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Holthuijsen DDB, Rijnhart JJM, Bours MJL, van Roekel EH, Ueland PM, Breukink SO, Janssen-Heijnen MLG, Konsten JL, Keulen ETP, McCann A, Brezina S, Gigic B, Ulrich CM, Weijenberg MP, Eussen SJPM. Longitudinal associations of dietary intake with fatigue in colorectal cancer survivors up to 1 year post-treatment, and the potential mediating role of the kynurenine pathway. Brain Behav Immun 2025; 126:144-159. [PMID: 39922470 DOI: 10.1016/j.bbi.2025.02.003] [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: 11/14/2024] [Revised: 01/22/2025] [Accepted: 02/01/2025] [Indexed: 02/10/2025] Open
Abstract
INTRODUCTION A healthy diet may help to reduce cancer-related fatigue, but evidence is limited and mechanisms remain unclear. Both diet and fatigue following colorectal cancer (CRC) have been linked to metabolites (kynurenines) of the kynurenine pathway (KP). We investigated longitudinal associations between dietary intake and fatigue, and the potential mediating role of the KP, in CRC survivors up to 1 year post-treatment. METHODS Measurements at 6 weeks, 6 months, and 1 year post-treatment were performed in 209 stage I-III CRC survivors. Diet was assessed by 7-day food records. Plasma kynurenines were analyzed using LC-MS/MS. Fatigue, including subjective fatigue, was assessed using validated questionnaires. To analyse longitudinal associations between diet and fatigue and to explore potential mediation by the KP, we used confounder-adjusted multilevel parallel-multiple mediator models with all kynurenines included simultaneously, and simple mediator models with established KP ratios to estimate total (c: diet-fatigue), direct (c': diet-fatigue, while controlling for mediators), metabolite-specific indirect (ab: diet-metabolite-fatigue), and total indirect (ab: diet-metabolites-fatigue) effects. RESULTS Higher intake of total carbohydrates and mono- and disaccharides was longitudinally associated with more subjective fatigue, while higher intake of plant protein, total fat, and unsaturated fats was associated with less subjective fatigue (c). Most associations remained statistically significant after controlling for KP metabolites, except for mono- and disaccharides (c'). All kynurenines simultaneously did not mediate longitudinal associations between diet and subjective fatigue (ab). The kynurenic acid-to-quinolinic acid (KA/QA) ratio significantly mediated associations of intakes of carbohydrate, mono- and disaccharides, alcohol, magnesium, and zinc with subjective fatigue, whereas the HKr significantly mediated the association between polysaccharide intake and subjective fatigue (ab). CONCLUSION Our findings suggest that carbohydrate intake is associated with greater fatigue, while protein and fat intake are associated with lower fatigue in CRC survivors up to 1 year post-treatment. While all KP metabolites simultaneously did not significantly mediate associations between diet and fatigue in our population, the KA/QA ratio and HKr were significant mediators in several diet-fatigue associations. These results should be repeated in larger observational studies.
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Affiliation(s)
- Daniëlle D B Holthuijsen
- Department of Epidemiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Department of Epidemiology, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.
| | | | - Martijn J L Bours
- Department of Epidemiology, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | - Eline H van Roekel
- Department of Epidemiology, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | | | - Stéphanie O Breukink
- Department of Epidemiology, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Surgery, Maastricht University Medical Centre+, Maastricht, the Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Maryska L G Janssen-Heijnen
- Department of Epidemiology, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Clinical Epidemiology, VieCuri Medical Centre, Venlo, the Netherlands
| | - Joop L Konsten
- Department of Surgery, VieCuri Medical Centre, Venlo, the Netherlands
| | - Eric T P Keulen
- Department of Internal Medicine and Gastroenterology, Zuyderland Medical Centre Sittard-Geleen, Geleen, the Netherlands
| | | | - Stefanie Brezina
- Center for Cancer Research, Medical University of Vienna, Vienna, Austria
| | - Biljana Gigic
- Department of General Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Cornelia M Ulrich
- Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
| | - Matty P Weijenberg
- Department of Epidemiology, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | - Simone J P M Eussen
- Department of Epidemiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands
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Faiad J, Andrade MF, de Castro G, de Resende J, Coêlho M, Aquino G, Seelaender M. Muscle loss in cancer cachexia: what is the basis for nutritional support? Front Pharmacol 2025; 16:1519278. [PMID: 40078277 PMCID: PMC11897308 DOI: 10.3389/fphar.2025.1519278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 01/27/2025] [Indexed: 03/14/2025] Open
Abstract
Cancer cachexia (CC) is characterized by significant skeletal muscle wasting, and contributes to diminished quality of life, while being associated with poorer response to treatment and with reduced survival. Chronic inflammation plays a central role in driving CC progression, within a complex interplay favoring catabolism. Although cachexia cannot be fully reversed by conventional nutritional support, nutritional intervention shows promise for the prevention and treatment of the syndrome. Of special interest are nutrients with antioxidant and anti-inflammatory potential and those that activate pathways involved in muscle mass synthesis and/or in the inhibition of muscle wasting. Extensive research has been carried out on novel nutritional supplements' power to mitigate CC impact, while the mechanisms through which some nutrients or bioactive compounds exert beneficial effects on muscle mass are still not totally clear. Here, we discuss the most studied supplements and nutritional strategies for dealing with muscle loss in CC.
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Affiliation(s)
| | | | | | | | | | | | - Marilia Seelaender
- Cancer Metabolism Research Group, Faculdade de Medicina da Universidade de São Paulo, Departamento de Cirurgia, LIM 26-HC-USP, São Paulo, Brazil
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Madeddu C, Gramignano G, Lai E, Pinna G, Tanca L, Cherchi MC, Floris C, Farci D, Pretta A, Scartozzi M, Macciò A. Leptin as a surrogate immune-metabolic marker to predict impact of anti-cachectic therapy: results of a prospective randomized trial in multiple solid tumors. ESMO Open 2024; 9:103738. [PMID: 39389003 PMCID: PMC11693429 DOI: 10.1016/j.esmoop.2024.103738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 08/28/2024] [Accepted: 09/02/2024] [Indexed: 10/12/2024] Open
Abstract
DESCRIPTION OF THE WORK Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia. PURPOSE To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment. PATIENTS AND METHODS From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus l-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life. RESULTS A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue. CONCLUSIONS Leptin is a reliable predictive marker for multitargeted anti-cachectic treatment outcomes. Thus, it can be an ideal candidate for monitoring and predicting the effects of anti-cachectic treatment and a surrogate marker of the immune-metabolic actions of the selected drugs.
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Affiliation(s)
- C Madeddu
- Department of Medical Sciences and Public Health, Medical Oncology Unit, "Azienda Ospedaliero Universitaria" of Cagliari, University of Cagliari, Cagliari, Italy.
| | - G Gramignano
- Medical Oncology Unit, San Gavino Hospital, San Gavino, Italy
| | - E Lai
- Department of Medical Sciences and Public Health, Medical Oncology Unit, "Azienda Ospedaliero Universitaria" of Cagliari, University of Cagliari, Cagliari, Italy
| | - G Pinna
- Department of Medical Sciences and Public Health, Medical Oncology Unit, "Azienda Ospedaliero Universitaria" of Cagliari, University of Cagliari, Cagliari, Italy
| | - L Tanca
- Medical Oncology Unit, A. Businco Hospital, ARNAS G Brotzu, Cagliari, Italy
| | - M C Cherchi
- Medical Oncology Unit, A. Businco Hospital, ARNAS G Brotzu, Cagliari, Italy
| | - C Floris
- Medical Oncology Unit, "Nuova Casa di Cura", Decimomannu, Cagliari, Italy
| | - D Farci
- Medical Oncology Unit, "Nuova Casa di Cura", Decimomannu, Cagliari, Italy
| | - A Pretta
- Department of Medical Sciences and Public Health, Medical Oncology Unit, "Azienda Ospedaliero Universitaria" of Cagliari, University of Cagliari, Cagliari, Italy
| | - M Scartozzi
- Department of Medical Sciences and Public Health, Medical Oncology Unit, "Azienda Ospedaliero Universitaria" of Cagliari, University of Cagliari, Cagliari, Italy
| | - A Macciò
- Department of Surgical Sciences, Gynecologic Oncology Unit, ARNAS G. Brotzu, University of Cagliari, Cagliari, Italy
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Pradhan R, Dieterich W, Natarajan A, Schwappacher R, Reljic D, Herrmann HJ, Neurath MF, Zopf Y. Influence of Amino Acids and Exercise on Muscle Protein Turnover, Particularly in Cancer Cachexia. Cancers (Basel) 2024; 16:1921. [PMID: 38791998 PMCID: PMC11119313 DOI: 10.3390/cancers16101921] [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: 04/23/2024] [Revised: 05/15/2024] [Accepted: 05/16/2024] [Indexed: 05/26/2024] Open
Abstract
Cancer cachexia is a multifaceted syndrome that impacts individuals with advanced cancer. It causes numerous pathological changes in cancer patients, such as inflammation and metabolic dysfunction, which further diminish their quality of life. Unfortunately, cancer cachexia also increases the risk of mortality in affected individuals, making it an important area of focus for cancer research and treatment. Several potential nutritional therapies are being tested in preclinical and clinical models for their efficacy in improving muscle metabolism in cancer patients. Despite promising results, no special nutritional therapies have yet been validated in clinical practice. Multiple studies provide evidence of the benefits of increasing muscle protein synthesis through an increased intake of amino acids or protein. There is also increasing evidence that exercise can reduce muscle atrophy by modulating protein synthesis. Therefore, the combination of protein intake and exercise may be more effective in improving cancer cachexia. This review provides an overview of the preclinical and clinical approaches for the use of amino acids with and without exercise therapy to improve muscle metabolism in cachexia.
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Affiliation(s)
- Rashmita Pradhan
- Department of Medicine, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (R.P.); (W.D.); (A.N.); (R.S.); (D.R.); (H.J.H.); (M.F.N.)
- Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Walburga Dieterich
- Department of Medicine, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (R.P.); (W.D.); (A.N.); (R.S.); (D.R.); (H.J.H.); (M.F.N.)
- Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Anirudh Natarajan
- Department of Medicine, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (R.P.); (W.D.); (A.N.); (R.S.); (D.R.); (H.J.H.); (M.F.N.)
- Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Raphaela Schwappacher
- Department of Medicine, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (R.P.); (W.D.); (A.N.); (R.S.); (D.R.); (H.J.H.); (M.F.N.)
- Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Dejan Reljic
- Department of Medicine, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (R.P.); (W.D.); (A.N.); (R.S.); (D.R.); (H.J.H.); (M.F.N.)
- Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Hans J. Herrmann
- Department of Medicine, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (R.P.); (W.D.); (A.N.); (R.S.); (D.R.); (H.J.H.); (M.F.N.)
- Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Markus F. Neurath
- Department of Medicine, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (R.P.); (W.D.); (A.N.); (R.S.); (D.R.); (H.J.H.); (M.F.N.)
| | - Yurdagül Zopf
- Department of Medicine, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; (R.P.); (W.D.); (A.N.); (R.S.); (D.R.); (H.J.H.); (M.F.N.)
- Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
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Norouzi M, Mahboobi S, Eftekhari MH, Salehipour M, Ghaem H, Mirzakhanlouei A, Mohsenpour MA. Effects of L-Carnitine and Coenzyme Q10 Supplementation on Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia: A Randomized, Controlled, Clinical Trial. Nutr Cancer 2024; 76:207-214. [PMID: 38105612 DOI: 10.1080/01635581.2023.2295578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 12/10/2023] [Accepted: 12/11/2023] [Indexed: 12/19/2023]
Abstract
The prevalence of benign prostatic hyperplasia (BPH) and its associated lower urinary tract symptoms (LUTS) increases with age. Considering that BPH drug treatment is associated with complications, this study aimed to investigate the effects of L-carnitine (LC) and Coenzyme Q10 (CoQ10) supplementation as an adjunct therapy to finasteride in the management of LUTS in older men affected with BPH. Fifty eligible volunteers (25 per group) were randomly assigned to either intervention (finasteride + LC and CoQ10 supplements) or control (finasteride + placebo) groups. International prostate symptom score (IPSS), international index of erectile function (IIEF), quality of life index (QoL), as well as serum levels of Prostate-specific antigen (PSA), were assessed. Prostate ultrasound evaluation was also performed, before and after 8 wk of intervention. Supplementation with LC and CoQ10 led to a significant decrease in prostate volume (p < 0.001) as well as a significant increase in IIEF (p < 0.001), compared to the control group. However, there were no significant between-group differences in IPSS (p = 0.503), QoL scores (p = 0.339), and PSA levels (p = 0.482). CoQ10 and LC supplements might be beneficial in combination with standard therapies in the management of BPH and its related complications.
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Affiliation(s)
- Mahsa Norouzi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sepideh Mahboobi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Hassan Eftekhari
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
- Research Center for Health Sciences, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Salehipour
- Department of Urology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Haleh Ghaem
- Department of Epidemiology, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Mirzakhanlouei
- Department of Urology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Ali Mohsenpour
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
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Wang X, Liu X, Gu Z, Li X, Shu Y. Experiences and requirements in nutritional management of patients with esophageal cancer: a systematic review and qualitative meta-synthesis. Support Care Cancer 2023; 31:633. [PMID: 37843658 PMCID: PMC10579144 DOI: 10.1007/s00520-023-08100-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 10/02/2023] [Indexed: 10/17/2023]
Abstract
PURPOSE Nutritional management of patients with esophageal cancer is a significant issue. This systematic review aimed to comprehensively synthesize qualitative research evidence on the experiences and requirements in nutritional management from the perspective of patients with esophageal cancer. METHODS A systematic review and meta-synthesis of qualitative studies were conducted. Studies written in Chinese or English were retrieved from nine databases, namely, PubMed, Web of Science, Cochrane Library, CINAHL, Embase, CNKI, WanFang, VIP, and SinoMed, from inception to December 23, 2022. After screening the titles, abstracts, and full texts, 19 articles were finally included for quality assessment and meta-synthesis. RESULTS Three comprehensive themes were derived. These were dietary experiences (perception of symptoms and dietary behaviors), emotional experiences (negative and positive emotions), and social support (inappropriate social support and inadequate nutritional management). CONCLUSIONS The experiences and requirements of esophageal cancer patients in terms of nutritional management during treatment and rehabilitation were reviewed and factors influencing nutritional management were discussed. The findings suggested that medical institutions should expedite the development of comprehensive nutritional management systems, create conducive nutritional environmental facilities, and establish interdisciplinary teams to implement personalized comprehensive interventional models for the management of patient nutrition. These steps would maximize the effectiveness of nutritional therapy, promote early patient recovery, and bridge the gap between healthcare professionals and patients in the understanding of nutritional management.
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Affiliation(s)
- Xinwei Wang
- School of Nursing and Public Health, Yangzhou University, 136 Jiangyang Middle Road, Yangzhou, 225009, Jiangsu Province, China
| | - Xingyu Liu
- School of Nursing and Public Health, Yangzhou University, 136 Jiangyang Middle Road, Yangzhou, 225009, Jiangsu Province, China
| | - Zhie Gu
- Northern Jiangsu People's Hospital, 98 Nantong West Road, Yangzhou, 225001, Jiangsu Province, China
| | - Xiaojie Li
- School of Nursing and Public Health, Yangzhou University, 136 Jiangyang Middle Road, Yangzhou, 225009, Jiangsu Province, China
| | - Yusheng Shu
- Northern Jiangsu People's Hospital, 98 Nantong West Road, Yangzhou, 225001, Jiangsu Province, China.
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Bel’skaya LV, Gundyrev IA, Solomatin DV. The Role of Amino Acids in the Diagnosis, Risk Assessment, and Treatment of Breast Cancer: A Review. Curr Issues Mol Biol 2023; 45:7513-7537. [PMID: 37754258 PMCID: PMC10527988 DOI: 10.3390/cimb45090474] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/05/2023] [Accepted: 09/12/2023] [Indexed: 09/28/2023] Open
Abstract
This review summarizes the role of amino acids in the diagnosis, risk assessment, imaging, and treatment of breast cancer. It was shown that the content of individual amino acids changes in breast cancer by an average of 10-15% compared with healthy controls. For some amino acids (Thr, Arg, Met, and Ser), an increase in concentration is more often observed in breast cancer, and for others, a decrease is observed (Asp, Pro, Trp, and His). The accuracy of diagnostics using individual amino acids is low and increases when a number of amino acids are combined with each other or with other metabolites. Gln/Glu, Asp, Arg, Leu/Ile, Lys, and Orn have the greatest significance in assessing the risk of breast cancer. The variability in the amino acid composition of biological fluids was shown to depend on the breast cancer phenotype, as well as the age, race, and menopausal status of patients. In general, the analysis of changes in the amino acid metabolism in breast cancer is a promising strategy not only for diagnosis, but also for developing new therapeutic agents, monitoring the treatment process, correcting complications after treatment, and evaluating survival rates.
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Affiliation(s)
- Lyudmila V. Bel’skaya
- Biochemistry Research Laboratory, Omsk State Pedagogical University, 644099 Omsk, Russia;
| | - Ivan A. Gundyrev
- Biochemistry Research Laboratory, Omsk State Pedagogical University, 644099 Omsk, Russia;
| | - Denis V. Solomatin
- Department of Mathematics and Mathematics Teaching Methods, Omsk State Pedagogical University, 644043 Omsk, Russia;
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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: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [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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Barnish M, Sheikh M, Scholey A. Nutrient Therapy for the Improvement of Fatigue Symptoms. Nutrients 2023; 15:2154. [PMID: 37432282 DOI: 10.3390/nu15092154] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 04/22/2023] [Accepted: 04/27/2023] [Indexed: 07/12/2023] Open
Abstract
Fatigue, characterised by lack of energy, mental exhaustion and poor muscle endurance which do not recover following a period of rest, is a common characteristic symptom of several conditions and negatively impacts the quality of life of those affected. Fatigue is often a symptom of concern for people suffering from conditions such as fibromyalgia, chronic fatigue syndrome, cancer, and multiple sclerosis. Vitamins and minerals, playing essential roles in a variety of basic metabolic pathways that support fundamental cellular functions, may be important in mitigating physical and mental fatigue. Several studies have examined the potential benefits of nutrients on fatigue in various populations. The current review aimed to gather the existing literature exploring different nutrients' effects on fatigue. From the searches of the literature conducted in PubMed, Ovid, Web of Science, and Google scholar, 60 articles met the inclusion criteria and were included in the review. Among the included studies, 50 showed significant beneficial effects (p < 0.05) of vitamin and mineral supplementation on fatigue. Altogether, the included studies investigated oral or parenteral administration of nutrients including Coenzyme Q10, L-carnitine, zinc, methionine, nicotinamide adenine dinucleotide (NAD), and vitamins C, D and B. In conclusion, the results of the literature review suggest that these nutrients have potentially significant benefits in reducing fatigue in healthy individuals as well as those with chronic illness, both when taken orally and parenterally. Further studies should explore these novel therapies, both as adjunctive treatments and as sole interventions.
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Affiliation(s)
- Michael Barnish
- REVIV Life Science Research, REVIV Global Ltd., Manchester M15 4PS, UK
| | - Mahsa Sheikh
- REVIV Life Science Research, REVIV Global Ltd., Manchester M15 4PS, UK
| | - Andrew Scholey
- Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC 3122, Australia
- Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, VIC 3168, Australia
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Jing Z, Iba T, Naito H, Xu P, Morishige JI, Nagata N, Okubo H, Ando H. L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy. Front Pharmacol 2023; 14:1182788. [PMID: 37089945 PMCID: PMC10116043 DOI: 10.3389/fphar.2023.1182788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 03/31/2023] [Indexed: 04/08/2023] Open
Abstract
Lenvatinib is an oral tyrosine kinase inhibitor that acts on multiple receptors involved in angiogenesis. Lenvatinib is a standard agent for the treatment of several types of advanced cancers; however, it frequently causes muscle-related adverse reactions. Our previous study revealed that lenvatinib treatment reduced carnitine content and the expression of carnitine-related and oxidative phosphorylation (OXPHOS) proteins in the skeletal muscle of rats. Therefore, this study aimed to evaluate the effects of L-carnitine on myotoxic and anti-angiogenic actions of lenvatinib. Co-administration of L-carnitine in rats treated with lenvatinib for 2 weeks completely prevented the decrease in carnitine content and expression levels of carnitine-related and OXPHOS proteins, including carnitine/organic cation transporter 2, in the skeletal muscle. Moreover, L-carnitine counteracted lenvatinib-induced protein synthesis inhibition, mitochondrial dysfunction, and cell toxicity in C2C12 myocytes. In contrast, L-carnitine had no influence on either lenvatinib-induced inhibition of vascular endothelial growth factor receptor 2 phosphorylation in human umbilical vein endothelial cells or angiogenesis in endothelial tube formation and mouse aortic ring assays. These results suggest that L-carnitine supplementation could prevent lenvatinib-induced muscle toxicity without diminishing its antineoplastic activity, although further clinical studies are needed to validate these findings.
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Affiliation(s)
- Zheng Jing
- Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Tomohiro Iba
- Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
- Department of Vascular Physiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Hisamichi Naito
- Department of Vascular Physiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Pingping Xu
- Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Jun-ichi Morishige
- Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Naoto Nagata
- Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, Bunkyō, Tokyo, Japan
| | - Hitoshi Ando
- Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
- *Correspondence: Hitoshi Ando,
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11
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Alhasaniah AH. l-carnitine: Nutrition, pathology, and health benefits. Saudi J Biol Sci 2023; 30:103555. [PMID: 36632072 PMCID: PMC9827390 DOI: 10.1016/j.sjbs.2022.103555] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/09/2022] [Accepted: 12/28/2022] [Indexed: 12/31/2022] Open
Abstract
Carnitine is a medically needful nutrient that contributes in the production of energy and the metabolism of fatty acids. Bioavailability is higher in vegetarians than in people who eat meat. Deficits in carnitine transporters occur as a result of genetic mutations or in combination with other illnesses such like hepatic or renal disease. Carnitine deficit can arise in diseases such endocrine maladies, cardiomyopathy, diabetes, malnutrition, aging, sepsis, and cirrhosis due to abnormalities in carnitine regulation. The exogenously provided molecule is obviously useful in people with primary carnitine deficits, which can be life-threatening, and also some secondary deficiencies, including such organic acidurias: by eradicating hypotonia, muscle weakness, motor skills, and wasting are all improved l-carnitine (LC) have reported to improve myocardial functionality and metabolism in ischemic heart disease patients, as well as athletic performance in individuals with angina pectoris. Furthermore, although some intriguing data indicates that LC could be useful in a variety of conditions, including carnitine deficiency caused by long-term total parenteral supplementation or chronic hemodialysis, hyperlipidemias, and the prevention of anthracyclines and valproate-induced toxicity, such findings must be viewed with caution.
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Key Words
- AD, Alzheimer's disease
- AIF, Apoptosis-inducing factor
- Anti-wasting effect
- BBB, Blood–brain barrier
- CC, Cancer cachexia
- CHF, Chronic heart failure
- COPD, Chronic obstructive pulmonary disease
- ESRD, End-stage renal disease
- GOT, Glutamic oxaloacetic transaminase
- HCC, Hepatocellular carcinoma
- HFD, High-Fat Diet
- HOI, Highest observed intake
- Health benefits
- LC, l-carnitine
- MI, myocardial infarction
- MTX, Methotrexate
- NF-kB, Nuclear factor-kB
- Nutrition
- OSL, Observed safe level
- PCD, Primary carnitine deficiency
- Pathology
- ROS, Reactive oxygen species
- SCD, Secondary carnitine deficiency
- TLE, Temporal lobe epilepsy
- VD, Vascular dementia
- l-carnitine
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Affiliation(s)
- Abdulaziz Hassan Alhasaniah
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia
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12
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Al-Dhuayan IS. Biomedical role of L-carnitine in several organ systems, cellular tissues, and COVID-19. BRAZ J BIOL 2023; 82:e267633. [PMID: 36629544 DOI: 10.1590/1519-6984.267633] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 11/20/2022] [Indexed: 01/11/2023] Open
Abstract
Carnitine is a conditionally necessary vitamin that aids in energy creation and fatty acid metabolism. Its bioavailability is higher in vegetarians than in meat-eaters. Deficits in carnitine transporters occur because of genetic mutations or in conjunction with other illnesses. Carnitine shortage can arise in health issues and diseases-including hypoglycaemia, heart disease, starvation, cirrhosis, and ageing-because of abnormalities in carnitine control. The physiologically active form of L-carnitine supports immunological function in diabetic patients. Carnitine has been demonstrated to be effective in the treatment of Alzheimer's disease, several painful neuropathies, and other conditions. It has been used as a dietary supplement for the treatment of heart disease, and it also aids in the treatment of obesity and reduces blood glucose levels. Therefore, L-carnitine shows the potential to eliminate the influences of fatigue in COVID-19, and its consumption is recommended in future clinical trials to estimate its efficacy and safety. This review focused on carnitine and its effect on tissues, covering the biosynthesis, metabolism, bioavailability, biological actions, and its effects on various body systems and COVID-19.
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Affiliation(s)
- I S Al-Dhuayan
- Imam Abdulrahman Bin Faisal University, College of Science, Department of Biology, Dammam, Saudi Arabia
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13
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The Association of Serum L-Carnitine Concentrations with the Risk of Cancer in Chinese Adults with Hypertension. Nutrients 2022; 14:nu14234999. [PMID: 36501029 PMCID: PMC9738465 DOI: 10.3390/nu14234999] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 11/20/2022] [Accepted: 11/23/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND The effect of serum L-carnitine (LC) concentrations on cancer risk remains unclear. This study aims to explore the association between serum LC and the risk of incident cancer. METHODS This is a case-control study, including 574 patients with incident cancer and 574 controls matched in a 1:1 ratio by age, sex, and residence, nested within the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analysis was used to assess the association of serum LC and incident cancer risk. RESULTS When LC was assessed as quartiles, compared with patients with low LC (Q1), patients in the highest quartile (Q4) had a 33% (OR = 0.67, 95% CI: 0.46 to 0.99), 52% (OR = 0.48, 95% CI: 0.23 to 0.99), and 39% (OR = 0.61, 95% CI: 0.38 to 0.99) decreased risk of overall, digestive system, and non-digestive system cancer in the adjusted models, respectively. In subgroup analyses, an inverse association of LC with cancer risk was observed in individuals who were overweight (obese), who never drink, who never smoke, and who were female. In the mediation analysis, serum trimethylamine-N-oxide (TMAO) concentrations did not mediate the reversed association of LC with cancer risk. CONCLUSIONS This study showed that serum LC concentrations had a protective impact on overall, digestive system, and non-digestive system cancer risk.
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14
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Johal J, Han CY, Joseph R, Munn Z, Agbejule OA, Crawford-Williams F, Wallen MP, Chan RJ, Hart NH. Dietary Supplements in People with Metastatic Cancer Who Are Experiencing Malnutrition, Cachexia, Sarcopenia, and Frailty: A Scoping Review. Nutrients 2022; 14:2642. [PMID: 35807823 PMCID: PMC9268679 DOI: 10.3390/nu14132642] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/22/2022] [Accepted: 06/23/2022] [Indexed: 02/01/2023] Open
Abstract
Cancer-associated malnutrition, or cachexia, stemming from cancer or its treatments, is particularly prevalent in metastatic cancers, and is often interrelated with sarcopenia and frailty. Evidence suggests that dietary supplements play a role in managing these conditions. As metastatic cancer cells are associated with notable genomic and phenotypic alterations, response to dietary supplements may differ between metastatic and non-metastatic cancers. However, research in this area is lacking. This scoping review aims to identify the dietary supplements that have been studied in patients with metastatic cancers and malnutrition-related conditions, along with their proposed effects, mechanisms, outcome measures, and tools used. A systematic search was conducted across databases, including MEDLINE, EMBASE, CINAHL, and clinical trial registries. Of the initial 6535 records screened, a total of 48 studies were included, covering a range of dietary supplements-vitamins, minerals, antioxidants, proteins, amino acids, fatty acids, fiber, and others. While the types of dietary supplements included varied across cancer types, omega-3 and carnitine were investigated most often. Proposed relevant attributes of dietary supplements included their antioxidant, anti-inflammatory, anti-cancer, and immunomodulatory properties. Overall, there was a paucity of interventional studies, and more randomized controlled trials are warranted.
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Affiliation(s)
- Jolyn Johal
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia; (J.J.); (C.Y.H.); (R.J.); (O.A.A.); (F.C.-W.); (M.P.W.); (R.J.C.)
| | - Chad Yixian Han
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia; (J.J.); (C.Y.H.); (R.J.); (O.A.A.); (F.C.-W.); (M.P.W.); (R.J.C.)
| | - Ria Joseph
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia; (J.J.); (C.Y.H.); (R.J.); (O.A.A.); (F.C.-W.); (M.P.W.); (R.J.C.)
| | - Zachary Munn
- Joanna Briggs Institute (JBI), The University of Adelaide, Adelaide, SA 5001, Australia;
| | - Oluwaseyifunmi Andi Agbejule
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia; (J.J.); (C.Y.H.); (R.J.); (O.A.A.); (F.C.-W.); (M.P.W.); (R.J.C.)
| | - Fiona Crawford-Williams
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia; (J.J.); (C.Y.H.); (R.J.); (O.A.A.); (F.C.-W.); (M.P.W.); (R.J.C.)
- Cancer and Palliative Care Outcomes Centre, School of Nursing, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia
| | - Matthew P. Wallen
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia; (J.J.); (C.Y.H.); (R.J.); (O.A.A.); (F.C.-W.); (M.P.W.); (R.J.C.)
- School of Science, Psychology and Sport, Federation University, Mount Helen, VIC 3350, Australia
| | - Raymond J. Chan
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia; (J.J.); (C.Y.H.); (R.J.); (O.A.A.); (F.C.-W.); (M.P.W.); (R.J.C.)
- Cancer and Palliative Care Outcomes Centre, School of Nursing, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia
| | - Nicolas H. Hart
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia; (J.J.); (C.Y.H.); (R.J.); (O.A.A.); (F.C.-W.); (M.P.W.); (R.J.C.)
- Cancer and Palliative Care Outcomes Centre, School of Nursing, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia
- Exercise Medicine Research Institute, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia
- Institute for Health Research, The University of Notre Dame Australia, Fremantle, WA 6160, Australia
- Precision Medicine (Cancer), South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia
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15
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Lin YC, Wang CH, Ling HH, Pan YP, Chang PH, Chou WC, Chen FP, Yeh KY. Inflammation Status and Body Composition Predict Two-Year Mortality of Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma under Provision of Recommended Energy Intake during Concurrent Chemoradiotherapy. Biomedicines 2022; 10:biomedicines10020388. [PMID: 35203597 PMCID: PMC8962429 DOI: 10.3390/biomedicines10020388] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 01/27/2023] Open
Abstract
Only few prospective cohort trials have evaluated the risk factors for the 2-year mortality rate between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC): oral cavity cancer with adjuvant concurrent chemoradiotherapy (CCRT) (OCC) and non-oral cavity cancer with primary CCRT (NOCC), under the recommended calorie intake and investigated the interplay among calorie supply, nutrition–inflammation biomarkers (NIBs), and total body composition change (TBC), as assessed using dual-energy X-ray absorptiometry (DXA). Patients with LAHNSCC who consumed at least 25 kcal/kg/day during CCRT were prospectively recruited. Clinicopathological variables, blood NIBs, CCRT-related factors, and TBC data before and after treatment were collected. Factor analysis was performed to reduce the number of anthropometric and DXA-derived measurements. Cox proportional hazards models were used for analysis. We enrolled 123 patients with LAHNSCC (69 with OCC and 54 with NOCC). The mean daily calorie intake correlated with the treatment interval changes in total body muscle and fat. Patients consuming ≥30 kcal/kg/day had lower pretreatment levels but exhibited fewer treatment interval changes in anthropometric and DXA measurements than patients consuming <30 kcal/kg/day. In the multivariate analysis of the 2-year mortality rate, the prognostic influence of the recommended calorie intake could not be confirmed, but different risk factors (performance status, pretreatment platelet-to-lymphocyte ratio, and treatment interval body muscle changes in patients with OCC; age, pretreatment neutrophil-to-lymphocyte ratio, and body fat storage in patients with NOCC) showed independent effects. Therefore, the inflammation status and body composition, but not the recommended calorie supply, contribute to the 2-year mortality rate for patients with LAHNSCC receiving CCRT.
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Affiliation(s)
- Yu-Ching Lin
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 333007, Taiwan;
- Osteoporosis Prevention and Treatment Center, Chang Gung Memorial Hospital, Keelung 20401, Taiwan;
| | - Cheng-Hsu Wang
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 333007, Taiwan; (C.-H.W.); (H.H.L.); (P.-H.C.)
| | - Hang Huong Ling
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 333007, Taiwan; (C.-H.W.); (H.H.L.); (P.-H.C.)
| | - Yi-Ping Pan
- Department of Nutrition, Chang Gung Memorial Hospital, Keelung 20401, Taiwan;
| | - Pei-Hung Chang
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 333007, Taiwan; (C.-H.W.); (H.H.L.); (P.-H.C.)
| | - Wen-Chi Chou
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Linkou & Chang Gung University, Taoyuan 333007, Taiwan;
| | - Fang-Ping Chen
- Osteoporosis Prevention and Treatment Center, Chang Gung Memorial Hospital, Keelung 20401, Taiwan;
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Keelung 20401, Taiwan
- Healthy Aging Research Center, College of Medicine, Chang Gung University, Taoyuan 333007, Taiwan
| | - Kun-Yun Yeh
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Keelung & Chang Gung University, Taoyuan 333007, Taiwan; (C.-H.W.); (H.H.L.); (P.-H.C.)
- Correspondence: ; Tel.: +886-2-24329292 (ext. 2360); Fax: +886-2-2435342
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16
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Takagi A, Hawke P, Tokuda S, Toda T, Higashizono K, Nagai E, Watanabe M, Nakatani E, Kanemoto H, Oba N. Serum carnitine as a biomarker of sarcopenia and nutritional status in preoperative gastrointestinal cancer patients. J Cachexia Sarcopenia Muscle 2022; 13:287-295. [PMID: 34939358 PMCID: PMC8818668 DOI: 10.1002/jcsm.12906] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 09/05/2021] [Accepted: 11/29/2021] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Sarcopenia is an important factor in the postoperative outcome of gastrointestinal cancer patients. However, little research has been carried out on potential biomarkers of sarcopenia. Carnitine is an amino acid derivative that is stored in skeletal muscle and is essential for muscle energy metabolism. The primary purpose of this study was to investigate whether serum carnitine level is a biomarker of sarcopenia in preoperative patients with gastrointestinal cancer. The secondary purposes were (i) to examine the associations between carnitine, nutritional status, and albumin level, and (ii) to determine whether carnitine is a prognostic factor for postoperative complications. METHODS One hundred fourteen patients scheduled to undergo gastroenterological surgery between August 2016 and January 2017 were enrolled. Their mean age was 68.4 ± 10.5, and 64.9% were male. Serum carnitine fractions [total carnitine (TC), free l-carnitine (FC), and acylcarnitine (AC)] were measured prior to surgery. The correlation between carnitine level and a variety of clinical features was analysed, including skeletal muscle index (SMI), sarcopenia, prognostic nutritional index (PNI), and postoperative complications. RESULTS Tumour locations included the oesophagus (n = 17), stomach (n = 16), pancreas (n = 20), bile duct (n = 9), liver [n = 33; primary liver cancer (n = 18), liver metastasis (n = 15)], and colorectal region (n = 19). TC and FC levels varied significantly by tumour location. TC and FC showed significant positive correlations with SMI [TC (r = 0.295, P = 0.0014), FC (r = 0.286, P = 0.0020)] and PNI [TC (P = 0.0178, r = 0.222), FC (P = 0.0067, r = 0.2526)]. These levels were significantly lower in the sarcopenia group (TC, P = 0.0124; FC, P = 0.0243). In addition, TC and FC showed significant positive correlations with ALB level [TC (P = 0.038 r = 0.19), FC (P = 0.016 r = 0.23)]. When patients were divided into high ALB (≥3.5 g/dL, 96 patients) and low ALB (<3.5 g/dL, 18 patients) groups, these correlations were no longer significant, but in the low ALB group there was a tendency towards a negative relationship between ALB level and both TC and FC. No significant relationship was found between postoperative complications and carnitine level. CONCLUSIONS This study suggests that carnitine level is a biomarker of sarcopenia and nutritional status. However, it did not find an association between carnitine level and postoperative complications.
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Affiliation(s)
- Akihiko Takagi
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Philip Hawke
- School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
| | - Satoshi Tokuda
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Takeo Toda
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Kazuya Higashizono
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Erina Nagai
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Masaya Watanabe
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Eiji Nakatani
- Division of Statistical Analysis, Research Support Center, Shizuoka General Hospital, Shizuoka, Japan
| | - Hideyuki Kanemoto
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Noriyuki Oba
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
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17
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Tanaka K, Nakamura S, Narimatsu H. Nutritional Approach to Cancer Cachexia: A Proposal for Dietitians. Nutrients 2022; 14:nu14020345. [PMID: 35057531 PMCID: PMC8779386 DOI: 10.3390/nu14020345] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/10/2022] [Accepted: 01/11/2022] [Indexed: 02/04/2023] Open
Abstract
Cachexia is one of the most common, related factors of malnutrition in cancer patients. Cancer cachexia is a multifactorial syndrome characterized by persistent loss of skeletal muscle mass and fat mass, resulting in irreversible and progressive functional impairment. The skeletal muscle loss cannot be reversed by conventional nutritional support, and a combination of anti-inflammatory agents and other nutrients is recommended. In this review, we reviewed the effects of nutrients that are expected to combat muscle loss caused by cancer cachexia (eicosapentaenoic acid, β-hydroxy-β-methylbutyrate, creatine, and carnitine) to propose nutritional approaches that can be taken at present. Current evidence is based on the intake of nutrients as supplements; however, the long-term and continuous intake of nutrients as food has the potential to be useful for the body. Therefore, in addition to conventional nutritional support, we believe that it is important for the dietitian to work with the clinical team to first fully assess the patient’s condition and then to safely incorporate nutrients that are expected to have specific functions for cancer cachexia from foods and supplements.
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Affiliation(s)
- Kotone Tanaka
- School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services 1-10-1 Heiseicho, Yokosuka-shi 238-0013, Japan
- Correspondence:
| | - Sho Nakamura
- Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan; (S.N.); (H.N.)
- Graduate School of Health Innovation, Kanagawa University of Human Services, 3-25-10 Research Gate Building 2-A, Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan
| | - Hiroto Narimatsu
- Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan; (S.N.); (H.N.)
- Graduate School of Health Innovation, Kanagawa University of Human Services, 3-25-10 Research Gate Building 2-A, Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan
- Department of Genetic Medicine, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan
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18
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Kiryukova MA, Dubtsova EA, Vinokurova LV, Malykh MV, Bordin DS. Nutritional status disorders and methods of their correction in patients with advanced pancreatic cancer. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:66-74. [DOI: 10.31146/1682-8658-ecg-195-11-66-74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Despite of achieved progress in advanced pancreatic cancer treatment, the disease outcomes remain far from satisfying. The peculiarity of malnutrition treatment in these patients is the result of its causes complexity and progressively growing manifestations extent. The review represents mechanisms of malnutrition and approaches to their treatment.
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Affiliation(s)
| | - E. A. Dubtsova
- Moscow Clinical Research Center named after A. S. Loginov
| | | | - M. V. Malykh
- Moscow Clinical Research Center named after A. S. Loginov
| | - D. S. Bordin
- Moscow Clinical Research Center named after A. S. Loginov; Moscow State University of Medicine and Dentistry named after A. I. Yevdokimov; Tver State Medical University
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19
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Vaziri-Harami R, Delkash P. Can l-carnitine reduce post-COVID-19 fatigue? Ann Med Surg (Lond) 2021; 73:103145. [PMID: 34925826 PMCID: PMC8667465 DOI: 10.1016/j.amsu.2021.103145] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/01/2021] [Accepted: 12/01/2021] [Indexed: 12/16/2022] Open
Abstract
A significant number of patients infected with the new coronavirus suffer from chronic fatigue syndrome after COVID-19, and their symptoms may persist for months after the infection. Nevertheless, no particular treatment for post-disease fatigue has been found. At the same time, many clinical trials have shown the effectiveness of l-carnitine in relieving fatigue caused by the treatment of diseases such as cancer, MS, and many other diseases. Therefore, it can be considered as a potential option to eliminate the effects of fatigue caused by COVID-19, and its consumption is recommended in future clinical trials to evaluate its effectiveness and safety.
The coronavirus disease is a viral infection that could induce different respiratory. A significant number of patients infected with the new coronavirus suffer from chronic fatigue. Clinical trials have shown the effectiveness of L-carnitine in relieving fatigue.
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Affiliation(s)
- Roya Vaziri-Harami
- Department of Psychiatry, School of Medicine, Behavioural Sciences Research Center, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parisa Delkash
- Department of Adult Rheumatology, School of Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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20
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Baba MR, Buch SA. Revisiting Cancer Cachexia: Pathogenesis, Diagnosis, and Current Treatment Approaches. Asia Pac J Oncol Nurs 2021; 8:508-518. [PMID: 34527780 PMCID: PMC8420916 DOI: 10.4103/apjon.apjon-2126] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 04/15/2021] [Indexed: 01/06/2023] Open
Abstract
The objective of this article is to group together various management strategies and to highlight the recent treatment modifications that attempt to target the multimodal etiological factors involved in cancer cachexia. The contemporary role of nursing fraternity in psychosocial and nutritional assessment of cancer patients is briefly discussed. Cachexia is a syndrome of metabolic disturbance, characterized by the inflammation and loss of muscle with or without loss of adipose tissue. In cancer cachexia, a multifaceted condition, patients suffer from loss of body weight that leads to a negative impact on the quality of life and survival of the patients. The main cancers associated with cachexia are that of pancreas, stomach, lung, esophagus, liver, and that of bowel. The changes include increased proteolysis, lipolysis, insulin resistance, high energy expenditure, and reduced intake of food, all leading to impaired response to different treatments. There is no standardized treatment for cancer cachexia that can stabilize or reverse this complex metabolic disorder at present. The mainstay of cancer cachexia therapy remains to be sufficient nutritional supplements with on-going efforts to explore the drugs that target heightened catabolic processes and complex inflammation. There is a need to develop a multimodal treatment approach combining pharmacology, exercise program, and nutritional support to target anorexia and the severe metabolic changes encountered in cancer cachexia.
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Affiliation(s)
- Mudasir Rashid Baba
- Department of Paediatric Rehabilitation, Yenepoya Physiotherapy College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - Sajad Ahmad Buch
- Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
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21
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Turcott JG, Zatarain-Barrón ZL, Cárdenas Fernández D, Castañares Bolaños DT, Arrieta O. Appetite stimulants for patients with cancer: current evidence for clinical practice. Nutr Rev 2021; 80:857-873. [PMID: 34389868 DOI: 10.1093/nutrit/nuab045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
The incidence of neoplastic diseases has increased worldwide, with an estimated global burden of 19.3 million incident cases and 10 million deaths in 2020-a considerable increase compared with 9.6 million deaths in 2018. One of the most prevalent problems faced by patients with cancer and their physicians is malnutrition. It is estimated that patients with cancer have important nutritional alterations in 25% to 70% of cases, which directly affects many spheres of patient care and well-being, including quality of life, treatment toxicity, and survival outcomes. Despite the overwhelming need to address this pressing issue, current evidence in terms of pharmacologic interventions for cancer-related anorexia remains inconclusive, and there is no current standard of care for patients with cancer-related anorexia. Nonetheless, international guidelines recommend promoting anabolism through nutritional, physical, and pharmacologic therapies. In this review, the available information is summarized regarding pharmacologic therapies to treat cancer-related anorexia and findings are highlighted from a clinical stance.
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Affiliation(s)
- Jenny G Turcott
- Thoracic Oncology Unit, Instituto Nacional de Cancerología, Mexico City, Mexico
| | | | | | | | - Oscar Arrieta
- Thoracic Oncology Unit, Instituto Nacional de Cancerología, Mexico City, Mexico
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22
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Ito T, Tsukahara K, Sato H, Shimizu A, Okamoto I. Changes in carnitine levels through induction chemotherapy in head and neck cancer patients as a potential cause of therapy-related malaise. BMC Cancer 2021; 21:742. [PMID: 34182942 PMCID: PMC8237460 DOI: 10.1186/s12885-021-08471-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 06/09/2021] [Indexed: 11/15/2022] Open
Abstract
Background Carnitine is related to malaise, and cisplatin is associated with decreased carnitine. The purpose of this study was to elucidate the effects of one course of induction chemotherapy (IC) for head and neck cancer on blood carnitine levels, focusing on free carnitine (FC). Methods This single-center prospective study investigated 20 patients diagnosed with primary head and neck cancer who underwent IC with cisplatin, docetaxel, and 5-fluorouracil. FC, acylcarnitine (AC), and total carnitine (TC) levels were measured before starting therapy and on Days 7 and 21 after starting IC. In addition, malaise was evaluated before and after therapy using a visual analog scale (VAS). Results All subjects were men and the most common primary cancer site was the hypopharynx (9 patients). FC levels before starting therapy and on Days 7 and 21 were 47.7 ± 2.2 μM/mL, 56.7 ± 2.2 μM/mL, and 41.1 ± 1.9 μM/mL, respectively. Compared with the baseline before starting therapy, FC had significantly decreased on Day 21 (p = 0.007). AC levels before starting therapy and on Days 7 and 21 were 12.5 ± 1.2 μM/mL, 13.6 ± 1.4 μM/mL, and 10.7 ± 0.7 μM/mL, respectively. TC levels before starting therapy and on Days 7 and 21 were 60.2 ± 2.5 μM/mL, 70.2 ± 3.3 μM/mL, and 51.7 ± 2.3 μM/mL, respectively. No significant differences in AC, TC or VAS were seen before the start of therapy and on Day 21. Conclusions After IC, a latent decrease in FC occurred without any absolute deficiency or subjective malaise.
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Affiliation(s)
- Tatsuya Ito
- Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjyuku-ku, Tokyo, Japan
| | - Kiyoaki Tsukahara
- Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjyuku-ku, Tokyo, Japan.
| | - Hiroki Sato
- Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjyuku-ku, Tokyo, Japan
| | - Akira Shimizu
- Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjyuku-ku, Tokyo, Japan
| | - Isaku Okamoto
- Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjyuku-ku, Tokyo, Japan
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23
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Maccio A, Sanna E, Neri M, Oppi S, Madeddu C. Cachexia as Evidence of the Mechanisms of Resistance and Tolerance during the Evolution of Cancer Disease. Int J Mol Sci 2021; 22:2890. [PMID: 33809200 PMCID: PMC8001015 DOI: 10.3390/ijms22062890] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 03/06/2021] [Accepted: 03/09/2021] [Indexed: 02/07/2023] Open
Abstract
During its evolution, cancer induces changes in patients' energy metabolism that strongly affect the overall clinical state and are responsible for cancer-related cachexia syndrome. To better understand the mechanisms underlying cachexia and its metabolic derangements, research efforts should focus on the events that are driven by the immune system activation during the evolution of neoplastic disease and on the phenomena of "resistance" and "tolerance" typically involved in the human body response against stress, pathogens, or cancer. Indeed, in the case where resistance is not able to eliminate the cancer, tolerance mechanisms can utilize the symptoms of cachexia (anemia, anorexia, and fatigue) to counteract unregulated cancer growth. These notions are also sustained by the evidence that cancer cachexia may be reversible if the resistance and tolerance phases are supported by appropriate antineoplastic treatments. Accordingly, there is no doubt that anticachectic therapies have an irreplaceable role in cases of reversible cancer cachexia where, if harmoniously associated with effective antineoplastic therapies, they can contribute to preserve the quality of life and improve prognosis. Such anticachectic treatments should be based on targeting the complex immunological, inflammatory, and metabolic pathways involved in the complex pathogenesis of cachexia. Meanwhile, the role of the anticachectic therapies is very different in the stage of irreversible cachexia when the available antineoplastic treatments are not able to control the disease and the resistance mechanisms fail with the prevalence of the tolerance phenomena. At this stage, they can be useful only to improve the quality of life, allowing the patient and their family to get a better awareness of the final phases of life, thereby opening to the best spiritual remodulation of the final event, death.
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Affiliation(s)
- Antonio Maccio
- Department of Gynecologic Oncology, Businco Hospital, ARNAS G. Brotzu, 09121 Cagliari, Italy; (E.S.); (M.N.)
| | - Elisabetta Sanna
- Department of Gynecologic Oncology, Businco Hospital, ARNAS G. Brotzu, 09121 Cagliari, Italy; (E.S.); (M.N.)
| | - Manuela Neri
- Department of Gynecologic Oncology, Businco Hospital, ARNAS G. Brotzu, 09121 Cagliari, Italy; (E.S.); (M.N.)
| | - Sara Oppi
- Hematology and Transplant Center, Businco Hospital, ARNAS G. Brotzu, 09121 Cagliari, Italy;
| | - Clelia Madeddu
- Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy;
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24
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Ebrahim OFA, Nafea OE, Samy W, Shawky LM. L-carnitine suppresses cisplatin-induced renal injury in rats: impact on cytoskeleton proteins expression. Toxicol Res (Camb) 2021; 10:51-59. [PMID: 33613972 DOI: 10.1093/toxres/tfaa092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 10/26/2020] [Accepted: 11/03/2020] [Indexed: 12/29/2022] Open
Abstract
We designed this work to examine the curative role of L-carnitine (LCAR) in a rat model of cisplatin (CDDP)-induced kidney injury. We induced kidney injury in rats by a single intraperitoneal injection of 5 mg/kg of CDDP. Fifteen days post injection, rats were orally supplemented with 354 mg/kg of LCAR for another 15 days. Kidney tissues were subjected to histo-biochemical analysis along with mRNA gene expression quantification for cytoskeleton proteins encoding genes (vimentin, nestin, and connexin 43) by real-time reverse transcription polymerase chain reaction. LCAR reversed CDDP-induced renal structural and functional impairments. LCAR significantly declined serum urea and creatinine concentrations, restored oxidant/antioxidant balance, reversed inflammation, and antagonized caspase 3-mediated apoptotic cell death in renal tissues. Moreover, LCAR effectively down-regulated cytoskeleton proteins mRNA levels, reflecting amelioration of CDDP-provoked podocyte injury. We concluded that LCAR has a favorable therapeutic utility against CDDP-induced kidney injury.
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Affiliation(s)
| | - Ola Elsayed Nafea
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Walaa Samy
- Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Lamiaa Mohamed Shawky
- Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt
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25
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González-Haro C, Ross R, AlDuhishy A. Plasma oxidative stress (hydrogen peroxide/trolox) responses during a 7-day road cycling stage race and a competitive football match in top-level athletes. SPORT SCIENCES FOR HEALTH 2020. [DOI: 10.1007/s11332-020-00645-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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26
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Gu Q, Ali SF, Kanungo J. Effects of acetyl L-carnitine on zebrafish embryos: Phenotypic and gene expression studies. J Appl Toxicol 2020; 41:256-264. [PMID: 32691447 DOI: 10.1002/jat.4041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/23/2020] [Accepted: 06/27/2020] [Indexed: 01/21/2023]
Abstract
Acetyl L-carnitine (ALCAR), a dietary supplement and an antioxidant, plays a vital role in the bioenergetic process that produces ATP. Although there are reports on antioxidant toxicity, there is no information on the potential toxicity of ALCAR. Here, using zebrafish embryos, we explored whether ALCAR modulated ATP synthesis, generation of reactive oxygen species (ROS) and expression of specific genes related to major signaling pathways that control metabolism, growth, differentiation, apoptosis and oxidative stress. First, we show that ALCAR elicits a physiologic response, as ATP levels increased after ALCAR treatment. Simultaneously, an increase in the expression of ROS, a by-product of ATP synthesis, was observed in the ALCAR-treated embryos. Consistent with higher ROS expression, the level of cysteine, a precursor of glutathione, was significantly reduced. ALCAR did not have any drastic effect on overall development and heart rate. Polymerase chain reaction-based gene expression array analyses showed no significant change in the expression of 83 genes related to 10 major signaling pathways including: the transforming growth factor β (TGFβ), Wingless and Int-1 (Wnt), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), Janus kinase/signal transducers and activators of transcription (JAK/STAT), p53, Notch, Hedgehog, Peroxisome proliferator-activated receptor (PPAR), oxidative stress, and hypoxia pathways. Our results show that the expression of 83 genes related to these major signaling pathways did not change significantly.
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Affiliation(s)
- Qiang Gu
- Division of Neurotoxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR, USA
| | - Syed F Ali
- Division of Neurotoxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR, USA
| | - Jyotshna Kanungo
- Division of Neurotoxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR, USA
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Prado CM, Purcell SA, Laviano A. Nutrition interventions to treat low muscle mass in cancer. J Cachexia Sarcopenia Muscle 2020; 11:366-380. [PMID: 31916411 PMCID: PMC7113510 DOI: 10.1002/jcsm.12525] [Citation(s) in RCA: 229] [Impact Index Per Article: 45.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 09/27/2019] [Accepted: 11/15/2019] [Indexed: 12/20/2022] Open
Abstract
Many patients with cancer experience poor nutritional status, which detrimentally impacts clinical outcomes. Poor nutritional status in cancer is primarily manifested by severe muscle mass (MM) depletion, which may occur at any stage (from curative to palliative) and often co-exists with obesity. The objective of this article was to discuss gaps and opportunities related to the role of nutrition in preventing and reversing low MM in cancer. It also provides a narrative review of relevant nutritional interventions for patients capable of oral intake. The impact of nutrition interventions to prevent/treat low MM in cancer is not well understood, potentially due to the limited number of studies and of clinically viable, accurate body composition assessment tools. Additionally, the type of study designs, inclusion criteria, length of intervention, and choice of nutritional strategies have not been optimal, likely underestimating the anabolic potential of nutrition interventions. Nutrition studies are also often of short duration, and interventions that adapt to the metabolic and behavioural changes during the clinical journey are needed. We discuss energy requirements (25-30 kcal/kg/day) and interventions of protein (1.0-1.5 g/kg/day), branched-chain amino acids (leucine: 2-4 g/day), β-hydroxy β-methylbutyrate (3 g/day), glutamine (0.3 g/kg/day), carnitine (4-6 g/day), creatine (5 g/day), fish oil/eicosapentanoic acid (2.0-2.2 g/day EPA and 1.5 g/day DHA), vitamin/minerals (e.g. vitamin D: 600-800 international units per day), and multimodal approaches (nutrition, exercise, and pharmaceutical) to countermeasure low MM in cancer. Although the evidence is variable by modality type, interventions were generally not specifically studied in the context of cancer. Understanding patients' nutritional requirements could lead to targeted prescriptions to prevent or attenuate low MM in cancer, with the overall aim of minimizing muscle loss during anti-cancer therapy and maximizing muscle anabolism during recovery. It is anticipated that this will, in turn, improve overall health and prognostication including tolerance to treatment and survival. However, oncology-specific interventions with more robust study designs are needed to facilitate these goals.
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Affiliation(s)
- Carla M Prado
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Sarah A Purcell
- Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.,Division of Endocrinology, Metabolism, and Diabetes, and Division of Nutrition, School of Medicine, University of Colorado, Aurora, CO, USA
| | - Alessandro Laviano
- Department of Translational and Precision Medicine, La Sapienza University, Rome, Italy
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28
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Signorelli MS, Surace T, Migliore M, Aguglia E. Mood disorders and outcomes in lung cancer patients undergoing surgery: a brief summery. Future Oncol 2020; 16:41-44. [PMID: 32166972 DOI: 10.2217/fon-2018-0835] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Cancer is a leading cause of death worldwide. Literature reports depression and anxiety are the most common psychiatric symptoms in cancer patients. Notably, lung cancer is associated with major depressive disorder in 5-13% of cases. The present article aims to give an overview regarding the impact of mood disorders on the outcomes of patients affected by lung cancer. Our review showed that pharmacological treatment and psychotherapy can be useful to improve the quality of life of patients with lung cancer. Moreover, the treatment of depression and anxiety can be associated with a reduced mortality. In conclusion, it is important to consider psychiatric care as important as other adjuvant oncologic therapies in patients with cancer.
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Affiliation(s)
- Maria Salvina Signorelli
- Department of Clinical & Experimental Medicine, Policlinico University Hospital, University of Catania, Catania, 95123, Italy
| | - Teresa Surace
- Department of Clinical & Experimental Medicine, Policlinico University Hospital, University of Catania, Catania, 95123, Italy
| | - Marcello Migliore
- Department of Surgery & Medical Specialities, Policlinico University Hospital, University of Catania, Catania, 95123, Italy
| | - Eugenio Aguglia
- Department of Clinical & Experimental Medicine, Policlinico University Hospital, University of Catania, Catania, 95123, Italy
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29
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Marceca GP, Londhe P, Calore F. Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options. Front Oncol 2020; 10:298. [PMID: 32195193 PMCID: PMC7064558 DOI: 10.3389/fonc.2020.00298] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 02/20/2020] [Indexed: 12/17/2022] Open
Abstract
Cancer cachexia (CC) is a multifactorial syndrome characterized by systemic inflammation, uncontrolled weight loss and dramatic metabolic alterations. This includes myofibrillar protein breakdown, increased lipolysis, insulin resistance, elevated energy expediture, and reduced food intake, hence impairing the patient's response to anti-cancer therapies and quality of life. While a decade ago the syndrome was considered incurable, over the most recent years much efforts have been put into the study of such disease, leading to the development of potential therapeutic strategies. Several important improvements have been reached in the management of CC from both the diagnostic-prognostic and the pharmacological viewpoint. However, given the heterogeneity of the disease, it is impossible to rely only on single variables to properly treat patients presenting this metabolic syndrome. Moreover, the cachexia symptoms are strictly dependent on the type of tumor, stage and the specific patient's response to cancer therapy. Thus, the attempt to translate experimentally effective therapies into the clinical practice results in a great challenge. For this reason, it is of crucial importance to further improve our understanding on the interplay of molecular mechanisms implicated in the onset and progression of CC, giving the opportunity to develop new effective, safe pharmacological treatments. In this review we outline the recent knowledge regarding cachexia mediators and pathways involved in skeletal muscle (SM) and adipose tissue (AT) loss, mainly from the experimental cachexia standpoint, then retracing the unimodal treatment options that have been developed to the present day.
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Affiliation(s)
- Gioacchino P Marceca
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Priya Londhe
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Federica Calore
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
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30
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Effects of acute oral feeding on protein metabolism and muscle protein synthesis in individuals with cancer. Nutrition 2019; 67-68:110531. [DOI: 10.1016/j.nut.2019.06.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 06/19/2019] [Indexed: 11/15/2022]
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31
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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: 26] [Impact Index Per Article: 4.3] [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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32
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Busquets S, Pérez-Peiró M, Salazar-Degracia A, Argilés JM, Serpe R, Rojano-Toimil A, López-Soriano FJ, Barreiro E. Differential structural features in soleus and gastrocnemius of carnitine-treated cancer cachectic rats. J Cell Physiol 2019; 235:526-537. [PMID: 31241186 DOI: 10.1002/jcp.28992] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 05/31/2019] [Indexed: 01/06/2023]
Abstract
Muscle wasting is associated with chronic diseases and cancer. Elucidation of the biological mechanism involved in the process of muscle mass loss and cachexia may help identify therapeutic targets. We hypothesized that l-carnitine treatment may differentially revert muscle fiber atrophy and other structural alterations in slow- and fast-twitch limb muscles of rats bearing the Yoshida ascites hepatoma. In soleus and gastrocnemius of tumor-bearing rats (108 AH-130 Yoshida ascites hepatoma cells inoculated intraperitoneally) with and without treatment with l-carnitine (1 g/kg body weight for 7 days, intragastric), food intake, body and muscle weights, fiber typing and morphometry, morphological features, redox balance, autophagy and proteolytic, and signaling markers were explored. Levels of carnitine palmitoyl transferase were also measured in all the study muscles. l-Carnitine treatment ameliorated the atrophy of both slow- and fast-twitch fibers (gastrocnemius particularly), muscle structural alterations (both muscles), and attenuated oxidative stress, proteolytic and signaling markers (gastrocnemius). Despite that carnitine palmitoyl transferase-1 levels increased in both muscle types in a similar fashion, l-carnitine ameliorated muscle atrophy and proteolysis in a muscle-specific manner in cancer-induced cachexia. These data reveal the need to study muscles of different fiber type composition and function to better understand whereby l-carnitine exerts its beneficial effects on the myofibers in muscle wasting processes. These findings also have potential clinical implications, since combinations of various exercise and muscle training modalities with l-carnitine should be specifically targeted for the muscle groups to be trained.
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Affiliation(s)
- Sílvia Busquets
- Departament de Bioquímica i Biomedicina Molecular, Cancer Research Group, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain
| | - Maria Pérez-Peiró
- Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, and Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
| | - Anna Salazar-Degracia
- Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, and Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
| | - Josep M Argilés
- Departament de Bioquímica i Biomedicina Molecular, Cancer Research Group, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain
| | - Roberto Serpe
- Department of Medical Sciences and Public Health "M. Aresu,", University of Cagliari, Cagliari, Italy
| | - Alba Rojano-Toimil
- Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, and Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
| | - Francisco J López-Soriano
- Departament de Bioquímica i Biomedicina Molecular, Cancer Research Group, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain
| | - Esther Barreiro
- Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, and Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
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Lin SC, Lin KH, Lee YC, Peng HY, Chiu EC. Test-retest reliability of the Mini Nutritional Assessment and its relationship with quality of life in patients with stroke. PLoS One 2019; 14:e0218749. [PMID: 31220156 PMCID: PMC6586339 DOI: 10.1371/journal.pone.0218749] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 06/09/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND & OBJECTIVE Malnutrition is one of commonly issues in patients with stroke. The Mini Nutritional Assessment (MNA) is a widely used measure for assessing nutritional status in patients with stroke. A nutritional measure with acceptable test-retest reliability allows clinicians to consistently assess patients' nutritional status. Knowledge of the relationship between nutritional status and quality of life (QOL) could guide clinicians to improve QOL in patients with stroke more effectively. This study aimed to examine test-retest reliability of the MNA and its relationship with QOL in patients with stroke. METHODS Fifty-nine patients participated in the test-retest reliability study and the correlation between the MNA and WHO Quality of Life-BREF (WHOQOL-BREF) study. A repeated-assessments design (1 week apart) was used to examine the test-retest reliability of the MNA. RESULTS The intraclass correlation coefficient for the MNA was 0.91. The minimal detectable change and percentage of minimal detectable change for the MNA were 2.1 and 8.2%, respectively. The MNA was positively associated with the QOL (r = 0.32; p = 0.013). The result of linear regression analysis shows that after controlling for age, sex and activities of daily living functions, only the MNA was significantly associated with the WHOQOL-BREF (r2 = 0.104; p = 0.008). CONCLUSIONS The MNA has satisfactory test-retest reliability that is useful for repeatedly assessing the nutritional status of patients with stroke. The MDC of the MNA has acceptable random measurement error which is useful for determining whether the change score of a patient is outside the range of random measurement error. Future studies that recruit stroke patients in the acute stage is needed to further examine the relationship between the nutritional status and QOL.
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Affiliation(s)
- Shu-Chi Lin
- Department of Nutrition, Taiwan Adventist Hospital, Taipei, Taiwan
| | - Kuan-Hung Lin
- Department of Neurology, Taiwan Adventist Hospital, Taipei, Taiwan
| | - Ya-Chen Lee
- Department of Occupational Therapy, College of Medical and Health Science, Asia University, Taichung, Taiwan
| | - Hsiao-Yun Peng
- Department of Long-Term Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
| | - En-Chi Chiu
- Department of Long-Term Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
- * E-mail:
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Effect of lifelong carnitine supplementation on plasma and tissue carnitine status, hepatic lipid metabolism and stress signalling pathways and skeletal muscle transcriptome in mice at advanced age. Br J Nutr 2019; 121:1323-1333. [DOI: 10.1017/s0007114519000709] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
AbstractWhile strong evidence from clinical studies suggests beneficial effects of carnitine supplementation on metabolic health, serious safety concerns associated with carnitine supplementation have been raised from studies in mice. Considering that the carnitine doses in these mice studies were up to 100 times higher than those used in clinical studies, the present study aimed to address possible safety concerns associated with long-term supplementation of a carnitine dose used in clinical trials. Two groups of NMRI mice were fed either a control or a carnitine-supplemented diet (1 g/kg diet) from weaning to 19 months of age, and parameters of hepatic lipid metabolism and stress signalling and skeletal muscle gene expression were analysed in the mice at 19 months of age. Concentrations of free carnitine and acetylcarnitine in plasma and tissues were higher in the carnitine than in the control group (P<0·05). Plasma concentrations of free carnitine and acetylcarnitine were higher in mice at adult age (10 and 15 months) than at advanced age (19 months) (P<0·05). Hepatic mRNA and protein levels of genes involved in lipid metabolism and stress signalling and hepatic and plasma lipid concentrations did not differ between the carnitine and the control group. Skeletal muscle transcriptome analysis in 19-month-old mice revealed only a moderate regulation between carnitine and control group. Lifelong carnitine supplementation prevents an age-dependent impairment of plasma carnitine status, but safety concerns associated with long-term supplementation of carnitine at doses used in clinical trials can be considered as unfounded.
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Inglis JE, Lin PJ, Kerns SL, Kleckner IR, Kleckner AS, Castillo DA, Mustian KM, Peppone LJ. Nutritional Interventions for Treating Cancer-Related Fatigue: A Qualitative Review. Nutr Cancer 2019; 71:21-40. [PMID: 30688088 DOI: 10.1080/01635581.2018.1513046] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cancer-related fatigue (CRF) is a debilitating syndrome that persists for many cancer survivors for years after treatment. Symptoms include early and persistent fatigue, functional decline, depression, and cognitive difficulties. Inflammation, assessed using pro-inflammatory biomarkers, is increased in cancer survivors with fatigue and treatments for fatigue are often aimed at reducing inflammation. Additionally, cancer and its treatment lead to nutritional complications, changes in body composition, and nutritional deficiencies that potentially weaken the cancer survivor and impact CRF. We conducted a qualitative review of clinical trials that assessed nutritional interventions for preventing and treating CRF. Further studies were examined that used nutritional interventions to address inflammation and fatigue, due to the dearth of nutrition research directly related to CRF. Dietary intake prior to, during, and after cancer treatment appears to affect fatigue levels. Increased protein intake may help preserve lean mass and body composition. Dietary patterns that reduce inflammation, such as the Mediterranean diet and other plant-based diets, appear tolerable to cancer survivors and may reduce fatigue. Supplementation with ginseng, ginger, or probiotics may improve cancer survivors' energy levels. Nutritional interventions, alone or in combination with other interventions should be considered as therapy for fatigue in cancer survivors.
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Affiliation(s)
- Julia E Inglis
- a Department of Surgery , University of Rochester Medical Center (URMC) , Rochester , New York , USA
| | - Po-Ju Lin
- a Department of Surgery , University of Rochester Medical Center (URMC) , Rochester , New York , USA
| | - Sarah L Kerns
- b Department of Radiation Oncology , University of Rochester Medical Center (URMC) , Rochester , New York , USA
| | - Ian R Kleckner
- a Department of Surgery , University of Rochester Medical Center (URMC) , Rochester , New York , USA
| | - Amber S Kleckner
- a Department of Surgery , University of Rochester Medical Center (URMC) , Rochester , New York , USA
| | - Daniel A Castillo
- c Edward G. Miner Library, University of Rochester Medical Center (URMC) , Rochester , New York , USA
| | - Karen M Mustian
- a Department of Surgery , University of Rochester Medical Center (URMC) , Rochester , New York , USA
| | - Luke J Peppone
- a Department of Surgery , University of Rochester Medical Center (URMC) , Rochester , New York , USA
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Can levocarnitine supplementation improve fatigue caused by sunitinib as a treatment for renal cell carcinoma? A single-center prospective pilot study. Support Care Cancer 2018; 27:1491-1496. [PMID: 30374764 DOI: 10.1007/s00520-018-4521-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 09/26/2018] [Indexed: 01/17/2023]
Abstract
PURPOSE To evaluate the potential role of levocarnitine supplementation for cancer-related fatigue in patients treated with sunitinib. METHODS Patients treated with sunitinib for unresectable or metastatic renal cell carcinoma were enrolled prospectively. Assessment of fatigue in each patient was done using the Brief Fatigue Inventory (BFI) questionnaire. Evaluation of fatigue and the serum carnitine level was done at baseline, 2 weeks, and 4 weeks after sunitinib therapy was initiated. All patients were treated with sunitinib 37.5 mg or 50 mg/day orally, with a 4-week administration and 2-week discontinuation schedule. RESULTS Ten patients were finally enrolled in the study. Seven of them had worsened fatigue at the 2-week assessment and levocarnitine was administrated. All these seven patients whose serum carnitine level at 2 weeks was worse than at the baseline improved after 2-week-L-carnitine supplementation. For six of the seven (85.7%) patients who had L-carnitine supplementation, the BFI score at 4 weeks decreased compared to that at 2 weeks, which indicated improvement of fatigue. CONCLUSIONS Levocarnitine supplementation for cancer-related fatigue in patients treated with sunitinib appears to have a potential benefit. However, further study with a larger number of patients and longer follow-up is crucial to confirm this.
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Cancer cachexia: Diagnosis, assessment, and treatment. Crit Rev Oncol Hematol 2018; 127:91-104. [PMID: 29891116 DOI: 10.1016/j.critrevonc.2018.05.006] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 04/16/2018] [Accepted: 05/09/2018] [Indexed: 02/07/2023] Open
Abstract
Cancer cachexia is a multi-factorial syndrome, which negatively affects quality of life, responsiveness to chemotherapy, and survival in advanced cancer patients. Our understanding of cachexia has grown greatly in recent years and the roles of many tumor-derived and host-derived compounds have been elucidated as mediators of cancer cachexia. However, cancer cachexia remains an unmet medical need and attempts towards a standard treatment guideline have been unsuccessful. This review covers the diagnosis, assessment, and treatment of cancer cachexia; the elements impeding the formulation of a standard management guideline; and future directions of research for the improvement and standardization of current treatment procedures.
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Repka CP, Hayward R. Effects of an Exercise Intervention on Cancer-Related Fatigue and Its Relationship to Markers of Oxidative Stress. Integr Cancer Ther 2018; 17:503-510. [PMID: 29649913 PMCID: PMC6041925 DOI: 10.1177/1534735418766402] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background: Although the underlying mechanisms of cancer-related fatigue (CRF) are not fully characterized, treatment-associated oxidative stress may play a role. The purpose of this study was to determine the effect of an exercise intervention on the relationship between CRF and oxidative stress. Methods: Upon cessation of radiation or chemotherapy, 8 cancer patients participated in a 10-week exercise intervention (EX), while 7 continued standard care (CON). Blood draws and fatigue questionnaires were administered to cancer patients before and after the intervention as well as to 7 age-matched individuals with no cancer history. Changes in plasma 8-hydroxy-deoxyguanosine (8-OHdG), protein carbonyls, antioxidant capacity, and fatigue were compared between groups. Correlations between CRF and oxidative stress were evaluated. Results: Mean total fatigue scores decreased significantly (5.0 ± 2.2 to 2.6 ± 1.5, P < .05) in EX, but not in CON. Antioxidant capacity significantly increased (+41%; P < .05) and protein carbonyls significantly decreased (−36%; P < .05) in EX, but not in CON. Increases in antioxidant capacity were significantly correlated with reductions in affective (r = −.49), sensory (r = −.47), and cognitive fatigue (r = −.58). Changes in total (r = .46) and affective (r = .47) fatigue exhibited significant correlations with changes in 8-OHdG over time, while behavioral (r = .46) and sensory (r = .47) fatigue changes were significantly correlated with protein carbonyls. Conclusions: Oxidative stress may be implicated in CRF, while improved antioxidant capacity following an exercise intervention may play a role in mitigating CRF in cancer survivors.
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Affiliation(s)
- Chris P Repka
- 1 Department of Health Sciences, Northern Arizona University, Flagstaff, AZ, USA.,2 Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO, USA
| | - Reid Hayward
- 2 Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO, USA
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Matsui H, Einama T, Shichi S, Kanazawa R, Shibuya K, Suzuki T, Matsuzawa F, Hashimoto T, Homma S, Yamamoto J, Taketomi A, Abe H. L-Carnitine supplementation reduces the general fatigue of cancer patients during chemotherapy. Mol Clin Oncol 2018; 8:413-416. [PMID: 29456846 PMCID: PMC5795559 DOI: 10.3892/mco.2018.1557] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 11/22/2017] [Indexed: 11/16/2022] Open
Abstract
L-Carnitine (LC) plays an important role in the metabolism of fatty acids, and LC deficiency is associated with a feeling of weakness or general fatigue. Cancer patients receiving chemotherapy often develop LC deficiency, which is considered to be a factor contributing to general fatigue. The aim of the present study was to evaluate the efficacy of LC supplementation as a treatment for general fatigue in cancer patients during chemotherapy. A total of 11 cancer patients who were suffering from general fatigue during chemotherapy in our hospital between September 2014 and December 2015 were examined (6 cases involved adjuvant chemotherapy and 5 cases involved chemotherapy for unresectable or recurrent disease). The patients were administered 1,500 mg/day of levocarnitine per os, and the change in mean daily fatigue from the baseline to 8 weeks was assessed using the Brief Fatigue Inventory. The change in the plasma levels of albumin and the lymphocyte counts from the baseline to 8 weeks were also assessed. LC supplementation reduced general fatigue in all cases. Moreover, LC supplementation maintained the plasma levels of albumin and lymphocyte counts during chemotherapy, and enabled patients to continue chemotherapy sequentially without dose reduction. Therefore, LC supplementation improved general fatigue in all the examined cancer patients during chemotherapy. This treatment may make improve the tolerability of chemotherapy in cancer patients by reducing general fatigue and improving the nutritional status.
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Affiliation(s)
- Hiroki Matsui
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Takahiro Einama
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan.,Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.,Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Shunsuke Shichi
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Ryo Kanazawa
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Kazuaki Shibuya
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Takashi Suzuki
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Fumihiko Matsuzawa
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Taku Hashimoto
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Shigenori Homma
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
| | - Junji Yamamoto
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
| | - Hironori Abe
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
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Noh T, Walbert T. Brain metastasis: clinical manifestations, symptom management, and palliative care. HANDBOOK OF CLINICAL NEUROLOGY 2018; 149:75-88. [PMID: 29307363 DOI: 10.1016/b978-0-12-811161-1.00006-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Patients who have brain metastases can suffer from a medley of symptoms, including headaches, seizures, cognitive impairment, fatigue, and focal deficits. As therapies have evolved, so has the management of these symptoms as patients survive longer. This chapter focuses on the clinical presentation of brain metastases, the treatment of those symptoms, and palliation in end-of-life management. Brain metastases are the most common cerebral malignancy. They can present with various symptoms, which can have significant impact on patients' quality of life throughout the course of their disease. Most of these symptoms are related to direct brain compression from the tumor or from edema. The location of the metastases will determine the focal deficits incurred and most patients will be on a course of steroids tapered according to their clinical status. The chapter includes a list of potential side-effects and considerations for management. Palliative care is an essential and important part of approaching patients with metastases. Early and clear communication about end-of-life decision making is encouraged with multiple easily accessible tools. For patients near the end of life, comfort is the ultimate goal in providing a good quality of life.
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Affiliation(s)
- Thomas Noh
- Department of Neurosurgery, Henry Ford Health System, Detroit, MI, United States
| | - Tobias Walbert
- Department of Neurosurgery, Henry Ford Health System, Detroit, MI, United States; Department of Neurology, Henry Ford Health System, Detroit, MI, United States.
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Cancer Induced Infertility and the Role of L-Carnitine: A Review for Possible Future Clinical Applications. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2017. [DOI: 10.5812/ijcm.9857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Marx W, Teleni L, Opie RS, Kelly J, Marshall S, Itsiopoulos C, Isenring E. Efficacy and Effectiveness of Carnitine Supplementation for Cancer-Related Fatigue: A Systematic Literature Review and Meta-Analysis. Nutrients 2017; 9:nu9111224. [PMID: 29112178 PMCID: PMC5707696 DOI: 10.3390/nu9111224] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 10/29/2017] [Accepted: 11/03/2017] [Indexed: 11/29/2022] Open
Abstract
Background: Carnitine deficiency has been implicated as a potential pathway for cancer-related fatigue that could be treated with carnitine supplementation. The aim of this systematic literature review and meta-analysis was to evaluate the literature regarding the use of supplemental carnitine as a treatment for cancer-related fatigue. Methods: Using the PRISMA guidelines, an electronic search of the Cochrane Library, MEDLINE, Embase, CINAHL and reference lists was conducted. Data were extracted and independently assessed for quality using the Academy of Nutrition and Dietetics evidence analysis by two reviewers. In studies with positive quality ratings, a meta-analysis was performed using the random-effects model on Carnitine and cancer-related fatigue. Results: Twelve studies were included for review with eight reporting improvement in measures of fatigue, while four reported no benefit. However, many studies were non-randomized, open-label and/or used inappropriate dose or comparators. Meta-analysis was performed in three studies with sufficient data. Carnitine did not significantly reduce cancer-related fatigue with a standardized mean difference (SMD) of 0.06 points ((95% CI −0.09, 0.21); p = 0.45). Conclusion: Results from studies with lower risk of bias do not support the use of carnitine supplementation for cancer-related fatigue.
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Affiliation(s)
- Wolfgang Marx
- School of Allied Health, College of Science, Health and Engineering, La Trobe University, Melbourne, VIC 3086, Australia.
- Faculty of Health Sciences & Medicine, Bond University, Gold Coast, QLD 4226, Australia.
| | - Laisa Teleni
- Faculty of Health Sciences & Medicine, Bond University, Gold Coast, QLD 4226, Australia.
| | - Rachelle S Opie
- School of Allied Health, College of Science, Health and Engineering, La Trobe University, Melbourne, VIC 3086, Australia.
| | - Jaimon Kelly
- Faculty of Health Sciences & Medicine, Bond University, Gold Coast, QLD 4226, Australia.
| | - Skye Marshall
- Faculty of Health Sciences & Medicine, Bond University, Gold Coast, QLD 4226, Australia.
| | - Catherine Itsiopoulos
- School of Allied Health, College of Science, Health and Engineering, La Trobe University, Melbourne, VIC 3086, Australia.
| | - Elizabeth Isenring
- Faculty of Health Sciences & Medicine, Bond University, Gold Coast, QLD 4226, Australia.
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Badrasawi M, Shahar S, Zahara AM, Nor Fadilah R, Singh DKA. Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial. Clin Interv Aging 2016; 11:1675-1686. [PMID: 27895474 PMCID: PMC5117993 DOI: 10.2147/cia.s113287] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. Methodology This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. Results The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine (P<0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. Conclusion L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults.
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Affiliation(s)
- M Badrasawi
- Dietetic Programme, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; Nutrition Program, Faulty of Applied Sciences, Palestine Polytechnic University, Hebron, Palestine
| | - Suzana Shahar
- Dietetic Programme, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - A M Zahara
- Dietetic Programme, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - R Nor Fadilah
- Biomedical Programme, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Devinder Kaur Ajit Singh
- Physiotherapy Programme, School of Rehabilitation Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Cats in Positive Energy Balance Have Lower Rates of Adipose Gain When Fed Diets Containing 188 versus 121 ppm L-Carnitine. ScientificWorldJournal 2016; 2016:2649093. [PMID: 27652290 PMCID: PMC5019939 DOI: 10.1155/2016/2649093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 07/12/2016] [Accepted: 08/02/2016] [Indexed: 11/17/2022] Open
Abstract
L-carnitine (LC) is included in select adult feline diets for weight management. This study investigated whether feeding adult cats with diets containing either 188 ppm of LC (LC188) or 121 ppm of LC (LC121) and feeding them 120% of maintenance energy requirement (MER) resulted in differences in total energy expenditure (EE), metabolic fuel selection, BW, body composition, and behavior. Cats (n = 20, 4 ± 1.2 yrs) were stratified for BCS and randomly assigned to one of two dietary treatments and fed for 16 weeks. BW was measured weekly, and indirect calorimetry, body composition, physical activity, play motivation, and cognition were measured at baseline and throughout the study. A mixed, repeated measures, ANCOVA model was used. Cats in both treatments gained BW (P < 0.05) throughout the study, with no differences between treatments at any time point (P > 0.05). There were no differences in body composition between groups at baseline; however, body fat (g) and body fat : lean mass ratio were greater in cats fed LC121 in contrast to cats fed LC188 (P < 0.05) on week 16. No other outcomes differed between treatments (P > 0.05). Supplying dietary LC at a dose of at least 188 ppm may be beneficial for the health and well-being of cats fed above MER.
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Tsai MY, Hung YC, Chen YH, Chen YH, Huang YC, Kao CW, Su YL, Chiu HHE, Rau KM. A preliminary randomised controlled study of short-term Antrodia cinnamomea treatment combined with chemotherapy for patients with advanced cancer. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:322. [PMID: 27565426 PMCID: PMC5002173 DOI: 10.1186/s12906-016-1312-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 08/23/2016] [Indexed: 01/19/2023]
Abstract
Background Antrodia cinnamomea (AC) is a popular medicinal mushroom in Taiwan that has been widely used for treatment of various cancers. Few clinical studies have reported its application and efficiency in therapeutic chemotherapy strategies. We performed a double-blind, randomized clinical study to investigate whether AC given for 30 days had acceptable safety and efficacy in advanced cancer patients receiving chemotherapy. Methods Patients with advanced and/or metastatic adenocarcinoma, performance status (PS) 0–2, and adequate organ function who had previously been treated with standard chemotherapy were randomly assigned to receive routine chemotherapy regimens with AC (20 ml twice daily) orally for 30 days or placebo. The primary endpoint was 6-month overall survival (OS); the secondary endpoints were disease control rate (DCR), quality of life (QoL), adverse event (AE), and biochemical features within 30 days of treatment. Results From August 2010 to July 2012, 37 subjects with gastric, lung, liver, breast, and colorectal cancer (17 in the AC group, 20 in the placebo group) were enrolled in the study. Disease progression was the primary cause of death in 4 (33.3 %) AC and 8 (66.7 %) placebo recipients. Mean OSs were 5.4 months for the AC group and 5.0 months for the placebo group (p = 0.340), and the DCRs were 41.2 and 55 %, respectively (p = 0.33). Most hematologic, liver, or kidney functions did not differ significantly between the two groups, but platelet counts were lower in the AC group than in the placebo group (p = 0.02). QoL assessments were similar in the two groups, except that the AC group showed significant improvements in quality of sleep (p = 0.04). Conclusions Although we found a lower mortality rate and longer mean OS in the AC group than in the control group, A. cinnamomea combined with chemotherapy was not shown to improve the outcome of advanced cancer patients, possibly due to the small sample size. In fact, the combination may present a potential risk of lowered platelet counts. Adequately powered clinical trials will be necessary to address this question. Trial registration ClinicalTrials.gov NCT01287286.
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Yao CA, Chen CC, Wang NP, Chien CT. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide. Nutrients 2016; 8:192. [PMID: 27043621 PMCID: PMC4848661 DOI: 10.3390/nu8040192] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Revised: 03/08/2016] [Accepted: 03/22/2016] [Indexed: 12/16/2022] Open
Abstract
The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids' oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis.
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Affiliation(s)
- Chien-An Yao
- Department of Life Science, No. 88, Sec. 4, Tingzhou Road, National Taiwan Normal University, Taipei 11677, Taiwan.
- Department of Family Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
| | - Chin-Chu Chen
- Biotechnology Center, Grape King Inc., Chung-Li 320, Taiwan.
| | - Nai-Phog Wang
- Department of Orthopedic, Kuang-Tien General Hospital, Taichung 433, Taiwan.
| | - Chiang-Ting Chien
- Department of Life Science, No. 88, Sec. 4, Tingzhou Road, National Taiwan Normal University, Taipei 11677, Taiwan.
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Gröber U, Holzhauer P, Kisters K, Holick MF, Adamietz IA. Micronutrients in Oncological Intervention. Nutrients 2016; 8:163. [PMID: 26985904 PMCID: PMC4808891 DOI: 10.3390/nu8030163] [Citation(s) in RCA: 59] [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: 11/23/2015] [Revised: 02/16/2016] [Accepted: 02/24/2016] [Indexed: 12/14/2022] Open
Abstract
Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Depending on the type of malignancy and the gender 30%-90% of the cancer patients supplement their diets with antioxidant and immuno-stabilizing micronutrients, such as selenium, vitamin C, and vitamin D, often without the knowledge of the treating physician. From the oncological viewpoint, there are justifiable concerns that dietary supplements decrease the effectiveness of chemotherapy and radiotherapy. Recent studies, however, have provided increasing evidence that treatment is tolerated better-with an increase in patient compliance and a lower rate of treatment discontinuations-when micronutrients, such as selenium, are added as appropriate to the patient's medication. Nutritional supplementation tailored to an individual's background diet, genetics, tumor histology, and treatments may yield benefits in subsets of patients. Clinicians should have an open dialogue with patients about nutritional supplements. Supplement advice needs to be individualized and come from a credible source, and it is best communicated by the physician.
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Affiliation(s)
- Uwe Gröber
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
| | - Peter Holzhauer
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
- Interdisziplinäres onkologisches Zentrum (IOZ), München, Nußbaumstrasse 12, München 80336, Germany.
- Klinik Bad Trissl, Innere Medizin II-Onkologie und Komplementärmedizin, Oberaudorf 83080, Germany.
| | - Klaus Kisters
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
- St. Anna Hospital, Medizinische Klinik I, Herne, Hospitalstrasse 19, Herne 44649, Germany.
| | - Michael F Holick
- Boston University Medical Center, 85 East Newton Street M-1033, Boston, MA 02118, USA.
| | - Irenäus A Adamietz
- Klinik für Strahlentherapie und Radio-Onkologie, Ruhr Universität Bochum (RUB), Hölkeskampring 40, Herne 44625, Germany.
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A cross-sectional study of carnitine deficiency and fatigue in pediatric cancer patients. Childs Nerv Syst 2016; 32:475-83. [PMID: 26812488 PMCID: PMC5872812 DOI: 10.1007/s00381-015-2983-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 12/18/2015] [Indexed: 10/22/2022]
Abstract
PURPOSE Carnitine deficiency has been found in cancer patients and has been associated with fatigue. This study aimed to explore the prevalence of carnitine deficiency in pediatric cancer patients and its relationship with fatigue and other potential contributing factors. METHODS Children with cancer or Langerhans cell histiocytosis who were receiving treatment or had completed therapy were eligible. Patients completed the Pediatric Functional Assessment of Chronic Illness-Fatigue, the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale, a numeric fatigue rating, and had carnitine levels obtained. Carnitine deficiency was defined as a total and/or free carnitine level less than normal for age or an acylcarnitine value higher than normal for age. RESULTS Data from 142 children aged 8-17 were analyzed. Twenty-eight of 142 (19.7 %) had decreased total and 42.8 % (12/28) had decreased free carnitine levels. No patients had elevated acylcarnitine levels or elevated ratios. Patients with versus without carnitine deficiency differed by age (p = 0.043), treatment (p = 0.037), duration since last chemotherapy (p = 0.020), and body mass index (p = 0.010), but not fatigue, when all data were analyzed together. Yet, a negative relationship between fatigue and carnitine levels was found on a subgroup (off-therapy; fatigue worse than the norm). CONCLUSION No significant association between fatigue and carnitine level was demonstrated when data from all patients were analyzed together; however, a significant yet unexpected relationship was found for patients who completed therapy and reported elevated fatigue. Given the small sample size, these results should be interpreted with caution. Future studies to explore impact upon excessive carnitine levels are warranted.
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Madeddu C, Mantovani G, Gramignano G, Macciò A. Advances in pharmacologic strategies for cancer cachexia. Expert Opin Pharmacother 2015; 16:2163-2177. [PMID: 26330024 DOI: 10.1517/14656566.2015.1079621] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Cancer cachexia is a severe inflammatory metabolic syndrome accounting for fatigue, an impairment of normal activities and, eventually, death. The loss of muscle mass associated with body weight loss is the main feature of this syndrome. AREAS COVERED The present review aims to describe the advances in the pharmacological approaches for cancer cachexia, highlighting the impact on weight loss, muscle wasting and related outcomes. EXPERT OPINION Among the pharmacological agents, attention should yet be given to the currently most widely studied drugs, such as progestogens and NSAIDs. Emerging drugs, such as ghrelin and selective androgen receptor modulators, have obtained promising results in recent randomized clinical trials. Larger sample sizes and more robust data on the effectiveness of anti-cytokine agents are needed. Any pharmacological approach to counteract cancer cachexia should always be associated with an adequate caloric intake, obtained by diet or through enteral or parenteral supplementation, if indicated. Finally, we can currently state that a combined approach that simultaneously targets the fundamental pathways involved in the pathogenesis of cancer cachexia is likely to be the most effective in terms of improvements in body weight as well as muscle wasting, function, physical performance and quality of life.
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Affiliation(s)
- Clelia Madeddu
- a 1 University of Cagliari, AOU Cagliari, Department of Medical Sciences M. Aresu , Cagliari, Italy
| | - Giovanni Mantovani
- b 2 University of Cagliari, AOU Cagliari, Department of Medical Sciences M. Aresu , Via Catalani 1b, 09100 Cagliari, Italy
| | - Giulia Gramignano
- c 3 N.S. Bonaria Hospital, Medical Oncology Unit , San Gavino, Italy
| | - Antonio Macciò
- d 4 A. Businco Hospital, Regional Referral Center for Cancer Diseases, Department of Gynecologic Oncology , Cagliari, Italy
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Mitchell SA, Hoffman AJ, Clark JC, DeGennaro RM, Poirier P, Robinson CB, Weisbrod BL. Putting evidence into practice: an update of evidence-based interventions for cancer-related fatigue during and following treatment. Clin J Oncol Nurs 2015; 18 Suppl:38-58. [PMID: 25427608 DOI: 10.1188/14.cjon.s3.38-58] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Cancer-related fatigue (CRF) has deleterious effects on physical, social, cognitive, and vocational functioning, and causes emotional and spiritual distress for patients and their families; however, it remains under-recognized and undertreated. This article critically reviews and integrates the available empirical evidence supporting the efficacy of pharmacologic and nonpharmacologic treatment approaches to CRF, highlighting new evidence since 2007 and 2009 Putting Evidence Into Practice publications. Interventions that are recommended for practice or likely to be effective in improving fatigue outcomes include exercise; screening for treatable risk factors; management of concurrent symptoms; yoga; structured rehabilitation; Wisconsin ginseng; cognitive-behavioral therapies for insomnia, pain, and depression; mindfulness-based stress reduction; and psychoeducational interventions such as anticipatory guidance, psychosocial support, and energy conservation and activity management. This information can be applied to improve the management of CRF, inform health policy and program development, shape the design of clinical trials of new therapies for CRF, and drive basic and translational research.
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Affiliation(s)
- Sandra A Mitchell
- Division of Cancer Control and Population Sciences, National Cancer Center, Bethesda, MD
| | - Amy J Hoffman
- College of Nursing, Michigan State University, East Lansing
| | - Jane C Clark
- Georgia Center for Oncology Research and Education in Atlanta
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