Redox therapy

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Redox therapy is an unproven but demonstrated treatment of cancer with redox agents, usually nutritionally. Redox therapy can be described as an antioxidant reacting with an oxidant-type free radical to produce a neutralized free radical and an oxidant.

This form of treatment involves the use of high doses of antioxidant chemicals, especially vitamin C (as nutritional ascorbic acid or more usually intravenous sodium ascorbate but also lipoic acid, Vitamin K3 and coenzyme Q10, to kill cancer cells while leaving healthy cells alive. Much of the research in this area follows from the pioneering work by double Nobel Prize winner Linus Pauling.

Proponents of this therapy claim that these treatments can be effective against cancer in multiple ways. Ki Won Lee and colleagues from the University of Seoul have described how vitamin C can enable cancer cells to receive the body's signals to stop growing - signals that normally healthy cells can receive, but cancer cells usually can't.

However, the main way in which it is suggested vitamin C (and other antioxidants) kills cancer cells is, paradoxically, by acting as an oxidant. In the redox cycle in cancer cells, vitamin C cycles between ascorbate and dehydroascorbate. In this process, hydrogen peroxide is produced within the cell. Cancer cells, unlike other cells, have low amounts of antioxidant enzymes, notably catalase. In a healthy cell, catalase would convert peroxide to oxygen and water. However, in a cancer cell, the peroxide quickly builds up to toxic levels and kills the cell.

Cancer cells have a much higher uptake of vitamin C than other cells. Vitamin C is structurally similar to glucose and can be transported by glucose pumps in cells, and cancer cells have a higher glucose uptake than other cells. As cancer cells rely on an oxidating environment to assist their growth and division, the ascorbate is converted into dehydroascorbate and thence to peroxide much more readily than in healthy cells.

While levels of vitamin C in the blood high enough to kill some cancers can be achieved orally, most cancers require, according to proponents of the therapy, intravenous injections of up to 100g of sodium ascorbate per day, at spaced intervals. Dr Robert Cathcart, one of the most prominent proponents of vitamin C treatment, reports that he has never cured cancer with oral (as opposed to intravenous) doses but may have prolonged life.

A simple, self-admininstered program of near maximum oral intake of vitamin C would be guided by bowel tolerance and inexpensive urinary spill measurements of ascorbate with normal precautions for stone formers.

[edit] 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 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.^[1][2][3] 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 K-2). 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 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.^[4] 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.^[5]

This treatment is still a controversial one, and needs further study before being accepted by the medical establishment, but there are an increasing number of doctors who are reporting remarkable effects with this treatment, suggesting that such further study would be beneficial. Drs Michael J Gonzalez and Jorge R Miranda-Massari recently reviewed 25 years of ascorbate therapy indicating its promise as a future treatment.^[6]

Prevention trials

Five large scale clinical trials involving inexpensive, synthetic anti-oxidants were undertaken in the 1990's. The first, the Chinese Cancer Prevention Study, published in 1993, did show a favorable result, a significantly reduced incidence of both gastric cancer and cancer overall. The others, the 1994 Alpha-Tocopherol ("[vitmain E]")/Beta-Carotene Cancer Prevention Study (ATBC) showed an increase in the rate of lung cancer among smokers taking betacarotene, and no effect with synthetic all racemic-alpha-tocopheryl acetate. The 1994 Beta-Carotene and Retinol (vitamin A) Efficacy Trial (CARET) showed a possible increase in lung cancer with antioxidants. The 1996 Physicians' Health Study I (PHS) showed no difference in cancer rates. The 1992-2004 Women's Health Study (WHS) showed no net benefit or harm from d-alpha-tocopheryl acetate supplementation every other day. ^[7] More recently in 2005 the HOPE-TOO trial showed that long term d-alpha-tocopheryl acetate supplementation showed no benefit over placebo. ^[8]

Prevention trials have little relevance to redox therapy. Typical antioxidants require a supply of free electrons to provide reducing potential which is made available by metabolism in healthy tissues. In stressed or sick tissues "antioxidants" can become oxidants if the supply of electrons is removed. Redox therapy is based on a supply of electrons from dynamic flow of ascorbate. None of the published clinical trials to date have incorporated an appropriate supply of vitamin C and therefore their relevance to redox therapy is scientifically questioned.^[9] Also, the claimed action of redox therapy in cancer involves an oxidation process and only selected antioxidants are cytotoxic.^[10] Finally the doses used in these studies are not in the range considered to be effective.

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

[edit] References

1. ^ Gonzalez M.J. Miranda-Massari J.R. Mora E.M. Guzman A. Riordan N.H. Riordan H.D. Casciari J.J. Jackson J.A. Roman-Franco A. (2005) Orthomolecular oncology review: ascorbic acid and cancer 25 years later, Integr Cancer Ther, 4(1), 32-44.
2. ^ Cameron E. Pauling L. (1993) Cancer and vitamin C, Camino Books, Philadelphia.
3. ^ Hoffer A. (2001) Vitamin C and Cancer, Quarry Health Books, Quebec, Canada.
4. ^  González MJ, Mora EM, Miranda-Massari JR. et al. Inhibition of Human Breast Carcinoma Cell Proliferation by Ascorbate and Copper. (2002) PR Health Sci J;21(1) 21-3.
5. ^ Chen, Q; Levine, M et al : Pharmacologic ascorbic acid concentrations selectively kill cancer cells (2005) Proc Natl Acad Sci USA Sep 12
6. ^ Gonzalez M.J. Miranda-Massari J.R. Mora E.M. Guzman A. Riordan N.H. Riordan H.D. Casciari J.J. Jackson J.A. Roman-Franco A. (2005) Orthomolecular oncology review: ascorbic acid and cancer 25 years later, Integr Cancer Ther, 4(1), 32-44.
7. ^  Antioxidants and Cancer Prevention: Questions and Answers from the National Cancer Institute
8. ^  HOPE-TOO: NCI Comment on Published Results