DOI QR코드

DOI QR Code

Food Ingredients That Inhibit Cholesterol Absorption

  • Jesch, Elliot D. ;
  • Carr, Timothy P.
  • 투고 : 2017.03.27
  • 심사 : 2017.05.23
  • 발행 : 2017.06.30

초록

Cholesterol is a vital component of the human body. It stabilizes cell membranes and is the precursor of bile acids, vitamin D and steroid hormones. However, cholesterol accumulation in the bloodstream (hypercholesterolemia) can cause atherosclerotic plaques within artery walls, leading to heart attacks and strokes. The efficiency of cholesterol absorption in the small intestine is of great interest because human and animal studies have linked cholesterol absorption with plasma concentration of total and low density lipoprotein cholesterol. Cholesterol absorption is highly regulated and influenced by particular compounds in the food supply. Therefore, it is desirable to learn more about natural food components that inhibit cholesterol absorption so that food ingredients and dietary supplements can be developed for consumers who wish to manage their plasma cholesterol levels by non-pharmacological means. Food components thus far identified as inhibitors of cholesterol absorption include phytosterols, soluble fibers, phospholipids, and stearic acid.

키워드

cholesterol absorption;functional food;nutraceutical;dietary supplement

참고문헌

  1. Horikawa K, Hashimoto C, Kikuchi Y, Makita M, Fukudome SI, Okita K, Wada N, Oishi K. 2017. Wheat alkylresorcinols reduce micellar solubility of cholesterol in vitro and increase cholesterol excretion in mice. Nat Prod Res 31: 578-582. https://doi.org/10.1080/14786419.2016.1198347
  2. Castano G, Mas R, Fernandez L, Illnait J, Mesa M, Alvarez E, Lezcay M. 2003. Comparison of the efficacy and tolerability of policosanol with atorvastatin in elderly patients with type II hypercholesterolaemia. Drugs Aging 20: 153-163. https://doi.org/10.2165/00002512-200320020-00006
  3. Harwood HJ Jr, Chandler CE, Pellarin LD, Bangerter FW, Wilkins RW, Long CA, Cosgrove PG, Malinow MR, Marzetta CA, Pettini JL, Savoy YE, Mayne JT. 1993. Pharmacologic consequences of cholesterol absorption inhibition: alteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin $beta$-tigogenin cellobioside (CP-88818; tiqueside). J Lipid Res 34: 377-395.
  4. Oishi K, Yamamoto S, Itoh N, Nakao R, Yasumoto Y, Tanaka K, Kikuchi Y, Fukudome S, Okita K, Takano-Ishikawa Y. 2015. Wheat alkylresorcinols suppress high-fat, high-sucrose diet-induced obesity and glucose intolerance by increasing insulin sensitivity and cholesterol excretion in male mice. J Nutr 145: 199-206. https://doi.org/10.3945/jn.114.202754
  5. Torres O, Agramonte AJ, Illnait J, Mas Ferreiro R, Fernandez L, Fernandez JC. 1995. Treatment of hypercholesterolemia in NIDDM with policosanol. Diabetes Care 18: 393-397. https://doi.org/10.2337/diacare.18.3.393
  6. Swanson B, Keithley JK, Sha BE, Fogg L, Nerad J, Novak RM, Adeyemi O, Spear GT. 2011. Policosanol for managing human immunodeficiency virus-related dyslipidemia in a medically underserved population: a randomized, controlled clinical trial. Altern Ther Health Med 17: 30-35.
  7. Vyas KY, Bedarkar P, Galib R, Prajapati PK. 2015. Comparative anti-hyperlipidaemic activity of Navina (fresh) and Purana (old) Guggulu. Anc Sci Life 35: 101-109. https://doi.org/10.4103/0257-7941.171672
  8. Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ, Moore DD. 2002. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 296: 1703-1706. https://doi.org/10.1126/science.1072891
  9. Furune T, Ikuta N, Ishida Y, Okamoto H, Nakata D, Terao K, Sakamoto N. 2014. A study on the inhibitory mechanism for cholesterol absorption by $alpha$-cyclodextrin administration. Beilstein J Org Chem 10: 2827-2835. https://doi.org/10.3762/bjoc.10.300
  10. Zimmer S, Grebe A, Bakke SS, Bode N, Halvorsen B, Ulas T, Skjelland M, De Nardo D, Labzin L, Kerksiek A, Hempel C, Heneka MT, Hawxhurst V, Fitzgerald ML, Trebicka J, Bjorkhem I, Gustafsson JA, Westerterp M, Tall AR, Wright SD, Espevik T, Schultze JL, Nickenig G, Lütjohann D, Latz E. 2016. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Sci Transl Med 8: 333ra50. https://doi.org/10.1126/scitranslmed.aad6100
  11. Sun J, Buys N. 2015. Effects of probiotics consumption on lowering lipids and CVD risk factors: a systematic review and meta-analysis of randomized controlled trials. Ann Med 47: 430-440. https://doi.org/10.3109/07853890.2015.1071872
  12. Reis SA, Conceicao LL, Rosa DD, Siqueira NP, Peluzio MCG. 2016. Mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotics. Nutr Res Rev 30: 36-49.
  13. Gestetner B, Assa Y, Henis Y, Tencer Y, Rotman M, Birk Y, Bondi A. 1972. Interaction of lucerne saponins with sterols. Biochim Biophys Acta 270: 181-187. https://doi.org/10.1016/0005-2760(72)90190-7
  14. Vinarova L, Vinarov Z, Atanasov V, Pantcheva I, Tcholakova S, Denkov N, Stoyanov S. 2015. Lowering of cholesterol bioaccessibility and serum concentrations by saponins: in vitro and in vivo studies. Food Funct 6: 501-512. https://doi.org/10.1039/C4FO00785A
  15. Feldman EB, Russell BS, Schnare FH, Moretti-Rojas I, Miles BC, Doyle EA. 1979. Effects of diets of homogeneous saturated triglycerides on cholesterol balance in rats. J Nutr 109: 2237-2246. https://doi.org/10.1093/jn/109.12.2237
  16. Feldman EB, Russell BS, Schnare FH, Miles BC, Doyle EA, Moretti-Rojas I. 1979. Effects of tristearin, triolein and safflower oil diets on cholesterol balance in rats. J Nutr 109: 2226-2236. https://doi.org/10.1093/jn/109.12.2226
  17. Chen IS, Subramaniam S, Vahouny GV, Cassidy MM, Ikeda I, Kritchevsky D. 1989. A comparison of the digestion and absorption of cocoa butter and palm kernel oil and their effects on cholesterol absorption in rats. J Nutr 119: 1569-1573. https://doi.org/10.1093/jn/119.11.1569
  18. Ikeda I, Imasato Y, Nakayama M, Imaizumi K, Sugano M. 1994. Lymphatic transport of stearic acid and its effect on cholesterol transport in rats. J Nutr Sci Vitaminol 40: 275-282. https://doi.org/10.3177/jnsv.40.275
  19. Schneider CL, Cowles RL, Stuefer-Powell CL, Carr TP. 2000. Dietary stearic acid reduces cholesterol absorption and increases endogenous cholesterol excretion in hamsters fed cereal-based diets. J Nutr 130: 1232-1238. https://doi.org/10.1093/jn/130.5.1232
  20. Imaizumi K, Abe K, Kuroiwa C, Sugano M. 1993. Fat containing stearic acid increases fecal neutral steroid excretion and catabolism of low density lipoproteins without affecting plasma cholesterol concentration in hamsters fed a cholesterol- containing diet. J Nutr 123: 1693-1702. https://doi.org/10.1093/jn/123.10.1693
  21. Kamei M, Ohgaki S, Kanbe T, Niiya I, Mizutani H, Matsui- Yuasa I, Otani S, Morita S. 1995. Effects of highly hydrogenated soybean oil and cholesterol on plasma, liver cholesterol, and fecal steroids in rats. Lipids 30: 533-539. https://doi.org/10.1007/BF02537028
  22. Schmidt K, Gallaher D. 1997. Reduced cholesterol absorption and intestinal solubilization by stearic acid-rich fats in rats. Abstract No A378 presented at Experimental Biology 97. New Orleans, LA, USA.
  23. Wang S, Koo SI. 1993. Plasma clearance and hepatic utilization of stearic, myristic and linoleic acids introduced via chylomicrons in rats. Lipids 28: 697-703. https://doi.org/10.1007/BF02535989
  24. Wang S, Koo S. 1993. Evidence for distinct metabolic utilization of stearic acid in comparison with palmitic and oleic acids in rats. J Nutr Biochem 4: 594-601. https://doi.org/10.1016/0955-2863(93)90028-U
  25. Cohen DE, Carey MC. 1991. Acyl chain unsaturation modulates distribution of lecithin molecular species between mixed micelles and vesicles in model bile. Implications for particle structure and metastable cholesterol solubilities. J Lipid Res 32: 1291-1302.
  26. Cowles RL, Lee JY, Gallaher DD, Stuefer-Powell CL, Carr TP. 2002. Dietary stearic acid alters gallbladder bile acid composition in hamsters fed cereal-based diets. J Nutr 132: 3119-3122. https://doi.org/10.1093/jn/131.10.3119
  27. Hassel CA, Mensing EA, Gallaher DD. 1997. Dietary stearic acid reduces plasma and hepatic cholesterol concentrations without increasing bile acid excretion in cholesterol-fed hamsters. J Nutr 127: 1148-1155. https://doi.org/10.1093/jn/127.6.1148
  28. Patton JS, Carey MC. 1981. Inhibition of human pancreatic lipase-colipase activity by mixed bile salt-phospholipid micelles. Am J Physiol 241: G328-G336.
  29. Young SC, Hui DY. 1999. Pancreatic lipase/colipase-mediated triacylglycerol hydrolysis is required for cholesterol transport from lipid emulsions to intestinal cells. Biochem J 339: 615-620. https://doi.org/10.1042/bj3390615
  30. Homan R, Hamelehle KL. 1998. Phospholipase A2 relieves phosphatidylcholine inhibition of micellar cholesterol absorption and transport by human intestinal cell line Caco-2. J Lipid Res 39: 1197-1209.
  31. van Dijck PW. 1979. Negatively charged phospholipids and their position in the cholesterol affinity sequence. Biochim Biophys Acta 555: 89-101. https://doi.org/10.1016/0005-2736(79)90074-9
  32. Halling KK, Ramstedt B, Nystrom JH, Slotte JP, Nyholm TKM. 2008. Cholesterol interactions with fluid-phase phospholipids: effect on the lateral organization of the bilayer. Biophys J 95: 3861-3871. https://doi.org/10.1529/biophysj.108.133744
  33. Engberg O, Hautala V, Yasuda T, Dehio H, Murata M, Slotte JP, Nyholm TKM. 2016. The affinity of cholesterol for different phospholipids affects lateral segregation in bilayers. Biophys J 111: 546-556. https://doi.org/10.1016/j.bpj.2016.06.036
  34. Garmy N, Taïeb N, Yahi N, Fantini J. 2004. Interaction of cholesterol with sphingosine: physicochemical characterization and impact on intestinal absorption. J Lipid Res 46: 36-45.
  35. Zhang P, Chen Y, Cheng Y, Hertervig E, Ohlsson L, Nilsson A, Duan RD. 2014. Alkaline sphingomyelinase (NPP7) promotes cholesterol absorption by affecting sphingomyelin levels in the gut: a study with NPP7 knockout mice. Am J Physiol Gastrointest Liver Physiol 306: G903-G908. https://doi.org/10.1152/ajpgi.00319.2013
  36. Bhattacharyya DK. 2002. Lesser-known Indian plant sources for fats and oils. Inform 13: 151-157.
  37. Keys A, Anderson JT, Grande F. 1965. Serum cholesterol response to changes in the diet: IV. Particular saturated fatty acids in the diet. Metabolism 14: 776-787. https://doi.org/10.1016/0026-0495(65)90004-1
  38. Hegsted DM, McGandy RB, Myers ML, Stare FJ. 1965. Quantitative effects of dietary fat on serum cholesterol in man. Am J Clin Nutr 17: 281-295. https://doi.org/10.1093/ajcn/17.5.281
  39. Hunter JE, Zhang J, Kris-Etherton PM. 2010. Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review. Am J Clin Nutr 91: 46-63. https://doi.org/10.3945/ajcn.2009.27661
  40. Grundy SM, Denke MA. 1990. Dietary influences on serum lipids and lipoproteins. J Lipid Res 31: 1149-1172.
  41. Kris-Etherton PM, Yu S. 1997. Individual fatty acid effects on plasma lipids and lipoproteins: human studies. Am J Clin Nutr 65: 1628S-1644S. https://doi.org/10.1093/ajcn/65.5.1628S
  42. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, Erdman JW Jr, Kris-Etherton P, Goldberg IJ, Kotchen TA, Lichtenstein AH, Mitch WE, Mullis R, Robinson K, Wylie-Rosett J, St Jeor S, Suttie J, Tribble DL, Bazzarre TL. 2000. AHA Dietary Guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 102: 2284-2299. https://doi.org/10.1161/01.CIR.102.18.2284
  43. Demel RA, Jansen JWCM, van Dijck PWM, van Deenen LLM. 1977. The preferential interactions of cholesterol with different classes of phospholipids. Biochim Biophys Acta 465: 1-10. https://doi.org/10.1016/0005-2736(77)90350-9
  44. McIntosh TJ, Simon SA, Needham D, Huang CH. 1992. Structure and cohesive properties of sphingomyelin/cholesterol bilayers. Biochemistry 31: 2012-2020. https://doi.org/10.1021/bi00122a017
  45. Rampone AJ. 1972. Bile salt and non-bile salt components in bile affecting micellar cholesterol uptake by rat intestine in vitro. J Physiol 227: 889-898. https://doi.org/10.1113/jphysiol.1972.sp010064
  46. Rampone AJ. 1973. The effect of lecithin on intestinal cholesterol uptake by rat intestine in vitro. J Physiol 229: 505-514. https://doi.org/10.1113/jphysiol.1973.sp010150
  47. Beil FU, Grundy SM. 1980. Studies on plasma lipoproteins during absorption of exogenous lecithin in man. J Lipid Res 21: 525-536.
  48. Kesaniemi YA, Grundy SM. 1986. Effects of dietary polyenylphosphatidylcholine on metabolism of cholesterol and triglycerides in hypertriglyceridemic patients. Am J Clin Nutr 43: 98-107. https://doi.org/10.1093/ajcn/43.1.98
  49. Koo SI, Noh SK. 2001. Phosphatidylcholine inhibits and lysophosphatidylcholine enhances the lymphatic absorption of $\alpha$-tocopherol in adult rats. J Nutr 131: 717-722. https://doi.org/10.1093/jn/131.3.717
  50. Jiang Y, Noh SK, Koo SI. 2001. Egg phosphatidylcholine decreases the lymphatic absorption of cholesterol in rats. J Nutr 131: 2358-2363. https://doi.org/10.1093/jn/131.9.2358
  51. Nyberg L, Duan RD, Nilsson A. 2000. A mutual inhibitory effect on absorption of sphingomyelin and cholesterol. J Nutr Biochem 11: 244-249. https://doi.org/10.1016/S0955-2863(00)00069-3
  52. Noh SK, Koo SI. 2003. Egg sphingomyelin lowers the lymphatic absorption of cholesterol and $\alpha$-tocopherol in rats. J Nutr 133: 3571-3576. https://doi.org/10.1093/jn/133.11.3571
  53. Noh SK, Koo SI. 2004. Milk sphingomyelin is more effective than egg sphingomyelin in inhibiting intestinal absorption of cholesterol and fat in rats. J Nutr 134: 2611-2616. https://doi.org/10.1093/jn/134.10.2611
  54. Chung RW, Kamili A, Tandy S, Weir JM, Gaire R, Wong G, Meikle PJ, Cohn JS, Rye KA. 2013. Dietary sphingomyelin lowers hepatic lipid levels and inhibits intestinal cholesterol absorption in high-fat-fed mice. PLoS One 8: e55949. https://doi.org/10.1371/journal.pone.0055949
  55. Duivenvoorden I, Voshol PJ, Rensen PC, van Duyvenvoorde W, Romijn JA, Emeis JJ, Havekes LM, Nieuwenhuizen WF. 2006. Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis in APOE*3Leiden mice. Am J Clin Nutr 84: 312-321.
  56. Ohlsson L, Burling H, Nilsson A. 2009. Long term effects on human plasma lipoproteins of a formulation enriched in butter milk polar lipid. Lipids Health Dis 8: 44. https://doi.org/10.1186/1476-511X-8-44
  57. Ramprasath VR, Jones PJ, Buckley DD, Woollett LA, Heubi JE. 2013. Effect of dietary sphingomyelin on absorption and fractional synthetic rate of cholesterol and serum lipid profile in humans. Lipids Health Dis 12: 125. https://doi.org/10.1186/1476-511X-12-125
  58. Borgstrom B. 1980. Importance of phospholipids, pancreatic phospholipase A2, and fatty acid for the digestion of dietary fat: in vitro experiments with the porcine enzymes. Gastroenterology 78: 954-962.
  59. Kang J, Lee J, Kwon D, Song Y. 2013. Effect of Opuntia humifusa supplementation and acute exercise on insulin sensitivity and associations with PPAR-$gamma$ and PGC-$1{\alpha}$ protein expression in skeletal muscle of rats. Int J Mol Sci 14: 7140-7154. https://doi.org/10.3390/ijms14047140
  60. Grube B, Chong PW, Lau KZ, Orzechowski HD. 2013. A natural fiber complex reduces body weight in the overweight and obese: a double-blind, randomized, placebo-controlled study. Obesity 21: 58-64. https://doi.org/10.1002/oby.20244
  61. Parnell JA, Reimer RA. 2010. Effect of prebiotic fibre supplementation on hepatic gene expression and serum lipids: a dose-response study in JCR:LA-cp rats. Br J Nutr 103: 1577-1584. https://doi.org/10.1017/S0007114509993539
  62. Vahouny GV, Satchithanandam S, Chen I, Tepper SA, Kritchevsky D, Lightfoot FG, Cassidy MM. 1988. Dietary fiber and intestinal adaptation: effects on lipid absorption and lymphatic transport in the rat. Am J Clin Nutr 47: 201-206. https://doi.org/10.1093/ajcn/47.2.201
  63. Ebihara K, Schneeman BO. 1989. Interaction of bile acids, phospholipids, cholesterol and triglyceride with dietary fibers in the small intestine of rats. J Nutr 119: 1100-1106. https://doi.org/10.1093/jn/119.8.1100
  64. Miettinen TA, Tarpila S. 1989. Serum lipids and cholesterol metabolism during guar gum, plantago ovata and high fibre treatments. Clin Chim Acta 183: 253-262. https://doi.org/10.1016/0009-8981(89)90359-8
  65. Evans AJ, Hood RL, Oakenfull DG, Sidhu GS. 1992. Relationship between structure and function of dietary fibre: a comparative study of the effects of three galactomannans on cholesterol metabolism in the rat. Br J Nutr 68: 217-229. https://doi.org/10.1079/BJN19920079
  66. Mathé D, Lutton C, Rautureau J, Coste T, Gouffier E, Sulpice JC, Chevallier F. 1977. Effects of dietary fiber and salt mixtures on the cholesterol metabolism of rats. J Nutr 107: 466-474. https://doi.org/10.1093/jn/107.3.466
  67. Fernandez ML, Lin EC, Trejo A, McNamara DJ. 1994. Prickly pear (Opuntia sp.) pectin alters hepatic cholesterol metabolism without affecting cholesterol absorption in guinea pigs fed a hypercholesterolemic diet. J Nutr 124: 817-824. https://doi.org/10.1093/jn/124.6.817
  68. Johnson IT, Gee JM. 1981. Effect of gel-forming gums on the intestinal unstirred layer and sugar transport in vitro. Gut 22: 398-403. https://doi.org/10.1136/gut.22.5.398
  69. Flourie B, Vidon N, Florent CH, Bernier JJ. 1984. Effect of pectin on jejunal glucose absorption and unstirred layer thickness in normal man. Gut 25: 936-941. https://doi.org/10.1136/gut.25.9.936
  70. Turley SD, Daggy BP, Dietschy JM. 1991. Cholesterol-lowering action of psyllium mucilloid in the hamster: sites and possible mechanisms of action. Metabolism 40: 1063-1073. https://doi.org/10.1016/0026-0495(91)90131-F
  71. Turley SD, Daggy BP, Dietschy JM. 1994. Psyllium augments the cholesterol-lowering action of cholestyramine in hamsters by enhancing sterol loss from the liver. Gastroenterology 107: 444-452. https://doi.org/10.1016/0016-5085(94)90170-8
  72. Eckhardt ER, Wang DQ, Donovan JM, Carey MC. 2002. Dietary sphingomyelin suppresses intestinal cholesterol absorption by decreasing thermodynamic activity of cholesterol monomers. Gastroenterology 122: 948-956. https://doi.org/10.1053/gast.2002.32539
  73. Yeagle PL, Hutton WC, Huang CH, Martin RB. 1976. Structure in the polar head region of phospholipid bilayers: a $^{31}P$ ${^{1}H}$ nuclear Overhauser effect study. Biochemistry 15: 2121- 2124. https://doi.org/10.1021/bi00655a014
  74. Zhu RG, Sun YD, Li TP, Chen G, Peng X, Duan WB, Zheng ZZ, Shi SL, Xu JG, Liu YH, Jin XY. 2015. Comparative effects of hawthorn (Crataegus pinnatifida Bunge) pectin and pectin hydrolyzates on the cholesterol homeostasis of hamsters fed high-cholesterol diets. Chem Biol Interact 238: 42-47. https://doi.org/10.1016/j.cbi.2015.06.006
  75. Bell S, Goldman VM, Bistrian BR, Arnold AH, Ostroff G, Forse RA. 1999. Effect of $beta$-glucan from oats and yeast on serum lipids. Crit Rev Food Sci Nutr 39: 189-202. https://doi.org/10.1080/10408399908500493
  76. Queenan KM, Stewart ML, Smith KN, Thomas W, Fulcher RG, Slavin JL. 2007. Concentrated oat $beta$-glucan, a fermentable fiber, lowers serum cholesterol in hypercholesterolemic adults in a randomized controlled trial. Nutr J 6: 6. https://doi.org/10.1186/1475-2891-6-6
  77. Schneeman BO. 1999. Fiber, inulin and oligofructose: similarities and differences. J Nutr 129: 1424S-1427S. https://doi.org/10.1093/jn/129.7.1424S
  78. Boeckner LS, Schnepf MI, Tungland BC. 2001. Inulin: a review of nutritional and health implications. Adv Food Nutr Res 43: 1-63.
  79. Pszczola DE. 2003. Plot thickens, as gums add special effects ingredients. Food Technol 57: 34-47.
  80. Khan AR, Khan GY, Mitchel A, Qadeer MA. 1981. Effect of guar gum on blood lipids. Am J Clin Nutr 34: 2446-2449. https://doi.org/10.1093/ajcn/34.11.2446
  81. Kelley JJ, Tsai AC. 1978. Effect of pectin, gum arabic and agar on cholesterol absorption, synthesis, and turnover in rats. J Nutr 108: 630-639. https://doi.org/10.1093/jn/108.4.630
  82. Pande S, Platel K, Srinivasan K. 2012. Antihypercholesterolaemic influence of dietary tender cluster beans (Cyamopsis tetragonoloba) in cholesterol fed rats. Indian J Med Res 135: 401-406.
  83. Mohamed RE, Gadour MO, Adam I. 2015. The lowering effect of Gum Arabic on hyperlipidemia in Sudanese patients. Front Physiol 6: 160.
  84. Kendall CWC, Emam A, Augustin LSA, Jenkins DJA. 2004. Resistant starches and health. J AOAC Int 87: 769-774.
  85. Haub MD, Hubach KL, Al-tamimi EK, Ornelas S, Seib PA. 2010. Different types of resistant starch elicit different glucose reponses in humans. J Nutr Metab (Online) 10.1155/ 2010/230501. https://doi.org/10.1155/2010/230501
  86. Martínez I, Kim J, Duffy PR, Schlegel VL, Walter J. 2010. Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLoS One 5: e15046. https://doi.org/10.1371/journal.pone.0015046
  87. Nichenametla SN, Weidauer LA, Wey HE, Beare TM, Specker BL, Dey M. 2014. Resistant starch type 4-enriched diet lowered blood cholesterols and improved body composition in a double blind controlled cross-over intervention. Mol Nutr Food Res 58: 1365-1369. https://doi.org/10.1002/mnfr.201300829
  88. Kuo SM. 2013. The interplay between fiber and the intestinal microbiome in the inflammatory response. Adv Nutr 4: 16-28. https://doi.org/10.3945/an.112.003046
  89. Hamaker BR, Tuncil YE. 2014. A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota. J Mol Biol 426: 3838-3850. https://doi.org/10.1016/j.jmb.2014.07.028
  90. Yamaoka I, Kikuchi T, Endo N, Ebisu G. 2014. Fluorescence imaging in vivo visualizes delayed gastric emptying of liquid enteral nutrition containing pectin. BMC Gastroenterol 14:168. https://doi.org/10.1186/1471-230X-14-168
  91. Gylling H, Miettinen TA. 1995. The effect of cholesterol absorption inhibition on low density lipoprotein cholesterol level. Atherosclerosis 117: 305-308. https://doi.org/10.1016/0021-9150(95)05566-F
  92. Carr TP, Gallaher DD, Yang CH, Hassel CA. 1996. Increased intestinal contents viscosity reduces cholesterol absorption efficiency in hamsters fed hydroxypropyl methylcellulose. J Nutr 126: 1463-1469. https://doi.org/10.1093/jn/126.5.1463
  93. Carr TP, Cornelison RM, Illston BJ, Stuefer-Powell CL, Gallaher DD. 2002. Plant sterols alter bile acid metabolism and reduce cholesterol absorption in hamsters fed a beefbased diet. Nutr Res 22: 745-754. https://doi.org/10.1016/S0271-5317(02)00389-5
  94. Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP. 2004. Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science 303: 1201-1204. https://doi.org/10.1126/science.1093131
  95. Burnett DA. 2004. $beta$-Lactam cholesterol absorption inhibitors. Curr Med Chem 11: 1873-1887. https://doi.org/10.2174/0929867043364865
  96. Mc Auley MT, Wilkinson DJ, Jones JJ, Kirkwood TB. 2012. A whole-body mathematical model of cholesterol metabolism and its age-associated dysregulation. BMC Syst Biol 6:130. https://doi.org/10.1186/1752-0509-6-130
  97. Briefel RR, Johnson CL. 2004. Secular trends in dietary intake in the United States. Annu Rev Nutr 24: 401-431. https://doi.org/10.1146/annurev.nutr.23.011702.073349
  98. Valsta LM, Lemstrom A, Ovaskainen ML, Lampi AM, Toivo J, Korhonen T, Piironen V. 2004. Estimation of plant sterol and cholesterol intake in Finland: quality of new values and their effect on intake. Br J Nutr 92: 671-678. https://doi.org/10.1079/BJN20041234
  99. Ishinaga M, Ueda A, Mochizuki T, Sugiyama S, Kobayashi T. 2005. Cholesterol intake is associated with lecithin intake in Japanese people. J Nutr 135: 1451-1455. https://doi.org/10.1093/jn/135.6.1451
  100. Kesaniemi YA, Miettinen TA. 1987. Cholesterol absorption efficiency regulates plasma cholesterol level in the Finnish population. Eur J Clin Invest 17: 391-395. https://doi.org/10.1111/j.1365-2362.1987.tb01132.x
  101. Rudel L, Deckelman C, Wilson M, Scobey M, Anderson R. 1994. Dietary cholesterol and downregulation of cholesterol 7 alpha-hydroxylase and cholesterol absorption in African green monkeys. J Clin Invest 93: 2463-2472. https://doi.org/10.1172/JCI117255
  102. Grundy SM, Metzger AL. 1972. A physiological method for estimation of hepatic secretion of biliary lipids in man. Gastroenterology 62: 1200-1217.
  103. Duane WC. 1993. Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects. J Clin Invest 92: 911-918. https://doi.org/10.1172/JCI116666
  104. Yao L, Heubi JE, Buckley DD, Fierra H, Setchell KD, Granholm NA, Tso P, Hui DY, Woollett LA. 2002. Separation of micelles and vesicles within lumenal aspirates from healthy humans: solubilization of cholesterol after a meal. J Lipid Res 43: 654-660.
  105. Dawson PA, Oelkers P. 1995. Bile acid transporters. Curr Opin Lipidol 6: 109-114. https://doi.org/10.1097/00041433-199504000-00009
  106. Packard CJ, Shepherd J. 1982. The hepatobiliary axis and lipoprotein metabolism: effects of bile acid sequestrants and ileal bypass surgery. J Lipid Res 23: 1081-1098.
  107. Hui DY, Howles PN. 2005. Molecular mechanisms of cholesterol absorption and transport in the intestine. Semin Cell Dev Biol 16: 183-192. https://doi.org/10.1016/j.semcdb.2005.01.003
  108. Davis HR Jr, Zhu LJ, Hoos LM, Tetzloff G, Maguire M, Liu J, Yao X, Iyer SP, Lam MH, Lund EG, Detmers PA, Graziano MP, Altmann SW. 2004. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem 279: 33586-33592. https://doi.org/10.1074/jbc.M405817200
  109. Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, Kwiterovich P, Shan B, Barnes R, Hobbs HH. 2000. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290: 1771-1775. https://doi.org/10.1126/science.290.5497.1771
  110. Lee MH, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivastava AK, Salen G, Dean M, Patel SB. 2001. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet 27: 79-83.
  111. Lee MH, Lu K, Patel SB. 2001. Genetic basis of sitosterolemia. Curr Opin Lipidol 12: 141-149. https://doi.org/10.1097/00041433-200104000-00007
  112. Singh V, Jain M, Misra A, Khanna V, Rana M, Prakash P, Malasoni R, Dwivedi AK, Dikshit M, Barthwal MK. 2013. Curcuma oil ameliorates hyperlipidaemia and associated deleterious effects in golden Syrian hamsters. Br J Nutr 110: 437-446. https://doi.org/10.1017/S0007114512005363
  113. Matthan NR, Lichtenstein AH. 2004. Approaches to measuring cholesterol absorption in humans. Atherosclerosis 174: 197-205. https://doi.org/10.1016/S0021-9150(03)00248-X
  114. Wilson MD, Rudel LL. 1994. Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. J Lipid Res 35: 943-955.
  115. Normen AL, Brants HA, Voorrips LE, Andersson HA, van den Brandt PA, Goldbohm RA. 2001. Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study on Diet and Cancer. Am J Clin Nutr 74: 141-148. https://doi.org/10.1093/ajcn/74.1.141
  116. Andersson SW, Skinner J, Ellegard L, Welch AA, Bingham S, Mulligan A, Andersson H, Khaw KT. 2004. Intake of dietary plant sterols is inversely related to serum cholesterol concentration in men and women in the EPIC Norfolk population: a cross-sectional study. Eur J Clin Nutr 58: 1378-1385. https://doi.org/10.1038/sj.ejcn.1601980
  117. de Vries JHM, Jansen A, Kromhout D, van de Bovenkamp P, van Staveren WA, Mensink RP, Katan MB. 1997. The fatty acid and sterol content of food composites of middle-aged men in seven countries. J Food Compos Anal 10: 115-141. https://doi.org/10.1006/jfca.1997.0525
  118. Sioen I, Matthys C, Huybrechts I, Van Camp J, De Henauw S. 2011. Consumption of plant sterols in Belgium: estimated intakes and sources of naturally occurring plant sterols and $beta$-carotene. Br J Nutr 105: 960-966. https://doi.org/10.1017/S0007114510004587
  119. Klingberg S, Ellegard L, Johansson I, Hallmans G, Weinehall L, Andersson H, Winkvist A. 2008. Inverse relation between dietary intake of naturally occurring plant sterols and serum cholesterol in northern Sweden. Am J Clin Nutr 87: 993-1001. https://doi.org/10.1093/ajcn/87.4.993
  120. Jimenez-Escrig A, Santos-Hidalgo AB, Saura-Calixto F. 2006. Common sources and estimated intake of plant sterols in the Spanish diet. J Agric Food Chem 54: 3462-3471. https://doi.org/10.1021/jf053188k
  121. Vuoristo M, Miettinen TA. 1994. Absorption, metabolism, and serum concentrations of cholesterol in vegetarians: effects of cholesterol feeding. Am J Clin Nutr 59: 1325-1331. https://doi.org/10.1093/ajcn/59.6.1325
  122. Zhou BF, Stamler J, Dennis B, Moag-Stahlberg A, Okuda N, Robertson C, Zhao L, Chan Q, Elliott P; INTERMAP Research Group. 2003. Nutrient intakes of middle-aged men and women in China, Japan, United Kingdom, and United States in the late 1990s: The INTERMAP Study. J Hum Hypertens 17: 623-630. https://doi.org/10.1038/sj.jhh.1001605
  123. Law M. 2000. Plant sterol and stanol margarines and health. BMJ 320: 861-864. https://doi.org/10.1136/bmj.320.7238.861
  124. Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R; Stresa Workshop Participants. 2003. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 78: 965-978. https://doi.org/10.1016/S0025-6196(11)63144-3
  125. AbuMweis SS, Barake R, Jones PJH. 2008. Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials. Food Nutr Res 52: DOI: 10.3402/fnr.v52i0.1811. https://doi.org/10.3402/fnr.v52i0.1811
  126. Demonty I, Ras RT, van der Knaap HC, Duchateau GS, Meijer L, Zock PL, Geleijnse JM, Trautwein EA. 2009. Continuous dose-response relationship of the LDL-cholesterollowering effect of phytosterol intake. J Nutr 139: 271-284. https://doi.org/10.3945/jn.108.095125
  127. Ras RT, Geleijnse JM, Trautwein EA. 2014. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br J Nutr 112: 214-219. https://doi.org/10.1017/S0007114514000750
  128. Nissinen M, Gylling H, Vuoristo M, Miettinen TA. 2002. Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am J Physiol Gastrointest Liver Physiol 282: G1009-G1015. https://doi.org/10.1152/ajpgi.00446.2001
  129. Trautwein EA, Duchateau GSMJE, Lin Y, Mel’nikov SM, Molhuizen HOF, Ntanios FY. 2003. Proposed mechanisms of cholesterol-lowering action of plant sterols. Eur J Lipid Sci Technol 105: 171-185. https://doi.org/10.1002/ejlt.200390033
  130. Armstrong MJ, Carey MC. 1987. Thermodynamic and molecular determinants of sterol solubilities in bile salt micelles. J Lipid Res 28: 1144-1155.
  131. Brown AW, Hang J, Dussault PH, Carr TP. 2010. Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase. J Nutr Biochem 21: 736-740. https://doi.org/10.1016/j.jnutbio.2009.04.008
  132. Carden TJ, Hang J, Dussault PH, Carr TP. 2015. Dietary plant sterol esters must be hydrolyzed to reduce intestinal cholesterol absorption in hamsters. J Nutr 145: 1402-1407. https://doi.org/10.3945/jn.114.207662
  133. Hofmann AF, Small DM. 1967. Detergent properties of bile salts: correlation with physiological function. Annu Rev Med 18: 333-376. https://doi.org/10.1146/annurev.me.18.020167.002001
  134. Ikeda I, Sugano M. 1983. Some aspects of mechanism of inhibition of cholesterol absorption by beta-sitosterol. Biochim Biophys Acta 732: 651-658. https://doi.org/10.1016/0005-2736(83)90243-2
  135. Ikeda I, Tanaka K, Sugano M, Vahouny GV, Gallo LL. 1988. Inhibition of cholesterol absorption in rats by plant sterols. J Lipid Res 29: 1573-1582.
  136. Ikeda I, Tanabe Y, Sugano M. 1989. Effects of sitosterol and sitostanol on micellar solubility of cholesterol. J Nutr Sci Vitaminol 35: 361-369. https://doi.org/10.3177/jnsv.35.361
  137. Jesch ED, Carr TP. 2006. Sitosterol reduces micellar cholesterol solubility in model bile. Nutr Res 26: 579-584. https://doi.org/10.1016/j.nutres.2006.08.006
  138. Heinemann T, Kullak-Ublick GA, Pietruck B, von Bergmann K. 1991. Mechanisms of action of plant sterols on inhibition of cholesterol absorption. Comparison of sitosterol and sitostanol. Eur J Clin Pharmacol 40: S59-S63. https://doi.org/10.1007/BF03216292
  139. Mel’nikov SM, Seijen ten Hoorn JWM, Eijkelenboom APAM. 2004. Effect of phytosterols and phytostanols on the solubilization of cholesterol by dietary mixed micelles: an in vitro study. Chem Phys Lipids 127: 121-141. https://doi.org/10.1016/j.chemphyslip.2003.09.015
  140. Christiansen L, Karjalainen M, Seppanen-Laakso T, Hiltunen R, Yliruusi J. 2003. Effect of $beta$-sitosterol on precipitation of cholesterol from non-aqueous and aqueous solutions. Int J Pharm 254: 155-166. https://doi.org/10.1016/S0378-5173(03)00007-3
  141. Mel'nikov SM, Seijen ten Hoorn JW, Bertrand B. 2004. Can cholesterol absorption be reduced by phytosterols and phytostanols via a cocrystallization mechanism?. Chem Phys Lipids 127: 15-33. https://doi.org/10.1016/j.chemphyslip.2003.08.007
  142. Salen G, von Bergmann K, Lutjohann D, Kwiterovich P, Kane J, Patel SB, Musliner T, Stein P, Musser B; Multicenter Sitosterolemia Study Group. 2004. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation 109: 966-971. https://doi.org/10.1161/01.CIR.0000116766.31036.03
  143. Davies JP, Scott C, Oishi K, Liapis A, Ioannou YA. 2005. Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia. J Biol Chem 280: 12710-12720. https://doi.org/10.1074/jbc.M409110200
  144. Tang W, Ma Y, Jia L, Ioannou YA, Davies JP, Yu L. 2008. Genetic inactivation of NPC1L1 protects against sitosterolemia in mice lacking ABCG5/ABCG8. J Lipid Res 50: 293-300.
  145. Jesch ED, Seo JM, Carr TP, Lee JY. 2009. Sitosterol reduces messenger RNA and protein expression levels of Niemann- Pick C1-like 1 in FHs 74 Int cells. Nutr Res 29: 859-866. https://doi.org/10.1016/j.nutres.2009.10.016
  146. Field FJ, Born E, Mathur SN. 2004. Stanol esters decrease plasma cholesterol independently of intestinal ABC sterol transporters and Niemann-Pick C1-like 1 protein gene expression. J Lipid Res 45: 2252-2259. https://doi.org/10.1194/jlr.M400208-JLR200
  147. Field FJ, Mathur SN. 1983. $beta$-Sitosterol: esterification by intestinal acylcoenzyme A:cholesterol acyltransferase (ACAT) and its effect on cholesterol esterification. J Lipid Res 24: 409-417.
  148. Tavani DM, Nes WR, Billheimer JT. 1982. The sterol substrate specificity of acyl CoA:cholesterol acyltransferase from rat liver. J Lipid Res 23: 774-781.
  149. Temel RE, Gebre AK, Parks JS, Rudel LL. 2003. Compared with acyl-CoA:cholesterol O-acyltransferase (ACAT) 1 and lecithin:cholesterol acyltransferase, ACAT2 displays the greatest capacity to differentiate cholesterol from sitosterol. J Biol Chem 278: 47594-47601. https://doi.org/10.1074/jbc.M308235200
  150. Institute of Medicine. 2001. Dietary Reference Intakes: proposed definition of dietary fiber. The National Academies Press, Washington DC, USA. p 3-11.
  151. Trumbo P, Schlicker S, Yates AA, Poos M; Food and Nutrition Board of the Institute of Medicine, The National Academies. 2002. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc 102: 1621-1630. https://doi.org/10.1016/S0002-8223(02)90346-9
  152. McRorie JW Jr, McKeown NM. 2017. Understanding the physics of functional fibers in the gastrointestinal tract: an evidence-based approach to resolving enduring misconceptions about insoluble and soluble fiber. J Acad Nutr Diet 117: 251-264. https://doi.org/10.1016/j.jand.2016.09.021
  153. Hsu PK, Chien PJ, Chen CH, Chau CF. 2006. Carrot insoluble fiber-rich fraction lowers lipid and cholesterol absorption in hamsters. LWT-Food Sci Technol 39: 338-343. https://doi.org/10.1016/j.lwt.2005.02.009
  154. Meyer KA, Kushi LH, Jacobs DR Jr, Slavin J, Sellers TA, Folsom AR. 2000. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr 71: 921-930. https://doi.org/10.1093/ajcn/71.4.921
  155. Bazzano LA. 2008. Effects of soluble dietary fiber on lowdensity lipoprotein cholesterol and coronary heart disease risk. Curr Atheroscler Rep 10: 473-477. https://doi.org/10.1007/s11883-008-0074-3
  156. Threapleton DE, Greenwood DC, Evans CE, Cleghorn CL, Nykjaer C, Woodhead C, Cade JE, Gale CP, Burley VJ. 2013. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ 347: f6879. https://doi.org/10.1136/bmj.f6879
  157. Xu R, Ding Z, Zhao P, Tang L, Tang X, Xiao S. 2016. The effects of early post-operative soluble dietary fiber enteral nutrition for colon cancer. Nutrients 8: E584. https://doi.org/10.3390/nu8090584
  158. van Bennekum AM, Nguyen DV, Schulthess G, Hauser H, Phillips MC. 2005. Mechanisms of cholesterol-lowering effects of dietary insoluble fibres: relationships with intestinal and hepatic cholesterol parameters. Br J Nutr 94: 331-337. https://doi.org/10.1079/BJN20051498
  159. Venkatesan N, Devaraj SN, Devaraj H. 2007. A fibre cocktail of fenugreek, guar gum and wheat bran reduces oxidative modification of LDL induced by an atherogenic diet in rats. Mol Cell Biochem 294: 145-153. https://doi.org/10.1007/s11010-006-9254-z
  160. Anderson JW, Davidson MH, Blonde L, Brown WV, Howard WJ, Ginsberg H, Allgood LD, Weingand KW. 2000. Longterm cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia. Am J Clin Nutr 71: 1433-1438. https://doi.org/10.1093/ajcn/71.6.1433
  161. Naumann E, van Rees AB, Onning G, Oste R, Wydra M, Mensink RP. 2006. $beta$-Glucan incorporated into a fruit drink effectively lowers serum LDL-cholesterol concentrations. Am J Clin Nutr 83: 601-605. https://doi.org/10.1093/ajcn.83.3.601
  162. Castro IA, Barroso LP, Sinnecker P. 2005. Functional foods for coronary heart disease risk reduction: a meta-analysis using a multivariate approach. Am J Clin Nutr 82: 32-40. https://doi.org/10.1093/ajcn/82.1.32
  163. Malhotra A, Shafiq N, Arora A, Singh M, Kumar R, Malhotra S. 2014. Dietary interventions (plant sterols, stanols, omega-3 fatty acids, soy protein and dietary fibers) for familial hypercholesterolaemia. Cochrane Database Syst Rev 10.1002/14651858.CD001918.pub3. https://doi.org/10.1002/14651858.CD001918.pub3
  164. U.S. Food and Drug Administration. Code of Federal Regulations: 21CFR101.76. https://www.accessdata.fda. gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=101.76 (accessed Mar 2017).
  165. U.S. Food and Drug Administration. Code of Federal Regulations: 21CFR101.77. https://www.accessdata.fda. gov/ scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=101.77 (accessed Mar 2017).