Алексей Башкирцев
Chief Physician of the Edem Resort Medical & SPA Complex, Candidate of Medical Sciences
Forever young
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VITAMIN C AND CANCER: what will win?

VITAMIN C AND CANCER: what will win?
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Photos courtesy of Edem Resort Medical & SPA

 

Over the past decade, a growing body of research has demonstrated that vitamin C at millimolar concentrations can kill cancer cells in vitro and slow tumor growth in vivo. However, the mechanisms by which some cancer cells become sensitive to vitamin C and normal cells remain resistant are poorly understood.

Nowadays, we will talk about the importance of vitamin C and its fight against cancer with Alexey Bashkirtsev, the chief physician of the Edem Resort Medical & SPA complex, the candidate of Medical Sciences, the academician of the European Academy of Natural Sciences, the member of the Supervisory Board of Singularity University (Kiev) in the field of exponential medicine, the international expert on Anti-Aging Medicine, the Fellow of the American Academy of Anti-Aging Medicine.

One of these mechanisms was discovered quite recently by a group of analysts led by Lewis Cantley, an American scientist known for his work in the field of cell biology and oncology. Their research on the role of vitamin C in cancer patients received grant support from the US National Institutes of Health and were published in the renowned scientific journals Nature Reviews Cancer, Science.

The essence of the scientists’ discovery is in the following. Colorectal cancer cells are known to contain mutations in KRAS or BRAF in more than half of cases and are therefore often immune to approved targeted therapies. Scientists have found that these cancer cells are selectively killed when exposed to high levels of vitamin C. This effect is associated with increased absorption of dehydroascorbate (an oxidized form of vitamin C) by the glucose transporter GLUT-1.

Increased absorption of dehydroascorbate causes oxidative stress as intracellular dehydroascorbate is reduced to vitamin C while depleting glutathione. Reactive oxygen species accumulate and inactivate glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic mutant KRAS or BRAF cancer cells leads to their energy crisis and death.

A growing body of research suggests that vitamin C, a natural ingredient with a high safety profile, may interfere with multiple pathogenic pathways in cancer. It targets various mechanisms that cancer cells use to survive and grow, namely redox imbalance, epigenetic reprogramming, and regulation of oxygen sensitivity.

While these mechanisms and predictive biomarkers need to be validated in well-controlled clinical trials, new discoveries regarding the antitumor properties of vitamin C hold promise for identifying patient populations that may benefit mostly from high-dose vitamin C therapy.

Over the past century, the claim that vitamin C can be used to treat cancer has generated a lot of controversy. The history of using high doses of vitamin C to treat cancer began about 60 years ago when Canadian physician William McCormick noticed that cancer patients often have low levels of vitamin C in their blood and suggested that vitamin C might protect against cancer.

In 1972, Scottish surgeon Evan Cameron formulated a hypothesis in which he suggested that ascorbic acid could stop the development of cancer by inhibiting the enzyme hyaluronidase, which breaks down the extracellular matrix, thereby promoting metastasis.

To confirm the correctness of his hypothesis, he began treating patients with terminal cancer and published an article describing 50 cases in which the administration of vitamin C had a positive effect on the course of the disease.

Inspired by this result, Cameron, in a team with renowned scientist Linus Pauling, conducted clinical trials involving 100 terminal cancer patients. Their disease progress and survival rates were compared with a group of 1000 patients, similar in age, sex and diagnosis, but not taking vitamin C. The results showed that 22% of cancer patients who received intravenous vitamin C at a dose of 10 g/day lived 1 year longer in comparison with the control group, in which this indicator was only 0.4% of cases.

 

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But the link between vitamin C supplementation and prolonging the life of cancer patients has been challenged by other studies conducted at the Mayo Clinic and published in the renowned medical journal NEJM. The appearance of this publication-refutation of the effectiveness of ascorbic acid in the treatment of cancer patients in such a reputable journal from the specialists of the leading world clinic led to a decrease in interest in this topic.

But why did these studies show such the opposite result? Their comparison revealed two main differences. Firstly, the average duration of vitamin C treatment in the Mayo Clinic trials was only 2.5 months. Vitamin C treatment was discontinued as soon as signs of tumor progression appeared.

The second significant difference was that in the Mayo Clinic studies, vitamin C was taken at a dose of 10 g/day orally. Whereas in the Cameron’s and Pauling’s studies, vitamin C treatment was long-term using the intravenous route.

Given the new knowledge about the pharmacokinetics of vitamin C, its peak plasma concentration in the Mayo Clinic study was 25 times lower than in the Cameron’s and Pauling’s trials. It is due to the fact that when taken orally, the plasma concentration is highly dependent on many factors (absorption in the intestine, renal reabsorption and secretion). At the same time, the desired concentration of ascorbic acid can be easily obtained by intravenous administration.

Thus, in the first phase of a clinical study of metastatic pancreatic cancer, it was revealed that the concentration of vitamin C can safely reach 25-30 mmol with its intravenous infusion at a dose of 100 g. Considering the fact that at the Mayo Clinic, cancer patients received vitamin C only orally, thе study cannot disprove the effectiveness of high doses of this vitamin in cancer treatment.

New knowledge of the pharmacokinetic properties of vitamin C and recent high-profile preclinical trials have revived interest in the use of high doses of ascorbic acid for cancer treatment. New studies of its clinical potential have appeared, in particular phase I/II, testing the safety and efficacy of high doses for the treatment of various cancer patients in the form of monotherapy or combination therapy.

 

VITAMIN C AND CANCER: what will win?

 

Virtually all of these studies show improvements in the quality of life of cancer patients by minimizing pain and protecting normal tissues from chemotherapy-induced toxicity.

In addition, vitamin C has shown synergistic effects when combined with radiation therapy and standard chemotherapy. Unfortunately, these studies were not designed as large randomized controlled trials, so the effectiveness of high-dose vitamin C therapy remains to be proven.

There are at least three problems that have hindered large-scale randomized controlled trials of vitamin C for cancer treatment so far. Firstly, vitamin C is not patented.

Thus, pharmaceutical companies have no financial incentive to support vitamin C clinical trials, and those that have been conducted have relied heavily on government subsidies and small private donations.

Secondly, as discussed above, vitamin C cancer therapy has been controversial for a long time. Due to Mayo’s clinical research in the 1980s, many orthodox clinicians have a bias against vitamin C therapy.

Thirdly, although many preclinical studies have shown that high doses of vitamin C can kill cancer cells or slow down tumor growth in vivo, the mechanisms of action of vitamin C are unclear, making it difficult to predict pharmacodynamics, rational design of combination therapy, and biomarkers for patient stratification.

Fortunately, a growing body of rigorous preclinical research has begun to tackle the third problem, which can also lead to overcoming the first and second hurdles. Understanding the pharmacological action of vitamin C will lead to clearer scientific hypotheses and enable clinicians to design more effective studies to test them, ultimately leading to a definitive answer to the question. Can intravenous vitamin C benefit cancer patients?

 

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