Not everybody must get stones: how to avoid gallbladder disease.

When John Ashcroft experienced sudden abdominal pains so severe he couldn't attend a press conference last March, the Attorney General of the United States became another of the one million Americans to suffer from gallbladder disease this year.

In Ashcroft's case, an errant gallstone was blocking the flow of digestive enzymes from his pancreas to his small intestine. That caused the enzymes to back up and begin eating away at the pancreas itself, an extremely painful and sometimes fatal condition called acute gallstone pancreatitis.

Ashcroft's gallstone later slipped free and passed into his intestines. But when his doctors found more stones waiting in his gallbladder, they decided to prevent a future blockage by removing the organ. The procedure, called a cholecystectomy, is performed 500,000 times a year, making it more common than knee or hip replacements or appendectomies. (The organ isn't essential--bile can flow directly from the liver to the intestines--and most people notice little difference after it's gone.)

Some 80 percent of cholecystectomies are done via laparoscopy, in which surgical instruments and a tiny video camera are inserted into several small incisions in the abdomen. Because no abdominal muscles are cut, the surgery means less pain, quicker healing, less scarring, and a lower risk of infection.

Ashcroft was able to return to work three weeks after his surgery.

Gallbladders 101

Few people know where their gallbladder is, much less what it does.

"The gallbladder is located under the rib cage on the right side of the abdomen," says gastroenterologist Cynthia Ko of the University of Washington in Seattle. It's a pear-shaped sac that stores and concentrates the two to three cups of bile that the liver produces each day.

Bile is a thick, yellow-brown fluid that consists of water, cholesterol, bile salts, and pigments. After a meal, the gallbladder contracts and injects several tablespoons of bile into the small intestines, where the detergent-like bile salts break up fats. That helps the body digest fat and absorb fat-soluble nutrients like vitamins D and E.

But if the bile contains too much cholesterol and not enough bile salts, gallstones can form. That's what happens to most of the estimated 10 to 20 percent of U.S. adults who develop gallstones. Stones can be as small as grains of sand or as big as golf balls.

"Fortunately, a majority of people with gallstones don't have symptoms and don't need medical intervention," says Ko, who is a spokesperson for the American Gastroenterological Association.

Problems occur when a gallstone makes its way out of the gallbladder (see "A Lot of Gall"). If it lodges in the cystic duct--the channel that leads from the gallbladder to the common bile duct, which empties into the small intestine--the stone can block the flow of bile. That can cause cholecystitis, a painful inflammation of the gallbladder.

A more serious--but less common--problem occurs when a stone lodges in the common bile duct. That can block the flow of bile from the gallbladder and liver, which can cause serious abdominal pain and, in some cases, can lead to cholecystitis.

In the worst cases, a stone can lodge just where the pancreatic duct joins the common bile duct, trapping digestive enzymes in the pancreas, where they start destroying tissue. That's what happened to John Ashcroft.

And while the vast majority of people with gallstones don't develop gallbladder cancer, between 75 percent and 90 percent of those who get gallbladder cancer have had gallstones. So anything that lowers your risk of gallstones may also lower your risk of gallbladder cancer, which kills some 3,500 Americans every year.

Cutting Your Risk

"It's not exactly clear why some people develop gallstones and others don't, although we do have a number of potentially important leads," says Michael Leitzmann, an epidemiologist at the National Cancer Institute in Bethesda, Maryland.

Some factors that increase risk are out of your control. For example:

* Gender. Women are twice as likely to develop gallstones as men. In part, that's because estrogen concentrates more cholesterol in the bile. "The gender gap is particularly evident in younger people, then narrows as we get older," says Leitzmann.

* Age. People over age 60 have a higher risk than younger people, possibly because their gallbladders don't always contract fully. "When the gallbladder doesn't contract, what's called biliary sludge is left behind to form crystals of cholesterol that grow into gallstones," Leitzmann explains.

But there are things you can control. "A healthy lifestyle of watching your weight, eating the right kinds of foods, and getting physical exercise can reduce your risk of gallbladder disease," says Ko. Specifically:

* Weight. "It's clear that being overweight or obese increases the risk of forming gallstones," says Andrew Diehl of the University of Texas Health Science Center at San Antonio.

"The research is unanimous," adds Leitzmann. "It's clearly the number-one modifiable risk factor for gallstones."

Middle-aged men and women who are overweight are twice as likely to develop gallstones as people whose weight is normal. (1) And the more weight you gain, the worse off you are.

"The risk starts increasing with overweight," says Leitzmann, "and then increases substantially with obesity."

Why? "It's believed that overweight and obese women and men synthesize increased amounts of cholesterol and secrete more of it into the bile," explains Diehl. The more cholesterol in the bile, the more likely gallstones will form.

"The increased insulin resistance that comes with being overweight or obese, especially around the waist, may also be a factor," adds Leitzmann. "High insulin levels increase the concentration of cholesterol in the bile, too."

While excess weight is bad, so is shedding pounds too quickly.

"Rapid weight loss is associated with an incredibly rapid development of gallstones, within just weeks," says Diehl. "It's absolutely astonishing."

In a 1995 study, researchers found gallstones in 28 percent of 202 obese men and women who lost an average of 3.3 pounds a week on a 520-calorie diet over a four-month period. (2) The National Institute of Diabetes and Digestive and Kidney Diseases warns dieters not to lose more than three pounds a week.

It's not clear why gallstones form so readily when weight drops quickly. "It may be due to gallbladder stasis," suggests Diehl. "If you're not putting much into your stomach, your gallbladder may not be contracting and emptying as often or as vigorously." That allows bile to pool and form stones.

* Plant foods. When researchers at the Harvard School of Public Health compared the nearly 8,000 women in the Nurses Health Study who had their gallbladders removed over the past 20 years with similar women who hadn't, they saw that certain plant foods lowered the odds that the women would need surgery:

Fiber. Those who ate the most fiber (they averaged 24 grams a day) had a 15 percent lower risk than those who ate the least (around 11 grams a day). (3)

"It may be that dietary fiber increases the bulk of food passing through the intestines, or speeds up the passage of food through the intestines, or decreases insulin resistance," says Leitzmann, who co-authored the study. "Any of the three could decrease the level of cholesterol in the bile."

Plant protein. Those who ate the most protein from plant sources (they averaged 22 grams a day from foods like beans and soy) had a 20 percent lower risk than those who ate the least (about 12 grams a day). (4)

"Animal protein didn't affect the risk of gallbladder disease," reports Leitzmann, who adds that "plant protein may inhibit the formation of cholesterol crystals from bile."

Nuts. Those who ate the most nuts (five or more ounces a week), including peanuts, had a 25 percent lower risk than those who ate the least (less than one ounce--about 1/4 cup--a month). (5)

"The nuts could be decreasing insulin resistance," says Leitzmann. "Or their fiber, vitamin E, magnesium, or unsaturated fats might affect the development of gallstones."

"Fiber, nuts, and plant protein each lowers the risk of gallstone disease by 15 to 25 percent," says Leitzmann. "But someone who combines several of them might well see a protective effect greater than 25 percent."

* Added sugars. "There's some evidence that added sugars in food can increase the risk of gallstones," says Diehl. In a 25-year study of middle-aged men in the Netherlands, those who ate the most sugars were more than twice as likely to be diagnosed with gallstones as those who ate the least. (6)

* Regular exercise. Among the more than 45,000 men in the Health Professionals Follow-up Study, those who were the most physically active were some 35 percent less likely to need gallbladder surgery than those who were the least active. (7) And men 65 or older in the study who watched more than 40 hours of television a week had three times the risk of men who watched less than six hours a week.

In the Nurses Health Study, women who averaged two to three hours a week of recreational exercise (jogging, running, playing tennis, doing calisthenics, or walking briskly) were 20 percent less likely to need their gallbladders removed than women who did little or no exercise. (8)

Why? "Physical exercise could be increasing insulin sensitivity, speeding up the passage of food through the intestines, or stimulating the contraction of the gallbladder to flush out the bile fluid," says Leitzmann. "We know that marathon runners have increased levels of cholecystokinin, a chemical messenger found in the intestines that triggers the contraction of the gallbladder."

* Coffee. In both the Nurses Health Study and the Health Professionals Follow-Up Study, people who drank two to three cups of regular coffee a day had about a 20 percent lower risk than those who drank no coffee at all. (9,10)

"Tea, decaf coffee, and caffeinated soft drinks weren't protective, probably because they don't contain enough of what's making the difference, caffeine," says Leitzmann, who co-authored the study.

Why might caffeine make a difference? One theory: it stimulates the gallbladder to contract, which helps empty it of stone-forming cholesterol and bile pigments.

* Alcohol. "Men and women who drink moderate amounts of beer, wine, or liquor have a substantially lower incidence of gallstone disease compared to people who don't drink at all," says Diehl. "The reduction is generally in the 30 percent range and has been shown dozens of times."

Moderate means one to two drinks a day for men and one-half to one drink a day for women.

"Just small amounts of alcohol taken regularly are enough to start providing protection," says Leitzmann. "But binge drinking isn't protective." And, given alcohol's devastating toll, it would make no sense to start drinking to try to cut your risk of gallstones.

Why does alcohol lower risk? "It somehow affects the secretion of cholesterol and bile acids by the liver into the gallbladder," explains Diehl. Drinking more than a moderate amount, however, can lead to cirrhosis of the liver. Among its complications: gallstones.

(1) Arch. Intern. Med. 161: 1581, 2001.

(2) Ann. Intern. Med. 122: 899, 1995.

(3) Amer. J. Gastroenterol. 99:1364, 2004.

(4) Amer. J. Epidemiol. 160:11, 2004.

(5) Amer. J. Clin. Nutr. 80: 76, 2004.

(6) Ann. Epidemiol. 4: 248, 1994.

(7) Ann. Intern. Med. 128:417, 1998.

(8) New Eng. J. Med. 341: 777, 1999.

(9) Gastroenterology 123:1823, 2002.

(10) J. Amer. Med. Assoc. 281: 2106, 1999.

Under Attack?

Many people with gallstones have no symptoms ("silent stones") and need no treatment. For others, symptoms occur so suddenly that they're referred to as an "attack." A typical attack can cause:

* steady pain in the upper abdomen that increases rapidly and lasts from 30 minutes to several hours

* pain in the back between the shoulder blades or under the left or right shoulder

* nausea or vomiting

If you have any of the above and any of the following symptoms, see a doctor immediately. You might have a serious bile duct obstruction or infection:

* repeated episodes of pain

* fever or chills

* yellowish color of the skin or whites of the eyes

* clay-colored stools

Sources: Andrew Diehl of the University of Texas Health Science Center at San Antonio and Stephen Hanauer of the University of Chicago Pritzker School of Medicine.