Hype or Hope? Killing Cancer with Vitamin C

There are few cancer treatments that give patients long-term hope of survival. Could vitamin C be the missing link?

The number of people who die from cancer each year in the United States has gradually been falling. While this might seem to be good news, cancer remains the second biggest killer worldwide.

According to the National Cancer Institute (NCI), the cancer death rate for men fell by 1.8 percent between 2004 and 2013, by 1.4 percent for women during the same period, and by 1.4 percent for children between 2009 and 2013.

But 1,960 children still died of cancer in 2014, and 595,690 adults died in 2016.

For patients, family members, and friends, as well as those involved in cancer care and research, these numbers are a stark reminder that despite the many medical advances of the past century, cancer still holds a firm grip on our lives.

The use of vitamin C, or ascorbic acid, as an alternative method to treat cancer has been making headlines since the 1970s.

What does vitamin C do?

Humans cannot make vitamin C because we lack the necessary enzymes. Instead, we need to consume this essential vitamin in our diet.

Vitamin C has several crucial functions, including playing a key role in the production of collagen, which is the central component of connective tissue.

It is also involved in the synthesis of neurotransmitters, such as dopamine and norepinephrine, and in the addition of the protective myelin coat to nerve cells in the brain’s white matter. In addition, it is known to have strong antioxidant properties, protecting cells from oxidative damage.

As vitamin C is involved in a host of processes that help to keep our bodies healthy, it may be no great surprise that research has pointed to several different ways that ascorbic acid can affect cancer.

Three different mechanisms have recently been described.

1. Switch from antioxidant to pro-oxidant

Mark Levine, from the Molecular and Clinical Nutrition Section at the National Institutes of Health (NIH) in Bethesda, MD and colleagues showed that in the presence of metals, vitamin C produces hydrogen peroxide.

This molecule is a powerful oxidant and is very toxic to cells – especially cancer cells.

However, targeting cancer is not as simple as eating some extra oranges each day. Our bodies are extremely good at maintaining healthy levels of vitamin C when it is consumed in our diet. And when there is too much vitamin C in the system, it is simply cleared in the urine.

Levine shows that administering vitamin C by injection at high levels allows it to outfox our body’s control mechanisms.

Dr. Lewis Cantley, from Weill Cornell Medicine in New York City, NY, and colleagues also found that vitamin C had a strong pro-oxidant effect in a study using colorectal cancer cells.

Treatment with high levels of vitamin C caused enough oxidative damage to these cells to kill them by a cell death process known as apoptosis.

In addition to the pro-oxidant effect that vitamin C had on cells in this study, Dr. Cantley found that it inhibited glycolysis, which is a metabolic pathway that cells use to convert glucose into energy.

2. Starving cancer cells from the inside

Making use of the cancer cell’s own metabolic pathways is key to the findings of Michael P. Lisanti, from the Biomedical Research Centre at the University of Salford in Manchester, U.K., and his colleagues.

In a cell model, they showed that cancer stem cells (CSCs) rely heavily on mitochondria for their metabolism. Mitochondria are small structures within cells that generate energy. Glycolysis and mitochondrial metabolism are intricately linked.

Once energy is released from glucose by glycolysis, the end product of this pathway, pyruvate, is taken into mitochondria, where it is the starting point for a series of biochemical reactions that release energy from the molecule.

Lisanti’s work is in agreement with the findings of Dr. Cantley’s study: vitamin C induces oxidative stress in CSCs and inhibits a key enzyme involved in glycolysis.

No glycolysis means no pyruvate, which, in turn, means that the mitochondrial powerhouses cannot generate any energy. The CSCs starve as a result.

And in a follow-up study, the researchers used this knowledge to design a new way of killing CSCs by using a combination of antibiotics and vitamin C. Some antibiotics, such as doxycycline, affect how well mitochondrial work.

Treating CSCs with this antibiotic knocked out mitochondrial function, leaving the cells dependent on glycolysis to generate enough energy to keep them alive. But hitting CSCs with a dose of vitamin C shut off that alternative by inhibiting glycolysis.

The cells were left without energy. The only option was death.

But energy metabolism is not the only weapon in vitamin C’s arsenal, it seems; vitamin C can also act on DNA and affect stem cell development.

3. Switching genetic control mechanism back on

DNA methylation switches off individual genes. Small chemical groups called methyl groups are added to stretches of DNA, making them inaccessible to the enzymes responsible for initiating gene expression.

This process is essential to normal cell function because an individual cell does not need to make use of the thousands of genes encoded in its DNA.

When a stem cell becomes a more differentiated cell type, certain genes must be demethylated, or have the methyl tag removed, to allow them to be switched back on.

But in the case of many leukemia patients, who have a mutation in a gene called TET2, this control mechanism does not function properly.

TET2 demethylates DNA and therefore allows access to certain genes. A mutation in TET2 in blood stem cells means that they do not develop into mature blood cells, leaving the body notoriously short of these vital cells. Instead, the stem cells continue to divide, resulting in blood cancers such as leukemia.

Luisa Cimmino, from the Department of Pathology at New York University School of Medicine, and colleagues used a genetically engineered mouse to study this.

In these mice, TET2 could be switched off in stem cells, leading to abnormal cell growth. When high doses of vitamin C were added, DNA demethylation was switched back on, and cell behavior returned to normal.

TET mutations or lower TET levels have also been found in other cancers, including melanoma, colorectal, gastric, prostate, liver, lung, and breast cancer, as well as glioblastoma.

Using vitamin C to turn back the clock on CSCs’ disastrous growth allows them to develop into mature cells instead. This is a completely different approach to killing cancer cells by oxidative damage.

Research shows that both strategies may have merit. But can cancer patients look to vitamin C for real hope?

Hype or hope?

According to the NCI, clinical studies using vitamin C in combination with other cancer drugs have shown mixed results. In some cases, patients felt that their quality of life improved. Other studies showed that tumors had stopped growing.

In some studies, however, vitamin C and conventional drugs used to treat cancer reacted with each other, and the result was that the treatment did not work.

A 2010 study by Levine revealed that U.S. complementary and alternative medicine practitioners frequently use vitamin C injections for a range of conditions – including cancer treatment – despite the fact that vitamin C is not licensed by the U.S. Food and Drug Administration (FDA) for this purpose.

So is vitamin C just another hype? There is no simple answer to this question. Research has certainly shown that vitamin C has the power to kill cancer cells or change how cancer stem cells behave, at least in laboratory studies.

The NCI currently report five active trials investigating vitamin C in combination with other cancer drugs.

What is clear, however, is the passion and drive with which scientific and medical researchers are pursuing this question. Lives are at stake, and everyone wants to know if vitamin C will soon be at the frontline in the fight against cancer.

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