A new study published in Science presents evidence that perhaps some of the apparently extravagant ideas about vitamin C were not completely off base. The study in question examined human colorectal cancers containing specific genetic mutations that are found in up to half of these cancers. These cells ended up drawing in so much vitamin C that it caused their death.

The researchers used a cell culture and subsequent experiments in mice to explore the effects of high doses of vitamin C on cancer cells. The initial data came from an application of vitamin C and metabolized versions of vitamin C to a cell culture that included both mutated cancer cells and wild type control cells. The cancerous cells carried two mutations (in KRAS and BRAF) that are commonly found in colorectal cancers.

Their results indicated that the colorectal cancer cells were more likely to absorb the vitamin C metabolite than the cells without those mutations. This is due to an up regulation of the protein that pulls vitamin C and its metabolites into cells. These cells imported so much of these chemicals that they experienced cell death.

The researchers then grafted tumors with these mutations into mice to see if these results would hold within an animal. They again found that the vitamin C was selectively toxic to the tumors containing KRAS mutations, effectively killing these cells.

Further examination of the effects of vitamin C revealed that it reduced the availability of intracellular energy units known as ATP, causing a critical lack of energy in these cells.

This study’s most important finding is its identification of the cellular pathway involved in cancer killing. The researchers found that the therapeutically active chemical is the vitamin C metabolite dehydroascorbate. It caused increased vitamin C uptake through the upregulation of GLUT1 transporters in mutated cells, but this didn’t take place in normal cells.

Use of vitamin C as a cancer therapy has been controversial. Early studies showed it to have some utility in treating cancer, whereas others indicated it had little effect.

The most famous advocate of vitamin C as a cancer treatment was Linus Pauling, a scientist and activist who received Nobel Prizes in Chemistry and Peace. His later years were marked by an obsession with using high doses of vitamin C as a panacea to treat everything from cancer to the common cold, even though the evidence supporting this was patchy at best. This largely earned him contempt from the scientific community.

This research, as well as other emerging research on the potential therapeutic uses of high-dose vitamin C to treat cancer, has the potential to vindicate this part of Pauling’s legacy—rather than a brilliant scientist who became a heretic later in life, he may simply have been a scientist with an idea that wasn’t yet supported by the available evidence.

Science, 2015. DOI: 10.1126/science.aaa5004 (About DOIs).