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The term sarcopenia was introduced in 1988. The original definition was a "muscle loss" of the appendicular muscle mass in the older people as measured by dual energy x-ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC-F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease-related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age-related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age-related and disease-related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life-long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.

BackgroundCurcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models.Methods and resultsRetrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change -4.8[-9.1,-0.1] vs. -0.05%[-4.2, 2.6] in controls,p

BackgroundBody weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown.MethodsWe reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI); body composition was evaluated utilizing computerized tomography(CT) images. A body mass index (BMI)≥25 kg/m² was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria.ResultsMost patients were overweight (n = 65, 63%); 53 patients were sarcopenic (51%), including 79% of patients with a BMI

Author(s): Vickie E. Baracos [sup.1] Author Affiliations: (1) Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue Edmonton, Alberta, Canada What is already known about cancer-associated malnutrition? [...]

Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is higher resting energy expenditure levels than in healthy individuals, which has been linked to greater thermogenesis by brown fat (1-6). How tumours induce brown fat activity is unknown. Here, using a Lewis lung carcinoma model of cancer cachexia, we show that tumour-derived parathyroid-hormone-related protein (PTHrP) has an important role in wasting, through driving the expression of genes involved in thermogenesis in adipose tissues. Neutralization of PTHrP in tumour-bearing mice blocked adipose tissue browning and the loss of muscle mass and strength. Our results demonstrate that PTHrP mediates energy wasting in fat tissues and contributes to the broader aspects of cancer cachexia. Thus, neutralization of PTHrP might hold promise for ameliorating cancer cachexia and improving patient survival., Cachexia is a wasting disorder that accompanies many chronic diseases such as cancer and congestive heart failure. The hallmarks of cachexia are weight loss with atrophy of fat and skeletal [...]

Dietary glutamine has been suggested to preserve structural and functional integrity of the gut and high dose bolus glutamine has been hypothesized to protect against potentially fatal endotoxic shock, hyperthermic stress, and side effects of chemotherapy. In this study, we aimed to relate the ability of high dose oral bolus glutamine to mitigate the severe diarrhea induced by 7-ethyl-10-[4-(1-piperidino)-1-piperidinolcarbonyloxy-camptothecin (CPT-11) chemotherapy to specific cytoprotective mechanisms [heat shock response, glutathione (GSH)] in gut and tumor tissues. Female rats bearing Ward colon tumor received CPT-11 (125 mg.[kg.sup.-1].[d.sup.-1] x 3 d) with or without an oral glutamine bolus (0.75 g/kg) administered 30 min prior to each CPT-11 dose. Glutamine reduced incidence aor -] CPT-11 treatment (P < 0.05) and was associated with potentially beneficial and protective responses in the colon: 1) a 3.1 to 7.2-fold increase of heat shock protein (Hsp)25,-70, and -90[alpha] (P< 0.05); 2)increased reduced GSH (rGSH):oxidized GSH ratio (P < 0.05); 3) prevention of upregulated activity of a key bacterial enzyme ([beta]-glucuronidase) in the cecal content that mediates CPT-11 intestinal toxicity (P < 0.05); and 4) increased proportions of CD3+CD8+ lymphocytes and memory antitumor activity, the amino acid concentrations, Hsp expression, or the ratio of rGSH:oxidized GSH in the tumor. Our data demonstrate a striking dichotomy in the response of tumor and host to oral glutamine administration, concurring with the concept that this nutrient may favorably alter the balance between the host and tumor.

Many of the features of BCAA metabolism in the tumor-bearing state are similar to the other disease states that feature involuntary weight loss and skeletal muscle atrophy. These states are generally characterized by altered BCAA availability (low BCAA intakes, elevated rates of BCAA oxidation, and gluconeogenesis), which are concurrent with activation of proteolysis and suppression of protein synthesis in skeletal muscle and ultimately lead to erosion of lean tissue mass. These features in turn imply BCAA deficiency compared with whole-body requirements and are the basis of suggestions for dietary supplementation with BCAA or their metabolites. Recent studies on BCAA supplementation in cancer focus on leucine and its derivative, [beta]-methyl [beta]-hydroxybutyrate, as regulators of skeletal muscle metabolism, although their relative efficacy is unknown. However, what would otherwise be a relatively straightforward consideration of amino acid supply and demand is confounded by the presence of the tumor and its potential utilization of BCAA for its proliferative and invasive activities. Positron emission tomography with [sup.11]C-leucine, used for in vivo tumor imaging, points to the high avidity of tumor amino acid uptake. These features have incited research in opposing directions, probing BCAA deprivation, with a view to limiting tumor growth, as well as BCAA supplementation, with a view to supporting maintenance of host lean tissue. No clear conclusion is presently available from the sum of these efforts. Animal models with relevant clinical features are essential to determine if amino acid therapy can alter the balance between the host and the tumor in a manner that favors the host overall. KEY WORDS: * amino acids * tumor * cachexia * supplementation * muscle wasting

One important advantage of animal models is that they permit invasive approaches and can be especially valuable when evaluating tissue and specific features of metabolism in situ. The focus of this presentation is current models, which are providing insights into the pivotal importance of the gastrointestinal tract in amino acid metabolism. Intestinal amino acid metabolism is conceptually and technically difficult to approach and multiple processes must be accounted for: protein synthesis and degradation; transit of amino acids in both directions across the basolateral surface of enterocytes, in addition to uptake on the apical side; arterio-portal differences as well as net portal appearance during uptake of defined amino acid mixtures appearing on the luminal side; first pass amino acid metabolism. These key features are largely impossible to study without access to invasive approaches in vivo and cannot be reproduced in vitro. Douglas Burrin, Ron Ball, and Vickie Baracos and their co-workers have used the domestic piglet to study intestinal protein metabolism in situ in three distinctly different and complementary approaches. Collectively, their approaches allow a means to describe the key elements of intestinal amino acid capture (and release) and the means to probe their physiological and pathological variation. It seems evident that the portal-drained viscera represent sites of quantitatively important amino acid catabolism, and that this capacity combined with hepatic metabolism would largely limit the possibility of toxic sequelae of amino acids taken orally. KEY WORDS: * intestine * protein metabolism * amino acid metabolism * piglet * animal models