| High basal fractional cholesterol synthesis is associated with nonresponse of plasma LDL cholesterol to plant sterol therapy. | |
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MedLine Citation:
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PMID: 20444957 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The cholesterol-lowering effectiveness of plant sterol (PS) therapy is hindered by wide-ranging variability in LDL-cholesterol responsiveness across individuals. To capitalize on the LDL-cholesterol-lowering potential of PS in the clinical setting, it is paramount to characterize the metabolic factors that underlie this heterogeneity of responsiveness. OBJECTIVE: The objective was to investigate the relation between cholesterol synthesis and plasma LDL-cholesterol reductions in response to PS consumption. DESIGN: We evaluated previously conducted clinical PS interventions incorporating stable-isotope measures of cholesterol synthesis and conducted feeding studies in animal models of response (Syrian Golden hamsters) and nonresponse (C57BL/6J mice) to PS consumption. RESULTS: From our clinical study population (n = 113), we identified 47 nonresponders (3.73 +/- 1.10% change in LDL cholesterol) and 66 responders (-15.16 +/- 1.04% change in LDL cholesterol) to PS therapy. The basal cholesterol fractional synthesis rate (FSR) as measured by direct deuterium incorporation was 23% higher (P = 0.003) in the nonresponder subgroup than in responders to PS therapy. The basal cholesterol FSR correlated (r = 0.22, P = 0.02) with the percentage change in LDL cholesterol after PS intervention. In support of our clinical observations, nonresponding mice showed a 77% higher (P = 0.001) basal cholesterol FSR than that of responding hamsters. Compared with control mice, PS-fed mice showed an increase in hepatic nuclear sterol regulatory element binding protein 2 abundance (1.3-fold of control, P = 0.04) and beta-hydroxy-beta-methylglutaryl coenzyme A reductase-mRNA expression (2.4-fold of control, P = 0.00). CONCLUSION: The results suggest that subjects with high basal cholesterol synthesis are less responsive to PS treatment than are subjects with low basal cholesterol synthesis. |
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Authors:
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Todd C Rideout; Scott V Harding; Dylan Mackay; Suhad S Abumweis; Peter Jh Jones |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-05-05 |
Journal Detail:
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Title: The American journal of clinical nutrition Volume: 92 ISSN: 1938-3207 ISO Abbreviation: Am. J. Clin. Nutr. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-21 Completed Date: 2010-07-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376027 Medline TA: Am J Clin Nutr Country: United States |
Other Details:
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Languages: eng Pagination: 41-6 Citation Subset: AIM; IM |
Affiliation:
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Richardson Centre for Functional Foods and Nutraceuticals, Winnipeg, Canada. t_rideout@umanitoba.ca |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Cholesterol / biosynthesis*, blood* Cholesterol, HDL / blood Cholesterol, LDL / blood*, drug effects Cricetinae Cross-Over Studies Female Humans Liver / metabolism Male Mesocricetus Mice Mice, Inbred C57BL Middle Aged Phytosterols / pharmacology, therapeutic use* RNA / isolation & purification Reverse Transcriptase Polymerase Chain Reaction Triglycerides / blood |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Phytosterols; 0/Triglycerides; 57-88-5/Cholesterol; 63231-63-0/RNA |
| Comments/Corrections | |
Comment In:
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Am J Clin Nutr. 2010 Jul;92(1):3-4
[PMID:
20519556
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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