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Intravenous Vitamin C

Vitamin C or Ascorbic Acid (AA) was first implicated as an anti-cancer agent through the research of nobel Prize Winner Dr. Linus Pauling PhD and Dr. Ewan Cameron MD. Their first clinical trial began in 1971 and the results of this and other research was published in the book “Cancer and Vitamin C” in 1979. In their clinical trial they found a four-fold increase in survival time by those individuals treated with 10,000 mg of AA intravenously. A later trial done by the Mayo clinic could not repeat these findings leading to a dismissal of AA’s potential role in oncology. Dr. Pauling’s subsequent work in this field led to him being widely criticized as a “quack”. Due to his ongoing research and years of anecdotal evidence from naturopathic and medical doctors alike there is a renewed interest and research into high doses of AA.

High dose intravenous AA is gaining acceptance around the world as an additive treatment in cancer therapy. New research from the National Institutes of Health in the United States has determined several mechanisms of actions leading to its cancer inhibiting effects. Intravenous treatments with vitamin C can be used to enhance the effectiveness and reduce side effects of conventional treatments while also acting as a cancer inhibitory agent.

Oral AA is absorbed through the intestinal lumen in an energy and dose dependant process. However, AA rapidly peaks so that at doses over 2g orally, less than 20% is actually absorbed. The AA not absorbed will result in attracting water into the intestinal tract, causing gastrointestinal discomfort and diarrhea.

Recent research has shown that high doses of AA have significant cytotoxic effects. These doses can only be achieved in humans by high dose intravenous AA administration where absorption is not a factor. 

The mechanism of action of high dose AA in cancer are various. AA is an important extracellular anti-oxidant and plays a role in a host of biochemical reactions in the body. AA has been validated as supportive therapy in case studies, preclinical trials and cancer cell research. The results of these studies show that AA acts in the following ways:

1) Selective Cytotoxicity (cancer cell killing) Effect – vitamin C in high doses leads to the production of large amounts of hydrogen peroxide in the connective tissue of the body. Hydrogen peroxide is an important oxidative molecule involved in many immune reactions in the body. In healthy cells the hydrogen peroxide is absorbed and then quenched with intra-cellular anti-oxidants but in cancer cells they often lack sufficient levels of anti-oxidants so hydrogen peroxide will build up. As levels of hydrogen peroxide rise in cancer cells they eventually go through apoptosis (programmed cell death).

2) Inhibition of Tumor Growth and Metastasis – most tumors require the activity of various enzymes in order to invade and metastasize. Ascorbic Acid inhibits the activity of these enzymes and promotes the production of collagen which may play a role in stabilizing the tumor and preventing local tissue invasion.

3) Chemosensitization – Ascorbic Acid has been tested in tissue cultures and animal models in combination with many different chemotherapeutics to evaluate a combined effect on tumors. Most well designed studies have shown a generally positive enhancement of chemotherapeutic success in studies where chemotherapy is combined with AA. There are only a few select studies that show a negative interaction and we avoid concomitant therapy in those cases.

 There have been clinical trials evaluating the use of vitamin C in combination with conventional treatments in patients with pancreatic cancer, ovarian cancer, and breast cancer.  These studies are small, but have shown that high dose vitamin c is well tolerated in cancer patients undergoing certain conventional treatments.   It also showed that vitamin C may reduce side effects of conventional treatments, improve patient quality of life and potentially positively impact treatment response.

References:

  1. Chen, Q., Espey, M. G., Krishna, M. C., Mitchell, J. B., Corpe, C. P., Buettner, G. R., … Levine, M. (2005). 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, 102(38), 13604–9. doi:10.1073/pnas.0506390102
  2. Pathi, S. S., Lei, P., Sreevalsan, S., Chadalapaka, G., Jutooru, I., & Safe, S. (2011). Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutrition and Cancer, 63(7), 1133–42. doi:10.1080/01635581.2011.605984
  3. Chen, Q., Espey, M. G., Sun, A. Y., Lee, J.-H., Krishna, M. C., Shacter, E., … Levine, M. (2007). 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, 104(21), 8749–54. doi:10.1073/pnas.0702854104
  4. Chen, Q., Espey, M. G., Sun, A. Y., Pooput, C., Kirk, K. L., Krishna, M. C., … Levine, M. (2008). 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, 105(32), 11105–9. doi:10.1073/pnas.0804226105
  5. Hoffer, L. J., Levine, M., Assouline, S., Melnychuk, D., Padayatty, S. J., Rosadiuk, K., … Miller, W. H. (2008). 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, 19(11), 1969–74. doi:10.1093/annonc/mdn377
  6. Monti, D. a, Mitchell, E., Bazzan, A. J., Littman, S., Zabrecky, G., Yeo, C. J., … Levine, M. (2012). Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PloS One, 7(1), e29794. doi:10.1371/journal.pone.0029794
  7. Welsh, J. L., Wagner, B. a, Van’t Erve, T. J., Zehr, P. S., Berg, D. J., Halfdanarson, T. R., … Cullen, J. J. (2013). Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemotherapy and Pharmacology, 71(3), 765–75. doi:10.1007/s00280-013-2070-8
  8. Vollbracht, C., Schneider, B., Leendert, V., Weiss, G., Auerbach, L., & Beuth, J. (2011). 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 (Athens, Greece), 25(6), 983–990. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22021693
  9. Ma, Y., Chapman, J., Levine, M., Polireddy, K., Drisko, J., & Chen, Q. (2014). High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Science Translational Medicine, 6(222), 222ra18. doi:10.1126/scitranslmed.3007154