Vitamin C and Cancer, Applications in Oncology

By on March 10, 2018

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 and its 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 (to bowel tolerance) to fight off infections such as the common cold. Some integrative physicians use mega doses (5-100g) administered through an intravenous (IV) route in 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? This article attempts to answer these key questions, examine the evidence and resolve any remaining confusion. The goal is that both vitamin C devotees and skeptics will have a better understanding of how vitamin C can impact cancer metabolism and how it may be safely and effectively applied in integrative cancer care.

A History of Vitamin C
Vitamin C has a broad spectrum antioxidant function with the ability to protect cell structures and DNA from free radical damage. It particularly has a leading antioxidant role in the intercellular space, surrounding each cell. Its also has the ability to regenerate and optimize other key antioxidants such as vitamin E. Vitamin C is a water soluble vitamin that is 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 the possibility for overdose through oral ingestion. Humans are one of the few mammals that are not able to produce vitamins C. We rely on dietary intake to maintain levels. While scurvy rarely occurs anymore many people with low dietary intakes of fruits and vegetables have suboptimal levels of vitamin C. In fact patients with advanced cancer have been shown to have very low levels of vitamin C.

Beginnings of Vitamin C and Cancer
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 that did not receive treatments. The initial excitement in the medical community was short lived when a follow up study by the Mayo clinic failed to show any benefit. However, the key difference was that the mayo clinic study only used oral doses while the initial studies used oral and IV vitamin C. Ever since the failure of the mayo clinic study vitamin C has been considered controversial and inconclusive in the treatment of cancer. In the last 30 years there have been hundreds of articles published on use of vitamin C in cancer therapy. It remains one of the safest and most commonly used natural chemotherapeutic agents.

A Dual Role in Treatment
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. When it comes to cancer prevention, it has already been mentioned that 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 2g) and is achievable by dietary intake or oral supplementation.

The second mechanism of action is actually a pro-oxidant effect. Doses above 15g have been shown to have a “pro-oxidant” effect by generating hydrogen peroxide, which in turn selectively destroys cancer cells. High doses of vitamin C are preferentially delivered to the areas surrounding the tumor because the vitamin molecule looks similar to a sugar molecule and cancer cells have an increased demand for sugar to fuel its 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. While still not confirmed, one proposed idea on why cancer cells are particularly vulnerable to hydrogen peroxide is that they don’t have the enzyme catalase to break it down, while healthy cells do.

The paradoxical pro and anti-oxidant roles of vitamin C really create a large degree of confusion for many traditional oncologists and conventional scientists. It is further complicated by the many other effects vitamin C has in the body, especially in cancer treatment. 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). A recent study also found high dose vitamin C reduced C-reactive protein levels and pro-inflammation cytokines in cancer patients, which in turn had positive effects on tumor markers (Mikirova N et al, Transl Med. 2012, Sept).  There are a number of other distinct benefits of vitamin C in relation to cancer treatment such as improved response and reduced side effects during chemotherapy and the promotion of collagen formation in the extracellular space to prevent the spread of cancer.

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-tumor action or a supportive, antioxidant function. To achieve higher these higher anti-cancer levels, IV doses of 25-50g are required. Intravenous administration of vitamin C achieved a 50-150 fold greater blood level compare to oral supplementation. Oral supplementation is insufficient due to very limited absorption in the digestive tract.

Vitamin C (and in turn hydrogen peroxide) levels peak within 30mins after IV administration and then return to normal within 24 hours. 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 the fear of interactions. Most practitioners 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 tumor markers and progression.

A number of review papers and case studies by integrative cancer physicians and researchers have reported improved cancer survival times, quality of life and even tumor regression in some cases after weekly IV treatments done consistently over 12 months or longer. 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 50% positive responder rate. 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. 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 damaging to healthy cells, therefore reducing unwanted side effects. An emerging theory is that antioxidants do not interfere but rather compliment the anti-cancer effect of chemo and radiation and help promote the death of cancer cells (apoptosis). 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, Cautions and Conclusions  
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. 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 especially in high dose therapy. A trained physician should test liver and kidney function plus an enzyme called Glucose-6-phosphate dehydrogenase (G6PD). If you are deficient in this enzyme or have poor liver and/or kidney function then you may not be a good candidate for high dose vitamin C therapy.

Vitamin C is a commonly used vitamin therapy in alternative and complementary cancer treatment. Dietary and oral supplemental are encouraged for cancer prevention. Fruits and vegetables that are good sources of vitamin C include red bell peppers, black currents, kale, kiwi, guava and oranges. These dietary sources are a superior source of vitamin C since they also contain other phytonutrients and antioxidants that increase the effectiveness of vitamin c in the body.  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, quality of life and works synergistically with conventional such chemotherapy. Vitamin C is one of the most studied, effective and safest natural treatment options for cancer. To harness the 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 to fully understand how vitamin C work and confirms its clinical benefits there is a large body of evidence making it a safe and effective vitamin that can play a major role as part on an integrative cancer treatment plan.

Paul Hrkal, ND is a board certified Naturopathic physician and is an active member of the Canadian and Ontario Associations of Naturopathic doctors. He also is a member of the Oncology Association of Naturopathic Physicians.  Hrkal is an expert in nutrition and supplemental treatments and has additional training and certification in intravenous and injection therapy. He currently is a medical advisor for Advanced Orthomolecular Research and maintains a clinical practice in Mississauga. Visit www.paulhrkalnd.com and www.mypurebalance.ca 

References:

1) De Tullio, M. C. (2010) 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.

 

About Charleen Wyman

One Comment

  1. William Whitney

    April 16, 2014 at 6:11 pm

    Dear Editor;

    Thanks for the article on vitamin C and cancer. But I must say, for a champion of natural care, Dr. Hrkal is quite timid about getting out his message.
    Ascorbate may be the most important health discovery of the 20th century.

    The following points should be clarified:

    Vitamin C is not really a “vitamin” at all but a natural nutrient, that all animals and green plants manufacture. Man has 3 out of 4 of the enzymes that other animals used to make their own ascorbate from glucose. This is extremely strong evidence that man’s ancestors manufactured their own ascorbate, but man lost that ability through a genetic flaw, a long, long time ago.
    Excess vitamin C is not just “excreted” but increases immune function and acts as an anti-oxidant to recharge other anti-oxidants, like vitamin E, before it leaves the body. This is the language of the medical establishment who want people to stop taking vitamin C.
    You should mention more facts. Cameron treated terminal cancer patients with 10g per day, patients that were already written off by the medical establishment and kept some alive for over 3 years. Normally they were expected to die in a few weeks or months.
    Talking about an “overdose” through oral ingestion of vitamin C is ridiculous. The therapeutic index for C is a very large number. The only way to take an overdose would be to choke yourself on a bottle full of powdered C.
    Dietary intake of vitamin C is not adequate and the doctor should certainly know this. The medical establishment says that Canadians are not even getting the RDA allowances, which are set ridiculously low to begin with. Our typical diet will never suffice to give us any more than maybe 350 mg per day, even if we ate plenty of raw, fresh fruit. Even ten times this much would not be as much as Pauling recommended. A goat, that weighs as much as a man, makes over 12,000 mg of C per day in its body.
    The truth with the Mayo experiment was that the medical establishment was angered by Pauling’s claims and were much relieved when Dr. Moertel at the Mayo clinic said (falsely) that the stuff didn’t really work. The journal that published it refused to publish Pauling’s comments about it until a year after the initial article. Even 20 years after Pauling died, doctors are still calling Pauling insulting names.
    If ascorbate is not the safest natural substance to consume, then what is the safest substance?
    The doctor names two main ways that C fights cancer. What about increasing the number of white blood cells and the phagocytic action of these cells in killing cancer cells? What about Cameron’s observation that C produced a fibrous net around a tumour and starved it to death, causing all the cancer to die at once? (Causing the patient to die of shock) How about Hickey and Saul’s book that says the cancer cells are killed in blood when it is saturated with C?

    W.G. Whitney
    St. Albert, Alberta

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