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High Dose Vitamin C IV Therapy

Creating a pro-oxidant effect to support cancer and work alongside conventional therapies.

While many patients have experienced the benefits of high-dose vitamin C IV therapy, the majority of our patients are undergoing treatment for cancer or related illnesses. Wellbeing Medical Group offers a range of high dose vitamin C IV infusions designed to support you when undergoing western-style cancer treatment, each designed specifically for your medical situation, lifestyle, treatment plan and specific needs. Vitamin C is one of the most vital elements of health and well-being. Without the proper amounts of vitamin C in your system, you can struggle to create many neurotransmitters, important chemicals like L-carnitine and vital body structural materials like collagen. It also a potent antioxidant that can help the body in numerous ways when given in, what we call, “low” doses (15g or less).

The power of intravenous high dose Vitamin C
Increasing research is starting to show the myriad of anticancer properties, such as targeting vulnerabilities many cancer cells share, such as redox imbalance, epigenetic reprogramming and oxygen-sensing regulation[1]

A vast number of studies have shown encouraging anti-cancer activity of Vitamin C at high doses in various cancer types [3]. The most investigated have been leukaemia [20–24], colon cancer [13–20], melanoma [21–25], pancreatic cancer [2, 19, 26] and prostate cancer [27–29]. Similar results have been described for the treatment of non-small-cell lung cancer (NSCLC) [4], breast cancer [29, 30], ovarian cancer [29, 31, 32], hepatocellular carcinoma [33, 34], malignant mesothelioma [35, 36], thyroid cancer [37, 38], oral squamous cell carcinoma [39], neuroblastoma [40] and glioma, including the difficult-to-treat glioblastoma multiform (GBM) [4, 41, 42].

One notable example of the progress in Vitamin C pre- clinical research is the recent work in hard-to-treat Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) driven tumours, such as KRAS mutant colorectal cancer (CRC) [13, 15, 20]. Based on prior studies by Yun et al. [25] and Aguilera et al. [25], Cenigaonan- dia-Campillo et al. [15] used elevated doses of Vitamin C (5–10mM) in KRAS mutant CRC tumours, both in vitro and in vivo. They showed that Vitamin C was able to target common metabolic aberrancies by decreasing adenosine triphosphate (ATP) and glucose transporter 1 (GLUT-1) levels, as well as by dissipating the mito- chondrial membrane potential, which could sensitize KRAS mutant CRC cells to current treatments such as chemotherapy. Given the importance of develop- ing better treatments for patients with KRAS driven tumours, non-toxic combinations with Vitamin C are also being explored and will be discussed in the following section 2.

In the majority of cancer types, most of the in vivo studies have shown inhibition of tumour growth (40–60%) by using elevated doses of ascorbate (1-4g/ kg) either intravenously (IV) or intraperitoneally (IP) [13, 43–45]

According to research[47] a fully competent immune system is required to maximize the antiproliferative effect of Vitamin C in breast, colorectal, melanoma, and pancreatic tumors. High-dose Vitamin C modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell-dependent manner. Vitamin C not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of this vitamin and ICT can be curative in models of mismatch repair-deficient tumors with high mutational burden.

More literature [48] states that mounting evidence indicates that Vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and boosting immune response. Moreover, high-dose IVC is powerful as an adjuvant treatment for cancer, acting synergistically with many standard (chemo-) therapies, as well as a method for mitigating the toxic side effects of chemotherapy.

In more scientific terms, research[49] has shown that due to vitamin C complex pharmacokinetics, only intravenous administration allows reaching sufficiently high plasma concentrations required for most of the antitumor effects observed in preclinical studies (>0.250 mM). Moreover, vitamin C entry into cells is tightly regulated by SVCT and GLUT transporters, and is cell type-dependent. Importantly, besides its well-recognized pro-oxidant effects, vitamin C modulates TET enzymes promoting DNA demethylation and acts as cofactor of HIF hydroxylases, whose activity is required for HIF-1α proteasomal degradation. Furthermore, at pharmacological concentrations lower than those required for its pro-oxidant activity (<1 mM), vitamin C in specific genetic contexts may alter the DNA damage response by increasing 5-hydroxymethylcytosine levels. These more recently described vitamin C mechanisms offer new treatment opportunities for tumors with specific molecular defects (e.g., HIF-1α over-expression or TET2, IDH1/2, and WT1 alterations). Moreover, vitamin C action at DNA levels may provide the rationale basis for combination therapies with PARP inhibitors and hypomethylating agents.

Vitamin C monotherapy in palliative care and quality of life (EOL)
In palliative care, high-dose VitC is currently gaining ground due to its highly safe and tolerable profile. Not only is high-dose Vitamin C known to relieve pain in cancer patients [6], vast clinical evidence suggests that it has a significant positive impact on patients’ well-being [1, 2-5, 7-10]. This might be due to the frequent hypovitaminosis and Vitamin C deficiency in cancer patients [6, 11, 12], which are commonly enhanced by anti-neo- plastic treatments [3].

For instance, a retrospective, multicentre, epidemiological cohort study [3] showed amelioration of appetite, fatigue, depression and sleep disorders in breast cancer and terminal cancer patients suffering from a wide variety of cancer types that received complementary 7.5g IVC while being treated by respective standard regimens. More recently, a single-center, parallel-group, single-blind interventional study also in breast cancer patients [13] showed a similar and significant reduction of symptoms such as nausea, fatigue, tumor pain and loss of appetite by administering 25g of IVC per week in addition to their current standard treatment. Favourably, no new side effects were reported after initiation of IVC treatment.

Moreover, another retrospective study showed that patients with radiotherapy- resistant bone metastasis did not only have less pain and better performance measures when given high-dose VitC, they had a median survival time of 10 months as compared to the 2 months median survival time within the control group [7].

Overall, high dose VitC administered as a single agent has not only been shown to be safe and well-tolerated in cancer patients, but also to ameliorate pain and to improve quality of life in the palliative care setting.

High dose vitamin C therapy can help you by

Ensuring that your body rapidly absorbs the necessary levels of vitamin C, even if you were already running at a vast deficit

Improving your appetite and relieving or mitigating other common side effects of cancer treatment

Support the action of other complementary therapies, such as our mistletoe IV infusion

High doses of vitamin C have even been found to may slow the growth of some kinds of cancerous tissues.

Our vitamin C programmes are designed bespoke to fit your medical background, and ongoing conventional treatment. Our process is simple, please contact our clinic to discuss high dose vitamin C options. You will receive a call back from our dedicated cancer care consultant who will design your plan according to your medical diagnosis.

Research

1. Bryan Ngo et al, Targeting cancer vulnerabilities with high-dose vitamin C, Nat Rev Cancer 2019 May;19(5):271-282. doi: 10.1038/s41568-019-0135-7.
2. Polireddy K, Dong R, Reed G, Yu J, Chen P, Williamson S, et al. High dose parenteral Ascorbate inhibited pancreatic Cancer growth and metastasis: mechanisms and a phase I/IIa study. Sci Rep. 2017;7(1):17188.
3. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci. 2008;105(32):11105–9.
4. Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer Morales KL, Furqan M, et al. O 2 ·− and H 2 O 2 Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell. 2017;31(4):487–500.e8.
5. Takahashi H, Mizuno H, Yanagisawa A. High dose intravenous vitamin C improves quality of life in cancer patients. Pers Med Universe. 2012;1(1):49–53.
6. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. 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. 2011;25(6):983–90.
7. 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(1):7.
8. Agathocleous M, Meacham CE, Burgess RJ, Piskounova E, Zhao Z, Crane GM, et al. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature. 2017;549(7673):476–81.
9. Bonilla‐Porras AR, Jimenez‐Del‐Rio M, Velez‐Pardo C. Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism. Cancer Cell Int. 2011;11(1):19.
10. Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, et al. Res‐ toration of TET2 Function Blocks Aberrant Self‐Renewal and Leukemia Progression. Cell. 2017;170(6):1079–1095.e20.
11. Iamsawat S, Tian L, Daenthanasanmak A, Wu Y, Nguyen HD, Bastian D, et al. Vitamin C stabilizes CD81 iTregs and enhances their therapeutic potential in controlling murine GVHD and leukemia relapse. Blood Adv. 2019;3(24):4187–201.
12. Mingay M, Chaturvedi A, Bilenky M, Cao Q, Jackson L, Hui T, et al. Vita‐ min C‐induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia. Leukemia. 2018;32(1):11–20.
13. Aguilera O, Muñoz‐Sagastibelza M, Torrejón B, Borrero‐Palacios A, del Puerto‐Nevado L, Martínez‐Useros J, et al. Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer. Oncotarget. 2016;7(30):47954–65.
14. Brandt KE, Falls KC, Schoenfeld JD, Rodman SN, Gu Z, Zhan F, et al. Augmentation of intracellular iron using iron sucrose enhances the toxicity of pharmacological ascorbate in colon cancer cells. Redox Biol. 2018;14(July 2017):82–7
15. Cenigaonandia‐Campillo A, Serna‐Blasco R, Gómez‐Ocabo L, Solanes‐ Casado S, Baños‐Herraiz N, Del Puerto‐ Nevado L, et al. Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxic KRAS mutant colon cancer. Theranostics. 2021;11(8):3595–606.
16. Mamede AC, Pires AS, Abrantes AM, Tavares SD, Gonçalves AC, Casalta‐ Lopes JE, et al. Cytotoxicity of ascorbic acid in a human colorectal adenocarcinoma cell line (WiDr): in vitro and in vivo studies. Nutr Cancer. 2012;64(7):1049–57.
17. Nakanishi K, Hiramoto K, Ooi K. High‐dose vitamin C exerts its anti‐ cancer effects in a Xenograft model of Colon Cancer by suppressing angiogenesis. Biol Pharm Bull. 2021;44(6):884–7.
18. Pires AS, Marques CR, Encarnação JC, Abrantes AM, Mamede AC, Laranjo M, et al. Ascorbic acid and colon cancer: an oxidative stimulus to cell death depending on cell profile. Eur J Cell Biol. 2016;95(6–7):208–18.
19. Wang G, Yin T, Wang Y. In vitro and in vivo assessment of high‐dose vitamin C against murine tumors. Exp Ther Med. 2016;12(5):3058–62.
20. Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by target‐ ing GAPDH. Science (80‐ ). 2015;350(6266):1391–6.
21. Nakanishi K, Hiramoto K, Sato EF, Ooi K. High‐dose vitamin C adminis‐ tration inhibits the invasion and proliferation of melanoma cells in mice ovary. Biol Pharm Bull. 2021;44(1):75–81.
22. Chen XY, Chen Y, Qu CJ, Pan ZH, Qin Y, Zhang X, et al. Vitamin C induces human melanoma A375 cell apoptosis via Bax‐ and Bcl‐2‐mediated mitochondrial pathways. Oncol Lett. 2019;18(4):3880–6.
23. Kang JS, Cho D, Kim Y‐I, Hahm E, Yang Y, Kim D, et al. L‐ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase‐8?Independent pathway. Cancer Immunol Immunother. 2003;52(11):693–8.
24. Mustafi S, Sant DW, Liu Z‐J, Wang G. Ascorbate induces apoptosis in melanoma cells by suppressing Clusterin expression. Sci Rep. 2017;7(1):3671.
25. Serrano OK, Parrow NL, Violet P‐C, Yang J, Zornjak J, Basseville A, et al. Antitumor effect of pharmacologic ascorbate in the B16 murine mela‐ noma model. Free Radic Biol Med. 2015;87:193–203.
26. Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang S, et al. Mechanisms of Ascorbate‐induced cytotoxicity in pancreatic Cancer. Clin Cancer Res. 2010;16(2):509–20.
27. Pollard HB, Levine MA, Eidelman O, Pollard M. Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone‐ refractory prostate cancer. In Vivo. 2010;24(3):249–55.
28. Li Z, He P, Luo G, Shi X, Yuan G, Zhang B, et al. Increased Tumoral micro‐ environmental pH improves cytotoxic effect of pharmacologic ascorbic acid in castration‐resistant prostate Cancer cells. Front Pharmacol. 2020;11:570939.
29. Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li B, et al. Pharmacologi‐ cal ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anti‐Cancer Drugs. 2012;23(4):437–44.
30. Ramezankhani B, Taha MF, Javeri A. Vitamin C counteracts miR‐302/367‐in‐ duced reprogramming of human breast cancer cells and restores their invasive and proliferative capacity. J Cell Physiol. 2019;234(3):2672–82.
31. Xu Y, Guo X, Wang G, Zhou C. Vitamin C inhibits metastasis of peritoneal tumors by preventing spheroid formation in ID8 murine epithelial peritoneal Cancer model. Front Pharmacol. 2020;11:645.
32. Gregoraszczuk EL, Zajda K, Tekla J, Respekta N, Zdybał P, Such A. Vitamin C supplementation had no side effect in non‐cancer, but had antican‐ cer properties in ovarian cancer cells. Int J Vitam Nutr Res. 2020;3:1–11.
33. Lv H, Wang C, Fang T, Li T, Lv G, Han Q, et al. Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT‐2. npj Precis Oncol. 2018;2(1):1.
34. Alyoussef A, Al‐Gayyar MMH. Cytotoxic and partial hepatoprotective activity of sodium ascorbate against hepatocellular carcinoma through inhibition of sulfatase‐2 in vivo and in vitro. Biomed Pharmacother. 2018;103:362–72.
35. Volta V, Ranzato E, Martinotti S, Gallo S, Russo MV, Mutti L, et al. Preclini‐ cal Demonstration of Synergistic Active Nutrients/Drug (AND) Com‐ bination as a Potential Treatment for Malignant Pleural Mesothelioma. McCormick DL, editor. PLoS One. 2013;8(3):e58051.
36. Ranzato E, Biffo S, Burlando B. Selective Ascorbate toxicity in malignant mesothelioma. Am J Respir Cell Mol Biol. 2011;44(1):108–17.
37. Su X, Shen Z, Yang Q, Sui F, Pu J, Ma J, et al. Vitamin C kills thyroid cancer cells through ROS‐dependent inhibition
of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms. Theranostics. 2019;9(15):4461–73.
38. Tronci L, Serreli G, Piras C, Frau DV, Dettori T, Deiana M, et al. Vitamin C cytotoxicity and its effects in redox homeostasis and energetic metabolism in papillary thyroid carcinoma cell lines. Antioxidants. 2021;10(5):809.
39. Zhou J, Chen C, Chen X, Fei Y, Jiang L, Wang G. Vitamin C promotes apoptosis and cell cycle arrest in Oral squamous cell carcinoma. Front Oncol. 2020;10:976.
40. Deubzer B, Mayer F, Kuçi Z, Niewisch M, Merkel G, Handgretinger R,et al. H2O2‐mediated cytotoxicity of
pharmacologic Ascorbate concen‐ trations to neuroblastoma cells: potential role of lactate and ferritin. Cell Physiol
Biochem. 2010;25(6):767–74.
41. Castro M,Carson G, McConnell M, Herst P. High dose Ascorbate causes both Genotoxic and metabolic stress in Glioma cells. Antioxidants. 2017;6(3):58.
42. Gokturk D, Kelebek H, Ceylan S, Yilmaz DM. The effect of ascorbic acid over the Etoposide‐ and Temozolomide‐ mediated cytotoxic‐ ity in Glioblastoma cell culture: a molecular study. Turk Neurosurg. 2018;28(1):13–8.
43. Campbell EJ, Dachs GU. Current limitations of murine models in oncol‐ ogy for Ascorbate research. Front Oncol. 2014;4:282.
44. Campbell EJ, Vissers MCM, Wohlrab C, Hicks KO, Strother RM, Bozonet SM, et al. Pharmacokinetic and anti‐ cancer properties of high dose ascorbate in solid tumours of ascorbate‐dependent mice. Free Radic Biol Med. 2016;99:451–62.
45. Chen P, Stone J, Sullivan G, Drisko JA, Chen Q. Anti‐cancer effect of pharmacologic ascorbate and its interaction with supplementary par‐ enteral glutathione in preclinical cancer models. Free Radic Biol Med. 2011;51(3):681–7.
46. Taper HS, Jamison JM, Gilloteaux J, Summers JL, Calderon PB. Inhibition of the development of metastases by dietary vitamin C:K 3 combination. Life Sci. 2004;75(8):955–67.
47. Alessandro Magrì et al: High-dose vitamin C enhances cancer immunotherapy: Sci Transl Med 2020 Feb 26;12(532):eaay8707. doi: 10.1126/scitranslmed.aay8707.
48. Franziska Böttger et al. High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer: J Exp Cain Cancer Res 2021 Oct 30;40(1):343. doi: 10.1186/s13046-021-02134-y.
49. Manuela Giansanti et al: High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients Cancers (Basel) 2021 Mar 20;13(6):1428. doi: 10.3390/cancers13061428.

References for IVC monotherapy in palliative care and quality of life (EOL)
1. Polireddy K, Dong R, Reed G, Yu J, Chen P, Williamson S, et al. High dose parenteral Ascorbate inhibited pancreatic Cancer growth and metasta‐ sis: mechanisms and a phase I/IIa study. Sci Rep. 2017;7(1):17188.
2. Takahashi H, Mizuno H, Yanagisawa A. High‐dose intravenous vitamin C improves quality of life in cancer patients. Pers Med Universe. 2012;1(1):49–53.
3. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. 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. 2011;25(6):983–90.
4. 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(1):7.

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