Effects of phytosterols supplementation on blood pressure: A systematic review and meta-analysis

  • Ehsan Ghaedi
    Affiliations
    Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Sahar Foshati
    Affiliations
    Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
    Search for articles by this author
  • Rahele Ziaei
    Affiliations
    Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
    Search for articles by this author
  • Sara Beigrezaei
    Affiliations
    Nutrition and Food Security Research Center, Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
    Search for articles by this author
  • Hamed Kord-Varkaneh
    Affiliations
    Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Abed Ghavami
    Correspondence
    Corresponding author. School of Nutrition and Food Science, Isfahan University of Medical Sciences, PO Box 81745, Isfahan, Iran. Fax: +98 31 37922776.
    Affiliations
    Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
    Search for articles by this author
  • Maryam Miraghajani
    Correspondence
    Corresponding author. Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    Affiliations
    Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    The Early Life Research Unit, Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK
    Search for articles by this author
Published:December 23, 2019DOI:https://doi.org/10.1016/j.clnu.2019.12.020

      Summary

      Several reports have indicated a positive effect of phytosterols on blood pressure (BP), nevertheless these findings have been controversial. Therefore, a systematic review and meta-analysis of randomized controlled trials (RCTs) was aimed to investigate the effects of phytosterol supplementation on BP.
      An online search was carried out in PubMed, Scopus, ISI Web of Science, Cochrane library and Google Scholar up to May 2019. Weighted Mean difference (WMD) with 95% confidence intervals (CIs) were calculated using a fixed-effects model.
      The present meta-analysis of 19 RCTs showed that supplementation with phytosterols can decrease both systolic BP (WMD: −1.55 mmHg, 95% CI: −2.67 to −0.42, p = 0.007) and diastolic BP (WMD: −0.84 mmHg, 95% CI: −1.60 to −0.08, p = 0.03). Dose–response analysis revealed that phytosterol intake change SBP significantly based on treatment dose in nonlinear fashion. Subgroup analysis based on duration showed a significant effect of phytosterol on SBP and DBP in subsets of <12 weeks. In addition, a significant effect of phytosterol was observed in dosage of ≥2000 mg for SBP and <2000 mg for DBP.
      Based on current findings supplementation with phytosterol may be a beneficial adjuvant therapy in hypertensive patients as well as a complementary preventive option in prehypertensive and normotensive individuals. However, this issue is still open and requires further investigation in future studies.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Nutrition
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kearney P.M.
        • Whelton M.
        • Reynolds K.
        • Muntner P.
        • Whelton P.K.
        • He J.
        Global burden of hypertension: analysis of worldwide data.
        The Lancet. 2005; 365: 217-223
        • Shin H.
        • Yoon Y.S.
        • Lee Y.
        • Kim C-i
        • Oh S.W.
        Dairy product intake is inversely associated with metabolic syndrome in Korean adults: Anseong and Ansan cohort of the Korean Genome and Epidemiology Study.
        J Korean Med Sci. 2013; 28: 1482-1488
        • Hutton B.
        • Tetzlaff J.
        • Yazdi F.
        • Thielman J.
        • Kanji S.
        • Fergusson D.
        • et al.
        Comparative effectiveness of monotherapies and combination therapies for patients with hypertension: protocol for a systematic review with network meta-analyses.
        Syst Rev. 2013; 2: 44
        • Artero E.G.
        • Lee D-c
        • Ruiz J.R.
        • Sui X.
        • Ortega F.B.
        • Church T.S.
        • et al.
        A prospective study of muscular strength and all-cause mortality in men with hypertension.
        J Am Coll Cardiol. 2011; 57: 1831-1837
        • Carretero O.A.
        • Oparil S.
        Essential hypertension: part I: definition and etiology.
        Circulation. 2000; 101: 329-335
        • Smith P.J.
        • Blumenthal J.A.
        • Babyak M.A.
        • Craighead L.
        • Welsh-Bohmer K.A.
        • Browndyke J.N.
        • et al.
        Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure.
        Hypertension. 2010; 55: 1331-1338
        • Dauchet L.
        • Amouyel P.
        • Dallongeville J.
        Fruits, vegetables and coronary heart disease.
        Nat Rev Cardiol. 2009; 6: 599
        • Sales A.R.
        • Silva B.M.
        • Neves F.J.
        • Rocha N.G.
        • Medeiros R.F.
        • Castro R.R.
        • et al.
        Diet and exercise training reduce blood pressure and improve autonomic modulation in women with prehypertension.
        Eur J Appl Physiol. 2012; 112: 3369-3378
        • Hu F.
        • Liu Y.
        • Willett W.
        Preventing chronic diseases by promoting healthy diet and lifestyle: public policy implications for China.
        Obes Rev. 2011; 12: 552-559
        • Ling W.
        • Jones P.
        Dietary phytosterols: a review of metabolism, benefits and side effects.
        Life Sci. 1995; 57: 195-206
        • Peluso I.
        • Palmery M.
        • Serafini M.
        Association of flavonoid-rich foods and statins in the management of hypercholesterolemia: a dangerous or helpful combination?.
        Curr Drug Metabol. 2015; 16: 833-846
        • Devaraj S.
        • Jialal I.
        The role of dietary supplementation with plant sterols and stanols in the prevention of cardiovascular disease.
        Nutr Rev. 2006; 64: 348-354
        • Yue S.Y.P.
        • Rideout T.C.
        • Harding S.V.
        Effects of plant sterol and stanol consumption on blood pressure and endothelial function.
        J AOAC Int. 2015; 98: 729-734
        • Medina-Remón A.
        • Tresserra-Rimbau A.
        • Pons A.
        • Tur J.A.
        • Martorell M.
        • Ros E.
        • et al.
        Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial.
        Nutr Metab Cardiovasc Dis. 2015; 25: 60-67
        • Cheung C.-L.
        • Ho D.K.-C.
        • Sing C.-W.
        • Tsoi M.-F.
        • Cheng V.K.-F.
        • Lee G.K.-Y.
        • et al.
        Randomized controlled trial of the effect of phytosterols-enriched low-fat milk on lipid profile in Chinese.
        Sci Rep. 2017; 7: 41084
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        Ann Intern Med. 2009; 151: 264-269
        • Higgins J.P.
        • Altman D.G.
        • Gøtzsche P.C.
        • Jüni P.
        • Moher D.
        • Oxman A.D.
        • et al.
        The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
        • Borenstein M.
        • Hedges L.V.
        • Higgins J.P.
        • Rothstein H.R.
        Introduction to meta-analysis.
        John Wiley & Sons, 2011
        • Allen R.R.
        • Carson L.
        • Kwik-Uribe C.
        • Evans E.M.
        • Erdman Jr., J.W.
        Daily consumption of a dark chocolate containing flavanols and added sterol esters affects cardiovascular risk factors in a normotensive population with elevated cholesterol.
        J Nutr. 2008; 138: 725-731
        • Athyros V.G.
        • Kakafika A.I.
        • Papageorgiou A.A.
        • Tziomalos K.
        • Peletidou A.
        • Vosikis C.
        • et al.
        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: 213-221
        • Bañuls C.
        • Martínez-Triguero M.L.
        • López-Ruiz A.
        • Morillas C.
        • Lacomba R.
        • Víctor V.M.
        • et al.
        Evaluation of cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects on a standard healthy diet including low-fat milk enriched with plant sterols.
        J Nutr Biochem. 2010; 21: 881-886
        • Gylling H.
        • Hallikainen M.
        • Nissinen M.J.
        • Miettinen T.A.
        The effect of a very high daily plant stanol ester intake on serum lipids, carotenoids, and fat-soluble vitamins.
        Clin Nutr. 2010; 29: 112-118
        • Gylling H.
        • Halonen J.
        • Lindholm H.
        • Konttinen J.
        • Simonen P.
        • Nissinen M.J.
        • et al.
        The effects of plant stanol ester consumption on arterial stiffness and endothelial function in adults: a randomised controlled clinical trial.
        BMC Cardiovasc Disord. 2013; 13: 50
        • Hallikainen M.
        • Lyyra-Laitinen T.
        • Laitinen T.
        • Agren J.J.
        • Pihlajamaki J.
        • Rauramaa R.
        • et al.
        Endothelial function in hypercholesterolemic subjects: effects of plant stanol and sterol esters.
        Atherosclerosis. 2006; 188: 425-432
        • Hallikainen M.
        • Lyyra-Laitinen T.
        • Laitinen T.
        • Moilanen L.
        • Miettinen T.A.
        • Gylling H.
        Effects of plant stanol esters on serum cholesterol concentrations, relative markers of cholesterol metabolism and endothelial function in type 1 diabetes.
        Atherosclerosis. 2008; 199: 432-439
        • Hironaka T.
        • Shioya N.
        • Matsubara H.
        • MATSUOKA Y.
        • ITAKURA H.
        Double-blind, placebo-controlled study of effects of plant sterol enriched vegetable juice on serum cholesterol concentrations in mildly hypercholesterolemic subjects and safety evaluation.
        J Oleo Sci. 2006; 55: 593-606
        • Ho X.L.
        • Liu J.J.H.
        • Loke W.M.
        Plant sterol-enriched soy milk consumption modulates 5-lipoxygenase, 12-lipoxygenase, and myeloperoxidase activities in healthy adults–a randomized-controlled trial.
        Free Radic Res. 2016; 50: 1396-1407
        • Hongu N.
        • Kitts D.D.
        • Zawistowski J.
        • Dossett C.M.
        • Kopeć A.
        • Pope B.T.
        • et al.
        Pigmented rice bran and plant sterol combination reduces serum lipids in overweight and obese adults.
        J Am Coll Nutr. 2014; 33: 231-238
        • Hsu C.-C.
        • Kuo H.-C.
        • Huang K.-E.
        The effects of phytosterols extracted from Diascorea alata on the antioxidant activity, plasma lipids, and hematological profiles in Taiwanese menopausal women.
        Nutrients. 2017; 9: 1320
        • Ishizaki T.
        • Wakabayashi M.
        • Tanimoto H.
        • Shima A.
        • Yabune M.
        • Kajimoto O.
        • et al.
        Effects of long-term intake of mayonnaise containing phytosterolester on blood cholesterol concentration in Japanese with borderline or mild cholesterolemia.
        J Clin Biochem Nutr. 2003; 33: 75-82
        • Kurokawa M.
        • Masuda Y.
        • Noda M.
        • Marushima R.
        • Usuda M.
        • Takeda S.
        • et al.
        Minimal effective dose on serum cholesterol concentration and the safety evaluation of dressing containing plant sterol in Japanese subjects.
        J Oleo Sci. 2008; 57: 23-33
        • Kurokawa M.
        • Masuda Y.
        • Noda M.
        • Usuda M.
        • Takeda S.
        • Hasegawa M.
        • et al.
        Effects of dressing containing plant sterol on serum cholesterol concentration and the safety evaluation in borderline or mildly hypercholesterolemic Japanese subjects.
        J Oleo Sci. 2008; 57: 35-45
        • Ras R.T.
        • Fuchs D.
        • Koppenol W.P.
        • Garczarek U.
        • Greyling A.
        • Keicher C.
        • et al.
        The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study.
        Am J Clin Nutr. 2015; 101: 733-741
        • Sialvera T.
        • Pounis G.
        • Koutelidakis A.
        • Richter D.
        • Yfanti G.
        • Kapsokefalou M.
        • et al.
        Phytosterols supplementation decreases plasma small and dense LDL levels in metabolic syndrome patients on a westernized type diet.
        Nutr Metab Cardiovasc Dis. 2012; 22: 843-848
        • Sukmaniah S.
        • Bardosono S.
        • Oetoro S.
        • Permadhi I.
        • Lestarina L.
        The effects of phytosterol in low fat milk on serum lipid levels among mild-moderately hypercholesterolemic subjects.
        Med J Indones. 2008; 17: 5-12
        • Woodgate D.
        • Chan C.H.
        • Conquer J.A.
        Cholesterol-lowering ability of a phytostanol softgel supplement in adults with mild to moderate hypercholesterolemia.
        Lipids. 2006; 41: 127-132
        • Cabral C.E.
        • Klein M.R.S.T.
        Phytosterols in the treatment of hypercholesterolemia and prevention of cardiovascular diseases.
        Arq Bras Cardiol. 2017; 109: 475-482
        • Moreau R.A.
        • Nyström L.
        • Whitaker B.D.
        • Winkler-Moser J.K.
        • Baer D.J.
        • Gebauer S.K.
        • et al.
        Phytosterols and their derivatives: structural diversity, distribution, metabolism, analysis, and health-promoting uses.
        . 2018; 70: 35-61
        • Westover E.J.
        • Lin X.
        • Riehl T.E.
        • Ma L.
        • Stenson W.F.
        • Covey D.F.
        • et al.
        Rapid transient absorption and biliary secretion of enantiomeric cholesterol in hamsters.
        J Lipid Res. 2006; 47: 2374-2381
        • Gylling H.
        • Plat J.
        • Turley S.
        • Ginsberg H.N.
        • Ellegård L.
        • Jessup W.
        • et al.
        Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease.
        Atherosclerosis. 2014; 232: 346-360
        • Moreau R.A.
        • Whitaker B.D.
        • Hicks K.B.
        Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses.
        Prog Lipid Res. 2002; 41: 457-500
        • QuÍlez J.
        • GarcÍa-Lorda P.
        • Salas-Salvadó J.
        Potential uses and benefits of phytosterols in diet: present situation and future directions.
        Clin Nutr. 2003; 22: 343-351
        • Trautwein E.A.
        • Vermeer M.A.
        • Hiemstra H.
        • Ras R.T.
        LDL-cholesterol lowering of plant sterols and stanols-which factors influence their efficacy?.
        Nutrients. 2018; 10
        • Racette S.B.
        • Lin X.
        • Ma L.
        • Ostlund Jr., R.E.
        Natural dietary phytosterols.
        J AOAC Int. 2015; 98: 679-684
        • Law M.
        • Morris J.
        • Wald N.
        Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.
        Br Med J. 2009; 338: b1665
        • Prospective Studies Collaboration
        Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.
        Lancet. 2002; 360: 1903-1913
        • Li Y-c
        • Li C-l
        • Li R.
        • Chen Y.
        • Zhang M.
        • Guo P-p
        • et al.
        Associations of dietary phytosterols with blood lipid profiles and prevalence of obesity in Chinese adults, a cross-sectional study.
        Lipids Health Dis. 2018; 17: 54
        • Cofan M.
        • Escurriol V.
        • Garcia-Otin A.
        • Moreno-Iribas C.
        • Larranaga N.
        • Sanchez M.
        • et al.
        Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study.
        Nutr Metab Cardiovasc Dis. 2011; 21: 651-657
        • Ogawa H.
        • Yamamoto K.
        • Kamisako T.
        • Meguro T.
        Phytosterol additives increase blood pressure and promote stroke onset in salt-loaded stroke-prone spontaneously hypertensive rats.
        Clin Exp Pharmacol Physiol. 2003; 30: 919-924
        • Jakala P.
        • Pere E.
        • Lehtinen R.
        • Turpeinen A.
        • Korpela R.
        • Vapaatalo H.
        Cardiovascular activity of milk casein-derived tripeptides and plant sterols in spontaneously hypertensive rats.
        J Physiol Pharmacol. 2009; 60: 11-20
        • Chen Q.
        • Gruber H.
        • Swist E.
        • Pakenham C.
        • Ratnayake W.M.
        • Scoggan K.A.
        Influence of dietary phytosterols and phytostanols on diastolic blood pressure and the expression of blood pressure regulatory genes in SHRSP and WKY inbred rats.
        Br J Nutr. 2009; 102: 93-101
        • Awad A.
        • Smith A.
        • Fink C.
        Plant sterols regulate rat vascular smooth muscle cell growth and prostacyclin release in culture.
        Prostagl Leukot Essent Fat Acids. 2001; 64: 323-330
        • Lin X.
        • Racette S.B.
        • Ma L.
        • Wallendorf M.
        • Spearie C.A.
        • Ostlund Jr., R.E.
        Plasma biomarker of dietary phytosterol intake.
        PLoS One. 2015; 10e0116912
        • Fetalvero K.M.
        • Martin K.A.
        • Hwa J.
        Cardioprotective prostacyclin signaling in vascular smooth muscle.
        Prostaglandins Other Lipid Mediat. 2007; 82: 109-118
        • Ghaedi E.
        • Varkaneh H.K.
        • Rahmani J.
        • Mousavi S.M.
        • Mohammadi H.
        • Fatahi S.
        • et al.
        Possible anti-obesity effects of phytosterols and phytostanols supplementation in humans: a systematic review and dose–response meta-analysis of randomized controlled trials.
        Phytother Res. 2019; : 1-12
        • Paramsothy P.
        • Knopp R.H.
        • Kahn S.E.
        • Retzlaff B.M.
        • Fish B.
        • Ma L.
        • et al.
        Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity.
        Am J Clin Nutr. 2011; 94: 1182-1188
        • Neter J.E.
        • Stam B.E.
        • Kok F.J.
        • Grobbee D.E.
        • Geleijnse J.M.
        Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials.
        Hypertension. 2003; 42: 878-884
        • Abumweis S.
        • Barake R.
        • Jones P.J.F.
        Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials.
        . 2008; 52: 1811
        • Demonty I.
        • Ras R.T.
        • van der Knaap H.C.
        • Duchateau G.S.
        • Meijer L.
        • Zock P.L.
        • et al.
        Continuous dose-response relationship of the LDL-cholesterol–lowering effect of phytosterol intake.
        . 2008; 139: 271-284
        • Ras R.T.
        • Geleijnse J.M.
        • Trautwein E.A.
        LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies.
        . 2014; 112: 214-219
        • Ferrier K.E.
        • Muhlmann M.H.
        • Baguet J.P.
        • Cameron J.D.
        • Jennings G.L.
        • Dart A.M.
        • et al.
        Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension.
        J Am Coll Cardiol. 2002; 39: 1020-1025
        • Spósito A.C.
        • Mansur A.P.
        • Coelho O.R.
        • Nicolau J.C.
        • Ramires J.A.
        Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensin-converting enzyme inhibitors (enalapril or lisinopril).
        . 1999; 83 (A8): 1497-1499
        • Strazzullo P.
        • Kerry S.M.
        • Barbato A.
        • Versiero M.
        • D'Elia L.
        • Cappuccio F.P.
        Do statins reduce blood pressure? A meta-analysis of randomized, controlled trials.
        . 2007; 49: 792-798
        • Ostlund Jr., R.E.
        • Racette S.B.
        • Stenson W.F.
        Inhibition of cholesterol absorption by phytosterol-replete wheat germ compared with phytosterol-depleted wheat germ.
        Am J Clin Nutr. 2003; 77: 1385-1389
        • Lin X.
        • Ma L.
        • Racette S.B.
        • Swaney W.P.
        • Ostlund Jr., R.E.
        Preparation of intravenous cholesterol tracer using current good manufacturing practices.
        J Lipid Res. 2015; 56: 2393-2398
        • Ratnayake W.M.
        • L'Abbé M.R.
        • Mueller R.
        • Hayward S.
        • Plouffe L.
        • Hollywood R.
        • et al.
        Vegetable oils high in phytosterols make erythrocytes less deformable and shorten the life span of stroke-prone spontaneously hypertensive rats.
        J Nutr. 2000; 130: 1166-1178
        • Chen Q.
        • Gruber H.
        • Swist E.
        • Coville K.
        • Pakenham C.
        • Ratnayake W.M.
        • et al.
        Dietary phytosterols and phytostanols decrease cholesterol levels but increase blood pressure in WKY inbred rats in the absence of salt-loading.
        Nutr Metab. 2010; 7: 11
        • Sehgel N.L.
        • Zhu Y.
        • Sun Z.
        • Trzeciakowski J.P.
        • Hong Z.
        • Hunter W.C.
        • et al.
        Increased vascular smooth muscle cell stiffness: a novel mechanism for aortic stiffness in hypertension.
        Am J Physiol Heart Circ Physiol. 2013; 305: H1281-H1287
        • MacGregor G.A.
        • Rotellar C.
        • Markandu N.D.
        • Smith S.J.
        • Sagnella G.A.
        Contrasting effects of nifedipine, captopril, and propranolol in normotensive and hypertensive subjects.
        J Cardiovasc Pharmacol. 1982; 4: S358-S362
        • Cornelissen V.A.
        • Fagard R.H.
        Effects of endurance training on blood pressure, blood pressure–regulating mechanisms, and cardiovascular risk factors.
        Hypertension. 2005; 46: 667-675
        • Weinberger M.H.
        • Miller J.Z.
        • Luft F.C.
        • Grim C.E.
        • Fineberg N.S.
        Definitions and characteristics of sodium sensitivity and blood pressure resistance.
        Hypertension. 1986; 8: II127-II134
        • Wolfreys A.M.
        • Hepburn P.A.
        Safety evaluation of phytosterol esters. Part 7. Assessment of mutagenic activity of phytosterols, phytosterol esters and the cholesterol derivative, 4-cholesten-3-one.
        Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc. 2002; 40: 461-470
        • Jones P.J.H.
        • Shamloo M.
        • MacKay D.S.
        • Rideout T.C.
        • Myrie S.B.
        • Plat J.
        • et al.
        Progress and perspectives in plant sterol and plant stanol research.
        Nutr Rev. 2018; 76: 725-746
        • Dumolt J.H.
        • Rideout T.C.
        The lipid-lowering effects and associated mechanisms of dietary phytosterol supplementation.
        Curr Pharmaceut Des. 2017; 23: 5077-5085
        • Fardet A.
        • Morise A.
        • Kalonji E.
        • Margaritis I.
        • Mariotti F.
        Influence of phytosterol and phytostanol food supplementation on plasma liposoluble vitamins and provitamin A carotenoid levels in humans: an updated review of the evidence.
        Crit Rev Food Sci Nutr. 2017; 57: 1906-1921
        • Ostlund Jr., R.E.
        • McGill J.B.
        • Zeng C.M.
        • Covey D.F.
        • Stearns J.
        • Stenson W.F.
        • et al.
        Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans.
        Am J Physiol Endocrinol Metab. 2002; 282: E911-E916
        • Gura K.M.
        • Lee S.
        • Valim C.
        • Zhou J.
        • Kim S.
        • Modi B.P.
        • et al.
        Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease.
        Pediatrics. 2008; 121: e678-e686
        • El Kasmi K.C.
        • Anderson A.L.
        • Devereaux M.W.
        • Vue P.M.
        • Zhang W.
        • Setchell K.D.
        • et al.
        Phytosterols promote liver injury and Kupffer cell activation in parenteral nutrition-associated liver disease.
        Sci Transl Med. 2013; 5 (206ra137)