Intravenous (IV) vitamin C history

For years, since 2008 to be exact, I have been an advocate for the IV use of Vitamin C (IVC), also called ascorbic acid, when treating cancer and a variety of other conditions, but the science for IVC has been around for quite some time.   Linus Pauling and Ewan Cameron published the landmark study, Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer, on the use of IV vitamin C in cancer in 1976.  In this early study, Cameron and Pauling found that IVC increased the survival time of those who received a low dose of IVC (10 grams) with advanced cancer compared to those who did not.  Linus Pauling won the Nobel Prize in chemistry in 1954 “for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances”, but it was WJ McCormick that was the first to propose the benefit of vitamin C in Cancer all the way back in 1954. The use of IV vitamin C in cancer is currently being studied at numerous sites across the world, including the University of Iowa, Thomas Jefferson University, the University of Kansas Medical Center, and Johns Hopkins University.

Intravenous vitamin C is a natural, yet very powerful tool to attack cancer and yes, kill cancer. In general, cancer patients have been shown to have significantly depleted levels of Vitamin C compared to individuals without cancer. The lower the lower the plasma concentrations of vitamin C, the higher the risk of cancer. The scientific evidence for the use of IV Vitamin C as a treatment option in cancer continues to grow.  I have 100’s of studies on IV vitamin C on the Seasons Wellness Diigo account. It is my opinion that the evidence for the IV use of vitamin C in cancer is so strong, it should be considered a standard of care for all individuals with cancer.

riordanclinic.org

Why not just use oral vitamin C?  This is technical but important question.  The simple answer to this very common question is pharmacokinetics.  Pharmacokinetics is the study of the body’s absorption, distribution, metabolism and the excretion of drugs–what the body does with the drug, vitamin, or compound and how the delivery route influences its effect.  The perfect example of pharmacokinetics is the very powerful antibiotic vancomycin.  Oral and IV vancomycin have different absorption, distribution, metabolism and excretion properties which cause their different dosing, efficacy, and toxicities. The same drug results in different effects and side effects because of the different delivery routes. Pharmacokinetics can also apply to vitamins and in this case, vitamin C.  Oral vitamin C is limited by 2 significant factors.  First, vitamin C has a maximum absorption rate of 200 mg/hour. If one takes > 200 mg oral vitamin C, the vast majority of it is flushed out of the body by the kidneys not to be used by the body.  Second, and probably most important, oral vitamin C has a very low peak plasma concentration.  Oral vitamin C will not raise plasma concentration significantly higher than 200 microMolar.  The lowest plasma concentration that has been shown to be toxic to cancer cells is 500 microMolar with the target maximum cancer kill rate in the 10 – 20 miliMolar range (see diagram to above).  In contrast, IV vitamin C has been shown to reach peak plasma concentrations of 20-40 miliMolar and higher.  That is at least a 20,000 x higher peak plasma concentration with IV vitamin C compared to oral vitamin C.  That is the power of pharmacokinetics.  Pharmacokinetics is the reason Pauling and Cameron’s research and the majority of research (100s) on IV vitamin C have shown benefit while the 2 follow up studies (1975 and 1985) to Pauling’s original 1976 research found no benefit from oral vitamin C.

Benefits of IV vitamin C in Cancer

The use of IV vitamin C in patients with cancer has shown broad-spectrum benefits. The published evidence for the benefits of IV vitamin C in cancer include:

    • Improved Quality of Life
    • Increased overall survival
    • Increased 5 year disease-free survival
    • Reduction in pain
    • Increased energy
    • Increased appetite
    • Decreased cancer-associated inflammation
    • Prevents cancer-associated sepsis
    • Combats infections (viral, bacterial, fungi)
    • Non-toxic to healthy cells
    • Reduces side effects and toxicity of chemotherapy
    • Reduces side effects and toxicity of radiation
    • Augments the cancer kill rate of chemotherapy
    • Augments the cancer kill rate of radiation
    • Kills cancer cells
    • Allows a decrease in dose of chemotherapy, yet maintains the same cancer kill rate
    • Improves surgery recovery
    • May even decrease post-surgery cancer recurrence
    • Kills Cancer Stem Cells (CSC)

Most importantly, the IV use of vitamin C has repeatedly been shown to be safe at therapeutic levels as high as 125 grams.  The safety, the increased quality of life and the increased overall survival alone are reasons all people with cancer should be offered IV vitamin C.  Any therapy that is safe, improves outcome, and reduces side effects should be a go in the fight against cancer!

Cancers responsive to IV vitamin C

The use of IV vitamin C has been shown to be effective both in solid (i.e. breast, prostate…) and blood-borne cancers (i.e. leukemia, multiple myeloma…) including:

    • Brain (Glioblastoma)
    • Ovarian
    • Lung (Non-small cell lung cancer)
    • Leukemia
    • Pancreatic
    • Breast
    • Prostate
    • Melanoma
    • Liver
    • Colon
    • Bladder
    • Neuroblastoma
    • Multiple myeloma
    • Sarcoma

The IV use of vitamin C has even been shown to be beneficial in the pre-cancerous state of multiple myeloma, called smoldering myeloma.

IV vitamin C is not created equally for all cancers and is not a one-size-fits-all approach.  The tumor burden (amount of cancer present), metastasis or spread of the cancer, the type of cancer, the aggressive nature of the cancer, and whether the cancer is initial in presentation or recurrent all play a role in determining the dose and the frequency of the IV vitamin C.  In addition, levels need to be monitored to ensure that optimal vitamin C levels are obtained and maintained through therapy.  These are the many reasons that IV vitamin C therapy must be continuously monitored by someone knowledgeable in the use of IV vitamin C therapy in the fight against cancer.  The one-size-fits-all approach never works, and the use of IVC in cancer is no different.

Cancer is a metabolic disease

Cancer is a metabolic disease.  The scientific literature really leaves little evidence for any other conclusion.  I have had the pleasure of speaking at the 2016 AFMA conference with Dr. Thomas N. Seyfried (center of image to left), the author of Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer.  Dr. Seyfried has authored or co-authored many scientific articles on the mechanisms of the metabolism of cancer.  His 2015 article entitled Cancer as a mitochondrial metabolic disease, published in the journal Frontiers In Cell and Developmental Biology is a heavy, but very good read on the metabolic mechanisms of cancer.  In addition, Dr. Dominic P. D’Agostino at the University of South Florida spoke at the same conference on the use of the ketogenic diet in the management of metastatic cancer. These and other pillars in the cancer research community have helped to decipher the mechanisms of action of IV vitamin C in cancer.  The combination of the knowledge of cancer metabolism, the use of the ketogenic diet in cancer, and the mechanism and use of IV vitamin C in cancer are a lethal combination in the fight against cancer.

Schoenfeld et al., O2, and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate, Cancer Cell (2017), http://dx.doi.org/10.1016/j.ccell.2017.02.018

To describe the mechanism of action of IV vitamin C in cancer, I need to get a little technical.  Hold on to your hats. Humans are one of several species that have lost the ability to make vitamin C, hence what vitamin C we have in our body comes through our diet and/or supplementation.   In addition, the human body has a very limited capacity to store vitamin C.  One of the benefits of vitamin C in the battle against cancer is that vitamin C looks just like glucose.  Vitamin C is made from glucose by the enzyme gulonolactone oxidase. Humans lack this enzyme, which requires us to get continuous vitamin C from our diet.  As concerning as this enzymatic deficiency can be, this deficiency provides a silver lining in the fight against cancer.  Cancer thrives in the typical glucose-rich environment of the western American diet. A ketogenic diet starves the cancer of its primary fuel source—glucose.  In the low glucose state, induced by a ketogenic diet, vitamin C is readily taken up by cancer cells by specific receptors, called SVCT1 and SVCT2, because of its resemblance to glucose. This allows vitamin C, in conjunction with a ketogenic diet, to act as a stealth way to deliver and attack cancer because of the different effects of vitamin C inside cancer cells compared to inside healthy cells.

Most think of vitamin C as an antioxidant, however, IV vitamin C has been shown to be a potent pro-oxidant in cancer cells, especially at the higher dosages.  It is this pro-oxidant activity of vitamin C in cancer cells that generate the high levels of Reactive Oxygen Species (ROS), such as H2O2 (hydrogen peroxide), OH− (hydroxyl free radicals), ·O2− (superoxide anions), within cancer and healthy cells (see image above). The key factor that separates cancer cells from healthy cells is that cancer cells lack certain enzymes, such as catalase, to handle these high ROS levels.  Healthy cells retain appropriate catalase activity (see image below) and are perfectly capable of handling the high ROS levels. This allows vitamin C to function as an anti-oxidant in healthy cells, but as a pro-oxidant in cancer cells.  This high ROS presence in cancer cells then interacts with the high levels of Iron (designated as LIP in above image) in the cancer cells and depletes the glutathione pool (designated as GSH in above image) in the cancer cells.  Glutathione is one of the most important detoxification molecules in the body.  A depletion of the glutathione pool leads to cellular oxidative stress which triggers cell death of the cancer cell. That is a very good thing in the fight against cancer.  In addition, vitamin C also behaves as an inhibitor of glycolysis (a key step in the cell cycle of energy production in mitochondria) by targeting the activity of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a key glycolytic enzyme. Mitochondria are the energy powerhouses of the cell where glycolysis occurs. The disruption of the energy production pathways in mitochondria of the cancer cells means certain death for the cancer cell.  These functions make vitamin C a potent anti-cancer therapy without harming healthy cells—a great combination!  That is just a discussion of the activities of vitamin C alone. Imagine what vitamin C can do if added to other therapies whether they be traditional (i.e. chemotherapy, radiation) or alternative (ketogenic diet, insulin potentiation therapy, curcumin…)?

Ohno Satoshi et al., High-dose Vitamin C (Ascorbic Acid) Therapy in the Treatment of Patients with Advanced Cancer, AntiCancer Research (2009), DOI: 10.1126/scitranslmed.3007154

 

The story will continue with the next blog post which will highlight the exciting new research on the use of IV vitamin C in the attack against the ultimate cancer back-up: Cancer Stem Cells (CSC).