Eicosapentaenoic Acid

Abstract

Cancer cachexia affects about half of all cancer patients and is associated with negative effects on functional status and quality of life. This condition is also a major contributor to the morbidity and mortality of patients with advanced malignancy. Although current strategies to improve appetite and lean body mass by administering appetite stimulants, increasing physical activity and using nutritional supplementation have a scientific rationale, randomised studies have continued to demonstrate that a reduction in the loss of lean body mass is difficult to achieve unless the underlying metabolic abnormalities in cancer cachexia are corrected. Initial studies using animal models have demonstrated that nuclear factor-κ B (NF-κB) is upregulated in cancer cachexia, increasing proteolysis and breakdown of myofibrillar proteins, which results in sarcopenia. Laboratory studies have shown that eicosapentaenoic acid (EPA), an n-3 fatty acid, has anticachectic effects and may attenuate protein degradation by preventing NF-κB accumulation in the nucleus. EPA is associated with weight stabilisation, gain in lean body mass, and improvement in quality-of-life markers in weight-losing patients with advanced pancreatic cancer. Although animal studies have demonstrated the molecular basis of the effects of EPA, this has never been validated in human clinical trials. On the basis of the promising results of the laboratory and clinical studies, we hypothesise that selective targeting of proteasome activity by EPA (a polyunsaturated fatty acid) administered to cancer patients, including elderly patients, with cancer cachexia will alter metabolic abnormalities by downregulating NF-κB, modulating immune and inflammatory response and thus preventing the breakdown of myofibrillar proteins. This will result in promotion of anabolism, reduction of weight loss and increase in lean body mass and physical function, thus establishing a case for future, prospective clinical trials.