Vitamin C and Dose?

What is the proper dose of vitamin C? What is an actual low dose of vitamin C? What is an actual high dose of vitamin C? An even better question would be what is the actual right dose of vitamin C? A caveat for perspective. I am the Medical Director at An Oasis of Healing. We are a cancer healing center in Arizona. We treat patients with cancer and most of our patients have advanced cancer. It is in that context that we require the use of the high dosing discussed below. The inflammation, cytokine burst, that is being described in pneumonia associated with the current COVID19 is not too different than the inflammation seen in patients with cancer.

A recent media headline, that was more sensationalism than truth, highlighted the use of “massive” vitamin C dosing by a hospital for the treatment of the COVID19 virus in New York City. Interestingly, this article has since been removed. In this “massive” reality, the dose of intravenous (IV) vitamin C was only 1.5 grams every 6 to 8 hours given daily. This dosing followed that of the work published by Marik PE et al in 2017 in the study Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock. The same oral dose of vitamin C would be tolerated by most people and is in no way “massive” or even can be considered a high dose. I would call it a low dose or more appropriately—inadequate dose. This was just the use of sensationalism as click-bait to cloud an already contentious issue—the use of “alternative” therapies like IV vitamin C. That being said, the fact that this pulmonologist in New York City is using the IV vitamin C delivery to bypass the gastrointestinal system and the limiting factors it presents is excellent. My hats off to this doctor and this hospital for thinking outside the box to help patients.

Whatever the adjective that is given to describe the dose is not important. The right dose is the key. The right dose is what is most important. Whether that be an actual low IV dose of vitamin C like the story highlighted above or whether it is a true high dose of IV vitamin C with doses up to 300 grams IV over 24 hours by the fathers of high dose vitamin C, Dr. Frederick Klenner and Dr. Robert Cathcart in the treatment of tens of thousands of patients with viral infections, including pneumonia, encephalitis, and terminal cancer, the dose that provides the intended and desired effect is the goal. The desired effect is the target, the dose is the means to get there. Too low a dose will fail and too high a dose will lead to the potential for increase side effects, though that is limited.

A trip through the historical use of IV vitamin C helps to provide some insight into the dosing used by true pioneers, that include Nobel prize winners (Linus Pauling) to NASA flight surgeons (Robert Davis), in the medicinal use of IV vitamin C for advanced cancer and other illnesses. Also important, it provides some context and contrast to some of the current sensationalized adjectives, as highlighted above, used to highlight some of the dosings during this COVID19 pandemic. The physicians highlighted below include these IV vitamin C true pioneers: Dr. Frederick Klenner [1] [2] [3] [4], Dr Ewan Cameron [5] [6] [7], Dr. Linus Pauling [8] [9], Dr’s A. Murata/F. Morishige/H. Yamaguchi [10],  Dr. Abram Hoffer [11], Dr. Hugh Riordan [12] [13] [14], Dr. Robert Cathcart [15] [16] [17], and Dr. Richard Davis. Beyond this list, there are many other significant contributors to the use of vitamin C for the treatment of a wide-variety of illnesses.

 

Physican(s) Target IV Dose
Dr. Frederick Klenner Advanced cancer, wide variety of virus illnesses, pneumonia, autoimmune disease, encephalitis… Up to 300 grams
Dr. Ewan Cameron/Dr. Linus Pauling Terminal cancer 10 grams
Dr. Abram Hoffer Cancer 10 grams
Murata A, Morishige F, Yamaguchi H Terminal cancer 5-29 grams
Dr. Hugh Riordan Advanced cancer 50-75 grams
Dr. Robert Cathcart Advanced cancer, wide variety of virus illnesses, autoimmune disease… Up to 300 grams
Dr. Richard Davis Cancer Up to 300 grams

 

In contrast in recent published studies in sepsis/ICU patients [18], ongoing studies in China, and media highlighted use:

 

Focus of Treatment IV Dose Additional therapies
sepsis/ICU 1.5 grams IV every 6 hours Hydrocortisone, thiamine
COVID19 in China 24 grams IV every 6-8 hours None
COVID19 in New York City 1.5 gram IV every 6 hours Unknown

 

WHAT IS LOW DOSE?

This is a great question and one that needs to be answered.  But first, what is an inadequate vitamin C dose? When it comes to the treatment of cancer and other significant illnesses, any oral dose can be deemed inadequate beyond its use to supplement a primary IV vitamin C treatment program. Oral vitamin C can provide a short-lived spike through stomach absorption [19], but this falls far short of the minimum levels needed (discussed below) to destroy cancer cells. However, the addition of oral vitamin C to an IV vitamin C program can help provide an increase in plasma vitamin C before the big punch with IV vitamin C is started.

Back to what is a low dose? Any dose that does not achieve a therapeutic level of ascorbic acid (350 mg/dl—450 mg/dl) should be considered low-dose. This includes either the oral or IV routes. The 350–450 mg/dl is the therapeutic plasma vitamin C target described by Dr. Hugh Riordan. Oral dosing of vitamin C NEVER achieves the therapeutic window of 350—450 mg/dl of plasma ascorbic acid. This is in part due to the pharmacokinetics, the reduced bioavailability of oral vitamin C and the downregulation of the vitamin C receptors (SVCT) in the gut lining with the higher doses. Oral doses typically only reach plasma levels of 70-80 µM [20], compared to the > 20,000 µM [21] achieved through the IV route of delivery of vitamin C. That is a full 50-70 fold increase concentration of vitamin C with IV versus the oral route of delivery. Research has been shown that 30 grams [22] of IV vitamin C does not kill most cancer cells. For cancer, we know that doses of 1000 µM [23] of vitamin C is toxic to cancer cells. This is the floor threshold of desired vitamin C plasma concentration required for minimal effective anti-cancer treatment with vitamin C. Even with the newer liposomal vitamin C products available, only levels of 500 µM max on the best, but more reliably 200 µM [24] have been achieved, which is still far below the desired minimum of 1000 µM and light-years away from the +20,000 µM target range threshold. As stated in the conclusion of the article, Vitamin C pharmacokinetics: implications for oral and intravenous use [25], “Intravenous vitamin C may have a role in the treatment of cancer as a result of the plasma concentrations that can be achieved only by this route.”

What about IV vitamin C dose? Is there an IV vitamin C dose that would be considered a low dose? Absolutely! It is important to realize that IV administration of vitamin C does not de facto equal therapeutic dose. Any IV dose at 25 grams or less, I would consider being a low dose. This fits with the research that 30 grams of IV vitamin C does not kill most cancer cells [26]. From this study, it is clear that 30 grams will fall far below the 350-450 mg/dl therapeutic window.

WHAT IS HIGH DOSE?

Even with the historical journey above, it is hard to provide an accurate definition of what high dose IV vitamin C is. After all, it was the media headline that said 1.5 grams IV 3-4 x daily was “massive”. Based on our experience at An Oasis of Healing in treating advanced cancer and the historical studies of IV vitamin C in the treatment of cancer, viral illnesses, pneumonia, encephalitis highlighted above…the best definition of high dose IV vitamin C is a dose that achieves and sustains the most time in the therapeutic plasma window of 350-450 mg/dl. People that are sick, simply require higher doses of vitamin C compared to healthy individuals [27]. Dr. Riordan has shown doses of 50-75 grams IV can achieve this target. The lower IV vitamin C dose of 10 grams used in Dr. Cameron and Dr. Pauling’s studies doesn’t pass the mark of 30 grams highlighted above and plasma levels were not evaluated. Thus it is safe to say that the 10 grams is achieving sub 20 mM, but most likely achieving plasma concentrations > 1000 µM. Also, the probability of achieving the therapeutic target range with 300 gram IV vitamin C as performed by Dr. Klenner and Dr. Cathcart is unknown as well, for the same reason. Beyond the lack of testing to determine the exact vitamin C plasma concentration in older research, many other variables can affect the dose and the ability to achieve the targeted range, which will be highlighted below.

The better question is, what is the right dose of IV vitamin C? The right dose is; the dose that maximizes the direct cancer-killing effect (cytotoxicity), the dose that blocks the inflammation of autoimmune disease or the out of control inflammatory response of the cytokine burst found in COVID19 pneumonia, sepsis, and septic shock…The right dose is simply the dose the provides the desired, intended effect. There is no way to expect this to be the same for each individual. Just look, no 2 persons are alike, no 2 cancers are alike, and no 2 inflammatory conditions are alike. I think you get the picture. We are beautifully and wonderfully created unique. These differences are the sources of the potential variables that can affect IV vitamin C dose and the ability to achieve the therapeutic window. These variables include:

  • The health of the individual
  • The presence of disease
  • The status of vitamin C levels in the body before treatment
  • Smoking status
  • Amount of cancer in the body (called tumor burden)
  • Level of inflammation

The healthier the individual, the higher the vitamin C levels in the body will be and the lower the dose to achieve the higher plasma levels mentioned above. In contrast, the presence and amount of cancer and inflammation in the body results in significantly lower vitamin C levels and thus will require significantly higher doses of IV vitamin C to reach the targeted range of 350-450 mg/dl. Smoking [28] also significantly reduces the level of vitamin C in the body—just another reason to stop smoking.

A one-size-fits-all approach never works. The same applies to the use of IV vitamin C. High dose, low dose, massive dose…need not apply. Only, the dose for each individual that will achieve the intended anti-cancer effects, the anti-inflammatory effects, the anti-viral effects (including COVID19) is the right dose, whether low, high, or “massive”.

_____________________________________________

[1] Klenner FR. The role of ascorbic acid in therapeutics. (Letter) Tri-State Medical J. Nov 1955; 34.

[2] Klenner FR. Massive Doses of Vitamin C and the Virus Diseases. South Med J. Ap 1951;113(4):101-7. PMID: 14855098.

[3] Klenner FR. The Treatment of Poliomyelitis and Other Virus Diseases with Vitamin C. South Med J. July 1949; 3(7):209-214.

[4] Klenner FR. Observations on the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology. J Applied Nutrition. 1971; 23:3-4.

[5] Cameron, E., Pauling, L. & Leibovitz, B. Ascorbic acid and cancer, a review. Cancer Res. 1979;(39):663–81.

[6] Cameron E, Rotman D. Ascorbic acid, cell proliferation, and cancer. Lancet. 1972;1:542.

[7] Cameron E, Campbell A. The orthomolecular treatment of cancer, II: clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact. 1974;9:285–315.

[8] Cameron, E. & Pauling, L. Supplemental ascorbate in the supportive  treatment  of  cancer:  Prolongation  of  survival  times  in terminal human cancer. PNAS USA. 1976; (73):3685–9.

[9] Cameron E, Pauling L. 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. 1978;75(9):4538–4542. doi:10.1073/pnas.75.9.4538

[10] Murata A, Morishige F, Yamaguchi H. Prolongation of survival times of terminal cancer patients by administration of large doses of ascorbate. Int J Vitam Nutr Res Suppl. 1982;23:103-13.

[11] Hoffer A & Pauling L. Hardin Jones biostatistical analysis of mortality data for a second set of cohorts of cancer patients with a large fraction surviving at the termination of the study and a comparison of survival times of cancer patients receiving large regular oral doses of vitamin C and other nutrients with similar patients not receiving these doses. J of Orthomolecular Medicine. 1993;8:1547-167.

[12] Riordan H. D., Riordan N. H., Jackson J. A., Casciari J. J., Hunninghake R., Gonzalez M. J., et al. Intravenous vitamin C as a chemotherapy agent: a report on clinical cases. PR Health Sci. J. 2004;23:115–118.

[13] Riordan H. D., Casciari J. J., Gonzalez M. J., Riordan N. H., Miranda-Massari J. R., Taylor P., et al. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. PR Health Sci. J. 2005;24:269–276.

[14] Riordan, H. et al. Intravenous ascorbic acid: protocol for its application and use. PR Health Sci. J. 2003;(22):225–32.

[15] Cathcart R. Vitamin C in the treatment of Acquired Immune Deficiency Syndrome (AIDS).

Medical Hypothesis. Aug 1984;14(4):423-433.

[16] Cathcart R. A Unique Function for Ascorbate. Medical Hypothesis. May 1991;35:32-37.

[17] Cathcart RF. Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med Hypotheses. 1981;7:1359-76.

[18] Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock.

[19] Fonorrow O, Hickey S. Unexpected early response in Oral Bioavailability of Ascorbic Acid. Townsend Letter. March 13, 2020.

[20] Levine M, Conry-Cantilena C,  Wang  Y.  et al. Vitamin  C pharmacokinetics in healthy volunteers: Evidence for  a recommended dietary allowance. PNAS. 1996;93:3704–3709.

[21] Duconge J1, Miranda-Massari JR, Gonzalez MJ, Jackson JA, Warnock W, Riordan NH. Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate. P R Health Sci J. Mar 2008;27(1):7-19.

[22] Riordan NH, Riordan HD, Casciari JJ. Clinical and Experimental Experiences with Intravenous Vitamin C. J of Orthomolecular Medicine 2000;15(4):201-213.

[23] Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M.  Ascorbic  acid at pharmacologic concentrations selectively kills cancer cells: ascorbic acid as a pro-drug for hydrogen peroxide delivery to tissues. Proc Natl  Acad  Sci USA 2005;102:13604-13609.

[24] Davis, J.L.; Paris, H.L.; Beals, J.W.; Binns, S.E.; Giordano, G.R.; Scalzo, R.L.; Schweder, M.M.; Blair, E.; Bell, C. Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia-Reperfusion Injury. Nutr. Metab. Insights. 2016;9:25–30.

[25] Padayatty SJ, Sun H, Wang Y, et al. Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Ann Intern Med. 2004;140:533–537. doi: https://doi.org/10.7326/0003-4819-140-7-200404060-00010

[26] Riordan NH, Riordan HD, Casciari JJ. Clinical and Experimental Experiences with Intravenous Vitamin C. J of Orthomolecular Medicine 2000;15(4):201-213.

[27] Carr, A.C.; Rosengrave, P.C.; Bayer, S.; Chambers, S.; Mehrtens, J.; Shaw, G.M. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit. Care. 2017; 21;300.

[28] Murata A, Shiraishi I, Fukuzaki K, Kitahara T, Harada Y. Lower levels of vitamin C in plasma and urine of Japanese male smokers. Int J Vitam Nutr Res. 1989;59(2):184-9.

Would you like to speak with a caring member of our team to answer your specific questions? Call (480) 834-5414