Have any preclinical (laboratory or animal) studies been conducted using high-dose vitamin C?

Laboratory studies and animal studies have been done to find out if high-dose vitamin C may be useful in preventing or treating cancer.

 

Laboratory studies

 

Many laboratory studies have been done to find out how high-dose vitamin C may cause the death of cancer cells. The anticancer effect of vitamin C in different types of cancer cells involves a chemical reaction that makes hydrogen peroxide, which may kill cancer cells.

Laboratory studies have shown the following:

 

Treatment with high-dose vitamin C slowed the growth and spread of prostate, pancreatic, liver, colon, malignant mesothelioma, neuroblastoma, and other types of cancer cells.

Combining high-dose vitamin C with certain types of chemotherapy may be more effective than chemotherapy alone:

Ascorbic acid with arsenic trioxide may be more effective in ovarian cancercells.

Ascorbic acid with gemcitabine may be more effective in pancreatic cancercells.

Ascorbic acid with gemcitabine and epigallocatechin-3-gallate (EGCG) may be more effective in malignant mesothelioma cells.

Another laboratory study suggested that combining high-dose vitamin C with radiation therapy killed more glioblastoma multiforme cells than radiation therapy alone.

However, not all laboratory studies combining vitamin C with anticancer therapies have shown benefit. Combining dehydroascorbic acid, a particular form of vitamin C, with chemotherapy made it less effective in killing some kinds of cancer cells.

Animal studies

Studies of high-dose vitamin C have been done in animal models (animals given a disease either the same as or like a disease in humans).

 

Some of the studies showed the vitamin C helped kill more cancer cells:

 

High-dose vitamin C blocked tumor growth in animal models of pancreatic, liver, prostate, sarcoma, and ovarian cancers and malignant mesothelioma.

High-dose vitamin C combined with chemotherapy in a mouse model of pancreatic cancer showed that the combination treatment shrank tumors more than chemotherapy treatment alone.

Another study showed that vitamin C made a type of light therapy more effective when used to treat mice injected with breast cancer cells.

A study in a mouse model of ovarian cancer showed that combining intravenous high-dose vitamin C with the anticancer drugs carboplatin and paclitaxel made them more effective in treating ovarian cancer.

However, other animal studies have shown that vitamin C interferes with the anticancer action of certain drugs, including the following:

Mouse models of human lymphoma and multiple myeloma treated with combinations of vitamin C and chemotherapy or the drug bortezomib had more tumor growth than mice treated with bortezomib alone.

 

Have any clinical trials (research studies with people) of high-dose intravenous (IV) vitamin C been conducted?

Several studies of high-dose vitamin C in patients with cancer have been done in recent years, including the following:

 

Studies of vitamin C alone

 

Intravenous (IV) vitamin C was studied in patients with breast cancer who were treated with adjuvant chemotherapy and radiation therapy. The study found that patients who received IV vitamin C had better quality of life and fewer side effects than those who did not.

A study of IV vitamin C and high doses of vitamin C taken by mouth was done in patients with cancer that could not be cured. Vitamin C was shown to be a safe and effective therapy to improve quality of life in these patients, including physical, mental, and emotional functions, symptoms of fatigue, nausea and vomiting, pain, and appetite loss.

Vitamin C has been shown to be safe when given to healthy volunteers and cancer patients at doses up to 1.5 g/kg, while screening out patients with certain risk factors who should avoid vitamin C. Studies have also shown that Vitamin C levels in the blood are higher when taken by IV than when taken by mouth, and last for more than 4 hours.

Studies of vitamin C combined with other drugs

 

Studies of vitamin C combined with other drugs have shown mixed results:

 

In a small study of 14 patients with advanced pancreatic cancer, IV vitamin C was given along with chemotherapy and treatment with a targeted therapy. Patients had very few bad side effects from the vitamin C treatment. The nine patients who completed the treatment had stable disease as shown by imaging studies.

In another small study of 9 patients with advanced pancreatic cancer, patients were given chemotherapy in treatment cycles of once per week for 3 weeks along with IV vitamin C twice per week for 4 weeks. These patients had disease that did not progress for a period of months. The combined treatment was well tolerated and no serious side effects were reported.

In a 2014 study of 27 patients with advanced ovarian cancer, treatment with chemotherapy alone was compared to chemotherapy along with IV vitamin C. Patients who received IV vitamin C along with chemotherapy had fewer serious side effects from the chemotherapy.

Patients with acute myeloid leukemia, refractory metastatic colorectal cancer, or metastatic melanoma treated with IV vitamin C combined with other drugs had serious side effects and the disease got worse.

More studies of combining high-dose IV vitamin C with other drugs are in progress.

 

Have any side effects or risks been reported from high-dose vitamin C?

Intravenous high-dose ascorbic acid has caused very few side effects in clinical trials. However, high-dose vitamin C may be harmful in patients with certain risk factors.

In patients with a history of kidney disorders, kidney failure has been reported after ascorbic acid treatment. Patients with a tendency to develop kidney stones should not be treated with high-dose vitamin C.

Case reports have shown that patients with an inherited disorder called G-6-PD deficiency should not be given high doses of vitamin C, due to the risk of hemolysis (a condition in which red blood cells are destroyed).

Since vitamin C may make iron more easily absorbed and used by the body, high doses of the vitamin are not recommended for patients with hemochromatosis (a condition in which the body takes up and stores more iron than it needs).

 

Have any drug interactions been reported from combining high-dose vitamin C with anticancer drugs?

A drug interaction is a change in the way a drug acts in the body when taken with certain other drugs. High-dose vitamin C, when combined with some anticancer drugs, may cause them to be less effective. So far, these effects have been seen only in some laboratory and animal studies. No clinical trials have been done to further research these drug interactions in humans.

See Question 5 and Question 6 for more information on combining vitamin C with anticancer drugs.

Combining vitamin C with an anticancer drug called bortezomib has been studied in cell cultures and in animal models. Bortezomib is a targeted therapy that blocks several molecular pathways in a cell, causing cancer cells to die. Several studies showed that vitamin C given by mouth made bortezomib less effective, including in multiple myeloma cells. A study in mice transplanted with human prostate cancer cells, however, did not show that giving the mice different doses of vitamin C by mouth made bortezomib therapy less effective.

An oxidized form of vitamin C called dehydroascorbic acid has been studied in cell cultures and in animals with tumors. Several studies have found that high doses of dehydroascorbic acid can interfere with the anticancer effects of several chemotherapy drugs. Dehydroascorbic acid is found in only small amounts in dietary supplements and in fresh foods.

 

Is high-dose vitamin C approved by the U.S. Food and Drug Administration for use as a cancer treatment in the United States?

The U.S. Food and Drug Administration (FDA) has not approved the use of high-dose vitamin C as a treatment for cancer or any other medical condition

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Other Studies on IV Vitamin C

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1. Dosky CM., et al. Tumor cells have decreased ability to metabolize H2O2 : Implications for pharmacological ascorbate in cancer therapy. Redox Biology 10 (2016) 274-284. 

 

2. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Annals of internal medicine. 2004;140(7):533-7. Epub 2004/04/08. 2.

 

3. Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, et al. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(21):8749-54. Epub 2007/05/16. 3.

 

4. Verrax J, Calderon PB. Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free radical biology & medicine. 2009;47(1):32-40. Epub 2009/03/04.

 

5. Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(38):13604-9. Epub 2005/09/15.  

 

6. Duconge J, Miranda-Massari JR, Gonzalez MJ, Jackson JA, Warnock W, Riordan NH. Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate. Puerto Rico health sciences journal. 2008;27(1):7-19. Epub 2008/05/03.

 

7. Robitaille L, Mamer OA, Miller WH, Jr., Levine M, Assouline S, Melnychuk D, et al. Oxalic acid excretion after intravenous ascorbic acid administration. Metabolism: clinical and experimental. 2009;58(2):263-9. Epub 2009/01/22.

 

8. Lee YJ, Shacter E. Oxidative stress inhibits apoptosis in human lymphoma cells. The Journal of biological chemistry. 1999;274(28):19792-8. Epub 1999/07/03.

 

9. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(32):11105-9. Epub 2008/08/06.

 

10. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. Journal of the American College of Nutrition. 2003;22(1):18- 35. Epub 2003/02/06.

 

11. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, et al. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2008;19(11):1969-74. Epub 2008/06/12.

 

11. Yeom CH, Jung GC, Song KJ. Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration. Journal of Korean medical science. 2007;22(1):7

 

12. 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;25(6):983-90. Epub 2011/10/25.

 

13. Drisko JA, Chapman J, Hunter VJ. The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer. Journal of the American College of Nutrition. 2003;22(2):118-23. Epub 2003/04/04.

 

14. Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2006;174(7):937-42. Epub 2006/03/29. Page | 6

 

15. Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li B, et al. Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anti-cancer drugs. 2012;23(4):437-44. Epub 2011/12/30.

 

16. 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. British journal of cancer. 2001;84(11):1544-50. Epub 2001/06/01.

 

17. Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang SH, et al. Mechanisms of ascorbateinduced cytotoxicity in pancreatic cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2010;16(2):509-20. Epub 2010/01/14.

 

18. Sullivan G, Chen Q, Chen P, Chapman J, Levine M, Drisko J. Prospective Randomized Phase I/IIa Pilot Trial to Assess Safety and Benefit Administering High-Dose Intravenous Ascorbate in Combination with Chemotherapy in Newly Diagnosed Advanced Stage III or Stage IV Ovarian Cancer. 8th Annual Conference of the Society for Integrative Oncology; November 9-12, 2011; Cleveland, Ohio2011.

 

19. Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, 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. Epub 2012/01/25.

 

20. Chen P, Chalmers B, Drisko J, Chen Q. Pharmacologic Ascorbate Synergizes with Gemcitabine in Pre-Clinical Models of Pancreatic Cancer 8th Annual Conference of the Society for Integrative Oncology; November 9-12, 2011; Cleveland, Ohio2011.

 

21. Ma Y, Drisko J, Polireddy K, Chen Q. Synergistic Effects of Ascorbate with Carboplatin against Human Ovarian Cancer In Vitro and In Vivo 8th Annual Conference of the Society for Integrative Oncology; November 9-12, 2011; Cleveland, Ohio2011.

 

22. Abdel-Latif MM, Raouf AA, Sabra K, Kelleher D, Reynolds JV. Vitamin C enhances chemosensitization of esophageal cancer cells in vitro. Journal of chemotherapy. 2005;17(5):539-49. Epub 2005/12/06.

 

23. Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D, Bruckner HW. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer letters. 1996;103(2):183-9. Epub 1996/06/05.

 

24. Fromberg A, Gutsch D, Schulze D, Vollbracht C, Weiss G, Czubayko F, et al. Ascorbate exerts antiproliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs. Cancer chemotherapy and pharmacology. 2011;67(5):1157-66. Epub 2010/08/10.

 

25. Heaney ML, Gardner JR, Karasavvas N, Golde DW, Scheinberg DA, Smith EA, et al. Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer research. 2008;68(19):8031-8. Epub 2008/10/03.

 

26. Drisko J. Intravenous Vitamin C and Other IV Therapies in Cancer Care. Confronting Cancer as a Chronic Disease: Primary Care Takes a 360-degree May 20-23, 2010; San Diego, California2010.

 

27. Levine M, Espey MG, Chen Q. Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment. Free radical biology & medicine. 2009;47(1):27-9. Epub 2009/04/14.

 

28. Chen P, Stone J, Sullivan G, Drisko JA, Chen Q. Anti-cancer effect of pharmacologic ascorbate and its interaction with supplementary parenteral glutathione in preclinical cancer models. Free radical biology & medicine. 2011;51(3):681-7. Epub 2011/06/16.

 

29. Riordan HD, Casciari JJ, Gonzalez MJ, Riordan NH, Miranda-Massari JR, Taylor P, et al. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. Puerto Rico health sciences journal. 2005;24(4):269-76. Epub 2006/03/31.

 

30. 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;5(7):e11414. Epub 2010/07/16. Page | 7

 

31. Auer BL, Auer D, Rodgers AL. Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of vitamin C. European journal of clinical investigation. 1998;28(9):695-700. Epub 1998/10/10.

 

32. Mashour S, Turner JF, Jr., Merrell R. Acute renal failure, oxalosis, and vitamin C supplementation: a case report and review of the literature. Chest. 2000;118(2):561-3. Epub 2000/08/11.

 

33. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men. The Journal of urology. 1996;155(6):1847-51. Epub 1996/06/01.

 

34. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Intake of vitamins B6 and C and the risk of kidney stones in women. Journal of the American Society of Nephrology : JASN. 1999;10(4):840-5. Epub 1999/04/15.

 

35. Canavese C, Petrarulo M, Massarenti P, Berutti S, Fenoglio R, Pauletto D, et al. Long-term, lowdose, intravenous vitamin C leads to plasma calcium oxalate supersaturation in hemodialysis patients. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2005;45(3):540-9. Epub 2005/03/09.

 

36. McAllister CJ, Scowden EB, Dewberry FL, Richman A. Renal failure secondary to massive infusion of vitamin C. JAMA : the journal of the American Medical Association. 1984;252(13):1684. Epub 1984/10/05.

 

37. Lawton JM, Conway LT, Crosson JT, Smith CL, Abraham PA. Acute oxalate nephropathy after massive ascorbic acid administration. Archives of internal medicine. 1985;145(5):950-1. Epub 1985/05/01.

 

38. 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. Journal of Orthomolecular Medicine. 1998;13:72-3.

 

39. Campbell GD, Jr., Steinberg MH, Bower JD. Letter: Ascorbic acid-induced hemolysis in G-6-PD deficiency. Annals of internal medicine. 1975;82(6):810. Epub 1975/06/11.

 

40. Rees DC, Kelsey H, Richards JD. Acute haemolysis induced by high dose ascorbic acid in glucose- 6-phosphate dehydrogenase deficiency. Bmj. 1993;306(6881):841-2. Epub 1993/03/27.

 

41. Barton JC, McDonnell SM, Adams PC, Brissot P, Powell LW, Edwards CQ, et al. Management of hemochromatosis. Hemochromatosis Management Working Group. Annals of internal medicine. 1998;129(11):932-9. Epub 1998/12/29.

 

42. Shahrbanoo K, Taziki O. Effect of intravenous ascorbic acid in hemodialysis patients with anemia and hyperferritinemia. Saudi journal of kidney diseases and transplantation : an official publication of

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