The Harvard Medical School Guide to Men's Health: Lessons from the Harvard Men's Health Studiesby Harvey B. Simon (Editor), Harriet Greenfield (Illustrator), Julie E. Buring (Other), Harriet Greenfield (Illustrator)
The Harvard Medical School Guide to Men's Health is the ultimate state of the art in men's health, assembled into a single volume containing a quarter-century's worth of hard-won knowledge -- knowledge that men need to lead longer, healthier lives. And it's assembled here because more than twenty-five years ago, researchers at Harvard Medical School and the Harvard School of Public Health began what have become the largest aggregate studies ever of men's health: the Harvard Alumni Study, the Physicians' Health Study, and the Health Professionals Follow-Up Study. Tracking the behavior and health of more than 96,000 American men over decades, the studies have regularly generated front-page health news, such as demonstrating the health benefits of low-dose aspirin, documenting the reduction in heart disease enjoyed by men who consume large amounts of dietary fiber, scientifically proving the life-prolonging effects of regular exercise, showing which supplements help and which do more harm than good, and much, much more. These studies represent the ultimate resource on what keeps men healthy -- and what doesn't.
The Harvard Medical School Guide to Men's Health features the best and most current information on the health-preserving functions of diet, exercise, and over-the-counter drugs and supplements -- the ones that really work, the ones that don't, and the ones that are dangerous. It gives straight answers on when drinking alcohol is beneficial and when it's not. It incorporates programs and advice on behavior modification and stress control. The Harvard Medical School Guide to Men's Health is the most comprehensive, easy-to-use reference to the diseases that are particularly important to men, including prostate cancer and testicular cancer, erectile dysfunction, kidney and bladder problems, and more. And it even features an easy-to-navigate guide to the health-care system that can help men work with their doctors to achieve better health. With the authority that only the world's largest and best-known medical school can provide, and the lively, clear presentation that is the hallmark of Harvard Men's Health Watch, the monthly newsletter edited by Dr. Simon, The Harvard Medical School Guide to Men's Health is an essential reference for every man -- and for everyone who cares about a man's health.
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The Harvard Medical School Guide to Men's HealthLessons from the Harvard Men's Health Studies
By Harvey B. Simon
Free PressCopyright © 2002 Presidents and Fellows of Harvard College
All right reserved.
Chapter OneThe Answers: Aspirin and Other Supplements
"If only there were a pill."
Every man would like an easy way to stay healthy. Good nutrition and regular exercise are the keys for preventing illness, but diets take discipline and exercise takes time. Is there a shortcut? Can a few pills do the trick? Can "all-natural" supplements replace the physical activity and healthful eating that should be part of human nature?
If you look for the answer on the Internet or listen for it on TV or radio, you are likely to come away with a resounding "yes." That's mostly because vitamins, herbs, and other supplements are not subject to the jurisdiction of the Food and Drug Administration. Congress took care of that in 1994, when it passed the Dietary Supplement Health and Education Act. As a result, the supplement industry can tout its products without having to substantiate their claims for efficacy and safety. With billions of dollars at stake, the hype is relentless. In all, more than 50 percent of all Americans take supplements, spending upwards of $4 billion a year to buy health in a bottle.
Most doctors have been skeptical of supplements, pointing out correctly that anecdotes and testimonials can never be relied on in place of sound scientific studies. In the past few years, though, good studies have started to appear. While few herbs have been scrutinized, research by the Physicians' Health Study, the Health Professionals Study, and other investigations suggests that some supplements may be helpful while others are wasteful or even harmful. Surprisingly, perhaps, one of the most promising of all is not a vitamin or an herb, but an inexpensive, old-fashioned, medicine chest standby: aspirin.
Its name is more than a century old, but its parent compound has been in use for thousands of years. The ancient Assyrians, Egyptians, and Greeks all used willow leaves to treat inflammation, fever, and pain. The practice was popularized in England by Reverend Edward Stone in 1763. The active ingredient was purified from willow bark in Germany sixty-five years later. At the tail end of the nineteenth century, scientists at the Bayer Company succeeded in producing the modern derivative, acetylsalicylic acid, or aspirin. The very same drug has been used for fever and pain ever since. In the past thirty years, it has gained new importance in the management of heart disease and stroke, and current studies suggest it may someday assume a role in preventing colon cancer and possibly even Alzheimer's disease. And just as aspirin is finding new uses, scientists are finding out exactly how it works. It is important research that is likely to result in a new generation of even better drugs. But even in the dawning era of "super-aspirins," the original drug is certain to retain much of its value.
How It Works
Aspirin does its job by inhibiting the body's production of prostaglandins. Although you may never have heard of them, prostaglandins have a wide-ranging impact on human health. For example, they keep the stomach lining healthy, they regulate blood flow to the kidneys, and they enable platelets to trigger blood clotting. But prostaglandins also contribute to disease; in the brain they cause fever, and in joints and other tissues they can produce inflammation and pain.
Aspirin is not the only drug that inhibits prostaglandins. In fact all the nonsteroidal antiinflammatory drugs (NSAIDs) act in similar fashion (see Table 6.1, page 168). But although acetaminophen (Tylenol and other brands) fights fever and pain as well as aspirin, it does not inhibit prostaglandins. As a result, it does not share either the antiinflammatory benefits or the major side effects of aspirin and other NSAIDs.
Aspirin and Atherosclerosis
Aspirin does not prevent or even minimize atherosclerosis, but it can help prevent heart attacks and some strokes. It sounds like a paradox, but it is not. Aspirin cannot prevent cholesterol-laden plaques from building up in the wall of an artery, though it may be able to reduce the inflammation that perpetuates the damage (see Chapter Three and Figure 3.1). But while plaques narrow arteries, rarely do they produce the complete blockages that cause heart attacks. Instead, the culprit is a blood clot or thrombus that forms on the surface of a ruptured plaque. The clot completes the blockage, and aspirin exerts its protective effect by inhibiting clot formation.
Clots are triggered by platelets, fragmentary blood cells that are produced in the bone marrow, and then pour into the bloodstream. A man's blood contains a total of 100 million platelets, but because each platelet only lasts about ten days, the marrow must produce them continuously at a prodigious rate. Aspirin does not reduce the number of platelets in the blood, but it does inhibit their ability to trigger clots.
Platelets are extremely sensitive to aspirin. In some studies, doses as low as 10-30 milligrams can inhibit all the platelets in a man's body. Once platelets are inhibited by aspirin, they stay inhibited, but since new platelets are entering the blood continuously, the aspirin dose must be repeated every twenty-four to forty-eight hours to keep the majority of platelets under control.
Primary Prevention of Heart Attacks
You would probably call it staying healthy, but doctors call it primary prevention. By either name, it means heading off a problem before it makes its first appearance. Can aspirin prevent a first heart attack in men without diagnosed heart disease?
This is the question that the Physicians' Health Study set out to answer in 1982. A total of 22,071 male physicians volunteered to be subjects in a randomized clinical trial of low-dose aspirin. Half the men were assigned to take 325 milligrams of aspirin every other day, while the others each were given an identical-appearing placebo tablet every other day. To eliminate bias, the assignments were made randomly and neither the subjects nor the researchers knew which men were taking aspirin and which the placebo.
The researchers had planned to continue the trial until 1990, but it was terminated three years ahead of schedule. That was because an independent Data Monitoring Board that was tracking the results declared it would be unethical to continue the study since a clear winner was already evident. The winner was aspirin.
In the Physicians' Health Study, the men who took aspirin had a 44 percent reduction in the risk of suffering a heart attack. Benefit did not depend on a man's family history of heart disease or on his cholesterol, blood pressure, blood sugar, body fat, amount of exercise, or his drinking or smoking habits. But one risk factor did predict benefit: age. Aspirin was highly effective in men older than fifty, but not in younger individuals.
The results of the Physicians' Health Study were published in the same year as the report of the British Doctors Trial, which found no benefit from aspirin. Does that mean men should take aspirin in America but not in Europe? Not at all. The British trial was much smaller than the U.S. study, involving just 5,139 men. It was also less carefully controlled. But the biggest difference was in the dose of aspirin; the British doctors took 500 milligrams every day, the Americans just 325 milligrams every other day.
When you have a headache or a fever, you are likely to take two 325 milligram aspirin tablets every four to six hours. Even the British doctors' dose is tiny in comparison, but it may still be too high to produce maximum protection against heart attacks. That is because tiny doses of aspirin will inhibit only thromboxane A2, the enzyme in platelets that triggers the clotting process, but higher doses can also inhibit prostacyclin, an enzyme in blood vessels that reduces clotting. In theory, at least, low doses of aspirin will reduce clot formation, but even slightly higher doses might lessen that benefit. Two 1998 studies found that 75 milligrams of aspirin a day can reduce the risk of a first heart attack by about one-third, and a 2001 investigation found that 100 milligrams a day reduced the risk of cardiovascular death by 44 percent, but none of these reports investigated varying amounts of aspirin. However, a 1999 study from six European countries compared four aspirin doses and found that low amounts (81 or 325 milligrams a day) were actually better than higher doses (650 or 1,300 milligrams a day) in preventing strokes.
When it comes to aspirin for prevention, less is more.
Although the Physicians' Health Study demonstrated that low-dose aspirin could help prevent heart attacks in healthy men fifty or older, its 1989 report did not link aspirin use with a reduction in overall cardiovascular deaths. The aspirin trial was terminated early, and its five-year span may have been too short to discern an effect on mortality. But even after the randomized clinical trial was terminated, 11,010 of the subjects continued to take the drug on at least 180 days a year, while 3,849 took little or no aspirin. In 2000, the study reported that over a seven-year period, a low-dose aspirin was associated with a 35 percent reduction in cardiovascular deaths and a 36 percent drop in total mortality.
The Physicians' Health Study trial has provided additional information about aspirin's effect on the heart. The drug seems most effective in the early morning hours, when platelets are particularly likely to stick together and produce clots. It is a good thing, since that is when heart attacks are most likely to occur. Aspirin begins working rapidly and it remains effective as long as it is being taken. That is because the very first dose will inhibit all the platelets in a man's blood, but the body does not build up resistance to the drug. Aspirin was effective in preventing heart attacks in men who had angina, but it did not prevent healthy men from developing angina. That's because angina is caused by plaques that produce partial blockages, but heart attacks are the result of clots that form on plaques.
Secondary Prevention of Heart Attacks
The Physicians' Health Study was the first to show aspirin can protect healthy men older than fifty against heart attacks, but it was not the first to show that aspirin can help the heart. In fact, dozens of studies dating back to 1971 have demonstrated that aspirin has an important role in secondary prevention, in preventing second or third heart attacks in patients who have survived a first attack. In all, aspirin reduced the risk of recurrent heart attacks by about 25 percent. It only takes low doses of aspirin, between 75 and 325 milligrams a day, to produce this major benefit. At present, up to 25 percent of American heart attack survivors fail to take aspirin. It is a shame, since if all the heart attack patients who could take aspirin did so, it could prevent another 20,000 deaths annually.
Other Vascular Diseases
Atherosclerosis can strike any artery in the body; in addition to the heart, its most important targets are arteries in the legs and brain.
The Physicians' Health Study found that low-dose aspirin might protect the legs against severe blockages of peripheral artery disease. During an observation period that averaged about five years, men who took 325 milligrams of aspirin every other day were 46 percent less likely to require surgery for leg artery blockages than men who took placebos.
The issue of stroke is more complex because there are two types of strokes (see Chapter Three): hemorrhagic strokes occur when an artery in the brain ruptures, releasing blood into the tissue, but ischemic strokes result when clots block arteries in the brain. The Physicians' Health Study found that low-dose aspirin produces a slight increase in hemorrhagic strokes, but the heightened risk was too small to be statistically significant; other studies have reported similar results. At the same time, though, aspirin can help prevent ischemic strokes, which are four times more common than hemorrhagic strokes. In fact, two 1997 studies of more than 40,000 stroke patients found that low-dose aspirin (100 or 300 milligrams a day) produced a small but significant benefit, both by improving recovery and reducing the risk of a second stroke. More recently, a 1999 meta-analysis of eleven randomized, placebo-controlled trials found that low-dose aspirin reduced the risk of both types of stroke, combined, by 15 percent. But because high blood pressure increases the risk of hemorrhagic stroke, men with hypertension should not use low-dose aspirin until their blood pressures are brought under control (see Chapter Three).
Other Possible Benefits
Although the Physicians' Health Study was most interested in aspirin's effect on atherosclerosis, it also investigated other conditions. For example, it found that low-dose aspirin reduced the occurrence of migraine headaches by 20 percent. It also found a slight decrease in cataracts, but the difference was not statistically significant, and other research has failed to demonstrate protection against cataracts.
An area of much greater importance is the possibility that aspirin may reduce the risk of colon cancer. It is an unresolved question, and it is one of the few areas of disagreement among the Harvard men's health studies. The Physicians' Health Study found no reduction in colon cancer among the men who took 325 milligrams of aspirin every other day. In contrast, the Health Professionals Study found that men who used aspirin at least twice a week were 32 percent less likely to develop colon cancer than men who took it less often.
Although the issue is far from resolved, other research suggests that aspirin may help. In laboratory experiments, aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) can influence apoptosis, programmed cell death that prevents the unchecked growth of cancer cells (see Chapter Three). In rodents exposed to cancer-causing chemicals, NSAIDs inhibit the development of tumors in the colon. In animals and humans with hereditary polyps, NSAIDs can reverse the formation of the benign polyps from which colon cancers develop. In ten of twelve observational studies in humans, aspirin or other NSAIDs seemed protective. For example, in a 1991 American Cancer Society study of 662,424 people, aspirin use was associated with a 40 percent lower risk of dying from colon cancer over a six-year period. In all, the majority of studies report that NSAIDs use is associated with a 40 to 50 percent reduction in the risk of colon cancer.
The effects of NSAIDs on cognitive function are also intriguing. A sixteen-year study of 1,686 people in Baltimore linked the use of various NSAIDs to a 50 percent reduction in Alzheimer's disease.
Excerpted from The Harvard Medical School Guide to Men's Health by Harvey B. Simon Copyright © 2002 by Presidents and Fellows of Harvard College. Excerpted by permission.
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