Intravenous vitamin C is an effective cancer therapy delivering independent cytotoxic effects to tumour cells, as well as enhancing cytotoxicity of several conventional chemotherapeutic drugs. While many medical professionals condemn the therapy, recent advances have shown a very large increase in the use of intravenous vitamin C among several leading oncology units across North America. The following review highlights the basis for intravenous route of administration, preclinical evidence of selective cytotoxicity to tumour cells while sparing non-cancerous cells, evidence of safety regarding combination antioxidant therapy and chemotherapy, as well as a selection of controlled human trials of intravenous vitamin C in cancer management.

Origins of Vitamin C in Cancer Therapy

The landmark study of Cameron and Pauling outlining success of vitamin C for cancer management in 100 patients relative to 1,000 disease matched controls (Cameron 1976) is often credited as the origins of investigation into vitamin C as a complementary cancer therapy. In their book, Cancer and Vitamin C, Cameron and Pauling outline the work of Dr. W.J. McCormick through the 1950’s, a Canadian Physician who formulated the hypothesis that cancer is a collagen disease, secondary to a deficiency of vitamin C (Cameron 1993). Dr. McCormick recognized that the generalized stromal changes of scurvy were consistent with the local stromal changes observed in the immediate vicinity of invading neoplastic cells. Dr. McCormick surmised that the nutrient (vitamin C) that is known to be capable of preventing such generalized changes in scurvy might have similar effects in cancer. Evidence that cancer patients are commonly depleted of ascorbate (vitamin C) supported this view.

Cameron and Pauling stated the following: “Most important of all, we are led to the conclusion that the administration of this harmless substance, ascorbic acid (vitamin C), might provide us with an effective means of permanently suppressing neoplastic cellular proliferation and invasiveness, in other words an effective means of controlling cancer. Ascorbic acid (vitamin C) in adequate doses might prove to be the ideal cytostatic agent.” (Cameron 1993).

Preclinical Evidence Relating to Vitamin C in Cancer Therapy

From a mean baseline of 70micromol/L, repeated oral dosing achieves plasma vitamin C concentrations of 220micromol/L. Intravenous administration of large dosages (18+g of vitamin C) can achieve plasma vitamin C concentrations of up to 14000micromol/L. In vitro models have demonstrated that concentrations of 1,000- 5,000micromol/L of vitamin C are selectively toxic to several cancer cell lines (Padayatty 2006).

Ten cancerous cell lines and four normal cell lines were exposed to varying concentrations of vitamin C in vitro. EC50 values (concentration of vitamin C required to reduce cell survival by 50%) were calculated for each cell line. Human lymphoma cells proved to be highly sensitive to vitamin C, with an EC50 value of 0.5micromol/L. Five additional cell lines demonstrated EC50 values of less than 4.0micromol/L, a concentration easily achieved through I.V. administration of vitamin C. 20micromol/L of vitamin C was incapable of significantly reducing survival in normal cell lines, highlighting that cytotoxic effects of vitamin C appear to be confined to cancerous cells (Chen 2005).

Guinea pigs bearing intradermal L-10 hepatocarcinoma tumors received oral or subcutaneous (SC) injections of vitamin C, with tumour mass and intra-tumour vitamin C concentrations determined at necropsy. Tumour burden reached nearly 50g in untreated animals. SC injections of ascorbate (500mg/kg/day) inhibited tumour growth by as much as 65%. “Tumor growth correlated inversely with intratumour ascorbate concentration, the latter exceeding 2mM in some cases. Ascorbate concentrations sufficient to kill tumour cells can be safely achieved in solid tumours in vivo, suggesting a possible role for high dose intravenous ascorbate in treating cancer.” (Casciari 2005).

At low concentrations in cell culture (less than 500micromol/L), vitamin C appears to inhibit intra- tumour generation of oxygen radical species. Endogenous catalase appears readily able to quench ascorbate-derived radical formation. The ascorbate-derived radical, however, inhibits catalase in a doseresponse manner. Once concentrations in cell culture reach 2,000micromol/L or greater, catalase appears to be incapable of preventing the formation of ascorbate radical (Nemoto 1997, Asano 1999, Sakagami 2000). Taken in context with the evidence presented above, it appears as though 2000 micromol/L is the lowest target plasma concentration of vitamin C, which would be desirable for use of vitamin C as a chemotherapeutic agent. Such a concentration is readily achieved through intravenous administration of vitamin C.

Intravenous Vitamin C in Cancer Therapy; A Synopsis

  • I.V. vitamin C increases quality of life.
  • I.V. vitamin C prolongs survival.
  • I.V. vitamin C works synergistically with conventional cancer therapies.
  • I.V. route of administration achieves plasma levels of vitamin C consistent with concentrations demonstrated in vitro to be cytotoxic to several cancer cell lines.
  • I.V. vitamin C inhibits hyaluronidase, an enzyme produced by cancer cells responsible for the breakdown of healthy tissue facilitating tumour progression and metastasis.
  • I.V. vitamin C increases intracellular hydrogen peroxide. Hydrogen peroxide is directly cytotoxic to tumour cells. At concentrations achieved through I.V. administration, vitamin C overwhelms the ability of tumour cells to suppress hydrogen peroxide production.
  • I.V. vitamin C corrects an ascorbate deficiency, often seen in cancer patients.
  • I.V. vitamin C helps prevent systemic free radical injury.

Interaction of Vitamin C with Chemotherapy

A recent systematic review examined evidence from randomized controlled trials of supplemental antioxidant nutrients administered concurrently with conventional cancer treatments. The paper included 19 controlled human trials of single or combination antioxidant therapies in combination with chemotherapeutic regimes (Block 2007). The authors conclude, “From the 19 studies included in this review, no evidence was found that supported concerns that antioxidant supplementation given concurrently with ROS-generating chemotherapy diminished the efficacy of the chemotherapy in study populations comprising mostly advanced or relapsed patients. In contrast, 17 of the RCTs included in this review showed either a statistically significant advantage or nonstatistically higher survival and/or treatment response in those patients given antioxidants.”

A separate review included preclinical evidence in addition to evidence from controlled human trials. Over 280 peer-reviewed papers are presented, including 50 human trials of collectively over 8,500 subjects, approximately 5,000 of whom were actively receiving antioxidant therapies. Again, a comprehensive review of the area highlights a lack of adverse interaction from combined antioxidant and chemotherapy intervention. Studies collectively including almost 4,000 patients actively receiving antioxidant therapy find increased survival as a treatment outcome (Simone 2007).

Intravenous Vitamin C as Cancer Treatment; Controlled Human Trials

Table 1 presents 12 controlled human trials of intravenous vitamin C for the management of several cancer types. In some reports the specific cancer types are poorly defined, while in others, a clearly defined protocol of combined chemotherapy and intravenous vitamin C is described.

One paper presented (Padayatty 2006), published in the Canadian Medical Association Journal, highlights what is likely to become the future of intravenous Vitamin C therapy in cancer. The paper includes contributions from the National Cancer Institute, the National Institute of Health, Centers for Cancer Research, and McGill University. The paper presents only three cases, however each case is of advanced, incurable cancer, documented with the highest standard of objective histopathological assessment. All three cases achieved long-term remission, with intravenous vitamin C the likely basis for the observed outcomes. The authors call for a reevaluation of intravenous vitamin C as a complementary tool for cancer management. Since the publication of this paper, several leading cancer clinics across North America have begun adding intravenous vitamin C to various cocktails used for the treatment of refractory multiple myeloma (See table 1). Please refer to table 2 for a commonly implemented protocol of intravenous vitamin C in complementary cancer management.

While it may remain the generally held opinion of oncologists across the country that intravenous use of vitamin C is inappropriate for cancer treatment, leading oncology units in North America have revived interest in this safe, non-toxic and effective chemotherapeutic strategy. It will invariably take several decades for the medical masses to become aware of recent successes of I.V. vitamin C in various clinical settings. Thankfully, the Naturopathic community never lost interest in this treatment strategy, and such therapies have remained available to patients since the pioneering work of Pauling and Cameron.

Conclusion

The ability of vitamin C to prolong survival, improve quality of life, and reduce adverse effects of conventional cancer therapies has been reproducibly demonstrated over several decades. Recent research efforts of leading cancer clinics strongly supports previous reports of profound positive impact from the intervention.

Opposition to the use of intravenous vitamin C by oncologists is frustrating. It forces us to question the motives of such practitioners; is the ultimate goal best-possible patient care, or compliance with rigorously controlled trials of experimental chemotherapeutic drugs. The use of complementary strategies confounds results of such studies, and is ultimately a common basis for discouraging the use of complementary medicine in cancer management.

The ultimate decision regarding the course of patient care lies in the hands of the patient. As the use of intravenous vitamin C and other complementary strategies in cancer management become more commonplace, medical practitioners will invariably be compelled to reexamine the evidence as it pertains to such strategies.

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References

Abou-Jawde RM, Reed J, Kelly M, Walker E, Andresen S, Baz R, Karam MA, Hussein M. Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial. Med Oncol. 2006;23(2): 263-72.

Asano K, Satoh K, Hosaka M, Arakawa H, Inagaki M, Hisamitsu T, Maeda M, Kochi M, Sakagami H. Production of hydrogen peroxide in cancerous tissue by intravenous administration of sodium 5,6-benzylidene-Lascorbate Anticancer Res. 1999 Jan-Feb;19(1A):229-36.

Bahlis NJ, McCafferty-Grad J, Jordan-McMurry I, Neil J, Reis I, Kharfan- Dabaja M, Eckman J, Goodman M, Fernandez HF, Boise LH, Lee KP. Feasibility and correlates of arsenic trioxide combined with ascorbic acidmediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin Cancer Res. 2002 Dec;8(12):3658-68.

Berenson JR, Boccia R, Siegel D, Bozdech M, Bessudo A, Stadtmauer E, Talisman Pomeroy J, Steis R, Flam M, Lutzky J, Jilani S, Volk J, Wong SF, Moss R, Patel R, Ferretti D, Russell K, Louie R, Yeh HS, Swift RA. Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single-arm study. Br J Haematol. 2006 Oct;135(2):174-83.

Berenson JR, Matous J, Swift RA, Mapes R, Morrison B, Yeh HS. A phase I/II study of arsenic trioxide/bortezomib/ascorbic acid combination therapy for the treatment of relapsed or refractory multiple myeloma. Clin Cancer Res. 2007 Mar 15;13(6):1762-8.

Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat Rev. 2007; 33(5):407-18.

Cameron E, Campbell A. Innovation vs. quality control: an 'unpublishable' clinical trial of supplemental ascorbate in incurable cancer. Med Hypotheses. 1991;36(3):185-9.

Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A. 1976;73(10):3685-9.

Cameron E and Pauling L: Cancer and Vitamin C. Philadelphia. Camino Books. 1993.

Campbell A, Jack T, Cameron E. Reticulum cell sarcoma: two complete 'spontaneous' regressions, in response to high-dose ascorbic acid therapy. A report on subsequent progress. Oncology. 1991;48(6):495-7.

Casciari JJ, Riordan HD, Miranda-Massari JR, Gonzalez MJ. Effects of high dose ascorbate administration on L-10 tumor growth in guinea pigs. P R Health Sci J. 2005 Jun;24(2):145-50.

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 Sep 20;102(38):13604-9.

Drisko JA, Chapman J, Hunter VJ. The use of antioxidants with firstline chemotherapy in two cases of ovarian cancer. J Am Coll Nutr. 2003;22(2):118-23.

Nemoto S, Otsuka M, Arakawa N. Effect of high concentration of ascorbate on catalase activity in cultured cells and tissues of guinea pigs. J Nutr Sci Vitaminol (Tokyo). 1997 Jun;43(3):297-309.

Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ. 2006;174(7):937-42.

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.

Sakagami H, Satoh K, Hakeda Y, Kumegawa M. Apoptosis-inducing activity of vitamin C and vitamin K. Cell Mol Biol (Noisy-le-grand). 2000 Feb;46(1):129-43.

Simone CB 2nd, Simone NL, Simone V, Simone CB. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, Part 2. Altern Ther Health Med. 2007 Mar-Apr;13(2):40-7.

Wu KL, Beksac M, van Droogenbroeck J, Amadori S, Zweegman S, Sonneveld P.Phase II multicenter study of arsenic trioxide, ascorbic acid and dexamethasone in patients with relapsed or refractory multiple myeloma. Haematologica. 2006;91(12):1722-3.

Yeom CH, Jung GC, Song KJ. Changes of terminal cancer patients' healthrelated quality of life after high dose vitamin C administration. J Korean Med Sci. 2007;22(1):7-11.