Inflammation hinders anabolic potential of nutritional support in cancer: findings from the Protein Recommendation to Increase Muscle (PRIMe) trial

BACKGROUND: Our recent Protein Recommendation to Increase Muscle (PRIMe) trial suggested that increasing daily protein intake via nutrition counseling in patients with colorectal cancer positively impacts muscle mass. OBJECTIVES: This post hoc analysis investigated whether baseline systemic inflammation, hormone, and/or amino acid disturbances influenced the effectiveness of nutrition support (focused on high protein) to increase lean soft tissue (LST). Outcomes were analyzed based on actual achieved protein intake, allowing exploration of dose-response effects. METHODS: In patients with stage II-IV colorectal cancer who received nutritional counseling to reach protein intake of 1.0 or 2.0 g/kg/d for 12 wk, LST was assessed by dual-energy X-ray absorptiometry, dietary protein intake by weighted 3-d food records, and cytokine, hormone (Luminex), and amino acid concentrations (liquid chromatography-tandem mass spectroscopy) at baseline and 6 and 12 wk. RESULTS: The mean protein intake of the entire group [50 patients, age 57 y (SD 11 y)] was 88.7 g/d, and baseline cytokines were elevated. Although protein intake (in grams) increased by 22% (9.34%) and 29% (16.42%) at 6 and 12 wk of supplementation, respectively, the LST response varied widely. At 6 wk, 77% of LST response variation was explained by baseline concentrations of interleukin (IL)-6, insulin, and specific amino acids (hydroxyproline, aspartate, taurine) and protein intake changes (P = 0.021). By 12 wk, IL-6 and methionine explained only 32% (P = 0.030). Tumor stage and concurrent chemotherapy type did not play a role. Positive LST change after 6 wk occurred at daily protein increase of 27 g. CONCLUSIONS: Elevated IL-6 blunts the anabolic capacity of protein support in colorectal cancer. At least 27 g/d of supplemental protein is needed to reach anabolism, although higher amounts may be needed in patients with higher IL-6 levels. These findings support the need to consider baseline inflammation to optimize the effectiveness of nutritional support in cancer. This trial was registered at clinicaltrials.gov as NCT02788955. https://clinicaltrials.gov/study/NCT02788955.