Colorectal cancer, or cancer of the rectum and large intestine (colon), is a major public health problem in every corner of the developed world. In the U.S. alone, approximately 120,000 Americans are diagnosed with colorectal cancer annually; each year, 55,000 Americans die from it. For too long, it has been the second most deadly form of cancer. Unfortunately, we are making frustratingly little progress in our fight against this killer.

Decades of advances in surgery, radiation therapy and chemotherapy that have conquered or tamed many once-deadly diseases have brought only modest declines in the death rate from colorectal cancer. Many are beginning to ask whether we ought to be expanding our efforts to prevent this cancer, as opposed to treating it.

Since colorectal cancer, of all the major cancers, seems to be the most intimately tied to diet, many researchers have been looking into into ways in which the cancer might be prevented through changing how, what and how much we eat.

Joel, you are an expert in the field of colorectal cancer prevention. Despite two recent, well-publicized studies that cast doubt on the health benefits of dietary fiber — which we'll discuss a little later — I think you'd agree that just about every expert believes that certain "healthy" diets appear to help protect against colorectal cancer. What we are talking about are diets that are high in fruits and vegetables, high in fiber, low in calories and low in animal fat.

The key components shared by these diets are significant amounts of calcium, vitamin D, folate or folic acid, vitamin E, fiber, selenium and garlic. Before getting into these components, I would like to ask you about the link between animal fat and red meat, and colorectal cancer. I think there is some fairly strong evidence that a diet high in saturated animal fat and red meat (beef, pork and lamb) can increase your risk.

My question is, how much animal fat are we talking about and how many servings of red meat are healthy? What guidelines should people follow on this issue?

There is a lot of scientific evidence that red meat and saturated animal fat, by themselves, increase your risk of getting colorectal cancer. And many people are unaware that the amount of red meat in your diet is a risk factor in itself, whether the meat contains a lot of fat or very little. Roughly speaking, a diet containing less than 40 grams of animal fat per day conveys one-half the risk of colon cancer of a diet containing 65 grams or more per day. Similarly, a diet containing 60 grams or less of red meat per day carries half the risk of a diet containing 130 grams or more per day.

Furthermore, heavily cooked or well-done meat, in which the surface is browned or blackened, contains substances called heterocyclic amines, which in a laboratory setting have been found to cause cancer. More studies need to be done, however, to prove that eating well-done meat raises your actual cancer risk.

Fiber: Is There Anything to It?

Experts have long believed that eating a diet rich in fiber is good for cancer prevention and good health in general. However,two recent intervention studies have raised serious questions about this.

Joel, what do you think about the role of fiber in a healthy diet?

What you are referring to are two papers presented in The New England Journal of Medicine (Spring 2000). Both of these dealt with the question of whether a high-fiber diet could prevent the growth of polyps. Polyps are small growths that can form inside the colon; even though these kinds of polyps are normally benign, people who develop them are more likely to develop colorectal cancer years down the line.

These papers looked at two polyp studies that appeared to show that the amount of fiber in a person's diet made little difference in their risk of developing polyps. From this, many have jumped to the conclusion that that these studies have proven that fiber does not prevent colorectal cancer. I disagree.

There are many problems with these studies but the most important is that they were conducted over a three- to four-year period. The natural history of colorectal cancer is much longer. The evolution from a tiny polyp to cancer takes decades, not years.

Given the huge body of evidence that fiber helps prevent colorectal cancer, I am not yet willing to close the door on that possibility. I continue to feel that it is reasonable to advise people who are concerned about a healthy diet to increase their fiber intake to 25 or 30 grams per day, emphasizing wheat bran. Of course, this should be done gradually, since the digestive system needs a little time to adjust to a drastic increase in fiber intake.

Calcium and Vitamin D

Calcium and vitamin D also seem to help protect against colorectal cancer. Joel, would you discuss what we know about this? Could you also address the connection between vitamin D, calcium and our metabolism?

It seems fairly certain that increasing your calcium intake can prevent both colorectal cancer and polyps.

The most compelling study found that people who were given regular calcium supplements developed far fewer polyps.

We don't have a good handle on what this means in terms of cancer risk but reducing polyp growth is probably a good thing for your chances of later developing colorectal cancer.

The issue of vitamin D has not been well studied. There is sketchy evidence that supplemental levels of vitamin D might have a beneficial effect. And the intimate interplay between vitamin D and the body's calcium metabolism certainly suggests that vitamin D could enhance the good effects of calcium.

Great Folate

Joel, now I want to return to your true love — folate and colorectal cancer prevention.

There is certainly just as much buzz about folate and colorectal cancer prevention as there has been about calcium. Can you tell us a bit about the theory that folate may prevent colorectal cancer and could you also review the current state of the evidence?

Rob, if being excited about folate is a crime, then I must plead guilty.

Folate happens to be a very important substance; it is a critical player in the synthesis of both DNA and RNA, the genetic building blocks, as well as other areas of the human metabolism. Therefore, in theory, it is not surprising that lack of folate in the diet leads to serious problems. Since most experts agree that cancer is caused by insufficiently repaired defects in our DNA, it makes sense that inadequate amounts of folate might lead to DNA abnormalities and a greater risk of cancer.

The first observations along these lines were made in the late 1980s in people with chronic colitis, who are prone both to folate deficiency and to colorectal cancer. Since then, there have been many studies that suggest that you can reduce your risk of colorectal cancer by 50 or 60% by increasing the amount of folate in your diet.

While studies of colorectal cancer and folate using animals have also been promising, we must remember that studies on humans are at a relatively early stage. We will have to await definite proof that folate helps prevent colorectal cancer.

Antioxidants: Pro and Con

The jury is still out on antioxidants and the prevention of colorectal cancer. Some research has indicated that taking antioxidants, such as vitamin C or carotenoids, may reduce cancer risk but other studies have failed to back up these results.

I think most researchers feel that the relationship between lower cancer risk and the consumption of these antioxidants is explained mostly by the fact that a diet high in antioxidants is usually also high in vegetables. These kind of diets seem to be protective against colon cancer, though we don't know exactly why or how.

The evidence for vitamin E is also mixed. Vitamin E is a good example of how observational studies can lead to interesting hypotheses that later turn out not to hold water. At this point, I certainly wouldn't recommend trying to reduce cancer risk by taking high-dose antioxidant supplements.

However, I would like to consider selenium, an antioxidant for which there is some evidence of possible protection. Joel, what do you think about selenium?

Selenium of Approval

Among all the antioxidants, selenium seems to be the only one that shows real promise in the prevention of colorectal cancer.

This is largely based on one study that showed that taking a selenium supplement over a period of several years led to a 25% decline in the incidence of colorectal cancers. As compelling as it is, this study currently stands alone; it certainly needs to be followed up with further research.

Today, I think it would be reasonable for people concerned about preventing colorectal cancer to take 200 ug of selenium per day. Remember that the safe upper limit of selenium is 400 ug/day.

Are there any other food components, such as garlic and aspirin, that may protect against colon cancer?

Garlic and Aspirin

Rob, the current data on garlic is far from convincing. I would not recommend using garlic to try to prevent colorectal cancer.

On the other hand, aspirin, as well as other non-steroidal inflammatory drugs, have clearly been shown to help prevent colorectal cancer.

What About Exercise?

Joel, hasn't exercise been shown to help prevent colorectal cancer? To my mind, this relationship has never really been explained. Do you have any theories about how exercise might influence cancer risk?

That is a wonderful question but there is no definitive answer. On the one hand, physical activity may lower cancer risk to the degree that it prevents obesity. People who are obese have higher circulating levels of insulin, which is associated with colorectal cancer. There may, however, be more to it than that. In some studies, physical activity seems to lower risk even when obesity and body weight are taken into account.

This may have something to do with the fact that exercise can affect our levels of sex hormones and some hormones seems to inhibit the development of cancer.

Alcohol and Caffeine

Our discussion wouldn't be complete unless we talked about alcohol and caffeine. There is some evidence that these substances can increase your risk of colorectal cancer. With regard to alcohol, do you feel that this may have something to do with folate and the metabolism?

There is strong evidence that alcohol is an independent risk factor for colorectal cancer. As you mentioned, alcohol is well known to interfere with folate metabolism in a number of ways so that excessive and chronic alcohol might increase cancer risk for this reason.

Regardless of how alcohol exerts its influence, it is worth remembering that following U.S. Dietary Guidelines — no more than one alcoholic drink for women and two drinks a day for men — is wise not only to prevent colorectal cancer but also for your overall health.

In regard to a link between cancer and caffeine or coffee or tea, I think there is not enough evidence at this point to say.

Joel, what advice would you give to someone who has, say, a family history of colorectal cancer? What can this person do to try to lower his or her risk of getting colorectal cancer?

The first thing I would recommend is a diet high in fruits and vegetables (5+ servings/day, emphasizing fresh vs. cooked items), high in whole grain fiber and low in red meat and saturated fat. I might also recommend taking a multivitamin each day that provides an additional 400 ug of folate and sufficient vitamin D. Finally, it would be reasonable to take a 1200 mg supplement of calcium, as well as a 200 ug supplement of selenium.

It is also important to aim for a desirable body weight, both through regular physical exercise and by watching calories. I'd also recommend adherence to the U.S. Dietary Guidelines for alcohol consumption. Lastly, although it is not directly applicable to dietary interventions, someone with a family history of colorectal cancer might want to take a single 325 mg tablet of aspirin, three or more times a week.

Many people will find that following these recommendations requires many years of effort, perhaps as long as a decade, to be truly effective. Serious cancer prevention does not come in a pill or a box — it means making long-term changes in diet and lifestyle.