Questions are always encouraged. How else are we to learn?
A question was recently sent my way from a 2018 conference which provides an opportunity to discuss some details on the bioavailability and pharmacokinetics of Na Ascorbate. I will present more detailed information on the bioavailability, pharmacokinetics, pharmacodynamics of vitamin C, and so much more information, at the upcoming Vitamin C International Consortium Institute (VCICI.org) in Clearwater Beach, Florida, September 9-10.
Question:
“I have been using ascorbic acid (AA) infusions for many years and was intrigued by the recent presentation regarding sodium ascorbate. After listening to the lecture state that sodium ascorbate is more absorbable than ascorbic acid, I asked the question, “Do you have any data to support that claim” since I was hoping that the speaker had some type of evidence to support that statement.”
“Previously, I had administered 100’s of infusions of AA to cancer (and other) patients and had measured their vitamin C blood levels before and after infusions. My goal was to bring their vitamin C blood level up to approximately 350-400 mg/dl which is the level that researchers from the NIH published (Drs. Jeanne Drisko and Mark Levine) that would be necessary for vitamin C to have a chemotherapeutic-like effect and be most effective to battle cancer.“ With a pre infusion vitamin C level of 0.6 mg/dl, I administered 50 grams of sodium ascorbate to a female cancer patient and her post vitamin C level was found to be 96 mg/dl. Upon measuring the vitamin C level the following week after infusing 50 grams of ascorbic acid, the vitamin C was found to be 318 mg/dl, an increase of more than 300% compared to sodium ascorbate. I would welcome your input regarding these findings and ask if you or anyone else you know may have noted similar results.“
Answer:
It is important to be very clear, vitamin C is not chemotherapy, chemotherapeutic, or chemotherapeutic-like, and to place it in the same strategy of therapies as chemotherapy lacks a basic understanding of the pharmacokinetics and pharmacodynamics of vitamin C. Chemotherapy is born out of war. Chemotherapy is designed to destroy. It can destroy cancer, but it destroys everything else in its wake—including the immune system. Chemotherapy follows the crazy logic that the pathway to healing is somehow through destruction. Yet, the same chemotherapy is toxic to healthy and cancer cells. Chemotherapy is a toxin, period. Vitamin C is not a toxin or a poison.
The historical definitions of a toxin do not etymologically, biologically, or pharmacodynamically connect or relate to vitamin C’s known effects against cancer. More recent research points to the simultaneous healing effects of vitamin C in healthy cells, yet destructive in cancer cells. Vitamin C and many other holistic, integrative therapies allow the ability to target the tumor and heal the body simultaneously. It is treatment dualism. This is something chemotherapy, i.e., chemotherapeutic, does not do.
Dualism can be defined as the division of concepts and effects into two, often opposing, or contrasted conditions. This treatment dualism is a new concept found repeated throughout published research with natural, holistic, and integrative treatments in cancer: natural therapies can have different and often opposite effects dictated by the different environments encountered within the body, i.e., vitamin C, hormones, hyperthermia, curcumin… The objectives are dualistic, and the different environments, again dualistic, dictate the different responses.
Word origin search on toxin defines a toxin as an ‘organic toxin’ or ‘poison.’ No matter that a toxin is produced endogenously, a toxicant is produced exogenously and then introduced into the body. More, the historical context of the word poison is that of a drug. A journey through the historical definition of a drug provides simple proof vitamin C is not a drug:
14th century—any substance used in the composition or preparation of medicines
16th century—poison
19th century—narcotics and/or opiates
Etymologically, a poison is a ‘toxic potion’ or ‘drink’. The origin definition of potion implies a drink, yet here, the reference is to intravenous administration. Esoteric, maybe, but if words, names, and labels are going to be used, we must understand their actual context of use. Vitamin C, on any level, is not a poison or a toxin.
Some advocate vitamin C as a toxin or a poison. But how could something like vitamin C be a toxin, or poison, yet be required for more than 150 enzymes in the body? For example, how could vitamin C be needed to activate HIF-prolyl hydroxylase to maintain collagen synthesis, which is critical to tissue repair, yet be a toxin? Tissue healing and repair are paradoxical to the actions of a toxin or poison.
Vitamin C is not toxic to healthy cells, yet it is toxic to cancer cells (treatment dualism) through a wide variety of mechanisms that are not chemotherapeutic related but in fact, are based on its effects in:
- Epigenetics
- Cytotoxicity
- Anti-proliferation
- Anti-inflammation
- Anti-lymphagenic
- Anti-angiogenic
- Prop-apoptotic
- Immunomodulatoion
- Anti-viral
- Mitochondrial effects
- Cancer stem cells
- DNA damage and repair
- Redox homeostasis
- Cancer metabolism
- Iron metabolism
- Hypoxia
- Collagen synthesis
- Extra-cellular matrix
- Tumor microenvironment
- Enzyme cofactors (>150)
In addition, high-dose intravenous vitamin C augments:
- Chemotherapy
- Radiation
- Surgery
- Immunotherapy
- Targeted therapies (“mabs” and “ibs”)
- Hormonal therapy
This question on bioavailability completely misses the mark on understanding the concept of bioavailability. Nothing to be ashamed of for sure. The authors of the Rochester Mayo studies, including Moertel CG, Creagan ET, and Fleming TR, did not understand the basic concept either, though the concepts of bioavailability and pharmacokinetics for vancomycin were widely known at the time.
Intravenous (IV) vitamin C is essentially 100% bioavailable. The debate between IV Na Ascorbate and Ascorbic acid is on the topics of compliance, and tolerability at the high doses required frequently for a long duration to non-chemotherapeutically treat cancer. This question amounts to a sort of verbal jiu-jitsu with the misstatement and mixing of the concept of similar bioavailability between oral and IV, which they are not. This happens to be the same mistakes made with the Rochester Mayo authors some 40 years later—they didn’t understand vitamin C bioavailability and pharmacokinetics!
The question pertinent to bioavailability is more around the oral dosing of vitamin C, which I believe Na Ascorbate is more bioavailable because of improved tolerability at the higher oral dosing. A Townsend study from 2021 found that Ascorbic Acid had better absorption through the stomach and Na Ascorbate had enhanced absorption in the small bowel [i]. The highest Na Ascorbate absorption occurs through the ilium.
Concerning the speaker at the conference, though I wasn’t there, it is that they did not know or explain the topic well. It would appear that the presentation lacked data to support statements made within the presentation , which is tantamount to opinion.
The question points out a self-conducted experiment that proves nothing other than Na Ascorbate and Ascorbic acid elevating plasma AA. This sequence of different therapies and the rise of plasma AA is the only association that can be said to be proven here. Still, the association here does not equal.
cause and effect! My experience with plasma AA levels following IV Na Ascorbate therapy matches that of other published research. An analysis published in 2021 highlights this experience:
Figure 1 above highlights an increasing plasma AA level with an increasing vitamin C dose. This correlation is repeated in other published research [ii] [iii] [iv] [v]. and has been my experience over five years of use of high-dose vitamin C in the treatment of cancer.
Figure 2 further, but with more direct evidence, provides correlation of plasma AA with increasing dose of IV vitamin C. Notice the increasing plasma concentration in mM on the far right column correlating with an increase in vitamin C dose of 5 grams in week #1, 30 grams in week #2, and 60 grams on week #3 and #4. More, the weekly dosing documented was only once per week, yet the plasma AA levels increased. Once a week dosing is inadequate to therapeutically saturate and treat the complexity that is the tumor and tumor microenvironment, let alone saturate the normoxic and hypoxic regions of the tumor [vi].
This data challenges the long-held thought that the body cannot store vitamin C. Though storage similar to fat soluble vitamins does not exist, it is obvious some limited capacity for vitamin C storage seems more and more likely. It is a limited capacity for storage that accounts for this steady climb in plasma AA levels documented. My clinical experience is that the first four weeks of vitamin C dosing provide a steady climb until tissue saturation is reached, at which times levels will maintain a more steady peak range. This is a routine but not a universal experience. Many variables can affect the increasing trend in plasma AA, i.e., tumor burden, BMI, inflammation, oxidative stress, metabolic demand, systemic deficiencies… Vitamin C deficient patients, cancer patients top this list, achieve lower plasma AA levels compared to non-deficient patients. Cancer patients with inflammation, high tumor burden, and metastasis, will achieve lower plasma AA levels compared to those without inflammation, small tumor burden, and localized disease [vii].
Another point of question here is how long were the two IV therapies given. Were they given over equal time? How many days in between? Was one IV given over 30 minutes and the other over 2 hours? The question seems to have no basic understanding of dosing, duration, frequency, and pharmacodynamics.
I think the only thing proved here is that the speaker referenced in the question did not adequately present the data in the lecture, did not explain it well, or had no data. This question highlights a profound fundamental misunderstanding of bioavailability differences between oral and IV vitamin C, nor an understanding of the pharmacokinetics and pharmacodynamics of vitamin C in cancer treatment.
I don’t want to come across as too critical of this speaker. But, it appears more questions, rather then answers, were the result of the lecture. Public speaking is very difficult, let alone in the field of medicine. It is paramount to lead with the science, not led the science. More, one must link and sequence the data in a memorable concept for future clinical application and implementation.
As to this “study” of one, and in addition to all the other points above, plasma AA levels are susceptible to degradation from time, light, and heat. What was the “study” design of the collection, storage, pickup, and transport to ensure proper preservation? What was the technique for collecting samples? When were the samples collected? Was the anatomical location used for collection identical and contralateral to the infusion? If samples were drawn on different arms, left and right, any plasma AA would be higher if infusion was given in the left arm versus the right. The same question applies to the central line versus the peripheral.
Join us at the upcoming VCICI annual conference at the beautiful Clearwater Beach, Florida, September 9-10 to learn more from a star-studded line-up of speakers. See you there!
[i] Fonorow OR. Unexpected Early Response in Oral Bioavailability of Ascorbic Acid Vitamin. 2019. Townsend Letter. Found online: CLICK HERE
[ii] Levine M., Conry-Cantilena C., Wang Y., Welch R.W., Washko P.W., Dhariwal K.R., Park J.B., Lazarev A., Graumlich J.F., King J., et al. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA. 1996;93:3704–3709. doi: 10.1073/pnas.93.8.3704.
[iii] Padayatty S.J., Sun H., Wang Y., Riordan H.D., Hewitt S.M., Katz A., Wesley R.A., Levine M. Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Ann. Intern. Med. 2004;140:533. doi: 10.7326/0003-4819-140-7-200404060-00010.
[iv] Stephenson C.M., Levin R.D., Spector T., Lis C.G. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemother. Pharmacol. 2013 doi: 10.1007/s00280-013-2179-9.
[v] Hoffer L.J., Levine M., Assouline S., Melnychuk D., Padayatty S.J., Rosadiuk K., Rousseau C., Robitaille L., Miller W.H. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann. Oncol. 2008;19:1969–1974. doi: 10.1093/annonc/mdn377.
[vi] Shenoy N, Creagan E, Witzig T, Levine M. Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly. Cancer Cell. 2018 Nov 12;34(5):700-706. doi: 10.1016/j.ccell.2018.07.014.
[vii] Mikirova N, Casciari J, Riordan N, Hunninghake R. Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients. J Transl Med. 2013 Aug 15;11:191. doi: 10.1186/1479-5876-11-191.
