Redox therapy
Encyclopedia
Redox therapy is an unproven alternative cancer treatment that aims to treat cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 with redox
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

 chemical agents, usually given through the diet. This form of treatment involves the use of high doses of antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...

 chemicals, especially vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

 (as nutritional ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...

 or more usually intravenous sodium ascorbate
Sodium ascorbate
Sodium ascorbate is a more bioavailable form of vitamin C that is an alternative to taking ascorbic acid as a supplement. The molecular formula of this chemical compound is C6H7NaO6...

), but also lipoic acid
Lipoic acid
Lipoic acid , also known as α-lipoic acid and Alpha Lipoic Acid is an organosulfur compound derived from octanoic acid. LA contains two vicinal sulfur atoms attached via a disulfide bond and is thus considered to be oxidized...

, vitamin K3 and coenzyme Q10, attempting to kill cancer cells while leaving healthy cells alive. Much of the research in this area follows the work of Linus Pauling
Linus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...

, who was an early advocate of this idea.

However, the main way in which it is suggested that vitamin C (and other antioxidants) kills cancer cells is, paradoxically, by acting as a pro-oxidant
Pro-oxidant
Pro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...

. In the redox cycle in cancer cells, vitamin C cycles between ascorbate and dehydroascorbate. In this process, hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

 is produced within the cell. Cancer cells, unlike other cells, have low amounts of antioxidant enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s, notably catalase
Catalase
Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it catalyzes the decomposition of hydrogen peroxide to water and oxygen...

. In a healthy cell, catalase would convert peroxide to oxygen and water. However, in a cancer cell, the peroxide is thought to build up to toxic levels and kill the cell.

Some types of cancer cells have a much higher uptake of vitamin C than other cells. Vitamin C is structurally similar to glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 and can be transported by glucose pumps in cells, and cancer cells have a higher glucose uptake than other cells.

While levels of vitamin C in the blood are high enough to kill some cancers, vitamin C can be received orally, most cancers require, according to proponents of the therapy, intravenous injections of up to 100g of sodium ascorbate per day, at spaced intervals.

Clinical trials

Mayo-Moertel studies

While ascorbate treatments have been proposed by many professionals over a period of decades, it is not considered medically orthodox. This is mainly due to a series of studies conducted in the late 1970s in response to Linus Pauling's vitamin C claims for Ewan Cameron's cancer patients. Moertel et al. of the Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...

 concluded that there was no statistically significant difference in survival rate between cancer patients briefly given 10 g daily oral doses of vitamin C, mostly before or after chemotherapy, and those given a placebo instead of oral vitamin C. Such was the reputation of the Mayo that Moertel's studies, using vastly different, more conventional chemotherapy protocols, became considered the definitive negation of vitamin C cancer treatment by many physicians for a generation.

Proponents of the treatment, however, point out that the Moertel results do not show that vitamin C is ineffective against cancer. They point out that the dose given was oral, not intravenous (uptake of vitamin C from oral dosage is very low), of short duration (averaging 72 days rather than lifelong, roughly 2 years more) stopped the vitamin C abruptly (generally bad) after which death rates rose, used a different oral form (dry AA caps vs neutralized AA-DHA-sorbitol solution) and that the Mayo patients died after stoppage of vitamin C usually on or after chemotherapy. The ascorbate monitoring was poor and compliance controls of outpatient treatment were flawed, despite Ewan Cameron's specific request to Moertel for better monitoring. Moertel (1985) tested only 6 of 49 placebo patients for a very high threshold of urinary residuals of ascorbate spillage, over 550 mg/day. This urinary threshold might roughly correspond to 2g-4g/day in healthy patients or about 8+g/day in less severe cancer cases vs ~0.06g/day intake (RDA then) assumed with a placebo. Still one of only six placebo "controls" measured higher than this threshold, belatedly dismissed as only a potential measurement interference. In one of Klenner's rare comments on cancer, intravenous administration of 17g/day ascorbate for 92 days yielded no measurable urinary residual in a severe cancer case. The Moertel (1985) tests were poorly analyzed in terms of radically changing test conditions (initial delays, brief vitamin C; abrupt stop & repeated chemo) and quality of life improvements.

Moertel's oral dosage - less than ten grams - is far lower than doses one would expect to be cytotoxic. Note that ten grams per day administered intravenously might well lead to increased expected lifetime according to proponents. Typical redox therapies today range from 20g to over 100g IV vitamin C daily initially, sometimes with nontoxic adjuvants (e.g. bindweed extract, alpha lipoic acid or the menaquinone-4 form of vitamin K2). Oral adjuvant vitamin therapies are typically 12g to bowel tolerance (40g-200g) of vitamin C daily plus very high potency vitamins, special nutrients and mineral supplementation. Oral uptake of vitamin C may be increased through the use of liposomic preparations.

Other issues

Many physicians have also been under the impression that the work of Mark Levine at the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

 which set the current US RDA for vitamin C showed that the blood becomes saturated with vitamin C at fairly low doses, and thus higher doses would just be excreted.

However, many have argued that these studies actually used the word 'saturated' in an incorrect and misleading way, and it has also been pointed out that they did not take the relatively short elimination half life of vitamin C in the body into account. In 2002, Drs. Michael J Gonzalez and Jorge R Miranda-Massari provided preliminary evidence that vitamin C can be used as effective tumor cell growth inhibitor. Later, Levine himself, in 2005, headed a study which concluded that vitamin C was toxic to cancer cells in vitro, and that it was an extremely promising treatment.

Michael J Gonzalez and Jorge R Miranda-Massari recently reviewed 25 years of ascorbate therapy indicating its potential as a future treatment.

Proponents and critics have yet to produce prospective, double blind, randomized controlled trials of high dose antioxidant formulas that decisively settle the efficacy claims.
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