An Overview of Cachexia

Symptoms, Importance, Diagnosis, and Treatment

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Cachexia is a syndrome that happens in people who are very sick with a chronic illness or serious disease. Cachexia is the medical term for unintentional weight loss, progressive muscle wasting, and a loss of appetite.

A number of treatment approaches have been evaluated ranging from diet to dietary supplements, to medications, but can be challenging as cachexia is more than just a lack of calories in the body. Newer research suggests that exercise, though counterintuitive, may help.

This article will go over the causes of cachexia in people with cancer and other conditions. It also covers how cancer cachexia can affect treatment and how the syndrome can be managed.

Symptoms of Cachexia
Verywell / JR Bee

Causes and Risk Factors

Cachexia is a complex metabolic syndrome where the basal metabolic rate increases without compensation in calorie/protein intake. Cachexia is dominated by catabolic metabolism (which occurs when digesting food). If you think of normal metabolism as the building of tissue and muscle (anabolic metabolism), the opposite is true with cachexia, which is the breakdown of these normal bodily processes.

This abnormal metabolic rate is caused by the immune system’s response to diseases such as cancer. This and other causes of cachexia are being studied to try and understand the all underlying factors influencing this complex condition.

Cancer

People who have cancer often develop cachexia. The syndrome is thought to be directly responsible for 20% of cancer deaths in the United States. Cachexia occurs in up to 80% of people with advanced cancer. Cancer cachexia is also referred to as cancer anorexia cachexia syndrome.

Cachexia is sometimes referred to as a paraneoplastic syndrome, which simply means symptoms that are caused by substances made by cancer or by the body’s reaction to cancer.

In cancer, cachexia may be caused by “tumor factors,” substances manufactured and secreted by a tumor, or by the “host response.” Host response simply means the body’s response to the tumor. It can develop with any advanced cancer but most frequently with lung, pancreatic, and stomach cancers.

Other Conditions

Along with cancer, cachexia is also associated with a multitude of other chronic conditions. These include:

  • Chronic obstructive pulmonary disease (COPD)
  • AIDS/HIV 
  • Heart failure
  • Emphysema
  • Chronic kidney disease
  • Organ failure

Cachexia Symptoms

Recent research suggests that cachexia often begins even before any weight loss occurs, so early on there may not be any symptoms. When symptoms occur, they include:

Involuntary (Unintentional) Weight Loss

Weight loss with cachexia is involuntary, meaning that it occurs without trying. Yet it goes further than unexplained weight loss. Weight loss may occur even if calorie intake is adequate; energy output matters. Unintentional weight loss is defined as the loss of 5% of body weight over a six-month to 12-month period, but even smaller amounts of weight loss could be of concern.

Skeletal Muscle Wasting

Muscle wasting is a hallmark of cachexia and occurs along with a loss of fat. It can also be fairly insidious. In people who are overweight at the time of their diagnosis, significant loss of muscle mass can occur without an obvious outward appearance of weight loss.

Anorexia/Loss of Appetite

Cachexia can cause loss of appetite, which is not the same as the typical “loss of appetite” symptom. In this case, it’s not just a reduced desire for food, but a complete lack of interest in eating.

Complications

One of the most detrimental effects of cachexia is the interference with treatments of the condition causing it and lowering the body’s response to that treatment. For example, people with cancer are less able to tolerate treatments, such as chemotherapy and radiation, and often have more side effects and complications after surgeries.

Cachexia also increases the symptom burden of the underlying disease. It worsens cancer fatigue, one of the most common symptoms of cancer, and lowers tolerance to the pain of conditions such as respiratory disease.

The process of muscle wasting that accompanies cachexia can lead to difficulty walking and participating in enjoyable activities. It can eventually lead to the loss of the ability to live independently.

All of these changes and more can significantly diminish your quality of life and increase risk of morbidity.

Can a Person Recover From Cachexia?

The best hope for recovery from cachexia is to improve the underlying condition at the root of it. Treatment approaches to date have been fairly disappointing, and even with adequate calorie intake, it is difficult to reverse the process of cachexia once it begins.

Diagnosis

Even though the symptoms and signs of cachexia may be noticed well after the onset of disease, researchers are learning that the process leading to muscle wasting begins very early on after a diagnosis. As such, cachexia is often present before any weight loss occurs.

There are several ways that cachexia can be evaluated. Some of these measures include:

  • Body mass index (BMI): Body mass index describes not only relative body weight but can give more information about a healthy weight. BMI is calculated using a formula of height and weight. Since BMI does not identify the proportions of muscle mass and fat, however, it cannot be used alone to evaluate cachexia.
  • Lean muscle mass: Measuring body composition can help determine the ratio of lean muscle mass to body fat. Tests used to do this may include skin folds and bioimpedance.
  • Food intake diaries: Keeping a food diary is an important activity when looking to prevent or cope with cachexia. At the same time, it’s important to note that the malnutrition of cachexia can occur even with an adequate intake of calories.
  • Blood tests: Some lab tests that are useful in evaluating cachexia include white blood cell counts (WBC), serum albumin, transferrin levels, uric acid, and inflammatory markers, such as C-reactive protein (CRP). Thyroid levels should also be assessed to rule out hyperthyroidism (thyroid conditions are common with cancer treatment), and conditions such as adrenal insufficiency or hypogonadism.

There are a number of screening tools that look at a combination of the above in order to identify cachexia, such as the Malnutrition Universal Screening Tool (MUST). However, there is no single screening tool that is effective in detecting cachexia in every case. Dividing cachexia into stages or grades can give healthcare providers a better understanding of its natural history, but of greatest concern is that cachexia is diagnosed as early as possible.

Despite the number of tools available, following a person over time and checking serial body weights can give a better idea of changes.

Researchers have developed a cachexia staging score for people with advanced cancer. A different number of points are assigned to each component and added together to separate cachexia into three stages. These components include:

  • Weight loss in the past six months (scored from 0–3)
  • A questionnaire that addresses muscle function and sarcopenia (scored from 0–3)
  • ECOG performance status (scored from 0–3). Performance status is a scoring of physical ability.
  • Loss of appetite (scored from 0–2)
  • Abnormal lab tests (scored 0–2)

Stages

Based on scoring, precachexia and cachexia can then be broken down into four stages:

  • Non-cachexia (a score from 0–2)
  • Precachexia (score from 3–4): Overall weight loss is less than 5%, and people may have symptoms such as loss of appetite and impaired glucose tolerance
  • Cachexia (score from 5–8): Weight loss is greater than 5% and other symptoms or conditions associated with cachexia are present
  • Refractory Cachexia (score 9–12): This usually includes people who are no longer responding to cancer treatments, have a low performance score, and have a life expectancy of less than three months

Grades

A study published in 2015 in the Journal of Clinical Oncology divided cancer cachexia into 5 grades. Researchers found that for each increase in grade, survival decreased significantly. Grades were as follows:

  • Grade 0: No significant weight loss (a loss or gain of less than 2.4% of body weight), and a BMI of less than or equal to 25 kg/m2
  • Grade 1: BMI of 20 to 25 and weight loss greater to or equal to 2.4%, or a BMI less than 28 with weight loss of 2.5% to 6%
  • Grade 2: BMI of 20 to 28, with a weight loss of 2.5% to 6%, or a BMI less than or equal to 28 with a weight loss of 6% to 11%
  • Grade 3: This includes people with a BMI less than 20 and weight loss of less than 6%, those with a BMI of 20 to 28 and a weight loss of 6% to 11%, a BMI of 22 to over 28 and weight loss of 11% to 15%, or a BMI less than 28 and weight loss more than 15%
  • Grade 4: BMI less than 20 and weight stable or loss of 6% to 11%, a BMI of less than 22 and weight loss of 11% to 15%, or a BMI less than 28 and weight loss of over 15%

Treatment

The first step in treatment is to treat any physical symptoms or conditions that could lead to a decreased appetite or ability to eat. These include:

In many cases, simple changes in diet can reduce symptoms, such as eating with plastic utensils if you have "metal mouth" or choosing foods to manage gastroparesis.

The aim of treatment is to stimulate "anabolic processes" (that is, muscle building) while inhibiting "catabolic processes" (the actions that result in the breakdown of muscle).

At the current time, most researchers believe a combination of treatments (multimodality therapy) is essential. These include:

Diet

Contrary to what may seem obvious, replacing and supplementing calories in the diet has not made a big difference in the syndrome of cachexia. That said, it’s very important to make sure that people coping with cancer (and similar conditions that cause cachexia) have a healthy diet.

One important point to keep in mind is that if someone has not been eating much for a period of time, intake should be increased gradually. If calories are pushed too rapidly, a side effect called “overfeeding syndrome” may occur. When eating is not possible orally (or is limited), a feeding tube may be recommended.

Many healthcare providers recommend eating frequent small meals with an emphasis on calorie-dense foods.

Nutrition counseling may be helpful in addressing any symptoms that lead to decreased intake and giving you ideas for foods to try that you may not have thought about.

Nutritional supplements such as Ensure are often recommended, but should not be used as a substitute for meals. It’s usually recommended that when used, these products should be consumed between meals.

Omega-3 Fatty Acids

It’s ideal if nutrients can be obtained through food, but we know that’s not always the case. Fish oil has been evaluated for its ability to treat cachexia with some studies (but not all) suggesting it may be helpful.

In one study, patients who received eicosapentaenoic acid (EPA), an omega-3 fatty acid that people get in their diets by eating fish, had reduced levels of inflammatory markers associated with cachexia. They also had improvements in fatigue, loss of appetite, and neuropathy (dysfunction in the nervous system).

Amino Acid Supplements

Centers focused on recognizing and treating cachexia also often recommend amino acid supplements, particularly glutamine, L-carnitine, and L-arginine. These amino acids are being evaluated in combination with other therapies to assess their potential benefit.

Exercise

It may seem counterintuitive, but increasing activity (if possible) may help. An obvious benefit of exercise is increased appetite, but endurance training may go beyond eating habits to help slow the decline in muscle mass seen with cachexia. It’s thought that exercise may reduce inflammation and also affect metabolism in muscles themselves.

Appetite Stimulants

Appetite stimulants have been used for treating cachexia, though their effects are unclear. These include:

  • Corticosteroids such as prednisone and dexamethasone, though significant side effects can occur
  • Megace (megestrol): While Megace can result in weight gain, it hasn’t thus far appeared to improve quality of life. It may also increase the risk of blood clots which are already common in people with cancer
  • Medroxyprogesterone
  • Testosterone

One study of an appetite stimulant called megestrol acetate (MA) found that for people with cachexia syndrome, it is associated with a greater risk of blood clots, fluid retention (which causes foot and hand swelling), and even death.

Anti-Inflammatory Medications

Anti-inflammatory medications such as Celebrex (celecoxib) have shown some promise, particularly if evidence of inflammation is present (for example, if C-reactive protein is elevated). There is some evidence that these medications may improve prognosis.

Medical Marijuana

Thus far the evidence for the use of cannabis for cancer-related cachexia-anorexia is equivocal. Hopefully, with changes in regulations leading to a greater ability to study substances such as THC and CBD in clinical trials, the question of their efficacy will be addressed.

Clinical Trials

A wide range of medications have been investigated to some degree for their potential role in addressing cachexia. Both selective androgen receptor modulators and medications that target the ghrelin receptor (ghrelin is the hunger hormone) are being studied.

Drugs that target inflammatory compounds such as cytokines (which contribute to muscle breakdown) are intriguing. The body produces cytokines to help kill cancer cells, but cytokines also tend to shift the body towards a state of catabolism (breakdown). Finally, as with many conditions, efforts to target gut bacteria deserve further study.

Summary

Cachexia is a condition that causes severe weight loss and muscle wastage during the later stages of illnesses such as cancer, heart failure, or HIV/AIDS. It is often irreversible.

It can lower the body’s immunity, interfere with the treatment and healing of the underlying cause, and greatly diminish one’s quality of life.

Treatment incorporates several types of therapies including medications like appetite stimulants, nutritional supplements, and exercise.

13 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading

By Lynne Eldridge, MD
 Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."