Immunological perspectives on nutritional support during cancer

Abstract

Cachexia is a major problem in many cancer patients with a global incidence of malnutrition ranging from 30% to 90% during the course of cancer. The main characteristics of this chronic condition of catabolism include progressive weight loss, anorexia, wasting of muscle and adipose tissue, muscle weakness and fatigue. Tumor-derived factors, therapeutic strategies, but also nutritional status, age and even stress and depression are involved in this process, resulting in a chronic inflammatory state and paradoxically, impaired immune responsiveness. Together, these factors may lead to disease progression, increased (infectious) complications and a delayed or suboptimal treatment regimen resulting in a reduced quality of life and a poor prognosis. Accordingly, a multi-disciplinary approach, including nutritional support is recommended which is initiated at the moment of diagnosis and runs parallel to the pathway of anti-cancer therapies. For that reason, a specific nutritional combination (SNC) has been developed for application in cancer patients. This concept is high in protein and leucine and is enriched with emulsified fish oil (containing EPA and DHA) and specific oligosaccharides. In preclinical experiments the SNC significantly improved the immune response and reduced the inflammatory state in tumor-bearing mice prior to weight loss. Translated to a setting investigating the resistance to infections with a relevant living pathogen, dietary intervention with the SNC significantly reduced the incidence and severity of Pseudomonas aeruginosa translocation in a mouse model of chemotherapy-induced neutropenia. Plasma levels of pro-inflammatory cytokines tended to be reduced and a strong correlation was observed with bacterial translocation. Several mechanisms might have played a role, including the modulation of the intestinal microbiota, an improved gut barrier function, improved immune function and a reduced inflammatory state. In a study in healthy human volunteers, both the efficacy as well as safety of the SNC was investigated as it was applied in a specific medical food. An additional objective was to investigate the incorporation kinetics of EPA and DHA (from fish-oil) into white blood cell (WBC) phospholipids within one week of intervention, since a rapid and effective incorporation of these n-3 PUFA might be important for cancer patients starting a treatment regimen soon after diagnosis. The nutritional intervention significantly increased the percentage of EPA in phospholipids of WBC within one week. Simultaneously, ex vivo immune responsiveness to LPS was increased significantly. In a study in newly diagnosed esophageal cancer patients, intervention with the specific medical food significantly reduced serum PGE2 levels. This effect was accompanied by a significant increase in body weight and an improved performance status. In cancer patients receiving radiotherapy, intervention with the specific medical food rapidly increased the percentage EPA and DHA in WBC phospholipids and reduced serum levels of the inflammatory mediator PGE2 within one week. Consequently, these results show that nutritional intervention with the specific medical food may represent a new opportunity for applications in cancer patients being an integral part of disease management to provide optimal treatment support. Additional research is recommended to elucidate the potential immunological effects and clinical benefits in different types and stages of cancer.