Vitamin C and Cancer: Forty-Five Years of Data and Propaganda and What it Means for 2022 and Beyond

Modern Ignorance and Ancient Wisdom: Part III

I wrote this lay article about five years ago. I thought it would be interesting to share it now from the perspective of what has gone on in the covid pandemic the past two years.

In retrospect, you will be able to identify several hurdles that have always needed to be overcome in conventional, allopathic, “Big Oil” medicine, including financial incentives, epistemological weaknesses, and bunkered mentalities.

Without further ado:

Introduction

Nearly 80% of alternative clinics use large doses intravenous vitamin C (ascorbate) for a variety of health conditions including cancer. (1)  The practice dates back to the 1940s, when Dr. Frederick Klenner used it to treat a variety of infectious diseases.   

High dose intravenous ascorbate is now making inroads in relatively mainstream “integrative” oncology clinics after being neglected for nearly a half century, because cancer patients who are regularly treated with it experience fewer side effects such as fatigue, nausea, pain, vomiting, and appetite loss.  They also have better performance status, better quality of life, and longer survival. (2-4) 

The mainstream oncology community is still relatively opposed to ascorbate, however.  There are a variety of reasons, but chief among them are:

• The belief that alternative therapies will steer people away from conventional treatment.

• The belief that alternative therapies will interfere with chemotherapy, because ascorbate is an anti-oxidant. 

The problem with the second line of reasoning is that pharmacological doses of this vitamin are not antioxidant: they are pro-oxidant, and Vitamin C may offer lengthened survival to terminal cancer patients that have exhausted their conventional options.  

Let’s look at all of this in more detail.

Evidence for Use of High-Dose IV Vitamin C 

A landmark study was published in 1976 by Linus Pauling (Nobel Prize winner in chemistry, 1959) and his colleague Ewan Cameron.  This study demonstrated that 10 g. intravenous ascorbate per day for 10 days, followed by 10 g. oral vitamin C per day thereafter, resulted in a two- to seven-fold increase in survival in 100 terminal cancer patients, depending on the type of cancer. (5)

Each of these 100 patients was considered untreatable and “totally hopeless” by at least two physicians.  In the modern day this is what we call terminal cancer.  In this 1976 study, survival time across all cancers was more than 210 days for those treated with vitamin C, compared to only 50 days for the untreated matched controls.  Because the study wasn’t blinded, and in order to ensure that these results were real, Pauling and Cameron retrospectively had a colleague select ten matched controls for each treated patient.

Because the result was received with skepticism, they published a new study in 1978, in which they discarded the original 1000 control patients from the study and re-analyzed the original treatment group of 100 patients with newly selected controls.  The mean survival time in the treated group was found to be 300 days more than the matched controls this time, an increase of 90 days on average. (6)

Vitamin C was shown to perform even better than in the first study. (!)

This seems like powerful evidence in favor of using high-dose intravenous ascorbate, and the doses administered are more than 100 times the FDA’s Recommended Daily Allowance.  

What happened? 

These two studies created a storm of controversy in the scientific community.  Shortly thereafter, two more studies were conducted at the Mayo Clinic attempting to replicate these results. (7, 8)  Those studies resulted in Vitamin C being dismissed as a cancer treatment.  Why?

The authors found no difference in symptoms or survival between treatment and control groups using 10 g. vitamin C for treatment.  However, there is one very crucial difference between these two sets of studies.  The cancer patients in the Mayo Clinic study did not get the preliminary 10 days of intravenous treatments: they received only oral vitamin C.

Many researchers now believe this is a critical distinction. (9, 10)    Studies performed by Mark Levine and colleagues at the National Institutes of Health have shown that ascorbate administered intravenously can cause plasma levels 100 times higher than that achievable by the same dose administered by mouth. (11-15)      

Second, new studies demonstrate that at such high doses, ascorbate does not act as an antioxidant.  It acts a pro-drug to deliver hydrogen peroxide to cancer cells.  First, let’s look at a bit more additional evidence that ascorbate is an effective cancer treatment.

More Detective Work: Vitamin C Levels and Survival

Pauling and Cameron observed that cancer patients are significantly depleted of ascorbate, and that this depletion substantially increases their requirements. (5)  

Cancer patients who are deficient in ascorbate prior to therapy also achieve lower plasma levels post-infusion. (16)

When a patient has higher inflammation or tumor burdens (as measured by CRP or tumor antigen levels) they will achieve lower plasma levels after receiving intravenous ascorbate. (16)

Patients with metastatic tumors also achieve lower post-infusion plasma levels of ascorbate than patients with localized tumors. (16)

Higher tumor ascorbate levels are correlated to increased length of survival in colorectal cancer patients. (17)

The greater the burden of infection or toxins, the more quickly one will deplete stores of ascorbate.  One of the foremost experts in clinical applications of ascorbate, Dr. Thomas Levy, has noted that he must use more ascorbate today to achieve the same effect in patients when compared to the amounts Dr. Klenner used for the same health problems in the 1940s.  He believes this is because people are more nutritionally depleted today and more exposed to toxins which rapidly eliminate stores of ascorbate. (18)

Cameron has also pointed out that the frequency of dosing is important. (19)  The Cameron/Pauling 1976 study patients used ascorbate on a daily basis. 

One high profile clinical study carried out by Levine and colleagues showed that the combination of IV ascorbate with two chemotherapies inhibited ovarian cancer in mice more than the chemotherapy alone.  The ascorbate also reduced chemotherapy-associated toxicity in human patients with ovarian cancer, and it increased the amount of time until they relapsed back into cancer. (13) Similar results have been seen in pancreatic cancer patients. (20)

Although ascorbate usually simply slows the growth of the cancer, in some rare cases remission can actually occur.  Pauling and Cameron noted that around 10% of the terminal cancer patients treated with ascorbate lived an unusually long time of several years or more.

Why Aren’t High Dose Vitamin C IVs for Cancer Patients Mainstream? 

It’s pretty simple.  First, administering high doses of vitamins now has a tainted association with “alternative medicine” due to its supposed de-bunking by the Mayo Clinic studies.  Not even a chemistry Nobel Prize Winner like Linus Pauling can escape accusations of quackery (just do a brief web search for his name and Vitamin C).

Second, while high dose IV ascorbate isn’t usually a cure, it seems a bit unbelievable to the medical profession that something simple and non-technological could work so well at slowing the growth of cancer.  That’s partly because the mechanism wasn’t understood until well after the clinical studies were published, and the more we go down the rabbit hole, the more we realize we don’t know about the multiple biochemical mechanisms for how the treatment works.

Third, in the 1960s, the FDA started demanding that drugs not only be tested for safety, but also efficacy.  This is a major hurdle toward adoption of any new therapy: it can cost drug companies hundreds of millions of dollars just to conduct the studies that prove that the drugs work.  

Fourth, there’s simply no financial incentive to pour this type of research into ascorbate.  There’s nothing to be patented and thus, no financial reward to offset the amounts of money required to fund more studies. Studies will thus remain small and limited in number. (21) 

Finally, don’t discount the brainwashing and lack of attention to nutrition that physicians receive in their med school training. 

How Does High Dose IV Vitamin C Work?

Linus Pauling did not understand the mechanisms for why ascorbate was effective against cancer, and more than four decades later, we still have incomplete understanding.  This is a common thread in much medical history, from hand-washing to cancer therapy.  If doctors don’t understand how a treatment works, they will resist using it for decades.

Hydrogen Peroxide Generation 

Most people think of ascorbate as an antioxidant, but recent research shows that at high doses it is actually a pro-oxidant. (22, 23)  Large amounts of ascorbate in the bloodstream result in the creation of hydrogen peroxide through Fenton reactions when ascorbate encounters metal ions.  These reactions occur close to cell membranes. (24)

Because these reactions are localized in the extracellular space, and because cancer cells are much more sensitive to hydrogen peroxide than normal cells, this creates oxidative stress that cancer cells can’t handle nearly as well as normal cells. (13, 15, 20)

Cancer cells produce superoxide in greater than normal amounts, which can interact with the hydrogen peroxide produced via ascorbate, in order to create deadly hydroxyl radicals. (25, 26) 

Other mechanisms of action include:

• disrupting the cell cycle of division (27)

• causing apoptosis (a particular type of programmed cell death) (27)

• suppressing angiogenesis (the development of a blood supply to a tumor) (27)

• oxidizing intracellular-reduced glutathione in cancer cells, making them more susceptible to oxidative damage (13)

• disrupting disulfide bond formation in proteins (13)

• depleting cellular ATP (the cell’s source of energy) in the cancer cell (13, 26, 27)

• inducing DNA and protein damage in the cancer cell through hydroxylation and demethylation (13, 26) 

• increasing immunity, which is important for cancer patients. (26)

As you can see, there is an arsenal of biochemical mechanisms for how the single simple chemical, ascorbate, fights cancer.  It is difficult to obtain so many different effects in multiple biochemical pathways with a typical drug that has a single, defined mechanism of action. (Side note: as a parallel, it’s interesting to observe that there have been nearly 2 dozen potential antiviral mechanisms for ivermectin in this published paper. Ivermectin is an unusual pharmaceutical in this regard.)

Hindsight is 20/20.  Even though Linus Pauling didn’t understand why ascorbate worked, modern science is piecing the mechanisms together today, over 40 years later.  And as the research continues to unfold, it’s clear that it can be safely added to most conventional first line cancer treatments. (27)

Contraindications 

With proper patient screening, intravenous ascorbate is extremely safe and has minimal risk. (1, 3)  However, the following conditions may prevent you from using intravenous ascorbate: renal insufficiency, renal failure, undergoing dialysis, history of oxalate kidney stones, iron overload, glucose-6-phosphate dehydrogenase deficiency. (1, 3, 14) 

Further Note

It is here that I want to draw your attention to Colleen Huber NMD’s excellent short article “Re-imagine Healthcare” in which she unequivocally states:

Affirmative action for Pharma should end. The breadth of available medicine and doctors are suppressed by Pharma, with censorship of alternative voices, which is not a benefit to the public.

Dr. Huber is 100% correct. We must roll back the health tyranny of the last 100 years, and we will not stop until we get there.

References

1) Padayatty, S. J., Sun, A. Y., Chen, Q., Espey, M. G., Drisko, J., & Levine, M. (2010). Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects. PLoS ONE, 5(7), e11414. http://doi.org/10.1371/journal.pone.0011414

2)  Fritz H, Flower G, Weeks L, Cooley K, Callachan M, McGowan J, Skidmore B, Kirchner L, Seely D. 2014. Intravenous Vitamin C and Cancer: A Systematic Review.  Integr Cancer Ther. 13(4):280-300. doi: 10.1177/1534735414534463

3) Violet, P.-C., & Levine, M. (2017). Pharmacologic Ascorbate in Myeloma Treatment: Doses Matter. EBioMedicine, 18, 9–10. http://doi.org/10.1016/j.ebiom.2017.03.014

4)  Carr, A. C., Vissers, M. C. M., & Cook, J. S. (2014). The Effect of Intravenous Vitamin C on Cancer- and Chemotherapy-Related Fatigue and Quality of Life. Frontiers in Oncology, 4, 283. http://doi.org/10.3389/fonc.2014.00283

5) Cameron E, Pauling L. 1976. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A.73:3685-3689.

6) Cameron E, Pauling L. 1978. Supplemental ascorbate in the supportive treatment of cancer: Reevaluation of prolongation of survival times in terminal human cancer.  Proc Natl Acad Sci U S A. 75(9): 4538–4542.

7)  Creagan ET, Moertel CG, O'Fallon JR, 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;301:687-90.

8)  Moertel CG, Fleming TR, Creagan ET, et al. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med 1985;312:137-41.

9)  Levine, M., Espey, M. G., & Chen, Q. (2009). Losing and finding a way at C: New promise for pharmacologic ascorbate in cancer treatment. Free Radical Biology & Medicine, 47(1), 27–29. http://doi.org/10.1016/j.freeradbiomed.2009.04.001

10)  Padayatty SJ, Levine M. 2000. Reevaluation of ascorbate in cancer treatment: emerging evidence, open minds and serendipity. J Am Coll Nutr. 19(4):423-5.

11)  Levine, M., Padayatty, S. J., & Espey, M. G. (2011). Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries. Advances in Nutrition, 2(2), 78–88. http://doi.org/10.3945/an.110.000109

12)  Cieslak, J. A., & Cullen, J. J. (2015). Treatment of Pancreatic Cancer with Pharmacological Ascorbate. Current Pharmaceutical Biotechnology, 16(9), 759–770.

13)  Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. Sci Transl Med. 2014. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. 6(222):222ra18. doi: 10.1126/scitranslmed.3007154.

14)  Padayatty, S. J., Riordan, H. D., Hewitt, S. M., Katz, A., Hoffer, L. J., & Levine, M. (2006). Intravenously administered vitamin C as cancer therapy: three cases. CMAJ : Canadian Medical Association Journal, 174(7), 937–942. http://doi.org/10.1503/cmaj.050346

15)  Park, S. (2013). The Effects of High Concentrations of Vitamin C on Cancer Cells. Nutrients, 5(9), 3496–3505. http://doi.org/10.3390/nu5093496

16)  Mikirova, N., Casciari, J., Riordan, N., & Hunninghake, R. (2013). Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients. Journal of Translational Medicine, 11, 191. http://doi.org/10.1186/1479-5876-11-191

17)  Kuiper, C., Dachs, G. U., Munn, D., Currie, M. J., Robinson, B. A., Pearson, J. F., & Vissers, M. C. M. (2014). Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreased Hypoxia-Inducible Factor-1 Activation in Human Colorectal Cancer. Frontiers in Oncology, 4, 10. http://doi.org/10.3389/fonc.2014.00010

18)

19)  Cameron E. 1991. Med Hypotheses. Protocol for the use of vitamin C in the treatment of cancer. 36(3):190-4.

20)  Cieslak, J. A., & Cullen, J. J. (2015). Treatment of Pancreatic Cancer with Pharmacological Ascorbate. Current Pharmaceutical Biotechnology, 16(9), 759–770.

21)  Hoffer, L. J., Robitaille, L., Zakarian, R., Melnychuk, D., Kavan, P., Agulnik, J., … Miller, W. H. (2015). High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial. PLoS ONE, 10(4), e0120228. http://doi.org/10.1371/journal.pone.0120228

22)  Levine, M., Padayatty, S. J., & Espey, M. G. (2011). Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries. Advances in Nutrition, 2(2), 78–88. http://doi.org/10.3945/an.110.000109

23)  Levine M, Daruwala RC, Park JB, Rumsey SC, Wang Y. 1998. Does vitamin C have a pro-oxidant effect? Nature. 17;395(6699):231; author reply 232.

24)  Chen, Q., Espey, M. G., Krishna, M. C., Mitchell, J. B., Corpe, C. P., Buettner, G. R., … Levine, M. (2005). Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proceedings of the National Academy of Sciences of the United States of America, 102(38), 13604–13609. http://doi.org/10.1073/pnas.0506390102

25)  McCarty, M. F., & Contreras, F. (2014). Increasing Superoxide Production and the Labile Iron Pool in Tumor Cells may Sensitize Them to Extracellular Ascorbate. Frontiers in Oncology, 4, 249. http://doi.org/10.3389/fonc.2014.00249

26)  Ploumakis A, Coleman ML. 2015. OH, the Places You'll Go! Hydroxylation, Gene Expression, and Cancer. Mol Cell. 4;58(5):729-41. doi: 10.1016/j.molcel.2015.05.026.

27)  Parrow, N. L., Leshin, J. A., & Levine, M. (2013). Parenteral Ascorbate As a Cancer Therapeutic: A Reassessment Based on Pharmacokinetics. Antioxidants & Redox Signaling, 19(17), 2141–2156. http://doi.org/10.1089/ars.2013.5372