比较生育三烯酚和α-生育酚对非酒精性脂肪性肝病患者肝脂肪变性和炎症生物标志物的影响：一项随机、双盲、活性对照试验。

Comparison of delta-tocotrienol and alpha-tocopherol effects on hepatic steatosis and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: A randomized double-blind active-controlled trial.

机构信息

Armed Forces Institute of Pathology, National University of Medical Sciences, Rawalpindi, Pakistan.

出版信息

Complement Ther Med. 2022 Nov;70:102866. doi: 10.1016/j.ctim.2022.102866. Epub 2022 Aug 3.

DOI:10.1016/j.ctim.2022.102866

PMID:35933083

Abstract

OBJECTIVE

We aimed to compare the efficacy of δ-tocotrienol with α-tocopherol in the treatment of patients with non-alcoholic fatty liver disease (NAFLD).

DESIGN AND INTERVENTIONS

This study was a double-blinded, active-controlled trial. The patients with NAFLD were randomly assigned to receive either δ-tocotrienol 300 mg or α-tocopherol 268 mg twice daily for 48 weeks.

ENDPOINTS

The primary endpoints were change from baseline in fatty liver index (FLI), liver-to-spleen attenuation ratio (L/S ratio), and homeostatic model assessment for insulin resistance (HOMA-IR) at 48 weeks. Key secondary endpoints were change in markers of inflammation, oxidative stress, and hepatocyte apoptosis. Clinical assessment, biochemical analysis, and computed tomography scan of the liver were conducted at baseline, 24 and 48 weeks.

RESULTS

A total of 100 patients (δ-tocotrienol = 50, α-tocopherol = 50) were randomized and included in the intention to treat analysis. Compared with baseline, there was a significant improvement (p < .001) in FLI, L/S ratio, HOMA-IR, and serum malondialdehyde in both groups at 48 weeks that was not significant between the two groups. However, there was a significantly greater decrease in body weight, serum interleukin-6, tumor necrosis factor-alpha, leptin, cytokeratin-18, and increase in adiponectin in the δ-tocotrienol group compared to the α-tocopherol group at 48 weeks (p < .05). No adverse events were reported.

CONCLUSION

δ-tocotrienol and α-tocopherol exerted equally beneficial effects in terms of improvement in hepatic steatosis, oxidative stress, and insulin resistance in patients with NAFLD. However, δ-tocotrienol was more potent than α-tocopherol in reducing body weight, inflammation, and apoptosis associated with NAFLD. TRIAL REGISTRATION: Sri Lankan Clinical Trials Registry (https://slctr.lk/SLCTR/2019/038).

摘要

目的

我们旨在比较 δ-生育三烯酚与 α-生育酚治疗非酒精性脂肪性肝病（NAFLD）患者的疗效。

设计和干预

这是一项双盲、活性对照试验。将 NAFLD 患者随机分为两组，分别接受每日两次 δ-生育三烯酚 300mg 或 α-生育酚 268mg，治疗 48 周。

终点

主要终点为治疗 48 周时脂肪性肝病指数（FLI）、肝脾衰减比（L/S 比值）和稳态模型评估的胰岛素抵抗（HOMA-IR）自基线的变化。次要终点为炎症、氧化应激和肝细胞凋亡标志物的变化。在基线、24 周和 48 周时进行临床评估、生化分析和肝脏计算机断层扫描。

结果

共纳入 100 例患者（δ-生育三烯酚组=50 例，α-生育酚组=50 例），进行意向治疗分析。与基线相比，两组患者在 48 周时 FLI、L/S 比值、HOMA-IR 和血清丙二醛均显著改善（均 p<0.001），但两组间无显著差异。然而，与 α-生育酚组相比，δ-生育三烯酚组在 48 周时体重明显下降，血清白细胞介素-6、肿瘤坏死因子-α、瘦素、细胞角蛋白-18 明显下降，脂联素明显增加（均 p<0.05）。未报告不良事件。