• May be without symptoms or may be associated with periods of intense pain in the abdomen that radiates to the upper back
• Ultrasound provides definitive diagnosis
Gallstones are definitely another example of a Western-diet-induced disease.1 Conservative estimates suggest that about 20 million Americans (10% of the U.S. adult population) and 5 to 22% of the population in the Western world have gallstones.2 Each year in the United States another 1 million people develop gallstones, and more than 300,000 gallbladders are removed owing to the presence of gallstones. While often considered a nuisance, gallstones are a serious health concern. Persons with gallstone disease or a history of gallbladder removal (cholecystectomy) have a shorter life span, primarily due to increased mortality from cardiovascular disease and cancer, particularly gallbladder cancer.3,4 Of course, obesity, type 2 diabetes, and insulin resistance are primary risk factors for gallstones and also carry with them the risk of early death.
Bile has many components, including bile salts, bilirubin, cholesterol, phospholipids, fatty acids, water, electrolytes, and other organic and inorganic substances. Bile also contains toxins the body is trying to eliminate, such as persistent organic pollutants (POPs) and mercury. The following table shows the characteristics of the major bile components. Gallstones arise when the concentration of a normal bile component becomes too high. Gallstones can be divided into four major categories:
• Pure cholesterol
• Pure pigment (calcium bilirubinate)
• Mixed, containing cholesterol and its derivatives along with varying amounts of bile salts, bile pigments, and inorganic salts of calcium
• Stones composed entirely of minerals
Pure stones, either cholesterol or calcium bilirubinate, are uncommon in the United States. Recent studies indicate that in the United States, approximately 80% of stones are of the mixed variety. The remaining 20% of stones are composed entirely of minerals, principally calcium salts, although some stones contain oxides of silicon and aluminum.
The formation of gallstones occurs in three steps:
1. Increase in the concentration of a bile component
2. Formation of a small solid mass (the gallstone)
3. Enlargement of the gallstone by accretion
The requisite step in cholesterol and mixed stone formation is the increased concentration of cholesterol within the gallbladder. Because free cholesterol is insoluble in water, it must be incorporated into a lecithin-bile salt emulsion. Either an increase in cholesterol secretion or a decrease in bile acid or lecithin secretion will result in too much free cholesterol in the bile. Once that has occurred, stone formation is initiated by factors such as decreased bile flow, infection, and increased mucin secretion by the gallbladder lining. Once the stone begins to form, it becomes larger year by year. Symptoms typically occur an average of eight years after formation begins. Gallstones are present in 95% of patients with gallbladder pain and inflammation.
Characteristics of the Major Bile Components |
|||
COMPONENT |
% OF BILE |
WATER SOLUBILITY |
PHYSIOCHEMICAL PROPERTIES |
Cholesterol |
5 |
Very poor |
Will precipitate from aqueous solutions |
Bile salts |
65–90 |
Soluble; have polar and nonpolar regions |
Capable of solubilizing cholesterol and phospholipids in aqueous phase |
Phospholipids |
2–25 |
Poor |
Fit between bile salt molecules, thus increasing their capacity to solubilize cholesterol |
Causes
The major risk factors for the development of cholesterol and mixed gallstones include the following:
• Diet
• Obesity
• Gender
• Race
• High caloric intake
• Estrogens
• Gastrointestinal tract diseases (especially Crohn’s disease and cystic fibrosis)
• Drugs
• Age
The role of a low-fiber, high-fat diet in the development of gallstones, as well as other dietary factors, is discussed later; the remaining factors are briefly discussed here.
Obesity, type 2 diabetes, insulin resistance, and elevated blood triglyceride levels are well-known risk factors for gallstones. Obesity causes increased cholesterol manufacture in the liver with increased secretion of cholesterol in the bile. Therefore obesity is associated with a significantly increased incidence of gallstones.
Important to note is that during active weight reduction, changes in body fat and diet can actually promote gallstone problems.5 During the first stages of weight loss, the amount of cholesterol in the bile initially increases, because the secretion of bile acids decreases more than the secretion of cholesterol. Once weight is stabilized, bile acid output returns to normal levels, while the cholesterol output remains low. The net effect is a significant reduction in cholesterol concentration in the bile. Obese patients with a high risk of gallstones should realize that prolonged dietary fat reduction can also promote a condition called biliary stasis, thus contributing to the risk of gallstone formation.1 Studies show that at least 10 g fat per day is necessary in order to ensure proper gallbladder emptying.6
The frequency of gallstones is two to four times greater in women than in men. Women are thought to be predisposed to gallstones because of either increased cholesterol synthesis or suppression of bile acids by estrogens. Pregnancy, use of oral contraceptives or other causes of elevated estrogen levels, and the chemotherapy drug tamoxifen greatly increase the incidence of gallstones.
The prevalence of gallstones appears to have some genetic aspects. Gallstones are most common in Native American women older than 30. Nearly 70% of the women in this group have gallstones. In contrast, only 10% of black women older than 30 have gallstones.
The difference in the prevalence rate between different ethnic and genetic groups reflects the concentration of cholesterol in the bile. The extent to which dietary factors affect this value probably outweighs genetic factors.
Malabsorption of bile acids from the small intestine disturbs the natural circulation of excreted bile acids back to the liver, thereby reducing the bile acid pool and the rate of secretion of bile. Diseases associated with this phenomenon include Crohn’s disease and cystic fibrosis.
Tamoxifen treatment in postmenopausal breast cancer patients greatly increases gallstones. One study of 703 women demonstrated that after five years, the incidence of stone formation in the tamoxifen-treated patients was 37.4%, whereas it was 2% in patients who did not receive tamoxifen.7 Most gallstones became apparent after three years.
In addition to oral contraceptives and other estrogens, as discussed earlier, drugs that increase the risk of gallstones include ceftriaxone, octreotide, statins, and possibly other lipid-lowering drugs.
Gallstones have been reported in fetuses and extremely old people and at all ages in between, but the average patient is 40 to 50 years old. Decline in the activity of enzymes that manufacture bile acids with age leads to an increase in biliary cholesterol hypersecretion and thus cholesterol saturation with accelerated formation of gallstones. Aging itself appears to be a risk factor for gallstones.8
Risk factors for pigmented gallstones are not related to diet as much as they are to geography, sun exposure, and severe diseases. Pigmented gallstones are more common in Asia, owing to the higher incidence of parasitic infection of the liver and gallbladder by various organisms including the liver fluke Clonorchis sinensis. Bacteria and protozoa can cause stagnation of bile flow or initiate the process of stone formation. In the United States, pigmented stones are usually caused by chronic hemolysis or alcoholic cirrhosis of the liver.
Therapeutic Considerations
Gallstones are easier to prevent than to reverse. Primary treatment, therefore, involves reducing the controllable risk factors discussed earlier. Once gallstones have formed, therapeutic intervention involves avoiding aggravating foods and employing measures that increase the solubility of cholesterol in bile and possibly help dissolve the stones. If symptoms persist or worsen, surgery may be required.
A number of dietary factors are important in the prevention and treatment of gallstones. Foremost is the elimination of foods that can produce symptoms. Also important are increasing dietary fiber, eliminating food allergies, and reducing the intake of refined carbohydrates and animal protein. Vegetables and fruits have a protective effect against gallbladder cancer, while red meat was found to be associated with increased risk of gallbladder cancer.9 Because gallstones are a risk factor for gallbladder cancer, a healthful diet will protect against both cancer and development of gallstones.
Other treatment measures involve the use of nutritional lipotropic compounds, herbal choleretics, and other natural compounds in an attempt to increase the solubility of bile.
Biliary cholesterol concentration and serum cholesterol levels do not seem to correlate.10 However, there is a link between high triglyceride levels and gallstone formation.11,12 Drugs to lower triglycerides actually worsen the situation by reducing bile acid content, while fish oils produce the exact opposite effect.12 In general, the higher the level of triglycerides the more saturated the bile is and the more likely it is that a stone will form.
The natural history of silent or asymptomatic gallstones supports the contention that elective gallbladder removal is not warranted. There is a cumulative chance of developing symptoms—10% at 5 years, 15% at 10 years, and 18% at 15 years—but if controllable risk factors are eliminated or reduced, a person should never experience discomfort and require surgery.
Dietary Fiber
The theory that the main cause of gallstones is the consumption of fiber-depleted, refined foods has considerable research support.1 Gallstones are clearly associated with the Western diet in population studies. Such a diet, high in refined carbohydrates and fat and low in fiber, leads to a reduction in the synthesis of bile acids by the liver and a lower bile acid concentration in the gallbladder.
Another way in which fiber may prevent gallstone formation is by reducing the absorption of deoxycholic acid. This compound is produced from bile acids by bacteria in the intestine. Deoxycholic acid greatly lessens the solubility of cholesterol in bile. Dietary fiber has been shown both to decrease the formation of deoxycholic acid and to bind deoxycholic acid and promote its excretion in the feces. This greatly increases the solubility of cholesterol in the bile. A diet high in fiber, especially soluble fiber, which is capable of binding to deoxycholic acid, is extremely important in both the prevention and the reversal of gallstones.
Interestingly, diets rich in legumes, which are high in soluble fiber, are associated with an increased risk for gallstones in some populations.13 Specifically, Chileans, Pima Indians, and other North American Indians have the highest prevalence rates for cholesterol gallstones, and all typically consume a diet rich in legumes. Evidently legume intake may increase biliary cholesterol saturation in these populations. A study conducted in the Netherlands showed just the opposite, as legume intake was shown to offer significant protection against gallstones.14 Until this issue is clarified, it might be best to restrict legume intake in individuals with existing gallstones.
Vegetarian Diet
A vegetarian diet has been shown to be protective against gallstone formation.15 A recent study in England compared a large group of healthy nonvegetarian women with a group of vegetarian women. Ultrasound diagnosis showed that gallstones occurred significantly less frequently in the vegetarian group.
Although this may simply be a result of the increased fiber content of the vegetarian diet, other factors may be equally important. Animal proteins, such as casein from dairy products, have been shown to increase the formation of gallstones in animals, while vegetable proteins such as soy were shown to be preventive against gallstone formation.16
Food Allergies
In 1948 Dr. J. C. Breneman, author of Basics of Food Allergy, began to use a therapeutic regimen that proved very successful in preventing prevent gallbladder attacks: allergy elimination diets. The idea that food allergies cause gallbladder pain has some support in the scientific literature.17–20 A 1968 study revealed that 100% of a group of patients were free from symptoms while they were on a basic elimination diet (beef, rye, soybean, rice, cherry, peach, apricot, beet, and spinach).17 Foods inducing symptoms were as follows (those that most frequently caused symptoms are listed first):
• Eggs
• Pork
• Onion
• Poultry
• Milk
• Coffee
• Citrus fruits
• Corn
• Beans
• Nuts
Adding eggs to the diet caused gallbladder attacks in 93% of the patients.
Several mechanisms have been proposed to explain the association of food allergy and gallbladder attacks. Dr. Breneman believes the ingestion of allergy-causing substances causes swelling of the bile ducts, resulting in impairment of bile flow from the gallbladder.
Buckwheat
Buckwheat is a well-known alternative for those avoiding wheat for hypoallergenic purposes. Giving three groups of eight hamsters a buckwheat-, soy-, or casein-based diet, one Japanese research group demonstrated that buckwheat can significantly decrease gallstone formation and reduce the concentration of cholesterol in the gallbladder, plasma, and liver of hamsters, compared with the casein diet.21 Even though soy itself prevents gallstones,22 these researchers found that the positive effects of buckwheat were far stronger than those of soy. Gallstones were clearly visible in all eight hamsters fed the casein diet, whereas two of seven hamsters fed the soy diet (29%) and none of the buckwheat-fed animals had gallstones. Studies of rats have corroborated these findings.23 The hypothesis is that buckwheat can enhance bile acid synthesis and fecal excretion of steroidal compounds. Buckwheat may be useful to treat patients with both high cholesterol and gallstones and may reduce colon cancer cell proliferation.24 It is also possible that higher levels of arginine and glycine may play a role in buckwheat’s protective function.
Diets high in refined carbohydrates and sugar have been found to be associated with increased cholesterol concentration in the bile and an increased risk for both gallstones and gallbladder cancer.25–30
Caloric Restriction
Rapid weight loss31 and fasting32 increase the risk of gallstones (see the section “Obesity” earlier in the chapter). For example, in 179 obese patients, 9% of whom had preexisting gallstones, a low-calorie diet (605 calories) resulted in 11% of the patients developing gallstones either while on the diet or within six months of completing it.31 A study of a 925-calorie diet found that 12.8% of the 47 women patients had ultrasound evidence of gallstones at week 17. Those who developed gallstones had significantly higher baseline triglyceride and total cholesterol levels than those who did not. They also had a significantly greater rate of weight loss.33
Coffee
Although coffee can exacerbate the symptoms of gallstones, it may also inhibit their formation. In one interesting study, 400 ml regular coffee and 165 ml regular and decaffeinated coffee were assessed for their effect on cholecystokinin secretion. Regular coffee at both dosages and decaffeinated coffee caused significant gallbladder contractions in six healthy regular coffee drinkers.34 Another study, of 80,898 female nurses between the ages of 34 and 59, found that drinking four cups of caffeinated coffee per day lowered the risk of developing symptoms of gallstones by 28%. Even one to three cups seemed to have some protective effect, though not as great.35 It may be that the gallbladder contractions from coffee consumption were able to either inhibit the development of stones or clear small ones. In women who already have large stones, the increased contractions produced by coffee may worsen their condition.
Lecithin (Phosphatidylcholine)
Because lecithin is the main cholesterol solubilizer in bile, a low lecithin concentration may be a causative factor for many people with gallstones. Studies have shown that ingestion of lecithin can have a direct effect on cholesterol solubilization.36 Taking as little as 100 mg lecithin three times per day will increase the concentration of lecithin in the bile, while larger doses (up to 10 g) produce even greater increases.37,38 This effect is significant, as an increased lecithin content of bile usually increases the solubility of cholesterol. However, no significant effects on gallstone dissolution have been obtained using lecithin supplementation alone. Therefore, moderate dosages are recommended as supportive therapy.
Vitamins E and C
A deficiency of either vitamin E or vitamin C has been shown to cause gallstones in experimental studies of animals.39,40
Olive Oil Liver Flush
A popular remedy for gallstones is the so-called olive oil liver flush. There are several variations. A typical one involves drinking 1 cup of unrefined olive oil with the juice of two lemons in the morning for several days.
Many people tell tales of passing huge stones while on the liver flush. However, what they think are gallstones are simply a complex of minerals, olive oil, and lemon juice produced within the gastrointestinal tract.41
The olive oil liver flush is potentially dangerous for people with gallstones for several reasons. First, consuming a large quantity of any oil results in contraction of the gallbladder, which may increase the likelihood of a stone blocking the bile duct. This may result in inflammation of the gallbladder (cholecystitis), requiring immediate surgery to prevent death. Second, in animal studies high doses of olive oil have been shown to increase the development of gallstones by increasing the content of cholesterol in the gallbladder.42–44 Although this effect has not yet been observed in humans, common sense and the animal research suggest it is unwise to use an olive oil liver flush as a treatment for gallbladder disease.
Fish Oils
In animal studies, fish oil supplementation has been shown to reduce gallstone formation.45,46 In human studies, fish oil supplementation improves bile acid content and increases the solubility of cholesterol in the bile in obese women losing weight.12,47,48 As mentioned above, fish oils increase bile acid content of the bile and lower triglycerides; this effect makes them a very important recommendation in gallstone prevention and treatment.
Lipotropic Factors and Botanical Choleretics
The naturopathic approach to the treatment of gallstones has typically involved the use of lipotropic and choleretic formulas. Lipotropic factors are, by definition, substances that hasten the removal of fat from, or decrease the deposit of fat in, the liver through their interaction with fat metabolism. Compounds commonly employed as lipotropic agents include choline, methionine, betaine, folic acid, and vitamin B12.
Often these nutritional factors are used with herbal cholagogues and choleretics. Cholagogues stimulate gallbladder contraction to promote bile flow, while choleretics increase bile secretion by the liver.
Herbal choleretics that are appropriate to use in the treatment of gallstones include dandelion (Taraxacum officinale), milk thistle (Silybum marianum) and its active ingredient silymarin, artichoke (Cynara scolymus), turmeric (Curcuma longa) and its active ingredient curcumin, and boldo (Peumus boldo).
One study of rats given a diet that promoted gallstones demonstrated that the animals given supplemental curcumin for 10 weeks had only a 26% incidence of gallstone formation, compared with a 100% incidence in the group fed the stone-forming diet alone.49 This effect was found to be dose-dependent.
As described above, the formation of gallstones depends on either increased accumulation of cholesterol or reduced levels of bile acids or lecithin. So decreasing gallbladder cholesterol levels or increasing bile acid or lecithin levels should result in dissolution of the stone over time. Chemical dissolution is especially indicated in the treatment of gallstones in children, elderly patients who cannot withstand the stress of surgery, and other cases where surgery is contraindicated.50,51
Several successful nonsurgical alternatives for the treatment of gallstones now exist. For example, use of prescription bile acids such as ursodeoxycholic acid and tauroursodeoxycholic acid are effective in dissolving small, uncalcified cholesterol gallstones. About 15% of all patients with cholesterol gallstones would meet this criterion. Treatment with bile acids will lead to complete dissolution in about 90% of cases after six months of therapy. Once the stones have been dissolved, it is important to follow the recommendations given here for gallstone prevention in order to reduce the risk of recurrence. The typical daily dosage of prescription bile acids is 12 mg/kg.
In several studies, gallstone dissolution has also been accomplished with Rowachol, a proprietary combination of natural terpenes such as menthol, menthone, pinene, borneol, cineol, and camphene.52–56 Although terpenes are effective alone, the best results appear to be achieved when plant terpene complexes are used in combination with bile acid therapy.56–58 This combined approach offers better results than either bile acids or plant terpenes used alone.57,58 Furthermore, when plant terpenes are used, a lower dose of bile acids can be taken, significantly reducing the risk of complications or side effects and the cost of bile acid therapy. As menthol is the major component of this formula, peppermint oil, especially enteric-coated capsules, may offer similar results and is more readily available.
QUICK REVIEW
• Gallstones can be prevented through diet and lifestyle measures.
• Obesity, type 2 diabetes, insulin resistance, and elevated blood triglyceride levels are well-known risk factors for gallstones.
• Fasting or severe calorie restriction can lead to gallstone formation.
• Food allergies can lead to gallbladder symptoms. A 1968 study revealed that 100% of a group of patients were free from symptoms while they were on a basic elimination diet.
• Biliary cholesterol concentration and serum cholesterol levels do not seem to correlate.
• There is a link between high triglyceride levels and gallstone formation.
• Coffee can aggravate symptoms of gallstones by causing the gallbladder to contract, but it may also help prevent formation.
• A low lecithin concentration in the bile may be a causative factor for many individuals with gallstones.
• Diets high in refined carbohydrates and sugar have been associated with increased cholesterol concentration in the bile and an increased risk for both gallstones and gallbladder cancer.
• Vitamin C supplementation (2,000 mg per day) has been shown to produce positive effects on bile composition and reduces cholesterol stone formation.
• Milk thistle extract and other herbal choleretics may help dissolve gallstones through their ability to increase the solubility of the bile.
• Bile acids such as ursodeoxycholic acid and tauroursodeoxycholic acid are effective in dissolving small, uncalcified cholesterol gallstones in about 90% of cases after six months of therapy.
• A complex of plant terpenes alone or, preferably, in combination with oral bile acids can help dissolve gallstones.
As is typical of most diseases, gallstones are much easier to prevent than reverse. The risk factors and causes of gallstones are well known, and in most cases a healthful diet rich in dietary fiber, moderate in calories, and low in saturated fats is adequate prevention.
Once gallstones have developed, measures to avoid gallbladder attacks and increase the solubility of the bile are necessary. To limit the incidence of symptoms, avoid allergenic foods (see the chapter “Food Allergy”) and fatty foods.
Follow the general guidelines given in the chapter “A Health-Promoting Diet.” Definitely increase the intake of vegetables, fruits, dietary fiber (especially soluble fiber, found in, for example, flaxseed, oat bran, guar gum, and pectin), and buckwheat. Reduce the consumption of saturated fats, refined carbohydrates, cholesterol, sugar, and animal proteins. Avoid fried foods.
An allergy elimination diet can be used to reduce gallbladder attacks (see the chapter “Food Allergy”).
Drink six to eight glasses of water each day to maintain the water content of the bile.
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”
• Key individual nutrients:
Vitamin C: 500 to 1,000 mg three times per day
Vitamin E (mixed tocopherols): 100 to 200 IU per day
Vitamin D3: 2,000 to 4,000 IU per day (ideally, measure blood levels and adjust dosage accordingly)
Fish oils: 1,000 mg EPA + DHA per day
• Take one of the following:
Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Some other flavonoid-rich extract with a similar flavonoid content, super greens formula, or another plant-based antioxidant that can provide an oxygen radical absorption capacity (ORAC) of 3,000 to 6,000 units or higher per day
• One of the following:
Lipotropic formula providing 1,000 mg betaine, 1,000 mg choline, and 1,000 mg cysteine or methionine
SAM-e: 200 to 400 mg per day
• Phosphatidylcholine: 500 mg per day
• Fiber supplement (guar gum, pectin, psyllium, or PGX): 2.5 to 5 g per day
• One or more of the following:
Dandelion (Taraxacum officinale):
– Dried root: 4 g three times per day
– Fluid extract (1:1): 4 to 8 ml three times per day
– Solid extract (4:1): 250 to 500 mg three times per day
Pneumus boldo:
– Dried leaves (or by infusion): 250 to 500 mg three times per day
– Tincture (1:10): 2 to 4 ml three times per day
– Fluid extract (1:1): 0.5 to 1 ml three times per day
Milk thistle (Silybum marianum): sufficient dosage to yield 70 to 210 mg silymarin, three times per day
Artichoke (Cynara scolymus) extract (15% cynarin): 500 mg three times per day
Curcumin: 200 to 400 mg three times per day
One of the following:
– Rowachol (proprietary gallstone-dissolving formula): 1 capsule three times per day with meals
– Peppermint oil: 1 to 2 enteric-coated capsules (0.2 ml per capsule) three times per day between meals