Pierre-Etienne Bost

THE CHOLESTEROL-LOWERING EFFECT OF GUAR GUM IS NOT THE RESULT OF A SIMPLE DIVERSION OF BILE ACIDS TOWARD FECAL EXCRETION

The effects of partially hydrolyzed, nonviscous, guar gum (PHGG) on cholesterol metabolism and digestive balance have been compared with those of native guar gum (GUAR) in rats adapted to 0.4% cholesterol diets. Both types of guar gum elicited acidic fermentations in the large intestine, but only GUAR effectively lowered plasma cholesterol (P<0.001), chiefly in the triglyceride-rich lipoprotein fraction. The biliary bile acid excretion was significantly enhanced in rats fed GUAR (P<0.05), as well as the intestinal and cecal bile acid pool (P<0.001). In rats fed GUAR and to a lesser extent in those fed PHGG, the fecal excretion of bile acids and neutral sterol was higher than in controls (P<0.01). The digestive balance (cholesterol intake-steroid excretion) was positive in control rats (+47 μmol/d), whereas it was negative in rats fed GUAR (−20 μmol/d), which could involve a higher rate of endogenous cholesterol synthesis. In rats fed PHGG, the steroid balance remained slightly positive. Liver 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was very low (22 pmol/min/mg protein), owing to cholesterol supplementation, in control rats or in rats fed PHGG, whereas it was markedly higher (+463%) in rats fed GUAR. In conclusion, even if PHGG does alter some parameters of the enterohepatic cycle of cholesterol and bile acids, its effects are not sufficient to elicit a significant cholesterol-lowering effect. The intestinal (ileal or cecal) reabsorption of bile acids was not reduced, but rather increased, by GUAR; nevertheless the intestinal capacities of reabsorption were overwhelmed by the enlargement of the digestive pool of bile acids. In the present model, induction of HMG-CoA reductase probably takes place in the presence of elevated portal bile acid concentrations.

The cholesterol-lowering effect of guar gum in rats is not accompanied by an interruption of bile acid cycling.

A viscous hydrocolloid (guar gum, GG; 2.5% of the diet) or a steroid sequestrant (cholestyramine; 0.5% of the diet) was included in semipurified diets containing 0.2% cholesterol to compare the cholesterol-lowering effects of each agent in rats. In the present model, GG significantly lowered plasma cholesterol (−25%), especially in the density <1.040 kg/L fraction, whereas cholestyramine was less potent. Bile acid fecal excretion significantly increased only in rats fed cholestyramine, similar to the cecal bile acid pool; the biliary bile acid secretion was accelerated by GG, but not their fecal excretion, whereas GG effectively enhanced neutral sterol excretion. As a result, the total steroid balance (+13 μmol/d in the control) was shifted toward negative values in rats fed the GG or cholestyramine diets (−27 or −50 μmol/d, respectively). Both agents induced liver 3-hydroxy-3-methylglutaryl-CoA reductase, but cholestyramine was more potent than GG in this respect. The present data suggest that, at a relative low dose in the diet, GG may be more effective than cholestyramine in lowering plasma cholesterol by impairing cholesterol absorption and by accelerating the small intestine/liver cycling of bile acids, which is interestingly, accompanied by reduction of bile acid concentration in the large intestine.

Reciprocal influence of fermentations and bile acid excretion on cholesterol-lowering effect of fermentable carbohydrate

Abstract The lipid-lowering capacity of two different polysaccharides, a high viscosity or a low viscosity guar-gum (HV-GG or LV-GG) were investigated in male Wistar rats. Guar gum (GG) was broken down in the large bowel, yielding fermentation rich in propionic acid, up to 50% of total short-chain-fatty-acid (SCFA) with the LV-GG diet. Compared with the LV-GG diet, the HV-GG diet was more potent in enhancing bile acid excretion and producing a potent cholesterol-lowering effect. There was also a marked effect of HV-GG on sterol excretion, whereas LV-GG had a marginal effect on this process. Both LV-GG and HV-GG depressed plasma triglycerides, and lowered high-density lipoprotein 2 (HDL2) cholesterol, whereas only the HV-GG diet depressed low-density lipoprotein (LDL) and high-density lipoprotein 1 (HDL1) cholesterol. The decreased efficiency of the LV-GG diet to produce a hypocholesterolemic response resulted in a decreased stimulation of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, and this could explain the lesser efficiency of LV-GG diet to develop a cholesterol-lowering effect. Moreover, the induction of hepatic HMG-CoA reductase in the two GG diets was concomittant to a decrease in fatty acid synthase (FAS) activity. Large bowel fermentations do not appear to significantly influence cholesterol metabolism when soluble fibers fail to enhance bile acid secretion.