Vitamin C: Intravenous Use

Vitamin C can be given intravenously to achieve much higher blood levels and enhance its antioxidant and anti-inflammatory effects, with limited evidence of improved cancer survival when used with conventional treatments.

Safety and precautions

Overall, intravenous vitamin C has a good safety profile,¹ Simmons G, Sabo R et al. Safety and tolerability of intra-venous ascorbic acid in allogeneic hematopoietic cell transplant recipients: a matched historical control study. Blood. 2020;136 Supplement 1): 29–30; Kawada H, Sawanobori M et al. Phase I clinical trial of intravenous l-ascorbic acid following salvage chemotherapy for relapsed B-cell nonHodgkin’s lymphoma. Tokai Journal of Experimental and Clinical Medicine. 2014;39(3):111-5; Ou J, Zhu X et al. A phase I-II clinical trial to evaluate the safety, pharmacokinetics, and efficacy of high-dose intravenous ascorbic acid synergy with mEHT in Chinese patients with stage III–IV non-small cell lung cancer. Journal of Clinical Oncology. 2017;35(15); Stephenson CM, Levin RD, Spector T, Lis CG. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemotherapy and Pharmacology. 2013;72(1):139-46; Hoffer LJ, Levine M et al. Phase I clinical trial of IV ascorbic acid in advanced malignancy. Annals of Oncology. 2008;19(11):1969-74; Vollbracht C, Schneider B et al. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo. 2011;25(6):983-90; Mikirova NA, Jackson JA, Riordan NH. The effect of high dose IV vitamin C on plasma antioxidant capacity and level of oxidative stress in cancer patients and healthy subjects. Journal of Orthomolecular Medicine. 2007;22:153-160; Qazilbash MH, Saliba RM et al. Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial. Biology of Blood and Marrow Transplantation. 2008;14(12):1401-7; Abou-Jawde RM, Reed J et al. Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial. Medical Oncology. 2006;23(2):263-72; Allen BG, Bodeker KL et al. First-in-human phase I clinical trial of pharmacologic ascorbate combined with radiation and temozolomide for newly diagnosed glioblastoma. Clinical Cancer Research. 2019 Nov 15;25(22):6590-6597; Wang F, He MM et al. Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. BMC Cancer. 2019 May 16;19(1):460. with an adverse events rate of about 1%.²Klimant E, Wright H, Rubin D, Seely D, Markman M. Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach. Current Oncology. 2018;25(2):139-48. 

Interactions with cancer treatments

Oral supplemental and low-dose intravenous vitamin C have antioxidant effects. However, when vitamin C is given in high doses intravenously, “it becomes a pro-oxidant working similar to chemotherapy but offering greater protection to healthy cells.”³Winters N, Kelley JH. The Metabolic Approach to Cancer. White River Junction, Vermont: Chelsea Green Publishing. p. 155. Studies have found that intravenous vitamin C does not appear to increase toxicity or interfere with antitumor effects of gemcitabine/erlotinib therapy, paclitaxel and carboplatin,⁴Fritz H, Flower G et al. Intravenous vitamin C and cancer: a systematic review. Integrative Cancer Therapies. 2014;13(4):280-300; Monti DA, Mitchell E et al. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One. 2012;7(1):e29794. gemcitabine,⁵Polireddy K, Dong R et al. High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: mechanisms and a phase I/IIa study. Scientific Reports. 2017;7(1):17188. or myeloablative conditioning for allogeneic hematopoietic cell transplant.⁶Simmons G, Sabo R et al. Safety and tolerability of intra-venous ascorbic acid in allogeneic hematopoietic cell transplant recipients: a matched historical control study. Blood. 2020;136(SUPPL 1):29.

Side effects or adverse events

Intravenous high doses of vitamin C have been found to be safe and tolerable,⁷Kawada H, Sawanobori M et al. Phase I clinical trial of intravenous l-ascorbic acid following salvage chemotherapy for relapsed B-cell non-Hodgkin’s lymphoma. Tokai Journal of Experimental and Clinical Medicine. 2014 Sep 20;39(3):111-5; Chen P, Reed G et al. Pharmacokinetic evaluation of intravenous vitamin C: a classic pharmacokinetic study. Clinical Pharmacokinetics. 2022 Sep;61(9):1237-1249. although it can produce many short-term side effects:⁸Zasowska-Nowak A, Nowak PJ, Ciałkowska-Rysz A. High-dose vitamin C in advanced-stage cancer patients. Nutrients. 2021;13(3):735; Bazzan AJ, Zabrecky G, Wintering N, Newberg AB, Monti DA. Retrospective evaluation of clinical experience with intravenous ascorbic acid in patients with cancer. Integrative Cancer Therapies. 2018;17(3):912-20; Klimant E, Wright H, Rubin D, Seely D, Markman M. Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach. Current Oncology. 2018;25(2):139-48; Padayatty SJ, Sun AY et al. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One. 2010;5(7):e11414; Riordan HD, Casciari JJ et al. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. Puerto Rico Health Sciences Journal. 2005;24(4):269-76; Kiziltan HS, Bayir AG et al. Ascorbic-acid treatment for progressive bone metastases after radiotherapy: a pilot study. Alternative Therapies in Health and Medicine. 2014;20 Suppl 2:16-20; Hoffer LJ, Robitaille L et al. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS One. 2015;10(4):e0120228; Bánvölgyi A, Lőrincz K et al. Efficiency of long-term high-dose intravenous ascorbic acid therapy in locally advanced basal cell carcinoma—a pilot study. Postepy Dermatologii i Alergologii. 2020;37(4):548-58; Nielsen TK, Højgaard M, Andersen JT, et al. Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial. Translational Andrology and Urology. 2017;6(3):517-528; Aldoss I, Mark L et al. Adding ascorbic acid to arsenic trioxide produces limited benefit in patients with acute myeloid leukemia excluding acute promyelocytic leukemia. Annals of Hematology. 2014;93(11):1839-43; Bael TE, Peterson BL, Gollob JA. Phase II trial of arsenic trioxide and ascorbic acid with temozolomide in patients with metastatic melanoma with or without central nervous system metastases. Melanoma Research. 2008;18(2):147-51; Berenson JR, Yellin O et al. Bortezomib, ascorbic acid and melphalan (BAM) therapy for patients with newly diagnosed multiple myeloma: an effective and well-tolerated frontline regimen. European Journal of Haematology. 2009;82(6):433-439. 

More serious side effects can result from high-dose IV vitamin C:⁹Zasowska-Nowak A, Nowak PJ, Ciałkowska-Rysz A. High-dose vitamin C in advanced-stage cancer patients. Nutrients. 2021;13(3):735; Nielsen TK, Hojgaard M et al. Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial. Translational Andrology and Urology. 2017;6(3):517-28; Lo YH, Mok KL. High dose vitamin C induced methemoglobinemia and hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency. American Journal of Emergency Medicine. 2020;38(11):2488.e3-2488.e5; Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial. Translational Andrology and Urology. 2017;6(3):517-528; Sebastian S, Paul A, Joby J, Saijan S, Vilapurathu JK. Effect of high-dose intravenous ascorbic acid on cancer patients following ketogenic diet. Journal of Cancer Research and Therapeutics. 2021;17(6):1583-1586; Wang F, He MM et al. A randomized, open-label, multicenter, phase 3 study of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab in unresectable untreated metastatic colorectal cancer (VITALITY Study). Clinical Cancer Research. 2022;28(19):4232-4239; Aldoss I, Mark L et al. Adding ascorbic acid to arsenic trioxide produces limited benefit in patients with acute myeloid leukemia excluding acute promyelocytic leukemia. Annals of Hematology. 2014;93(11):1839-43; Bael TE, Peterson BL, Gollob JA. Phase II trial of arsenic trioxide and ascorbic acid with temozolomide in patients with metastatic melanoma with or without central nervous system metastases. Melanoma Research. 2008;18(2):147-51; Berenson JR, Matous J et al. A phase I/II study of arsenic trioxide/bortezomib/ascorbic acid combination therapy for the treatment of relapsed or refractory multiple myeloma. Clinical Cancer Research. 2007;13(6):1762-8; Berenson JR, Yellin O et al. Bortezomib, ascorbic acid and melphalan (BAM) therapy for patients with newly diagnosed multiple myeloma: an effective and well-tolerated frontline regimen. European Journal of Haematology. 2009;82(6):433-439; Mussa A, Mohd Idris RA et al. High-dose vitamin C for cancer therapy. Pharmaceuticals (Basel). 2022 Jun 3;15(6):711.

Both short-term, high-dose¹⁰Giffen MA, McLemore JL. Hyperoxalosis secondary to intravenous vitamin c administration as a non-allopathic treatment for cancer. Academic Forensic Pathology. 2019;9(1-2):118-26; Wissanji T, Dupuis ME, Royal V, Pichette V, Wang HT. Vitamin C-induced oxalate nephropathy in a septic patient. Critical Care Explorations. 2021;3(4):e0389; Wong K, Thomson C, Bailey RR, McDiarmid S, Gardner J. Acute oxalate nephropathy after a massive intravenous dose of vitamin C. Australian and New Zealand Journal of Medicine. 1994 Aug;24(4):410-1.. and long-term, low-dose intravenous vitamin C¹¹Canavese C, Petrarulo M et al. Long-term, low-dose, intravenous vitamin C leads to plasma calcium oxalate supersaturation in hemodialysis patients. American Journal of Kidney Diseases. 2005;45(3):540-9. can lead to plasma calcium oxalate supersaturation, which can lead to kidney stones and possibly even kidney failure. 

Interactions with other therapies

Treatment with intravenous vitamin C can lead to inaccurate readings from some strip-based glucose meters, which can lead to inappropriate treatment.¹²Katzman BM, Kelley BR et al. Unintended consequence of high-dose vitamin C therapy for an oncology patient: evaluation of ascorbic acid interference with three hospital-use glucose meters. Journal of Diabetes Science and Technology. 2021;15(4):897-900; Orija IB, Zahid SH. Pseudohyperglycemia secondary to high-dose intravenous vitamin C managed as diabetic ketoacidosis: an endocrinological catastrophe. AACE Clinical Case Reports. 2020;7(4):239-242; Lachance O, Goyer F et al. High-dose vitamin-C induced prolonged factitious hyperglycemia in a peritoneal dialysis patient: a case report. Journal of Medical Case Reports. 2021;15(1):297; He J, Zheng G, Qian X, et al. Effect of high-dose intravenous vitamin C on point-of-care blood glucose level in septic patients: a retrospective, single-center, observational case series. Current Medical Research and Opinion. 2021;37(4):555-565.

Moderate to severe toxic side effects were seen in a small study of intravenous arsenic trioxide and vitamin C (ascorbic acid) therapy among people with colorectal cancer who had failed to respond to previous standard chemotherapy.¹³Subbarayan PR, Lima M, Ardalan B. Arsenic trioxide/ascorbic acid therapy in patients with refractory metastatic colorectal carcinoma: a clinical experience. Acta Oncologica. 2007;46(4):557-61. Using vitamin C with arsenic trioxide requires caution.

Do not use (contraindications) or precautions

“Vitamin C in gram doses is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of developing intravascular hemolysis [destruction of red blood cells].”¹⁴Zasowska-Nowak A, Nowak PJ, Ciałkowska-Rysz A. High-dose vitamin C in advanced-stage cancer patients. Nutrients. 2021;13(3):735.

IV vitamin C is contraindicated when there is “uncontrolled serum glucose above 300 mg/dl (16.7 mmol/L).”¹⁵Parmar G, Kaczor T. Textbook of Naturopathic Oncology: A Desktop Guide of Integrative Cancer Care. 1st edition. Medicatrix Holdings Ltd. p 434.

Caution is advised among people with these conditions:¹⁶Klimant E, Wright H, Rubin D, Seely D, Markman M. Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach. Current Oncology. 2018;25(2):139-48; Parmar G, Kaczor T. Textbook of Naturopathic Oncology: A Desktop Guide of Integrative Cancer Care. 1st edition. Medicatrix Holdings Ltd; Riordan HD, Riordan NH et al. Intravenous vitamin C as a chemotherapy agent: a report on clinical cases. Puerto Rico Health Sciences Journal. 2004 Jun;23(2):115-8; McAllister CJ, Scowden EB, Dewberry FL, Richman A. Renal failure secondary to massive infusion of vitamin C. JAMA. 1984 Oct 5;252(13):1684; Rees DC, Kelsey H, Richards JD. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ. 1993 Mar 27;306(6881):841-2..

• End-stage renal failure predisposed to oxaluria; high oxalates in urine increases risk of kidney stones and other serious problems
• Hypercalcemia
• Metal storage disease, such as Wilson’s disease
• Glucose 6-phosphate (G6PD) deficiency

“Caution should be used during adjuvant therapy with curative intent because of limited data about treatment efficacy.”¹⁷Parmar G, Kaczor T. Textbook of Naturopathic Oncology: A Desktop Guide of Integrative Cancer Care. 1st edition. Medicatrix Holdings Ltd. p 434. 

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