Carla Wunderle, Claudia Ciobanu, Jacqueline Ritz, Pascal Tribolet, Peter Neyer, Luca Bernasconi, Zeno Stanga, Beat Mueller, Philipp Schuetz
{"title":"亮氨酸和其他支链氨基酸与营养不良住院患者临床疗效的关系：随机临床试验 EFFORT 的二次分析。","authors":"Carla Wunderle, Claudia Ciobanu, Jacqueline Ritz, Pascal Tribolet, Peter Neyer, Luca Bernasconi, Zeno Stanga, Beat Mueller, Philipp Schuetz","doi":"10.1038/s41430-024-01507-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial registration: </strong>clinicaltrials.gov as NCT02517476 (registered 7 August 2015).</p>","PeriodicalId":11927,"journal":{"name":"European Journal of Clinical Nutrition","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association of leucine and other branched chain amino acids with clinical outcomes in malnourished inpatients: a secondary analysis of the randomized clinical trial EFFORT.\",\"authors\":\"Carla Wunderle, Claudia Ciobanu, Jacqueline Ritz, Pascal Tribolet, Peter Neyer, Luca Bernasconi, Zeno Stanga, Beat Mueller, Philipp Schuetz\",\"doi\":\"10.1038/s41430-024-01507-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial registration: </strong>clinicaltrials.gov as NCT02517476 (registered 7 August 2015).</p>\",\"PeriodicalId\":11927,\"journal\":{\"name\":\"European Journal of Clinical Nutrition\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Clinical Nutrition\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41430-024-01507-8\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Clinical Nutrition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41430-024-01507-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
Association of leucine and other branched chain amino acids with clinical outcomes in malnourished inpatients: a secondary analysis of the randomized clinical trial EFFORT.
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).
期刊介绍：
The European Journal of Clinical Nutrition (EJCN) is an international, peer-reviewed journal covering all aspects of human and clinical nutrition. The journal welcomes original research, reviews, case reports and brief communications based on clinical, metabolic and epidemiological studies that describe methodologies, mechanisms, associations and benefits of nutritional interventions for clinical disease and health promotion.
Topics of interest include but are not limited to:
Nutrition and Health (including climate and ecological aspects)
Metabolism & Metabolomics
Genomics and personalized strategies in nutrition
Nutrition during the early life cycle
Health issues and nutrition in the elderly
Phenotyping in clinical nutrition
Nutrition in acute and chronic diseases
The double burden of ''malnutrition'': Under-nutrition and Obesity
Prevention of Non Communicable Diseases (NCD)
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