Cachexia: Disordered Eating as a Cancer Side Effect

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Eating disorders are often thought of as body image disorders with symptoms of food restriction and purging. In most cases, the goal of these behaviors is to prevent weight gain.

Not all eating disorders have symptoms of body dissatisfaction, though. Some eating disorders are strictly illnesses of appetite dysfunction unrelated to how one feels about their body. Individuals with these types of eating disorders want to gain weight for their survival, but can't. An example of such an eating disorder is cancer cachexia.

What Is Cancer Cachexia?

Cancer cachexia is a disorder of severe weight loss, reduced appetite, fatigue, and muscle deterioration.¹⁷ Unlike anorexia nervosa (AN), which is a different illness involving food restriction and weight loss, cancer cachexia develops in the late stages of various cancers. Another differentiating factor between cancer cachexia and AN is the body’s response to caloric restoration during illness. With cancer cachexia, restoring a cancer patient's caloric intake does not greatly reverse muscle wasting.³ In contrast, those with AN regain strength and body weight when they start to eat more.

Cancer cachexia, therefore, is not AN, despite people with both illnesses experiencing severe appetite loss and weight reductions, leading to possible death.

Understanding what causes cancer cachexia is important because roughly 85% of individuals with cancer will develop this illness,¹² which interferes with cancer treatment and causes one-fifth of cancer deaths.⁶ We need to know what causes cancer cachexia to prevent and treat it.

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Inflammation as a Cause of Cancer Cachexia

Causes for cancer cachexia, however, remain unclear.³

One suspected cause of cancer cachexia is tumor-induced inflammation (e.g., cytokines).¹⁸ How excessive inflammation contributes to the development of cancer cachexia is complex and not entirely understood. Emerging evidence, however, suggests that elevated inflammation during this illness alters how the hormone leptin is able to regulate appetite¹ and muscle growth.⁴

Leptin, a hormone produced by fat cells, is best known for making us feel full when we have eaten the number of calories our bodies need to function optimally.¹⁹ A lesser-known function of leptin is inflammation regulation and muscle maintenance.⁵ Food intake and body weight, therefore, influence how well our bodies can fight off health threats.

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Because individuals who food restrict are in an energy deficit, they have low leptin levels; this motivates them to eat more.¹⁹ Food restriction, when done in short spurts, can help the body get rid of unwanted inflammation via reduced leptin.²⁵ Food restriction to the point of malnourishment, though, becomes a problem. The problem with having very low leptin levels is that this can cause immunosuppression.²⁰ Too little leptin in the body makes it harder for the immune system to attack and defeat health threats, as it is "dormant."

People with cancer cachexia, however, respond to malnourishment differently than healthy people. Despite having low leptin levels, individuals with cancer cachexia have high levels of inflammation and experience appetite loss.¹ These unusual effects suggest that leptin’s ability to regulate appetite and inflammation in people with cancer cachexia is broken. For people with cancer cachexia, excessive inflammation increases satiation⁷ and stops the creation of muscle protein.²

Why some people's bodies respond to cancer in this way and others do not is still a mystery. Emerging evidence, however, suggests that there is a genetic susceptibility to excessive inflammation during cancer illness.¹⁶

Treating Cancer Cachexia

Currently, there are no cures for cancer cachexia. This illness can, however, be managed for some individuals.

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Treatment options for cancer cachexia are limited and there are currently no FDA-approved drugs to treat it. Consequently, patients with cancer cachexia are prescribed drugs that have shown effectiveness in increasing appetite and muscle synthesis in other illnesses. For example, synthetic forms of progesterone, a hormone best known for its role in pregnancy, have shown promise in increasing appetite and body weight in cancer patients by reducing inflammation.^{8; 9}

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Another approach when treating cancer cachexia is to target muscle wasting. For example, the drug oxandrolone has been shown to stimulate muscle protein synthesis, leading to increased protein production and reduced muscle wasting.¹¹ A alternative approach is to block certain functions by proteins called type IIB activin receptors (ActRIIB).^{21; 22} ActRIIB receptors have the important job of determining when our muscles grow and when they weaken. Several research studies have shown that preventing ActRIIB receptors from causing muscle wasting can initiate muscle growth in animal models of cancer cachexia.^{21; 22; 23}

Nonetheless, for the few treatments that have shown effectiveness in managing cancer cachexia, many more are ineffective or have shown mixed results.^{13; 14; 15} For example, in most research, omega-3 fatty acids have been ineffective in treating cancer cachexia by failing to reduce inflammation.¹⁴ Some patients, however, see weight increases after taking omega-3 fatty acids,¹⁵ while other cancer patients taking omega-3 fatty acids experience muscle depletion.¹³

Conclusions

Why cancer cachexia develops in some individuals remains unclear, creating an obstacle for treatment development. Future research will need to explore genetic susceptibility to cancer cachexia, the exact causes of inflammation leading to the development of cancer cachexia, and how this inflammation contributes to appetite loss and muscle wasting. Researchers will also need to explore what role specific organs (e.g., brain; gastrointestinal tract) play in the development of cancer cachexia.²⁴ Finally, more individualized treatments will be necessary for managing cancer cachexia more effectively in more individuals.