Niesor Eric J, Gauthamadasa Kekulawalage, Silva R A Gangani D, Suchankova Gabriela, Kallend David, Gylling Helena, Asztalos Bela, Damonte Elisabetta, Rossomanno Simona, Abt Markus, Davidson W Sean, Benghozi Renee
Pharma Research and Early Development, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, Metabolic DBA, Bldg. 70/411 Grenzacherstrasse 124, 4070, Basel, Switzerland,
Lipids. 2013 Dec;48(12):1185-96. doi: 10.1007/s11745-013-3841-z. Epub 2013 Sep 26.
Fenofibrate and extended-release (ER) niacin similarly raise high-density lipoprotein cholesterol (HDL-C) concentration but their effects on levels of potent plasma antioxidant xanthophylls (lutein and zeaxanthin) and phytosterols obtained from dietary sources, and any relationship with plasma lipoproteins and pre-β1-HDL levels, have not been investigated. We studied these parameters in 66 dyslipidemic patients treated for 6 week with fenofibrate (160 mg/day) or ER-niacin (0.5 g/day for 3 week, then 1 g/day) in a cross-over study. Both treatments increased HDL-C (16 %) and apolipoprotein (apo) A-I (7 %) but only fenofibrate increased apoA-II (28 %). Lutein and zeaxanthin levels were unaffected by fenofibrate but inversely correlated with percentage change in apoB and low-density lipoprotein cholesterol and positively correlated with end of treatment apoA-II. ApoA-II in isolated HDL in vitro bound more lutein than apoA-I. Xanthophylls were increased by ER-niacin (each ~30 %) without any correlation to lipoprotein or apo levels. Only fenofibrate markedly decreased plasma markers of cholesterol absorption; pre-β1-HDL was significantly decreased by fenofibrate (-19 %, p < 0.0001), with little change (3.4 %) for ER-niacin. Although fenofibrate and ER-niacin similarly increased plasma HDL-C and apoA-I, effects on plasma xanthophylls, phytosterols and pre-β1-HDL differed markedly, suggesting differences in intestinal lipidation of HDL. In addition, the in vitro investigations suggest an important role of plasma apoA-II in xanthophyll metabolism.
非诺贝特和缓释烟酸同样能提高高密度脂蛋白胆固醇(HDL-C)浓度,但它们对从饮食中获取的强效血浆抗氧化剂叶黄素(黄体素和玉米黄质)及植物甾醇水平的影响,以及与血浆脂蛋白和前β1-HDL水平的任何关系,尚未得到研究。在一项交叉研究中,我们对66名血脂异常患者进行了研究,这些患者分别接受非诺贝特(160毫克/天)或缓释烟酸(前3周0.5克/天,然后1克/天)治疗6周。两种治疗均使HDL-C升高(16%)和载脂蛋白(apo)A-I升高(7%),但只有非诺贝特使apoA-II升高(28%)。叶黄素和玉米黄质水平不受非诺贝特影响,但与apoB和低密度脂蛋白胆固醇的百分比变化呈负相关,与治疗结束时的apoA-II呈正相关。体外分离的HDL中的apoA-II比apoA-I结合更多的叶黄素。缓释烟酸使叶黄素升高(各约30%),与脂蛋白或载脂蛋白水平无任何相关性。只有非诺贝特显著降低胆固醇吸收的血浆标志物;非诺贝特使前β1-HDL显著降低(-19%,p<0.0001),而缓释烟酸变化很小(3.4%)。尽管非诺贝特和缓释烟酸同样升高血浆HDL-C和apoA-I,但对血浆叶黄素、植物甾醇和前β1-HDL的影响明显不同,提示HDL肠道脂质化存在差异。此外,体外研究表明血浆apoA-II在叶黄素代谢中起重要作用。