The Atherogenicity of Plant Sterols: The Evidence from Genetics to Clinical Trials
Abstract
The human diet is naturally varied and contains not only essential nutrients, but also contains molecules that the body actively excludes or minimizes exposure. Among these molecules are xenosterols, of which plant sterols comprise the greatest exposure risk. These sterols comprise approximately 50% of the total sterols we eat, yet we retain <0.5% of these in our bodies. The bulk of this exclusion takes place in the intestine and the heterodimeric transporters ABCG5 and ABCG8 are key to keeping these xenosterols out of our bodies. In normal humans, pharmacological supplementation with plant sterols (and stanols) has been used to lower cholesterol as these impair intestinal absorption/ re-absorption of this molecule; lowering plasma cholesterol has cardiovascular risk benefits. This review challenges whether this intervention is beneficial and may even be harmful. We summarize the evidence involving humans who have genetic disruption of ABCG5/ABCG8 function, from clinical trial data examining plant sterols and cardiovascular risk, from genetic data affecting normal humans and ABCG5/ABCG8 variations to data obtained using animal models. Accumulation of xenosterols in any significant amount is clearly associated with increased toxicity, and data suggest that at even low levels there may be effects. Importantly, there is also a paucity of data showing cardiovascular end-point benefits with plant sterol/stanol supplementation. The summary of evidence highlights not only caution in recommending such strategies to lower plasma cholesterol, but also in investigating how these xenosterols can affect processes ranging from cardiovascular, endocrine, and neurological function.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714 · see citing works
Mendelian randomization studies in coronary artery disease
Jansen, H., Samani, N. J., & Schunkert, H. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu208 · Cited by 210 · see citing works
Safety Profile of Extended-Release Niacin in the AIM-HIGH Trial
Anderson, T. J., Boden, W. E., Desvigne-Nickens, P. M., Fleg, J. L., Kashyap, M. L., McBride, R., & Probstfield, J. L. (2014) · New England Journal of Medicine · doi:10.1056/nejmc1311039 · Cited by 81 · see citing works
Coronary bypass grafts in a young girl with sitosterolemia
KOLOVOU, C., Voudris, V. V., Drogari, E., Palatianos, G. M., & Cokkinos, D. (1996) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a014983 · Cited by 47 · see citing works
Vanmierlo, T., Rutten, K., van der Zee, L. C. V. V. –., Friedrichs, S., Bloks, V. W., Blokland, A., Ramaekers, F. C. S., Sijbrands, E. J. G., Steinbusch, H. W. M., Prickaerts, J., et al. (2011) · Plant Foods for Human Nutrition · doi:10.1007/s11130-011-0219-3 · Cited by 40 · see citing works
Evidence-based Management of Lipid Disorders
Stroes, E. S. G., Kastelein, J. J. P., & Vissers, M. N. (2010) · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mozaffarian, D. (2016) · Circulation · doi:10.1161/circulationaha.115.018585 · Cited by 2,216 · see citing works
“Based on cholesterol-lowering effects, some organizations suggest that functional foods with plant sterols/stanols can be considered for people with higher cholesterol levels who do not qualify for or have insufficient response to pharmacotherapy(116); although others have concluded that plant sterols/stanols could ha…”
Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management
Yoo, E.-G. (2016) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2016.21.1.7 · Cited by 166 · see citing works
Patel, S. B., Graf, G. A., & Temel, R. E. (2018) · Journal of Lipid Research · doi:10.1194/jlr.r084244 · Cited by 108 · see citing works
Self-citationGenetic variability in the absorption of dietary sterols affects the risk of coronary artery disease
Helgadóttir, A., Þorleifsson, G., Alexandersson, K. F., Tragante, V., Þorsteinsdóttir, M., Eiríksson, F. F., Grétarsdóttir, S., Björnsson, E., Magnússon, Ó. Þ., Sveinbjörnsson, G., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa531 · Cited by 84 · see citing works
Stellaard, F. (2022) · Nutrients · doi:10.3390/nu14081643 · Cited by 57 · see citing works
Kopylov, A. T., Malsagova, K. A., Stepanov, A. A., & Kaysheva, A. L. (2021) · Nutrients · doi:10.3390/nu13051623 · Cited by 51 · see citing works
Bastida, J. M., Girós, M., Benito, R., Janusz, K., Hernández‐Rivas, J. M., & González‐Porras, J. R. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180705145900 · Cited by 49 · see citing works
Is there a role for lifestyle changes in cardiovascular prevention? What, when and how?
Masana, L., Ros, E., Sudano, I., Angoulvant, D., Ibarretxe, D., Eizagaechevarría, N. M., Arrarte, V., Quintana, A. G., Zamora, A., Silva, A. M. E., et al. (2017) · Atherosclerosis Supplements · doi:10.1016/s1567-5688(17)30020-x · Cited by 47 · see citing works
Self-citationLiwa, A. C., Barton, E. N., Cole, W. C., & Nwokocha, C. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802104-0.00015-9 · Cited by 46 · see citing works
Scholz, M. R., Horn, K., Pott, J., Gross, A., Kleber, M. E., Delgado, G. E., Mishra, P. P., Kirsten, H., Gieger, C., Müller‐Nurasyid, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27706-6 · Cited by 45 · see citing works
Self-citationSitosterolemia: A multifaceted metabolic disorder with important clinical consequences
Tzavella, E., Hatzimichael, E. C., Kostara, C. E., Bairaktari, E. T., Elisaf, M., & Tsimihodimos, V. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.04.116 · Cited by 33 · see citing works
Weingärtner, O., Bogeski, I., Kummerow, C., Schirmer, S. H., Husche, C., Vanmierlo, T., Wagenpfeil, G., Hoth, M., Böhm, M., Lütjohann, D., et al. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.07.016 · Cited by 31 · see citing works
Self-citationPlasma levels of the oxyphytosterol 7α-hydroxycampesterol are associated with cardiovascular events
Fuhrmann, A., Weingärtner, O., Meyer, S., Cremers, B., Seiler-Mußler, S., Schött, H.-F., Kerksiek, A., Friedrichs, S., Ulbricht, U., Zawada, A. M., et al. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.10.010 · Cited by 22 · see citing works
Self-citationDumolt, J. H., Radhakrishnan, S. K., Moghadasian, M. H., Le, K., Patel, M. S., Browne, R. W., & Rideout, T. C. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.09.013 · Cited by 21 · see citing works
Windler, E., Beil, F.-U., Berthold, H. K., Gouni‐Berthold, I., Kassner, U., Klose, G., Lorkowski, S., März, W., Parhofer, K. G., Plat, J., et al. (2023) · Nutrients · doi:10.3390/nu15040828 · Cited by 19 · see citing works
Self-citationFerro, Y., Mazza, E., Angotti, E., Pujia, R., Mirarchi, A., Salvati, M. A., Terracciano, R., Savino, R., Romeo, S., Scuteri, A., et al. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-020-02676-3 · Cited by 17 · see citing works
Phytosterol-Enriched Dietary Supplements for Lowering Plasma LDL-Cholesterol: Yes or No?
Stellaard, F., & Lütjohann, D. (2025) · Nutrients · doi:10.3390/nu17040654 · Cited by 15 · see citing works
Ono, S., Matsuda, J., Saito, A., Yamamoto, T., Fujimoto, W., Shimizu, H., Dateki, S., & Ouchi, K. (2017) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.26.17 · Cited by 15 · see citing works
Tanaka, H., Watanabe, Y. S., Hirano, S., Tada, H., Nomura, A., Kawashiri, M., & Takenaga, M. (2020) · Internal Medicine · doi:10.2169/internalmedicine.3811-19 · Cited by 14 · see citing works
Мирошникова, В. В., Vasiluev, P. A., Linkova, S. V., Soloviov, V. M., Ivanova, O. N., Ричардовна, Т. Е., Udalova, V., Baranova, P. V., Aleksandrova, D. Y., Строкова, Т. В., et al. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13101492 · Cited by 7 · see citing works
Nunes, V. S., Cazita, P. M., Catanozi, S., Nakandakare, E. R., & Quintão, E. C. R. (2019) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-019-09786-8 · Cited by 6 · see citing works
Anagnostis, P. G., Kotsis, V., Banach, M., & Mikhailidis, D. P. (2023) · Metabolites · doi:10.3390/metabo13020145 · Cited by 4 · see citing works
Limonova, A. S., Ershova, A. I., Meshkov, A. N., Kiseleva, A. V., Дивашук, М. Г., Kurkina, M. V., & Drapkina, O. M. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.778961 · Cited by 3 · see citing works
Sitosterolemia caused by mutations in the ABCG8 gene. First case report in Colombia
Saavedra-López, H. F., Lagos, S. Y. O., & Blanco-Bustos, M. P. (2023) · Revista de la Facultad de Medicina · doi:10.15446/revfacmed.v71n4.107181 · Cited by 1 · see citing works
Rare monogenic disorders of cholesterol metabolism
Bednarska‐Makaruk, M., & Ługowska, A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85857-1.00024-9 · Cited by 1 · see citing works
Supplementierung von Phytosterinen
Windler, E. E. T., Zyriax, B., & Beil, F. U. (2015) · CardioVasc · doi:10.1007/s15027-015-0777-7
Xenosterolemia: emerging molecular and clinical insights
Kane, J. P., Schaefer, E. J., & Malloy, M. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000463
Call for an ezetimibe effectiveness test
Lütjohann, D., Laufs, U., Schulze, P. C., & Weingärtner, O. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.08.028
Self-citationFerro, Y., Mazza, E., Angotti, E., Pujia, R., Mirarchi, A., Salvati, M. A., Terracciano, R., Savino, R., Romeo, S., Scuteri, A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13534423
- Authors
- Weingärtner, O., Teupser, D., & Patel, S. B.
- Affiliations
- Carl von Ossietzky Universität Oldenburg (DE)
- Corresponding author
- Weingärtner, Oliver
- Venue
- Journal of AOAC INTERNATIONAL
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05-01
- Volume
- 98
- Issue
- 3
- Pages
- 742-749
- ISSN
- 1060-3271 (ISSN-L)
- 1944-7922
- OpenAlex
- W2400149594
- Cited by
- 29
- References
- 6
- Citations by year
- 2025: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 1
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of AOAC International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- phytosterols, stanols, ABCG5, ABCG8, cardiovascular risk, genetic variants, serum cholesterol, endocrine effects, neurological effects
- MeSH terms
- Animals, Clinical Trials as Topic, Humans, Hypercholesterolemia, Intestinal Diseases, Lipid Metabolism, Inborn Errors, Phytosterols, Plants, Atherosclerosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review