The role of high-dose vitamin c in management of hematological malignancies: Asystematic review and meta-analysis

Abstract Introduction: Multiple studies have demonstrated the role of Vitamin C in normal hematopoiesis; however, its involvement in cancer has long been a topic of debate. It has been proposed that, through its antioxidant properties, gene transcription, and cell-signaling pathways, vitamin C may inhibit tumor growth and/or reduce the cytotoxic effects of chemotherapy in hematological malignancies. We aim to investigate the outcomes of high-dose ascorbic acid in hematological malignancies. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted on PubMed, Cochrane, Clinicaltrials.gov, Embase, and Google Scholar databases from inception until January 2025 using MeSH terms and keywords related to “malignancy”, " cancer" and "vitamin C”, Out of 796 search results, 19 studies were included where Vitamin C was used as adjunct to chemotherapy. The inter-study variance was calculated using the DerSimonian-Laird estimator. Proportions, along with a 95% confidence Interval (CI), were extracted to compute a pooled analysis using the ‘MetaSurvival’ package in the R programming language (version 4.16-2). Results: A total of 19 studies, involving 695 patients, were included in this meta-analysis and systematic review. The median age was 60.92 years, and 49.07% (n= 264/538) were males. Underlying conditions included multiple myeloma (35%, n = 240), followed by acute myeloid leukemia (33%, n = 232), and others (32%, n = 223). Vitamin C was most commonly administered intravenously (84% of studies), and the majority of studies (79%) were conducted in the United States. The pooled median overall survival (mOS) was observed to be 34.42 months (95% CI: not estimable). Survival rates at 6, 12, 18, and 24 months were 85.43%, 75.87%, 68.23%, and 59.18%, respectively. The pooled median progression-free survival (mPFS) was 14.09 months (95% CI: 9.54–20.50), with survival rates of 74.05%, 56.21%, 43.17%, and 34.75% at the corresponding time points. The estimated mean OS was 27.80 months (95% CI: 22.78 – 31.58), while the mean PFS was 19.63 months (95% CI: 15.97 – 22.53). The pooled rates of overall response (OR) and complete response (CR) were 41% (95% CI 0.24-0.57, I 2 = 94.03%, p < 0.001) and 20% (95% CI 0.005-0.36, I 2 = 97.99%, p < 0.001), respectively. Similarly, the pooled rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 27% (95% 0.12-0.42, I 2 =94.23%, p < 0.001), 24% (95% CI 0.12-0.35, I 2 =88.15%, p < 0.001), and 8% (95% CI 0.04-0.13, I 2 =33.40%, p < 0.001), respectively. Conclusion: High-dose vitamin C may offer favorable survival outcomes and moderate response rates in patients with hematologic malignancies. Progressive disease rates remained low across studies. The high heterogeneity among studies underscores the need for further randomized studies to consolidate the findings.