Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, and the University of Pennsylvania Health System, Philadelphia, PA 19104, USA.
Am J Med. 2012 Oct;125(10):1026-35. doi: 10.1016/j.amjmed.2012.03.017. Epub 2012 Jul 25.
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.
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.
By combining 43 fat challenges from 22 subjects, postprandial triglycerides incremental AUC was +312 ± 200 mg/dLh on placebo versus +199 ± 200 mg/dLh 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/Lh to +1.5 ± 1.5 mmol/Lh 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).
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.
餐后甘油三酯可预测心血管事件。烟酸可通过限制游离脂肪酸来降低餐后甘油三酯。速释烟酸可降低餐后甘油三酯，但在脂肪挑战前一晚给药的情况下，缓释烟酸则不能。本研究旨在确定脂肪挑战前给予缓释烟酸是否可抑制餐后甘油三酯，以及餐后甘油三酯是否与游离脂肪酸限制有关。
进行了一项双盲、安慰剂对照、随机交叉试验，健康志愿者在进食高脂乳剂前 1 小时服用 2 g 缓释烟酸或安慰剂。我们在 12 小时内取样血液，并报告甘油三酯和游离脂肪酸作为增量曲线下面积（AUC）和最低点的平均值 ± 标准差。
结合 22 名受试者的 43 次脂肪挑战，安慰剂组餐后甘油三酯增量 AUC 为+312±200mg/dLh，而缓释烟酸组为+199±200mg/dLh（降低 33%，P=.02）。安慰剂组游离脂肪酸增量最低点为-0.07±0.15mmol/L，而缓释烟酸组为-0.27±0.13mmol/L（P<.0001），缓释烟酸组游离脂肪酸增量 AUC 从+2.9±1.5mmol/Lh 降至+1.5±1.5mmol/Lh（降低 20%，P=.0015）。甘油三酯增量 AUC 与餐后游离脂肪酸下降呈强相关（r=+0.58，P=.0007）。
即使是在脂肪餐前进食单次剂量的缓释烟酸，也可抑制餐后甘油三酯。这表明餐后甘油三酯的抑制是缓释烟酸的一种急性药效学效应，可能是由于游离脂肪酸的显著限制。进一步的研究需要确定在进餐时给予药物是否会增强缓释烟酸治疗的临床疗效。
