Conventional nutritional supplements are not or only partly successful in inducing protein accretion in advanced cancer, suggesting an attenuated anabolic response. To prevent muscle wasting and its deleterious consequences, generating an anabolic response is crucial. Dietary essential amino acids (EAA) have anabolic properties in other wasting diseases; however, data in advanced cancer are lacking. In 13 patients with advanced nonsmall-cell lung cancer (NSCLC) (stage III and IV) and 11 healthy age-matched subjects, we measured protein synthesis and breakdown of the whole body, and net protein anabolism (difference between protein synthesis and breakdown) after intake of 14 g of free EAA with high leucine levels (EAA/leucine) versus a balanced amino acid mixture containing both EAA and non-EAA as present in whey protein, according to a randomized, double-blind, crossover design. Protein synthesis and net protein anabolism were higher after intake of the EAA/leucine than the balanced amino acid mixture (P < 0.001), independent of presence of cancer. A highly significant linear relationship between net protein anabolism and the amount of EAA available in the systemic circulation (R²: 0.85, P < 0.001) was found in both groups. The presence of muscle or recent weight loss, systemic inflammatory response, or length of survival did not influence this relationship. High leucine levels in the EAA/leucine mixture was of no anabolic benefit. There is no anabolic resistance or attenuated anabolic potential to intake of 14 g of EAA/leucine or balanced amino acid mixture in advanced (mainly stage III) NSCLC. The high anabolic potential of dietary EAA in cancer patients is independent of their nutritional status, systemic inflammatory response or disease trajectory, suggesting a key role of EAA in new nutritional approaches to prevent muscle loss, thereby improving outcome of patients with advanced cancer. NCT01172314.

This opinion paper presents a short review of the potential impact of protein on muscle anabolism in cancer, which is associated with better patient outcomes. Protein source is a topic of interest for patients and clinicians, partly due to recent emphasis on the supposed non-beneficial effect of proteins; therefore, misconceptions involving animal-based (e.g., meat, fish, dairy) and plant-based (e.g., legumes) proteins in cancer are acknowledged and addressed. Although the optimal dietary amino acid composition to support muscle health in cancer is yet to be established, animal-based proteins have a composition that offers superior anabolic potential, compared to plant-derived proteins. Thus, animal-based foods should represent the majority (i.e., ≥65%) of protein intake during active cancer treatment. A diet rich in plant-derived proteins may support muscle anabolism in cancer, albeit requiring a larger quantity of protein to fulfill the optimal amino acid intake. We caution that translating dietary recommendations for cancer prevention to cancer treatment may be inadequate to support the pro-inflammatory and catabolic nature of the disease. We further caution against initiating an exclusively plant-based (i.e., vegan) diet upon a diagnosis of cancer, given the presence of elevated protein requirements and risk of inadequate protein intake to support muscle anabolism. Amino acid combination and the long-term sustainability of a dietary pattern void of animal-based foods requires careful and laborious management of protein intake for patients with cancer. Ultimately, a dietary amino acid composition that promotes muscle anabolism is optimally obtained through combination of animal- and plant-based protein sources.