A Surprising Way Green Tea Is Good for Your Heart

by Mika Pringle Tolson

Asheesh Tiwary may have discovered a safer human heart medication using a compound found in green tea

What do animals, oleander, green tea, and heart medication have in common? Plenty, if you're Asheesh Tiwary, a doctor of veterinary medicine and researcher at UC Davis. Tiwary accidentally discovered a way to make potentially safer human heart medications while trying to find a better antidote for oleander poisoning in animals.

Tiwary began work as a veterinary toxicologist in the California Animal Health and Food Safety Lab while pursuing his doctoral degree in Pharmacology and Toxicology. "I wanted to work on a disease that is most commonly presented from a toxicological perspective," says Tiwary. "The largest number of toxicology-related cases in our database were those of oleander intoxication."

The UC Davis School of Veterinary Medicine sees on average two to three potential cases of oleander poisoning a week and hundreds a year. "This is just a small representation of what is happening out there," says Tiwary.

Current treatments for oleander poisoning leave a lot to be desired. There is no known specific antidote. Only 5-10 leaves of oleander are enough to cause clinical disease in a cow or horse. Death can occur within a day or two after exposure. Oleander poisoning can also cause mild problems in animals that can go on for weeks.

Tiwary was awarded a TSR&TP fellowship to investigate how oleandrin damages the heart and screen for drugs to prevent this damage. "Because of TSR&TP I was able to follow up on a project that I wanted to do," he says. "In most cases grad students do a project already ongoing in a lab. This one I started from scratch. From a grad student perspective that's big."

Oleandrin is structurally similar to digoxin, a commonly used human heart medication. Oleandrin binds to the heart and inhibits the normal sodium-potassium pump. Calcium accumulates in the cells and "as a result, the heart pumps harder and in some cases of overdose, arrhythmically," explains Tiwary.

Tiwary and his group looked at several FDA approved drugs for animals and humans and only three showed effects. DigiFab, an antibody to digoxin limited the inhibition of the sodium-potassium pump. A non-steroidal anti-inflammatory drug phenylbutazone also provided protection against oleandrin. They now recommend a combination therapy of activated charcoal, DigiFab and phenylbutazone for treatment of oleander poisoning in animals.

A third compound tested showed opposite results. Epigallocatechin gallate (EGCG), a potent antioxidant found in green tea increased the toxic effect of oleandrin by enhancing sodium-potassium pump inhibition. This gave Tiwary pause. "Several studies recommend 5-10 cups of green tea a day," he says. This dose of green tea can provide a blood serum concentration of 3-4 micomolars of EGCG. Tiwary evaluated EGCG concentrations of up to 20 micromolars and found no toxicity on heart cells.

Digoxin has a narrow therapeutic index - the margin between effectiveness and injury. EGCG may be able to increase the effectiveness of digoxin while decreasing total toxicity. Tiwary and his group are investigating whether they can reduce the dose of digoxin and replace it with EGCG with the same therapeutic results.

"If this model works," he explains. "There's a potential to incorporate EGCG as a part of routine heart failure treatment. You get the same beneficial effects, but less potential for toxicity."

Tiwary received his PhD in spring 2008 and will continue his research as a veterinary toxicologist with new collaborations in the UCD School of Medicine and potential funding from the American Heart Association.

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