The Enhancement of C-Max

As a cancer-oriented product, C-Max has always heeded the best oncological vitamin C research available. And by "best," the focus points have always been twofold: 1) oncologocially significant therapeutic effect; and 2) safety to normal human physiology. C-Max has always utilized vitamins C and K3, as this combination is so well-suited to these objectives; as one oncology research team has put it,

While C-Max has always employed these two potent natural substances, an upgrade was necessary.

What will be different with it? Scores of studies have indicated that CK3 therapy is highly effective for killing a wide variety of cancer cell types. But in the past, C-Max leveraged a subset of CK3 therapies. This subset utilizes vitamin C, Alpha Lipoic Acid, (ALA) and vitamin K3. In this modality, ALA performs a function similar to that of K3. Both are redox cycling quinones that potentiate vitamin C. In short, they, when co-administered with vitamin C, kill cancer through the uniquely efficient process of autoschizis - a systematic degradation of cancer cell walls and organelles. 

Subsequent and ongoing research into autoschizis has found that K3 and vitamin C seem to stimulate greater cancer cell degradation, and thus provoke increased autoschizis, when given alone (without ALA) . Additionally, the lion's share of these studies have found that the greatest cancer killing effect occurs when the ratio of vitamin C to vitamin K3 administered is 100:1. In light of these findings, the new version of C-Max will be constituted with vitamin C and K3 only, and at the validated ratio of 100:1.

Of course, the differentiator with C-Max, beyond the vitamins that are used, is the delivery method. C-Max delivers C and K3 with highly absorbed liposomes. Compared to IV and traditional oral forms, liposomes possess many important advantages. For example, they provide a greater therapeutic timeframe, i.e., doses stay in circulation for a longer time period; they achieve better concentrations in the lymphatic system (where most immune cells reside and where solid cancers spread); and they attain up to 100-fold better absorption into human cells than non-liposome encapsulated vitamins.

Following the Science

The research that has guided the C-Max enhancement includes the following studies. For reference, these papers have been organized according to cancer type:

Bladder Cancer

[T24 Cell Line] Gilloteaux, Jacques, et al. "Ultrastructural aspects of autoschizis: a new cancer cell death induced by the synergistic action of ascorbate/menadione on human bladder carcinoma cells." Ultrastructural pathology 25.3 (2001): 183-192.

Brain Cancer

Sumiyoshi A, Shibata S, Zhelev Z, Miller T, Lazarova D, Aoki I, Obata T, Higashi T, Bakalova R. Targeting Glioblastoma via Selective Alteration of Mitochondrial Redox State. Cancers (Basel). 2022 Jan 19;14(3):485. doi: 10.3390/cancers14030485. PMID: 35158753; PMCID: PMC8833725.

Despotović A, Mirčić A, Misirlić-Denčić S, Harhaji-Trajković L, Trajković V, Zogović N, Tovilović-Kovačević G. Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells. Oxid Med Cell Longev. 2022 Mar 23;2022:2998132. doi: 10.1155/2022/2998132. PMID: 35368869; PMCID: PMC8967583.

Sumiyoshi A, Shibata S, Zhelev Z, Miller T, Lazarova D, Zlateva G, Aoki I, Bakalova R. Pharmacological Strategy for Selective Targeting of Glioblastoma by Redox-active Combination Drug - Comparison With the Chemotherapeutic Standard-of-care Temozolomide. Anticancer Res. 2021 Dec;41(12):6067-6076. doi: 10.21873/anticanres.15426. PMID: 34848461.

Breast Cancer

Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells: Bajor M, Graczyk-Jarzynka A, Marhelava K, Kurkowiak M, Rahman A, Aura C, Russell N, Zych AO, Firczuk M, Winiarska M, Gallagher WM, Zagozdzon R. Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells. Antioxidants (Basel). 2020 Apr 16;9(4):320. doi: 10.3390/antiox9040320. PMID: 32316111; PMCID: PMC7222372.

[MFC7 Cell Line] Bakalova R, Semkova S, Ivanova D, Zhelev Z, Miller T, Takeshima T, Shibata S, Lazarova D, Aoki I, Higashi T. Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant. Oxid Med Cell Longev. 2020 Nov 2;2020:6212935. doi: 10.1155/2020/6212935. PMID: 33204397; PMCID: PMC7652615.

[MFC7 Cell Line] Semkova S, Zhelev Z, Miller T, Sugaya K, Aoki I, Higashi T, Bakalova R. Menadione/Ascorbate Induces Overproduction of Mitochondrial Superoxide and Impairs Mitochondrial Function in Cancer: Comparative Study on Cancer and Normal Cells of the Same Origin. Anticancer Res. 2020 Apr;40(4):1963-1972. doi: 10.21873/anticanres.14151. PMID: 32234885.

Colon Cancer

[Colon 26 Cell Line] Bakalova R, Semkova S, Ivanova D, Zhelev Z, Miller T, Takeshima T, Shibata S, Lazarova D, Aoki I, Higashi T. Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant. Oxid Med Cell Longev. 2020 Nov 2;2020:6212935. doi: 10.1155/2020/6212935. PMID: 33204397; PMCID: PMC7652615.

[Colon 26 Cell Line] Semkova S, Zhelev Z, Miller T, Sugaya K, Aoki I, Higashi T, Bakalova R. Menadione/Ascorbate Induces Overproduction of Mitochondrial Superoxide and Impairs Mitochondrial Function in Cancer: Comparative Study on Cancer and Normal Cells of the Same Origin. Anticancer Res. 2020 Apr;40(4):1963-1972. doi: 10.21873/anticanres.14151. PMID: 32234885.

A D'Odorico, G C Sturniolo, R F Bilton, A I Morris, I T Gilmore, R Naccarato, Quinone-induced DNA single strand breaks in a human colon carcinoma cell line., Carcinogenesis, Volume 18, Issue 1, Jan 1997, Pages 43–46, https://doi.org/10.1093/carcin/18.1.43

Leukemia

[Jurkat Cell Line] Bakalova R, Semkova S, Ivanova D, Zhelev Z, Miller T, Takeshima T, Shibata S, Lazarova D, Aoki I, Higashi T. Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant. Oxid Med Cell Longev. 2020 Nov 2;2020:6212935. doi: 10.1155/2020/6212935. PMID: 33204397; PMCID: PMC7652615.

Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib: Ivanova D, Zhelev Z, Lazarova D, Getsov P, Bakalova R, Aoki I. Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib. Anticancer Res. 2018 Mar;38(3):1407-1414. doi: 10.21873/anticanres.12364. PMID: 29491065.

[Jurkat Cell Line] CK3 kills cancer cells, leaving healthy cells intact: Semkova S, Zhelev Z, Miller T, Sugaya K, Aoki I, Higashi T, Bakalova R. Menadione/Ascorbate Induces Overproduction of Mitochondrial Superoxide and Impairs Mitochondrial Function in Cancer: Comparative Study on Cancer and Normal Cells of the Same Origin. Anticancer Res. 2020 Apr;40(4):1963-1972. doi: 10.21873/anticanres.14151. PMID: 32234885.

Liver Cancer

Verrax J, Cadrobbi J, Marques C, Taper H, Habraken Y, Piette J, Calderon PB. Ascorbate potentiates the cytotoxicity of menadione leading to an oxidative stress that kills cancer cells by a non-apoptotic caspase-3 independent form of cell death. Apoptosis. 2004 Mar;9(2):223-33. doi: 10.1023/B:APPT.0000018804.26026.1a. PMID: 15004519.

Ovarian Cancer

Jacques Gilloteaux, H. Lee Lau, Ioulia Gourari, Deborah Neal, James M. Jamison, J.L. Summers, Apatone® induces endometrioid ovarian carcinoma (MDAH 2774) cells to undergo karyolysis and cell death by autoschizis: A potent and safe anticancer treatment, Translational Research in Anatomy, Volume 1, 2015, Pages 25-39, ISSN 2214-854X.

Prostate Cancer

Gilloteaux J, Jamison JM, Summers JL. Pro-oxidant treatment of human prostate carcinoma (DU145) induces autoschizis cell death: autophagosomes build up out of injured endomembranes and mitochondria. Ultrastruct Pathol. 2014 Oct;38(5):315-28. doi: 10.3109/01913123.2014.927404. Epub 2014 Jun 23. PMID: 24955925.

Tareen B, Summers JL, Jamison JM, Neal DR, McGuire K, Gerson L, Diokno A. A 12 week, open label, phase I/IIa study using apatone for the treatment of prostate cancer patients who have failed standard therapy. Int J Med Sci. 2008 Mar 24;5(2):62-7. doi: 10.7150/ijms.5.62. PMID: 18392145; PMCID: PMC2288789.

General Cancer Studies

The combination of ascorbate and menadione causes cancer cell death by oxidative stress and replicative stress: Ren X, Santhosh SM, Coppo L, Ogata FT, Lu J, Holmgren A. The combination of ascorbate and menadione causes cancer cell death by oxidative stress and replicative stress. Free Radic Biol Med. 2019 Apr;134:350-358. doi: 10.1016/j.freeradbiomed.2019.01.037. Epub 2019 Jan 28. PMID: 30703479.

Improved redox anti-cancer treatment efficacy through reactive species rhythm manipulation: Kizhuveetil U, Omer S, Karunagaran D, Suraishkumar GK. Improved redox anti-cancer treatment efficacy through reactive species rhythm manipulation. Sci Rep. 2020 Jan 31;10(1):1588. doi: 10.1038/s41598-020-58579-2. PMID: 32005913; PMCID: PMC6994657.

Thank you for reading. Should you have any questions about the new C-Max release, feel free to email us at sales@ivtogo.com. We'll be glad to help!