scholarly journals Narrative Review of n-3 Polyunsaturated Fatty Acid Supplementation upon Immune Functions, Resolution Molecules and Lipid Peroxidation

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 662
Author(s):  
Gary P. Zaloga

Fish oil supplementation is commonplace in human nutrition and is being used in both enteral and parenteral formulations during the treatment of patients with a large variety of diseases and immune status. The biological effects of fish oil are believed to result from their content of n-3 polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These fatty acids are known to have numerous effects upon immune functions and are described as immunomodulatory. However, immunomodulatory is a nondescript term that encompasses immunostimulation and immunosuppression. The primary goal of this review is to better describe the immune effects of n-3 PUFA as they relate to immunostimulatory vs. immunosuppressive effects. One mechanism proposed for the immune effects of n-3 PUFA relates to the production of specialized pro-resolving mediators (SPMs). A second goal of this review is to evaluate the effects of n-3 PUFA supplementation upon production of SPMs. Although n-3 PUFA are stated to possess anti-oxidative properties, these molecules are highly oxidizable due to multiple double bonds and may increase oxidative stress. Thus, the third goal of this review is to evaluate the effects of n-3 PUFA upon lipid oxidation. We conclude, based upon current scientific evidence, that n-3 PUFA suppress inflammatory responses and most cellular immune responses such as chemotaxis, transmigration, antigen presentation, and lymphocyte functions and should be considered immunosuppressive. n-3 PUFA induced production of resolution molecules is inconsistent with many resolution molecules failing to respond to n-3 PUFA supplementation. n-3 PUFA supplementation is associated with increased lipid peroxidation in most studies. Vitamin E co-administration is unreliable for prevention of the lipid peroxidation. These effects should be considered when administering n-3 PUFA to patients that may be immunosuppressed or under high oxidative stress due to illness or other treatments.

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 555
Author(s):  
Bernat Miralles-Pérez ◽  
Lucía Méndez ◽  
Maria Rosa Nogués ◽  
Vanessa Sánchez-Martos ◽  
Àngels Fortuño-Mar ◽  
...  

Omega-3 polyunsaturated fatty acids are associated with a lower risk of cardiometabolic diseases. However, docosahexaenoic acid (DHA) is easily oxidized, leading to cellular damage. The present study examined the effects of an increased concentration of DHA in fish oil (80% of total fatty acids) on cardiometabolic risk factors and oxidative stress compared to coconut oil, soybean oil, and fish oil containing eicosapentaenoic acid (EPA) and DHA in a balanced ratio. Forty healthy male Sprague–Dawley rats were supplemented with corresponding oil for 10 weeks. Supplementation with the fish oil containing 80% DHA decreased plasma fat, plasma total cholesterol and muscle fat compared to the coconut oil and the soybean oil. Increasing concentrations of DHA induced incorporation of DHA and EPA in cell membranes and tissues along with a decrease in ω-6 arachidonic acid. The increase in DHA promoted lipid peroxidation, protein carbonylation and antioxidant response. Taken together, the increased concentration of DHA in fish oil reduced fat accumulation compared to the coconut oil and the soybean oil. This benefit was accompanied by high lipid peroxidation and subsequent protein carbonylation in plasma and in liver. In our healthy framework, the slightly higher carbonylation found after receiving fish oil containing 80% DHA might be a protecting mechanism, which fit with the general improvement of antioxidant defense observed in those rats.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christina D’Agrosa ◽  
Charles L. Cai ◽  
Faisal Siddiqui ◽  
Karen Deslouches ◽  
Stephen Wadowski ◽  
...  

Abstract Background Neonatal intermittent hypoxia (IH) results in oxidative distress in preterm infants with immature antioxidant systems, contributing to lung injury. Coenzyme Q10 (CoQ10) and fish oil protect against oxidative injury. We tested the hypothesis that CoQ10 is more effective than fish oil for prevention of IH-induced lung injury in neonatal rats. Methods Newborn rats were exposed to two clinically relevant IH paradigms at birth (P0): (1) 50% O2 with brief hypoxia (12% O2); or (2) room air (RA) with brief hypoxia (12% O2), until P14 during which they were supplemented with daily oral CoQ10, fish oil, or olive oil from P0 to P14. Pups were studied at P14 or placed in RA until P21 with no further treatment. Lungs were assessed for histopathology and morphometry; biomarkers of oxidative stress and lipid peroxidation; and antioxidants. Results Of the two neonatal IH paradigms 21%/12% O2 IH resulted in the most severe outcomes, evidenced by histopathology and morphometry. CoQ10 was effective for preserving lung architecture and reduction of IH-induced oxidative stress biomarkers. In contrast, fish oil resulted in significant adverse outcomes including oversimplified alveoli, hemorrhage, reduced secondary crest formation and thickened septae. This was associated with elevated oxidants and antioxidants activities. Conclusions Data suggest that higher FiO2 may be needed between IH episodes to curtail the damaging effects of IH, and to provide the lungs with necessary respite. The negative outcomes with fish oil supplementation suggest oxidative stress-induced lipid peroxidation.


Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 45
Author(s):  
Helena Beatriz Ferreira ◽  
Tânia Melo ◽  
Artur Paiva ◽  
Maria do Rosário Domingues

Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. However, oxidative stress and lipid peroxidation are associated with the development and pathogenesis of RA. In this case, oxidative damage biomarkers have been found to be significantly higher in RA patients, associated with the oxidation of biomolecules and the stimulation of inflammatory responses. Lipid peroxidation is one of the major consequences of oxidative stress, with the formation of deleterious lipid hydroperoxides and electrophilic reactive lipid species. Additionally, changes in the lipoprotein profile seem to be common in RA, contributing to cardiovascular diseases and a chronic inflammatory environment. Nevertheless, changes in the lipid profile at a molecular level in RA are still poorly understood. Therefore, the goal of this review was to gather all the information regarding lipid alterations in RA analyzed by mass spectrometry. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid metabolisms, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Marlene Grenon ◽  
Christopher Owens ◽  
Hugh Alley ◽  
Karen Chong ◽  
Priscilla Yen ◽  
...  

OBJECTIVES: Patients with peripheral artery disease (PAD) experience significant morbidity and mortality, at least partially related to vascular inflammation and endothelial dysfunction. The OMEGA-PAD I Trial (NCT01310270), a randomized, double-blinded, placebo-controlled trial addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function (EF) and inflammation in subjects with PAD. METHODS: Eighty patients with stable, mild-severe claudication and ABI<0.9 received 4.1gm of fish oil (FISH) vs placebo capsules (CTL) for 1 month. The primary endpoint was EF as measured by brachial artery flow-mediated vasodilation (FMD). Secondary endpoints included biomarkers of inflammation, generation of n-3 fatty acid-derived lipid metabolites, lipid profile and walking impairment questionnaires. RESULTS: The FISH and CTL group were no different with regards to age, baseline EF, inflammation and lipid profiles. Following treatment, there was a significant reduction in triglycerides (-34 ± 46, p=0.0001) and an improvement in HDL (+2 ± 6, p=0.03) in the FISH group. These changes were accompanied by an increase in the omega-3 index of 4 ± 1% (p<0.00001). We observed a significant increase in the production of downstream metabolites of n-3 fatty acids including 18-, 15- and 5-hydroxy eicosapentaenoic acids and 4-hydroxy docosahexaenoic acid in the FISH group. n-3 PUFA led to a significant improvement in FMD in the FISH group (+0.7 ± 4.0%, p=0.04) and a non-significant improvement in the CTL (+0.6 ± 2.5, p=0.18) group. There were no significant differences between groups in pro-inflammatory markers or walking parameters post-treatment. CONCLUSIONS: High-dose, short-duration n-3 PUFA supplementation significantly improves the metabolo-lipidomic profile of patients with PAD. Longer studies are needed to assess the effects of n-3 PUFA on inflammation, vascular function, and clinical endpoints in patients with established PAD and to determine whether generation of n-3 fatty acid-derived bioactive lipid mediators is related to clinical outcomes.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3372
Author(s):  
Kátia Cansanção ◽  
Marta Citelli ◽  
Nathalie Carvalho Leite ◽  
María-Carmen López de las Hazas ◽  
Alberto Dávalos ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease affecting up to 25% of the population worldwide. n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) have been associated with improved clinical parameters of NAFLD. Our purpose was to conduct a pilot study to evaluate the effects of n-3 PUFA supplementation in a randomized, double-blind, placebo-controlled clinical study performed on NAFLD individuals diagnosed by ultrasound. Patients received n-3 PUFA (n = 13) or placebo (n = 11) supplementation for six months. Circulating miR-122 expression (determined by quantitative real time-polymerase chain reaction (qRT-PCR), liver fibrosis (FibroScan®), red blood cells (RBC) fatty acids (gas chromatography), and biochemical tests were performed at baseline and after intervention. After the intervention, in the n-3 PUFA group, docosahexaenoic acid (DHA) and omega index increased significantly in RBC (p = 0.022 and p = 0.012, respectively), in addition to a significant reduction in alkaline phosphatase (ALP) (p = 0.002) and liver fibrosis (p = 0.039). However, there was no change in the expression of circulating miR-122 in both groups. Our results showed that omega-3 PUFA were incorporated in erythrocytes after six months of fish oil supplementary intake, and that n-3 PUFA were effective in reducing ALP and liver fibrosis without altering the expression of circulating miR-122 in individuals with NAFLD.


2019 ◽  
Vol 75 (5) ◽  
pp. 875-884 ◽  
Author(s):  
Souzana-Eirini Xyda ◽  
Ivan Vuckovic ◽  
Xuan-Mai Petterson ◽  
Surendra Dasari ◽  
Antigoni Z Lalia ◽  
...  

Abstract Omega-3 polyunsaturated fatty acids (n3-PUFA) are well recognized for their potent triglyceride-lowering effects, but the potential influence of these bioactive lipids on other biological processes, particularly in the context of healthy aging, remains unknown. With the goal of gaining new insight into some less well-characterized biological effects of n3-PUFAs in healthy older adults, we performed metabolomics of fasting peripheral blood plasma collected from 12 young adults and 12 older adults before and after an open-label intervention of n3-PUFA (3.9 g/day, 2.7 g eicosapentaenoic [EPA], 1.2 g docosahexaenoic [DHA]). Proton nuclear magnetic resonance (1H-NMR) based lipoprotein subclass analysis revealed the expected reduction in total triglyceride (TG), but also demonstrated that n3-PUFA supplementation reduced very low-density lipoprotein (VLDL) particle number, modestly increased high-density lipoprotein (HDL) cholesterol, and shifted the composition of HDL subclasses. Further metabolite profiling by 1H-NMR and mass spectrometry revealed pronounced changes in phospholipids, cholesterol esters, diglycerides, and triglycerides following n3-PUFA supplementation. Furthermore, significant changes in hydroxyproline, kynurenine, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) following n3-PUFA supplementation provide further insight into some less well-recognized biological effects of n3-PUFA supplementation, including possible effects on protein metabolism, the kynurenine pathway, and glucose metabolism.


2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Alexander V. Panov ◽  
Sergey I. Dikalov

Mitochondrial dysfunctions caused by oxidative stress are currently regarded as the main cause of aging. Accumulation of mutations and deletions of mtDNA is a hallmark of aging. So far, however, there is no evidence that most studied oxygen radicals are directly responsible for mutations of mtDNA. Oxidative damages to cardiolipin (CL) and phosphatidylethanolamine (PEA) are also hallmarks of oxidative stress, but the mechanisms of their damage remain obscure. CL is the only phospholipid present almost exclusively in the inner mitochondrial membrane (IMM) where it is responsible, together with PEA, for the maintenance of the superstructures of oxidative phosphorylation enzymes. CL has negative charges at the headgroups and due to specific localization at the negative curves of the IMM, it creates areas with the strong negative charge where local pH may be several units lower than in the surrounding bulk phases. At these sites with the higher acidity, the chance of protonation of the superoxide radical (O2•), generated by the respiratory chain, is much higher with the formation of the highly reactive hydrophobic perhydroxyl radical (HO2•). HO2• specifically reacts with the double bonds of polyunsaturated fatty acids (PUFA) initiating the isoprostane pathway of lipid peroxidation. Because HO2• is formed close to CL aggregates and PEA, it causes peroxidation of the linoleic acid in CL and also damages PEA. This causes disruption of the structural and functional integrity of the respirosomes and ATP synthase. We provide evidence that in elderly individuals with metabolic syndrome (MetS), fatty acids become the major substrates for production of ATP and this may increase several-fold generation of O2• and thus HO2•. We conclude that MetS accelerates aging and the mitochondrial dysfunctions are caused by the HO2•-induced direct oxidation of CL and the isoprostane pathway of lipid peroxidation (IPLP). The toxic products of IPLP damage not only PEA, but also mtDNA and OXPHOS proteins. This results in gradual disruption of the structural and functional integrity of mitochondria and cells.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 429-429
Author(s):  
Bing-Xiang Liu ◽  
Hui-Chen Lo ◽  
Chien-Hsing Lee

Abstract Objectives Oxidative stress has been demonstrated to be the cause of cellular and organ damage in patients with trauma hemorrhagic shock and reperfusion (THR). Our previous study showed that resuscitation fluids supplemented with glutamine and fish oil, the antioxidants with anti-inflammatory activities, may alleviate systemic inflammatory response and oxidative stress in the THR rats. The aim of this study was to further investigate the mechanisms of these supplements on alleviating THR-induced damage in the lung and liver, i.e., the 2 vulnerable organs in THR. Methods Male Wistar rats were suffered with 5 cm midline laparotomy and 2 catheterizations in the left carotid artery and right jugular vein individually for blood drawn to a mean arterial pressure 30 to 35 mmHg for 60 minutes and for resuscitation of shed blood and lactate Ringer's solution with or without L-alanyl-L-glutamine (13.5 mmole/kg/day) and/or fish oil (0.5 g/kg/day) within 10 minutes. The different resuscitation fluids were continuous infused (∼1.4 ml/h) for 42 hr. Normal healthy rats and intubation sham-operated rats were included as controls. Results In the lung, the THR-increased lipid peroxidation and toll-like receptor 4 (TLR4) were significantly decreased by glutamine with or without fish oil (one-way ANOVA, P &lt; 0.05). Fish oil was the main factor to decrease myeloperoxidase and activated caspase 3 in the lung of the THR rats (two-way ANOVA, P &lt; 0.05). In the liver, the THR-increased lipid peroxidation and TLR4 and the THR-decreased catalase activity were improved by glutamine and/or fish oil. In addition, fish oil was the main factor to decrease inducible and endothelial nitric oxide synthase (NOS) and to increase IkB and phosphorylated NF-kB and glutamine was the main factor to decrease activated caspase 3 in the liver of the THR rats. Conclusions These results suggest that fish oil may alleviate neutrophil infiltration and NOS activation and fish oil and glutamine may elevate catalase activity and alleviate apoptosis to attenuate the THR-induced damage in the lung and liver. Funding Sources MOST 102-2320-B-030-005-MY3.


2010 ◽  
Vol 69 (3) ◽  
pp. 373-380 ◽  
Author(s):  
Philip C. Calder ◽  
Lefkothea-Stella Kremmyda ◽  
Maria Vlachava ◽  
Paul S. Noakes ◽  
Elizabeth A. Miles

There may be a causal relationship betweenn-6 PUFA intake and allergic disease and there are biologically plausible mechanisms, involving eicosanoid mediators of then-6 PUFA arachidonic acid, that could explain this. There is some evidence that high linoleic acid intake is linked with increased risk of atopic sensitisation and allergic manifestations. Fish and fish oils are sources of long-chainn-3 PUFA and these fatty acids act to oppose the actions ofn-6 PUFA. It is considered thatn-3 PUFA will protect against atopic sensitisation and against the clinical manifestations of atopy. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. Epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children are inconsistent, although the majority of the studies (9/14) showed a protective effect of fish. Fish oil provision to pregnant women is associated with immunologic changes in cord blood. Provision of fish oil during pregnancy may reduce sensitisation to common food allergens and reduce the prevalence and severity of atopic dermatitis in the first year of life. This effect may persist until adolescence with a reduction in prevalence and/or severity of eczema, hayfever and asthma. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but whether this benefit persists as other factors come into play remains to be determined.


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