Impact of Dietary Oxidative Balance Score and Circulating Antioxidant Index on All-Cause Mortality Risk in Cancer Patients: A Depression-Stratified Analysis of NHANES Cohorts

Background: The relationship between dietary oxidative balance and mortality among cancer patients remains unclear, particularly concerning the moderating effects of depression and cancer-specific mortality. This study aimed to evaluate the associations of Dietary Oxidative Balance Score (DOBS) and Circulating Antioxidants Index (CAI) with mortality risk in cancer patients, emphasizing the influence of depression status. Methods: Data were derived from two National Health and Nutrition Examination Survey (NHANES) cohorts: Cohort 1 (2005–2018, n=2,856) for assessing DOBS, and Cohort 2 (2017–2018, n=585) for developing CAI. DOBS was calculated based on dietary antioxidant and pro-oxidant intake obtained from validated food frequency questionnaires. CAI was constructed by standardizing and aggregating 12 serum antioxidant biomarkers. Generalized additive models with penalized splines and segmented regression analyses were utilized to explore potential non-linear relationships and threshold effects between DOBS/CAI and all-cause mortality. Cox proportional hazards models were employed to evaluate the associations of DOBS and CAI with all-cause mortality. Both analyses were adjusted for potential confounders and further stratified by depression status. Fine-Gray competing risk models were used to assess cancer-specific mortality, accounting for non-cancer deaths as competing events. Results: Results: During a median follow-up of 20,008.58 person-years in the DOBS cohort and 1,159.58 person-years in the CAI cohort, after multivariable adjustment, DOBS demonstrated inverse associations with both all-cause mortality (HR=0.99, 95% CI: 0.97-1.00, P=0.042) and cancer-specific mortality (SHR=0.98, 95% CI: 0.98-0.98, P<0.001). A non-linear relationship between DOBS and all-cause mortality was identified, with an inflection point at 11 points (HR=0.96, 95% CI: 0.92-1.00, P=0.066). . Stratified analyses by depression status revealed an inflection point at 8 points with subsequent plateau in depressed patients, while no threshold effect was observed in non-depressed individuals. For CAI, a significant threshold effect was detected at -6.91, with stronger protective effects below this value (HR=0.60, 95% CI: 0.42-0.86, P=0.0048) compared to above it (HR=0.93, 95% CI: 0.86-1.01, P=0.0683). Depression-stratified analyses showed a stable linear association in non-depressive groups but a declining trend at higher values in depressive groups. Furthermore, DOBS exhibited a positive correlation with CAI, with a threshold effect at DOBS of 11 points, showing stronger positive association below the threshold (OR=0.3, 95% CI: 0.1-0.4, P=0.001) and non-significant association above it (OR=-0.3, 95% CI: -0.6-0.1, P=0.141). Conclusion: Both DOBS and CAI demonstrated protective effects against mortality risk, with distinct threshold effects and depression-dependent patterns. These findings underscore the importance of considering depression in both behavioral and biochemical nutritional assessments for cancer patients and support the development of personalized nutritional strategies.