Nutritional modulation of oxaliplatin-induced peripheral neuropathy: a serum metabolomics study in colorectal cancer patients

The link between nutritional status and chemotherapy toxicity in cancer patients requires further clarification. This study used serum metabolomics to examine how nutritional status affects oxaliplatin-induced peripheral neuropathy (OIPN) in patients with colorectal cancer (CRC). We analyzed samples from 219 CRC patients receiving oxaliplatin-based therapy, grouped by nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002) into two cohorts: malnourished (NRS ≥ 3) and well-nourished (NRS < 3) cohorts. Liquid chromatography-mass spectrometry (LC–MS) and multivariate statistics were used to identify differentially expressed metabolites (DEMs). We found 179 DEMs between OIPN and non-neuropathic controls (CONT), with amino acids and derivatives being the most prevalent. Enrichment analysis pinpointed arginine biosynthesis as a key pathway, exhibiting nutrition-dependent regulation. While L-arginine and ornithine were downregulated and L-glutamine was upregulated in OIPN patients overall, this pattern was reversed in the malnutrition subgroup. Concurrently, arginine pathway enrichment was reduced in malnourished patients. These results indicate that OIPN is associated with significant serum metabolite alterations, primarily affecting amino acid metabolism, which are distinctly modulated by malnutrition. Our findings highlight the role of nutritional status in OIPN occurrence and may provide a basis for future research into targeted nutritional support to alleviate this neurotoxicity in CRC patients, although confirmatory studies are needed.