Article

Nutritional Intervention With Fish Oil Provides a Benefit Over Standard of Care for Weight and Skeletal Muscle Mass in Patients With Nonsmall Cell Lung Cancer Receiving Chemotherapy

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Abstract

Involuntary weight loss is a major contributor to mortality and morbidity in patients with advanced cancer. Nutritional intervention with fish oil (FO)-derived eicosapentaenoic acid (EPA) may prevent deterioration of body composition. This study compared intervention with FO with standard of care (SOC; no intervention) with regard to weight, skeletal muscle, and adipose tissue in newly referred patients with nonsmall cell lung cancer from the time of initiation to completion of first-line chemotherapy. Forty patients completed the study; there were 16 in the FO group (dose of 2.2 g of EPA/day) and 24 patients in the SOC group. Skeletal muscle and adipose tissue were measured using computed tomography images. Blood was collected and weight was recorded at baseline and throughout chemotherapy. Patients in the SOC group experienced an average weight loss of 2.3 ± 0.9 kg whereas patients receiving FO maintained their weight (0.5 ± 1.0 kg) (P = .05). Patients with the greatest increase in plasma EPA concentration after FO supplementation were found to have the greatest gains in muscle (r(2) = 0.55; P = .01). Approximately 69% of patients in the FO group gained or maintained muscle mass. Comparatively, only 29% of patients in the SOC group maintained muscle mass, and overall the SOC group lost 1 kg of muscle. No difference in total adipose tissue was observed between the 2 groups. Nutritional intervention with 2.2 g of FO per day appears to provide a benefit over SOC, resulting in the maintenance of weight and muscle mass during chemotherapy.

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... These effects can further worsen sarcopenia. The etiologic role of inflammation in sarcopenia is underlined by the fact that anti-inflammatory substances such as eicosapentaenoic acid or fish oils have been reported to increase lean body mass in lung patients with cancer [54,55]. ...
... These dietary interventions are summarized on Table 3. It is noted that most studies contain at least 2 out of 3 criteria according to EWGSOP 2, except As it is seen, several studies have been conducted using protein supplements [68,69], oral nutritional supplements with n − 3 polyunsaturated fatty acids [54,55,70], dietary counseling [71] and multimodal interventions [72][73][74]. The studies had relatively small size (10-120 subjects) and were quite heterogeneous as far as duration and results are concerned, but the results were mostly positive. ...
... More particularly, studies with oral nutritional supplement (not containing n − 3) had positive effects on physical strength [68,69]. Most [54,55,70,75] but not all [76] studies using n − 3 polyunsaturated fatty acids had an effect on muscle/lean mass and/or physical strength. In these studies the intervention started at the beginning of chemotherapy and patients had high compliance [54,55,70,75]. ...
Article
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Lung cancer is the most common cause of cancer death and is associated with malnutrition and sarcopenia. The detection of sarcopenia and conduction of simple body composition measurements, such as the phase angle (PhA) deriving from bioelectrical impedance analysis (BIA), can help to early identify, monitor, prevent and treat malnutrition. The present review aims to clarify the relationship between PhA and sarcopenia with the pathophysiology, clinical outcomes, and therapeutic aspects of lung cancer. PhA and sarcopenia are connected to lung cancer prognosis through various mechanisms including inflammation and oxidative stress, although more research is needed to identify the critical thresholds for increased mortality risk. Moreover, emphasis is given on the role of dietary interventions (oral nutritional supplementation, and dietary counseling) to manage sarcopenia and related variables in patients with lung cancer. Oral nutritional supplements and/or those containing n − 3 polyunsaturated fatty acids may have a positive effect on physical strength measures and muscle mass if administered at the beginning of chemotherapy. Data on sole dietary counseling or multimodal interventions are less promising so far. In the future, sophisticated body composition phenotypes deriving from the described methods along with artificial intelligence techniques could be used to design personalized nutrition interventions and timely treat these patients.
... The 48 articles were classified into the following categories: full text peer-reviewed manuscripts (n = 38), conference abstracts (n = 8), and clinical trial registrations (n = 2). Of the full text peer-reviewed manuscripts, the majority reported on randomized controlled trials (RCTs) (n = 18) [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51], followed by quasi-experimental trials (n = 15) [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66], retrospective cohort observational studies (n = 2) [67,68], and case studies (n = 3) [69][70][71]. Conference abstracts reported on RCTs (n = 3) [72][73][74], quasi-experimental trials (n = 4) [75][76][77][78], and a case study (n = 1) [79]. ...
... Omega-3 fatty acids, EPA and DHA, were the most commonly investigated dietary supplement overall (n = 18), and were studied in nine RCTs [37,39,44,[47][48][49][50][51]80], six quasiexperimental trials [54,55,58,63,65,78], one observational study [67], and two case studies [69,71]. Omega-3 fatty acids were administered in the form of free EPA acids [65], purified EPA + DHA capsules [69], krill oil capsules [78], fish oil capsules [37,39,47,55], fish oil liquid [55], marine phospholipids [63], or in fortified ONS [44,[48][49][50][51]54,58,67,71,80]. ...
... Omega-3 fatty acids, EPA and DHA, were the most commonly investigated dietary supplement overall (n = 18), and were studied in nine RCTs [37,39,44,[47][48][49][50][51]80], six quasiexperimental trials [54,55,58,63,65,78], one observational study [67], and two case studies [69,71]. Omega-3 fatty acids were administered in the form of free EPA acids [65], purified EPA + DHA capsules [69], krill oil capsules [78], fish oil capsules [37,39,47,55], fish oil liquid [55], marine phospholipids [63], or in fortified ONS [44,[48][49][50][51]54,58,67,71,80]. Marine phospholipids and krill oil consisted of omega-3 fatty acids that were bound to phospholipids, which were suggested by study authors to have a different uptake and metabolism from those bound to triacylglycerols (such as those in fish oil) [63,78]. ...
Article
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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.
... The screening and selection processes for the included studies are shown in Figure 2. We identified 230 potentially relevant records through multiple database searches (n = 226) and manual searching (n = 4). After excluding duplicate records (n = 11) and irrelevant articles by screening the titles and abstracts (n = 181), thirty-eight studies were evaluated in detail, of which 12 RCTs [20,21,25,[31][32][33][34][35][36][37][38][39] (692 participants) met the inclusion criteria. Smith et al. [21] and Grenon et al. [33] were not considered for meta-analysis due to the lack of numerical data for the functional outcomes in the former and the reporting of only patient-perceived walking performance in the latter. ...
... Smith et al. [21] and Grenon et al. [33] were not considered for meta-analysis due to the lack of numerical data for the functional outcomes in the former and the reporting of only patient-perceived walking performance in the latter. Finally, data from 10 RCTs (552 participants) were submitted to the meta-analysis [20,25,31,32,[34][35][36][37][38][39]. ...
... Nutrients 2020, 12, 3739 5 of 14 [20,21,25,[31][32][33][34][35][36][37][38][39] (692 participants) met the inclusion criteria. Smith et al. [21] and Grenon et al. [33] were not considered for meta-analysis due to the lack of numerical data for the functional outcomes in the former and the reporting of only patient-perceived walking performance in the latter. ...
Article
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There is increasing evidence showing the role of fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass synthesis and function. However, the role of omega-3 fatty acids remains unclear. Therefore, we conducted a meta-analysis to evaluate the potential effects of omega-3 fatty acids on sarcopenia-related performances among the elderly. Eligible literature and reports of randomized controlled trials were comprehensively searched from the PubMed, Cochrane Library, ClinicalTrials.gov, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases until July 2018. A total of 10 articles were available for the meta-analysis. There were minor benefits for muscle mass gain (0.33 kg; 95% CI: 0.05, 0.62) and timed up and go performance (−0.30 s; 95% CI: −0.43, −0.17). Subgroup analyses regarding muscle mass and walk speed indicated that omega-3 fatty acid supplements at more than 2 g/day may contribute to muscle mass gain (0.67 kg; 95% CI: 0.16, 1.18) and improve walking speed, especially for those receiving more than 6 months of intervention (1.78 m/sec; 95% CI: 1.38, 2.17). Our findings provide some insight into the effects of omega-3 fatty acids on muscle mass, especially for those taking supplements at more than 2 g/day. We also observed that a long period of omega-3 fatty acids supplementation may improve walking speed.
... The effect of EPA in cancer cachexia patients is currently unknown. Studies in patients with advanced pancreatic cancer [27,28] or in lung cancer patients undergoing chemotherapy [29] reported that EPA intake resulted in an increase in body weight or LBM. Conversely, in a study of advanced cancer patients, EPA intake did not improve nutritional status or function [30]. ...
... Conversely, in a study of advanced cancer patients, EPA intake did not improve nutritional status or function [30]. Three studies [27][28][29] found increases in muscle mass and ADLs, suggesting that EPA may be effective in preventing muscle loss and increasing muscle mass in cancer cachexia patients. ...
... The recommended intake of EPA for cancer cachexia patients is about 2 g/day. The studies that reported EPA-induced increases in body weight or muscle mass [27,29,31] generally took between 1.8 and 2.2 g. In interpreting this result, we need to consider the side effects associated with EPA overdose [26]. ...
Article
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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.
... Ninety-six patients were included in the survival analysis: 45 from the in-house glioblastoma patient data set and 51 from the TCGA-GBM data set. Subjects were aged 29-78 and 23-76 years, with median (interquartile range (IQR)) age of 55 (47-63) and 58 (51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66) in the in-house and TCGA-GBM data sets, respectively. There were 34 males (75.6%) in the in-house data set and 33 males (64.7%) in the TCGA-GBM data set. ...
... stratification to shorter, hypo-fractionated radiotherapy or temozolomide monotherapy, for which there is evidence of better outcomes in frail patients [48][49][50]. Our work suggests the possibility of using deep learningbased screening of sarcopenia in cancer care, without additional scanning time, cost or radiation exposure; this could inform muscle preservation interventions, such as nutrition, physiotherapy and pharmacotherapy [51][52][53]. Our tool is time and memory efficient, is applicable to large data sets and real-time assessment without specialist hardware and thus can feasibly be deployed in a routine clinical workflow. ...
Article
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Background Glioblastoma is the commonest malignant brain tumour. Sarcopenia is associated with worse cancer survival, but manually quantifying muscle on imaging is time-consuming. We present a deep learning-based system for quantification of temporalis muscle, a surrogate for skeletal muscle mass, and assess its prognostic value in glioblastoma. Methods A neural network for temporalis segmentation was trained with 366 MRI head images from 132 patients from 4 different glioblastoma data sets and used to quantify muscle cross-sectional area (CSA). Association between temporalis CSA and survival was determined in 96 glioblastoma patients from internal and external data sets. Results The model achieved high segmentation accuracy (Dice coefficient 0.893). Median age was 55 and 58 years and 75.6 and 64.7% were males in the in-house and TCGA-GBM data sets, respectively. CSA was an independently significant predictor for survival in both the in-house and TCGA-GBM data sets (HR 0.464, 95% CI 0.218–0.988, p = 0.046; HR 0.466, 95% CI 0.235–0.925, p = 0.029, respectively). Conclusions Temporalis CSA is a prognostic marker in patients with glioblastoma, rapidly and accurately assessable with deep learning. We are the first to show that a head/neck muscle-derived sarcopenia metric generated using deep learning is associated with oncological outcomes and one of the first to show deep learning-based muscle quantification has prognostic value in cancer.
... EPA and DHA supplementation attenuate depletion of skeletal muscle mass in individuals with cancer, a wellestablished prognostic factor [17][18][19][20] . EPA and DHA are lower in plasma phospholipids of patients with sarcopenia compared to patients with normal muscle mass 9 . ...
... The highest concentrations of EPA and DHA in plasma phospholipids were observed in lung cancer patients who maintained or gained skeletal muscle during cancer treatment 9 . Several studies have shown an association between attenuation of muscle loss and n-3 fatty acid supplementation, however, these studies assessed fatty acid composition of plasma only and not of the muscle membrane 17,19 . ...
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Background: Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in membrane of blood plasma and serum in humans, however the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients. Methods: Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acid content of the muscle. Cut-points for fatty acids were established using optimal stratification. Results: Median survival was between 450-500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid above the cut-point compared to 720-800 days for patients below. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11-10.87), p=0.03], EPA [HR 3.92 (1.1-14.0), p=0.04] and DHA [HR 4.08 (1.1-14.6), p=0.03] when adjusted for sex. Conclusion: Lower amount of essential fatty acids in skeletal muscle membrane is predictor of survival in cancer patients. These results warrant investigation to restore depletion of bioactive fatty acids in cancer.
... Involuntary weight loss for HNC of greater than 5% in 1 month, or greater than 1 to 2% per week is a reliable indicator of malnourishment, which has been linked with treatment interruptions and hospitalization. 41 Radiation-therapy-associated weight loss can reduce the effectiveness and safety of the treatment in HNCs. 42 The weight loss that is due to obstruction, treatment, or/and sideeffects, which ceases on completion of treatment, should not be termed as cachexia, rather a result of inadequate dietary intake. ...
... Studies with underweight people affected with malignant cancers have shown that optimal nutrition can be provided with the addition of systemic anti-inflammatory treatment, and administering erythropoietin is reported to improve muscle mass as well as survival. 41 In cancer dietetics, there are no specific recommended dietary allowances for lipids. However, studies with n-3 polyunsaturated fatty acids and EPA are shown to confer beneficial effects, to improve immunity and prevent weight loss. ...
Article
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Background Weight loss is a common observation in head and neck cancer (HNC) patients and the severity depends on the modalities used. The purpose of this study was to evaluate the effectiveness of providing two capsules of fish oil supplement each day during the course of curative radiotherapy for HNC patients. Materials and Methods This was a retrospective single-center study, and files of HNC patients treated with radiotherapy between the months of January 2015 and March 2015 were evaluated. Data on gender, age, tumor, treatment details, adverse effects, weight before and at the end of the treatment, and treatment response were obtained from the patient files. The data collected were entered into Excel sheet and subjected to statistical analysis using chi-square tests, unpaired t-test, and analysis of variance with post hoc Tukey test. A p-value of 5 kg) was more in the control than in the fish oil cohort (68.89 vs. 43.48) and was significant (p = 0.042). In addition to this, the incidence of mucositis was delayed and also lesser in severity in the cohorts that had received fish oil. At the dose used, fish oil capsules did not have any adverse effects and importantly there was no significant difference in treatment response. Conclusion The results of the study indicate that administering fish oil capsules was effective in arresting weight loss and delaying and mitigating mucositis in HNC patients undergoing curative radiotherapy. Fish oil capsule has good safety profile, was devoid of any toxic effects, and has a good clinical application value.
... In the current trial, EPA and nutrients were provided by fish oil use and dietary counselling including medical nutrition when considered necessary and/or preferred. Similar to the current results, previous trials have reported excellent compliance with fish oil use [45] and dietary counselling [39]. Thus, both seem superior to standard ONS use and are considered viable strategies to support EPA and nutrient intake. ...
Article
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Background Wasting of body mass and skeletal muscle frequently develops in patients with cancer and is associated with impaired functional ability and poor clinical outcome and quality of life. This study aimed to evaluate the feasibility and explore the effect of a multimodal intervention targeting nutritional status in patients with non-small cell lung cancer receiving primary anti-neoplastic treatment. Additionally, predictive and prognostic factors of gaining skeletal muscle were explored. Methods This was a single-centre multimodal intervention trial using a historical control group. The multimodal intervention involved fish oil intake (2 g of eicosapentaenoic acid or docosahexaenoic acid daily), regular dietary counselling and unsupervised physical exercise twice weekly during the first three cycles of primary anti-neoplastic treatment. Feasibility was assessed through recruitment rate, completion rate and compliance rate with the intervention. Differences in skeletal muscle, body weight, and physical function between the intervention and historical control groups were analysed. Factors contributing to increased skeletal muscle were explored using univariate and multivariate ordinal logistic regression analyses. Results The recruitment and completion rates were 0.49 (n=59/123) and 0.78 (n=46/59), respectively. The overall compliance rate with all five individual interventions was 0.60 (n=28/47). The individual compliance rates were 0.81 (n=38/47) with fish oil intake, 0.93 (n=44/47) with energy intake, 0.99 (n=46/47) with protein intake, 0.50 (n=26/47) with resistance exercise and 0.60 (n=27/47) with aerobic exercise. No mean differences in skeletal muscle, body weight, or physical function were found between the intervention and control groups. However, a larger proportion of patients in the intervention group gained skeletal muscle (p<0.02). The identified contributing factors of muscle gain were weight gain (OR, 1.3; p=0.01), adherence to treatment plan (OR, 4.6; p=0.02), stable/partial response (OR, 3.3; p=0.04) and compliance to the intervention (OR, 7.4; p=0.01). Age, sex, tumour stage, performance status, treatment type and baseline cachexia did not predict muscle gain. Conclusion This three-dimensional intervention in patients with lung cancer undergoing primary anti-neoplastic treatment was feasible and increased the proportion of patients gaining skeletal muscle. Dietary counselling and fish oil use were useful strategies. The motivation for conducting unsupervised physical intervention was low. Clinical trials.gov identifier: NCT04161794.
... Patients receiving an oral nutritional supplement containing fish oil (2.2 g/day EPA) compared to those receiving a control supplement maintained better body weight, lean body mass, and reported less symptoms of anorexia, fatigue, and neuropathic toxicity [279]. Beneficial effects of fish oil were observed especially in trials studying patients undergoing chemotherapy; this included improvements in physical activity and quality of life [276] (RCT; n ¼ 40; 2 g/day EPA), appetite as well as intake of energy and protein [279], body weight [277] and lean body mass [279]. In contrast to these positive findings, there were several randomized trials, including from 60 to 518 patients, which did not demonstrate a benefit associated with supplemental intake of fish oil (n ¼ 60; 1.8 g/ day EPA [282], n ¼ 200; 2.2 g/day EPA [275], n ¼ 421; 2.2 g/day EPA [283] or purified EPA ethyl ester (n ¼ 518; 0 vs 2 vs 4 g/day EPA [284]. ...
Article
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Background This practical guideline is based on the current scientific ESPEN guidelines on nutrition in cancer patients. Methods ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with cancer. Results A total of 43 recommendations are presented with short commentaries for the nutritional and metabolic management of patients with neoplastic diseases. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in cancer patients. Conclusion This practical guideline gives guidance to health care providers involved in the management of cancer patients to offer optimal nutritional care.
... Compared to control, EPA-enriched enteral nutrition resulted in a maintenance of all aspects of body composition including lean mass. Nutritional supplementation of 2.2 g of EPA/day in patients receiving chemotherapy for non-small cell lung carcinoma was associated with maintenance of weight (kg) compared to the control group (treatment; 0.5 ± 1.0, control; À2.3 kg ± 0.9, p < 0.05) [77]. In a RCT of 126 post-menopausal women, fish oil supplementation improved walking speed compared to placebo [86]. ...
Article
Background and aims Sarcopenia, defined as loss of muscle mass, strength and function, is associated with adverse clinical outcomes in patients with cirrhosis. Despite improved understanding of the multifaceted pathogenesis, there are few established therapies to treat or prevent muscle loss in this population. This narrative review examines the available literature investigating the role of nutraceuticals for the prevention or treatment of muscle wasting in chronic liver disease. Methods A comprehensive search or Medline and PubMED databases was conducted. Reference lists were screened to identify additional articles. Results A number of nutritional supplements and vitamins target the specific metabolic derangements that contribute to sarcopenia in cirrhosis including altered amino acid metabolism, hyperammonaemia and inflammation. Branched chain amino acid (BCAA) supplementation has proposed anabolic effects through dual pathways of enhanced ammonia clearance and stimulation of muscle protein synthesis. l-carnitine also has multimodal effects on muscle and shows promise as a therapy for muscle loss through anti-inflammatory, antioxidant and ammonia lowering properties. Other nutraceuticals including l-ornithine l-aspartate, omega-3 polyunsaturated fatty acids and zinc and vitamin D supplementation, may similarly have positive effects on muscle homeostasis, however further evidence to support their use in cirrhotic populations is required. Conclusion Nutraceuticals offer a promising and likely safe adjunct to standard care for sarcopenia in cirrhosis. While there is most evidence to support the use of BCAA and l-carnitine supplementation, further well-designed clinical trials are needed to elucidate their efficacy as a therapy for muscle loss in this population.
... Much of this imbalance originates with the inflammatory environment (increased IL-6 or TNF-α) induced by cancer [20]. Omega -3 PUFAs have been shown to be beneficial in preventing lean body mass loss with cancer [20,21]. ...
Article
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Cancer cachexia contributes to 30% of cancer-related deaths. There is currently no treatment or standard of care for cancer cachexia. Many nutritional interventions show promise for the treatment and or prevention of cachexia. Supplementation with omega-3 fatty acids, protein and vitamins either alone or in combination has shown some beneficial effects in the prevention and treatment of cancer cachexia. The mechanisms through which many nutritional interventions work to attenuate cachexia are just beginning to be understood. Therefore, the purpose of this review is to examine several nutritional strategies that have been investigated in the prevention and or treatment of cancer cachexia and provide evidence for the use of additional nutritional interventions to combat cachexia.
... Participants received a dosing cup, pre-marked to measure 7.5 mL, providing 1500 IU vitamin D 3 and 1125 mg eicosapentaenoic acid (EPA)+750 mg docosahexaenoic acid (DHA) as triglycerides and were instructed to consume this amount once daily. These doses were selected based on prior work demonstrating maintenance or gain of muscle mass in cancer patients undergoing chemotherapy with ingestion of these doses over 10 weeks [17]. The vitamin D dose was chosen to be higher than an effective dose of 800 IU/d associated with decreased risks of falls [18] and is commensurate with prescribed vitamin D supplements of 10,000 IU per week, to adults of 65 years and older in the province of Quebec. ...
Article
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Background Low functional capacity may lead to the loss of independence and institutionalization of older adults. A nutritional intervention within a rehabilitation program may attenuate loss of muscle function in this understudied population. Objective This pilot study assessed the feasibility for a larger RCT of a nutritional supplementation in older adults referred to an outpatient assessment and rehabilitation program. Methods Participants were randomized to receive a supplement (EXP: 2g fish oil with 1500 IU vitamin D3 1x/d + 20-30g whey protein powder with 3g leucine 2x/d) or isocaloric placebo (CTR: corn oil + maltodextrin powder) for 16 weeks. Handgrip and knee extension strength (using dynamometry), physical performance tests and plasma phospholipid n -3 fatty acids (using GCMS) were evaluated at weeks 0, 8 and 16; and lean soft tissue mass (using DXA), at weeks 0 and 16. Results Over 2 years, 244 patients were screened, 46 were eligible (18.9%), 20 were randomized, 10 completed the study (6 CTR, 4 EXP). Median age was 87 y (77–94 y; 75% women) and gait speed was 0.69 m/s; 55% had low strength, and all performed under 420m on the 6-minute walk test, at baseline. Overall self-reported compliance to powder and oil was high (96% and 85%) but declined at 16 weeks for fish oil (55%). The EXP median protein intake surpassed the target 1.2–1.5 g/kg/d, without altering usual diet. Proportions of plasma phospholipid EPA and DHA increased significantly 3- and 1.5-fold respectively, at week 8 in EXP, with no change in CTR. Participants were able to complete most assessments with sustained guidance. Conclusion Because of low eligibility, the pilot study was interrupted and deemed non-feasible; adherence to rigorous study assessments and to supplements was adequate except for long-term fish oil. The non-amended protocol may be applied to populations with greater functional capacity. Trial registration ClinicalTrials.gov NCT04454359 .
... [52] An increase of 300-400 kcal and 50% of extraprotein is required daily for an effective anabolic resistance. A favorable effect in cachetic states was seen with some nutritional supplements such as β-hydroxy-β-methylbutyrate (HMB), [53,54] eico-sapentaenoic acid, [55,56] and with L-carnitine. [57,58] However, recent review pointed out at limited evidence in favor of using HMB and L-carnitine. ...
Article
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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 the nursing fraternity in the 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 ongoing 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.
... The current study showed that cancer cachexia during chemotherapy may cause appetite loss and fatigue, and these AEs may be related to poor PS, suggesting that dietary intervention and nutritional counseling may be important for dealing with such poor PS and cancer cachexia during chemotherapy. Murphy et al. reported that nutritional intervention with 2.2 g of fish oil-derived eicosapentaenoic acid per day in patients with NSCLC appears to provide a benefit over standard of care, resulting in the maintenance of weight and muscle mass during first-line chemotherapy [23]. Mouri et al. reported the excellent feasibility of, and compliance with, multimodal intervention that included nutritional treatment during first-line chemotherapy in elderly patients with advanced cancer who were at risk for cancer cachexia [24]. ...
Article
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Introduction: This retrospective study focused on cancer cachexia in clinical practice. We evaluated the incidence of cancer cachexia and the relationship between cancer cachexia and overall survival (OS) or toxicities in patients with advanced colorectal cancer after undergoing first-line systemic chemotherapy. Methods: We examined 150 patients with colorectal cancer who underwent first-line systemic chemotherapy between February 1, 2010 and August 31, 2016 at Shizuoka Cancer Center Hospital and Kurume University Hospital. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20 kg/m2 within the past 6 months according to the European Palliative Care Research Collaborative criteria. Results: One hundred patients from Shizuoka Cancer Center and 50 from Kurume University Hospital were registered. Median age and body mass index were 65 years (range 29-85) and 21.7 kg/m2 (14.8-32.5), respectively. Cumulative incidence of cancer cachexia was 50.7% at 24 weeks, and reached 91.3% over the whole study period. OS was significantly different between patients with and without cancer cachexia within 24 weeks after starting first-line treatment, although the onset of cancer cachexia within 24 weeks could not be considered as an independent prognostic factor for OS. Severe appetite loss and fatigue tended to occur more frequently in patients with cancer cachexia within 24 weeks. Conclusion: Cancer cachexia appears to have an onset in approximately half of patients with advanced colorectal cancer within 24 weeks after starting first-line treatment. Although causal relationships were controversial, the onset of cancer cachexia within 24 weeks tends to be related to worse outcomes. Thus, it would be better to monitor weight loss leading to cachexia in patients with advanced colorectal cancer, especially within 24 weeks after starting first-line chemotherapy. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN000035002).
... There is mixed evidence for fish oil 1.5-2.2 mg daily supporting skeletal muscle mass (Murphy et al. 2011;Ries et al. 2012). Current American and European nutritional guidelines for cancer patients do not recommend cannabinoids to treat anorexia in cancer patients due lack of research and evidence at this time (Arends et al. 2017;August and Huhmann 2009). ...
Chapter
Hematopoietic stem cell transplant results in a variety of treatment-related side effects other than pain. The side effects encountered may include prolonged, late, or permanent side effects of prior cancer therapy in addition to treatment-related effects from transplant chemotherapy, prolonged cytopenias, and therapy used for supportive care during transplant. Systemic side effects to address during and after transplant may include fatigue, delirium, and malnutrition. Gastrointestinal side effects may include mucositis, nausea, vomiting, diarrhea, and constipation. In this chapter we discuss the recognition, approach, and therapeutic interventions for the management of these non-pain-related side effects of Hematopoietic stem cell transplant.
... The highest concentrations of EPA and DHA in plasma phospholipids were observed in lung cancer patients who maintained or gained skeletal muscle during cancer treatment 9 . Several studies have shown an association between attenuation of muscle loss and n-3 fatty acid supplementation, however, these studies assessed fatty acid composition of plasma only and not of the muscle membrane 17,19 . ...
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Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in erythrocytes and plasma in humans. However the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients. Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acids. Cutpoints for survival were defined using optimal stratification. Median survival was between 450 and 500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid below the cut-point compared to 720–800 days for patients above. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11–10.87), p = 0.03], EPA [HR 3.92 (1.1–14.0), p = 0.04] and DHA [HR 4.08 (1.1–14.6), p = 0.03] when adjusted for sex. Lower amounts of essential fatty acids in skeletal muscle membrane is a predictor of survival in cancer patients. These results warrant investigation to restore bioactive fatty acids in people with cancer.
... Glutathione plays a pivotal role as it acts directly as an antioxidant and maintains other components of defence in a reduced state. It has more specific effect on the function of lymphocytes via the thioredoxin system [41]. ...
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Gastro-esophageal cancer is a very common malignant tumours arising from the digestive tract. Hypoalbuminemia and weight loss often result from malnourishment. Malnourished patients have a higher incidence of mortality and morbidity causing prolonged hospital stay. To discuss the incidence and effects of Gastro-esophageal cancer related malnutrition and demonstrate different methods to solve this problem. The current review revealed that malnutrition increases the risk of complications and duration of stay in hospital and ICU in GIT cancer patients, as such, accounts for burden on ICU budget.
... Remarkably, the P. purpurogenum extracellular extract was able to improve mouse survival at all doses compared to the negative control and even the cyclophosphamide, providing 100% survival at the end of the study. The extract also preserved the body weight of the animals, preventing the wasting syndrome that is often associated with cancer and intensified by chemotherapy [49][50][51][52][53], as previously reviewed [54,55]. ...
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Background: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. Methods: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for antitumor activity. Female Swiss mice were divided into groups (n = 10/group) as follows: The negative control (CTL-), treated with a phosphate buffered solution; the positive control (CTL+), treated with cyclophosphamide (25 mg/kg); extract treatments at doses of 4, 20, and 100 mg/kg; animals without tumors or treatments (Sham); and animals without tumors treated with an intermediate dose (EAE20). All treatments were performed intraperitoneally, daily, for 15 days. Subsequently, the animals were euthanized, and the tumor, lymphoid organs, and serum were used for immunological, histological, and biochemical parameter evaluations. Results: The extract was rich in meroterpenoids. All doses significantly reduced tumor size, and the 20 and 100 mg/kg doses reduced tumor-associated inflammation and tumor necrosis. The extract also reduced the cellular infiltration of lymphoid organs and circulating TNF-α levels. The extract did not induce weight loss or renal and hepatic toxic changes. Conclusions: These results indicate that P. purpurogenum exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a valid biotechnological approach to the production of antitumor agents.
... 7,8 Because of the pathophysiological complexity and multifactorial characteristics of this clinical syndrome, there is currently no effective treatment for cancer cachexia. Current research have focused on a multimodal approach, 9 which includes adapted anticancer treatment [10][11][12] ; pharmacological treatment that aims in particular at reducing systemic inflammation, counteracting the hypercatabolic state of patients, and/or stimulating their appetite 13,14 ; nutrition care [15][16][17][18][19][20][21] ; adapted physical activity [22][23][24] ; and psychosocial care. 25,26 It is therefore essential to further improve our understanding regarding the interplay of the molecular mechanisms involved in the onset and progression of cancer cachexia. ...
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Research investigators have shown a growing interest in investigating alterations underlying skeletal muscle wasting inpatients with cancer. However, skeletal muscle dysfunctions associated with cancer cachexia have mainly been studied inpreclinical models. In the present review, we summarize the results of clinical studies in which skeletal muscle biopsies werecollected from cachectic vs. noncachectic cancer patients. Most of these studies suggest the presence of signicant physio-logical alterations in skeletal muscle from cachectic cancer patients. We suggest a hypothesis, which connects structuraland metabolic parameters that may, at least in part, be responsible for the skeletal muscle atrophy characteristic of cancercachexia. Finally, we discuss the importance of a better standardization of the diagnostic criteria for cancer cachexia, as wellas the requirement for additional clinical studies to improve the robustness of these conclusions.
... Excess or absence of white adipose tissue (WAT) can affect cancer growth in the host, modulate cancer treatment and quality of life in patients. While large adipose tissue may secrete inflammatory factors related to cancer development and impair the efficacy of chemotherapy by modifying adipokine and fatty acid composition [4], the loss of adiposity in patients with advanced cancer may contribute to mortality and even affect the response of chemotherapy against cancer [5,6]. Thus, low or high body mass are associated with elevated mortality after cancer diagnosis [6,7]. ...
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White adipose tissue is an essential reservoir of energy that stores and releases fatty acids and secretes hormones, inflammatory cytokines and adipokines in health and cancer. The adipose tissue modulates cancer development and treatment, affecting responsiveness to chemotherapy, quality of life and survival. In addition, adipose tissue is damaged by doxorubicin, which is a non-selective anticancer drug widely used in clinical practice.
... Excess or absence of white adipose tissue (WAT) can affect cancer growth in the host, modulate cancer treatment and quality of life in patients. While large adipose tissue may secrete inflammatory factors related to cancer development and impair the efficacy of chemotherapy by modifying adipokine and fatty acid composition [4], the loss of adiposity in patients with advanced cancer may contribute to mortality and even affect the response of chemotherapy against cancer [5,6]. Thus, low or high body mass are associated with elevated mortality after cancer diagnosis [6,7]. ...
... The assessment criteria for sarcopenia in liver disease was published by the Japan Society of Hepatology (13) . For nutrition and, especially, for essential fatty acids, there is an association between SMM and omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (14), (15), (16) . However, to date, SMM in patients with HCC and its association with PUFAs have not been fully examined. ...
Article
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... Interestingly, in contrast to traditional therapies, omega-3 appears to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. It was also observed that omega-3 supplementation can improve the condition of tumor patients with weight loss [78,79]. The results of omega-3 trials were well described in reviews, where readers can have a broader presentation of the subject [80,81]. ...
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Fatty acids have an important place in both biological and nutritional contexts and, from a clinical point of view, they have known consequences for diseases’ onset and development, including cancer. The use of fatty acid-based food and nutraceuticals to support cancer therapy is a multidisciplinary subject, involving molecular and clinical research. Knowledge regarding polyunsaturated fatty acids essentiality/oxidizability and the role of lipogenesis-desaturase pathways for cell growth, as well as oxidative reactivity in cancer cells, are discussed, since they can drive the choice of fatty acids using their multiple roles to support antitumoral drug activity. The central role of membrane fatty acid composition is highlighted for the application of membrane lipid therapy. As fatty acids are also known as biomarkers of cancer onset and progression, the personalization of the fatty acid-based therapy is also possible, taking into account other important factors such as formulation, bioavailability and the distribution of the supplementation. A holistic approach emerges combining nutra- and pharma-strategies in an appropriate manner, to develop further knowledge and applications in cancer therapy.
... Although it is unlikely that muscle quantity can be augmented in the short window of opportunity before surgery, some evidence suggests that exercise prehabilitation preserves fatfree mass before surgery (93) and multimodal prehabilitation attenuates loss of fat-free mass after surgery (67). Additionally, improvement in muscle quality may be attainable before surgery with the inclusion of relatively short-term(94) eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) supplementation, which has been found to attenuate intermuscular fat accumulation (95) and improve walking speed (96). The mechanism is thought to be related to signalling cascades generated when EPA and DHA are enriched in plasma membranes to support protein anabolism and attenuate inflammation in muscle (97). ...
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Mounting evidence suggests that recovery begins before the surgical incision. The pre‐surgery phase of recovery – the preparation for optimal surgical recovery – can be reinforced with prehabilitation. Prehabilitation is the approach of enhancing the functional capacity of the individual to enable them to withstand a stressful event. With this narrative review, we apply the Wilson & Cleary conceptual model of patient outcomes to specify the complex and integrative relationship of health factors that limit functional capacity before surgery. To have the greatest impact on patient outcomes, prehabilitation programs require individualized and coordinated care from medical, nutritional, psychosocial, and exercise services. This article is protected by copyright. All rights reserved.
... Daily supplementation with n-3 PUFA is associated with improving muscle mass and physical performance in healthy aging adults [190]. Improvements in muscle composition have also been observed in patients with cancer receiving omega 3 supplementation [191,192]. A metaanalysis also reported a positive effect of n-3 PUFA supplementation on measures of muscle mass (i.e., lean soft tissue, fat-free mass, skeletal muscle) and lower-body strength (i.e., quadriceps maximum voluntary capacity) in healthy and clinical populations [193]. ...
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Low muscle mass and malnutrition are prevalent conditions among adults of all ages, with any body weight or body mass index, and with acute or chronic conditions, including COVID-19. This article synthesizes the latest research advancements in muscle health and malnutrition, and their impact on immune function, and clinical outcomes. We provide a toolkit of illustrations and scientific information that healthcare professionals can use for knowledge translation, educating patients about the importance of identifying and treating low muscle mass and malnutrition. We focus on the emerging evidence of mitochondrial dysfunction in the context of aging and disease, as well as the cross-talk between skeletal muscle and the immune system. We address the importance of myosteatosis as a component of muscle composition, and discuss direct, indirect and surrogate assessments of muscle mass including ultrasound, computerized tomography, deuterated creatine dilution, and calf circumference. Assessments of muscle function are also included (handgrip strength, and physical performance tests). Finally, we address nutrition interventions to support anabolism, reduce catabolism, and improve patient outcomes. These include protein and amino acids, branched-chain amino acids, with a focus on leucine; β-hydroxy-β-methylbutyrate (HMB), vitamin D; n-3 polyunsaturated fatty acids (n-3 PUFA), polyphenols, and oral nutritional supplements. We concluded with recommendations for clinical practice and a call for action on research focusing on evaluating the impact of body composition assessments on targeted nutrition interventions, and consequently their ability to improve patient outcomes.
... Several products might be useful in contrasting sarcopenia during cancer (Branched-chain amino acids, carnitine, fish oil, Eicosapentaenoic acid (EPA), vitamins and mineral, [59]. Specifically, in lung cancer, supplementation of diet with EPA and PUFA improves the maintenance of weight and muscle mass in advanced NSCLC patients undergoing chemotherapy as well as physical and cognitive functioning [60][61][62]. ...
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Lung cancer still represents the leading cause of cancer-related death, globally. Likewise, malnutrition and inactivity represent a major risk for loss of functional pulmonary capacities influencing overall lung cancer severity. Therefore, the adhesion to an appropriate health lifestyle is crucial in the management of lung cancer patients despite the subtype of cancer. This review aims to summarize the available knowledge about dietary approaches as well as physical activity as the major factors that decrease the risk towards lung cancer, and improve the response to therapies. We discuss the most significant dietary schemes positively associated to body composition and prognosis of lung cancer and the main molecular processes regulated by specific diet schemes, functional foods and physical activity, i.e., inflammation and oxidative stress. Finally, we report evidence demonstrating that dysbiosis of lung and/or gut microbiome, as well as their interconnection (the gut–lung axis), are strictly related to dietary patterns and regular physical activity playing a key role in lung cancer formation and progression, opening to the avenue of modulating the microbiome as coadjuvant therapy. Altogether, the evidence reported in this review highlights the necessity to consider non-pharmacological interventions (nutrition and physical activity) as effective adjunctive strategies in the management of lung cancer.
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Lung cancer (LC) represents the most commonly diagnosed neoplasm worldwide for both sexes and is the leading cause of cancer mortality. Malnutrition is a comorbidity frequently found in neoplastic patients, but it remains often underestimated and thus undertreated. In this review we aim to investigate the incidence of malnutrition among LC patients according to different screening and assessment tools, to evaluate the impact of weight loss (WL) and body composition (BC) on survival, and, finally, to analyze the efficacy of different nutritional interventions in this setting. While malnutrition, WL, and BC changes can affect survival and other clinical outcomes in LC patients, the role of nutritional interventions is not yet strongly proven, and further studies are recommended. Nevertheless, screening, assessing, and eventually treating malnutrition in LC patients are strongly recommended, according to the most recent nutritional intervention guidelines for oncological patients.
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Background & Aims Reductions in skeletal muscle mass during neoadjuvant therapy can have a negative effect on short- and long-term outcomes in patients with esophageal cancer. However, effective treatment for suppressing reductions in skeletal muscle mass during neoadjuvant therapy has not been established. Methods Eighty-seven patients were included in this study who were enrolled in a previous randomized study comparing the effects of enteral nutrition (EN) and parenteral nutrition (PN) on chemotherapy-related toxicities during neoadjuvant chemotherapy in esophageal cancer patients. Changes in skeletal muscle mass during neoadjuvant therapy were compared between the two groups. Results Skeletal muscle mass index (SMI) decreased from 45.8 cm²/m² before treatment to 43.7 cm²/m² after neoadjuvant chemotherapy in 87 patients (p = 0.092). The total calorie intake during neoadjuvant therapy was equal between the two groups. SMI reduction was significantly smaller in the EN group than in the PN group (-1.4 cm²/m² vs -3.0 cm²/m², p<0.001). EN support was identified as the only independent factor adversely associated with severe SMI reduction (p < 0.001). Patients with low SMI after neoadjuvant chemotherapy were more susceptible to postoperative complications than patients with moderate SMI (47.6% vs 16.7%, p = 0.007), especially pulmonary complications (31.8% vs 10.8%, p = 0.003). Patients with low SMI after neoadjuvant chemotherapy tended to show worse prognosis than patients with moderate SMI (5-year overall survival rate: 43.8% vs 62.1%, p = 0.194). Conclusions Compared with PN support, EN support during neoadjuvant chemotherapy suppressed reductions in skeletal muscle mass in patients with esophageal cancer.
Chapter
Cancer is the second-leading cause of death worldwide. Notably, 40% of all patients suffer from cachexia, a debilitating muscle wasting syndrome that represents one of the primary causes of death in advanced cancer patients. Despite their known side effects, such as vomiting, anorexia, mucositis, neuropathy, musculoskeletal and metabolic alterations, chemotherapy treatments are the most effective and extensively used strategies against cancer. Moreover, chemotherapeutic agents may participate in and even exacerbate the pathophysiological alterations driving cachexia. Indeed, skeletal muscle atrophy and cardiac abnormalities occurring as a consequence of chemotherapy administration can worsen the response to anticancer therapies, reduce physical activity and severely impede the quality of life in cancer patients. Hence, chemotherapy-induced cachexia has recently emerged as a critical clinical problem impacting outcomes and overall survival in cancer patients. Here, we review some of the mechanism(s) through which chemotherapeutics induce musculoskeletal deficits related to cachexia. Lastly, we discuss different strategies currently under consideration to protect muscle tissue from chemotherapy-related toxicities, including nutritional interventions, mitochondria-targeted molecules, ghrelin, bisphosphonates, ACVR2B antagonists, and physical exercise.KeywordsChemotherapySkeletal muscleCachexiaMuscle weakness
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This study investigated the nephroprotective role of acylated ghrelin (AG) against DOX‐induced nephropathy and examined if the protection involves SIRT1. Rats were divided into control, control + AG, DOX, DOX + AG, DOX + AG + [D‐Lys3] ‐GHRP‐6 (a ghrelin receptor antagonist), and DOX + AG + EX‐527 (a sirt1 inhibitor). DOX was given over the first 2 weeks. AG (10 ng/kg) and both inhibitors were given as 3 doses/week for 5 weeks. AG improved the structure and the function of the kidneys, downregulated the renal expression of TGF‐β1, collagen 1A1, and α‐SMA, and inhibited the renal collagen deposition in the kidneys of DOX‐treated rats. Concomitantly, it reduced the renal levels of ROS, MDA, TNF‐α, and IL‐6 and protein levels of cytochrome‐c, TGF‐β1, Smad3, and α‐SMA in these rats. In both the control and DOX‐treated rats, AG significantly increased the renal levels of SOD and GSH, decreased the expression of cleaved caspase‐3 and Bax, increased the total levels and the nuclear activity of SIRT1, and reduced the deacetylation of p53, NF‐κB, and FOXO‐31. All the effects were abolished by the concurrent administration of EX‐527 and [D‐Lys3] ‐GHRP‐6. In conclusion, AG prevents DOX‐induced nephropathy in SIRT1 and GSHRa1‐dependent mechanism.
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We investigated the effects of long-term supplementation of omega-3 fatty acids-enriched fish oil (FO) on preserving muscle mass. We found that dietary supplementation with 5% FO has a direct impact on preventing obesity and skeletal muscle loss in rats fed a high-fat diet for 16 weeks. The increased protein expression for ubiquitin ligases atrogin-1 and muscle RING-finger protein 1 (MuRF1) and the autophagy-related protein, PTEN-induced putative kinase 1 (PINK1) in muscles were both abrogated by FO. The AKT and mammalian target of rapamycin (mTOR) phosphorylation and the AMP‐activated protein kinase (AMPK)/peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) signaling activation in muscles were up-regulated by FO. FO supplementation effectively reversed the increased plasma TNF-α levels and NF‐κB activation in muscles. These results suggest that FO supplementation prevents skeletal muscle wasting under obesity through activating AKT/mTOR and AMPK/PGC-1α signals and blocking NF-κB-mediated inflammatory pathway to improve the balance between protein synthesis and degradation.
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Background: Radiotherapy and chemotherapy in patients with lung cancer can lead to a series of problems such as malnutrition and inflammatory reaction. Some studies have shown that ω-3 polyunsaturated fatty acids (PUFAs) could improve malnutrition and regulate inflammatory reaction in these patients, but no relevant meta-analysis exists. Methods: We systematically searched randomized controlled trials of ω-3 PUFAs in the adjuvant treatment of lung cancer in the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang databases. Relevant outcomes were extracted, and we pooled standardized mean differences (SMDs) using a random or fixed-effects model. The risk of bias was evaluated according to the Cochrane Handbook (version 15.1). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: A total of 7 studies were included. The SMDs (95% CI) of body weight change, albumin change, energy intake, and protein intake at the end of intervention were 1.15 (0.50, 1.80), 0.60 (0.11, 1.09), 0.39 (-0.10, 0.89), and 0.27 (-0.04, 0.58), respectively. The SMDs (95% CI) of CRP change and TNF-α change were -3.44 (-6.15, -0.73) and -1.63 (-2.53, -0.73), respectively. Conclusions: ω-3 PUFAs can improve nutritional status and regulate indicators of inflammation in patients with lung cancer undergoing radiotherapy and chemotherapy. This study was registered in the PROSPERO (registration number: CRD42022307699).
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Bioactive compounds (bioactives) derived from plants and animals, are effective in increasing the safety and health of society through the treatment and prevention of diseases such as cancer. Fortifying conventional foods with bioactives is an accepted strategy by scientists, food manufacturers, and consumers. Milk and dairy products are among the most important foods used in our daily diet and can be a suitable option to deliver bioactives to the body, but there are challenges towards using these compounds in their original unprotected/free form. They can be degraded before reaching the target location in the body and interact with milk compounds, resulting in a negative impact on the quality characteristics of the corresponding foods. Thus, a suitable encapsulation technique can help to protect these sensitive compounds from environmental stresses and the process they encounter during the manufacture of food. This also prevents adverse interactions of bioactives with compounds in milk. This article aimed to review the recent literature about the addition of encapsulated bioactives such as vitamins, essential fatty acids, phenolic compounds, minerals, and enzymes into milk and dairy products, with a focus on common applied bioactives, methods of encapsulation, the interaction of bioactives with milk components, and the challenges facing the use of this technology in the dairy industry.
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About 60% of chemotherapeutic agents used for the treatment of cancer diseases today have been derived from natural products. While some of these agents are identical to the natural molecules found in plants; the others are semisynthetic derivative of the foundational molecule found naturally in the raw sources. Cancers have been reported to express 10 specific hallmark which are used as the key points or steps for targeted therapy against these cancers. Extending the number of these hallmarks to 12 this review article throws light on 43 natural products classifying them according to their target of action. Further, the natural products under consideration are categorized according to the level of evidence present for their anticancer activities.
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The goal of this study was to evaluate if combinations of ingredients with known anti-cachexia benefits (Fish oil-FO with either curcumin or Green tea extract-GTE), have adverse effects on tumor growth, using human carcinoma xenograft mice models. FO (EPA/DHA 360 mg/kg bw), GTE (90 mg/kg bw), and curcumin (180 mg/kg bw) were administered orally, alone or in combination, to nude mice bearing either A549 human non-small cell lung carcinoma or SW620 human colon carcinoma tumors. Bodyweight, tumor growth, survival time, and other clinical endpoints were assessed. The ingredients either alone or in combinations were well tolerated in both lung and colon tumor-bearing mice. There were no significant group differences between individual or combination treatments for tumor growth (A549 or SW620) as measured by the median time in days to endpoint of tumor volume (TTE). TTE results indicate that these ingredients (alone or combinations) did not adversely impact tumor growth. No significant differences in body weights or survival were observed between controls and treatment groups indicating no adverse health effects of the ingredients. In conclusion, FO, GTE or curcumin administered as monotherapies and in combination were well tolerated and displayed no adverse effects on tumor growth in mouse xenograft models of lung and colon cancer.
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To determine the association between fish intake and dietary polyunsaturated fatty acids (PUFA) and incidence of lung cancer. We systematically reviewed and meta-analyzed all available studies to quantify the associations of fish and PUFA consumption with risk of lung cancer. Relative risk (RR) with 95% confidence interval (CI) was calculated. 13 population-based prospective cohort studies involving 1,785,000 participants and two randomized control trials were included. Our study demonstrated that dietary PUFA significant reduced risk of lung cancer for men (RR 0.99, 95%CI 0.98 to 1.00) and the U.S. population (RR 0.99, 95%CI 0.98 to 1.00). Dose-response analysis indicated that a 5 g/day increment of dietary PUFA was associated with 5% lower risk of lung cancer (RR 0.95, 95%CI 0.91 to 0.99). In addition, PUFA supplementation is significant improved overall survival in patients with lung cancer (RR 1.98, 95%CI 1.09 to 3.59). Our study showed an inverse association between dietary PUFA and risk of lung cancer in males and among the U.S. population. Although smoking cessation is the single biggest factor associated with lung cancer risk reduction, this study adds to a growing body of evidence that diet may have a role in modestly reducing lung cancer risk.
Chapter
Cachexia is one of the most devastating conditions associated to cancer. Severe wasting produces both a high symptomatic burden and secondary psychological distress, and it is estimated to directly cause 20% of cancer deaths. Its pathophysiology is characterized by tumor-host interactions that, mediated mainly by tumor- and host-derived molecules, lead to profound metabolic changes that predominantly affect the central nervous system, the gastrointestinal tract, the adipose and the skeletal muscle tissue, and the immune system. Due to its clinical variability, consensus definitions were established, which defined cancer cachexia as the consequence of a variable combination of decreased oral intake and impaired metabolism that is refractory to conventional nutritional support. The establishment of clinical stages in which lean body mass evaluations were progressively incorporated to improve tissue wasting detection has increasingly stressed the early detection of the syndrome. Although cancer cachexia treatment has been an active research field in the last decades, no single drug has clinically demonstrated a robust benefit, and progestogens remain the only drugs specifically approved for this condition. Ongoing research is being conducted to elucidate whether intervening earlier in the natural history of the syndrome or combining drugs, nutritional interventions, and/or physical activity programs is able to improve outcomes. Additionally, the bottleneck-shaped pathophysiology of cancer cachexia, which begins within tumor cells, raises hope that better oncologic treatments will decisively contribute to decrease the dramatic impact of this condition.
Article
Background & Aims Malnutrition occurs frequently in patients with cancer during and after radiotherapy to the gastrointestinal (GI) and pelvic area and can lead to negative outcomes. N-3 fatty acids from fish, especially eicosapentaenoic acid (EPA) may possess anticachectic properties. The aim of this study was to investigate the effect of two nutritional interventions; dietary counselling and a daily oral nutritional supplement (ONS) containing 33.8 g of protein and 2.2 g EPA and 1.1 g docosahexaenoic acid (DHA) or standard care, including dietary counselling and protein supplementation when needed. Methods Outpatients commencing radiotherapy to the GI area were randomized to receive dietary counselling and daily supplementation over a 5-7-week period or standard care. Outcome parameters were measured at baseline (onset of radiotherapy), week 5, and 12 weeks after commencing radiotherapy, with one additional measurement of body weight at week 2. Quality of life (QoL) was measured using the EORTC QLQ-C30 questionnaire. Radiotherapy-related side effects were assessed using a questionnaire developed specifically for this study. Data from a historical control group collected in a previous observational study were included in this study to compare incidence of weight loss. Results In total, 30 patients were recruited to this study and 26 patients were enrolled and randomised. The rate of withdrawals was 7.7% at week 2, 15.4% at week 5, and 19.2% at week 12. In total, 22 patients completed the intervention. All the patients in the ONS-group and 85% in the control group experienced weight-loss. Using the intention to treat principle, there were no significant differences between groups in any of the outcomes. All patients experienced side effects. Five out of 11 patients consumed more than 75% of prescribed dose of the fish oil enriched oral nutritional supplement. Post hoc analysis showed that at week 2 the weight changed in high-compliant patients was +1.7% (1.0 to 2.6) compared with -0.7% (-2.8 to -0.1) in low compliant patients (p<0,01). The results indicated a dose-response relationship, as correlation analysis recovered a significant positive correlation between weight change and compliance to the fish oil enriched nutritional supplement at both week 2 and 5 (p<0.05 and p<0.01, respectively), but not at week 12, indicating a dose-response relationship during radiotherapy but not after. The proportion of patients experiencing weight loss throughout the study period was higher in this study (84.2%) than in the historical control group (73%) (p<0.05%). Conclusion This study showed no effect from dietary counselling and intended protein/fish-oil supplementation on weight loss, quality of life, and nutritional intake, micronutrient status in plasma or radiotherapy-related side effects compared to the control group. However, the compliance to the fish oil enriched oral nutritional supplement was low. Post hoc analysis of dose-response relations indicate a positive correlation between the compliance and the ability to reduce weight loss in cancer patients during radiotherapy treatment. Trial registration ClinicalTrials.gov Identifier NCT04687124.
Article
Although data indicate omega-3 polyunsaturated fatty acids are beneficial nutrients in cancer therapy, the evidences for efficacy of nutritional interventions during chemo (radio) therapy are still limited. The leading goal of the present meta-analysis was to summarize randomized controlled trials involving the administration of ω-3 PUFA-enriched oral nutritional supplements during chemo (radio) therapy, and evaluate the effects on nutritional status and clinical outcomes in patients. We systematically searched PubMed, Embase, Web of Science, Cochrane databases to identify interventions assessing body weight, BMI, immune and inflammatory indicators, plasma omega-3 fatty acids and adverse events, with subgroup analyses for region, types of ω-3 fatty acids, dose, duration and dosage form. In total, 22 studies including 1155 participants met the inclusion criteria. Meta-analysis showed a significant increase in body weight (BW) (WMD = 0.59 kg, 95% CI: 0.06, 1.13, P = 0.03), body mass index (BMI) (WMD = 0.43 kg/m², 95% CI: 0.07, 0.79, P = 0.02), and plasma total ω-3 fatty acids (SMD = 2.52, 95% CI: 1.27, 3.78, P<0.0001), and a significant reduction in plasma levels of C-reactive protein (CRP) (SMD= −0.53, 95% CI: −0.80, −0.25, P = 0.0001), tumor necrosis factor-α (TNF-α) (WMD = −0.40 pg/mL, 95% CI: −0.80, −0.01, P = 0.05), interleukin 6 (IL-6) (WMD = −1.25 pg/mL, 95% CI: −2.41, −0.10, P = 0.03) and the incidence of adverse events (RR= 0.72, 95% CI: 0.54, 0.95, P = 0.02). However, plasma albumin levels (WMD = 0.02 mg/dL, 95% CI: −0.13, 0.18, P = 0.75) was remained unaffected. Overall, our meta-analysis provides evidences that the consumption of ω-3 PUFA-enriched oral nutritional supplements exert beneficial effects on nutritional status and clinical outcomes in patients undergoing chemo (radio) therapy.
Article
The purpose of this study was to evaluate the effects of highly concentrated enteral nutrition (ENORAS®, Otsuka Pharmaceutical Factory, Tokushima, Japan; hereinafter, ED) on the maintenance of nutritional status and bodyweight in chemotherapy-treated patients with gastrointestinal cancer who received ED between July 2019 and January 2020. For 21 patients (15 men and 6 women, age range: 57-87 years old), we investigated serum albumin level, cholinesterase level, lymphocyte count, hemoglobin level, and bodyweight at baseline and after receiving ED. None of the patients showed any differences in albumin level, cholinesterase level, lymphocyte count, hemoglobin level, or bodyweight before and after receiving ED. Survivors had significantly favorable changes in cholinesterase level compared with non-survivors (p=0.0258). The group that received ED for 30 days or longer tended to show more favorable changes in bodyweight than the group that received ED for less than 30 days (p=0.0696). The group with stage I-III disease had more favorable changes in albumin level than the group with stage IV disease or recurrence (p=0.0932). Our results suggest that the ED is useful for helping to maintain nutritional status and bodyweight in chemotherapy-treated patients with gastrointestinal cancer.
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Many patients with lung cancer undergo surgery, which can increase the risk for muscle loss, leading to worsened outcomes. A multimodal prehabilitation intervention integrating dietary and muscle assessment may help clinicians better understand changes in these outcomes. This pilot assessed feasibility of multimodal prehabilitation in early-stage surgical lung cancer patients and explored relationships between body composition, muscle characteristics and dietary intake, as well as muscle changes due to prehabilitation. Patients were randomized to 1 of 2 groups: multimodal prehabilitation including nutritional supplements (fish oil with vitamin D3 + whey protein with leucine), exercise and relaxation, or standard of care. Physical function, dietary intake and muscle were evaluated at 0 and 4 weeks pre-operatively. Of 87 patients assessed for eligibility, 34 (39%) were randomized and 3 (9%) were lost to follow-up. Median age was 69 years and baseline protein intake was 1.0 g/kg/day. Adherence to exercise (86%) and supplements was high (93%); 3 patients (16%) reported side effects. Supplements significantly increased protein, omega-3 fatty acid, leucine and vitamin D intake. There were no significant changes in muscle characteristics. Multimodal prehabilitation with dietary and muscle analyses proved to be feasible. An adequately powered randomized controlled trial is warranted. ClinicalTrials.gov registration no: NCT04610606. Novelty: Multimodal prehabilitation incorporating dietary assessment and muscle analysis is feasible for early-stage surgical lung cancer patients. An adequately powered randomized controlled trial is warranted to further explore functional and post-operative outcomes.
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Introduction: No global consensus exists on diagnostic criteria for malnutrition. Muscular deficits and functional impairments are major components of available malnutrition diagnostic frameworks (SGA, MCC, EDC, GLIM), because these facets of nutritional status significantly impact outcomes. The purpose of this review is to explore which body composition (BCA) and functional status assessment (FSA) tools are being used for nutritional assessment (NA) and monitoring response to nutritional interventions (RNI) in adult inpatients. Methods: A literature search of Embase, Medline (Ovid), Web of Science and Cochrane Central was performed to identify studies that utilized BCA and/or FSA tools for NA (along with an accepted NA diagnostic framework) and/or for monitoring RNI in adult inpatients. Results: The search yielded 3,667 articles; 94 were included in the review. The number of studies using BCA and/or FSA tools for NA was 47, and for monitoring RNI was also 47. 79% of studies used bioimpedance for BCA and 97% that included FSA utilized hand-grip strength. When compared against sets of diagnostic criteria, many of the BCA and FSA tools showed promising associations with nutritional status. Conclusions: Bioimpedance methods are the most widely used bedside BCA tools, and HGS is the most widely used FSA tool; however, these methods are being used with a variety of protocols, algorithms, and interpretation practices in heterogeneous populations. In order to create a standardized NSA process there is a need for validation studies on bedside methods and development of globally standardized assessment protocols in clinical inpatient settings. This article is protected by copyright. All rights reserved.
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PurposeTo clarify the prognostic value of the preoperative nutrition status of patients undergoing conversion surgery (CS) for initially unresectable pancreatic adenocarcinoma (UR-PA).Methods The subjects of this retrospective study were 41 consecutive patients with initially UR-PA treated with chemo-/radiotherapy and subsequent CS between 2007 and 2014, at Tohoku University Hospital. The preoperative Glasgow Prognostic Score (GPS) was 0, conveying normal nutrition, in 25 patients (N group) and 1–2, conveying malnutrition, in 16 patients (M group). The clinicopathological factors influencing overall survival were defined by uni- and multivariate analyses.ResultsThe M group had a significantly worse prognosis than the N group (median overall survival (mOS) 9.6 vs 40.7 months, p = 0.001). Multivariate analysis identified a GPS of 1–2 as an independent predictor of worse prognosis [hazard ratio (HR)3.437, p = 0.032], followed by CA19-9 elevation before CS (HR4.089, p = 0.012) and pathological lymph node metastases (HR2.314, p = 0.046). Patients who maintained a favorable nutritional status (GPS 0) during preoperative treatment had a significantly better prognosis, whereas those whose nutritional status deteriorated (elevated to GPS 1–2) had poorer survival (mOS 40.7 vs. 9.7 months, p = 0.003)Conclusion Preoperative malnutrition status (GPS 1–2) is considered an independent predictor of a worse prognosis for patients undergoing CS for initially UR-PA.
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The most studied n-3 polyunsaturated fatty acids (n-3 PUFAs) are eicosapentaenoic acid (EPA; 20:5n−3) and docosahexaenoic acid (DHA; 22:6n−3), and their intake seem to have a positive effect on skeletal muscle. This systematic review and meta-analysis aims to investigate the effect of n-3 EPA and DHA supplementation on fat free mass, and on different indexes of physical performance in the elderly. Eligible studies included RCT studies that investigated EPA and DHA intervention. Random-effects models have been used in order to estimate pooled effect sizes, the mean differences, and 95% CIs. Findings from 14 studies (n = 2220 participants) lasting from 6 to 144 weeks have been summarized in this article. The meta-analyzed mean differences for random effects showed that daily n-3 EPA + DHA supplementation (from 0.7 g to 3.36 g) decreases the time of Time Up and Go (TUG) test of -0.28 seconds (CI 95% -0.43, -0.13;). No statistically significant effects on physical performance indicators, such as 4-meter Walking Test, Chair Rise Test and Handgrip Strength, have been found. The fat free mass follows an improvement trend of +0.30 kg (CI 95% -0.39, 0.99) but not statistically significant. N-3 EPA + DHA supplementation could be a promising strategy in order to enhance muscle quality and prevent or treat frailty.
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Fish contain many important nutrients and are primarily known for high n-3 polyunsaturated fatty acids (n-3 PUFA) content. Studies have shown that supplementation of fish oil-derived n-3 PUFA improves muscle mass and strength. Here, we hypothesized that fish consumption might improve muscle strength. To test this hypothesis, we performed this cross-sectional study (n=29,084) in Tianjin, China. The frequency of fish consumption was assessed using a valid self-administered food frequency questionnaire. Handgrip strength (HGS) was used as the indicator of muscle strength, and was measured using a handheld digital dynamometer. Analysis of covariance was used to examine the relationship between fish consumption and HGS. In men, after adjusted potential confounding factors, the least square means (LSM) (95% confidence intervals (CI)) of HGS across saltwater fish consumption categories were 41.5 (41.1, 43.7) kg for <1 time/week, 44.6 (43.2, 45.8) kg for 1 time/week, and 44.7 (43.3, 46.1) kg for ≥2-3 times/week (P for trend <0.001). In men, the LSM (95% CI) of HGS across the ascending quartiles of dietary n-3 PUFA intake were 43.6 (43.2, 44.4) kg, 43.7 (43.2, 44.6) kg, 44.4 (43.0, 45.8) kg, and 44.6 (43.1, 46.0) kg (P for trend <0.01). The results showed that saltwater fish consumption was positively related to HGS in men, but not in women, suggesting that saltwater fish contain nutrients that may be used to improve HGS.
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Upwards of 50% of newly diagnosed advanced lung cancer patients have severe muscle wasting (sarcopenia). Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in advanced cancer has been shown to attenuate lean tissue wasting. However, the relationship between muscle mass and plasma (n-3) fatty acids in the absence of supplementation is unclear. We aimed to determine how plasma phospholipid (n-3) fatty acids relate to sarcopenia and change in muscle mass in non-small cell lung cancer patients receiving chemotherapy. Computed tomography images were used to measure muscle mass. Patients were classified as sarcopenic or nonsarcopenic based on sex-specific cutpoints. Change in muscle mass during chemotherapy (2.5 mo) was calculated and patients were divided into quartiles based on the rate of muscle loss or gain. Patients with sarcopenia had lower plasma EPA (16.7 +/- 2.1 micromol/L vs. 31.6 +/- 4.4 micromol/L; P = 0.001), DHA (36.6 +/- 4.0 micromol/L vs. 55.3 +/- 4.0 micromol/L; P = 0.003), and Sigma(n-3) fatty acids (63.6 +/- 5.6 micromol/L vs. 95.0 +/- 7.7 micromol/L; P = 0.002) than nonsarcopenic patients. Patients with maximal muscle loss (mean - 3.5 kg) had lower plasma EPA (12.2 +/- 3.3 micromol/L vs. 35.0 +/- 7.1 micromol/L; P = 0.03), DHA (26.9 +/- 8.7 micromol/L vs. 59.6 +/- 5.3 micromol/L; P = 0.01), and Sigma(n-3) fatty acids (57.8 +/- 13.5 micromol/L vs. 104.6 +/- 11.1 micromol/L; P = 0.005) compared with patients who were gaining muscle (mean +1 kg). Plasma (n-3) fatty acids are depleted in cancer patients with sarcopenia, which may contribute to accelerated rates of muscle loss.
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Human body composition is important in numerous cancer research domains. Our objective was to evaluate clinically accessible methods to achieve practical and precise measures of body composition in cancer patients. Dual-energy X-ray absorptiometry (DXA)-based analysis of fat and fat-free mass was performed in 50 cancer patients and compared with bioelectrical impedance analysis (BIA) and with regional computed tomography (CT) images available in the patients' medical records. BIA overestimated or underestimated fat-free mass substantially compared with DXA as the method of reference (up to 9.3 kg difference). Significant changes in fat-free mass over time detected with DXA in a subset of 21 patients (+2.2 +/- 3.2%/100 days, p = 0.003), was beyond the limits of detection of BIA. Regional analysis of fat and fat-free tissue at the 3rd lumbar vertebra with either DXA or CT strongly predicted whole-body fat and fat-free mass (r = 0.86-0.94; p < 0.001). CT images provided detail on specific muscles, adipose tissues and organs, not provided by DXA or BIA. CT presents great practical significance due to the prevalence of these images in patient diagnosis and follow-up, thus marrying clinical accessibility with high precision to quantify specific tissues and to predict whole-body composition.
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Previous studies have suggested that administration of oral eicosapentaenoic acid (EPA) will stabilize weight in patients with advanced pancreatic cancer. The aim of the present study was to determine if a combination of EPA with a conventional oral nutritional supplement could produce weight gain in these patients. Twenty patients with unresectable pancreatic adenocarcinoma were asked to consume two cans of a fish oil-enriched nutritional supplement per day in addition to their normal food intake. Each can contained 310 kcal, 16.1 g protein and 1.09 g EPA. Patients were assessed for weight, body composition, dietary intake, resting energy expenditure (REE) and performance status. Patients consumed a median of 1.9 cans day(-1). All patients were losing weight at baseline at a median rate of 2.9 kg month(-1). After administration of the fish oil-enriched supplement, patients had significant weight-gain at both 3 (median 1 kg, P= 0.024) and 7 weeks (median 2 kg, P = 0.033). Dietary intake increased significantly by almost 400 kcal day(-1) (P = 0.002). REE per kg body weight and per kg lean body mass fell significantly. Performance status and appetite were significantly improved at 3 weeks. In contrast to previous studies of oral conventional nutritional supplements in weight-losing cancer patients, this study suggests that an EPA-enriched supplement may reverse cachexia in advanced pancreatic cancer.
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Eicosapentaenoic acid (EPA) has been shown to modulate aspects of the inflammatory response that may contribute to weight loss in cancer. This study aimed to evaluate the acceptability and effects of oral supplementation with high-purity EPA in weight-losing patients with advanced pancreatic cancer. Twenty-six patients were entered into the study. EPA (95% pure) was administered as free acid starting at 1 g/day; the dose was increased to 6 g/day over four weeks, and then a maintenance dose of 6 g/day was administered. Patients were assessed before EPA and at 4, 8, and 12 weeks while receiving EPA, for weight, body composition, hematologic and clinical chemistry variables, acute-phase protein response, and performance status. Overall survival was noted. Supplementation was well tolerated, with only five patients experiencing side effects possibly attributable to the EPA. Before starting EPA, all patients had been losing weight at a median rate of 2 kg/mo. In general, after EPA supplementation, weight was stable. After four weeks of EPA supplementation, patients had a median weight gain of 0.5 kg (p = 0.0009 vs. rate of weight loss at baseline), and this stabilization of weight persisted over the 12-week study period. Total body water as a percentage of body weight remained stable, as did the proportion of patients with an acute-phase protein response, patients' nutritional intake, and performance status. Overall median survival from diagnosis in this study was 203 days. This study suggests that EPA is well tolerated, may stabilize weight in cachectic pancreatic cancer patients, and should be tested as an anticachectic agent in controlled trials.
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Obesity is a frequent cause of insulin resistance and poses a major risk for diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. We tested the hypothesis that dietary lipid deprivation may selectively deplete intramyocellular lipids, thereby reversing insulin resistance. Whole-body insulin sensitivity (by the insulin clamp technique), intramyocellular lipids (by quantitative histochemistry on quadriceps muscle biopsies), muscle insulin action (as the expression of Glut4 glucose transporters), and postprandial lipemia were measured in 20 morbidly obese patients (BMI = 49 +/- 8 [mean +/- SD] kg x m(-2)) and 7 nonobese control subjects. Patients were restudied 6 months later after biliopancreatic diversion (BPD; n = 8), an operation that induces predominant lipid malabsorption, or hypocaloric diet (n = 9). At 6 months, BPD had caused the loss of 33 +/- 10 kg through lipid malabsorption (documented by a flat postprandial triglyceride profile). Despite an attained BMI still in the obese range (39 +/- 8 kg x m(-2)), insulin resistance (23 +/- 3 micromol/min per kg of fat-free mass; P < 0.001 vs. 53 +/- 13 of control subjects) was fully reversed (52 +/- 11 micromol/min per kg of fat-free mass; NS versus control subjects). In parallel with this change, intramyocellular-but not perivascular or interfibrillar-lipid accumulation decreased (1.63 +/- 1.06 to 0.22 +/- 0.44 score units; P < 0.01; NS vs. 0.07 +/- 0.19 of control subjects), Glut4 expression was restored, and circulating leptin concentrations were normalized. In the diet group, a weight loss of 14 +/- 12 kg was accompanied by very modest changes in insulin sensitivity and intramyocellular lipid contents. We conclude that lipid deprivation selectively depletes intramyocellular lipid stores and induces a normal metabolic state (in terms of insulin-mediated whole-body glucose disposal, intracellular insulin signaling, and circulating leptin levels) despite a persistent excess of total body fat mass.
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N-3 fatty acids, especially eicosapentaenoic acid (EPA), may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein +/- 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. At enrolment, patients' mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (delta weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM (Delta LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.
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Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA. Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d. A smaller percentage taking the EPA supplement gained >or= 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P =.004). Combination therapy resulted in weight gain of >or= 10% in 11% of patients (P =.17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P =.69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P =.004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable. This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone.
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To investigate whether the substitution of fish oil for visible fats in a control diet (52% carbohydrates, 16% protein, 32% fat; P:S 0.2) influences body fat mass and substrate oxidation in healthy adults. Six volunteers (5 men; 23 +/- 2 y; BMI: 21.9 +/- 1.6) were fed a control diet (C) ad libitum during a period of three weeks and, 10-12 weeks later, the same diet where 6 g/d of visible fat were replaced by 6 g/d of fish oil (FO) for another three weeks. Energy intakes (IKA-calorimeter) were unchanged. Body fat mass (Dual-energy X-ray absorptiometry) decreased with FO (-0.88 +/- 0.16 vs -0.3 +/- 0.34 kg; FO vs C; P < 0.05). When adjusted for lean body mass (Ancova), resting metabolic rate (indirect calorimetry) was unchanged. Basal respiratory quotient decreased with FO (0.815 +/- 0.02 vs 0.834 +/- 0.02; P < 0.05) and basal lipid oxidation increased with FO (1.06 +/- 0.17 vs 0.87 +/- 0.13 mg kg(-1) min(-1); P < 0.05). Dietary FO reduces body fat mass and stimulates lipid oxidation in healthy adults.
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The aim of the study was to assess the total energy expenditure (TEE), resting energy expenditure (REE) and physical activity level (PAL) in home-living cachectic patients with advanced pancreatic cancer. The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid (EPA) and administered over an 8-week period was also determined. In total, 24 patients were studied at baseline. The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry. Patients were studied at baseline and then randomised to either oral nutritional supplement. Measurements were repeated at 8 weeks. At baseline, REE was increased compared with predicted values for healthy individuals (1387(42) vs 1268(32) kcal day(-1), P=0.001), but TEE (1732(82) vs 1903(48) kcal day(-1), P=0.023) and PAL (1.24(0.04) vs 1.50) were reduced. After 8 weeks, the REE, TEE and PAL of patients who received the control supplement did not change significantly. In contrast, although REE did not change, TEE and PAL increased significantly in those who received the n-3 (EPA) enriched supplement. In summary, patients with advanced pancreatic cancer were hypermetabolic. However, TEE was reduced and this was secondary to a reduction in physical activity. The control energy and protein dense oral supplement did not influence the physical activity component of TEE. In contrast, administration of the supplement enriched with EPA was associated with an increase in physical activity, which may reflect improved quality of life.
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Eicosapentaenoic acid (EPA) has been proposed to have specific anticachectic effects. This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass. Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter, double-blind, placebo controlled trial. Patients were randomly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo (2g EPA, n = 175; 4 g EPA, n = 172; placebo, n = 171). Patients were assessed at 4 weeks and 8 weeks. The groups were well balanced at baseline. Mean weight loss at baseline was 18% (n = 518). Over the 8-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight, or other nutritional variables. There was, however, a trend in favor of EPA with analysis of the primary end point, weight, at 8 weeks showing a borderline, nonsignificant treatment effect (P = .066). Relative to placebo, mean weight increased by 1.2 kg with 2 g EPA (95% CI, 0 kg to 2.3 kg) and by 0.3 kg with 4 g EPA (-0.9 kg to 1.5 kg). The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies should concentrate on other agents or combination regimens.
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The aim of the study was to assess the impact of an eicosapentanoic acid-containing protein and energy dense oral nutritional supplement (EPA-ONS) on nutritional and inflammatory status, quality of life (QOL), plasma phospholipids (PPL) and cytokine profile, tolerance of irinotecan-containing chemotherapy and EPA-ONS in patients with advanced colorectal cancer (CRC) receiving chemotherapy. Patients with advanced CRC having one prior chemotherapy regimen received 480 ml of EPA-ONS daily for 3 weeks before commencing chemotherapy with folinic acid, 5-fluorouracil, irinotecan (FOLFIRI), and continued for 3 cycles of treatment (9 weeks). All assessments including weight, body composition, C-reactive protein (CRP), QOL, dietary intake, PPL and cytokine analyses were performed at baseline, 3 and 9 weeks. Twenty-three patients were enrolled, 20 completed 3 weeks, and 15 completed 9 weeks. The mean EPA-ONS intake was 1.7 tetrapaks (408 ml) daily. There was a significant increase in mean weight (2.5 kg) at 3 weeks (p=0.03). Lean body mass (LBM) was maintained. Protein and energy intake significantly decreased after the commencement of chemotherapy (protein p=0.003, energy p=0.02). There was a significant increase in energy levels (p=0.03), whilst all other QOL measures were maintained. PPL EPA levels increased significantly over the first 3 weeks. Mean CRP increased by 14.9 mg/L over the first 3 weeks (p=0.004), but decreased to baseline levels by the end of the trial. There was a significant correlation between plasma IL-6 and IL-10 concentrations and survival, and between IL-12 and toxicity. Dietary counseling and the provision of EPA-ONS may result in maintenance of nutritional status and QOL, however randomized trials are required to evaluate the impact of EPA on toxicity from chemotherapy.
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Dietary PUFAs (polyunsaturated fatty acids) co-ordinately suppress transcription of a group of hepatic genes encoding glycolytic and lipogenic enzymes. Suppression of Fasn (fatty acid synthase) transcription involves two PUFA-responsive regions, but the majority of PUFA sensitivity maps to a region within the proximal promoter containing binding sites for NF-Y (nuclear factor-Y), Sp1 (stimulatory protein 1), SREBP (sterol-regulatory-elementbinding protein), and USF (upstream stimulatory factor). Promoter activation assays indicate that altered NF-Y is the key component in regulation of Fasn promoter activity by PUFA. Using electrophoretic mobility-shift assay and chromatin immunoprecipitation analysis, we demonstrate for the first time that PUFAs decrease in vivo binding of NF-Y and SREBP-1c to the proximal promoter of the hepatic Fasn gene and the promoters of three additional genes, spot 14, stearoyl-CoA desaturase and farnesyl diphosphate synthase that are also down-regulated by PUFA. The comparable 50% decrease in NF-Y and SREBP-1c binding to the promoters of the respective PUFA-sensitive genes occurred despite no change in nuclear NF-Y content and a 4-fold decrease in SREBP-1c. Together, these findings support a mechanism whereby PUFA reciprocally regulates the binding of NF-Y and SREBP-1c to a subset of genes which share similar contiguous arrangements of sterol regulatory elements and NF-Y response elements within their promoters. PUFA-dependent regulation of SREBP-1c and NF-Y binding to this unique configuration of response elements may represent a nutrient-sensitive motif through which PUFA selectively and co-ordinately targets subsets of hepatic genes involved in lipid metabolism.
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Use of n-3 fatty acids (FA) has been reported to be beneficial for cancer patients. We performed a systematic review of the literature in order to issue recommendations on the clinical use of n-3 FA in the cancer setting. A systematic search was performed in MEDLINE, EMBASE, Cochrane and Healthstar databases. We selected clinical trials or prospective observational studies including patients with cancer and life expectancy >2 months, in which enteral supplements with n-3 FA were administered. Parameters evaluated individually were clinical (nutritional status, tolerance, survival and hospital stays), biochemical (inflammatory mediators), and functional (functional status, appetite and quality of life (QoL)). Seventeen studies met the inclusion criteria; eight were of high quality. The panel of experts established the following evidence: (1) oral supplements with n-3 FA benefit patients with advanced cancer and weight loss, and are indicated in tumours of the upper digestive tract and pancreas; (2) the advantages observed were: increased weight and appetite, improved QoL, and reduced post-surgical morbidity; (3) there is no defined pattern for combining different n-3 FA, and it is recommended to administer > 1.5 g/day; and (4) better tolerance is obtained administering low-fat formulas for a period of at least 8 weeks. All the evidences were grade B but for 'length of treatment' and 'advantage of survival' it was grade C. Our findings suggest that administration of n-3 FA (EPA and DHA) in doses of at least 1.5 g/day for a prolonged period of time to patients with advanced cancer is associated with an improvement in clinical, biological and QoL parameters.
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Purpose: To determine whether high doses of fish oil, administered over 2 weeks, improve symptoms in patients with advanced cancer and decreased weight and appetite. Patients and Methods: Sixty patients were randomly assigned to fish oil capsules or placebo. Appetite, tiredness, nausea, well-being, caloric intake, nutritional status, and function were prospectively assessed at days 1 and 14. Results: The baseline weight loss was 16 ± 11 and 16 ± 8 kg in the fish oil (n = 30) and placebo (n = 30) group respectively, whereas the baseline appetite (0 mm = best and 10 mm = worst) was 58 ± 24 mm and 67 ± 19 mm, respectively (P = not significant). The mean daily dose was 10 ± 4 (fish oil group) and 9 ± 3 (placebo group) capsules, which provided 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid in the fish oil group. No significant differences in symptomatic or nutritional parameters were found (P < .05), and there was no correlation between changes in different variables between days 1 and 14 and the fish oil doses. Finally, the majority of the patients were not able to swallow more than 10 fish oil capsules per day, mainly because of burping and aftertaste. Conclusion: Fish oil did not significantly influence appetite, tiredness, nausea, well-being, caloric intake, nutritional status, or function after 2 weeks compared with placebo in patients with advanced cancer and loss of both weight and appetite.
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The prognostic effect of weight loss prior to chemotherapy was analyzedusing data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.
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Lifestyle and nutritional factors have been recognized to influence breast cancer survival, irrespective of genomic alterations that are the hallmarks of the disease. The biological and molecular mechanisms involved in the effects of dietary polyunsaturated fatty acids and breast cancer response to treatments in clinical and preclinical studies have been reviewed. Among nutrients, rumenic acid, a naturally occurring CLA isomer and n-3 docosahexaenoic acid (DHA) a highly unsaturated fatty acid, have emerged due to their potential to increase cancer treatment efficacy without additional side effects. In this review, we analyze the literature evidence that breast cancer treatment and outcome could be improved through an adjuvant dietary supplementation. Such an original approach would involve two successive phases of breast cancer treatment: an initial sensitization of residual tumor cells to chemotherapy and to radiation therapy with dietary DHA; then a prevention of metastatic re-growth with a prolonged rumenic acid supplementation. Safety is not anticipated to be a critical issue, although it has to be assessed in the long term. Dietary supplements, used in combination to anti-cancer agents, should be provided under medical prescription. Such an original use of fatty acids in breast cancer treatment could provide the lipid field with a new avenue to impact public health.
Article
Although loss of muscle mass is considered a cause of diminished muscle strength with aging, little is known regarding whether composition of aging muscle affects strength. The skeletal muscle attenuation coefficient, as determined by computed tomography, is a noninvasive measure of muscle density, and lower values reflect increased muscle lipid content. This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60 degrees/s in 2,627 men and women aged 70-79 yr participating in baseline studies of the Health ABC Study, a longitudinal study of health, aging, and body composition. Strength was higher in men than in women (132.3 +/- 34.5 vs. 81.4 +/- 22.0 N x m, P < 0.01). Men had greater muscle attenuation values (37.3 +/- 6.5 vs. 34.7 +/- 7.0 Hounsfield units) and muscle cross-sectional area (CSA) at the midthigh than women (132.7 +/- 22.4 vs. 93.3 +/- 17.5 cm(2), P < 0.01 for both). The strength per muscle CSA (specific force) was also higher in men (1.00 +/- 0.21 vs. 0.88 +/- 0.21 N x m x cm(-2)). The attenuation coefficient was significantly lower for hamstrings than for quadriceps (28.7 +/- 8.7 vs. 41.1 +/- 6.9 Hounsfield units, P < 0.01). Midthigh muscle attenuation values were lowest (P < 0.01) in the eldest men and women and were negatively associated with total body fat (r = -0.53, P < 0.01). Higher muscle attenuation values were also associated with greater specific force production (r = 0.26, P < 0.01). Multivariate regression analysis revealed that the attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women. These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity.
Article
Adipose tissue (AT) content of the thigh is generally not considered to be associated with insulin resistance (IR), but it is unclear whether the distribution of AT in the thigh is a determinant of IR. We investigated whether subcompartments of AT within the thigh are determinants of IR. Midthigh AT, muscle composition, and insulin sensitivity were compared in 11 obese patients with type 2 diabetes mellitus (DM); 40 obese, glucose-tolerant (GT) and 15 lean, GT volunteers; and 38 obese subjects who completed a weight-loss program. Midthigh AT area measured with computed tomography was partitioned into 3 components: subcutaneous AT (SCAT), AT beneath the fascia (SFAT), and AT infiltrating muscle groups (IMAT). Muscle attenuation characteristics were determined. Obese DM and obese GT subjects had lower insulin sensitivity than lean GT subjects. SCAT was greater in obesity, yet did not correlate with insulin sensitivity. SFAT was approximately 8% of total thigh AT and correlated with insulin sensitivity. IMAT was highest in obese DM, and although it accounted for only approximately 3% of thigh AT, it was a strong correlate of insulin sensitivity. Mean attenuation was highest in lean subjects and was associated with higher insulin sensitivity. Weight loss reduced the amount of thigh AT, the proportion of thigh IMAT, and the amount of low-density thigh muscle. SFAT and IMAT are markers of IR in obesity and DM although they are much smaller than SCAT, which does not predict IR. Muscle composition reflecting increased fat content is also associated with IR.
Article
Extensive loss of adipose tissue is a key feature of cancer cachexia. Advanced cancer patients also exhibit low plasma phospholipids. It is not known whether these processes coincide across the cancer trajectory nor has their relationship with survival been defined. Changes in adipose tissue mass and plasma phospholipids were characterized within 500days prior to death and prognostic significance assessed. Adipose tissue rate of change was determined in a retrospective cohort of patients who died of colorectal and lung cancers (n=108) and who underwent >2 computed tomography scans in the last 500days of life. Plasma phospholipid fatty acids were measured prospectively in a similar cohort of patients with metastatic cancer (n=72). Accelerated loss of adipose tissue begins at 7months from death reaching an average loss of 29% of total AT 2months from death. Plasma phospholipid fatty acids were 35% lower in patients closest to death versus those surviving >8months. Losses of phospholipid fatty acids and adipose tissue occur in tandem and are predictive of survival. Depletion of plasma phospholipids likely indicates a deficit of essential fatty acids in the periphery which may contribute to loss of adipose tissue.
Article
Cancer cachexia is a syndrome of unintentional weight loss that is characterized by wasting of both skeletal muscle and adipose tissue. Glucose intolerance and insulin resistance have been associated with cancer cachexia. However, it is unknown whether resistance to insulin has a role in the development of cachexia. In the present study, male CD2F1 mice with colon-26 adenocarcinoma tumors underwent an insulin tolerance test before the onset of weight loss. Compared to mice without tumors, mice with tumors had a profoundly blunted blood glucose response to insulin. Corroborating these findings, mice with tumors had decreased phosphorylation of Akt in quadriceps muscle and epididymal adipose tissue at the end of the study. Expression of Akt-regulated genes Atrogin-1, MuRF-1, and Bnip3 was increased in muscle, suggesting a role for decreased insulin signaling in the induction of both proteasomal proteolysis and autophagy in cachectic muscle. Rosiglitazone treatment increased serum adiponectin, insulin sensitivity, and body weight, and decreased Atrogin-1 and MuRF-1 expression in the skeletal muscle of tumor-bearing mice. In conclusion, insulin resistance is an early event in mice with cachexia induced by colon-26 tumors. Rosiglitazone improves insulin sensitivity and decreases early markers of cachexia. These data provide evidence that insulin resistance is not only present in cachexia, but also has a role in cachexia pathogenesis. Correction of insulin resistance may be a novel therapeutic target for the treatment of cancer cachexia.
Article
Cancer cachexia-associated weight loss is poorly understood; energetically demanding tissues (eg, organ and tumor mass) and resting energy expenditure (REE) are reported to increase with advanced cancer. The objective was to quantify the potential contribution of increasing masses of energetically demanding tissues to REE with colorectal cancer cachexia progression. A longitudinal computed tomography (CT) image review was performed to quantify organ size (liver, including metastases, and spleen) and peripheral tissues (skeletal muscle and adipose tissue) during colorectal cancer cachexia progression (n = 34). Body composition was prospectively evaluated by CT and dual-energy X-ray absorptiometry, and REE was determined by indirect calorimetry in advanced colorectal cancer patients (n = 18). Eleven months from death, the liver (2.3 +/- 0.7 kg) and spleen (0.32 +/- 0.2 kg) were larger than reference values. One month from death, liver weight increased to 3.0 +/- 1.5 kg (P = 0.010), spleen showed a trend to increase (P = 0.077), and concurrent losses of muscle (4.2 kg) and fat (3.5 kg) (P < 0.05) were observed. The estimated percentage of fat-free mass (FFM) occupied by the liver increased from 4.5% to 7.0% (P < 0.001). The most rapid loss of peripheral tissues and liver and metastases gain occurred within 3 mo of death. A positive linear relation existed between liver mass and measured whole-body REE (r(2) = 0.35, P = 0.010); because liver accounted for a larger percentage of FFM, measured REE . kg FFM(-1) . d(-1) increased (r(2) = 0.35, P = 0.010). Increases in mass and in the proportion of high metabolic rate tissues, including liver and tumor, represented a cumulative incremental REE of approximately 17,700 kcal during the last 3 mo of life and may contribute substantially to cachexia-associated weight loss.
Article
The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.
Article
The aim of the current prospective, randomized control study was to investigate the effect of dietary omega-3 polyunsaturated fatty acids plus vitamin E on the immune status and survival of well-nourished and malnourished patients with generalized malignancy. Sixty patients with generalized solid tumors were randomized to receive dietary supplementation with either fish oil (18 g of omega-3 polyunsaturated fatty acids, PUFA) or placebo daily until death. Each group included 15 well-nourished and 15 malnourished patients. The authors measured total T cells, T-helper cells, T-suppressor cells, natural killer cells, and the synthesis of interleukin-1, interleukin-6, and tumor necrosis factor by peripheral blood mononuclear cells before and on Day 40 of fish oil supplementation. Karnofsky performance status, nutritional state, and survival were also estimated. The ratio of T-helper cells to T-suppressor cells was significantly lower in malnourished patients. Omega-3 PUFA had a considerable immunomodulating effect by increasing this ratio in the subgroup of malnourished patients. There were no significant differences in cytokine production among the various groups, except for a decrease in tumor necrosis factor production in malnourished cancer patients, which was restored by omega-3 fatty acids. The mean survival was significantly higher for the subgroup of well-nourished patients in both groups, whereas omega-3 fatty acids prolonged the survival of all the patients. Malnutrition appears to be an important predictor of survival for patients with end stage malignant disease. Omega-3 polyunsaturated fatty acids had a significant immunomodulating effect and seemed to prolong the survival of malnourished patients with generalized malignancy.
Article
The purpose of this investigation was to validate that in vivo measurement of skeletal muscle attenuation (MA) with computed tomography (CT) is associated with muscle lipid content. Single-slice CT scans performed on phantoms of varying lipid concentrations revealed good concordance between attenuation and lipid concentration (r(2) = 0.995); increasing the phantom's lipid concentration by 1 g/100 ml decreased its attenuation by approximately 1 Hounsfield unit (HU). The test-retest coefficient of variation for two CT scans performed in six volunteers was 0.51% for the midthigh and 0.85% for the midcalf, indicating that the methodological variability is low. Lean subjects had significantly higher (P < 0.01) MA values (49.2 +/- 2.8 HU) than did obese nondiabetic (39.3 +/- 7.5 HU) and obese Type 2 diabetic (33.9 +/- 4. 1 HU) subjects, whereas obese Type 2 diabetic subjects had lower MA values that were not different from obese nondiabetic subjects. There was also good concordance between MA in midthigh and midcalf (r = 0.60, P < 0.01), psoas (r = 0.65, P < 0.01), and erector spinae (r = 0.77, P < 0.01) in subsets of volunteers. In 45 men and women who ranged from lean to obese (body mass index = 18.5 to 35.9 kg/m(2)), including 10 patients with Type 2 diabetes mellitus, reduced MA was associated with increased muscle fiber lipid content determined with histological oil red O staining (P = -0.43, P < 0. 01). In a subset of these volunteers (n = 19), triglyceride content in percutaneous biopsy specimens from vastus lateralis was also associated with MA (r = -0.58, P = 0.019). We conclude that the attenuation of skeletal muscle in vivo determined by CT is related to its lipid content and that this noninvasive method may provide additional information regarding the association between muscle composition and muscle function.
Article
The objective of this study was to examine compositional and quantitative changes in fatty acids of plasma components and red blood cell phospholipids (PL) immediately following and during recovery from burn injury. Subjects (n = 10) with >10% total body surface area burn had blood drawn at specific timepoints (0 to >50 d) following burn injury. Fatty acid composition of red blood cell PL and plasma PL, cholesteryl esters (CE), and triglycerides was determined using gas-liquid chromatography after separating each fraction from extracted lipids by thin-layer chromatography. Total plasma PL and CE in burn patients were lower than in healthy control subjects with reduced 20:4n-6, n-6, and n-3 fatty acids and higher levels of monounsaturated and saturated fatty acids early after burn. CE levels remained half that of healthy control values up to 50 d post-burn. Red blood cell PL had decreased 20:4n-6 content and profiles similar to that of an essential fatty acid deficiency early after burn. These results suggest an impairment in lipoprotein and polyunsaturated fatty acid metabolism in the early post-burn period. Lower levels of 20:4n-6 and n-3 fatty acids in every plasma fraction suggest increased use of these fatty acids for wound healing and immune function following burn injury. Further work is needed to determine the ability of burn patients to utilize essential fatty acids in order to design nutritional intervention that promotes wound healing and immunological functions consistent with recovery in these patients.