Sterol absorption

Cohen JC, Pertsemlidis A, Fahmi S, Esmail S, Vega GL, et al. 2006. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc Natl Acad Sci USA 103 1810-1815. 

The relative importance of each of these contributions to pool C is likely to be different in epithelial cells located at different points along the villus-crypt axis. The fact that cholesterol derived from synthesis and from the uptake of LDL is critically important for membrane formation and differentiation is suggested by the finding that 70-80% of total mucosal sterol synthetic activity and LDL transport activity are localized to the immature cells of the lower villus and crypt regions in both the proximal and distal intestine. In the mature absorptive cells of the upper villus in the jejunum, where most sterol absorption takes place, the rate of cholesterol synthesis appears to be suppressed. In the absence of fat absorption, cholesterol newly synthesized in these cells apparently is sloughed into the lumen and not reabsorbed. However, with active triglyceride absorption cholesterol synthesis in these cells is increased and a portion of this sterol appears in the intestinal lymph. Only under this condition does pool B apparently supply sterol for lipoprotein formation. 

The only detergent so far shown to replace bile salts in cholesterol absorption is the closely structurally related taurofusidate, a steroid antibiotic [96], The mechanism of the absolute requirement of bile salts for sterol absorption is presently not understood. 

Cholesterol and fat-soluble vitamins require bile acid induced micellar solubilization for absorption, which takes place in the upper small intestine (c/. 32,116-118). Accordingly, in bile salt deficiency states, cholesterol absorption should be markedly impaired and fecal neutral sterol excretion increased. The fact that fecal neutral steroid excretion on a low-cholesterol diet is actually normal, as after ileal resection, ileal bypass, and cholestyramine treatment, or even decreased, as in cirrhosis of the liver or biliary occlusion (11), is due to a markedly reduced biliary secretion of cholesterol. In gluten enteropathy, in which no excessive bile salt loss usually exists, fecal neutral sterol excretion is markedly augmented (119). However, in occasional cases in which fecal bile salt elimination is markedly enhanced, the fecal neutral steroid excretion is quite normal, probably owing to decreased biliary cholesterol secretion as a consequence of low biliary bile salt secretion. Detailed information on the role of bile salts in both intraluminal and mucosal phases of fat and sterol absorption is presented in many recent reviews (6,10,113,114,117). 

In Barton s laboratory, ergosterol was irradiated in a quartz apparatus at room temperature with a high pressure mercury arc lamp until the starting sterol absorption reached a minimmn (24 hours in... 

Jones ML, Martoni CJ, Prakash S. Cholesterol lowering and inhibition of sterol absorption by lactnhacillus reuteri NQMB 30242 a randomized controlled trial. Eur Clin Nutr. 2012 66 1234—1241. 

Like cholesterol, PS are absorbed in the proximal part of the small intestine after being incorporated into mixed micelles. Compared to cholesterol, the intestinal absorption of PS is low. While 40-60% of dietary cholesterol is absorbed, only about 5% of the PS are absorbed [18]. In addition, the efficiency of PS absorption is critically dependent on the structure of both sterol nucleus and side chain. For instance, the rate of plant sterol absorption was investigated in a human study... 

Miettinen TA (1980) Phytosterolaemia, xanthomatosis and prtanatnre athc sclerotic arterial disease a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis. Eur J Qin Invest I0(I) 27—35... 

L. L. Gallo, Cholesterol and other sterols Absorption, metab-... 

The practical development of plant sterol drugs as cholesterol-lowering agents will depend both on structural features of the sterols themselves and on the form of the administered agent. For example, the unsaturated sterol sitosterol is poorly absorbed in the human intestine, whereas sitostanol, the saturated analog, is almost totally unabsorbable. In addition, there is evidence that plant sterols administered in a soluble, micellar form (see page 261 for a description of micelles) are more effective in blocking cholesterol absorption than plant sterols administered in a solid, crystalline form. 

Various mechanisms have been proposed to explain the hypocholesterolemic effect of GA (Annison et al., 1995 Tiss et al., 2001). Some studies have suggested that the viscosity of fermentable dietary fiber contributes substantially to the reduction of lipids in animals and humans (Gallaher et al., 1993 Moundras et al., 1994). However, other studies suggested that this property is not related to plasma lipids (Evans et al., 1992). The mechanism involved is clearly linked to increased bile acid excretion and fecal neutral sterol or a modification of digestion and absorption of lipids (Moundras et al., 1994). 

Irrespective of the physical form of the carotenoid in the plant tissue it needs to be dissolved directly into the bulk lipid phase (emulsion) and then into the mixed micelles formed from the emulsion droplets by the action of lipases and bile. Alternatively it can dissolve directly into the mixed micelles. The micelles then diffuse through the unstirred water layer covering the brush border of the enterocytes and dissociate, and the components are then absorbed. Although lipid absorption at this point is essentially complete, bile salts and sterols (cholesterol) may not be fully absorbed and are not wholly recovered more distally, some being lost into the large intestine. It is not known whether carotenoids incorporated into mixed micelles are fully or only partially absorbed. 

Ezetimibe is the first drug in a new class of agents referred to as cholesterol absorption inhibitors. Ezetimibe blocks biliary and dietary cholesterol as well as phytosterol (plant sterol)... 

Richelle, M. et al. (2004). Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans. Am. J. Clin. Nutr. 80(1) 171-177. 

In the stomach, carotenoids are exposed to acid environments. This can lead to carotenoid isomerization, which can change carotenoid antioxidant properties, solubility, and absorption. In humans, (3-carotene absorption is reduced when the pH of the gastric fluids is below 4.5 (Tang and others 1995). Vitamin E consumption seems to reduce carotenoid absorption in animals, presumably because vitamin E and carotenoids compete for absorption (Furr and Clark 1997). Dietary sterols, such as those in sterol-supplemented functional foods, are also known to decrease carotenoid absorption. 

Heinemann T, Axtmann G and Von Bergmann. K 1993. Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur J Clin Invest 23(12) 827—831. 

Normen L, Dutta P, Lia A and Andersson H. 2000. Soy sterol esters and 3-sitostanol ester as inhibitors of cholesterol absorption in human small bowel. Am J Clin Nutt 71(4) 908—913. 

In addition to more rapid absorption of lipids in animals fed casein, another mechanism that may be operative is decreased clearance of circulating lipids. Rabbits fed a casein-based semipurified diet excreted significantly less cholesterol but more bile acids in their feces than animals fed a commercial diet (18). The total sterol excretion in feces of the animals fed the casein diet was half that of the rabbits fed the stock diet. Huff and Carroll (19) found that rabbits fed soy protein had a much faster turnover rate of cholesterol and a significantly reduced rapidly exchangeable cholesterol pool compared with rabbits fed casein. Similar studies performed in our laboratory revealed that the mean transit time for cholesterol was 18.4 days in rabbits fed soy protein, 36.8 days in rabbits fed casein, 33.7 days in rabbits fed soy plus lysine, and 36.3 days in rabbits fed casein plus arginine. These data suggest that addition of lysine to soy protein... 

The intestinal absorption of dietary cholesterol esters occurs only after hydrolysis by sterol esterase steryl-ester acylhydrolase (cholesterol esterase, EC 3.1.1.13) in the presence of taurocholate [113][114], This enzyme is synthesized and secreted by the pancreas. The free cholesterol so produced then diffuses through the lumen to the plasma membrane of the intestinal epithelial cells, where it is re-esterified. The resulting cholesterol esters are then transported into the intestinal lymph [115]. The mechanism of cholesterol reesterification remained unclear until it was shown that cholesterol esterase EC 3.1.1.13 has both bile-salt-independent and bile-salt-dependent cholesterol ester synthetic activities, and that it may catalyze the net synthesis of cholesterol esters under physiological conditions [116-118], It seems that cholesterol esterase can switch between hydrolytic and synthetic activities, controlled by the bile salt and/or proton concentration in the enzyme s microenvironment. Cholesterol esterase is also found in other tissues, e.g., in the liver and testis [119][120], The enzyme is able to catalyze the hydrolysis of acylglycerols and phospholipids at the micellar interface, but also to act as a cholesterol transfer protein in phospholipid vesicles independently of esterase activity [121],... 

Some of the more interesting examples of nutrient - nonnutrient interactions include some of the compounds that are analogs of nutrients. Mattson et al (16) found that cholesterol absorption decreased when various plant sterols were added to the diets of rats. A number of plant amino acids are not ordinarily required by herbivores and are usually not incorporated into proteins. For example, the structure of 3,4-dihydroxyphenyl-alanlne (L-dopa) is similar to that of tyrosine. L-Dopa may play a role in favism (17), as well as having a number of other deleterious effects (18, 19, 20). Essential amino acids themselves can be deleterious if they are ingested in excessive quantities or if they are not in balance with other amino acids... 

Plant sterols Commercially available margarines containing hydrogenated plant sterols and sterol esters (predominantly sitostanol esters), when used in place of regular margarine, can reduce LDL plasma cholesterol concentrations. The mechanism by which these compounds lower LDL cholesterol concentrations is to inhibit intestinal absorption of dietary cholesterol and cholesterol secreted into the bile. 

One of the best therapeutic approaches may be to prevent absorption of cholesterol from the intestines by inclusion of a higher fiber content in the diet.66 Supplementation with a cholesterol-binding resin may provide additional protection. Plant sterols also interfere with cholesterol absorption. Incorporation of esters of sitostanol into margarine provides an easy method of administration. Supplemental vitamin E may also be of value.q Another effective approach is to decrease the rate of cholesterol synthesis by administration of drugs that inhibit the synthesis of cholesterol. Inhibitors of HMG-CoA reductase,s hh (e.g., vaLostatin) iso-pentenyl-PP isomerase, squalene synthase (e.g.,... 

Soybean-derived sterol mixture (SS), soybean-derived steryl glucosides (SG), and their individual components have been extensively studied for their ability to promote the nasal absorption of drugs, particularly insulin [79,80], Maitani et al. [79] demonstrated that the nasal administration of SG plus insulin to rabbits resulted in significant reductions in blood glucose. The effect of SG was dose dependent to 1%, with a plateau being reached thereafter. Muramatsu et al. [81] have demonstrated that SG perturbs the phospholipids in artificial membranes (i.e., liposomes). Furthermore, circular dichroism studies with insulin in the presence or absence of SG have indicated that the enhancer had little effect on the dissociation of insulin hexamers to monomers. These results suggest that the action of SS and SG involves interaction with the nasal membrane rather than interaction with insulin molecules. 

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