@article{Zhao2026, 
author = {Hanzheng Zhao and Wentao Fu and Xiaobao Yang and Wenhui Zhang and Si Wu and Jingxin Ma and Tianzhen Zhang and Hongwei Yao and Zhongtao Zhang},
title = {High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges},
year = {2026},
journal = {Genes & Diseases},
volume = {13},
number = {2},
keywords = {Cancer therapy, Clinical trials, Ascorbic acid, Vitamin C, High-dose, Intravenous injection},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2025.101742},
doi = {10.1016/j.gendis.2025.101742},
abstract = {Vitamin C, also known as ascorbic acid, has sparked controversy since it first emerged as a potential anti-cancer agent. However, an increasing number of preclinical studies have demonstrated that high-dose vitamin C exhibits selective anti-tumor effects, including “pro-oxidative cytotoxicity”, “anti-cancer epigenetic regulation”, and “immune modulation”. Consequently, vitamin C has reemerged as a promising anti-cancer therapy in the form of high-dose administration. Advancements in pharmacokinetic research have facilitated the development of clinical trials. Early clinical studies across various cancer types have confirmed the safety of high-dose vitamin C administered via intravenous injection. Moreover, its use as an adjuvant therapy in combination with standard treatments, such as chemotherapy and radiotherapy, has shown promising therapeutic potential. However, there remains a lack of consensus regarding optimal dosage, administration methods, tumor specificity, and patient selection. These factors have contributed to the inconsistent outcomes observed in phase Ⅱ clinical trials and have hindered the widespread conduct of phase Ⅲ trials. Without robust clinical evidence, high-dose vitamin C, despite being a non-toxic and promising anti-cancer agent, risks being “shelved” once again. In this review, we provide a comprehensive overview of the anti-tumor mechanisms of high-dose vitamin C and a detailed analysis of preclinical and clinical studies investigating its role as an anti-cancer agent. Additionally, we explore emerging trends in high-dose vitamin C therapy for cancer treatment and offer recommendations for future research in this field.}
}