New Study Identifies the Optimal Dose of Intravenous Vitamin C for Future Anticancer Clinical Trials

Study Results Show Promise and Indicate Further Investigation is Warranted

May 20, 2013, 11:26 ET from Cancer Treatment Centers of America

SCHAUMBURG, Ill., May 20, 2013 /PRNewswire-USNewswire/ -- The use of vitamin C to treat cancer patients first became popular in the 1970s as a result of the work of Nobel Laureate Linus Pauling.  However, studies conducted with orally dosed supplements did not demonstrate any clinical benefit in cancer patients, most likely due to the finding that the levels of orally-administered vitamin C delivered to a patient's blood stream were considerably lower than the levels needed to kill cancer cells in either test tube or animal models.  Recent studies in which vitamin C was administered intravenously (by IV) resulted in higher levels delivered to the patient's bloodstream suggest that vitamin C may, in fact, promote anti-cancer activity.  


A research team at Cancer Treatment Centers of America (CTCA), led by Robert Levin, MD, and Christopher M. Stephenson, DO, recently completed a phase I clinical trial to determine the pharmacokinetics, safety and tolerability of IV-administered, high dose vitamin C at levels that could potentially achieve the serum concentrations adequate for anti-cancer activity.  The results have been published in the May edition of Cancer Chemotherapy and Pharmacology.

As noted in the study, a previous hPase I IV vitamin C trial[1] stopped dose escalation at approximately 56 g/m2, when peak blood levels approached 26 mM, a level that inhibited tumor growth in mice[2].  However, 30-40 mM ascorbic acid in mouse blood only partially inhibited the rate of tumor growth and did not result in tumor regression.  Dr. Stephenson and his team were seeking to obtain even higher blood concentrations. Their 70-80 g/m2 dose delivered blood concentrations of 49 mM.  These levels appear to have a greater potential for producing anti-cancer activity in future studies.

"While this may be the baseline for treatment potential," said Dr. Stephenson, "it suggests we are on the right track for future studies and eventual use in fighting cancer."

The use of IV-administered vitamin C in combination with cytotoxic chemotherapy is further encouraged by a recent report showing that vitamin C potentiated the antitumor activity of gemcitabine against seven human and one murine pancreatic cancer cell lines[3].  This observation is of particular interest as two of the human lines were resistant to gemcitabine.  Synergistic antitumor activity occurred in tissue culture and in vivo studies with implanted tumors in mice.  In addition, a recently published phase I clinical trial evaluated IV-administered vitamin C combined with gemcitabine and erlotinib in nine patients with stage IV metastatic pancreatic cancer.  Pharmacologic levels of vitamin C were potentially achieved in all participants and tumor volumes decreased in eight out of nine patients[4]. 

The findings of the CTCA study, coupled with the emerging evidence from the available literature, suggest that the combination of IV-administered vitamin C with gemcitabine to treat pancreatic cancer is therapeutic approach that warrants further evaluation.  The CTCA research team is planning to conduct a phase 2 study using the higher dose of 70-80 g/m2 to achieve more adequate and longer lasting blood concentrations of vitamin C to better understand the possible outcome of this increased dosage.   

About Cancer Treatment Centers of America®
Cancer Treatment Centers of America, Inc. (CTCA) is a national network of hospitals focusing on complex and advanced stage cancer.  CTCA offers a comprehensive, fully integrative approach to cancer treatment and serves patients from all 50 states at facilities located in Atlanta, Chicago, Philadelphia, Phoenix and Tulsa.  Known for delivering the Mother Standard® of care and Patient Empowerment Medicine®, CTCA provides patients with information about cancer and their treatment options so they can control their treatment decisions. For more information about CTCA, go to

[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, 19:1969-1974.

[2] 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 U S A 2005, 20;102:13604-13609.

[3] 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, 50:1610-1619.

[4] 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:e29794.

SOURCE Cancer Treatment Centers of America