AGEs—Exposed

What evidence do we have that it benefits us to restrict AGEs in food? Population studies showed that subjects with elevated AGE levels in the blood have a higher risk of anemia; stiffening of arteries and cartilage; cardiovascular disease; chronic kidney disease; osteoarthritis; and osteoporosis, but most studies focused on the harmful effects of AGEs on muscles, mortality rate, and memory. For a quick overview, see my video see.nf/ages.

There is a noninvasive method to estimate the accumulation of AGEs over time that gets around the problem that blood levels vary from day to day. It is based on the peculiar fact that some AGEs that accumulate in our skin fluoresce. Using a special detector, long-term AGE exposure can be linked to frailty, premature death, and accelerated loss of brain mass. The influential article “Oral glycotoxins are a modifiable cause of dementia … [in] humans” suggests reducing AGEs from foods, which would be a feasible and efficient strategy to combat our dementia epidemic.

AGEs partially explain why those who eat the most meat have a threefold higher risk of dementia than long-term vegetarians, but other factors contribute as well. For example, a high intake of saturated fat, mostly from meat, dairy products, and junk food, is associated with a 40 percent higher risk of cognitive impairment and a 90 percent higher risk of Alzheimer’s. Just a few days of a high-fat, low-carbohydrate diet may cause cognitive dysfunction. With all these studies, however, there is a problem. Perhaps the correlation between AGEs and chronic diseases is simply a correlation between high-AGE foods such as processed meat and chronic diseases. What is cause and what is effect can be shown only by testing it through intervention studies.

The AGE Diet Trials

Journal articles with titles like “Extending life span by dietary restriction of advanced glycation end products in mice” are examples of the studies showing that lowering dietary AGE intake increases life span, whereas increasing it can impair learning and memory performance and shorten the lives of rodents and other model organisms. In one study, for example, 76 percent of mice fed low-AGE chow lived at least 56 weeks, but none of the mice fed a high-AGE diet was still alive after 44 weeks.

The negative effects of AGEs are so great that they can even cancel out the benefit of calorie restriction. While lifelong calorie restriction predictably extends the life span of mice, if you feed them high-AGE pellets, they not only die earlier than mice that eat normal chow, but also do worse in every test category—inflammation, oxidative stress, insulin resistance, and marked heart and kidney fibrosis (accumulation of scar tissue). Whatever benefit restriction in the amount of food brings can be undone by the reduction in food quality. We will see this in the next chapter, where the well-being of the members of the Calorie Restriction Society may be limited by their relatively high protein intake.

At see.nf/agetrials I discuss the AGE studies in humans, but in principle, a single meal of grilled chicken causes “severe impairment” of arterial function within hours, compared with eating the same amount of boiled chicken. The boiled chicken also harmed arterial function, but significantly less than the grilled. The difference was attributed to the AGEs, but when meat is cooked, heat also creates other toxins, such as heterocyclic amines, which come mainly from the creatine in muscle. Therefore, it is impossible to judge with absolute certainty what accounts for the difference.

The Glycemic Load

Although most AGEs are supplied to the body from the outside through eating, it also forms them itself. Normally, this happens slowly and steadily, but in the context of high blood sugar it happens faster. In my previous books, I examine the prevention, halting, and reversal of prediabetes and type 2 diabetes. But even people with normal fasting blood sugar can develop spikes after meals with a high glycemic load that are too high.

Shedding the Load

In my chapter on glycemic load in How Not to Diet, I go into detail about the effects different carbohydrate-rich foods have on our blood sugar, focusing on the value of glycemic load. The higher the glycemic load, the more sharply blood sugar generally spikes when we eat it. Below is a breakdown of some common sweet and starchy foods:

Glycemic load per serving

Low-Glycemic Diets Put to the Test

In the study that compared boiled chicken with grilled, even the boiled chicken caused some degree of arterial dysfunction in the eaters, whereas a low-glycemic-load, high-fiber meal can actually improve arterial function in the four hours after consumption. But just as with the AGE studies on reducing meat consumption, it is difficult to tease out the specific effect of the changes in glycemic value. Many high-glycemic foods have had the fiber removed, and they are highly processed, so you are changing more than just glycemic load when you swap them out for beans, fruit, or other low-glycemic-index foods. A persistent problem in nutrition studies is swapping out only one component. In drug studies, that is easy, because the researchers can administer either the active ingredient or a sugar pill. If a change then occurs, they know it was the active ingredient. If only we could put a change in glycemic load into a tablet! Well, as it turns out, that is possible.

The active ingredient acarbose partially blocks starch- and sugar-breaking enzymes in the digestive tract, which slows the absorption of carbohydrates in the body. If we take the medication with meals, a high-glycemic meal is practically transformed into one with a low glycemic load—without changing anything about the foods. With acarbose, scientists were able to show that reducing glycemic load leads to weight loss independent of fiber intake, and the same is true for reducing AGEs.

In twelve weeks, acarbose lowered blood AGE levels in diabetics by about 30 percent. No wonder acarbose improves the health span and life span of mice and increases their maximum life span by about 10 percent. For a medication, acarbose has proved enormously safe. However, gas, a bloated belly, and diarrhea are frequently reported. If we want to enjoy the benefits of the medication without side effects, we only need to eat carbohydrates with a lower glycemic load, such as legumes (beans, chickpeas, yellow peas, and lentils), fruit, and grains.