Vitamin C for Cancer Treatment

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Health Benefits and Applications – Oral and Intravenous

Vitamin C is one of the most well-known and widely used vitamins for the promotion of health. While many people consider vitamin C a natural “cure-all,” there is still some confusion when it comes to vitamin C’s effect on cancer and immunity. Much of the confusion stems from the wide range of vitamin C dosages suggested by various sources. Some people swear by large oral doses (up to bowel tolerance) to fight off infections such as the common cold. Some integrative physicians use megadoses (5 to 100 grams) administered through an intravenous (IV) route for cancer and microbial infection treatment protocols.

The exact mechanism of vitamin C’s anti-cancer effect has also been debated. Is it an antioxidant or does it have a direct cancer killing action? Can it do both?

Vitamin C History and Background

In the 1920s, Albert von Szent Györgyi discovered that vitamin C was able to prevent and cure scurvy. He later went on to win the prestigious Nobel Prize for his research on the function of vitamin C in human metabolism. Vitamin C plays a pivotal role in activating enzymes that produce collagen, a key structural protein in blood vessels, skin and other tissues. Its also is required for the activation of neurotransmitters and carnitine for energy production. This why the symptoms of scurvy are fatigue, neurological dysfunction, and, more commonly, bleeding gums and easy bruising due to blood vessel fragility.(1)

In addition, vitamin C has a broad spectrum antioxidant function with the ability to protect cell structures and DNA from free radical damage.(1) It particularly has a leading antioxidant role in the intercellular space surrounding each cell. It also has the ability to regenerate and optimize other key antioxidants such as vitamin E.(2)
Vitamin C is a water soluble vitamin scientifically known as ascorbic acid (reduced form). Its absorption is relatively efficient at 70-90% for low doses. Any excess vitamin C that is not absorbed in the digestive tract is excreted. This prevents overdose by oral ingestion. Humans are one of the few species of animal that are not able to produce vitamins C. We rely on dietary intake to maintain stores. While scurvy rarely occurs anymore, many people with low dietary intakes of fruits and vegetables have sub-optimal levels of vitamin C. In fact, cancer patients are often shown to have very low levels of vitamin C.(3)

History of Vitamin C in Cancer Treatment

In the 1970s, doctors Ewan Cameron, Nikolaas Campbell, and Linus Pauling were the first to report the use of high dose vitamin C to treat terminally ill cancer patients. They found that IV and oral treatments increased survival times compared to those patients who did not receive treatments.(4) Since the initial studies by Cameron and Pauling, the exact anti-cancer mechanism of vitamin C has been studied and clarified. Considering the various functions of vitamin C in the human body, two distinct modes of action have been identified when it comes to cancer. For prevention, vitamin C has antioxidant effects that protect key cellular structure and functions. It also prevents the formation of dangerous cancer-causing compounds. The dose to achieve an antioxidant effect is low (under 2 grams) and is achievable by dietary intake or oral supplementation.

The second mechanism of action is actually a pro-oxidant effect. Doses above 15 grams are proven to have a “pro-oxidant” effect by generating hydrogen peroxide, which in turn selectively destroys cancer cells.(6) High doses of vitamin C are preferentially delivered to the areas surrounding the tumour because the vitamin molecule looks similar to a sugar molecule and cancer cells have an increased demand for sugar to fuel their unregulated growth. When in the area surrounding the cells, the vitamin C molecule reacts with a metal ion such as iron or copper and forms a hydrogen peroxide molecule that damages the cancer cell. (7)

Over and above the pro- and antioxidant effects, vitamin C has been shown to regulate cell division via the p53 protein (essential in cancer treatment and prevention), improve immune response, and reduce the severity of cachexia (weight loss due to cancer).(7) A recent study also found that high dose vitamin C reduced C-reactive protein levels and pro-inflammation cytokines in cancer patients, which in turn had positive effects on tumour markers.(8) Other distinct benefits of vitamin C in relation to cancer treatment include improved response and reduced side effects during chemotherapy, and the promotion of collagen formation in the extracellular space to prevent the spread of cancer.(2)

Expectations, Outcomes and Dosage

We have established that vitamin C has benefit in cancer treatment but the dosage and route of administration is essential to determine if it has a direct anti-tumour action or a supportive, antioxidant function.  The levels needed to achieve direct tumorcidal effects are at least 200-1000 micromol/L. (6,9) To achieve these higher anti-cancer levels, IV doses of 25-50 grams are required. 50 grams of IV vitamin C can achieve a plasma level of over 14,000 micromol/L.(9)  Oral supplementation is insufficient due to very limited absorption in the digestive tract. Plasma vitamin C levels peak after 200 mg of oral supplementation, and maximal oral dosing before loose stools occur is around 4 grams.(9) Oral absorption can be increased if doses are split up during the day, taken with a meal, or in a sustained released formula. Even when using the same 10 gram dose, intravenous administration achieved a 50-150 fold greater plasma vitamin C level compared to oral supplementation. (6,10)

Vitamin C (and in turn hydrogen peroxide) levels peak within 30 minutes after IV administration and then return to normal within 24 hours.(7) This makes the direct anti-cancer treatment effective for only a short period time and therefore frequent treatments are needed. The benefit of this is that other therapies can be used in short succession after vitamin C without fear of interactions. Most integrative oncologists recommend IV treatments once or twice a week, with oral supplementation on all the other days, for at least 12 months, with regular lab testing to assess tumour markers and progression.

A number of review papers and case studies by integrative cancer physicians and researchers have reported improved cancer survival times and quality of life, and even tumour regression in some cases, after weekly IV vitamin C treatments done consistently over 12 months or longer.(2,10) It is also important to note that vitamin C therapy may not work for everyone and for every type of cancer. The consensus among practitioners and from recent evidence is that there is a 50% positive responder rate.(11) It is always recommended to consult your Naturopathic doctor to see if vitamin C therapy is right for you.

Vitamin C With Chemo And Radiation

One of the most common concerns patients have is that they were told by their oncologist to stop all natural supplements, especially vitamin C, when on chemo or radiation. This caution is still based on the one dimensional, antioxidant-only, understanding of vitamin C. Since the primary mechanism of radiation and most chemotherapeutics is to damage the cancer through a pro-oxidant mechanism, theoretically high dose antioxidant supplementation will counteract the chemo and radiation – making is less effective. Recent studies have actually found that vitamin C therapy works synergistically with chemotherapies in various cancers.(12,13)

Just to be conservative, most integrative doctors do not use vitamin C during active chemo or radiation treatment. They will often do high dose, IV treatments leading up to and after conventional treatments. Low dose IV and oral vitamin C treatments are sometimes used between chemo treatments to reduce side effects and promote recovery. I want to emphasize that you should only do this under the supervision of a trained practitioner.

Despite the ultra conservative stance of conventional medicine, vitamin C has also been shown to be safe with the majority of chemotherapeutic agents and it improves quality of life by preventing damage to healthy cells, therefore reducing unwanted side effects.(14)  An emerging theory is that antioxidants do not interfere but rather complement the anti-cancer effect of chemo and radiation and help promote the death of cancer cells (apoptosis).(15)  The safest and most effective approach is to work with a naturopathic physician with experience in integrative oncology to find a treatment plan that is safe and effective for you.

Safety and Cautions

A recent survey of integrative healthcare practitioners using IV vitamin C found no substantial adverse effects over two years of use in almost 10,000 patients. The most common side effects found were fatigue and vein irritation.(16)  While vitamin C stands as one of the best and safest natural treatment options for cancer, there are a number of key points to consider. Before high dose treatment, a test for an enzyme called Glucose-6-phosphate dehydrogenase (G6PD) should be completed. If you are deficient in this enzyme than you may not be a good candidate.

Another common concern is the formation of oxalate kidney stones, yet only a few cases have ever been reported in patients with poor kidney function.(17)   More recent studies found that vitamin C use prevented stone formation in most healthy people. Since most oxalate stones are formed in alkaline urine, and vitamin C acidifies the urine, it would seem that it counteracts the potential to form stones.(2)   To be safe, prospective patients should have their kidney function measured before the start of treatment.

Concurrent use of antioxidants such as green tea or glutathione should be avoided during or after high dose vitamin C therapy since it can reduce the pro-oxidant, anti-cancer mechanism. A recent study evaluated this interaction and found that using glutathione and vitamin C at the same time inhibited the cytotoxic effect of vitamin C alone and failed to provide further survival benefit.(18)   If you are undergoing high dose vitamin C therapy it is also important to supplement with oral vitamin C to maintain baseline level between treatments. A trained physician can help you identify if vitamin C therapy is a safe treatment option for you.

Conclusions

Vitamin C is a commonly used vitamin therapy in alternative and complementary cancer treatment. Dietary and oral supplementation are encouraged for cancer prevention. Fruits and vegetables that are good sources of vitamin C include red bell peppers, black currants, kale, kiwi, guava and oranges. These dietary sources also contain other phytonutrients and antioxidants that increase the effectiveness of vitamin C.  While oral doses can correct deficiencies and maintain antioxidant levels within the body, IV infusions are required to reach pro-oxidant, anti-cancer plasma levels. The evidence suggests that vitamin C improves cancer survival times and quality of life, and works synergistically with conventional treatments such as chemotherapy.

To harness maximum benefit, both oral and IV treatments are needed to take advantage of the wide range of anti-cancer effects. While more studies are needed, there is a large body of evidence proving that it is a effective vitamin that can play a major role in an integrative cancer treatment plan.


References

(1) De Tullio, M. C. The Mystery of Vitamin C. Nature Education 3(9):48
(2) González MJ, Miranda-Massari JR, Mora EM, Guzmán A, Riordan NH, Riordan HD, Casciari JJ, Jackson JA, Román-Franco A. Orthomolecular oncology review: ascorbic acid and cancer 25 years later. Integr Cancer Ther. 2005 Mar;4(1):32-44.
(3) Mayland CR, Bennett MI, Allan K. Vitamin C deficiency in cancer patients. Palliat Med. 2005 Jan;19(1):17-20.
(4) Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3685-9.
(5) Creagan et al. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med. 1979 Sep 27;301(13):687-90.
(6) Chen et al. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8749-54.
(7) Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A. 2008 Aug
(8) Mikirova N, Casciari J, Rogers A, Taylor P. Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J Transl Med. 2012 Sep 11;10:189.
(9) Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr. 2011 Mar;2(2):78-88.
(10) Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ. 2006 Mar 28;174(7):937-42.
(11) Anderson, Nadis, Standish. (2011, November). High dose ascorbic acid therapy the Bastyr experience. Poster session presented at the Society of Integrative Oncology, Clevland OH.
(12) Vollbracht et al. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo. 2011 Nov-Dec;25(6):983-90.
(13) Welsh et al.  Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol. 2013 Mar;71(3):765-75.
(14) Verrax J, Calderon PB. The controversial place of vitamin C in cancer treatment. Biochem Pharmacol. 2008 Dec 15;76(12):1644-52.
(15) Pizzorno 2008. Cancer – Integrative Naturopathic Support by Paul Reilly ND Lac. Textbook of Natural Medicine. P.549-71.
16) Padayatty et al.  Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One. 2010 Jul 7;5(7):e11414.
17) Lawton et al. Acute oxalate nephropathy after massive ascorbic acid administration. Arch Intern Med. 1985 May;145(5):950-1.
18) Chen P, Stone J, Sullivan G, Drisko JA, Chen Q. Anti-cancer effect of pharmacologic ascorbate and its interaction with supplementary parenteral glutathi-one in preclinical cancer models. Free Radic Biol Med. 2011Aug1;51(3):681-7

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