Biochemistry Department, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France; INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France.
Calvagone, Liergues, France.
J Lipid Res. 2018 Sep;59(9):1640-1648. doi: 10.1194/jlr.M085043. Epub 2018 Jul 18.
Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption considerably limits correction of the deficiency. In this crossover study, we administered two different forms of vitamin E, tocofersolan (a water-soluble derivative of RRR-α-tocopherol) and α-tocopherol acetate, to three patients with ABL and four patients with CMRD. The aims of this study were to evaluate the intestinal absorption characteristics of tocofersolan versus α-tocopherol acetate by measuring the plasma concentrations of α-tocopherol over time after a single oral load and to compare efficacy by evaluating the ability of each formulation to restore vitamin E storage after 4 months of treatment. In patients with ABL, tocofersolan and α-tocopherol acetate bioavailabilities were extremely low (2.8% and 3.1%, respectively). In contrast, bioavailabilities were higher in patients with CMRD (tocofersolan, 24.7%; α-tocopherol acetate, 11.4%). Plasma concentrations of α-tocopherol at 4 months were not significantly different by formulation type in ABL or CMRD. This study provides new insights about vitamin E status in ABL and CMRD and suggests the potential of different formulations as treatment options.
载脂蛋白 B100 缺乏症(ABL)和乳糜微粒滞留病(CMRD)是两种极为罕见的隐性低β脂蛋白血症,其特征为肠脂质吸收不良和严重的维生素 E 缺乏。维生素 E 通常以脂溶性维生素 E 醋酸酯的形式补充,但脂肪吸收不良极大地限制了缺乏症的纠正。在这项交叉研究中,我们给三名 ABL 患者和四名 CMRD 患者使用了两种不同形式的维生素 E,即生育酚琥珀酸酯(RRR-α-生育酚的水溶性衍生物)和α-生育酚醋酸酯。本研究的目的是通过测量单次口服负荷后 α-生育酚的血浆浓度随时间的变化来评估生育酚琥珀酸酯与α-生育酚醋酸酯的肠道吸收特征,并通过评估每种制剂在 4 个月治疗后恢复维生素 E 储存的能力来比较疗效。在 ABL 患者中,生育酚琥珀酸酯和α-生育酚醋酸酯的生物利用度极低(分别为 2.8%和 3.1%)。相比之下,CMRD 患者的生物利用度较高(生育酚琥珀酸酯,24.7%;α-生育酚醋酸酯,11.4%)。ABL 或 CMRD 患者的α-生育酚血浆浓度在 4 个月时,两种制剂类型之间没有显著差异。本研究为 ABL 和 CMRD 的维生素 E 状态提供了新的见解,并提示不同制剂作为治疗选择的潜力。