What does cachectic mean?

Cachectic: Having cachexia, physical wasting with loss of weight and muscle mass due to disease. Patients with advanced cancer, AIDS, severe heart failure and some other major chronic progressive diseases may appear cachectic.

what is cachectic?

A general state of ill health involving marked weight loss and muscle loss. Wasting syndrome is often a sign of disease, such as cancer, AIDS, heart failure or advanced chronic obstructive pulmonary disease (COPD). Symptoms include weight loss, muscle loss, a lack of appetite, fatigue and decreased strength.

what is cachectic appearance?

Symptoms. Symptoms of cachexia include: Involuntary weight loss: Weight loss occurs despite getting adequate nutrition or a high number of calories. … Loss of appetite, or anorexia: Not only does food become not appealing, but a person with cachexia will also lose their desire to eat any food at all.


what is a cachectic patient?

Cachectic: Having cachexia, physical wasting with loss of weight and muscle mass due to disease. Patients with advanced cancer, AIDS, severe heart failure and some other major chronic progressive diseases may appear cachectic. Weight loss is greater than 5 percent or other symptoms and conditions consistent with the diagnostic criteria for cachexia. Patients experiencing cachexia who are no longer responsive to cancer treatment, have a low performance score, and have a life expectancy of less than 3 months.

Symptoms of cachexia

  • severe weight loss, including loss of fat and muscle mass.
  • loss of appetite.
  • anaemia (low red blood cells)
  • weakness and fatigue.

what is cachectic state?

Having cachexia, physical wasting with loss of weight and muscle mass due to disease. Patients with advanced cancer, AIDS, severe heart failure and some other major chronic progressive diseases may appear cachectic.

Can cardiac cachexia be reversed?

Cachexia is a complex syndrome associated with an underlying illness causing ongoing muscle loss that is not entirely reversed with nutritional supplementation.


Cardiac Cachexia Syndrome

Heart failure is a chronic, progressive, and incurable disease. Cardiac cachexia is a strong predictor of poor prognosis, regardless of other important variables. This review intends to gather evidence to enable recognition of cardiac cachexia, identification of early stages of muscle waste and sarcopenia, and improve identification of patients with terminal heart failure in need of palliative care, whose symptoms are no longer controlled by usual medical measures.

The pathophysiology is complex and multifactorial. There are many treatment options to prevent or revert muscle waste and sarcopenia; although, these strategies are less effective in advanced stages of cardiac cachexia. In these final stages, symptomatic palliation plays an important role, focussing on the patient’s comfort and avoiding the ‘acute model’ treatment of aggressive, disproportionate, and inefficient care. Heart failure (HF) is a progressive organ failure disorder, characterised by dyspnoea, fatigue, depression, and fluid retention, and affects ≤2% of the Western population.

It is a dynamic situation that, in the later stages, has high mortality rates. It is associated with several hospital readmissions due to its chronic and progressive disease evolution. There is a gradual loss of functional capacity and self-sufficiency of the patient, which is portrayed by a pattern of sudden worsening without complete recovery. In general, elderly patients with HF have other comorbidities, which cause different outcomes for these patients.


CardioSmart is the American College of Cardiology’s patient education and empowerment initiative. CardioSmart provides resources for health care providers, patients, and caregivers to support and extend the clinical/patient relationship. CardioSmart, the patient education and empowerment initiative of the American College of Cardiology, has unveiled a newly redesigned and enhanced website (www.CardioSmart.org) with thousands of pages created by members of the cardiac care team to meet the unique health needs of heart patients.

Through CardioSmart.org, individuals trying to manage their heart disease have access to a variety of tools to help in understanding their disease, complying with medication adherence, losing and maintaining weight, implementing a heart healthy diet and making other necessary lifestyle changes to improve and maintain heart health. Information and tips on preventing heart disease and caring for a heart disease patient are also available. “Prevention is key in the fight against heart disease, and CardioSmart.org has a variety of resources for people who want to change their lifestyle habits now to avoid heart disease in the future,” said CardioSmart Chief Medical Expert JoAnne Foody, MD, FACC. “CardioSmart.org also has tools and resources for heart disease patients. The site has physician-created content to help patients manage their heart disease and establish heart healthy habits. We want every patient to succeed in battling this terrible disease.”

Some of the key features now available are:

  • Patients and their caregivers will have access to over 30 heart condition centers, which provide information on each stage of heart disease, including details on the disease, questions for patients to ask their doctors,  patient responsibilities, where to find support and more.
  • Registered users can create a personalized dashboard and select topic areas of interest, save pages of the site for easier access, set health goals (weight, waist circumference, blood pressure and activity) and track their progress.
  • Users can participate in CardioSmart Challenges and earn points through activities such as exercise and weight loss. Points can be used toward items in the CardioSmart store.
  • Patients can find a community-based peer to peer support program or connect virtually via online support groups.
  • The medication manager allows users to enter in the name, dose and frequency of each of their medications to help patients comply with their doctor’s orders.
  • Mi Corazon section offers CardioSmart content translated into Spanish, where available.

The mission of the American College of Cardiology is to transform cardiovascular care and improve heart health. The College is a 43,000-member medical society comprised of physicians, surgeons, nurses, physician assistants, pharmacists and practice managers. The College is a leader in the formulation of health policy, standards and guidelines. The ACC provides professional education, operates national registries to measure and improve quality of care, disseminates cardiovascular research, and bestows credentials upon cardiovascular specialists who meet stringent qualifications.

How is Cachexia defined?


Cachexia has been defined as a loss of lean tissue mass, involving a weight loss greater than 5% of body weight in 12 months or less in the presence of chronic illness or as a body mass index (BMI) lower than 20 kg/m2. In addition, usually three of the following five criteria are required: decreased muscle strength, fatigue, anorexia, low fat-free mass index and increase of inflammation markers such as C – reactive protein or interleukin (IL)-6 as well as anaemia or low serum albumin. Cachexia can occur in most major diseases including infections, cancer, heart disease, chronic kidney disease, chronic obstructive pulmonary disease, and stroke.

Cachexia is a complex syndrome associated with an underlying illness causing ongoing muscle loss that is not entirely reversed with nutritional supplementation.

Sarcopenia and Cachexia

Muscle wasting and weakness are common in many disease states and conditions including aging and cancer. Muscle wasting in advanced cancer is related to age, sex, tumor type, and inflammation. It can be caused by inflammation and malnutrition in patients with cancer. Patients with cancer have problems including anorexia, weight loss, negative nitrogen balance, and skeletal muscle wasting. The loss of muscle and fat tissue due to chronic illness is referred to as cachexia, and the general loss of muscle mass with advancing age is referred to as sarcopenia. Sarcopenia diagnosis requires documentation of low muscle mass along with either low muscle strength or low physical performance.

Cachexia and sarcopenia share some pathological muscle wasting mechanisms characterized by inflammation and oxidative stress. In both cachexia and sarcopenia, muscle loss can lead to frailty and adversely affect various clinical outcomes.

Many oncologists and rehabilitation staffs confuse cancer cachexia with simple starvation or physiological processes such as sarcopenia. Since cancer cachexia and sarcopenia can both involve muscle wasting, we speculate that the two conditions can be confused in patients with cancer. However, sarcopenia and cachexia should not be confused in patients with cancer (Figure 1). Instead, it should be understood that the loss of skeletal muscle mass occurs in patients with cancer (cachexia) as well as during aging (sarcopenia).

Cachexia involves muscle wasting and weakness as a result of cancer-related inflammation, while sarcopenia involves muscle wasting and weakness as a result of age-related inflammation. Thus, the underlying pathological processes leading to muscle wasting and weakness differ between the two conditions.

Muscle wasting due to cancer cachexia and sarcopenia.


What can cause cachexia?

Cachexia can be caused by diverse medical conditions, but is most often associated with end-stage cancer, known as cancer cachexia. About 50% of all cancer patients suffer from cachexia. Those with upper gastrointestinal and pancreatic cancers have the highest frequency of developing a cachexic symptom. Prevalence of cachexia rises in more advanced stages and is estimated to affect 80% of terminal cancer patients. Congestive heart failureAIDSchronic obstructive pulmonary disease, and chronic kidney disease are other conditions that often cause cachexia. Cachexia can also be the result of advanced stages of cystic fibrosismultiple sclerosismotor neuron diseaseParkinson’s diseasedementiatuberculosismultiple system atrophymercury poisoningCrohn’s diseaserheumatoid arthritis, and celiac disease as well as other systemic diseases.

Can you survive cachexia?

Many patients with advanced cancer anorexia and cachexia, however, do not survive long enough to suffer from these toxicities. Refractory Cachexia – refers to patients with cachexia whose cancer treatments are no longer working and have a life expectancy of less than 3 months. Cachexia: Weight loss greater than 5 percent or other symptoms and conditions consistent with the diagnostic criteria for cachexia. Refractory cachexia: Patients experiencing cachexia who are no longer responsive to cancer treatment, have a low performance score, and have a life expectancy of less than 3 months.

Is cachexia a cancer?

Cachexia, also called cancer cachexia or cancer anorexia cachexia, is a wasting syndrome. It is the loss of fat and muscle due to a chronic disease, such as cancer, and not eating enough nutrients (malnourishment). Cachexia causes weight loss, loss of appetite, weakness and fatigue.

How does cachexia kill you?

The association is consistent with known biological or pathological processes. PRO: Cachexia may lead to thromboembolic events, arrhythmia, sudden cardiac death, immune system disarrays and higher rates of cardiovascular and infectious disease events and death. Cachexia is an often irreversible side effect of diseases including cancer and HIV. It causes severe weight loss and muscle wastage. It is responsible for one-fifth of deaths from cancer. The best way to prevent cachexia is taking action to reduce the risk of underlying conditions, such as cancer and kidney failure.

Can cachexia be stopped?

Although by definition cachexia cannot be fully reversed by nutritional support, serial studies of CT imaging in cancer patients have identified a window of anabolic potential early in the disease trajectory where there may be an opportunity for nutritional intervention to stop or reverse cachexia.

Cachexinol is a patent-pending based formula that has two mouse studies showing mice with cancer tumor-induced cachexia live for the full length of time and regain weight. Using a proprietary liposome technology, Cachexinol was developed by an award-winning chemist and is clinically proven to increase nutrient absorption. It bypasses digestion, and therefore can often circumvent nutritional impact symptoms, like poor appetite and nausea. When something new—that hasn’t been tried before—like Cachexinol comes along, that packages the therapeutic benefits of a natural spice in a custom developed delivery package (liposome) and is guaranteed to get it into the bloodstream … it’s important that patients, caregivers, and their care team are made aware and discuss it as an option moving forward. As an advocate for your loved one, you have the right to advocate for new options. Just like you have the right, along with our doctors and researchers and to not accept that cachexia has to be a terminal disease.

How long can you survive with cachexia?

Many patients with advanced cancer anorexia and cachexia, however, do not survive long enough to suffer from these toxicities. Refractory Cachexia – refers to patients with cachexia whose cancer treatments are no longer working and have a life expectancy of less than 3 months.


What does cachexia look like?

Muscle wasting: This is the characteristic symptom of cachexia. However, despite the ongoing loss of muscle, not all people with cachexia appear malnourished. A person who was overweight before developing cachexia may appear to be of average size despite having lost a significant amount of weight. Cachectic: Having cachexia, physical wasting with loss of weight and muscle mass due to disease. Patients with advanced cancer, AIDS, severe heart failure and some other major chronic progressive diseases may appear cachectic.


Can you gain weight with cachexia?

Cachexia is defined as ongoing weight loss, often with muscle wasting, associated with a long-standing disease. In cachexia, refeeding often does not induce weight gain. evidence exists that any diet can reverse muscle wasting and prolong life in a person with cachexia as a result of advanced cancer. However, some researchers believe that eating a high-calorie diet may slow the muscle

Top 5 ways to Define Cardiac Cachexia

  • Cardiac cachexia is unintentional severe weight loss caused by heart disease. The weight loss might be life-threatening.
  • Heart failure may cause blood to back up into the liver and intestines, and they may swell. This swelling can lead to nausea and decreased appetite.
  • Swelling of the intestines may not allow for adequate absorption of nutrients from the food you eat.
  • Heart failure may force you to work harder to breathe and cause your body temperature to increase. Both of these conditions burn calories.
  • In people with severe heart failure, tumor necrosis factor (TNF) and other signaling molecules in the bloodstream called cytokines can increase the metabolic rate of the tissues, thus burning more calories.

Heart failure (HF) is a progressive organ failure disorder, characterized by dyspnoea, fatigue, depression, and fluid retention, and affects ≤2% of the Western population. It is a dynamic situation that, in the later stages, has high mortality rates. It is associated with several hospital readmissions due to its chronic and progressive disease evolution. There is a gradual loss of functional capacity and self-sufficiency of the patient, which is portrayed by a pattern of sudden worsening without complete recovery (Figure 1). In general, elderly patients with HF have other comorbidities, which cause different outcomes for these patients.


Figure 1: Progression model of heart failure towards the end of life.

Patients with HF tend to have a poor quality of life, especially those with a higher score in the New York Heart Association (NYHA) Functional Classification, weak socioeconomic status, and lack of social support. The benefits of palliative care (PC) are often forgotten. Such care, which goes far beyond symptomatic control, should be considered in an appropriate manner according to the patients’ needs. Given that we are facing an incurable and irreversible illness, there cannot be a rigid division between curative care and overall care designed to maximise comfort (Figure 2). This model balances the life-prolonging therapy with PC through most of the disease trajectory. When the active therapy is a viable option, minimal PC interventions are initiated. Once life-prolonging therapy becomes less of an alternative, PC becomes the primary method of clinical management. The proper palliation of symptoms should not be delayed until the last days or hours of life. The importance of PC and its inclusion in the therapeutic approach of HF is stated in the guidelines of the American Heart Association (AHA), the American College of Cardiology (ACC), the International Society of Heart and Lung Transplantation (ISHLT), and the European Heart Association (EHA).


Figure 2: Multifactorial interactions between curative and palliative care.
There is compatibility between curative treatment, which permits life extension, and palliative care for symptomatic relief and quality of life; therefore, both approaches should be combined. Family/caregivers should also be included during the disease progress.


In the later stages of HF, it is important to identify patients with end-of-life HF (HF in the last 12 months of life) in order to offer appropriate care for the patients’ needs. Always acting on the basis of an acute care model, characterized by aggressive, disproportionate, and inefficient care, is not suitable in these clinical settings. Known scales, such as CARING or Gold Standard Framework, present global and specific deterioration indicators allowing the identification of patients with end-of-life HF.

Cardiac cachexia (CC) is defined as the loss of >5% of body weight over 12 months in the presence of HF. This pathological entity affects around 5–15% of patients with HF and is generally present in NYHA III or IV functional classes. CC corresponds to a strong predictive factor of poor prognosis in HF, independent of other important variables, such as age, functional class, ejection fraction, and physical capacity, although it is related to them.


CC pathophysiology is complex and multifactorial and, when fully established, it is hard to treat and reverse the process. The palliative approach to this class of non-oncological terminal patients has proven to be suboptimal.

The objective of this review is to gather evidence to correctly recognise CC and contribute to the improvement of clinical practice; namely, identification of early stages of muscle waste and sarcopenia, and better recognition of a patient with CC and terminal HF who is in need of PC due to their symptoms being no longer controlled by the usual medical measures.


Sarcopenia is defined as muscle wasting associated with functional impairment. It is characterised by a progressive and generalised loss of skeletal muscle mass in the limbs that exceeds two standard deviations of the mean of a healthy young reference and may be seen as a precursor of cachexia. Sarcopenia is found in 19.5% of patients with HF, and 68.0% of patients show muscle waste and reduced capillary density. If there is no intervention in cases of HF, there is a progressive loss of skeletal muscle mass and, in the latter stages, fat and bone mass loss leads to fully established CC. CC is present in 5–15% of advanced HF patients, and the mechanisms involved in the pathophysiology are multifactorial, involving reduced food intake, gastrointestinal malabsorption, neurohormonal disorders, overexpression of proinflammatory cytokines, increased oxidative stress, and an imbalance between anabolic and catabolic states.

Reduced Food Intake

Several factors may be involved in the reduction of food intake, such as unsavoury diets due to low sodium content, severe depression, and visceral vascular congestion. Some drugs commonly used to treat HF may also be related to a reduced food intake; for example, captopril can cause palate changes; digitalis is sometimes responsible for anorexia and vomiting; and diuretics used in a vigorous way may lead to zinc and potassium depletion, which in turn reduces the intestinal motility and causes palate changes. The proinflammatory body status and the abnormal increase in serum levels of leptin and adiponectin are also responsible for anorexia. Early satiety due to hepatomegaly with gastric compression and the occurrence of dyspnoea at rest in NYHA Class IV functional class patients contribute to a reduced food intake.

Functional Modifications in the Gastrointestinal Tract

Vascular splanchnic congestion and collagen accumulation in the intestinal mucosa are typical findings in these patients. Such mucosal changes lead to a thickening of the gastrointestinal wall, reducing the number of intestinal villi and increasing the distance between the capillaries and the enterocytes. The accumulation of these modifications leads to intestinal malabsorption with a reduction in lipoprotein absorption. Additionally, there is an increasing concentration of the intestinal bacterial flora and higher adhesion of the biofilm to the sigmoid mucosa. Increased paracellular permeability leads to bacterial translocation with the release of endotoxins (lipopolysaccharides), which in turn stimulates the production of tumour necrosis factor (TNF)-α and other proinflammatory substances, contributing to a state of systemic inflammation.


Neurohormonal Activation

In HF, activation of the sympathetic nervous system (SNS) occurs, raising the levels of noradrenaline and cortisol. This adrenergic stimulus promotes a cellular catabolic state and   peripheral vasoconstriction that exacerbates splanchnic congestion. Permanent activation of the SNS leads to increased basal energy expenditure and activation of the renin-angiotensin-aldosterone system. As proven by animal models, angiotensin II, a significant mediator in CC development, induces muscle wastage by activating the ubiquitin-proteasome system (UPS), leading to apoptosis, a reduction in protein synthesis, and appetite impairment.

Imbalance Between Anabolic and Catabolic Metabolism

The preservation and maintenance of skeletal muscle depends on the delicate balance between catabolic and anabolic mechanisms. The imbalance of these chemical processes forms the basis of the pathogenesis of sarcopenia and CC. The anabolic mediators are reduced, such as growth hormone, testosterone, insulin-like growth factor 1, ghrelin, and insulin. The major negative chemical processes concerned are the UPS, autophagy, apoptosis, inflammation, and oxidative stress. Proinflammatory cytokines, such as TNF-α, interleukin (IL)-1, IL-6, glucocorticoids, and adiponectin, play a cardinal role in muscle wastage by reducing the intracellular anabolic pathways. The activation of the UPS leads to lysosomal proteolysis by ubiquitination. Autophagy, a catabolic process that involves the lysosomal system, seems to be regulated by transcription factors (e.g. nuclear factor kappa B [NF-κB]), reactive oxygen species, and TNF-α. All of these elements lead to a disproportionate oxidative stress response, which in turn raises angiotensin II levels. It seems that the loss of mitochondria and mitochondrial dysfunction may also be implicated in the increase of cell-damaging oxygen free radicals.


The clinical consequences of CC syndrome are related to muscle proteolysis, weight loss, and systemic inflammatory status, including changes in the cardiovascular and respiratory function; depletion of muscle mass due to atrophy, apoptosis, or necrosis, lowering the number of mitochondria and capillaries and increasing the predisposition for anaerobic metabolism with lactic acid production; impairment of urinary acidification and concentration; predisposition to pressure ulcers due to decreased healing capacity; gastrointestinal tract dysfunction; multifactorial anaemia due to nutrient malabsorption, systemic inflammatory status, iron deficiency and reduced erythropoiesis; and a decline in immunity, leading to a higher risk of infection. Due to the occurrence of these major metabolic alterations in CC, HF symptoms worsen.


It is difficult to establish a specific and effective therapy for CC syndrome due to its multifactorial pathogenesis. Physicians should be aware of muscle waste and sarcopenia even when the therapeutic options are effective and the full establishment of CC is delayed.

CC cannot be treated solely with an increase in nutritional uptake; exercise is also an important therapeutic approach. A combination of both strategies is recommended, including appropriate rehabilitation nutrition. Aerobic and resistance exercise training has the potential to reduce cytokine expression and increase anti-apoptotic factors, having an anti-inflammatory effect and improving functional capacity, therefore enhancing muscular regeneration. In patients with advanced HF, advanced age, or frailty, who are unable to tolerate daily aerobic and resistance exercise, neuromuscular electrical stimulation (NMES) might be an option. It has been demonstrated that NMES has the same anti-inflammatory properties as aerobic and resistance exercise training. In animal models, high frequency NMES (>50 Hz) induces an anabolic metabolic state due to an increase in glycolytic capacity, protein synthesis, expression of insulin-like growth factor 1, and muscle fibre size, which is also related to resistance training. Low frequency NMES (<20 Hz) has a similar activity to aerobic training exercise, inducing endurance and reducing autophagy. Although rehabilitation nutrition is of extreme importance, there is no dietary standardisation; it is characterised by an increase in protein uptake and an adequate vitamin supply of both soluble and lipo-soluble vitamins (vitamins A, D, E, and K).

The pharmacological treatment approach for CC involves appetite stimulators, anti-inflammatory drugs, hormones, and anabolic stimulants. In the appetite stimulators category, treatment with megestrol acetate (160 mg twice daily) and L-carnitine (4 g per day) have both proven to increase body mass in clinical trials. Megestrol acetate is a derivative of progesterone widely used by oncologists, not only for the treatment of hormonal-related cancers but also as an appetite stimulant when appropriate. Since inflammation is a major contributor to sarcopenia, immunomodulatory and anti-inflammatory therapies were thought to be a logical option. Small clinical trials with pentoxifylline, thalidomide, methotrexate, and immunoglobulins showed no sustained benefit as pharmacological treatments. Clinical trials with beta-blockers demonstrated a delay in the development of CC and promoted a partial improvement in those with CC, since the drugs limit activation of the SNS.

Ghrelin is a hormone produced by the stomach and acts on the pituitary gland to release growth hormone, which, in turn, reduces anorexia. It constrains the production of proinflammatory factors and induces the production of IL-10, a potent anti-inflammatory cytokine. Clinical trials demonstrated that ghrelin lead to an increase in body weight, body fat mass, and lean tissue mass, which ultimately permit appropriate exercise training.

Anabolic steroids are effective at reverting and treating muscle wasting, although the risks associated with their administration surpass the possible benefits. Selective androgen receptor modulators have the same anabolic characteristics as treatments with testosterone, without the associated side effects on the skin, hair, and prostate. Enobosarm, an example of this new pharmacological drug class, has tissue-specific anabolic and androgenic activity, which improves lean muscle mass and physical function.

In animal models, espindolol is a beta-blocker that increases body weight, lean tissue, and fat mass without affecting cardiac function, having a more favourable effect on preventing muscle waste than other beta-blockers. The ACT-ONE trial demonstrated these beneficial effects in cancer cachexia. The COPERNICUS trial proved that carvedilol reduced cachexia development and stimulated a partial reversal of cachexia in patients with severe HF.


Discussing end-of-life issues with patients is challenging, especially with patients who often have a limited understanding of the nature and seriousness of their condition. Many patients defer to their clinicians for important decisions, choosing a more passive role. The PC approach is directed at improving the patient’s quality of life and addressing their family’s challenges related to their refractory symptoms. Routine comprehensive symptom assessment with validated instruments enables the prevention and relief of suffering and allows treatment of physical and psychological symptoms. Suitable acknowledgement of the shift from curative care to comfort care allows appropriate end-of-life care to be provided for both the patient and their family.

When CC is fully established, it is fundamental to explain to caregivers and family members that clinical reversibility is less probable and emphasise the importance of the patient’s comfort. In these situations, the main medical practices that should be involved are general practice, internal medicine, cardiology, and palliative medicine. There should be a collaborative approach including physicians, nurses, therapists, psychologists, dietitians, social workers, and other health professionals to improve communication and understanding of the patient’s objectives to a have a better end-of-life. This methodology has shown to improve survival through patient education, including promotion of self-management skills, improving medication and dietary compliance, encouraging daily weighing and exercise, assuring close follow-up, and introducing end-of-life issues. Clear communication between the medical team, family members/caregivers, and the patient is vital to shared decision-making and various assumptions about the palliative approach should be demystified.

from National Cancer Instutue : Intravenous High-Dose Vitamin C in Cancer Therapy

The discovery and isolation of vitamin C was one of the most important advances in improving human nutrition. Scurvy, a severe vitamin C deficiency disease characterized by weakness, lethargy, easy bruising and bleeding, was particularly problematic for sailors on long voyages during the 16th century, where access to fresh fruits and vegetables was limited. In fact, scurvy was the leading cause of naval deaths between the 16th and 18th centuries, killing more sailors than all battles, storms and other diseases combined. It wasn’t until 1747 that Scottish naval physician James LindExit Disclaimer demonstrated that consuming oranges and lemons cured and prevented scurvy. However, it took scientists nearly two more centuries to identify the nature of the curative substance contained in citrus fruits, now commonly known as vitamin C. The search for this elusive substance ended in 1932 when Albert Szent-GyorgyiExit Disclaimer, a Hungarian biochemist, isolated and identified a 6-carbon carbohydrate, hexuronic acid, as the anti-scurvy factor. Shortly thereafter, Szent-Gyorgyi renamed it “a-scorbic acid”, a reference to its anti-scorbutic properties, and later went on to receive the Nobel Prize in Physiology and Medicine in 1937 for his discoveries.

Today vitamin C is a popular dietary supplement, and due to improved accessibility to fruits, vegetables and vitamin supplements, disability and death from scurvy are rare. However, it is worth noting that a significant number of people even in developed countries are still vitamin C deficient. For example, approximately 7% of the US population has a plasma vitamin C concentration of less than 11 μM, that is considered scurvy. Vitamin C has many essential functions in our body in addition to its well-known role as an antioxidant. Thus, prolonged periods of sub-optimal vitamin C exposure could have adverse health effects, including an increased susceptibility to a plethora of diseases. In fact, the optimal dosage of vitamin C required to maximize its health benefits has been hotly debated ever since its discovery a century ago. Linus Pauling, a world-renowned chemist and two-time Nobel Prize Laureate, strongly advocated that megadose quantities of vitamin C (above 1 g intake per day) would prevent and treat many illnesses including the common cold and heart diseases. However, mainstream medicine has largely ignored or even ridiculed Pauling’s claim. This controversy is still very much alive today.

The controversial history of high-dose vitamin C in cancer treatment

Utilizing high doses of vitamin C as a cancer therapy is no exception to this controversy. Nearly 60 years ago Toronto physician William McCormick observed that cancer patients often presented with severely low levels of vitamin C in their blood and featured scurvy-like symptoms, leading him to postulate that vitamin C might protect against cancer by increasing collagen synthesis. In 1972, extending this theory, Ewan Cameron, a Scottish surgeon, hypothesized that ascorbate could suppress cancer development by inhibiting hyaluronidase, which otherwise weakens the extracellular matrix and enables cancer to metastasize. He began treating terminally ill cancer patients and published a case report of 50 patients in which some of the treated patients benefited from high dose vitamin C.

Encouraged by the result, Cameron teamed up with Linus Pauling to conduct clinical trials involving terminal cancer patients. In 1976, they published a study of 100 patients with terminal cancer treated with ascorbate. Their disease progression and survival rates were compared to 1000 retrospective control patients who were matched with the vitamin C-treated patients regarding age, sex, type of cancer and clinical stage and who were treated by the same physicians in the same hospital, and in the same way except that they did not receive vitamin C. Although the study was not well designed by modern standards, mainly because they lacked the placebo-control group, the results demonstrated that patients treated with vitamin C had improved quality of life and a four-fold increase in their mean survival time. In a follow up study, Cameron and Pauling reported that 22% of vitamin C-treated cancer patients survived for more than one year compared to only 0.4% of control patients. A clinical trial in Japan independently showed a similar result. With these promising outcomes, interest in the potential of vitamin C for cancer therapy grew. However, double-blind randomized clinical trials directed by Charles Moertel of the Mayo Clinic failed to show any positive effects of high dose vitamin C in cancer patients, as reported in two papers in the journal of New England Journal of Medicine. Because the Mayo Clinic’s clinical trials were conducted more rigorously, people trusted the Mayo Clinic’s data and discredited the Cameron-Pauling trials, dampening the enthusiasm for vitamin C as a cancer therapy.

So why did the Pauling and Mayo Clinic trials have different results? There are at least two crucial differences. First, the Mayo Clinic trials abruptly stopped the ascorbate administration, switching to traditional chemotherapy, when the patient developed signs of tumor progression. Thus, the overall median time of vitamin C treatment under the Mayo Clinic trials was only 2.5 months, while the Pauling and Cameron trials treated patients for the duration of the entire study period or as long as 12 years. Secondly, the Mayo Clinic trials administered 10 g of daily ascorbate to patients only orally, while the Cameron and Pauling trials administered their vitamin C both orally and intravenously. This difference in the two dosage routes proved highly consequential.

More info

What are Cachexia Symptoms?

What is Cachexia?

Cachexia, also known as Wasting Syndrome or Anorexia Cachexia Syndrome, is a weakness and wasting of the body, caused by severe illness and disease. Cachexia is much more than just a loss of appetite – it is a serious problem. Ultimately, it changes the way your body uses protein, carbohydrate, and fat. In addition, it can also cause your body to burn calories at a much faster rate than usual. Though this sounds like a great thing to have, it can often result in serious consequences. People with cachexia often lose fat as well as muscle, which sometimes cannot be reversed with nutritional supplements.


What is Cardiac Cachexia?

Cardiac cachexia is where serious weight loss is caused by heart disease. At times, this weight loss can be life-threatening. In addition, it can also happen to patients that experience severe heart failure. Patients may have a decent appetite and consume a lot of calories but still unfortunately lose muscle and weight.


How is Cardiac Cachexia caused?

Heart failure can cause blood to go back up into the liver and intestines – which could cause these organs to swell. This swelling could lead to feelings of nausea and a loss of appetite. Furthermore, the swelling of the intestines could reduce the level of absorption of nutrients from food that is consumed.


Heart failure could also make it harder to breathe and therefore cause strain on your lungs and body. As a result, this could cause your body temperature to rise. An increase in body temperature as well as working harder to breathe can burn calories. Also, patients with severe heart failure, Tumor Necrosis Factor (TNF for short), and Cytokines (small proteins important in cell signaling) can increase the metabolic rate of tissues. This would lead to more calories being burned.


What are Cachexia Symptoms?

Cachexia seems to be more common in patients suffering from lung cancer or cancers anywhere in the digestive system.

The main symptoms can include:

  • Severe weight loss, including muscle mass
  • Loss of appetite
  • Anemia (lacking enough healthy red blood cells)
  • Tiredness, weakness, and fatigue
  • Lack of any taste

Cachexia isn’t just associated with cancer though. It is also common in the later stages of other illnesses and diseases like; heart disease, HIV, AIDS, chronic kidney disease, congestive heart failure, and chronic obstructive lung disease,



Cancer Cachexia and Life Expectancy

As Cancer Cachexia is seen in the later stages of cancer, it can significantly reduce a patients life expectancy. Many patients with chronic diseases are more likely to die when they lose weight, as well as develop progressive cachexia. Patients with cancer cachexia are also less able to endure treatments, like Chemotherapy which could be crucial for the patient. For patients that need to have surgery, the risk of post-operative complications can increase. Although the loss of body weight, anemia, and the other symptoms listed previously all characterize the status of cancer cachexia, the main cause of death is due to respiratory failure.


How is Cachexia Diagnosed?

Cachexia is diagnosed by using a variety of measurements and tests. These include:

  • Body Mass Index
  • Lean Muscle Mass
  • Blood Tests
  • Food intake diaries

Since cachexia can often be present before weight loss begins, it is crucial to recognize it as soon as possible. This is so that the amount of weight loss, especially muscle loss, can be kept to a minimum.


Diagnosis Criteria

Researchers have created a cachexia staging score (CSS for short) for patients with late-stage cancer. A number of points are assigned to each specific component and then added together to sort cachexia into three different stages. Here is a breakdown of these components:

  • Weight loss over the last 6 months (0 – 3 points)
  • A SARC-F questionnaire (aimed at muscle function and sarcopenia) (0 – 3 points)
  • ECOG (Eastern Cooperative Oncology Group) performance status (0 – 3 points)
  • Loss of appetite (0 – 2 points)
  • Abnormal biochemistry tests (0 – 2 points)


Diagnosis Stages:

Based on the above components, the total score will indicate the stage of cachexia the patient is at. These stages include:

  • Non-Cachexia (a score of 0 – 2 points)
  • Precachexia (a score of 3 – 4 points)
    • This is characterized by a weight loss of less than 5%. Patients may have symptoms like a loss of appetite and impaired glucose tolerance.
  • Cachexia (a score of from 5 – 8 points)
    • This is characterized by a weight loss of greater than 5%. Patients may have other symptoms or conditions associated with cachexia.
  • Refractory Cachexia (a score of from 9 – 12 points)
    • This is characterized by patients who are no longer responding to cancer treatments and have a life expectancy of less than 3 months or so.







Cachexia: Current and New Approaches to A Deleterious Syndrome in Oncology

Although many consider cachexia to be a pathology, the truth is that cachexia is defined as a metabolic disorder caused secondarily by some underlying disease, which brings various consequences to our body such as loss of muscle mass, fat, immune deficit, infections, etc.

Although there are many causes, it is usually associated with serious diseases such as AIDS, tuberculosis, severe autoimmune diseases, etc. However, the one that worries doctors the most (and is the first thing that comes to mind when we talk about cachexia is cancer, a “consumer” disease, closely related to the abnormal and unhealthy weight loss that accompanies this disorder.

What happens in Cachexia

In principle, there is a “consuming” pathology that attacks your body from within. Imagine that one day you do not eat the amount of food necessary to support all the energy expenditure of those 24 hours. What does your body do? It begins to take energy from other sources housed in reservoirs that you have in various sectors of your body.

Fats, proteins, carbohydrates, all come from your own body to maintain the expenditure of the metabolism. Something similar is what happens with consuming pathologies, such as cancer. Cellular turnover and tumor growth require the use of a lot of energy that has to come from somewhere. Because of the physiopathology and the development of the disease, it usually comes from your body.

In principle, it is only weight loss, however, as it progresses disorders begin to appear that stem from the metabolic alterations caused by cachexia, such as Anorexia, insulin resistance, problems with protein degradation, chronic inflammation, etc. Your body does not know how to respond to a permanent energy deficit. It’s like if you have an engine running without gasoline, it eventually breaks down or explodes, right?

Also, it is necessary to emphasize that cachexia is not just “starving”, it is a complex clinical syndrome, which is accompanied by the release of multiple cytokines and millions of other pro-inflammatory factors, which ends up affecting the muscle metabolism and causing anorexia.

Although being hungry triggers various responses, the hormonal involvement is not as severe, nor are the alterations in the metabolism of lipids, carbohydrates, and proteins, which are crucial for life. Cachexia stems from this alteration in the regulation of cytokines, which alter specific regions of our body that control both orexigenic and anorexigenic signals.

Our brain understands (mistakenly) that it must limit food intake and increase energy expenditure at rest (something illogical and anomalous), causing weight loss and altering various systems in our body.

What is a Cachectic Appearance?

A person with cachexia will appear thin, excessively thin. With difficulty moving, slow thinking, speech problems, inability to stay awake (drowsiness), with bones protruding over thin, dry skin. Most cases are associated with difficulty breathing or maintaining some other basic vital functions, but this depends on the patient’s overall condition and how advanced the cachexia is.

Is Cachexia a sign of dying?

Cachexia is a sign that your body is doing its best to stand up and fight a disease that overcomes it. Cachexia is best thought of as a syndrome that indicates that you have a serious illness or a major commitment, but not one that causes imminent death. Some malignancies are curable with proper treatment.

The question should be: How long can you live with Cachexia? And it’s hard to answer. It depends on what pathology is behind the cachexia, how severe it is and how much time you have with it. Those will be the real determinants of your life after cachexia.

Overcoming Cachexia: New Treatments and Options

The best management for cachexia will always be to treat the underlying cause. For example, if you have cancer, then treating cancer will be the way to reverse the syndrome completely. However, many adults with advanced disease or in palliative treatments do not have this option, so the solution is to try to reverse and counteract the cachexia without altering the underlying cause along the way.

There are several approaches, some try to adjust their measures to counteract the weight loss by improving the nutritional intake, however, in almost all patients the nutritional part is only one side of the problem. Others try multiple approach therapies trying to control certain variables at the same time, but not all have been successful.

Many studies have been based on interventions involving the use of drugs in conjunction with nutritional changes. Some even seek to manipulate the development of cachexia (despite that progress) to decrease symptoms and improve health status. However, success has not been unequivocal and this is due to the multifactorial pathogenesis of cachexia.

We will discuss the most effective options and science’s approach to new treatments and therapies for cachexia:

Effective Treatments Approved for Use

  1. Progestogens

Both Medroxyprogesterone Acetate and megestrol Acetate (progestins) are considered the best available therapy for the cachexia syndrome associated with cancer. There is evidence confirming how it stimulates the appetite through the release of certain specific neuropeptides, as well as downregulating the synthesis and release of proinflammatory cytokines.

There are various presentations of these drugs (oral solution, pills, powder, etc.), and almost all have been shown to have a positive effect. The FDA is evaluating them for approval as a treatment for other types of cachexia, such as AIDS-derived cachexia.

  1. Corticosteroids

Corticosteroids are the most widely used or known of the orexigenic agents. Not only for cachexia but for other states associated with nutritional disorders. This drug has been shown to cause a radical and significant increase in appetite.

Still, it can alter other effects such as protein metabolism, insulin resistance, water retention, and even cause adrenal infarction. The only way to use them as therapy is under the strict supervision of doctors and in the short term, as complications are worse in the long term.

Emerging Drugs with Effective Results

  1. Thalidomide

As mentioned above, cachexia is a syndrome characterized by the abnormal release of cytokines, pro-inflammatory molecules capable of altering the body’s metabolic regulation. Thalidomide is an immunomodulator capable of regulating inflammatory processes through effects on certain key molecules of our immune system, such as IL-6 and TNF-alpha.

  1. Selective COX-2 Inhibitors

Nonsteroidal anti-inflammatories are abundant in our home and are used in various aspects of neoplastic pathologies. Several scientific studies have been conducted on various drugs, and one of the ones that have provided better results is Celecoxib, which suppresses the systemic inflammatory response, improving the weight and body mass of patients.

Several animal studies have been conducted previously with this drug and all have yielded positive results, which encourage the formal indication of Celecoxib in patients with cachexia, although more studies are needed.

  1. Ghrelin

This drug is a peptide of only 28 amino acids capable of regulating the secretion of certain hormones and neuropeptides, which promote appetite and food intake. Besides, it appears to have some interaction with the sympathetic nervous system, promoting muscle wasting and functional capacity in cancer patients, crucial markers for anyone with severe body involvement.

  1. Insulin

Insulin has also been considered as a possible drug affecting the hormonal and metabolic system. According to available studies, it attenuates the progression of cancer-associated cachexia and improves metabolic and physical parameters in patients in palliative stages.

Thousands of studies have focused on this hormone, which also appears to significantly stimulate carbohydrate intake and promote the development of body fat, especially in the trunk and legs.

Also, let us remember that there is insulin resistance in cachexia patients, which prevents glucose absorption in the muscles and promotes the general disorder. Using insulin increases the number of nutrients and energy that tissues in general receive, promoting body weight gain, and regulation of metabolic balance.

  1. Branched-Chain Amino Acids (BCAA)

This is one of the more recent alternatives, which could be listed as food for cachexia associated with cancer. Its metabolic effects are quite interesting. They seem to intervene with the release of appetite-related neurotransmitters and inhibit the expression of molecules that favor muscle proteolysis, improving the condition of patients with cachexia.

BCAA has been proposed as a potential regulator of the antianorexic and anti-cachexic quality of our body. Recently, several studies have been conducted that support this premise, based on the objective decrease in weight loss and the regulation and increase of muscle mass.

  1. Oxanlodrone

Several recent scientific studies have determined that this drug, a steroidal anabolic agent, improves body composition and quality of life in palliative care patients with solid tumors. This information is relevant because these patients in addition to having cancer were under chemotherapy, which also acts as “consumption pathologies”. Achieving that effect is remarkable.

The Future Therapy

Many drugs are under research or development currently. One of these may be the anti-IL-6 humanized monoclonal antibody, which appears to inhibit cachexia directly, although only the one related to cancer has been studied.

Other compounds that may also be on this list of novel drugs are IL-16, formoterol, new classes of nonsteroidal MRSA, Ostarine, Melanocortin MC4 antagonists, among others. The future is quite promising, but it is directed towards only one aspect: treating cachexia as an immune-compromised syndrome.

Regulation of abnormal cytokine release may be the secret to overcoming cachexia, however, many scientific studies need to be conducted and a thorough investigation of how this syndrome works and what the ultimate solution might be.

How My Family Suffer From Cachexia


While living with your family it is very essential to prevent you family and Childs from diseases and illness like Cachexia, it is a term regularly comprehended by social insurance experts. It depicts a condition described by the nearness of automatic weight reduction and coming full circle in a condition of skinniness. This was portrayed apropos by Hippocrates: “a sharp nose, empty eyes, indented sanctuaries. As of not long ago, no understanding had been reached on an operational meaning of and symptomatic rules for cachexia; this absence of definition persuaded worldwide gatherings of specialists to build up a consistently acknowledged definition, analytic standards, and characterization to progress clinical practice. Obviously characterized demonstrative standards are additionally fundamental for advancement and endorsement of potential restorative specialists. The definition gave by a global accord bunch led by Evans and colleagues1 is as per the following:

Cachexia is a complex metabolic disorder related with hidden sickness and described by loss of muscle with or without loss of fat mass. The conspicuous clinical element of cachexia is weight reduction in grown-ups (rectified for liquid maintenance) or development disappointment in kids (barring endocrine issue). Anorexia, irritation, insulin opposition and expanded muscle protein breakdown are every now and again connected with cachexia. Cachexia is particular from starvation, age-related loss of bulk, essential discouragement, mal absorption and hyperthyroidism and is related with expanded grimness.

This definition makes a few key qualifications. In spite of the fact that cachexia is frequently connected with decreased nourishment consumption, it varies from basic hunger by the nearness of fundamental disease1,2; automatic weight reduction doesn’t happen in sound people and alternately is related with a large group of incessant conditions, including malignant growth, diabetes, untreated (AIDS), constant obstructive pneumonic infection (COPD), ceaseless cardiovascular breakdown, interminable renal disappointment, and rheumatoid joint pain. Part 28 talks about malignant growth cachexia, the most very much considered cachexia in constant illnesses. It ought to be noticed that few intense conditions, for example, injury, consume, and sepsis, are related with intense and some of the time serious weight reduction identified with the cachexia of ceaseless illness. In these conditions the hidden ailment or injury differently adds to the improvement of weight reduction through irritation, insulin opposition, expanded catabolism of skeletal muscle, and expanded generally speaking vitality use.

Cachexia is a condition that causes outrageous weight reduction and muscle squandering. It is an indication of numerous ceaseless conditions, for example, malignancy, interminable renal disappointment, HIV, and various scleroses. An ongoing appraisal recommended that more than 160,000 individuals in the United States who remain in emergency clinic with a cachexia analysis consistently. There are different conditions that cause an individual to shed pounds, yet individuals with cachexia get thinner regardless of whether they are as yet eating. Generally, an individual who doesn’t eat enough nourishment will lose just fat. An individual with cachexia will lose both fat and bulk.


The collaboration of a wide range of elements causes cachexia. Individuals with cachexia have strange degrees of specific substances in their body. These uneven characters cause weight reduction and muscle squandering. Various elements add to cachexia, including the degrees of these substances, the conditions that cause them, and the response they incite from the body. These substances collaborate with one another and lead to cachexia through a few pathways, including:

  • increasing digestion and the burning through of effort
  • causing irritation
  • increasing the breakdown of muscle
  • preventing muscle development

Specialists are as yet considering the numerous connections and other potential causes that can prompt cachexia.

Hazard factors

There are sure ceaseless conditions connected to cachexia, generally at long last phases of the infection.

An individual with one of the accompanying conditions should converse with their PCP about strides to forestall the advancement of cachexia and how to improve personal satisfaction.

Instances of these conditions include:

  • Cancer, particularly in the lung, pancreas, and stomach
  • Chronic obstructive aspiratory illness (COPD)
  • Chronic renal disappointment, with an expected fourth surprisingly with the condition giving indications of malnourishment
  • Congestive cardiovascular breakdown


  • Cystic fibrosis
  • HIV
  • Rheumatoid joint inflammation



The cachexia syndrome is seen across a wide range of chronic diseases and is especially evident in the cancer patient. Weight loss causes difficulties for the patient and clinician alike as it reduces quality of life and also reduces tolerance of anti-cancer therapy. It is now recognised that cachexia exists through a range of phases (pre-cachexia, cachexia syndrome and refractory cachexia); however, not all patients traverse the entire spectrum. The risk of progression varies and depends on numerous clinical factors that should be taken into account when risk stratifying and counselling patients about weight loss and possible interventions. Tumour type, tumour stage, co-morbidities, systemic inflammation, low food intake and response to anti-cancer therapy all play roles in determining whether a patient will be at risk of cachexia progression. The acknowledgement that multiple components are responsible for the development of cachexia has led to the view that any cachexia intervention strategy should target all components i.e. multimodal therapy for a multimodal problem. There is growing acceptance that anti-cachexia therapy must form a major component of supportive oncology and be given along with anti-cancer therapy. The critical concern remains when to start such treatment and in which individuals?


Cachexia, cancer, weight loss, inflammation


The authors have no conflicts of interest to declare.


December 28, 2012




Ross W Stewart, Clinical Research Fellow Department of Clinical Surgery, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK. E: [email protected]

The cachexia syndrome is seen across a wide range of chronic diseases and is especially evident in the cancer patient. This weight loss causes difficulties for the patient and clinician as it reduces quality of life (QoL) and also reduces tolerance of treatment. Weight loss is significantly associated with cancer morbidity and mortality.1,2 It is believed that up to 20 % of cancer patients die as a direct consequence of cachexia and that up to 50 % of cancer patients die with some degree of cachexia.3,4 The incidence of cachexia varies with tumour type, being lowest in sarcoma and breast cancers, whereas 80–90 % of pancreatic and gastric cancer patients experience weight loss.5

In cachexia, weight loss is attributed to a loss of both adipose tissue and skeletal muscle. However, it is the skeletal muscle wasting that likely contributes to excess morbidity and mortality in cancer patients.An international consensus recently defined cancer cachexia as a multifactorial syndrome characterised 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. The pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism.7 A combination of primary and secondary anorexia, hyper-metabolism, hyper-catabolism and hypo-anabolism act together to aggravate weight loss.

It is now recognised that cachexia exists through a range of phases (precachexia, cachexia syndrome and refractory cachexia) and it may be that even within the cachexia syndrome itself the more severe stages are less amenable to treatment and reversal. Clearly once a patient is confined to bed and moribund, the chances of reversal in muscle mass by multimodal rehabilitation are virtually gone. The greatest potential for prevention, recognition and reversal therefore lies with the precachectic state and during early cachexia syndrome.

According to international consensus, pre-cachexia may be recognised before any significant involuntary weight loss (i.e. >5 %) by clinical and metabolic signs such as anorexia and impaired glucose tolerance.8 Patients with >5 % loss of stable bodyweight over the past 6 months, or a body mass index (BMI) <20 kg/m2 and ongoing weight loss of more than 2 %, or sarcopenia and ongoing weight loss of more than 2 %, but have not entered the refractory stage, are classified as having cachexia.7 Refractory cachexia is characterised by a low performance status (World Health Organization [WHO] score 3 or 4) and a life expectancy of less than 3 months. This is an actively catabolic state where alleviation of symptoms is the mainstay of intervention.

Treating cachexia posses a difficult challenge to the cancer multidisciplinary team. The heterogeneity in presentation of cachexia has, in part, delayed formal descriptive terminology.

In addition, there is no validated classification of pre-cachexia. Moreover, although there are a range of biomarkers that might be used in this context (e.g. circulatory interleukin [IL]-6 or C-reactive protein [CRP] levels), the lack of longitudinal studies to integrate clinical classification with biological mechanism coupled with the complexity and duration of modern oncological management (chemotherapy, surgery, radiotherapy) makes this a difficult task.

Risk Stratification
Cancer cachexia is a continuum (pre-cachexia, cachexia syndrome, and refractory cachexia); however, not all patients traverse the entire spectrum. In fact it is plausible that some patients demonstrate protective mechanisms against progression. The risk of progression varies and depends on numerous clinical factors that should be taken into account when risk stratifying and counselling patients about weight loss in cancer and possible interventions.

Tumour type, tumour stage, co-morbidities, systemic inflammation, low food intake and response to anti-cancer therapy all play roles in determining whether a patient will be at risk of cachexia progression. Depending upon the tumour type, weight loss occurs in 30 to 80 % of cancer patients. Patients with pancreatic or gastric cancer have the highest frequency of weight loss, while patients with non-Hodgkin’s lymphoma, breast cancer, acute non-lymphocytic leukaemia and sarcomas have the lowest frequency of weight loss.Cross-sectional imaging analysis of skeletal muscle depletion is a powerful prognostic indicator. Utilising staging computed tomography (CT) scans and routinely collected patient clinical information, analysis of images can demonstrate previously occult muscle depletion that carries with it a poorer overall prognosis and likelihood to progress in cachexia severity.10 Measurements of systemic inflammation (Glasgow Prognostic Scale) have been shown to be reliable predictors of survival, independent of tumour stage, performance status, treatment (active or palliative) and has been shown in a variety of advanced common solid tumours.11 Knowing that cachexia is a metabolic process driven by the systemic inflammatory response the utilisation of such scores to risk stratify progression of cachexia seems intuitive. Clearly the most pertinent of these factors in risk stratification will be response to oncological treatment and therefore disease progression, for if the disease picture progresses the patient will almost certainly definitely succumb to weight loss. Moreover, as the clinical picture evolves through the treatment phase, the necessity to continually risk stratify and treat is heightened (see Figure 1)

A Complex Multidimensional Problem
The tumour’s role in the aetiology of cachexia includes the local secretion of pro-inflammatory cytokines (tumourkines) that initiate the host systemic inflammatory response/acute phase protein response (APPR),12 and the production of pro-cachectic factors that have direct catabolic effects on host tissues.13,14 Host mechanisms involve an aberrant response to the tumour’s presence, and include activation of both the APPR12 and the neuroendocrine stress response.15,16 The net result of such host–tumour interaction is an alteration in body composition, a major feature of which is a severe and specific loss of skeletal muscle mass.17

Besides the primary role of fat in storing excess lipids, adipose tissue is a major endocrine organ secreting hormones and cytokines (adipokines) that modulate appetite and nutrient metabolism. Therefore, alterations in adipose tissue mass can have significant effects on whole-body energy homeostasis.18 In the setting of cancer cachexia, there is emerging evidence that inflammatory signals from tumours intersect with the normal crosstalk between adipose tissue and other organs, leading to impaired energy balance and catabolism of fat and muscle.19

Although there may be loss of both fat and muscle tissue in cancer cachexia, it is the loss of skeletal muscle that will have the most profound effects on patients’ function and activities of daily living. In healthy adults, skeletal muscle mass is maintained by nutritional status and physical activity, reflecting a dynamic balance between protein synthesis and degradation. A predominance of either will result in muscle hypertrophy or atrophy. In cachexia, there is ongoing debate as to whether a reduction in protein synthesis, an increase in protein degradation or a combination of both is more relevant. Several functional studies have examined protein synthesis and protein degradation in rodent models of cancerassociated muscle wasting and revealed both reduced protein synthesis and increased protein degradation.20, 21



Special thanks to Touch Oncology

Inflammation and Signalling
Cachexia is an integrated physiological response of substrate mobilisation driven perhaps, mostly by inflammation. The consistent associations between inflammatory markers, such as circulating CRP and weight loss in cancer patients,22 reinforce the idea that cancer cachexia is linked to systemic inflammation that might be provoked by the spillover effects of excessive cytokines.

The tumour initiates a cytokine cascade that has multiple, direct, distant effects including the central induction of anorexia and the peripheral initiation of net skeletal muscle protein loss and the APPR.23

Cancer cells may rely on production of pro-inflammatory mediators for growth, protection from apoptosis and promotion of angiogenesis/ metastasis. A variety of human cancer cell lines have been shown to produce both pro-inflammatory and anti-inflammatory cytokines such as tumour necrosis α (TNF-α) and interferon γ (IFN-γ).24–27 TNF-α and IFN-γ work co-operatively to downregulate transcription of the myosin heavy chain (MyHC) gene in vitro and in vivo, but not other core myofibrillar proteins.28 TNF-α has been shown in vitro to inhibit both adipocyte and skeletal myocyte differentiation.29,30 It also plays a role in insulin resistance attenuating the insulin signalling pathway.31

Some cytokines may be potential repressors of cachexia. For example, IL-4, IL-10 and IL-13 all demonstrate anti-inflammatory, and hence presumably anti-cachectic, activity.32 Other cytokines (e.g. IL-15) may have potential ‘antioxidant’ properties that can counter the excess levels of reactive oxygen and nitrogen species.33,34 The final wasting status of the cachectic patient presumably depends on the balance between pro-inflammatory and anti-inflammatory cytokines.

Even with the same tumour type and burden, one individual may become cachectic whereas another will not. Such variation may relate to host genotype. Single nucleotide polymorphisms in the IL-1, IL-6 and IL-10 genes that are linked to production rates of these cytokines have been associated with the prevalence of cachexia in gastric or pancreatic cancer.35

The majority of known signalling pathways that contribute to muscle atrophy in pre-clinical models mediate their effects through activation of the ubiquitin proteasome pathway (UPP).36 Identification of up-regulation of two muscle-specific E3 ubiquitin ligases, MuRF-1 and MAFbx/atrogin-1, in at least 13 distinct animal models of atrophy,37,38 provides a compelling argument for a major contribution of the UPP in muscle wasting. Whether this is relevant to the clinical situation is still not clear. Moreover, although cytokines are known to activate the UPP pathway, the role of systemic versus intramuscular inflammatory signalling is poorly understood.

Myostatin, a TGF-b family member, is synthesised and secreted mainly from skeletal muscle cells and signals through the activin type II receptor, which then recruits an Alk family kinase, resulting in the activation of a Smad2 and Smad3 transcription factor complex.39 Overexpression of myostatin in mice leads to pronounced skeletal muscle atrophy,40 in the tumour-bearing state, although in animal models and patient muscle biopsy samples, evidence does indicate that myostatin levels and myostatin-associated signalling are activated as a result of a tumour burden.41

In addition to myostatin, there are other TGF-b family members induced by inflammatory cytokines. In particular, activin-A has been found to be upregulated in skeletal muscle after activation of the TNFa/TA K-1 signalling pathway.39 Furthermore, blockade of activin A in this model was sufficient to block atrophy. This finding demonstrates that, similar to the case of individual cytokines, blocking individual TGF-b family members such as myostatin alone may not be sufficient in settings of cancer cachexia.

Neural Control of Cancer Cachexia
The main molecular mechanisms regulating the cancer anorexiacachexia syndrome are alterations in brain neurochemistry, in particular, the hypothalamic melanocortin system with its activity diverted largely toward the promotion of catabolic stimuli leading to insulin resistance, increased lipolysis and accelerated muscle proteolysis.42 Proinflammatory cytokines (TNF-α and IL-1) and hypothalamic serotonergic neurons have been implicated in the dysfunction of the hypothalamic melanocortin system.43 Two peptide systems in particular appear to be strongly influential in the control of feeding behaviour: these are the orexigenic neuropeptide Y (NPY) and the anorexigenic proopiomelanocortin (POMC) systems.44 Many of these mediators exert their effects through induced changes in these two systems. They have been shown to be linked intricately with each other and to operate in parallel. POMC neurons are the source of the potent melanocortin neuropeptides, such as a-melanocyte-stimulating hormone which, via interaction with the central melanocortin receptors, induce an anorectic state. The role of cytokines in cancer anorexia may be affected through influence on both the NPY and POMC systems.45,46 These data strongly suggest proinflammatory cytokines such as IL-1 and TNF-α are involved in mediating the dysfunction of the melanocortin system leading to a catabolic state.

Human leptin is a protein of that is manufactured in and secreted primarily by adipocytes within white adipose tissue47 and is directly proportional to the total amount of fat in the body.48 Leptin is known to increase the frequency of action potentials in POMC neurons.49 In human cancer cachexia, leptin levels are markedly low,15 presumably because of weight loss, although other mechanisms may also be at play. Ghrelin, a 28 amino acid peptide produced by the P/D1 cells of the stomach, acts as the natural counterpart to leptin. Not only does ghrelin stimulate growth hormone (GH) secretion, but it also promotes food intake50 and decreases sympathetic nerve activity.51 Ghrelin has therefore been proposed as an alternative measure to GH therapy in muscle wasting. Patients with cancer cachexia demonstrate increased plasma concentrations of active ghrelin, suggesting a compensatory response to weight loss.52

Heterogeneity of Cachexia
Heterogeneity in all models of clinical and animal cachexia is one of the major factors that has impaired research into cancer cachexia. Rates of cachexia are influenced by tumour type, site and mass.Translation from a relatively acute setting of cachexia seen in animal models to the more chronic wasting seen in humans has been seen as a major stumbling block to develop therapies for human cancer cachexia. In humans, the cause of weight loss relates to not only the clinical status of the patient and specific effects of the tumour (e.g. causing bowel obstruction, tissue destruction or concomitant infection) but also to coexisting morbidities (e.g. heart failure, chronic renal failure or chronic obstructive pulmonary disease), age-related sarcopenia and the possibility of a genetic predisposition to develop cachexia.

The classical presentation of cachexia is of an extremely thin and wasted individual. However, heterogeneity in this clinical presentation is introduced by the current epidemic of obesity in the developed world. When healthy individuals develop a chronic disease, the higher risk associated with obesity is reversed and obesity becomes ‘protective’. This is known as the obesity paradox; however, this protective mechanism may not be afforded to cancer patients. Mean BMI of advanced cancer patients is now commonly measured at >25. There is, however, a subgroup of these overweight patients who hide gross muscle wasting under a mantle of adipose tissue. Approximately 40 % of overweight or obese patients with advanced pancreatic cancer have significant skeletal muscle wasting and this ‘myopenic or sarcopenic obesity’’ is an independent risk factor for accelerated demise.53 A recent survival analysis of 1,473 cancer patients highlighted the obesity/overweight epidemic in cancer patients with 52 % of this population being obese or overweight. Using CT cross-sectional imaging to visualise and quantify occult muscle depletion, they demonstrated that patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall bodyweight.10

As skeletal muscle is a major target in cachexia, it is also relevant to consider heterogeneity as a result of sexual dimorphism. Men have more muscle mass than women and one might assume that this greater ‘reserve’ would be protective. However, weight loss and loss of muscle mass are greater in male than female cancer patients,54 and this may further relate to a high prevalence of hypogonadism in males.55

Treatment Options in Cancer Cachexia
Currently there is not an agreed protocol or guideline for the treatment of cancer cachexia. This problem is multifactorial including unsuitability of effective treatments due to side effects, failure of unimodal treatments at the clinical trial phase and a lack of therapies/clinical trials taking into account the multifactorial aetiology of cachexia. Unimodal therapies are less likely to achieve success against a complex metabolic process compared with a structured multimodal therapy tackling the interdependence of skeletal muscle, adipose tissue, the central nervous and immune systems combined. Future trials therefore require a stronger emphasis on combined treatment including nutritional support, appetite stimulation, exercise initiatives and multiple pharmacological treatments targeting this complex metabolism at several levels. The mainstay of treatment obviously remains eliminating the cancer; however, as this is often not possible. integration of nutrition, exercise and drugs must coincide with ongoing adjuvant cancer therapies.

Total energy expenditure is a combination of both the resting energy expenditure and the energy expenditure of physical activity. It is estimated that the cancer patient has a calorific deficit of roughly 200 Kcal/day.56 Protein intake should generally be maintained between 1–1.5 g/kg/ day.57 If these individuals were to participate in a diet that not only met basic nutritional needs but also have a net weight gain, they would need to increase calorific intake by 300–400 Kcal/day. This target becomes somewhat more difficult to achieve if the patient is already in the later stages of cachexia with significant anorexia and other co-morbidities. The most recent review of nutrition in malnourished cancer patients suffered from variability in the quality of studies and heterogeneity of endpoints.58 The findings suggested that oral nutritional interventions demonstrated no effect on survival and that the effect on bodyweight and energy intake was inconsistent but that there were some statistically significant improvements in some aspects of QOL. However it is not clear whether this represented clinically meaningful changes to the patient.

No one class of drug has demonstrated any measurable advantage over the other in the treatment of cachexia. Either they have failed to demonstrate efficacy in clinical trials or they have an unwanted sideeffect profile. Many drugs have demonstrated promising results at the in vitro stage, however, have fallen down at the clinical trial phase. With increasing understanding of the metabolic interplay in cachexia, the rationale for therapy is trending towards agents designed to interfere with the inflammatory cascade and metabolic signalling.

Megestrol acetate (MA) is a synthetic progestogen agent first developed as an oral contraceptive in the 1960s. MA is currently used to improve appetite and to increase weight in cancer-associated anorexia. Although the mechanism is poorly understood its effect on appetite are thought to be exerted through an increase in the levels of NPY resulting in an attenuation of the firing of the ventromedial hypothalamic nucleus neurones, involved in the satiety mechanism.59 Other recent studies suggest that MA exerts effect on cytokines, which inhibit the action of TNF on fatty tissue and its products.60 In 2005 a systematic review was performed of MA for the treatment of anorexia-cachexia syndrome in patients with cancer, AIDS or other underlying pathologies. They concluded that MA improves appetite and weight gain in patients with cancer. However no advantage in QoL markers could be demonstrated due to the heterogeneity of data and endpoints.61

Corticosteroids have been shown to demonstrate an improvement in appetite and QoL. However due to their significant side-effect profile they should not be administered for long periods. Steroids are used extensively in routine oncology practice to counteract the effects of cytotoxic chemotherapy. Steroids are also used extensively to promote mood and appetite in the terminal stages of cancer.62

Inflammatory mediators contribute to the metabolic cascade and reduce appetite. Cyclooxygenase 2 (COX2) inhibitors reduce levels of acute phase reactants. N-3 fatty acids are also competitive antagonists of the inflammatory precursor arachidonic acid and can be given as fish oil capsules.63 A Cochrane review in 2007 concluded that the evidence was insufficient to give a recommendation. More recently small studies suggest that N-3 fatty acids may beneficially affect QoL, performance status and physical activity in patients with non-small-cell lung carcinoma (NSCLC) undergoing multimodality treatment.64,65

Thalidomide, which is thought to help reduce weight loss associated with cachexia in patients with cancer,66 modifies the cytokine triggers of the wasting response through its potent anti-TNF-α effects.67 A Cochrane review published in 2012 concluded due to the small number of studies and high heterogeneity among them, meta-analysis was not possible.68

IL-6 is a putative mediator of the systemic inflammatory response and muscle wasting. The humanised anti-IL-6 antibody BMS 945429 has been shown in pre-clinical phase I/II trials to reduce cachexia and improve fatigue of patients with NSCLC.69 In patients with cholangiocarcinoma, the administration of selumetinib (an inhibitor of mitogen-activated protein/extracellular signal-regulated kinase and of IL-6 secretion) demonstrated statistically significant mean muscle gain of 2.3 kg. The untreated group had a mean muscle loss of 1.2 kg. Neither group underwent assessment of QoL endpoints.70

Etanercept is a recombinant human TNF-α that specifically binds and renders soluble TNF-α biologically inactive by blocking their interaction with cell surface TNF-α receptors. In a recent phase I/II study of etanercept and gemcitabine, the only statistically significant outcome was a lowering IL-10 concentration.71

Two other studies have examined the role anti-TNF directed therapy in the treatment of pancreatic cancer and cachexia. One phase II study with thalidomide, an immunomodulator known to decrease TNF-α levels, demonstrated an improvement in weight and lean body mass at 8 weeks compared with placebo.66 By contrast, a phase II study of gemcitabine and infliximab, a monoclonal antibody blocking TNF-α, did not show a benefit in preserving lean body mass or survival.72

Despite a strong emphasis on targeting signalling pathways in cachexia, further study is necessary to demonstrate translational clinical benefit from in vitro studies to patient centred outcomes. Thus far, clinical trials targeting signalling pathways have struggled to demonstrate such an effect. Future studies targeting such pathways may consider utilising a multimodal approach to treatment and doing so at an early stage of disease/cachexia.

Anamorelin is a novel, oral mimetic of ghrelin.73 A randomised, doubleblind, placebo-controlled, crossover pilot study was conducted and demonstrated significant increase in GH, significant gains in weight and a significant improvement in patient-reported symptoms.74 Anamorelin is currently undergoing a phase III clinical trial (NCT 01395914)

GTx-024 (Enobosarm) is a non-steroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. Enobosarm showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated during a phase IIb trial of varied cancer types.75 Enobosarm is currently undergoing a phase III clinical trial for effects on cachexia in NSCLC (NCT01355484).
Myostatin is a member of the TGF-b family of secreted proteins, but unlike TGF-b, it is predominantly expressed in skeletal muscle (cardiac muscle and adipose tissue have low levels of myostatin), which plays a pivotal role in regulating skeletal muscle mass and function. Genetic evidence demonstrates this conclusively as deletion or knockout of the myostatin gene produces mice with a phenotype exhibiting a dramatic increase in the size and number of skeletal muscle fibres.76 Rodent models of cancer with cachexia clearly demonstrate raised levels of myostatin.77 Pharmacological blockade of the myostatin/activin-ActRIIB signalling pathway not only prevented further muscle wasting, but also reversed pre-existent loss of skeletal muscle. NCT 01505530 is a multicentre, randomised, double-blind, placebo-controlled trial in participants with locally advanced/inoperable or metastatic pancreatic cancer, and will investigate two doses of a myostatin monoclonal antibody (LY 2495655) in combination with chemotherapy. Its primary endpoint is survival however lean body mass and patient performance levels are secondary outcomes.

The acknowledgement that multiple components are responsible for the development of cachexia has led to the view that any cachexia intervention strategy should target all components i.e. multimodal therapy for a multimodal problem.78 Such strategies tend to target reversible clinical factors such as nutrition or exercise in combination with non-steroidal anti-inflammatory drugs or progestogens. Several recent studies conducting phase III trials have demonstrated favourable results that concluded that further multimodal studies are necessary.79,80

The critical concern remains when to start such treatment? Current multimodal anti-cancer therapy can take months or years, and patients frequently receive cytotoxic chemotherapy within 3 months of death. There is growing acceptance that anti-cachexia therapy cannot wait until such anti-cancer therapy is over (as has been the case with the majority of cachexia therapy trials in the past), but must form a major component of supportive oncology and be given along with potentially curative or palliative anti-cancer therapy.

Recent studies have emphasised that systemic cytotoxic chemotherapy can be associated with loss of skeletal muscle mass81 and it is potentially at this time, where muscle wasting may be both treatment and tumour induced, that cachexia therapy can have maximal impact. The results of several trials that aim to treat cachexia during chemotherapy are eagerly awaited.

special thanks to https://touchoncology.com/prevention-of-cachexia-in-cancer/

for lending us the content.

European Oncology & Haematology 2013;9(1):46–50 DOI: https://doi.org/10.17925/EOH.2013.09.1.46

Cancer Cachexia Symptoms & Controls

Cachexia is a wasting syndrome with symptoms of weight loss, anorexia, asthenia and anemia. In Greek, ‘Kakos’ signifies ‘terrible things,’ and hexus, signifies ‘condition.’ It is typically connected with interminable provocative conditions and malignancy. Disease cachexia is a multi factorial disorder portrayed by checked loss of body weight, anorexia, asthenia, and sickliness; be that as it may, in early cases these components show with variable extent. it is the most widely recognized appearance of the progressed threatening sickness, prompting demise. Cachexia is ruinous to such an extent that it takes advantage of different wellsprings of vitality, to be specific skeletal muscle and fat tissue when the body detects an absence of nourishment. Dietary status is undermined in direct reaction to tumor-actuated modifications in the metabolism. Cachexia antagonistically influences the patients’ capacity to battle against contamination and with stand treatment by chemotherapy and radiotherapy. Because of all these negative impacts, the body starts to squander away.


Weight reduction in malignant growth cachexia and starvation, have various components. Weight reduction in disease patients is because of equivalent loss of fat tissue and skeletal bulk, while, in starvation or anorexia nervosa, weight reduction is predominantly from the fat and just a limited quantity from the muscle. In starvation, ketone bodies are delivered from fat digestion in the liver, and fat replaces glucose as a vitality source and forestalls loss of bulk. Contingent on the tumor type, weight reduction happens in 30% to 80% of malignant growth patients. Patients with pancreatic or gastric malignant growth have the most noteworthy recurrence of weight reduction, while patients with non-Hodgkin’s lymphoma, bosom disease, intense non-lymphocytic leukemia, and sarcomas have the least recurrence of weight loss. In head and neck disease, dysphasia and change of taste likewise assume a huge job in weight loss. Weight misfortune is a significant prognostic factor in malignancy; the higher the degree of weight reduction, the shorter the endurance time.


Vitality use is a metabolic adding machine dictated by three variables: Basal metabolic rate, diet-actuated thermo genesis, and physical movement. The best indicator for 24-hour vitality consumption is Resting Energy Expenditure which can be determined by aberrant calorimeter. It gives the idea that about 70% of the absolute vitality misfortune in sedentary people is from the resting vitality. In disease, patients shifts with the kind of threat. It is high in lung and pancreatic malignancy and there is no expansion in gastric and colorectal disease patients. two principle purposes behind adjustment REE are the intense stage reaction (APR) protein and thermo genesis.  APR is a progression of changes in liver protein blend, where there is move from creation of egg whites to intense stage proteins (APP) like C-responsive protein (CRP), fibrinogen, serum amyloids, macroglobulin, and α-1 antitrypsin. In the head and neck squamous cell carcinoma an expansion in CRP has been noted in patients with cachexia.6 these substances are delivered because of tissue injury, disease, or aggravation. Intense stage reaction upgrades the pace of loss of body mass.


Anorexia, the loss of want to eat or loss of craving, is a significant part causing weight reduction in disease cachexia and it is random with the impact of chemotherapy. In patients with malignancy prompted anorexia, no useful impact is acquired even with nourishment supplementation (expanded caloric admission either by the oral course or by parenteral sustenance), and the stoppage of chemotherapeutic medication consumption neglects to balance the squandering procedure. In this way, malignancy instigated anorexia is an autonomous and irreversible procedure. The variant metabolic rate is the immediate reaction by the tumor and the invulnerable framework to disturb the pathways that control the homeostatic circle of body-weight regulation.

Anorexia & Role of Neuropeptide

Irregularity between orexigenic signals (increment craving) by neuropeptide Y (NPY) and anorexigenic signs (decline hunger) by Pro-opiomelanocortin (POMC) assume a job in anorexia. NPY neurons increment the parasympathetic yield and lessening the resting vitality consumption, while, POMC invigorates the thoughtful movement and expands the resting vitality use. Tumor items may restrain NPY transport or discharge or meddle with the neuronal downstream of NPY.20 Hypothalamic melanocortin α-MSH (a result of POMC) initiates anorexia by enacting two particular melnocortin receptors, Mc3r and Mc4r. In malignant growth patients with anorexia, the NPY levels are lower than in the controls, and expanded CNS melanocortin flagging is seen in disease anorexia.

Anorexia & Role of cytokines

Malignancy and irritation have been connected since the hour of Virchow. Malignancy cells are fit for delivering cytokines constitutively. They may have an autocrine work, supporting tissues, for example, fibroblasts and veins, along these lines creating an appropriate situation for malignant growth development. These cytokines likewise have a significant job in inciting anorexia.23 Macrophage inhibitory cytokine-1 (MIC-1), an individual from the changing development factor (TGF) β super family, has been embroiled in anorexia. Cytokines transport substrates over the blood mind boundary that connect with the cerebrum endothelial cells to discharge cytokines like TNF-α and IL-1 in the locale of the hypothalamus.24 likewise, interferon-γ (IFN-γ), delivered by actuated T and common executioner cells, has natural exercises that cover those of TNF-α.


This Substance (AIS) in disease cachexia had been accounted for in 1987 It is a substance that made the Red Blood Cells (RBCs) osmotic ally delicate and diminished their deformability, in the plasma of the patient with terminal cancer.28 It is a 50 kD protein emitted by the dangerous cells that discourages erythrocyte and insusceptible able cell capacities. AIS ties to the cell layer of the RBCs and brings down the glucose convergence and pyruvate kinase action, prompting RBC brokenness and lysis, which prompts anemia.29 AIS has been involved in lipolysis, along these lines causing weight loss.30 notwithstanding pallor the patients with head and neck malignant growth are seriously malnourished.

Is Cachexia a Sign of Dying?

The honest answer, until recently, is — yes. But saying something is a sign of death
sounds like it’s a fact, as if cachexia means certain death. There is no definitive
prevention or treatment of cachexia, so let’s just accept it and proceed to expiration. Or
could it be that we just have not figured out the pathology of cachexia yet — that is, how
it comes to exist in the body — and therefore we just can’t stop it yet?

That’s how we figure out diseases, right? Either by trial and error — testing certain
drugs to see if they work. Or by figuring out how the disease happens and interfering
with that.

So, perhaps the better question is: Is cachexia associated with death because it’s a
stigma of life-threatening disease? The answer is still a resounding yes. Doctors and
health care professionals still associate cachexia with death. And patients and their
families see it with their own eyes … and well, a person with advanced cachexia is
emaciated and looks like they are dying. It’s difficult not to make the association.

But there’s a growing number of researchers and doctors that believe that resigning
cachexia patients to a death sentence is BS. That sticking a patient’s cachexia under
the palliative care column once diagnosed is not good enough.

So, what is being done about it?

Why is Cachexia Associated with Death?
A 2013 study called the causes of Cachexia a “century-long uncertainty”. But cachexia
has been perplexing healers since ancient times. Long before cachexia was defined in
these last two decades, medical experts were recognizing cachexia in the late stages of
disease and identifying it as a sign of death. Hippocrates, the ancient physician and

philosopher, described a cachexia patient as having “a sharp nose, hollow eyes, sunken
temples. . . .”

Cachexia hsd a constellation of causes, such as, anorexia, inflammation, insulin
resistance, increased muscle protein breakdown, and how these causes play out
depends on the underlying disease, but not the disease alone. Cachexia can result from
many different diseases that have at least one thing in common: they are all life-
threatening. Cancer, diabetes, untreated AIDS, COPD, chronic heart failure, chronic
renal failure, and rheumatoid arthritis are just some of these diseases associated with
cachexia, with cancer cachexia being the most studied so far. According to leading
researchers, Stefan D. Anker and Stephon von Haeling, the most frequent cachexia
subtypes in order are COPD cachexia, cardiac cachexia, cancer cachexia, and
cachexia of chronic renal failure. They estimate that in industrialized nations, about 9
million people are affected by cachexia.

It’s almost as if the disease puts the patient on a Cachexia roadmap, where the
destination is basically the same, but the way it can take can vary. This could explain
why we still associate cachexia with death. From history until very recently, we have
only recognized cachexia in late stages, so it is associated with death. This lack of early
recognition has led to a lack of attention. Lack of attention has led to a lack of
understanding. Lack of understanding has led to a lack of treatment and a resolve to
continue to to equate cachexia with death. Like the disease itself, this cycle feeds on

Lack of Early Recognition of Cachexia
The emaciated description given by Hippocrates above, still persists as “first signs” for
doctors today. Some of the first signs of cachexia doctors look for are changes at the
temple of the head and the emergence of more prominent bone structures.

In a 2017 multinational survey of 742 oncology health care professionals (HCPs), 86%
defined cachexia as weight loss, with 46% throwing anorexia into the definition. Half of

the respondents said they would diagnose cachexia after 10% weight loss, 35% said
they would wait for a 15% to 20% loss, and 10% of these professionals said they would
wait for a weight loss &gt;25%.

Pause for dramatic effect.

In 2008 (that’s 9 years prior to this study), official diagnostic criteria for cachexia was
developed by scientists and clinicians at an international conference in Washington,
D.C. The percentage of weight loss necessary to diagnose a patient with cachexia
is 5%. As you can see, most HCPs diagnose cachexia too late.

Lack of Attention to Cachexia
“We believe that cachexia requires more attention, not only by physicians and other
health care professionals, but also by the general public.” This is one of the reasons
Ander and von Haehling gave for starting their Journal of Cachexia, Sarcopenia, and
Muscle in 2011.

In 2015, Anker told Nature journal of science that the biggest challenge to the field of
cachexia is that it has to compete for funding and recognition with research into other
major diseases.

Jose Garcia, a clinical researcher focused on wasting disorders at the Michael
E. DeBakey Veterans Affairs Medical Center in Houston, Texas, expressed in the same
article, “I’m a little bit worried that if we don’t see a successful clinical trial in the next five
years, the dollars from the pharmaceutical industry to develop a treatment will go
somewhere else.”

If we continue to think of cachexia as just a part of the death process for the 9 million
people suffering from it, then his worries are probably justified.

Lack of Understanding of Cachexia

The lack of understanding of cachexia, like the causes of cachexia themselves, spring
from a variety of reasons. For one, only recently was cachexia defined in the mid 2000s,
and since then the definition has continued to be refined. It’s difficult to institute a
standard when criteria keep evolving. But it appears that knowledge of cachexia will
continue to develop, which means HCPs must stay on top of it.

It’s apparent from the previously mentioned 2017 survey of HCPs that defining and
diagnosing cachexia is not well understood. Lead author and professor in the
department of medicine at Sapienza University of Rome in Italy, Maurizio Muscaritoli,
MD, says, “The recent definition, classification, and diagnostic criteria for cancer
cachexia clearly describe cancer cachexia as spectrum of conditions, ranging from
pre‐cachexia, to cachexia, and refractory cachexia.”

In a nutshell, that means that we don’t have to wait until a patient is dying to determine
that they have cachexia.

How to Deal with Cachexia
“…treatment of cachexia should not be considered peculiar of palliative care medicine.”
—Maurizio Muscaritoli, MD

Palliative care is important. According to the World Health Organization (WHO), it is “an
approach that improves the quality of life of patients and their families facing the
problem associated with life-threatening illness, through the prevention and relief of
suffering by means of early identification and impeccable assessment and treatment of
pain and other problems, physical, psychosocial and spiritual.”

Where in there does it say consider a problem a sign of death and don’t treat it? In fact,
it says “early identification” and “impeccable assessment and treatment”.

Palliative care is an approach, not a place where we assign patients with the cachexia
mark of death. Yes, cachexia patients need palliative care, but what cachexia patients
need most — like with any other disease — is to not be cachexia patients. There’s only
one way to begin to do that: Stop treating cachexia like a death sentence and get on
with finding a novel approach to preventing and treating it.

New Ways to Stop Cachexia
“Many oncologists think that a cachectic patient is a profoundly wasted and almost
moribund patient. Cachexia is not to be seen as unavoidable, but rather as a partially
preventable cancer comorbidity.” —Maurizio Muscaritoli, MD

To change the way health care professionals, patients and their caregivers, and the
public view cachexia — and not as a sign of death — it is going to take experts who
believe it is worth the resources to continue to seek out new solutions.

Many drugs have been tried in the treatment of cachexia along the way. Corticosteroids,
progestins, NSAIDs and thalidomide, to name a few, showed some improvement in
areas of cachexia, but often at the expense of side effects that outweighed the benefits.
Not good enough, since cachexia is already a complex condition that needs no more
wrenches thrown in.

Researchers believe it’s a novel solution that will change how we view and treat
cachexia. Cachexinol is one such next-generation treatment for cachexia.

Can Wasting Syndrome Be Reversed?
Mice with Cancer Cachexia Recover with Cachexinol
Cachexinol is a patent-pending curcumin-based formula that has two mouse studies
showing mice with cancer tumor-induced cachexia live for the full length of time and
regain weight.

Using a proprietary liposome technology, Cachexinol was developed by an award-
winning chemist and is clinically proven to increase nutrient absorption. It bypasses
digestion, and therefore can often circumvent nutritional impact symptoms, like poor
appetite and nausea.

Researchers are still studying exactly how Cachexinol works, but it’s believed to have
to do with immune function and metabolism, two of the major contributing causes of

When something new like Cachexinol comes along, that packages the therapeutic
benefits of a natural spice in a custom developed delivery package (liposome) and is
guaranteed to get it into the bloodstream … it’s important that patients, caregivers, and
their care team know and discuss it as an option moving forward.

You have the right to talk with your doctor about new options. Just like you have the
right, along with our researchers, to believe that cachexia is not just a sign of death, but
a treatable, reversible disease that with treatments like Cachenxinol can give patients a
fighting chance.