05 August 2008

Vitamin C and cancer: is Linus Pauling partially vindicated?

Chen, Q., Espey, M.G., Sun, A.Y., Pooput, C., Kirk, K.L., Krishna, M.C., Khosh, D.B., Drisko, J., Levine, M. (2008). Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0804226105

In his paper1 Evolution and the Need for Ascorbic Acid, Linus Pauling concluded that the optimum daily requirement of ascorbic acid (vitamin C) for a human being was about 2.3 grams. Pauling’s argument was based on his calculation showing that 2.3 g was the total amount of ascorbic acid in foods (mainly vegetables and fruits, but no meats) that a human would need to consume to fullfil a daily average energy requirement of 2500 kcal.

From there, Pauling went on to claim that mega doses of ingested vitamin C were good to cure not only relatively minor inconveniences like the common cold but also deadly cancers. Ironically, Pauling died of prostate cancer.

There were two flaws in Pauling’s original argument. First, he seems to have ignored the fact that Homo sapiens evolved to be an omnivore. Consequently, Pauling’s exclusion from his menu of animal flesh, which doesn’t contain much ascorbic acid (also see this post), but provides a lot of calories, created a skewed daily menu that was unnaturally high in ascorbic acid. Second, just because a daily food composition, put together to provide enough calories, contains 2.3 g of ascorbic acid, doesn’t necessarily mean that that much ascorbic acid is optimally required. The amount of ascorbic acid or any other micro nutrient in a menu created solely to provide enough calories could be an incidental outcome of the specific composition of that particular menu.

Subsequently, it was demonstrated that in rodents oral intake of ascorbic acid could not produce plasma concentrations larger than 0.2x10-3 M (information from reference 2). Presumably, a similar limit also exists in humans, making oral intakes of large doses of ascorbic acid pharmacologically useless.

Now a paper2 that just got published demonstrates that direct injections of high doses of ascorbic acid significantly decreases growth rates of various tumors in mice. Injections result in elevated levels of ascorbic acid within the tumors, because they by-pass the gastrointestinal barriers that otherwise prevent the passage of high amounts ascorbic acid into the blood. The mechanism of action of ascorbic acid is believed to involve the creation of hydrogen peroxide, which appears to be more toxic to cancer cells than to normal cells.

In this example, daily injection of 4 g ascorbic acid per kilogram of body weight slowed down the growth of pancreatic tumors in mice (bottom curve) as compared to the control group (top curve). [Fig. 2E from Chen et al.]

However, the catch is that ascorbic acid did not cure the mice of their cancers; it only slowed the growth of their tumors. Nevertheless, Chen et al. end their paper on a cautiously optimistic note:
Although our preclinical mouse data showed that tumor growth was significantly decreased (Fig. 2), the use of pharmacologic ascorbate as a single agent was not curative. As modalities in cancer are often combined, these data suggest that pharmacologic ascorbate in combination with other therapies deserves further exploration for treatment of cancers that otherwise have poor outcomes, such as pancreatic and ovarian carcinomas and glioblastoma.
Some of the credit still goes to Pauling.

1. Linus Pauling (1970). Evolution and the Need for Ascorbic Acid. PNAS, 67:1643-1648. (pdf).
2. Chen et al., Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. PNAS, published ahead of print August 4, 2008, doi:10.1073/pnas.0804226105 (abstract).

1 comment:

xoggoth said...

I drink vast quantities of lime juice and am never ill. Pity about the vast quantities of vodka I mix it with.