AGEs-DescriptionHyperglycemia is still considered the principal cause of diabetes complications. Its deleterious effects are attributable, among other things, to the formation of sugar-derived substances called advanced glycation end products (AGEs). AGEs form at a constant but slow rate in the normal body, starting in early embryonic development, and accumulate with time. However, their formation is markedly accelerated in diabetes because of the increased availability of glucose.

A large body of evidence suggests that AGEs are important pathogenetic mediators of almost all diabetes complications, conventionally grouped into micro- or macroangiopathies. For instance, AGEs are found in retinal vessels of diabetic patients, and their levels correlate with those in serum as well as with severity of retinopathy.

Animal and human studies have shown that AGEs play a significant role in the formation and progression of atherosclerotic lesions. Increased AGE accumulation in the diabetic vascular tissues has been associated with changes in endothelial cell, macrophage, and smooth muscle cell function. In addition, AGEs can modify LDL cholesterol in such a way that it tends to become easily oxidized and deposited within vessel walls, causing streak formation and, in time, atheroma. AGE-crosslink formation results in arterial stiffening with loss of elasticity of large vessels.

In addition to those endogenously formed, AGEs can also be introduced in the body from exogenous sources. Recent studies have provided evidence that diet is a significant exogenous source of highly reactive AGEs. Food processing, heating in particular, has a significant accelerating effect in the generation of glyco- and lipoxidation products. Heat helps create tasteful flavors that humans have learned to enjoy. In recent decades, food manufacturers have been using this knowledge to boost the flavor of natural foods by incorporating synthetic AGEs into foods. Consequently, the AGEs content of the Western diet has increased vastly in the past 50 years, as has the quantity of food consumed.

A significant proportion (∼10%) of ingested AGEs is absorbed with food. There is apparently a direct correlation between circulating AGE levels and those consumed. Studies in animals have demonstrated an important relationship between high dietary AGE intake and development or progression of diabetes-related tissue damage, e.g., vascular and renal. In all instances, this was prevented by dietary AGE restriction.

A similarly significant contribution to the human body AGE pool by diet was demonstrated recently. More importantly, its effective reduction by a restriction of dietary AGEs was associated with a significant suppression of circulating levels of vascular disease markers (e.g., adhesion molecules) as well as of inflammatory mediators.

This new evidence suggests that modulation of food-AGE content could become an important ingredient of the therapeutic armamentarium in the management of diabetic patients. Until effective and safe drugs become available, physicians and dieticians can, for instance, advise increased reliance on fresh foods, cooked by brief applications of heat, in the presence of ample water or humidity. A diet designed to be low in AGEs is apparently not lacking in taste, while not requiring compromises in important nutrients. Such a regimen can decrease AGE intake by more than 50%; this in turn was shown to reduce circulating AGEs by 30% within a month without a change in A1C. On the contrary, short-term euglycemia or temporary normalization of A1C are not sufficient means for reducing serum AGEs; instead this requires extended periods of time, e.g., months or years.

In conclusion, current evidence points to glucose not only as the body’s main short-term energy source, but also as the long-term fuel of diabetes complications, mainly in the form of oxidative, pro-inflammatory AGEs. Food commonly consumed after exposure to heat contains a significant amount of pre-formed AGEs, a fact that offers a new perspective on food as a major environmental risk factor. It may be necessary, for instance, to restructure our guidelines to include methods of food preparation along with or in addition to routine recommendations about food quantity and composition.

It is reasonable to consider that good glycemic control, in combination with a careful diet in terms of reduced AGE consumption, should be among the new goals for optimal management of diabetic patients. Addressing dietary habits from a new perspective, while difficult, could achieve the best long-term effects as novel drug interventions become available for clinical use in the future.

Health-e-Solutions comment: Now this is a very interesting article brought to my attention by Ailsa in Canada. It certainly gives weight to the argument for eating primarily raw foods. In the diabetic-alkaline lifestyle, we like to say 75% of your plate should be raw, green, alkaline foods and the other 25% can be cooked, therapeutic foods.

Note that just good short term blood glucose control alone is not enough to reduce AGEs. It is important to maintain good control long term, but fresh, uncooked foods were able to reduce AGEs within a month!  So enjoy our “Rootin Tootin Raw Tacos” recipe and many other fresh food recipes in the alkaline lifestyle recipe e-books you can purchase on our web site. Focus on fresh food for the best management of all types of diabetes.