analyses were used to evaluate the relationship between omega-3 PUFA intake and mortality. The dose-response relationship was examined using a restricted cubic spline (RCS) model. Among the 3,467 OA patients, there were 459 all-cause deaths and 175 CV deaths. Omega-3 PUFAs were significantly negatively correlated with all-cause mortality (95% CI: 0.59–0.93, p = 0.011) but not with CV mortality (95% CI: 0.29–1.04, p = 0.056). Higher omega-3 PUFA intake was associated with a 49% decrease in all-cause mortality. Kaplan-Meier curves showed lower all-cause mortality rates in those with higher omega-3 PUFA intake. The inverse correlation was more pronounced among individuals living with a partner. The dose-response analysis indicated a linear negative relationship between omega-3 PUFA intake and all-cause mortality. Increased intake of omega-3 PUFAs is associated with a decreased risk of all-cause mortality in OA patients.

A correlation between omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and osteoarthritis (OA) incidence has been established, but research on the long-term outlook of OA patients remains limited. This study investigates the association between omega-3 PUFA intake and the risk of all-cause and cardiovascular (CV) mortality in the U.S. OA population. A cohort of 3,467 OA patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was studied. Cox proportional hazards regression models, Kaplan-Meier curves, and subgroup analyses were used to evaluate the relationship between omega-3 PUFA intake and mortality. The dose-response relationship was examined using a restricted cubic spline (RCS) model. Among the 3,467 OA patients, there were 459 all-cause deaths and 175 CV deaths. Omega-3 PUFAs were significantly negatively correlated with all-cause mortality (95% CI: 0.59–0.93, p = 0.011) but not with CV mortality (95% CI: 0.29–1.04, p = 0.056). Higher omega-3 PUFA intake was associated with a 49% decrease in all-cause mortality. Kaplan-Meier curves showed lower all-cause mortality rates in those with higher omega-3 PUFA intake. The inverse correlation was more pronounced among individuals living with a partner. The dose-response analysis indicated a linear negative relationship between omega-3 PUFA intake and all-cause mortality. Increased intake of omega-3 PUFAs is associated with a decreased risk of all-cause mortality in OA patients. [ABSTRACT FROM AUTHOR]

Literature is inconsistent regarding the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) supplementation on patients with metabolic syndrome (MetS) and related cardiovascular diseases (CVDs). Therefore, the aim of this systematic review and meta-analysis is to summarize data from available randomized controlled trials (RCTs) on the effect of omega-3 PUFAs on lipid profiles, blood pressure, and inflammatory markers. We systematically searched PubMed, Embase, and Cochrane Library databases to identify the relevant RCTs until 1 November 2022. Weighed mean difference (WMD) was combined using a random-effects model. Standard methods were applied to assess publication bias, sensitivity analysis, and heterogeneity among included studies. A total of 48 RCTs involving 8,489 subjects met the inclusion criteria. The meta-analysis demonstrated that omega-3 PUFAs supplementation significantly reduced triglyceride (TG) (WMD: −18.18 mg/dl; 95% CI: −25.41, −10.95; p < 0.001), total cholesterol (TC) (WMD: −3.38 mg/dl; 95% CI: −5.97, −0.79; p = 0.01), systolic blood pressure (SBP) (WMD: −3.52 mmHg; 95% CI: −5.69, −1.35; p = 0.001), diastolic blood pressure (DBP) (WMD: −1.70 mmHg; 95% CI: −2.88, −0.51; p = 0.005), interleukin-6 (IL-6) (WMD: −0.64 pg/ml; 95% CI: −1.04, −0.25; p = 0.001), tumor necrosis factor-α (TNF-α) (WMD: −0.58 pg/ml; 95% CI: −0.96, −0.19; p = 0.004), C-reactive protein (CRP) (WMD: −0.32 mg/l; 95% CI: −0.50, −0.14; p < 0.001), and interleukin-1 (IL-1) (WMD: −242.95 pg/ml; 95% CI: −299.40, −186.50; p < 0.001), and significantly increased in high-density lipoprotein (HDL) (WMD: 0.99 mg/dl; 95% CI: 0.18, 1.80; p = 0.02). However, low-density lipoprotein (LDL), monocyte chemoattractant protein-1 (MCP-1), intracellular adhesion molecule-1 (ICAM-1), and soluble endothelial selectin (sE-selectin) were not affected. In subgroup analyses, a more beneficial effect on overall health was observed when the dose was ≤ 2 g/day; Omega-3 PUFAs had a stronger anti-inflammatory effect in patients with CVDs, particularly heart failure; Supplementation with omega-3 PUFAs was more effective in improving blood pressure in MetS patients and blood lipids in CVDs patients, respectively. Meta-regression analysis showed a linear relationship between the duration of omega-3 PUFAs and changes in TG (p = 0.023), IL-6 (p = 0.008), TNF-α (p = 0.005), and CRP (p = 0.025). Supplementation of omega-3 PUFAs had a favorable effect on improving TG, TC, HDL, SBP, DBP, IL-6, TNF-α, CRP, and IL-1 levels, yet did not affect LDL, MCP-1, ICAM-1, and sE-selectin among patients with MetS and related CVDs. [ABSTRACT FROM AUTHOR]

Introduction: Blast injury has been implicated as the major cause of traumatic brain injury (TBI) and ocular system injury, in military operations in Iraq and Afghanistan. Soldiers exposed to traumatic stress also have undiagnosed, chronic vision problems. Here we hypothesize that excessive intake of ω-6 fatty acid linoleic acid (LA) and insufficiency of dietary long chain ω-3 polyunsaturated fatty acids (PUFAs, e.g., docosahexaenoic acid; DHA) would dysregulate endocannabinoid-mediated neuronal plasticity and immune response. The study objective was to determine the effect of blast-TBI and traumatic stress on retinal gene expression and assess the role of dietary deficiency of long chain ω-3 PUFAs on the vulnerability to these injury models. Methods: Linoleic acid was used as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% present in the current western diets, and these custom LA diets were also devoid of long chain ω-3 PUFAs. Animals were exposed to a simulated blast overpressure wave followed by a weight drop head-concussion to induce TBI. A Separate group of rats were subjected to traumatic stress by a forced immersion underwater. Results: Our findings showed that blast-TBI exposure, post 14 days, produced significant neuropathological changes such as axonal degeneration in the brain optic tracts from all the three diet groups, especially in rats fed the DHA-deprived 1 en% LA diet. Transcriptomic analysis showed that presence of DHA in the house chow diet prevented blast-induced disruption of neuronal plasticity by activating molecular networks like SNARE signaling, endocannabinoid pathway, and synaptic long-term depression when compared to DHA-deprived 8 en% LA diet group. Under traumatic stress, retinal synaptic function, neurovascular coupling, and opioid signaling mechanisms were dysregulated in rodents fed DHA-deficient diets (i.e., 8 en% LA and 1 en% LA), where reducing the levels of ω-6 linoleic acid from 8 en% to 1 en% was associated with increased neuronal plasticity and suppressed immune signaling. Conclusion: The findings of our study suggest that deprivation of long chain ω-3 PUFAs in the diet affects endocannabinoid-mediated neuronal plasticity, vascular function and inflammatory response that could influence the resistance of veterans to TBI and psychological trauma. [ABSTRACT FROM AUTHOR]

Some individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience anosmia, or loss of smell. Although the prevalence of anosmia has decreased with the emergence of the Omicron variant, it remains a significant concern. This review examines the potential role of polyunsaturated fatty acids (PUFAs), particularly omega-3 PUFAs, in treating COVID-19-induced anosmia by focusing on the underlying mechanisms of the condition. Omega-3 PUFAs are known for their anti-inflammatory, neuroprotective, and neurotransmission-enhancing properties, which could potentially aid in olfactory recovery. However, study findings are inconsistent. For instance, a placebo-controlled randomized clinical trial found no significant effect of omega-3 PUFA supplementation on olfactory recovery in patients with COVID-19-induced anosmia. These mixed results highlight the limitations of existing research, including small sample sizes, lack of placebo controls, short follow-up periods, and combined treatments. Therefore, more rigorous, large-scale studies are urgently needed to definitively assess the therapeutic potential of omega-3 PUFAs for olfactory dysfunction. Further research is also crucial to explore the broader role of PUFAs in managing viral infections and promoting sensory recovery. [ABSTRACT FROM AUTHOR]

Energy metabolism disorder, mainly exhibiting the inhibition of fatty acid degradation and lipid accumulation, is highly related with aging acceleration. However, the intervention measures are deficient. Here, we reported Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), especially EPA, exerted beneficial effects on maintaining energy metabolism and lipid homeostasis to slow organ aging. As the endogenous agonist of peroxisome proliferator–activated receptor α (PPARα), Omega-3 PUFAs significantly boosted fatty acid β-oxidation and ATP production in multiple aged organs. Consequently, Omega-3 PUFAs effectively inhibited age-related pathological changes, preserved organ function, and retarded aging process. The beneficial effects of Omega-3 PUFAs were also testified in mfat-1 transgenic mice, which spontaneously generate abundant endogenous Omega-3 PUFAs. In conclusion, our study innovatively demonstrated Omega-3 PUFAs administration in diet slow aging through promoting energy metabolism. The supplement of Omega-3 PUFAs or fat-1 transgene provides a promising therapeutic approach to promote healthy aging in the elderly.

This study is a critical review to ascertain whether Omega-3 (Poly Unsaturated Fatty Acids) PUFAs can help reduce the risk of Coronary Heart disease (CHD) and (CHD) mortality. Omega-3 PUFAs (Poly Unsaturated Fatty Acids) are supplements regularly recommended globally to equalise essential body nutrients and to maintain or improve health. The review captured Mediterranean diets, fatty fish and heart disease, Omega-3 supplements, Clinical Evidence, Positive Clinical Studies, Negative Clinical Outcomes, Net Benefit of Clinical Evidence, the evaluation of the advantages Omega-3 PUFAs on CVD risk factors, especially on CHD and the explanation of the differences in clinical studies. The omega-supplements was found to have been used for different medical problems such as pulmonary, psychiatric, dermatologic, gastrointestinal, renal, rheumatic, and metabolic conditions, they have also commonly been used to prevent or reduce both primary and secondary cardiovascular diseases, particularly coronary heart disease. Many epidemiological studies, as well as extensive randomised clinical (RCTs), indicate that average dosage omega-3 PUFAs substantially minimise the dangers of coronary artery disease (CHD). Based on scientific evidence, it was recommended that patients with CHD, those with or at risk of CHD should take the right dose of omega-3 PUFAs. Much higher doses are required to decrease triglyceride levels. Nonetheless, recent RCTs raise questions about the function of omega-3 PUFAs in CHD treatment. The review also analysed the RCTs and systematic evidence of omega-3 PUFAs to have a clear understanding of the present role of omega-3 PUFAs in reducing or preventing the risk of CHD and CHD mortality. [ABSTRACT FROM AUTHOR]

Late-life depression (LLD) is associated with risk of dementia, yet intervention of LLD provides an opportunity to attenuate subsequent cognitive decline. Omega-3 polyunsaturated fatty acids (PUFAs) supplement is a potential intervention due to their beneficial effect in depressive symptoms and cognitive function. To explore the underlying neural mechanism, we used resting-state functional MRI (rs-fMRI) before and after omega-3 PUFAs supplement in older adults with LLD. A 52-week double-blind randomized controlled trial was conducted. We used multi-scale sample entropy to analyze rs-fMRI data. Comprehensive cognitive tests and inflammatory markers were collected to correlate with brain entropy changes. A total of 20 patients completed the trial with 11 under omega-3 PUFAs and nine under placebo. While no significant global cognitive improvement was observed, a marginal enhancement in processing speed was noted in the omega-3 PUFAs group. Importantly, participants receiving omega-3 PUFAs exhibited decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. The brain entropy changes of the PCG in the omega-3 PUFAs group correlated with improvement of language function and attenuation of interleukin-6 levels. Sample size is small with only marginal clinical effect. These findings suggest that omega-3 PUFAs supplement may mitigate cognitive decline in LLD through anti-inflammatory mechanisms and modulation of brain entropy. Larger clinical trials are warranted to validate the potential therapeutic implications of omega-3 PUFAs for deterring cognitive decline in patients with late-life depression. • Brain entropy decreased in left posterior cingulate gyrus (PCC) and various brain regions after omega-3 PUFAs use in late-life depressed patients. • The reduction of brain entropy in left PCG correlated with improvement in language function and IL-6 level. • Only marginal improvement in processing speed was found clinically after omega-3 PUFAs supplement. • The anti-inflammatory and beneficial cognitive effects of omega-3 PUFAs in late-life depression are associated with brain entropy changes in left PCG. [ABSTRACT FROM AUTHOR]

IntroductionBlast injury has been implicated as the major cause of traumatic brain injury (TBI) and ocular system injury, in military operations in Iraq and Afghanistan. Soldiers exposed to traumatic stress also have undiagnosed, chronic vision problems. Here we hypothesize that excessive intake of ω-6 fatty acid linoleic acid (LA) and insufficiency of dietary long chain ω-3 polyunsaturated fatty acids (PUFAs, e.g., docosahexaenoic acid; DHA) would dysregulate endocannabinoid-mediated neuronal plasticity and immune response. The study objective was to determine the effect of blast-TBI and traumatic stress on retinal gene expression and assess the role of dietary deficiency of long chain ω-3 PUFAs on the vulnerability to these injury models.MethodsLinoleic acid was used as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% present in the current western diets, and these custom LA diets were also devoid of long chain ω-3 PUFAs. Animals were exposed to a simulated blast overpressure wave followed by a weight drop head-concussion to induce TBI. A Separate group of rats were subjected to traumatic stress by a forced immersion underwater.ResultsOur findings showed that blast-TBI exposure, post 14 days, produced significant neuropathological changes such as axonal degeneration in the brain optic tracts from all the three diet groups, especially in rats fed the DHA-deprived 1 en% LA diet. Transcriptomic analysis showed that presence of DHA in the house chow diet prevented blast-induced disruption of neuronal plasticity by activating molecular networks like SNARE signaling, endocannabinoid pathway, and synaptic long-term depression when compared to DHA-deprived 8 en% LA diet group. Under traumatic stress, retinal synaptic function, neurovascular coupling, and opioid signaling mechanisms were dysregulated in rodents fed DHA-deficient diets (i.e., 8 en% LA and 1 en% LA), where reducing the levels of ω-6 linoleic acid from 8 en% to 1 en% was associated with increased neuronal plasticity and suppressed immune signaling.ConclusionThe findings of our study suggest that deprivation of long chain ω-3 PUFAs in the diet affects endocannabinoid-mediated neuronal plasticity, vascular function and inflammatory response that could influence the resistance of veterans to TBI and psychological trauma.

The gut microbiota forms a complex and metabolically active ecosystem. Changes in gut microbiota activity correlate with the health status.. It is not known whether the dysfunction of the intestinal microbiota due to undesirable changes in the qualitative and quantitative composition (so-called dysbiosis) is a cause or effect of disease states. Long-term dietary habits play a key role in the formation of the human-specific gut microbiota. Despite many publications on the effects of carbohydrates with prebiotic properties, the effects of dietary fats, such as omega-3 polyunsaturated fatty acids (PUFAs), on the gut microbiota are not fully explained. The main bioactive forms in humans among omega-3 PUFAs, are eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6). These compounds play an important role in the proper functioning of the human body, as well as in the prevention and treatment of many diseases, so they are widely used as nutraceuticals. Few studies with adults have shown changes in gut microbiota after omega-3 PUFAs supplementation and a reduction in dysbiosis. Omega-3 PUFAs can influence the diversity and abundance of the gut microbiome, on the other hand, gut microbes can affect the metabolism and absorption of these compounds. Omega-3 PUFAs affect the gut microbiome in three main ways: by modulating the type and abundance of intestinal microbes, by altering the levels of proinflammatory mediators such as endotoxins (lipopolysaccharides) and interleukine 17; and by regulating the levels of short-chain fatty acids (SCFAs). The aim of this study was to summarize the current state of knowledge on the biological activity of the intestinal microbiota, particularly the interactions of the microbiota and omega-3 polyunsaturated fatty acids in humans. The data search was performed in July 2023 in the PubMed database and publicly available literature using the following queries: "intestinal microbiota", "microbiome", "omega-3 polyunsaturated acids intestinal microbiota", "EPA intestinal microbiota", "DHA intestinal microbiota". The article discusses the interactions between the intestinal microbiota and omega-3 PUFAs. The issues presented allow to conclude that elucidating the mechanisms of interaction between the gut microbiota and omega-3 PUFAs, may provide the basis for developing more effective therapeutic strategies.

Background and AimsPhysical performance is a major contributor of mobility and independence during older life. Despite a progressive decline in musculoskeletal function starts from middle age, several factors acting during the life-course can negatively influence musculoskeletal functional capacities. Lifestyle interventions incorporating nutrition and physical exercise can help maximizing the muscle functional capacities in early life as well as preserving them later in life. Among various dietary compounds, omega-3 polyunsaturated fatty acids (PUFAs) are gaining growing attention for their potential effects on muscle membrane composition and muscle function. Indeed, several pathways are enhanced, such as an attenuation of pro-inflammatory oxidative stress, mitochondrial function, activation of the mammalian target of rapamycin (mTOR) signaling and reduction of insulin resistance.MethodsWe performed a narrative review to explore the existing literature on the relationship between omega-3 PUFAs and physical performance across the life-course.ResultsGrowing evidence from randomized controlled trials (RCTs) suggests beneficial effects of omega-3 PUFAs on muscle function, including physical performance parameters in mid to later life. On the other hand, despite a direct association in early life is not available in literature, some mechanisms by which omega-3 PUFAs may contribute to improved adult physical performance could be hypothesized.ConclusionOmega-3 PUFAs are gaining growing attention for their positive effect on muscle function parameters. The integration of physical function measures in future studies would be of great interest to explore whether omega-3 PUFAs could contribute to improved muscle function, starting from early life and extending throughout the lifespan. However, larger and high-quality RCTs are needed to fully elucidate the beneficial effects of omega-3 PUFAs supplementation on muscle mass and function.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. Methods We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. Results We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1β, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. Conclusion These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.

Some individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience anosmia, or loss of smell. Although the prevalence of anosmia has decreased with the emergence of the Omicron variant, it remains a significant concern. This review examines the potential role of polyunsaturated fatty acids (PUFAs), particularly omega-3 PUFAs, in treating COVID-19-induced anosmia by focusing on the underlying mechanisms of the condition. Omega-3 PUFAs are known for their anti-inflammatory, neuroprotective, and neurotransmission-enhancing properties, which could potentially aid in olfactory recovery. However, study findings are inconsistent. For instance, a placebo-controlled randomized clinical trial found no significant effect of omega-3 PUFA supplementation on olfactory recovery in patients with COVID-19-induced anosmia. These mixed results highlight the limitations of existing research, including small sample sizes, lack of placebo controls, short follow-up periods, and combined treatments. Therefore, more rigorous, large-scale studies are urgently needed to definitively assess the therapeutic potential of omega-3 PUFAs for olfactory dysfunction. Further research is also crucial to explore the broader role of PUFAs in managing viral infections and promoting sensory recovery.

• Omega-3 PUFA supplementation is associated with a reduced risk of long-term psychiatric sequelae, including depression, anxiety, and insomnia, following SARS-CoV-2 infection. • The beneficial effects of omega-3 PUFAs were consistent across different demographic groups. • These findings suggest the potential of omega-3 PUFAs as a preventive strategy for post-COVID-19 mental health outcomes, warranting further investigation through placebo-controlled clinical trials. Early prevention and management of psychiatric symptoms in long COVID (or post-COVID-19 conditions) are crucial for reducing long-term disability. Existing clinical guidelines recommend the use of omega-3 polyunsaturated fatty acids (PUFAs) as a promising therapeutic approach for various common psychiatric disorders due to their anti-inflammatory and neuroprotective characteristics. This study aims to investigate the potential efficacy of omega-3 PUFAs in alleviating the psychiatric sequelae following COVID-19. This 1-year retrospective cohort study used the TriNetX electronic health records network to examine the effects of omega-3 PUFAs supplements on psychiatric sequelae in adults diagnosed with COVID-19. Using propensity-score matching, the study compared those who used omega-3 PUFAs supplements with those who did not, assessing outcomes including depression, anxiety disorders, insomnia, and other somatic conditions up to a year after COVID-19 diagnosis. In 16,962 patients who received omega-3 PUFAs supplements and 2,248,803 who did not, omega-3 supplementation significantly reduced the risk of developing psychiatric sequelae post-COVID-19 diagnosis (HR, 0.804; 95% CI, 0.729 to 0.888). Specifically, the risks for depression (HR, 0.828; 95% CI, 0.714 to 0.960), anxiety disorders (HR, 0.833; 95% CI, 0.743 to 0.933), and insomnia (HR, 0.679; 95% CI, 0.531 to 0.869) were reduced in the omega-3 group. This effect was consistent across sex, race, 18–59 age group, and patients with less than two doses of the COVID-19 vaccine. The omega-3 group also had a lower risk of cough and myalgia, but no significant difference was noted for other symptoms like chest pain, abnormal breathing, abdominal issues, fatigue, headache, and cognitive symptoms. Omega-3 PUFAs may require re-evaluation as a preventive strategy against adverse mental health outcomes post-COVID-19 in placebo-controlled clinical trials. [ABSTRACT FROM AUTHOR]

Resolvin E1 is a metabolite of eicosapentaenoic acid (EPA) which is one of the omega-3 polyunsaturated fatty acids (omega-3 PUFAs). The antiplatelet properties of omega-3 PUFAs are well known, but the effect of resolvin E1 on platelets via the collagen receptors is extremely poorly reported. We investigated the effect of resolvin E1 on collagen-induced platelet aggregation, activation, and reactivity, and also platelet membrane fluidity. The ultimate and statistically significant results showed that resolvin E1 may inhibit platelet reactivity due to the reduction of collagen-induced platelet aggregation in platelet-rich plasma and isolated platelets, but not in whole blood. Also, resolvin E1 significantly reduced P-selectin exposure on collagen-stimulated platelets. Moreover, we demonstrated that resolvin E1 can maintain platelet membrane structure (without increasing membrane fluidity). The association between platelet reactivity and membrane fluidity, including resolvin E1 and collagen receptors requires further research. However, the goal of this study was to shed light on the molecular mechanisms behind the anti-aggregative effects of resolvin E1 on platelets, which are still not fully clarified. We also indicate an innovative research direction focused on further analysis and then use of omega-3 PUFAs metabolites as antiplatelet compounds for future applications in the treatment and prevention of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Although data indicate omega-3 polyunsaturated fatty acids are beneficial nutrients in cancer therapy, the evidences for efficacy of nutritional interventions during chemo (radio) therapy are still limited. The leading goal of the present meta-analysis was to summarize randomized controlled trials involving the administration of ω-3 PUFA-enriched oral nutritional supplements during chemo (radio) therapy, and evaluate the effects on nutritional status and clinical outcomes in patients. We systematically searched PubMed, Embase, Web of Science, Cochrane databases to identify interventions assessing body weight, BMI, immune and inflammatory indicators, plasma omega-3 fatty acids and adverse events, with subgroup analyses for region, types of ω-3 fatty acids, dose, duration and dosage form. In total, 22 studies including 1155 participants met the inclusion criteria. Meta-analysis showed a significant increase in body weight (BW) (WMD = 0.59 kg, 95% CI: 0.06, 1.13, P = 0.03), body mass index (BMI) (WMD = 0.43 kg/m2, 95% CI: 0.07, 0.79, P = 0.02), and plasma total ω-3 fatty acids (SMD = 2.52, 95% CI: 1.27, 3.78, P<0.0001), and a significant reduction in plasma levels of C-reactive protein (CRP) (SMD= −0.53, 95% CI: −0.80, −0.25, P = 0.0001), tumor necrosis factor-α (TNF-α) (WMD = −0.40 pg/mL, 95% CI: −0.80, −0.01, P = 0.05), interleukin 6 (IL-6) (WMD = −1.25 pg/mL, 95% CI: −2.41, −0.10, P = 0.03) and the incidence of adverse events (RR= 0.72, 95% CI: 0.54, 0.95, P = 0.02). However, plasma albumin levels (WMD = 0.02 mg/dL, 95% CI: −0.13, 0.18, P = 0.75) was remained unaffected. Overall, our meta-analysis provides evidences that the consumption of ω-3 PUFA-enriched oral nutritional supplements exert beneficial effects on nutritional status and clinical outcomes in patients undergoing chemo (radio) therapy. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. Methods: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. Results: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1β, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. Conclusion: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance. [ABSTRACT FROM AUTHOR]

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Introduction: Rheumatoid arthritis (RA) is a chronic disease that causes deformity in most productive age and can lead to death as disease activity increases. Omega-3 polyunsaturated fatty acids have the potential to complement available therapies in reducing disease activity. Currently, the effect of omega-3 PUFAs on disease activity components is still unclear. The current systematic reviews determine the effect of omega-3 PUFAs’ supplementation on the components of RA disease activity. Methods: This research is guided by the PRISMA guidelines systematically. Literature was searched in the databases: PubMed, MDPI, and Clinicaltrials.gov. The inclusion criteria used were: giving omega-3 PUFAs, free full-text, RCT, in English or Indonesian, assessing disease activity and its components; while the exclusion criteria were: unpublished, comparisons were inappropriate. Assessment of literature quality with the Cochrane Collaboration's tool. The study included six studies from 1994 to 2017. Results: The effect of omega-3 PUFAs is diversity in changes of disease activity in 4 of 5 studies. There are significant reductions in the number of joint pains in the literature by daily doses above 2.9 grams or at lower doses taking longer; and swollen joints in 2 studies that were only affected in doses above 2.9 grams. There are significant reductions in pain severity in the studies. Change increases with higher doses. There are variable LED and CRP changes. Conclusion: Depending on their dose and administration duration, omega-3 PUFAs can directly and indirectly affect disease activity through the influence of most of its components, namely: the number of joints affected and the degree of pain.

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Purpose: To assess the relationship between dietary oily fish intake and all-cause mortality in a population of frequent fish consumers of Amerindian ancestry living in rural Ecuador. Methods: Individuals aged ≥ 40 years enrolled in the prospective population-based Atahualpa Project cohort received annual questionnaires to estimate their dietary oily fish intake. Only fish served broiled or cooked in the soup were included for analysis. Poisson regression and Cox-proportional hazards models adjusted for demographics, education level and cardiovascular risk factors were obtained to estimate mortality risk according to the amount of oily fish intake stratified in tertiles. Results: Analysis included 909 individuals (mean age: 55.1 ± 12.8 years) followed by a median of 7.5 ± 3 years. Mean oily fish intake was 9.4 ± 5.7 servings per week. A total of 142 (16%) individuals died during the follow-up. The mortality rate for individuals in the first tertile de oily fish intake (0.0–6.29 servings) was 2.87 per 100 person-years, which decreased to 1.78 for those in the third tertile (10.59–35.0 servings). An adjusted Cox-proportional hazards model showed that individuals allocated to the second (HR 0.61; 95% CI 0.41–0.92) and third (HR 0.60; 95% CI 0.40–0.91) tertiles of dietary oily fish intake had significantly lower mortality risk than those in the first tertile. Conclusion: Sustained oily fish intake of more than six servings per week reduces mortality risk in middle-aged and older adults of Amerindian ancestry. [ABSTRACT FROM AUTHOR]

Background: Late-life depression (LLD) is a risk factor for dementia and cognitive decline. Fish oil supplement is efficacious for depressive symptoms with cognitive protective benefits. While there is limited strategy to deter cognitive decline in older adults, examining the cognitive protection in LLD by using fish oil can potentially provide a new promise. Aims & Objectives: In addition to using double-blind randomized controlled trial to examine the clinical effects of fish oil in LLD, we also explore the neural mechanism by using pre-and post fMRI scans. Method: A 52-week trial was conducted. Complexity analysis (multi-scale sample entropy) was employed to analyze rs-fMRI data. We also correlate the MRI changes with changes in cognitive function and inflammatory profiles. Results: Limited by the pandemic, we only included 20 patients with 11 u nder fish oil and nine under placebo. Only marginal improvement in processing speed was found in fish oil group. We found decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. Brain entropy changes in PCG in the fish oil group was associated with language function improvement and decrease in interleukin-6 levels. Discussion & Conclusion: Our results confirm the anti-inflammatory effects of fish oil in LLD could be the underlying mechanism of cognitive protective effects. Also, fish oil may exert its function through modulation of brain entropy changes in key area in default-mode network, a network strategic both in depression and dementia. [ABSTRACT FROM AUTHOR]

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.

BackgroundClinical studies on effects of marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) on lipoprotein-lipid components and glucose-insulin homeostasis have shown conflicting results, which may partly be explained by differential responses in females and males. However, we have lacked data on sexual dimorphism in the response of cardiometabolic risk markers following increased consumption of n-3 or n-6 PUFAs.ObjectiveTo explore sex-specific responses after n-3 (EPA + DHA) or n-6 (LA) PUFA supplementation on circulating lipoprotein subfractions, standard lipids, apolipoproteins, fatty acids in red blood cell membranes, and markers of glycemic control/insulin sensitivity among people with abdominal obesity.MethodsThis was a randomized double-blind crossover study with two 7-week intervention periods separated by a 9-week washout phase. Females (n = 16) were supplemented with 3 g/d of EPA + DHA (fish oil) or 15 g/d of LA (safflower oil), while males (n = 23) received a dose of 4 g/d of EPA + DHA or 20 g/d of LA. In fasting blood samples, we measured lipoprotein particle subclasses, standard lipids, apolipoproteins, fatty acid profiles, and markers of glycemic control/insulin sensitivity.ResultsThe between-sex difference in relative change scores was significant after n-3 for total high-density lipoproteins (females/males: −11%*/−3.3%, p = 0.036; *: significant within-sex change), high-density lipoprotein particle size (+2.1%*/−0.1%, p = 0.045), and arachidonic acid (−8.3%*/−12%*, p = 0.012), and after n-6 for total (+37%*/+2.1%, p = 0.041) and small very-low-density lipoproteins (+97%*/+14%, p = 0.021), and lipoprotein (a) (−16%*/+0.1%, p = 0.028). Circulating markers of glucose-insulin homeostasis differed significantly after n-3 for glucose (females/males: −2.1%/+3.9%*, p = 0.029), insulin (−31%*/+16%, p

Background: Omega-3 polyunsaturated fatty acids (PUFAs) play beneficial roles in metabolism and health. Little is known about the effects of different doses of omega-3 PUFAs on gut microbiota. Objective: In this study, we focus on the effects of different doses of omega-3 PUFAs on gut microbiota and immunity. Design: BALB/c mice was first treated with ceftriaxone sodium for 7 days, and then they received saline or different doses of omega-3 PUFAs (30, 60 and 90 mg omega-3 PUFAs) via daily gavage for 21 days. Alterations of cecum microbiota; the tight junction proteins, zonula occludens 3 (ZO3) and occludin, in the ileal wall; serum lipopolysaccharide (LPS); Interleukin-10 (IL-10), interleukin-1β (IL-1β), and Tumour Necrosis Factor α (TNF-α) ; mucus SIgA levels were measured. Results: Compared with the ceftriaxone sodium administration group, significant increases in bacterial richness and diversity were observed in the 60- and 90-mg omega-3 PUFA groups, while only a slight increase was observed in the 30-mg omega-3 PUFA group. A higher percentage of several genera, including Lactobacillus, Helicobacter, and Ruminococcus, and a lower percentage of Bacteroides, Clostridium, and Prevotella were observed in the 60- and 90-mg omega-3 PUFA groups when compared with those in the 30-mg group. The expression of ZO3 and occludin proteins increased in 60- and 90-mg omega-3 PUFA groups compared with the natural recovery group. The mucus SIgA and serum IL-10 levels were increased, and serum levels of LPS, IL-1β, and TNF-α were decreased in the 60- and 90-mg omega-3 PUFA groups when compared with those in the ceftriaxone sodium-treated group. Conclusion: Different doses of omega-3 PUFAs have different therapeutic effects on the intestinal microbiota. The 60- and 90-mg omega-3 PUFA supplementation had better recovery effects on the gut microbiota and immunity than those of the 30 mg omega-3 PUFAs supplementation.

Throughout history, pollution has become a part of our daily life with the improvement of life quality and the advancement of industry and heavy industry. In recent years, the adverse effects of heavy metals, such as cadmium (Cd), on human health have been widely discussed, particularly on the immune system. Here, this review summarizes the available evidence on how Cd exposure may affect health. By analyzing the general manifestations of inflammation caused by Cd exposure, we find that the role of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in vivo can counteract Cd-induced harm. Additionally, we elucidate the effects of n-3 PUFAs on the immune system, and analyze their prophylactic and therapeutic effects on Cd exposure. Overall, this review highlights the role of n-3 PUFAs in the pathological changes induced by Cd exposure. Although n-3 PUFAs remain to be verified whether they can be used as therapeutic agents, as rehabilitation therapy, supplementation with n-3 PUFAs is reliable and effective. [ABSTRACT FROM AUTHOR]

An increase in CYP2E1 expression is a key factor in the development of diabetic oxidative liver damage. Long-term treatment with omega-3 PUFAs, which are CYP2E1 substrates, may affect CYP2E1 expression in the liver. In this work, we performed Western blot analysis, biochemical methods, and microscopic ultrastructural studies of the liver in a streptozotocin-induced rat model of type 1 diabetes to investigate whether long-term treatment with omega-3 PUFAs could induce CYP2E1-dependent oxidative stress and diabetic liver pathology. Significant hyperglycemia and lack of natural weight gain were observed in the diabetic rats compared to non-diabetic controls. A 2.5-fold increase in CYP2E1 expression (protein content and activity) was also observed in the diabetic rats. In addition, signs of oxidative stress were found in the liver of the diabetic rats. A significant increase in transaminases and GGT level in blood serum was also observed, which could indicate marked destruction of liver tissue. Diabetic dyslipidemia (increased triacylglycerol levels and decreased HDL-C levels) was found. Treatment of the diabetic animals with an omega-3-enriched pharmaceutical composition of PUFAs had no effect on CYP2E1 levels but contributed to a two-fold decrease in enzyme activity. The intensity of lipid peroxidation also remained close to the diabetic group. However, at the same time, antioxidant protection was provided by induction of antioxidant enzyme activity. Examination of the liver ultrastructure revealed no characteristic signs of diabetic pathology. However, omega-3 PUFAs did not normalize blood glucose levels and serum lipid profile. Thus, long-term treatment of diabetic rats with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and development of liver pathology but prevents some diabetic ultrastructural damage to hepatocytes. [ABSTRACT FROM AUTHOR]

The large, randomized, doubleblind, placebo-controlled trial VITAL (Vitamin D and omega 3 trial) recently confirmed that vitamin D and omega-3 polyunsaturated fatty acid (PUFA) co-supplementation (VIDOM) can reduce the incidence of autoimmune diseases. Based on these relevant results, this commentary summarizes the molecular mechanisms behind the anti-inflammatory and immunomodulatory properties of vitamin D and omega-3 PUFAs. We also describe the potential bidirectional interplay between vitamin D metabolism and omega-3 PUFA metabolism that underlies the rationale for VIDOM co-supplementation and that may contribute to enhance the anti-inflammatory and immunomodulatory actions of vitamin D and omega-3 PUFAs when these compounds are administered in combination. [ABSTRACT FROM AUTHOR]

Omega-3 polyunsaturated fatty acids (PUFAs) can play important roles in maintaining mental health and resistance to stress, and omega-3 PUFAs supplementation can display beneficial effects on both the prevention and treatment of depressive disorders. Although the underlying mechanisms are still unclear, accumulated evidence indicates that omega-3 PUFAs can exhibit pleiotropic effects on the neural structure and function. Thus, they play fundamental roles in brain activities involved in the mood regulation. Since depressive symptoms have been assumed to be of central origin, this review aims to summarize the recently published studies to identify the potential neurobiological mechanisms underlying the anti-depressant effects of omega-3 PUFAs. These include that of (1) anti-neuroinflammatory; (2) hypothalamus-pituitary-adrenal (HPA) axis; (3) anti-oxidative stress; (4) anti-neurodegeneration; (5) neuroplasticity and synaptic plasticity; and (6) modulation of neurotransmitter systems. Despite many lines of evidence have hinted that these mechanisms may co-exist and work in concert to produce anti-depressive effects, the potentially multiple sites of action of omega-3 PUFAs need to be fully established.We also discussed the limitations of current studies and suggest future directions for preclinical and translational research in this field. [ABSTRACT FROM AUTHOR]

[Display omitted] • SARS-CoV-2 has led to the lasting pandemic of COVID-19 and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the "long COVID." • The mechanisms of neuropsychiatric complications of long COVID damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and HPA axis, and the psychosocial stress imposed by societal changes in response to this pandemic. • Long chain omega-3 PUFAs might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. • Omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation, altering the HPA axis, modulating neurotransmission via lipid rafts and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the lasting pandemic of coronavirus disease 2019 (COVID-19) and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the "long COVID." The mechanisms of neuropsychiatric complications of long COVID are multifactorial, including long-term tissue damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and hypothalamus–pituitaryadrenal (HPA) axis, and the psychosocial stress imposed by societal changes in response to this pandemic. The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis. Long chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. Omega-3 PUFAs, particularly EPA, have shown effects in treating mood and neurocognitive disorders by reducing pro-inflammatory cytokines, altering the HPA axis, and modulating neurotransmission via lipid rafts. In addition, omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity. [ABSTRACT FROM AUTHOR]

Dietary supplementation with fish oil is promising as a complementary therapy for inflammatory pain. However, further studies are needed to support its therapeutic potential. For example, the antinociceptive effect of fish oil is widely suggested to be dependent on decreased prostaglandin E2 (PGE2) synthesis, but no previous study has investigated if it affects PGE2-induced nociceptive response. Similarly, beneficial long-term effects on inflammatory response are related to early exposure to fish oil, however, whether these effects include decreased inflammatory pain throughout life is not known. The aim of this study was to investigate the short- and long-term effects of fish oil on inflammatory pain. Dietary fish oil supplementation was performed through two protocols: in adult rats, during 20 days, or in dams, during pregnancy and lactation, with tests performed in adult offspring. The hyperalgesic response induced by carrageenan and its final mediators PGE2 and norepinephrine was used to model inflammatory pain. The findings demonstrated for the first time that dietary fish oil (1) decreases the hyperalgesia induced by carrageenan; (2) but not that induced by its final mediator PGE2 and norepinephrine; (3) increase omega-3 polyunsaturated fatty acids in peripheral neural tissue; and (4) attenuates inflammatory pain in individuals exposed to fish oil during pre-natal life and lactation. Together, these findings support that fish oil decreases inflammatory pain either when consumed during adult life or during prenatal development. Future studies should confirm the therapeutic potential of fish oil in humans, which is essential for the development of public policies to encourage a fish oil richer diet. [ABSTRACT FROM AUTHOR]

An increase in CYP2E1 expression is a key factor in the development of diabetic oxidative liver damage. Long-term treatment with omega-3 PUFAs, which are CYP2E1 substrates, may affect CYP2E1 expression in the liver. In this work, we performed Western blot analysis, biochemical methods, and microscopic ultrastructural studies of the liver in a streptozotocin-induced rat model of type 1 diabetes to investigate whether long-term treatment with omega-3 PUFAs could induce CYP2E1-dependent oxidative stress and diabetic liver pathology. Significant hyperglycemia and lack of natural weight gain were observed in the diabetic rats compared to non-diabetic controls. A 2.5-fold increase in CYP2E1 expression (protein content and activity) was also observed in the diabetic rats. In addition, signs of oxidative stress were found in the liver of the diabetic rats. A significant increase in transaminases and GGT level in blood serum was also observed, which could indicate marked destruction of liver tissue. Diabetic dyslipidemia (increased triacylglycerol levels and decreased HDL-C levels) was found. Treatment of the diabetic animals with an omega-3-enriched pharmaceutical composition of PUFAs had no effect on CYP2E1 levels but contributed to a two-fold decrease in enzyme activity. The intensity of lipid peroxidation also remained close to the diabetic group. However, at the same time, antioxidant protection was provided by induction of antioxidant enzyme activity. Examination of the liver ultrastructure revealed no characteristic signs of diabetic pathology. However, omega-3 PUFAs did not normalize blood glucose levels and serum lipid profile. Thus, long-term treatment of diabetic rats with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and development of liver pathology but prevents some diabetic ultrastructural damage to hepatocytes.

Background and objective: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which no treatments exist. Fragile X syndrome (FXS) is the most common form of inherited mental retardation and the most frequent monogenic cause of ASD. Given the lack of pharmacological treatments for ASD, increasing interest is devoted to non-pharmacological approaches, including dietary interventions. Omega-3 polyunsaturated fatty acids (PUFAs) are critical for neurobehavioraldevelopment. This study had two aims: 1. To validatethe recently developed Fmr1-Δexon 8 rat model of FXS; 2. To assess the impact of omega-3 PUFAs dietary supplementation during pregnancy and lactation on the altered behavior displayed by Fmr1-Δexon 8 rats. Methods: Female Fmr1-Δexon 8 and wild-type Sprague–Dawley rats were fed with either an omega-3 PUFAs enriched diet or with an isocaloric control diet during pregnancy and lactation. Behavioral experiments were carried out on the infant (Postnatal days (PNDs) 9 and 13), juvenile (PND 35) and adult (PND 90) male offspring. Results:Fmr1-Δexon 8 pups showed hypolocomotion, reduced ultrasonic vocalizations (USVs) emission and impaired social discrimination compared to wild-type controls. Juvenile and adult Fmr1-Δexon 8 rats showed deficits in the social and cognitive domains, that were counteracted by perinatal omega-3 PUFAs supplementation. Conclusion: Our results support the validity of the Fmr1-Δexon 8 rat model to mimic key autistic-like features and support an important role of omega-3 PUFAs during of neurodevelopment. Although the mechanisms underlying the beneficial effects of omega-3 PUFAs supplementation in ASD needs to be clarified, this dietary intervention holds promise to mitigate core and comorbid autistic features. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is characterized by a high rate of treatment resistance. Omega (ω)−3 polyunsaturated fatty acids (PUFAs) were shown to correlate with depressive phenotype both in rodents and in humans. However, few studies to date have investigated the role of PUFAs in antidepressant response. The primary aim of this study was to assess the link between baseline PUFA composition and changes in depressive symptoms as well as antidepressant response in a multicenter study of depressed patients. Methods: Sixty depressed adults who met criteria for MDD according to DSM‐IV‐TR were recruited. Neuropsychiatric evaluations occurred at baseline and after 4 and 8 weeks of treatment with standard antidepressants, including escitalopram (N = 45), sertraline (N = 13) and venlafaxine (N = 2). At study endpoint, patients were stratified into responders (R) or non‐responders (NR) based on their MADRS (Montgomery‐Åsberg Depression Rating Scale) score. Baseline PUFA levels were assessed and their association with clinical response was determined. Results: Lower ω−3 PUFA levels were associated to worse baseline symptomatology. Baseline levels of PUFAs were significantly different between R and NR, with R exhibiting lower docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and ω−3 index; and higher ω‐6/ω−3 ratio than NR before the start of antidepressant treatment. DHA levels as well as the ω−3 index and ω‐6/ω−3 ratio significantly predicted response to antidepressants at study endpoint. Conclusions: These results show that baseline levels of PUFAs predict later response to standard antidepressants in depressed subjects. They suggest that PUFA intake and/or metabolism represent a novel modifiable tool for the management of unresponsive depressed patients. [ABSTRACT FROM AUTHOR]

Abstract Background Omega-3 polyunsaturated fatty acids (PUFAs) were proposed to have potential effects against inflammation and cancer. However, results from epidemiology studies remain inconsistent. We aimed to explore the associations of plasma PUFAs with EC recurrence and all-cause mortality. Method Women diagnosed with endometrial cancer (EC) between 2008 and 2013 and underwent surgery at Fudan University Shanghai Cancer Center of China were recruited. Survival status was followed up through September 2017. EC recurrence and total cause deaths were identified through medical record and telephone interview. In total, 202 patients with enough plasma samples at time of surgery were included. There were 195 patients who provided baseline plasma and survival information included in the current study. Plasma omega-3 PUFAs were measured by GC-FID. Cox Proportional Hazard model adjusted for potential cofounders was used to estimate HRs and 95% CIs. Results Median follow-up time for patients was 58 months after surgery. A total of 13 recurrences and 11 all-cause deaths, of which, 2 deaths from EC, were identified. Level of plasma EPA was higher in recurrent patients than total patients (0.78% vs 0.51%, P = 0.015). Higher plasma eicosapentaenoic acid (EPA) level trended to have positive association with EC recurrence (P-trend = 0.04), although comparing to the lowest tertile, the highest tertile of EPA level was not significantly associated with increased risk of EC recurrence (HRT3vsT1 = 6.02; 95%CI = 0.7–52.06). The association between total omega-3 PUFA and EC recurrence tended to be stronger among patients with deeper myometrial invasion (OR = 3.41; 95%CI = 1.06–10.95; P-interaction = 0.04). Conclusions Higher plasma EPA level was significantly associated with EC recurrence. Further studies are warranted to confirm these findings. Trial registration ChiCTR1900025418 ; Retrospectively registered (26 August 2019); Chinses Clinical Trial Registry.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe complications that can occur in infections caused by any Plasmodium species. Due to the high lethality rate and the lack of specific treatment for ALI/ARDS, studies aimed at understanding and searching for treatment strategies for such complications have been fundamental. Here, we investigated the protective role of dietary supplementation with DHA-rich fish oil against lung damage induced by Plasmodium berghei ANKA in a murine model. Our results demonstrated that alveolar vascular damage, lung edema, and histopathological alterations were significantly reduced in mice that received dietary supplementation compared to those that did not receive the supplementation. Furthermore, a significant reduction in the number of CD8+ T lymphocytes, in addition to reduced infiltration of inflammatory cells in the bronchoalveolar lavage fluid was also observed. High levels of IL-10, but not of TNF-α and IFN-γ, were also observed in infected mice that received the supplementation, along with a reduction in local oxidative stress. Together, the data suggest that dietary supplementation with DHA-rich fish oil in malarial endemic areas may help reduce lung damage resulting from the infection, thus preventing worsening of the condition.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) is currently considered an autoimmune disease characterized by the destruction of pancreatic β-cells, insulin deficiency, and dysglycemia. Dietary factors, including omega-3 polyunsaturated fatty acids (ω-3 PUFAs), were reported to influence T1DM. Therefore, a better understanding of the potential role of ω-3 PUFAs in the development and progression of T1DM will help to improve the clinical management of the disease. In this review, we explored the current understanding of molecular mechanisms and signaling pathways induced by ω-3 PUFAs and the beneficial effects of ω-3 PUFAs intake in the prevention and treatment of T1DM, as well as the underlying possible metabolomic (lipidomics) changes.

In opinion the Expert council provides management tactics for patients with hypertriglyceridemia (HTG). It is demonstrated that HTG is a common condition in overweight patients and is an important component of residual risk. HTG creates additional conditions for the progression of atherosclerosis, so the level of triglycerides (TG) is recommended to be measured in patients with a high, very high and extremely high risk level. An indication for the appointment of drugs that reduce the concentration of TG is its level of more than 2,3 mmol/L. Statins are the agents of choice to reduce the risk of cardiovascular disease in high-risk patients with hypercholesterolemia and HTG. Fenofibrate is used to correct HTG, and in case of intolerance to it or when the target level of TG is not reached, omega-3 ethers of polyunsaturated fatty acids in a dose of 2-4 g/day are recommended. In patients with HTG with a TG level >5,6 mmol/L, fenofibrate is the agent of choice.

Introduction: The lipid-modifying potential of omega-3 polyunsaturated fatty acids in Chinese patients is under-researched. We conducted a multicenter, randomized, placebo-controlled, double-blind, parallel-group study of twice-daily treatment with OMACOR (OM3EE), a prescription-only formulation of highly purified ethyl esters of omega-3 polyunsaturated fatty acids in Chinese adult patients (≥ 18 years) who had elevated baseline fasting serum triglycerides (TG). Methods: Patients were stratified according to the severity of their hypertriglyceridemia (severe HTG, with baseline TG ≥ 500 and < 1000 mg/dL or moderate HTG, with baseline TG > 200 and < 500 mg/dL) or use of statins. Patients randomized to OM3EE therapy received 2 g/day for 4 weeks, then 4 g/day for 8 weeks. The primary efficacy endpoint was the percentage change in fasting serum TG between baseline and the end of treatment in patients with severe HTG. The study was concluded after a planned interim analysis demonstrated a significant TG-lowering effect of OM3EE in that contingent (p=0.0019). Results: The mean TG end-of-treatment effect of OM3EE was – 29.46% (standard deviation 40.60%) in the severe HTG contingent compared with +0.26% (standard deviation 54.68%) in the placebo group. Corresponding changes were – 12.12% and – 23.25% in the moderate HTG and combination cohorts (vs +55.45% and +6.24% in relevant placebo groups). A dose-dependent reduction in TG was evident in all patient contingents. Safety and tolerability of OM3EE were in line with previous experience. Discussion: These data indicate that OMACOR therapy at a dose of 2– 4 g/day is an effective treatment for Chinese patients with raised TG levels and is well tolerated. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia may hasten the risk of mortality in women with breast cancer. Long-chain omega-3 (n-3) polyunsaturated fatty acids (LCn-3PUFAs) may favor muscle mass which, in turn, could enhance resilience of cancer patients toward cancer treatment.Objectives: The objective of this study was to measure the relation of erythrocyte LCn-3PUFA concentrations with lean mass, grip strength, and postprandial energy metabolism in women with newly diagnosed breast cancer.Methods: This cross-sectional analysis evaluated women (n = 150) ages 65 y and younger who were recently diagnosed with breast cancer (stages I-III). Erythrocyte LCn-3PUFA composition was measured using GC. Body composition was measured by DXA. Grip strength was assessed at the same visit. Postprandial energy metabolism was measured for 7.5 h after the consumption of a high-calorie, high-saturated-fat test meal using indirect calorimetry. Associations of fatty acids with outcomes were analyzed using multiple linear regression models and linear mixed-effects models.Results: The ω-3 index, a measurement of LCn-3PUFA status, was positively associated with appendicular lean mass (ALM)/BMI (β = 0.015, P = 0.01) and grip strength (β = 0.757, P = 0.04) after adjusting data for age and cancer stage. However, when cardiorespiratory fitness was also included in the analyses, these relations were no longer significant (P > 0.08). After a test meal, a higher ω-3 index was associated with a less steep rise in fat oxidation (P = 0.02) and a steeper decline in glucose (P = 0.01) when adjusting for age, BMI, cancer stage, and cardiorespiratory fitness.Conclusions: The ω-3 index was positively associated with ALM/BMI and grip strength in women newly diagnosed with breast cancer and was associated with altered postprandial substrate metabolism. These findings warrant further studies to determine whether enriching the diet with LCn-3PUFAs during and after cancer treatments is causally linked with better muscle health and metabolic outcomes in breast cancer survivors. [ABSTRACT FROM AUTHOR]

Marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower circulating levels of triacylglycerols (TAGs), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) may reduce cholesterol levels. Clinical studies on effects of these dietary or supplemental PUFAs on other blood fat fractions are few and have shown conflicting results. This study aimed to determine effects of high-dose supplemental n-3 (EPA + DHA) and n-6 (LA) PUFAs from high-quality oils on circulating lipoprotein subfractions and standard lipids (primary outcomes), as well as apolipoproteins, fatty acids, and glycemic control (secondary outcomes), in females and males with abdominal obesity. This was a randomized double-blind crossover study with two 7-wk intervention periods separated by a 9-wk washout phase. Females (n = 16) were supplemented with 3 g/d of EPA + DHA (TAG fish oil) or 15 g/d of LA (safflower oil), while males (n = 23) received a dose of 4 g/d of EPA + DHA or 20 g/d of LA. In fasting blood samples, we investigated lipoprotein particle subclasses by nuclear magnetic resonance spectroscopy, as well as standard lipids, apolipoproteins, fatty acid profiles, and glucose and insulin. Data were analyzed by linear mixed-effects modeling with 'subjects' as the random factor. The difference between interventions in relative change scores was among the lipoprotein subfractions significant for total very-low-density lipoproteins (VLDLs) (n-3 vs. n-6: −38%∗ vs. +16%, p < 0.001; ∗: significant within-treatment change score), large VLDLs (−58%∗ vs. −0.91%, p < 0.001), small VLDLs (−57%∗ vs. +41%∗, p < 0.001), total low-density lipoproteins (LDLs) (+5.8%∗ vs. −4.3%∗, p = 0.002), large LDLs (+23%∗ vs. −2.1%, p = 0.004), total high-density lipoproteins (HDLs) (−6.0%∗ vs. +3.7%, p < 0.001), large HDLs (+11%∗ vs. −5.3%, p = 0.001), medium HDLs (−24%∗ vs. +6.2%, p = 0.030), and small HDLs (−9.9%∗ vs. +9.6%∗, p = 0.002), and among standard lipids for TAGs (−16%∗ vs. −2.6%, p = 0.014), non-esterified fatty acids (−19%∗ vs. +5.5%, p = 0.033), and total cholesterol (−0.28% vs. −4.4%∗, p = 0.042). A differential response in relative change scores was also found for apolipoprotein (apo)B (+0.40% vs. −6.0%∗, p = 0.008), apoA-II (−6.0%∗ vs. +1.5%, p = 0.001), apoC-II (−11%∗ vs. −1.7%, p = 0.025), and apoE (+3.3% vs. −3.8%, p = 0.028). High-dose supplementation of high-quality oils with n-3 (EPA + DHA) or n-6 (LA) PUFAs was followed by reductions in primarily TAG- or cholesterol-related markers, respectively. The responses after both interventions point to changes in the lipoprotein–lipid–apolipoprotein profile that have been associated with reduced cardiometabolic risk, also among people with TAG or LDL-C levels within the normal range. Registered under ClinicalTrials.gov Identifier: NCT02647333. Registered at https://clinicaltrials.gov/ct2/show/NCT02647333. [ABSTRACT FROM AUTHOR]

[Display omitted] • Black soldier fly larvae (BSFL) did not accumulate Se in their bodies. • More than 35% of Se-rich silkworm pre-pupae (SWP) residuals have been reduced. • BSFL converted Se-rich SWP to a safe nutritionally valuable product with high ω-3 content. Waste disposal and utilisation of its important components are pioneering goals for achieving sustainable development and a clean environment. Silkworm pupae (SWP) are considered a by-product of the sericulture industry and may contain a high concentration of selenium (Se) in some regions, making them a potentially hazardous waste posing health risks. This study examined six treatments of Se-rich SWP (0–100%) as a substrate for black soldier fly (BSF) larvae. Growth performance and protein content of BSF larvae were not affected by increasing SWP content. The total fat, mono-, and poly-unsaturated fatty acids in BSF pre-pupae increased with increasing SWP inclusion in the substrate, from P0 (pre-pupae fed control treatment) through P100 (pre-pupae fed 100% SWP treatment), by 18.83, 61.14, and 62.42%, respectively. The results of significance were: (1) BSF pre-pupae did not accumulate Se, maintaining the same amount of Se in their bodies (~0.18 mg/kg); (2) omega-3 fatty acids represented by linolenic acid in BSF increased by 1,223.35% from P0 to P100, with 70.65% recovered from the SWP; (3) valine percentage increased in BSF compared with the percentage of SWP by 25.30%; and (4) BSF larvae were observed reducing SWP waste by more than one-third. BSF larvae can reduce the waste from sericulture industry and exploit the beneficial properties and components of SWP, converting them into safe and highly nutritious products. [ABSTRACT FROM AUTHOR]

Obesity has a significant impact on predisposition to various diseases and also affects the viabil­ity and choice of haematopoietic stem cells (HSCs) to favour myeloid cell production and/or turnover, all of which are extremely important for the functioning of immune system. As the production of blood cells and mobilization of HSCs and their progeny are regulated, at least in part, by multifaceted interactions through signals that come from the bone marrow (BM) microenvironment, it does not seem astonishing to assume that circumstances that cause alterations in BM structure will unavoidably cause alterations in mesenchymal cells such as adipocytes and lineages from HSCs. The existence of adipose tissue in BM or marrow fat (BMAT) is well known, although its origin, expansion, and functions are poorly understood. Inspired by other studies showing the potential role for olive oil and omega-3 long chain polyunsaturated fatty acids (omega-3 PUFAs) on BM health, and by our own preliminary findings showing the effects of monounsaturated (olive oil) but not saturated (milk cream) dietary fats to contain neutrophils and CD14high monocytes in BM during postprandial periods in healthy volunteers, herein we asked whether dietary fats (saturated fatty acids, SFAs, monounsatu­rated fatty acids, MUFAs, and omega-3 PUFAs) may be a candidate lifestyle factor to modulate the expansion, composition, and function of BMAT, the infiltration of adipose tissue macrophages (ATMs) in BMAT and the mobilization of HSCs and mature myeloid cells from BM during high-fat-induced obesity in mice. This is the first time that the interplay between different dietary fatty acids, obesity, and BM is addressed.

Omega-3 polyunsaturated fatty acids (PUFAs) represent valuable dietary adjuncts for subjects with hypertriglyceridemia and at increased risk of cardiovascular disease, including subjects with type 1 diabetes (T1D). However, the exact role of omega-3 PUFAs in the regulation of glucose homeostasis and chronic complications in patients with diabetes remains uncertain. Herein, we report a 3-year follow-up of an athlete adolescent with T1D who started to use continuous glucose monitoring (CGM) two years after the diagnosis, and initiated omega-3 PUFA supplementation four years after the clinical onset of T1D. CGM metrics related to a 18-month period of omega-3 PUFA supplementation (50 mg/Kg/day of EPA and DHA) was compared to CGM metrics referring to a 18-month period prior to the nutrition intervention. Omega-3 PUFA supplementation resulted in a significant reduction of mean glucose and glucose variability, along with a significant increase in Time in range (TIR) 70-180 mg/dL. No significant changes were observed in daily insulin requirements between the two study periods. Future studies will be of assistance to better understand the exact impact of omega-3 PUFAs on the regulation of glucose homeostasis in patients with type 1 and its complications.