Glycotoxins: a possible threat to health?

AGEs are produced by a nonenzymatic glycation process called the Maillard reaction which involves the condensation of a reducing sugar or an aldehydic group and a protein amino group, with the formation of a series of reactive intermediates leading to stable, irreversible, seldom fluorescent, compounds known as advanced glycation end-products (AGEs). The reaction occurs both in food during heating and in animal and human tissues. During the heating of food containing sugars, lipids and proteins, nonenzymatic protein browning reaction occurs, resulting in the formation of a large series of compounds, which include the melanoidins and other AGEs. Accumulation of AGEs in the cells and in the extracellular matrix in animals is also observed; it is age-dependent, is related to cell or tissue turnover and is species-specific. These processes are accelerated in chronic diseases in which the production of pathogenetic AGEs and their accumulation rate are increased. The two research fields, the Maillard reaction in food chemistry and the glycation cascade in medicine, ran in parallel independently for a long time, but recently a new scientific society (the International Maillard Reaction Society, IMARS) has opened the way for an exciting fusion of knowledge. Pioneering studies resulted in concerns about the non-negligible bioavailability of dietary AGEs and related plasma concentrations in humans, and there are now claims that dietary AGEs may be toxic because of their bioreactivity in different chronic diseases. This has been confirmed by several studies in animals and in humans (AGEs-restricted diets resulted in a reduction of serum and tissue AGEs, related AGE receptors, inflammatory cells, and proatherosclerotic factors) and by in vitro studies on cells in culture. In view of the emerging evidence of a pathogenetic role of glycotoxins, an assessment of the benefits of a shift to a specific nutritional approach (the Mediterranean diet being the healthiest in terms of the low amount of AGEs and high amount of antioxidants) and an innovative therapeutic approach, aimed at directly breaking AGEs molecules or reversing their impaired gut absorption to favour their renal or faecal excretion, may be warranted. At any rate, a new scientific field is open for an interdisciplinary debate (involving chemists, geriatricians, and specialists in metabolic disorders, diabetes, and diet) paving the way for possible, remarkable clinical progress.