vitamina C uso en cancer, beneficios

VITAMIN C: Use in Cancer


Since the proposal in 1976 by Linus Pauling (Nobel Prize Winner) and Irwin Stone (National Cancer Institute), and Ewan Cameron (NIH), "complementary" management schemes for cancer with Vitamin C or Sodium Ascorbate have been increasing [ 2]. In cancer, vitamin C is associated with prevention, progression, and treatment, either because of its general properties or because of its role as a pro-oxidant at high concentrations [12].


In the literature there are clinical trials of the use of Vitamin C as a single therapy and in other scientific studies combining chemotherapy with Vitamin C for the management of cancer with favorable results [3].


In systematic versions (clinical and lab), myths and controversies have been elucidated that demonstrate the efficacy and safety in the use of megadoses of Sodium Ascorbate in cancer [4-5].


The average serum level of Vitamin C is significantly lower in cancer patients compared to healthy people. Deficient nutrient must be replenished [5-6].

Route of Administration

It has been shown that Vitamin C administered orally does not achieve the same levels in blood and tissue as that administered intravenously [5 and 7].

Mechanism of action

Vitamin C selectively kills cancer cells without harming normal cells. In vitro tests show that Sodium Ascorbate acts as a prodrug in the production of hydrogen peroxide (H2O2) in tissues, in which it exerts a selective cytotoxic effect on tumor cells [8].


The figure illustrates the highly differential distribution of Vitamin C (vitC) in the normal human body. Several organs have concentration-dependent mechanisms for vitC retention, maintaining high levels during times of inadequate supply at the expense of other organs. Particularly protected is the brain. In addition, concentration-dependent mechanisms of absorption and reabsorption contribute to the homeostatic control of vitC in the body [14].

Normal concentration of Vitamin C in the body

Many studies have shown that cancer patients present with a high level of oxidative stress [9]. For many of the cancer cell lines, ascorbate concentrations caused a 50% decrease in cell survival. Half-maximal concentration (IC50) values ​​were less than 5 mM, and all normal cells tested were insensitive to 20 mM ascorbate [13].

MIC concentration of Vitamin C in tumors

Intravenous Vitamin C Dosage

In a study of patients with prostate cancer, they evaluated the kinetics of Vitamin C, finding that 5 grams of Vitamin in 5% Dextrose (with a total volume of 510 mL) passed in 30 minutes reaches a mean peak concentration of 1.9 mmol. /L[16]. 5% Dextrose is a hypotonic solution that probably mobilized the vitamin inside the cells or intracellular compartment, decreasing [Vitamin C] in the extracellular compartment and [Vitamin C] was measured in the blood ( extracellular compartment). A dose of 60.3 mg/kg or 2.48 g/m2 of intravenous Vitamin C generates an average maximum concentration of 1.9 mmol/L, which is sufficient to decrease cell survival by 50% (IC50) of most cancers as we observed in the table above. The half-life is 99.6 minutes and the area under the curve is plus or minus 4 hours. The volume of distribution was 0.19 L/Kg and the clearance was 6.84 L/hr [16].

Treatment with high doses of vitamin C (>15g/day) intravenously can be considered a palliative treatment in patients with advanced cancer. However, its effects can be influenced by many factors, such as the initial general condition of the patient, comorbidities, the pathogenesis of the reported symptoms (eg, pain), and the stage of the disease that can determine the appearance of side effects. severe (acute renal failure, hyperkalemia, anemia). Further studies are required to better understand the properties of vitamin C described above and its efficacy needs to be determined in high-quality controlled studies with appropriate comparators [5].

Studies reviewed in [12] show that vitamin C intake from natural sources can prevent the development of lung and breast cancer, and that vitamin C acts synergistically with gemcitabine and erlotinib in pancreatic cancer. In vitro assays reveal that vitamin C acts synergistically with DNA methyl transferase inhibitors [12].

The role of vitamin C in the prevention and treatment of cancer

Mechanisms of action of Vitamin C to produce cell death of tumor cells

Recent studies conclusively show how vitamin C (ascorbate) causes cell death specifically in cancer cells. The following image shows the mechanisms of action described for intravenous doses of VitC in combination with anticancer agents in preclinical studies [17] .

Mechanisms of action of vitamin C to treat cancer

The interrelation of different mechanisms of cell death and treatments with high / low doses of ascorbate or Vitamin C:

  1. apoptosis

The reduced cellular level of Bcl2 induced the accumulation of Beclin 1 which mediates autophagosome formation. Therefore, ascorbate-induced autophagy in cancer cells can lead to cell death without apoptosis.

  1. Necroptosis

The independence of caspase from cell death induced by high doses of ascorbate suggested the possible involvement of necroptosis and autophagy. The inhibitory effect of the necroptosis inhibitor, necrostatin-1, and the increase of the necroptosis marker, RIPK1, at a moderate concentration of ascorbate suggested the possible role of necroptosis in cell death induced by ascorbate at a moderately high concentration.

  1. autophagy

Ascorbate also promoted caspase-independent autocannibalism in a dose-dependent manner. Autophagosome formation was enhanced by the increased LC3II/LC3I ratio due to ascorbate treatment. Furthermore, ascorbic acid-dependent cell death was suppressed by knockdown of Beclin1, a key inducer of autophagosome formation. Pharmacological inhibition of autophagy by wortmannin and bafilomycin A1 resulted in inhibition of cell death due to mild ascorbate treatment; however, its protective role was lost at higher concentrations of ascorbate. All these results assume the presence of an autophagic response during ascorbate treatment. RIPK, receptor-interacting protein kinase.

Vitamin C and cancer cell death

  1. ferroptosis

The oxidative nature of pharmacological ascorbate-induced cytotoxicity and the similar features of ROS-driven cell death, ferroptosis, raised the possibility of a close connection between these two processes; however, recent results showed that inhibitors of ferroptosis (ferrostatin-1 and liproxstatin-1) were unable to increase the viability of cancer cell lines treated with high doses of ascorbate. Furthermore, it was found that, at low to moderate concentrations, ascorbate behaved as an inhibitor of RSL3 and erastin-induced ferroptosis.

  1. Pro-oxidant or ROS generation mechanisms
"The amount of antioxidants you keep in your body is directly proportional to how long you will live" Richard Cutler MD, Director of Anti-Aging Research, National Institutes of Health (NIH) [1].
  1. Epigenetic mechanisms or genetic regulator

Recently, information has emerged on the participation of vitamin C in the epigenetic regulation of gene expression, as a cofactor in the methylation of cytosine in DNA, and the methylation or deacetylation of lysine and arginine in histones. These actions could be important in the early stages of the development of scurvy or cancer, or could alter the pathogenesis of neurodegenerative diseases. The epigenetic role of vitamin C in health and disease. Ascorbate bioavailability influences health and disease by regulating the demethylation of DNA and histones, as well as the transcriptome. [fifteen].

  1. Immuno-modulation mechanism
The role of vitamin C in the prevention and treatment of cancer: the anti-cancer effect of vitamin C is related to its pro-oxidant capacity and its ability to modulate epigenetic mechanisms in cancer cells and to stimulate the anti-cancer immune response [13]. .

The role of vitamin C in cancer

  1. Other types of cell death mechanisms

Ascorbate should soon be introduced as part of the broad-spectrum therapeutic approach to cancer. A deeper understanding of the molecular pathways of the different mechanisms of cell death and of those behind the resistance of tumors to cell death may provide us with an approach to develop targeted molecular therapies. Based on the above observations, at least two of the key features of cancer cells can be targeted by ascorbate individually or rather in a combined therapeutic approach. These two targets are intrinsic or acquired resistance to apoptosis and dysregulated metabolism of cancer cells. This knowledge will allow us physicians to include vitamin C as part of anticancer therapy [10].

Doctor Saliarmo's recommendation: route of administration, dose and frequency

The ideal is to dilute it in the saline solution since it hydrates and makes it easier for the vitamin C to reach where it needs to go (inside the cells). For reasons of effectiveness and cost, the maximum daily dose of intravenous (IV) Vitamin C that I recommend in cases of Cancer is 50 milliliters (mL) or 5 grams (diluted in SSN) per day. Pharmacologically, no toxicity has been found in doses of 2 grams to 5 grams per day. It is beneficial to add 5 mL of procaine to the same serum for pain management.


[1] Leung, PY, Miyashita, K., Young, M., & Tsao, CS (1993). Cytotoxic effect of ascorbate and its derivatives on cultured malignant and nonmalignant cell lines. Anticancer research , 13 (2), 475-480.

[2] 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 Oct; 73(10):3685-9.

[ 3] JLWelsh, BAWagner, TJ van´t Erve, PSZehr, DJBerg, TRHalfdanarson, NSYee, KLBodeker, J.Du, LJRoberts II, J.Drisko, M.Levine, GRBuettner, JJ Cullen. Pharmacological ascorbe with gencitabine for the control of metastatic and node.positive pancreatic cancer (PACMAN) results from a phase I clinical trial, Cancer Chemother Pharmacol (2013) 71:765-775.

[4] James A Jackson, et al. Sixteen-Year History with High Dose Intravenous Vitamin C Treatment for Various Types of Cancer and Other Diseases. Journal of Orthomolecular Medicine Vol.17, No 2,2002.

[5] Zasowska-Nowak A, Nowak PJ, Ciałkowska-Rysz A. High-Dose Vitamin C in Advanced-Stage Cancer Patients. Nutrients. 2021 Feb 26;13(3):735. doi: 10.3390/nu13030735. PMID: 33652579; PMCID: PMC7996511.

[6] Mahdavi R, et al. Evaluation of Oxidative Stress, Antioxidant Status ans Serum Vitamin C Levels in Cancer Patients. Biol Trace Elem Res. 2009 Gan 17. PMID: 19148586

[7] Duconge J, et al Pharmacokinetics of vitamin C: insights into the oral intravenous administration of ascorbate. PR Health Sci J. 2008 Mar; 27(1):7-19. Review. PMID: 18450228.

[8] Chen Q, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as prodrug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA 2005.

[9] NA Nikirova, et al. The effect of high dose IV Vitamin C on plasma antioxidant capacity and level of oxidative stress in cancer patients and healthy subject. Journal of Orthomulecular Medicine Vol. 22, No. 3, 2007.

[10] András Szarka, Orsolya Kapuy, Tamás Lőrincz, and Gábor Bánhegyi. Vitamin C and Cell Death. Antioxidants & Redox Signaling. Apr 2021. 831844.

[ 11] Bedhiafi, T., Inchakalody, VP, Fernandes, Q., Mestiri, S., Billa, N., Uddin, S., ... & Dermime, S. (2022). The potential role of vitamin C in empowering cancer immunotherapy. Biomedicine & Pharmacotherapy , 146 , 112553.

[12] Villagran, M., Ferreira, J., Martorell, M., & Mardones, L. (2021). The role of vitamin C in cancer prevention and therapy: a literature review. Antioxidants , 10 (12), 1894.

[13] Chen, Q., Espey, MG, Krishna, MC, Mitchell, JB, Corpe, CP, Buettner, GR, ... & Levine, M. (2005). Ascorbic acid at pharmacologic concentrations selectively kills cancer cells: ascorbic acid as a pro-drug for hydrogen peroxide delivery to tissues. Proc Natl Acad Sci USA , 102 , 13604-13609.

[14] Lykkesfeldt, J., & Tveden-Nyborg, P. (2019). The pharmacokinetics of vitamin C. Nutrients , 11 (10), 2412.

[15] Camarena, V., & Wang, G. (2016). The epigenetic role of vitamin C in health and disease. Cellular and Molecular Life Sciences , 73 , 1645-1658.

[16] Nielsen TK, Højgaard M, Andersen JT, Poulsen HE, Lykkesfeldt J, Mikines KJ. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: a pharmacokinetic evaluation. Basic Clin Pharmacol Toxicol. 2015 Apr;116(4):343-8. doi: 10.1111/bcpt.12323. Epub 2014 Oct 7. PMID: 25220574.

[17] Böttger, F., Vallés-Martí, A., Cahn, L., & Jimenez, CR (2021). High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer. Journal of experimental & clinical cancer research , 40 (1), 1-44.

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