Elliott Jonathan E, Keil Allison T, Mithani Sara, Gill Jessica M, O'Neil Maya E, Cohen Akiva S, Lim Miranda M
VA Portland Health Care System, Portland, OR, United States.
Department of Neurology, Oregon Health & Science University, Portland, OR, United States.
Front Syst Neurosci. 2022 May 4;16:854874. doi: 10.3389/fnsys.2022.854874. eCollection 2022.
Traumatic brain injury (TBI) is associated with chronic sleep disturbances and cognitive impairment. Our prior preclinical work demonstrated dietary supplementation with branched chain amino acids (BCAA: leucine, isoleucine, and valine), precursors to glutamate production, restored impairments in glutamate, orexin/hypocretin neurons, sleep, and memory in rodent models of TBI. This pilot study assessed the feasibility and preliminary efficacy of dietary supplementation with BCAA on sleep and cognition in Veterans with TBI.
Thirty-two Veterans with TBI were prospectively enrolled in a randomized, double-blinded, placebo-controlled trial comparing BCAA (30 g, b.i.d. for 21-days) with one of two placebo arms (microcrystalline cellulose or rice protein, both 30 g, b.i.d. for 21-days). Pre- and post-intervention outcomes included sleep measures (questionnaires, daily sleep/study diaries, and wrist actigraphy), neuropsychological testing, and blood-based biomarkers related to BCAA consumption.
Six subjects withdrew from the study (2/group), leaving 26 remaining subjects who were highly adherent to the protocol (BCAA, 93%; rice protein, 96%; microcrystalline, 95%; actigraphy 87%). BCAA were well-tolerated with few side effects and no adverse events. BCAA significantly improved subjective insomnia symptoms and objective sleep latency and wake after sleep onset on actigraphy.
Dietary supplementation with BCAA is a mechanism-based, promising intervention that shows feasibility, acceptability, and preliminary efficacy to treat insomnia and objective sleep disruption in Veterans with TBI. A larger scale randomized clinical trial is warranted to further evaluate the efficacy, dosing, and duration of BCAA effects on sleep and other related outcome measures in individuals with TBI.
[http://clinicaltrials.gov/], identifier [NCT03990909].
创伤性脑损伤（TBI）与慢性睡眠障碍和认知障碍相关。我们之前的临床前研究表明，补充饮食中的支链氨基酸（BCAA：亮氨酸、异亮氨酸和缬氨酸），即谷氨酸产生的前体，可恢复TBI啮齿动物模型中谷氨酸、食欲素/下丘脑泌素神经元、睡眠和记忆的损伤。这项初步研究评估了补充BCAA饮食对TBI退伍军人睡眠和认知的可行性和初步疗效。
32名患有TBI的退伍军人被前瞻性纳入一项随机、双盲、安慰剂对照试验，比较BCAA（30克，每日两次，共21天）与两个安慰剂组之一（微晶纤维素或大米蛋白，均为30克，每日两次，共21天）。干预前后的结果包括睡眠测量（问卷、每日睡眠/研究日记和手腕活动记录仪）、神经心理学测试以及与BCAA摄入相关的血液生物标志物。
6名受试者退出研究（每组2名），剩下26名受试者高度遵守方案（BCAA组为93%；大米蛋白组为96%；微晶纤维素组为95%；活动记录仪组为87%）。BCAA耐受性良好，副作用少，无不良事件。BCAA显著改善了主观失眠症状以及活动记录仪上的客观睡眠潜伏期和睡眠后觉醒时间。
补充BCAA饮食是一种基于机制的、有前景的干预措施，对治疗TBI退伍军人的失眠和客观睡眠障碍具有可行性、可接受性和初步疗效。有必要进行更大规模的随机临床试验，以进一步评估BCAA对TBI患者睡眠和其他相关结局指标的疗效、剂量和作用持续时间。
