Intravenous Vitamin C and Cancer

Vitamin C

Vitamin C has long been known for its effects on immune stimulation and function. Because of vitamin C’s role in maintaining normal immune function, many people use it for treating and preventing infectious conditions such as the common cold. Activity of several major immune cells and the messengers they produce seem to be increased by vitamin C.  An additional viewpoint is that vitamin C serves as an antioxidant and increased intake from either foods or dietary supplements may promote good health.

Cancer chemoprevention studies i.e., studies that have looked at the use of chemical agents, drugs, or food supplements to prevent the development of cancer,  have used this antioxidant rationale to examine any association between decreased tumor incidence and Vitamin C ingestion. Unfortunately, these studies have not revealed tumor reduction with use of ORAL vitamin C. In contrast to this line of investigation, there is also the hypothesis that high doses of intravenous Vitamin C may create a pro-oxidant or “cell-killing” state within tumors and possibly improve quality of life.

Evolving research speaks to this hypothesis and the use of vitamin C, intravenously, as a cancer fighter. So far, high dose vitamin C has been tested in phase I clinical trials in patients with advanced cancer and was found to be safe and well tolerated. If given at high enough doses Vitamin C is capable of turning into hydrogen peroxide within cancer cells causing these cells to die and thereby promoting tumor regression and improving quality of life.

Research continues to elucidate the mechanism behind pharmacologic concentrations of ascorbic acid and its cytotoxic effects.  It has been found that administration of high dose ascorbic acid results in the formation of the ascorbate radical and H2O2 in the extracellular fluid of the tissue parenchyma (spaces around the cells). This production of H2O2 has the ability to degrade DNA integrity, disrupt glucose metabolism and compromise cell membranes in susceptible cells (cancer cells.) Studies support the idea that this production of hydrogen peroxide leads to oxidative stress and subsequent necrotic death of cancer cells and spares healthy cells.

Additional benefits of IV Vitamin C include the promotion of healthy mitochondria function, stimulation of the immune system to produce interferon,  increase NK cell numbers, and an increase in phagocytosis (the destruction and ingestion of cancer cells my the immune system) with enhanced migration and killing function. Vitamin C also reduces oxidative damage to the p53 (apoptosis-regulating) gene due to chemo and radiation. This helps prevent the DNA damage and mutation that would otherwise render cancer cell apoptosis and death nonfunctional.

There are now multiple studies underway showing tumor reduction and improved survival with high dose ascorbic acid using pharmacologic doses (intravenous administration.)

Why Intravenous?

Vitamin C is well absorbed by tablet or capsule at low doses, but the absorption of vitamin C decreases as the dose increases. Approximately 87% of a 30 mg oral dose is absorbed, 80% of a 100 mg dose is absorbed, 63 % of a 500 mg dose is absorbed, and less than 50% of a 1250 mg does is absorbed. Most of what is absorbed is excreted in the urine. Decreased absorption with increasing dose and increased excretion in the urine limits the ability of the blood plasma to become high in Vitamin C.

Research in this field has shown that high blood plasma levels of vitamin C allow the nutrient to be carried to the area where tumors exist in the body. When given intravenously, it is possible to elevate blood plasma levels of antioxidant Vitamin C over longer periods of time which may fight cancer and produce health benefits.

It is important to note that normal levels of Vitamin C are important. These levels function to block free radical generation and maintain the oxidation reduction reaction intracellularly; i.e., its principle action is as an anti-oxidant.  However, to act as a pro-oxidant, cancer fighter, intravenous administration is imperative.

Studies:

• 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.
• Chen et. al. 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):8749-875
• Chen Q, et al. Pharmacologic doses of ascorbate act as a prooxidant and decreased growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci USA. 2008;105:11105–11109.
• Drisko JA, Chapman J, Hunter VJ. The use of antioxidant with first-line chemotherapy in two cases of ovarian cancer. J Am Coll Nutr. 2003 Apr;22(2):118-23.
• Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang S, Taghiyev AF, Du C, Knudson CM, Cullen JJ; Mechanisms of Ascorbate-induced Cytotoxicity in Pancreatic Cancer; Clin Cancer Res; 2010; 16:509-520.
• 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. P R Health Sci J 2008, 27:7-19.
• Duconge J, Miranda Massari JR, Gonzalez MJ, Riordan NH; Schedule-dependence in Cancer Therapy: What is the true scenario for Viamin C? Journal of Orthomolecular Medicine. 2007. 22(1):21-26.
• Espey MG, Chen P, Chalmers B, Drisko J, Sun AY, Levine M, Chen Q; Pharmacologic ascorbate synergizes with gemcitibine in preclinical models of pancreatic cancer; Free Radic Biol Med. 2011 Jun 1;50(11):1610-9. Epub 2011
• Hickey Ds, Roberts HJ, Cathcart RF; Dynamic Flow: A Model for Ascorbate. J of Orthomolecular Medicine; 2005; 20(4):237-244.
• 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 Nov;19(11):1969-74.
• Intravenous Vitamin C in Combination with Standard Chemotherapy for Pancreatic Cancer. [http://www.clinicaltrials.gov/ct2/show/NCT00954525].
• Jackson JA, Riordan HD, Hunninghake RE, Riordan NH.  High dose intravenous vitamin C and long time survival of a patient with cancer of the head of the pancreas. J Ortho Med. 1995; 10:87-88.
• Juan Du, Sean M. Martin, Mark Levine, Brett A. Wagner, Garry R. Buettner, Sih-han Wang, agshin F. Taghiyev, Changbin Du, Charles M. Knudson, and Joseph J. Cullen. Mechanisms of Ascorbate-induced cytoxicity in Pancreatic Cancer. Clin Cancer Res: 16(2) January 15 2010.
• Kassouf W, Highshaw R, Nelkin GM, Dinney CP, Kama AM. Vitamins C and K3 sensitize human urothelial tumors to gemcitabine. J Urol. 2006. Oct;176(4 Pt 1):1642-7.
• Mayland CR, Bennett MI, Allan K. Vitamin C deficiency in cancer patients. Palliative Medicine 2005; 19: 17-20
• 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 Vol. 22. No. 3, 2007.
• Murata A, Morishige F, Yamaguchi H; Prolongation of survival times of terminal cancer patients by administration of large doses of ascorbate; Int J Vitam Nutr Res Suppl; 1982; 23:103-113.
• 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; 140:533-537.
• Pilot Trial of Intravenous Vitamin C in Refractory Non-Hodgkin Lymphoma (NHL). [http://www.clinicaltrials.gov/ct2/show/NCT00626444].
• Qi Chen, Michael Graham Epsey, Andrew Y. Sun, Chaya Pooput, Kenneth L. Kirk, Murali C. Krishna, Deena Beneda Khosh, Jeanne Drisko, and Mark Levine. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice.
• Riordan HD, Casciari JJ, Gonzalez MJ, Riordan NH, Miranda-Massari JR, Taylor P, Jackson JA. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. PR Health Sci J. 2005;24:269–276
• Schorah et. al. Depletion of Plasma Antioxidants in Surgical Intensive Care Room Patients Requiring Parenteral Feeding: Effects of Parenteral nutrition with or without Alanyl-Glutamine dipeptide supplementation. Am J Clin Nutr.1996.(63)5:760-765.
• Sebastian J. Padayatty, Hugh D. Riordan, Stephen M. Hewitt, Arie Katz, L. John Hoffer, Mark Levine. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ. 2006 March 28; 174(7): 937–942.
• Study of High Dose Intravenous (IV) Ascorbic Acid in measurable Solid Tumor disease. [http://www.clinicaltrials.gov/ct2/show/NCT01125449].
• Study of High-Dose Intravenous (IV) Vitamin C Treatment in Patients With Solid Tumors. [http://www.clinicaltrials.gov/ct2/show/NCT00441207].
• Trial of Chemotherapy Plus Intravenous Vitamin C in Patients With Advanced Caner for Whom Chemotherapy Alone is Only Marginally Effective. [http://www.clinicaltrials.gov/ct2/show/NCT01050621].
• Tsantes AE, Bonovas S, Travlou A, Sitaras NM. 2006. Redox imbalance, macrocytosis, and RBC homeostasis. Antioxid Redox Signal. 8:1205-1216.
• Verrax J, Calderon PB. Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free Radic Biol Med. 2009 Jul 1;47(1):32-40.
• Vitamin C as an Anti-cancer Drug. [http://www.clinicaltrials.gov/ct2/show/NCT01080352].
• 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; 22:7-11.