There's a novel form of chemotherapy that’s so safe it can be taken daily without ill effect. The treatment is selectively toxic to tumors while sparing normal, healthy tissue. And even as it’s impeding cancer, this “natural chemo” is also bolstering immunity and quelling inflammation, a pivotal driving force behind the growth and progression of all cancers.
The treatment to which I’m referring is intravenous vitamin C, also called IVC therapy or IV ascorbate. Mainstream oncologists typically either dismiss the modality or view it as a last resort for patients facing cancers that have become resistant to standard therapies. But with dozens of published case reports and several recent clinical studies showing efficacy against aggressive, late-stage cancers, there can be little doubt as to IVC's therapeutic potential. Moreover, its range of applications appears to be steadily expanding.
My own experience with this nutritional-pharmacologic approach, based on my certification training at the Riordan Clinic's IVC Academy as well as collaborations with several integrative medicine clinics, suggests that IVC may play the following roles for optimizing cancer care:
- Post-surgery support: speeding up healing after surgery and eliminating residual cancer and micrometastases;
- Chemotherapy & radiotherapy: bolstering chemo and radiotherapy treatments while reducing toxic side effects;
- Disease stabilization: curbing the progression of cancer, especially with more aggressive, chemoresistant disease;
- Physical & mental well-being: improving energy, mood, appetite, sleep quality, and overall quality of life;
- Immune system support: boosting immunity and knocking out infections resistant to antibiotics and other drugs;
- Antiinflammatory support: curbing whole-body inflammation, reducing post-op pain, and improving cancer control;
- Remission maintenance: prolonging remissions with the help of periodic infusions doled out over the long term.
That last one—extending remissions—is perhaps the most overlooked of IVC's potential benefits. It also brings us back to the point about using IVC following surgery and echoes the basic principle behind adjuvant chemotherapy, which is to get rid of microscopic clusters of cancer cells that remain after the operation and may begin to proliferate in reaction to the surgery itself. In general, decisions around the number and frequency of IVC infusions will depend on the risk of recurrence. Thus, individuals at higher risk of experiencing a relapse would undergo more frequent infusions in order to keep their malignancy from either advancing or returning.
Here's an example. This past summer, I interviewed Alice M., a 52-year-old woman living in Montreal who was diagnosed with Stage IV breast cancer nearly three years ago. Alice has developed a strong firsthand appreciation for IVC therapy. After deciding to postpone the intensive chemotherapy treatments recommended by her oncologists, she opted for an anti-estrogen drug along with a clinically approved light-based approach called photodynamic therapy or PDT.
Following these non-toxic treatments, Alice received weekly infusions of IVC for two solid years, after which she received the IVC once every two weeks. She also self-administers the PDT at home. (For an in-depth exploration of PDT, check out my 2014 book and ebook, The Medicine of Light, coauthored with Andrei Reshetnickov, PhD.) Throughout these infusions, Alice has suffered no adverse side effects nor any decline in her quality of life. All scans and blood tests indicate that she is presently in the clear.
Medical scientists have been studying IVC since the 1960s, yet only recently have key pieces of the puzzle begun falling into place. Much of this therapy's success depends on how it's administered, including how much, how often and for how long to administer IVC. Other factors to consider include the person's lifestyle patterns, emotional well-being, the inherent aggressiveness of the cancer (based on genomics and biochemistry), and synergistic factors like oxygen and vitamin K3.
WATCH Antonio Jimenez, MD, ND, of the Hope4Cancer Treatment Centers talk about IVC Therapy for Cancer.
How IVC Therapy Got Mythologized
In the early 1970s, Nobel Prize-winning chemist Linus Pauling and Scottish physician Ewan Cameron launched two landmark studies of advanced cancer patients who received a combination of IVC and oral vitamin C. These and other investigations at the time suggested a two- to six-fold increase in survival for IVC-treated cancer cases, many of which were considered “terminal”. (For details, please refer to our 2003 historical review in Integrative Cancer Therapies,) Though the studies garnered a great deal of media attention, they were sharply criticized by the medical establishment due to various design flaws, notably the lack of randomization.
To address the study design concerns, the Mayo Clinic conducted two randomized clinical trials in the 1980s. Patients were randomly assigned to either vitamin C or placebo; however, the trials used only oral vitamin C, not the intravenous protocol favored by Pauling and Cameron. Both of the Mayo trials failed to show any improvement with the exception of some quality-of-life benefits. As a result, the medical community rejected high-dose vitamin C as a potential cancer therapy, a view that prevails right up to the present day.
You can have the best study design there is, but that study will fail miserably if the intervention lacks potency or is poorly administered. With oral vitamin C, even with a whopping 10 grams (the same dose Pauling and Cameron used, albeit intravenously), it's simply impossible to have any substantial anticancer effect. That's because, with any oral dose above 1 gram, absorption of the vitamin drops to under 50%, and much of what is absorbed will not be metabolized and thus gets rapidly excreted via urination.
Hindsight, as they say, is 20/20. We now know that the exclusively oral doses used in the Mayo studies would have produced peak blood levels of vitamin C that were approximately 25 times lower than the same dose given intravenously! Thus, each clinical trial was an exercise in futility, as most of the 10-gram dose was excreted. No matter how much vitamin C is taken by mouth, you simply cannot attain the blood levels needed to put the brakes on cancer, even after taking multiple oral doses throughout the day.
In addition, most of the cancer patients who participated in the Mayo trials simply couldn’t tolerate the 10-gram dose of vitamin C. Oral doses higher than 5 or 6 grams typically cause diarrhea, which may explain why 60% of the study participants who were taking vitamin C had dropped out by the end of the second month.
Although oral vitamin C may help fend off the common cold, it seems to fail magnificently against cancer. Moreover, taking vitamin C orally could interfere with some anticancer supplements and natural medicines being used to support cancer care. This is one reason why it's important to consult with a nutritional oncology expert before setting up your own supplement regimen or adopting a "kitchen sink" approach to supplementation.
Thankfully, IVC bypasses the limitations of the oral method. Only with IVC can you achieve the very high blood levels needed to keep cancer in check and possibly even reverse it. In general, the more frequent the infusions, the greater the likelihood of therapeutic success. Longer, slower infusions are important as well, since infusions that are too fast will result in excessive losses of vitamin C in the urine.
WATCH this video on how and why Linus Pauling, PhD, was attacked by the medical community for his heretical views on IVC therapy.
How High Should You Go?
When it comes to countering cancer, there’s a big difference between high-dose and low-dose IVC. Whereas very high doses can achieve a direct tumor-killing effect, lower or more moderate doses tend to have a more indirect and intermediate impact, mainly by reducing inflammation and bolstering anticancer immunity. Both high and low doses can be useful depending on the situation.
Low-dose IVC generally refers to vitamin C infusion doses in the neighborhood of 10 to 40 grams, depending on the individual's body mass. But don't let the "low-dose" label fool you. These doses are still quite capable of stimulating the immune system, curbing inflammation, and knocking out infections that may accompany many cancers and potentially play a covert role in tumor progression. They can also help people who are very weak and fatigued, individuals who could benefit from some additional antioxidant support and may not be facing an active disease situation.
Low-dose IVC can also serve as a supportive immunotherapy strategy in conjunction with other treatments. Synergistic factors like vitamin K3 and UBI ozone will further amplify the therapeutic impact of low-dose IVC.
With high-dose IVC, the effects are more complex. First off, high-dose IVC generates far more hydrogen peroxide than the more moderate doses. This means that high-dose IVC is functioning mainly as a prooxidant treatment, meaning that it pumps out lots of oxidizing molecules that help damage and destroy tumors directly. In the early part of the infusion, however, the vitamin C blood levels are increasing and thus having an antioxidant impact; after the infusion, with blood levels dropping, the antioxidant effects kick in once again, enhancing immunity and boosting antioxidant protection to normal tissues (which is helpful in the event that chemotherapy or radiotherapy follows the iVC).
As a basic principle, the amount of vitamin C provided by high-dose IVC is relative to body mass: bigger bodies need more C. Thus, high-dose IVC means receiving a target dose of 1 to 1.5 grams of ascorbate per kilogram of body weight. For example, a person weighing 175 pounds (about 80 kilograms) would start at 50 grams and increase up to 80 grams over the next two infusions, eventually working up to 120 grams as the optimal dose.
In short, the larger the individual, the higher the vitamin C infusion dose. With more aggressive cancer and high levels of inflammation, the same individual might even receive as much as 160 grams in a single infusion. That’s about 160 times more vitamin C than people typically take by mouth! If you consider that there’s a little over 100 mg of vitamin C in a glass of Florida Orange Juice; you’d need to drink about 1600 glasses to match the amount in a single high-dose IVC infusion—not a very practical proposition.
Another consideration for the anti-cancer success of high-dose IVC is the blood level. Measurements should be taken after the first and last infusion to check the blood level of vitamin C. The target blood concentration is between 250 and 400 mg/dl (milligrams per deciliter). At the higher concentration, tumors are more likely to shrink while tumor markers (cancer-related proteins in the blood) begin to decline.
Even with blood vitamin C levels in the 250-300 range, cancer markers will often decrease. However, the best results are consistently seen when the blood level reaches 300-400 mg/dl. Individuals who have major inflammation and advanced cancer will often not show the higher blood levels until the IVC dose is substantially increased.
Earlier I brought up the paradoxical point that high-dose IVC has both prooxidant and antioxidant effects. This dual effect helps explain the growing body of research showing that IVC protects normal tissues while sensitizing tumors to the effects of both chemotherapy and radiation treatments. Many integrative and naturopathic physicians are excited about the prospect of using IVC to enhance the activities of various chemotherapy drugs while simultaneously improving the patient's quality of life—the best of both worlds, as it were.
WATCH Ron Hunninghake MD of the Riordan Clinic talk about IVC and Cancer Care.
The Kindest, Gentlest Form of Chemotherapy
Since the 1990s, IVC has been referred to in the medical literature as a chemotherapeutic approach with considerable promise for treating cancer. Indeed, IVC shows “the potential to selectively kill tumor cells in a manner similar to other tumor cytotoxic chemotherapeutic agents,” according to scientists at the Bio-Communications Research Institute in Wichita, Kansas. But of course, there are also some very important differences.
With mainstream chemotherapy, treatment sessions must be sufficiently spaced out to allow the patient’s body time to recover from the toxic effects. Unfortunately, this means the cancer also has a chance to recover via the process of cancer cell repopulation. This rebound effect is known to occur between chemotherapy (as well as radiotherapy) cycles.
High-dose IVC is able to circumvent this issue entirely, allowing patients to receive the treatment on a daily basis or at least with greater frequency than what would take place with the usual chemo drugs. The objective of doing regular and frequent IVC infusions is to continually knock down the cancer until either a remission or disease stabilization is achieved.
A recent systematic review of research on IVC therapy for cancer considered the best available evidence to date from clinical trials and other studies. The IVC dosing ranged from 1 gram to more than 200 grams of vitamin C per infusion, typically administered 2 to 3 times weekly. Because of the great diversity of doses and methods used, it is difficult to draw meaningful conclusions from the research as a whole.
Nonetheless, the authors concluded that IVC therapy “may improve time to relapse and possibly enhance reductions in tumor mass and improve survival in combination with chemotherapy. IVC may improve quality of life, physical function, and toxicities associated with chemotherapy, including fatigue, nausea, insomnia, constipation, and depression,” as reported in a 2014 issue of Integrative Cancer Therapies.
Studies that aimed for the higher doses with greater frequency generally showed more promising results. Lower doses of IVC may still have an impact, but again mostly in terms of stimulating immunity and countering infections. (As an aside, Lyme disease has been successfully controlled with a combination of IVC and various antiviral botanicals.)
How IVC Targets Cancer Cells and Metastases
How does high-dose vitamin C kill cancer cells and help put the disease in check? This occurs through the cancer cell’s generation of hydrogen peroxide, which in turn damages the cell and triggers programmed cell death. This basic mechanism is thought to explain the favorable interactions that can result when IVC therapy is combined with different chemotherapy drugs.
The selective killing effect of high-dose vitamin C has been attributed to a lack of the enzyme catalase in many cancer cells. Without this enzyme's protective effects, cancer cells are at the mercy of hydrogen peroxide’s destructive power. Normal cells maintain a proper balance of catalase and other enzymes to protect against the damaging effects of hydrogen peroxide and free radicals.
The hydrogen peroxide mechanism may sound unique but in fact is nothing particularly novel as cancer therapies go. Indeed, many cancer researchers are currently seeking to identify new cancer drugs that can boost hydrogen peroxide levels. According to a recent article published online by the Massachusetts Institute of Technology (MIT):
“Cancer cells often have mutations that cause their metabolism to go awry and produce abnormally high fluxes of hydrogen peroxide. When too much of the molecule is produced, it can damage cells, so cancer cells become highly dependent on antioxidant systems [e.g., catalase] that remove hydrogen peroxide from cells.”
The MIT article goes on to point out that drugs that target this vulnerability, dubbed "redox drugs", can either disrupt the cancer cell’s internal antioxidant systems or further raise the cell’s hydrogen peroxide output. In essence, IVC is a “redox therapy” that takes its cue from this dynamic principle.
Another related mechanism focuses on oxygen. A nuclear factor called hypoxia-inducible factor-1, or HIF-1, has been linked with metastases and more aggressive malignant behavior in the context of oxygen-poor conditions (which are especially common in big tumors). By boosting vitamin C levels, HIF-1 activation is reduced inside the tumor, and this leads to a slowing of tumor growth and progression.
Now, under normal oxygen conditions, high-dose vitamin C is able to kill cancer cells quite effectively. But when oxygen becomes very scarce, the killing effect associated with IVC is reduced. In fact, a severe oxygen deficit can render the tumor resistant to both IVC and conventional chemotherapy drugs.
By inhibiting HIF-1, high-dose vitamin C therapy may work well under mild oxygen-poor (hypoxic) conditions, but not under conditions of severe oxygen deficiency. Therefore, high-dose IVC in cancer patients ideally should be complemented by some form of oxygen therapy, such as hyperbaric oxygen (HBO) or different types of ozone therapy. Such strategies should improve the therapeutic index of high-dose IVC, as reported in the March 2014 Journal of Cellular and Molecular Medicine.
On a fundamental level, IVC could also block cancer-related inflammation. Studies at the Riordan Clinic in Wichita (Kansas) showed that IVC led to reduced blood levels of inflammatory cytokines (natural chemicals), many of which play key roles in tumor growth and progression. At the same time, the Riordan team observed that various tumor markers also decreased during IVC. Their findings were published online in the 3 January 2016 issue of Medical Science Monitor.
IVC for Pancreatic Cancer: A Promising Strategy
Pancreatic cancer is among the deadliest of all cancers, and most cases are diagnosed at a very late and aggressive stage. Thus treatments that disrupt the cancer’s biology are attracting a great deal of interest. Researchers at the University of Iowa Carver College of Medicine recently reported that IVC may have an impact on metastatic pancreatic cancer. Daily treatment with high-dose IVC led to decreases in both HIF-1 and VEGF,a key factor involved in tumor growth and metastases.
Two small pilot clinical trials have recently explored the possibility that IVC could impact survival for patients with advanced-stage pancreatic cancer. The first trial enrolled only nine patients with stage IV pancreatic cancer and suggested (in the most preliminary, speculative way) better survival and fewer metastases following IVC therapy.
The second trial enrolled 12 Stage IV patients and found a median overall survival of 15.1 months by adding high-dose IVC to Gemzar chemotherapy. This is more than twice the survival rate that’s typically seen with Gemzar alone (6-7 months). The better-than-expected outcome suggests that adjunctive IVC therapy may be superior to Gemzar chemotherapy alone.
Because these findings are only preliminary, large controlled clinical trials will be needed to test the hypothesis that IVC can improve survival for pancreatic cancer patients. In the meantime, given the dismal prognosis linked with Stage IV pancreatic cancer, the IVC-Gemzar combo may offer a reasonable alternative to those patients who cannot tolerate the highly toxic chemo regimens (e.g., FOLFIRINOX) that have recently begun to replace Gemzar.
One of the prevailing myths about vitamin C is that, as an antioxidant, it may interfere with both chemotherapy and radiotherapy. Thus far, however, IVC has yielded favorable results in several clinical trials when combined with chemotherapy. As I pointed out earlier, high-dose vitamin C may sensitize aggressive tumors to the effects of chemoradiation (chemo plus radiotherapy) while simultaneously protecting normal tissues, as reported in the January 2019 issue of Seminars in Radiation Oncology.
This is exactly what has been seen with a number of natural medicines that show antioxidant-protective effects in normal cells. For example, the addition of curcumin, with or without high-dose vitamin C, may further boost the efficacy of chemotherapy while also directly blocking pancreatic tumor growth. Curcumin, too, has long been regarded as a form of non-toxic chemotherapy. As with IVC, it seems to sensitize cancer cells to chemotherapy while simultaneously protecting normal cells.
Overcoming Ovarian Cancer and Other Cancers
Laboratory research suggests that IVC therapy may slow the growth of not only pancreatic tumors, but also ovarian tumors, glioblastoma (advanced brain tumor), prostate cancer, hepatoma, colon cancer, sarcoma, leukemia, mesothelioma, breast cancer, and neuroblastoma. Keep in mind that many of these are very aggressive cancers, and yet in many cases IVC can have at least a disease-stabilizing impact, as documented at the Riordan clinic in Wichita, Kansas.
Moreover, there are many well-documented, published cases of cancers that have responded well to IVC, including complete remissions in cases that had not responded previously to conventional chemotherapy (see references). The most recent report of nine cancer cases cited prolonged survival when compared to the established prognosis for each patient. Nevertheless, the patients also showed a deterioration or relapsing of their disease after discontinuing the IVC therapy.
To date, only one randomized clinical trial has examined the impact of IVC therapy in cancer treatment. Conducted in Kansas City, this trial involved 25 newly diagnosed ovarian cancer patients who received both high-dose IVC therapy and standard chemotherapy (paclitaxel plus carboplatin) at Kansas University Medical Center (KUMC). Chemotherapy was given for 6 months and IVC therapy for 12 months.
In the KUMC clinical trial, the addition of high-dose vitamin C to the regimen did not increase any of the more severe side effects (grade 3 and 4 toxicities). Moreover, IVC therapy led to a reduction in the more moderate toxicities (grade 1 and 2), including markedly less damage to the kidneys, lungs, pancreas, bone marrow, and nervous system.
Infections also occurred significantly less often in those patients receiving IVC therapy. Overall, patients not receiving IVC therapy experienced twice the level of toxicity from chemotherapy as those receiving IVC therapy. Both of these effects could have implications for survival and longevity.
Along these same lines, patients receiving IVC showed a trend toward better overall survival, a finding that was considered preliminary due to the relatively small size of the study. Surviving patients also remained stable longer: the median time to disease progression was approximately nine months longer in the IVC-plus-chemo group compared with the placebo-chemo alone group.
Again, however, due to the relatively small size of this clinical trial, there was not enough statistical power to determine the true efficacy of IVC therapy. It seems likely, too, that a more frequent administration of the IVC would have had a more pronounced effect. These patients were receiving IVC twice a week for 12 months. It’s possible that a shorter period of treatment on consecutive days would have achieved better results.
At this time, we can conclude that evidence for IVC therapy as a supportive treatment for cancer patients is limited but on the rise. On the other hand, IVC may not be a viable option for all types of cancer, given that laboratory studies have shown that the sensitivity of different tumor types to high-dose vitamin C varies.
Safety of IVC Therapy
According to Dr. Paul Anderson, research professor and former director of IV Services Bastyr University Oncology Research, IVC therapy is “extremely safe” as long as the patient does not have a G6PD deficiency. G6PD is an enzyme used by red blood cells to transform hydrogen peroxide into water.
With any G6PD deficiency, there is an increased risk of destruction of the red blood cells (hemolysis); however, this is an extremely rare event. If it occurs, you will typically see the urine turn a reddish or rusty color.
Patients with preexisting kidney disease or poor kidney functioning (renal insufficiency) may be more prone to forming stones after IVC therapy. For these reasons, most doctors will pre-screen their patients for G6PD status and kidney functioning. Deficient G6PD and renal insufficiency are contraindications for IVC therapy.
LISTEN to Naturopathic Oncologist Paul Anderson discuss some of the challenges of using IVC and other IV therapies.
Using IVC in Tandem with Standard Chemotherapy
If standard chemotherapy is planned, IV vitamin C may be taken shortly before receiving the drug treatment (depending on the chemo agents), in order to enhance the effectiveness of the treatment. However, the precise clinical plan will depend on the diagnosis and configuration of conventional treatments. IVC may not be appropriate for supporting all types of chemotherapy.
The KUMC study cited earlier showed that IVC not only did not increase the toxicity of chemotherapy, but actually resulted in fewer side effects related to chemotherapy, affecting virtually every category of toxicity, including neurotoxicity, bone marrow toxicity, infection, hepatobiliary/pancreatic toxicity, toxicities in the renal/genitourinary, pulmonary, and gastrointestinal systems, as well as dermatological.
A 2014 review published in Frontiers in Oncology concluded that “intravenous (IV) vitamin C alleviates a number of cancer- and chemotherapy-related symptoms, such as fatigue, insomnia, loss of appetite, nausea, and pain. Improvements in physical, role, cognitive, emotional, and social functioning, as well as an improvement in overall health, were also observed.”
Synergizing with IVC Therapy
Most of the integrative medicine clinics I work with now recommend that IVC infusions be accompanied by oral liposomal vitamin C (3-5 grams) along with vitamin K, to be taken on and between the IVC infusions days. Vitamin K2 and K3 are both synergistic with vitamin C in terms of countering cancer.
Please note that oral liposomal vitamin C is not equivalent to IVC. The latter is probably more effective in terms of attacking cancer because it generates more hydrogen peroxide around the outer cell membrane, where most of the destruction takes place. Again, however, the oral liposomal C can be quite useful when taken between infusions.
Other synergists such as vitamin B1 and green tea catechins may also be considered. In addition, some form of oxygen therapy such as hyperbaric oxygen therapy or UBI ozone may be helpful 1-3 hours prior to the IVC therapy. The logic of this combination was explained earlier in the discussion about HIF-1.
As I see it, there are several major obstacles to the advancement of IVC as a cancer therapy. The first is that the treatment is rarely covered by insurance, and thus most cancer patients can only afford to receive it intermittently, often on the order of two to three infusions per week for three to four weeks at a time. Unfortunately, some cancers may continue to progress unless the frequency of infusions is increased. I know of several cases of Stage IV cancers that were stopped dead in their tracks after six to eight weeks of IVC infusions (one case entailed 64 consecutive days!) but not everyone has the time and resources for such an extensive treatment plan.
A second major hitch is ideological: mainstream oncologists tend to reject IVC therapy out of hand, mostly because the treatment is not part of their arduous medical training. Meanwhile, propaganda issued by the American Cancer Society and Memorial Sloan Kettering Cancer Center (among other large centers that are heavily influenced by Big Pharma interests) generally eschews any claims regarding therapeutic potential.
A third challenge is the lack of a level playing field in the clinical research domain. Because vitamin C is not patentable, it’s unlikely to garner the vast amounts of funding needed to support large randomized clinical trials. This means that we may have to be satisfied with smaller, suboptimal studies and thus IVC's true impact on cancer survival may remain difficult to estimate for quite some time. (This also happens to be the case with many chemo drug combinations for advanced-stage cancers.)
In the long run, we may have to place our trust in a mechanism-based rationale coupled with the best available evidence and the realization that IVC has a very wide margin of safety, much wider than any of the mainstream chemo drugs currently in use.
In time, I believe there will be sufficient clinical evidence showing that IVC can help reduce the risk of recurrence after successful treatment, just as adjuvant chemotherapy has been shown to do following surgery. Given that mainstream chemotherapy has proved unable to cure most cancers after they have metastasized, the door is still open for a minimally toxic therapy like IVC to prove its worth.
If you have questions or would like to schedule an integrative cancer coaching session, please reach out.
© 2019 Mark Nathaniel Mead, MSc.
Block KI, Mead MN. Vitamin C in alternative cancer treatment: historical background. Integr Cancer Ther. 2003; 2(2):147-54
Carr AC, Vissers MC, Cook JS. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Front Oncol. 2014;4:283. doi: 10.3389/fonc.2014.00283
Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11105-9.
Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, Choyke PL, Pooput C, Kirk KL, Buettner GR, Levine M. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci U S A. 2007;104(21):8749-54.
Drisko JA, Chapman J, Hunter VJ. The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer. J Am Coll Nutr. 2003 Apr;22(2):118-23.
Fritz H, Flower G, Weeks L, Cooley K, Callachan M, McGowan J, Skidmore B, Kirchner L, Seely D. Intravenous Vitamin C and Cancer: A Systematic Review. Integr Cancer Ther. 2014;13(4):280-300
Gonzalez MJ, Miranda-Massari JR, Mora EM, Jimenez IZ, Matos MI, Riordan HD, et al. Orthomolecular oncology: a mechanistic view of intravenous ascorbate's chemotherapeutic activity. P R Health Sci J. 2002;21(1):39-41
Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014;6:222ra218.
Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ. 2006 Mar 28;174(7):937-42.
Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004;140(7):533-7
Raymond YC, Glenda CS, Meng LK. Effects of High Doses of Vitamin C on Cancer Patients in Singapore: Nine Cases. Integr Cancer Ther. 2016;15(2):197-204.
Riordan HD, Riordan NH, Jackson JA, Casciari JJ, Hunninghake R, Gonzalez MJ, Mora EM, Miranda-Massari JR, Rosario N, Rivera A. Intravenous vitamin C as a chemotherapy agent: a report on clinical cases. P R Health Sci J. 2004 Jun;23(2):115-8
Riordan NH, Riordan HD, Meng X, Li Y, Jackson JA. Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent. Med Hypotheses. 1995;44(3):207-13
Schoenfeld JD, Alexander MS, Waldron TJ, Sibenaller ZA, Spitz DR, Buettner GR, Allen BG, Cullen JJ. Pharmacological Ascorbate as a Means of Sensitizing Cancer Cells to Radio-Chemotherapy While Protecting Normal Tissue. Semin Radiat Oncol. 2019 Jan;29(1):25-32.
Welsh JL, Wagner BA, van't Erve TJ, Zehr PS, Berg DJ, et al. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial.Cancer Chemother Pharmacol. 2013;71(3):765-75