Alternative Medicine Review Voiume 14, Number 3 2009

Review A

Nutritional Approaches toPrevention and Treatment of

GallstonesAlan R* Gaby, MD

Abstract

Cholesterol gaiistones are among the most common

gastrointestinai disorders in Western societies, individuáis witii

gaiistones may experience various gastrointestinai symptoms

and are aiso at risk of developing acute or chronic ciiolecystitis.

Ciioiecystectomy is the most frequentiy recommended

conventional treatment for symptomatic gaiistones. Biie acids

(ursodeoxychoiic acid or chenodeoxychoiic acid) are aiso used

in some cases to dissoive radiolucent stones, but these drugs

can cause gastrointestinai side effects and there is a high rate of

stone recurrence after treatment is discontinued. Lithotripsy is

used in some cases in conjunction with ursodeoxychoiic acid for

patients who have a singie symptomatic non-calcified gailstone.

There is evidence that dietary factors influence the risk of

developing choiesterol gaiistones. Dietary factors that may

increase risk include choiesteroi, saturated fat, trans fatty acids,

refined sugar, and possibiy iegumes. Obesity is aiso a risk factor

for gaiistones. Dietary factors that may prevent the deveiopment

of gaiistones inciude poiyunsaturated fat, monounsaturated

fat, fiber, and caffeine. Consuming a vegetarian diet is also

associated with decreased risk, in addition, identification and

avoidance of aiiergenic foods frequently reiieves symptoms of

gaiibiadder disease, although it does not dissolve gallstones.

Nutritionai suppiements that might help prevent gaiistones

inciude vitamin C, soy lecithin, and iron. In addition, a mixture

of plant terpenes (Rowachol®) has been used with some

success to dissolve radiolucent gallstones. The "gallbladder

flush" is a folk remedy said to promote the passage of

gallstones. While minimal scientific evidence supports

the efficacy of this treatment, anecdotal reports suggest

the gallbladder flush may be bénéficiai for some people.

(Altern Med Rev 2009;14(3):258-267)

IntroductionGallstones arc among the most common gas-

rrointestinal disorders in Western populations. Ap-proximately 80 percent of gallstones contain cholesterol(as cholesterol monohydrate crystals). The remaining20 percent are pigment stones, which consist mainly otcalcium hiliruhinate and will not be discussed in this ar-ticle. Cholesterol-containing gallstones are divided intotwo subtypes: cholesterol stones (which contain 90- to100-percent cholesterol) and mixed stones (which con-tain 50- to 90-percent cholesterol). Each subtype mayalso contain varying amounts of calcium salts, bile acids,and other components of bile.

Cholelithiasis (gallstone formation) resultsfrom a combination of several factors, including super-saturation of bile with cholesterol, accelerated nucle-ation of cholesterol monohydrate in bile, and bile stasisor delayed gallbladder emptying due to impaired gall-bladder motility. Cholesterol supersaturation can resultfrom an excessive concentration of cholesterol in bile, adeficiency of substances that keep cholesterol in solu-tion (i.e., bile salts and phospholipids), or a combinationof these factors. Accelerated nucleation of cholesterol is

Alan R. Gaby. MD - Private pracllce 17 ^ars, specializing in nutritional medicine;past-president, American Holistic Medical Association: contributing editor,Alternative Medicine Review; author. Preventing and Reversing Osteoporosis(Prima, 1994) and The Doctoi's Guide to Vitamin 86 (Rodale Press. 1984);co-author, í?ie Patient's Book of Natural Healing (Prima, 1999); publishednumerous scientific papéis in the fieiil of nutritional medicine; contributingmedical editor. The Townsend Letter tor Doctors and Patients since 1985-Correspondence address: 12 Spaulding Street, Concord. NH 03301

Page 258

Alternative Medicine Review Voiume 14. Number 3 2009

a phenomenon not well understood. Gallbladder hypo-motility may occur during pregnancy, with the use oforal contraceptives, after surgery or burns, and in pa-tients with diabetes. However, in many cases, the causeis not clear.

While most gallstones are asymptomatic, somepatients experience biliary colic, which is characterizedby sudden and severe right-upper-quadrant pain (of-ten accompanied by nausea and vomiting), occurringpostprandially and lasting one to tour hours. Acute orchronic cholecystitis may also occur in association withgallstones. Complications of cholecystitis may includeinfection, perforation, and gangrene.

The most widely used conventional treatmentfor symptomatic gallstones is cholecystectomy. Mostpatients experience a resolution of symptoms after cho-Iecystectomy, but about 10-15 percent of patients sufferfrom postcholecystectomy syndrome, which is charac-terized either by a continuation of symptoms that hadbeen attributed to gallbladder disease or the develop-ment oí new gastrointestinal symptoms. Another con-ventional treatment is oral administration of a naturallyoccurring bile acid (ursodeoxycholic acid or chenode-oxycholic acid), that may promote gradual dissolutionot radiolucent gall-stones ovet a period of six months totwo years. However, these treatments can cause vari-ous gastrointestinal symptoms and other side effects.In addition, recurrences are seen in up to 50 percent ofpatients after treatment is discontinued. It is generallyagreed that patients with asymptomatic gallstones donot require treatment with drugs or surgery.

Dietary FactorsObesity and Weight Loss

Obesity is associated with an increased riskof gallstones.' Weight loss may reduce the risk of gall-stone formation in overweight individuals, but exces-sively rapid weight loss (i.e., more than three poundsper week) may promote the development of gallstonesor increase the risk that silent gallstones will becomesymptomatic. The increased risk associated with rapidweight loss may be due to an increase in the ratio of cho-lesterol to bile salts in the gallbladder and to bile stasisresulting from a decrease in gallbladder contractions.'

Food AllergyOne practitioner stated as early as 1941 that

food allergy is a common cause of gallbladder disease,and that failure to recognize food allergy has resulted inmany unnecessary cholecystectomies.'

Tliat the gallbladder can be a target organ forallergic reactions has been demonstrated in experimen-tal animals. In one study an allergic reaction was in-duced in the gallbladder of a Rhesus monkey by admin-istering an intravenous injection of cottonseed proteinafter passively sensitizing the gallbladder. The reactionwas characterized by edema, hyperemia, increased mu-cus secretion, and eosinophilic infiltration.*' A similarreaction was seen in the gallbladder of rabbits sensitizedto sheep serum and then inoculated with sheep seruminto the gallbladder cavity. These reactions were called"allergic cholecystitis" by the researchers who performedthe two studies.

In addition to potentially evoking an inflamma-tory response, food allergy or intolerance might causedelayed gallbladder emptying, an abnormality knownto play a role in the pathogenesis of cholelithiasis. Tliispossibility is suggested by a study of patients with ce-liac disease. Six healthy volunteers, six patients withuntreated celiac disease, and six patients with celiac dis-ease controlled on a gluten-free diet, drank a liquid fattymeal after an overnight fast. The mean time until thegallbladder emptied by 50 percent was approximately20 minutes in the healthy individuals and patients withdiet-con trolled celiac disease, as compared with 154minutes in the patients with untreated celiac disease(p<0.02).'' These results indicate that patients with ce-hac disease have a gallbladder emptying defect that canbe reversed by consumption of a gluten-free diet.

In an uncontrolled trial, identification andavoidance of ailergenic foods eliminated gallbladdersymptoms in 100 percent of 69 patients with gallstonesor postcholecystectomy syndrome. Sixty-nine patients(ages 31-97 years) with gallstones or postcholecystec-tomy syndrome were placed on an eHmination diet con-sisting of beef, rye, soy, rice, cherry, peach, apricot, beet,and spinach; fat intake was not restricted. After oneweek on the diet the patients were challenged with indi-vidual foods. If a food evoked typicar'gallbladder symp-toms,' that food was discontinued and not retested forseveral weeks. All components of each person's diet were

Page 259

Alternative Medicine Review Volume 14, Number 3 2009

tested, and each symptom-evoking food was retestedseveral times. All 69 patients were symptom-free withinone week of starting the elimination diet, with improve-ments usually occurring in 3-5 days. Egg, pork, and on-ion were the most frequent offending foods, with reac-tions occurring in 93-, 64-, and 52-percent of patients,respectively. Table 1 lists the most common offendingfoods and percentage or patients reacting. Between oneand nine foods were eventually eliminated from eachpersons diet (average 4.4).'

Although long-term follow-up informationwas not provided for these patients, this study suggeststood allergy is an important factor in the developmentof gallbladder-related symptoms. Tlie author of this re-port pointed out that, since each patient had differentfood allergies, the standard dietary recommendation toavoid fatty, greasy, and rich foods may not always pro-duce satisfactory results in patients with gallbladderdisease.

Dietary Cholesterol and FatIn a rhree-week randomized trial, increasing

intake of cholesterol (over a range of 500-1,000 mg perday) resulted in increasing biliary cholesterol saturationin both healthy volunteers and patients with asymp-tomatic gallstones.^ This rise in biliary cholesterol satu-ration would presumably increase the risk of gallstoneformation.

In observational studies, higher intake of satu-rated fat or trans fatty acids was associated with an in-creased incidence of gallstones.^'" In contrast, higherintake of polyunsaturated or monounsaturated fatty ac-ids was associated with ciecreased risk.'' The apparentprotective effect of polyunsaturated tatty acids is con-sistent with experimental observations, in which ham-sters fed an essential fatty acid-deficient diet had a highincidence of cholesterol gallstones and lithogenic bile(diets low in essential fatty acids are, in general, also lowin polyunsaturated fatty acids).'*'''' In addition, in pa-tients with gallstones, supplementation with 11.3 g perday of fish oil (which is high in polyunsaturated fattyacids) decreased the cholesterol saturation of bile by 25percent.'^ While both omega-3 and -6 polyunsaturatedfatty acids may be protective, tiirther research is neededto determine the optimal amounts and ratios of thesefatty acids.

Table 1. Foods Evoking Symptoms ofGallbladder Disease

Offending Food

Eggs

Pork

Onions

Fowl

Milk

Coffee

Oranges

Corn

Beans

Nuts

Apples

Tomatoes

Percent ofPatients Reacting

93%

64%

52%

35%

25%

22%

19%

15%

15%

15%

6%

6%

Refined SugarObservational studies in humans have found

that higher intake of refined sugars such as sucrose andfructose is associated with a higher frequency of gall-

While the association between refined sugarstones.intake and gallstones could be due in part to the factthat consuming large amounts of sugar can lead to obe-sity, there is evidence that refined sugars are themselveslithogenic. In rabbits fed a lithogenic diet containing34-percent sucrose, replacing sucrose with starch pro-tected against the development of gallstones.^" In anoth-er study in rabbits, replacing dietary sucrose with starchdecreased rhe total weight of gallstones by 48 percent infemales and 20 percent in males, although these differ-ences were nor statistically significanr.-' In patients withgallstones randomly assigned to consume a diet high orlow in refined carbohydrates (providing a mean of 106 gper day versus 6 g per day of refined sugar), the choles-terol saturation of bile was significantly greater on thediet high in refined carbohydrates (p<0.005)."" How-ever, another study was unable to confirm those find-ings.'' Although it has not been proven that consuming

Page 260

Alternative Medicine Review Volume 14, Number 3 2009

gallstones

refined sugar promotes gallstone formation, it would beprudent for people at risk of developing gallstones toavoid excessive intake oí refined sugar.

Vegetarian DietIn a cross-sectional study, rhe prevalence of

gallbladder disease (asympromatic gallstones or historyof cholecystectomy) was significantly lower in femalevcgcrariiuis than female omnivores (12% versus 25%;p<Ü.()l).''' In addition, a 20-year prospective study of80,898 women found that increased consumption ofvegetable protein was associated with a decreased riskof having a cholecystectomy.^^ A separate evaluation ofthe same cohort ot women found that increasing con-sumption of fruits and vegetables was associated witha decreased incidence of gallstones. Similar results wereseen for both total fruits and total vegetables examinedseparately."" In hamsters fed a lithogenic diet the inci-dence of gallstones was decreased in a dose-^dependentmanner by progressively replacing casein (a milk pro-tein) with soy protein in the diet."^"'* These observa-tions suggest that consumption of a vegetarian diet, andparticularly vegetable protein, may decrease the risk ofdeveloping gallstones.

Dietary FiberIn observational studies, higher intake of fiber

was associated with a lower prevalence of gallstones.^*^"In addition, supplementation oí the diet with 10-50 gper day or more of wheat bran for 4-6 weeks decreasedthe cholesterol saturation of bile in healthy volunteers,individuals with constipation, and patients with gall-stones." *' Bran is thought to work primarily in thecolon, decreasing the formation of deoxycholic acidby intestinal bacteria and increasing the synthesis ofchenodeoxycholic acid.*"* Deoxycholic acid appears toincrease the lithogenicity of bile, whereas chenodeoxy-cholic acid decreases lithogenicity and has been usedtherapeutically to promote dissolution of gallstones.Based on these observational and biochemical studiesit would be reasonable to recommend a high-fiber dietas part of a comprehensive nutritional program for pre-venting gallstones.

CaffeineIn dogs, admini.stration of caffeine in drinking

water at a concentration of 1 ing/mL prevented the de-velopment of gallstones induced by feeding a high-cho-lesterol diet. The protective effect of caffeine appearedto be due in part to stimulation of bile flow.'''

Two large, prospective cohort studies foundconsumption of caffeinated coffee may protect againstthe development of symptomatic gallstones. Comparedwith non-coffee drinkers, the reduction in risk associ-ated with consumption of two or more cups of coffeeper day was 40-45 percent in men *" and 22-28 percentin women.'^ Consumption of decaffeinated coffee wasnot associated with lower gallbladder disease risk, sug-gesting the beneficial effect of coffee is due to cafieinc. Alarge cross-sectional study found little or no protectiveeffect of coffee consumption;"* however, cross-sectionalstudies tend to be less reliable than prospective cohortstudies.

Other Dietary FactorsIn a prospective study of 80,718 women par-

ticipating in the Nurses' Health Study, increased con-sumption of peanuts and other nuts was each associ-ated with a lower risk of cholecystectomy. Women whoconsumed five or more ounces of nuts per week had a25-percent lower risk of having a cbolecystectomy, com-pared with women who rarely or never ate nuts.'^

Circumstantial evidence suggests consump-tion of large amounts of legumes may increase the inci-dence of gallbladder disease. In a study of healthy youngmen, consumption of a diet containing 120 g per dayof legumes tor 30-35 days increased biliaiy cholesterolsaturation, compared with a control diet. Tliis effect wasdue to a combination of an increase in the concentra-tion of cholesterol and a decrease in the concentrationof phospholipids in the bile."' In addition, Chileansand American Indians, who have some of the highestprevalence rates of cholesterol gallstones in the world,both consume legumes as dietary staples.'"' However, acase-control study conducted in the Netherlands foundan inverse association between legume intake and gall-stone risk. Tliis association did not appear to be due toa decrease in legume consumption as a result of gastro-intestinal intolerance to this food group." Thus, the re-lationship between legume consumption and gallstonerisk remains uncertain. Tíie possibihty that legume

Page 261

Alternative Medicine Review Volume 14, Number 3 2009

consumption promotes the development of gallstonesshould be weighed against the known beneficial effectsof legumes, which include improvements in blood glu-cose regulation and a reduction in serum cholesterollevels.

In healthy volunteers who rarely consumed al-cohol, consumption of 39 g per day of alcohol (equiva-lent to 3-4 drinks daily) for six weeks decreased cho-lesterol saturation of hile.'^ If the same effect could beachieved with smaller amounts of alcohol, then moder-ate alcohol consumption might decrease the risk of de-veloping gallstones.

In mice fed a lithogenic diet containing 0.5-per-cent cholesterol, feeding of garlic or onion reduced theincidence of gallstones and decreased the Uthogenicityof the bile."" It is not known whether these findings arerelevant to gallstones in hutnans.

Nutritional SupplementsVitamin C

Several animal studies indicate vitamin C mayhelp prevent gallstones, Guinea pigs developed gall-stones when fed a diet high in cholesterol and low invitamin C, but not when fed the same diet with an ad-equate amount of vitamin C'"'*'' Vitamin C is a cofactorfor the enzyme 7a-hydroxylase, the rate-limiting stepin the conversion of cholesterol to bile acids (Figure 1).Thus, vitamin C appeared to prevent gallstone forma-tion by promoting the conversion of cholesterol to bilesalts, thereby decreasing the lithogenicity of bile. ^ '**'Vitamin C supplementation also inhibited cholelithia-sis and accelerated rhe conversion of cholesterol to bilesalts in hamsters.''^

In a cross-sectional study of 7,042 women par-ticipating in the Third National Health and NutritionExamination Survey, 1988-1994, a significant inverseassociation was found between serum vitamin C lev-els and prevalence of gallbladder disease. No such as-sociation was found in men participating in the samesurvey.^" In a study of patients with gallstones, dailysupplementation with 2 g vitamin C for two weeks de-creased the lithogenicity of bile. Sixteen patients withgallstones scheduled for cholecystectomy received 500mg vitamin C four times daily for two weeks prior tosurgery; another 16 patients scheduled for cholecystec-tomy did not receive vitamin C (control group). Dur-ing surgery, bile was taken from the gallbladder of each

patient. Compared with control patients, vitamin C-treated patients had significantly higher concentrationsof phospholipids in bile. Tlie mean nucleation time ofbile (the time required for the formation of cholesterolcrystals, the first step in stone formation) was sevendays in the vitamin C group and two days in the controlgroup (p<0.01).''

These findings suggest increasing vitamin Cintake decreases the risk of developing gallstones. How-ever, additional research is needed to confirm that pos-sibility and determine the optimal dosage.

IronDogs fed an iron-deficient diet had a higher in-

cidence of cholesterol crystals in their bile than animalsfed a control diet (80% versus 20%; p<0.05). The activi-ty of hepatic 7a-hydroxylase (Figure 1), was nonsignifi-candy lower by 64 percent in iron-deficient dogs than incontrols (p=0.07)." Tliese findings raise the possibilitythat iron deficiency plays a role in the pathogenesis ofgallstone formation in humans.

LecithinPhospholipids increase the solubility of biliary

cholesterol. Some studies have found biliary pliospho-lipid concentrations are lower in patients with gallstonesthan in those without gallstones, whereas other studieshave found no difference in the phospholipid content oflithogenic and normal bile.''^ Supplementation with lec-ithin (which contains high concentrations of phospho-lipids) has the potential to decrease the lithogenicity ofbile by increasing biliary phospholipid concentrations.

In an uncontrolled trial, supplementation ofeight gallstone patients with a relatively low dose of leci-thin (100 mg three times daily) for 18-24 months wasassociated with a significant increase in biliary phos-pholipid content and a significant decrease in biliarycholesterol levels. In one patient, gallstones decreased insize and changed in shape, but no changes were seen inthe other patients."' In another study, daily administra-tion of 4.5 g soybean lecithin tor three weeks resulted ina nonsignificant eight-percent improvement in the cho-lesterol saturation index of bile. ^ It is not clear whetherthe changes observed in these studies are of clinicalvalue, and there is at present no strong evidence to sup-port the use of lecithin to prevent or treat gallbladderdisease.

Page 262

Alternative Medicine Review Volume 14, Number 3 2009

Figure 1, Conversion of Cholesterol to Bile Acids

(rate-limiting step)

NADPH + H+ NADP+

Vitamin C

Cholestérol

7u- hydroxylaseInhibited by:Vitamin C deficiencyBile acid

NADPH + H+02

2C0A-SH ^

7- Hydroxycholesterol

several steps

Propionyi-CoA

C-S-CoA

NADPH + H

2CoA-SH

Propionyl-CoA

C-S-CoA

Cholyl-CoA

taurtne or glycine

Chenodeoxychoiyl-CoA

Conjugation withtaurine or gl^ne

(taurineor glycineattached)

(taurmeor glycineattached)

Cholic acid Chenodeoxychoiic acid

Other Factors Associated withGallstonesHypoch lorhydria

Hypochlorhydria is common in parients withgallbladder disease,^" occurring in 52 percent of 50 pa-tients with gallstones in one study." While there is noevidence hypochlorhydria contributes to the pathogen-esis of gallstones, it may be responsible in part for some

of the nonspecific symptoms associated with chroniccholecystitis, such as belching, bloating, abdominal pain,and nausea. In hypochlorhydric patients, hydrochloricacid-replace ment therapy with meals may relieve thesesymptoms. ** Hydrochloric acid is usually administeredas betaine hydrochloride. Tlie dosage of betaine hydro-chloride recommended tor hypochlorhydric patientsvaries among diffèrent practitioners from 600 mg permeal to 3,000 mg or more per

Page 263

Alternative Medicine Review Volume 14, Number 3 2009

Rowachol^Rowachol* is a proprietary preparation that

contains six plant monoterpenes (Table 2). Each cap-sule contains 100 mg of the mixture. Rowachol hascholeretic properties (i.e., it stimulates bile productionby the liver) and inhibits the formation of cholesterolcrystals in bile.' '"''' In clinical trials, treatment withRowachol for six months resulted in complete or partialgallstone dissolution in 29 percent of 27 patients withradiolucent gallstones. In addition, Rowachol enhancedthe efficacy of chenodeoxycholic acid in dissolving gall-stones, allowing for the use of lower (and better toler-ated) doses of chenodeoxycholic acid. Rowachol couldpresumably also be used to enhance the efficacy of urso-deoxycholic acid.

Table 2, Monoterpenc Content ofRowachol

Constituent

IVIenthol

Menthone

Pinene

Borneoi

Camphene

Cineol

Base of Olive Oii

Percent ofTotal Content

32%

6%

17%

5%

5%

2%

33%

Twenty-four patients with radiolucent gall-stones received one capsule of Rowachol per 10 kg bodyweight per day, in most cases for six months. Sevenpatients (29%) showed radiological and/or surgicalevidence of partial (n-4) or complete (n-3) gallstonedissolution. No side effects were seen and there was nolaboratory evidence of hepatotoxicity or hematologicalabnormalities."

Tliirty patients with radiolucent gallstones anda functioning gallbladder were treated for up to twoyears with a combination of Rowachol ( 1 capsule twicedaily) and chenodeoxycholic acid (7-10.5 mg per kgbody weight per day). The dosage of chenodeoxycholic

acid was slightly lower than the usual 750 mg per dayin order to minimize side effects and cost. The treat-ment was well tolerated; only one patient reported diar-rhea. Stones disappeared in 11 patients (37%) withinone year and in 15 patients (50%) within two years.In comparison, in the National Cooperative GallstoneStudy, in which chenodeoxycholic acid was given aloneat a dose of 750 mg per day, complete dissolution wasseen in only 13.5 percent of patients after two years.The authors of this report concluded that a combina-tion of medium-dose chenodeoxycholic acid and Rowa-chol is economical, effective, and likely to have feweradverse effects than higher doses of chenodeoxycholicacid alone.'''

Twenty-two patients with radiolucent gall-stones and a ftanctioning gallbladder received two orthree capsules per day of Rowachol plus chenodeoxy-cholic acid (375 mg at bedtime, equivalent to a meanof 38% of the recommended dose) for 12 months. Thecombination was well tolerated; only one patient dis-continued treatment because of gastrointestinal side ef-fects. Tliirteen patients (59%) had complete (n=6) orpartial (n=7) dissolution of stones.'*^

Rowachol at a dosage of three capsules per day,alone or in combination with chenodeoxycholic acidor ursodeoxycholic acid, was also used with some suc-cess by one group of investigators to dissolve radiolu-cent stones in the common bile duct. However, duringthe treatment, eight of 31 patients required emergencyhospitalization for biliary colic, obstructive jaundice,pancreatitis, or cholangitis. These complications weresuccessfully managed and all but one patient continuedwith the treatment. Tlie investigators concluded thatdissolution therapy may be considered in patients withradiolucent common bile duct stones when endoscopiesphincterotomy or surgery is not feasible. However,careftil attention to potential complications is requiredwhile stones persist.''^*''

Rowachol has been on the market for morethan 50 years and has not been reported to cause anyserious side effects. "* The usual dosage is 2-3 capsulesdaily. Larger doses are not recommended as they mayincrease biliary cholesterol saturation.*"

Page 264

Alternative Medicine Review Volume 14, Number 3 2009

gallstones

Gallbladder FlushA gallbladder flush (also called a liver flush)

is a folk remedy that is said to promote the p;issage ofgallstones.^-'^ Several different versions are used. Onemethod is to fast for 12 hours and then, beginning at7 p.m., ingest four tablespoons of olive oil followed byone tablespoon of lemon juice every 15 minutes for atotal of eight treatmenr cycles. Another method is toconsume only apple juice and vegetable juice (no food)during the day until 5-6 p.m., and then ingest 18 mL ofolive oil followed by 9 mL of fresh lemon juice every 15minutes until eight ounces of oil have been consumed.Some practitioners use Gi.-itiini sagn^da and garlic/cas-tile enemas in combination with the olive oil and lemonjuice treatment. According to published and anecdotalreports, patients often experience diarrhea and abdomi-nal pain from this treatment, and by the next morningthey typically pass multiple soft green or brown spher-oids that have been presumed to be gallstones.

However, in most cases these spheroids werenot subjectecl to chemical analysis and the patients didnot undergo follow-up evaluations to document they nolonger had gallstones. Analysis of one group of passed"gallstones" revealed they consisted of 75-percent fattyacids and contained no cholesterol, bilirubin, or calci-um. Further experimentation suggested the spheroidswere "soap stones" created by the interaction of diges-tive enzymes with certain components of olive oil andlemon juice." Analysis of another spheroid passed aftera gallbladder flush revealed it was not a gallstone.'''

One case report did document ultrasono-graphic evidence of a reduction in the number of gall-stones following the ingestion of olive oil and lemonjuice,^* and there are several other anecdotal reports ofgallstones resolving on follow-up ultra.sound evaluationafter a gallbladder flush.' ^ If this treatment can promotethe passage of gallstones, then it might also cause stonesto become trapped in the common bile duct, potentiallyleading to a medical emergency. However, to this au-thors knowledge, such an adverse efîect has not beenreported.

ConclusionThe evidence reviewed in this article suggests

chat the risk of developing gallstones can be reduced bymaintaining an ideal body weight and by consuming adiet similar to diets recommended for preventing other

common diseases, such as heart disease, diabetes, andhypertension. Certain nutritional supplements may alsohelp prevent gallstones, but the evidence supportingthat possibility is not strong. Based on the available evi-dence, it would be reasonable to recommend 500-2,000mg per day of supplemental vitamin C for patients atrisk of developing gallstones, in order to reduce thelithogenicity of their bile. Iron status should also be as-sessed, and deficiencies should be treated appropriately.In patients with symptomatic gallstones, identificationand avoidance of allergenic foods appears to be a viablealternative to cholecystectomy. In most cases, food aller-gies can be identified by an elimination diet followed byindividual food challenges. A mixture of plant terpenesmay also be useful for dissolving radiolucent gallstones,particularly when used in combination with a bile acid.

References1. Must A, Spadano J, Coakley EH, er al. The disease

burden associated with overweight and obesity.JAMA 1999:282:1523-1529.

2. Anonymous. Dieting and gallstones. NacionalInstimte of Diabetes and Digestive and KidneyDiseases (NIDDK). htrp://www.win.niddk.nih.gov/publications/gallstones.htni. [Accessed June 5,2009]

3. Black JH. Allergic reactions in the gastrointestinaltract. Rev Gastroenterol 1941:8:17-22.

4. Walser M, Gray I, Harten M, et al. The allergicre.icrion in the gallbladder. Experimental studies inthe rhesus monkey. Gaitrocnterology 1943; 1:565-572.

5. De Muro P, Ficari A. Experimental studies on allergiccholecystitis. Gastroenterology 1946;6;302-314.

6. Maron PN, Seiden AC, Fitzpatrick ML,Chadwick VS. Defective gallbladder emptying andcholecystokinin release in celiac disease. Reversal bygluten-frcc diet. GoifrocHipro/o^)' 1985;88:391-396.

7. Brenenian JC. Allergy elimination diet as the mostefiective gallbladder diet, ^tiii Allergy 1968:26:83-87.

8. Lee DW, Gilmore CJ, Bonorris G, cr al. Elffct ofdietary cholesterol on biliary lipids in patients withi^allstones and normal subjects. Arti / Clin Nutr1985:42:414-420.

9. Misciagna G, Centonzc S, Leoci C, et al. Diet,physical acriviry, and gallstones - a population-based,case-control study in southern Italy. AmJ Clin Nutr1999:69:120-126.

10. Tsai CJ, Leitzmann MF, Willett WC, GiovannucciEL. Long-term intake of trans-fatty acids andrisk of gallstone disease in men. Arch Intern Med2005:165:1011-1015.

Page 265

Alternative Medicine Review Volume 14, Number 3 2009

U. Tsai C|, Lcitsmann MB Willett WC, GiovannucciEL. Long-chain saturated fatty acids consumptionand risk of gallsronc disease among men. Ann Surg2008;247;95-103.

12. Tsai CJ, Leitzmann MF, Willert WC, GiovannucciEL. Tlie effect of long-term intake of eis unsaturatedfats on the risk for gallstone disease in men:a prospective cohort study. Ann Intern Aied2004;141:514-522.

13. Rotstein OD, Kay RM, Wayman M, StrasbergSM. Prevention of cholesterol gallstones by Hgninand lactulose in the hamster. Gastroenterology1981;81:1098-1103.

14. Robins SJ, FasuloJ. Mechanism of lithogenicbile production: studies in the hamster fed anessential fatty acid-deficient diet. Gastroenterotogy1973;65:104-114.

15. Berr F, HollJ, Jungst D, et al. Dietary n-3polyunsaturated fatty acids decrease biliarycholesterol saturation in gallstone disease. Hepatology1992;]6:96Ü-967.

16. LoeHer IJ. Gallstones and glaciers: hypothesis meltingat the equator. Ltiíia-í 1988;2:683.

17. Tamimi TM, Wosornu L, AI-Khozaim A, Abdul-Ghani A. Increased cholecystectomy rates in SaudiArabia. Lancet 1990;336:1235-l237.

18. Tsai CJ, Leitzmann ME Willett WC, GiovannucciEL. Dietary carbohydrates and glycaemic load and theincidence of symptomatic gall stone disease in men.GHt 2005:54:823-828.

19. Moerman CJ, Smeets FW, Kromiiüut D. Dietary riskfactors for clinically diagnosed gallstones in middle-aged men. A 25-year follow-up study (The ZutphenStudy). Ann Epidemiol 1994:4:248-254.

20. Bergman F, Bogrcn H, Lindelof G, et al. Influenceof the carbohydrate source of the diet on gallstoneformation in rabbits and mice. Acta Chir Scand1966;132:715-723.

21. Moersen TJ, Borgman RF. Relation of dietarycarbohydrates to lipid metabolism and the statusof zinc and chromium in rabbits. Am] Vet Res1984:45:1238-1241.

22. Thornton JR, Emmect PM, Heaton KW. Dietand gallstones: effects of refined and unrefinedcarbohydrate diets on bile cholesterol saturation andbile acid metabolism. Gui 1983:24:2-6.

23. Werner D, Emmctt PM, Heaton KW Effects ofdietary sucrose on factors influencing cholesterol gallstone formation. Gut 1984:25:269-274.

24. Pixley F, Wilson D, McPherson K, Mann J. Effectof vegetarianism on development of gall stones inwomen, ßr Med J (Clin Res Ed) 1985;291:11-12.

25. Tsai CJ, Leitzmann MF, Willett WC, GiovannucciEL. Dietary protein and the risk of cholecystectomyin a cohort of US women; the Nurses' Health Study.Am J Epidemiol 2004; 160:11 -18.

26. Tsai CJ, Leitzmann MF, Willett WC, GiovannucciEL. Fruit and vegetable consumption and risk ofcholecystectomy in women. AmJ Med 2006;119:760-767.

27. Kritchevsky D, Klurfeld DM. Influence of vegetableprotein on gallstone formation in hamsters. Am] ClinNutr 1979:32:2174-2176.

28. Kritchevsky D, Klurfeld DM. Gallstone formationin hamscers: effect of varying animal and vegetableprotein levels. Am] Clm Nutr 1983:37:802-804.

29. Kameda H, Ishihara F, Shibata K, Tsukie E. Clinicaland nutritional study on gallstone disease in Japan.>»JMc.il984;23:109-113.

30. Scaggion G, Domanin S, Robbi R, Susanna S.Influence of dietary fibres in the genesis of cholesterolgallstone disease, itoij Mea 1988:4:158-161.

31. Marcus SN, Hearon KW. Effects of a new,concentrated wheat fibre preparation on intestinaltransit, deoxycholic acid metabolism and thecomposition of bile. Gut 1986:27:893-900.

32. Pomare EW, Heaton KW, Low-Beer TS, E.spiner HJ.The effect of wheat bran upon bile salt metabolismand upon the lipid composition of bile in gallstonepatients. A»JDj^Diil976;21:521-526.

33. McDougall RM, Yakymyshyn L. Walker K, TliursronOG. Effect of wheat bran on serum lipoproteins andbiliary lipids. GiHJStir T 1978:21:433-435.

34. Heaton KW, Wicks AC. Bran and bile: time-courseof changes in normal young men given a standarddose.G»il977;18:951.

35. LiUemoe KD, Magnuson TH, High RC, et al.Caffeine prevents cholesterol gallstone formation.Surgery 1989:106:400-406.

36. Leitzmann MF, Willett WC, Rimm EB, et al. Aprospective study of coffee consumption and the riskof symptomatic gallstone disease in men. JAMA1999;281:21Ü6-2U2.

37. Leitzmann MF, Stampfer MJ, Willett WC, eral. Coffee intake is associated with lower riskof symptomatic gallstone disease in women.Gastroenterology 2002;m:lS23'lS30.

38. Ruhl CE, Everhart JE. Association of coffeeconsumption with gallbladder disease. Am]Epidemiol 2O00;152:l034-1038.

39. Tsai CJ, Leitzmann MF, Hu FB, et al. Frequent nutconsumption and decreased risk of cholecystectomyin women. Am] Clin Nutr 2004;80:76-81.

40. Nervi F, Covarrubias C, Bravo P, et al. Influenceof legume intake on biliary lipids and cholesterolsaturation in young Chilean men. Identificationof a dietary risk factor for cholesterol gallstoneformation in a highly prevalent area. Gastroenterology1989:96:825-830.

41. Thijs C, Knip.schild P. Legume intake and gallstonerisk: results from a case-control study, hit] Epndemiol1990:19:660-663.

Page 266

Alternative Medicine Review Volume 14, Number 3 2009

42. Tliornton J, Synies C, Heaton K. Moderate alcohol 58.intake reduces bile cholesterol saturation and raisesHDL cholesterol. Lancet 1983;2:819-822.

43. Vidy.ishankar S, Sambaiah K, Srinivasan K. Dietary 59.garlic and onion reduce clie incidence of atherogenicdiet-induced choltsrorol gallstones in experimentalmice. BrJ Nutr 2009:101:1621-1629. 60.

44. Jenkins SA. Biliary lipids, bile acids and gallstoneformarion in hypovitaminotic C guinea-pigs. BrJ 61.iV«(r 1978:40:317-322.

45. Jenkin.s SA. Vitamin C and gallstone formation: apreliminary report. Experientia 1977:33:1616-1617.

46. Holloway DE, Rivers JM. Influence of chronicascorbic acid deficiency and excessive ascorbic acid 62.intake on bile acid metabolism and bile compositionin the guinea p igJNui r l981 ; l 11:412-424. 63.

47. Hornig D. Weiser H. Ascorbic acid and cholesterol:ertcct of graded oral intakes on cholesterol conversionto bile acids in guinea-pigs. Experientia 1976;32;687-689.

48. Ginter E, Bobek P, Vargova D. Tissue levels and 64.optimum dosage ot vitamin C in guinea pigs. NutrMetab 1979:23:217-226.

49. Ginter E, Mikus L. Reduction of gallstoneformarion by ascorbic acid in hamsters. Experientia1977:33:716-717. 65.

50. Simon JA, Hudes ES. Serum ascorbic acid andgallbladder disease prevalence among US adults: theThird National Health and Nutrition Examination 66.Survey (NHANES III). Arch Intern Med2000:160:931-936,

51. Gustafsson U Wang FH, Axelson M, et al. Tlie effect 67.of vitamin C in high doses on plasma and biliary lipidcomposition in patients with cholesterol gallstones: 68.prolongation of the nucleation rime. EurJ Clin Invest1997:27:387-391. 69.

52. Johnston SM, Murray KP, Marrin SA, et al. Irondeficiency enhances cholesterol gallstone formation. 70.Surgery 1997:122:354-361.

53. Anderson F, Bouchier IA, Phospholipids in human 71.lithogenic gall bLidder bile. Nature 1969:221:372-373. 72.

54. Tuzhilin SA, Drciling DA, Narodetskaja RV. LukashLK. ll ie treatment ot parients with gallstones by 73.lecithin. AmJ Gastroenterol 1976;65:231-235.

55. Holan KR, Holzbach RT, Hsieh jY. et al. Effect oforal adminisrrarion of essential'phospholipid, bera-glycerophosphare, and linoleic acid on biliary lipids inpariencs with cholelithiasis. Digestion 1979:19:251-258.

56. Oliver T H , Wilkinson JF. Achlorhydria. Q } Med1933:2:431-462.

57. Capper WM, Butler TJ. Kllhy JO, Gib.son MJ.Gallstones, gastric secretion and Katulent dyspepsia.Lancet 1967;1:413-415.

Goodman l.S, Gilman A, eds. Tije PharmacologicalBasis oj Iherapeutics, Fourth Edition. London,England; 1970:1014-1015.Gaby AR, Wright JV. Nutritional Iherapy in MedicalPractice. Seminar presented in Las Vegas, NV,January 25-28, 2007.Bell GD. Medical rreatment of gallstones. / R CollPhysicians Lond 1979:13:47-52.von Bergmann K, Beck A, Engel C, Leis.s O.Adminisrrarion of a terpene mixture inhibitscholesterol nuclearion in bile from patients withcholesterol gallstones. Klin Wochenschr 1987;65:458-462.Bell GD, Doran J. Gall stone dissolution in man usingan essential oil prepararion. Hr Med } 1979;1:24.Ellis WR, Somerville KW, Whitten BH, BellGD. Pilot -Study of combinarion treatment for gallstones with medium dose chenodeoxycholic acidand a terpene prepararion. Br Mcd } (Clin Res Ed)1984.289:153-156.Ellis WR, Bell GD. Middleron B. White DA.Adjunct to bile-acid treatment forg.iIl'Stonedissolution: low-dose clienodeoxycliolic acidcombined with a terpene prepararion. Br MedJ (ClinRes Ed) 1981:282:611-612.hilis WR. Bell GD. Treatment of bihary duct stoneswith a terpene preparation. Br MedJ (Clin Res Ed)1981;282:611.Somerville KW, Ellis WR, Wliitten BH, et al. Sconesin the common bile duct: experience with medicaldissolution therapy. Postgrad MedJ 1985;61:313-316.Ellis WR, Bell GD. Rowachol treatment forgallstones: small doses are best. Gui 1979:20:A931.Kotkas L. Spontaneous pa.ssage of gallstones. / R SocMed 1985:78:971.Dekkers R. Apple juice and the chemical-contactsoftening of gallstones. Lancet 1999:354:2171.Sies CW. Brooker ). Could these be gallstones? Lancet2005:365:1388.Bhalotra R."The liver and gallbladder flush". / Cli»Gastroenterol I990;12:243.Savage AP, O'Brien T, Lamont PM. Adjuvant herbaltreatment for gallstones. BrJ Surg 1992:79:168.Issacs LL. Gonzalez NJ. More on gallbladder flush.Townsend Letter 2008:299:113-114.

Page 267