Can Vitamin C Intake and Physical Activity Individually and Jointly Lower Inflammation in Chronically Infected Populations? Insights from NHANES 2005–2018

Background: Systemic immune-inflammation is a key contributor to chronic disease pathogenesis. Whether vitamin C intake and physical activity influence inflammatory status in individuals with latent viral infections remains unclear. Methods: We conducted a cross-sectional analysis of 33,590 U.S. adults from NHANES 2005–2018. Vitamin C intake was assessed by two 24-hour dietary recalls; physical activity was self-reported. The primary outcome was the systemic immune-inflammation index (SII), with secondary outcomes including NLR, PLR, PPN, PC, NC, and LC. Multivariable linear regression models adjusted for sociodemographic and behavioral covariates. Analyses were stratified by serostatus to hepatitis viruses, HIV, HPV, and HSV. Results: Higher vitamin C intake was associated with lower SII, PC, NC, and PPN, particularly among HSV-seropositive and seronegative individuals. Moderate/vigorous physical activity was independently associated with lower inflammatory markers in these same subgroups. Joint exposure to high vitamin C intake and higher activity showed the most consistent anti-inflammatory profiles. Conclusions: Higher vitamin C intake and physical activity were independently and jointly associated with lower systemic inflammation, with pronounced effects among those with HSV infection or no viral exposure. These findings support the role of lifestyle modification in mitigating inflammation, particularly in populations with chronic immune activation.