Nutritional Interventions for Cancer-Induced Cachexia

Abstract

Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathologic mechanisms causing cachexia resulting in well-meaning advice to increase caloric intake with minimal results. Our goal is to describe the pathologic basis of cancer-induced cachexia and to detail accompanying metabolic derangements. Understanding the causes of cachexia sheds light on the subsequent need for multi-modality therapy including clinical intervention with specialized nutrition support, drug therapy, lifestyle and diet changes. In addition to nutrition support modalities, practicing oncologists may prescribe medical therapies designed to increase body weight and lean body mass, including megestrol acetate, tetrahydrocannibinol, oxandrolone, and non-steroidal anti-inflammatory drugs. A variety of experimental therapies are also being investigated for cancer-induced cachexia including tumor necrosis factor-alpha inhibitors and ghrelin infusions. We review the available data to support nutrition-oriented interventions in cancer-induced cachexia, including omega-3 fatty acids, amino-acid loading/protein supplementation, parenteral and enteral nutrition support, and food-derived compounds such as curcumin, reservatrol, and pomegranate.

Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials

“…This condition has deleterious effects on patient quality of life; make them more susceptible to the toxic effects of radiotherapy and chemotherapy and consequently limits treatment outcome and elevates mortality rate [189][190][191]. After one-third weight loss, death became imminent due to respiratory failure caused by diaphragm muscle devastating [188,192]. Cachexia-induced muscle loss is a result of decrease in synthesis/degradation ratio of protein through imbalance of ubiquitin-proteasome as well as dystrophin glycoprotein complex pathways [193][194][195].…”

“…It is believed that near four fifths of advanced stage cancer patients experience cancer-induced cachexia [185]. Cancer-induced cachexia is responsible of about one-fifth of cancer-related death especially in patients who suffer from head and neck, pancreatic, lung, colorectal, gastric, liver, esophageal, malignancies [186][187][188]. This condition has deleterious effects on patient quality of life; make them more susceptible to the toxic effects of radiotherapy and chemotherapy and consequently limits treatment outcome and elevates mortality rate [189][190][191].…”

Myostatin Neutralization Results in Preservation of Muscle Mass and Strength in Preclinical Models of Tumor-Induced Muscle Wasting

“…The mechanism behind this effect is unclear. Reduced caloric intake is another key component of cancer cachexia and opposing this is part of the current strategy to treat cachexia in cancer patients through administration of appetite stimulants and nutritional support (34). Myostatin expression has been shown to increase in specific muscles and contribute to muscle atrophy during food deprivation in mice (35).…”

n-3 Polyunsaturated Fatty Acids and Their Role in Cancer Chemoprevention

“…Studies show that an inflammatory reaction to a local tumor can also trigger a cascade of systemic inflammation that eventually lead to development of anorexia and catabolic processes, such as muscle proteolysis and lipolysis, the early stage of fatigue and cachexia [112]. Several clinical trials have been reported using EPA or marine fish oil (EPA + DHA) in purified form or in the form of oral supplements in an effort to prevent or reduce weight and muscle loss in cancer patients.…”