Re-evaluating an Old Controversy in Cancer Care
Exploring the renewed scientific interest in intravenous vitamin C for cancer therapy
For decades, the idea that vitamin C could fight cancer existed in the shadowy realm of dismissed medical folklore. Championed by a Nobel laureate but rejected by mainstream oncology, its story served as a cautionary tale about the dangers of science by celebrity. Yet today, this simple molecule is making an unexpected comeback in cancer research labs and clinical trials worldwide.
What changed? The answer lies in a critical distinction overlooked for years—the profound difference between swallowing a vitamin pill and receiving it intravenously.
This article explores the compelling new science revealing how high-dose intravenous vitamin C, once relegated to alternative medicine, is now being re-evaluated as a potential multi-targeting anti-cancer agent with the power to selectively kill cancer cells while improving patients' quality of life.
Key difference from oral supplements
Affects cancer cells differently than healthy cells
New research renewing interest in old therapy
The story of vitamin C as a cancer therapy begins in the 1970s with Scottish surgeon Ewan Cameron and double Nobel laureate Linus Pauling. Their observational study of 100 terminal cancer patients treated with intravenous vitamin C reported stunning results.
Cameron and Pauling report extended survival in terminal cancer patients with IV vitamin C.
Mayo Clinic trials using oral vitamin C show no benefit, discrediting the therapy.
Researchers identify the crucial difference between oral and IV administration.
Modern research with proper IV protocols shows promising anti-cancer mechanisms.
For over two decades, this contradiction remained unresolved until researchers discovered a crucial methodological difference: the Mayo Clinic trials had administered vitamin C orally, while Cameron and Pauling had used intravenous infusions 5 . This route of administration, it turned out, made all the difference.
The resolution to the decades-long controversy lies in basic pharmacokinetics—how the body processes substances differently based on how they're administered.
When vitamin C is taken orally, our bodies tightly control its absorption through multiple mechanisms, including intestinal regulation and renal excretion.
Even with massive oral doses approaching tolerance limits, plasma concentrations of vitamin C never exceed 250 μmol/L 1 .
When administered intravenously, vitamin C bypasses the digestive system's strict controls, allowing much higher plasma concentrations.
IV administration allows plasma concentrations to reach millimolar levels—up to 25,000 μmol/L, which is more than 100 times higher than achievable through oral administration 1 5 .
| Route of Administration | Typical Dose | Peak Plasma Concentration | Key Limiting Factors |
|---|---|---|---|
| Oral | 10 grams | <220-250 μM | Intestinal absorption, renal excretion |
| Intravenous (IV) | 10 grams | ~6,000 μM | None (bypasses GI regulation) |
| Intravenous (IV) | 50-100 grams | 13,000-25,000 μM | Renal threshold (after infusion) |
These dramatically different concentration levels explain the conflicting historical results. The anti-cancer effects of vitamin C appear to require the millimolar concentrations that are only achievable through intravenous administration 1 . At these pharmacological concentrations, vitamin C ceases to function primarily as an antioxidant and begins generating hydrogen peroxide and other reactive oxygen species that can selectively damage cancer cells while leaving healthy cells largely unaffected 7 .
While early research focused on vitamin C as a general cancer treatment, recent studies have identified specific cancer types that might be particularly vulnerable. One groundbreaking experiment focused on colorectal cancers with KRAS and BRAF mutations—precisely the types that are most refractory to conventional targeted therapies 5 .
The team first examined colorectal cancer cell lines with either KRAS or BRAF mutations alongside cells with normal versions of these genes. They treated all cell lines with pharmacological concentrations of vitamin C (equivalent to those achieved by IV administration in humans) and measured cell death.
Researchers tracked the uptake of vitamin C's oxidized form (dehydroascorbic acid or DHA) into cancer cells, specifically monitoring the glucose transporter GLUT1, which cancer cells with KRAS/BRAF mutations overexpress to fuel their growth.
The team measured the effect on a key glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which is essential for energy production in cancer cells.
The most promising in vitro findings were then tested in mouse models of KRAS-mutant colorectal cancer. Mice received daily intraperitoneal injections of high-dose vitamin C (equivalent to IV administration in humans), and tumor growth was monitored over time.
The findings were striking. Cancer cells with KRAS or BRAF mutations showed significantly increased uptake of vitamin C's oxidized form because they overexpressed the GLUT1 transporter 5 . Once inside the cells, the vitamin C accumulation led to oxidative stress that inactivated the GAPDH enzyme, effectively shutting down glycolysis—the primary energy production method these cancer cells depend on 7 .
| Parameter Measured | KRAS/BRAF Mutant Cells | Normal (Wild-type) Cells | Biological Significance |
|---|---|---|---|
| GLUT1 Expression | Significantly increased | Normal levels | Mutant cells take up more oxidized vitamin C |
| Glycolytic Dependence | High | Variable | Mutant cells rely heavily on glycolysis for energy |
| GAPDH Inhibition | Marked | Minimal | Vitamin C disrupts energy production in mutant cells |
| Cell Death | Significant | Minimal | Selective toxicity to cancer cells with these mutations |
In mouse models, daily high-dose vitamin C administration significantly inhibited tumor growth in KRAS-mutant cancers while causing minimal toxicity to healthy tissues 5 . This selective effect represents a potential therapeutic window—the ability to target cancer cells while sparing healthy ones.
Clinical trials of high-dose IV vitamin C have generally shown it to be well-tolerated and safe at doses up to 1.5-2 grams per kilogram of body weight 2 3 . The most common side effects include mild lethargy or fatigue, while serious adverse events are rare and primarily occur in patients with specific risk factors such as kidney impairment or glucose-6-phosphate dehydrogenase deficiency 6 8 .
While evidence for vitamin C as a standalone cure remains limited, research increasingly focuses on its potential as an adjuvant therapy—enhancing the effectiveness of conventional treatments while reducing their side effects. Studies have reported that IV vitamin C can improve quality of life for cancer patients by reducing cancer-related symptoms such as fatigue, bone pain, and chemotherapy-induced toxicities 1 6 .
Identifying which patients with specific tumor types and genetic profiles will benefit most.
Exploring optimal dosing strategies for different cancer types and stages.
Finding synergistic combinations with conventional therapies.
The story of intravenous vitamin C in cancer therapy exemplifies how scientific understanding evolves through rigorous questioning, methodological refinement, and willingness to re-examine dismissed ideas. What was once rejected by mainstream oncology is now being systematically investigated with modern scientific tools.
While high-dose IV vitamin C is not yet a standard cancer treatment and should only be administered in the context of clinical trials, its journey from medical pariah to promising investigational agent offers compelling insights into how simple substances, when understood deeply, may reveal unexpected complexities in the challenging fight against cancer.