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<p>High-dose vitamin C (HDVC) has emerged as a potential adjunct for cancer treatment because of its selective toxicity against malignant cells. When administered at pharmacological concentrations, it typically operates as a pro-oxidant, generating hydrogen peroxide, which predominantly targets cancer cells with weakened antioxidant defenses. The anticancer mechanisms of HDVC extend beyond oxidative stress and include: (1) disruption of glycolytic metabolism in tumors that exhibit the Warburg effect, (2) epigenetic modulation via TET enzyme activation, (3) degradation of hypoxia-inducible factors, and (4) boosting of immune surveillance. Preclinical studies have demonstrated that HDVC enhances the effectiveness of conventional therapies such as chemotherapy and radiotherapy by intensifying DNA damage and overcoming treatment resistance. Results from clinical trials in pancreatic, colorectal, and hematologic malignancies showed improved tolerability of standard regimens when combined with HDVC and reduced chemotherapy-associated toxicity in 40% of patients. However, the clinical outcomes remain inconsistent, with response rates ranging from 20 to 60%. Key challenges include rapid renal clearance, lack of standardized dosing protocols, and patient selection criteria. Emerging solutions include nanoparticle delivery systems and biomarker-guided approaches targeting tumors with specific vulnerabilities (e.g., KRAS mutations and TET2 deficiencies).This review aims to provide a comprehensive analysis of the mechanistic details of this versatile molecule at pharmacological doses as an adjunct to cancer treatment, preclinical and clinical evidence on HDVC in cancer treatment, and identify key challenges limiting its clinical translation and futuristic measures to fully exploit this molecule for its therapeutic efficacy. Although not as a standalone therapy, HDVC’s safety profile and multimodal operational mechanisms support its integration into personalized treatment paradigms. Future research should focus on optimizing administration protocols, verifying predictive biomarkers, and developing novel combinatorial approaches to fully exploit therapeutic capabilities.</p>

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Therapeutic Potential of High Dose Vitamin C in Cancer: Mechanisms, Clinical Evidence and Future Directions

  • 期刊论文

  • 发表日期：

    2025年8月13日

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  • Ragini D. Singh,
  • Deepak N. Parchwani,
  • Gaurav Sharma,
  • Praveen Sharma

摘要

High-dose vitamin C (HDVC) has emerged as a potential adjunct for cancer treatment because of its selective toxicity against malignant cells. When administered at pharmacological concentrations, it typically operates as a pro-oxidant, generating hydrogen peroxide, which predominantly targets cancer cells with weakened antioxidant defenses. The anticancer mechanisms of HDVC extend beyond oxidative stress and include: (1) disruption of glycolytic metabolism in tumors that exhibit the Warburg effect, (2) epigenetic modulation via TET enzyme activation, (3) degradation of hypoxia-inducible factors, and (4) boosting of immune surveillance. Preclinical studies have demonstrated that HDVC enhances the effectiveness of conventional therapies such as chemotherapy and radiotherapy by intensifying DNA damage and overcoming treatment resistance. Results from clinical trials in pancreatic, colorectal, and hematologic malignancies showed improved tolerability of standard regimens when combined with HDVC and reduced chemotherapy-associated toxicity in 40% of patients. However, the clinical outcomes remain inconsistent, with response rates ranging from 20 to 60%. Key challenges include rapid renal clearance, lack of standardized dosing protocols, and patient selection criteria. Emerging solutions include nanoparticle delivery systems and biomarker-guided approaches targeting tumors with specific vulnerabilities (e.g., KRAS mutations and TET2 deficiencies).This review aims to provide a comprehensive analysis of the mechanistic details of this versatile molecule at pharmacological doses as an adjunct to cancer treatment, preclinical and clinical evidence on HDVC in cancer treatment, and identify key challenges limiting its clinical translation and futuristic measures to fully exploit this molecule for its therapeutic efficacy. Although not as a standalone therapy, HDVC’s safety profile and multimodal operational mechanisms support its integration into personalized treatment paradigms. Future research should focus on optimizing administration protocols, verifying predictive biomarkers, and developing novel combinatorial approaches to fully exploit therapeutic capabilities.