Gut 1993; 34: 531-536

Sex differences in colonic function: a randomisedtrial

JW Lampe, S B Fredstrom, J L Slavin, J D Potter

AbstractThere are sex differences in large bowel cancerrates and a variety of other gastrointestinaldisorders possibly because of differences ingut biology. To determine whether menand women have different gastrointestinalresponses when consuming identical intakes ofdietary fibre, 16 women and 18 men consumedliquid formula diets and 'quick breads' with0 g, and 10 g, and 30 g offibre as wheat bran andvegetable fibre. The five test diets were con-sumed in random order, each treatment lasting23 days. Mean transit time was faster(p=0.02), and stool weights (g/day) weregreater (p=0O0005) for men than women.Neutral detergent fibre (NDF) excretion wasgreater in men (p=0 01), and women tended todigest more NDF (p=006). Men and womenseemed to respond differently to wheat branand vegetable fibre with regard to NDFexcretion and digestibility. There were nogender differences in the faecalpH or moisturecontent. Concentrations and daily excretionof the secondary bile acids, lithocholic anddeoxycholic acid, were greater for men thanwomen (p<005). Gender differences in bowelfunction and bile acid excretion, observedwhen men and women consumed the sameamounts of dietary fibre, may be relevant forunderstanding colonic disease aetiology andfor undertaking future dietary interventiontrials.(Gut 1993; 34: 531-536)

Department ofFoodScience and Nutrition,University of Minnesota,St PaulJW LampeJ L Slavin

Division ofEpidemiology, School ofPublic Health, Universityof Minnesota,MinneapolisJW LampeJ D Potter

Division ofGastroenterology,Hepatology andNutrition, University ofMinnesota Hospital andClnics, Minneapolis,Minnesota, USAS B FredstromCorrespondence to:Dr J D Potter, Division ofEpidemiology, University ofMinnesota, 1300 South SecondStreet, Minneapolis, MN55454, USA.Accepted for publication31 August 1992

There is a male excess for most chronic diseases,and particularly cancer. Diseases of the biliaryand intestinal systems, however, frequentlyshow an excess in women. This is often evenmore noticeable before the age of menopause.Real sex differences in the physiological func-tioning of the biliary and intestinal organs mayexist, differences that may be pertinent to theaetiology of colon cancer particularly, and are

certainly pertinent to the gender differences inthe age and subsite distribution of that cancer.'In Western societies, rates of colon cancer inpremenopausal women are often similar' or

exceed2 the male rates at all ages. These womentend to experience their colon cancers somewhatyounger and more proximally, while men pre-sent older with more distal cancers. 1 2There are data from epidemiological, clinical,

and animal studies to show that gender,hormonal status, and reproductive events mayinfluence variously, bile composition,3" transittime,7-9 faecal weight,8 '0 "' and faecal bio-chemistry.8 12 Furthermore, in ecologicalstudies, an increased risk for colon cancer hasbeen associated with reduced stool bulk,'3 more

alkaline faecal pH,'4 and increased faecal bileacid concentrations.'5 Typically, women haveslower transit times and lower faecal bulk.9 1617These gender differences, however, have notalways been observed'89 and results are oftenconfounded by differences in dietary intake,with the men consuming more dietary fibre thanthe women.Few studies have examined gender differences

in colonic function under tightly controlleddietary conditions. We report here the results ofa randomised trial designed to compare transittime, faecal weight, faecal pH, faecal bile acidexcretion, and fibre digestibility in healthy menand women. The hypothesis tested was thatpremenopausal women would have slower tran-sit times, smaller faecal mass, higher total bileacid excretion, and more alkaline pH than agroup of similarly aged men consuming the samedefined diets.

Methods

SUBJECTSSubjects were recruited from the University ofMinnesota community. Healthy, non-smokerswho had not used antibiotics within 6 months ofthe start of the study were screened for theirability to complete a rigorous schedule of defineddiet ingestion and extensive biological samplecollection. All subjects were healthy, had notbeen taking medication, and had no historyof diabetes, heart disease, gastrointestinalmalabsorption, or renal disease. The design ofthe study was approved by the Committee onUse of Human Subjects in Research at theUniversity of Minnesota, and informed writtenconsent was obtained from all subjects before thestart of the study.

Forty six subjects were initially randomisedinto the study, but because of commitmentrequired, nine people dropped out during thefirst week on the defined diet and three moredropped out after two diet periods. Thirty foursubjects (16 women, 18 men) finished all aspectsof the study. All the women were premenopausaland none were using oral contraceptives. Themean (SD) age, height, weight, and body massindex for the men and women were 25 9 (7 5)years, 1-79 (007) metres, 74 5 (9-1) kg, 23-3.(2 6) kg/M2 and 26-7 (5-3) years, 169 (006)metres 63-4 (7 9) kg, 22d1 (1-9) kg/m2, respec-tively.

STUDY DESIGN AND SAMPLE ANALYSISBefore the start of the randomised fibre trial,baseline data were collected for 9 days whilesubjects ate their normal diet (self selected

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diet). Radiopaque pellets (Portex Ltd, Hythe,England) were swallowed on days 1 and 7to measure transit time, and all stools wereindividually collected and frozen at -20°C overthe 9 day period. Five day diet records wereanalysed for nutrient and dietary fibre contentusing a computerised nutrient analysis program(Nutritionist III, N-Squared Computing,Silverton, OR, USA).

Five test diets, varying in absolute amountsand type of fibre, were consumed by all subjectsin assigned random order: (1) 0 g added fibre;(2) 10 g total dietary fibre (TDF) as white wheatbran (American Association of Cereal Chemists,St Paul, MN, USA); (3) 30 g TDF as white wheatbran; (4) 10 g TDF as mixed vegetable fibre(VF); (5) 30 g TDF as VF. The vegetable fibre inthe 10 g VF and 30 g VF breads was a mixtureof pea hull fibre (Fiberich Technologies Inc,Minneapolis, MN, USA), soy polysaccharide(Protein Technologies International, St Louis,MO, USA) and citrus pectin (Hercules,Wilmington, DE, USA), added at levels of 62,33, and 5% by weight of total fibre, respectively.A 'quick bread', prepared in our laboratory, wasthe vehicle to deliver the fibres, and a quickbread without added fibre was provided duringthe 0 g fibre diet. The quick breads formulationswere based on the TDF content of the productsas reported by the companies. TDF content wasalso determined in our laboratory by a modi-fication of the current Association of OfficialAnalytical Chemists method.20The subjects consumed a fibre free enteral

supplement (Resource, Sandoz Nutrition,Minneapolis, MN, USA), deionised water, andone loaf of quick bread daily. Subjects wereinstructed to eat all of the quick bread andconsume enough liquid supplement daily (inaddition to the quick bread) to maintain theirusual weight. The quick breads were consumedplain, without spreads. To limit formation ofMaillard products in the breads, subjects wereinstructed not to heat the breads in a conven-tional oven and instead warm them in a micro-wave oven.Each test diet was consumed for 23 days. No

adjustment was made for the phase of menstrualcycle. There was a washout period of at least10 days between each diet period during whichsubjects resumed their habitual diets. Subjectsconsumed the test diets for 1 week before anysamples were collected. Radiopaque pellets wereswallowed on days 7, 13, and 19 of each periodfor transit time determinations, and all stoolswere individually collected and frozen from days7-23.

Subjects recorded all quick bread and nutri-tion supplement intake and daily exercise foreach feeding period. Any bread that was noteaten was returned by the subjects and theuneaten portions were weighed and subtractedfrom the average bread weight. To ensuregreatest compliance by this 'outpatient' group,subjects reported daily to pick up food and dropoff faecal samples and diet records. The import-ance of total faecal collections and adherence tothe diet were stressed continuously with thesubjects. Daily nutrient and fibre intakes for 6days during the last week of each feeding period

were calculated using the nutrient content of theliquid supplement as reported by the companyand the nutrient content of the quick breadsanalysed in our laboratory as previouslydescribed.2'

All faecal samples were weighed and meanstool weight and mean daily faecal weight weredetermined. The samples were x rayed for pelletcontent and the time needed to pass each pelletwas averaged to calculate mean transit time(MTT).22 The appearance of the first pelletsswallowed on days 13 and 19 were used as thelimit markers for faecal composites: starting withstools containing pellets swallowed on day 13,all stools up to the appearance of pelletsswallowed on day 19 were included. Compositeswere homogenised with addition of deionizedwater and faecal pH was measured. Duplicatealiquots of the homogenates were freeze dried todetermine faecal dry weight and faecal moisturecontent was calculated after correcting for theadded water. Faecal acidic sterols were measuredby gas chromatography as described pre-viously.23 Minor bile acids detected in smallamounts, were summed and presented as'miscellaneous bile acids'.To determine the amount offibre excreted and

digested, the neutral detergent fibre (NDF)content of freeze dried faeces and food samplesfrom the five test diets was analysed by themethod of Robertson and Van Soest.24 Heatstable ca amylase (Sigma, St Louis, MO,USA) and sodium sulphite (Aldrich Chemical,Milwaukee, WI, USA) were added to improvethe removal of starch and protein. Fibredigestibility was calculated as: (g faecal fibre - gfibre ingested)/g fibre ingested.

STATISTICAL ANALYSISBowel function parameters, bile acid excretion,and fibre digestibility in men and women werecompared using repeated measures analysis ofvariance where gender was used as a groupvariable for subjects and the interaction ofgender and diet was included in the model. Dataare presented as means (SD) by gender.

ResultsThe effects of fibre type and dose on bowelfunction characteristics were published pre-viously25 and are not discussed here.Mean transit times were consistently faster

(p=002) and faecal wet weights were consis-tently greater (p=00005) for men than womenon all diets (Fig 1), despite the same fibreintakes by men and women (Table I). Faecal dryweights, 35 (2) and 26 (3) g/day for men andwomen, respectively, followed an identical pat-tern to that of wet weights (p<0-0001). Theoverall faecal moisture content (70 7 (1 8) and70 5 (1 9)% for men and women, respectively)and the faecal pH (7-4 (0- 1) and 7-4 (0-2) for menand women, respectively) were similar betweenthe sexes.The concentrations and daily excretion of

faecal bile acids are presented in Figure 2 andTables II and III. Both the concentrations anddaily excretion of the secondary bile acids,

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533Sex differences in colonicfunction

* Men

0 Women

A100 4

.80-EC:cn

4

60-

40-

20-

0

SS 0 Fibre 10 WB 30 WB 10 VF 30 VFDiet

200 B

IiQ)100

CUa.)

SS 0 Fibre 1OWB 3OWB 10VF 30VFDiet

Figure 1: Mean transit time (A) andfaecal wet weight (B)formen and women consuming self-selected (SS), fibre-free, andwheat bran (WB) and vegetablefibre (VF) test diets. (Values,mean (SD).)

lithocholic and deoxycholic acid, were signific-antly greater (p<005) for men than women, as

was daily excretion of chenodeoxycholic acid.As a result, the total bile acid concentrationwas greater for men than women on all diets(p=002) and, with the added effect of greaterstool weights among men, daily total bile acidexcretion was also greater for men (p<00001)(Fig 2). The only significant gender by dietinteraction observed for the bile acid data was fordaily lithocholic acid excretion (p=0 04), wheremen and women seemed to respond differentlyto the two doses of wheat bran and vegetablefibre. When the data were analysed for men andwomen separately, lithocholic acid excretiontended to decrease in men (350 (103) v 311 (95)imol/day, p=009) but not women (168 (50) v

164 (49) [tmol/day, p=0 5) with higher wheatbran (10 g v 30 g); it tended to decrease in women(169 (71) v 134 (89) imol/day, p=0 08), but notmen (256 (82) v 253 (67) [imol/day, p=0 9), with

* Men

| Women

a) 40 AC.)

30'0

CD

0

20

co 10 V

Co

00 Fibre 10WB 30WB 10 VF 30 VF

Diet

800

0E 600

C

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a) 400x

i3 200a)

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00 Fibre 10WB 30WB 10 VF 30 VF

DietFigure 2: Mean total bile acids (A) and bile acid excretion (B)for men and women consumingfibrefree and wheat bran (WB)and vegetablefibre (VF) test diets. (Values, mean (SD).)

higher vegetable fibre (10 g v 30 g). There was no

difference in the ratios of secondary to primarybile acids or of lithocholic acid to deoxycholicacid between the sexes.

Dietary fibre intakes during the test dietperiods, calculated as TDF and NDF, are pre-

sented in Table IV. The amount of fibre as TDFand NDF were the same for the 0 g fibre breadand for the two wheat bran breads; NDF was

60% of the TDF value for the vegetable fibrebreads. Faecal NDF excretion was greater inmen than women (p=001) (Table IV) and theinteraction of gender and diet was highly sig-nificant (p<0O0001). Men excreted more NDFthan women with consumption of the 30 g fibredoses. Individual NDF digestibilities variedwidely on all diets. However, digestibilitytended to be greater in women than men (TableIV) (p=0 06). The interaction of gender and diet(p=0 015) seemed to be due primarily to greaterdigestion of the 10 g wheat bran and 30 gvegetable fibre diets in women.

Despite similar dietary fibre consumption by

TABLE I Comparison ofdaily macronutrient and dietaryfibre intakes for men and womenduring the self-selected diet period and the controlledfeeding periods. (Values mean (SD))

Self-selected Controlledfeeding

Men Women p value Men Women p value

Energy (MJ) 10-54 (1-98) 8-34 (1-76) 0 003 12 64 (2 3)* 8-62 (0 80) 0 0001Protein (g) 86 (19) 67 (18) 0-007 109 (19) 75 (7) 0 0001Fat (g) 105 (29) 78 (21) 0-005 120 (19) 85 (7) 0 0001Total dietary fibre (g) 12-1 (5 6) 13-8 (8 3) 0 5 19-0 (0 8) 18-8 (0 5) 0 4

* Data for individuals were averaged across all test diets prior to calculation of gender mean.

TABLE II Faecal bile acid concentrations (Ismollg dryfaeces) for men (n= 18) and women (n= 16).(Values mean (SD))

Men Women p value

Lithocholic acid 1009 (115) 766 (113) 0005Deoxycholic acid 9 47 (1-21) 7 56 (1-48) 0 049Chenodeoxycholic acid 0-87 (0 16) 0-81 (015) 0-7Cholicacid 0-20(0-15) 0-15(0-08) 06Miscellaneous 1-07 (028) 1-39 (026) 0-12Total* 21 69(2-39) 17 58(2 63) 0-024

* Summation of the individual and miscellaneous bile acids.

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TABLE in Daily faecal bile acid excretion (ymollday) formen (n= 18) and women (n= 16). (Values mean (SD))

Men Women p value

Lithocholic acid 294 (24) 164 (26) 0-0001Deoxycholic acid 272 (31) 158 (30) 0-0001Chenodeoxycholic acid 25 (5) 17 (3) 0-02Cholic acid 7 (6) 3 (2) 0-23Miscellaneous 32 (7) 32 (4) 1-0

both sexes during the self selected and controlledfeeding periods, energy and macronutrient in-takes were greater for men and women (Table I).When energy intake was included as a covariatein the statistical model, bowel function differ-ences between the sexes were no longer statistic-ally significant. This suggests that the sexdifferences may be partly the result of differ-ences in energy intake between men and women.In these subjects, sex and energy intake were soclosely correlated as to exclude virtually anyoverlap in the male and female energy intakedistributions. This ensured almost completeconfounding between energy intake and sex.However, means adjusted for energy intake weresimilar to the unadjusted means. Unlike thebowel function parameters, faecal bile acid con-centrations were still significantly higher in menthan women even after adjusting for energy andfat intake.

Regression analysis of the data undertaken formen and women separately does not show aclear diet dependent association between energyintake and faecal output: there was no associa-tion between daily energy intake and daily faecalwet weights on the self selected diet (men: r=0-18, p=0 5; women: r=0-4, p=0 2) and 30 glevels of wheat bran (men: r=0-34, p=0-2;women: r=0 0, p=0 9) and vegetable fibre(men: r=0-06, p=0 8; women: r=0-2, p=0.5);the association was significant for men, but notwomen, when the subjects consumed 10 g dosesof wheat bran (men: r=0-53; p=0 03; women:r=0-4, p=0-14) and vegetable fibre (men: r=0-6, p=0Q01; women: r=0-09, p=0 7); for the0 g fibre diet, there was a positive association forboth men and women (men: r=0 51, p=0 03;women: r=0-7, p=0001). Similar results wereobserved when energy intake and faecal dryweight were analysed.

DiscussionWe have previously postulated an important rolefor sex differences in gut function in explainingdifferences in the risk of colon cancer23 and othergastrointestinal disorders.3 In the present study,

TABLE IV Total dietary fibre (TDF) intake and neutral detergent fibre (NDF) intake,excretion, and digestibility with consumption of wheat bran (WB) and vegetable fibre (VF)breads by 18 men and 16 women. (Values mean (SD))

Fibre intake from quick breads Faecal NDF excretion NDF digestibilitv(gld) (gNDFId) (%)

Diet TDF NDF Men Women Men Women

O g fibre 2-2 (0-1) 3-2 (0-1) 1*1(0 6) 1*1(0 6) 64 (21) 66 (21)lOgWB 11-2(0-8) 11-5(1-1) 7-5(1 7) 6 3(1-4) 34(15) 42(17)3OgWB 28-9(2 0) 30 4(1 4) 19-2(2-4) 17-2(4-2) 37(8) 43(13)1OgVF 14 7 (0-8) 10-2 (0 5) 6-7 (1-9) 6-5 (2-4) 33 (20) 33 (26)3OgVF 36-8(1-8) 26-6(1-2) 19-0(4-4) 13-0(5-9) 29(17) 51(22)

we observed significant gender differences inbowel function parameters, faecal bile acidexcretion, and faecal NDF excretion, eventhough men and women consumed the sameabsolute amount of fibre on each test diet.

Gastrointestinal transit times were shorter andfaecal output greater for men than women.Similar results have been reported previouslywhen men and women consumed their habitualdiets9 101617 and when fed controlled fibre diets.7"Using a single film technique for assessment ofsegmental colon transit, Metcalf et al9 showedthat the sex difference in transit time was mostapparent in the right colon, with a smallerdifference in the left colon, and no difference inthe rectosigmoid. Ecological studies show higherstool weights in those populations with lowercolon cancer risks,2627 but to date no studieshave shown an association between colon cancerrisk and transit time. The findings of Metcalfet al9 provide additional detail on the sex differ-ence we report here and are especially interestingin light ofthe epidemiological data that show thatwomen have an excess of proximal cancerscompared with men throughout life.'

Faecal moisture content was the same for menand women. Thus, the significant sex differencein faecal wet weight was a function of differencein faecal dry matter. By administering drugswhich change colonic motility, Stephen et a121showed that changing transit time altered micro-bial growth. Greater faecal bulk as a function offaster transit time was due to an increase in faecalbacterial mass and in excretion of non-starchpolysaccharides.28 Stephen et al attributed theefficiency of anaerobic microbial growth not onlyto substrate availability but also to the rate ofpassage of material through the lumen: some-what counter intuitively, microbial growth isgreater and a greater mass of bacteria is producedwith faster transit.28 The pattern of faster gastro-intestinal transit and greater faecal weight andNDF excretion in men compared with women inour study suggests that men have greater faecalbacterial mass than women despite a tendency toferment less fibre. This suggests either that morenon-fibre substrate is available in male colons(consistent with their higher energy intake andthe possible influence of energy intake on stoolweight) or that male and female colonic floradiffer substantially. One possible explanation forthe positive relationship between faster transittime and greater stool mass is that a more rapidtransit time may reduce the likelihood of buildup of 'toxic'/'antibiotic' metabolites in thecolonic microenvironment (for example com-pounds which may inhibit bacterial growth). Itdoes suggest that, for whatever reason, thereare male/female differences in the capacity tosupport the colonic microflora.

It has been reported previously that faecaloutput is positively correlated and gastro-intestinal transit is negatively correlated withenergy intake and total food consumption.'69Thus, reported sex differences in bowel functionmay be the result of energy intake differencesbetween men and women. Unfortunately, in ourstudy, the complete confounding of energyintake and gender made it difficult to resolve thisissue. Men and women had similar fibre intakes

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Sex differences in colonicfunction 535

during the self selected diet period despitesignificant differences in intakes of other macro-nutrients (Table I). Interestingly, no associationbetween energy intake and faecal output wasobserved when the subjects consumed the selfselected diet or 30 g fibre doses. The strongestassociation was observed on the 0 g fibre diet.This suggests that when fibre availability in thecolonic lumen is low (that is, no or low fibre) thevolume of other macronutrients entering thecolonic lumen may become more important indetermining faecal output. In our study, menand women consumed the same amount ofstarchand dietary fibre since both ate one loaf of quickbread/day. The only difference in carbohydrateintake between the sexes was as maltodextrin andsugar from the liquid formula. Refined sugars,30in addition to starch,3' are known to influence gutfunction and the composition of bowel contents.Thus, these other aspects of diet must beconsidered. Additional controlled studies areneeded to address this problem.The colonic pH is largely determined by

fermentation and the production of short chainfatty acids (SCFA).32 In humans, fibre fermenta-tion occurs predominantly in the caecum andproximal colon, and SCFA concentrations arehighest and the pH is lowest in these areas.33SCFA are rapidly absorbed and the pH rises asthe contents proceed distally.33 Stephen et al8found the faecal pH, corrected for stool weight,to be indeed lower in men than women. In astudy in the US and China, faecal pH, notcorrected for fibre intake differences, was alsoobserved to be lower in men (6-4) than women(6-9) when study subjects consumed theirhabitual diets.4 In men, if less fibre is fermentedin the caecum and proximal colon, continuedfermentation and SCFA production the length ofthe colon and in the rectosigmoid may contributeto the output of more acidic stools. In women,slower transit and greater fermentation in theproximal colon with concomitant absorption ofSCFA may reduce the substrate available forfermentation in the rectosigmoid and result inmore alkaline stools. In our study, however,where fibre intakes were the same for men andwomen, faecal pH was not significantly differentbetween the sexes. It is not clear what explainsthe failure to observe the gender differencesin faecal pH that others have reported. Oneimportant difference is that subjects in our studyconsumed a highly controlled liquid diet, ratherthan a diet of regular food.

Based on the epidemiological research whichsuggests: (1) that female rates of colon cancer atpremenopausal ages may exceed male rates2and (2) that concentrations of faecal bile acidsare higher in populations at high risk for thedevelopment of colon cancer,'3 262734 we' hypo-thesised that women would have higher bileacid excretion than men. However, our resultsindicate that secondary bile acid concentrationsand daily bile acid excretion were actually greaterin men than women.

There are few studies of faecal bile acidexcretion in men and women with which tocompare our results, and the results of thesestudies are conflicting. No significant sex differ-ence in faecal bile acid excretion was detected in

a group of 25 subjects habitually consuming lowfibre diets,35 or in men and women with meandaily fibre intakes of 15-4 and 11-9 g, respec-tively.'9 Likewise, Reddy et all' found no sexdifference in faecal bile acid excretion when menand women ate their usual diets and dietssupplemented with wheat and rye flour. Morerecently, Yeung et a14 reported significantlyhigher concentrations of bile acids in womenthan men consuming their habitual diets in ShaGiao, People's Republic of China and in SanFrancisco County, United States. In a controlledfibre feeding study, Stasse-Wolthuis et al"observed that when men and women consumedtest diets containing various dietary fibres, menand women seemed to respond differently to thefibre containing diets. Bile acid excretion wasgreater for male subjects consuming citrus pectinor fruits and vegetables compared with womenon the same diets, while excretion was reducedfor men on the bran diet and was enhanced forwomen consuming bran. None of the studies,including ours, controlled for women'smenstrual cycles. Despite this lack of control,significant, albeit disparate, differences in bileacid excretion have been observed. Since femalehormones are known to alter bile acid secretion,37controlled, long term studies taking into accountthe subjects' hormone status are warranted.

In conclusion, there were significant differ-ences in transit time, faecal bulk, and bile acidexcretion between men and women consumingthe same absolute amounts of fibre. Further-more, faecal fibre excretion was greater in menthan women; correspondingly, women tended todigest more fibre than men. The findings areconsistent with a lower degree of colonic fermen-tation in men than women and provide addi-tional evidence for important sex differences inbowel function between men and women.

This study was supported by NCI Grant CA46618 andthe Minnesota Agricultural Experiment Station (18-64). JWLcurrently receives support from NCI (5T32 CA09607).

Presented in part at the American Association for CancerResearch meeting, Washington DC, May 1990.The authors thank Dr W C Duane, GI Section, Veterans

Administration Medical Center, Minneapolis, MN for faecal bileacid determination, and Dr W 0 Thompson, Office of ResearchComputing and Statistics, Medical College of Georgia, Augusta,GA, for advice and assistance with statistical analyses. The authorsare also grateful to Mrs E A Melcher and Mrs K S Baglien for theirassistance during the study. Resource® was provided by SandozNutrition Inc.

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3 McMichael AJ, Potter JD. Do intrinsic sex differences inlower alimentary tract physiology influence the sex-specificrisks for bowel cancer and other biliary and intestinaldiseases? Am]7 Epidemiol 1983; 118: 620-7.

4 Yeung KS, McKeown-Eyssen GE, Li GF, Glazer E, Hay K,Child P, et al. Comparisons of diet and biochemical charac-teristics of stool and urine between Chinese populations withlow and high colorectal cancer rates.] Nati CancerInst 1991;83: 46-50.

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6 Fisher MM, Yousef TM. Sex differences in the bile composi-tion of human bile: studies in patients with and withoutgallstones. CMA3Journal 1973;-109: 190-3.

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10 Davies GJ, Crowder M, Reid B, Dickerson JWT. Bowelfunction measurements of individuals with different eatingpatterns. Gut 1986; 27: 164-9.

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12 Storer GB, Illman RJ, Trimble RP, Snoswell AM, ToppingDL. Plasma and caecal volatile fatty acids in male and femalerats: effects of dietary gum arabic and cellulose. Nutr Res1984; 4: 701-7.

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