Inflammation Hinders Anabolic Potential of Nutritional Support in Cancer: Findings from the PRIMe trial.

BACKGROUND: Our recent PRIMe trial suggested that increasing daily protein intake via nutrition counseling in patients with colorectal cancer positively impacts muscle mass. OBJECTIVE: This post-hoc analysis investigated if baseline systemic inflammation, hormone and/or amino acid disturbances influenced 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/day for 12 weeks, LST was assessed by Dual energy X-ray Absorptiometry, dietary protein intake by weighted 3-day food records, and cytokine-, hormone- (Luminex), and amino acid concentrations (LC-MS/MS) at baseline and 6 and 12 weeks. RESULTS: Mean protein intake of the entire group (50 patients, age:57 y (SD:11)) was 88.7 g/day and baseline cytokines were elevated. Although protein intake in grams increased by 22(9,34)% and 29(16,42)% at 6 and 12 weeks of supplementation, respectively, the LST response varied widely. At 6 weeks, 77% of LST response variation was explained by baseline IL-6, insulin, and specific amino acids (hydroxyproline, aspartate, taurine), and protein intake change (p=0.021). By 12 weeks, 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 weeks occurred at daily protein increase of 27 grams. CONCLUSION: Elevated IL-6 blunted the anabolic capacity of protein support in colorectal cancer. At least 27 grams/day of supplemental protein was needed to reach anabolism, though higher amounts may be needed in patients with greater IL-6 levels. These findings support the need to consider baseline inflammation to optimize effectiveness of nutritional support in cancer. CLINICAL TRIAL REGISTRY: https://clinicaltrials.gov/study/NCT02788955, date of registration: 2016-06-02 Data described in the manuscript, code book, and analytic code will be made available upon request pending approval of the principal investigator.