Vitamin C as an Adjunctive Therapy in Cancer Treatment: Exploring Therapeutic Potential: Systematic Review

Abstract

Specific Aims: This systematic review evaluates the anticancer effects of high-dose vitamin C, with a focus on its role in generating reactive oxygen species (ROS) and influencing tumor cell outcomes. The review investigates: (1) the efficacy of vitamin C in combination with chemotherapy on progression-free survival and quality of life; (2) its relationship with tumor cell size; (3) variations in response across cancer types and stages; and (4) the incidence of toxicity and adverse effects. Methods: This review followed PRISMA guidelines. A comprehensive search was conducted across PubMed, EMBASE, and Cochrane databases. Of 10,538 records screened, 21 studies published between 2007 and 2024 met inclusion criteria. Eligible studies included clinical trials, cohort studies, and retrospective analyses. Results: There are 21 studies that involved over 1,100 patients diagnosed with the following malignancies: hematologic, colorectal, pancreatic, lung, and breast. Most studies assessed high-dose intravenous vitamin C (IVC) in combination with chemotherapy, at doses ranging from 1 g/kg to 125 g. While survival benefits were inconsistent, several studies reported enhanced tumor responses, particularly in non-small cell lung and rectal cancers, and improved quality of life metrics such as reduced fatigue and nausea (p < 0.05). One rectal cancer study reported a 44.4% pathological complete response rate. Adverse events were minimal across studies. Conclusions: High-dose IVC is generally safe and may improve treatment tolerability and quality of life when used with chemotherapy. While survival outcomes remain unclear, the evidence supports further investigation in large-scale randomized trials to clarify its clinical utility.