Uribarri Jaime, Tuttle Katherine R
Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington.
Clin J Am Soc Nephrol. 2025 Aug 8. doi: 10.2215/CJN.0000000859.
Cardiovascular-kidney-metabolic (CKM) syndrome is a new term indicating a health condition that emphasizes the interconnection of diabetes (type 2 diabetes [T2D]), insulin resistance (IR), CKD, and cardiovascular disease; the pathogenic links between these conditions seem to start with IR/T2D. The incidence and prevalence of this condition are increasing in parallel with the contemporary Western culture consumption of ultra-processed foods. Thermic processing of food increases the formation of pro-oxidant and proinflammatory advanced glycation end products (AGEs), which are partially absorbed into the body increasing the body pool of AGEs, which eventually produces chronic tissue injury, including IR. In this article, we review the literature and present experimental and human data supporting the hypothesis that AGEs in food are major contributory factors to toxicity of ultra-processed foods. We postulate that although hyperglycemia accompanying the diabetic state increases endogenous AGE production, ingestion of these compounds in food may also initiate oxidative stress that eventually causes IR and T2D. Several small clinical trials have studied the effect of dietary AGE intake restriction over variable periods of time, and most of them have demonstrated significant reduction not only in circulating markers of AGEs but also in markers of inflammation and oxidative stress in healthy as well as in CKM subjects. An AGE-restricted diet has also been shown to improve markers of IR. Final proof of a therapeutic role for the low AGE diet will require large, prospective, and randomized clinical trials, which may be challenging to accomplish. We believe, however, that current available data make it reasonable and prudent to advise limitation of dietary AGEs in the general population as well as in CKM patients. Importantly, the simple changes in culinary techniques suggested here can markedly affect AGE content in food and be incorporated as meal patterns consistent with most currently available recommendations promoting CKM health.
