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Palliative care: Assessment and management of anorexia and cachexia

Authors
Eduardo Bruera, MD
Rony Dev, DO
Section Editor
Robert M Arnold, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Hippocrates described a syndrome of wasting and progressive inanition among patients who were ill and dying. Derived from the Greek words kakos, meaning "bad things", and hexus, meaning "state of being", the term cachexia has been used to describe this syndrome. Cachexia, a hypercatabolic state that is defined by an accelerated loss of skeletal muscle in the context of a chronic inflammatory response, is best described in the setting of cancer but is also seen in other advanced chronic illnesses including AIDS, heart failure, and chronic obstructive pulmonary disease (COPD) [1]. Although body composition changes are not identical in all of these disease states, the term cachexia is used in all of these settings.

Loss of appetite and weight loss is common among patients with an advanced serious life threatening illness such as cancer. However, the profound weight loss suffered by patients with cachexia cannot be entirely attributed to poor caloric intake. In contrast to simple starvation, which is characterized by a caloric deficiency that can be reversed with appropriate feeding, cachexia is not reversed by the supplementation of calories [2].

Over the past several years, there has been an alarming increase in obesity in industrialized nations. Within the general population, obesity is generally associated with an increased risk of adverse outcomes, and loss of weight is seen as desirable and health-promoting. However, in patients with a chronic serious and/or life threatening illness, weight loss is associated with poorer outcomes, and studies suggest that overweight and obese patients may paradoxically have better outcomes than lean patients with a wide variety of advanced illnesses including cancer [3], heart failure [4-6], chronic kidney disease [7], and COPD [8].

This topic review will cover the diagnosis, evaluation, and management of anorexia and cachexia in palliative care patients. A more detailed review of the clinical features, pathogenesis, and management of cancer-associated anorexia and cachexia is available elsewhere. (See "Pathogenesis, clinical features, and assessment of cancer cachexia" and "Pharmacologic management of cancer anorexia/cachexia".)

DEFINITIONS

Anorexia may be simply defined as either loss of appetite or reduced caloric intake [9].

                                           

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References
Top
  1. Kotler DP. Cachexia. Ann Intern Med 2000; 133:622.
  2. McGeer AJ, Detsky AS, O'Rourke K. Parenteral nutrition in cancer patients undergoing chemotherapy: a meta-analysis. Nutrition 1990; 6:233.
  3. Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 1980; 69:491.
  4. Horwich TB, Fonarow GC, Hamilton MA, et al. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol 2001; 38:789.
  5. Curtis JP, Selter JG, Wang Y, et al. The obesity paradox: body mass index and outcomes in patients with heart failure. Arch Intern Med 2005; 165:55.
  6. Kenchaiah S, Pocock SJ, Wang D, et al. Body mass index and prognosis in patients with chronic heart failure: insights from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Circulation 2007; 116:627.
  7. Kovesdy CP, Czira ME, Rudas A, et al. Body mass index, waist circumference and mortality in kidney transplant recipients. Am J Transplant 2010; 10:2644.
  8. Kalantar-Zadeh K, Horwich TB, Oreopoulos A, et al. Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care 2007; 10:433.
  9. Bruera E. ABC of palliative care. Anorexia, cachexia, and nutrition. BMJ 1997; 315:1219.
  10. Davis MP, Dickerson D. Cachexia and anorexia: cancer's covert killer. Support Care Cancer 2000; 8:180.
  11. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12:489.
  12. Blum D, Strasser F. Cachexia assessment tools. Curr Opin Support Palliat Care 2011; 5:350.
  13. Evans WJ, Morley JE, Argilés J, et al. Cachexia: a new definition. Clin Nutr 2008; 27:793.
  14. Strasser F. Diagnostic criteria of cachexia and their assessment: decreased muscle strength and fatigue. Curr Opin Clin Nutr Metab Care 2008; 11:417.
  15. Vigano A, Del Fabbro E, Bruera E, Borod M. The cachexia clinic: from staging to managing nutritional and functional problems in advanced cancer patients. Crit Rev Oncog 2012; 17:293.
  16. EPCRC Clinical Practice Guidelines on cancer cachexia available online at http://www.epcrc.org/publication_listfiles.php?id=mWdBCMI5eXVlcNFk7Gnq (Accessed on July 15, 2013).
  17. Wallengren O, Lundholm K, Bosaeus I. Diagnostic criteria of cancer cachexia: relation to quality of life, exercise capacity and survival in unselected palliative care patients. Support Care Cancer 2013; 21:1569.
  18. Baumgartner RN, Koehler KM, Gallagher D, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998; 147:755.
  19. Kim TN, Yang SJ, Yoo HJ, et al. Prevalence of sarcopenia and sarcopenic obesity in Korean adults: the Korean sarcopenic obesity study. Int J Obes (Lond) 2009; 33:885.
  20. Rolland Y, Lauwers-Cances V, Cristini C, et al. Difficulties with physical function associated with obesity, sarcopenia, and sarcopenic-obesity in community-dwelling elderly women: the EPIDOS (EPIDemiologie de l'OSteoporose) Study. Am J Clin Nutr 2009; 89:1895.
  21. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 2008; 9:629.
  22. Collins J, Noble S, Chester J, et al. The assessment and impact of sarcopenia in lung cancer: a systematic literature review. BMJ Open 2014; 4:e003697.
  23. Baracos VE, Reiman T, Mourtzakis M, et al. Body composition in patients with non-small cell lung cancer: a contemporary view of cancer cachexia with the use of computed tomography image analysis. Am J Clin Nutr 2010; 91:1133S.
  24. Laugsand EA, Kaasa S, de Conno F, et al. Intensity and treatment of symptoms in 3,030 palliative care patients: a cross-sectional survey of the EAPC Research Network. J Opioid Manag 2009; 5:11.
  25. Olden AM, Holloway R, Ladwig S, et al. Palliative care needs and symptom patterns of hospitalized elders referred for consultation. J Pain Symptom Manage 2011; 42:410.
  26. Kalantar-Zadeh K, Block G, McAllister CJ, et al. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am J Clin Nutr 2004; 80:299.
  27. Bosaeus I, Daneryd P, Svanberg E, Lundholm K. Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients. Int J Cancer 2001; 93:380.
  28. Hutton JL, Martin L, Field CJ, et al. Dietary patterns in patients with advanced cancer: implications for anorexia-cachexia therapy. Am J Clin Nutr 2006; 84:1163.
  29. Hughes CM, Woodside JV, McGartland C, et al. Nutritional intake and oxidative stress in chronic heart failure. Nutr Metab Cardiovasc Dis 2012; 22:376.
  30. von Haehling S, Anker SD. Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachexia Sarcopenia Muscle 2010; 1:1.
  31. Ebner N, Springer J, Kalantar-Zadeh K, et al. Mechanism and novel therapeutic approaches to wasting in chronic disease. Maturitas 2013; 75:199.
  32. von Haehling S, Lainscak M, Springer J, Anker SD. Cardiac cachexia: a systematic overview. Pharmacol Ther 2009; 121:227.
  33. Mak RH, Ikizler AT, Kovesdy CP, et al. Wasting in chronic kidney disease. J Cachexia Sarcopenia Muscle 2011; 2:9.
  34. Kalantar-Zadeh K, Ikizler TA, Block G, et al. Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. Am J Kidney Dis 2003; 42:864.
  35. Fouque D, Kalantar-Zadeh K, Kopple J, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int 2008; 73:391.
  36. Wanke CA, Silva M, Knox TA, et al. Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin Infect Dis 2000; 31:803.
  37. Rhondali W, Chisholm GB, Daneshmand M, et al. Association between body image dissatisfaction and weight loss among patients with advanced cancer and their caregivers: a preliminary report. J Pain Symptom Manage 2013; 45:1039.
  38. Oberholzer R, Hopkinson JB, Baumann K, et al. Psychosocial effects of cancer cachexia: a systematic literature search and qualitative analysis. J Pain Symptom Manage 2013; 46:77.
  39. Del Río MI, Shand B, Bonati P, et al. Hydration and nutrition at the end of life: a systematic review of emotional impact, perceptions, and decision-making among patients, family, and health care staff. Psychooncology 2012; 21:913.
  40. Raijmakers NJ, Clark JB, van Zuylen L, et al. Bereaved relatives' perspectives of the patient's oral intake towards the end of life: a qualitative study. Palliat Med 2013; 27:665.
  41. Yamagishi A, Morita T, Miyashita M, et al. The care strategy for families of terminally ill cancer patients who become unable to take nourishment orally: recommendations from a nationwide survey of bereaved family members' experiences. J Pain Symptom Manage 2010; 40:671.
  42. Reuben DB, Mor V, Hiris J. Clinical symptoms and length of survival in patients with terminal cancer. Arch Intern Med 1988; 148:1586.
  43. Wong CS, Gipson DS, Gillen DL, et al. Anthropometric measures and risk of death in children with end-stage renal disease. Am J Kidney Dis 2000; 36:811.
  44. Anker SD, Ponikowski P, Varney S, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet 1997; 349:1050.
  45. Wheeler DA, Gibert CL, Launer CA, et al. Weight loss as a predictor of survival and disease progression in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 18:80.
  46. Guenter P, Muurahainen N, Simons G, et al. Relationships among nutritional status, disease progression, and survival in HIV infection. J Acquir Immune Defic Syndr 1993; 6:1130.
  47. Morishita S, Kaida K, Tanaka T, et al. Prevalence of sarcopenia and relevance of body composition, physiological function, fatigue, and health-related quality of life in patients before allogeneic hematopoietic stem cell transplantation. Support Care Cancer 2012; 20:3161.
  48. Capuano G, Gentile PC, Bianciardi F, et al. Prevalence and influence of malnutrition on quality of life and performance status in patients with locally advanced head and neck cancer before treatment. Support Care Cancer 2010; 18:433.
  49. Cone RD. The Central Melanocortin System and Energy Homeostasis. Trends Endocrinol Metab 1999; 10:211.
  50. Elmquist JK. Anatomic basis of leptin action in the hypothalamus. Front Horm Res 2000; 26:21.
  51. Sleeman MW, Anderson KD, Lambert PD, et al. The ciliary neurotrophic factor and its receptor, CNTFR alpha. Pharm Acta Helv 2000; 74:265.
  52. Williams G, Harrold JA, Cutler DJ. The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box. Proc Nutr Soc 2000; 59:385.
  53. Woods SC, Schwartz MW, Baskin DG, Seeley RJ. Food intake and the regulation of body weight. Annu Rev Psychol 2000; 51:255.
  54. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409:194.
  55. Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407:908.
  56. Ahima RS, Flier JS. Leptin. Annu Rev Physiol 2000; 62:413.
  57. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395:763.
  58. Soeters PB, Grimble RF. Dangers, and benefits of the cytokine mediated response to injury and infection. Clin Nutr 2009; 28:583.
  59. Argilés JM, Alvarez B, López-Soriano FJ. The metabolic basis of cancer cachexia. Med Res Rev 1997; 17:477.
  60. Wiffen PJ, Derry S, Moore RA. Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain. Cochrane Database Syst Rev 2014; :CD011056.
  61. Carrero JJ, Qureshi AR, Axelsson J, et al. Comparison of nutritional and inflammatory markers in dialysis patients with reduced appetite. Am J Clin Nutr 2007; 85:695.
  62. Heckel M, Stiel S, Ostgathe C. Smell and taste in palliative care: a systematic analysis of literature. Eur Arch Otorhinolaryngol 2015; 272:279.
  63. Sarkisian CA, Lachs MS. "Failure to thrive" in older adults. Ann Intern Med 1996; 124:1072.
  64. Hamerman D. Toward an understanding of frailty. Ann Intern Med 1999; 130:945.
  65. Goshen I, Yirmiya R. Interleukin-1 (IL-1): a central regulator of stress responses. Front Neuroendocrinol 2009; 30:30.
  66. Dinarello CA. Proinflammatory cytokines. Chest 2000; 118:503.
  67. Argilés JM, López-Soriano FJ. The role of cytokines in cancer cachexia. Med Res Rev 1999; 19:223.
  68. Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol 2003; 5:87.
  69. Hall DT, Ma JF, Marco SD, Gallouzi IE. Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia. Aging (Albany NY) 2011; 3:702.
  70. Reed SA, Sandesara PB, Senf SM, Judge AR. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J 2012; 26:987.
  71. Costelli P, Reffo P, Penna F, et al. Ca(2+)-dependent proteolysis in muscle wasting. Int J Biochem Cell Biol 2005; 37:2134.
  72. Levine B, Kalman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990; 323:236.
  73. Anker SD, Coats AJ. Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest 1999; 115:836.
  74. Nagaya N, Uematsu M, Kojima M, et al. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001; 104:2034.
  75. Swan JW, Anker SD, Walton C, et al. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol 1997; 30:527.
  76. Araújo JP, Lourenço P, Rocha-Gonçalves F, et al. Adiponectin is increased in cardiac cachexia irrespective of body mass index. Eur J Heart Fail 2009; 11:567.
  77. Benedik B, Farkas J, Kosnik M, et al. Mini nutritional assessment, body composition, and hospitalisations in patients with chronic obstructive pulmonary disease. Respir Med 2011; 105 Suppl 1:S38.
  78. Debigaré R, Côté CH, Maltais F. Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. Am J Respir Crit Care Med 2001; 164:1712.
  79. Mitch WE. Insights into the abnormalities of chronic renal disease attributed to malnutrition. J Am Soc Nephrol 2002; 13 Suppl 1:S22.
  80. Mitch WE. Proteolytic mechanisms, not malnutrition, cause loss of muscle mass in kidney failure. J Ren Nutr 2006; 16:208.
  81. Del Fabbro E, Jatoi A, Davis M, et al. Health professionals' attitudes toward the detection and management of cancer-related anorexia-cachexia syndrome, and a proposal for standardized assessment. J Community Support Oncol 2015; 13:181.
  82. Ribaudo JM, Cella D, Hahn EA, et al. Re-validation and shortening of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire. Qual Life Res 2000; 9:1137.
  83. Del Fabbro E, Hui D, Dalal S, et al. Clinical outcomes and contributors to weight loss in a cancer cachexia clinic. J Palliat Med 2011; 14:1004.
  84. Kwang AY, Kandiah M. Objective and subjective nutritional assessment of patients with cancer in palliative care. Am J Hosp Palliat Care 2010; 27:117.
  85. Dev R, Hui D, Del Fabbro E, et al. Association between hypogonadism, symptom burden, and survival in male patients with advanced cancer. Cancer 2014; 120:1586.
  86. Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond) 2008; 32:959.
  87. Kyle UG, Unger P, Dupertuis YM, et al. Body composition in 995 acutely ill or chronically ill patients at hospital admission: a controlled population study. J Am Diet Assoc 2002; 102:944.
  88. Martin L, Senesse P, Gioulbasanis I, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol 2015; 33:90.
  89. Bingham J. The dietary assessment of individuals; methods accuracy, new techniques and recommendations. Nutrition Abstracts Review 1987; 57:705.
  90. von Gruenigen VE, Courneya KS, Gibbons HE, et al. Feasibility and effectiveness of a lifestyle intervention program in obese endometrial cancer patients: a randomized trial. Gynecol Oncol 2008; 109:19.
  91. Bruera E, Chadwick S, Cowan L, et al. Caloric intake assessment in advanced cancer patients: comparison of three methods. Cancer Treat Rep 1986; 70:981.
  92. Thoresen L, Fjeldstad I, Krogstad K, et al. Nutritional status of patients with advanced cancer: the value of using the subjective global assessment of nutritional status as a screening tool. Palliat Med 2002; 16:33.
  93. Bauer J, Capra S, Ferguson M. Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur J Clin Nutr 2002; 56:779.
  94. Kondrup J, Rasmussen HH, Hamberg O, et al. Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr 2003; 22:321.
  95. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, Part II: Laboratory evaluation. Nutrition 2000; 16:131.
  96. Cansado P, Ravasco P, Camilo M. A longitudinal study of hospital undernutrition in the elderly: comparison of four validated methods. J Nutr Health Aging 2009; 13:159.
  97. Boléo-Tomé C, Chaves M, Monteiro-Grillo I, et al. Teaching nutrition integration: MUST screening in cancer. Oncologist 2011; 16:239.
  98. Ellegård LH, Ahlén M, Körner U, et al. Bioelectric impedance spectroscopy underestimates fat-free mass compared to dual energy X-ray absorptiometry in incurable cancer patients. Eur J Clin Nutr 2009; 63:794.
  99. Gibney E, Elia M, Jebb SA, et al. Total energy expenditure in patients with small-cell lung cancer: results of a validated study using the bicarbonate-urea method. Metabolism 1997; 46:1412.
  100. Reilly JJ, Blacklock CJ, Dale E, et al. Resting metabolic rate and obesity in childhood acute lymphoblastic leukaemia. Int J Obes Relat Metab Disord 1996; 20:1130.
  101. Demark-Wahnefried W, Peterson BL, Winer EP, et al. Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 2001; 19:2381.
  102. Harris JA, Benedict FG. A Biometric Study of Human Basal Metabolism. Proc Natl Acad Sci U S A 1918; 4:370.
  103. McDoniel SO. Systematic review on use of a handheld indirect calorimeter to assess energy needs in adults and children. Int J Sport Nutr Exerc Metab 2007; 17:491.
  104. Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Dietary counseling improves patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy. J Clin Oncol 2005; 23:1431.
  105. Ovesen L, Allingstrup L, Hannibal J, et al. Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study. J Clin Oncol 1993; 11:2043.
  106. Neumann F. The physiological action of progesterone and the pharmacological effects of progestogens--a short review. Postgrad Med J 1978; 54 Suppl 2:11.
  107. Maltoni M, Nanni O, Scarpi E, et al. High-dose progestins for the treatment of cancer anorexia-cachexia syndrome: a systematic review of randomised clinical trials. Ann Oncol 2001; 12:289.
  108. Ruiz-García V, Juan O, Pérez Hoyos S, et al. [Megestrol acetate: a systematic review usefulness about the weight gain in neoplastic patients with cachexia]. Med Clin (Barc) 2002; 119:166.
  109. Berenstein EG, Ortiz Z. Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2005; :CD004310.
  110. Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, et al. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2013; :CD004310.
  111. Dev R, Del Fabbro E, Bruera E. Association between megestrol acetate treatment and symptomatic adrenal insufficiency with hypogonadism in male patients with cancer. Cancer 2007; 110:1173.
  112. Loprinzi CL, Michalak JC, Schaid DJ, et al. Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia. J Clin Oncol 1993; 11:762.
  113. Miller S, McNutt L, McCann MA, McCorry N. Use of corticosteroids for anorexia in palliative medicine: a systematic review. J Palliat Med 2014; 17:482.
  114. Loprinzi CL, Kugler JW, Sloan JA, et al. Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol 1999; 17:3299.
  115. Abrams DI, Hilton JF, Leiser RJ, et al. Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Ann Intern Med 2003; 139:258.
  116. Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995; 10:89.
  117. Beal JE, Olson R, Lefkowitz L, et al. Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J Pain Symptom Manage 1997; 14:7.
  118. Timpone JG, Wright DJ, Li N, et al. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Res Hum Retroviruses 1997; 13:305.
  119. Jatoi A, Windschitl HE, Loprinzi CL, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 2002; 20:567.
  120. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA 2015; 313:2456.
  121. Yeh SS, DeGuzman B, Kramer T, M012 Study Group. Reversal of COPD-associated weight loss using the anabolic agent oxandrolone. Chest 2002; 122:421.
  122. Bhasin S, Storer TW, Javanbakht M, et al. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA 2000; 283:763.
  123. Bhasin S, Storer TW, Asbel-Sethi N, et al. Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab 1998; 83:3155.
  124. Grinspoon S, Corcoran C, Askari H, et al. Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1998; 129:18.
  125. Crawford J, Prado CM, Johnston MA, et al. Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials). Curr Oncol Rep 2016; 18:37.
  126. Bruera ED, MacEachern TJ, Spachynski KA, et al. Comparison of the efficacy, safety, and pharmacokinetics of controlled release and immediate release metoclopramide for the management of chronic nausea in patients with advanced cancer. Cancer 1994; 74:3204.
  127. Gogos CA, Ginopoulos P, Salsa B, et al. Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Cancer 1998; 82:395.
  128. Barber MD, Ross JA, Voss AC, et al. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer 1999; 81:80.
  129. Wigmore SJ, Barber MD, Ross JA, et al. Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr Cancer 2000; 36:177.
  130. Moses AW, Slater C, Preston T, et al. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. Br J Cancer 2004; 90:996.
  131. Dewey A, Baughan C, Dean T, et al. Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database Syst Rev 2007; :CD004597.
  132. Murphy RA, Mourtzakis M, Chu QS, et al. 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. Cancer 2011; 117:1775.
  133. Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid? Nutr Rev 1990; 48:297.
  134. Topkan E, Yavuz MN, Onal C, Yavuz AA. Prevention of acute radiation-induced esophagitis with glutamine in non-small cell lung cancer patients treated with radiotherapy: evaluation of clinical and dosimetric parameters. Lung Cancer 2009; 63:393.
  135. May PE, Barber A, D'Olimpio JT, et al. Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg 2002; 183:471.
  136. Steiber A, Kerner J, Hoppel CL. Carnitine: a nutritional, biosynthetic, and functional perspective. Mol Aspects Med 2004; 25:455.
  137. Vinci E, Rampello E, Zanoli L, et al. Serum carnitine levels in patients with tumoral cachexia. Eur J Intern Med 2005; 16:419.
  138. Gramignano G, Lusso MR, Madeddu C, et al. Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition 2006; 22:136.
  139. Kraft M, Kraft K, Gärtner S, et al. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)--a randomized multicentre trial. Nutr J 2012; 11:52.
  140. Engelen MP, Safar AM, Bartter T, et al. High anabolic potential of essential amino acid mixtures in advanced nonsmall cell lung cancer. Ann Oncol 2015; 26:1960.
  141. Lai V, George J, Richey L, et al. Results of a pilot study of the effects of celecoxib on cancer cachexia in patients with cancer of the head, neck, and gastrointestinal tract. Head Neck 2008; 30:67.
  142. McMillan DC, Wigmore SJ, Fearon KC, et al. A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. Br J Cancer 1999; 79:495.
  143. Tramontana JM, Utaipat U, Molloy A, et al. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Mol Med 1995; 1:384.
  144. Klausner JD, Makonkawkeyoon S, Akarasewi P, et al. The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 11:247.
  145. Reyes-Terán G, Sierra-Madero JG, Martínez del Cerro V, et al. Effects of thalidomide on HIV-associated wasting syndrome: a randomized, double-blind, placebo-controlled clinical trial. AIDS 1996; 10:1501.
  146. Jacobson JM, Greenspan JS, Spritzler J, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 1997; 336:1487.
  147. Kaplan G, Thomas S, Fierer DS, et al. Thalidomide for the treatment of AIDS-associated wasting. AIDS Res Hum Retroviruses 2000; 16:1345.
  148. Gordon JN, Trebble TM, Ellis RD, et al. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut 2005; 54:540.
  149. Reid J, Mills M, Cantwell M, et al. Thalidomide for managing cancer cachexia. Cochrane Database Syst Rev 2012; :CD008664.
  150. Khoo SY, Quinlan N. Mirtazapine: A Drug with Many Palliative Uses #314. J Palliat Med 2016; 19:1116.
  151. Pape GS, Friedman M, Underwood LE, Clemmons DR. The effect of growth hormone on weight gain and pulmonary function in patients with chronic obstructive lung disease. Chest 1991; 99:1495.
  152. Takala J, Ruokonen E, Webster NR, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 1999; 341:785.
  153. Temel JS, Abernethy AP, Currow DC, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol 2016; 17:519.
  154. Madeddu C, Dessì M, Panzone F, et al. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr 2012; 31:176.
  155. Good P, Cavenagh J, Mather M, Ravenscroft P. Medically assisted nutrition for palliative care in adult patients. Cochrane Database Syst Rev 2008; :CD006274.
  156. Hoda D, Jatoi A, Burnes J, et al. Should patients with advanced, incurable cancers ever be sent home with total parenteral nutrition? A single institution's 20-year experience. Cancer 2005; 103:863.
  157. Brard L, Weitzen S, Strubel-Lagan SL, et al. The effect of total parenteral nutrition on the survival of terminally ill ovarian cancer patients. Gynecol Oncol 2006; 103:176.
  158. Sampson EL, Candy B, Jones L. Enteral tube feeding for older people with advanced dementia. Cochrane Database Syst Rev 2009; :CD007209.
  159. Lamont LS, Brown T, Riebe D, Caldwell M. The major components of human energy balance during chronic beta-adrenergic blockade. J Cardiopulm Rehabil 2000; 20:247.
  160. Hryniewicz K, Androne AS, Hudaihed A, Katz SD. Partial reversal of cachexia by beta-adrenergic receptor blocker therapy in patients with chronic heart failure. J Card Fail 2003; 9:464.
  161. Yusuf S, Gerstein H, Hoogwerf B, et al. Ramipril and the development of diabetes. JAMA 2001; 286:1882.
  162. Anker SD, Negassa A, Coats AJ, et al. Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study. Lancet 2003; 361:1077.
  163. Mehra MR, Lavie CJ, Ventura HO, Milani RV. Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure. J Heart Lung Transplant 2006; 25:834.
  164. Pasini E, Aquilani R, Dioguardi FS, et al. Hypercatabolic syndrome: molecular basis and effects of nutritional supplements with amino acids. Am J Cardiol 2008; 101:11E.
  165. Pasini E, Aquilani R, Gheorghiade M, Dioguardi FS. Malnutrition, muscle wasting and cachexia in chronic heart failure: the nutritional approach. Ital Heart J 2003; 4:232.
  166. van Wetering CR, Hoogendoorn M, Broekhuizen R, et al. Efficacy and costs of nutritional rehabilitation in muscle-wasted patients with chronic obstructive pulmonary disease in a community-based setting: a prespecified subgroup analysis of the INTERCOM trial. J Am Med Dir Assoc 2010; 11:179.
  167. Boccanfuso JA, Hutton M, McAllister B. The effects of megestrol acetate on nutritional parameters in a dialysis population. J Ren Nutr 2000; 10:36.
  168. Burrowes JD, Bluestone PA, Wang J, Pierson RN Jr. The effects of moderate doses of megestrol acetate on nutritional status and body composition in a hemodialysis patient. J Ren Nutr 1999; 9:89.
  169. Cheema B, Abas H, Smith B, et al. Progressive exercise for anabolism in kidney disease (PEAK): a randomized, controlled trial of resistance training during hemodialysis. J Am Soc Nephrol 2007; 18:1594.
  170. Johansen KL, Painter PL, Sakkas GK, et al. Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: A randomized, controlled trial. J Am Soc Nephrol 2006; 17:2307.