Tag: ascorbic acid

High-dose intravenous vitamin C therapy is a promising cancer treatment

Claus Hancke

February 21, 2026

A new review article with thorough analysis can hopefully increase public interest in this safe and side-effect-free cancer treatment.

A few weeks ago you could read the above headline, published in Genes & Diseases af Zhao et al.,  (https://www.sciencedirect.com/science/article/pii/S2352304225002314?via%3Dihub).

Normally one would expect such a headline formulated something like “a new, promising treatment….”, but that is not possible here, because the treatment is certainly not new. Vitamin C (ascorbic acid) has been the subject of intense debate in cancer research since the 1950s. Yes, in fact we have to go back 90 years to 1936, when the later renowned Danish professor of pediatrics at Rigshospitalet Preben Plum published a scientific article in “Ugeskrift for læger”, in which he describes remission of leukemia after intravenous treatment with vitamin C (IVC). But interest was really aroused in the 1970s by Cameron and Nobel Prize winner Linus Pauling, who reported greatly prolonged survival in cancer patients treated with IVC. However, interest stopped after the Mayo Clinic conducted a few studies with oral vitamin C treatment, which of course had no effect. When I write “naturally”, it is because oral dosing is impossible in the doses that would theoretically be required to achieve the same concentration in the blood.

Intravenous or oral intake: I can illustrate this with the following: For vitamin C to have an anti-cancer effect, it requires a serum concentration of 3.5g/L (grams per liter). We have 5 liters of blood plus at least 5 liters of tissue fluid between the cells. For the concentration in these 10 liters to reach 3.5g/L, an intravenous infusion of at least 35 g is required. Since the half-life is short and turnover is rapid, vitamin C must be continuously supplied to the bloodstream so that this concentration can be maintained for 2-3 hours. This means that you typically give an infusion of 75-100g over 3 hours. This is completely without side effects other than a slight stinging at the injection site. And this problem can be easily resolved.

What about eating it? With an oral absorption of around 50%, we can quickly calculate that if you were to theoretically reach the same concentration in the blood, you would have to eat 150-200g of vitamin C over a few hours. First, it is impossible. Second, the gastrointestinal system would break down, so you would never get further than 15-20g before you got severe diarrhea. In other words, it is not possible to eat vitamin C to achieve an antitumor effect in the body.

The article also describes that oral administration can achieve a maximum plasma concentration of approximately 220 μmol/L, whereas IV administration bypasses the physiological barrier of the intestine, thereby achieving a plasma concentration of 20-30 mmol/l, which is 100 times higher than plasma concentration. And this is necessary to achieve a direct cytotoxic effect on cancer cells.

Anti-tumor mechanisms: The article identifies four primary mechanisms through which IV vitamin C fights cancer:

1. Pro-oxidative activity (Killing cells via free radicals)

It is well known that vitamin C in low doses functions as an antioxidant, but not so well known that in high doses it functions as a pro-oxidant, i.e. creates free radicals (especially in cancer cells that have poor antioxidant defenses.)

  • Iron-dependent ROS generation: Cancer cells often contain large amounts of free iron (labile iron). IVC reacts with this iron and produces H2O2, which via the Fenton reaction forms hydroxyl radicals (OH*). These radicals damage the mitochondria, DNA and cell membranes of cancer cells, causing the cell to die.
  • Selectivity: Normal cells have an effective defense (including catalase) that breaks down OH*, while cancer cells often lack this defense, making them vulnerable.

2. Metabolic (The Warburg effect)

Cancer cells with specific mutations (e.g. KRAS or BRAF) overexpress the glucose transporter GLUT1.

  • The DHA molecule (the oxidized form of vitamin C) resembles glucose and is taken up by GLUT1.
  • Inside the cell, DHA is converted back to ascorbate, depleting the cell’s stores of NAD+ and glutathione. This leads to metabolic collapse, where energy production stops and the cell dies.

3. Epigenetic regulation

IVC functions as an important cofactor for TET enzymes that control DNA demethylation.

  • Cancer cells often “turn off” tumor suppressor genes via hypermethylation.
  • IVC can reactivate these genes by promoting TET activity, which slows tumor growth and promotes cell differentiation.

4. Immunomodulation

IVC improves the immune system’s ability to recognize and kill cancer cells by:

  • Increase the infiltration and activity of CD8+ T cells and NK cells (Natural Killer cells.)
  • Lower the effect of PD-L1 (a protein that cancer cells use to “hide” from the immune system.)
  • Act synergistically with modern immunotherapy (checkpoint inhibitors.)

Synergy with standard treatment

Research to date has shown that IVC is less effective as a monotherapy, but excellent in combination with:

Effect of IVC:

Radiation therapy: Acts as a “radiosensitizer” (makes cancer cells more sensitive) while protecting normal tissue from radiation damage (such as e.g. pulmonary fibrosis.)

Chemotherapy: Increases the effect of chemotherapeutics such as cisplatin and carboplatin by weakening the antioxidant defenses of cancer cells.

Targeted therapy: Enhances the effect of e.g. EGFR inhibitors by creating an imbalance in the redox status of cancer cells.

Immunotherapy: Improves the response rate to PD-1/CTLA-4 blockade by altering the tumor microenvironment.

Early phase I and II clinical studies have confirmed:

1. High safety: Intravenous vitamin C is well tolerated, even at doses up to 1.5 g/kg body weight.

2. Quality of life: Patients report fewer side effects from chemotherapy (less fatigue, fewer gastrointestinal problems, and better appetite) when they receive IVC concomitantly.

3. Challenges: Results for longer survival are still inconsistent in phase II studies, which has slowed the transition to large phase III studies. This is likely due to differences in dosing, frequency, and patient selection.

Challenges and future recommendations

For intravenous vitamin C therapy to become a standardized part of cancer treatment, the article points to several critical points:

Optimal dosing: There is still debate about dosing, so there is a lack of consensus on whether to dose according to body weight or up to a specific plasma level.

Patient selection: Future studies should focus on patients with specific genetic markers (e.g. KRAS mutations or low TET2 levels), who theoretically should benefit greatly from the treatment.

Timing: The order of administration (before, during or after chemotherapy) is crucial and has not yet been fully optimized, which is why there is a lack of consensus.

Risks: There has been concern about the theoretical risk of kidney stones in the past, but this theory has long been disproven. On the other hand, there is a real risk for those patients who may suffer from Glucose-6-phosphatase dehydrogenase (G6PD) deficiency, who are at risk of bleeding at the IVC. However, this can be easily avoided by testing or careful initiation.

(Note from the undersigned: For more than 30 years, I have performed approximately 100,000 IVC treatments without a single case of kidney stones or G6PD bleeding. In Danes, the incidence of G6PD deficiency is 0.1%, whereas it is 10-20% in immigrants from the Middle East, which is why special attention must be paid here.)

Conclusion

High-dose intravenous vitamin C therapy has been used for the past 50 years outside the orthodox healthcare system and without much public interest, but has now reemerged as a serious candidate in the treatment of cancer. The treatment’s unique ability to act as a pro-oxidative tool that selectively targets cancer cell metabolism and epigenetics makes it a promising adjuvant therapy. It is not a miracle cure, but there is every indication that it can improve the efficacy of existing treatments and reduce patients’ suffering during the course.

Take care of yourself and others.

Claus Hancke
Specialist in general medicine

Refs:

Zhao H et al, Genes & Diseases (2026) 13, 101742. https://www.sciencedirect.com/science/article/pii/S2352304225002314?via%3Dihub

Plum P, Thomsen S, Remission under forløbet af akut, aleukæmisk leukæmi, 1936 Ugeskr Læg Særtryk 98.årg. 1062-1067.

Bodeker KL et al, (2024) A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer, Redox Biology, Vol.77, Nov-2024, 103375

https://www.sciencedirect.com/science/article/pii/S2213231724003537?ref=pdf_download&fr=RR-2&rr=9cce1dfc69066707

Vitamin C, Research references

Admin

January1999

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Sources
Joseph E. Pizzorno Jr., Michael T. Murrey & Melvyn R. Werbach.