Advanced Glycation Endproducts, Part 2

Yet Another Black Eye for Sugar

BY DR. BAYNE FRENCH

AGEs formed in our DIET:

Uribarri et al. (J Am Diet Assoc. 2013) wrote an article on dietary AGEs (dAGEs). These are advanced glycation endproducts already formed in the foods that we eat. Different foods and how they’re cooked makes a big difference in the amount of dAGEs consumed. In this article multiple foods and cooking methods were studied and will be discussed later.

Animal-derived foods, even when uncooked, already possess naturally accumulated AGEs. Cooking creates more, especially with dry, high heat. Moist heat with lower temperatures with the addition of acid like lemon juice or vinegar results in dAGEs being “significantly reduced”.

Let’s take a look at mice. What happens to them correlates with what happens to us. Maybe I’ll write a book one day. I’ll title it Of Mice and Men or something like that. Will probably win a Pulitzer like some of my other stuff. Anyway, it was thought for a long time that these nasty dietary AGEs are not absorbed into our bloodstream. Koschinsky et al. (Proc Natl Acad Sci USA. 1997) showed decades ago that mice clearly absorbed these nasty chemicals—poor little reptiles.

Multiple researchers have since shown that mice fed a high dAGE diet developed cardiovascular and kidney disease. And restricting dAGEs in the mice diet prevented cardiovascular and kidney disease, and the development of both type 1 and 2 diabetes. Cai et al. (Am J Pathol. 2008) reported on two very interesting things: First, mice that ate less (time-restricted feeding/intermittent fasting) lived longer. Second, mice that ate less dAGEs also had a longer lifespan.

But what about humans? There’s been a study on us, too. I mean beyond what aliens do. Uribarri et al. (J Gerontol A Biol Sci Met Sci. 2007) showed that consumed AGEs correlate with how much AGE is in our bloodstream. So, we, like mice, absorb these toxic compounds quite well.

There are lab tests that measure inflammation and oxidative stress. Elevated levels correlate with a much higher incidence of numerous diseases. Numerous authors have shown that minimizing dAGE’s result in reductions in these abnormal lab tests. “Together, the findings from animal and human studies suggest that avoidance of dAGEs in food helps delay chronic diseases and aging in animals and possibly in human beings” (Uribarri et al. J Am Diet Assoc. 2013).

Now, more on cooking. I recently learned how to do this out of necessity. Uribarri et al. at Mount Sinai School of Medicine studied the effects of boiling (100 degrees C), broiling (225 deg C), deep-frying (180 deg C), oven-frying (230 deg C), and roasting (177 deg C). The numbers below are a measure of AGEs and illustrate that raw food already possess AGEs, and how cooking increases the AGE burden:

Chestnuts raw 817; roasted 1,606
Beef frank boiled 6,736; broiled 10,143
Beef steak raw 720; pan-fried with olive oil 9,052
Chicken raw 769; grilled 4,848
Salmon raw 527; pan-fried with olive oil 3,083; broiled with olive oil 4,334

Here’s a frustrating bit of trivia…many foods I consider to be metabolically unfavorable like bread, ice cream, juice, and beer have a very low amount of dAGEs. Easy now, think this through. The damage these substances cause occur endogenously, meaning after they’re consumed and absorbed into our bloodstream.

The effect of marinating was also examined. Remember several paragraphs above: …with the addition of acid like lemon juice or vinegar results in dAGEs being “significantly reduced”.

The amount of dAGE in raw meat, marinated cooked, and non-marinated cooked meat were compared:

The raw meat clearly has the lowest dAGE content (#1). The take-home here I think is in #3. Simply marinating for 1 hour in an acidic solution like vinegar and lemon juice resulted in much less dAGE formation.

To summarize Uribarri et al. findings, animal product had the highest dAGE content. Fruits and vegetables the lowest. In all food categories, exposure to higher temperatures and lower moisture levels coincided with higher AGE levels for equal weight of food as compared to foods prepared at lower temperatures or with more moisture. As an example, scrambled eggs cooked on medium heat had half as much dAGEs as cooked on high heat. Poached and steamed chicken had less than a fourth of dAGEs compared to chicken that was roasted or broiled.

Grilling, roasting, broiling, and frying yielded more dAGEs compared to stewing, steaming, boiling and poaching.

Also observed is that higher fat foods had a higher level of dAGEs. As an example, full-fat dairy had higher dAGE than low-fat dairy. There are numerous benefits to the consumption of dietary fat. It is satiating, a great source of energy, results in weight loss, and generates ketones. The modest increase in dAGEs in higher fat foods needs to reconciled with these other benefits.

Type 2 Diabetes:

Let’s do a little diabetes in-service. It is a metabolic disease from chronically elevated blood sugars. The main categories are type 1 and type 2. For our purposes, it’s ALL about type 2 and, according to Salazar et al., represents “one of the most massive epidemics of the twenty-first century.” If your goal is just to be left alone in your later years, then one of the best ways to achieve this is not to develop type 2 diabetes. And it IS dramatically preventable by human animals usually consistently eating human food.

This disease is a microcosm. Not that I know what microcosm means exactly, but it’s a way of viewing what’s in store for most humans that are habitual consumers of carbohydrates, especially sugar. It is driven by consistently eating what we are not designed to eat, consistently.

Salazar et al. (Int J Environ res Public Health. 2021) put together a super cool review of recent data in regards to AGEs and how they are pivotal in all the problems as a result of diabetes.

There are different ways of diagnosing type 2 diabetes, like a couple of blood sugars over 126 and/or a hemoglobin A1c of 6.5 or higher. What’s most important to know, however, is that the diagnosis comes from many years of metabolic dysfunction. And when the diagnosis is made, the metabolic dysfunction is dramatically accelerated. It is very unusual to actually die of type 2 diabetes. Those acute deaths are a result of extremely low or high blood sugars, and the death is sudden. The majority of individuals with type 2 diabetes will meet their premature and through complications of the disease. The elevated blood sugars cause large blood vessel problems like cardiovascular disease (heart attacks and strokes) and also numerous small vessel problems like kidney disease and neuropathy. The burden of cancer is also dramatically higher in patients with type 2 diabetes. The principal player in all these type 2 diabetes-related complications is AGEs.

Goldin et al. (Circulation. 2006) authored a review article detailing the biochemical mayhem behind how AGEs cause arterial injury in patients with diabetes. It is well established that the burden of cardiovascular disease, both in small (microvascular) and large (macrovascular) arteries in patients with diabetes, is very high. AGEs, primarily those created in the body as a result of a high blood sugar environment, are at the forefront of arterial damage.

There are many mechanisms behind this damage. A primary one appears to be the interaction between AGE and RAGE. Yep, I can’t make this stuff up. RAGE stands for Receptor for Advanced Glycation End products. A receptor is a “docking port” that the AGE connects with. When RAGE is triggered, a host of unfavorable cellular signaling messages occur. The result is that the inside slippery lining (endothelium) of arteries becomes more permeable, allowing the influx of white blood cells, foam cells, macrophages, and cholesterol. This, then, is the crux of accelerated atherosclerosis, thus cardiovascular diseases like strokes, heart attacks, and kidney disease.

Once an AGE is formed, it is largely irreversible. When an AGE fits the RAGE like a lock and key, dramatic and unfavorable signaling takes place. Compounds like tumor necrosis factor are then created. I couldn’t even make up that name, and my imagination is freaky, as I’ve already said a few times. And there’s dozens of scary chemicals that are created as a result of RAGE being activated. The result is disease, suffering, and early death. It’s all driven by what we eat, and how we cook it.

Conclusion:

I’ve written extensively about the unfavorable metabolic actions that result from regular and excessive carbohydrate and sugar consumption. These compounds exert biological activity by numerous mechanisms. A major mechanism appears to be the formation of AGEs, and the resultant cauldron of unfavorable actions that ensue.

We want to prevent exactly what AGEs cause. And to do so we must prevent the formation and consumption of AGEs themselves.

Sun Tzu was a Chinese military strategist. He also dabbled in philosophy, like me. He hated burpees but was hell on wheels with a sword. He said, “Know thy enemy…”. We know it here. We have a very good idea about what causes AGEs, and about the damage that they then cause.

Simple action items involve cooking at a lower heat and with moisture. The fat content of an animal that did not eat their native food is much different than a grass fed, wild caught, wild game animal. Although I could not find any research comparing the amount of AGEs in animals depending on their feeding practices, it makes sense to me that animals that at their native foods have a much less inherent burden of AGEs to begin with. Grass just has a hell of a lot less carb than corn, sorghum, and oats.

It is paramount to avoid repetitive blood sugar excursions. With every blood sugar spike there is a potential for glycation. The irreversible sticking of sugar to other compounds resulting in AGEs. Fructose, which comprises 50% of sugar, is a potent former of AGEs. I highly advised it not being a staple, and certainly not a fuel for exercise. Reserve it for a special occasion, like celebrating my mullet.