Table1_A systematic review and meta-regression of exogenous ketone infusion rates and resulting ketosis—A tool for clinicians and researchers.DOCX

Introduction: Ketone bodies such as beta-hydroxybutyrate (BHB) have pleiotropic functional benefits as fuel and signaling metabolites and may have multiple clinical applications. An alternative to inducing ketosis by dietary modification is intravenous delivery of exogenous sources of ketones. It is unknown whether there is a strong relationship between BHB infusion rate and blood BHB concentrations in the published literature; this information is vital for clinical studies investigating therapeutic effects of ketosis. This systematic review aimed to aggregate available data and address this gap.
Methods: The PubMed and EMBASE databases were searched, and data were extracted from 23 manuscripts where BHB was infused and maximum and/or steady state BHB levels assessed. Infusion rate was adjusted when racemic BHB was infused but only D-BHB was measured.
Results: Using a random effects meta-regression, strong linear relationships between BHB infusion rate and maximal (y = 0.060 + 0.870x, R2 = 87.2%, p < 0.0001) and steady state (y = −0.022 + 0.849x, R2 = 86.9%, p < 0.0001) blood BHB concentrations were found. Sensitivity analysis found this relationship was stronger when studies in non-healthy populations were excluded (y = 0.059 + 0.831x, R2 = 96.3%, p < 0.0001).
Conclusion: There is a strong relationship between BHB infusion rate and blood BHB concentrations; the regressions described here can be used by clinicians or researchers to determine ketone delivery required for a target blood concentration.

引言：β-羟基丁酸（beta-hydroxybutyrate，BHB）等酮体作为供能与信号代谢物，具备多效性功能益处，拥有多项临床应用潜力。相较于通过饮食干预诱导酮症，静脉输注外源性酮体是另一种可行手段。现有公开文献中，BHB输注速率与血液BHB浓度间是否存在强关联尚不明确，而该信息对于探究酮症治疗效应的临床研究至关重要。本系统综述旨在整合现有数据，填补这一研究空白。
方法：检索PubMed与EMBASE数据库，从23篇涉及BHB输注且评估了最大及/或稳态BHB水平的文献中提取数据。当输注外消旋BHB但仅检测D-BHB时，需对输注速率进行校正调整。
结果：通过随机效应Meta回归分析，本研究发现BHB输注速率与血液最大BHB浓度（回归方程：y = 0.060 + 0.870x，R²=87.2%，p<0.0001）及稳态BHB浓度（回归方程：y = -0.022 + 0.849x，R²=86.9%，p<0.0001）均存在强线性关联。敏感性分析显示，排除针对非健康人群的研究后，该关联强度进一步提升（回归方程：y = 0.059 + 0.831x，R²=96.3%，p<0.0001）。
结论：BHB输注速率与血液BHB浓度间存在强线性关联；本文所提出的回归方程可供临床医师与科研人员用于计算达到目标血液酮体浓度所需的酮体输注剂量。