Cancer Weight Loss: Causes And Impact

A healthy weight or a normal weight are common goals as overweight and obesity plague our society. 

However, most of us will feel worried if we suddenly lose too much weight without reason. 

Achieving weight loss without any diet, exercise, or supplements prompts a medical concern for cancer diagnosis and other chronic ailments that also feature unexplained weight loss.

What happens in cancer that triggers weight loss? How severe is it, and what consequences it has? In this article, we’re answering these questions and more.

What causes weight loss in cancer patients?

Unexplained rapid weight loss is a symptom of intermediate-stage and late-stage cancer. When present, it is usually a part of a wasting syndrome known as cachexia. 

This syndrome has various signs and symptoms, including fatigue, muscle weakness, and a reduction in muscle mass. However, the best definition of cancer cachexia has to do with weight loss. 

It is defined as a 5% bodyweight reduction in 6 months without significant changes in dietary patterns and physical activity.

There are multiple causes of weight loss in these patients, including:

Loss of appetite

Cancer patients often suffer from loss of appetite. After losing their appetite, they typically reduce their energy intake. 

In contrast, energy expenditure increases because cancer cells consume many resources. As a result, there is a negative energy balance. 

In other words, cancer patients break down more energy than they consume in their diet. This can often cause anorexia due to altered taste sensitivity, nausea, vomiting, depression, stress, and anxiety. 

In some cases, the tumor may obstruct the gastrointestinal tract or cause oral ulcers. For these reasons, patients reduce their energy intake or have alterations in food processing.

Accelerated metabolism

There is something called basal metabolic rate, or BMR. It is an account of how much energy your body consumes, even when you’re doing no physical activity. In cancer patients, this measure increases because there’s something called hypermetabolism. 

Protein turnover is increased as an attempt to create more energy, and muscle mass reduces dramatically. At the same time, cancer cells divide rapidly, creating new blood vessels in the process. 

They rob the energy that should reach other parts of the body to keep replicating. Combined with a lower energy intake, an increased BMR reduces body weight significantly.

Tumor substances

The tumor may contribute directly to the process of cachexia by releasing a series of substances. For example, tumor necrosis factor-alpha and proteolysis-inducing factor. 

They also produce glucocorticoids, angiotensin II, and more substances. Altogether, they induce atrophy of the muscles, leading to muscle weakness and reducing the patient’s exercise capacity. 

Muscles are lost, and protein synthesis is impaired. At the same time, there is also degradation of the fat mass through lipolysis, which is triggered by the tumor itself.

Cytokines and inflammation

It is a fact that cancer feeds off inflammation and triggers an inflammatory condition to its advantage. Malignant inflammation features an increase in C-reactive protein, acute-phase response proteins, and other inflammatory substances. 

C-reactive protein is apparently behind muscle wasting. Acute-phase response proteins induce inflammation and speed up weight loss. Other inflammatory substances reach the brain and cause appetite suppression.

As you can see, the mechanism of weight loss in cancer patients is deeply co-dependent. All of the processes above usually happen simultaneously and feed one another, making the condition worse every time.

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What is the impact and is it dangerous?

The main problem of weight loss is not only aesthetic. As you can see above, all of the processes in cachexia deeply link to one another. 

Thus, patients do not only experience weight loss. They also go through muscle mass loss, body weakness, tiredness, and fatigue. 

Muscle mass can be as bad as to trigger cardiac cachexia, which is a weakening of the heart muscles leading to chronic heart failure. Even if that doesn’t happen, the quality of life is severely affected in patients with weight loss and other cachexia symptoms.

Besides affecting the quality of life, in several studies, weight loss severity predicts cancer aggressiveness. In most cases, the more aggressive cancer is, the more likely it is to trigger cachexia. 

Similarly, losing more weight means that cancer is more advanced and could be spread to other tissues. It affects the physical function of the patient and increases the risk of mortality.

Finally, it is also known that weight loss predicts the toxicity of cancer treatment. For example, in chemotherapy, the drug is administered after calculating body surface area. 

The problem is that body surface area does not account for the proportion of fat, muscle, and water. Changes in lean muscle mass found in patients with weight loss may lead to an abnormal distribution of cancer treatment.

Chemotherapy effectiveness depends on the dose. Thus, body weight changes may impact how effective treatment is. 

Moreover, advanced weight loss may increase the chance of toxicity and adverse events. This increase in toxicity rates has been found in colon cancer, esophageal cancer, breast cancer, lung cancer, and others.

Managing cancer weight loss

A recent review published in the Journal of Oncology Practice lists three main steps to manage cancer-related weight loss:

1) Recognizing cachexia

The first step is naturally identifying weight loss and other signs of cachexia in cancer patients. Doing so will allow us to treat the condition as soon as possible. 

To recognize cachexia, we should remember that it is not only about weight loss and BMI measures. Even patients who are still obese may undergo sarcopenia. 

Other patients may remain the same weight, but they lose significant fat and lean mass while maintaining their weight. 

The only weight gain is through water retention, though. Thus, doctors should measure the body composition of cancer patients instead of only measuring their weight.

2) Look for a multidisciplinary team

Only one doctor cannot treat this cancer complication effectively. Cancer patients also need care from dietitians, physical therapists, and other experts.

3) Start nutritional and exercise changes

Nutritional and physical activity interventions play a significant role in treating this complication. Several dietary supplements can prevent malnourishment and increase energy intake. 

Physical activity increases energy consumption but improves the patient’s body composition and reverses the effects of weight loss in quality-of-life measurements and toxicity rates.

Additionally, there are many pharmacologic approaches to address weight loss and cachexia. There are several drugs these patients could use to accelerate recovery or prevent further damage. 

The most commonly used are progestins, ghrelin, cannabinoids, melanocortin antagonists, thalidomide, and etanercept:

  • Progestins such as megestrol acetate increase appetite and help stabilize body weight. They also decrease the level of inflammatory cytokines in the blood of the patients.

  • Ghrelin is a peptide hormone that promotes appetite. It prevents the onset of cardiac cachexia and improves lean body mass and muscle strength.

  • Cannabinoids are also helpful in increasing food intake in cases of anorexia. However, oncology trials are still ongoing and bear conflicting results.

  • Melanocortin antagonists prevent the stimulation of a receptor that produces anorexia in cancer patients. It is ideal when the cause of cachexia is related to an increase of melanocortin-4 signaling.

  • Thalidomide and etanercept modulate cytokine expression in cancer patients. They inhibit inflammatory substance production or block their activity. Lean mass and the sensation of fatigue improve after treatment in clinical trials.

Conclusion

Unintentional weight loss is one of the clinical features of advanced cancer. It features fat loss, but more importantly, a high degree of muscle loss, and it relates to a reduced overall survival and worse outcomes in cancer patients.

Involuntary weight loss results from a combination of loss of appetite and changes in body metabolism due to cancer and cancer treatment. Thus, the management of this condition involves recovering appetite and modulating the inflammatory profile of the patient. 

Starting treatment early will not only improve the quality of life but may also improve survival outcomes and prevent side effects of cancer treatment. 

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Sources

  1. Bruggeman, A. R., Kamal, A. H., LeBlanc, T. W., Ma, J. D., Baracos, V. E., & Roeland, E. J. (2016). Cancer cachexia: beyond weight loss. Journal of oncology practice, 12(11), 1163-1171. https://pubmed.ncbi.nlm.nih.gov/27858548/
  2. Fearon, K. C. (1992). The mechanisms and treatment of weight loss in cancer. Proceedings of the Nutrition Society, 51(2), 251-265. https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/mechanisms-and-treatment-of-weight-loss-in-cancer/4EE07F0B5B67612E26C9C5EDE2AF9BA6
  3. Tisdale, M. J. (2009). Mechanisms of cancer cachexia. Physiological reviews, 89(2), 381-410. https://pubmed.ncbi.nlm.nih.gov/19342610/
  4. Aoyagi, T., Terracina, K. P., Raza, A., Matsubara, H., & Takabe, K. (2015). Cancer cachexia, mechanism and treatment. World journal of gastrointestinal oncology, 7(4), 17. https://pubmed.ncbi.nlm.nih.gov/25897346/

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