Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Bandar Tun RazakKuala Lumpur, 56000, Malaysia.
Department of Pediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000, Kuala Lumpur, Malaysia.
BMC Pediatr. 2024 Aug 20;24(1):529. doi: 10.1186/s12887-024-04993-8.
Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD.
A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored.
APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045).
The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children.
The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).
儿童肥胖是一个日益严重的问题，非酒精性脂肪性肝病（NAFLD）是其重要后果。目前，尚无批准用于治疗儿童 NAFLD 的药物。然而，最近的一项研究探讨了富含生育三烯酚（TRF）的维生素 E 作为治疗 NAFLD 的有效抗氧化剂的潜力。本研究的目的是探讨 TRF 治疗肥胖和 NAFLD 儿童的有效性和安全性。
29 名年龄在 10 至 18 岁的患者接受了为期 6 个月（2020 年 1 月至 2022 年 2 月）的每日口服 50mg TRF，所有患者均通过超声检查和丙氨酸氨基转移酶水平异常升高（至少比各自性别高两倍）发现患有脂肪肝疾病。监测了各种参数，包括生化标志物、FibroScan、LiverFASt、DNA 损伤和细胞因子表达。
TRF 组干预后 APO-A1 和 AST 水平分别从 1.39±0.3 降至 1.22±0.2g/L（P=0.002）和从 30±12 降至 22±10g/L（P=0.038）。安慰剂组肝内脂肪变性从 309.38±53.60db/m 显著减少到 277.62±39.55db/m（p=0.048），而 TRF 组则没有。彗星试验分析显示，TRF 组在干预后与基线相比，DNA 损伤参数显著减少，尾部长度从 28.34±10.9 减少到 21.69±9.84；（p=0.049）和尾部 DNA（%）从 54.13±22.1 减少到 46.23±17.9；（p=0.043）。与基线相比，TRF 组促炎细胞因子表达水平显著降低，IL-6（2.10 6.3 至 0.7 1.0pg/mL；p=0.047pg/mL）和 TNF-1（1.73 5.5pg/mL 至 0.7 0.5pg/mL；p=0.045）。
该研究提供了证据表明，TRF 补充剂可能为肥胖和 NAFLD 儿童提供一种无风险的治疗选择。TRF 的抗氧化和抗炎特性为 NAFLD 的治疗提供了一种有前途的辅助治疗方法。与运动和热量限制等生活方式改变相结合，TRF 可能在未来 NAFLD 的预防中发挥重要作用。然而，需要进一步的研究来探索 TRF 补充剂对儿童 NAFLD 的长期影响。
该研究已在国际临床试验注册处（NCT05905185）注册，参考号为（15/06/2023），为回顾性注册。
