Written by Luc Geeraert and the CAM-Cancer Consortium.
Updated February 7, 2011

Intravenous high-dose vitamin C

Abstract and key points

  • Vitamin C (L-ascorbate or L-ascorbic acid) has been used in the treatment of cancer patients.
  • Intravenous administration of vitamin C is used to attain pharmacologic concentrations.
  • Anti-cancer activity of high intravenous doses of vitamin C has not been confirmed in clinical trials.
  • There is limited evidence indicating that high-dose intravenous vitamin C might improve the quality of life of patients with advanced cancers.
  • Although high intravenous doses of vitamin C are safe, causing only minor side effects, they may reduce the therapeutic response to conventional anti-cancer therapy. Moreover, high-dose intravenous vitamin C is contraindicated in people with renal disease or glucose 6-phosphate dehydrogenase deficiency.

Physiological concentrations of vitamin C (L-ascorbate or L-ascorbic acid) in the body are controlled through intestinal absorption, tissue accumulation, and renal reabsorption and excretion. Therefore, intravenous administration is used to achieve pharmacologic doses.

In the context of cancer, high-dose intravenous vitamin C (> 0.5 g per kg body weight) is claimed to have several effects: a) cytotoxicity for cancer cells, but not for normal tissue, b) improved quality of life for cancer patients, c) protection of normal tissues from toxicity caused by chemotherapy, and d) reinforcement of the action of radiation and some types of chemotherapy.

To date, no randomized controlled clinical trial with high-dose intravenous vitamin C has been published. A limited number of Phase I clinical trials confirm the non-toxic character of the treatment, and give some indications that the treatment may improve quality of life, but do not suggest distinct anti-cancer effects. Several case reports argue for a positive effect on survival time, even reporting cancer remission, and improved quality of life.

High-dose vitamin C is essentially non-toxic. Reported side-effects are minor if patients are adequately screened for renal disease and glucose 6-phosphate dehydrogenase deficiency, and when doses are gradually increased with careful monitoring of the patient. Vitamin C might reduce the therapeutic response to conventional anti-cancer therapy.

Citation

Luc Geeraert, CAM-Cancer Consortium. Intravenous high-dose vitamin C [online document]. http://www.cam-cancer.org/CAM-Summaries/Dietary-approaches/Intravenous-high-dose-vitamin-C. February 7, 2011.

Document history

Summary first published in February 2011, authored by Luc Geeraert.

References

  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. 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.
  3. Allwood MC, Kearney MC. Compatibility and stability of additives in parenteral nutrition admixtures. Nutrition. 1998 September;14(9):697-706.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Cameron E, Pauling L, Leibovitz B. Ascorbic acid and cancer: a review. Cancer Research. 1979 March;39(3):663-681.
  9. 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 begin_of_the_skype_highlighting 3685-3689 end_of_the_skype_highlighting begin_of_the_skype_highlighting 3685-3689 end_of_the_skype_highlighting.
  10. 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.
  11. 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.
  12. 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.
  13. Wittes RE. Vitamin C and cancer. New Engl. J. Med. 1985 January;312(3):178-179.
  14. Golde DW. Vitamin C in cancer. Integr Cancer Ther. 2003 June;2(2):158-159.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. González MJ, Miranda-Massari JR, Mora EM, Guzmán A, Riordan NH, Riordan HD, Casciari JJ, Jackson JA, Román-Franco A. Orthomolecular oncology review: ascorbic acid and cancer 25 years later. Integr. Cancer. Ther. 2005 March; 4(1):32-44.
  24. Carr A, Frei B. Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J. 1999;13:1007-1024.
  25. 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.
  26. Frei B, Lawson S. Vitamin C and cancer revisited. Proc. Natl. Acad. Sci. USA. 2008 August;105(32):11037-11038.
  27. 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.
  28. 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.
  29. 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.
  30. Oberley TD, Oberley LW. Antioxidant enzyme levels in cancer. Histol. Histopathol. 1997 April;12(2):525-535.
  31. Takemura Y, Satoh M, Satoh K, Hamada H, Sekido Y, Kubota S. High dose of ascorbic acid induces cell death in mesothelioma cells. Biochem. Biophys. Res. Commun. 2010 April;394(2):249-253.
  32. Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang SH, Taghiyev AF, Du C, Knudson CM, Cullen JJ. Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin. Cancer Res. 2010 January;16(2):509-520.
  33. 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):269-76.
  34. 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.
  35. 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.
  36. 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.
  37. 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.
  38. Riordan N, Jackson J, Riordan HD. Intravenous Vitamin C in A Terminal Cancer Patient. J. Orthomol. Med. 1996;11:80-82.
  39. 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.
  40. Riordan NH, Riordan HD, Casciari, JJ. Clinical and Experimental Experiences with Intravenous Vitamin C. J. Orthomolec. Med. 2000;15(4):201-213.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. McAllister CJ, Scowden EB, Dewberry FL, Richman A. Renal failure secondary to massive infusion of vitamin C. JAMA. 1984 October;252(13):1684.
  47. 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.
  48. 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.
  49. 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.
  50. Campbell A, Jack T. Acute reactions to mega ascorbic acid therapy in malignant disease. Scott. Med. J. 1979 April;24(2):151-153.
  51. Verrax J, Calderon PB. The controversial place of vitamin C in cancer treatment. Biochem. Pharmacol. 2008 December;76(12):1644-1652.
  52. Lamson DW, Brignall MS. Antioxidants and cancer therapy II: quick reference guide. Altern. Med. Rev. 2000 April;5(2):152-163.
  53. Prasad KN, Cole WC, Kumar B, Che Prasad K. Pros and cons of antioxidant use during radiation therapy. Cancer Treat. Rev. 2002 April;28(2):79-91.
  54. 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.
  55. 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.
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