Ellagic Acid Miracle Under Our Nose, Part 1

Living causes cancer,’ said a sign on the back of a bicycle that whizzed by me about 20 years ago on the campus of U. C., Davis. Even at that time, we knew a little more about cancer than that, and we had an arsenal of anti-cancer drugs — drugs that had lots of side effects, including loss of hair, appetite, weight, and libido, as well as severe gastric upset and psychological problems.

We still use many of these drugs and their descendants, and to counter their side effects, the drug companies have responded in a predictable way — with more drugs — while patient survival rates have not increased significantly.

One very powerful and all-natural alternative to this “toximolecular medicine” is ellagic acid. Ellagic acid is a phenolic dilactone, which is found in high abundance in many kinds of berries and grapes, aa well as pomegranates and some nuts, such as walnuts and pecans. It is formed from gallic acid when two gallic acid molecules become polymerized and attached to glucose to form tannins. When two gallic acid molecules in polymeric chains facing in opposite directions become linked, it forms an ellagitannin. When the ellagitannin is hydrolyzed, usually by acid treatment, it releases hexahydroxydiphenoic acid (HHDP), which spontaneously forms the dilactone ellagic acid (Figure 1) (1). Four of the 6 hydroxyl (OH) groups of HHDP are still free in ellagic acid, and they enable it to perform some of its functions. Among the berries, the Meeker red raspberry, which grows in the Pacific Northwest and primarily in the state of Washington, has the highest content of ellagic acid, with the Chiliwak and the Willamette reed raspberries not far behind. Ellagic acid and some similar compounds have been more recently found in the bark of the tree Eschewilera coriacea, which grows in the Central American rainforest (2). While stripping the bark from this tree would kill it, it the leaves may contain ellagic acid, and/or it could be made from bark cells grown in culture. The walnut, however, may be an even better commercial source, for the ellagic acid in walnuts is found in the “skin,” the reddish-brown, membranous substance between the nut and the shell. Normally, this skin is simply thrown away, so ellagic acid can be produced less expensively from this source than from berries.

Scientists began studying the anticarcinogenic properties of ellagic acid in the early 80′s. They found that because of its free phenolic OH groups, ellagic acid had antioxidant properties similar to vitamin E and flavonoids. The OH group donates a proton and an electron to the free radical, turning it into a stable and relatively harmless compound. At the same time, the aromatic rings of ellagic acid stabilize this new free radical of ellagic acid until it receives an electron from the electron transport system or encounters another free radical, which regenerates the ellagic acid. Lipid peroxidation is both caused and propagated by free radicals, which can be generated by chemicals, radiation, or other sources. Early studies showed that ellagic acid dramatically reduces lipid peroxidation (3), and more recent studies show that it also reduces DNA damage induced by radiation.
However, the antioxidant activity of ellagic acid is hardly its best asset. It is better known for many other reactions, such as binding to active carcinogens in a way that renders them harmless. Most carcinogens are not active in their native form, but must be activated by “detoxifying” enzymes, usually in the liver, called the “cytochrome P450s.”

These enzymes “charge” oxygen by binding it to iron and polarize it, so that one atom of oxygen gets converted to water while the other one turns the stable foreign molecule into a reactive chemical in order to attach other molecules to it to make it more soluble. Researchers have used benzopyrene as a model carcinogen for decades due to its abundance in pollution and cigarette smoke. Benzopyrene itself is not active, but the P450s convert it into an epoxide, a highly reactive compound which attaches to many biological molecules, including DNA.

Other enzymes, such as glutathione S-transferase (GST), are supposed to attach other molecules, such as glutathione or glucuronic acid, onto the epoxide, making it not only harmless, but more soluble as well, so that it can be excreted.

However, they can only do this after the epoxide is released from the P450, which gives the epoxide a chance to do its dirty work.

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