亮氨酸及其他支链氨基酸与营养不良住院患者临床结局的关联：随机临床试验EFFORT的二次分析
Association of leucine and other branched chain amino acids with clinical outcomes in malnourished inpatients: a secondary analysis of the randomized clinical trial EFFORT.
作者信息
Wunderle Carla, Ciobanu Claudia, Ritz Jacqueline, Tribolet Pascal, Neyer Peter, Bernasconi Luca, Stanga Zeno, Mueller Beat, Schuetz Philipp
机构信息
Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Medical Faculty of the University of Basel, Basel, Switzerland.
出版信息
Eur J Clin Nutr. 2025 Jan;79(1):42-49. doi: 10.1038/s41430-024-01507-8. Epub 2024 Sep 8.
BACKGROUND
The essential branched-chain amino acids leucine, isoleucine and valine are considered anabolic and stimulate protein synthesis in the muscles as well in the liver. They also promote muscle recovery and contribute to glucose homeostasis. Recent studies in critically ill patients have demonstrated that depletion of plasma leucine is associated with increased mortality, but data in the non-critical care setting is lacking.
METHODS
This secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), investigated the impact of leucine, isoleucine, and valine metabolism on clinical outcomes. The primary endpoint was 180-day all-cause mortality.
RESULTS
Among 238 polymorbid patients with available metabolite measurements, low serum leucin levels were associated with a doubled risk of 180-day all-cause mortality in a fully adjusted regression model (adjusted HR 2.20 [95% CI 1.46-3.30], p < 0.001). There was also an association with mortality for isoleucine (1.56 [95% CI 1.03-2.35], p = 0.035) and valine (1.69 [95% CI 1.13-2.53], p = 0.011). When comparing effects of nutritional support on mortality in patients with high and low levels of leucine, there was no evidence of significant differences in effectiveness of the intervention. The same was true for isoleucine and valine.
CONCLUSION
Our data suggest that depletion of leucine, isoleucine, and valine among malnourished polymorbid patients is associated with increases in long-term mortality. However, patients with low metabolite levels did not show a pronounced benefit from nutritional support. Further research should focus on the clinical effects of nutritional support in patients with depleted stores of essential branched-chain amino acids.
CLINICAL TRIAL REGISTRATION
clinicaltrials.gov as NCT02517476 (registered 7 August 2015).
背景
必需支链氨基酸亮氨酸、异亮氨酸和缬氨酸被认为具有合成代谢作用，可刺激肌肉以及肝脏中的蛋白质合成。它们还能促进肌肉恢复并有助于维持葡萄糖稳态。最近对危重症患者的研究表明，血浆亮氨酸水平降低与死亡率增加有关，但非重症监护环境下的数据尚缺。
方法
这项对营养不良内科住院患者早期营养支持对虚弱、功能结局和恢复的影响的随机对照试验（EFFORT）的二次分析，研究了亮氨酸、异亮氨酸和缬氨酸代谢对临床结局的影响。主要终点是180天全因死亡率。
结果
在238例有可用代谢物测量值的多病共存患者中，在完全调整的回归模型中，低血清亮氨酸水平与180天全因死亡率风险加倍相关（调整后风险比2.20 [95%置信区间1.46 - 3.30]，p < 0.001）。异亮氨酸（1.56 [95%置信区间1.03 - 2.35]，p = 0.035）和缬氨酸（1.69 [95%置信区间1.13 - 2.53]，p = 0.011）与死亡率也存在关联。比较营养支持对亮氨酸水平高低患者死亡率的影响时，没有证据表明干预效果存在显著差异。异亮氨酸和缬氨酸情况相同。
结论
我们的数据表明，营养不良的多病共存患者中亮氨酸、异亮氨酸和缬氨酸的缺乏与长期死亡率增加有关。然而，代谢物水平低的患者并未显示出营养支持带来的明显益处。进一步的研究应聚焦于必需支链氨基酸储备不足患者营养支持的临床效果。
临床试验注册
clinicaltrials.gov，编号NCT02517476（2015年8月7日注册）
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