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Article

Increased Fecal Bile Acid Excretion and Changes in the Circulating Bile Acid Pool Are Involved in the Hypocholesterolemic and Gallstone-Preventive Actions of Psyllium in Hamsters¹

Institute of Human Nutrition and Food Science, University of Kiel, 24105 Kiel, Germany

²To whom correspondence should be addressed at Novarh's Nutrition Research Unit, Maastricht, The Netherlands.

	ABSTRACT

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The lipid-lowering effect of psyllium (PSY) is well established. Enhanced fecal bile acid excretion and a stimulation of hepatic bile acid synthesis are discussed as primary mechanisms of this action. To further examine the effect of bile acid excretion and specifically of compositional alterations in the bile acid pool on the cholesterol-lowering and gallstone-preventing action of PSY, male golden Syrian hamsters were fed lithogenic diets containing 5 g/100 g fat, 0.4 g/100 g cholesterol and 0 (control), 4 or 6% PSY or 1% cholestyramine (CHY). PSY significantly lowered plasma total cholesterol and triacylglycerol at a magnitude comparable to that induced by CHY. Although hepatic cholesteryl ester accumulation was completely inhibited by CHY, PSY did not prevent the hepatic storage of esterified cholesterol. PSY and CHY caused distinct alterations in the bile acid profile. PSY caused a selective reduction of taurine-conjugated bile acids, especially of taurochenodeoxycholate. As a result, the glycine:taurine conjugation and the cholate:chenodeoxycholate ratios were significantly higher in PSY-fed hamsters. PSY and CHY normalized the lithogenic index and prevented cholesterol gallstone formation compared with controls. Daily fecal bile acid excretion was ~400% greater in hamsters fed 6% PSY, whereas CHY caused an 11-fold increase. Daily neutral sterol excretion did not differ in PSY-fed hamsters but was >100% greater in those fed CHY than in controls. These data emphasize the potent lipid-lowering effect of PSY. Increased fecal bile acid excretion and alterations of the circulating bile acid pool by removal of dihydroxy bile acids (e.g., taurochenodeoxycholate) appear to be main modulators of the hypocholesterolemic action of PSY by leading to an up-regulation of hepatic bile acid synthesis.

KEY WORDS: • psyllium • cholestyramine • cholesterol-lowering • bile acids • hamsters

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
The hypocholesterolemic effect of psyllium (PSY),³ a concentrated source of soluble fiber, is well established in several animal species as well as in humans (Everson et al. 1992 , Fernandez et al. 1995 , Matheson et al. 1995 , McCall et al. 1992 , Olson et al. 1997 , Trautwein et al. 1993 and 1998 , Turley et al. 1991 ). Further, it has been demonstrated that the primary mechanism by which PSY lowers cholesterol is through an increased conversion of cholesterol into bile acids through stimulation of cholesterol 7-hydroxylase, the rate limiting enzyme in hepatic bile acid synthesis (Buhman et al. 1998 , Fernandez et al. 1995 , Horton et al. 1994 , Matheson et al. 1995 ). Although it was postulated that PSY does not bind bile acids in vivo (Turley et al. 1991 ), PSY ingestion resulted in an increase in fecal excretion of bile acids (Arjmandi et al. 1992 , Buhman et al. 1998 , Daggy et al. 1997 , Trautwein et al. 1993 and 1998 , Vahouny et al. 1987 ). In this respect, PSY seems to act similarly to cholestyramine (CHY), a known bile acid sequestrant with cholesterol-lowering potential. Although the mechanism by which CHY elicits its action is well established, involving a diminished bile acid reabsorption due to its ionic binding capacity to acidic sterols (Einarsson et al. 1991 ), PSY seems to interrupt the enterohepatic bile acid circulation by intraluminal entrapment of bile acids as a result of its high viscosity and gel-forming ability. Given the differences in the chemical structure of PSY and CHY and their different capacity to affect steroid absorption, differences in their potency in altering cholesterol metabolism seem likely.

In addition to the hypocholesterolemic effects, a protective role of PSY as well as CHY against cholesterol gallstone formation has also been demonstrated in hamsters (Bergman and van der Linden 1967 , Trautwein et al. 1993 and 1996 ). The mechanism of this protection is not fully elucidated but seems to relate to changes in the bile acid profile affecting the hydrophobicity of the bile acid pool. As previously demonstrated, CHY caused a dramatic reduction of chenodeoxycholic acid independent of its taurine-glycine conjugation, whereas PSY selectively removed taurine-conjugated bile acids, in particular, taurochenodeoxycholate, in a less efficient manner (Trautwein et al. 1993 ).

The aim of this study was to further elucidate the effect of compositional alterations in the bile acid pool on the cholesterol-lowering and gallstone-preventing action of PSY in comparison to CHY in cholesterol-fed hamsters. Syrian golden hamsters were chosen because of their well-established similaritites to humans in cholesterol as well as bile acid metabolism (Imray et al. 1992 , Spady and Dietschy 1983 , Spady et al. 1986 ).

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Animals.

Male golden Syrian hamsters (SASCO, Omaha, NE) weighing 52 ± 4 g were randomly assigned to four diet groups (n = 10 per group). Hamsters were housed in groups of 3–4 per cage in a temperature-controlled environment under a 12-h light:dark cycle (lights on 1800 h). All experimental protocols and procedures were approved by the Animal Care and Use Committee at the University of Kiel, Germany.

Diets and feeding procedures.

Hamsters were fed high cholesterol, gallstone-inducing diets for 5 wk. The semipurified diets contained 50 g/kg fat and 4 g/kg dietary cholesterol, the amount required to induce cholesterol gallstones. In the supplemented diets, 40 or 60 g/kg of psyllium (PSY) (Kellogg's, Battle Creek, MI) or 10 g/kg cholestyramine (CHY) (Bristol-Myers-Squibb, Regensburg, Germany) was added at the expense of wheat starch. Cellulose, as the only source of insoluble fiber, was maintained at 100 g/kg to assure normal bowel function and to prevent the lethal enteritis "wet tail," a common serious health problem in hamsters. The basal composition of the diet was as follows (g/kg dry weight): casein 200, wheat starch 385, glucose 200, cellulose 100, palm stearin 43, safflower oil 7, mineral mix 46, vitamin mix 12, cholesterol 4 and choline chloride 3. The composition of the Ausman-Hayes mineral mix (F8530 BioServ, Frenchtown, NJ) and the Hayes-Cathcart vitamin mix were detailed previously (Hayes et al. 1989 ). Hamsters were given free access to food and water and the actual food consumption was recorded daily. Body weights were monitored on a weekly basis.

Necropsy.

After 5 wk, hamsters were housed individually in wire-bottomed cages, deprived of food for 18 h and then exsanguinated under anesthesia using a gaseous mixture of CO₂/O₂ (50:50). Blood samples were drawn by cardiac puncture, and the liver and cecum were excised, blotted and weighed. A portion of the liver was removed and frozen for hepatic lipid analysis. Gallbladder bile was aspirated, weighed and analyzed for biliary lipids and bile acid composition. The gallbladder was dissected from the liver, opened under a dissecting microscope, and examined along with the remaining gallbladder bile for cholesterol or pigment gallstones and for cholesterol crystals under regular and polarized light by light microscopy as previously described (Hayes et al. 1989 ). Only spherical white cholesterol gallstones and/or liquid cholesterol crystals were identified.

Plasma lipid analysis.

Plasma total cholesterol (TC) and triacylglycerol (TG) concentrations were determined by enzymatic assays (Sigma kit #352 and #336, respectively, Sigma Chemicals, Deisenhofen, Germany).

Hepatic lipid analysis.

Cholesterol concentrations were analyzed according to the procedure described in detail previously (Trautwein et al. 1993 ). TC was determined enzymatically (Sigma kit #352) and free cholesterol (FC) was analyzed by using HPLC. Esterified cholesterol (EC) concentrations were calculated as the difference between TC and FC. TG concentrations were assayed after ~200 mg of zeolite (Sigma Chemicals, Deisenhofen, Germany) was added to the chloroform phase to remove phospholipids and other compounds that interfere with the enzymatic assay. After centrifugation at 2000 g for 5 min the clear supernatant was evaporated under N₂ and redissolved in ethanol; TG were analyzed in a portion of the ethanol phase (Sigma kit no. 336).

Bile analysis.

Gallbladder bile lipids were isolated using a modified Folch extraction (Folch et al. 1957 ). Biliary cholesterol (BC) and phospholipids (PL) were determined enzymatically in an aliquot of the chloroform phase (Wako Free Cholesterol C kit for BC and Wako Phospholipid B kit for PL, Wako Chemicals, Düsseldorf, Germany). Biliary bile acids were analyzed in an aliquot of the methanol/KCl phase as taurine- and glycine-conjugated bile acids by using an isocratic HPLC method as previously described in detail (Trautwein et al. 1993 ). Total bile acid concentration was calculated as the sum of individual bile acids (taurine and glycine conjugates of cholate, chenodeoxycholate, deoxycholate and lithocholate) as measured by HPLC. The lithogenic index (LI) was calculated on the basis of the relative molar ratios of lipid components and the actual total lipid concentration by using a computer version of cholesterol solubility (Carey 1978 , Kuroki et al. 1986 ). The hydrophobicity index (HI) was calculated as the sum of the molar fractions of individual bile acids multiplied by their individual HI values according to the procedure of Heuman (1989) .

Total bile acid concentrations in a portion of the homogenized cecal contents were extracted with the use of a modified Folch extraction and determined enzymatically (Sigma kit no. 450) The cecal bile acid pool was calculated as concentration (µmol/g) multiplied by the weight of cecal contents (g).

Determination of fecal bile acids and neutral sterols.

Fecal samples were collected over a 3-d period during wk 4 from six randomly selected hamsters per diet group. Fecal neutral sterol concentrations were analyzed in an oven-dried fecal sample by using a modification of the method of Suckling et al. (1991) detailed previously (Trautwein et al. 1993 ). Neutral sterols were determined by gas chromatography (GC) as free sterols according to the method of Ausman et al. (1993) as described in detail previously (Trautwein et al. 1998 ). Fecal total bile acids were determined by GC in the oven-dried fecal samples according to the micro-method of Czubayko et al. (1991) with some minor modifications as described in detail recently (Trautwein et al. 1998 ).

Statistical analysis.

Statistical differences were calculated using one-way ANOVA. If necessary, values were logarithmically transformed before ANOVA to improve normality and to compensate for unequal variance. When significant F-ratios were found, individual means were further compared by Scheffé's post-hoc test. The significance of differences in gallstone incidence was determined by applying the chi-square test, a nonparametric statistical test. All statistical analyses were performed using the StatView and SuperANOVA statistical software packages (Abacus Concepts, Berkeley, CA,). Differences were considered significant at P < 0.05. Results were expressed as means and SD.

	RESULTS

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Food intake and body weight.

Food intake, final body weights and body weight gain were not different among groups. Adding 6% PSY or 1% CHY to the diet produced a 30% increase in the weight of the small intestine (data not shown). The cecum was significantly enlarged in hamsters fed 4 and 6% PSY and 1% CHY, resulting from an increase in the weights of both the cecal contents and the cecal wall (Fig. 1 ).

View larger version (52K): [in this window] [in a new window]   Figure 1. Cecal weights of hamsters fed diets containing 0 (control), 4 and 6% supplements of psyllium (PSY) or 1% cholestyramine (CHY). Values are means ± SD (n = 10). Different letters indicate significantly different means (P < 0.05).

Plasma TC and TG concentrations were significantly lower in hamsters fed 4 and 6% PSY or 1% CHY; the hypolipidemic effects of 6% PSY (TC: -61%; TG: -75%) were comparable to those of 1% CHY (TC: -71%; TG: -80%) (Fig. 2 ).

View larger version (34K): [in this window] [in a new window]   Figure 2. Plasma total cholesterol (TC) and triacylglycerol (TG) concentrations of hamsters fed diets containing 0 (control), 4 and 6% supplements of psyllium (PSY) or 1% cholestyramine (CHY). Values are means ± SD (n = 10). Different letters indicate significantly different means (P < 0.05).

Relative liver weights of hamsters fed 6% PSY or 1% CHY were significantly lower than those of controls. TC and EC concentrations were lower in livers of hamsters fed 1% CHY (-93 and -97%, respectively) compared with control animals, whereas PSY feeding did not alter liver EC accumulation (Table 1). Hepatic FC concentrations were significantly lower in PSY- and CHY-fed hamsters. TG concentrations in the livers were higher in hamsters fed 6% PSY than in controls, whereas they were 80% lower in hamsters fed 1% CHY (Table 1) .

The molar percentages of the biliary lipids, BC, PL and bile acids, were significantly altered in PSY- and CHY-fed hamsters compared with controls. Feeding 6% PSY caused effects similar to those of 1% CHY in reducing the molar percentage of BC and increasing the molar percentage of bile acids (Table 2). In hamsters fed 6% PSY or 1% CHY, the LI was normalized to a value <1.0. Adding 4 and 6% PSY or 1% CHY to the gallstone-inducing diet significantly inhibited cholesterol gallstone formation. Although cholesterol stones were found in all 10 hamsters fed the gallstone-inducing control diet, only 5 of 10 hamsters (50%) fed 4% PSY and 1 of 9 hamsters (11%) fed 6% PSY revealed cholesterol gallstones or crystals. CHY completely prevented cholelithiasis (Table 2) .

PSY and CHY caused distinct alterations in the bile acid profile of gallbladder bile (Table 3). In CHY-fed hamsters the relative percentage of taurochenodeoxycholic and glycochenodeoxycholic acid was significantly lower by -68 and -88%, respectively, whereas the percentage of taurocholic acid was significantly higher than in controls. In contrast, PSY feeding caused a selective reduction of taurine-conjugated bile acids, especially of taurochenodeoxycholic acid, with a concurrent increase in glycocholic acid (Table 3) . As a result, the glycine to taurine conjugation ratio was significantly higher with 4 and 6% PSY. The cholate to chenodeoxycholate ratio was also 90% greater in hamsters fed 6% PSY than in controls. As a result of the depletion of chenodeoxycholate conjugates, the cholate to chenodeoxycholate ratio was sevenfold higher in gallbladder bile of hamsters fed CHY compared with controls. Because of the significant increase in taurocholic acid, the ratio of primary to secondary bile acids tended to be greater in hamsters fed CHY (P = 0.12), whereas this ratio was generally lower in hamsters fed PSY due to an increase in the percentage of glycodeoxycholic acid. The hydrophobicity index (HI), the measure of the hydrophobic-hydrophilic balance of biliary bile acids, was only slightly lower in hamsters fed 6% PSY than in controls. In those fed 1% CHY, it was less than half the control value (Table 3) .

The 3-d fecal output (g per dry feces) was significantly higher in hamsters fed 6% PSY and 1% CHY than in control hamsters (Table 4). The moisture content of the fecal samples was not different (data not shown). Daily fecal excretion of neutral sterol was not affected by PSY, whereas it was 140% higher in hamsters fed CHY than in controls (Table 4) . Among the neutral sterols excreted, cholesterol accounted for 98% in control hamsters, whereas the percentage of cholesterol was reduced to 62–73% by PSY and CHY ingestion, suggesting an increased microbial breakdown of cholesterol in the large intestine. Fecal concentration of coprostanol, the main breakdown product of cholesterol degradation, was significantly higher in fecal samples of hamsters fed 6% PSY or 1% CHY (Table 4 ).

In gallbladder bile, bile acid concentrations and the bile acid pool (µmol/gallbladder bile volume) were not altered by PSY and CHY (Table 5). The cecal bile acid pool was significantly expanded by 200% with 4 and 6% PSY and by 600% in those fed 1% CHY (Table 5) . Fecal total bile acid concentrations, as well as daily bile acid excretion, were significantly higher in hamsters fed 4 and 6% PSY and 1% CHY compared with controls (Table 5) . Daily fecal bile acid excretion was ~400% higher in hamsters fed 6% PSY, whereas CHY caused an 11-fold increase. Fecal bile acid composition was significantly altered by CHY and to a lesser extent by PSY (Table 6). Deoxycholic acid was the dominant bile acid excreted in hamsters fed CHY, and fecal concentration of deoxycholic acid was significantly higher in hamsters fed 1% CHY, and 4 and 6% PSY compared with controls. In contrast, the concentration of lithocholic acid was significantly higher in fecal samples of hamsters fed 4 and 6% PSY and 1% CHY than in controls. The concentration of 12-ketolithocholic acid tended to be higher (P = 0.07) in hamsters fed 6% PSY, whereas 12-ketolithocholic acid was significantly higher in CHY-fed hamsters than in controls. Further, fecal chenodeoxycholic acid was found in higher concentrations in hamsters fed 1% CHY or 4 and 6% PSY compared with control animals(Table 6) .

	DISCUSSION

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The most frequently suggested mechanism responsible for the cholesterol-lowering effect of PSY is the interference with intestinal cholesterol and bile acid absorption, leading to an increase in fecal neutral sterol and bile acid excretion. In this respect, our data confirm and extend previous findings. In this study, daily fecal excretion of neutral sterols were not altered by PSY, suggesting that cholesterol digestibility was not affected although cholesterol absorption was not measured directly. These data are consistent with previous findings that demonstrated that PSY had no effect on cholesterol absorption (Fernandez 1995 , Turley et al. 1994 ). In contrast, other studies have shown increases in neutral sterol excretion and a decreased cholesterol absorption in PSY-fed rats and hamsters as well as in humans (Buhman et al. 1998 , Everson et al. 1992 , Trautwein et al. 1998 ), rendering the effect of PSY on cholesterol elimination still inconclusive. On the other hand, CHY significantly increased neutral sterol excretion, apparently by blocking intestinal absorption of cholesterol. Although 1% CHY did not inhibit cholesterol absorption in a previous hamster study (Turley et al. 1994 ), the opposing outcome in this study is possibly attributable to the excessive dietary cholesterol load, causing an increase in unabsorbed cholesterol in the intestine. Fecal bile acid excretion was elevated in hamsters fed PSY, in line with previous findings (Buhman et al. 1998 , Trautwein et al. 1998 , Turley et al. 1996 ). However, the increment of bile acid removal was more than 100% greater with CHY than with PSY. Because PSY apparently does not bind bile acids (Turley et al. 1991 ), the physicochemical mechanism by which PSY affects bile acid removal is not completely clear. The different extent to which PSY and CHY enhanced bile acid excretion further suggests that PSY interrupts the enterohepatic circulation of bile acids by a different mechanism than CHY. It seems likely that due to its gel-forming ability, PSY exerts a volume expansion in the intestinal lumen and thus entraps and removes bile acids and preferentially taurine conjugates, e.g., taurochenodeoxycholate, as suggested by the changes found in the biliary bile acid pool. During intestinal transit, taurine-conjugated bile acids are not passively absorbed; they are less apt to be deconjugated and thus remain in the lumen longer than glycine conjugates and could therefore be preferentially entrapped (Zhang et al. 1992 ). Further, at acidic pH conditions, bile acids, especially dihydroxy bile acids such as chenodeoxycholate, are bound to microorganisms or calcium complexes, which effectively lower their solubility (Rémésy et al. 1993 ). The theory that taurochenodeoxycholic acid was selectively sequestered by PSY is further supported by the increased excretion of lithocholic acid, the secondary bile acid derived from bacterial conversion of chenodeoxycholate.

The plasma cholesterol-lowering effects of PSY and CHY were comparable, with only a moderate increase in fecal bile acid excretion induced by PSY compared with CHY. This suggests that, in addition to the proposed mechanism of interruption of the enterohepatic circulation and accelerated removal of bile acids, other mechanisms may come into play to fully explain the hypocholesterolemic action of PSY.

There is consistent evidence from a number of studies that PSY, like CHY, leads to an increase in cholesterol 7-hydroxylase activity in parallel with 7-hydroxylase mRNA (Buhman et al. 1998 , Fernandez 1995 , Horton et al. 1994 , Matheson et al. 1995 ). Whether PSY, like CHY, affects the transcriptional activity of the 7-hydroxylase gene is not clear. However, a comparison of data on stimulation of hepatic 7-hydroxylase again indicates that CHY is by far more effective than PSY.

Hepatic bile acid synthesis is thought to be regulated by quantitative (increased fecal excretion) and qualitative (composition of the bile acid pool) changes. Thus, the alterations induced by PSY in the biliary bile acid profile, e.g., the reduction in the percentage of taurochenodeoxycholic acid, may in part facilitate bile acid synthesis. However, the relative importance of this linkage is not sufficiently appreciated. PSY increased the glycine to taurine conjugation ratio and the cholate to chenodeoxycholate ratio and decreased the primary to secondary bile acid ratio, changes seen in previous studies (Trautwein et al.,1993 and 1998 ). Qualitative alterations in the recirculating bile acid pool that resulted in a lowering of the HI have been previously demonstrated in PSY-fed rats (Matheson and Story 1994 ). Therefore, these changes could possibly affect feedback regulation of bile acid synthesis (Heuman et al. 1989 ). In general, dihydroxy bile acids such as chenodeoxycholate are thought to be more effective in terms of feedback inhibition of bile acid synthesis than trihydroxy bile acids (cholate) (Vlahcevic et al. 1991 ). Further, it has been demonstrated that more hydrophobic bile acids such as chenodeoxycholate and deoxycholate repress cholesterol 7-hydroxylase at the level of gene transcription (Pandak et al. 1994 ). Therefore, a lower percentage of biliary chenodeoxycholate and a higher percentage of cholate returning to the liver as induced by 6% (and to a lesser extent with 4%) PSY may attenuate the feedback inhibition on bile acid synthesis and may stimulate cholesterol 7-hydroxylase activity. Further, it has been shown that compositional changes in the bile acid profile (less dihydroxy bile acids such as chenodeoxycholate) returning to the liver may stimulate cholesterol 7-hydroxylase activity by interfering with a bile acid-responsive element acting as a gene promoter (Chiang and Stroup, 1994 ). Taken together, the PSY-induced changes in the bile acid pool along with reductions in bile taurochenodeoxycholate and taurodeoxycholate could possibly up-regulate bile acid synthesis. In line with the observed changes in the bile acid profile, PSY, like CHY, seems to favor cholic over chenodeoxycholic acid synthesis as demonstrated by others (Daggy et al. 1997 ). It has been proposed that in hamsters, cholesterol used for bile acid synthesis is preferentially derived from preformed (plasma) rather than newly synthesized cholesterol (Scheibner et al. 1994 ). Possibly, lipoprotein cholesterol processed via LDL receptors tends to undergo 12-hydroxylation, favoring cholic acid synthesis (Trautwein et al. 1993 ).

Although the plasma cholesterol-lowering action of PSY and CHY was similar in magnitude, both exerted different effects on hepatic cholesterol. Although hepatic cholesterol concentration was sufficiently decreased and cholesteryl ester accumulation almost completely suppressed by CHY, PSY did not alter the hepatic storage of esterified cholesterol, in contrast to previous studies (Trautwein et al. 1998 , Turley et al. 1991 ). However, it must be noted that in this study, the dietary cholesterol load (0.4% dietary cholesterol) was extreme, possibly leading to the observed hepatic hypercholesterolemia. The fact that PSY did not prevent hepatic cholesteryl ester accumulation suggests that cholesterol absorption was not impaired and dietary cholesterol was stored to a large extent in the liver. CHY possibly stimulated hepatic cholesterol synthesis because of the greater demand for cholesterol as substrate for 7-hydroxylase, which is supported by the prevention of hepatic cholesteryl ester storage (Turley et al. 1991 and 1996 ). In contrast, the hepatic storage of metabolically inert cholesteryl esters suggests that in this study, unlike in studies using low cholesterol diets, PSY did not stimulate hepatic sterol synthesis (Fernandez 1995 , Horton et al. 1994 , Turley et al. 1991 ). Thus, cholesterol needed as precursor for bile acid synthesis seems to be generated from lipoprotein cholesterol via up-regulated receptor uptake rather than from newly synthesized cholesterol.

Last, PSY effectively reduced lithogenicity and prevented cholesterol gallstone formation, consistent with our previous study (Trautwein et al. 1993 ). The decrease in biliary cholesterol concentration, the lower LI associated with the increase in fecal bile acid excretion and the predominant cholate profile may all contribute to the gallstone prevention in the hamster model.

In conclusion, these findings demonstrate the cholesterol- and triacylglycerol-lowering potential of PSY. In addition to an increased fecal bile acid excretion, alterations of the circulating bile acid pool, particularly the decrease in chenodeoxycholate and the increase in cholate (possibly facilitating hepatic bile acid synthesis) are the main modulators responsible for the hypocholesterolemic action of PSY.

	ACKNOWLEDGMENTS

 
The authors thank Uta Jürgensen, Swantje Möller and Claire Mermet for their excellent technical assistance and for their help with animal care.

	FOOTNOTES

 
¹ Supported in part by a grant from FEI (Forschungskreis der Ernährungsindustrie e.V., Bonn, Germany, the AIF and the Ministry of Economics (Project No. 9670).

² Abbreviations used: BC, biliary cholesterol; CHY, cholestyramine; EC, esterified cholesterol; FC, free cholesterol; GC, gas chromatography; HI, hydrophobicity index; LI, lithogenic index; PL, phospholipids; PSY, psyllium; TC, total cholesterol; TG, triacylglycerol.

Manuscript received August 4, 1998. Initial review completed October 27, 1998. Revision accepted January 8, 1999.

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