What are AGEs and why are they bad for you?

By Naveed Saleh, MD, MS, for MDLinx
Published April 15, 2019

Key Takeaways

Many people have yet to hear of advanced glycation end products (AGEs). But AGEs are a hot topic in nutrition for their role in metabolic disease. AGEs have likely played a crucial part in the rise of diabetes and metabolic disease experienced across the world.

AGEs are toxic compounds, or glycotoxins, produced by nonenzymatic glycoxidation reactions that take place between reducing sugars and free amino groups of proteins, lipids, or nucleic acids. The resulting end products are structurally and functionally compromised. In other words, AGEs are proteins, lipids, or nucleic acids that become glycated in the presence of sugars.

A rapid increase in the incidence of metabolic disease during the past 3 decades has been tied to the addition of simple sugars, such as glucose and fructose, to foods and beverages. With respect to AGE formation, fructose is 7.5 times more reactive than glucose. Fructose is commonly used as a sweetener. High sugar consumption may play a role in AGE formation.

Protein glycation happens in the human body slowly over the course of a lifetime. This reaction results in AGE accumulation in tissues during senescence. AGEs play a role in age-related illness, including neurodegenerative disease, atherosclerosis, and chronic inflammatory disease.

In diabetes and insulin resistance, however, the accumulation of AGEs is faster, resulting in the hastening of comorbidities. In a vicious cycle, hyperglycemia triggers high rates of protein glycation, leading to the development of long-term complications.

The sources of AGEs can be either exogenous or endogenous. Highly processed foods tend to be rich in AGEs due to thermal processing methods, which entail cooking at high temperatures for long periods of time. These thermal processing methods are meant to preserve and improve flavor, color, and appearance. AGEs are also found in meat, and the grilling, broiling, roasting, searing, and frying of meat increases AGE formation. 

AGEs in the body

For some time, researchers dismissed the role of AGEs in the body because it was thought that these compounds could not be absorbed. Further studies, however, demonstrated that they are not only absorbable, but dietary AGEs added greatly to total body stores of AGE.

The pathological effects of AGEs are due to their potential to increase oxidative stress and inflammation, which stymies tissue repair and organ function, and contributes to diabetes and cardiovascular disease.

AGEs in the diet

The role of AGEs in the diet is just emerging, and there is no consensus data on normal AGE levels. Once low and high levels of AGE in the diet are defined, it will be possible to develop low-AGE diets. Notably, the current trend in therapeutic diets for diabetes, heart disease, and weight loss are high in protein and fat, and low in carbohydrates, which could result in high levels of exogenous AGE.

Although it’s too early to issue evidence-based recommendations supporting a diet low in AGEs, it may be a good idea for clinicians to consider this intervention in patients with diabetes, according to experts.

AGEs from diet exert many effects on the body’s fundamental metabolic processes. They have been shown to enhance lipogenesis and intracellular lipid deposition. They may also interfere with lipid synthesis, inflammation, mitochondrial metabolism, and antioxidant defenses. Dietary AGEs may also affect various signaling pathways, thus contributing to organ damage of the liver, brain, skeletal muscle, and cardiac muscle.

In patients with diabetes or kidney disease, and otherwise healthy individuals, restriction of dietary AGEs may lead to lower levels of oxidative stress and inflammatory biomarkers, according to some studies. In light of these and other findings, some researchers have suggested that avoiding AGEs in the diet might delay the development of chronic disease and aging in humans.

Moist cooking methods may decrease the formation of AGEs. These methods include poaching, simmering, boiling, braising, stewing, pot roasting, and steaming. Comparatively, cooking with dry heat, grilling, broiling, roasting, searing, and frying have all been shown to increase AGE production.

The consumption of sugars—especially fructose—should be curbed to prevent excess production of AGEs.

Vegetables, fish, legumes, fruits, milk, and whole grains have relatively low levels of AGE. They remain low in AGE even after cooking.

Other things that decrease the production of AGEs in food include shorter cooking times, lower cooking temperatures, and utilizing acidic ingredients, such as lemon juice or vinegar.

On a final note, should the limitation of AGE consumption in the diet become a formal nutrition guideline, this change should jibe well with current nutrition recommendations to eat fish, fruits, and vegetables as part of a healthy diet. Additionally, decreasing the dietary consumption of AGEs also involves eating less red meat and highly processed foods, as well as steering clear of grilling—a cooking practice that has recently come under fire for concerns over carcinogens.

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