By Peggy O'Farrell
The Cincinnati Enquirer

"Take two aspirin and call me in the morning."

The old joke has proved to be sound medical advice, as researchers tout the medicine chest staple as a cheap preventative for heart disease and stroke.

Scientists seem to be only beginning to understand aspirin's potential, though the drug can trace its history to ancient times. What is understood is that aspirin, which costs less than a penny a tablet, could be a prevention powerhouse for everything from Alzheimer's disease to cancer.

ASPIRIN'S HISTORY

Aspirin - acetylsalicylic acid - can trace its roots to the Greek physician Hippocrates, who prescribed its precursor, willow bark, for fever and pain. In 1829, scientists isolated salicin, the chemical that made willow bark an effective treatment. In 1875, sodium salicylate and salicylic acid were developed from salicin. But they irritated the stomach too much and, in 1897, a German chemist named Felix Hoffmann synthesized acetylsalicylic acid from the earlier drugs as he was looking for a less-acidic remedy for his father's arthritis. We should mention that Mr. Hoffmann worked for the Friedrich Bayer Co., , now the Bayer Corp.

WHAT ASPIRIN DOES

Practically speaking, aspirin has two primary functions: It eases inflammation, which is how it alleviates pain and fever and some of the mechanism of heart disease, and it prevents blood clots, which is how it prevents heart attack and stroke. Aspirin inhibits the action of prostaglandin, hormone-like compounds in the body that cause inflammation and other reactions, including, some researchers believe, a role in cancer development. There are several types of prostaglandin, and each has a different function.

"It's an old drug that continues to be interesting," says Dr. Marianne Ivey, corporate director of pharmacy services for the Health Alliance. "We keep learning new things. If it were discovered today, it would be extremely expensive."

Preventative medicine

For decades, aspirin served as an inexpensive, non-addictive painkiller.

Today, there are numerous over-the-counter painkillers that work more effectively than aspirin without its side effects.

Americans take 80 million aspirin tablets every day, according to the Bayer Corp. Most of those pills are popped to prevent heart attack and stroke, not to cure headaches. People who think they are having a heart attack routinely are advised to take an aspirin before heading to the emergency room.

Aspirin made headlines as recently as October when researchers announced it reduced mortality among heart bypass patients who took aspirin therapy after surgery. There had been concern that aspirin would cause increased bleeding, but the benefits outweigh the risks, researchers concluded.

The American College of Chest Physicians issued a consensus in 2001 that aspirin should be administered daily beginning six hours after bypass surgery, says Dr. Walter Merrill, a cardiothoracic surgeon at University Hospital. But there's some debate on the dosage that patients should receive.

In addition to its benefit for heart patients, researchers have identified several diseases that could be alleviated or prevented by aspirin:

Alzheimer's disease: A Utah study suggests that aspirin and other anti-inflammatory drugs could reduce the risk of developing Alzheimer's. There's some speculation that aspirin and similar drugs which reduce the inflammation that causes arthritis and other ailments, could reduce inflammation in the brain. But scientists don't know whether the inflammation is a result of Alzheimer's or the cause of the disease.

Lung cancer: Data from the New York University Women's Health Study, which followed 14,000 women for 12 years, showed that women who took aspirin three or four times a week for at least six months showed a 60 percent reduction in non-small cell lung cancer, the most common form.

Ovarian cancer: Data from the same study showed that women who took aspirin three or more times a week for at least six months showed a 40 percent reduction in ovarian cancer risk - results that could be significant since the disease has no early warning symptoms and often is caught in late stages.

Colon cancer: A National Cancer Institute study released in April showed that people who took a baby aspirin daily - 81 milligrams of aspirin - reduced their risk of recurrent precancerous polyps by 19 percent. The same dose reduced the risk of recurrence for advanced colon cancer by 40 percent. Numerous earlier studies show that aspirin reduces polyp formation, colon cancer development and colon cancer-related deaths.

Balancing effects

Despite its promise, experts warn no one should take aspirin to prevent disease without talking to a doctor. Aspirin is sold over the counter, but it can cause gastric bleeding and other potentially serious complications, including allergic reactions.

The little pill millions of Americans take daily has a big impact on the body, and its effects have to be carefully balanced, says Dr. Fred Finkelman, a rheumatologist and director of the division of immunology at the University of Cincinnati.

"People think because something is over-the-counter, it's perfectly safe," Dr. Finkelman says.

Dosage is a big issue in aspirin therapy, and, surprisingly, in some cases, smaller doses are more protective than larger doses.

But no one can reach a consensus on what dose is best as preventive medicine, says Dr. Charles Youngs, clinical director of pharmacy services for the Health Alliance.

The key is to take advantage of aspirin's protective effects without triggering gastric bleeding or other negative effects.

That's harder than it sounds, experts say.

In treating heart disease, aspirin inhibits the action of compounds called thromboxanes that affect blood clotting. But it doesn't affect the action of another prostaglandin, prostacyclin, which helps blood vessels dilate and also prevents blood clotting, says Dr. Youngs.

Aspirin also blocks two specific compounds, the COX-1 and COX-2 enzymes, which makes it a good news/bad news proposition. COX-2 is the culprit behind the inflammation that causes arthritis pain. But COX-1 protects the lining of the stomach from the action of digestive acids, which is why aspirin causes upset stomach and gastric bleeding in some people, and it helps regulate kidney function.

COX-2 inhibitors such as Vioxx and Celebrex successfully treat arthritis pain without doing as much damage to the stomach as aspirin - though they might still pose some danger to kidney function.

But patients who take COX-2 inhibitors for their arthritis don't get the anti-clotting effect that aspirin provides to prevent heart attack and stroke. And medications like ibuprofen can also inhibit aspirin's anti-clotting effect if the doses aren't properly timed

So if you're at risk for heart attack and arthritis, it's important to talk to your doctor about what medications are best.

"The data are not totally clear. I think it's fair to say that there's no proof that it's an advantage to take a COX-2 inhibitor over a non-selective NSAID like ibuprofen if you're already taking a baby aspirin a day for your heart," Dr. Finkelman says.

Not for everyone

Aspirin - its chemical name is acetylsalicylic acid - was synthesized from earlier medications in 1897 by a German chemist. Originally sold in powder form, water-soluble aspirin tablets weren't introduced until 1900.

It wasn't until the 1970s, when a British pharmacologist identified prostaglandin, that scientists began to understand how the drug worked.

Now that they have a better understanding of aspirin's potential, doctors also have a very clear picture of who shouldn't be taking it.

People with a history of gastrointestinal bleeding shouldn't take aspirin. Neither should people with certain types of asthma. And anyone who's taking a blood thinner like Coumadin should avoid aspirin, because it can cause excessive bleeding.

"A basic message here is that it's a drug a lot of people take for granted, and we shouldn't," says Dr. Ivey. "It can be extremely effective if used correctly. It can also have some serious side effects."