Should I Be Taking Aspirin, Antioxidants or Folic Acid?

Should I Be Taking Aspirin, Antioxidants or Folic Acid?

Ask your doctor! Whether or not to take these common non- prescription medications in hopes of helping reduce the risk of a heart attack has been the subject of countless reports, studies and strongly opinionated articles. Before you finish reading an article extolling the benefits of one of these preparations, you’ll see another article that concludes it is exactly the wrong thing to do.

The final answers are not available. Until they are, it is important to know what the controversies are about-and what the situation is as this book went to press. Even when apparently definitive evidence comes in, those conclusions may change. Keep asking your physician for guidance on what to do before you start any treatment regime or stop a treatment plan your physician has put you on.

Aspirin for Those at Risk

Let’s start by talking about who should use aspirin to help decrease heart-attack risk. Those who are at high risk include:

• men over 50 • anyone with a cholesterol/HDL ratio over 4

• a triglyceride level over 150
• an LDL level over 130

• anyone with excessive weight • anyone with high blood pressure • people who smoke

Taking a low dose of aspirin regularly seems to lower the risk of lit- tle blood clots forming on the inside of coronary arteries narrowed by fat plaques.¹ Aspirin does not reduce cholesterol or triglycerides or help to clean out plaques that have formed. Aspirin’s anti-clotting properties help keep dangerous blood clots from forming on the plaques in the coronary arteries.

A couple of possible problems must be recognized before deciding to take aspirin for any purpose. Some people are allergic to aspirin- extremely allergic. It isn’t very common, but those who are allergic to aspirin can have a serious problem in taking even small amounts. The most common problem is swelling, often of the facial tissues. Swelling can also occur in the air passageway which can be fatal. Other aspirin allergies cause rashes and asthmatic wheezing.

Still another serious problem some have with low doses of aspirin is too much thinning of the blood. In other words, the normal benefit of aspirin, keeping the platelet cells from clumping together and clot- ting, is exaggerated so bleeding occurs. Sometimes this is a nosebleed. This bleeding can also cause easy bruising, even from minor bumps. This may be slight or quite severe. Aspirin can cause bleeding in the stomach or intestinal tract, which can be quite serious. In others, bleeding may occur from a tiny blood vessel in the brain, which is a hemorrhagic stroke.

Because aspirin can cause these and other problems, it is not some- thing to take without thought. Someone with a bleeding tendency, or with a history of aspirin allergy, should not take it. Period. it. Period.

What about those who don’t have these problems or don’t know if they do? As with every decision in medicine, this is a judgment call. Is the risk of taking the medicine greater than not taking it? Why, with all these possible problems, would anyone want to take aspirin to try to cut down on the risk of a heart attack that hasn’t even happened?

There is good evidence that shows low doses of aspirin decrease a high-risk person’s chance of a heart attack. This may be advisable if someone is not allergic to aspirin and does not have a bleeding ten- dency. At this point, this is not an official indication of the United States Food and Drug Administration (FDA).

Many medications are accepted as standard treatments without having official approval from the FDA. The reason is that if a medica- tion has received FDA approval for treatment of one problem, it can be used for other indications without a new official FDA approval. New approvals cost drug companies tens of millions of dollars.

The best evidence that aspirin works to help prevent heart attacks comes from a 5-year study of 22,000 low-risk U.S physicians who took one aspirin every other day. Their heart attack rate decreased by 47%. That’s impressive!

That’s the aspirin story. If you fit into a high-risk group for a heart attack, do not have an allergy to aspirin or a bleeding problem, ask your physician if you should be on low-dose aspirin. If so, ask how much you should take and how often. If you do this, be sure to report any evidence of bruising, bleeding of any kind, headaches, swelling, difficulty breathing, wheezing, obvious asthma or ringing in your ears.

One more word about aspirin: Taking aspirin is not a substitute to get your cholesterol and triglycerides down, your blood pressure treated, your weight down or a good exercise program in place (with- out smoking, of course).

What about Antioxidants?

Antioxidants are compounds that seem to protect the lining of cell membranes from being attacked and oxidized by free radicals. That’s terrific! What are free radicals?

Well, free radicals are sort of a garbage result of body metabolism. The chemistry is a process of oxidation-something like rusting metal. Fortunately, these free radicals are usually neutralized by normal body antioxidants. But, when an overload of free radicals occurs. they attack cell membranes and harmful LDL cholesterol is oxidized into a killer form of LDL. This killer LDL is even more harmful to the heart than ordinary LDL cholesterol, which is bad enough. Antioxidants seem to help block the damaging chain reactions that do this.

The big question is, do the good effects of blocking the production of killer LDL result from the antioxidants in these vegetables and fruits-or are they due to something else in them? We don’t know for sure, but we have good reason to consider antioxidants as “good guys.”

The interest in antioxidants in atherosclerosis began with studies of how the fat particles, particularly the LDL cholesterol, entered cells. In the beginning, LDL didn’t seem to enter cells very rapidly. Only after LDL was oxidized did it go into these cells to produce a deposit of fat. Then we realized the importance of oxidation.

This is probably all you want to know about free-radicals, but hopefully you can see that antioxidants may help in decreasing the risk of heart attacks.

There is good evidence that eating lots of green leafy vegetables helps protect against heart attacks and maybe even some kinds of cancer. It just so happens that dark-green leafy vegetables like spinach and chard, yellow vegetables like carrots and squash and yellow fruits like cantaloupe and mango are filled with carotinoids, which is one kind of antioxidant. Carotinoids are red and yellow pigments with a chemical composition similar to carotene. Carotene is converted to vitamin A in the liver.

Citrus fruits, including oranges, lemons and grapefruit, dark-green vegetables like broccoli and asparagus, as well as potatoes, contain vit- amin C (ascorbic acid), another antioxidant. Nuts, whole grains, oils from soybean, sunflower, corn and cottonseed contain vitamin E (alpha tocopherol), yet another antioxidant.

Do Vitamins and Supplements Help and Are They Safe?

If it is proved that antioxidants block the production of killer LDL, then taking supplements of some of these vitamins may be a very good idea. Anyone who is allergic to one of them should not take it, but allergies are unusual. There is always the possibility of another undesirable result from taking large doses of these vitamin supple- ments, even though they are generally regarded as ordinary and safe.

So, how do we know the answers to these questions: “Do they help?” and “Are they safe?” The answer is to do well designed and care- fully controlled studies, some of which are under way. Unfortunately, the studies are not yet complete, so the results are not available.

“What about studies that have already been done?” you ask, remembering reading newspaper reports about various studies that attracted considerable attention in the media.

Vitamin E

Two earlier studies that seemed to show taking supplemental vitamin E protects both men and women from coronary-artery disease used data based on the diet histories of 87,245 female nurses2 and 39,910 male health professionals.3 It is important to point out that non- controlled diet-history studies, like these two, are among the weakest kinds of research from a scientific viewpoint. So, though these two studies seem impressive, they are not the final answer.

The Cambridge study took a big step in the direction of a defini- tive answer. In this study, people who had a heart attack were ran- domly assigned to take vitamin E or not to take it. Although those in the study who took vitamin E didn’t live any longer, the folks who took vitamin E had 77% fewer heart attacks. Think about it-77% fewer heart attacks! That’s better than pretty good.

Here’s the point: Some people think that something useful must decrease death rates. Of course we want to decrease death rates. If we can reduce heart attacks, that’s a big benefit. Although everyone who has a heart attack doesn’t die, everyone who has a heart attack is mis- erable. They spend a lot of time in intensive care. It’s painful and costs lots of money. Besides that, everyone who has a heart attack is out of commission for a while. Many people who have a heart attack lose the ability to do things they like doing. Many end up in surgery. When a skeptic tries to convince you not to do healthy things because a cer- tain study didn’t prove a drop in death rate, don’t be misled into thinking the strategy doesn’t have some merit.

How do we get more evidence about the role of antioxidants in helping protect against heart disease?

We need larger, randomized, double-blind trials to protect us from all the potential biases that are so rampant in the diet-history studies. So far, only three carefully designed double-blind research studies have been done to see if taking these products really makes a differ- ence. One of these-the ongoing Physicians’ Health study (started in 1984)-included 22,000 physicians who were randomized to take aspirin, beta carotene, both or nothing. This trial showed that young, low-risk physicians (average age 49), who took one aspirin every other day, cut their heart attack rate 47% in five years. The beta-carotene part of the study was stopped because there was no change in health outcomes after 12 years.

Also, a National Cancer Institute study showed a higher death rate among smokers (and people who just quit smoking) who had been taking beta carotene. So, even though it seemed for a while that peo- ple at risk should be taking beta-carotene supplements, we don’t think they should.

We do need to eat plenty of rich yellow vegetables and fruits such as carrots, squash, cantaloupes and mangos to get the antioxidants that are helpful without causing other problems.

No one should expect vitamins to solve all their problems. This is the flaw in many well-intended but misguided programs in which huge doses of vitamins are given. It’s never a good idea to listen to those who say, “Take this big dose of vitamins, a magic bullet, which will cure you.” This is exactly the wrong way to use vitamins. Treating high-risk people only with vitamins is not good medicine.

In other words, antioxidant vitamin supplements may play a help- ful role in preventing heart attacks. We repeat: They may. Vitamins are not going to help reduce coronary-artery disease in people who keep smoking and eating fat-laden foods.

It is also very difficult to interpret what some so-called studies are reported to prove. When seemingly sensational study conclusions are reduced to a sound bite on the six o’clock news or to a few inches of copy in your daily paper, it is easy to see how people become misled and confused. It’s hard enough to know for sure about these study results when you are looking at all the data.

Preventing Coronary Disease

What do we know for sure about preventing coronary-artery disease? The most important things for anyone to do who wants to beat the odds of a heart attack are to carefully limit the bad fat they eat, to exercise, to not smoke and to do whatever else it takes to get choles- terol and triglycerides under control.

This still doesn’t answer the question about the value of anti- oxidants. After a treatment plan is underway, what about the anti- oxidants?

Eating seven to eight servings of fruit and vegetables a day will sup- ply most of the needed vitamins. The benefits may be from vitamin E and vitamin C or something else. Right now it seems that, in addition to a good solid medical program to lower cholesterol and triglyc- erides, it may be helpful for people at high risk to take extra vitamin E and vitamin C. There seems to be enough evidence that they may help without much risk.

Anyone who takes these antioxidant vitamins should know they are not a substitute for controlling cholesterol and triglycerides with a low-fat diet and medications. In other words, don’t expect vitamins to be a “magic bullet.”

Ask your doctor if you should be taking antioxidants. If so, how much? While we don’t have a final answer as to how much vitamin E is the right dose, if it should be given, a recent study seems to show the optimal amount may be 400 international units a day.

The question is what can you do now, before the answers are in? If someone tells you to eat lots of vegetables and fruits and forget the supplements, that may be right. On the other hand, there are some strong clues that antioxidant supplements may provide some valuable help to those at risk.

What about Folic Acid to Counter Homocysteine?

One more bad substance that can increase the risk of coronary arter- ies becoming plugged is homocysteine. People who don’t get enough folate to metabolize harmful homocysteine have three times the risk of a heart attack as those who do.4

Evidence from the Framingham Study showed that the higher the level of homocysteine in the body, the greater the risk of blockage in a person’s carotid arteries. That’s a strong indication that there is also blockage in the coronary arteries.4,5 Folic acid is a B-complex vitamin found abundantly in dark-green leafy vegetables such as chard, spinach and romaine lettuce, and dry beans, peanuts, wheat germ, whole grains and yeast.

Recent reports indicated that some pregnant women in the United States are not getting sufficient folic acid in what they eat. This insuf- ficiency is resulting in tragic occurrences of neural-tube (spina bifida) and other defects, such as cleft palate, in some babies. The good news is that these defects have sharply decreased as women of childbearing age have been given supplemental folic acid along with their prenatal vitamins. Because the eating habits of men and women in our culture are pretty much the same, the lack of enough dietary folic acid in our culture is almost certainly not limited to women.

Should You Take Vitamins and Other Supplements?

There’s no question that it’s a good idea to eat dark-green vegetables, dried beans, whole-wheat and the other basic wholesome foods we’ve been talking about. But what about supplements? It usually makes sense to wait for conclusive evidence before starting to take a medica- tion-even a vitamin or other so-called natural supplement.

To date, there are only two well-controlled trials showing benefits for vitamin E at 400 iu (international units) and selenium at 200µg (micrograms). Vitamin E lowers ordinary heart disease and selenium protects against breast, colon and prostate cancers.

In this instance, there is a legitimate argument that the possible benefit of taking these antioxidant supplements may outweigh the risk of taking them. We caution that this line of reasoning is usually unwise even though we all hope that these supplements will be help- ful in reducing the odds of a heart attack. There is good reason to believe that folic acid is a helpful part of heart insurance.

So, should you be taking supplemental folic acid, vitamin E and/or vitamin C? Ask your physician. Taking extra vitamin E or vitamin C is not a substitute for getting your cholesterol down, your blood pres- sure down, your exercise down and not smoking. Be sure to eat seven to eight servings of fruit and vegetables every day. Include a plentiful variety of dark-green and yellow vegetables-particularly apples, pears, cantaloupes and mangos and yellow and orange fruits like oranges and other citrus. You can make dried beans, whole-wheat and the other basic wholesome foods we’ve been talking about a regular part of your eating choices.

NOTES

1. Steering Committee of the Physicians’ Health Study Research Group: Preliminary report: findings from the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med, 1988, 318(4):262-264.
2. Stampfer, M.J., Hennekens, C.H., Manson, J.E., et al: Vitamin E consumption and the risk of coronary artery disease in women. N Engl J Med, 1993, 328 (20):1444- 1449.
3. Rimm, E.B., Stampfer, M.J., Ascherio, A., et al: Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med, 1994, 328 (20):1450-1456.
4. Forty percent of the people in Framingham have elevated levels of homocysteine which seems to be associated with a very low intake of folic acid and vitamin B-6. These people also have significant deposits of plaque in their carotid arteries as visualized on ultrasound studies which strongly suggests they also have consider- able plaque formation in their coronary arteries.
5. Selhub, J., Jacques, P.F., Boston, A.G., D’Agostino, R.B., Wilson, P.W.F., Belanger, A.J., O’Leary, D.H., Wolf, P.A., Rosenberg, I.H. Association between plasma homo- cysteine concentrations and extracranial carotid artery stenosis, N Engl J Med, 332, 1995, p. 286.