Extended-release Niacin Acutely Suppresses Postprandial Triglyceridemia - 20/09/12
Requests for reprints should be addressed to Richard L. Dunbar, MD, MSTR, Perelman School of Medicine at the University of Pennsylvania, Translational Medicine & Human Genetics, 3600 Spruce St, 8046 Maloney Building, Philadelphia, PA 19104Abstract |
Objective |
Postprandial triglyceridemia predicts cardiovascular events. Niacin might lower postprandial triglycerides by restricting free fatty acids. Immediate-release niacin reduced postprandial triglycerides, but extended-release niacin failed to do so when dosed the night before a fat challenge. The study aims were to determine whether extended-release niacin dosed before a fat challenge suppresses postprandial triglycerides and whether postprandial triglycerides are related to free fatty acid restriction.
Methods |
A double-blinded, placebo-controlled, random-order crossover experiment was performed, in which healthy volunteers took 2 g extended-release niacin or placebo 1 hour before heavy cream. We sampled blood over 12 hours and report triglycerides and free fatty acid as means±standard deviation for incremental area under the curve (AUC) and nadir.
Results |
By combining 43 fat challenges from 22 subjects, postprandial triglycerides incremental AUC was +312±200 mg/dL*h on placebo versus +199±200 mg/dL*h on extended-release niacin (33% decrease, P=.02). The incremental nadir for free fatty acid was −0.07±0.15 mmol/L on placebo versus −0.27±0.13 mmol/L on extended-release niacin (P<.0001), and free fatty acid incremental AUC decreased from +2.9±1.5 mmol/L*h to +1.5±1.5 mmol/L*h on extended-release niacin (20% decrease, P=.0015). The incremental AUC for triglycerides was strongly related to the post-dose decrease in free fatty acid (r = +0.58, P=.0007).
Conclusions |
Given right before a fat meal, even a single dose of extended-release niacin suppresses postprandial triglyceridemia. This establishes that postprandial triglycerides suppression is an acute pharmacodynamic effect of extended-release niacin, probably the result of marked free fatty acid restriction. Further study is warranted to determine whether mealtime dosing would augment the clinical efficacy of extended-release niacin therapy.
Le texte complet de cet article est disponible en PDF.Keywords : Adult, African Americans, Clinical trial, Dietary fats, Drug, Evaluation, Free fatty acids, Humans, Hydroxybutyrate, Ketones, Lipids, Lipoprotein, Niacin, Niacin/pharmacology, Niacin/therapeutic use, Postprandial, Randomized controlled trial, Triglycerides
Plan
| Funding: Support provided by NIH grants K23HL091130 and 5-K12-RR-017625-05 (RLD), SCCOR P50-HL-083799 (DJR), and RFA-HL-05-002 (MHUU) from the NHLBI; AHA grants 09SDG2180013 and 0725480U (RLD), and UL1RR024134 from the NCRR, including a Junior Investigator Pilot Grant (RLD) by the UPenn Institute for Diabetes, Obesity, and Metabolism and the UPenn Institute for Translational Medicine and Therapeutics. The content is solely the responsibility of the authors and not sponsoring institutions. |
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| Conflict of Interest: None. |
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| Authorship: All authors had access to the data and played a role in writing this manuscript. |
Vol 125 - N° 10
P. 1026-1035 - octobre 2012 Retour au numéro
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