Harvard Men's Health Watch

Supplements vs. exercise for heart disease and cancer

Dietary supplements are wildly popular in America. According to the third National Health and Nutrition Examination Survey, 40% of all American adults take one or more.

It's easy to see why supplements are so popular. Because few are regulated by the FDA, manufacturers and retailers can assert many benefits and advertise them aggressively. It's a good strategy, bringing more than $20 billion a year to the supplement industry. But is it good for your health? Are there other ways to gain the benefits claimed for supplements?

Diet is certainly one alternative; it is clear that a good diet can reduce the risk of many serious diseases. Most scientists agree that extra vitamins in pills or powders add little, if anything, to a well-balanced diet that adheres to current guidelines. Another alternative is at hand (or, perhaps, at foot). In fact, regular exercise is a proven way to achieve many of the benefits claimed for vitamins and other supplements, even for people who also eat properly.

Here's how exercise and supplements stack up with regard to heart disease and cancer.

Cancer

Cancer is the second-leading cause of death in the United States, taking some 560,000 lives this year alone. It's no wonder that possible protection against cancer is one of the leading reasons that people take supplements in general and antioxidants in particular.

The idea has great appeal. For one thing, many studies confirm that people who eat lots of vitamin-rich fruits, vegetables, and whole grains enjoy a lower risk of cancer than folks who shun these foods. In theory, antioxidants should help counter the harmful effects of free radicals, unstable, high-energy, electrically charged molecules that can damage DNA and cell membranes. Cell damage of this sort could increase the risk of cancer and other diseases. Antioxidants such as vitamin E, vitamin C, and members of the vitamin A–beta carotene family can neutralize free radicals, at least in laboratory experiments.

In the 1980s and early '90s, antioxidants became the great hope against both cancer and heart disease. Sadly, they have been a flop against both (see table). Two major randomized clinical trials found that beta carotene actually increases the risk of lung cancer in smokers, just the people who need protection most. A third study reported that vitamin E increases the risk of second cancers in survivors of head and neck cancer. And a 2007 meta-analysis of 68 randomized clinical trials involving 232,606 subjects concluded that beta carotene, vitamin A, and vitamin E, singly or in combination, may actually increase the overall death rate in adults.

Major clinical trials of antioxidants

Trial

Subjects*

Vitamin

Results

Cambridge Heart Antioxidant Study (CHAOS)

2,000 patients with heart disease

Vitamin E

Reduced risk of heart attacks but not death

Physicians' Health Study

22,000 healthy men

Beta carotene

No cardiac protection

Alpha-Tocopherol, Beta Carotene Cancer Prevention Study (ATBC)

29,000 male smokers

Beta carotene

No cardiac protection

Increased risk of lung cancer in smokers

Vitamin E

No cardiac protection

Increased risk of hemorrhagic stroke

Decreased risk of prostate cancer in smokers

Beta Carotene and Retinol Efficacy Trial (CARET)

18,000 smokers and former smokers

Beta carotene

No cardiac protection

Increased risk of lung cancer in smokers

Women's Health Study

40,000 healthy women

Beta carotene

No cardiac protection

Vitamin E

No cardiac protection

GISSI-Prevenzione

11,000 patients with cardiovascular disease

Vitamin E

No cardiac protection

Heart Outcomes Prevention Evaluation Study (HOPE)

10,000 patients with cardiovascular disease risk factors

Vitamin E

No cardiac protection

HOPE-TOO

7,000 patients with cardiovascular disease or diabetes

Vitamin E

No cancer protection

Slight increased risk of heart failure

Heart Protection Study

20,000 people at high risk of heart disease

Vitamin E and C plus beta carotene

No cardiac protection

*Round numbers

The role of supplements in prostate cancer is still being studied. Beta carotene may offer some protection against prostate cancer, but only in nonsmoking men who have very low blood levels due to dietary deficiencies. According to the ATBC Trial (see table), vitamin E may reduce the risk of prostate cancer in smokers, but other randomized clinical trials in nonsmokers found no benefit. Selenium, a mineral with antioxidant properties, may reduce a man's risk of prostate cancer; the results of individual trials are mixed, but a Canadian meta-analysis reported a 26% overall reduction in risk. More study is needed, and the 32,400-person SELECT Trial of selenium and vitamin E should help answer these questions. And although many men take supplements of soy or lycopene to reduce their risk of prostate cancer, there is no good evidence that they work. Another ingredient of many popular "prostate supplements" is zinc, which may actually do more harm than good. Very large doses of multivitamins or folic acid may also backfire.

Folic acid, a B vitamin, may help reduce the risk of colon cancer, at least in women. Harvard's Nurses' Health Study linked the prolonged use of multivitamins containing folic acid with a 75% lower risk of colon cancer. More research is needed to confirm the findings, but it may be a moot point, since folic acid added to cereals and other grains has made it easier than ever to get enough of it from diet, even in people who don't always get their daily veggies. And a 2007 study found that very high doses of folic acid — 1,000 micrograms (mcg) a day, which is two and a half times the RDA — increases the risk of colon polyps in people with previous polyps; men may also face an increased risk of prostate cancer.

The authoritative U.S. Preventive Services Task Force has concluded that vitamin supplements do not reduce the risk of cancer. Low-dose aspirin may help, but although you can buy it everywhere without a prescription, it's a medication, not a supplement, and more research is needed to learn if it really helps.

If supplements won't protect you against cancer, can you walk away from it? More research is needed here, too, but the evidence suggests that exercise may reduce the risk of certain common malignancies. It makes biological sense, since exercise reduces body fat, and obesity is an important cancer risk factor. Exercise also lowers levels of insulin and various growth factors that appear to stimulate the runaway growth of cancer cells.

The evidence is best for colon cancer. More than 50 studies from around the world show that physically active people are less likely to develop colon cancer than sedentary individuals. The apparent protection is substantial, amounting to a 30% to 40% reduction in risk. And you don't have to labor for long hours in the gym to benefit; moderate exercise, such as walking for two to three miles a day, will suffice. Although the mechanisms of protection are still under study, something as simple as more rapid emptying of the colon may turn out to be the answer.

Breast cancer is the other big target of physical activity. More than 60 studies suggest that women who exercise regularly can expect a 20% to 30% reduction in the chance of getting breast cancer, possibly because exercise lowers estrogen levels. A few studies raise the possibility that reduced hormone levels may also lower the risk of uterine cancer.

Where does that leave men? The prostate is also responsive to hormones, but in this case the driving force is testosterone. Prostate cancer displays much more clinical variability than most other malignancies, and investigations of exercise and prostate cancer have produced widely varying results. Some suggest protection from modest exercise (such as walking), others indicate benefit only from very intensive exercise, and still others find no link at all. Clearly, more study is needed.

Evidence is also incomplete for lung cancer and pancreatic cancer, with several studies hinting that exercise can help. A large effect is unlikely, but even a little protection would be welcome. In any case, exercise may help restore energy and self-confidence to cancer patients, even when prevention has failed. In fact, a 2005 Harvard study of 2,987 women noted that moderate exercise, such as walking for 25 to 45 minutes a day, was associated with improved survival in breast cancer patients. In contrast, new studies suggest that antioxidants may actually blunt the benefits of radiation treatments for certain cancers.

Heart disease

Because they were the greatest hope against heart disease, antioxidants have been the greatest disappointment (see table). But an entirely different group of vitamins has also been investigated.

Until recently, folic acid, B6, and B12 were hopeful candidates for cardiac protection. Either singly, in the case of folic acid, or in combination, these three B vitamins can reduce blood levels of homocysteine, an amino acid. Many studies show that high levels of homocysteine are linked to an increased risk of vascular diseases, including heart attacks, strokes, and blood clots in veins. Homocysteine is also associated with a high likelihood of cognitive dysfunction and dementia.

That should make these three Bs a slam-dunk. Indeed, they do seem to help people with genetic abnormalities that lead to very high homocysteine levels. But randomized clinical trials of B supplements have failed to demonstrate any protection against heart disease. More study is needed; for now, leafy green vegetables and whole grains rate a resounding "yes" for protection against heart disease, supplements a regretful sigh. At present, the U.S. Preventive Services Task Force does not recommend vitamins to prevent heart disease.

For heart disease, like cancer, good foods outshine supplements. But one supplement can help. People who eat fish regularly, even just twice a week, enjoy a reduced risk of heart attack and sudden cardiac death. The same GISSI Trial (see table) that found no benefit for vitamin E also studied fish oil capsules in the modest dose of 850 milligrams (mg) a day. The benefit was substantial, amounting to a 20% reduction in risk. It's a major reason that the American Heart Association recommends 1,000 mg a day of fish oil for people with heart disease who do not eat fish regularly. It's good advice for people at high risk, too. And although it's not actually a supplement, remember that low-dose aspirin can reduce the risk of heart attacks in men over 50 and in everyone with coronary artery disease.

When it comes to reducing the risk of heart disease, exercise is the hands-down winner. The 1978 report of the Harvard Alumni Health Study was one of the first conclusive demonstrations; men who exercised enough to burn at least 2,000 calories a week were 39% less likely to suffer heart attacks than their sedentary classmates. Since then, more than 100 studies have evaluated exercise and health in men and women of diverse ethnic and socioeconomic backgrounds. Although the details vary, the vast majority agree that regular exercise is associated with a sharp reduction in heart attacks and cardiac deaths; most cite protection in the range of 35% to 55%. Studies show that modest exercise, such as walking about two miles a day or burning about 1,000 calories a week, can provide enormous protection against heart disease. And exercise helps even people who don't start exercising until later in life, as well as patients who don't start until they suffer a heart attack. In fact, a meta-analysis of 48 trials involving nearly 9,000 cardiac patients found that exercise-based rehabilitation reduced the patients' risk of dying from heart disease by 26%.

Scientists are learning just how exercise fights cardiovascular disease. Exercise improves the efficiency of the muscles that it puts to work, including the heart itself. It improves blood flow to the heart muscle and reduces the risk of abnormal pumping rhythms. In addition, exercise lowers LDL ("bad") cholesterol and triglyceride levels while boosting HDL ("good") cholesterol. It also reduces body fat, insulin levels, and the risk of diabetes — all cardiac risk factors. Regular exercise improves the body's defenses against artery-blocking blood clots and quiets the vascular inflammation that fuels the fire of atherosclerosis. Exciting new research also shows that exercise improves the function of the arteries' crucial inner layer, the endothelium, while boosting the supply of progenitor cells that renew aging arteries. And in all these respects, moderate exercise is all you need to benefit.

Heart attacks and sudden cardiac deaths are the most dramatic forms of cardiovascular disease, but hypertension is even more common, and over the years, this stealthy "silent killer" can cause congestive heart failure and strokes as well as heart attacks. Moderate exercise lowers blood pressure; when performed regularly, it reduces the risk of developing hypertension, and it can help treat the 72 million Americans who already have the disease. No vitamin even begins to claim that important result.

It's heartening to know that exercise can reduce your risk of cardiovascular disease.