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Chemotherapy can result in toxic side effects in the brain. Intake of marine-based omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alter brain fatty acids, potentially improving brain function. However, it is unclear if alpha-linolenic acid (ALA), the plant-based n-3, affects brain PUFAs during chemotherapy. The objective of this study was to examine the effects of dietary ALA, EPA and DHA, with high or low sucrose, on brain PUFAs in a mouse model of chemotherapy. Secondarily, the use of liver PUFAs as surrogate measures of brain PUFAs was examined. Lipid peroxidation (4-HNE) and neurotrophic markers (BDNF) were assessed. Female C57Bl/6 mice (n = 90) were randomized to 1 of 5 diets (high EPA + DHA/high or low sucrose, high ALA/high or low sucrose, or control with no EPA + DHA/low ALA/low sucrose) and injected with doxorubicin-based chemotherapy or saline. Brain EPA and DHA were greater (p < 0.0001) with high EPA + DHA diets, regardless of sucrose; there were no significant differences in brain PUFAs between high ALA diets and control. Chemotherapy-treated mice had higher brain and liver DHA (p < 0.05) and lower brain and liver linoleic acid (p < 0.0001). Brain n-3 and n-6 PUFAs were strongly correlated with liver n-3 (r = 0.8214, p < 0.0001) and n-6 PUFAs (r = 0.7568, p < 0.0001). BDNF was correlated with brain total PUFAs (r = 0.36; p < 0.05). In conclusion, dietary ALA in proportions approximately two times greater than consumed by humans did not appreciably increase brain n-3 PUFAs compared to low ALA intake. Liver PUFAs may be a useful surrogate marker of brain PUFAs in this mouse model.

BACKGROUND Sickle cell disease (SCD) is a genetic hemoglobinopathy associated with high morbidity and mortality. The primary cause of hospitalization in SCD is vaso-occlusive crisis (VOC), mediated by alteration of red blood cells, platelets, immune cells and a pro-adhesive endothelium. OBJECTIVES We investigated the potential therapeutic use of the plant-derived omega-3 alpha-linolenic acid (ALA) in SCD. METHODS Berkeley mice were fed a low- or high-ALA diet for 4 weeks, followed by analysis of liver fibrosis, endothelial activation, platelet activation and formation of platelet-neutrophils aggregates. Aggregation of platelets over collagen under flow after high-ALA was compared to a blocking P-selectin Fab. RESULTS Dietary high-ALA was able to reduce the number of sickle cells in blood smear, liver fibrosis, and the expression of adhesion molecules on the endothelium of aorta, lungs, liver and kidneys (VCAM-1, ICAM-1 and vWF). Specific parameters of platelet activation were blunted after high-ALA feeding, notably P-selectin exposure and the formation of neutrophil-platelet aggregates, along with a correspondingly reduced expression of PSGL-1 on neutrophils. By comparison, in vivo treatment of SCD mice with the anti-P-selectin Fab was able to similarly reduce the formation of neutrophil-platelet aggregates, but did not reduce GpIbα shedding nor the activation of the αIIb β3 integrin in response to thrombin. Both ALA feeding and P-selectin blocking significantly reduced collagen-mediated cell adhesion under flow. CONCLUSIONS Dietary ALA is able to reduce the pro-inflammatory and pro-thrombotic state occurring in the SCD mouse model and may represent a novel, inexpensive and readily available therapeutic strategy for SCD.

The efficacy of n-3 polyunsaturated fatty acids (PUFAs) in improving outcomes in a renal ischemia-reperfusion injury (IRI) model has previously been reported. However, the underlying mechanisms remain poorly understood and few reports demonstrate how dietary n-3 PUFAs influence the composition of membrane phospholipids in the kidney. Additionally, it has not been elucidated whether perilla oil (PO), which is mainly composed of the n-3 alpha-linolenic acid, mitigates renal IRI. In this study, we investigated the effect of dietary n-3 PUFAs (PO), compared with an n-6 PUFA-rich soybean oil (SO) diet, on IRI-induced renal insufficiency in a rat model. Levels of membrane phospholipids containing n-3 PUFAs were higher in the kidney of PO-rich diet-fed rats than the SO-rich diet-fed rats. Levels of blood urea nitrogen and serum creatinine were significantly higher in the ischemia-reperfusion group than the sham group under both dietary conditions. However, no significant differences were observed in blood urea nitrogen, serum creatinine, or histological damage between PO-rich diet-fed rats and SO-rich diet-fed rats. In the kidney of PO-rich diet-fed rats, levels of arachidonic acid and arachidonic acid-derived pro-inflammatory lipid mediators were lower than SO-rich diet-fed rats. Eicosapentaenoic acid and eicosapentaenoic acid-derived lipid mediators were significantly higher in the kidney of PO-rich than SO-rich diet-fed rats. These results suggest that dietary n-3 PUFAs alter the fatty acid composition of membrane phospholipids and lipid mediators in the kidney; however, this does not attenuate renal insufficiency or histological damage in a renal IRI model.

Background Effects of soy foods on cerebral blood flow (CBF)-a marker of cerebrovascular function-may contribute to the beneficial effects of plant-based diets on cognitive performance. Objectives We aimed to investigate longer-term effects of soy nut consumption on CBF in older adults. Changes in 3 different domains of cognitive performance were also studied. Methods Twenty-three healthy participants (age: 60-70 y; BMI: 20-30 kg/m(2)) participated in a randomized, controlled, single-blinded crossover trial with an intervention (67 g/d of soy nuts providing similar to 25.5 g protein and 174 mg isoflavones) and control period (no nuts) of 16 wk, separated by an 8-wk washout period. Adults followed the Dutch food-based dietary guidelines. At the end of each period, CBF was assessed with arterial spin labeling MRI. Psychomotor speed, executive function, and memory were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results No serious adverse events were reported, and soy nut intake was well tolerated. Body weights remained stable during the study. Serum isoflavone concentrations increased (daidzein mean difference +/- SD: 128 +/- 113 ng/mL, P < 0.001; genistein: 454 +/- 256 ng/mL, P < 0.001), indicating excellent compliance. Regional CBF increased in 4 brain clusters located in the left occipital and temporal lobes (mean +/- SD increase: 11.1 +/- 12.4 mL center dot 100 g(-1) center dot min(-1), volume: 11,296 mm(3), P < 0.001), bilateral occipital lobe (12.1 +/- 15.0 mL center dot 100 g(-1) center dot min(-1), volume: 2632 mm(3), P = 0.002), right occipital and parietal lobes (12.7 +/- 14.3 mL center dot 100 g(-1) center dot min(-1), volume: 2280 mm(3), P = 0.005), and left frontal lobe (12.4 +/- 14.5 mL center dot 100 g(-1) center dot min(-1), volume: 2120 mm(3), P = 0.009) which is part of the ventral network. These 4 regions are involved in psychomotor speed performance, which improved as the movement time reduced by (mean +/- SD) 20 +/- 37 ms (P = 0.005). Executive function and memory did not change. Conclusions Longer-term soy nut consumption may improve cerebrovascular function of older adults, because regional CBF increased. Effects may underlie observed improvements in psychomotor speed. This trial was registered at clinicaltrials.gov as NCT03627637.

Background The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs). Methods Genetic variants strongly (p –8) and independently (r2 > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649). Results Genetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was − 1.173 (95% confidence interval − 2.214 to − 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs. Conclusions Our study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors.

Purpose Fatty acid (FA) abnormalities are found in various inflammatory disorders and have been related to disturbed gut microbiota. Patients with common variable immunodeficiency (CVID) have inflammatory complications associated with altered gut microbial composition. We hypothesized that there is an altered FA profile in CVID patients, related to gut microbial dysbiosis. Methods Plasma FAs were measured in 39 CVID patients and 30 healthy controls. Gut microbial profile, a food frequency questionnaire, and the effect of the oral antibiotic rifaximin were investigated in CVID patients. Results The n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) (1.4 [1.0–1.8] vs. 1.9 [1.2–2.5], median (IQR), P P n-6 PUFAs (34.3 ± 3.4 vs. 37.1 ± 2.8, mean ± SD, P P P n-6 PUFAs (r = 0.41, P r = 0.51, P n-3 PUFAs (P = 0.78). Moreover, a 2-week course of rifaximin significantly reduced the proportion of n-6 PUFAs (P = 0.04, UNIANOVA). Serum immunoglobulin G (IgG) levels correlated with plasma n-3 PUFAs (rho = 0.36, P = 0.03) and DHA (rho = 0.41, P = 0.009). Conclusion We found a potentially unfavorable FA profile in CVID, related to low IgG levels. High plasma n-6 PUFAs were related to increased gut microbial diversity and altered by rifaximin therapy.

α-linolenic acid (ALA, 18:3n-3) is a carboxylic acid composed of 18 carbon atoms and three cis double bonds, and is an essential fatty acid indispensable to the human body. This study aims to systematically review related studies on the dietary sources, metabolism, and pharmacological effects of ALA. Information on ALA was collected from the internet database PubMed, Elsevier, ResearchGate, Web of Science, Wiley Online Library, and Europe PMC using a combination of keywords including "pharmacology," "metabolism," "sources." The following findings are mainly contained. (a) ALA can only be ingested from food and then converted into eicosapentaenoic acid and docosahexaenoic acid in the body. (b) This conversion process is relatively limited and affected by many factors such as dose, gender, and disease. (c) Pharmacological research shows that ALA has the anti-metabolic syndrome, anticancer, antiinflammatory, anti-oxidant, anti-obesity, neuroprotection, and regulation of the intestinal flora properties. (d) There are the most studies that prove ALA has anti-metabolic syndrome effects, including experimental studies and clinical trials. (e) The therapeutic effect of ALA will be affected by the dosage. In short, ALA is expected to treat many diseases, but further high quality studies are needed to firmly establish the clinical efficacy of ALA.

Perilla seed oil (PSO) has a special aromatic odor, which is unpleasant to the personal preferences of some consumers. To this end, this article evaluated the differences in volatile organic compounds (VOCs), physicochemical characteristics, and fatty acid composition of PSO treated with ethanol (PSO-EA), activated carbon (PSO-AC), and activated kaolin (PSO-AK). The results showed that in the PSO, PSO-EA, PSO-AC, and PSO-AK samples, the content of linolenic acid, oleic acid, and linoleic acid hardly changed. Among the physicochemical characteristics of the four samples, the color difference between PSO and PSO-EA was greater than the color difference between PSO and PSO-AC, PSO-AK. The three treatment methods had the greatest impact on the PSO peroxide value but had little effect on other indicators. Gas chromatography-ion mobility spectrum results identified 28 known volatiles, of which aldehydes, alkenals, alcohols, ketones, and esters were the main groups. Fingerprint analysis found that PSO had an aromatic odor, which includes 1-hexanol, hexanal, and 2-pentylfuran; the removal effect of ethanol on VOCs in PSO was better than that of activated carbon and activated kaolin. The difference between the four oil samples was found from the strength of the VOCs' signals in a two-dimensional map. From the principal components analysis and the "nearest neighbor" fingerprint analysis, it was found that PSO is generally quite different from PSO-EA, PSO-AC, and PSO-AK, while in the "nearest neighbor" fingerprint analysis, PSO-AC and PSO-AK are similar in general. In short, PSO will have better applications in the food field. PRACTICAL APPLICATION: Treatment of PSO with ethanol, activated carbon, and activated kaolin is conducive to the comprehensive utilization of edible resources. In this work, ethanol, activated carbon, and activated kaolin were used to remove VOCs in PSO, and PSO-EA, PSO-AC, and PSO-AK were obtained. The perilla seed oil after these three treatment methods was tested for VOCs, physicochemical characteristics, and fatty acid composition. They can meet the needs of more consumers without affecting the fatty acid composition in the PSO, and have broad development prospects.

Background: There is little knowledge on the effects of alpha-linolenic acid (ALA) and n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on the LDL lipidome and aggregation of LDL particles. Objective: We examined if consumption of Camelina sativa oil (CSO) as a source of ALA, fatty fish (FF) as a source of n-3 LCPUFA and lean fish (LF) as a source of fish protein affect the lipidome of LDL as compared to a control diet. Methods: Participants with impaired glucose tolerance (39 women and 40 men) were randomized to 4 study groups (CSO providing 10 g/d ALA, FF and LF [both 4 fish meals/wk] and control limiting their fish and ALA intake) in a 12-week, parallel trial. Diets were instructed and dietary fats were provided to the participants. The lipidome of LDL particles isolated from samples collected at baseline and after intervention was analyzed with electrospray ionization-tandem mass spectrometry. Results: In the CSO group, the relative concentrations of saturated and monounsaturated cholesteryl ester species in LDL decreased and the species with ALA increased. In the FF group, LDL phosphatidylcholine (PC) species containing n-3 LCPUFA increased. There was a significant positive correlation between the change in total sphingomyelin and change in LDL aggregation, while total PC and triunsaturated PC species were inversely associated with LDL aggregation when all the study participants were included in the analysis. Conclusion: Dietary intake of CSO and FF modifies the LDL lipidome to contain more polyunsaturated and less saturated lipid species. The LDL surface lipids are associated with LDL aggregation. (c) 2021 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects many older people around the world. Numerous studies are underway to evaluate the protective effects of natural products in AD. Alpha-linoleic acid (ALA) is an essential unsaturated fatty acid that exhibits neuroprotective outcomes in rat models of ischemic stroke and Parkinson's disease. This research aimed to investigate the effect of ALA on oxidative stress, neuroinflammation, neuronal death, and memory deficit induced by amyloid-beta (Aβ) peptide. After intrahippocampal injection of Aβ1-42, rats received ALA (150 μg/kg, subcutaneously) for 14 consecutive days. ALA decreased the levels of malondialdehyde and nitric oxide, enhanced glutathione content, and increased the activity of catalase in the hippocampus of the rat model of AD. It also reduced the expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, nuclear factor-kappa B, and N-methyl-d-aspartate receptor subunits NR2A and NR2B mRNAs in the hippocampus, prevented the neuronal loss in the CA1 region, and enhanced the expression of α7 nicotinic acetylcholine receptor. In addition, ALA allowed Aβ1-42-injected rats to spend less time and distance to reach the hidden platform in the Morris water maze test and to swim longer in the target quadrant. We concluded that ALA reduces the biochemical, molecular, histological, and behavioral changes caused by Aβ1-42 and it may be an effective option for treating AD.

Background The beneficial effects of ω−3 polyunsaturated fatty acids (PUFA) vary between different sources. However, there is a paucity of comparative studies regarding the effects and mechanisms of marine and plant ω−3 PUFA on obesity. Objective The aim of this study was to evaluate the effects of fish oil (FO) and perilla oil (PO) on glucolipid metabolism, inflammation, and adipokine in mice fed a high-fat (HF) diet in association with the contribution of toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) pathway. Methods C57BL/6J mice and MyD88−/− mice were randomly divided into 4 groups: normal chow diet, HF diet, HF diet accompanied by daily gavage with either FO or PO. After 4 weeks, blood biochemistries, adipocyte histology, mRNA, and protein expression of MyD88-dependent and -independent pathways of TLR4 signaling in epididymal adipose tissue were measured. Results In C57BL/6J mice, there were no statistical differences between FO and PO in decreasing body weight, glucose, insulin, triglyceride, total cholesterol, interleukin-6, and increasing adipocyte counts. FO and PO decreased mRNA and protein expression of TLR4, MyD88, tumor necrosis factor receptor-associated factor 6, inhibitor of nuclear factor kappa B kinase beta and nuclear factor-kappa B p65. In MyD88−/− mice, the beneficial effects of FO and PO on HF diet-induced metabolism abnormalities and inflammation were abolished. FO and PO had no impacts on mRNA and protein expression of receptor-interacting protein-1, interferon regulate factor 3, and nuclear factor-kappa B p65. Conclusion FO and PO exhibit similar protective effects on metabolic disorders and inflammation through inhibiting TLR4 signaling in a manner dependent on MyD88. These findings highlight plant ω−3 PUFA as an attractive alternative source of marine ω−3 PUFA and reveal a mechanistic insight for preventive benefits of ω−3 PUFA in obesity and related metabolic diseases.

In this research communication we describe the composition of fatty acids (FA) present in the milk of the Nordestina donkey breed, and how they differ during lactation. Milk samples were taken from 24 multiparous lactating Nordestina donkeys that grazed the Caatinga, comprising 5 animals at each of around 30, 60 and 90 d in milk (DIM) and a further 9 animals ranging from 120 to 180 DIM. The milk fat content was analysed by mid infrared spectroscopy and the FA profile by gas chromatography. The milk fat percentage ranged from 0.45 to 0.61%. The main FA found in milk were 16:0 and 18:1c9. These did not differ among DIM classes and comprised 23% and 25% of total FA. Notably, the α-Linolenic acid (18:3 n-3) was the third most abundant FA and differed (P < 0.05) with DIM, being lowest in the 30 and 60 DIM samples (around 10.7% of total FA) and highest in the 60 and 90 DIM classes (around 14.6% of total FA). The low-fat content and the FA profile of the donkey milk gives it potential as a functional ingredient, which could help to preserve the commercial viability of the Nordestina donkey breed.

Introduction: L-arginine supplementation may improve vascular endothelial function. As tree nuts and groundnuts are a source of the amino acid L-arginine, we performed a meta-analysis of human ran-domized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of L-arginine supplementation on fasting and postprandial endothelial function as assessed by flow-mediated vasodilation of the brachial artery (FMD).Methods: Summary estimates of weighted mean differences (WMDs) in FMD and 95% confidence in-tervals (CIs) were calculated using random-effect meta-analyses.Results: A total of thirteen RCTs focusing on tree nut and groundnut consumption and nineteen RCTs investigating effects of L-arginine supplementation were included. Longer-term consumption of tree nuts and groundnuts increased fasting FMD by 1.09 %-point (PP) (95% CI: 0.49, 1.69, P < 0.001; I-2: 76.7%, P < 0.001), while L-arginine supplementation (daily range: 3-21 g) increased fasting FMD by 0.53 PP (95% CI: 0.12, 0.93; P = 0.012; I-2: 91.6%, P < 0.001). Effects between treatments were not statistically different (P = 0.31). Tree nut and groundnut consumption did not affect postprandial FMD responses (1.25 PP, 95% CI: -0.31, 2.81, P = 0.12; I-2: 91.4%, P < 0.001), whereas L-arginine supplementation (range: 3-15 g) improved FMD during the postprandial phase by 2.02 PP (95% CI: 0.92, 3.13, P < 0.001; I-2: 99.1%, P < 0.001). However, treatment effects did not differ significantly (P = 0.60). Overall, these results derive from high-quality evidence.Conclusion: Longer-term consumption of tree nuts and groundnuts, as well as L-arginine supplementa-tion did improve fasting endothelial function, as assessed by FMD. However, the positive effects of tree nuts and groundnuts could not be fully explained by the amount of L-arginine in these nuts. Only L-arginine supplementation did improve postprandial FMD, but effects were not different from those of tree nuts and groundnuts. Future studies should focus on the identifications of the bioactive nutrients in tree nuts and groundnuts and mechanistic pathways behind differences in postprandial and longer-term fasting changes in FMD. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

In the study, new polymeric micelles loaded with azithromycin were prepared to enhance azithromycin's solubility and evaluate its in vitro/in vivo antibacterial activity against Staphylococcus aureus. Amphiphilic α-Linolenic acid-methoxy poly (ethylene glycol) polymer (MPEG-LNA) was synthesized through DCC-DMAP esterification procedure. Through thin-film hydration method, optimized azithromycin-loaded micelles (AZI-M) were prepared with 87.15% of encapsulation efficiency and 11.07% of drug loading capacity when the ratio of LNA to MPEG was 4. Azithromycin's water-solubility was obviously enhanced due to its loading into the polymeric micelles. The azithromycin-loaded micelles were characterized in terms of x-ray diffraction, Fourier transform infrared spectroscopy, in vitro release, and in vitro/in vivo antibacterial experiments. Although the drug-loaded micelles provided a slow and continuous azithromycin's release in comparison with free azithromycin, in vitro antibacterial activity results confirmed that its effect on the inhibition of bacterial growth and biofilm formation was similar to free azithromycin. It is more interesting that the azithromycin-loaded micelles achieved good in vivo antibacterial therapeutic effect like QiXian® (azithromycin lactobionate injection) in mouse model of intraperitoneal infection. AZI-M can be considered as a potential candidate for in vivo antibiotic therapy of Staphylococcus aureus infections.

Background Differences in health effects of dietary α-linolenic acid (ALA) and DHA are mediated at least in part by differences in their effects on oxylipins. Objectives Time course and sex differences of plasma oxylipins in response to ALA- compared with DHA-rich supplements were examined. Methods Healthy men and women, aged 19-34 y and BMI 18-28 kg/m2, were provided with capsules containing ∼4 g/d of ALA or DHA in a randomized double-blind crossover study with >6-wk wash-in and wash-out phases. Plasma PUFA and oxylipin (primary outcome) concentrations at days 0, 1, 3, 7, 14, and 28 of supplementation were analyzed by GC and HPLC-MS/MS, respectively. Sex differences, supplementation and time effects, and days to plateau were analyzed. Results ALA supplementation doubled ALA concentrations, but had no effects on ALA oxylipins after 28 d, whereas DHA supplementation tripled both DHA and its oxylipins. Increases in DHA oxylipins were detected as early as day 1, and a plateau was reached by days 5-7 for 11 of 12 individual DHA oxylipins and for total DHA oxylipins. Nine individual DHA oxylipins reached a plateau in females with DHA supplementation, compared with only 4 in males. A similar time course and sex difference pattern occurred with EPA and its oxylipins with DHA supplementation. DHA compared with ALA supplementation also resulted in higher concentrations of 4 individual arachidonic acids, 1 linoleic acid, and 1 dihomo-γ-linolenic acid oxylipin, despite not increasing the concentrations of these fatty acids, further demonstrating that oxylipins do not always reflect their precursor PUFA. Conclusions DHA compared with a similar dose of ALA has greater effects on both n-3 and n-6 oxylipins in young, healthy adults, with differences in response to DHA supplementation occurring earlier and being greater in females. These findings can help explain differences in dietary effects of ALA and DHA.This study was registered at clinicaltrials.gov as NCT02317588.

Omega-3 (n-3) fatty acids offer a plethora of health benefits with the majority of evidence showing beneficial effects from marine sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Emerging research examines the effects of n-3 dietary intakes on blood markers of vegetarians and vegans, but official guidance for plant based marine alternatives is yet to reach consensus. This scoping review provides an overview of trials investigating bioavailability of plant n-3 oils including EPA and DHA conversion. Searches of MEDLINE, PubMed, CINAHL and clinical trial registers identified randomized controlled trials from January 2010 to September 2020. The ‘Omega-3 index’ (EPA + DHA (O3I)), was used to compare n-3 status, metabolic conversion and bioavailability. Two reviewers independently screened articles and extracted data on outcomes. From 639 identified articles, screening and eligibility checks gave 13 articles. High dose flaxseed or echium seed oil supplements, provided no increases to O3I and some studies showed reductions. However, microalgal oil supplementation increased O3I levels for all studies. Findings indicate preliminary advice for vegetarians and vegans is regular consumption of preformed EPA and DHA supplements may help maintain optimal O3I. Further studies should establish optimum EPA and DHA ratios and dosages in vegetarian and vegan populations.

Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer’s disease (AD). The extracellular burden of amyloid-β plaques and Tau seed fabricate the activation of microglia. The seeding effect of extracellular Tau species is an emerging aspect to study about Tauopathies in AD. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. The excessive neuroinflammation cumulatively hampers phagocytic function of microglia reducing the clearance of extracellular protein aggregates. Omega-3 fatty acids, especially docosahexaenoic acid and eicosapentaenoic acid, are recognized to induce anti-inflammatory phenotype of microglia. In addition to increased cytokine production, omega-3 fatty acids enhance phagocytic receptors expression in microglia. In this study, we have observed the phagocytosis of extracellular Tau in the presence of α-linolenic acid (ALA). The increased phagocytosis of extracellular Tau monomer and aggregates have been observed upon ALA exposure to microglia cells. After internalization, the degradation status of Tau has been studied with early and late endosomal markers Rab5 and Rab7. Further, the lysosome-mediated degradation of internalized Tau was studied with LAMP-2A, a lysosome marker. The enhanced migratory ability in the presence of ALA could be beneficial for microglia to access the target and clear it. The increased migration of microglia was found to induce the microtubule-organizing center repolarization. The data indicate that the dietary fatty acids ALA could significantly enhance phagocytosis and intracellular degradation of internalized Tau. Our results suggest that microglia could be influenced to reduce extracellular Tau seed with dietary fatty acids.

International audience; Myocardial infarction (MI) is an irreversible event caused by cardiac ischemia and may be fatal. Studies reported that increased intake of n-3 polyunsaturated fatty acids (PUFA) namely, eicosapentaenoic acid and docosahexaenoic acid reduce the risk of cardiovascular disease and lower the incidence of MI. Nonetheless, the cardioprotective effect of plant n-3-PUFA such as α-linolenic acid (ALA) in the diet is not conclusive. In this study, Sprague Dawley rats were supplemented with isocaloric diets enriched with ALA rich flaxseed (FS) and flaxseed oil (FSO), and normal chow (Control) for 4 weeks. MI was induced by isoproterenol (ISO) injection. Results showed that all ALA-enriched diets displayed cardioprotection against MI. The heart to body weight ratio, plasma LDH activity and plasma cTnI were reduced compared to ISO and was prominent in FS diet. ALA and EPA were up-regulated in both tissues and plasma by ALA-diets compared to Control and remained higher than ISO groups. Notably, LOX-mediated HETEs decreased whereas LOX-mediated HDHAs were elevated in both tissues and plasma of ALA-enriched diets compared to ISO. In addition, non-enzymatic oxidized products from arachidonic acid including 15-F2t-IsoP were reduced in both tissues and plasma of MI rats supplemented with ALA-enriched diets while those from n-3 PUFAs including F4-NeuroPs, PhytoPs and PhytoFs were elevated compared to control. ALA-enriched diets particularly flaxseed reduced gene expressions of inflammatory cytokines namely IL-1β, IL-6 and TNFα and prevented the down regulation of antioxidant catalase in the heart tissues. In conclusion ALA-enriched diets potentially exerted cardioprotection through the regulation of anti-inflammatory and anti-oxidative mediators from n-3 PUFA autooxidation.

International audience; α-Linolenic acid (ALA) and its non-enzymatic oxidized products, namely, phytoprostanes and phytofurans, are found in some nuts. The uptake and deposition of these compounds are not well-defined. Walnut has high ALA and a considerable amount of phytoprostanes and phytofurans compared to other common nuts. When fed to rodents, ALA and eicosapentaenoic acid levels increased in the liver and heart tissues compared to the control diet. Furthermore, phytoprostanes and phytofurans were elevated 3fold in both tissues after a walnut diet, indicating that they are not only contributed from the diet but also generated through in vivo autoxidation of ALA found in the walnuts. It was further noted that a walnut diet reduced 5-F 2t-isoprostanes and 12hydroxyeicosatetraenoic acid and induced 4-F 4t-neuroprostane and significant amounts of anti-inflammatory hydroxydocosahexaenoic acid in the liver only. Altogether, high ALA in a walnut diet elevated phytoprostanes and phytofurans in the liver and heart tissues and showed the regulation of anti-inflammatory lipid mediators in the liver only.

The aim of present study was to investigate regulatory mechanism of alpha-linolenic acid (ALA) during in vitro maturation (IVM) on nuclear and cytoplasmic maturation of porcine oocytes. Basically, immature cumulus-oocyte complexes (COCs) were incubated for 22 h in IVM-I to which hormone was added, and then further incubated for 22 h in IVM-II without hormone. As a result, relative cumulus expansion was increased at 22 h after IVM and it was enhanced by treatment of ALA compared with control group (p < 0.05). During IVM process within 22 h, cAMP level in oocytes was decreased at 6 h (p < 0.05) and it was recovered at 12 h in ALA-treated group, while oocytes in control group recovered cAMP level at 22 h. In cumulus cells, it was reduced in all time point (p < 0.05) and ALA did not affect. Treatment of ALA enhanced metaphase-I (MI) and MII population of oocytes compared with oocytes in control group at 22 and 44 h, respectively (p < 0.05). Intracellular GSH levels in ALA group was increased at 22 and 44 h after IVM (p < 0.05), whereas it was increased in control group at 44 h after IVM (p < 0.05). In particular, the GSH in ALA-treated oocytes during 22 h of IVM was higher than control group at 22 h (p < 0.05). Lipid amount in oocytes from ALA group was higher than control group (p < 0.05). Treatment of ALA did not influence to absorption of glucose from medium. Cleavage and blastocyst formation of ALA-treated oocytes were enhanced compared with control group (p < 0.05). These findings suggest that supplementation of ALA could improve oocyte maturation and development competence through increasing GSH synthesis, lipid storage, and regulation of cAMP accumulation during early 22 h of IVM, and these might be mediated by cumulus expansion.

Lipid peroxidation is a key to a portfolio of neurodegenerative diseases and plays a central role in α-synuclein (α-syn) toxicity, mitochondrial dysfunction and neuronal death, all key processes in the pathogenesis of Parkinson’s disease (PD). Polyunsaturated fatty acids (PUFAs) are important constituents of the synaptic and mitochondrial membranes and are often the first molecular targets attacked by reactive oxygen species (ROS). The rate-limiting step of the chain reaction of ROS-initiated PUFAs autoxidation involves hydrogen abstraction at bis-allylic sites, which can be slowed down if hydrogens are replaced with deuteriums. In this study, we show that targeted overexpression of human A53T α-syn using an AAV vector unilaterally in the rat substantia nigra reproduces some of pathological features seen in PD patients. Chronic dietary supplementation with deuterated PUFAs (D-PUFAs), specifically 0.8% D-linoleic and 0.3% H-linolenic, produced significant disease-modifying beneficial effects against α-syn-induced motor deficits, synaptic pathology, oxidative damage, mitochondrial dysfunction, disrupted trafficking along axons, inflammation and DA neuronal loss. These findings support the clinical evaluation of D-PUFAs as a neuroprotective therapy for PD.

The omega 3 fatty acids (ω3FA) have been recommended for the treatment of Type 2 Diabetes Mellitus (T2DM) and its complications, but there are studies questioning those beneficial effects. In this research, we supplemented the short-chain ω3FA, alpha-linolenic acid (ALA), to a model of rats with T2DM and normoglycemic controls, for 5 months. We were mainly interested in studying the effects of diabetes and ALA on the physicochemical properties of mitochondrial membranes and the consequences on mitochondrial respiration. We found that the Respiratory Control (RC) of diabetic rats was 46% lower than in control rats; in diabetic rats with ALA supplement, it was only 23.9% lower, but in control rats with ALA supplement, the RC was 29.5% higher, apparently improving. Diabetes also decreased the membrane fluidity, changed the thermotropic characteristics of membranes, and increased the proportion of saturated fatty acids. ALA supplement partially kept regulated the physicochemical properties of mitochondrial membranes in induced rats. Our data indicate that diabetes decreased the membrane fluidity through changes in the fatty acids composition that simultaneously affected the RC, which means that the mitochondrial respiration is highly dependent on the physicochemical properties of the membranes. Simultaneously, it was followed the effects of ALA on the progress of diabetes and we found also that the supplementation of ALA helped in controlling glycaemia in rats induced to T2DM; however, in control non-induced rats, the supplementation of ALA derived in characteristics of initial development of diabetes.

Background: Flaxseed (Linum usitatissimum) is an oil-based seed that contains high amounts of alpha-linolenic acid, linoleic acid, lignans, fiber and many other bioactive components which is suggested for a healthier life. Nowadays, flaxseed is known as a remarkable functional food with different health benefits for humans and protects against cardiovascular disease, diabetes, dyslipidemia, obesity and altogether metabolic syndrome. Methods: To review the bioactive components of flaxseed and their potential health effects, PubMed and Scopus were searched from commencement to July 2019. Keywords including: "flaxseed", "Linum usitatissimum", "metabolic syndrome", "obesity", "inflammation", "insulin resistance", "diabetes", "hyperlipidemia" and "menopause" were searched in the databases with varying combinations. Conclusions: Consumption of flaxseed in different forms has valuable effects and protects against cardiovascular disease, hypertension, diabetes, dyslipidemia, inflammation and some other complications. Flaxseed can serve as a promising candidate for the management of metabolic syndrome to control blood lipid levels, fasting blood sugar, insulin resistance, body weight, waist circumference, body mass and blood pressure.

Background Current dietary recommendations for cardiovascular disease (CVD) prevention focus more on dietary patterns than on single nutrients. However, randomized controlled trials using whole-diet approaches to study effects on both fasting and postprandial CVD risk markers are limited. Objective This randomized parallel trial compared the effects of a healthy diet (HD) with those of a typical Western diet (WD) on fasting and postprandial CVD risk markers in overweight and obese adults. Methods After a 2-wk run-in period, 40 men and women (50–70 y; BMI: 25–35 kg/m2) consumed the HD (high in fruit and vegetables, pulses, fibers, nuts, fatty fish, polyunsaturated fatty acids; low in salt and high-glycemic carbohydrates; n = 19) or the WD (less fruit, vegetables, and fibers; no nuts and fatty fish; and more saturated fatty acids and simple carbohydrates; n = 21) for 6 wk. Fasting and postprandial cardiometabolic risk markers were assessed as secondary outcome parameters during a 5-h mixed-meal challenge, and a per protocol analysis was performed using 1-factor ANCOVA or linear mixed models. Results Differences in diet-induced changes are expressed relative to the HD group. Changes in fasting plasma total cholesterol (–0.57 ± 0.12 mmol/L, P

BACKGROUND Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function. OBJECTIVES The authors investigated whether serum-PC EPA (proxy for marine omega-3 consumption) levels at the time of STEMI were associated with a lower incidence of major adverse cardiovascular events (MACE), all-cause mortality, and readmission for cardiovascular (CV) causes at 3 years' follow-up. We also explored the association of alpha-linolenic acid (ALA, proxy for vegetable omega-3 intake) with all-cause mortality and MACE. METHODS The authors prospectively included 944 consecutive patients with STEMI (mean age 61 years, 209 women) undergoing primary percutaneous coronary intervention. We determined serum-PC fatty acids with gas chromatography. RESULTS During follow-up, 211 patients had MACE, 108 died, and 130 were readmitted for CV causes. A Cox propor-tional hazards model adjusted for known clinical predictors showed that serum-PC EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62 to 0.94, and HR: 0.74; 95% CI: 0.58 to 0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95% CI: 0.44 to 0.96, for a 1-SD increase). CONCLUSIONS Elevated serum-PC EPA and ALA levels at the time of STEMI were associated with a lower risk of clinical adverse events. Consumption of foods rich in these fatty acids might improve the prognosis of STEMI. (c) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Stroke severely impairs quality of life and has a high mortality rate. On the other hand, dietary docosahexaenoic acid (DHA) prevents neuronal damage. In this review, we describe the effects of dietary DHA on ischemic stroke-associated neuronal damage and its role in stroke prevention. Recent epidemiological studies have been conducted to analyze stroke prevention through DHA intake. The effects of dietary intake and supply of DHA to neuronal cells, DHA-mediated inhibition of neuronal damage, and its mechanism, including the effects of the DHA metabolite, neuroprotectin D1 (NPD1), were investigated. These studies revealed that DHA intake was associated with a reduced risk of stroke. Moreover, studies have shown that DHA intake may reduce stroke mortality rates. DHA, which is abundant in fish oil, passes through the blood-brain barrier to accumulate as a constituent of phospholipids in the cell membranes of neuronal cells and astrocytes. Astrocytes supply DHA to neuronal cells, and neuronal DHA, in turn, activates Akt and Raf-1 to prevent neuronal death or damage. Therefore, DHA indirectly prevents neuronal damage. Furthermore, NDP1 blocks neuronal apoptosis. DHA, together with NPD1, may block neuronal damage and prevent stroke. The inhibitory effect on neuronal damage is achieved through the antioxidant (via inducing the Nrf2/HO-1 system) and anti-inflammatory effects (via promoting JNK/AP-1 signaling) of DHA.

Background Perilla seed oil (PSO) is the main constituent of perilla seeds currently being used in the food industry, however it also has great clinical potential in the regulation of lung function as a nutrition supplement because of the high content of α-linolenic acid (ALA). In this study, the pharmacological activities including anti-tussive, expectorant and anti-inflammatory effect of PSO were performed. Besides, the 90-day sub-chronic oral toxicity with a 30 day recovery period was evaluated in Wistar rats. Results The pharmacological studies demonstrated that PSO inhibited cough frequency induced by capsaicine in mice. PSO also inhibited the leukotriene B4 (LTB4) release from the calcium ionophore A23187-induced polymorphonuclear neutrophils (PMNs) to some extent. In this sub-chronic toxicity study, mortality, clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, organ weight, necropsy, and histopathology were used to evaluate the toxicity of PSO. Lower body weight and various negative impacts on liver related parameters without histopathological lesion were observed in the 16 g kg-1 groups. No clinically significant changes were discovered in the 4 g kg-1 group during the test period. Conclusion In summary, PSO exhibited anti-tussive and anti-inflammatory activities in vivo and in vitro. These sub-chronic toxicity study inferred that the "no-observed adverse effect level" (NOAEL) of PSO in Wistar rats was determined to be 4 g kg-1 . These results may provide a safety profile and a valuable reference for the use of the PSO. This article is protected by copyright. All rights reserved.

Organ transplant recipients have over 100-fold higher risk of developing skin cancer than the general population and are in need of further preventive strategies. We assessed the possible preventive effects of omega-3 polyunsaturated fatty acid (PUFA) intake from food on the two main skin cancers, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in kidney and liver transplant recipients. Adult kidney or liver transplant recipients transplanted for at least 1 year and at high risk of skin cancer were recruited from the main transplant hospital in Queensland, 2012–2014 and followed until mid-2016. We estimated their dietary total long-chain omega-3 PUFAs and α-linolenic acid intakes at baseline using a food frequency questionnaire and ranked PUFA intakes as low, medium, or high. Relative risks (RRsadj) of skin cancer adjusted for confounding factors with 95% confidence intervals (CIs) were calculated. There were 449 transplant recipients (mean age, 55 years; 286 (64%) male). During follow-up, 149 (33%) patients developed SCC (median 2/person; range 1–40) and 134 (30%), BCC. Transplant recipients with high total long-chain omega-3 PUFA compared with low intakes showed substantially reduced SCC tumour risk (RRadj 0.33, 95% CI 0.18–0.60), and those with high α-linolenic acid intakes experienced significantly fewer BCCs (RRadj 0.40, 95% CI 0.22–0.74). No other significant associations were seen. Among organ transplant recipients, relatively high intakes of long-chain omega-3 PUFAs and of α-linolenic acid may reduce risks of SCC and BCC, respectively.

BACKGROUND: Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled trial focusing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre-)hypertensive individuals.METHODS: In a double-blind randomized, placebo-controlled parallel study, 59 overweight and obese adults (40 men and 19 women, aged 60 ± 8 years) with a high-normal blood pressure or mild (stage I) hypertension consumed daily either 10 g of refined cold-pressed flaxseed oil, providing 4.7 g ALA (n = 29), or 10 g of high-oleic sunflower (control) oil (n = 30) for 12 weeks.RESULTS: As compared with the high-oleic oil control, intake of flaxseed oil did not change brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, retinal microvascular calibers and plasma markers of microvascular endothelial function during the fasting and postprandial phase. Fasting plasma concentrations of free fatty acid (FFA) and TNF-α decreased by 58 μmol/L (P = 0.02) and 0.14 pg/mL (P = 0.03), respectively. No differences were found in other fasting markers of lipid and glucose metabolism, and low-grade systemic inflammation. In addition, dietary ALA did not affect postprandial changes in glucose, insulin, triacylglycerol, FFA and plasma inflammatory markers after meal intake.CONCLUSION: A high intake of ALA, about 3-5 times the recommended daily intake, for 12 weeks decreased fasting FFA and TNF-α plasma concentrations. No effects were found on other metabolic risk markers and vascular function during the fasting and postprandial phase in untreated high-normal and stage I hypertensive individuals.

For decades, genetic engineering approaches to produce unusual fatty acids (UFAs) in crops has reached a bottleneck, including reduced seed oil production and seed vigor. Currently, plant models in the field of research are primarily used to investigate defects in oil production and seedling development, while the role of UFAs in embryonic developmental defects remains unknown. In this study, we developed a transgenic Arabidopsis plant model, in which the embryo exhibits severely wrinkled appearance owing to α-linolenic acid (ALA) accumulation. RNA-seq analysis in the defective embryo suggested that brassinosteroid synthesis, fatty acid (FA) synthesis, and photosynthesis were inhibited, while FA degradation, endoplasmic reticulum (ER) stress, and oxidative stress were activated. Lipidomics analysis showed that ultra-accumulated ALA is released from Phosphatidylcholine (PC) as a free fatty acid (FFA) in cell, inducing severe ER and oxidative stress. Furthermore, we identified that overexpression of lysophosphatidic acid acyltransferase 2 (LPAT2) rescued the defective phenotype. In the rescue line, the pool capacity of the Kennedy pathway was increased, and the esterification of ALA indirectly to triacylglycerol (TAG) was enhanced to avoid stress. This study provides a plant model that aids in understanding the molecular mechanism of embryonic developmental defects, and generate strategies to produce higher levels of UFAs.

To investigate the effect of ALA intake on blood lipid profiles, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein (VLDL-C) and ratio of TC to HDL-C. We systematically searched randomized controlled trials of ALA intervention on PubMed, Embase, Cochrane library and related references up to March 2018. The final values were calculated as weighted mean difference (WMD) by using a random effects model. Subgroup analysis and meta-regression were used to explore the source of heterogeneity. Generalized least square was performed for dose-response analysis. Forty-seven studies with 1305 individuals in the ALA arm and 1325 individuals in the control arm were identified. Compared with control group, dietary intake of ALA significantly reduced the concentrations of TG (WMD -0.101 mmol/L; 95% CI: -0.158 to -0.044 mmol/L

Background Lipid metabolism is altered in Alzheimer's disease (AD); however, the relationship between AD risk factors (age, APOEɛ4, and gender) and lipid metabolism is not well defined. Objective We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals. Methods We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore the relationship between risk factors and plasma lipid species. Results We observed strong associations between plasma lipid species with gender and increasing age in cognitively normal individuals. However, APOEɛ4 was relatively weakly associated with plasma lipid species. Interaction analysis identified differential associations of sphingolipids and polyunsaturated fatty acid esterified lipid species with AD based on age and gender, respectively. These data indicate that the risk associated with age, gender, and APOEɛ4 may, in part, be mediated by changes in lipid metabolism. Conclusion This study extends our existing knowledge of the relationship between the lipidome and AD and highlights the complexity of the relationships between lipid metabolism and AD at different ages and between men and women. This has important implications for how we assess AD risk and also for potential therapeutic strategies involving modulation of lipid metabolic pathways.

BACKGROUND Linoleic acid (LA; 18:2n-6) has been considered to promote low-grade chronic inflammation and adiposity. Studies show adiposity and inflammation are inversely associated with bone mass. OBJECTIVES This study tested the hypothesis that decreasing the dietary ratio of LA to α-linolenic acid (ALA, 18:3n-3), while keeping ALA constant, mitigates high-fat diet (HF)-induced adiposity and bone loss. METHODS Male C57BL/6 mice at 6 wk old were assigned to 4 treatment groups and fed 1 of the following diets ad libitum for 6 mo: a normal-fat diet (NF; 3.85 kcal/g and 10% energy as fat) with the ratio of the PUFAs LA to ALA at 6; or HFs (4.73 kcal/g and 45% energy as fat) with the ratio of LA to ALA at 10:1, 7:1, or 4:1, respectively. ALA content in the diets was kept the same for all groups at 1% energy. Bone structure, body composition, bone-related cytokines in serum, and gene expression in bone were measured. Data were analyzed using 1-factor ANOVA. RESULTS Compared with those fed the NF, mice fed the HFs had 19.6% higher fat mass (P

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by inflammation of the large intestine, rectal bleeding, and abdominal pain. It can be alleviated by certain bioactive compounds, including α-linolenic acid (ALA), which is a bioactive component in fermented black radish (Raphanus sativus L. var. niger). The aim of this study was to evaluate the anti-inflammatory effects of ALA in dextran sulfate sodium (DSS)-induced UC in mice. UC was induced in C57BL/6 mice by allowing them to freely drink water containing 2.5% DSS for 7 days, followed by oral administration of ALA (30 and 60 mg/kg/day) or vehicle control for 7 days. DSS-induced colitis was evaluated using the Disease Activity Index (DAI) and by measuring colon length and performing a histopathological examination. Compared to the control group, the vehicle-treated group showed a higher DAI score, shorter colon, goblet cell loss, and crypt shortening. The ALA treatment mitigated clinical signs of UC and histopathological changes. Furthermore, it mitigated intestinal inflammation by reducing the expression of ionized calcium binding adaptor molecule 1-positive macrophages in the colon. These results show that ALA alleviates DSS-induced UC by suppressing colon damage, which includes goblet cell loss, crypt shortening, and a reduction of macrophages in the colon.

Background Non-alcoholic fatty liver disease (NAFLD) is a public health problem lacking an approved pharmacological treatment. Omega-3 fatty acids have shown to reverse NAFLD. Chia is a seed rich in α-linolenic acid (ALA), antioxidants, and fiber; therefore, it could be useful to treat NAFLD. Methods In a single arm experimental design study, the effect of 25 g/day of milled chia was assessed in 25 patients with NAFLD. After two weeks of dietary stabilization (basal condition) and eight weeks of a chia-supplemented isocaloric diet, liver:spleen attenuation index and visceral abdominal fat (VAF) were measured by computed tomography. Lipids, lipoproteins, free fatty acids (FFA), and ALA plasma concentrations were also determined. Results Dietary chia supplementation induced an increase in plasma ALA concentration (75%) and dietary fiber (55%) consumption. After chia supplementation, VAF (9%), body weight (1.4%), total cholesterol (2.5%), non-high density lipoprotein cholesterol (3.2%), and circulating FFA (8%) decreased. Furthermore, NAFLD regressed in 52% of the treated patients (P Conclusions The results of the present study show that 25 g/day of milled chia ameliorates NAFLD. Chia is an accessible vegetal source of omega-3 fatty acids, antioxidants, and fiber, which could have the potential to prevent metabolic abnormalities in NAFLD patients. Considering that there is no pharmacological treatment approved for NAFLD, the findings of the present study suggest that a chia-supplemented diet could be an innovative alternative to control this disease. Retrospectively registered https://clinicaltrials.gov/show/NCT03942822

This study aimed to estimate the influences of flax oil and a mixture of ethyl esters of fatty acids from flax oil added to a milk replacer (MR) formulation on the biochemical, immunological, and antioxidant status of blood, production parameters, and health of calves. Twenty-seven Holstein-Frisian calves were assigned to 3 groups: the control group without fat added to the diet (CON, n = 9), a group receiving ethyl esters of flax oil (10 g/d) with lyophilized apples (25 g; MRE), or a group receiving flax oil (10 g/d) with lyophilized apples (25 g; MRL). The study was conducted from d 14 to d 42 of life. Intake of MR and feed were recorded daily, and fecal scores, rectal temperature, and body weight were recorded weekly. Laboratory blood tests were conducted every 7 d from d 14 to 42. Supplementation with the formulation containing ethyl esters of flax oil (MRE) positively affected health, average daily weight gain, growth rate, and feed efficiency. Intake of the starter feed was lower in the calves receiving the formulation with flax oil (MRL). The MRE formulations lowered the concentrations of triglycerides, total cholesterol, and LDL fraction in blood serum and decreased the total antioxidant capacity (TAS) and levels of glutathione peroxidase (GPx). The MRL formulation increased TAS and GPx levels in blood serum. The MRE treatment limited the circulating levels of tumor necrosis factor. The MRE and MRL preparations lowered the concentration of SFA (C16:0, C18:0, C18:1) in blood serum, and MRE significantly increased levels of α-linolenic acid. The MRE and MRL preparations beneficially affected production and physiological parameters. Our data support the idea that supplementation with n-3 fatty acids improves calf growth and metabolic and oxidative functions in young calves.

The aim of this review was to compile evidence and understand chia seed effects on unbalanced diet animal studies and the molecular mechanisms on metabolic biomarker modulation. A systematic review was conducted in electronic databases, following PRISMA recommendations. Risk of bias and quality was assessed using SYRCLE toll and ARRIVE guidelines. Seventeen articles were included. Throughout the studies, chia's main effects are associated with AMPK modulation: improvement of glucose and insulin tolerance, lipogenesis, antioxidant activity, and inflammation. Details about randomization and allocation concealment were insufficient, as well as information about blind protocols. Sample size, chia dose, and number of animals evaluated for each parameter were found to be lacking information among the studies. Based on experimental study data, chia has bioactive potential, and its daily consumption may reduce the risk of chronic disease development, mainly due to the antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic effects of the seed. PRACTICAL APPLICATION: The consumption of chia seeds may improve lipid profile, insulin and glucose tolerance, and reduce risk of cardiovascular disease. Whole seed or its oil presents positive effect, but the effects of chia oil can act faster than the seed.

Platelet adhesion to the sub-endothelial matrix and damaged endothelium occurs through a multi-step process mediated in the initial phase by glycoprotein Ib binding to von Willebrand factor (vWF), which leads to the subsequent formation of a platelet plug. The plant-derived ω-3 fatty acid α-linolenic acid is an abundant alternative to fish-derived n-3 fatty acids and has anti-inflammatory and antithrombotic properties. In this study, we investigated the impact of α-linolenic acid on human platelet binding to vWF under high-shear flow conditions (mimicking blood flow in stenosed arteries). Pre-incubation of fresh human blood from healthy donors with α-linolenic acid at dietary relevant concentrations reduced platelet binding and rolling on vWF-coated microchannels at a shear rate of 100 dyn/cm2. Depletion of membrane cholesterol by incubation of platelet-rich plasma with methyl-β cyclodextrin abrogated platelet rolling on vWF. Analysis of glycoprotein Ib by applying cryo-electron tomography to intact platelets revealed local clusters of glycoprotein Ib complexes upon exposure to shear force: the formation of these complexes could be prevented by treatment with α-linolenic acid. This study provides novel findings on the rapid local rearrangement of glycoprotein Ib complexes in response to high-shear flow and highlights the mechanism of in vitro inhibition of platelet binding to and rolling on vWF by α-linolenic acid.

The role of the major plant-derived n-3 PUFA, alpha-linolenic acid (ALA), on the risk of atherosclerotic cardiovascular (ASCVD) remains unclear, but most studies have reported no association. However, the association between intake of ALA and the risk of ASCVD may depend on the intake of marine n-3 PUFAs. We investigated this hypothesis among more than 53,909 middle-aged, Danish men and women followed for a median of 13.4 years. We found a statistically significant inverse association between ALA intake modelled as a restricted cubic spline and the rate of ASCVD in subjects with a low intake of marine n-3 PUFAs, while no association was observed among subjects with a higher intake of marine n-3 PUFAs. Our findings suggest that the intake of ALA may be associated with a lower risk of total ASCVD, but only among subjects with a low intake of marine n-3 PUFAs.

Some studies suggested a positive effect against cardiometabolic diseases of supplementation of alpha-linolenic acid (ALA, C18:3 n-3) rich foods in pathological subjects, even if the total literatu...

Industrially, after the removal of oil from perilla seeds (PS) by screw-type compression, the large quantities of residual perilla seed meal (PSM) becomes non-valuable waste. Therefore, to increase the health value and price of PS and PSM, we focused on the biological effects of perilla seed oil (PSO) and rosmarinic acid-rich fraction (RA-RF) extracted from PSM for their role in preventing oxidative stress and inflammation caused by TNF-α exposure in an A549 lung adenocarcinoma culture model. The A549 cells were pretreated with PSO or RA-RF and followed by TNF-α treatment. We found that PSO and RA-RF were not toxic to TNF-α-induced A549 cells. Both extracts significantly decreased the generation of reactive oxygen species (ROS) in this cell line. The mRNA expression levels of IL-1β, IL-6, IL-8, TNF-α, and COX-2 were significantly decreased by the treatment of PSO and RA-RF. The Western blot indicated that the expression of MnSOD, FOXO1, and NF-κB and phosphorylation of JNK were also significantly diminished by PSO and RA-RF treatment. The results demonstrated that PSO and RA-RF act as antioxidants to scavenge TNF-α induced ROS levels, resulting in decreased the expression of MnSOD, FOXO1, NF-κB and JNK signaling pathway in a human lung cell culture exposed to TNF-α.

ObjectiveTo examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer.DesignSystematic review and meta-analysis of prospective cohort studies.Data sourcesPubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021.Study selectionProspective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer.Data synthesisSummary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality.Results41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I2=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I2=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I2=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I2=3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I2=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I2=30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I2=8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I2=37.1%, n=14).ConclusionsThe findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only.Systematic review registrationPROSPERO CRD42021229487.

Findings from the associations between dietary intakes of different fatty acids and longevity are of particular interest to researchers, healthcare providers, and patients. Based on our meta-analysis of 41 articles from cohort studies, dietary intake of alpha linolenic acid (ALA) was associated with a reduced risk of mortality from all causes, cardiovascular disease, and coronary heart disease, and a slightly higher risk of cancer mortality. In a mixed diet, however, ALA is consumed with other fatty acids with different effects. Therefore, finding the effects of other fatty acids might help us to determine the overall effect of a diet that includes fats.

SCOPE The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs; however, the regulation effect of α-linolenic acid (ALA) has seldom been reported. METHODS AND RESULTS After intervening mice with different doses of ALA for 30 days, it is found that ALA (0.5 g kg-1 ) promotes small intestinal and villus growth by activating the Wnt/β-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation. CONCLUSION These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/β-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.

Alpha-Linolenic acid (ALA), an omega-3 polyunsaturated fatty acid, is extracted from plant sources and has been shown to be one of the anti-inflammatory and antioxidant agents. Herein, we revealed the molecular mechanism underlying the anti-inflammatory and antioxidant potential of (ALA), against cadmium in the adult mouse brain. We evaluated the neuroprotective effect of ALA (60 mg/kg per oral for 6 weeks) against CdCl2 (5 mg/kg)-induced oxidative stress, neuroinflammation, and neuronal apoptosis. According to our findings, ALA markedly reduced ROS production and nitric oxide synthase 2 (NOS2) and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and heme oxygenase-1 (HO-1) in mice treated with CdCl2. Most importantly, the molecular docking study revealed that ALA allosterically decreases the overexpression of c-Jun N-terminal kinase (JNK) activity and inhibited the detrimental effect against CdCl2. Moreover, ALA suppressed CdCl2-induced glial fibrillary acidic protein (GFAP), nuclear factor-kappa b (NF-κB), and interleukin-1β (IL-1β) in the mouse brain. Further, we also checked the pro- and anti-apoptotic proteins markers such as Bax, Bcl-2, and caspase-3, which were regulated in the cortex of ALA co-treated mouse brain. Overall, our study suggests that oral administration of ALA can impede oxidative stress, neuroinflammation, and increase neuronal apoptosis in the cortex of Cd-injected mouse brain.

Background: High-fat diet (HFD) consumption induced gut dysbiosis, inflammation, obese-insulin resistance. Perilla seed oil (PSO) is a rich source of omega-3 polyunsaturated fatty acids with health promotional effects. However, the effects of PSO on gut microbiota/inflammation and metabolic disturbance in HFD-induced obesity have not been investigated. Therefore, we aimed to compare the effects of different doses of PSO and metformin on gut microbiota/inflammation, and metabolic parameters in HFD-fed rats. Methods: Thirty-six male Wistar rats were fed either a normal diet or an HFD for 24 weeks. At week 13, HFD-fed rats received either 50, 100, and 500 mg/kg/day of PSO or 300 mg/kg/day metformin for 12 weeks. After 24 weeks, the metabolic parameters, gut microbiota, gut barrier, inflammation, and oxidative stress were determined. Results: HFD-fed rats showed gut dysbiosis, gut barrier disruption with inflammation, increased oxidative stress, metabolic endotoxemia, and insulin resistance. Treatment with PSO and metformin not only effectively attenuated gut dysbiosis, but also improved gut barrier integrity and decreased gut inflammation. PSO also decreased oxidative stress, metabolic endotoxemia, and insulin resistance in HFD-fed rats. Metformin had greater benefits than PSO. Conclusion: PSO and metformin had the beneficial effect on attenuating gut inflammation and metabolic disturbance in obese-insulin resistance.

Flaxseed oil (FO) is an alpha linolenic acid source important for growth and body development. However, there is little literature on the role of FO in critical stages of bone development and formation.This study evaluated the influence of a diet containing FO on rat femurs.After birth, mothers and pups were divided into control and flaxseed groups (n = 6 pups each) fed diets containing 7% soybean oil (C) or 7% FO. At 21 days, pups were weaned and separated from the mothers, and control or experimental diets were continued. At 67 days, the following were analyzed: osteocalcin and osteoprotegerin (OPG) levels, bone mineral density (BMD) and content, and bone area; the dimension, BMD, head radiodensity, and biomechanical proprieties of the right femur; and histomorphometric parameters of the left femur.Compared to the C group, the FO group presented (The FO diet contributed to femur quality in healthy male Wistar rats.

Alcoholic beverages like apple cider are considered functional beverages with several health benefits, when consumed in moderation, which are mainly attributed to their microbiota and the plethora of their bioactive compounds. Among them, bio-functional polar lipids (PL) have recently been found in apple cider, which despite low quantities, have exhibited strong anti-inflammatory and anti-platelet properties, while fermentation seems to affect the functionality of apple cider’s PL bioactives. The aim of the present study was to elaborate yeast strains isolated from the complex mixtures of apple surface and must yeasts for evaluating their effects on the anti-platelet functional properties of PL bioactives from their final fermented apple cider products. First, bio-functional PL were extracted and separated from the biomass of the different isolated apple surface/must yeast strains, and were further assessed for their anti-platelet potency against human platelet aggregation induced by the potent inflammatory and thrombotic mediator platelet-activating factor (PAF), or by a classic platelet agonist like adenosine diphopshate (ADP). Novel functional apple ciders were then produced from the fermentation of apple juice by elaborating the most bioactive and resilient yeast strains isolated from the apple must with optimum fermentation properties. PL bioactives extracted from these novel apple cider products were also further assessed for their anti-platelet properties against both the PAF and ADP pathways of human platelet aggregation. These novel cider products were found to contain PL bioactives with lower IC50 values (~40 μg) and thus increased anti-platelet potency against platelet aggregation induced by PAF and ADP. GC-MS analysis of the PL bioactives extracted from these novel apple ciders showed that apple cider PL bioactives are rich in monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), such as the omega-6 linoleic acid (LA) and the omega-3 alpha linolenic acid (ALA), with favorably lower levels for their omega-6/omega-3 PUFA ratio, which further support the observed strong anti-platelet properties putative anti-inflammatory potency for the apple cider PL bioactives. However, further studies are needed in order to elucidate and fully characterize the apple yeast strains that can be utilized for increasing the anti-inflammatory, anti-platelet and cardioprotective functional properties of their fermented apple cider products.