Background/Objectives: This study explored the relationship between serum vitamin C levels, antioxidant defense mechanisms, and the severity of pulmonary tuberculosis (TB) among Romanian patients. Methods: This study enrolled 53 patients with bacteriologically confirmed pulmonary tuberculosis at Victor Babes University Hospital in Craiova between January 2023 and August 2024. Participants were stratified into two groups based on their serum vitamin C levels: 26 patients with normal levels and 27 patients with low levels. Clinical, demographic, and biological parameters, including inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were assessed at baseline and after 60 days of TB treatment. Serum vitamin C levels were measured using ELISA. The persistence of Mycobacterium tuberculosis (MTB) was evaluated using sputum smear microscopy and culture at baseline and after 2 months of treatment. Results: The results showed that patients with low vitamin C levels had significantly higher baseline ESR (92.63 ± 27.69 mm/h) and CRP (43.89 ± 12.00 mg/L) levels compared to those with normal levels (ESR: 65.11 ± 13.27 mm/h, CRP: 31.19 ± 9.76 mg/L). After 60 days, 66.67% of patients with low vitamin C levels remained culture-positive compared to 26.92% in the normal vitamin C group (p = 0.004). Multivariate analysis indicated that vitamin C deficiency was significantly associated with a higher TB culture load. Conclusions: These findings suggest that vitamin C deficiency may contribute to the persistence of MTB and highlight the potential role of vitamin C supplementation as an adjunct to standard TB treatment, particularly in the context of global efforts to eradicate the disease by 2035.
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