Phytosterols and Inflammation

Author(s): Gemma Vilahur, Soumaya Ben-Aicha, Elisa Diaz-Riera, Lina Badimon, Teresa Padró*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 37 , 2019

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Abstract:

Besides the well-characterized effect of foods and supplements enriched with plant sterols/stanols on serum LDL-C concentrations, evidence is now emerging that phytosterols exert beneficial effects on non-lipid variables such as inflammatory and oxidative stress markers, coagulation parameters and endothelial function. This makes sterols and stanols an attractive alternative for dietary interventions in cardiovascular disease prevention, particularly in populations at low or medium risk. This review aims to summarize the current knowledge derived from experimental studies and human data on the anti-inflammatory effects of phytosterols/stanols and their relevance in promoting atheroprotection and preventing cardiovascular disease. The anti-inflammatory effects induced by plant sterols/stanols have been demonstrated in in vitro studies and in experimental animal models. However, not all the beneficial effects seen at an experimental level have translated into clinical benefit. Indeed, clinical studies that evaluate the association between phytosterols consumption and inflammatory variables (CRP and cytokines) are inconsistent and have not yet provided a solid answer. Plant sterols have been proposed as useful adjuncts to statin therapy to further reduce the risk of cardiovascular disease. However, there is limited available data and more research needs to be done.

Keywords: Phytosterols, inflammation, oxidative stress, LDL, cholesterol, CRP, cytokines.

[1]
Nichols, M.; Townsend, N.; Scarborough, P.; Rayner, M. Cardiovascular disease in Europe 2014: epidemiological update. Eur. Heart J., 2014, 35(42), 2929.
[http://dx.doi.org/10.1093/eurheartj/ehu299] [PMID: 25381246]
[2]
Badimon, L.; Padró, T.; Vilahur, G. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. Eur. Heart J. Acute Cardiovasc. Care, 2012, 1(1), 60-74.
[http://dx.doi.org/10.1177/2048872612441582] [PMID: 24062891]
[3]
Tabas, I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat. Rev. Immunol., 2010, 10(1), 36-46.
[http://dx.doi.org/10.1038/nri2675] [PMID: 19960040]
[4]
McLaren, J.E.; Michael, D.R.; Ashlin, T.G.; Ramji, D.P. Cytokines, macrophage lipid metabolism and foam cells: implications for cardiovascular disease therapy. Prog. Lipid Res., 2011, 50(4), 331-347.
[http://dx.doi.org/10.1016/j.plipres.2011.04.002] [PMID: 21601592]
[5]
Libby, P.; Ridker, P.M.; Hansson, G.K. Progress and challenges in translating the biology of atherosclerosis. Nature, 2011, 473(7347), 317-325.
[http://dx.doi.org/10.1038/nature10146] [PMID: 21593864]
[6]
Tabas, I.; Lichtman, A.H. Monocyte-Macrophages and T Cells in Atherosclerosis. Immunity, 2017, 47(4), 621-634.
[http://dx.doi.org/10.1016/j.immuni.2017.09.008] [PMID: 29045897]
[7]
Krupinski, J.; Turu, M.M.; Martinez-Gonzalez, J.; Carvajal, A.; Juan-Babot, J.O.; Iborra, E.; Slevin, M.; Rubio, F.; Badimon, L. Endogenous expression of C-reactive protein is increased in active (ulcerated noncomplicated) human carotid artery plaques. Stroke, 2006, 37(5), 1200-1204.
[http://dx.doi.org/10.1161/01.STR.0000217386.37107.be] [PMID: 16601222]
[8]
Ridker, P.M.; Lüscher, T.F. Anti-inflammatory therapies for cardiovascular disease. Eur. Heart J., 2014, 35(27), 1782-1791.
[http://dx.doi.org/10.1093/eurheartj/ehu203] [PMID: 24864079]
[9]
Kocarnik, J.M.; Pendergrass, S.A.; Carty, C.L.; Pankow, J.S.; Schumacher, F.R.; Cheng, I.; Durda, P.; Ambite, J.L.; Deelman, E.; Cook, N.R.; Liu, S.; Wactawski-Wende, J.; Hutter, C.; Brown-Gentry, K.; Wilson, S.; Best, L.G.; Pankratz, N.; Hong, C.P.; Cole, S.A.; Voruganti, V.S.; Bůžkova, P.; Jorgensen, N.W.; Jenny, N.S.; Wilkens, L.R.; Haiman, C.A.; Kolonel, L.N.; Lacroix, A.; North, K.; Jackson, R.; Le Marchand, L.; Hindorff, L.A.; Crawford, D.C.; Gross, M.; Peters, U. Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study. Circ Cardiovasc Genet, 2014, 7(2), 178-188.
[http://dx.doi.org/10.1161/CIRCGENETICS.113.000173] [PMID: 24622110]
[10]
Suades, R.; Padró, T.; Alonso, R.; López-Miranda, J.; Mata, P.; Badimon, L. Circulating CD45+/CD3+ lymphocyte-derived microparticles map lipid-rich atherosclerotic plaques in familial hypercholesterolaemia patients. Thromb. Haemost., 2014, 111(1), 111-121.
[http://dx.doi.org/10.1160/TH13-07-0612] [PMID: 24085382]
[11]
Escate, R.; Mata, P.; Cepeda, J.M.; Padro, T.; Badimon, L. miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia. FASEB J., 2018. fj201700476R
[http://dx.doi.org/10.1096/fj.201700476R] [PMID: 29089446]
[12]
de Carvalho, J.F.; Bonfá, E.; Borba, E.F. Systemic lupus erythematosus and “lupus dyslipoproteinemia”. Autoimmun. Rev., 2008, 7(3), 246-250.
[http://dx.doi.org/10.1016/j.autrev.2007.11.016] [PMID: 18190886]
[13]
Gylling, H.; Plat, J.; Turley, S.; Ginsberg, H.N.; Ellegård, L.; Jessup, W.; Jones, P.J.; Lütjohann, D.; Maerz, W.; Masana, L.; Silbernagel, G.; Staels, B.; Borén, J.; Catapano, A.L.; De Backer, G.; Deanfield, J.; Descamps, O.S.; Kovanen, P.T.; Riccardi, G.; Tokgözoglu, L.; Chapman, M.J. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis, 2014, 232(2), 346-360.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.11.043] [PMID: 24468148]
[14]
Sabeva, N.S.; McPhaul, C.M.; Li, X.; Cory, T.J.; Feola, D.J.; Graf, G.A. Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells. J. Nutr. Biochem., 2011, 22(8), 777-783.
[http://dx.doi.org/10.1016/j.jnutbio.2010.07.002] [PMID: 21111593]
[15]
Plat, J.; Hendrikx, T.; Bieghs, V.; Jeurissen, M.L.; Walenbergh, S.M.; van Gorp, P.J.; De Smet, E.; Konings, M.; Vreugdenhil, A.C.; Guichot, Y.D.; Rensen, S.S.; Buurman, W.A.; Greve, J.W.; Lütjohann, D.; Mensink, R.P.; Shiri-Sverdlov, R. Protective role of plant sterol and stanol esters in liver inflammation: insights from mice and humans. PLoS One, 2014, 9(10)e110758
[http://dx.doi.org/10.1371/journal.pone.0110758] [PMID: 25356831]
[16]
Ekroos, K.; Jänis, M.; Tarasov, K.; Hurme, R.; Laaksonen, R. Lipidomics: a tool for studies of atherosclerosis. Curr. Atheroscler. Rep., 2010, 12(4), 273-281.
[http://dx.doi.org/10.1007/s11883-010-0110-y] [PMID: 20425241]
[17]
de Mello, V.D.; Lankinen, M.; Schwab, U.; Kolehmainen, M.; Lehto, S.; Seppänen-Laakso, T.; Oresic, M.; Pulkkinen, L.; Uusitupa, M.; Erkkilä, A.T. Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease. Diabetologia, 2009, 52(12), 2612-2615.
[http://dx.doi.org/10.1007/s00125-009-1482-9] [PMID: 19669729]
[18]
Boon, J.; Hoy, A.J.; Stark, R.; Brown, R.D.; Meex, R.C.; Henstridge, D.C.; Schenk, S.; Meikle, P.J.; Horowitz, J.F.; Kingwell, B.A.; Bruce, C.R.; Watt, M.J. Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance. Diabetes, 2013, 62(2), 401-410.
[http://dx.doi.org/10.2337/db12-0686] [PMID: 23139352]
[19]
Laaksonen, R.; Ekroos, K.; Sysi-Aho, M.; Hilvo, M.; Vihervaara, T.; Kauhanen, D.; Suoniemi, M.; Hurme, R.; März, W.; Scharnagl, H.; Stojakovic, T.; Vlachopoulou, E.; Lokki, M.L.; Nieminen, M.S.; Klingenberg, R.; Matter, C.M.; Hornemann, T.; Jüni, P.; Rodondi, N.; Räber, L.; Windecker, S.; Gencer, B.; Pedersen, E.R.; Tell, G.S.; Nygård, O.; Mach, F.; Sinisalo, J.; Lüscher, T.F. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol. Eur. Heart J., 2016, 37(25), 1967-1976.
[http://dx.doi.org/10.1093/eurheartj/ehw148] [PMID: 27125947]
[20]
Havulinna, A.S.; Sysi-Aho, M.; Hilvo, M.; Kauhanen, D.; Hurme, R.; Ekroos, K.; Salomaa, V.; Laaksonen, R. Circulating ceramides predict cardiovascular outcomes in the population-based FINRISK 2002 Cohort. Arterioscler. Thromb. Vasc. Biol., 2016, 36(12), 2424-2430.
[http://dx.doi.org/10.1161/ATVBAHA.116.307497] [PMID: 27765765]
[21]
Wallace, M.; Morris, C.; O’Grada, C.M.; Ryan, M.; Dillon, E.T.; Coleman, E.; Gibney, E.R.; Gibney, M.J.; Roche, H.M.; Brennan, L. Relationship between the lipidome, inflammatory markers and insulin resistance. Mol. Biosyst., 2014, 10(6), 1586-1595.
[http://dx.doi.org/10.1039/C3MB70529C] [PMID: 24714806]
[22]
Floegel, A.; Kuhn, T.; Sookthai, D.; Johnson, T.; Prehn, C.; Rolle-Kampczyk, U.; Otto, W.; Weikert, C.; Illig, T.; von Bergen, M.; Adamski, J.; Boeing, H.; Kaaks, R.; Pischon, T. Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts. Eur. J. Epidemiol., 2018, 33(1), 55-66.
[http://dx.doi.org/10.1007/s10654-017-0333-0] [PMID: 29181692]
[23]
Szymańska, E.; van Dorsten, F.A.; Troost, J.; Paliukhovich, I.; van Velzen, E.J.; Hendriks, M.M.; Trautwein, E.A.; van Duynhoven, J.P.; Vreeken, R.J.; Smilde, A.K. A lipidomic analysis approach to evaluate the response to cholesterol-lowering food intake. Metabolomics, 2012, 8(5), 894-906.
[http://dx.doi.org/10.1007/s11306-011-0384-2] [PMID: 23060736]
[24]
Padro, T.; Vilahur, G.; Sánchez-Hernández, J.; Hernández, M.; Antonijoan, R.M.; Perez, A.; Badimon, L. Lipidomic changes of LDL in overweight and moderately hypercholesterolemic subjects taking phytosterol- and omega-3-supplemented milk. J. Lipid Res., 2015, 56(5), 1043-1056.
[http://dx.doi.org/10.1194/jlr.P052217] [PMID: 25773888]
[25]
Huang, Y.H.; Schäfer-Elinder, L.; Wu, R.; Claesson, H.E.; Frostegård, J. Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism. Clin. Exp. Immunol., 1999, 116(2), 326-331.
[http://dx.doi.org/10.1046/j.1365-2249.1999.00871.x] [PMID: 10337026]
[26]
Sigruener, A.; Kleber, M.E.; Heimerl, S.; Liebisch, G.; Schmitz, G.; Maerz, W. Glycerophospholipid and sphingolipid species and mortality: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. PLoS One, 2014, 9(1)e85724
[http://dx.doi.org/10.1371/journal.pone.0085724] [PMID: 24465667]
[27]
Kim, S.J.; Jeong, H.J.; Yi, B.J.; Kang, T.H.; An, N.H.; Lee, E.H.; Yang, D.C.; Kim, H.M.; Hong, S.H.; Um, J.Y. Transgenic Panax ginseng inhibits the production of TNF-alpha, IL-6, and IL-8 as well as COX-2 expression in human mast cells. Am. J. Chin. Med., 2007, 35(2), 329-339.
[http://dx.doi.org/10.1142/S0192415X07004850] [PMID: 17436372]
[28]
Nashed, B.; Yeganeh, B. HayGlass, K.T.; Moghadasian, M.H. Antiatherogenic effects of dietary plant sterols are associated with inhibition of proinflammatory cytokine production in Apo E-KO mice. J. Nutr., 2005, 135(10), 2438-2444.
[http://dx.doi.org/10.1093/jn/135.10.2438] [PMID: 16177209]
[29]
Perez-Ternero, C.; Claro, C.; Parrado, J.; Herrera, M.D.; Alvarez de Sotomayor, M. Rice bran enzymatic extract reduces atherosclerotic plaque development and steatosis in high-fat fed ApoE-/- mice. Nutrition, 2017, 37, 22-29.
[http://dx.doi.org/10.1016/j.nut.2016.12.005] [PMID: 28359358]
[30]
Calpe-Berdiel, L.; Escolà-Gil, J.C.; Benítez, S.; Bancells, C.; González-Sastre, F.; Palomer, X.; Blanco-Vaca, F. Dietary phytosterols modulate T-helper immune response but do not induce apparent anti-inflammatory effects in a mouse model of acute, aseptic inflammation. Life Sci., 2007, 80(21), 1951-1956.
[http://dx.doi.org/10.1016/j.lfs.2007.02.032] [PMID: 17382351]
[31]
Hu, Q.; Zhuo, Z.; Fang, S.; Zhang, Y.; Feng, J. Phytosterols improve immunity and exert anti-inflammatory activity in weaned piglets. J. Sci. Food Agric., 2017, 97(12), 4103-4109.
[http://dx.doi.org/10.1002/jsfa.8277] [PMID: 28218810]
[32]
Awad, A.B.; Toczek, J.; Fink, C.S. Phytosterols decrease prostaglandin release in cultured P388D1/MAB macrophages. Prostaglandins Leukot. Essent. Fatty Acids, 2004, 70(6), 511-520.
[http://dx.doi.org/10.1016/j.plefa.2003.11.005] [PMID: 15120714]
[33]
Feigin, A.M.; Teeter, J.H.; Brand, J.G. The influence of sterols on the sensitivity of lipid bilayers to melittin. Biochem. Biophys. Res. Commun., 1995, 211(1), 312-317.
[http://dx.doi.org/10.1006/bbrc.1995.1812] [PMID: 7779101]
[34]
Awad, A.B.; Downie, A.C.; Fink, C.S. Inhibition of growth and stimulation of apoptosis by beta-sitosterol treatment of MDA-MB-231 human breast cancer cells in culture. Int. J. Mol. Med., 2000, 5(5), 541-545.
[http://dx.doi.org/10.3892/ijmm.5.5.541] [PMID: 10762659]
[35]
Tovey, F.I.; Bardhan, K.D.; Hobsley, M. Dietary phosphilipids and sterols protective against peptic ulceration. Phytother. Res., 2013, 27(9), 1265-1269.
[http://dx.doi.org/10.1002/ptr.4865] [PMID: 23097339]
[36]
Antonisamy, P.; Subash-Babu, P.; Alshatwi, A.A.; Aravinthan, A.; Ignacimuthu, S.; Choi, K.C.; Kim, J.H. Gastroprotective effect of nymphayol isolated from Nymphaea stellata (Willd.) flowers: contribution of antioxidant, anti-inflammatory and anti-apoptotic activities. Chem. Biol. Interact., 2014, 224, 157-163.
[http://dx.doi.org/10.1016/j.cbi.2014.09.020] [PMID: 25289771]
[37]
Aldini, R.; Micucci, M.; Cevenini, M.; Fato, R.; Bergamini, C.; Nanni, C.; Cont, M.; Camborata, C.; Spinozzi, S.; Montagnani, M.; Roda, G.; D’Errico-Grigioni, A.; Rosini, F.; Roda, A.; Mazzella, G.; Chiarini, A.; Budriesi, R. Antiinflammatory effect of phytosterols in experimental murine colitis model: prevention, induction, remission study. PLoS One, 2014, 9(9) e108112
[http://dx.doi.org/10.1371/journal.pone.0108112] [PMID: 25268769]
[38]
Al-Okbi, S.Y. Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis. Toxicol. Ind. Health, 2014, 30(8), 738-749.
[http://dx.doi.org/10.1177/0748233712462468] [PMID: 23104728]
[39]
Khan, S.; Mehmood, M.H.; Ali, A.N.; Ahmed, F.S.; Dar, A.; Gilani, A.H. Studies on anti-inflammatory and analgesic activities of betel nut in rodents. J. Ethnopharmacol., 2011, 135(3), 654-661.
[http://dx.doi.org/10.1016/j.jep.2011.03.064] [PMID: 21501676]
[40]
la Torre Fabiola, V.D.; Ralf, K.; Gabriel, B.; Victor Ermilo, A.A.; Martha, M.G.; Mirbella, C.F.; Rocio, B.A. Anti-inflammatory and immunomodulatory effects of Critonia aromatisans leaves: Downregulation of pro-inflammatory cytokines. J. Ethnopharmacol., 2016, 190, 174-182.
[http://dx.doi.org/10.1016/j.jep.2016.06.006] [PMID: 27282666]
[41]
Al-Yousuf, M.H.; Ali, B.H.; Bashir, A.K.; Tanira, M.O.; Blunden, G. Central nervous system activity of Leucas inflata Benth. in mice. Phytomedicine, 2002, 9(6), 501-507.
[http://dx.doi.org/10.1078/09447110260573128] [PMID: 12403158]
[42]
Villaseñor, I.M.; Angelada, J.; Canlas, A.P.; Echegoyen, D. Bioactivity studies on beta-sitosterol and its glucoside. Phytother. Res., 2002, 16(5), 417-421.
[http://dx.doi.org/10.1002/ptr.910] [PMID: 12203259]
[43]
Gao, S.; Li, H.; Zhou, X.Q.; You, J.B.; Tu, D.N.; Xia, G.; Jiang, J.X.; Xin, C. Withaferin A attenuates lipopolysaccharide-induced acute lung injury in neonatal rats. Cell. Mol. Biol., 2015, 61(3), 102-106.
[PMID: 26255139]
[44]
Yan, X.; Huang, G.; Liu, Q.; Zheng, J.; Chen, H.; Huang, Q.; Chen, J.; Huang, H. Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice. Pharm. Biol., 2017, 55(1), 1171-1176.
[http://dx.doi.org/10.1080/13880209.2017.1288262] [PMID: 28228044]
[45]
Shishodia, S.; Aggarwal, B.B. Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. J. Biol. Chem., 2004, 279(45), 47148-47158.
[http://dx.doi.org/10.1074/jbc.M408093200] [PMID: 15322087]
[46]
Devaraj, S.; Jialal, I.; Rockwood, J.; Zak, D. Effect of orange juice and beverage with phytosterols on cytokines and PAI-1 activity. Clin. Nutr., 2011, 30(5), 668-671.
[http://dx.doi.org/10.1016/j.clnu.2011.03.009] [PMID: 21477901]
[47]
Devaraj, S.; Autret, B.C.; Jialal, I. Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers. Am. J. Clin. Nutr., 2006, 84(4), 756-761.
[http://dx.doi.org/10.1093/ajcn/84.4.756] [PMID: 17023701]
[48]
Athyros, V.G.; Kakafika, A.I.; Papageorgiou, A.A.; Tziomalos, K.; Peletidou, A.; Vosikis, C.; Karagiannis, A.; Mikhailidis, D.P. Effect of a plant stanol ester-containing spread, placebo spread, or Mediterranean diet on estimated cardiovascular risk and lipid, inflammatory and haemostatic factors. Nutr. Metab. Cardiovasc. Dis., 2011, 21(3), 213-221.
[http://dx.doi.org/10.1016/j.numecd.2009.08.014] [PMID: 19939653]
[49]
Clifton, P.M.; Mano, M.; Duchateau, G.S.; van der Knaap, H.C.; Trautwein, E.A. Dose-response effects of different plant sterol sources in fat spreads on serum lipids and C-reactive protein and on the kinetic behavior of serum plant sterols. Eur. J. Clin. Nutr., 2008, 62(8), 968-977.
[http://dx.doi.org/10.1038/sj.ejcn.1602814] [PMID: 17538539]
[50]
Lambert, C.; Cubedo, J.; Padró, T.; Sánchez-Hernández, J.; Antonijoan, R.M.; Perez, A.; Badimon, L. Phytosterols and Omega 3 supplementation exert novel regulatory effects on metabolic and inflammatory pathways: a proteomic study. Nutrients, 2017, 9(6), 9.
[http://dx.doi.org/10.3390/nu9060599] [PMID: 28608804]
[51]
Ras, R.T.; Fuchs, D.; Koppenol, W.P.; Schalkwijk, C.G.; Otten-Hofman, A.; Garczarek, U.; Greyling, A.; Wagner, F.; Trautwein, E.A. Effect of a plant sterol-enriched spread on biomarkers of endothelial dysfunction and low-grade inflammation in hypercholesterolaemic subjects. J. Nutr. Sci., 2016, 5 e44
[http://dx.doi.org/10.1017/jns.2016.40] [PMID: 28620471]
[52]
Heggen, E.; Kirkhus, B.; Pedersen, J.I.; Tonstad, S. Effects of margarine enriched with plant sterol esters from rapeseed and tall oils on markers of endothelial function, inflammation and hemostasis. Scand. J. Clin. Lab. Invest., 2015, 75(2), 189-192.
[http://dx.doi.org/10.3109/00365513.2014.992040] [PMID: 25553599]
[53]
Rocha, V.Z.; Ras, R.T.; Gagliardi, A.C.; Mangili, L.C.; Trautwein, E.A.; Santos, R.D. Effects of phytosterols on markers of inflammation: A systematic review and meta-analysis. Atherosclerosis, 2016, 248, 76-83.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.01.035] [PMID: 26987068]
[54]
Micallef, M.A.; Garg, M.L. Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals. Atherosclerosis, 2009, 204(2), 476-482.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.09.020] [PMID: 18977480]
[55]
Plat, J.; Brufau, G.; Dallinga-Thie, G.M.; Dasselaar, M.; Mensink, R.P. A plant stanol yogurt drink alone or combined with a low-dose statin lowers serum triacylglycerol and non-HDL cholesterol in metabolic syndrome patients. J. Nutr., 2009, 139(6), 1143-1149.
[http://dx.doi.org/10.3945/jn.108.103481] [PMID: 19403719]
[56]
Ras, R.T.; Hiemstra, H.; Lin, Y.; Vermeer, M.A.; Duchateau, G.S.; Trautwein, E.A. Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations--a meta-analysis of randomized controlled studies. Atherosclerosis, 2013, 230(2), 336-346.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.08.012] [PMID: 24075766]


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VOLUME: 26
ISSUE: 37
Year: 2019
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DOI: 10.2174/0929867325666180622151438
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