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Summary of Recent Research with Three Nutrients in the War Against Cancer

by Michael Passwater

FOR IMMEDIATE RELEASE

Orthomolecular Medicine News Service, November 11, 2021

OMNS (Nov. 11, 2021) We have much to learn about preventing and treating cancer. Each disease in the cohort of cancers is potentially a different disease related to the specific genetic mutations that drive it. In the interest of promoting further efforts to improve our understanding of these complex diseases, here is an update on research involving three essential nutrients: vitamin C, selenium (selenite and methyl selenocysteine), and vitamin E (delta tocotrienol). Although much progress has been made in the fight against some types of cancer, many types still remain literally a death sentence. Each year, more than 1.3 million people are diagnosed with one of the ten most deadly types of cancer in the United States and over 400,000 people die from these dreaded diseases.

2021 Estimated Cancer Deaths and New Cases in the United States [1]


Ascorbic Acid (Vitamin C)

By definition, a vitamin is essential for life, and vitamin C (ascorbic acid) is no exception. The health benefits of vitamin C are so extensive that it would be an important tool in the battle against cancer even without its powerful anti-tumor effect. Vitamin C is important for many aspects of immune and endothelial health; synthesis of catecholamines, carnitine, neuropeptides, neurotransmitters, collagen, and elastin; breakdown of L-tyrosine and hypoxic inducible factor 1-alpha (HIF-1a); epigenomic regulation; somatic stem cell reprogramming; and redox regulation including scavenging damaging free radicals, breaking chains of lipid peroxidation, and recycling other antioxidants. [2-8]

In 1976, Cameron and Pauling reported longer survival in terminal cancer patients given vitamin C. [9] Was this from improvement to the patients' constitution, was there an anti-tumor effect, or both? We now know that high doses of vitamin C can have a prooxidant effect, especially in combination with iron, which can selectively kill tumor cells containing less catalase than healthy human cells. [10, 11] The catalase enzyme is necessary for nearly all cells to remove hydrogen peroxide that can cause free radicals and damage the cell's biomolecules, including proteins and DNA. And vitamin C can also disrupt the "Warburg Effect" in tumor cells. [12,13,14] The Warburg Effect is the tendency of tumor cells to switch from using mitochondrial oxidative phosphorylation to aerobic glycolysis for the production of cellular energy (ATP). While greatly reducing the efficiency of energy production (2 ATP molecules generated per glucose molecule vs. 36 ATP molecules generated per glucose molecule), aerobic glycolysis enhances the ability of the cell to proliferate. Efficiency is only important when resources are scarce. In a glucose rich environment, 2 ATP molecules per glucose will work just fine, and allows more of the glucose, along with the amino acid glutamine, to provide the structures necessary to make additional tumor cells. This primitive, yet streamlined, tumor metabolism allows abundantly available glucose and glutamine to supply the biochemical needs of cell growth and division. Many tumor cells over-express glucose transporters, particularly GLUT1 to increase intake of glucose. Ascorbic acid, and especially oxidized ascorbic acid (dehydroascorbic acid) is similar in molecular shape to glucose, and can enter cells through these membrane transport channels. Not only does this disrupt the supply of glucose to the tumor cell, it also allows increased vitamin C concentrations within the cell where it can cause epigenetic effects including increasing TET enzyme activity, re-expression of tumor suppressor genes, or cause cell death through metabolic disruption. Depletion of intracellular glutathione leads to inactivation of glyceraldehyde 3-phosphate dehydrogenase and inhibition of glycolysis. In the setting of high vitamin C concentrations, the reliance of some tumor cells on aerobic glycolysis becomes their "Achilles' heel". [15]

In recent years, cell culture studies and human clinical trials have confirmed that tumor cells with KRAS and BRAF mutations can be selectively killed by appropriate doses of vitamin C. [16] KRAS and BRAF mutations are common in solid tumors, especially pancreatic, colon, and lung cancers. Synergistic effects have been seen by combining vitamin C with some chemotherapy drugs, radiation treatment, or in combination with a fasting-mimicking diet. [17-23] Mark Levine, Channing Paller, Tami Tamashiro, Thomas Luechtefeld and Amy Gravell recently reviewed 53 cancer clinical trials involving IV and/or oral vitamin C. [15] These trials give a clear signal of safety when patients with glucose 6 phosphate dehydrogenase (G6PD) deficiency are excluded from high dose IVC administration. Most studies were small, and involved a wide variety of late stage cancers. Nonetheless, encouraging signals were seen, including a few patients surviving years later eventually dying of causes other than cancer. Studies involving pancreatic ductal adenocarcinoma (PDAC) show a median survival following diagnosis of 3.5 months untreated, 6.7 months when treated with gemcitabine, 8.5 - 13 months when treated with gemcitabine and nab-paclitaxel, and 15.1 months when IVC with or without gemcitabine was used. [17,24] It is likely that with refinement of dosing and route of administration, earlier intervention, and improved knowledge of which tumors are most susceptible to high dose vitamin C therapy, more consistent positive results will be seen.

Three promising active clinical trials:

A Phase II Trial of Pharmacological Ascorbate, Gemcitabine, and Nab-Paclitaxel for Metastatic Pancreatic Cancer (PACMAN 2.1; University of Iowa Holden Comprehensive Cancer Center) [25]

A Phase II Study of High Dose Vitamin C Intravenous Infusion in Patients with Resectable or Metastatic Solid Tumor Malignancies (Weill Cornell Medicine, NYC) [26]

To download an informative description of "IV Vitamin C for Cancer Care", please click https://riordanclinic.org/wp-content/uploads/2017/09/IVChandout.pdf. (Riordan Clinic, Kansas, >250,000 IVC treatments provided) [27]

Selenium

Selenium is a micronutrient essential for human health. There are 25 human selenoproteins known to be involved in numerous functions throughout the body, including brain, blood vessel, heart, and immune system health. These proteins perform diverse functions including antioxidant and redox recycling, gene "proof-reading", vitamin D metabolism, and hemostasis. Like vitamin C, even if there were no direct tumor effect of selenium, it would be an important tool in the battle for wellness and against cancer. [28-31]