DIET & DISEASE: THE STORY SO FAR.

Heart disease. Stroke. Cancer. Osteoporosis. Diabetes. It's been 40-odd years since researchers first started to link these diseases to the average American's diet.

Since then, they have hunted for connections between food and Alzheimer's, arthritis, macular degeneration, gallstones, and other illnesses. * For no disease are all the questions answered.

But for some, we've learned how to reduce our risk, while for others, the causes remain largely elusive.

As the year, decade, and millennium come to a close, it's time to take stock of the evidence.

DISEASES WE CAN PREVENT

Heart Disease

It's the number-one killer of both men and women in the U.S. Each year, more than a million Americans suffer a heart attack. Nearly half haven't yet turned 65.

Two out of three heart attack victims never make a complete recovery. Roughly half a million die. The death rate has dropped dramatically over the last few decades, in part because of coronary care units, clot-busting drugs, and other treatments. But in theory, the death rate should have fallen much further.

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"The essentials of preventing heart disease have been before us since the late 1950s," says pioneering heart disease researcher Jeremiah Stamler, professor emeritus at Northwestern University Medical School in Chicago. "We've known that severe atherosclerosis--the underlying disease--is a reflection of the Western lifestyle in the 20th century."

Diet's role has become clearer over the last 40 years:[1]

* Too much saturated and trans fat and cholesterol, largely from meat, dairy products, pastries, and eggs--raise blood cholesterol.

* Too many calories lead to obesity.

* Too little fiber, folate, and possibly omega-3 fatty acids (like the fat in fish) and antioxidants (like vitamin E) leave the heart unprotected.

* Too much sodium and too little potassium, magnesium; and protein (in foods like fruits, vegetables, and low-fat dairy products) raise blood pressure. So do obesity, lack of exercise, and excess alcohol.

"Sedentary living compounds our nutritional problems and cigarette smoking raises coronary risk," says Stamler. "That triad of an unhealthy lifestyle--adverse dietary patterns, inactivity, and smoking--is unprecedented in human evolution."

Over the decades, scientists have also come to recognize that preventing heart disease isn't just a matter of avoiding high blood cholesterol or high blood pressure. It's a matter of moving most of the population down below so-called normal levels, to optimal levels--that is, to blood cholesterol below 200 and blood pressure below 120 (systolic) and below 80 (diastolic).[2] Right now, less than ten percent of the population is in that optimal group.

"If we want to break the back of this disease, we've got to end the situation where optimal levels are a rare event," says Stamler. "That won't eliminate heart disease, but it would end the epidemic."

[1] Circulation 94:1795, 1996.

[2] Cardiology 82:191, 1993.

Stroke

It's a classic success story. Since 1970, the death rate due to strokes has dropped by 55 percent. But strokes still kill more than 150,000 Americans a year, making it the number-three killer (after heart disease and cancer). And that number will rise as the population ages. Still, the 30-year decline is a remarkable achievement.

The key: keeping a lid on blood pressure. High blood pressure raises the risk of a heart attack, but "the impact on stroke is much greater," says Norman Kaplan of the University of Texas Southwestern Medical Center in Dallas.

And it doesn't matter how old the patient is. "We used to think that older people needed higher pressure to push blood through the blood vessels," says Kaplan.

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But in a recent paper pooling data from a number of trials on more than 1,600 patients over age 80, he says, lowering blood pressure protected them against strokes as well as it did in younger people.[1]

"We've learned that we need to attack high blood pressure at any age," says Kaplan. That's critical "because among 70-year-olds, 60 percent have high blood pressure."

That's one reason why Kaplan and others recommend lifestyle changes for everyone.[2] Among them:

* Limit sodium. "Sixty to 70 percent of us will end up with hypertension," says Kaplan. "And older people are even more responsive to lowering sodium."

* Control weight. Losing as little as ten pounds can make a difference.

* Keep active. Just 20 minutes a day of walking or similar exercise can help prevent high blood pressure. "We're not talking about running a marathon,' says Kaplan. "Even moderate activity can really pay off."

* Limit alcohol. Up to two drinks a day in men and one in women lower the overall risk of cardiovascular disease. But more than that can raise blood pressure.

* Do the DASH. The DASH (Dietary Approaches to Stop Hypertension) study showed that a lower-fat diet with eight to ten servings a day of fruits and vegetables and two or three servings of low-fat dairy products lowered blood pressure in people with "high-normal" levels.[3] (See Oct. 1997, p. 10.)

The diet had more potassium, calcium, fiber, magnesium, and protein than a typical American diet. Other studies show that potassium can lower blood pressure, but it's not clear which other nutrients--or what else in fruits and vegetables--might have made a difference. "In two studies, we've seen a striking reduction in the risk of stroke in people who eat more fruits and vegetables," says Kaplan (see p. 10).

Of course, what lowers blood pressure also lowers the risk of cancer, heart disease, and diabetes. Says Kaplan: "Everyone ought to be making these lifestyle changes as a preventive measure."

[1] Lancet 353: 793, 1999.

[2] Arch. Intern. Med. 153: 186, 1993.

[3] New Eng. J. Med. 336: 1117, 1997.

Diabetes

An explosion. That's how experts describe worldwide diabetes rates, which are expected to double in the next ten years.

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And type 2 diabetes--which used to be called "adult-onset"--is now being diagnosed in adolescents. So why does diabetes belong in the "Diseases We Can Prevent" group?

We know that obesity is, by far, the most important cause of diabetes. "Studies suggest that more than 80 percent of diabetes is due to overweight and obesity," says JoAnn Manson of Harvard Medical School. "It has an enormous impact on risk."

That's one reason why experts predict a surge in diabetes: worldwide obesity rates are soaring. In the U.S., "the prevalence of obesity has increased 30 percent in the last ten to 15 years," explains Manson. The incidence of diabetes has also climbed.

As a nation, we're paying the piper for years of "super-size" fries and all-you-can-eat buffets. "Obesity is more closely linked to diabetes than any other health problem," says Manson. "A woman of average weight in the U.S. is at risk for diabetes. She has double the risk of a woman of optimal weight."[1]

A sedentary lifestyle also boosts the odds, whether you're overweight or not.[2] "Physical activity can reduce the risk of diabetes," says Manson. "Even moderate exercise such as walking is protective."

One of her studies suggests that foods that are higher in fiber and that are less likely to raise blood sugar may help prevent the disease.[3] "Whole-grain foods are associated with a lower risk," she says. "Calcium, magnesium, potassium, and antioxidants may also lower the risk, but it's surprising how little is known about their impact on diabetes."

[1] Ann. Intern. Med. 122: 481, 1995.

[2] Lancet 338: 774, 1991.

[3] J. Amer. Med. Assoc. 277: 472, 1997.

Colon & Rectal Cancer 

If you're not a smoker, the cancer that's most likely to kill you--other than breast or prostate--is cancer of the colon or rectum. In 1999, an estimated 94,700 Americans will be diagnosed with colon cancer and 34,700 with rectal cancer. Within ten years, 55 percent of them will die. Yet researchers are optimistic.

"With colorectal cancer, we have better evidence and a longer list of nutritional and behavioral risk factors than we have for other cancers," says Tim Byers of the University of Colorado Health Sciences Center in Denver.

"Avoiding excess weight around the waist, increasing physical activity, and eating more fruits and vegetables add up to a fairly substantial reduction in risk," he adds. "Getting sufficient calcium and limiting red meat or saturated fat intake are smaller factors."[1-3] And there's a possibility that the trace element selenium may cut the risk (see "Prostate Cancer," p. 7).

What's more, people can slash their risk of colon cancer by getting a colonoscopy every ten years starting at age 50 (or more often if the first findings are suspicious). "The most important message is that we can find and remove polyps before they grow into cancer," says Byers.

That's good news for individuals, but it has actually made it tougher for researchers to figure out whether diet can prevent the disease.

Two major, soon-to-be-released trials have tested whether fiber-rich foods like bran cereals, fruits, and vegetables can prevent new polyps--which often turn into cancer--in people who have already had at least one polyp removed.

"Trials that test diets on polyps are convenient, but they have important limits," says Byers. The biggest one: People in the trials get frequent colonoscopies to detect and remove new polyps.

"Most of the new polyps are tiny and won't evolve into cancer," he explains. "But it would be unethical to wait to see which ones turn into large polyps," because they could easily become cancerous.

So even if the trials find that diet has no impact on polyps, that doesn't mean that diet has no impact on cancer. "We have to look at a whole range of studies, not just experimental trials," says Byers.

Those studies make a compelling case that fruits and vegetables cut the risk, he adds. The evidence for fiber from grains is weaker. It may help prevent heart disease, and it's good for bowel function. But, says Byers, "it may not necessarily be good for preventing colorectal cancer."

[1] Ann. Intern. Med. 122: 327, 1995.

[2] J. Nat. Cancer Inst. 84: 91, 1992.

[3] New Eng. J. Med. 340:101, 1999.

Osteoporosis

One in two women and one in eight men over age 50 will fracture a bone because of osteoporosis in his or her lifetime, according to the National Osteoporosis Foundation. Ten million Americans already have the disease and 18 million others have bone density low enough to increase their risk of osteoporosis.

Every year, osteoporosis fractures 300,000 hips, 700,000 spines, 250,000 wrists, and 300,000 other bones. And hip fracture can mean the loss of independence. A quarter of those who could walk before a hip fracture require long-term care afterwards. The total cost to the nation: an estimated $13.8 billion in 1995.

And don't think you can sense a weakening of your bones. The disease has no symptoms, unless collapsed vertebrae cause back pain, loss of height, or stooping. Only a bone-density test can detect bone loss.

Women are at greatest risk. They can lose 20 percent of their bone mass during the five to seven years following menopause.

Yet osteoporosis can be prevented.

"Consuming adequate calcium and vitamin D lowers fracture rates in older people--we know that," says Bess Dawson-Hughes of the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tuffs University in Boston.

What's more, she adds, "calcium appears to promote the positive effect of exercise and estrogen on bone.' When women are given calcium supplements as well as estrogen (hormone replacement therapy), they gain more bone density than the women who are given estrogen without calcium.[1]

"Exercise didn't have a significant effect on bone density at low levels of calcium intake," says Dawson-Hughes. Exercise had the greatest effect when women consumed more than 1,000 mg of calcium a day (from food and supplements).[2]

Any exercise done in a full weight-bearing position--that is, standing--can strengthen bones. That boils down to almost anything except swimming, bicycling, and rowing.

As for vitamin D, she adds, "it's very helpful to bone because it promotes the absorption of calcium." The National Academy of Sciences recently raised its recommended vitamin D intakes. It is now trying to determine whether Medicare would save money by boosting vitamin D and calcium intakes in older people.

"It might be cost-effective to simply give seniors free calcium and vitamin D supplements," says Dawson-Hughes. "The cost of the supplements is so little compared to the cost of the fractures."

[1] Am. J. Clin. Nutr. 67: 18, 1998.

[2] J. Bone Min. Res. 11: 1539, 1996.

DISEASES WE CAN'T CRACK

Breast Cancer

An estimated 175,000 American women will be diagnosed with breast cancer this year. If survival rates stay steady, 69 percent of them will be alive after ten years and 5 7 percent after 15 years. Yet only heart disease and lung cancer claim the lives of more American women.

Scientists suspect that diet is linked to breast cancer, in part because the incidence varies so much around the world. Yet, despite years of research, "we're definitely still in the dark," says Regina Ziegler, a nutritional epidemiologist at the National Cancer Institute in Bethesda, Maryland.

"We still don't have consistent evidence that breast cancer is associated with physical inactivity, elevated intakes of fat or pesticides, or with reduced intake of fruits and vegetables or soy or other foods that contain phytoestrogens," she explains.

The only exceptions: A growing number of studies show that excess weight raises the risk of breast cancer in postmenopausal women.[1] And women who drink alcohol--even as little as one drink a day--have a slightly elevated risk.[2]

Other risk factors include age, family history, atypical hyperplasia (irregular cells in benign breast lumps) confirmed by biopsy, never having given birth to children or having had the first live birth at a late age, early age at first menstrual period, late menopause, recent use of oral contraceptives or postmenopausal estrogens, and higher education and socioeconomic status.

"But most U.S. women have at least one of those risk factors," says Ziegler. "None raises risk enough to explain why breast cancer is so much more prevalent in the U.S. than in Asia."

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[1] J. Amer. Med. Assoc. 278: 1407, 1997.

[2] J. Amer. Med. Assoc. 279: 535, 1998.

Prostate Cancer

The good news: 60 percent of all prostate cancers are discovered before the tumor has spread, and for those patients the five-year survival rate is 100 percent.

The bad news: Roughly 179,000 American men will be diagnosed with prostate cancer--and an estimated 37,000 will die of the disease--in 1999. And, so far, attempts to nail down a link with diet--or any other preventive strategy--haven't come up with much. Among the candidates:

* Selenium. In 1996, a trial testing selenium's ability to prevent skin cancer in the Southeastern U.S. (where levels of the trace mineral are low) had an unexpected finding: Selenium-takers got prostate, lung, and colon cancers only about half as often as placebo-takers. (Selenium had no effect on skin cancer rates.)[1]

"Even if the true effect is only half what the trial found, it would still have an enormous public health impact," says Tim Byers of the University of Colorado Health Sciences Center in Denver. "We should jump on it."

New trials are under way, but most researchers have viewed the 1996 trial with surprising skepticism that borders on disbelief. "If it turns out that selenium works, looking back we won't have anything but embarrassment and shame about how slowly we responded to the first trial," says Byers, who served on its safety monitoring panel.

While Byers doesn't recommend that people take selenium, he does add that "the risk is low as long as you take only 200 micrograms a day in the form of the brewer's yeast compound that was used in the trial. Its safety is confirmed and it might be effective."

(Selenium supplements that contain the patented brand of selenium used in the trial have the word "Selenomax" on their labels. See illustration.)

* Vitamin E. In a trial on 29,000 Finnish smokers, those who were given 50 IU of vitamin E a day had a 32 percent lower risk of prostate cancer than those who got a placebo.[2] (That dose is about five times the amount of vitamin E the average Finn gets from his or her diet.)

"It's an exciting lead that's worth testing," says Byers.

But, he adds, the death rate from all causes among vitamin-E-takers in the Finnish trial was actually higher than in the placebo-takers, mostly due to a higher rate of hemorrhagic stroke.

"We know that vitamin E has bleeding risks," says Byers. But how much risk, especially in non-smokers? A large trial, now under way, should yield some answers.

* Saturated fat. In a number of studies, men who ate more animal fat had a higher risk of prostate cancer. But it's not clear whether it's the fat or the red meat in their diets that matters.[3]

"It's biologically plausible that there would be some relationship with saturated fat or red meat, because men on high-fat diets have higher testosterone levels," says Byers. (Testosterone promotes prostate cancer.) But it's hard to sort out, because diets high in red meat are also high in saturated fat.

* Lycopene. Ketchup as a vegetable? Thanks in part to optimistic--some would say opportunistic--advertising by Heinz, the link between prostate cancer and lycopene, a carotenoid in tomatoes and other fruits and vegetables, has made news.

But so far, two studies show a lower risk in lycopene-eaters and two show no link.[4,5]

"If you look at the range of studies, most don't show an association with fruits, vegetables, or tomato products," says Byers. "It's a lead worth following up, but I wouldn't put my money on it yet."

[1] J. Amer. Med. Assoc. 276:1957, 1996.

[2] J. Nat. Cancer Inst. 90: 440, 1998.

[3] J. Nat. Cancer Inst. 85:1571, 1993.

[4] Cancer Epidem. Bio. Prev. 6: 487, 1997.

[5] Cancer Research 59:1225, 1999.

Esophageal Cancer 

It's not one of the most common cancers, but if you're white, male, and middle-aged, it should be one of the most frightening. Rates of one kind of esophageal cancer--adenocarcinoma of the esophagus--have risen six-to-eight-fold since the 1970s, more rapidly than any other cancer in the U.S.

And it's a killer. The five-year survival rate is just 12 percent (that includes squamous cell esophageal cancer, which typically strikes men who drink alcohol, smoke cigarettes, and have below-average weight and educational levels).

Researchers are just beginning to search for clues to explain why adenocarcinoma rates are climbing. One clear risk factor: reflux, or heartburn.

Men who reported symptoms of heartburn--which occurs when stomach acid backs up into the esophagus--were nearly eight times more likely to have the cancer in a recent Swedish study.[1] In men who had longstanding and severe heartburn, the risk was 44 times higher than in men without symptoms.

But what contributes to heartburn? "The general prescription for people with reflux is to avoid caffeine, chocolate, alcohol, and high-fat foods," says Susan Taylor Mayne, an epidemiologist at Yale University Medical School.

"Those foods supposedly relax the sphincter between the stomach and the esophagus," she explains. But researchers are just starting to investigate whether foods--or habits like eating before bedtime--promote esophageal cancer.

Meanwhile, scientists have fingered some other culprits.

"Obesity is probably the best of the candidates," says Mayne. "The heavier you get, the greater the risk." The rise in obesity certainly mirrors the rise in esophageal cancer.[2]

Alcohol and smoking also raise the risk, while a plant-based diet lowers it, according to Mayne's latest study) "Nutrients that are found in fruits, vegetables, and whole grains are protective," she says. "The strongest protector was fiber, followed by vitamin C, folate, and beta-carotene."

People who took vitamin C supplements had a lower risk. But, she adds, it's still not clear whether it's the vitamins or something else in a plant-based diet that protects the esophagus.

On the flip side, people who ate more animal products had a higher risk. "All of the nutrients in meat--fat, cholesterol, and animal protein--are associated with a higher risk," says Mayne.

Calcium wasn't a risk factor, so dairy products may not promote the disease. But it's hard to say whether it's the meat--or the lack of fruits and vegetables--in meat-based diets that makes a difference.

The only clear advice right now: "Avoid cigarettes and alcohol, maintain appropriate body weight, and get enough fruits, vegetables, and whole grains--the same recommendations that reduce the risk of other diseases," says Mayne.

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[1] New Eng. J. Med. 340: 825, 1999.

[2] J. Nat. Cancer Inst. 90: 150, 1998.

[3] FASEB 13: A1021, 1999.

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Alzheimer's Disease 

An estimated four million Americans have Alzheimer's disease. The prevalence doubles every five years beyond age 65. The annual cost--in terms of health care and lost wages for both patients and caregivers--is a staggering $80 billion to $100 billion.

But any link with diet is murky.

"A lot of laboratory research suggests that oxygen radical accumulation--which is known to increase with aging--is not a good thing to have around if you want to prevent neurodegenerative disease," says Steven Ferris of New York University. "But the notion that antioxidants might slow changes in Alzheimer's or reduce the risk of the disease is still in the category of speculation."

In people, only ginkgo biloba and vitamin E have been tested on large groups of people. The results on ginkgo are questionable.[1]

"The effect of ginkgo was only half that of the drugs that have been approved to treat Alzheimer's, and those drugs are considered minimally effective," says Ferris.

What's more, half of the people in the trial dropped out and the placebo group didn't get much worse over the one-year trial. "The placebo group either had extremely mild Alzheimer's or was misdiagnosed as having the disease," he suggests.

"The bottom line is that we can't conclude that ginkgo works based on this study," says Ferris. A new trial giving ginkgo to Alzheimer's patients is under way.

Also in the works: Researchers will give 2,000 healthy older people either 240 mg of ginkgo or a placebo every day and wait six years to see if one group is more often diagnosed with Alzheimer's or other dementia.

As for vitamin E, a well-designed trial found that a huge dose--2,000 IU a day--slowed the clinical progression of Alzheimer's in people who already had the disease. The average vitamin-E-taker reached one of four "endpoints" (death, institutionalization, inability to perform basic activities of daily living, or severe dementia) about seven months later than the average patient who was given a placebo.[2]

Ferris and others are conducting a new study. "We want to see whether vitamin E can delay the diagnosis of Alzheimer's in people with mild memory impairment," he says.

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[1] J. Amer. Med. Assoc. 278:1327, 1997.

[2] New Eng. J. Med. 336:1216, 1997.

Arthritis

Twenty million Americans have osteoarthritis. In four out of five, the problem is severe enough to limit their movement or activities. And the number of arthritis patients is expected to swell as the population ages. But the disease isn't a natural part of aging.

It occurs when the cartilage that covers the ends of bones in elbows, knees, and other joints starts to deteriorate. As bone begins to rub against bone, moving an arm, leg, or backbone becomes difficult ... and painful.

Among the known causes: Genes play a role, obesity promotes arthritis in the knees, and joint injuries--from sports, work, or accidents--can lead to arthritis years later. What about diet? So far we have only clues.

"Two studies now suggest that people with low blood levels of vitamin D are at high risk for getting arthritis and having it progress," says David Felson of the Boston University Arthritis Center.[1,2] "It's reassuring that two studies agree, but we need more information."

(Another study found that in people with higher vitamin C intakes, arthritis progressed more slowly.[3] But it, too, needs corroboration, he adds.)

Still, says Felson, "because low vitamin D levels have other consequences, like low bone density, they need to be addressed, especially in older persons living in northern climes."

Older people have a higher risk of vitamin D deficiency, he explains, because "they don't drink as much milk, they don't get out in the sun, and their skin doesn't convert the precursor of vitamin D to the active form as well as younger skin does."

Even more promising, supplements of glucosamine and chondroitin--two natural substances found in cartilage--seem to curb the symptoms of arthritis. In a recent study, 34 Navy divers who took glucosamine (1,500 mg a day) and chondroitin (1,200 mg a day) reported less knee pain than those who took a placebo.[4] In February, the National Institutes of Health will start testing glucosamine, chondroitin, or the combination in more than 1,000 people with arthritis of the knee.

[1] Arth. Rheum. 42: 854, 1999.

[2] Ann. Intern. Med. 125: 353, 1996.

[3] Arth. Rheum. 39: 648, 1996.

[4] Mil. Med. 164: 85, 1999.