cachexia

Cachexia is hard to define because it often happens alongside malnutrition and sarcopenia.{{cite journal |vauthors=Peterson SJ, Mozer M |date=February 2017 |title=Differentiating Sarcopenia and Cachexia Among Patients With Cancer |journal=Nutrition in Clinical Practice |volume=32 |issue=1 |pages=30–39 |doi=10.1177/0884533616680354 |pmid=28124947 |s2cid=206555460}} Since there are no clear rules separating these conditions, experts continue working to agree on definitions to help treat these nutrition-related problems.

In the past, cachexia was described as "a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass." In 2011, experts updated this definition, saying cachexia is "a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment."{{cite journal |display-authors=6 |vauthors=Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE |date=May 2011 |title=Definition and classification of cancer cachexia: an international consensus |journal=The Lancet Oncology |volume=12 |issue=5 |pages=489–95 |doi=10.1016/s1470-2045(10)70218-7 |pmid=21296615}} They also suggested breaking it into three stages: pre-cachexia, cachexia, and refractory cachexia.

Cachexia and malnutrition are related but not the same. Malnutrition happens when the body doesn't get enough nutrients, leading to changes in body weight, physical strength, and mental function. Malnutrition includes both disease-related malnutrition as well as malnutrition without disease such as seen in starvation or aging. Cachexia should be viewed as a type of malnutrition in which inflammation from a long-term illness causes unwanted muscle loss.

Cachexia and sarcopenia are similar because both cause weight and muscle loss, along with symptoms like weakness and loss of appetite.{{Cite journal |last1=Meza-Valderrama |first1=Delky |last2=Marco |first2=Ester |last3=Dávalos-Yerovi |first3=Vanesa |last4=Muns |first4=Maria Dolors |last5=Tejero-Sánchez |first5=Marta |last6=Duarte |first6=Esther |last7=Sánchez-Rodríguez |first7=Dolores |date=2021-02-26 |title=Sarcopenia, Malnutrition, and Cachexia: Adapting Definitions and Terminology of Nutritional Disorders in Older People with Cancer |journal=Nutrients |language=en |volume=13 |issue=3 |pages=761 |doi=10.3390/nu13030761 |doi-access=free |issn=2072-6643 |pmc=7996854 |pmid=33652812}} The difference is sarcopenia is caused by aging, while cachexia happens due to long-term disease and inflammation.

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Cachexia is most commonly associated with end-stage cancer, often called cancer cachexia.{{cite journal |vauthors=Fearon KC, Moses AG |date=September 2002 |title=Cancer cachexia |journal=International Journal of Cardiology |volume=85 |issue=1 |pages=73–81 |doi=10.1016/S0167-5273(02)00235-8 |pmid=12163211}}

Other conditions that frequently cause cachexia include:

• Congestive heart failure
• AIDS
• Chronic obstructive pulmonary disease
• Chronic kidney disease{{cite journal | vauthors = Ebner N, Springer J, Kalantar-Zadeh K, Lainscak M, Doehner W, Anker SD, von Haehling S | title = Mechanism and novel therapeutic approaches to wasting in chronic disease | journal = Maturitas | volume = 75 | issue = 3 | pages = 199–206 | date = July 2013 | pmid = 23664695 | doi = 10.1016/j.maturitas.2013.03.014 | s2cid = 42148927 | url = https://zenodo.org/record/3420540 }}{{Dead link|date=November 2023 |bot=InternetArchiveBot |fix-attempted=yes }}

Cachexia can happen in late stages of diseases like cystic fibrosis, multiple sclerosis, motor neuron disease, Parkinson's disease, dementia, tuberculosis, multiple system atrophy, mercury poisoning, Crohn's disease, trypanosomiasis, rheumatoid arthritis,celiac disease, and other diseases that effect the entire body.{{cite journal | vauthors = Meresse B, Ripoche J, Heyman M, Cerf-Bensussan N | title = Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis | journal = Mucosal Immunology | volume = 2 | issue = 1 | pages = 8–23 | date = January 2009 | pmid = 19079330 | doi = 10.1038/mi.2008.75 | s2cid = 24980464 | doi-access = free }}{{cite journal | vauthors = Morley JE, Thomas DR, Wilson MM | title = Cachexia: pathophysiology and clinical relevance | journal = The American Journal of Clinical Nutrition | volume = 83 | issue = 4 | pages = 735–43 | date = April 2006 | pmid = 16600922 | doi = 10.1093/ajcn/83.4.735 | doi-access = free }}

File:Cancer-associated cachexia diagram.jpg

The way cachexia works is not well understood, but research suggests it is linked to inflammation, changes in metabolism, and hormone changes in the body .

Certain molecules in the body, called Inflammatory cytokines, play a big role in causing cachexia. Two important ones are tumor necrosis factor (TNF) and interleukin 6 (IL-6).

TNF breaks down muscle and fat while stopping new muscle and fat cells from forming by activating the ubiquitin proteasome pathway.{{Cite journal |last1=Petruzzelli |first1=Michele |last2=Wagner |first2=Erwin F. |date=2016-03-01 |title=Mechanisms of metabolic dysfunction in cancer-associated cachexia |journal=Genes & Development |language=en |volume=30 |issue=5 |pages=489–501 |doi=10.1101/gad.276733.115 |issn=0890-9369 |pmc=4782044 |pmid=26944676}}{{Cite journal |last1=Setiawan |first1=Tania |last2=Sari |first2=Ita Novita |last3=Wijaya |first3=Yoseph Toni |last4=Julianto |first4=Nadya Marcelina |last5=Muhammad |first5=Jabir Aliyu |last6=Lee |first6=Hyeok |last7=Chae |first7=Ji Heon |last8=Kwon |first8=Hyog Young |date=2023-05-22 |title=Cancer cachexia: molecular mechanisms and treatment strategies |journal=Journal of Hematology & Oncology |language=en |volume=16 |issue=1 |page=54 |doi=10.1186/s13045-023-01454-0 |doi-access=free |issn=1756-8722 |pmc=10204324 |pmid=37217930}} It also triggers the release of other cytokines that also speed up muscle loss. Since this process is very complex, cachexia is unlikely to be caused by one molecule. While it is thought to be produced by immune cells called macrophages, scientists are still unsure of exactly where TNF is produced in cachexia.

IL-6 is thought to cause muscle loss by starting a pathway called the JAK/STAT pathway.{{Cite journal |last1=Moresi |first1=Viviana |last2=Adamo |first2=Sergio |last3=Berghella |first3=Libera |date=2019-04-30 |title=The JAK/STAT Pathway in Skeletal Muscle Pathophysiology |journal=Frontiers in Physiology |volume=10 |page=500 |doi=10.3389/fphys.2019.00500 |doi-access=free |issn=1664-042X |pmc=6502894 |pmid=31114509}} IL-6 is produced by immune cells called macrophages, potentially producing acute phase reactants which may worsen muscle loss.

Other molecules may include:

• Myostatin - Prevents muscle growth and is often higher in people with cancer.{{cite journal |vauthors=Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R, Rodriguez-Mañas L |date=September 2016 |title=Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease |journal=Journal of the American Medical Directors Association |volume=17 |issue=9 |pages=789–96 |doi=10.1016/j.jamda.2016.04.019 |pmid=27324808 |doi-access=free}}
• Activin - May contribute to muscle loss when TNF is also active.
• Growth Differentiation Factor 15 (GDF-15) - Normally produced during cellular stress. Thought to play a role in food aversion and is associated with reduced food intake.

Cachexia can also result from changes in metabolism. Tumors sometimes release molecules that break down fat and muscle, causing cachexia by making it harder for the body to keep up with energy needs. These molecules include lipid mobilizing factor, proteolysis-inducing factor, and mitochondrial uncoupling proteins.{{cite journal | vauthors = Martignoni ME, Kunze P, Friess H | title = Cancer cachexia | journal = Molecular Cancer | volume = 2 | issue = 1 | pages = 36 | date = November 2003 | pmid = 14613583 | pmc = 280692 | doi = 10.1186/1476-4598-2-36 | doi-access = free }} In addition, uncontrolled inflammation in people with cachexia increases the body's need for nutrients.

The way the body uses nutrients is also changed in cachexia. People with cachexia can have loss of appetite, are less responsive to insulin, and can have increased fat breakdown, all of which make it difficult for the body to properly use food. This is especially true in people with cancer.

Hormones are signaling molecules used to regulate bodily behavior and are believed to play a role in cachexia as well.

Glucocorticoids are produced as part of the body's natural response to stress. They are also known to play a role in muscle breakdown.{{Cite journal |last1=Salehian |first1=Behrouz |last2=Kejriwal |first2=Kamal |date=1999 |title=Glucocorticoid-Induced Muscle Atrophy: Mechanisms And Therapeutic Strategies |url=https://linkinghub.elsevier.com/retrieve/pii/S1530891X20402952 |journal=Endocrine Practice |language=en |volume=5 |issue=5 |pages=277–281 |doi=10.4158/EP.5.5.277|pmid=15251668 }} Furthermore, people with long-term illness such as cancer are frequently treated with glucocorticoids, making cachexia more likely in these individuals.

Some tumors produce a molecule called parathyroid-related peptide (PTHrP). It increases metabolism by stimulating energy production in the mitochondria of fat cells.

Leptin is a hormone known to decrease appetite. People with cachexia often have high leptin levels, making them feel less hungry.

The hypothalamus, the brain's appetite control center, is also affected in cachexia. Given the hypothalamic function in controlling appetite, it is believed to play a role in cachexia. The appetite-controlling center of the hypothalamus is controlled by neuropeptide Y (NPY) and agouti gene-related protein (AgRP) that increase appetite, as well as proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcrip (CART) that decrease appetite. Inflammation may disrupt these appetite signals, causing reduced hunger and leading to further weight and muscle loss. However, scientists are still studying exactly how this process works.

Doctors used to diagnose cachexia mainly by looking at changes in body weight. A person was considered to have cachexia if they had a low BMI or unwanted weight loss of more than 10%. However, only using weight is not always a reliable method. Factors like fluid buildup (edema), tumor size, and obesity can make it difficult to diagnose cachexia.{{cite journal | vauthors = Dev R | title = Measuring cachexia-diagnostic criteria | journal = Annals of Palliative Medicine | volume = 8 | issue = 1 | pages = 24–32 | date = January 2019 | pmid = 30525765 | doi = 10.21037/apm.2018.08.07 | doi-access = free }} These weight-based criteria do not account for muscle loss, which is a key part in cachexia. .

To improve diagnosis of cachexia, experts proposed adding lab tests and symptom evaluations. With that, a person might have cachexia if they lost at least 5% of their total body weight in 12 months or had a BMI under less 22 kg/m² with at least three of the following: weak muscles, fatigue, loss of appetite, low muscle mass, or abnormal labs.

There have also been attempts to define specific types of cachexia, such as cardiac cachexia, which can occur in people with congestive heart failure.{{Cite journal |last1=Anker |first1=Stefan D. |last2=Coats |first2=Andrew J.S. |date=1999 |title=Cardiac Cachexia |url=https://linkinghub.elsevier.com/retrieve/pii/S0012369216356586 |journal=Chest |language=en |volume=115 |issue=3 |pages=836–847 |doi=10.1378/chest.115.3.836 |pmid=10084500}} However, there is no widely accepted definition for it.

Cancer cachexia is now diagnosed based on:

1. Unwanted weight loss of more than 5% within 6 months.{{Cite journal |last1=Nishikawa |first1=Hiroki |last2=Goto |first2=Masahiro |last3=Fukunishi |first3=Shinya |last4=Asai |first4=Akira |last5=Nishiguchi |first5=Shuhei |last6=Higuchi |first6=Kazuhide |date=2021-08-06 |title=Cancer Cachexia: Its Mechanism and Clinical Significance |journal=International Journal of Molecular Sciences |language=en |volume=22 |issue=16 |pages=8491 |doi=10.3390/ijms22168491 |doi-access=free |issn=1422-0067 |pmc=8395185 |pmid=34445197}}
2. For people with a BMI of less than 20 kg/m², weight loss of more than 2%.
3. For people with sarcopenia, weight loss of more than 2%.

New ways to score and stage cachexia are being explored, particularly in people with advanced cancer.

To better understand how bad cachexia is in each person, doctors now use scoring systems like the Cachexia Staging Score and Cachexia Score.

The Cachexia Staging Score (CSS) looks at weight loss, muscle function, appetite loss, and lab test results to categorize people into four stages: non-cachexia, pre-cachexia, cachexia, and refractory cachexia. Those in more advanced stages have less muscle mass, more frequent age-related muscle loss, worse symptoms, poorer quality of life, as well as shorter survival periods.

• Non-cachexia (0-2 points) - No major weight loss or problems with appetite.
• Pre-cachexia (3-4 points) - Mild weight loss and appetite issues. Early treatment at this stage might slow progression of cachexia.
• Cachexia (5-8 points) - Significant muscle loss that is difficult to reverse and affects daily function.{{Cite journal |last=Arends |first=J. |last2=Baracos |first2=V. |last3=Bertz |first3=H. |last4=Bozzetti |first4=F. |last5=Calder |first5=P.C. |last6=Deutz |first6=N.E.P. |last7=Erickson |first7=N. |last8=Laviano |first8=A. |last9=Lisanti |first9=M.P. |last10=Lobo |first10=D.N. |last11=McMillan |first11=D.C. |last12=Muscaritoli |first12=M. |last13=Ockenga |first13=J. |last14=Pirlich |first14=M. |last15=Strasser |first15=F. |date=October 2017 |title=ESPEN expert group recommendations for action against cancer-related malnutrition |url=https://linkinghub.elsevier.com/retrieve/pii/S0261561417302285 |journal=Clinical Nutrition |language=en |volume=36 |issue=5 |pages=1187–1196 |doi=10.1016/j.clnu.2017.06.017}}
• Refractory cachexia (9-12 points) - Severe weight and muscle loss with poor response to treatment and a life expectancy of less than 3 months.

The Cachexia SCOre (CASCO) is another scoring system that looks at weight loss, inflammation, metabolism, immune function, physical ability, appetite, and quality of life to provide a more detailed assessment.

Laboratory tests are sometimes used to check for cachexia. Tests that are used include albumin, C-reactive protein, ghrelin, IGF-2, and leptin. Acute phase reactants (IL-6, IL-1b, tumor necrosis factor, IL-8, interferon gamma and serum cytokines are also studied but are not always reliable for predicting cachexia. Laboratory cut-off values are also not the same across different institutions. There is no single lab test that can confirm cachexia or predict who will develop it.

One challenge in diagnosing cachexia is measuring muscle loss in an easy and affordable way. Some imaging techniques that can help assess body composition include:

• Bioelectrical impedance analysis (BIA)
• Computed tomography (CT scans)
• Dual-energy X-ray absorptiometry (DEXA)
• Magnetic resonance imaging (MRI)

However, these methods are not widely used because they can be expensive and difficult to access.

Because cachexia is a complex condition with several potential causes, treatment requires multiple approaches at the same time. The best strategy is to treat the cause of the cachexia, if known.{{cite web|title=Care Management Guidelines Fatigue, Anorexia and Cachexia|url=http://www.dhhs.tas.gov.au/__data/assets/pdf_file/0006/36942/Fatigue_Anorexia_Cachexia_Final290909_PCSSubComm.pdf|access-date=23 February 2014|archive-url=https://web.archive.org/web/20140514022343/http://www.dhhs.tas.gov.au/__data/assets/pdf_file/0006/36942/Fatigue_Anorexia_Cachexia_Final290909_PCSSubComm.pdf|archive-date=2014-05-14|url-status=dead}} For example, people with cachexia caused by AIDS often improve after starting treatment for AIDS.{{Cite web|url=https://www.webmd.com/hiv-aids/guide/aids-wasting-syndrome|title=AIDS Wasting Syndrome|website=WebMD}} However, because the exact mechanism of cachexia is unclear, there is no single medication that can effectively treat it. Instead, treatment focuses on a combination of exercise, nutrition, medications, and psychosocial support.

Regular physical exercise is recommended for the treatment of cachexia because of its positive effects on muscle function. Exercise can reduce protein breakdown, improve muscle strength, decrease inflammation, and enhance metabolism. However, its effectiveness in cancer patients - especially those who are frail or have sarcopenia - remains uncertain.{{cite journal | vauthors = Grande AJ, Silva V, Sawaris Neto L, Teixeira Basmage JP, Peccin MS, Maddocks M | title = Exercise for cancer cachexia in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 3| pages = CD010804 | date = March 2021 | pmid = 33735441 | doi = 10.1002/14651858.CD010804.pub3|pmc=8094916 }} Many people with cachexia also avoid exercise because they lack motivation or fear that it will worsen their symptoms.{{cite journal | vauthors = Wasley D, Gale N, Roberts S, Backx K, Nelson A, van Deursen R, Byrne A | title = Patients with established cancer cachexia lack the motivation and self-efficacy to undertake regular structured exercise | journal = Psycho-Oncology | volume = 27 | issue = 2 | pages = 458–464 | date = February 2018 | pmid = 28758698 | doi = 10.1002/pon.4512 | s2cid = 206378678 | url = http://orca.cf.ac.uk/103309/1/Structured%20exercise%20and%20patients%20with%20cancer%20cachexia%20main%20document%20with%20bold%20revisions%20final17.pdf | hdl = 10369/8759 | hdl-access = free }}

Cachexia can increase metabolism and suppress appetite, worsening the present muscle loss. Studies show that high-calorie, protein-rich diets may help stabilize weight, though they do not necessarily improve muscle mass.{{cite journal | vauthors = Kumar NB, Kazi A, Smith T, Crocker T, Yu D, Reich RR, Reddy K, Hastings S, Exterman M, Balducci L, Dalton K, Bepler G | title = Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment | journal = Current Treatment Options in Oncology | volume = 11 | issue = 3–4 | pages = 107–17 | date = December 2010 | pmid = 21128029 | pmc = 3016925 | doi = 10.1007/s11864-010-0127-z }} Current recommendations include 1.5g/kg/day of protein, making up 15-20% of daily calories. However, feeding tubes (enteral nutrition) should not be used routinely.{{Cite journal |last=Roeland |first=Eric J. |last2=Bohlke |first2=Kari |last3=Baracos |first3=Vickie E. |last4=Bruera |first4=Eduardo |last5=del Fabbro |first5=Egidio |last6=Dixon |first6=Suzanne |last7=Fallon |first7=Marie |last8=Herrstedt |first8=Jørn |last9=Lau |first9=Harold |last10=Platek |first10=Mary |last11=Rugo |first11=Hope S. |last12=Schnipper |first12=Hester H. |last13=Smith |first13=Thomas J. |last14=Tan |first14=Winston |last15=Loprinzi |first15=Charles L. |date=2020-07-20 |title=Management of Cancer Cachexia: ASCO Guideline |url=https://ascopubs.org/doi/10.1200/JCO.20.00611 |journal=Journal of Clinical Oncology |language=en |volume=38 |issue=21 |pages=2438–2453 |doi=10.1200/JCO.20.00611 |issn=0732-183X}}

Some medications, such as glucocorticoids, cannabinoids, and progestins were initially used in treating cachexia and aim to increase appetite. Progestins showed promise initially, but they do not stop muscle wasting and may cause fluid retention, fat gain, and other side effects.

Ghrelin agonists, such as Anamorelin are commonly used in cancer treatment to boost appetite, increase weight, and increase muscle mass. However, its use and effectiveness in cachexia is not well studied.

Selective androgen receptor modulators (SARMs) such as Enobosarm show promise in increasing physical performance and muscle mass, but more studies are needed to confirm their effectiveness in cachexia.

The use of anti-inflammatory medications have been investigated. Thalidomide, an anti-inflammatory agent, has shown promise in preventing weight loss, but the use of this medication in cachexia is not widely accepted.{{cite journal |vauthors=Reid J, Mills M, Cantwell M, Cardwell CR, Murray LJ, Donnelly M |date=April 2012 |title=Thalidomide for managing cancer cachexia |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=4 |pages=CD008664 |doi=10.1002/14651858.cd008664.pub2 |pmc=6353113 |pmid=22513961}} However, other TNF inhibitors have not shown the same promising results. NSAIDs such as celecoxib and ibuprofen showed some early benefits, but side effects (renal injury, GI bleeding) limit their use.

Anti-nausea drugs such as 5-HT₃ antagonists are also commonly used if nausea is a prominent symptom.

Anabolic steroids like oxandrolone may help but are only recommended for short term use due to side effects including liver toxicity.{{cite book |author=Giovanni Mantovani |url=https://books.google.com/books?id=lQyGxrmQ17AC&pg=PA673 |title=Cachexia and Wasting: A Modern Approach |date=6 October 2007 |publisher=Springer Science & Business Media |isbn=978-88-470-0552-5 |pages=673–}}

The use of certain amino acids may slow muscle breakdown by providing the body with the building blocks needed for metabolism of muscle and glucose. Specifically, leucine and valine may block muscle breakdown.{{cite journal | vauthors = Eley HL, Russell ST, Tisdale MJ | title = Effect of branched-chain amino acids on muscle atrophy in cancer cachexia | journal = The Biochemical Journal | volume = 407 | issue = 1 | pages = 113–20 | date = October 2007 | pmid = 17623010 | pmc = 2267397 | doi = 10.1042/BJ20070651 }} Glutamine is used in oral supplements for people with advanced cancer{{cite journal | vauthors = May PE, Barber A, D'Olimpio JT, Hourihane A, Abumrad NN |author5-link=Naji Abumrad | title = Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine | journal = American Journal of Surgery | volume = 183 | issue = 4 | pages = 471–9 | date = April 2002 | pmid = 11975938 | doi = 10.1016/s0002-9610(02)00823-1 }} or HIV/AIDS.{{cite web|title=Glutamine|url=http://www.webmd.com/vitamins-supplements/ingredientmono-878-glutamine.aspx?activeingredientid=878&activeingredientname=glutamine|website=WebMD|publisher=WebMD, LLC|access-date=2015-03-15}}

β-hydroxy β-methylbutyrate (HMB) is a molecule that comes from leucine that promotes muscle growth. Studies show positive results for chronic pulmonary disease, hip fracture, and in AIDS-related and cancer-related cachexia. However, it is often studied along with other nutrients, making it difficult to assess its effects alone.{{cite journal | vauthors = Brioche T, Pagano AF, Py G, Chopard A | title = Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention | journal = Molecular Aspects of Medicine | volume = 50 | pages = 56–87 | date = August 2016 | pmid = 27106402 | doi = 10.1016/j.mam.2016.04.006 | s2cid = 29717535 | url = https://hal.archives-ouvertes.fr/hal-01837630/file/2016_Brioche_MAM_1.pdf }}{{cite journal | vauthors = Holeček M | title = Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions | journal = Journal of Cachexia, Sarcopenia and Muscle | volume = 8 | issue = 4 | pages = 529–541 | date = August 2017 | pmid = 28493406 | pmc = 5566641 | doi = 10.1002/jcsm.12208 }}

Creatine supplementation may help reduce muscle wasting, though more research is needed.{{cite journal | vauthors = Lulu W, Ranran W, Kai L, Xiaolu J, Li L | title = Creatine modulates cellular energy metabolism and protects against cancer cachexia-associated muscle wasting | journal = Frontiers in Pharmacology | date = 7 December 2022 | volume = 13 | pmid = 36569317 | doi = 10.3389/fphar.2022.1086662 | doi-access = free | pmc = 9767983 }}

Accurate epidemiological data on the prevalence of cachexia is lacking due to changing diagnostic criteria and under-identification of people with the disorder.{{cite journal | vauthors = von Haehling S, Anker SD | title = Cachexia as a major underestimated and unmet medical need: facts and numbers | journal = Journal of Cachexia, Sarcopenia and Muscle | volume = 1 | issue = 1 | pages = 1–5 | date = September 2010 | pmid = 21475699 | pmc = 3060651 | doi = 10.1007/s13539-010-0002-6 }} It is estimated that cachexia from any disease is estimated to affect more than 5 million people in the United States. The prevalence of cachexia is growing and estimated at 1% of the population. The prevalence is lower in Asia but due to the larger population, represents a similar burden. Cachexia is also a significant problem in South America and Africa.

Within people with cancer, prevalence of cachexia was previously reported to range from 11%-71%.{{Cite journal |last1=Anker |first1=Markus S. |last2=Holcomb |first2=Richard |last3=Muscaritoli |first3=Maurizio |last4=von Haehling |first4=Stephan |last5=Haverkamp |first5=Wilhelm |last6=Jatoi |first6=Aminah |last7=Morley |first7=John E. |last8=Strasser |first8=Florian |last9=Landmesser |first9=Ulf |last10=Coats |first10=Andrew J.S. |last11=Anker |first11=Stefan D. |date=2019 |title=Orphan disease status of cancer cachexia in the USA and in the European Union: a systematic review |journal=Journal of Cachexia, Sarcopenia and Muscle |language=en |volume=10 |issue=1 |pages=22–34 |doi=10.1002/jcsm.12402 |issn=2190-5991 |pmc=6438416 |pmid=30920776}} Recent updates show that 33%-51.8% of people with cancer develop cachexia, though current estimates of prevalence vary widely and may be unreliable due to absence of consensus guidelines for diagnosis, variability in cancer populations, and variability in timing of diagnosis.{{Cite journal |last1=Takaoka |first1=Tomoya |last2=Yaegashi |first2=Akinori |last3=Watanabe |first3=Daiki |date=2024 |title=Prevalence of and Survival with Cachexia among Patients with Cancer: A Systematic Review and Meta-Analysis |journal=Advances in Nutrition |language=en |volume=15 |issue=9 |pages=100282 |doi=10.1016/j.advnut.2024.100282 |pmc=11402144 |pmid=39127425}}{{Cite journal |last1=Poisson |first1=Johanne |last2=Martinez-Tapia |first2=Claudia |last3=Heitz |first3=Damien |last4=Geiss |first4=Romain |last5=Albrand |first5=Gilles |last6=Falandry |first6=Claire |last7=Gisselbrecht |first7=Mathilde |last8=Couderc |first8=Anne-Laure |last9=Boulahssass |first9=Rabia |last10=Liuu |first10=Evelyne |last11=Boudou-Rouquette |first11=Pascaline |last12=Chah Wakilian |first12=Anne |last13=Gaxatte |first13=Cedric |last14=Pamoukdjian |first14=Fréderic |last15=de Decker |first15=Laure |date=2021 |title=Prevalence and prognostic impact of cachexia among older people with cancer: a nationwide cross-sectional survey (NutriAgeCancer) |journal=Journal of Cachexia, Sarcopenia and Muscle |language=en |volume=12 |issue=6 |pages=1477–1488 |doi=10.1002/jcsm.12776 |issn=2190-5991 |pmc=8718093 |pmid=34519440}} Specifically, the highest rates were seen in older populations as well as those with upper gastrointestinal, colorectal, and lung cancers, respectively. The prevalence increases in advanced cancer stages, affecting up to 80% of terminal cancer cases.

The most frequent diseases causing cachexia in the United States are: 1) Cancer , 2) chronic heart failure, 3) chronic kidney disease, 4) COPD.

Cachexia contributes to significant loss of function and healthcare utilization. Estimates suggest that cachexia accounted for 177,640 hospital stays in 2016 in the United States.Barrett ML, Bailey MK, Owens PL. Non-maternal and Non-neonatal Inpatient Stays in the United States Involving Malnutrition, 2016. ONLINE. August 30, 2018. U.S. Agency for Healthcare Research and Quality. Available: https://www.hcup-us.ahrq.gov/reports/HCUPMalnutritionHospReport_083018.pdf {{Webarchive|url=https://web.archive.org/web/20211127012911/https://hcup-us.ahrq.gov/reports/HCUPMalnutritionHospReport_083018.pdf |date=2021-11-27 }}. Cachexia is considered the immediate cause of death of many people with cancer, estimated between 22 and 40%.{{cite journal|vauthors=Alhamarneh O, Agada F, Madden L, Stafford N, Greenman J|date=March 2011|title=Serum IL10 and circulating CD4(+) CD25(high) regulatory T cell numbers as predictors of clinical outcome and survival in patients with head and neck squamous cell carcinoma|journal=Head & Neck|volume=33|issue=3|pages=415–23|doi=10.1002/hed.21464|pmid=20645289|s2cid=20061488|doi-access=free}}

The word "cachexia" is derived from the Greek words "Kakos" (bad) and "hexis" (condition). English ophthalmologist John Zachariah Laurence was the first to use the phrase "cancerous cachexia", doing so in 1858. He applied the phrase to the chronic wasting associated with malignancy. It was not until 2011 that the term "cancer-associated cachexia" was given a formal definition, with a publication by Kenneth Fearon. Fearon defined it as "a multifactorial syndrome characterized by ongoing loss of skeletal muscle (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment".{{cite journal|doi=10.1146/annurev-cancerbio-030419-033642|doi-access=free|title=Cancer-Associated Cachexia: A Systemic Consequence of Cancer Progression|year=2020|last1=Biswas|first1=Anup K.|last2=Acharyya|first2=Swarnali|journal=Annual Review of Cancer Biology|volume=4|pages=391–411}}

Several medications are under investigation or have been previously trialed for use in cachexia but are currently not in widespread clinical use:

• Thalidomide
• Cytokine antagonists
• Cannabinoids
• Omega-3 fatty acids, including eicosapentaenoic acid (EPA){{cite journal | vauthors = Ries A, Trottenberg P, Elsner F, Stiel S, Haugen D, Kaasa S, Radbruch L | title = A systematic review on the role of fish oil for the treatment of cachexia in advanced cancer: an EPCRC cachexia guidelines project | journal = Palliative Medicine | volume = 26 | issue = 4 | pages = 294–304 | date = June 2012 | pmid = 21865295 | doi = 10.1177/0269216311418709 | s2cid = 2801425 | url = https://opus4.kobv.de/opus4-fau/files/3468/ries_systematic.pdf }}
• Non-steroidal anti-inflammatory drugs
• Prokinetics
• Ghrelin and ghrelin receptor agonist
• Anabolic catabolic transforming agents such as MT-102
• Selective androgen receptor modulators
• Cyproheptadine{{cite journal | vauthors = Suzuki H, Asakawa A, Amitani H, Nakamura N, Inui A | title = Cancer cachexia--pathophysiology and management | journal = Journal of Gastroenterology | volume = 48 | issue = 5 | pages = 574–94 | date = May 2013 | pmid = 23512346 | pmc = 3698426 | doi = 10.1007/s00535-013-0787-0 }}
• Hydrazine sulfate

Medical marijuana has been allowed for the treatment of cachexia in some US states, such as Missouri, Illinois, Maryland, Delaware, Nevada, Michigan, Washington, Oregon, California, Colorado, New Mexico, Arizona, Vermont, New Jersey, Rhode Island, Maine, and New York {{Cite web|url=https://www.health.ny.gov/regulations/medical_marijuana/about.htm|title=Program Information and News - New York State Medical Marijuana Program|website=www.health.ny.gov}}[http://www.maine.gov/dhhs/dlrs/mmm/documents/MMMP-Rules-144c122.pdf Rules Governing the Maine Medical Use of Marijuana Program] {{Webarchive|url=https://web.archive.org/web/20141112003735/http://www.maine.gov/dhhs/dlrs/mmm/documents/MMMP-Rules-144c122.pdf |date=2014-11-12 }} - 10-144 CMR Chapter 122 - Section 3.1.3 Hawaii{{Cite web|url=http://health.hawaii.gov/medicalmarijuanaregistry/providers/debilitating-medical-conditions/|title=Medical Marijuana Registry Program {{!}} Eligible Debilitating Medical Conditions|website=health.hawaii.gov|access-date=2016-04-27|archive-url=https://web.archive.org/web/20160522062325/http://health.hawaii.gov/medicalmarijuanaregistry/providers/debilitating-medical-conditions/|archive-date=2016-05-22|url-status=dead}} and Connecticut.{{cite journal | vauthors = Gagnon B, Bruera E | title = A review of the drug treatment of cachexia associated with cancer | journal = Drugs | volume = 55 | issue = 5 | pages = 675–88 | date = May 1998 | pmid = 9585863 | doi = 10.2165/00003495-199855050-00005 | s2cid = 22180434 }}{{cite journal | vauthors = Yavuzsen T, Davis MP, Walsh D, LeGrand S, Lagman R | title = Systematic review of the treatment of cancer-associated anorexia and weight loss | journal = Journal of Clinical Oncology | volume = 23 | issue = 33 | pages = 8500–11 | date = November 2005 | pmid = 16293879 | doi = 10.1200/JCO.2005.01.8010 }}

Despite the extensive investigation into single therapeutic targets for cachexia, the most effective treatments use multi-targeted therapies. In Europe, a combination of non-drug approaches including physical training, nutritional counseling, and psychotherapeutic intervention are used in belief this approach may be more effective than monotherapy.{{cite web|url=http://www.epcrc.org/guidelines.php?p=cachexia|title=New European Guidelines: Clinical Practice Guidelines on Cancer Cachexia in Advanced Cancer Patients|publisher=European Palliative Care Research Collaborative|url-status=dead|archive-url=https://web.archive.org/web/20140502215044/http://www.epcrc.org/guidelines.php?p=cachexia|archive-date=2 May 2014|access-date=23 February 2014}} Administration of anti-inflammatory drugs showed efficacy and safety in the treatment of people with advanced cancer cachexia.{{cite journal | vauthors = Argilés JM, Busquets S, López-Soriano FJ | title = Anti-inflammatory therapies in cancer cachexia | journal = European Journal of Pharmacology | volume = 668 | pages = S81–6 | date = September 2011 | issue = Suppl 1 | pmid = 21835173 | doi = 10.1016/j.ejphar.2011.07.007 }}

• Malnutrition
• Sarcopenia
• Muscle atrophy
• Marasmus
• Cancer
• Progressive disease
• Refeeding syndrome
• Journal of Cachexia, Sarcopenia and Muscle

{{Reflist}}

{{Medical resources

| ICD10 = {{ICD10|R|64||r|50}}

| ICD9 = {{ICD9|799.4}}

| MeshID = D002100

| DiseasesDB = 28890

| SNOMED CT = 238108007

}}

{{Nutritional pathology}}

{{General symptoms and signs}}

{{Wiktionary}}

{{Authority control}}

Category:Geriatrics

Category:Rehabilitation medicine

Category:Symptoms and signs: Endocrinology, nutrition, and metabolism