Cachexia is weight loss, muscle atrophy, fatigue, weakness, and significant loss of appetite in a person who is not actively trying to lose weight. The official definition of cachexia is a loss of body mass, with minimal accumulation of adipose tissue, that cannot be reversed nutritionally: even if the person eats more calories, some of the body mass is lost, reflecting the presence of an underlying disease. Cachexia is seen in patients with cancer, AIDS, celiac disease, chronic obstructive pulmonary disease, multiple sclerosis, rheumatoid arthritis, congestive heart failure, tuberculosis, familial amyloid polyneuropathy, mercury poisoning, and hormonal imbalances. Cachexia is a well-established risk factor, meaning that if a patient has cachexia, the chance of dying from the underlying disease is greatly increased. Cachexia can be a clinical sign of various underlying disorders. When a patient with cachexia is seen by a doctor, he or she will generally consider the possibility of adverse drug interactions, cancer, metabolic acidosis, certain infectious diseases, chronic pancreatitis, and some autoimmune diseases. Cachexia weakens patients Physically to a state of immobility caused by loss of appetite, weakness, and anemia, and the response to standard therapy is usually poor. Cachexia includes sarcopenia as part of its disease course. Cachexia is usually seen in the final stages of cancer and is called cancer cachexia. Patients with congestive heart failure may suffer from wasting syndrome. Cachexia is also seen in patients with any of the group of diseases classified as chronic obstructive pulmonary disease. Cachexia is also associated with advanced stages of chronic kidney disease, cystic fibrosis, multiple sclerosis, motor neuron disease, Parkinson's disease, dementia, HIV, and progressive diseases. About 50% of all cancer patients suffer from cachexia. Those with pancreatic and upper gastrointestinal cancers have a higher incidence of developing cachexia symptoms. This figure rises to 80% in patients with terminal cancer. In addition to increased morbidity and mortality, worsening side effects of chemotherapy, and decreased quality of life, cachexia is a direct cause of death for a large proportion of cancer patients, ranging from 22% to 40% of patients. Symptoms of cachexia include progressive weight loss and depletion of host stores of adipose tissue and skeletal muscle. Cachexia should be suspected if 5% of precachexia weight is lost involuntarily within 6 months. Conventional treatment approaches, such as appetite stimulants, 5-HT3 antagonists, nutritional supplements, and COX-2 inhibitors, have not been shown to reverse the metabolic abnormalities in cachexia. The exact mechanism by which these diseases cause cachexia is not understood, but there may be a role for inflammatory cytokines, such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-6, as well as tumor-secreted proteolytic factor. Syndromes associated with cachexia include kwashiorkor and marasmus, although these syndromes have no underlying cause and are often symptoms of severe malnutrition. Those with eating disorders such as anorexia nervosa have elevated levels of ghrelin in Plasma. Ghrelin levels are also elevated in patients with cancer-induced cachexia. Much research is currently focused on determining the mechanism of cachexia. The two main theories for the pathogenesis of cancer cachexia are: Although the mechanism by which cancer cachexia occurs is not understood, the involvement of biological pathways can be discerned, including pro-inflammatory cytokines such as tumor necrosis factor-alpha, neuroendocrine hormones, insulin-like factor 1, and tumor-specific factors such as protein degradation-inducing factor. Inflammatory cytokines involved in wasting diseases are interleukin-6, tumor necrosis factor-alpha, interleukin-1β, and interferon-gamma. Although many different tissues and cell types may be responsible for the increased cytokines in circulation in some cancers, evidence points to tumors as an important source. Cytokines are capable of weight loss. TNF-alpha has been shown to have a direct catabolic effect on skeletal muscle and adipose tissue and to cause muscle atrophy through a pathway Ubiquitin – a proteolytic proteasome. The mechanism involves the formation of reactive oxygen species that leads to increased expression of the transcription factor nuclear factor kappa light chain enhancer in activated B cells. NF-κB is a known regulator of genes encoding cytokine synthesis and cytokine receptors. Excess cytokine secretion stimulates proteolysis and breakdown of myofibrillar proteins. How cachexia is treated depends on the underlying cause, overall prognosis, and related factors related to the individual. Reversible causes, underlying diseases, and contributing factors are treated if feasible and acceptable. A growing body of evidence supports the efficacy of β-hydroxy β-methylbutyrate as a treatment to reduce, or even reverse, the loss of muscle mass, muscle function, and muscle strength that occurs in hypercatabolic conditions such as cachexia. Consequently, as of June 2016, it is recommended that prevention and treatment of cachexia include HMB supplementation, regular strength training, and high-protein diets. Progestins such as megestrol acetate are used as an option Treatment for intractable cachexia with anorexia as the main symptom. Cachexia now occurs less frequently in HIV/AIDS than in the past due to the advent of HAART. Combination therapy for cancer cachexia is recommended in Europe, as a combination of nutrition, medication, and non-drug therapy may be more effective than monotherapy. Non-drug therapies that have been shown to be effective in cancers caused by cachexia include nutritional counseling, psychotherapeutic interventions, and physical training. Anabolic androgenic steroids such as oxandrolone may be helpful in cancer cachexia but are recommended for use for a maximum of two weeks; Longer treatment times increase the burden of side effects. Other medications that have been used or are being investigated for the treatment of cachexia, but conclusive evidence of efficacy or safety is lacking, and are generally not recommended: Medical marijuana is legal for the treatment of cachexia in some states, including Illinois, Maryland, Delaware, Nevada, Michigan, Washington, Oregon, California, Colorado, New Mexico, Arizona, Vermont, New Jersey, Rhode Island, Maine, New York, Hawaii, and Connecticut. There is insufficient evidence to support the use of oral fish oil for the treatment of cachexia associated with advanced cancer. There are limited options for treating cancer cachexia patients. The current strategy is to improve appetite using aphrodisiacs to ensure adequate nutrient intake. Pharmacological interventions using appetite stimulants, nutritional supplements, 5-HT3 antagonists, and COX-2 inhibitors have been used to treat cancer cachexia, but with limited effect. Studies have suggested that increasing calorie-dense calories and increasing protein intake can at least stabilize weight, although lean body mass did not improve in these studies. Treatment strategies are based on Inhibition of cytokine synthesis or action. Thalidomide has been shown to inhibit the production of TNF-α in mononuclear cells in vitro and to normalize TNF-α levels in vivo. A randomized, placebo-controlled trial in patients with cachexia cancer showed that it was well tolerated and effective in reducing weight loss and lean body mass in patients with advanced pancreatic cancer. Improvement in lean body mass and quality of life was also observed in a randomized, double-blind trial of a protein- and calorie-dense, omega-3 fatty acid supplement, provided that its consumption was equal to or greater than 2.2 g eicosapentaenoic acid (EPA) per day. It also works by reducing TNF-α production. However, data from a large, double-blind, placebo-controlled, multicenter trial suggest that EPA alone is not successful in treating weight loss in patients with advanced gastrointestinal or lung cancer. Peripheral muscle protein degradation, as occurs in cancer Cachexia, mobilizes amino acids required for liver and tumor protein synthesis. Therefore, the administration of amino acids from an exogenous source theoretically acts as a metabolic fuel for protein conservation by providing substrates for muscle metabolism and gluconeogenesis. Studies have shown that dietary supplementation using a specific combination of high-protein, leucine and fish oil improves muscle function, daily activity and immune response in cachexia-bearing mice. In addition, the use of beta-hydroxy beta-methylbutyrate derived from leucine catabolism as a nutritional supplement in tumor-bearing mice prevents cachexia by modulating NF-κB gene expression. A phase II study involving the use of antioxidants, nutritional-pharmacologic support, progestins (megestrol acetate and medroxyprogesterone acetate), and cyclooxygenase-2 inhibitors, demonstrated efficacy and safety in the treatment of advanced cancer patients with cachexia in different locations. These data support the use of multi-step therapies in the treatment of cachexia cancer. New studies It is suggested that nonsteroidal anti-inflammatory drugs, such as sulindac, significantly reduced cachexia. Studies have also shown that branched-chain amino acids can revert the metabolism of cachexia patients from catabolic weight loss to anabolic muscle gain, in 55% of patients. Branched-chain amino acids are composed primarily of leucine and valine. A paper published in the Indian Journal of Palliative Care concluded that branched-chain amino acids interfere with the activity of serotonin in the brain and prevent the stimulation of critical muscle protein degradation pathways. The potential role of branched-chain amino acids as appetite suppressants and anti-wasting agents was suggested many years ago, but since then experimental studies and clinical trials have tested their ability to stimulate food intake and counteract muscle loss in anorexic and overweight patients. In experimental models of cancer cachexia, BCAAs were able to induce significant suppression of body weight loss, produce significant increases in skeletal muscle wet weight, and improve muscle performance and daily activities. The essential amino acid glutamine has been used as a component of oral supplements to reverse cachexia in patients with advanced cancer or HIV/AIDS. According to the 2007 AHRQ National Inpatient Sample, in 129,164 hospitals surveyed in the United States, cachexia was listed as at least one of 14 recorded diagnosis codes for 26,325 unweighted cases. A sample of 32,778 unweighted outpatients in the United States collected in the CDC National Ambulatory Care Survey did not list any cases in which cachexia was one of up to three recorded diagnoses during visits.