Jones & MacKay: Journal of AOAC International Vol. 98, No. 3, 2015 671
SPECIAL GUEST EDITOR SECTION
Safety, Health, and Methodological Aspects of Plant Sterols and Stanols
T
he intention of this Special Section was to draw together viewpoints from experts in the field of plant sterols and stanols (PS) to arrive at a consensus position document that serves as a demarcation point as to where the field stands as of 2015, a full 20 years after the classic Miettinen et al. (1) article reignited the thendormant discipline of clinical uses of PS in 1995. Indeed, the editors would wish to dedicate this volume to the late Dr. Tatu Miettinen, without whose spark and creativity, the field would not have experienced such an energetic resurgence shortly after his classic 1995 paper was released. The present collection of papers is intended to improve our understanding of where the field of PS presently resides in terms of its accomplishments and addresses challenges, permitting the charting of new courses of inquiry. The global prowess and expertise gathered in this compendium captures the myriad of accomplishments garnered thus far in what is indisputably one of the greatest commercial success stories across modern nutrition (2) as well as within its more recent outgrowth subdiscipline of functional foods. Although the field is replete with comprehensive reviews (3–6) and position statements from international meetings (7–9), not since the early 1980s with David Kritchevsky’s seminal contribution (10) has a collection of individual papers been assembled into a comprehensive monograph providing a state-of-the art snapshot of progress and future hurdles in this scientific area of pursuit. A unique feature of the area of PS is how diverse the sub-issues are across the discipline. In addition to the basic biochemistry surrounding metabolic disposal of this family of compounds there are vital considerations including sourcing for the food supply, food matrixing to optimize efficacy, clinical usage, toxicity considerations, as DOI: 10.5740/jaoacint.SGE_Jones_Intro
well as health claim considerations of penetration of food systems with these ingredients. The present monograph has endeavored to cover many of these topics to deliver a rounded perspective on the overall impact of the field in terms of promotion of health across global populations. Based on the issuance of authoritative statements from various jurisdictions (9, 11), it is quite clear that despite some possible persistence gaps and challenges within the field, this area has had a positive impact on population health. The example of PS used in diet to improve health also serves to illustrate the paradigm shift occurring across several other distinct but parallel areas of nutrition. Whether for omega-3 fats, fiber, or polyphenols, it is most probable that our ancestors’ diets were likely much more abundant in these entities than ours are today. It has been suggested that Paleolithic diets provided over 1 g of PS/day, more than twice what modern diets supply (12). It has also been shown that varying levels of PS in the diet well below those in the multigram/day range can induce health advantages (13, 14). As such, as with other functional ingredients, it has been argued that we ought to be setting our ancestral levels of intake of dietary ingredients as “habitual” to confer optimal health, thus begging the question as to whether PS could possess a semi-essential role in our diet (15). If adequate intakes of PS suppress the absorption of cholesterol in the gut, then it can be argued that dietary deficiency invokes a situation of hypercholesterolemia and suboptimal health. Thus, PS exist as a test case to explore issues surrounding essentiality of functional food ingredients (16). Accordingly, the present monograph was organized in such a manner as to provide a spectrum of articles along a continuum spanning all facets of the field of PS. The Special Section commences with a consideration by Dieter Lütjohann
Peter Jones Special Guest Editor
Dylan MacKay Special Guest Editor
as to how PS levels are optimally measured using what types of analytical tools for accuracy and precision. Particularly, the very low circulating levels of some PS components requires careful methodological considerations. The paper that follows by Peter Clifton underscores the importance of food formulation and matrixing in the context of efficacy of PS, which is a critical consideration for food companies wishing to optimize the health benefits of products containing these ingredients. Issues such as particle size for PS are pointed out as important in determining efficacy of use. The narrative then turns to looking at health benefits of PS, commencing with an examination by Richard Ostlund and co-authors (Racette et al.) of advantages conferred by PS levels already present in the diet. The effect on cholesterol
672 Jones & MacKay: Journal of AOAC International Vol. 98, No. 3, 2015 metabolism and circulating levels of PS at intakes below what are typically found in functional foods has only more recently been identified. Robert Moreau follows by considering ways of configuring functional foods fortified in PS to confer cholesterol lowering benefits using PS sources from pine wood or vegetable oils. How these sources are prepared for use in foods is considered. Following this paper, we turn to the biology of action of PS with a consideration of what has been learned in various animal models, as articulated by Zahra Solati and Mohammed Moghadasian. Next, Jogchum Plat et al. consider how PS intervention results in lipid lowering, providing insight into mechanisms underpinning the processes at the gut level that result in reduced circulating low density lipoprotein cholesterol (LDL-C). Then the focus shifts from food chemistry and nutrition aspects to how PS can be used successfully in clinical practice to manage lipid levels. Montserrat Cofán and Emilio Ros provide a comprehensive picture of how PS can be applied in various clinical settings, alone or as a combined therapeutic approach, for effective management of lipids. Following that discussion is whether PS can be used in the clinical management of circulating triglyceride levels, a controversial area capably addressed by Todd Rideout et al. A further clinical consideration is the disorder associated with hyperabsorption of PS, sitosterolemia; Bridget Ajagbe and Semone Myrie address important aspects of how this disorder is managed by diet and what it provides in terms of a model system to better understand PS trafficking. Peter Jones then considers the aspect existing across studies of variability in responsiveness and contemplates whether genetic predisposition can contribute to the pattern of LDL-C lowering responsiveness of a given individual to PS. The last section of the monograph focuses on aspects of PS metabolism beyond lipid lowering in humans. Scott Harding and co-authors (Yue et al.) provide an overview on potential advantages of the use of PS in nontraditional areas related to inflammatory processes, blood pressure, and endothelial function. Vanu Ramprasath and Atif Awad consider the not unsubstantial amount of data that exist supporting the notion that PS protect against cancer risk in humans, examining in vitro and in vivo evidence in support of that hypothesis. Following consideration of these positive attributes for PS, focus shifts to an equally critical issue surrounding possible safety concerns. Günther Silbernagel et al. address the possible negative aspects of PS directly through a discussion of the potential downside risks of longer term consumption of these dietary ingredients. Safety is a key element of the commercial success of any functional food entity. Oliver Weingärtner et al. address one safety aspect directly: a deeply debated issue that calls to question whether atherogenicity is associated with use of PS. The last paper, by Jerzy Zawistowski and Peter Jones, examines a topic that encompasses all of the issues considered above and looks at global regulatory issues. The health claims allowed for PS in foods and natural health products represent a critical component of the commercial success of this product category. Overall, it is the expectation that the flow of topics provided offers a continuum across a complicated multifaceted topic
that spans from food science and safety to clinical management of disease. In terms of housekeeping, unless referred to specifically, the term PS can be taken to represent both categories of plant sterols (or phytosterols) and their saturated derivatives plant stanols (or phytostanols); however, in a number of instances their impact on biological systems is distinct. Where intakes of plant sterol levels from natural foods are referred to, the level of intake is usually below 400 mg/day. Where functional foods are referred to, generally intakes of between 1 to 3 g/day are considered appropriate for cholesterol lowering. It is intakes in that range that are generally considered to confer optimal LDL-C lowering. Other terms of reference are referred to within individual papers to follow. On behalf of both co-editors and all our contributing authors, it is our collective wish that you as a readership derive value from the information contained in this monograph in a manner that will permit the field to grow and prosper. —Peter Jones and Dylan MacKay University of Manitoba Richardson Centre for Functional Foods and Nutraceuticals Winnipeg, MB, Canada References (1) Miettinen, T.A., Puska, P., Gylling, H., Vanhanen, H., & Vartiainen, E. (1995) N. Engl. J. Med. 333, 1308–1312. http://dx.doi.org/10.1056/NEJM199511163332002 (2) Katan, M.B., Boekschoten, M.V., Connor, W.E., Mensink, R.P., Seidell, J., Vessby, B., & Willett, W.(2009) Eur. J. Clin. Nutr. 63, 2–10. http://dx.doi.org/10.1038/sj.ejcn.1602923 (3) Demonty, I., Ras, R.T., van der Knaap, H.C.M, Duchateau, G.S.M.J.E., Meijer, L., Zock, P.L., Geleijnse, J.M., & Trautwein, E.A. (2009) J. Nutr. 139, 271–284. http://dx.doi.org/10.3945/jn.108.095125 (4) AbuMweis, S.S., Barake, R., & Jones, P.J. (2008) Food Nutr. Res. 52. http://dx.doi.org/10.3402/fnr.v52i0.1811 (5) Musa-Veloso, K., Poon, T.H., Elliot, J.A., & Chung, C. (2011) Prostag. Leukotr. Ess. 85, 9–28. http://dx.doi.org/10.1016/j.plefa.2011.02.001 (6) AbuMweis, S.S., Marinangeli, C.P.F., Frohlich, J., & Jones, P.J.H (2014) Can. J. Cardiol. 30, 1225–1232. http://dx.doi.org/10.1016/j.cjca.2014.04.022 (7) Katan, M.B., Grundy, S.M., Jones, P., Law, M., Miettinen, T., & Paoletti, R. (2003) Mayo Clin. Proc. 78, 965–978. http://doi.org/fx9wfd (8) Plat, J., MacKay, D.S., Baumgartner, S., Clifton, P.M., Gylling, H., & Jones, P.J.H. (2012) Atherosclerosis 225, 521–533. http://dx.doi.org/10.1016/j.atherosclerosis.2012.09.018 (9) Gylling, H., Plat, J., Turley, S., Ginsberg, H.N., Ellegård, L., Jessup, W., Jones, P.J., Lütjohann, D., Maerz, W., Masana, L., Silbernagelm, 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.(2014) Atherosclerosis 232, 346–360. http://dx.doi.org/10.1016/j.atherosclerosis.2013.11.043 (10) Pollak, O.J., & Kritchevsky, D. (1981) in Monographs on Atherosclerosis, Vol. 10, T.B. Clarkson, D. Kritchevsky, & O.J. Pollak (Eds), Krager, Philadelphia, PA, pp 1–219 (11) National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report (2002) Circulation 106, 3143–3421 (12) Jenkins, D.J., Kendall, C.W., Marchie, A., Jenkins, A.L.,
Jones & MacKay: Journal of AOAC International Vol. 98, No. 3, 2015 673 Connelly, P.W., Jones, P.J., & Vuksan, V. (2003) Comp. Biochem. Physiol. A Mol. Integr. Physiol. 136, 141–151. http://doi.org/chsq79 (13) Howell, T.J., MacDougall, D.E., & Jones, P.J. (1998) J. Lipid Res. 39, 892–900 (14) Racette, S.B., Lin, X., Lefevre, M., Spearie, C.A., Most, M.M.,
Ma, L., & Ostlund, R.E. (2010) Am. J. Clin. Nutr. 91, 32–38. http://dx.doi.org/10.3945/ajcn.2009.28070 (15) Jones, P.J., & Varady, K.A. (2008) Appl. Physiol. Nutr. Metab. 33, 118–123. http://dx.doi.org/10.1139/H07-134 (16) Jew, S., Antoine, J., Bourdioux, P., Milner, J., Tapsell, L.C., Yang, Y., & Jones, P.J.H. (2015) J. Funct. Foods 14, 203–209. http://dx.doi.org/10.1016/j.jff.2015.01.024
SPECIAL GUEST EDITOR SECTION
Safety, Health, and Methodological Aspects of Plant Sterols and Stanols
T
he intention of this Special Section was to draw together viewpoints from experts in the field of plant sterols and stanols (PS) to arrive at a consensus position document that serves as a demarcation point as to where the field stands as of 2015, a full 20 years after the classic Miettinen et al. (1) article reignited the thendormant discipline of clinical uses of PS in 1995. Indeed, the editors would wish to dedicate this volume to the late Dr. Tatu Miettinen, without whose spark and creativity, the field would not have experienced such an energetic resurgence shortly after his classic 1995 paper was released. The present collection of papers is intended to improve our understanding of where the field of PS presently resides in terms of its accomplishments and addresses challenges, permitting the charting of new courses of inquiry. The global prowess and expertise gathered in this compendium captures the myriad of accomplishments garnered thus far in what is indisputably one of the greatest commercial success stories across modern nutrition (2) as well as within its more recent outgrowth subdiscipline of functional foods. Although the field is replete with comprehensive reviews (3–6) and position statements from international meetings (7–9), not since the early 1980s with David Kritchevsky’s seminal contribution (10) has a collection of individual papers been assembled into a comprehensive monograph providing a state-of-the art snapshot of progress and future hurdles in this scientific area of pursuit. A unique feature of the area of PS is how diverse the sub-issues are across the discipline. In addition to the basic biochemistry surrounding metabolic disposal of this family of compounds there are vital considerations including sourcing for the food supply, food matrixing to optimize efficacy, clinical usage, toxicity considerations, as DOI: 10.5740/jaoacint.SGE_Jones_Intro
well as health claim considerations of penetration of food systems with these ingredients. The present monograph has endeavored to cover many of these topics to deliver a rounded perspective on the overall impact of the field in terms of promotion of health across global populations. Based on the issuance of authoritative statements from various jurisdictions (9, 11), it is quite clear that despite some possible persistence gaps and challenges within the field, this area has had a positive impact on population health. The example of PS used in diet to improve health also serves to illustrate the paradigm shift occurring across several other distinct but parallel areas of nutrition. Whether for omega-3 fats, fiber, or polyphenols, it is most probable that our ancestors’ diets were likely much more abundant in these entities than ours are today. It has been suggested that Paleolithic diets provided over 1 g of PS/day, more than twice what modern diets supply (12). It has also been shown that varying levels of PS in the diet well below those in the multigram/day range can induce health advantages (13, 14). As such, as with other functional ingredients, it has been argued that we ought to be setting our ancestral levels of intake of dietary ingredients as “habitual” to confer optimal health, thus begging the question as to whether PS could possess a semi-essential role in our diet (15). If adequate intakes of PS suppress the absorption of cholesterol in the gut, then it can be argued that dietary deficiency invokes a situation of hypercholesterolemia and suboptimal health. Thus, PS exist as a test case to explore issues surrounding essentiality of functional food ingredients (16). Accordingly, the present monograph was organized in such a manner as to provide a spectrum of articles along a continuum spanning all facets of the field of PS. The Special Section commences with a consideration by Dieter Lütjohann
Peter Jones Special Guest Editor
Dylan MacKay Special Guest Editor
as to how PS levels are optimally measured using what types of analytical tools for accuracy and precision. Particularly, the very low circulating levels of some PS components requires careful methodological considerations. The paper that follows by Peter Clifton underscores the importance of food formulation and matrixing in the context of efficacy of PS, which is a critical consideration for food companies wishing to optimize the health benefits of products containing these ingredients. Issues such as particle size for PS are pointed out as important in determining efficacy of use. The narrative then turns to looking at health benefits of PS, commencing with an examination by Richard Ostlund and co-authors (Racette et al.) of advantages conferred by PS levels already present in the diet. The effect on cholesterol
672 Jones & MacKay: Journal of AOAC International Vol. 98, No. 3, 2015 metabolism and circulating levels of PS at intakes below what are typically found in functional foods has only more recently been identified. Robert Moreau follows by considering ways of configuring functional foods fortified in PS to confer cholesterol lowering benefits using PS sources from pine wood or vegetable oils. How these sources are prepared for use in foods is considered. Following this paper, we turn to the biology of action of PS with a consideration of what has been learned in various animal models, as articulated by Zahra Solati and Mohammed Moghadasian. Next, Jogchum Plat et al. consider how PS intervention results in lipid lowering, providing insight into mechanisms underpinning the processes at the gut level that result in reduced circulating low density lipoprotein cholesterol (LDL-C). Then the focus shifts from food chemistry and nutrition aspects to how PS can be used successfully in clinical practice to manage lipid levels. Montserrat Cofán and Emilio Ros provide a comprehensive picture of how PS can be applied in various clinical settings, alone or as a combined therapeutic approach, for effective management of lipids. Following that discussion is whether PS can be used in the clinical management of circulating triglyceride levels, a controversial area capably addressed by Todd Rideout et al. A further clinical consideration is the disorder associated with hyperabsorption of PS, sitosterolemia; Bridget Ajagbe and Semone Myrie address important aspects of how this disorder is managed by diet and what it provides in terms of a model system to better understand PS trafficking. Peter Jones then considers the aspect existing across studies of variability in responsiveness and contemplates whether genetic predisposition can contribute to the pattern of LDL-C lowering responsiveness of a given individual to PS. The last section of the monograph focuses on aspects of PS metabolism beyond lipid lowering in humans. Scott Harding and co-authors (Yue et al.) provide an overview on potential advantages of the use of PS in nontraditional areas related to inflammatory processes, blood pressure, and endothelial function. Vanu Ramprasath and Atif Awad consider the not unsubstantial amount of data that exist supporting the notion that PS protect against cancer risk in humans, examining in vitro and in vivo evidence in support of that hypothesis. Following consideration of these positive attributes for PS, focus shifts to an equally critical issue surrounding possible safety concerns. Günther Silbernagel et al. address the possible negative aspects of PS directly through a discussion of the potential downside risks of longer term consumption of these dietary ingredients. Safety is a key element of the commercial success of any functional food entity. Oliver Weingärtner et al. address one safety aspect directly: a deeply debated issue that calls to question whether atherogenicity is associated with use of PS. The last paper, by Jerzy Zawistowski and Peter Jones, examines a topic that encompasses all of the issues considered above and looks at global regulatory issues. The health claims allowed for PS in foods and natural health products represent a critical component of the commercial success of this product category. Overall, it is the expectation that the flow of topics provided offers a continuum across a complicated multifaceted topic
that spans from food science and safety to clinical management of disease. In terms of housekeeping, unless referred to specifically, the term PS can be taken to represent both categories of plant sterols (or phytosterols) and their saturated derivatives plant stanols (or phytostanols); however, in a number of instances their impact on biological systems is distinct. Where intakes of plant sterol levels from natural foods are referred to, the level of intake is usually below 400 mg/day. Where functional foods are referred to, generally intakes of between 1 to 3 g/day are considered appropriate for cholesterol lowering. It is intakes in that range that are generally considered to confer optimal LDL-C lowering. Other terms of reference are referred to within individual papers to follow. On behalf of both co-editors and all our contributing authors, it is our collective wish that you as a readership derive value from the information contained in this monograph in a manner that will permit the field to grow and prosper. —Peter Jones and Dylan MacKay University of Manitoba Richardson Centre for Functional Foods and Nutraceuticals Winnipeg, MB, Canada References (1) Miettinen, T.A., Puska, P., Gylling, H., Vanhanen, H., & Vartiainen, E. (1995) N. Engl. J. Med. 333, 1308–1312. http://dx.doi.org/10.1056/NEJM199511163332002 (2) Katan, M.B., Boekschoten, M.V., Connor, W.E., Mensink, R.P., Seidell, J., Vessby, B., & Willett, W.(2009) Eur. J. Clin. Nutr. 63, 2–10. http://dx.doi.org/10.1038/sj.ejcn.1602923 (3) Demonty, I., Ras, R.T., van der Knaap, H.C.M, Duchateau, G.S.M.J.E., Meijer, L., Zock, P.L., Geleijnse, J.M., & Trautwein, E.A. (2009) J. Nutr. 139, 271–284. http://dx.doi.org/10.3945/jn.108.095125 (4) AbuMweis, S.S., Barake, R., & Jones, P.J. (2008) Food Nutr. Res. 52. http://dx.doi.org/10.3402/fnr.v52i0.1811 (5) Musa-Veloso, K., Poon, T.H., Elliot, J.A., & Chung, C. (2011) Prostag. Leukotr. Ess. 85, 9–28. http://dx.doi.org/10.1016/j.plefa.2011.02.001 (6) AbuMweis, S.S., Marinangeli, C.P.F., Frohlich, J., & Jones, P.J.H (2014) Can. J. Cardiol. 30, 1225–1232. http://dx.doi.org/10.1016/j.cjca.2014.04.022 (7) Katan, M.B., Grundy, S.M., Jones, P., Law, M., Miettinen, T., & Paoletti, R. (2003) Mayo Clin. Proc. 78, 965–978. http://doi.org/fx9wfd (8) Plat, J., MacKay, D.S., Baumgartner, S., Clifton, P.M., Gylling, H., & Jones, P.J.H. (2012) Atherosclerosis 225, 521–533. http://dx.doi.org/10.1016/j.atherosclerosis.2012.09.018 (9) Gylling, H., Plat, J., Turley, S., Ginsberg, H.N., Ellegård, L., Jessup, W., Jones, P.J., Lütjohann, D., Maerz, W., Masana, L., Silbernagelm, 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.(2014) Atherosclerosis 232, 346–360. http://dx.doi.org/10.1016/j.atherosclerosis.2013.11.043 (10) Pollak, O.J., & Kritchevsky, D. (1981) in Monographs on Atherosclerosis, Vol. 10, T.B. Clarkson, D. Kritchevsky, & O.J. Pollak (Eds), Krager, Philadelphia, PA, pp 1–219 (11) National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report (2002) Circulation 106, 3143–3421 (12) Jenkins, D.J., Kendall, C.W., Marchie, A., Jenkins, A.L.,
Jones & MacKay: Journal of AOAC International Vol. 98, No. 3, 2015 673 Connelly, P.W., Jones, P.J., & Vuksan, V. (2003) Comp. Biochem. Physiol. A Mol. Integr. Physiol. 136, 141–151. http://doi.org/chsq79 (13) Howell, T.J., MacDougall, D.E., & Jones, P.J. (1998) J. Lipid Res. 39, 892–900 (14) Racette, S.B., Lin, X., Lefevre, M., Spearie, C.A., Most, M.M.,
Ma, L., & Ostlund, R.E. (2010) Am. J. Clin. Nutr. 91, 32–38. http://dx.doi.org/10.3945/ajcn.2009.28070 (15) Jones, P.J., & Varady, K.A. (2008) Appl. Physiol. Nutr. Metab. 33, 118–123. http://dx.doi.org/10.1139/H07-134 (16) Jew, S., Antoine, J., Bourdioux, P., Milner, J., Tapsell, L.C., Yang, Y., & Jones, P.J.H. (2015) J. Funct. Foods 14, 203–209. http://dx.doi.org/10.1016/j.jff.2015.01.024
