P291 - METABOLOMIC CHANGES TO HIGH-PROTEIN INTAKE IN PATIENTS WITH CANCER: TOWARD PRECISION NUTRITION APPROACH

P291

METABOLOMIC CHANGES TO HIGH-PROTEIN INTAKE IN PATIENTS WITH CANCER: TOWARD PRECISION NUTRITION APPROACH

B. R. da Silva^1,*, M. A. Horst^1,2, A. Zhang³, K. L. Ford¹, N. E. Deutz⁴, M. P. Engelen⁴, M. Siervo⁵, M. B. Sawyer⁶, D. S. Wishart³, C. M. Prado¹

¹Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Canada, ²Nutritional Genomics Research Group, Federal University of Goiás, Goiás, Brazil, ³Departments of Biological Sciences and Computing Science, University of Alberta, Edmonton, Canada, ⁴Center for Translational Research in Aging and Longevity, Texas A&M University, College Station, United States, ⁵School of Population Health , Curtin University, Perth, Australia, ⁶Department of Oncology, University of Alberta, Edmonton, Canada

Rationale: While high-protein diets may be beneficial to prevent muscle loss during cancer little is known regarding the metabolomics responses they stimulate. Identifying these patterns could support the development of metabotypes to guide precision nutrition interventions.

Methods: Patients with stage II-IV colorectal cancer enrolled in the Protein Recommendations to Increase Muscle (PRIMe) trial were randomized to either a normoprotein (1.0 g/kg/day) or high-protein (2.0 g/kg/day) diet. Plasma metabolomics were assessed at baseline and week 12.  Principal component analysis/ partial least squares discriminant analysis were used to assess group separation, and univariate analysis identified differences.

Results: Shifts in circulating metabolites were observed, with stronger group separation in the higher protein group, suggesting a greater impact of this level of protein intake on metabolism. Amino acid metabolism was significantly enhanced in the higher protein group, with increases in lysine (fold change [FC] = 4.12, p = 0.0004), ornithine (FC = 3.51, p = 0.0003), and citrulline (FC = 3.17, p = 0.0009). Similarly, metabolites associated with muscle metabolism, including sarcosine, quinoline-4-carboxylic acid, and kynurenine, were increased in the higher protein group.

Conclusion: Higher protein intake led to distinct metabolomic signatures indicative of increased amino acid availability and potentially anabolic signaling. While we did not directly assess muscle protein synthesis, this profile suggests that amino acids may have contributed to activating pathways such as mTOR, rather than being fully incorporated into muscle tissue. The potential signaling roles of indirect activators like lysine, citrulline, ornithine, and sarcosine remain to be clarified. Future studies are needed to explore the direct and indirect effects of these amino acids on muscle synthesis. Funding: CRC and Banting Fellowship.   

Disclosure of Interest: B. da Silva: None declared, M. A. Horst: None declared, A. Zhang: None declared, K. Ford Other: honoraria from Abbott Nutrition, N. Deutz Other: honoraria from Abbott Nutrition, M. Engelen: None declared, M. Siervo: None declared, M. Sawyer Speakers Bureau of: Viatris, Other: Viatris - Advisory board , D. Wishart: None declared, C. Prado Consultant for: Abbott Nutrition, Nutricia, Novo Nordisk, Other: Speaker engagement: Abbott Nutrition, Nutricia, Nestle Health Science, Novo Nordisk