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The ABCs of AGEs (Advanced Glycation End-Products)

by Jeanine Barone  

Remember when free radicals were all the buzz? They were said to be the root cause of nearly every chronic disease—and you were supposed to mop them up by consuming foods or supplements high in antioxidants. That turned out to be overly simplistic, at best (see Antioxidants and Free Radicals). The latest bogeymen are advanced glycation end-products, or AGEs. Various websites and books warn of the dangers of AGEs—claiming, for example, that they are “linked to almost every serious health concern”—and offer ways to reduce them. Should you add AGEs to your list of worries?

What are AGEs?

They are a diverse array of compounds produced in the body through a variety of chemical reactions. Typically they form when sugars combine with certain amino acids (the building blocks of proteins) or fats—a process called glycation. This is more likely to occur when blood sugar is elevated, which explains the higher levels of AGEs in people with poorly controlled type 2 diabetes. One danger of AGEs is that they can clog the very small blood vessels (microvascular system) throughout the body, especially in the kidneys, eyes, heart, and brain, which may contribute to the risk of various diabetic complications.

We also consume AGEs, mostly from many cooked or processed foods, and absorb them from tobacco smoke. The body has ways to eliminate AGEs via enzymes and the kidneys, but those formed in the body are more likely to accumulate.

The process by which AGEs are formed in food was discovered in 1912, when a French scientist, Louis-Camille Maillard, first explained the chemical reaction that results in the browning of certain foods when cooked, like bread (crust) and meat. This was subsequently named the Maillard reaction. Research on AGEs has accelerated during the past 20 years, with an increased focus on food sources.

With aging, AGEs accumulate in the cells and the bloodstream because of decades of formation and ingestion, along with a decline in kidney function. Not only is high blood sugar implicated in increased formation of AGEs, but so are fats (lipids) in the blood, as well as oxidative stress (the latter results from an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants). Accumulation of AGEs can wreak cellular havoc, contributing in turn to oxidative stress, chronic inflammation, and premature aging. It is also associated with many chronic diseases and conditions, including insulin resistance, type 2 diabetes, cardiovascular disease, Alzheimer’s, Parkinson’s, rheumatoid arthritis, cataracts, cancer, and kidney disease, though whether AGEs play a causative role remains controversial.

Many unknowns

High levels of AGEs are found in many healthy older people as well as in those with chronic diseases, so it’s unclear exactly what role (if any) these play exactly in human health. For instance, do high blood levels of AGEs contribute to the development and progression of diabetes, do they result from it, or do they simply accompany it? Will reducing AGEs lower the risk of chronic diseases? And since AGEs are highly diverse, are certain types particularly problematic? There’s even debate about how AGEs should be measured in the body and in food, since they result from diverse chemical reactions, some of which are not fully understood. It’s also not well understood how well AGEs in foods are absorbed in the intestines, nor whether vitamins and other nutrients accompanying them influence their effects in the body.

AGEs in food

AGEs are found naturally in many foods, especially animal-derived products that are rich in protein and fat. Various chemical reactions increase AGE formation, as when certain foods are cooked at high temperatures or others, like cheese, are aged. Certain processes used by food companies to add flavor or color to their products also boost AGEs.

More AGEs form when meats are grilled, roasted, seared, fried, or baked (all dry-heat methods) at relatively high temperatures and for longer times than when they are steamed, poached, stewed, or boiled (methods that retain food moisture). Microwaving produces few AGEs because of its relatively short cooking times. The source of animal protein also affects the generation of AGEs, with beef generally having the most, and fish (unless broiled or fried) the least. The fat in meat tends to contain the most AGEs. Carbohydrate-rich plant foods such as fruit, vegetables, and many grain products have a low AGE content, even when cooked. However, grain products such as crackers, chips, and cookies are higher in AGEs because of their dry heat processing and added fats and sugars, but still have much less than meats. Frying potatoes also boosts AGEs. Marinating meat with acidic ingredients such as lemon juice and vinegar inhibits AGE formation.

A look at some research

Much of the recent human research on AGEs has been done by several researchers from the Mount Sinai Medical Center in New York and has focused largely on the risk of type 2 diabetes. For instance:

  • In a study in Diabetologia in 2016, the Mount Sinai researchers randomized 61 obese people with metabolic syndrome (which includes insulin resistance, a risk factor for type 2 diabetes) into two groups: Half ate a diet low in AGEs (they were told, for instance, to avoid baking, grilling, or frying food), while the other half had a standard American diet that was high in AGEs. After one year, the low-AGE group had lower blood levels of AGEs, a reduction in insulin resistance, a decrease in markers for inflammation and oxidative stress, and a small amount of weight loss.
  • Similarly, in a small Australian study in theAmerican Journal of Clinical Nutrition in 2016, healthy overweight people who were put on a low-AGE diet for two weeks had improved insulin sensitivity compared to those on a high-AGE diet.
  • In an Italian study in theJournal of Clinical Lipidology in 2016, people with prediabetes were put on either a low-AGE or standard diet. After 24 weeks, the low-AGE group had improved cholesterol levels and reduced C-reactive protein (a marker for inflammation) compared to the control group.

Bottom line: More research is needed to fully understand the health effects of AGEs—both those produced by the body and those consumed from foods. Meanwhile, what we know about AGEs doesn’t change our thinking about healthy eating. We already have good reasons to limit fatty meats, especially those cooked over high heat (which produces potential carcinogens such as heterocyclic amines, or HCAs) and to limit fried or highly processed foods such as chips and French fries. Many heart-healthy eating patterns, including the Mediterranean diet, are low in AGEs. That would include any just about any diet rich in fruits, vegetables, whole grains, legumes, fish, and low-fat dairy and low in meat (especially cooked at high temperatures) and processed and fast foods.

Also see How Bad Is Meat, Really?