Serum Copper-to-Zinc and Copper-to-Selenium Ratios in Inflammatory Bowel Disease: Possible Associations with Clinical Disease Activity and Endoscopic Healing in a Cross-Sectional Study with Prospective Enrollment

Background/Objectives: The associations of serum copper-to-zinc (Cu/Zn) and copper-to-selenium (Cu/Se) ratios with clinical disease activity and endoscopic healing in inflammatory bowel disease (IBD) remain incompletely characterized. Although trace element imbalances have been linked to intestinal inflammation, the clinical utility of composite trace element ratios remains unclear. We investigated whether serum copper-to-zinc (Cu/Zn) and copper-to-selenium (Cu/Se) ratios reflect clinical disease activity and mucosal status in IBD. Methods: This cross-sectional study with prospective enrollment recruited patients with IBD and non-IBD controls between July 2023 and October 2024. Serum Cu, Zn, and Se concentrations were measured to calculate Cu/Zn and Cu/Se ratios. Clinical disease activity was assessed using the Crohn’s Disease Activity Index (CDAI) and partial Mayo score. Endoscopic healing was defined as the absence of ulcers or erosions on endoscopy within 3 months of enrollment. Results: Among 190 participants, 62 had Crohn’s disease (CD), 69 had ulcerative colitis (UC), and 59 were non-IBD controls. Cu/Zn and Cu/Se ratios differed across controls and clinical activity categories (both overall p = 0.001), with the highest mean values in patients with moderate-to-severe activity. In the overall IBD cohort, AUC values for distinguishing moderate-to-severe activity from remission or mild activity were 0.749 and 0.736 for Cu/Zn and Cu/Se, respectively. Both ratios remained higher in patients with moderate-to-severe activity than in controls after adjustment for age, sex, and BMI (both p < 0.001). In CD, both ratios correlated positively with CDAI (Cu/Zn: rho = 0.500; Cu/Se: rho = 0.498; both p < 0.001). Cu/Zn and Cu/Se ratios differed across controls and patients with and without endoscopic healing (overall p < 0.001 and p = 0.003, respectively); however, the Cu/Zn difference between the two patient groups was not statistically significant. Conclusions: Serum Cu/Zn and Cu/Se ratios were associated with clinical disease activity, but their utility for assessing endoscopic healing and their incremental value beyond established biomarkers remain uncertain. Longitudinal validation is needed before routine clinical use can be supported.