Individual and joint associations of vitamin C intake and physical activity with inflammation and mortality in chronically infected populations: Evidence from a cohort study of NHANES 2005 to 2018

Chronic low-grade inflammation contributes to the development of many chronic diseases, and both vitamin C intake and physical activity have individually been linked to reduced inflammatory responses; however, their combined effects on systemic inflammation and long-term survival in adults with chronic viral infections remain largely unknown. This study evaluated the individual and combined associations of dietary vitamin C intake and physical activity with inflammatory biomarkers and all-cause mortality in a nationally representative cohort of U.S. adults aged 20 years or older. Data from 33,590 participants in the National Health and Nutrition Examination Survey (NHANES 2005-2018) were analyzed, including 22,763 (67.8%) who were seropositive for at least 1 viral pathogen and 10,827 who were seronegative. Mortality status through 2019 was ascertained by probabilistic linkage of NHANES participants to the National Death Index (NDI) using a unique combination of identifiers provided by the National Center for Health Statistics. Higher vitamin C intake was associated with lower platelet count (PC), neutrophil count (NC), lymphocyte count (LC), platelet × neutrophil product (PPN), and systemic immune-inflammation index (SII) across the overall population, with consistent inverse associations in seronegative adults and those seropositive for hepatitis viruses, HSV, and HPV (e.g., PPN difference in the HSV subgroup, P < 1 × 10-9). Moderate-to-vigorous physical activity was linked to reduced PC, PLR, PPN, and SII, most prominently in seronegative and HSV-seropositive participants, while associations in the hepatitis, HPV, and HIV subgroups were weaker. Participants with both high vitamin C intake and higher activity demonstrated the most favorable inflammatory profiles, characterized by consistent reductions in platelet- and neutrophil-based indices. In HSV-seropositive adults (n = 10,306), elevated PC and PPN (above the median) were associated with significantly higher 10-year all-cause mortality (log-rank P < .05). These findings indicate that vitamin C intake and physical activity, individually and in combination, are associated with lower systemic inflammation and improved survival in adults with chronic viral infections, supporting the potential role of lifestyle interventions in reducing long-term mortality risk.