Genomes and Genes
Summary: A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and gamma-isomers have been characterized.
- Mensink R, de Jong A, Lutjohann D, Haenen G, Plat J. Plant stanols dose-dependently decrease LDL-cholesterol concentrations, but not cholesterol-standardized fat-soluble antioxidant concentrations, at intakes up to 9 g/d. Am J Clin Nutr. 2010;92:24-33 pubmed publisher..Daily consumption of plant stanols up to 9 g reduces serum LDL-cholesterol concentrations linearly up to 17.4%. For cholesterol-standardized fat-soluble antioxidant concentrations, such a relation could not be ascertained. ..
- Jesch E, Seo J, Carr T, Lee J. Sitosterol reduces messenger RNA and protein expression levels of Niemann-Pick C1-like 1 in FHs 74 Int cells. Nutr Res. 2009;29:859-66 pubmed publisher..In conclusion, sitosterol can inhibit the expression of NPC1L1 in the enterocytes, which could be an alternate mechanism for plant sterols to reduce intestinal cholesterol uptake. ..
- Schiepers O, de Groot R, van Boxtel M, Jolles J, de Jong A, Lutjohann D, et al. Consuming functional foods enriched with plant sterol or stanol esters for 85 weeks does not affect neurocognitive functioning or mood in statin-treated hypercholesterolemic individuals. J Nutr. 2009;139:1368-73 pubmed publisher..5 g/d does not affect neurocognitive functioning or mood in hypercholesterolemic individuals receiving statin treatment. ..
- Brüll F, Mensink R, van den Hurk K, Duijvestijn A, Plat J. TLR2 activation is essential to induce a Th1 shift in human peripheral blood mononuclear cells by plant stanols and plant sterols. J Biol Chem. 2010;285:2951-8 pubmed publisher..In these cells, no Th1 shift was observed. Our results, therefore, indicate that TLR2 activation is essential to induce a Th1 shift in human PBMCs by plant stanols and plant sterols. ..
- Valerio M, Awad A. ?-Sitosterol down-regulates some pro-inflammatory signal transduction pathways by increasing the activity of tyrosine phosphatase SHP-1 in J774A.1 murine macrophages. Int Immunopharmacol. 2011;11:1012-7 pubmed publisher..In conclusion, the present study demonstrates the anti-inflammatory effect on macrophages by inactivating STAT1 and NF-?B, which could be mediated by the activation of SHP-1. ..
- Matthan N, Resteghini N, Robertson M, Ford I, Shepherd J, Packard C, et al. Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial. J Lipid Res. 2010;51:202-9 pubmed publisher..The magnitude of these alterations were similar between cases and controls and do not explain differences in outcomes with pravastatin treatment. ..
- Hallikainen M, Kurl S, Laakso M, Miettinen T, Gylling H. Plant stanol esters lower LDL cholesterol level in statin-treated subjects with type 1 diabetes by interfering the absorption and synthesis of cholesterol. Atherosclerosis. 2011;217:473-8 pubmed publisher..STAEST significantly decreased serum total, LDL and non-HDL cholesterol concentrations and thus offers an additional benefit to cholesterol lowering in patients with type 1 diabetes who are on statin treatment. ..
- Valitova J, Minibayeva F, Kotlova E, Novikov A, Shavarda A, Murtazina L, et al. Effects of sterol-binding agent nystatin on wheat roots: the changes in membrane permeability, sterols and glycoceramides. Phytochemistry. 2011;72:1751-9 pubmed publisher..Our results suggest that changes in the sphingolipid composition can contribute to the changes in plasma membrane functioning induced by sterol depletion. ..
- Lee M, Gordon D, Ott J, Lu K, Ose L, Miettinen T, et al. Fine mapping of a gene responsible for regulating dietary cholesterol absorption; founder effects underlie cases of phytosterolaemia in multiple communities. Eur J Hum Genet. 2001;9:375-84 pubmed..Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM. ..
- Berge K, Tian H, Graf G, Yu L, Grishin N, Schultz J, et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 2000;290:1771-5 pubmed..These data suggest that ABCG5 and ABCG8 normally cooperate to limit intestinal absorption and to promote biliary excretion of sterols, and that mutated forms of these transporters predispose to sterol accumulation and atherosclerosis...
- Calpe Berdiel L, Escola Gil J, Blanco Vaca F. New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism. Atherosclerosis. 2009;203:18-31 pubmed publisher..This article reviews the progress to date in studying these effects of phytosterols/phytostanols and the molecular mechanisms involved. ..
- Aguirre Hernández E, Rosas Acevedo H, Soto Hernández M, Martínez A, Moreno J, González Trujano M. Bioactivity-guided isolation of beta-sitosterol and some fatty acids as active compounds in the anxiolytic and sedative effects of Tilia americana var. mexicana. Planta Med. 2007;73:1148-55 pubmed..mexicana produces depressant actions on the central nervous system, at least in part, because of the presence of beta-sitosterol and some fatty acids that remain to be identified...
- Li C, Zhou Z, Lin R, Zhu D, Sun Y, Tian L, et al. beta-sitosterol decreases irradiation-induced thymocyte early damage by regulation of the intracellular redox balance and maintenance of mitochondrial membrane stability. J Cell Biochem. 2007;102:748-58 pubmed..The results indicate that BSS confers a radioprotective effect on thymocytes by regulation of the intracellular redox balance which is carried out via the scavenging of ROS and maintenance of mitochondrial membrane stability. ..
- Päivä H, Thelen K, Van Coster R, Smet J, De Paepe B, Mattila K, et al. High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clin Pharmacol Ther. 2005;78:60-8 pubmed..High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume. ..
- Desai F, Ramanathan M, Fink C, Wilding G, Weinstock Guttman B, Awad A. Comparison of the immunomodulatory effects of the plant sterol beta-sitosterol to simvastatin in peripheral blood cells from multiple sclerosis patients. Int Immunopharmacol. 2009;9:153-7 pubmed publisher..The results show that SIT is effective in modulating the secretion of pro/anti-inflammatory cytokines and suggest a potential beneficial effect of SIT in MS management without the side effects associated with statin therapy. ..
- Silbernagel G, Fauler G, Renner W, Landl E, Hoffmann M, Winkelmann B, et al. The relationships of cholesterol metabolism and plasma plant sterols with the severity of coronary artery disease. J Lipid Res. 2009;50:334-41 pubmed publisher..An atherogenic role of plasma plant sterols themselves, however, seems unlikely in subjects without sitosterolaemia. ..
- Keller S, Helbig D, Härtl A, Jahreis G. Nanoscale and customary non-esterified sitosterols are equally enriched in different body compartments of the guinea pig. Mol Nutr Food Res. 2007;51:1503-9 pubmed..No differences in body compartment accumulation and intestinal absorption of the different sitosterol particle sizes were observed. ..
- Mannucci L, Guardamagna O, Bertucci P, Pisciotta L, Liberatoscioli L, Bertolini S, et al. Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene. Eur J Clin Invest. 2007;37:997-1000 pubmed..The plasma sterol profile and genetic analysis of a 10-year-old girl who had tuberous xanthomas is the subject of this report...
- Rajaratnam R, Gylling H, Miettinen T. Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women. J Am Coll Cardiol. 2000;35:1185-91 pubmed..Thus, enhanced absorption and reduced synthesis of cholesterol may be related to coronary atherosclerosis. ..
- Katan M, Grundy S, Jones P, Law M, Miettinen T, Paoletti R. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc. 2003;78:965-78 pubmed..However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease. ..
- Leusch F, Maclatchy D. In vivo implants of beta-sitosterol cause reductions of reactive cholesterol pools in mitochondria isolated from gonads of male goldfish (Carassius auratus). Gen Comp Endocrinol. 2003;134:255-63 pubmed..This finding is supported by the observation that 25-hydroxycholesterol, which passes through mitochondrial membranes without need for a membrane transporter, restores beta-sitosterol-induced reductions in pregnenolone production. ..
- Scoggan K, Gruber H, Lariviere K. A missense mutation in the Abcg5 gene causes phytosterolemia in SHR, stroke-prone SHR, and WKY rats. J Lipid Res. 2003;44:911-6 pubmed..The identification of this naturally occurring mutation confirms that these rat strains are important animal models of sitosterolemia in which to study the mechanisms of sterol trafficking...
- Awad A, von Holtz R, Cone J, Fink C, Chen Y. beta-Sitosterol inhibits growth of HT-29 human colon cancer cells by activating the sphingomyelin cycle. Anticancer Res. 1998;18:471-3 pubmed..Sterol supplementation had no effect on phospholipase C, a key enzyme in the PKC pathway. We concluded that the activation of the SM cycle may play a role in growth inhibition of HT-29 cells by SIT. ..
- Normén A, Brants H, Voorrips L, Andersson H, van den Brandt P, Goldbohm R. Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study on Diet and Cancer. Am J Clin Nutr. 2001;74:141-8 pubmed..A high dietary intake of plant sterols was not associated with a lower risk of colon and rectal cancers in the Netherlands Cohort Study on Diet and Cancer. ..
- Awad A, Fink C, Williams H, Kim U. In vitro and in vivo (SCID mice) effects of phytosterols on the growth and dissemination of human prostate cancer PC-3 cells. Eur J Cancer Prev. 2001;10:507-13 pubmed..beta-Sitosterol was more effective than campesterol in offering this protection in most of the parameters studied. ..
- Miettinen T, Railo M, Lepantalo M, Gylling H. Plant sterols in serum and in atherosclerotic plaques of patients undergoing carotid endarterectomy. J Am Coll Cardiol. 2005;45:1794-801 pubmed..However, the role of dietary plant sterols in the development of atherosclerotic plaque is not known. ..
- Awad A, Chinnam M, Fink C, Bradford P. beta-Sitosterol activates Fas signaling in human breast cancer cells. Phytomedicine. 2007;14:747-54 pubmed..These findings support the hypothesis that beta-sitosterol is an effective apoptosis-promoting agent and that incorporation of more phytosterols in the diet may serve a preventive measure for breast cancer. ..
- Ketomaki A, Gylling H, Miettinen T. Effects of plant stanol and sterol esters on serum phytosterols in a family with familial hypercholesterolemia including a homozygous subject. J Lab Clin Med. 2004;143:255-62 pubmed
- Plat J, Mensink R. Effects of plant sterols and stanols on lipid metabolism and cardiovascular risk. Nutr Metab Cardiovasc Dis. 2001;11:31-40 pubmed..However, post-marketing surveillance for example for functional foods in general is necessary to monitor possible adverse effects and describe consumers and consumption patterns. ..
- Ostlund R, McGill J, Zeng C, Covey D, Stearns J, Stenson W, et al. Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans. Am J Physiol Endocrinol Metab. 2002;282:E911-6 pubmed..We conclude that the efficiency of phytosterol absorption is lower than what was reported previously and is critically dependent on the structure of both sterol nucleus and side chain. ..
- Hallikainen M, Sarkkinen E, Wester I, Uusitupa M. Short-term LDL cholesterol-lowering efficacy of plant stanol esters. BMC Cardiovasc Disord. 2002;2:14 pubmed..3% less than the initial value (P = ns). The specific effect of plant stanol esters on serum LDL cholesterol can fully be obtained within 1-2 weeks of the use of plant stanol ester-enriched margarine. ..
- Atiyeh B, El Musa K, Dham R. Scar quality and physiologic barrier function restoration after moist and moist-exposed dressings of partial-thickness wounds. Dermatol Surg. 2003;29:14-20 pubmed..Moreover, the observed improved anatomic and physiologic healing indicates that MEBO may have a positive effect on healing more that the mere fact of passive moisture retention. ..
- Miettinen T, Gylling H. The effects of statins and sitosterols: benefit or not?. Curr Atheroscler Rep. 2009;11:23-7 pubmed..No convincing evidence is available that statin-induced phytosterolemia worsens atherosclerosis. ..
- Rader D, Cohen J, Hobbs H. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest. 2003;111:1795-803 pubmed
- Yu H, Pandit B, Klett E, Lee M, Lu K, Helou K, et al. The rat STSL locus: characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats. BMC Cardiovasc Disord. 2003;3:4 pubmed..This mutation allows for expression and apparent apical targeting of Abcg5 protein in the intestine. These rat strains may therefore allow us to study the pathophysiological mechanisms involved in the human disease of sitosterolemia. ..
- Fassbender K, Lutjohann D, Dik M, Bremmer M, König J, Walter S, et al. Moderately elevated plant sterol levels are associated with reduced cardiovascular risk--the LASA study. Atherosclerosis. 2008;196:283-8 pubmed..These data suggest that plant sterols could have neutral or even protective effects on development of coronary heart disease, which have to be confirmed in interventional trials. ..
- Plat J, Bragt M, Mensink R. Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers. J Lipid Res. 2005;46:68-75 pubmed
- Imanaka H, Koide H, Shimizu K, Asai T, Kinouchi Shimizu N, Ishikado A, et al. Chemoprevention of tumor metastasis by liposomal beta-sitosterol intake. Biol Pharm Bull. 2008;31:400-4 pubmed..These results suggest that daily liposomal beta-sitosterol intake prevents tumor metastasis may be due to enhancement of gut immune surveillance systems. ..
- Hallikainen M, Uusitupa M. Effects of 2 low-fat stanol ester-containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects. Am J Clin Nutr. 1999;69:403-10 pubmed..They offer an additional, clinically significant reduction in serum cholesterol concentrations to that obtained with a low-fat diet alone. ..
- Ratnayake W, Plouffe L, Hollywood R, L Abbé M, Hidiroglou N, Sarwar G, et al. Influence of sources of dietary oils on the life span of stroke-prone spontaneously hypertensive rats. Lipids. 2000;35:409-20 pubmed
- Lee M, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, et al. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet. 2001;27:79-83 pubmed..H.L. et al., manuscript submitted). We now report that a new member of the ABC transporter family, ABCG5, is mutant in nine unrelated sitosterolemia patients...
- Lu K, Lee M, Carpten J, Sekhon M, Patel S. High-resolution physical and transcript map of human chromosome 2p21 containing the sitosterolaemia locus. Eur J Hum Genet. 2001;9:364-74 pubmed..These results will not only facilitate cloning of the sitosterolaemia gene, but also other disease genes located in this region, and accelerate sequencing of the corresponding genomic clones. ..
- Salen G, von Bergmann K, Lutjohann D, Kwiterovich P, Kane J, Patel S, et al. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation. 2004;109:966-71 pubmed..As a consequence of markedly elevated plasma and tissue sitosterol and campesterol levels, premature atherosclerosis develops...
- Vivancos M, Moreno J. beta-Sitosterol modulates antioxidant enzyme response in RAW 264.7 macrophages. Free Radic Biol Med. 2005;39:91-7 pubmed..We also demonstrate that the effects of beta-sitosterol on antioxidant enzymes depend on the estrogen/phosphatidylinositol 3-kinase pathway. ..
- Lu K, Lee M, Patel S. Dietary cholesterol absorption; more than just bile. Trends Endocrinol Metab. 2001;12:314-20 pubmed..Such studies are now beginning to throw light on sterol absorption and excretion and elucidate the molecular mechanisms that govern these processes. ..
- Noakes M, Clifton P, Ntanios F, Shrapnel W, Record I, McInerney J. An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations. Am J Clin Nutr. 2002;75:79-86 pubmed
- Awad A, Burr A, Fink C. Effect of resveratrol and beta-sitosterol in combination on reactive oxygen species and prostaglandin release by PC-3 cells. Prostaglandins Leukot Essent Fatty Acids. 2005;72:219-26 pubmed
- Sutherland W, Scott R, Lintott C, Robertson M, Stapely S, Cox C. Plasma non-cholesterol sterols in patients with non-insulin dependent diabetes mellitus. Horm Metab Res. 1992;24:172-5 pubmed..295, P = 0.034). The results of this study suggest that absorption of plant sterols and possibly cholesterol from the diet may be reduced in hyperinsulinemic diabetics. ..
- Lee M, Lu K, Patel S. Genetic basis of sitosterolemia. Curr Opin Lipidol. 2001;12:141-9 pubmed..Indeed, it is the very existence of this disease that has given credence to the hypothesis that there is a molecular pathway that regulates dietary cholesterol absorption and sterol excretion by the body. ..
- Hallikainen M, Lyyra Laitinen T, Laitinen T, Agren J, Pihlajamaki J, Rauramaa R, et al. Endothelial function in hypercholesterolemic subjects: Effects of plant stanol and sterol esters. Atherosclerosis. 2006;188:425-32 pubmed..2% (p=0.012) from STAEST. In conclusion, variables of cholesterol metabolism are associated with brachial artery diameter at baseline. STEEST diminishes brachial artery diameter, but its clinical relevance remains unclear. ..
- Graf G, Yu L, Li W, Gerard R, Tuma P, Cohen J, et al. ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J Biol Chem. 2003;278:48275-82 pubmed..Finally, adenoviral expression of G2 in the presence or absence of G5 or G8 failed to promote sterol excretion into bile. These experiments indicate that G5 and G8 function as obligate heterodimers to promote sterol excretion into bile...
- Sudhop T, Gottwald B, von Bergmann K. Serum plant sterols as a potential risk factor for coronary heart disease. Metabolism. 2002;51:1519-21 pubmed..These findings support the hypothesis that plant sterols might be an additional risk factor for CHD. ..