Effects of legume consumption on serum cholesterol, biliary lipids, and sterol metabolism in humans

Legume consumption appears to lower serum chtr lesterol and to increase cholesterol saturation of bile, but the mechanisms of these effects have not been established. We studied nine human subjects on a metabolic ward during two randomly ordered 6-7 week periods: one during consump tion of a control diet and the other during consumption of' the same diet with 120 gm mixed legumes substituted for foods having equivalent calories, fat, protein, and carbohydrate. Mean serum LDL cholesterol was significantly lower during legume consumption (126 vs. 138 mg/dl, P = 0.039). Legume consumption significantly increased mean cholesterol saturation index of gallbladder bile from 1.07 to 1.26 ( P = 0.016), largely because of an increase in hepatic secretion of cholesterol from a mean of 90.2 pmol/h to 100.8 Fmol/ h ( P = 0.042). Fecal neutral sterol output was unaffected by legumes, but fecal acidic sterols increased from a mean of 861 to 1202 pmol/day ( P = 0.002) during legume consumption. Mean sterol balance became significantly more negative during legume consumption (-2140 vs. -2700 pmol/day, P = 0.037) indicating an increase in cholesterol synthesis. Mean fractional absorption of bile acid was lower during legume consumption than (0.947 vs. 0.960, P = 0.003).Q These data suggest that legume consumption lowers LDL cholesterol by partially interrupting the enterohepatic circulation of bile acids and increases cholesterol saturation of bile by increasing hepatic secretion of cholesterol.-Duane, W. C. Effects of legume consumption on serum cholesterol, biliary lipids, and sterol metabolism in humans. J. Zipid Hps. 1997. 3 8 11201128. Supplementary key words erosclerosis sapogenins triglycerides bile acids and s a h cholelithiasis A t h Elevation of serum low density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular disease. Recent studies have conclusively shown that lowering LDL cholesterol diminishes both cardiovascular and overall mortality with every 1% reduction in LDL cholesterol resulting in approximately a 1 % reduction in cardiovascular mortality (1, 2). This has led to more aggressive treatment of hypercholesterolemia as well as a renewed focus on modifications of life-style and diet which might promote reduction in LDL cholesterol even in subjects with relatively normal cholesterol levels. One dietary constituent with a propensity to lower LDL cholesterol is legumes. Soybean products are known to have hypocholesterolemic effects as documented in a recent meta-analysis (3). In addition, Nervi e t al. (4) found that a diet rich in mixed legumes, not including soybeans, lowered serum LDL cholesterol in Chilean men. That observation was all the more interesting because accompanying the reduction in serum cholesterol by mixed legumes was an increase in cholesterol saturation of bile. Supersaturation of bile with cholesterol predisposes to development of cholesterol gallstones (5). Interestingly, Pima and Papago Native Americans of the Southwest, like Chileans, consume diets rich in mixed legumes (4,6) suggesting that the legume component of the diet might be in part responsible for the increased incidence of gallstones and the decreased risk of coronary artery disease found in these populations (7, 8). There are several potential mechanisms by which dietary legumes might affect sterol metabolism. In general, cholesterol supersaturation of bile can occur either because of increased biliary secretion of' cholesterol or decreased secretion of bile acid and/or phospholipid, lipid constituents of bile that solubilize cholesterol (5). Studies in animal models have suggested that the mechanism by which legumes increase cholesterol saturation of bile is bv increasing biliary seAbbreviations: LDI,, low density lipoprotein; VLDI,, very low density lipoprotein; HDL, high density lipoprotein; CO, rarbon monoxide; HMGCoA, hydroxymethylglutaryl coeniyme A. 1120 Journal of Lipid Research Volume 38, 1997 by gest, on N ovem er 6, 2017 w w w .j.org D ow nladed fom cretion of cholesterol (9, lo), perhaps through effects of diosgenin, one of several sapogenins liberated from legumes during digestion (11) . Diosgenin is known to stimulate cholesterol secretion in the rat (12, 13). Aprimary increase in biliary cholesterol secretion could conceivably deplete hepatocellular cholesterol levels thus stimulating LDL receptors and lowering serum LDL cholesterol. However, there are few data available defining the effect of legumes on biliary lipid secretion in human subjects. Perhaps a more likely mechanism by which legumes lower serum LDL cholesterol would be reduction in intestinal re-uptake of bile acids, which would increase bile acid synthesis and lower LDL cholesterol by a mechanism similar to that of cholestyramine. It is know that legumes increase bile acid synthesis and output of fecal acidic sterols in the rat (10, 14). There is also one study in human subjects showing that consumption of soybean protein increased output of fecal acidic sterols (15). However, another study reported a reduction of fecal acidic sterol output with increased consumption of mixed legumes. In both studies, time on diet ranged between 1 and 3 weeks, an interval reported to be too short for reproducible measurement of fecal sterol outputs (16). To further evaluate the effects of mixed legumes on sterol metabolism we studied not only serum cholesterol and biliary cholesterol saturation, but also biliary lipid secretion and fecal sterol balance in human subjects living on a metabolic ward, alternately consuming a control diet and the same diet supplemented with legumes.