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Loyala JV, Down B, Wong E, Tan B. Treatment of Cachexia in Gastric Cancer: Exploring the Use of Anti-Inflammatory Natural Products and Their Derivatives. Nutrients 2024; 16:1246. [PMID: 38674936 PMCID: PMC11053965 DOI: 10.3390/nu16081246] [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: 03/22/2024] [Revised: 04/12/2024] [Accepted: 04/19/2024] [Indexed: 04/28/2024] Open
Abstract
(1) Background: Gastric cancer is a significant cause of cancer-related mortality worldwide. Weight loss and malnutrition associated with cancer are linked with increased mortality rates and reduced quality of life. Cancer cachexia, characterised by the loss of skeletal muscle, is associated with approximately 20% of cancer-related deaths and differs from malnutrition in that it cannot be fully reversed by nutritional support alone. It is now recognised that the primary pathophysiological process underlying cancer cachexia is chronic inflammation leading to increased calorie consumption. Current treatments that focus on nutritional supplementation, psychological counselling, appetite stimulation and reducing inflammation are lacking in efficacy. This review focuses on the evidence supporting the potential roles of natural anti-inflammatory products and their derivatives including fatty acids, probiotics, amino acids, curcumin, fucoidan, epigallocatechin-3-gallate, ginger, resveratrol and Boswellia serrata in the management of gastric cancer cachexia. (2) Results: While natural anti-inflammatory products show promise in a number of in vitro and in vivo studies, there are only a small number of human studies available. Where present, the evidence base is heterogeneous, with varying study methodologies and outcomes. (3) Conclusions: Natural anti-inflammatory products represent a potential adjunctive therapy for gastric cancer cachexia. Further research, particularly well-designed clinical trials, is needed to elucidate their optimal role, dosing and safety profiles in the management of gastric cancer cachexia.
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Affiliation(s)
- Jerocin Vishani Loyala
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK
| | - Billy Down
- High Wycombe Hospital, Buckinghamshire Healthcare NHS Trust, High Wycombe HP11 2TT, UK;
| | - Enoch Wong
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK
| | - Benjamin Tan
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK;
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2
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Sasanfar B, Toorang F, Salehi-Abarghouei A. Effects of n-3 polyunsaturated fatty acid supplementation on appetite: a systematic review and meta-analysis of controlled clinical trials. Syst Rev 2024; 13:44. [PMID: 38281014 PMCID: PMC10821539 DOI: 10.1186/s13643-023-02430-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 12/11/2023] [Indexed: 01/29/2024] Open
Abstract
BACKGROUND The current studies explore the effect of omega-3 polyunsaturated fatty acids (PUFAs) on appetite. OBJECTIVE To examine the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on appetite using a systematic review and meta-analysis of controlled clinical trials (CTs). PATIENTS AND METHODS Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched up to January 2022. A random-effects model was used to compare the overall standardized mean difference in appetite scores between n-3 PUFAs supplemented and control individuals. RESULTS Fifteen eligible CTs with 1504 participants (872 for n-3 PUFA supplementation and 632 for placebo groups) were included in our systematic review. The meta-analysis showed no significant difference in overall appetite score between n-3 PUFAs supplemented and control groups (standardized mean difference [SMD] = 0.458, 95% confidence interval [CI] - 0.327, 1.242, P value = 0.25). However, the n-3 PUFA supplementation significantly increased the desire to eat (SMD = 1.07, 95% CI 0.116, 2.029, P = 0.02) compared to control. CONCLUSION Although we found no effect of omega-3 supplementation on overall appetite score, it modestly increases the desire to eat. Further CTs evaluating the effect of PUFAs on appetite are still needed to confirm these findings.
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Affiliation(s)
- Bahareh Sasanfar
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Faculty of Health, Shahid Sadoughi University of Medical Sciences, P O Box 8915173160, Yazd, Iran
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
- Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Fatemeh Toorang
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
- Departments of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Amin Salehi-Abarghouei
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- Yazd Cardiovascular Research Center, Non-Communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- Department of Nutrition, School of Public Health, Faculty of Health, Shahid Sadoughi University of Medical Sciences, P O Box 8915173160, Yazd, Iran.
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Arcos D, Ng DQ, Ke Y, Toh YL, Chan A. Prediction of gastrointestinal symptoms trajectories using omega-3 and inflammatory biomarkers in early-stage breast cancer patients receiving chemotherapy. Support Care Cancer 2024; 32:76. [PMID: 38170327 PMCID: PMC10764400 DOI: 10.1007/s00520-023-08274-5] [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: 05/31/2023] [Accepted: 12/18/2023] [Indexed: 01/05/2024]
Abstract
PURPOSE Gastrointestinal (GI) symptoms are common among breast cancer patients undergoing chemotherapy, negatively impacting treatment outcomes and quality of life. Evidence points to inflammatory processes as the underlying cause of chemotherapy-associated GI symptoms. Relatedly, omega-3 (n-3) has been linked to anti-inflammatory processes. The primary objective of this study was to examine the associations between baseline n-3, baseline inflammatory markers and GI symptom progression in early-stage breast cancer patients receiving chemotherapy. METHODS In this secondary analysis of a prospective cohort study, we analyzed baseline levels of inflammatory biomarkers (measured using a Luminex bead-immunoassay) and plasma levels of DHA, EPA, and FFA (measured using enzyme-linked immunosorbent assay). GI symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Cancer Patients (EORTC QLQ-C30) symptom scale scores at baseline (T1) and at least 6 weeks after, during chemotherapy (T2). Inferential statistics were used to analyze associations between the variables of interest. RESULTS The analysis included 31 female breast cancer patients (mean age ± SD = 50.5 ± 8.8; 89.6% receiving anthracycline-based chemotherapy). Higher levels of docosahexaenoic acid (DHA) and interleukin-8 (IL-8) predicted increases in appetite loss. Similarly, higher IL-8 predicted worsened nausea and vomiting. CONCLUSION Baseline IL-8 and DHA predicted GI symptom progression in early-stage breast cancer patients undergoing chemotherapy. Future studies are required to evaluate how therapeutic intervention targeting these biomarkers may mitigate gastrointestinal symptoms in cancer patients.
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Affiliation(s)
- Daniela Arcos
- School of Pharmacy & Pharmaceutical Sciences, University of California Irvine, Irvine, USA
| | - Ding Quan Ng
- School of Pharmacy & Pharmaceutical Sciences, University of California Irvine, Irvine, USA
| | - Yu Ke
- Division of Supportive and Palliative Care, National Cancer Centre Singapore, Singapore, Singapore
| | - Yi Long Toh
- Department of Pharmacy, National University of Singapore, Singapore, Singapore
| | - Alexandre Chan
- School of Pharmacy & Pharmaceutical Sciences, University of California Irvine, Irvine, USA.
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Caeiro L, Gandhay D, Anderson LJ, Garcia JM. A Review of Nutraceuticals in Cancer Cachexia. Cancers (Basel) 2023; 15:3884. [PMID: 37568700 PMCID: PMC10417577 DOI: 10.3390/cancers15153884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 07/21/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
Cancer cachexia is largely characterized by muscle wasting and inflammation, leading to weight loss, functional impairment, poor quality of life (QOL), and reduced survival. The main barrier to therapeutic development is a lack of efficacy for improving clinically relevant outcomes, such as physical function or QOL, yet most nutraceutical studies focus on body weight. This review describes clinical and pre-clinical nutraceutical studies outside the context of complex nutritional and/or multimodal interventions, in the setting of cancer cachexia, in view of considerations for future clinical trial design. Clinical studies mostly utilized polyunsaturated fatty acids or amino acids/derivatives, and they primarily focused on body weight and, secondarily, on muscle mass and/or QOL. The few studies that measured physical function almost exclusively utilized handgrip strength with, predominantly, no time and/or group effect. Preclinical studies focused mainly on amino acids/derivatives and polyphenols, assessing body weight, muscle mass, and occasionally physical function. While this review does not provide sufficient evidence of the efficacy of nutraceuticals for cancer cachexia, more preclinical and adequately powered clinical studies are needed, and they should focus on clinically meaningful outcomes, including physical function and QOL.
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Affiliation(s)
- Lucas Caeiro
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA (L.J.A.)
- Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
| | - Devika Gandhay
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA (L.J.A.)
| | - Lindsey J. Anderson
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA (L.J.A.)
- Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
| | - Jose M. Garcia
- Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA (L.J.A.)
- Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
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5
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Jin X, Xu XT, Tian MX, Dai Z. Omega-3 polyunsaterated fatty acids improve quality of life and survival, but not body weight in cancer cachexia: A systematic review and meta-analysis of controlled trials. Nutr Res 2022; 107:165-178. [PMID: 36283229 DOI: 10.1016/j.nutres.2022.09.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 09/17/2022] [Accepted: 09/20/2022] [Indexed: 12/27/2022]
Abstract
Several clinical trials have reported that patients with cancer cachexia can benefit from n-3 polyunsaturated fatty acids (n-3 PUFAs) supplements; however, the results have been conflicting. This systematic review and meta-analysis aimed to evaluate the effect of n-3 PUFAs on cancer cachexia. A search of the PubMed, Embase, and Cochrane Library databases was performed to identify the included randomized controlled trials. Trials including patients with cancer cachexia who were administered a course of n-3 PUFAs were included. A meta-analysis on body weight, lean body weight, proinflammatory factors, quality of life, and median duration of survival was conducted. A total of 12 randomized controlled trials with 1184 patients were included. No effect on body weight (standard mean difference [SMD], 0.10; 95% CI, -0.06 to 0.26; P = .236), lean body weight (SMD, -0.17; 95% CI, -0.36 to 0.03, P = .095), or proinflammatory factors (interleukin-6: SMD, 0.31; 95% CI, -0.14 to 0.75; P = .18; tumor necrosis factor-α: SMD, -0.85; 95% CI, -2.39 to 0.69; P = .28) was observed. The use of n-3 PUFAs was associated with a significant improvement in quality of life (SMD, 0.70; 95% CI, 0.01-1.40; P = .048) and median duration of survival (median survival ratio, 1.10; 95% CI, 1.02-1.19; P = .014). For patients with cancer cachexia, our meta-analysis indicated that n-3 PUFAs improved quality of life and survival, but not body weight.
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Affiliation(s)
- Xin Jin
- Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Xin-Tian Xu
- Department of Pharmacy, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Meng-Xing Tian
- Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhu Dai
- Department of Pharmacy, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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6
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Inflammation as a Therapeutic Target in Cancer Cachexia. Cancers (Basel) 2022; 14:cancers14215262. [PMID: 36358681 PMCID: PMC9657920 DOI: 10.3390/cancers14215262] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/20/2022] [Accepted: 10/20/2022] [Indexed: 12/04/2022] Open
Abstract
Cachexia is a common complication of cancer and is associated with poor quality of life and a decrease in survival. Many patients with cancer cachexia suffer from inflammation associated with elevated cytokines, such as interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF). Single-agent trials to treat cancer cachexia have not led to substantial benefit as the type of cytokine which is elevated has rarely been specified and targeted. Cachexia may also be multifactorial, involving inflammation, anorexia, catabolism, depression, and pain, and targeting the multiple causes will likely be necessary to achieve improvement in weight and appetite. A PUBMED search revealed over 3000 articles on cancer cachexia in the past ten years. We attempted to review any studies related to inflammation and cancer cachexia identified by Google Scholar and PUBMED and further search for articles listed in their references. The National Comprehensive Cancer Network (NCCN) guidelines do not provide any suggestion for managing cancer cachexia except a dietary consult. A more targeted approach to developing therapies for cancer cachexia might lead to more personalized and effective therapy.
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7
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Wei L, Wu Z, Chen YQ. Multi-targeted therapy of cancer by omega-3 fatty acids-an update. Cancer Lett 2022; 526:193-204. [PMID: 34843864 DOI: 10.1016/j.canlet.2021.11.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/12/2021] [Accepted: 11/17/2021] [Indexed: 12/11/2022]
Abstract
Low in dietary ω3 polyunsaturated fatty acid (PUFA) consumption has been associated with increased incidence of cancers. Many basic and clinical studies have been conducted over the last several decades. We previously reviewed multi-targeted therapy of cancer by omega-3 fatty acids in 2008, and since hundreds of new clinical trials are being conducted to validate the effectiveness of ω3 PUFA in cancer therapy. Because of the availability of such large amount of clinical trial data, in this update we summarize clinical data, sort out trials that show promising results, and discuss potential mechanism(s) responsible for the clinical outcomes. It appears that ω3 PUFA mainly affects cancer-associated symptoms, namely cachexia, inflammation, neuropathy, post operative complications and quality of life. Mechanisms responsible for these effects are possible regulation of skeletal muscle protein turnover, inflammatory response and neuron cell survive by ω3 PUFA.
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Affiliation(s)
- Lengyun Wei
- Wuxi School of Medicine, Jiangnan University, Jiangsu Province, 214122, China; Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, China; School of Food Science and Technology, Jiangnan University, Jiangsu Province, 214122, China
| | - Zhipeng Wu
- Wuxi School of Medicine, Jiangnan University, Jiangsu Province, 214122, China
| | - Yong Q Chen
- Wuxi School of Medicine, Jiangnan University, Jiangsu Province, 214122, China; Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, China; School of Food Science and Technology, Jiangnan University, Jiangsu Province, 214122, China.
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Yoshida T, Kojima H, Sako K, Kondo H. Drug delivery to the intestinal lymph by oral formulations. Pharm Dev Technol 2022; 27:175-189. [PMID: 35037843 DOI: 10.1080/10837450.2022.2030353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Oral drug delivery systems (DDS) targeting lymphocytes in intestinal lymphatic vessels, ducts, and nodes are useful for treating diverse diseases. The intestinal lymph harbors numerous lymphocyte subsets, and DDS containing lipids such as triglycerides and fatty acids can deliver drugs to the lymph through the chylomicron pathway. DDS are efficient, thus allowing the administration of reduced drug doses, which mitigate systemic adverse effects. Here we review orally administered lipid formulations comprising oil solutions, suspensions, micro/nanoemulsions, self-micro/nano emulsifying DDS, liposomes, micelles, solid lipid nanoparticles, and nanostructured lipid carriers for targeting drugs to the lymph. We first describe the structures of lymphatic vessels and lymph nodes and the oral absorption of lipids and drugs into the intestinal lymph. We next summarize the effects of the properties and amounts of lipids and drugs delivered into the lymph and lymphocytes, as well as their effects on drug delivery ratios of lymph to blood. Finally, we describe lymphatic DDS containing saquinavir, tacrolimus, and methotrexate, and their potency that reduce drug concentrations in blood, which are associated with systemic adverse effects.
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Affiliation(s)
- Takayuki Yoshida
- Drug Delivery, Pharmaceutical Research and Technology Labs., Astellas Pharma Inc., Yaizu, Japan
| | - Hiroyuki Kojima
- Pharmaceutical Research and Technology Labs., Astellas Pharma Inc., Yaizu, Japan
| | - Kazuhiro Sako
- Corporate Advocacy, Astellas Pharma Inc., 2-5-1, Nihonbashi-honcho, Chuo-ku, Tokyo, 103-0023, Japan
| | - Hiromu Kondo
- School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
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Demirağ H, Kulakaç N, Hintistan S, Çilingir D. Relationship of Cachexia with Self-Care Agency and Quality of Life in Cancer Patients: The Case of Turkey. Asia Pac J Oncol Nurs 2021; 8:547-554. [PMID: 34527784 PMCID: PMC8420915 DOI: 10.4103/apjon.apjon-2135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 05/26/2021] [Indexed: 11/30/2022] Open
Abstract
Objective: This study aims to determine the effects of cachexia, causing major problems in the world and Turkey, on self-care agency and quality of life in cancer patients. Methods: The population of this cross-sectional and relationship-seeking study consisted of cancer patients in Turkey from April 1 to April 20, 2021. Using the snowball sampling method, 174 patients were sampled. “Patient Information Form,” “The European Organization for Research and Treatment of Cancer C30 Cancer Quality of Life Scale,” and “Exercise of Self-Care Agency Scale” were used as data collection tools. Results: In the study, 52 patients (29.9%) were found to have cachexia. Function, general well-being, symptom (except insomnia), and self-care agency, which are subdimensions of the quality-of-life scale, were found to be significantly lower in patients with cachexia than patients without cachexia (P < 0.001). It was determined that there was a significant negative correlation between the cachexia status of the patients and the five basic functions in the functional scale (physical, role, emotional, cognitive, and social function), general well-being, and self-care agency, and there was a significant positive correlation between the cachexia status of the patients and the symptom scale (P < 0.001). According to the results of multiple linear regression analysis, it was found that the factor that significantly affected the cachexia status of the patients was their self-care agency (P < 0.001). Conclusions: It was determined that cachexia caused significantly lower self-care agency and quality of life in cancer patients. Furthermore, quality of life was related to self-care agency.
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Affiliation(s)
- Hatice Demirağ
- Department of Medical Services and Techniques, First and Emergency Aid Program, Gümüşhane University, Gümüşhane, Turkey
| | - Nurşen Kulakaç
- Nursing Department, Faculty of Health Sciences, Gümüşhane University, Gümüşhane, Turkey
| | - Sevilay Hintistan
- Internal Medicine Nursing, Nursing Department, Faculty of Health Sciences, Karadeniz Technical University, Trabzon, Turkey
| | - Dilek Çilingir
- Medicine Surgical Nursing, Nursing Department, Faculty of Health Sciences, Karadeniz Technical University, Trabzon, Turkey
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10
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Ramalho R, Rao M, Zhang C, Agrati C, Ippolito G, Wang FS, Zumla A, Maeurer M. Immunometabolism: new insights and lessons from antigen-directed cellular immune responses. Semin Immunopathol 2020; 42:279-313. [PMID: 32519148 PMCID: PMC7282544 DOI: 10.1007/s00281-020-00798-w] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/02/2020] [Indexed: 02/06/2023]
Abstract
Modulation of immune responses by nutrients is an important area of study in cellular biology and clinical sciences in the context of cancer therapies and anti-pathogen-directed immune responses in health and disease. We review metabolic pathways that influence immune cell function and cellular persistence in chronic infections. We also highlight the role of nutrients in altering the tissue microenvironment with lessons from the tumor microenvironment that shapes the quality and quantity of cellular immune responses. Multiple layers of biological networks, including the nature of nutritional supplements, the genetic background, previous exposures, and gut microbiota status have impact on cellular performance and immune competence against molecularly defined targets. We discuss how immune metabolism determines the differentiation pathway of antigen-specific immune cells and how these insights can be explored to devise better strategies to strengthen anti-pathogen-directed immune responses, while curbing unwanted, non-productive inflammation.
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Affiliation(s)
- Renata Ramalho
- Centro de Investigação Interdisciplinar Egas Moniz (CiiEM, U4585 FCT), Applied Nutrition Studies Group G.E.N.A.-IUEM), Instituto Universitário Egas Moniz, Egas Moniz Higher Education School, Monte de Caparica, Portugal
| | - Martin Rao
- ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal
| | - Chao Zhang
- Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | | | | | - Fu-Sheng Wang
- Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Alimuddin Zumla
- Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK
| | - Markus Maeurer
- ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Lisbon, Portugal.
- I Medizinische Klinik, Johannes Gutenberg University Mainz, Mainz, Germany.
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11
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Randomized Study Design to Test Effects of Vitamin D and Omega-3 Fatty Acid Supplementation as Adjuvant Therapy in Colorectal Cancer Patients. Methods Mol Biol 2020; 2138:337-350. [PMID: 32219761 DOI: 10.1007/978-1-0716-0471-7_24] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
This study examines the effects of vitamin D and omega-3 fatty acid co-supplementation on inflammation and nutritional status in colorectal cancer patients. Patients were randomly assigned into four groups: (1) controls, receiving placebos; (2) omega-3 fatty acid arm, receiving two 330 mg omega-3 fatty acid capsules daily and placebo (for vitamin D3) weekly; (3) vitamin D arm, receiving a 50,000 IU vitamin D3 soft gel weekly and two placebos (for omega-3 fatty acids) daily; and (4) co-supplementation arm, receiving a 50,000 IU vitamin D3 soft gel weekly and two 330 mg omega-3 fatty acids capsules daily for 8 weeks. As outcomes, we measure height; weight; fat-free mass (FFM); serum levels of 25(OH)D, TNF-α, and IL-6; C-CRP; and albumin, before and after the intervention. The presented results show that vitamin D3 plus omega-3 fatty acid co-supplementation in colorectal cancer patients has beneficial impacts on inflammation and nutritional status.
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12
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Schmidt N, Møller G, Bæksgaard L, Østerlind K, Stark KD, Lauritzen L, Andersen JR. Fish oil supplementation in cancer patients. Capsules or nutritional drink supplements? A controlled study of compliance. Clin Nutr ESPEN 2020; 35:63-68. [DOI: 10.1016/j.clnesp.2019.12.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 12/16/2019] [Indexed: 11/24/2022]
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13
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Molfino A, Amabile MI, Giorgi A, Monti M, D’Andrea V, Muscaritoli M. Investigational drugs for the treatment of cancer cachexia: a focus on phase I and phase II clinical trials. Expert Opin Investig Drugs 2019; 28:733-740. [DOI: 10.1080/13543784.2019.1646727] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Alessio Molfino
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Maria Ida Amabile
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Antonella Giorgi
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Massimo Monti
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Vito D’Andrea
- Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
| | - Maurizio Muscaritoli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
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14
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Mitchell T, Clarke L, Goldberg A, Bishop KS. Pancreatic Cancer Cachexia: The Role of Nutritional Interventions. Healthcare (Basel) 2019; 7:healthcare7030089. [PMID: 31323984 PMCID: PMC6787643 DOI: 10.3390/healthcare7030089] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 07/04/2019] [Accepted: 07/05/2019] [Indexed: 12/13/2022] Open
Abstract
Pancreatic cancer is a cancer with one of the highest mortality rates and many pancreatic cancer patients present with cachexia at diagnosis. The definition of cancer cachexia is not consistently applied in the clinic or across studies. In general, it is “defined as a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass with or without loss of fat mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.” Many regard cancer cachexia as being resistant to dietary interventions. Cachexia is associated with a negative impact on survival and quality of life. In this article, we outline some of the mechanisms of pancreatic cancer cachexia and discuss nutritional interventions to support the management of pancreatic cancer cachexia. Cachexia is driven by a combination of reduced appetite leading to reduced calorie intake, increased metabolism, and systemic inflammation driven by a combination of host cytokines and tumour derived factors. The ketogenic diet showed promising results, but these are yet to be confirmed in human clinical trials over the long-term. L-carnitine supplementation showed improved quality of life and an increase in lean body mass. As a first step towards preventing and managing pancreatic cancer cachexia, nutritional support should be provided through counselling and the provision of oral nutritional supplements to prevent and minimise loss of lean body mass.
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Affiliation(s)
- Toni Mitchell
- School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand
| | - Lewis Clarke
- School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand
| | - Alexandra Goldberg
- School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand
| | - Karen S Bishop
- Department of Nutrition, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
- Auckland Cancer Society Research Centre, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
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15
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Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Randomized Study of the Effect of Vitamin D and Omega-3 Fatty Acids Cosupplementation as Adjuvant Chemotherapy on Inflammation and Nutritional Status in Colorectal Cancer Patients. J Diet Suppl 2019; 17:384-400. [DOI: 10.1080/19390211.2019.1600096] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Fatemeh Haidari
- Department of Nutrition, Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Behnaz Abiri
- Department of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Kambiz Ahmadi-Angali
- Faculty of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammadreza Vafa
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
- Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
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16
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Peppone LJ, Inglis JE, Mustian KM, Heckler CE, Padula GDA, Mohile SG, Kamen CS, Culakova E, Lin PJ, Kerns SL, Cole S, Janelsins MC. Multicenter Randomized Controlled Trial of Omega-3 Fatty Acids Versus Omega-6 Fatty Acids for the Control of Cancer-Related Fatigue Among Breast Cancer Survivors. JNCI Cancer Spectr 2019; 3:pkz005. [PMID: 31119206 PMCID: PMC6512349 DOI: 10.1093/jncics/pkz005] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 11/27/2018] [Accepted: 02/11/2019] [Indexed: 01/06/2023] Open
Abstract
Background Cancer-related fatigue (CRF) is a common side effect of adjuvant therapy and becomes a chronic problem for approximately one-third of survivors. Omega-3 polyunsaturated fatty acids (O3-PUFA) demonstrated preliminary antifatigue effects in previous research, but have not been investigated in fatigued cancer survivors. Methods Breast cancer survivors 4–36 months posttreatment with a CRF score of 4 or more of 10 using the symptom inventory (SI) were randomly assigned to O3-PUFA (fish oil, 6 g/d), omega-6 PUFA (O6-PUFA; soybean oil, 6 g/d), or a low-dose combination of O3-/O6-PUFA (3 g/d O3-PUFA and O6-PUFA) for 6 weeks. CRF was assessed by the SI (screening question), the Brief Fatigue Inventory, and the Multidimensional Fatigue Symptom Index. Protein and mRNA levels of inflammatory and antioxidant biomarkers, along with fatty acid and lipid levels, were assessed at baseline and week 6. Statistical tests were two-sided. Results A total of 108 breast cancer survivors consented; 97 subjects were randomly assigned and 81 completed the trial. The SI CRF score decreased by 2.51 points at week 6 with O6-PUFA and by 0.93 points with O3-PUFA, with statistically significant between-group difference (effect size = −0.86, P < .01). Similar changes were observed for the Brief Fatigue Inventory and Multidimensional Fatigue Symptom Index but were not statistically significant. Stratified analyses showed the largest benefit was observed in those with severe baseline CRF (≥7). Compared with O3-PUFA, O6-PUFA supplementation statistically significantly decreased proinflammatory markers in the TNF-α signaling pathway. Conclusion Contrary to our original hypothesis, O6-PUFA statistically significantly reduced CRF compared with O3-PUFA. Further research is needed to confirm these findings and to elucidate mechanisms of action.
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Affiliation(s)
- Luke J Peppone
- Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY
| | - Julia E Inglis
- Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY
| | - Karen M Mustian
- Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY
| | - Charles E Heckler
- Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY
| | - Gilbert D A Padula
- Cancer Research Consortium of West Michigan, Grand Rapids, MI, URMC, Rochester, NY
| | | | - Charles S Kamen
- Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY
| | - Eva Culakova
- Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY
| | - Po-Ju Lin
- Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY
| | - Sarah L Kerns
- Department of Radiation Oncology, URMC, Rochester, NY
| | - Sharon Cole
- Dayton Clinical Oncology Program, Dayton, OH
| | - Michelle C Janelsins
- Department of Surgery, University of Rochester Medical Center (URMC), Rochester, NY
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17
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Gorjao R, Dos Santos CMM, Serdan TDA, Diniz VLS, Alba-Loureiro TC, Cury-Boaventura MF, Hatanaka E, Levada-Pires AC, Sato FT, Pithon-Curi TC, Fernandes LC, Curi R, Hirabara SM. New insights on the regulation of cancer cachexia by N-3 polyunsaturated fatty acids. Pharmacol Ther 2018; 196:117-134. [PMID: 30521881 DOI: 10.1016/j.pharmthera.2018.12.001] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cancer cachexia is a multifactorial syndrome that develops during malignant tumor growth. Changes in plasma levels of several hormones and inflammatory factors result in an intense catabolic state, decreased activity of anabolic pathways, anorexia, and marked weight loss, leading to cachexia development and/or accentuation. Inflammatory mediators appear to be related to the control of a highly regulated process of muscle protein degradation that accelerates the process of cachexia. Several mediators have been postulated to participate in this process, including TNF-α, myostatin, and activated protein degradation pathways. Some interventional therapies have been proposed, including nutritional (dietary, omega-3 fatty acid supplementation), hormonal (insulin), pharmacological (clenbuterol), and nonpharmacological (physical exercise) therapies. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid, are recognized for their anti-inflammatory properties and have been used in therapeutic approaches to treat or attenuate cancer cachexia. In this review, we discuss recent findings on cellular and molecular mechanisms involved in inflammation in the cancer cachexia syndrome and the effectiveness of n-3 PUFAs to attenuate or prevent cancer cachexia.
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Affiliation(s)
- Renata Gorjao
- Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, Sao Paulo, Brazil
| | | | | | | | | | | | - Elaine Hatanaka
- Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, Sao Paulo, Brazil
| | | | - Fábio Takeo Sato
- Institute of Biology, State University of Campinas, Campinas, Brazil; School of Biomedical Sciences, Monash University, Melbourne, Australia
| | | | | | - Rui Curi
- Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, Sao Paulo, Brazil; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Sandro Massao Hirabara
- Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, Sao Paulo, Brazil; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
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18
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Moloudizargari M, Mortaz E, Asghari MH, Adcock IM, Redegeld FA, Garssen J. Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review. Oncotarget 2018; 9:11858-11875. [PMID: 29545942 PMCID: PMC5837752 DOI: 10.18632/oncotarget.24405] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 01/21/2018] [Indexed: 12/18/2022] Open
Abstract
Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens.
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Affiliation(s)
- Milad Moloudizargari
- Department of Immunology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Esmaeil Mortaz
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Mohammad Hossein Asghari
- Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Ian M Adcock
- Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK
| | - Frank A Redegeld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.,Nutricia Research Centre for Specialized Nutrition, Utrecht, Netherlands
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19
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Abstract
PURPOSE OF REVIEW Cachexia is a negative prognostic factor in cancer patients. The pathogenesis is related to a variable combination of reduced food intake and metabolic changes. However, whether nutritional support may contribute to effectively prevent and treat cachexia remains a debated issue. RECENT FINDINGS Consistent evidence demonstrates that anabolic windows of opportunity occur during the clinical trajectory of cancer patients. Also, the use of specific nutrients, namely omega-3 fatty acids, may enhance the efficacy of nutritional support when tumor-driven inflammatory response is high. Of greater interest, it is now becoming clearer that the use of nutritional support at key time points in the clinical journey of cancer patients (i.e., perioperative period) may extend its clinical benefits beyond those on nutritional status. SUMMARY Nutritional support plays a role in managing cancer cachexia, when it is timely delivered, when it provides adequate amounts of calories and proteins, and when it is part of a concurrent palliative care approach. Specific nutrients, that is, omega-3 fatty acids, may help in those cancer patients with high-inflammatory response, and may also contribute to positively influence long-term clinical outcomes.
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20
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Garcia JM, Shamliyan TA. Omega-3 Fatty Acids in Patients with Anorexia-Cachexia Syndrome Associated with Malignancy and Its Treatments. Am J Med 2017; 130:1151-1155. [PMID: 29016347 DOI: 10.1016/j.amjmed.2017.03.066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 03/16/2017] [Indexed: 11/18/2022]
Affiliation(s)
- Jose M Garcia
- Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Wash
| | - Tatyana A Shamliyan
- Quality Assurance, Evidence-Based Medicine Center Elsevier, Philadelphia, Pa.
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21
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Comparable reductions in hyperpnoea-induced bronchoconstriction and markers of airway inflammation after supplementation with 6·2 and 3·1 g/d of long-chain n-3 PUFA in adults with asthma. Br J Nutr 2017; 117:1379-1389. [PMID: 28606216 DOI: 10.1017/s0007114517001246] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Although high dose n-3 PUFA supplementation reduces exercise- and hyperpnoea-induced bronchoconstriction (EIB/HIB), there are concurrent issues with cost, compliance and gastrointestinal discomfort. It is thus pertinent to establish the efficacy of lower n-3 PUFA doses. Eight male adults with asthma and HIB and eight controls without asthma were randomly supplemented with two n-3 PUFA doses (6·2 g/d (3·7 g EPA and 2·5 g DHA) and 3·1 g/d (1·8 g EPA and 1·3 g DHA)) and a placebo, each for 21 d followed by 14 d washout. A eucapnic voluntary hyperpnoea (EVH) challenge was performed before and after treatments. Outcome measures remained unchanged in the control group. In the HIB group, the peak fall in forced expiratory volume in 1 s (FEV1) after EVH at day 0 (-1005 (sd 520) ml, -30 (sd 18) %) was unchanged after placebo. The peak fall in FEV1 was similarly reduced from day 0 to day 21 of 6·2 g/d n-3 PUFA (-1000 (sd 460) ml, -29 (sd 17) % v. -690 (sd 460) ml, -20 (sd 15) %) and 3·1 g/d n-3 PUFA (-970 (sd 480) ml, -28 (sd 18) % v. -700 (sd 420) ml, -21 (sd 15) %) (P<0·001). Baseline fraction of exhaled nitric oxide was reduced by 24 % (P=0·020) and 31 % (P=0·018) after 6·2 and 3·1 g/d n-3 PUFA, respectively. Peak increases in 9α, 11β PGF2 after EVH were reduced by 65 % (P=0·009) and 56 % (P=0·041) after 6·2 and 3·1 g/d n-3 PUFA, respectively. In conclusion, 3·1 g/d n-3 PUFA supplementation attenuated HIB and markers of airway inflammation to a similar extent as a higher dose. Lower doses of n-3 PUFA thus represent a potentially beneficial adjunct treatment for adults with asthma and EIB.
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22
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Werner K, Küllenberg de Gaudry D, Taylor LA, Keck T, Unger C, Hopt UT, Massing U. Dietary supplementation with n-3-fatty acids in patients with pancreatic cancer and cachexia: marine phospholipids versus fish oil - a randomized controlled double-blind trial. Lipids Health Dis 2017; 16:104. [PMID: 28578704 PMCID: PMC5455128 DOI: 10.1186/s12944-017-0495-5] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 05/23/2017] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Like many other cancer patients, most pancreatic carcinoma patients suffer from severe weight loss. As shown in numerous studies with fish oil (FO) supplementation, a minimum daily intake of 1.5 g n-3-fatty acids (n-3-FA) contributes to weight stabilization and improvement of quality of life (QoL) of cancer patients. Given n-3-FA not as triglycerides (FO), but mainly bound to marine phospholipids (MPL), weight stabilization and improvement of QoL has already been seen at much lower doses of n-3-FA (0,3 g), and MPL were much better tolerated. The objective of this double-blind randomized controlled trial was to compare low dose MPL and FO formulations, which had the same n-3-FA amount and composition, on weight and appetite stabilization, global health enhancement (QoL), and plasma FA-profiles in patients suffering from pancreatic cancer. METHODS Sixty pancreatic cancer patients were included into the study and randomized to take either FO- or MPL supplementation. Patients were treated with 0.3 g of n-3-fatty acids per day over six weeks. Since the n-3-FA content of FO is usually higher than that of MPL, FO was diluted with 40% of medium chain triglycerides (MCT) to achieve the same capsule size in both intervention groups and therefore assure blinding. Routine blood parameters, lipid profiles, body weight, and appetite were measured before and after intervention. Patient compliance was assessed through a patient diary. Quality of life and nutritional habits were assessed with validated questionnaires (EORTC-QLQ-C30, PAN26). Thirty one patients finalized the study protocol and were analyzed (per-protocol-analysis). RESULTS Intervention with low dose n-3-FAs, either as FO or MPL supplementation, resulted in similar and promising weight and appetite stabilization in pancreatic cancer patients. MPL capsules were slightly better tolerated and showed fewer side effects, when compared to FO supplementation. CONCLUSION The similar effects between both interventions were unexpected but reliable, since the MPL and FO formulations caused identical increases of n-3-FAs in plasma lipids of included patients after supplementation. The effects of FO with very low n-3-FA content might be explained by the addition of MCT. The results of this study suggest the need for further investigations of marine phospholipids for the improvement of QoL of cancer patients, optionally in combination with MCT.
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Affiliation(s)
- Kristin Werner
- Institute of Surgical Pathology, Medical Center-University of Freiburg, Freiburg, Germany. .,Institute of Pharmaceutical Science, University of Freiburg, Freiburg, Germany. .,Tumor Biology Center Freiburg, Freiburg, Germany.
| | - Daniela Küllenberg de Gaudry
- Cochrane Germany, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Tumor Biology Center Freiburg, Freiburg, Germany.,Cochrane Deutschland, Universitätsklinikum Freiburg, Breisacher Str. 153, D - 79110, Freiburg, Germany
| | - Lenka A Taylor
- Pharmacy, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.,Tumor Biology Center Freiburg, Freiburg, Germany
| | - Tobias Keck
- Clinic for Surgery, Medical Center University of Lübeck, Lübeck, Germany
| | - Clemens Unger
- Cancer Center Freiburg, Freiburg, Germany.,Tumor Biology Center Freiburg, Freiburg, Germany
| | - Ulrich T Hopt
- Department of Surgery, Medical Center-University of Freiburg, Freiburg, Germany
| | - Ulrich Massing
- Institute of Pharmaceutical Science, University of Freiburg, Freiburg, Germany.,Tumor Biology Center Freiburg, Freiburg, Germany
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23
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Thompson KL, Elliott L, Fuchs-Tarlovsky V, Levin RM, Voss AC, Piemonte T. Oncology Evidence-Based Nutrition Practice Guideline for Adults. J Acad Nutr Diet 2017; 117:297-310.e47. [DOI: 10.1016/j.jand.2016.05.010] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Indexed: 01/04/2023]
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24
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Abstract
Cachexia represents progressive wasting of muscle and adipose tissue and is associated with increased morbidity and mortality. Although anorexia usually accompanies cachexia, cachexia rarely responds to increased food intake alone. Our knowledge of the underlying mechanisms responsible for cachexia remains incomplete. However, most states of cachexia are associated with underlying inflammatory processes and/or cancer. These processes activate protein degradation and lipolytic pathways, resulting in tissue loss. In this article, we briefly review the pathophysiology of cachexia and discuss the role of specific nutrient supplements for the treatment of cachexia. The branched chain amino acid leucine, the leucine metabolite beta-hydroxy-beta-methylbutyrate, arginine, glutamine, omega-3 long chain fatty acids, conjugated linoleic acid, and polyphenols have demonstrated some efficacy in animal and/or human studies. Optimal treatment for cachexia is likely aimed at maximizing muscle and adipose synthesis while minimizing degradation.
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Affiliation(s)
- Rafat Siddiqui
- Methodist Research Institute, 1812 N Capitol Ave, Wile Hall, Room 120, Indianapolis, IN 46202, USA
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25
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Arshad A, Isherwood J, Dennison A. Could omega-3 fatty acids improve quality of life in cancer patients? Future Oncol 2015; 11:3225-8. [PMID: 26562498 DOI: 10.2217/fon.15.255] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Ali Arshad
- The Department of Hepatobiliary & Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester, UK
| | - John Isherwood
- The Department of Hepatobiliary & Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester, UK
| | - Ashley Dennison
- The Department of Hepatobiliary & Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester, UK
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26
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Lewis C, Xun P, Fly AD, Luo J, He K. Fish Oil Supplementation and Quality of Life in Stage II Colorectal Cancer Patients: A 24-Month Follow-Up Study. Nutr Cancer 2015; 67:1239-46. [PMID: 26380892 DOI: 10.1080/01635581.2015.1078900] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Research suggests that cancer survivors have an interest in lifestyle changes following a diagnosis. However, few studies have prospectively investigated whether these changes result in positive outcomes. The objective of this study was to examine the associations between fish oil supplementation and quality of life (QoL), cancer recurrence, and all-cause mortality in Stage 2 colorectal cancer (CRC) patients following diagnosis. Four hundred fifty-three patients were enrolled from the North Carolina Cancer Registry from 2009 to 2011. Data on demography, treatment, and health behaviors were collected at diagnosis, 12-, and 24 mo postdiagnosis. Generalized estimating equations were performed to examine fish oil supplementation in relation to QoL, recurrence, and all-cause mortality. An increase in fish oil supplementation over 24 mo postdiagnosis was associated with an increase in the physical component score of the 12-item Medical Outcomes Short Form (β = 2.43, 95% CI: 0.10-4.76). Supplementation showed no association with the Functional Assessment of Cancer-Colorectal, cancer recurrence or mortality across the 24-mo follow-up. This study suggests that fish oil supplementation may improve symptom-related QoL (i.e., physical functioning) in Stage 2 CRC patients following diagnosis. Future research should address the dose-dependent effects of this relationship.
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Affiliation(s)
- Cari Lewis
- a Department of Epidemiology and Biostatistics , School of Public Health, Indiana University , Bloomington , Indiana , USA
| | - Pengcheng Xun
- a Department of Epidemiology and Biostatistics , School of Public Health, Indiana University , Bloomington , Indiana , USA
| | - Alyce D Fly
- b Department of Applied Health Science (Alyce D. Fly) , School of Public Health, Indiana University , Bloomington , Indiana , USA
| | - Juhua Luo
- a Department of Epidemiology and Biostatistics , School of Public Health, Indiana University , Bloomington , Indiana , USA
| | - Ka He
- a Department of Epidemiology and Biostatistics , School of Public Health, Indiana University , Bloomington , Indiana , USA
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27
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Straka S, Lester JL, Cole RM, Andridge RR, Puchala S, Rose AM, Clinton SK, Belury MA, Yee LD. Incorporation of eicosapentaenioic and docosahexaenoic acids into breast adipose tissue of women at high risk of breast cancer: a randomized clinical trial of dietary fish and n-3 fatty acid capsules. Mol Nutr Food Res 2015; 59:1780-90. [PMID: 26081224 DOI: 10.1002/mnfr.201500161] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Revised: 06/01/2015] [Accepted: 06/07/2015] [Indexed: 01/04/2023]
Abstract
SCOPE The fatty acid profile of dietary lipids is reflected in mammary adipose tissue and may influence mammary gland biology and cancer risk. To determine the effects of fish consumption on breast adipose tissue fatty acids, we conducted a study of fish versus n-3 PUFA supplements in women at increased risk of breast cancer. METHODS AND RESULTS High risk women were randomized to comparable doses of marine n-3 PUFAs as canned salmon + albacore or capsules for 3 months. Pre- and posttreatment fatty acid profiles were obtained by GC. Dietary fish (n = 12) and n-3 PUFA capsules (n = 13) yielded increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma (p < 0.0001), erythrocyte membranes (p < 0.0001), and breast fat (p < 0.01) at 3 months. Women taking capsules had higher plasma and erythrocyte membrane EPA changes (∼four versus twofold, p = 0.002), without significant differences in DHA. Increases in breast adipose EPA, DHA were similar for both groups. Higher BMI correlated with smaller changes in plasma, erythrocyte membrane EPA, and breast adipose EPA, DHA. Adherence was excellent at 93.9% overall and higher in the fish arm (p = 0.01). CONCLUSION Fish provides an excellent source of n-3 PUFAs that increases breast adipose EPA, DHA similar to supplements and represents a well-tolerated intervention for future studies of the impact of n-3 PUFAs and dietary patterns on breast cancer.
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Affiliation(s)
- Shana Straka
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio, USA
| | - Joanne L Lester
- College of Nursing, The Ohio State University, Columbus, Ohio, USA
| | - Rachel M Cole
- Human Sciences, The Ohio State University, Columbus, Ohio, USA
| | - Rebecca R Andridge
- Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio, USA
| | - Sarah Puchala
- Human Sciences, The Ohio State University, Columbus, Ohio, USA
| | - Angela M Rose
- Human Sciences, The Ohio State University, Columbus, Ohio, USA
| | - Steven K Clinton
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.,Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
| | - Martha A Belury
- Human Sciences, The Ohio State University, Columbus, Ohio, USA.,Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
| | - Lisa D Yee
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio, USA.,Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
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28
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Abstract
Cancer patients experience multiple symptoms throughout their illness trajectory. Symptoms consistently occurring together, known as symptom clusters, share common pathophysiologic mechanisms. Understanding and targeting such symptom clusters may allow for more effective and efficient use of treatments for a variety of symptoms. Fatigue-anorexia-cachexia is one of the most prevalent symptom clusters and significantly impairs quality of life. In this review, we explore the fatigue-anorexia-cachexia symptom cluster and focus on current and emerging therapies with an emphasis on pharmacologic management.
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29
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Aoyagi T, Terracina KP, Raza A, Matsubara H, Takabe K. Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol 2015; 7:17-29. [PMID: 25897346 PMCID: PMC4398892 DOI: 10.4251/wjgo.v7.i4.17] [Citation(s) in RCA: 297] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 01/17/2015] [Accepted: 03/30/2015] [Indexed: 02/05/2023] Open
Abstract
It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.
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30
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Pastore CA, Orlandi SP, Gonzalez MC. Introduction of an Omega-3 Enriched Oral Supplementation for Cancer Patients Close to the First Chemotherapy: May It Be a Factor for Poor Compliance? Nutr Cancer 2014; 66:1285-92. [DOI: 10.1080/01635581.2014.956253] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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A systematic review of health-related quality of life instruments in patients with cancer cachexia. Support Care Cancer 2013; 21:2625-36. [PMID: 23797577 DOI: 10.1007/s00520-013-1881-9] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Accepted: 06/06/2013] [Indexed: 01/06/2023]
Abstract
PURPOSE Assessing the health-related quality of life (HRQOL) of cancer patients with cachexia is particularly important because treatments for cachexia are currently aimed at palliation and treatment efficacy must be measured in ways other than survival. The aim of this systematic review was to evaluate HRQOL assessment in cancer patients with cachexia. METHODS Using guidance from the Centre for Reviews and Dissemination, relevant databases were searched from January 1980 to January 2012 with terms relating to cancer, cachexia and HRQOL for papers including adult cancer patients with cachexia or documented weight loss at baseline. RESULTS We found one cachexia-specific instrument, the Functional Assessment of Anorexia/Cachexia Therapy, but the tool has not been fully validated, does not cover all the relevant domains and the consensus-based standards for the selection of health status measurement instruments checklist highlighted a number of weaknesses in the methodological quality of the validation study. Sixty-seven studies assessed HRQOL in cachectic or weight-losing cancer patients. Most used generic cancer HRQOL instruments, limiting the amount of useful information they provide. A modified version of the Efficace minimum data checklist demonstrated that the quality of reporting on HRQOL tool use was inadequate in many of the studies. A negative relationship between HRQOL and weight loss was found in 23 of the 27 studies which directly examined this. CONCLUSION There is a pressing need for a well-designed HRQOL tool for use with this patient group in both clinical trials and clinical practice.
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Wang H, Chan YL, Li TL, Bauer BA, Hsia S, Wang CH, Huang JS, Wang HM, Yeh KY, Huang TH, Wu GJ, Wu CJ. Reduction of splenic immunosuppressive cells and enhancement of anti-tumor immunity by synergy of fish oil and selenium yeast. PLoS One 2013; 8:e52912. [PMID: 23349693 PMCID: PMC3551929 DOI: 10.1371/journal.pone.0052912] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2012] [Accepted: 11/21/2012] [Indexed: 01/21/2023] Open
Abstract
Growing evidence has shown that regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) abnormally increase in cancer cachectic patients. Suppressions of Tregs and MDSCs may enhance anti-tumor immunity for cancer patients. Fish oil and selenium have been known to have many biological activities such as anti-inflammation and anti-oxidation. Whether fish oil and/or selenium have an additional effect on population of immunosuppressive cells in tumor-bearing hosts remained elusive and controversial. To gain insights into their roles on anti-tumor immunity, we studied the fish oil- and/or selenium-mediated tumor suppression and immunity on lung carcinoma, whereof cachexia develops. Advancement of cachexia in a murine lung cancer model manifested with such indicative symptoms as weight loss, chronic inflammation and disturbed immune functionality. The elevation of Tregs and MDSCs in spleens of tumor-bearing mice was positively correlated with tumor burdens. Consumption of either fish oil or selenium had little or no effect on the levels of Tregs and MDSCs. However, consumption of both fish oil and selenium together presented a synergistic effect-The population of Tregs and MDSCs decreased as opposed to increase of anti-tumor immunity when both fish oil and selenium were supplemented simultaneously, whereby losses of body weight and muscle/fat mass were alleviated significantly.
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Affiliation(s)
- Hang Wang
- Department of Food Science and Center of Excellence for Marine Bioenvironment and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan
| | - Yi-Lin Chan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Tsung-Lin Li
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Brent A. Bauer
- Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Simon Hsia
- Institute of Biomedical Nutrition, Hung Kuang University, Taichung, Taiwan
| | - Cheng-Hsu Wang
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, and College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Jen-Seng Huang
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, and College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Hung-Ming Wang
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kweishan, and College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Kun-Yun Yeh
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, and College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Tse-Hung Huang
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Kweishan, and Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Gwo-Jang Wu
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Chang-Jer Wu
- Department of Food Science and Center of Excellence for Marine Bioenvironment and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan
- * E-mail:
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Hajjaji N, Couet C, Besson P, Bougnoux P. DHA Effect on Chemotherapy-Induced Body Weight Loss: An Exploratory Study in a Rodent Model of Mammary Tumors. Nutr Cancer 2012; 64:1000-7. [DOI: 10.1080/01635581.2012.714832] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Ries A, Trottenberg P, Elsner F, Stiel S, Haugen D, Kaasa S, Radbruch L. A systematic review on the role of fish oil for the treatment of cachexia in advanced cancer: an EPCRC cachexia guidelines project. Palliat Med 2012; 26:294-304. [PMID: 21865295 DOI: 10.1177/0269216311418709] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The European Palliative Care Research Collaboration is developing clinical guidelines on cachexia in patients with advanced cancer. A systematic review on the use of fish oil/omega-3-fatty acids (n-3-FA)/eicosapentaenoic acids (EPA) in advanced cancer patients suffering from cancer cachexia was performed as part of the guideline development. METHODS The systematic literature search in Medline on the use of fish oil/n-3-FA/EPA identified 244 papers, with 38 publications included in the final evaluation. Some smaller trials, often unrandomized and without a control group, reported a good effect of n-3-FA in patients with advanced cancer and cachexia. However, the results of the larger randomized controlled trials could not support the positive results, as they mostly did not find a significant effect. RESULTS Adverse effects such as abdominal discomfort, fish belching, fish aftertaste, nausea and diarrhoea were reported with a low incidence. No serious adverse effects were documented, but adverse effects often had an impact on quality of life. This often limited dose escalations or even led to discontinuation of n-3-FA. CONCLUSION There is not enough evidence to support a net benefit of n-3-FA in cachexia in advanced cancer. On the other hand, adverse effects were infrequent, with no severe adverse effects. The results from the review led to a weak negative GRADE recommendation.
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Affiliation(s)
- Anke Ries
- Department of Palliative Medicine, University Hospital, RWTH Aachen, Germany
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Abstract
OBJECTIVES To review clinical trials in natural products and mind-body therapies for oncology symptom management, to discuss issues related to developing clinical trials in this area, and outline examples of rigorous and innovative study design. DATA SOURCES Peer reviewed literature. CONCLUSION Most of the evidence for the integrative therapies reviewed is derived from phase II trials, and is considered preliminary. More research is needed in these therapies to clearly articulate their role in the management of oncology symptoms. Innovative strategies and methodologies for studying integrative therapies have been demonstrated. IMPLICATIONS FOR NURSING PRACTICE It is necessary to critically evaluate the literature to be able to educate patients about integrative therapies. Investigators should expand on well-designed studies that demonstrate clinically important effects. Dissemination trials may be a good strategy, once data exists, to move integrative therapies into the care of patients.
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Rockett BD, Harris M, Shaikh SR. High dose of an n-3 polyunsaturated fatty acid diet lowers activity of C57BL/6 mice. Prostaglandins Leukot Essent Fatty Acids 2012; 86:137-40. [PMID: 22178389 PMCID: PMC3440001 DOI: 10.1016/j.plefa.2011.12.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2011] [Revised: 11/30/2011] [Accepted: 12/01/2011] [Indexed: 01/07/2023]
Abstract
n-3 Polyunsaturated fatty acids (PUFA) are increasingly consumed as food additives and supplements; however, the side effects of these fatty acids, especially at high doses, remain unclear. We previously discovered a high fat n-3 PUFA diet made of fish/flaxseed oils promoted significant weight gain in C57BL/6 mice, relative to a control, without changes in food consumption. Therefore, here we tested the effects of feeding mice high fat (HF) and low fat (LF) n-3 PUFA diets, relative to a purified control diet (CD), on locomotor activity using metabolic cages. Relative to CD, the HF n-3 PUFA diet, but not the LF n-3 PUFA diet, dramatically reduced ambulatory, rearing, and running wheel activities. Furthermore, the HF n-3 PUFA diet lowered the respiratory exchange ratio. The data suggest mixed fish/flaxseed oil diets at high doses could exert some negative side effects and likely have limited therapeutic applications.
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Affiliation(s)
- Benjamin Drew Rockett
- Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
- East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
| | - Mitchel Harris
- Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
- East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
| | - Saame Raza Shaikh
- Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
- East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
- Correspondence to: East Carolina University, 600 Moye Blvd, Brody 5S-18, Greenville, NC 27834, USA. Tel.: 252 744 2585; fax: 252 744 3383. (S. Raza Shaikh)
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Silva JDAP, Trindade EBSDM, Fabre MEDS, Menegotto VM, Gevaerd S, Buss ZDS, Frode TS. Fish Oil Supplement Alters Markers of Inflammatory and Nutritional Status in Colorectal Cancer Patients. Nutr Cancer 2012; 64:267-73. [DOI: 10.1080/01635581.2012.643133] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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Effect of n-3 fatty acids on patients with advanced lung cancer: a double-blind, placebo-controlled study. Br J Nutr 2011; 108:327-33. [DOI: 10.1017/s0007114511005551] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
PUFA from fish oil appear to have anti-inflammatory and anti-oxidative effects and improve nutritional status in cancer patients. With this as background, the aim of the present study was to investigate the effect of EPA plus DHA on inflammatory condition, and oxidative and nutritional status in patients with lung cancer. In our multicentre, randomised, double-blind trial, thirty-three patients with a diagnosis of advanced inoperable non-small-cell lung cancer and undergoing chemotherapy were divided into two groups, receiving four capsules/d containing 510 mg of EPA and 340 mg of DHA, or 850 mg of placebo, for 66 d. At the start of chemotherapy (T0), after 8 d (T1), 22 d (T2) and 66 d (T3), biochemical (inflammatory and oxidative status parameters) and anthropometric parameters were measured in both groups. A significant increase of body weight in the n-3 group at T3v. T0 was observed. Concerning inflammation, C-reactive protein and IL-6 levels differed significantly between the n-3 and placebo groups at T3, and progressively decreased during chemotherapy in the n-3 group, evidencing n-3 PUFA anti-inflammatory action. Concerning oxidative status, plasma reactive oxygen species levels increased in the placebo group v. the n-3 group at the later treatment times. Hydroxynonenal levels increased in the placebo group during the study, while they stabilised in the n-3 group. Our data confirm that the continual assumption of EPA plus DHA determined an anti-inflammatory and anti-oxidative action which could be considered a preliminary goal in anti-cachectic therapy.
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van der Meij BS, Langius JAE, Smit EF, Spreeuwenberg MD, von Blomberg BME, Heijboer AC, Paul MA, van Leeuwen PAM. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J Nutr 2010; 140:1774-80. [PMID: 20739445 DOI: 10.3945/jn.110.121202] [Citation(s) in RCA: 127] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.
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Affiliation(s)
- Barbara S van der Meij
- Department of Nutrition and Dietetics, Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
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Gullett NP, Ruhul Amin ARM, Bayraktar S, Pezzuto JM, Shin DM, Khuri FR, Aggarwal BB, Surh YJ, Kucuk O. Cancer prevention with natural compounds. Semin Oncol 2010; 37:258-81. [PMID: 20709209 DOI: 10.1053/j.seminoncol.2010.06.014] [Citation(s) in RCA: 314] [Impact Index Per Article: 20.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Botanical and nutritional compounds have been used for the treatment of cancer throughout history. These compounds also may be useful in the prevention of cancer. Population studies suggest that a reduced risk of cancer is associated with high consumption of vegetables and fruits. Thus, the cancer chemopreventive potential of naturally occurring phytochemicals is of great interest. There are numerous reports of cancer chemopreventive activity of dietary botanicals, including cruciferous vegetables such as cabbage and broccoli, Allium vegetables such as garlic and onion, green tea, Citrus fruits, soybeans, tomatoes, berries, and ginger, as well as medicinal plants. Several lead compounds, such as genistein (from soybeans), lycopene (from tomatoes), brassinin (from cruciferous vegetables), sulforaphane (from asparagus), indole-3-carbinol (from broccoli), and resveratrol (from grapes and peanuts) are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals have great potential in cancer prevention because of their safety, low cost, and oral bioavailability. In this review, we discuss potential natural cancer preventive compounds and their mechanisms of action.
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Affiliation(s)
- Norleena P Gullett
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
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Roy J, Lefkimmiatis K, Moyer MP, Curci S, Hofer AM. The {omega}-3 fatty acid eicosapentaenoic acid elicits cAMP generation in colonic epithelial cells via a "store-operated" mechanism. Am J Physiol Gastrointest Liver Physiol 2010; 299:G715-22. [PMID: 20576916 PMCID: PMC2950681 DOI: 10.1152/ajpgi.00028.2010] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid abundant in fish oil that exerts a wide spectrum of documented beneficial health effects in humans. Because dietary interventions are relatively inexpensive and are widely assumed to be safe, they have broad public appeal. Their endorsement can potentially have a major impact on human health, but hard mechanistic evidence that specifies how these derivatives work at the cellular level is limited. EPA (50 microM) caused a small elevation of cytoplasmic Ca(2+) concentration ([Ca(2+)]) in intact NCM460 human colonic epithelial cells as measured by fura 2 and a profound drop of [Ca(2+)] within the endoplasmic reticulum (ER) of permeabilized cells as monitored by compartmentalized mag-fura 2. Total internal reflection fluorescence microscopy showed that this loss of ER store [Ca(2+)] led to translocation of the ER-resident transmembrane Ca(2+) sensor STIM1. Using sensitive FRET-based sensors for cAMP in single cells, we further found that EPA caused a substantial increase in cellular cAMP concentration, a large fraction of which was dependent on the drop in ER [Ca(2+)], but independent of cytosolic Ca(2+). An additional component of the EPA-induced cAMP signal was sensitive to the phosphodiesterase inhibitor isobutyl methylxanthine. We conclude that EPA slowly releases ER Ca(2+) stores, resulting in the generation of cAMP. The elevated cAMP is apparently independent of classical G protein-coupled receptor activation and is likely the consequence of a newly described "store-operated" cAMP signaling pathway that is mediated by STIM1.
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Affiliation(s)
- Jessica Roy
- 1Veterans Affairs Boston Healthcare System and the Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, West Roxbury, Massachusetts; and
| | - Konstantinos Lefkimmiatis
- 1Veterans Affairs Boston Healthcare System and the Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, West Roxbury, Massachusetts; and
| | | | - Silvana Curci
- 1Veterans Affairs Boston Healthcare System and the Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, West Roxbury, Massachusetts; and
| | - Aldebaran M. Hofer
- 1Veterans Affairs Boston Healthcare System and the Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, West Roxbury, Massachusetts; and
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Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, Lehman A, Belury MA, Clinton SK. Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition. Am J Clin Nutr 2010; 91:1185-94. [PMID: 20335550 PMCID: PMC2854898 DOI: 10.3945/ajcn.2009.29036] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Preclinical evidence of the preventive benefits of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in breast cancer continues to fuel interest in the potential role of dietary fat content in reducing breast cancer risk. The dose of fish-oil/omega-3 PUFAs needed to achieve maximal target tissue effects for breast cancer prevention remains undefined. OBJECTIVE To determine the dose effects of omega-3 fatty acids on breast adipose tissue fatty acid profiles, we conducted a study of 4 doses of omega-3 PUFAs in women at high risk of breast cancer. DESIGN In this 6-mo randomized open-label study, 48 women with increased breast cancer risk received 1, 3, 6, or 9 capsules/d of an omega-3 PUFA supplement that provided 0.84, 2.52, 5.04, and 7.56 g docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) daily, respectively. Subjects made monthly visits, at which time pill counts were made and fasting blood samples were collected to determine fatty acid profiles; anthropometric measurements were made, breast adipose tissue samples were collected, and laboratory tests of toxicity (alanine aminotransferase, LDL cholesterol, and platelet function) were made at baseline and at 3 and 6 mo. RESULTS All doses led to increased serum and breast adipose tissue EPA and DHA concentrations, but the response to 0.84 g DHA+EPA/d was less than the maximum possible response with > or = 2.52 g/d. Body mass index attenuated the dose response for serum tissue DHA and EPA (P = 0.015 and 0.027, respectively) and breast adipose tissue DHA (P = 0.0022) in all of the treatment groups. The incremental increase in DHA and EPA correlated inversely with baseline fat and serum values. Compliance over 6 mo was 92.9 +/- 9.2% and was unaffected by treatment arm. No severe or serious toxicities were reported. CONCLUSIONS Daily doses up to 7.56 g DHA+EPA were well tolerated with excellent compliance in this cohort at high risk of breast cancer. Body mass index and baseline fatty acid concentrations modulated the dose-response effects of omega-3 PUFA supplements on serum EPA and DHA and breast adipose tissue DHA.
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Affiliation(s)
- Lisa D Yee
- Department of Surgery, The Ohio State University, Columbus, OH, USA.
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Kariyazono H, Nakamura K. Pleiotropic Effects of Dietary Fatty Acids and Fatty Acid Involvement in Chronic Mild Inflammation-related Diseases. ACTA ACUST UNITED AC 2010. [DOI: 10.1248/jhs.56.473] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Hiroko Kariyazono
- Division of Pharmaceutical Health Care and Sciences, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Nagasaki International University
| | - Kazuo Nakamura
- Department of Biopharmaceutics, Nihon Pharmaceutical University
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Miller SDM, Mansky PJ. Nutritional supplementation for pediatric cancer cachexia: What can we feed back? Pediatr Blood Cancer 2009; 52:557-8. [PMID: 19195032 DOI: 10.1002/pbc.21933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Scott D M Miller
- National Center for Complementary and Alternative Medicine, NIH, Bethesda, Maryland 20892, USA
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Taylor LA, Pletschen L, Arends J, Unger C, Massing U. Marine phospholipids—a promising new dietary approach to tumor-associated weight loss. Support Care Cancer 2009; 18:159-70. [DOI: 10.1007/s00520-009-0640-4] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2009] [Accepted: 04/03/2009] [Indexed: 01/22/2023]
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van Norren K, Kegler D, Argilés JM, Luiking Y, Gorselink M, Laviano A, Arts K, Faber J, Jansen H, van der Beek EM, van Helvoort A. Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice. Br J Cancer 2009; 100:713-22. [PMID: 19259092 PMCID: PMC2653763 DOI: 10.1038/sj.bjc.6604905] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6–7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumour-bearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (P<0.02)) and improved muscle performance (loss of max force reduced to 55–64% of TB-con (P<0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (P<0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided.
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Affiliation(s)
- Anna Hoekstra
- Division of Gynecologic Oncology, NorthShore University HealthSystem, Suite 1507, Walgreen Building, Evanston Hospital, 2650 Ridge Ave., Evanston, IL 60201, USA
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Abstract
Conventional wisdom generally recommends complete avoidance of all dietary supplements, especially during chemotherapy and radiation. This interdiction persists, in spite of high rates of dietary supplement use by patients throughout all phases of cancer care, and can result in patients' perceptions of physicians as negative, thus leading to widespread nondisclosure of use. A review of the clinical literature shows that some evidence for harm does exist; however, data also exist that show benefit from using certain well-qualified supplements. Physicians should increase their knowledge base about dietary supplement use in cancer and consider all of the data when advising patients. Strategies that are patient-centered and reflect the complete array of available evidence lead to more nuanced messages about dietary supplement use in cancer. This should encourage greater disclosure of use by patients and ultimately increase safety and efficacy for patients choosing to use dietary supplements during cancer care.
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Affiliation(s)
- Mary L Hardy
- Simms/Mann-UCLA Center for Integrative Oncology, University of California at Los Angeles, 200 UCLA Medical Plaza, Suite 502 Los Angeles, CA 90095-9615, USA.
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Berquin IM, Edwards IJ, Chen YQ. Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett 2008; 269:363-77. [PMID: 18479809 PMCID: PMC2572135 DOI: 10.1016/j.canlet.2008.03.044] [Citation(s) in RCA: 278] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2008] [Revised: 01/15/2008] [Accepted: 03/28/2008] [Indexed: 01/20/2023]
Abstract
Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are essential fatty acids necessary for human health. Currently, the Western diet contains a disproportionally high amount of n-6 PUFAs and low amount of n-3 PUFAs, and the resulting high n-6/n-3 ratio is thought to contribute to cardiovascular disease, inflammation, and cancer. Studies in human populations have linked high consumption of fish or fish oil to reduced risk of colon, prostate, and breast cancer, although other studies failed to find a significant association. Nonetheless, the available epidemiological evidence, combined with the demonstrated effects of n-3 PUFAs on cancer in animal and cell culture models, has motivated the development of clinical interventions using n-3 PUFAs in the prevention and treatment of cancer, as well as for nutritional support of cancer patients to reduce weight loss and modulate the immune system. In this review, we discuss the rationale for using long-chain n-3 PUFAs in cancer prevention and treatment and the challenges that such approaches pose in the design of clinical trials.
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Affiliation(s)
- Isabelle M. Berquin
- Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
- Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Iris J. Edwards
- Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Yong Q. Chen
- Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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Cerchietti LCA, Navigante AH, Castro MA. Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Nutr Cancer 2008; 59:14-20. [PMID: 17927497 DOI: 10.1080/01635580701365068] [Citation(s) in RCA: 96] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.
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Affiliation(s)
- Leandro C A Cerchietti
- Translational Research Unit, Angel H Roffo Cancer Institute, Universidad de Buenos Aires, Buenos Aires, Argentina.
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