Dietary Restriction of Advanced Glycation End-Products (AGEs) in Patients with Diabetes: A Systematic Review of Randomized Controlled Trials.

Advanced Glycation End Products (AGEs) are formed through non-enzymatic reactions between reducing sugars and proteins, nucleic acids or lipids (for example through hyperoxidation). In diabetes, elevated glucose levels provide more substrate for AGEs formation. AGEs can also be ingested through the diet from foods cooked at high temperatures, or containing much sugar. The present work aimed to review all published randomized controlled trials (RCT) on low-dietary AGE (L-dAGEs) interventions in patients with diabetes. Pubmed, Scopus and Cochrane databases were searched (until 29 February 2024) with appropriate keywords (inclusion criteria: RCT, patients with diabetes, age > 18 years, outcomes related to inflammation, glucose, and lipids; exclusion criteria: non-RCTs, case-series, case reports and Letter to the Editor, or animal studies). The present review was registered to the Open Science Framework (OSF). From 7091 studies, seven were ultimately included. Bias was assessed with the updated Cochrane Risk of Bias tool. A reduction in circulating AGEs was documented in 3/3 studies. No particular differences were documented in glycemic parameters after a L-dAGEs diet. Reductions in glucose levels were observed in one out of six studies (1/6), while HbA1c and HOMA did not change in any study (0/6 and 0/3, correspondingly). Lipid profile also changed in one out of four studies (1/4). More consistent results were observed for oxidative stress (beneficial effects in 3/3 studies) and inflammatory markers (beneficial effects in 4/4 studies). Other athero-protective effects, such as adiponectin increases, were reported. Limitations included the small sample size and the fact that dietary and physical activity habits were not considered in most studies. In conclusion, a L-dAGEs pattern may minimize AGEs accumulation and have beneficial effects on oxidative stress and inflammation indices, while its effects on glycemic and lipemic parameters are inconsistent and modest in patients with diabetes.