Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Weight Loss (Unintentional) article more useful, or one of our other health articles.
Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Cachexia is a wasting disorder that accompanies many chronic diseases, including cancer, and results from an imbalance between energy requirements and energy uptake.
What is cachexia?
Cachexia is not starvation; starvation may be part of cachexia and cachexia may result from starvation but they are different. It is associated with the advanced stages of various serious illnesses including:
- Many types of cancer (particularly pancreatic cancer, stomach cancer, oesophageal cancer, colorectal cancer).
- Congestive heart failure.
- Rheumatoid arthritis.
- Chronic obstructive pulmonary disease (COPD).
- Cystic fibrosis.
- Crohn's disease.
- Chronic kidney disease (CKD).
Cachexia is also seen in the elderly, without any apparent associated disease.
The prevalence of cachexia varies depending on the diagnostic criteria used: 5-15% in cardiac disease, 5-15% in COPD, 15-32% in rheumatoid arthritis, 50-75% in CKD, and between 60% and 80% in cancer patients. The prevalence exceeds 80% in the last 1-2 weeks of life.
Cancer cachexia is characterised by the loss of lean body mass with or without the loss of fat and is associated with reduced effectiveness of anti-cancer treatments, increased susceptibility to treatment-related toxicities, decreased quality of life, functional impairment, and increased cancer-related mortality.
Uncontrolled symptoms which impair nutritional intake, and metabolic derangements (including elevated energy expenditure and increased catabolism), and chronic inflammation, contribute to the development of cancer cachexia. Weight loss in cancer patients is not readily reversible by conventional nutritional support.
This is a common complication of chronic heart failure (CHF) which is associated with a poorer prognosis. Cardiac cachexia is defined as involuntary loss of 5% of body mass in twelve months or less. Myofibrillar proteins are degraded and there is also reduced protein synthesis. Endocrine factors are thought to play a regulatory role.
Adipose tissue cells (adipocytes) have been shown to release enzymes in CHF, which induce skeletal muscle wasting and reduce fat and bone mass.
Cancer cachexia represents the clinical consequence of an interaction between the tumour, the host metabolism and the involvement of pro-inflammatory cytokines (protein molecules which signal cells to produce an inflammatory reaction). The changes seen in cachexia may be characterised by an accelerated loss of skeletal muscle, often accompanied by loss of appetite and altered taste.
Skeletal muscle wasting is the principal cause of function impairment, fatigue and respiratory complications, The mechanisms involved have not been entirely elucidated but it is known that there is an increase in an enzyme, protein kinase R, which leads to muscle atrophy by a process of protein synthesis depression and an increase in degradation.
Adipose tissue loss is due to lipolysis. This is driven by a number of chemical triggers including lipid mobilising factor (LMF). Loss of adipose tissue and skeletal muscle mass is characteristic of cancer cachexia. Starvation on the other hand causes only loss of adipose tissue.
There is also an increase in the synthesis of proteins involved in the response to tissue injury - the so-called 'acute-phase response'.
Pathological changes occur in response to the body's acute-phase response to tissue damage, including synthesis by the liver of large amounts of proteins - eg, CRP, complement factors, fibrinogen and many others.
There are many causes of abnormal weight loss apart from cancer and cardiac failure. See the separate Abnormal Weight Loss article for a full list.
Cachexia treatment and management
Apart from maintaining optimal management of the underlying condition, there are currently no standardised treatments for cachexia or severe wasting. However there is a growing consensus advocating multimodal interventions to alleviate and/or stabilise cachexia and severe wasting. The different treatment modalities include pharmacological and non-pharmacological interventions, such as exercise and nutrition.
Hypercaloric feeding has repeatedly been shown as ineffective in increasing lean mass. It may cause weight gain but this is due to deposition of fat. The metabolic adaptations, notably the increase in the rate of protein catabolism, limit the ability of hypercaloric feeding to reverse the depletion of lean mass.
Parenteral nutritional support improves the way cancer patients withstand treatment and has a place in the palliative care of certain patients - eg, those with intestinal obstruction.
The National Institute for Health and Care Excellence (NICE) recommends oral, enteral or parenteral support (according to need and swallowing ability) for adults when:
- BMI is <18.5 kg/m3.
- There has been >10% of total body weight lost in the preceding 3-6 months.
- BMI is <20 and there has been 5% weight loss in the preceding 3-6 months.
- Insulin: insulin resistance is observed in cachexia. The possibility of utilising the insulin signalling system is currently being explored.
- Growth hormone, testosterone, oxandrolone and megestrol acetate have all been used with beneficial effect and the use of the orexigenic (= appetite-stimulating) peptide ghrelin is being explored.
- Enobosarm (a selected androgen receptor modulator) and anamorelin (a ghrelin agonist) have completed phase III trials. However, in 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion regarding anamorelin, recommending the refusal of the marketing authorisation for the intended use of treatment of anorexia, cachexia or unintended weight loss in patients with non-small cell lung cancer.
- Anti-inflammatory agents such as indometacin may be beneficial in patients with high CRP levels. The benefits of anti-inflammatory agents may be more apparent in non-malignant conditions and convey little benefit in patients with refractory cachexia.
- Steroids - eg, methylprednisolone - may be used in refractory cachexia for short periods (eg, two weeks).
- There may be a role for antioxidants in combating oxidative stress.
- Because of metabolic derangements seen in cancer cachexia, effective nutritional treatment regimens will probably require manipulation of host intermediary metabolism in addition to feeding: omega-3 fatty acids (eg, eicosapentaenoic acid) have been studied for their ability to reduce cytokine release but their benefits are not clearly established.
- Vitamin and mineral supplementation may be required in some cases.
Overall, the prognosis for the cachexia depends upon the severity of the underlying disease. However cachexia is often a complication with a very poor prognosis, and often represents the last step of several chronic diseases.
Exercise is a possible preventative measure against cancer cachexia. Nutritional counselling is also likely to be of benefit.
Further reading and references
Baker Rogers J, Syed K, Minteer JF; Cachexia. StatPearls, Aug 2021.
Grande AJ, Silva V, Sawaris Neto L, et al; Exercise for cancer cachexia in adults. Cochrane Database Syst Rev. 2021 Mar 183:CD010804. doi: 10.1002/14651858.CD010804.pub3.
Rohm M, Zeigerer A, Machado J, et al; Energy metabolism in cachexia. EMBO Rep. 2019 Apr20(4). pii: embr.201847258. doi: 10.15252/embr.201847258. Epub 2019 Mar 19.
McKeaveney C, Maxwell P, Noble H, et al; A Critical Review of Multimodal Interventions for Cachexia. Adv Nutr. 2021 Mar 3112(2):523-532. doi: 10.1093/advances/nmaa111.
Dev R; Measuring cachexia-diagnostic criteria. Ann Palliat Med. 2019 Jan8(1):24-32. doi: 10.21037/apm.2018.08.07. Epub 2018 Sep 7.
Ni J, Zhang L; Cancer Cachexia: Definition, Staging, and Emerging Treatments. Cancer Manag Res. 2020 Jul 912:5597-5605. doi: 10.2147/CMAR.S261585. eCollection 2020.
Mangner N, Matsuo Y, Schuler G, et al; Cachexia in chronic heart failure: endocrine determinants and treatment perspectives. Endocrine. 2012 Aug 19.
Loncar G, Fulster S, von Haehling S, et al; Metabolism and the heart: An overview of muscle, fat, and bone metabolism in heart failure. Int J Cardiol. 2011 Oct 6.
Lucia S, Esposito M, Rossi Fanelli F, et al; Cancer Cachexia: From Molecular Mechanisms to Patient's Care. Crit Rev Oncog. 201217(3):315-21.
Tisdale MJ; Cancer cachexia. Curr Opin Gastroenterol. 2010 Mar26(2):146-51.
Donohoe CL, Ryan AM, Reynolds JV; Cancer cachexia: mechanisms and clinical implications. Gastroenterol Res Pract. 20112011:601434. Epub 2011 Jun 13.
Suzuki H, Asakawa A, Amitani H, et al; Cancer cachexia--pathophysiology and management. J Gastroenterol. 2013 May48(5):574-94. doi: 10.1007/s00535-013-0787-0. Epub 2013 Mar 20.
Akbulut G; New perspective for nutritional support of cancer patients: Enteral/parenteral nutrition. Exp Ther Med. 2011 Jul2(4):675-684. Epub 2011 Apr 1.
Nutrition support in adults: oral nutrition support, enteral tube feeding and parenteral nutrition; NICE Clinical Guideline (2006 - last updated August 2017)
Aoyagi T, Terracina KP, Raza A, et al; Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol. 2015 Apr 157(4):17-29. doi: 10.4251/wjgo.v7.i4.17.
Honors MA, Kinzig KP; The role of insulin resistance in the development of muscle wasting during cancer cachexia. J Cachexia Sarcopenia Muscle. 2012 Mar3(1):5-11. Epub 2011 Dec 1.
Gullett NP, Hebbar G, Ziegler TR; Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting. Am J Clin Nutr. 2010 Apr91(4):1143S-1147S. Epub 2010 Feb 17.
Crawford J; Clinical results in cachexia therapeutics. Curr Opin Clin Nutr Metab Care. 2016 Mar 11.
Adlumiz; European Medicines Agency, 2017
Wyart E, Bindels LB, Mina E, et al; Cachexia, a Systemic Disease beyond Muscle Atrophy. Int J Mol Sci. 2020 Nov 1421(22). pii: ijms21228592. doi: 10.3390/ijms21228592.
Argiles JM, Busquets S, Lopez-Soriano FJ, et al; Are there any benefits of exercise training in cancer cachexia? J Cachexia Sarcopenia Muscle. 2012 Jun3(2):73-6. Epub 2012 May 8.