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Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 March 2019) | Viewed by 77446

Special Issue Editor

Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Interests: omega-3; omega-6/omega-3 ratio; nutrigenomics; nutri-biotechnology; cancer metabolism; lipidomics; gut microbiota; nutritional interventions; inflammation; metabolic syndrome; chronic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Omega-3 polyunsaturated fatty acids as essential nutrients, dietary supplements, and pharmaceutical drugs have been widely investigated and used over the past few decades. The continued interest and ever-growing volume of research in the field point to omega-3 fatty acids as a key player in the management of chronic diseases. However, the main challenge of omega-3 research lies in its complexity and confounding factors. Variations, inconsistencies, and controversies on the study outcomes of omega-3 fatty acids remain to be clarified. Recent advances in analytical technologies (such as the “omics”), new animal models (such as the fat-1 transgenic mouse model), and integrated experimental approaches have allowed us to more comprehensively and accurately elucidate the biological effects of omega-3 fatty acids and their mechanisms. Identification of biomarkers for efficacy evaluation will help the clinical application and implementation of omega-3-based interventions. This Special Issue of Nutrients is intended to highlight some of the recent omega-3 studies utilizing cutting-edge technologies and novel experimental models and those that investigated new health benefits (e.g. modulation of gut microbiota) of omega-3 fatty acids.

Prof. Dr. Jing X. Kang
Guest Editor

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Keywords

  • Omega-3 Fatty Acids
  • Lipidomics and Metabolomics
  • Fat-1 Transgenic Mouse Model
  • Gut Microbiota
  • Nutrition and Metabolism
  • Chronic Disease

Published Papers (8 papers)

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Research

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18 pages, 1505 KiB  
Article
The Effect of Omega-3 and Omega-6 Polyunsaturated Fatty Acids on the Production of Cyclooxygenase and Lipoxygenase Metabolites by Human Umbilical Vein Endothelial Cells
by Pedro Araujo, Ikram Belghit, Niels Aarsæther, Marit Espe, Eva Lucena and Elisabeth Holen
Nutrients 2019, 11(5), 966; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11050966 - 27 Apr 2019
Cited by 27 | Viewed by 4264
Abstract
Although the correlation between polyunsaturated fatty acids (PUFA) and the production of pro- and anti-inflammatory metabolites is well documented, little is known about the simultaneous effect of different PUFA on the production of cyclooxygenase and lipoxygenase metabolites. The present research examines the association [...] Read more.
Although the correlation between polyunsaturated fatty acids (PUFA) and the production of pro- and anti-inflammatory metabolites is well documented, little is known about the simultaneous effect of different PUFA on the production of cyclooxygenase and lipoxygenase metabolites. The present research examines the association between different omega-3 (ω-3) and omega-6 (ω-6) PUFA and the release of four cyclooxygenase and six lipoxygenase metabolites in cell medium by human umbilical vein endothelial cells (HUVEC). The different combinations of ω-3 and ω-6 PUFA were prepared according to a full 24 factorial design that enables studying not only the main effects but also the different interactions between fatty acids. In addition, interactions diagrams and principal component analysis were useful tools for interpreting higher order interactions. To the best of our knowledge, this is the first report addressing the combined effect of ω-3 and ω-6 PUFA on the signaling of prostaglandins, prostacyclins, leukotrienes and resolvins by HUVEC. Full article
(This article belongs to the Special Issue Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health)
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15 pages, 2559 KiB  
Article
Effects of Polyunsaturated Fatty Acids on Nonspecific Typical Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
by Sheng-Chu Chi, Hsin-I Tuan and Yi-No Kang
Nutrients 2019, 11(5), 942; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11050942 - 26 Apr 2019
Cited by 23 | Viewed by 5223
Abstract
To investigate the effects of polyunsaturated fatty acids (PUFAs) in patients with dry eye disease (DED), a multifactorial inflammatory disorder, we searched Cochrane Library, EMBASE, PubMed, and Web of Science for randomized clinical trials (RCTs) investigating the effect of PUFAs in patients with [...] Read more.
To investigate the effects of polyunsaturated fatty acids (PUFAs) in patients with dry eye disease (DED), a multifactorial inflammatory disorder, we searched Cochrane Library, EMBASE, PubMed, and Web of Science for randomized clinical trials (RCTs) investigating the effect of PUFAs in patients with DED before March 2019. Two reviewers independently abstracted data of tear breakup time (TBUT), Schirmer’s test, osmolarity, and ocular surface disease index (OSDI). We conducted pairwise meta-analysis using means and standard deviations (SDs) in a random-effects model for continuous outcomes. Thirteen eligible RCTs with 1782 patients with nonspecific typical DED were included. Patients who received PUFA treatment without other eye medications exhibited greater improvements in TBUT (MD = 1.80; p = 0.001), Schirmer test scores (MD = 0.50; p < 0.001), osmolarity (MD = −15.95; p < 0.001), and OSDI scores (MD = −10.19; p < 0.001) than those who received placebo treatment. However, the effects of PUFAs on TBUT (p < 0.001) and OSDI scores (p = 0.03) weakened with treatment duration. PUFAs are effective in treating nonspecific typical DED, particularly as a short-term treatment, with relatively few adverse events. Therefore, in real-world clinical practice, PUFA supplements are worth being suggested to patients with nonspecific typical DED who are not concurrently using other topical or systematic eye medications. Full article
(This article belongs to the Special Issue Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health)
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19 pages, 2254 KiB  
Article
Dietary Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) Operate by Different Mechanisms to Modulate Hepatic Steatosis and Hyperinsulemia in fa/fa Zucker Rats
by Lena Hong, Peter Zahradka, Luis Cordero-Monroy, Brenda Wright and Carla G. Taylor
Nutrients 2019, 11(4), 917; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11040917 - 24 Apr 2019
Cited by 26 | Viewed by 4671
Abstract
Hepatic steatosis, an early stage of non-alcoholic fatty liver disease, is commonly present in obesity and type 2 diabetes, and is associated with reduced hepatic omega-3 polyunsaturated fatty acid (n3-PUFA) status that impacts on the anti-inflammatory and insulin sensitizing functions of n3-PUFA. Our [...] Read more.
Hepatic steatosis, an early stage of non-alcoholic fatty liver disease, is commonly present in obesity and type 2 diabetes, and is associated with reduced hepatic omega-3 polyunsaturated fatty acid (n3-PUFA) status that impacts on the anti-inflammatory and insulin sensitizing functions of n3-PUFA. Our objective was to directly compare plant- and marine-based n3-PUFA (α-linoleic acid (ALA)), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)) for their effects on hepatic steatosis, markers of hepatic inflammation and fibrosis, and insulinemia in obese rats. Fa/fa Zucker rats were provided diets containing ALA, EPA, DHA, or linoleic acid (LA, n6-PUFA) for eight weeks and compared to baseline fa/fa rats and lean Zucker rats fed LA-rich diet for eight weeks. Both DHA and EPA groups had liver lipid similar to baseline, however, DHA was more effective than EPA for reducing hepatic fatty acid synthase (FAS), increasing the proportion of smaller lipid droplets, reversing early fibrotic damage, and reducing fasting hyperinsulinemia. EPA was more effective for reducing FoxO1. Dietary ALA did not attenuate hepatic steatosis, most inflammatory markers or FAS. In summary, amongst the n3-PUFA, DHA was the most effective for elevating hepatic DHA levels, and preventing progression of hepatic steatosis via reductions in FAS and a marker of fibrosis. Full article
(This article belongs to the Special Issue Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health)
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19 pages, 743 KiB  
Article
Enhanced Omega-3 Polyunsaturated Fatty Acid Contents in Muscle and Edible Organs of Australian Prime Lambs Grazing Lucerne and Cocksfoot Pastures
by Hung V. Le, Quang V. Nguyen, Don V. Nguyen, John R. Otto, Bunmi S. Malau-Aduli, Peter D. Nichols and Aduli E. O. Malau-Aduli
Nutrients 2018, 10(12), 1985; https://0-doi-org.brum.beds.ac.uk/10.3390/nu10121985 - 15 Dec 2018
Cited by 11 | Viewed by 4562
Abstract
The enhancement of health-beneficial omega-3 long–chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) contents in the muscle, liver, heart, and kidney of Australian prime lambs through pasture grazing and supplementation with oil infused pellets was investigated. Forty-eight first-cross prime lambs were randomly [...] Read more.
The enhancement of health-beneficial omega-3 long–chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) contents in the muscle, liver, heart, and kidney of Australian prime lambs through pasture grazing and supplementation with oil infused pellets was investigated. Forty-eight first-cross prime lambs were randomly assigned into a split-plot design with pasture type as the main plot effect and pellet supplementation as a sub-plot effect in a feeding trial that lasted for nine weeks. The n-3 LC-PUFA content in Longissimus dorsi muscle of all lambs was well above the 30 mg threshold for “omega-3 source” nutrition claim under the Australian Food Standards and Guidelines. Pasture type impacted the fatty acid contents in muscle, heart, and kidney of prime lambs. Lambs grazing cocksfoot grass only had high 18:3n-3 (ALA) and n-3 LC-PUFA contents (67.1 mg/100 g and 55.2 mg/100 g, respectively) in the Longissimus dorsi muscle, which was not significantly different (p > 0.8990) from the contents of lambs grazing only lucerne. Supplementation of pellets with or without oil infusion to grazing lambs generally decreased the ALA and n-3 LC-PUFA contents and increased the n-6/n-3 ratio in the Longissimus dorsi muscle. The fatty acid content in the internal organs of grazing lambs was also affected by pellet supplementation. The liver and kidney of grazing lambs were both “good sources” (60 mg/100 g) of omega-3. The cocksfoot grass showed considerable potential for producing healthy, premium quality meat with high contents of n-3 and n-3 LC-PUFA, which may consequently enhance the omega-3 intake of Australian lamb consumers. Full article
(This article belongs to the Special Issue Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health)
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17 pages, 5192 KiB  
Article
Endogenous Omega (n)-3 Fatty Acids in Fat-1 Mice Attenuated Depression-Like Behavior, Imbalance between Microglial M1 and M2 Phenotypes, and Dysfunction of Neurotrophins Induced by Lipopolysaccharide Administration
by Minqing Gu, Yuyu Li, Haiting Tang, Cai Zhang, Wende Li, Yongping Zhang, Yajuan Li, Yuntao Zhao and Cai Song
Nutrients 2018, 10(10), 1351; https://0-doi-org.brum.beds.ac.uk/10.3390/nu10101351 - 21 Sep 2018
Cited by 49 | Viewed by 5598
Abstract
n-3 polyunsaturated fatty acids (PUFAs) have been reported to improve depression. However, PUFA purities, caloric content, and ratios in different diets may affect the results. By using Fat-1 mice which convert n-6 to n-3 PUFAs in the brain, this study further evaluated anti-depressant [...] Read more.
n-3 polyunsaturated fatty acids (PUFAs) have been reported to improve depression. However, PUFA purities, caloric content, and ratios in different diets may affect the results. By using Fat-1 mice which convert n-6 to n-3 PUFAs in the brain, this study further evaluated anti-depressant mechanisms of n-3 PUFAs in a lipopolysaccharide (LPS)-induced model. Adult male Fat-1 and wild-type (WT) mice were fed soybean oil diet for 8 weeks. Depression-like behaviors were measured 24 h after saline or LPS central administration. In WT littermates, LPS reduced sucrose intake, but increased immobility in forced-swimming and tail suspension tests. Microglial M1 phenotype CD11b expression and concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-17 were elevated, while M2 phenotype-related IL-4, IL-10, and transforming growth factor (TGF)-β1 were decreased. LPS also reduced the expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (Trk B), while increasing glial fibrillary acidic protein expression and pro-BDNF, p75, NO, and iNOS levels. In Fat-1 mice, LPS-induced behavioral changes were attenuated, which were associated with decreased pro-inflammatory cytokines and reversed changes in p75, NO, iNOS, and BDNF. Gas chromatography assay confirmed increased n-3 PUFA levels and n-3/n-6 ratios in the brains of Fat-1 mice. In conclusion, endogenous n-3 PUFAs may improve LPS-induced depression-like behavior through balancing M1 and M2-phenotypes and normalizing BDNF function. Full article
(This article belongs to the Special Issue Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health)
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Review

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23 pages, 2063 KiB  
Review
Protective Effects of Omega-3 Fatty Acids in Cancer-Related Complications
by Raquel D. S. Freitas and Maria M. Campos
Nutrients 2019, 11(5), 945; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11050945 - 26 Apr 2019
Cited by 133 | Viewed by 16610
Abstract
Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs play essential roles in cell signaling and in the cell structure and fluidity of membranes. They [...] Read more.
Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs play essential roles in cell signaling and in the cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory and antinociceptive effects. Additionally, they can act as agonists of G protein-coupled receptors, namely, GPR40/FFA1 and GPR120/FFA4. Cancer patients undergo complications, such as anorexia-cachexia syndrome, pain, depression, and paraneoplastic syndromes. Interestingly, the 2017 European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for cancer patients only discuss the use of omega-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by omega-3 PUFA supplementation. This critical review aimed to discuss the effects and the possible underlying mechanisms of omega-3 PUFA supplementation in cancer-related complications. Data compilation in this critical review indicates that further investigation is still required to assess the factual benefits of omega-3 PUFA supplementation in cancer-associated illnesses. Nevertheless, preclinical evidence reveals that omega-3 PUFAs and their metabolites might modulate pivotal pathways underlying complications secondary to cancer, indicating that this is a promising field of knowledge to be explored. Full article
(This article belongs to the Special Issue Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health)
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23 pages, 950 KiB  
Review
Enhancing Omega-3 Long-Chain Polyunsaturated Fatty Acid Content of Dairy-Derived Foods for Human Consumption
by Quang V. Nguyen, Bunmi S. Malau-Aduli, John Cavalieri, Peter D. Nichols and Aduli E. O. Malau-Aduli
Nutrients 2019, 11(4), 743; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11040743 - 29 Mar 2019
Cited by 66 | Viewed by 7436
Abstract
Omega-3 polyunsaturated fatty acids (n-3 PUFA) are termed essential fatty acids because they cannot be synthesized de novo by humans due to the lack of delta-12 and delta-15 desaturase enzymes and must therefore be acquired from the diet. n-3 PUFA include α-linolenic acid [...] Read more.
Omega-3 polyunsaturated fatty acids (n-3 PUFA) are termed essential fatty acids because they cannot be synthesized de novo by humans due to the lack of delta-12 and delta-15 desaturase enzymes and must therefore be acquired from the diet. n-3 PUFA include α-linolenic acid (ALA, 18:3n-3), eicosapentaenoic (EPA, 20:5n-3), docosahexaenoic (DHA, 22:6n-3), and the less recognized docosapentaenoic acid (DPA, 22:5n-3). The three long-chain (≥C20) n-3 PUFA (n-3 LC-PUFA), EPA, DHA, and DPA play an important role in human health by reducing the risk of chronic diseases. Up to the present time, seafood, and in particular, fish oil-derived products, have been the richest sources of n-3 LC-PUFA. The human diet generally contains insufficient amounts of these essential FA due largely to the low consumption of seafood. This issue provides opportunities to enrich the content of n-3 PUFA in other common food groups. Milk and milk products have traditionally been a major component of human diets, but are also among some of the poorest sources of n-3 PUFA. Consideration of the high consumption of milk and its processed products worldwide and the human health benefits has led to a large number of studies targeting the enhancement of n-3 PUFA content in dairy products. The main objective of this review was to evaluate the major strategies that have been employed to enhance n-3 PUFA content in dairy products and to unravel potential knowledge gaps for further research on this topic. Nutritional manipulation to date has been the main approach for altering milk fatty acids (FA) in ruminants. However, the main challenge is ruminal biohydrogenation in which dietary PUFA are hydrogenated into monounsaturated FA and/or ultimately, saturated FA, due to rumen microbial activities. The inclusion of oil seed and vegetable oil in dairy animal diets significantly elevates ALA content, while the addition of rumen-protected marine-derived supplements is the most effective way to increase the concentration of EPA, DHA, and DPA in dairy products. In our view, the mechanisms of n-3 LC-PUFA biosynthesis pathway from ALA and the biohydrogenation of individual n-3 LC-PUFA in ruminants need to be better elucidated. Identified knowledge gaps regarding the activities of candidate genes regulating the concentrations of n-3 PUFA and the responses of ruminants to specific lipid supplementation regimes are also critical to a greater understanding of nutrition-genetics interactions driving lipid metabolism. Full article
(This article belongs to the Special Issue Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health)
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16 pages, 1019 KiB  
Review
Omega-3 Polyunsaturated Fatty Acids: Benefits and Endpoints in Sport
by Maria Alessandra Gammone, Graziano Riccioni, Gaspare Parrinello and Nicolantonio D’Orazio
Nutrients 2019, 11(1), 46; https://0-doi-org.brum.beds.ac.uk/10.3390/nu11010046 - 27 Dec 2018
Cited by 178 | Viewed by 28189
Abstract
The influence of nutrition has the potential to substantially affect physical function and body metabolism. Particular attention has been focused on omega-3 polyunsaturated fatty acids (n-3 PUFAs), which can be found both in terrestrial features and in the marine world. They [...] Read more.
The influence of nutrition has the potential to substantially affect physical function and body metabolism. Particular attention has been focused on omega-3 polyunsaturated fatty acids (n-3 PUFAs), which can be found both in terrestrial features and in the marine world. They are responsible for numerous cellular functions, such as signaling, cell membrane fluidity, and structural maintenance. They also regulate the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammatory processes, which may be useful in all inflammatory conditions. Animal models and cell-based models show that n-3 PUFAs can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that they can influence not only the exercise and the metabolic response of skeletal muscle, but also the functional response for a period of exercise training. In addition, their potential anti-inflammatory and antioxidant activity may provide health benefits and performance improvement especially in those who practice physical activity, due to their increased reactive oxygen production. This review highlights the importance of n-3 PUFAs in our diet, which focuses on their potential healthy effects in sport. Full article
(This article belongs to the Special Issue Effects of Omega-3 Polyunsaturated Fatty Acids and Human Health)
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