Gallstones

Diagnostic summary:

Asymptomatic or biliary colic with irregular pain-free intervals of days or months; real-time ultrasonography provides definitive diagnosis.

General considerations

‘Western diet’ – induced disease; 20% of women and 8% of men over the age 40; 20.  In the US 20 million have gallstones; each year 1 million more develop gallstones; > 300,000 cholecystectomies annually due to gallstones; bile components  =  bile salts, bilirubin, cholesterol, phospholipids, fatty acids, water, electrolytes, other organic and inorganic substances; gallstones arise when solubilized bile components become supersaturated and precipitate.

• Four categories:

• (1) pure cholesterol,
• (2) pure pigment (calcium bilirubinate),
• (3) mixed – containing cholesterol and derivatives plus bile salts, pigments, inorganic calcium salts,
• (4) stones composed entirely of minerals.

Pure stones (cholesterol or calcium bilirubinate) are rare, where 80% are mixed and 20% exclusively minerals (calcium salts, oxides of silicon and aluminium).

Pathogenesis

Three steps:

• (1) bile supersaturation,
• (2) nucleation and initiation of stone formation,
• (3) enlargement of gallstone by accretion.

Cholesterol and mixed stones: requisite step is cholesterol supersaturation of bile within gall bladder; bile solubility and supersaturation based on relative molar concentrations of cholesterol, bile acids, phosphatidylcholine (lecithin), and water; free cholesterol is water-insoluble – must be in lecithin-bile salt micelle; increased cholesterol secretion or decreased bile acid or lecithin secretion induces supersaturation; stone formation initiated by biliary stasis, infection or mucin; radius increases at 2.6 mm/year, eventually reaching size of a few millimetres to over a centimetre; symptomatic 8 years after formation begins; cholelithiasis in 95% of patients with cholecystitis.

Risk factors for cholesterol and mixed stones: diet, sex, race, obesity, high caloric intake, oestrogens, Gastrointestinal diseases (Crohn’s disease, cystic fibrosis), drugs, age.

• Sex: frequency two to four times greater in women than in men; women predisposed – either increased cholesterol synthesis or suppression of bile acids by oestrogens; pregnancy, oral contraceptives or other causes of elevated oestrogen increase incidence.

• Genetic and ethnic: most common in Native American women over age 30; only 10% of black women over 30; differences reflect extent of cholesterol saturation of bile; dietary factors outweigh genetic factors.

• Obesity: causes increased secretion of cholesterol in bile from increased cholesterol synthesis; obesity linked to much increased incidence – biliary cholesterol saturation; during active weight reduction, biliary cholesterol saturation initially increases; secretion of biliary lipids is reduced during weight loss, but secretion of bile acids decreases more than cholesterol; when weight is stabilised, bile acid output returns to normal and cholesterol output remains low; net effect is a significant reduction in cholesterol saturation.

• Gastrointestinal tract diseases: malabsorption of bile acids from terminal ileum disturbs enterohepatic circulation – reducing bile acid pool and rate of bile secretion  (Crohn’s disease and cystic fibrosis).

• Drugs: oral contraceptives, other oestrogens, clofibrate and possibly other lipid-lowering drugs.

• Age: average patient 40-50 years old; incidence increases with age.

Risk factors for pigmented gallstones: not related to diet as much as geography, sun exposure and severe diseases; more common in Asia – higher incidence of liver and gall bladder parasites – liver fluke Clonorchis sinensis; bacteria and protozoa cause stasis or act as nucleating agents; in US, pigmented stones are caused by chronic hemolysis or alcohol liver cirrhosis.

Therapeutic considerations

Easier to prevent than reverse; primary treatment is to reduce controllable risk factors; therapeutic intervention – avoid aggravating foods and increase solubility of cholesterol in bile; if symptoms persist or worsen, cholecystectomy is indicated; eliminate foods producing symptoms; increase dietary fiber; eliminate food allergens; reduce animal protein; use nutritional lipotropic compounds and herbal choleretics to increase solubility of bile; biliary cholesterol concentration and serum cholesterol do not correlate, but increased serum triglycerides are linked to bile saturation.

Asymptomatic gallstones: natural history of silent/asymptomatic gallstones suggests elective cholecystectomy is not warranted; cumulative chance for developing symptoms – 10% at 5 years, 15% at 10 years, and 18% at 15 years; if controllable risk factors eliminated or reduced, patient remains asymptomatic.

Diet

• Dietary fiber: diet high in refined carbohydrates and fat, low in fiber reduces liver synthesis of bile acids and lowers bile acids in gall bladder; fiber reduces absorption of deoxycholic acid, produced from bile acids by gut bacteria, which lessons solubility of cholesterol in bile; fiber decreases formation of deoxycholic acid and binds deoxycholic acid for faecal excretion; prefer water-soluble fibers; vegetables, fruits, pectin, oat bran, and guar gum; diets rich in legumes with water-soluble fiber (Native Americans) are linked to risk for gallstones; legumes increase biliary cholesterol saturation due to saponin content – restrict legume intake with gallstones.

• Vegetarian diet: protective against gallstones – fiber content of vegetarian diet; animal proteins (casein from dairy) increase formation of gallstones in animals; vegetable proteins (soy) are preventive against gallstones.

• Food allergies: food allergies may cause gall bladder pain; foods inducing symptoms, in decreasing order of occurrence are: egg, pork, onion, fowl, milk, coffee, citrus, corn, beans, nuts; ingestion of allergy-causing substances may cause swelling of bile ducts, resulting in impairment of bile flow from gall bladder.

• Sugar: increased risk of biliary tract cancer; increased cholesterol saturation of bile and gallstones linked to sugar intake – monosaccharides or disaccharides, independent of other energy sources.

• Caloric restriction: total calorie and carbohydrate intake and serum triglycerides are higher in gallstone patients than in controls; refined carbohydrate intake is higher in female gallstone patients; fat intake is higher in male gallstone patients; caloric restriction must be instituted carefully – rapid weight loss and fasting increase risk of gallstones.

• Coffee: avoid coffee until stones are resolved; coffee (regular and decaf) induces gall bladder contractions.

Nutritional factors

• Lecithin (phosphatidylcholine): low lecithin in bile may be a causative factor; a pure bile salt micelle requires 50 molecules to enclose a single molecule of cholesterol; a mixed bile salt/phospholipids micelle requires only seven molecules; taking lecithin increases lecithin in bile and larger doses provide greater increases; increased lecithin content of bile usually increases solubility of cholesterol; no significant effects on gallstone dissolution obtained using lecithin alone.

• Nutrient deficiencies: deficiencies of either vitamins E or C cause gallstones in animal studies.

• Olive oil: olive oil liver flush is undesirable for patients with gallstones; consuming large quantities of any oil will induce contraction of gall bladder, increasing risk of stone blocking bile duct = surgical emergency; oleic acid increase development of gallstones in lab animals by increasing cholesterol in gall bladder.

• Fish oils: in animal studies, fish oil reduces cholesterol concentration in gall bladder and rate of gallstone formation; omega-3 eicosapentaenoic and docosahexanoic acids inhibit gallstone formation and decrease biliary calcium and total protein; omega-3 fatty acids enhances stability of biliary phospholipid-cholesterol vesicles.

• Lipotrophic factors and botanical choleretics: lipotropic factors are substances hastening removal or decrease deposit of fat in liver by interaction with fat metabolism; lipotropic agents: choline, methionine, betaine, folic acid, and vitamin B12 – used with herbal cholagogues and choleretics; cholagogues stimulate gall bladder, while choleretics increase bile secretion by liver; herbal choleretics have favourable effect on solubility of bile; choleretics appropriate to gallstones are Taraxacum officinale, silymarin from Silybum marianum, Cynara scolymus, Curcuma longa, and Peumus boldo.

Chemical dissolution of gallstones

Use complex of plant terpenes alone or, preferably, in combination with oral bile acids; decreasing gall bladder cholesterol and/or increasing bile acids or lecithin should result in dissolution of stone; chemical dissolution is especially indicated for gallstones in the elderly who cannot withstand stress of surgery and in others for whom surgery is contraindicated.

• Bile acids: increase cholesterol solubility; oral chenodeoxycholic acid alone has completely dissolved gallstones in 13.5% and partially dissolved in 27% of patients in one study, but often takes several years with mild diarrhoea and possible liver damage; ursodeoxycholic acid is more effective with fewer side-effects.

• Terpenes: natural terpene combination (menthol, menthone, pinene, borneol, cineol, camphene) is effective alternative to surgery; safe even when consumed up to 4 years.

• Combined therapy: terpenes are effective alone, but best results come from combining plant terpenes and bile acid; lower dose of bile acid needed reduces risk of side-effects and cost of bile acid therapy; menthol is major component of formula – peppermint oil, especially enteric-coated, may offer similar results.

Lifestyle

Sunbathing: almost all cholesterol gallstones contain central, pigmented nucleus with radial or lamellar pigmented bands, alternating with layers of crystalline cholesterol; activation of pigmentary system by UV light may increase concentrations of indole metabolites in bile, triggering their polymerization; positive attitude towards sunbathing is linked to twice the risk of cholelithiasis compared with those with negative attitude; association almost entirely restricted to those who always burn after long sunbathing.

Therapeutic approach

Healthy diet rich in dietary fibers gives adequate prevention; after development of stones, require measures to avoid gall bladder attacks and increase bile solubility; limit incidence of symptoms – intolerant/allergic foods and fatty foods must be avoided; increase solubility of bile – follow dietary guidelines plus nutritional and herbal supplements below.

• Diet: increase vegetables, fruits and dietary fiber, especially gelforming/mucilaginous fibers (flaxseed, oat bran, guar gum, pectin); reduce saturated fats, cholesterol, sugar, animal proteins; avoid all fried foods, allergy elimination diet reduces gall bladder attacks.

• Water: six to eight glasses water x 4 daily to optimize water content of bile.

• Nutritional supplements:

• - vitamin C
• - vitamin E
• - phosphatidylcholine
• - choline
• - L-methionine
• - Fiber supplement (guar gum, pectin, psyllium, or oat bran)

• Botanical medicines

• - Taraxacum officinale
• - Peumus boldo
• - Silybum marianum
• - Cynara scolymus
• - Curcuma longa

For more information on this topic please call ICIM Medics on +353 45 844 819 or email us at info@icim.ie

Tags: Renal, Stomach pains