Overall and Progression-Free Survival of Patients With Malignant Neoplasm Following Intravenous Vitamin C: A Systematic Review and Meta-Analysis

Abstract

Background: This study aimed to determine whether administering intravenous vitamin C in patients with malignant neoplasm is associated with increased survival outcomes compared to no intravenous vitamin C administration.

Methods: The primary search was conducted using MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to October 13, 2024. Results were collected from randomized clinical trials and cohort studies that compared intravenous vitamin C and blank controls or placebo in patients with malignant neoplasm. Two reviewers independently assessed the data extraction process and the risk of bias, while the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. A frequentist framework was used as the primary analysis approach.

Results: A total of 8 studies with 2722 adult participants were included. The vitamin C dose ranged from 2.5 g/d to 1.5 g/kg of body weight per day, with the treatment duration ranging from 9 days to 1 year. The primary outcome was overall survival, with progression-free survival as a secondary measure. Intravenous vitamin C was associated with a significantly longer median overall survival (pooled estimated median survival ratio: 1.83; 95% confidence interval: 1.40-2.40; p < 0.001; moderate certainty), and a trend towards improved progression-free survival (pooled estimated median survival ratio: 1.80; 95% confidence interval: 0.95-3.41; p = 0.073). Subgroup analyses of overall survival showed higher median survival ratios with vitamin C doses <1 g/kg (vs. ≥1 g/kg), in non-Chinese regions (vs. Chinese regions), with non-chemotherapy combinations (vs. chemotherapy combinations), and in cohort studies (vs. randomized controlled trials).

Conclusions: The administration of intravenous vitamin C to adults with malignant neoplasm was associated with a longer median overall survival compared to no vitamin C administration. The current evidence indicates a moderate degree of certainty for considering intravenous vitamin C as a standard of care in managing malignant neoplasms. The PROSPERO Registration: CRD42024600634, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024600634.

Keywords: ascorbic acid; malignant neoplasms; meta-analysis; survival; vitamin C.