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Salinas-Nolasco C, Pérez-Hernández E, Garza S, Park HG, Brenna JT, Castañeda-Hernández G, Reyes-López CA, Pérez-Hernández N, Chávez-Piña AE. Antioxidative Action of Alpha-Linolenic Acid during Its Gastroprotective Effect in an Indomethacin-Induced Gastric Injury Model. Prev Nutr Food Sci 2025; 30:132-140. [PMID: 40352293 PMCID: PMC12061533 DOI: 10.3746/pnf.2025.30.2.132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/13/2025] [Accepted: 03/05/2025] [Indexed: 05/14/2025] Open
Abstract
Polyunsaturated fatty acids (PUFAs) are known to have beneficial effects. In particular, the consumption of omega-3 PUFAs has recently increased because of their effects on human health. Previous studies have investigated the activity of alpha-linolenic acid (ALA; C:18 omega-3) in metabolism and inflammation models. In a murine model of colitis, treatment with ALA effectively reduced inflammation. Previously, our research group identified the protective action of docosahexaenoic acid against gastric damage caused by nonsteroidal anti-inflammatory drugs. The present study aimed to examine the impact of ALA in an indomethacin-induced gastric injury model and to determine its antioxidant activity in gastric tissue. Female Wistar rats were administered ALA over 10 days (20 mg/kg, orally). Two hours after the final ALA administration, the rats were given indomethacin (30 mg/kg, orally) to induce gastric injury. After 3 h, the rats were euthanized, and each stomach lesion was measured to determine the total damage. Stomach tissue samples were collected for the analysis of various antioxidant indicators. The results show ALA's gastroprotective effect following 10-day administration. ALA treatment significantly reduced gastric reactive oxygen species and malondialdehyde levels in the indomethacin-induced injury group. Moreover, ALA treatment decreased the levels of nitric oxide, myeloperoxidase, leukotriene B4, and increased glutathione following indomethacin administration. These results suggest that the gastroprotective effects of ALA are likely attributed to its role in the antioxidant pathway in indomethacin-induced gastric injury.
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Affiliation(s)
- Cristina Salinas-Nolasco
- Laboratorio de Farmacología, Doctorado en Ciencias en Biotecnología, Ciudad de México 07320, México
| | - Elizabeth Pérez-Hernández
- Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México 07320, México
| | - Secilia Garza
- Department of Pediatrics, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
- Department of Chemistry, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
- Department of Nutrition, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
| | - Hui Gyu Park
- Department of Pediatrics, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
- Department of Chemistry, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
- Department of Nutrition, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
| | - J. Thomas Brenna
- Department of Pediatrics, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
- Department of Chemistry, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
- Department of Nutrition, Dell Pediatric Research Institute, University of Texas at Austin, Austin, TX 78723, USA
| | - Gilberto Castañeda-Hernández
- Departamento de Farmacología, Centro de Investigaciones y Estudios Avanzados, CINVESTAV, Mexico City 07360, México
| | - César A.S. Reyes-López
- Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México 07320, México
- Laboratorio de Bioquímica Estructural, Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México 07320, México
| | - Nury Pérez-Hernández
- Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México 07320, México
| | - Aracely Evangelina Chávez-Piña
- Laboratorio de Farmacología, Doctorado en Ciencias en Biotecnología, Ciudad de México 07320, México
- Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México 07320, México
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Ge X, Liu H, Wu Y, Liu W, Qi W, Ye L, Cao Q, Lian H, Bai R, Zhou W. Parenteral n-3 polyunsaturated fatty acids supplementation improves postoperative recovery for patients with Crohn's disease after bowel resection: a randomized, unblinded controlled clinical trial. Am J Clin Nutr 2024; 119:1027-1035. [PMID: 38569774 DOI: 10.1016/j.ajcnut.2023.12.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 04/05/2024] Open
Abstract
BACKGROUND The postoperative inflammatory response is associated with postoperative recovery in surgery. n-3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n-3 polyunsaturated fatty acids supplementation on outcomes in Crohn's disease after bowel resection is unclear. OBJECTIVES We aimed to investigate the effects of postoperative parenteral n-3 polyunsaturated fatty acids supplementation in Crohn's disease. METHODS A prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn's disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n-3 polyunsaturated fatty acids supplementation for 5 d postoperatively. RESULTS There were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n-3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention-to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n-3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1β (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. CONCLUSIONS Parenteral n-3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn's disease following bowel resection, with fewer complications and reduced inflammatory cytokines. This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic. CLINICALTRIALS gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.
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Affiliation(s)
- Xiaolong Ge
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Huaying Liu
- Department of Medicine, Guangxi Medical College, Nanning, China
| | - Yan Wu
- Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Wei Liu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Weilin Qi
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Linna Ye
- Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Qian Cao
- Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Haifeng Lian
- Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.
| | - Rongpan Bai
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Wei Zhou
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
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Jia X, Hu C, Wu X, Qi H, Lin L, Xu M, Xu Y, Wang T, Zhao Z, Chen Y, Li M, Zheng R, Lin H, Wang S, Wang W, Bi Y, Zheng J, Lu J. Evaluating the Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammatory Bowel Disease via Circulating Metabolites: A Mediation Mendelian Randomization Study. Metabolites 2023; 13:1041. [PMID: 37887366 PMCID: PMC10608743 DOI: 10.3390/metabo13101041] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/15/2023] [Accepted: 09/26/2023] [Indexed: 10/28/2023] Open
Abstract
Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63-0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the fatty acid desaturase 2 (FADS2) region, robust colocalization evidence was observed, suggesting the primary role of the FADS2 gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the FADS2 gene likely mediates the effects of omega-3 PUFAs on IBD risk.
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Affiliation(s)
- Xiaojing Jia
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Chunyan Hu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Xueyan Wu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Hongyan Qi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Lin Lin
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Tiange Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhiyun Zhao
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yuhong Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Mian Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Ruizhi Zheng
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Hong Lin
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Shuangyuan Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jie Zheng
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK
| | - Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Minhas HJ, Papamichael K, Cheifetz AS, Gianotti RJ. A primer on common supplements and dietary measures used by patients with inflammatory bowel disease. Ther Adv Chronic Dis 2023; 14:20406223231182367. [PMID: 37426698 PMCID: PMC10328183 DOI: 10.1177/20406223231182367] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 05/30/2023] [Indexed: 07/11/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic disease of the intestines. The pathophysiology of IBD, namely Crohn's disease and ulcerative colitis, is a complex interplay between environmental, genetic, and immune factors. Physicians and patients often seek complementary and alternative medicines (CAMs) as primary and supplementary treatment modalities. CAMs in IBD span a wide range of plants, herbs, pre/probiotics, and include formulations, such as cannabis, curcumin, fish oil, and De Simone Formulation. Dietary measures are also used to improve symptoms by attempting to target trigger foods and reducing inflammation. Examples include the specific carbohydrate diet, the Mediterranean diet, and a diet low in fermentable oligo-, di- and monosaccharides as well as polyols (FODMAP). We examine and review the most common complementary supplements and diets used by patients with IBD.
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Affiliation(s)
- Hadi J Minhas
- Department of Gastroenterology, Albany Medical Center, Albany NY, USA
| | - Konstantinos Papamichael
- Division of Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215, USA
- Harvard Medical School, Boston, MA, USA
| | - Adam S. Cheifetz
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Robert J. Gianotti
- Department of Gastroenterology, Albany Medical Center, Albany NY, USA
- Albany Gastroenterology Consultants, Albany, NY, USA
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Rohwer N, Jelleschitz J, Höhn A, Weber D, Kühl AA, Wang C, Ohno RI, Kampschulte N, Pietzner A, Schebb NH, Weylandt KH, Grune T. Prevention of colitis-induced liver oxidative stress and inflammation in a transgenic mouse model with increased omega-3 polyunsaturated fatty acids. Redox Biol 2023; 64:102803. [PMID: 37392516 DOI: 10.1016/j.redox.2023.102803] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/22/2023] [Accepted: 06/26/2023] [Indexed: 07/03/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an immune-mediated gut dysfunction, which might also be associated with an inflammatory phenotype in the liver. It is known that the nutritional intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) is inversely correlated to the severity and occurrence of IBD. In order to investigate whether n-3 PUFA can also reduce liver inflammation and oxidative liver damage due to colon inflammation, we explored the dextran sulfate sodium (DSS)-induced colitis model in wild-type and fat-1 mice with endogenously increased n-3 PUFA tissue content. Besides confirming previous data of alleviated DSS-induced colitis in the fat-1 mouse model, the increase of n-3 PUFA also resulted in a significant reduction of liver inflammation and oxidative damage in colitis-affected fat-1 mice as compared to wild-type littermates. This was accompanied by a remarkable increase of established inflammation-dampening n-3 PUFA oxylipins, namely docosahexaenoic acid-derived 19,20-epoxydocosapentaenoic acid and eicosapentaenoic acid-derived 15-hydroxyeicosapentaenoic acid and 17,18-epoxyeicosatetraenoic acid. Taken together, these observations demonstrate a strong inverse correlation between the anti-inflammatory lipidome derived from n-3 PUFA and the colitis-triggered inflammatory changes in the liver by reducing oxidative liver stress.
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Affiliation(s)
- Nadine Rohwer
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology and Diabetes, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, Brandenburg Medical School and University of Potsdam, Potsdam, Germany; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Julia Jelleschitz
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Annika Höhn
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany
| | - Daniela Weber
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Anja A Kühl
- iPATH.Berlin-Immunopathology for Experimental Models, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Chaoxuan Wang
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology and Diabetes, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, Brandenburg Medical School and University of Potsdam, Potsdam, Germany; Medical Department, Division of Psychosomatic Medicine, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Rei-Ichi Ohno
- University of Wuppertal, Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, Wuppertal, Germany
| | - Nadja Kampschulte
- University of Wuppertal, Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, Wuppertal, Germany
| | - Anne Pietzner
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology and Diabetes, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
| | - Nils Helge Schebb
- University of Wuppertal, Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, Wuppertal, Germany
| | - Karsten-H Weylandt
- Medical Department B, Division of Hepatology, Gastroenterology, Oncology, Hematology, Palliative Care, Endocrinology and Diabetes, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, Brandenburg Medical School and University of Potsdam, Potsdam, Germany
| | - Tilman Grune
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany.
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Yuan SN, Wang MX, Han JL, Feng CY, Wang M, Wang M, Sun JY, Li NY, Simal-Gandara J, Liu C. Improved colonic inflammation by nervonic acid via inhibition of NF-κB signaling pathway of DSS-induced colitis mice. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 112:154702. [PMID: 36764096 DOI: 10.1016/j.phymed.2023.154702] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 01/14/2023] [Accepted: 02/03/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Nervonic acid (C24:1∆15, 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fatty acid, plays an essential role in prevention of metabolic diseases, and immune regulation, and has anti-inflammatory properties. As a chronic, immune-mediated inflammatory disease, ulcerative colitis (UC) can affect the large intestine. The influences of NA on UC are largely unknown. PURPOSE The present study aimed to decipher the anti-UC effect of NA in the mouse colitis model. Specifically, we wanted to explore whether NA can regulate the levels of inflammatory factors in RAW264.7 cells and mouse colitis model. METHODS To address the above issues, the RAW264.7 cell inflammation model was established by lipopolysaccharide (LPS), then the inflammatory factors tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Interleukin-10 (IL-10) were detected by Enzyme-linked immunosorbent assay (ELISA). The therapeutic effects of NA for UC were evaluated using C57BL/6 mice gavaged dextran sodium sulfate (DSS). Hematoxylin and eosin (H&E) staining, Myeloperoxidase (MPO) kit assay, ELISA, immunofluorescence assay, and LC-MS/MS were used to assess histological changes, MPO levels, inflammatory factors release, expression and distribution of intestinal tight junction (TJ) protein ZO-1, and metabolic pathways, respectively. The levels of proteins involved in the nuclear factor kappa-B (NF-κB) pathway in the UC were investigated by western blotting and RT-qPCR. RESULTS In vitro experiments verified that NA could reduce inflammatory response and inhibit the activation of key signal pathways associated with inflammation in LPS-induced RAW264.7 cells. Further, results from the mouse colitis model suggested that NA could restore intestinal barrier function and suppress NF-κB signal pathways to ameliorate DSS-induced colitis. In addition, untargeted metabolomics analysis of NA protection against UC found that NA protected mice from colitis by regulating citrate cycle, amino acid metabolism, pyrimidine and purine metabolism. CONCLUSION These results suggested that NA could ameliorate the secretion of inflammatory factors, suppress the NF-κB signaling pathway, and protect the integrity of colon tissue, thereby having a novel role in prevention or treatment therapy for UC. This work for the first time indicated that NA might be a potential functional food ingredient for preventing and treating inflammatory bowel disease (IBD).
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Affiliation(s)
- Sheng-Nan Yuan
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Mu-Xuan Wang
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Jin-Long Han
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Cai-Yun Feng
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Meng Wang
- Shanxi Functional Food Engineering Center Co. Ltd, Xian 710000, China
| | - Min Wang
- College of Food Science and Engineering, Northwest A&F University, Xianyang 712100, China
| | - Jin-Yue Sun
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China; Shandong Huatai Nutrition and Health Industry Technology Research Institute Co. Ltd, Jinan 250100, China.
| | - Ning-Yang Li
- Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Taian, China.
| | - Jesus Simal-Gandara
- Universidade de Vigo, Nutrition and Bromatology Group, Analytical Chemistry and Food Science Department, Faculty of Science, E-32004 Ourense, Spain.
| | - Chao Liu
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China; Shandong Huatai Nutrition and Health Industry Technology Research Institute Co. Ltd, Jinan 250100, China.
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Abdelsameea AA, Alsemeh AE, Alabassery N, Samy W, Fawzy A, Abbas NAT. Icosapent ethyl alleviates acetic acid-induced ulcerative colitis via modulation of SIRT1 signaling pathway in rats. Int Immunopharmacol 2023; 115:109621. [PMID: 36574744 DOI: 10.1016/j.intimp.2022.109621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 12/08/2022] [Accepted: 12/17/2022] [Indexed: 12/26/2022]
Abstract
Ulcerative colitis (UC) is a global inflammatory bowel disease. This study aimed to assess the effects of icosapent ethyl on acetic acid-induced colitis in rats as well as the underlying mechanisms involved. 36 male Wister rats were equally divided into six groups: control, UC, mesalamine 100 mg/kg, icosapent 150mg/kg, icosapent 300 mg/kg, and EX527-icosapent 300 mg/kg groups. Except for control group, UC was induced by acetic acid instillation into colon. Drugs were administered once daily for one week then under thiopental anaesthesia, colons were excised. Colitis macroscopic and microscopic scores were assessed. A part of colon was homogenized for detection of malondialdehyde (MDA), inerleukin1 (IL-1β), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), phosphorylated Akt (pAkt) and caspase 3 levels. Silent information regulator 1 (SIRT1), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2 (Nrf2) mRNA expressions were detected. Mallory-stained colonic sections were examined for collagen fibres detection. Immunohistochemistry of NF-κB and p53 expressionsin colonic sections were assessed. Acetic acid induced colitis with increments in MDA, IL-1β, TNF-α, and caspase 3 levels while decreased SOD, pAkt, SIRT1, HO-1, and Nrf2 with increased collagen fibres as well as NF-κB and p53. Icosapent decreased macro& microscopic colitis scores, MDA, IL-1β, TNF-α, and caspase 3 levels while increased SOD, pAkt, SIRT1, HO-1, and Nrf2 with decreased collagen fibres as well as NF-κB and p53. The effects of icosapent 300 mg/kg were similar to mesalamine. Icosapent effects were antagonized by EX527. Icosapent alleviated acetic acid-induced colitis via its anti-inflammatory, antioxidant, and anti-apoptotic effects mediated in part by SIRT1 pathway activation.
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Affiliation(s)
| | - Amira Ebrahim Alsemeh
- Department of Human Anatomy and Embryology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
| | - Nadia Alabassery
- Department of Anatomy, Faculty of Medicine-Minia University, Zagazig, Egypt
| | - Walaa Samy
- Medical Biochemistry Department, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
| | - Amal Fawzy
- Medical Biochemistry Department, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
| | - Noha A T Abbas
- Department of Pharmacology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
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8
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Adolph TE, Meyer M, Schwärzler J, Mayr L, Grabherr F, Tilg H. The metabolic nature of inflammatory bowel diseases. Nat Rev Gastroenterol Hepatol 2022; 19:753-767. [PMID: 35906289 DOI: 10.1038/s41575-022-00658-y] [Citation(s) in RCA: 144] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/23/2022] [Indexed: 02/06/2023]
Abstract
Crohn's disease and ulcerative colitis, phenotypically comprising a spectrum of inflammatory bowel diseases (IBDs), spread globally during the westernization of lifestyle and dietary habits over the past few decades. Here, we review experimental and clinical evidence for the metabolic nature of gut inflammation in IBD and delineate distinct parallels to the inflammatory state in metabolic diseases. Experimental evidence indicates that excessive intake of specific macronutrients in a Western diet fuels an inflammatory response in the gut by exploiting sensors of innate immunity and perturbation of gut microbial metabolism. Genetic IBD risk partly affects metabolism and stress signalling of innate immunity, and immunometabolism controls susceptibility to gut inflammation. Epidemiological and clinical studies indicate that specific nutrients in the Western diet pose a risk for the development of IBD and a poor disease course. Translational studies in IBD indicate perturbation of energy metabolism in immune cells and perturbation of gut microbial metabolism, which can be shaped by diet. In turn, dietary restriction by exclusive enteral nutrition induces remission in patients with IBD. Collectively, these studies support a metabolic underpinning of gut inflammation in IBD as described for metabolic inflammation in obesity and related disorders.
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Affiliation(s)
- Timon E Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
| | - Moritz Meyer
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Julian Schwärzler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Lisa Mayr
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Felix Grabherr
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
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9
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KIANI AYSHAKARIM, BONETTI GABRIELE, DONATO KEVIN, BERTELLI MATTEO. Dietary supplements for intestinal inflammation. JOURNAL OF PREVENTIVE MEDICINE AND HYGIENE 2022; 63:E214-E220. [PMID: 36479492 PMCID: PMC9710413 DOI: 10.15167/2421-4248/jpmh2022.63.2s3.2763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Intestinal inflammation leads to various chronic diseases, collectively known as inflammatory bowel disease (IBD). IBD mainly affects the large intestine, but it can also affect the gastrointestinal tract as a whole. Its major symptoms are pain, diarrhea, and weight loss, and it is usually associated with deficiencies of both macro- and micronutrients. Unluckily, after some time the body develops resistance against the already available drugs: thus, many patients fail to maintain remission, which is achieved in less than 50% of cases. Diet is a major determinant of gut inflammation. An unbalanced diet can affect the gut microbiota and cause dysbiosis, which is related to a dysregulated host immune response. The Mediterranean Diet its renowned for its anti-inflammatory effects and for preventing dysbiosis. In order to improve management and treatment of intestinal inflammatory diseases, it should become common practice to integrate the patient's diet with dietary supplements with anti-inflammatory effects (probiotics, butyrate, phosphatidylcholine, lactoferrin, palmitoylethanolamide, silymarin, and omega 3), which maintain the stability of the intestinal microbial cohort and strengthen the mucosal barrier, thus preventing or soothing IBD symptoms. Dietary supplements may help fight the high costs, the adverse side effects, and the recurrent relapses typical of drug use.
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Affiliation(s)
| | | | | | - MATTEO BERTELLI
- MAGI Euregio, Bolzano, Italy
- MAGI’S LAB, Rovereto (TN), Italy
- MAGISNAT, Peachtree Corners (GA), USA
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10
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Schwärzler J, Mayr L, Vich Vila A, Grabherr F, Niederreiter L, Philipp M, Grander C, Meyer M, Jukic A, Tröger S, Enrich B, Przysiecki N, Tschurtschenthaler M, Sommer F, Kronberger I, Koch J, Hilbe R, Hess MW, Oberhuber G, Sprung S, Ran Q, Koch R, Effenberger M, Kaneider NC, Wieser V, Keller MA, Weersma RK, Aden K, Rosenstiel P, Blumberg RS, Kaser A, Tilg H, Adolph TE. PUFA-Induced Metabolic Enteritis as a Fuel for Crohn's Disease. Gastroenterology 2022; 162:1690-1704. [PMID: 35031299 DOI: 10.1053/j.gastro.2022.01.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 12/16/2021] [Accepted: 01/04/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Crohn's disease (CD) globally emerges with Westernization of lifestyle and nutritional habits. However, a specific dietary constituent that comprehensively evokes gut inflammation in human inflammatory bowel diseases remains elusive. We aimed to delineate how increased intake of polyunsaturated fatty acids (PUFAs) in a Western diet, known to impart risk for developing CD, affects gut inflammation and disease course. We hypothesized that the unfolded protein response and antioxidative activity of glutathione peroxidase 4 (GPX4), which are compromised in human CD epithelium, compensates for metabolic perturbation evoked by dietary PUFAs. METHODS We phenotyped and mechanistically dissected enteritis evoked by a PUFA-enriched Western diet in 2 mouse models exhibiting endoplasmic reticulum (ER) stress consequent to intestinal epithelial cell (IEC)-specific deletion of X-box binding protein 1 (Xbp1) or Gpx4. We translated the findings to human CD epithelial organoids and correlated PUFA intake, as estimated by a dietary questionnaire or stool metabolomics, with clinical disease course in 2 independent CD cohorts. RESULTS PUFA excess in a Western diet potently induced ER stress, driving enteritis in Xbp1-/-IEC and Gpx4+/-IEC mice. ω-3 and ω-6 PUFAs activated the epithelial endoplasmic reticulum sensor inositol-requiring enzyme 1α (IRE1α) by toll-like receptor 2 (TLR2) sensing of oxidation-specific epitopes. TLR2-controlled IRE1α activity governed PUFA-induced chemokine production and enteritis. In active human CD, ω-3 and ω-6 PUFAs instigated epithelial chemokine expression, and patients displayed a compatible inflammatory stress signature in the serum. Estimated PUFA intake correlated with clinical and biochemical disease activity in a cohort of 160 CD patients, which was similarly demonstrable in an independent metabolomic stool analysis from 199 CD patients. CONCLUSIONS We provide evidence for the concept of PUFA-induced metabolic gut inflammation which may worsen the course of human CD. Our findings provide a basis for targeted nutritional therapy.
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Affiliation(s)
- Julian Schwärzler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Lisa Mayr
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Arnau Vich Vila
- Department of Gastroenterology and Hepatology, University of Groningen and Groningen University Medical Center, Groningen, the Netherlands
| | - Felix Grabherr
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Lukas Niederreiter
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Maureen Philipp
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Christoph Grander
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Moritz Meyer
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Almina Jukic
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Simone Tröger
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Barbara Enrich
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Nicole Przysiecki
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus Tschurtschenthaler
- Institute for Experimental Cancer Therapy, Center for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Felix Sommer
- Institute of Clinical Molecular Biology, Christian Albrecht University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany
| | - Irmgard Kronberger
- Department of Visceral, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Jakob Koch
- Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria
| | - Richard Hilbe
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria
| | - Michael W Hess
- Institute of Histology and Embryology, Medical University of Innsbruck, Innsbruck, Austria
| | - Georg Oberhuber
- INNPATH, Innsbruck Medical University Hospital, Innsbruck, Austria
| | - Susanne Sprung
- Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria
| | - Qitao Ran
- Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, Texas
| | - Robert Koch
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Maria Effenberger
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Nicole C Kaneider
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Verena Wieser
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus A Keller
- Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and Groningen University Medical Center, Groningen, the Netherlands
| | - Konrad Aden
- Institute of Clinical Molecular Biology, Christian Albrecht University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany
| | - Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian Albrecht University Kiel and Schleswig-Holstein University Hospital, Kiel, Germany
| | - Richard S Blumberg
- Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Arthur Kaser
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Timon E Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
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Montgomery DR, Biklé A, Archuleta R, Brown P, Jordan J. Soil health and nutrient density: preliminary comparison of regenerative and conventional farming. PeerJ 2022; 10:e12848. [PMID: 35127297 PMCID: PMC8801175 DOI: 10.7717/peerj.12848] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 01/07/2022] [Indexed: 01/10/2023] Open
Abstract
Several independent comparisons indicate regenerative farming practices enhance the nutritional profiles of crops and livestock. Measurements from paired farms across the United States indicate differences in soil health and crop nutrient density between fields worked with conventional (synthetically-fertilized and herbicide-treated) or regenerative practices for 5 to 10 years. Specifically, regenerative farms that combined no-till, cover crops, and diverse rotations-a system known as Conservation Agriculture-produced crops with higher soil organic matter levels, soil health scores, and levels of certain vitamins, minerals, and phytochemicals. In addition, crops from two regenerative no-till vegetable farms, one in California and the other in Connecticut, had higher levels of phytochemicals than values reported previously from New York supermarkets. Moreover, a comparison of wheat from adjacent regenerative and conventional no-till fields in northern Oregon found a higher density of mineral micronutrients in the regenerative crop. Finally, a comparison of the unsaturated fatty acid profile of beef and pork raised on one of the regenerative farms to a regional health-promoting brand and conventional meat from local supermarkets, found higher levels of omega-3 fats and a more health-beneficial ratio of omega-6 to omega-3 fats. Despite small sample sizes, all three crop comparisons show differences in micronutrient and phytochemical concentrations that suggest soil health is an under appreciated influence on nutrient density, particularly for phytochemicals not conventionally considered nutrients but nonetheless relevant to chronic disease prevention. Likewise, regenerative grazing practices produced meat with a better fatty acid profile than conventional and regional health-promoting brands. Together these comparisons offer preliminary support for the conclusion that regenerative soil-building farming practices can enhance the nutritional profile of conventionally grown plant and animal foods.
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Affiliation(s)
- David R. Montgomery
- Department of Earth and Space Sciences, University of Washington, Seattle, WA, United States
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12
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Akazawa Y, Morisaki T, Fukuda H, Norimatsu K, Shiota J, Hashiguchi K, Tabuchi M, Kitayama M, Matsushima K, Yamaguchi N, Kondo H, Fujita F, Takeshita H, Nakao K, Takeshima F. Significance of serum palmitoleic acid levels in inflammatory bowel disease. Sci Rep 2021; 11:16260. [PMID: 34376800 PMCID: PMC8355139 DOI: 10.1038/s41598-021-95923-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 06/28/2021] [Indexed: 01/22/2023] Open
Abstract
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD.
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Affiliation(s)
- Yuko Akazawa
- Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
| | | | | | - Kiyuu Norimatsu
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Junya Shiota
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Keiichi Hashiguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Maiko Tabuchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Moto Kitayama
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Naoyuki Yamaguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hisayoshi Kondo
- Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medicine, Nagasaki, Japan
| | | | | | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Fuminao Takeshima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Nagasaki Goto Chuoh Hospital, Goto, Japan
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13
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Ajabnoor SM, Thorpe G, Abdelhamid A, Hooper L. Long-term effects of increasing omega-3, omega-6 and total polyunsaturated fats on inflammatory bowel disease and markers of inflammation: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr 2021; 60:2293-2316. [PMID: 33084958 DOI: 10.1007/s00394-020-02413-y] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 10/06/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Effects of long-chain omega-3 (LCn3) and omega-6 fatty acids on prevention and treatment of inflammatory bowel diseases (IBD, including Crohn's Disease, CD and ulcerative colitis, UC), and inflammation are unclear. We systematically reviewed long-term effects of omega-3, omega-6 and total polyunsaturated fats (PUFA) on IBD diagnosis, relapse, severity, pharmacotherapy, quality of life and key inflammatory markers. METHODS We searched Medline, Embase, Cochrane CENTRAL, and trials registries, including RCTs in adults with or without IBD comparing higher with lower omega-3, omega-6 and/or total PUFA intake for ≥ 24 weeks that assessed IBD-specific outcomes or inflammatory biomarkers. RESULTS We included 83 RCTs (41,751 participants), of which 13 recruited participants with IBD. Increasing LCn3 may reduce risk of IBD relapse (RR 0.85, 95% CI 0.72-1.01) and IBD worsening (RR 0.85, 95% CI 0.71-1.03), and reduce erythrocyte sedimentation rate (ESR, SMD - 0.23, 95% CI - 0.44 to - 0.01), but may increase IBD diagnosis risk (RR 1.10, 95% CI 0.63-1.92), and faecal calprotectin, a specific inflammatory marker for IBD (MD 16.1 μg/g, 95% CI - 37.6 to 69.8, all low-quality evidence). Outcomes for alpha-linolenic acid, omega-6 and total PUFA were sparse, but suggested little or no effect where data were available. CONCLUSION This is the most comprehensive meta-analysis of RCTs investigating long-term effects of omega-3, omega-6 and total PUFA on IBD and inflammatory markers. Our findings suggest that supplementation with PUFAs has little or no effect on prevention or treatment of IBD and provides little support for modification of long-term inflammatory status.
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Affiliation(s)
- Sarah M Ajabnoor
- Norwich Medical School, University of East Anglia, Norwich, UK.
- Clinical Nutrition Department, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80324, Jeddah, 21589, Saudi Arabia.
| | - Gabrielle Thorpe
- School of Health Sciences, University of East Anglia, Norwich, UK
| | | | - Lee Hooper
- Norwich Medical School, University of East Anglia, Norwich, UK
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Influences of dietary oils and fats, and the accompanied minor content of components on the gut microbiota and gut inflammation: A review. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.05.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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15
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LC R, EM B, DB H, H S, AR P. A pilot randomized controlled trial testing supplements of omega-3 fatty acids, probiotics, combination or placebo on symptoms of depression, anxiety and stress. JOURNAL OF AFFECTIVE DISORDERS REPORTS 2021. [DOI: 10.1016/j.jadr.2021.100141] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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16
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Mullin GE, Limketkai BN, Parian AM. Fish Oil for Inflammatory Bowel Disease: Panacea or Placebo? Gastroenterol Clin North Am 2021; 50:169-182. [PMID: 33518163 DOI: 10.1016/j.gtc.2020.10.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Dietary supplements have increasingly gained popularity over the years not only to replete micronutrient deficiencies but for their use in treatment of disease. The popularity of dietary supplements for inflammatory bowel diseases (IBD) arises from their perceived ease of use, potential disease-modifying benefits, and perceived safety. Overall, randomized controlled trials have not consistently shown a benefit of fish oil for the maintenance of remission with Crohn's disease. The inconsistency of these findings highlights the need for more studies that are powered to clarify the context in which omega-3 fatty acids might have a role in the treatment algorithm of IBD.
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Affiliation(s)
- Gerard E Mullin
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21205, USA.
| | - Berkeley N Limketkai
- Division of Digestive Diseases, UCLA School of Medicine, 100 UCLA Medical Center Plaza, Suite 345, Los Angeles, CA 90095, USA
| | - Alyssa M Parian
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21205, USA
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Caprara G. Mediterranean-Type Dietary Pattern and Physical Activity: The Winning Combination to Counteract the Rising Burden of Non-Communicable Diseases (NCDs). Nutrients 2021; 13:429. [PMID: 33525638 PMCID: PMC7910909 DOI: 10.3390/nu13020429] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 02/07/2023] Open
Abstract
Non-communicable diseases (NCDs) (mainly cardiovascular diseases, cancers, chronic respiratory diseases and type 2 diabetes) are the main causes of death worldwide. Their burden is expected to rise in the future, especially in less developed economies and among the poor spread across middle- and high-income countries. Indeed, the treatment and prevention of these pathologies constitute a crucial challenge for public health. The major non-communicable diseases share four modifiable behavioral risk factors: unhealthy diet, physical inactivity, tobacco usage and excess of alcohol consumption. Therefore, the adoption of healthy lifestyles, which include not excessive alcohol intake, no smoking, a healthy diet and regular physical activity, represents a crucial and economical strategy to counteract the global NCDs burden. This review summarizes the latest evidence demonstrating that Mediterranean-type dietary pattern and physical activity are, alone and in combination, key interventions to both prevent and control the rise of NCDs.
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Affiliation(s)
- Greta Caprara
- Department of Experimental Oncology, IEO, European Institute of Oncology, IRCCS, 20139 Milano, Italy
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18
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de Castro MM, Pascoal LB, Steigleder KM, Siqueira BP, Corona LP, Ayrizono MDLS, Milanski M, Leal RF. Role of diet and nutrition in inflammatory bowel disease. World J Exp Med 2021; 11:1-16. [PMID: 33585174 PMCID: PMC7852575 DOI: 10.5493/wjem.v11.i1.1] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 11/02/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are closely linked to nutrition. The latest research indicates that diet and nutrition are significantly involved in the etiopathogenesis of the disease, although their specific role throughout its clinical course still remains unclear. This study reviewed how diet and nutrition are associated with IBD development and management. Even though specific diets have been shown to bring about positive outcomes, there is currently no scientific consensus regarding an appropriate diet that would benefit all IBD patients. We suggest that individualized dietary recommendations are of the greatest importance and that diets should be planned to provide individual IBD patients with specific nutrient requirements while keeping all the clinical aspects of the patients in mind. Further research is clearly necessary to investigate nutritional factors involved in IBD development and, especially, to evaluate the applications of the diets during the course of the disease.
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Affiliation(s)
- Marina Moreira de Castro
- IBD Research Laboratory, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Lívia Bitencourt Pascoal
- IBD Research Laboratory, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Karine Mariane Steigleder
- IBD Research Laboratory, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Beatriz Piatezzi Siqueira
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (UNICAMP), Limeira 13484-350, São Paulo, Brazil
| | - Ligiana Pires Corona
- Laboratory of Nutritional Epidemiology, School of Applied Sciences, University of Campinas (UNICAMP), Limeira 13484-350, São Paulo, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- IBD Research Laboratory, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Marciane Milanski
- IBD Research Laboratory, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Raquel Franco Leal
- IBD Research Laboratory, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
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19
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Wang C, Han D, Feng X, Wu J. Omega-3 fatty acid supplementation is associated with favorable outcomes in patients with sepsis: an updated meta-analysis. J Int Med Res 2020; 48:300060520953684. [PMID: 33373266 PMCID: PMC7783898 DOI: 10.1177/0300060520953684] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Objectives The efficacy of omega-3 fatty acids in the treatment of sepsis is
controversial. We conducted an updated meta-analysis to clarify the efficacy
of omega-3 fatty acids in patients with sepsis. Methods PubMed, EMBASE, and the Cochrane Library were searched for randomized
clinical trials (RCTs) on omega-3 fatty acid supplementation in adults with
sepsis. Results Twenty eligible RCTs involving 1514 patients were included in the
meta-analysis. Omega-3 fatty acid supplementation was linked to reductions
of mortality (I2 = 0, relative risk [RR] = 0.82,
95% confidence interval [CI] = 0.69–0.97), the duration of mechanical
ventilation (DMV; I2 = 74%, weighted mean
difference [WMD] = −2.20, 95% CI = −4.00 to −0.40), and intensive care unit
(ICU) length of stay (LOS; I2 = 91%,
WMD = −3.86, 95% CI = −5.72 to −2.01). Subgroup analysis illustrated that
mortality was significantly reduced in patients with sepsis and
gastrointestinal dysfunction (RR = 0.5, 95% CI = 0.29–0.86,
I2 = 0). Conclusion Omega-3 fatty acid supplementation might be associated with reduced mortality
in patients with sepsis, especially those with gastrointestinal dysfunction.
Furthermore, omega-3 fatty acid administration could shorten DMV and ICU
LOS.
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Affiliation(s)
- Chenyang Wang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dong Han
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaojing Feng
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Wu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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20
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Controversies about the cardiovascular effects of OM3FA. Did inappropriate placebos skew clinical trial results? Pharmacol Res 2020; 164:105368. [PMID: 33316385 DOI: 10.1016/j.phrs.2020.105368] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 11/18/2020] [Accepted: 12/08/2020] [Indexed: 11/22/2022]
Abstract
Several observational studies suggest that greasy fish may reduce cardiovascular risk, whose benefits have been attributed to the presence Omega-3 polyunsaturated fatty acids (OM3FA). However, there are some randomized controlled trials (RCTs) that have shown contradictory results concerning the cardiovascular benefits of OM3FA. Analyzing these RCTs we found that the use of olive oil in some RCTs could be responsible for contradictory results, since both. since both olive oil and OM3FA, in addition to reduce triglycerides, have anti-platelet and anti-inflammatory activities, considered important for the stabilization of atherosclerotic plaques. This pharmacodynamic profile may have a cardio protective effect that was confirmed by several RCTs. Therefore, olive oil seems an active substance, and its use might have reduced the differences between groups masking the efficacy of OM3FA. This inferred lack of OM3FA cardiovascular benefits due to bias induced by a "false placebo" control, raises epistemological considerations on the choice of placebos that always should be pharmacologically inert substances. More studies are necessary to clarify the real efficacy of OM3FA that is more innocuous than many medicines, but it seems useful in future RCTs the use of a truly inert substance as a placebo, as well as the outline of a semi quantitative dose-response curve suggestive of a causal nexus between active substances and their outcomes.
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21
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Bhatt DL, Hull MA, Song M, Van Hulle C, Carlsson C, Chapman MJ, Toth PP. Beyond cardiovascular medicine: potential future uses of icosapent ethyl. Eur Heart J Suppl 2020; 22:J54-J64. [PMID: 33061868 PMCID: PMC7537800 DOI: 10.1093/eurheartj/suaa119] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The REDUCE-IT trial demonstrated that icosapent ethyl, an ethyl ester of eicosapentaenoic acid (EPA), reduced cardiovascular events in an at-risk population by a substantial degree. While the cardiovascular protective properties of this compound are now proven, several other potential uses are being actively explored in clinical studies. These areas of investigation include cancer, inflammatory bowel disease, infections, Alzheimer's disease, dementia, and depression. The next decade promises to deepen our understanding of the beneficial effects that EPA may offer beyond cardiovascular risk reduction.
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Affiliation(s)
- Deepak L Bhatt
- Brigham and Women’s Hospital, Heart & Vascular Center and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Mark A Hull
- Division of Gastrointestinal and Surgical Sciences, Leeds Institute of Medical Research, St James’s University Hospital, University of Leeds, Leeds, LS9 7TF, UK
| | - Mingyang Song
- Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA
- Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Boston, MA 02114, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 50 Fruit Street, Boston, MA 02114, USA
| | - Carol Van Hulle
- University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA
| | - Cindy Carlsson
- William S. Middleton Memorial Veterans Hospital, Madison VA Geriatric Research, Education and Clinical Center (GRECC), 2500 Overlook Terrace, Madison, WI 53705, USA
- Division of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
- Wisconsin Alzheimer’s Disease Research Center (ADRC), 600 Highland Ave, J5/1 Mezzanine, Madison, WI 53792, USA
- Wisconsin Alzheimer’s Institute (WAI), 610 Walnut St Suite 957, Madison, WI 53726, USA
| | - M John Chapman
- Sorbonne University, 21, Rue de l'Ecole de Medicine, 75006 Paris, France
- Endocrinology-Metabolism Division, Pitie-Salpetriere University Hospital, 47-83, Boulevard de lopital, 75651 Paris Cedex, France
| | - Peter P Toth
- CGH Medical Center, 101 East Miller Road, Sterling, IL 61081, USA
- Cicarrone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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22
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23
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Opening a Window on Attention: Adjuvant Therapies for Inflammatory Bowel Disease. Can J Gastroenterol Hepatol 2020; 2020:7397523. [PMID: 32850517 PMCID: PMC7441453 DOI: 10.1155/2020/7397523] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 01/17/2020] [Accepted: 01/27/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), most commonly known as Crohn's disease (CD) and ulcerative disease (UC), is a chronic and relapsing intestinal disease which cannot be cured completely. The prevalence of IBD in Europe and in North America has increased over the past 20 years. As most IBD patients are young at onset, their quality of life (QOL) can be influenced to varying degrees. Thus, current treatment goals are typically focused on preventing complications, including maintaining clinical remission and improving the QOL. Adjuvant therapies have been widely concerned as an effective treatment in alleviating IBD symptoms, including dietary intervention, traditional Chinese medicine, smoking, alcohol, and physical activities. This review focuses on different ancillary therapies for IBD treatments, in particular the mechanism of reducing inflammation based on the actual data from research studies. Moreover, comparing the latest data, this review also presented potential future prospect for adjuvant therapies.
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24
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Ho GT, Cartwright JA, Thompson EJ, Bain CC, Rossi AG. Resolution of Inflammation and Gut Repair in IBD: Translational Steps Towards Complete Mucosal Healing. Inflamm Bowel Dis 2020; 26:1131-1143. [PMID: 32232386 PMCID: PMC7365805 DOI: 10.1093/ibd/izaa045] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Indexed: 02/07/2023]
Abstract
Despite significant recent therapeutic advances, complete mucosal healing remains a difficult treatment target for many patients with inflammatory bowel diseases (IBD) to achieve. Our review focuses on the translational concept of promoting resolution of inflammation and repair as a necessary adjunctive step to reach this goal. We explore the roles of inflammatory cell apoptosis and efferocytosis to promote resolution, the new knowledge of gut monocyte-macrophage populations and their secreted prorepair mediators, and the processes of gut epithelial repair and regeneration to bridge this gap. We discuss the need and rationale for this vision and the tangible steps toward integrating proresolution therapies in IBD.
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Affiliation(s)
- Gwo-tzer Ho
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom,Address correspondence to: Gwo-tzer Ho, FRCP, PhD, Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, United Kingdom ()
| | - Jennifer A Cartwright
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom
| | - Emily J Thompson
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom
| | - Calum C Bain
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom
| | - Adriano G Rossi
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom
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25
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Intestinal Macrophages at the Crossroad between Diet, Inflammation, and Cancer. Int J Mol Sci 2020; 21:ijms21144825. [PMID: 32650452 PMCID: PMC7404402 DOI: 10.3390/ijms21144825] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/03/2020] [Accepted: 07/04/2020] [Indexed: 12/11/2022] Open
Abstract
Intestinal macrophages are key players in the regulation of the oral tolerance, controlling gut homeostasis by discriminating innocuous antigens from harmful pathogens. Diet exerts a significant impact on human health, influencing the composition of gut microbiota and the developing of several non-communicable diseases, including cancer. Nutrients and microbiota are able to modify the profile of intestinal macrophages, shaping their key function in the maintenance of the gut homeostasis. Intestinal disease often occurs as a breakdown of this balance: defects in monocyte-macrophage differentiation, wrong dietary habits, alteration of microbiota composition, and impairment in the resolution of inflammation may contribute to the development of intestinal chronic inflammation and colorectal cancer. Accordingly, dietary interventions and macrophage-targeted therapies are emerging as innovative tools for the treatment of several intestinal pathologies. In this review, we will describe the delicate balance between diet, microbiota and intestinal macrophages in homeostasis and how the perturbation of this equilibrium may lead to the occurrence of inflammatory conditions in the gut. The understanding of the molecular pathways and dietary factors regulating the activity of intestinal macrophages might result in the identification of innovative targets for the treatments of intestinal pathologies.
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26
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Kida M, Nakamura T, Murata T. A novel eicosapentaenoic acid-derived anti-inflammatory lipid mediator 5,6-DiHETE is abundant in blue back fish intestines. J Food Sci 2020; 85:1983-1987. [PMID: 32572984 DOI: 10.1111/1750-3841.15179] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 04/18/2020] [Accepted: 04/22/2020] [Indexed: 01/03/2023]
Abstract
Because omega-3 fatty acids, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites are known to possess anti-inflammatory and health-promoting functions in human and experimental animals, their intake is assumed to be beneficial for maintaining our health. We previously identified a cytochrome P450-metabolite of EPA, 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE), as a novel bioactive lipid, which inhibits vascular hyperpermeability in inflammation. Because blue back fishes including sardine, mackerel, and horse mackerel are reported to contain high concentrations of omega-3 fatty acids, we investigated which tissue of blue back fish is suitable as a source of 5,6-DiHETE. We measured the concentration of 5,6-DiHETE as well as major fatty acids in muscle, bone, heart, liver, and intestine of blue back fishes. Arachidonic acid was detected richer in intestines than other tissues of blue back fishes. The concentrations were between 4.45 and 5.62 µg/g tissue weight. EPA and DHA are also detected richer in intestines of blue back fishes. The concentrations were between 75.95 and 358.04 µg/g, and 203.09 and 464.88 µg/g, respectively. Especially, mackerel intestine contained the highest levels of both EPA and DHA. 5,6-DiHETE was present in greater amount in livers and intestines of blue back fishes. The livers contained 118.98 to 476.11 ng/g, whereas intestines contained 156.14 to 970.22 ng/g of 5,6-DiHETE. Of interest, sardine intestine contained much higher level of 5,6-DiHETE than the other fish tissues. These results suggest that visceral organs of blue back fishes, remarkably sardine intestine, can be a good source of 5,6-DiHETE. PRACTICAL APPLICATION: A novel anti-inflammatory lipid, 5,6-DiHETE, was detected in each tissues of blue back fishes. Especially their intestines contain the highest concentration of this lipid.
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Affiliation(s)
- Misato Kida
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
| | - Tatsuro Nakamura
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
| | - Takahisa Murata
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
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Rondanelli M, Lamburghini S, Faliva MA, Peroni G, Riva A, Allegrini P, Spadaccini D, Gasparri C, Iannello G, Infantino V, Alalwan TA, Perna S, Miccono A. A food pyramid, based on a review of the emerging literature, for subjects with inflammatory bowel disease. ACTA ACUST UNITED AC 2020; 68:17-46. [PMID: 32499202 DOI: 10.1016/j.endinu.2020.01.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 12/14/2019] [Accepted: 01/08/2020] [Indexed: 02/07/2023]
Abstract
Emerging literature suggests that diet plays an important modulatory role in inflammatory bowel disease (IBD) through the management of inflammation and oxidative stress. The aim of this narrative review is to evaluate the evidence collected up till now regarding optimum diet therapy for IBD and to design a food pyramid for these patients. The pyramid shows that carbohydrates should be consumed every day (3 portions), together with tolerated fruits and vegetables (5 portions), yogurt (125ml), and extra virgin olive oil; weekly, fish (4 portions), white meat (3 portions), eggs (3 portions), pureed legumes (2 portions), seasoned cheeses (2 portions), and red or processed meats (once a week). At the top of the pyramid, there are two pennants: the red one means that subjects with IBD need some personalized supplementation and the black one means that there are some foods that are banned. The food pyramid makes it easier for patients to decide what they should eat.
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Affiliation(s)
- Mariangela Rondanelli
- IRCCS Mondino Foundation, Pavia, Department of Public Health, Experimental and Forensic Medicine, Unit of Human and Clinical Nutrition, University of Pavia, Pavia 27100, Italy
| | - Silvia Lamburghini
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Milena A Faliva
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Gabriella Peroni
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Antonella Riva
- Research and Development Unit, Indena, Milan 20146, Italy
| | | | - Daniele Spadaccini
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Clara Gasparri
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
| | - Giancarlo Iannello
- General Management, Azienda di Servizi alla Persona "Istituto Santa Margherita", Pavia 27100, Italy
| | - Vittoria Infantino
- University of Bari Aldo Moro, Department of Biomedical Science and Human Oncology, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy.
| | - Tariq A Alalwan
- Department of Biology, College of Science, University of Bahrain, Sakhir Campus, P.O. Box 32038, Bahrain
| | - Simone Perna
- Department of Biology, College of Science, University of Bahrain, Sakhir Campus, P.O. Box 32038, Bahrain
| | - Alessandra Miccono
- University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia 27100, Italy
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Ouahed J, Spencer E, Kotlarz D, Shouval DS, Kowalik M, Peng K, Field M, Grushkin-Lerner L, Pai SY, Bousvaros A, Cho J, Argmann C, Schadt E, Mcgovern DPB, Mokry M, Nieuwenhuis E, Clevers H, Powrie F, Uhlig H, Klein C, Muise A, Dubinsky M, Snapper SB. Very Early Onset Inflammatory Bowel Disease: A Clinical Approach With a Focus on the Role of Genetics and Underlying Immune Deficiencies. Inflamm Bowel Dis 2020; 26:820-842. [PMID: 31833544 PMCID: PMC7216773 DOI: 10.1093/ibd/izz259] [Citation(s) in RCA: 125] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Indexed: 12/12/2022]
Abstract
Very early onset inflammatory bowel disease (VEO-IBD) is defined as IBD presenting before 6 years of age. When compared with IBD diagnosed in older children, VEO-IBD has some distinct characteristics such as a higher likelihood of an underlying monogenic etiology or primary immune deficiency. In addition, patients with VEO-IBD have a higher incidence of inflammatory bowel disease unclassified (IBD-U) as compared with older-onset IBD. In some populations, VEO-IBD represents the age group with the fastest growing incidence of IBD. There are contradicting reports on whether VEO-IBD is more resistant to conventional medical interventions. There is a strong need for ongoing research in the field of VEO-IBD to provide optimized management of these complex patients. Here, we provide an approach to diagnosis and management of patients with VEO-IBD. These recommendations are based on expert opinion from members of the VEO-IBD Consortium (www.VEOIBD.org). We highlight the importance of monogenic etiologies, underlying immune deficiencies, and provide a comprehensive description of monogenic etiologies identified to date that are responsible for VEO-IBD.
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Affiliation(s)
- Jodie Ouahed
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Elizabeth Spencer
- Division of Gastroenterology, Hepatology and Nutrition, Mount Sinai Hospital, New York City, NY, USA
| | - Daniel Kotlarz
- Department of Pediatrics, Dr. Von Haunder Children’s Hospital, University Hospital, Ludwig-Maximillians-University Munich, Munich, Germany
| | - Dror S Shouval
- Pediatric Gastroenterology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Matthew Kowalik
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Kaiyue Peng
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA,Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children’s Hospital of Fudan University, Shanghai, China
| | - Michael Field
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Leslie Grushkin-Lerner
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Sung-Yun Pai
- Division of Hematology-Oncology, Boston Children’s Hospital, Dana-Farber Cancer Institute, Boston, MA USA
| | - Athos Bousvaros
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA
| | - Judy Cho
- Icahn School of Medicine at Mount Sinai, Dr. Henry D. Janowitz Division of Gastroenterology, New York, NY, USA
| | - Carmen Argmann
- Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Eric Schadt
- Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA,Sema4, Stamford, CT, USA
| | - Dermot P B Mcgovern
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Michal Mokry
- Division of Pediatrics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Edward Nieuwenhuis
- Division of Pediatrics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Hans Clevers
- Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences, Utrecht, the Netherlands
| | - Fiona Powrie
- University of Oxford, Kennedy Institute of Rheumatology, Oxford, UK
| | - Holm Uhlig
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK; Department of Pediatrics, University of Oxford, Oxford, UK
| | - Christoph Klein
- Pediatric Gastroenterology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Aleixo Muise
- SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada. Department of Pediatrics and Biochemistry, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada
| | - Marla Dubinsky
- Division of Gastroenterology, Hepatology and Nutrition, Mount Sinai Hospital, New York City, NY, USA
| | - Scott B Snapper
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA,Address correspondence to: Scott B. Snapper, MD, PhD, Children's Hospital Boston, Boston, Massachusetts, USA.
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Mayr L, Grabherr F, Schwärzler J, Reitmeier I, Sommer F, Gehmacher T, Niederreiter L, He GW, Ruder B, Kunz KTR, Tymoszuk P, Hilbe R, Haschka D, Feistritzer C, Gerner RR, Enrich B, Przysiecki N, Seifert M, Keller MA, Oberhuber G, Sprung S, Ran Q, Koch R, Effenberger M, Tancevski I, Zoller H, Moschen AR, Weiss G, Becker C, Rosenstiel P, Kaser A, Tilg H, Adolph TE. Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease. Nat Commun 2020; 11:1775. [PMID: 32286299 PMCID: PMC7156516 DOI: 10.1038/s41467-020-15646-6] [Citation(s) in RCA: 191] [Impact Index Per Article: 38.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 03/23/2020] [Indexed: 12/19/2022] Open
Abstract
The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn’s disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD. Dietary lipids are linked to the development of inflammatory bowel diseases through unclear mechanisms. Here, the authors report that dietary polyunsaturated fatty acids trigger intestinal inflammation resembling aspects of Crohn’s disease, which is restricted by glutathione peroxidase 4 in the intestinal epithelium.
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Affiliation(s)
- Lisa Mayr
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Felix Grabherr
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Julian Schwärzler
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Isabelle Reitmeier
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Felix Sommer
- Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany
| | - Thomas Gehmacher
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Lukas Niederreiter
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Gui-Wei He
- Department of Medicine 1, Gastroenterology, Pneumology and Endocrinology, University Medical Center Erlangen, Erlangen, Germany
| | - Barbara Ruder
- Department of Medicine 1, Gastroenterology, Pneumology and Endocrinology, University Medical Center Erlangen, Erlangen, Germany
| | - Kai T R Kunz
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Piotr Tymoszuk
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria
| | - Richard Hilbe
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Innsbruck, Austria
| | - David Haschka
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria
| | - Clemens Feistritzer
- Department of Internal Medicine V, Haematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria
| | - Romana R Gerner
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Barbara Enrich
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Nicole Przysiecki
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Mucosal Immunology, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus Seifert
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus A Keller
- Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria
| | - Georg Oberhuber
- Pathology Department of Innsbruck Medical University Hospital, Innsbruck, Austria
| | - Susanne Sprung
- Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria
| | - Qitao Ran
- Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, Texas, USA
| | - Robert Koch
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Maria Effenberger
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Ivan Tancevski
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria
| | - Heinz Zoller
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Alexander R Moschen
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Mucosal Immunology, Medical University of Innsbruck, Innsbruck, Austria
| | - Günter Weiss
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria.,Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Innsbruck, Austria
| | - Christoph Becker
- Department of Medicine 1, Gastroenterology, Pneumology and Endocrinology, University Medical Center Erlangen, Erlangen, Germany
| | - Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Kiel, Germany
| | - Arthur Kaser
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Timon E Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria.
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Nutrition, IBD and Gut Microbiota: A Review. Nutrients 2020; 12:nu12040944. [PMID: 32235316 PMCID: PMC7230231 DOI: 10.3390/nu12040944] [Citation(s) in RCA: 206] [Impact Index Per Article: 41.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 03/11/2020] [Accepted: 03/25/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing–remitting systemic disease of the gastrointestinal tract, characterized by an inflammatory process that requires lifelong treatment. The underlying causes of IBD are still unclear, as this heterogeneous disorder results from a complex interplay between genetic variability, the host immune system and environmental factors. The current knowledge recognizes diet as a risk factor for the development of IBD and attributes a substantial pathogenic role to the intestinal dysbiosis inducing an aberrant mucosal immune response in genetically predisposed individuals. This review focused on the clinical evidence available that considers the impact of some nutrients on IBD onset and the role of different diets in the management of IBD and their effects on the gut microbiota composition. The effects of the Specific Carbohydrate Diet, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, gluten free diet, anti-inflammatory diet and Mediterranean diet are investigated with regard to their impact on microbiota and on the evolution of the disease. At present, no clear indications toward a specific diet are available but the assessment of dysbiosis prior to the recommendation of a specific diet should become a standard clinical approach in order to achieve a personalized therapy.
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Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, Summerbell CD, Worthington HV, Song F, Hooper L, Cochrane Heart Group. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020; 3:CD003177. [PMID: 32114706 PMCID: PMC7049091 DOI: 10.1002/14651858.cd003177.pub5] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES To assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids. SEARCH METHODS We searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors. SELECTION CRITERIA We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. MAIN RESULTS We included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily). Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high-certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate-certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high-certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate-certainty evidence) or arrhythmia (RR 0.99, 95% CI 0.92 to 1.06; 77,990 participants; 4586 people experienced arrhythmia in 30 RCTs; low-certainty evidence). Increasing LCn3 may slightly reduce coronary heart disease mortality (number needed to treat for an additional beneficial outcome (NNTB) 334, RR 0.90, 95% CI 0.81 to 1.00; 127,378 participants; 3598 coronary heart disease deaths in 24 RCTs, low-certainty evidence) and coronary heart disease events (NNTB 167, RR 0.91, 95% CI 0.85 to 0.97; 134,116 participants; 8791 people experienced coronary heart disease events in 32 RCTs, low-certainty evidence). Overall, effects did not differ by trial duration or LCn3 dose in pre-planned subgrouping or meta-regression. There is little evidence of effects of eating fish. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20; 19,327 participants; 459 deaths in 5 RCTs, moderate-certainty evidence),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25; 18,619 participants; 219 cardiovascular deaths in 4 RCTs; moderate-certainty evidence), coronary heart disease mortality (RR 0.95, 95% CI 0.72 to 1.26; 18,353 participants; 193 coronary heart disease deaths in 3 RCTs; moderate-certainty evidence) and coronary heart disease events (RR 1.00, 95% CI 0.82 to 1.22; 19,061 participants; 397 coronary heart disease events in 4 RCTs; low-certainty evidence). However, increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500, RR 0.95, 95% CI 0.83 to 1.07; but RR 0.91, 95% CI 0.79 to 1.04 in RCTs at low summary risk of bias; 19,327 participants; 884 cardiovascular disease events in 5 RCTs; low-certainty evidence), and probably slightly reduces risk of arrhythmia (NNTB 91, RR 0.73, 95% CI 0.55 to 0.97; 4912 participants; 173 events in 2 RCTs; moderate-certainty evidence). Effects on stroke are unclear. Increasing LCn3 and ALA had little or no effect on serious adverse events, adiposity, lipids and blood pressure, except increasing LCn3 reduced triglycerides by ˜15% in a dose-dependent way (high-certainty evidence). AUTHORS' CONCLUSIONS This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and low-certainty evidence suggests that increasing LCn3 slightly reduces risk of coronary heart disease mortality and events, and reduces serum triglycerides (evidence mainly from supplement trials). Increasing ALA slightly reduces risk of cardiovascular events and arrhythmia.
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Affiliation(s)
- Asmaa S Abdelhamid
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Tracey J Brown
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Julii S Brainard
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Priti Biswas
- University of East AngliaMED/HSCNorwich Research ParkNorwichUKNR4 7TJ
| | - Gabrielle C Thorpe
- University of East AngliaSchool of Health SciencesEarlham RoadNorwichUKNR4 7TJ
| | - Helen J Moore
- Teesside UniversitySchool of Social Sciences, Humanities and LawMiddlesboroughUKTS1 3BA
| | - Katherine HO Deane
- University of East AngliaSchool of Health SciencesEarlham RoadNorwichUKNR4 7TJ
| | - Carolyn D Summerbell
- Durham UniversityDepartment of Sport and Exercise Sciences42 Old ElvetDurhamUKDH13HN
| | - Helen V Worthington
- Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterCochrane Oral HealthCoupland Building 3Oxford RoadManchesterUKM13 9PL
| | - Fujian Song
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Lee Hooper
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
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Melocchi A, Uboldi M, Parietti F, Cerea M, Foppoli A, Palugan L, Gazzaniga A, Maroni A, Zema L. Lego-Inspired Capsular Devices for the Development of Personalized Dietary Supplements: Proof of Concept With Multimodal Release of Caffeine. J Pharm Sci 2020; 109:1990-1999. [PMID: 32112824 DOI: 10.1016/j.xphs.2020.02.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 02/03/2020] [Accepted: 02/18/2020] [Indexed: 12/19/2022]
Abstract
Dietary supplement companies have recently started to focus on the personalization of products and the improvement of the relevant performance. In this respect, a versatile, easy-to-handle capsular delivery platform with customizable content and release kinetics was here proposed and evaluated after filling with caffeine as a model dietary ingredient. In particular, capsular devices comprising 1 to 3 independent inner compartments were attained by Lego-inspired assembly of matching modular units with different wall compositions, manufactured by injection molding and fused deposition modeling 3D printing. Accordingly, one-, two- and three-pulse release profiles of the dietary ingredient were obtained from differently assembled devices following the breakup of the compartments occurring promptly (immediate-release), on pH change (delayed-release) or after tunable lag times (pulsatile-release). The latter release mode would enable the onset of the stimulating effect of caffeine at different times of the day after a single administration when convenient. The performance of each individual compartment only depended on the composition (i.e., promptly soluble, swellable/soluble or enteric soluble polymers) and thickness of its own wall, while it was not affected by the composition and number of joined modular units. Moreover, the delivery platform was extended to include an external gastroresistant shell enclosing previously assembled devices.
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Affiliation(s)
- Alice Melocchi
- Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via G. Colombo 71, Milan 20133, Italy; Multiply Labs, 1760 Cesar Chavez Street Unit D, 94124 San Francisco, California 94124
| | - Marco Uboldi
- Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via G. Colombo 71, Milan 20133, Italy
| | - Federico Parietti
- Multiply Labs, 1760 Cesar Chavez Street Unit D, 94124 San Francisco, California 94124
| | - Matteo Cerea
- Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via G. Colombo 71, Milan 20133, Italy
| | - Anastasia Foppoli
- Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via G. Colombo 71, Milan 20133, Italy
| | - Luca Palugan
- Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via G. Colombo 71, Milan 20133, Italy
| | - Andrea Gazzaniga
- Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via G. Colombo 71, Milan 20133, Italy
| | - Alessandra Maroni
- Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via G. Colombo 71, Milan 20133, Italy.
| | - Lucia Zema
- Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via G. Colombo 71, Milan 20133, Italy
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de Molon RS, Thurlings RM, Walgreen B, Helsen MM, van der Kraan PM, Cirelli JA, Koenders MI. Systemic Resolvin E1 (RvE1) Treatment Does Not Ameliorate the Severity of Collagen-Induced Arthritis (CIA) in Mice: A Randomized, Prospective, and Controlled Proof of Concept Study. Mediators Inflamm 2019; 2019:5689465. [PMID: 31780864 PMCID: PMC6875002 DOI: 10.1155/2019/5689465] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 07/17/2019] [Accepted: 09/03/2019] [Indexed: 12/23/2022] Open
Abstract
Specialized proresolving mediators (SPRM), which arise from n-3 long-chain polyunsaturated fatty acids (n-3FA), promote resolution of inflammation and may help to prevent progression of an acute inflammatory response into chronic inflammation in patients with arthritis. Thus, this study is aimed at determining whether systemic RvE1 treatment reduces arthritis onset and severity in murine collagen-induced arthritis (CIA) and spontaneous cytokine production by human rheumatoid arthritis (RA) synovial explants. 10-week-old DBA1/J male mice were subjected to CIA and treated systemically with 0.1 μg RvE1, 1 μg RvE1, 5 mg/kg anti-TNF (positive control group), PBS (negative control group), or with a combination of 1 μg of RvE1 plus 5 mg/kg anti-TNF using prophylactic or therapeutic strategies. After CIA immunization, mice were treated twice a week by RvE1 or anti-TNF for 10 days. Arthritis development was assessed by visual scoring of paw swelling and histology of ankle joints. Moreover, human RA synovial explants were incubated with 1 nM, 10 nM, or 100 nM of RvE1, and cytokine levels (IL-1β, IL-6, IL-8, IL-10, INF-γ, and TNF-α) were measured using Luminex bead array. CIA triggered significant inflammation in the synovial cavity, proteoglycan loss, and cartilage and bone destruction in the ankle joints of mice. Prophylactic and therapeutic RvE1 regimens did not ameliorate CIA incidence and severity. Anti-TNF treatment significantly abrogated signs of joint inflammation, bone erosion, and proteoglycan depletion, but additional RvE1 treatment did not further reduce the anti-TNF-mediated suppression of the disease. Treatment with different concentrations of RvE1 did not decrease the expression of proinflammatory cytokines in human RA synovial explants in the studied conditions. Collectively, our findings demonstrated that RvE1 treatment was not an effective approach to treat CIA in DBA1/J mice in both prophylactic and therapeutic strategies. Furthermore, no effects were noticed when human synovial explants were incubated with different concentrations of RvE1.
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Affiliation(s)
- Rafael Scaf de Molon
- Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Sao Paulo State University-UNESP, Araraquara, SP, Brazil
- Department of Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands
| | - Rogier M. Thurlings
- Department of Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands
| | - Birgitte Walgreen
- Department of Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands
| | - Monique M. Helsen
- Department of Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands
| | - Peter M. van der Kraan
- Department of Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands
| | - Joni Augusto Cirelli
- Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Sao Paulo State University-UNESP, Araraquara, SP, Brazil
| | - Marije I. Koenders
- Department of Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands
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Na YR, Stakenborg M, Seok SH, Matteoli G. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nat Rev Gastroenterol Hepatol 2019; 16:531-543. [PMID: 31312042 DOI: 10.1038/s41575-019-0172-4] [Citation(s) in RCA: 579] [Impact Index Per Article: 96.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/13/2019] [Indexed: 02/07/2023]
Abstract
Macrophages are the gatekeepers of intestinal immune homeostasis as they discriminate between innocuous antigens and potential pathogens to maintain oral tolerance. However, in individuals with a genetic and environmental predisposition, regulation of intestinal immunity is impaired, leading to chronic relapsing immune activation and pathologies of the gastrointestinal tract, such as IBD. As evidence suggests a causal link between defects in the resolution of intestinal inflammation and altered monocyte-macrophage differentiation in patients with IBD, macrophages have been considered as a novel potential target to develop new treatment approaches. This Review discusses the molecular and cellular mechanisms involved in the differentiation and function of intestinal macrophages in homeostasis and inflammation, and their role in resolving the inflammatory process. Understanding the molecular pathways involved in the specification of intestinal macrophages might lead to a new class of targets that promote remission in patients with IBD.
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Affiliation(s)
- Yi Rang Na
- Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University Medical College, Seoul, South Korea
| | - Michelle Stakenborg
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Seung Hyeok Seok
- Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University Medical College, Seoul, South Korea.
| | - Gianluca Matteoli
- Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
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El-Bayoumy K, Manni A. Customized Prevention Trials Could Resolve the Controversy of the Effects of Omega-3 Fatty Acids on Cancer. Nutr Cancer 2019; 72:183-186. [PMID: 31407927 DOI: 10.1080/01635581.2019.1651348] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Literature data revealed that the benefits of consuming omega-3 fatty acid (n-3FA) supplements such as fish oil with the goal of reducing the incidence of chronic diseases such as cardiovascular disease and cancer remain controversial. The purpose of this commentary is to discuss factors that may account for the inconsistency of results across different studies. Critical review of the published data, including our own preclinical and clinical studies, strongly suggests that customized clinical prevention trials are needed to resolve the above-mentioned controversy. Specifically, in order to develop a personalized cancer prevention strategy, more attention should be given to multiple factors including the dose of the n-3FA, the specific placebo used as a comparator, duration of administration, type of intervention (primary vs secondary prevention trial), specific compound (DHA vs EPA vs their metabolites), the ratio of n-3FA:n-6FA and the target population tested (high vs average risk).
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Affiliation(s)
- Karam El-Bayoumy
- Department of Biochemistry & Molecular Biology, College of Medicine, The Pennsylvania State University, Hershey, PA, USA
| | - Andrea Manni
- Department of Medicine, College of Medicine, The Pennsylvania State University, Hershey, PA, USA
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Affiliation(s)
- João Sabino
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Gastroenterology, University Hospitals of Leuven, Leuven, Belgium
| | - James D Lewis
- Department of Medicine, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jean-Fréderic Colombel
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
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Parolini C. Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System. Mar Drugs 2019; 17:E374. [PMID: 31234533 PMCID: PMC6627897 DOI: 10.3390/md17060374] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 06/13/2019] [Accepted: 06/20/2019] [Indexed: 02/06/2023] Open
Abstract
Studies over several decades have documented the beneficial actions of n-3 polyunsaturated fatty acids (PUFAs), which are plentiful in fish oil, in different disease states. Mechanisms responsible for the efficacy of n-3 PUFAs include: (1) Reduction of triglyceride levels; (2) anti-arrhythmic and antithrombotic effects, and (3) resolution of inflammatory processes. The human microbiota project and subsequent studies using next-generation sequencing technology have highlighted that thousands of different microbial species are present in the human gut, and that there has been a significant variability of taxa in the microbiota composition among people. Several factors (gestational age, mode of delivery, diet, sanitation and antibiotic treatment) influence the bacterial community in the human gastrointestinal tract, and among these diet habits play a crucial role. The disturbances in the gut microbiota composition, i.e., gut dysbiosis, have been associated with diseases ranging from localized gastrointestinal disorders to neurologic, respiratory, metabolic, ocular, and cardiovascular illnesses. Many studies have been published about the effects of probiotics and prebiotics on the gut microbiota/microbioma. On the contrary, PUFAs in the gut microbiota have been less well defined. However, experimental studies suggested that gut microbiota, n-3 PUFAs, and host immune cells work together to ensure the intestinal wall integrity. This review discussed current evidence concerning the links among gut microbiota, n-3 PUFAs intake, and human inflammatory disease.
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Affiliation(s)
- Cinzia Parolini
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20122 Milano, Italy.
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Wooster TJ, Acquistapace S, Mettraux C, Donato L, Dekkers BL. Hierarchically structured phase separated biopolymer hydrogels create tailorable delayed burst release during gastrointestinal digestion. J Colloid Interface Sci 2019; 553:308-319. [PMID: 31212230 DOI: 10.1016/j.jcis.2019.06.033] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 06/09/2019] [Accepted: 06/11/2019] [Indexed: 12/14/2022]
Abstract
The on demand delivery of novel peptide actives, traditional pharmaceuticals, nutrients and/or vitamins is a ever present challenge due to the digestive and metabolic degradation of the active and the delivery vehicle. Biodegradable biopolymer hydrogels have long held promise as candidates for creating tailored release profiles due to the ability to control gel porosity. The present study describes the creation of novel hierarchical biopolymer hydrogels for the controlled release of lipids/lipophilic actives pharmaceutical ingredients (APIs), and mathematically describes the mechanisms that affect the timing of release. The creation of phase separated protein/polysaccharide core (6.6 wt% gelatin, 40 wt% Oil in water emulsion) shell structures (7 g/L xanthan with 70-140 g/L β-lactoglobulin) altered enzyme mass transport processes. This core shell structure enabled the creation of a tailorable burst release of API during gastrointestinal digestion where there is a delay in the onset of release, without affecting the kinetics of release. The timing of the delay could be readily programmed (with release of between 60 and 240 min) by controlling either the thickness or protein concentration (between 70 g/L and 140 g/L β-lactoglobulin) of the outer mixed biopolymer hydrogel shell (7 g/L xanthan with 70-140 g/L β-lactoglobulin). Enzyme diffusion measurements demonstrated that surface erosion was the main degradation mechanism. A kinetic model was created to describe the delayed burst release behaviour of APIs encapsulated within the core, and successfully predicted the influence of shell thickness and shell protein density on the timing of gastro-intestinal release (in vitro). Our work highlights the creation of a novel family of core-shell hydrogel oral dosage forms capable of programmable delivery of lipids/lipophilic APIs. These findings could have considerable implications for the delivery of peptides, poorly soluble drugs, or the programmed delivery of lipids within the gastrointestinal tract.
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Affiliation(s)
- T J Wooster
- Nestec S.A., Nestlé Research Centre, Vers-chez-les-Blanc, CH 1000, Switzerland.
| | - S Acquistapace
- Nestec S.A., Nestlé Research Centre, Vers-chez-les-Blanc, CH 1000, Switzerland
| | - C Mettraux
- Nestec S.A., Nestlé Research Centre, Vers-chez-les-Blanc, CH 1000, Switzerland
| | - L Donato
- Nestec S.A., Nestlé Research Centre, Vers-chez-les-Blanc, CH 1000, Switzerland
| | - B L Dekkers
- Nestec S.A., Nestlé Research Centre, Vers-chez-les-Blanc, CH 1000, Switzerland
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Hébuterne X. Nutrition anti-inflammatoire et MICI : que dire à nos patients ? NUTR CLIN METAB 2019. [DOI: 10.1016/j.nupar.2019.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Kato S, Utsumi D, Matsumoto K. G protein-coupled receptor 40 activation ameliorates dextran sulfate sodium-induced colitis in mice via the upregulation of glucagon-likepeptide-2. J Pharmacol Sci 2019; 140:144-152. [DOI: 10.1016/j.jphs.2019.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 05/07/2019] [Accepted: 05/09/2019] [Indexed: 12/18/2022] Open
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Sharma M, Kaur R, Kaushik K, Kaushal N. Redox modulatory protective effects of ω-3 fatty acids rich fish oil against experimental colitis. Toxicol Mech Methods 2019; 29:244-254. [PMID: 30489199 DOI: 10.1080/15376516.2018.1553220] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is an immune-modulated disorder characterized by chronic and recurring inflammatory episodes. Oxidative stress and COX pathway of prostaglandin (PG) biosynthesis are indispensable to pathogenesis of UC. Any imbalance between PGs can compromise the mucosal homeostasis, leading to mucosal damage and chronic inflammation. However, blocking these PGs using classical Cox inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs) can instead aggravate signs of IBD. Therefore, realizing the need for safer and well tolerable alterative treatment approaches, currently, we evaluated the efficacy of n-3 fatty acids rich fish oil (FO) in the resolution of UC. Using a dextran sodium sulfate (DSS) model of experimental colitis, we have demonstrated that supplementation of FO containing 180 mg EPA and 120 mg DHA for 1 month relieved the signs (diarrhea, bloody stools, weight loss) of colitis-associated inflammation. To understand the biophysical changes associated with FO mediated inflammatory regulation, impedance measurement and Fourier transform infrared spectroscopy (FTIR) were done. These changes were also correlated with oxidative stress through markers such as GST, glutathione peroxidase (GPx), LPO, catalase, protein carbonyl content, GR, etc. in colonic mucosa. The modulation of COX mediated pathways in UC-associated inflammation was observed by protein expressions of various pro-inflammatory cytokines such as TNF-α and enzymes of PG synthesis such as COX-2, PGES, TXAS, and anti-inflammatory PGDS. Refuting the earlier reports that suggested the contradictory effects of FO, in the current study, we evidently demonstrated that the protective effects of FO are mediated through molecular mechanisms involving the redox-regulation of metabolism of key lipid metabolites.
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Affiliation(s)
- Mohita Sharma
- a Department of Biophysics , Panjab University , Chandigarh , India
| | - Ramanpreet Kaur
- a Department of Biophysics , Panjab University , Chandigarh , India
| | - Kuldeep Kaushik
- b Department of Zoology , Dev Samaj College for Women , Ferozepur City , India
| | - Naveen Kaushal
- a Department of Biophysics , Panjab University , Chandigarh , India
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Seyedian SS, Nokhostin F, Malamir MD. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life 2019; 12:113-122. [PMID: 31406511 PMCID: PMC6685307 DOI: 10.25122/jml-2018-0075] [Citation(s) in RCA: 407] [Impact Index Per Article: 67.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 01/27/2019] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) are classified as chronic inflammatory bowel diseases (IBD) which have similar symptoms and lead to digestive disorders and inflammation in the digestive system. The reason why they occur is still a mystery. A number of factors can be attributed to the prevalence of CD and UC, some of which include geographical location, inappropriate diet, genetics, and inappropriate immune response. Both diseases are more often diagnosed in urban areas compared to rural areas and both have their own challenges and side effects, but the patients can still have a good quality of life. Given the fact that the prevalence of this disease is higher at younger ages and that it disrupts half the life of the patient, it will, most likely, become a major health problem in the near future, even in developing countries. By reviewing valid scientific resources and evaluating new methods of addressing this disease, the present study aims to provide researchers and patients with new insights into this field and facilitate access to new treatments.
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Affiliation(s)
- Seyed Saeid Seyedian
- Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
| | - Forogh Nokhostin
- Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mehrdad Dargahi Malamir
- Faculty of Medicine, Medical doctor of Internal Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Catt H, Hughes D, Kirkham JJ, Bodger K. Systematic review: outcomes and adverse events from randomised trials in Crohn's disease. Aliment Pharmacol Ther 2019; 49:978-996. [PMID: 30828852 PMCID: PMC6492112 DOI: 10.1111/apt.15174] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 08/03/2018] [Accepted: 01/16/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The suitability of disease activity indices has been challenged, with growing interest in objective measures of inflammation. AIM To undertake a systematic review of efficacy and safety outcomes in placebo-controlled randomised controlled trials (RCTs) of patients with Crohn's disease. METHODS MEDLINE, EMBASE, CINAHL and Cochrane Library were searched until November 2015, for RCTs of adult Crohn's disease patients treated with medical or surgical therapies. Data on efficacy and safety outcomes, end-point definitions, and measurement instruments were extracted and stratified by publication date (pre-2009 and 2009 onwards). RESULTS One hundred and eighty-one RCTs (110 induction and 71 maintenance) were identified, including 23 850 patients. About 92.3% reported clinical efficacy endpoints. The Crohn's Disease Activity Index (CDAI) dominated, defining clinical response or remission in 63.5% of trials (35 definitions of response or remission). CDAI < 150 was the commonest endpoint, but reporting reduced between periods (46.4%-41.1%), whilst use of CDAI100 increased (16.8%-30.4%). Fistula studies most commonly reported fistula closure (9, 90.0%). Reporting of biomarker, endoscopy and histology endpoints increased overall (33.3%-40.6%, 14.4%-30.4% and 3.2%-12.5%, respectively), but were heterogeneous and rarely reported in fistula trials. Patient-reported outcome measures were reported in 41.4% of trials and safety endpoints in 35.4%. Many of the common adverse events relate to disease exacerbation or treatment failure. CONCLUSIONS Trial endpoints vary across studies, over time and are distinct in fistula studies. Despite growth in reporting of objective measures of inflammation and in patient-reported outcome measures, there is a lack of standardisation. This confirms the need for a core outcome set for comparative effectiveness research in Crohn's disease.
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Affiliation(s)
- Heather Catt
- Department of BiostatisticsUniversity of LiverpoolLiverpoolUK
| | - Dyfrig Hughes
- Centre for Health Economics and Medicines EvaluationBangor UniversityBangorUK
| | | | - Keith Bodger
- Department of BiostatisticsUniversity of LiverpoolLiverpoolUK,Digestive Diseases CentreAintree University Hospital NHS TrustLiverpoolUK
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Wu D, Lewis ED, Pae M, Meydani SN. Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance. Front Immunol 2019; 9:3160. [PMID: 30697214 PMCID: PMC6340979 DOI: 10.3389/fimmu.2018.03160] [Citation(s) in RCA: 264] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 12/21/2018] [Indexed: 12/12/2022] Open
Abstract
It is well-established that the nutritional deficiency or inadequacy can impair immune functions. Growing evidence suggests that for certain nutrients increased intake above currently recommended levels may help optimize immune functions including improving defense function and thus resistance to infection, while maintaining tolerance. This review will examine the data representing the research on prominent intervention agents n-3 polyunsaturated fatty acids (PUFA), micronutrients (zinc, vitamins D and E), and functional foods including probiotics and tea components for their immunological effects, working mechanisms, and clinical relevance. Many of these nutritive and non-nutritive food components are related in their functions to maintain or improve immune function including inhibition of pro-inflammatory mediators, promotion of anti-inflammatory functions, modulation of cell-mediated immunity, alteration of antigen-presenting cell functions, and communication between the innate and adaptive immune systems. Both animal and human studies present promising findings suggesting a clinical benefit of vitamin D, n-3 PUFA, and green tea catechin EGCG in autoimmune and inflammatory disorders, and vitamin D, vitamin E, zinc, and probiotics in reduction of infection. However, many studies report divergent and discrepant results/conclusions due to various factors. Chief among them, and thus call for attention, includes more standardized trial designs, better characterized populations, greater consideration for the intervention doses used, and more meaningful outcome measurements chosen.
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Affiliation(s)
- Dayong Wu
- Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States
| | - Erin D Lewis
- Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States
| | - Munyong Pae
- Department of Food and Nutrition, Chungbuk National University, Cheongju, South Korea
| | - Simin Nikbin Meydani
- Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States
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Vinogradov IV, Zhivulko AR, Vinogradova LM, Korolev SV. Docosahexaenoic acid in the treatment of male infertility. ANDROLOGY AND GENITAL SURGERY 2018. [DOI: 10.17650/2070-9781-2018-19-4-21-27] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Literature review is devoted to the analysis of modern data on the use of docosahexaenoic acid in the treatment of male infertility. A brief description of modern ideas about the possible causes of male infertility (a disturbance of function of the cell membrane and genetic damage of sperm) was conducted. The data on the anti-inflammatory properties of omega-3 polyunsaturated fatty acids are described in detail. The bioavailability of docosahexaenoic acid and the choice of drugs containing it for the treatment of male infertility are discussed. Increasing the content of polyunsaturated fatty acids, in particular docosahexaenoic acid, in the sperm membrane was associated with higher ejaculate quality. Therapy with the use of these substances led to the improvement of standard indicators of semen and a decrease in the proportion of sperm with fragmented DNA.
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Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L, Cochrane Heart Group. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2018; 11:CD003177. [PMID: 30521670 PMCID: PMC6517311 DOI: 10.1002/14651858.cd003177.pub4] [Citation(s) in RCA: 107] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Researchers have suggested that omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. SEARCH METHODS We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. SELECTION CRITERIA We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake. DATA COLLECTION AND ANALYSIS Two review authors independently assessed studies for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. MAIN RESULTS We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5g/d LCn3 to > 5 g/d (16 RCTs gave at least 3g/d LCn3).Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses - LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs) and ALA may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence with greater effects in trials at low summary risk of bias), and probably reduces risk of arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression.There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, except LCn3 reduced triglycerides by ˜15% in a dose-dependant way (high-quality evidence). AUTHORS' CONCLUSIONS This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event and arrhythmia risk.
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Affiliation(s)
- Asmaa S Abdelhamid
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Tracey J Brown
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Julii S Brainard
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Priti Biswas
- University of East AngliaMED/HSCNorwich Research ParkNorwichUKNR4 7TJ
| | - Gabrielle C Thorpe
- University of East AngliaSchool of Health SciencesEarlham RoadNorwichUKNR4 7TJ
| | - Helen J Moore
- Durham UniversityWolfson Research InstituteDurhamUKDH1 3LE
| | - Katherine HO Deane
- University of East AngliaSchool of Health SciencesEarlham RoadNorwichUKNR4 7TJ
| | - Fai K AlAbdulghafoor
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Carolyn D Summerbell
- Durham UniversityDepartment of Sport and Exercise Science42 Old ElvetDurhamUKDH13HN
| | - Helen V Worthington
- Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterCochrane Oral HealthJR Moore BuildingOxford RoadManchesterUKM13 9PL
| | - Fujian Song
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
| | - Lee Hooper
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichNorfolkUKNR4 7TJ
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Ferguson JF, Roberts-Lee K, Borcea C, Smith HM, Midgette Y, Shah R. Omega-3 polyunsaturated fatty acids attenuate inflammatory activation and alter differentiation in human adipocytes. J Nutr Biochem 2018; 64:45-49. [PMID: 30428424 DOI: 10.1016/j.jnutbio.2018.09.027] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 09/20/2018] [Accepted: 09/21/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Omega-3 polyunsaturated fatty acids, specifically the fish-oil-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been proposed as inflammation-resolving agents via their effects on adipose tissue. OBJECTIVE We proposed to determine the effects of EPA and DHA on human adipocyte differentiation and inflammatory activation in vitro. METHODS Primary human subcutaneous adipocytes from lean and obese subjects were treated with 100 μM EPA and/or DHA throughout differentiation (differentiation studies) or for 72 h postdifferentiation (inflammatory studies). THP-1 monocytes were added to adipocyte wells for co-culture experiments. Subcutaneous and visceral adipose explants from obese subjects were treated for 72 h with EPA and DHA. Oil Red O staining was performed on live cells. Cells were collected for mRNA analysis by quantitative polymerase chain reaction, and media were collected for protein quantification by enzyme-linked immunosorbent assay. RESULTS Incubation with EPA and/or DHA attenuated inflammatory response to lipopolysaccharide (LPS) and monocyte co-culture with reduction in post-LPS mRNA expression and protein levels of IL6, CCL2 and CX3CL1. Expression of inflammatory genes was also reduced in the endogenous inflammatory response in obese adipose. Both DHA and EPA reduced lipid droplet formation and lipogenic gene expression without alteration in expression of adipogenic genes or adiponectin secretion. CONCLUSIONS EPA and DHA attenuate inflammatory activation of in vitro human adipocytes and reduce lipogenesis.
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Affiliation(s)
- Jane F Ferguson
- Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kailey Roberts-Lee
- Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Cristina Borcea
- Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Holly M Smith
- Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Yasmeen Midgette
- Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Rachana Shah
- Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
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Laing B, Barnett MPG, Marlow G, Nasef NA, Ferguson LR. An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets. Expert Rev Gastroenterol Hepatol 2018; 12:969-983. [PMID: 30052094 DOI: 10.1080/17474124.2018.1505497] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.
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Affiliation(s)
- Bobbi Laing
- a Discipline of Nutrition and Dietetics, Faculty of Medical Health Sciences , The University of Auckland , Auckland , New Zealand.,b School of Nursing, Faculty of Medical and Health Sciences , The University of Auckland , Auckland , New Zealand
| | - Matthew P G Barnett
- c Food Nutrition & Health Team, Food & Bio-Based Products Group , AgResearch Limited , Palmerston North , New Zealand.,d Liggins Institute , The High-Value Nutrition National Science Challenge , Auckland , New Zealand.,e Riddet Institute , Massey University , Palmerston North , New Zealand
| | - Gareth Marlow
- f Institute of Medical Genetics , Cardiff University , Cardiff , Wales , UK
| | - Noha Ahmed Nasef
- e Riddet Institute , Massey University , Palmerston North , New Zealand.,g College of Health, Massey Institute of Food Science and Technology , Palmerston North , New Zealand
| | - Lynnette R Ferguson
- a Discipline of Nutrition and Dietetics, Faculty of Medical Health Sciences , The University of Auckland , Auckland , New Zealand.,h Auckland Cancer Research Society, Faculty of Medical and Health Sciences, Grafton Campus , The University of Auckland , Auckland , New Zealand
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Bauer E, Thiele I. From metagenomic data to personalized in silico microbiotas: predicting dietary supplements for Crohn's disease. NPJ Syst Biol Appl 2018; 4:27. [PMID: 30083388 PMCID: PMC6068170 DOI: 10.1038/s41540-018-0063-2] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 05/17/2018] [Accepted: 05/30/2018] [Indexed: 12/13/2022] Open
Abstract
Crohn's disease (CD) is associated with an ecological imbalance of the intestinal microbiota, consisting of hundreds of species. The underlying complexity as well as individual differences between patients contributes to the difficulty to define a standardized treatment. Computational modeling can systematically investigate metabolic interactions between gut microbes to unravel mechanistic insights. In this study, we integrated metagenomic data of CD patients and healthy controls with genome-scale metabolic models into personalized in silico microbiotas. We predicted short chain fatty acid (SFCA) levels for patients and controls, which were overall congruent with experimental findings. As an emergent property, low concentrations of SCFA were predicted for CD patients and the SCFA signatures were unique to each patient. Consequently, we suggest personalized dietary treatments that could improve each patient's SCFA levels. The underlying modeling approach could aid clinical practice to find dietary treatment and guide recovery by rationally proposing food aliments.
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Affiliation(s)
- Eugen Bauer
- Luxembourg Centre for Systems Biomedicine, Universite du Luxembourg, Esch-sur-Alzette, Luxembourg, L-4362 Luxembourg
| | - Ines Thiele
- Luxembourg Centre for Systems Biomedicine, Universite du Luxembourg, Esch-sur-Alzette, Luxembourg, L-4362 Luxembourg
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Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2018; 7:CD003177. [PMID: 30019766 PMCID: PMC6513557 DOI: 10.1002/14651858.cd003177.pub3] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Researchers have suggested that omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. SEARCH METHODS We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. SELECTION CRITERIA We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake. DATA COLLECTION AND ANALYSIS Two review authors independently assessed studies for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. MAIN RESULTS We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet.Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses - LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression.There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence). AUTHORS' CONCLUSIONS This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event risk, CHD mortality and arrhythmia.
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Affiliation(s)
- Asmaa S Abdelhamid
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichUKNR4 7TJ
| | - Tracey J Brown
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichUKNR4 7TJ
| | - Julii S Brainard
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichUKNR4 7TJ
| | - Priti Biswas
- University of East AngliaMED/HSCNorwich Research ParkNorwichUKNR4 7TJ
| | - Gabrielle C Thorpe
- University of East AngliaSchool of Health SciencesEarlham RoadNorwichUKNR4 7TJ
| | - Helen J Moore
- Durham UniversityWolfson Research InstituteDurhamUKDH1 3LE
| | - Katherine HO Deane
- University of East AngliaSchool of Health SciencesEarlham RoadNorwichUKNR4 7TJ
| | - Fai K AlAbdulghafoor
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichUKNR4 7TJ
| | - Carolyn D Summerbell
- Durham UniversityDepartment of Sport and Exercise Science42 Old ElvetDurhamUKDH13HN
| | - Helen V Worthington
- Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterCochrane Oral HealthJR Moore BuildingOxford RoadManchesterUKM13 9PL
| | - Fujian Song
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichUKNR4 7TJ
| | - Lee Hooper
- University of East AngliaNorwich Medical SchoolNorwich Research ParkNorwichUKNR4 7TJ
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