Biological responses during high-dose protein nutrition in the critically ill: a randomized controlled trial.

IF 6.5 1区医学 Q1 NUTRITION & DIETETICS

American Journal of Clinical Nutrition Pub Date : 2025-06-26 DOI:10.1016/j.ajcnut.2025.05.025

Arnold S Kristof, Mengyin Hong, Nadia Boufaied, Nihad Tousson-Abouelazm, Surya Dandamudi, Kwang-Bo Joung, Roupen Hatzakorzian, Michelle Port, Giuseppina Campisi, Ciriaco A Piccirillo, Gregory J Fonseca, Jun Ding, Daren K Heyland, David P Labbé, Linda Wykes, Thomas Schricker

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引用次数: 0

Abstract

Background: Reduced protein intake is associated with adverse outcomes in critically ill patients. Paradoxically, large-scale randomized controlled trials have failed to demonstrate a beneficial effect of protein supplementation, perhaps because the dose required to achieve an anabolic response is unknown, and because biological mechanisms that determine individual patient responses to nutrition are poorly understood.

Objectives: The objective of this study was to determine the effect of exogenous protein dose on whole-body protein balance (WBPB) and associated biological markers of metabolic response.

Methods: We conducted a randomized controlled trial to determine the effect of high dose (2.5 g/kg/d by parenteral amino acid infusion for 48 h) compared with usual (0.8 g/kg/d) or moderate (1.75 g/kg/d) doses on WBPB. By measuring ¹³C-leucine stable isotope kinetics, whole-body protein synthesis and breakdown were evaluated before and after the intervention. As a comprehensive and well-annotated method to achieve untargeted biomarker identification, the blood transcriptome was interrogated by RNA sequencing every 12 h to identify molecular signatures associated with increases in WBPB during protein supplementation.

Results: Thirty-three patients were randomly assigned, and 25 completed the study. The increase in WBPB for the high-dose group was 10.0±3.7, and that for the moderate and usual-dose groups were 6.7±2.9 and 6.6±3.6, μmol/kg/h (mean±SEM) respectively. After adjusting for baseline WBPB, high dose (P = 0.036 vs. usual dose, P = 0.047 vs. moderate dose), but not moderate dose (P = 0.893 vs. usual dose) protein led to larger increases in WBPB. Increased WBPB was associated with lower baseline protein balance (R² = 0.18, P = 0.03), and reduced expression of a distinct neutrophil bactericidal gene signature (normalized enrichment score = -1.613, P_adj = 0.003).

Conclusions: Larger increases in WBPB were observed in critically ill patients receiving a high-dose protein supplementation strategy, and these increases were associated with a biological program reflecting neutrophil-mediated bacterial killing.

Clinical trial registration: ClinicalTrials.gov NCT02865408.

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危重病人高剂量蛋白质营养期间的生物学反应：一项随机对照试验。

背景：减少蛋白质摄入与危重患者的不良结局相关。矛盾的是，大规模随机对照试验未能证明补充蛋白质的有益效果，这可能是因为实现合成代谢反应所需的剂量尚不清楚，也可能是因为确定个体患者对营养反应的生物学机制尚不清楚。目的：本研究的目的是确定外源蛋白质剂量对全身蛋白质平衡（WBPB）和代谢反应相关生物学标志物的影响。方法：我们进行了一项随机对照试验，以确定高剂量（静脉注射氨基酸2.5 g/kg/d，持续48 h）与普通剂量（0.8 g/kg/d）或中等剂量（1.75 g/kg/d）对WBPB的影响。通过测定13c -亮氨酸稳定同位素动力学，评估干预前后的全身蛋白质合成和分解情况。作为一种全面且注释良好的非靶向生物标志物鉴定方法，每12小时通过RNA测序对血液转录组进行查询，以鉴定蛋白质补充期间与WBPB增加相关的分子特征。结果：33例患者被随机分配，其中25例完成了研究。高剂量组WBPB增加10.0±3.7 μmol/kg/h，中、常剂量组分别增加6.7±2.9和6.6±3.6 μmol/kg/h （mean±SEM）。调整基线WBPB后，高剂量蛋白（P = 0.036 vs通常剂量，P = 0.047 vs中等剂量）导致WBPB增加较大，而非中等剂量蛋白（P = 0.893 vs通常剂量）导致WBPB增加较大。增加的WBPB与较低的基线蛋白平衡（R2 = 0.18, P = 0.03）和不同的中性粒细胞杀菌基因特征的表达减少相关（标准化富集评分= -1.613,Padj = 0.003）。结论：在接受高剂量蛋白质补充策略的危重患者中观察到更大的WBPB增加，这些增加与反映中性粒细胞介导的细菌杀伤的生物学程序有关。临床试验注册：ClinicalTrials.gov NCT02865408。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Clinical Nutrition 医学-营养学

CiteScore

12.40

自引率

4.20%

发文量

332

审稿时长

38 days

期刊介绍： American Journal of Clinical Nutrition is recognized as the most highly rated peer-reviewed, primary research journal in nutrition and dietetics.It focuses on publishing the latest research on various topics in nutrition, including but not limited to obesity, vitamins and minerals, nutrition and disease, and energy metabolism. Purpose: The purpose of AJCN is to: Publish original research studies relevant to human and clinical nutrition. Consider well-controlled clinical studies describing scientific mechanisms, efficacy, and safety of dietary interventions in the context of disease prevention or health benefits. Encourage public health and epidemiologic studies relevant to human nutrition. Promote innovative investigations of nutritional questions employing epigenetic, genomic, proteomic, and metabolomic approaches. Include solicited editorials, book reviews, solicited or unsolicited review articles, invited controversy position papers, and letters to the Editor related to prior AJCN articles. Peer Review Process: All submitted material with scientific content undergoes peer review by the Editors or their designees before acceptance for publication.