Dietary agents that target gastrointestinal and hepatic handling of bile acids and cholesterol

Abstract

Several food components have been demonstrated to exhibit cholesterol-lowering properties by interfering with cholesterol absorption and bile-acid trafficking. Such components include stearic acid, plant sterols, soluble fiber, and soy protein. Among saturated fatty acids, stearic acid is unique in its ability to reduce circulatory low-density lipoprotein cholesterol levels. This action is accompanied by an observed suppression in cholesterol absorption, an effect seen repeatedly in animal and human studies. Proposed mechanisms include micellar exclusion of cholesterol by this high melting point fatty acid, as well as the ability of stearate to alter the biliary ratios of primary to secondary bile acids, leading to a reduction in hydrophobicity index and lower overall solubility of sterols in micelles. Another dietary ingredient that interferes with absorption of sterols is soy protein, in which studies in animals and humans have identified that compared to casein, consumption of soy protein reduces intestinal absorption of cholesterol while enhancing fecal cholesterol excretion. Considerable investigation using free amino acid mixtures mirroring the composition of soy versus animal proteins has determined that co-existing agents other than soy’s amino acid pattern are likely responsible for the inhibitory action of soy protein on sterol uptake. Recently, it has been shown that hydrolysates of soy protein appear to be effective in reducing sterol absorption; these are now being targeted as the possible factor responsible for the overall effect of this dietary ingredient. Plant sterols appear to impact absorption of sterols through several mechanisms, including competition with cholesterol for incorporation into micelles, co-crystallization with cholesterol to form insoluble crystals, interaction with digestive enzymes, and inhibition of cholesterol transporter proteins. Clinical trials attest to plant sterols lowering cholesterol absorption by 20% to 40%, an extent beyond which cholesterogenesis can compensate to restore normal circulatory cholesterol levels. As such, 2 g/day of plant sterols effectively lowers low-density lipoprotein cholesterol by 8% to 12%. Dietary soluble fiber represents another means of reducing intestinal cholesterol uptake, in part through enhanced bile-acid clearance through the gut. Pectin, β-glucans, fructans, and gums have been identified as agents that can work through the production of a viscous matrix that hinders movement of cholesterol and bile acids into micelles as well as the subsequent uptake of micelles into the enterocyte. Additional work on design of novel fibers that impede sterol absorption is warranted. In summary, a number of novel dietary factors exist that contribute to heart disease risk reduction via mechanisms that involve cholesterol absorption inhibition and/or biliary pathway perturbation.