Saadati Saeede, Kabthymer Robel Hussen, Aldini Giancarlo, Thrimawithana Thilini R, Stevens Julie E, Ngyuen Kathy, Majid Arshad, Bell Simon M, Feehan Jack, Mousa Aya, de Courten Barbora
Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
Obes Rev. 2025 Nov;26(11):e13965. doi: 10.1111/obr.13965. Epub 2025 Jun 16.
Histidine-containing dipeptides (HCDs) have been reported to have anti-inflammatory and antidiabetic properties. Yet, no previous reviews have examined the impact of HCDs on Type 2 diabetes (T2D) risk factors (e.g., obesity) and progression (e.g., microvascular and macrovascular complications). In this scoping review, we aimed to thoroughly examine the evidence on the effects of HCDs, particularly carnosine, which is the most studied HCD, on T2D risk factors and complications and the underlying mechanisms of action.
We systematically searched Ovid-Medline, Embase, CINAHL, Scopus, Web of Science, and Cochrane Library from inception to December 2023. We included experimental studies (animal models and cell studies), observational studies, and randomized controlled trials (RCTs) investigating the mechanism of action of HCDs and the effects of supplementation in individuals with obesity and/or T2D.
The primary literature search yielded 10,973 articles and 121 studies were eligible for inclusion. HCDs have been shown to mitigate inflammation and improve lipid profile and glycemic control in obesity and T2D with or without microvascular and macrovascular complications. However, most studies are experimental, focusing on elucidating the potential mechanisms of action of HCDs, with limited observational data or RCTs of individuals with obesity and/or T2D. No RCTs have investigated the effects of HCDs in individuals with neuropathy, retinopathy, cerebrovascular disease, and cardiovascular disease within a diabetic context.
Although the existing evidence, predominantly from preclinical studies, generally supports the use of HCDs for improving cardiometabolic health, further human studies, especially RCTs with adequately powered sample sizes, are needed.
据报道，含组氨酸二肽（HCDs）具有抗炎和抗糖尿病特性。然而，以往尚无综述探讨HCDs对2型糖尿病（T2D）危险因素（如肥胖）和病情进展（如微血管和大血管并发症）的影响。在本范围综述中，我们旨在全面研究HCDs，特别是研究最多的HCD——肌肽，对T2D危险因素和并发症的影响及其潜在作用机制的证据。
我们系统检索了从创刊至2023年12月的Ovid-Medline、Embase、CINAHL、Scopus、Web of Science和Cochrane图书馆。我们纳入了实验研究（动物模型和细胞研究）、观察性研究以及随机对照试验（RCTs），这些研究调查了HCDs的作用机制以及对肥胖和/或T2D个体补充HCDs的效果。
初步文献检索得到10973篇文章，121项研究符合纳入标准。已表明HCDs可减轻肥胖和T2D（无论有无微血管和大血管并发症）中的炎症，改善脂质谱和血糖控制。然而，大多数研究是实验性的，侧重于阐明HCDs的潜在作用机制，针对肥胖和/或T2D个体的观察性数据或RCTs有限。尚无RCTs研究HCDs在糖尿病背景下对患有神经病变、视网膜病变、脑血管疾病和心血管疾病个体的影响。
尽管现有证据（主要来自临床前研究）总体上支持使用HCDs改善心脏代谢健康，但仍需要进一步的人体研究，尤其是样本量充足的RCTs。
