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• W2895847477 abstract "Resveratrol and pterostilbene are polyphenolic compounds found in fruits and nuts. Though resveratrol does not depend on sirtuin 1 for its metabolic effects [1Pacholec M. Bleasdale J.E. Chrunyk B. Cunningham D. Flynn D. Garofalo R.S. et al.SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1.J Biol Chem. 2010; 285: 8340-8351https://doi.org/10.1074/jbc.M109.088682Abstract Full Text Full Text PDF PubMed Scopus (752) Google Scholar, 2Park S.J. Ahmad F. Philp A. Baar K. Williams T. Luo H. et al.Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases.Cell. 2012; 148 (S0092-8674(12)00030-X): 421-433https://doi.org/10.1016/j.cell.2012.01.017Abstract Full Text Full Text PDF PubMed Scopus (1049) Google Scholar] and pterostilbene has not been shown to bind to sirtuin 1, Elysium Health combines nicotinamide riboside (NR) [[3]Bieganowski P. Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a preiss-handler independent route to NAD+ in fungi and humans.Cell. 2004; 117: 495-502https://doi.org/10.1016/S0092-8674(04)00416-7Abstract Full Text Full Text PDF PubMed Scopus (482) Google Scholar] with pterostilbene with the expressed purpose of increasing sirtuin 1 activity by a combined mechanism [[4]Dellinger R.W. Santos S.R. Morris M. Evans M. Alminana D. Guarente L. et al.Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD(+) levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.NPJ Aging Mech Dis. 2017; 3: 17https://doi.org/10.1038/s41514-017-0016-9Crossref PubMed Scopus (95) Google Scholar]. The literature indicates that sirtuin 1 activators would be expected to improve lipid management [5Purushotham A. Schug T.T. Xu Q. Surapureddi S. Guo X. Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation.Cell Metab. 2009; 9: 327-338https://doi.org/10.1016/j.cmet.2009.02.006Abstract Full Text Full Text PDF PubMed Scopus (831) Google Scholar, 6Hong S. Moreno-Navarrete J.M. Wei X. Kikukawa Y. Tzameli I. Prasad D. et al.Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization.Nat Med. 2015; 21: 887-894https://doi.org/10.1038/nm.3882Crossref Scopus (148) Google Scholar]. However, as summarized in Table 1, daily administration of NR plus pterostilbene produced a dose-dependent and clinically statistically significant increase in total cholesterol driven entirely by increased low density lipoprotein cholesterol (LDL-C) [[4]Dellinger R.W. Santos S.R. Morris M. Evans M. Alminana D. Guarente L. et al.Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD(+) levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.NPJ Aging Mech Dis. 2017; 3: 17https://doi.org/10.1038/s41514-017-0016-9Crossref PubMed Scopus (95) Google Scholar]. The authors did not release their primary data for independent assessment of significance and did not disclose results previously reported for pterostilbene [[7]Riche D.M. Riche K.D. Blackshear C.T. McEwen C.L. Sherman J.J. Wofford M.R. et al.Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial.Evid Based Complement Alternat Med. 2014; 2014: 459165https://doi.org/10.1155/2014/459165Crossref Scopus (51) Google Scholar] that are wholly consistent with the study's finding of what is clearly a clinically meaningful increase in LDL-C. While the authors cite this study to point out the earlier observation that pterostilbene reduced blood pressure, they neglected to cite clinically meaningful increases in LDL-C for treatment groups receiving 100 mg or 250 mg daily pterostilbene for 6–8 weeks (Table 1) as well as significantly decreased high density lipoprotein cholesterol in subjects who were not taking statins [[7]Riche D.M. Riche K.D. Blackshear C.T. McEwen C.L. Sherman J.J. Wofford M.R. et al.Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial.Evid Based Complement Alternat Med. 2014; 2014: 459165https://doi.org/10.1155/2014/459165Crossref Scopus (51) Google Scholar]. These data are inconsistent with pterostilbene as a sirtuin 1 activator and raise important questions about the safety of pterostilbene supplementation considering the importance of controlling LDL-C to cardiovascular health [8Goff D.C. Lloyd-Jones D.M. Bennett G. Coady S. D'Agostino R.B. Gibbons R. et al.2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines.J Am Coll Cardiol. 2014; 63: 2935-2959https://doi.org/10.1016/j.jacc.2013.11.005Crossref PubMed Scopus (1892) Google Scholar, 9Stone N.J. Robinson J.G. Lichtenstein A.H. Bairey Merz C.N. Blum C.B. Eckel R.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol. 2014; 63: 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002Crossref PubMed Scopus (3312) Google Scholar]. Significantly, clinical studies of NR alone (without pterostilbene) at higher doses than tested in the Elysium Health study established safety and showed no increase in LDL-C [10Martens C.R. Denman B.A. Mazzo M.R. Armstrong M.L. Reisdorph N. McQueen M.B. et al.Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults.Nat Commun. 2018; 9: 1286https://doi.org/10.1038/s41467-018-03421-7Crossref Scopus (291) Google Scholar, 11Dollerup O.L. Christensen B. Svart M. Schmidt M.S. Sulek K. Ringgaard S. et al.A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity and lipid-mobilizing effects.Am J Clin Nutr. 2018; 108: 343https://doi.org/10.1093/ajcn/nqy13Abstract Full Text Full Text PDF Scopus (138) Google Scholar].Table 1Pterostilbene elevates LDL-C.Pterostilbene dose (mg/day)Placebo-corrected increase in LDL-C (mg/dl)P-value100 (7)20.00.006250 (7)19.70.00750 with 250 mg NR (4)5.4≤0.05100 with 500 mg NR (4)14.7≤0.05 Open table in a new tab CB developed intellectual property exclusively licensed and developed by ChromaDex for nutritional and therapeutic uses of NR." @default.
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• W2895847477 title "Pterostilbene raises low density lipoprotein cholesterol in people" @default.
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