Written by Luc Geeraert and the CAM-Cancer Consortium.
Updated July 9, 2014

Intravenous high-dose vitamin C

Does it work?

Recent findings on the mechanism of action and pharmacokinetics of high-dose intravenous vitamin C triggered a renewed interest in its application as an anti-cancer agent. Therefore, several Phase I clinical trials were initiated and the results of one controlled and six uncontrolled trials have been published. Also, eight case studies and five retrospective studies have been reported. Several clinical trials are underway.36

While the case series and retrospective studies gave some indications for efficacy, the published clinical trials did not indicate tumour response. Overall, evidence for the non-toxic character of intravenous high-dose vitamin C, limited evidence for improved quality of life, and some suggestion of synergism with certain conventional therapy was offered.

Study details can be found in Table 1.

Controlled clinical trials

Only one controlled clinical trial has been published. In this Phase I/IIa randomized controlled clinical trial, Ma et al. randomized 27 patients with newly diagnosed stage III/IV ovarian cancer to receive either conventional paclitaxel/carboplatin therapy alone (control group), or combined with intravenous vitamin C (treatment group).37 Addition of intravenous high-dose vitamin C was found to reduce toxicities associated with chemotherapy.

Retrospective studies

Cameron et al. performed three controlled retrospective studies comparing terminal cancer patients receiving vitamin C with historical control patients that had not received vitamin C, and found increased survival times in the vitamin-C-treated groups.11,12,50 The study designs were criticized as they were not randomized nor placebo controlled. Moreover, some patients were treated with oral vitamin C, the treatment period with intravenous vitamin C was only about 10 days, and the doses were rather low.

Vollbracht et al. evaluated intravenous vitamin C administration in the first postoperative year of women with breast cancer, in an epidemiological retrospective cohort study, and found that vitamin C resulted in a significant reduction of complaints induced by the disease and chemo- or radiotherapy. Vitamin C was well-tolerated and had no effect on tumour status after 6 or 12 months.51

Uncontrolled clinical trials

Intravenous vitamin C was well-tolerated in a pilot clinical study in 24 late-stage terminal cancer patients, and one patient had stabilized disease during the trial.38 Noteworthy, applied doses of vitamin C were low.Several aspects of health-related quality of life were improved after administration of intravenous high-dose vitamin C to 39 terminal cancer patients: i.e., significantly higher scores for physical, role, emotional, and cognitive function, and significantly lower scores for fatigue, nausea/vomiting, pain, and appetite loss.39

In a dose-finding Phase I and pharmacokinetics study in 24 patients with advanced cancer or hematologic malignancy refractory to standard therapy, high-dose intravenous vitamin C was found to be safe and free of important toxicity. Patients receiving 0.6 g or more of vitamin C per kg body weight maintained physical quality of life throughout the trial. No patient experienced an objective anti-cancer response.1

The combination of intravenous vitamin C with standard treatment of gemcitabine and erlotinib was tested in an open-label, dose-escalating Phase I trial in 14 patients with metastatic pancreatic cancer.40 Nine subjects completed the study of which seven patients experienced stable disease. No increased toxicity was revealed with the addition of vitamin C to gemcitabine and erlotinib.

In a Phase I dose-escalation trial in 17 patients with advanced solid tumours not responding to standard therapy, pharmacokinetics of high-dose intravenous vitamin C were determined.2 Vitamin C was generally well tolerated and no objective antitumour responses were observed. The authors recommend a dose of 70 to 80 g/m2 (i.e., around 2 g per kg body weight) for future studies.

In a Phase I clinical trial in nine patients with biopsy-proven stage IV pancreatic adenocarcinoma, the concurrent administration of high-dose intravenous vitamin C with gemcitabine was well-tolerated and a suggestion of improved efficacy by vitamin C addition was found.41

Analysis of a database from 45 patients with different cancers treated with high-dose intravenous vitamin C by Mikirova et al. taught that this treatment affected levels of C-reactive protein and pro-inflammation cytokines, supporting the hypothesis that inflammation in cancer patients may be reduced by high-dose intravenous vitamin C.52

Case series/studies

Several case reports on the treatment of advanced cancer patients with high-dose intravenous vitamin C have been published.42-49 Vitamin C infusions were either used as sole treatment or combined with conventional therapy. Overall, the results indicated lack of toxicity. Also, in several cases tumour regression or even complete remission was observed.

Noteworthy, for all the successful case reports, alternative explanations for cancer remission are possible, e.g. spontaneous remission or remission due to the therapy received before intravenous vitamin C was initiated. Moreover, a general weakness of case reports is that they omit the number of patients having received high-dose intravenous vitamin C without any effect.

Citation Luc Geeraert, CAM-Cancer Consortium. Intravenous high-dose vitamin C [online document]. http://ws.cam-cancer.org/The-Summaries/Other-CAM/Intravenous-high-dose-vitamin-C. July 9, 2014.


  1. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, Rousseau C, Robitaille L, Miller WH Jr. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann. Oncol. 2008 November;19(11):1969-74.
  2. 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 Chemother Pharmacol. 2013 Jul;72(1):139-146.
  3. Riordan HD, Hunninghake RB, Riordan NH, Jackson JJ, Meng X, Taylor P, Casciari JJ, González MJ, Miranda-Massari JR, Mora EM, Rosario N, Rivera A. Intravenous ascorbic acid: protocol for its application and use. P R Health Sci. J. 2003 September;22(3):287-90.
  4. Allwood MC, Kearney MC. Compatibility and stability of additives in parenteral nutrition admixtures. Nutrition. 1998 September;14(9):697-706.
  5. Dupertuis YM, Morch A, Fathi M, Sierro C, Genton L, Kyle UG, Pichard C. Physical characteristics of total parenteral nutrition bags significantly affect the stability of vitamins C and B1: a controlled prospective study. JPEN J. Parenter. Enteral. Nutr. 2002 September-October;26(5):310-316.
  6. Lavoie JC, Chessex P, Rouleau T, Migneault D, Comte B. Light-induced byproducts of vitamin C in multivitamin solutions. Clin. Chem. 2004 January;50(1):135-140.
  7. Cabanillas F. Vitamin C and cancer: what can we conclude - 1,609 patients and 33 years later? P R Health Sci. J. 2010 September;29(3):215-217.
  8. Szent-Györgyi, A. Observations on the function of peroxidase systems and the chemistry or the adrenal cortex: description of a new carbohydrate derivative. Biochem. J. 1928;22:1387-1409.
  9. Du J, Cullen JJ, Buettner GR. Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim. Biophys. Acta. 2012 Dec;1826(2):443-457.
  10. Cameron E, Pauling L, Leibovitz B. Ascorbic acid and cancer: a review. Cancer Research. 1979 March;39(3):663-681.
  11. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc. Natl. Acad. Sci. USA. 1976;73:3685-3689.
  12. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc. Natl. Acad. Sci. USA. 1978;75:4538-4542.
  13. Creagan ET, Moertel CG, O’Fallon JR, Schutt AJ, O’Connel MJ, Rubin J, Frytak S. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. New Engl. J. Med. 1979 September;301(13):687-690.
  14. Moertel CG, Fleming TR, Creagan ET, Rubin J, O’Connel MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. New Engl. J. Med. 1985 January;312(3):137-141.
  15. Wittes RE. Vitamin C and cancer. New Engl. J. Med. 1985 January;312(3):178-179.
  16. Golde DW. Vitamin C in cancer. Integr. Cancer Ther. 2003 June;2(2):158-159.
  17. Levine M, Espey MG, Chen Q. Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment. Free Rad. Biol. Med. 2009 July;47(1):27-29.
  18. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA. 1996 April;93:3704-3709.
  19. Levine M, Wang Y, Padayatti SJ, Morrow J. A new recommended dietary allowance of vitamin C for healthy young women. Proc. Natl. Acad. Sci. USA. 2001 August;98(17):9842-9846.
  20. Graumlich JF, Ludden TM, Conry-Cantilena C, Cantilena Jr LR, Wang Y, Levine M. Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharm. Res. 1997 September;14(9):1133-1139.
  21. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann. Intern. Med. 2004 April;140(7):533-537.
  22. Casciari JJ, Riordan NH, Schmidt TL, Meng XL, Jackson JA, Riordan HD. Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Br. J. Cancer. 2001 June;84(11):1544-50.
  23. Duconge J, Miranda-Massari JR, González MJ, Taylor PR, Riordan HD, Riordan NH, Casciari JJ, Alliston K. Vitamin C pharmacokinetics after continuous infusion in a patient with prostate cancer. Ann. Pharmacother. 2007 June;41(6):1082-1083.
  24. Padayatty SJ, Levine M. Reevaluation of ascorbate in cancer treatment: emerging evidence, open minds and serendipity. J. Am. Coll. Nutr. 2000 August;19(4):423-425.
  25. Carr A, Frei B. Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J. 1999;13:1007-1024.
  26. Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc. Natl. Acad. Sci. USA. 2005 September;102(38):13604-13609.
  27. Frei B, Lawson S. Vitamin C and cancer revisited. Proc. Natl. Acad. Sci. USA. 2008 August;105(32):11037-11038.
  28. Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, Choyke PL, Pooput C, Kirk KL, Buettner GR, Levine M. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc. Natl. Acad. Sci. USA. 2007 May;104(21):8749-8754.
  29. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc. Natl. Acad. Sci. USA. 2008 August;105(32):11105-11109.
  30. Verrax J, Calderon PB. Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free Radic. Biol. Med. 2009 July;47(1):32-40.
  31. Oberley TD, Oberley LW. Antioxidant enzyme levels in cancer. Histol. Histopathol. 1997 April;12(2):525-535.
  32. Pollard HB, Levine MA, Eidelman O, Pollard M. Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer. In Vivo. 2010 May-June;24(3):249-255.
  33. Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li B, Chen Q. Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anticancer Drugs. 2012 April;23(4):437-444.
  34. Mamede AC, Pires AS, Abrantes AM, Tavares SD, Gonçalves AC, Casalta-Lopes JE, Sarmento-Ribeiro AB, Maia JM, Botelho MF. Cytotoxicity of ascorbic acid in a human colorectal adenocarcinoma cell line (WiDr): in vitro and in vivo studies. Nutr Cancer. 2012;64(7):1049-57.
  35. Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, Levine M. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One. 2010 July 7;5(7):e11414.
  36. Wilson MK, Baguley BC, Wall C, Jameson MB, Findlay MP. Review of high-dose intravenous vitamin C as an anticancer agent. Asia Pac J Clin Oncol. 2014 Mar;10(1):22-37.
  37. Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014 Feb 5;6(222):222ra18.
  38. Riordan HD, Casciari JJ, González MJ, Riordan NH, Miranda-Massari JR, Taylor P, Jackson JA. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P R Health Sci. J. 2005;24(4):269-276.
  39. Yeom CH, Jung GC, Song KJ. Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration. J. Korean Med. Sci. 2007 February;22(1):7-11.
  40. Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, Pillai MV, Newberg AB, Deshmukh S, Levine M. 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.
  41. Welsh JL, Wagner BA, van't Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, Yee NS, Bodeker KL, Du J, Roberts LJ 2nd, Drisko J, Levine M, Buettner GR, Cullen JJ. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol. 2013 Mar;71(3):765-775.
  42. Cameron E, Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem. Biol. Interact. 1974;9:285-315.
  43. Riordan H, Jackson J, Schultz M. Case Study: High Dose intravenous Vitamin C in the Treatment of a Patient with Adrenocarcinoma of the Kidney. J. Orthomol. Med. 1990;5:5-7.
  44. Jackson JA, Riordan HD, Hunninghake RE, Riordan N. High dose intravenous vitamin C and long time survival of a patient with cancer of head of the pancreas. J. Orthomol. Med. 1995;10:87-88.
  45. Riordan N, Jackson J, Riordan HD. Intravenous vitamin C in a terminal cancer patient. J. Orthomol. Med. 1996;11:80-82.
  46. Riordan HD, Jackson JA, Riordan NH, Schultz M. High-dose intravenous vitamin C in the treatment of a patient with renal cell carcinoma of the kidney. J. Orthomol. Med. 1998;13:72-73.
  47. Riordan NH, Riordan HD, Casciari, JJ. Clinical and experimental experiences with intravenous vitamin C. J. Orthomolec. Med. 2000;15(4):201-213.
  48. Drisko JA, Chapman J, Hunter VJ. The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer. J. Am. Coll. Nutr. 2003 April;22(2):118-123.
  49. Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ. 2006 March;174(7):937-942.
  50. Cameron E, Campbell A. Innovation vs. quality control: an 'unpublishable' clinical trial of supplemental ascorbate in incurable cancer. Med. Hypotheses. 1991 November;36(3):185-189.
  51. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. 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 November-December;25(6):983-990.
  52. Mikirova N, Casciari J, Rogers A, Taylor P. Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J Transl Med. 2012 Sep 11;10:189.
  53. Campbell GD Jr, Steinberg MH, Bower JD. Letter: Ascorbic acid-induced hemolysis in G-6-PD deficiency. Ann. Intern. Med. 1975 June;82(6):810.
  54. Rees DC, Kelsey H, Richards JD. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ. 1993 March;306(6881):841-842.
  55. McAllister CJ, Scowden EB, Dewberry FL, Richman A. Renal failure secondary to massive infusion of vitamin C. JAMA. 1984 October;252(13):1684.
  56. Lawton JM, Conway LT, Crosson JT, Smith CL, Abraham PA. Acute oxalate nephropathy after massive ascorbic acid administration. Arch. Intern. Med. 1985 May;145(5):950-951.
  57. Wong K, Thomson C, Bailey RR, McDiarmid S, Gardner J. Acute oxalate nephropathy after a massive intravenous dose of vitamin C. Aust. N. Z. J. Med. 1994 August;24(4):410-411.
  58. Robitaille L, Mamer OA, Miller WH Jr, Levine M, Assouline S, Melnychuk D, Rousseau C, Hoffer LJ. Oxalic acid excretion after intravenous ascorbic acid administration. Metabolism. 2009 February;58(2):263-269.
  59. Campbell A, Jack T. Acute reactions to mega ascorbic acid therapy in malignant disease. Scott. Med. J. 1979 April;24(2):151-153.
  60. Espey MG, Chen P, Chalmers B, Drisko J, Sun AY, Levine M, Chen Q. Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer. Free Radic Biol Med. 2011 June 1;50(11):1610-1619.
  61. Verrax J, Calderon PB. The controversial place of vitamin C in cancer treatment. Biochem. Pharmacol. 2008 December;76(12):1644-1652.
  62. Lamson DW, Brignall MS. Antioxidants and cancer therapy II: quick reference guide. Altern. Med. Rev. 2000 April;5(2):152-163.
  63. Frömberg A, Gutsch D, Schulze D, Vollbracht C, Weiss G, Czubayko F, Aigner A. Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs. Cancer Chemother Pharmacol. 2011 May;67(5):1157-1166.
  64. Shinozaki K, Hosokawa Y, Hazawa M, Kashiwakura I, Okumura K, Kaku T, Nakayama E. Ascorbic acid enhances radiation-induced apoptosis in an HL60 human leukemia cell line. J Radiat Res. 2011;52(2):229-237.
  65. Herst PM, Broadley KW, Harper JL, McConnell MJ. Pharmacological concentrations of ascorbate radiosensitize glioblastoma multiforme primary cells by increasing oxidative DNA damage and inhibiting G2/M arrest. Free Radic. Biol. Med. 2012 Apr 15;52(8):1486-1493.
  66. Park JH, Davis KR, Lee G, Jung M, Jung Y, Park J, Yi SY, Lee MA, Lee S, Yeom CH, Kim J. Ascorbic acid alleviates toxicity of paclitaxel without interfering with the anticancer efficacy in mice. Nutr Res. 2012 Nov;32(11):873-83.
  67. Vuyyuri SB, Rinkinen J, Worden E, Shim H, Lee S, Davis KR. Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells. PLoS One. 2013 Jun 11;8(6):e67081.
  68. Wei Y, Song J, Chen Q, Xing D. Enhancement of photodynamic antitumour effect with pro-oxidant ascorbate. Lasers Surg Med. 2012 Jan;44(1):69-75.
  69. Heaney ML, Gardner JR, Karasavvas N, Golde DW, Scheinberg DA, Smith EA, O'Connor OA. Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res. 2008 October 1;68(19):8031-8038.
  70. Perrone G, Hideshima T, Ikeda H, Okawa Y, Calabrese E, Gorgun G, Santo L, Cirstea D, Raje N, Chauhan D, Baccarani M, Cavo M, Anderson KC. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia. 2009 September;23(9):1679-1686.