Ketogenicdiet versus standard high-carbohydrate nutrition in sepsis: a randomized controlled trial

Sepsis patients suffer from severe metabolic and immunologic dysfunction that may be amplified by standard nutritional approaches relying primarily on carbohydrates. We here hypothesize that a ketogenic diet improves sepsis treatment. We conducted a monocentric open-labeled randomized controlled trial enrolling 40 adult sepsis patients. Patients were randomly assigned to either ketogenic diet (KD) or standard high-carbohydrate nutrition for 14 days and followed up until day 30. The primary outcome measure was ß-hydroxybutyrate (BHB) serum concentration on day 14. We assessed feasibility and safety of KD, as well as diet-associated clinical and immunological changes. The respective nutrition protocols were successfully applied, dropouts did not occur. Regression analysis revealed a greater increase in BHB concentrations from baseline to day 14 in KD patients compared to controls. Metabolic side effects were not observed under ketogenic diet. Ventilation-free, vasopressor-free, dialysis-free and ICU-free days significantly increased in patients under ketogenic diet. Transcriptome profiling of both CD4+ and CD8+ T cells at day 14 revealed substantial differential regulation of gene expression in the KD vs. the control group indicating a reduced T-cell activation and a shift towards a more regulated immunity. Overall design: To investiagte the impact of an ketogenic diet on septic patients treated on intensive care unit we conducted a monocentric open-labeled randomized controlled trial enrolling 40 adult sepsis patients. Patients were randomly assigned to either ketogenic diet (KD) or standard high-carbohydrate nutrition for 14 days and followed up until day 30. In order to analyse the influence of KD on the immune response in sepsis, we used Next-Generation Sequencing of mRNA from CD4+ and CD8+ T cells isolated before (T1) and after 14-day study phase (T14) for transcriptome profiling. CTRL=Control group, Keto = ketogenic group

脓毒症患者会出现严重的代谢与免疫功能紊乱，而以碳水化合物为核心的常规营养支持方案可能会加重该紊乱。本研究假设生酮饮食（ketogenic diet, KD）可改善脓毒症的临床治疗效果。我们开展了一项单中心开放标签随机对照试验，共纳入40名成人脓毒症患者。患者被随机分配至生酮饮食组或常规高碳水化合物营养支持组，干预时长为14天，随访至入院后第30天。本研究的主要结局指标为干预第14天的血清β-羟基丁酸（β-hydroxybutyrate, BHB）浓度。我们评估了生酮饮食的可行性与安全性，同时分析了饮食干预相关的临床及免疫学变化。两组营养方案均顺利实施，无受试者脱落。回归分析结果显示，与对照组相比，生酮饮食组患者从基线至第14天的血清BHB浓度升高幅度更为显著。生酮饮食干预期间未观察到代谢相关不良反应。生酮饮食组患者的无机械通气天数、无血管活性药物天数、无透析天数及非重症监护病房（intensive care unit, ICU）住院天数均显著增加。对第14天采集的CD4+及CD8+ T细胞进行转录组分析显示，生酮饮食组与对照组的基因表达存在显著差异调控，提示生酮饮食可降低T细胞活化程度，并使免疫状态向更具调控性的方向转变。研究设计：为探究生酮饮食对重症监护病房收治的脓毒症患者的干预效果，本研究开展了一项单中心开放标签随机对照试验，共纳入40名成人脓毒症患者。患者被随机分配至生酮饮食组或常规高碳水化合物营养支持组，干预时长为14天，随访至第30天。为分析生酮饮食对脓毒症患者免疫应答的影响，我们分别在干预前（T1）及14天干预阶段结束后（T14）分离CD4+与CD8+ T细胞，对其mRNA进行下一代测序（Next-Generation Sequencing, NGS）以开展转录组分析。CTRL=对照组，Keto=生酮饮食组