Helena Gylling1, Jogchum Plat2, Stephen Turley3, Henry N Ginsberg4, Lars Ellegård5, Wendy Jessup6, Peter J Jones7, Dieter Lütjohann8, Winfried Maerz9, Luis Masana10, Günther Silbernagel11, Bart Staels12, Jan Borén13, Alberico L Catapano14, Guy De Backer15, John Deanfield16, Olivier S Descamps17, Petri T Kovanen18, Gabriele Riccardi19, Lale Tokgözoglu20, M John Chapman21. 1. Department of Medicine, Division of Internal Medicine, University of Helsinki, Biomedicum Helsinki, Finland. Electronic address: Helena.Gylling@hus.fi. 2. Department of Human Biology, Maastricht University, The Netherlands. Electronic address: j.plat@maastrichtuniversity.nl. 3. Department of Internal Medicine, UT Southwestern Medical Center, Dallas, USA. Electronic address: Stephen.Turley@UTSouthwestern.edu. 4. Irving Institute for Clinical and Translational Research, Columbia University, New York, USA. Electronic address: hng1@columbia.edu. 5. Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Sweden. Electronic address: lasse.ellegard@nutrition.gu.se. 6. ANZAC Research Institute, Concord Hospital, Sydney, Australia. Electronic address: wendy.jessup@gmail.com. 7. Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Canada. Electronic address: Peter.Jones@umanitoba.ca. 8. Institute of Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, Germany. Electronic address: Dieter.Luetjohann@ukb.uni-bonn.de. 9. Synlab Academy, Synlab LLC, Mannheim Center of Laboratory Diagnostics, Heidelberg, Germany; Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, University of Heidelberg, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria. Electronic address: Winfried.Maerz@synlab.com. 10. Vascular Medicine and Metabolism Unit, University Hospital Sant Joan, IISPV, CIBERDEM, Rovira and Virgili University, Reus, Spain. Electronic address: luis.masana@urv.cat. 11. Department of Angiology, Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland. Electronic address: guenther.silbernagel@yahoo.com. 12. Faculty of Pharmacy, University of Lille 2, Lille, France. Electronic address: Bart.Staels@pasteur-lille.fr. 13. Strategic Research Center, Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR), University of Gothenburg, Sweden. Electronic address: Jan.Boren@wlab.gu.se. 14. Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; Multimedica IRCSS Milano, Italy. Electronic address: alberico.catapano@unimi.it. 15. Department of Public Health, University Hospital Ghent, Ghent, Belgium. Electronic address: guy.debacker@ugent.be. 16. National Centre for Cardiovascular Prevention and Outcomes, University College London, UK. Electronic address: john.deanfield@gmail.com. 17. Lipid Clinic, Hopital de Jolimont, Haine-Saint-Paul, Belgium. Electronic address: olivierdescamps@hotmail.com. 18. Wihuri Research Institute, Helsinki, Finland. Electronic address: Petri.Kovanen@wri.fi. 19. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. Electronic address: riccardi@unina.it. 20. Department of Cardiology, Hacettepe University, Ankara, Turkey. Electronic address: lalet@hacettepe.edu.tr. 21. University of Pierre and Marie Curie, Paris, France; Dyslipidaemia and Atherosclerosis Research Unit, INSERM U939, Pitié-Salpetriere University Hospital, Paris, France. Electronic address: john.chapman@upmc.fr.
Abstract
OBJECTIVE: This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. METHODS AND RESULTS: Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. CONCLUSION: Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols.
OBJECTIVE: This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. METHODS AND RESULTS: Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. CONCLUSION: Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols.