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Vitamin E Succinate Enhances Anti-cancer Effect of Vitamin K-3
Jacob Schor, ND, FABNO
April 2, 2010
Subject: Change in K-3/C protocol
For the last decade we have routinely prescribed a combination of vitamin K-3 and vitamin C to many of our patients undergoing cancer treatment. This treatment is based on the published work on the subject by Gilloteaux, Jamison, Neal, and Summers. The combination of vitamin C with vitamin K-3 causes a reaction in cancer cells that depletes the cell of glutathione. Glutathione, though a valuable antioxidant in healthy cells, protects cancer cells against chemotherapy, radiation and the cell’s own attempts to trigger the suicidal process known as apoptosis. Depleting a cancer cell of glutathione increases the effectiveness of most cancer treatments as well as triggering cancer cell self-destruction. Gilloteaux et al. received the credit for experimentally proving the ideal ratio between vitamin K-3 and vitamin C to achieve the best results. They have a patent on their one to one hundred ratio and the rights to this vitamin combination are now being developed as a chemotherapy adjunctive therapy.
A paper published in the March 23, 2010 edition of the British Journal of Cancer gives us reason to update this protocol. Tomasetti and fellow researchers from the Department of Molecular Pathology and Innovative Therapies at the Polytechnic University of Marche in Ancona, Italy tell us that adding a specific form of vitamin E to the earlier combination makes it work even better.
They added alpha tocopherol succinate to the standard combination of vitamin K-3 and C and tested this on prostate cancer cells. This supplement is just a water soluble semi-synthetic form of vitamin E, often used in making mulit-vitamins as it is a dry powder rather than an oil. We often suggest using this ‘E succinate’ during radiation treatment as appears to increase the tumor kill rate. In fact, now that I think about this, the early work on this was done here in Denver by Prasad.
The Italian researchers describe the addition of this E succinate to the Vitamin K-3 and C protocol as having a synergistic effect rather than simply additive. In other words, it worked better than predicted by simply adding the expected kill rate of the individual constituents together. This kind of language gets our attention.
For those of you already taking vitamin K-3 to treat cancer, it now makes sense to add this E-succinate to your pile of pills. Call us or email Dr. Schor for dosing details.
For those of you taking vitamin K-2 for osteoporosis, don’t get confused. We are talking about two different forms of vitamin K here. For those of you who may be taking vitamin K-2 for cancer prevention, for example those with chronic hepatitis, we do not know for sure whether E succinate will increase the protective effect, but there is a good chance that it will.
Past Newsletters related to this:
Vitamin K-2 prevents liver cancer in hepatitis C patients. 2004:
Autoschizis: the new word in cancer treatment
For those interested in this vitamin K-3 and C protocol, an interesting paper is this one on bladder cancer:
Gilloteaux J, Jamison JM, Arnold D, Neal DR, Summers JL. Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment. Anat Rec A Discov Mol Cell Evol Biol. 2006 Jan;288(1):58-83.
It is available for free download online and contains impressive before and after pictures of bladder cancer cells showing how quickly they respond to this treatment.
The Current Paper:
Br J Cancer. 2010 Mar 23.
alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.
Tomasetti M, Strafella E, Staffolani S, Santarelli L, Neuzil J, Guerrieri R.
Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona 60020, Italy.
Background:A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death.
Methods: The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells.
Results: Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA up to 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected.
Conclusion: These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.
British Journal of Cancer advance online publication, 23 March 2010; doi:10.1038/sj.bjc.6605617 www.bjcancer.com.
Ultrastruct Pathol. 2005 May-Aug;29(3-4):221-35.
Cell death by autoschizis in TRAMP prostate carcinoma cells as a result of treatment by ascorbate: menadione combination.
Gilloteaux J, Jamison JM, Neal DR, Summers JL.
American University of the Caribbean School of Medicine, Campus St. Maarten, M.E.I.O., Inc, Coral Gables, Florida 33134, USA. firstname.lastname@example.org
A prostate carcinoma cell line derived from the transgenic murine prostate cancer model (TRAMP) was treated with ascorbate (VC) alone, menadione (VK(3)) alone, or a combination of ascorbate:menadione (VC + VK(3)) for 1, 2, and 4 h. Cytotoxic cell alterations examined by light and electron microscopy were treatment-dependent with VC + VK(3) > VC > VK(3). Induced by oxidative stress, these alterations included cytokeletal changes conducive to cytoplasmic blebbing, self-excisions, and progressive nuclear alterations. While the excised parts contained ribosomes, they were devoid of nuclear fragments or other organelles. The organelle-free self-excisions caused an extreme reduction in cell size as well as chromatolysis and karyolysis that were consistent with cell death by autoschizis, but not with apoptosis.
PMID: 16036878 [PubMed - indexed for MEDLINE]
J Am Coll Nutr. 2003 Apr;22(2):108-17.
Alpha-tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: a review.
Prasad KN, Kumar B, Yan XD, Hanson AJ, Cole WC.
Center for Vitamins and Cancer Research, Department of Radiology, Campus Box C-278, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA. kedar.prasad@UCHSC.edu
In 1982, it was established that alpha-tocopheryl succinate (alpha-TS) was the most effective form of vitamin E in comparison to alpha-tocopherol, alpha-tocopheryl acetate and alpha-tocopheryl nicotinate in inducing differentiation, inhibition of proliferation and apoptosis in cancer cells, depending upon its concentration. During the last two decades, several studies have confirmed this observation in rodent and human cancer cells in culture and in vivo (animal model). The most exciting aspect of this alpha-TS effect is that it does not affect the proliferation of most normal cells. In spite of several studies published on the anti-cancer properties of alpha-TS, the value of this form of vitamin E has not drawn significant attention from researchers and clinicians. Therefore, a critical review on the potential role of alpha-TS in the management of cancer is needed. In addition, such a review can also provide in-depth analysis of existing literature on this subject. alpha-TS treatment causes extensive alterations in gene expression; however, only some can be attributed to differentiation, inhibition of proliferation and apoptosis. alpha-TS also enhances the growth-inhibitory effect of ionizing radiation, hyperthermia, some chemotherapeutic agents and biological response modifiers on tumor cells, while protecting normal cells against some of their adverse effects. Thus, alpha-TS alone or in combination with dietary micronutrients can be useful as an adjunct to standard cancer therapy by increasing tumor response and possibly decreasing some of the toxicities to normal cells.