Histidine-Containing Dipeptides in Obesity and Cardiometabolic Health: A Systematic Scoping Review

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.