Advanced Glycation Endproducts, Part 1

Yet Another Black Eye for Sugar

BY DR. BAYNE FRENCH

Let us define metabolism. Why? Because an unfavorable metabolism leads to the majority of diseases we will die from. So, if you want to avoid dis-ease, and stack the deck very significantly in favor of a longer (lifespan) and functional (health span) life, then come to understand what metabolism is and how to optimize it.

Metabolism is the vastly complicated and interwoven set of chemical processes that occur after digestion. So, you eat crap. That crap is acted on by chemicals and mechanical action in the intestine, making smaller bits of crap. These teensy bits of crap pass through the lining of the intestine and into the bloodstream. That’s when metabolism begins. What isn’t absorbed remains in the intestine, darkens from bile, and then you release a 5-pound Brown trout. Fire in the hole!

I do not have many idols. In fact, there are a few people that I actually like, myself included. Dr. Vanerkooi is an exception. I would have liked to meet her, and maybe tie one on. I enjoyed her book Your Inner Engine very much. She describes a simplistic view of metabolism as the conversion of food to energy. A slightly more extended definition would be the sum of total chemical reactions that result in either energy storage or burning.

Metabolism is perturbed over the course of one’s life. Maybe we should define perturb. It has a deeper meaning than just getting pissed off. I think that if I were musically inclined, I’d start a band. Headlining tonight, at Whitefish’s iconic Great Northern Bar, the Perterbers of Metabolism! Wild man Bayne French on the guitar, drums, harmonica, lead vocals, and other stuff musical and whatnot! I’m not sure who would actually say that or write it, but don’t be a dream snatcher.

Being able to bend over and pick up your grandchildren or drag a Whitetail deer out of the woods when you’re older depends on your ability to minimize the perturbation. Are you getting perturbed? If you’ve read my other stuff, you should be well accustomed to it.

We’re more metabolically efficient during childbearing and rearing years. After which point, things tend to go a bit south. We’ve already passed on our genetic code and, in the broad scheme of life, have fulfilled our usefulness. What befalls our health after blissful propagation and frustrating child-rearing depends on the genetic hand you’ve been dealt and how you play that hand. How do you nurture genetic advantages? How do you minimize genetic propensities for disease? How would I know? I’m a student like you. But I am convinced it has so much to do with dietary habits, physical conditioning, stress management, sleep quality, and mood. Advanced Glycation Endproducts (AGEs) offer yet another target for us to minimize in the foods we choose and how it’s been cooked.

AGEs formed in our BODIES:

I read a long article recently. Because I do stuff like that. Single-parenting is just so boring. Aragno et al. (Nutrients. 2017) put together a masterful tome on AGEs. It’s a bit frightening. “An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation End products (AGEs). AGE can be ingested with high temperature processed foods, but also endogenously formed as a consequence of a high dietary sugar intake”. Interpretation…you can eat AGEs, and you can form AGEs.

So, what in the hell is an AGE anyway? They are the products formed from sugars' interaction with other compounds, including proteins, fats, and our DNA (nucleic acids). They are considered toxic; in fact, they’re also termed glycotoxins. “The pathologic effects of AGEs are related to their ability to promote oxidative stress and inflammation by binding with cell surface receptors or cross-linking with body proteins, altering their structure and function” (Uribarri et al. J Am Diet Assoc. 2013).

Many of you are familiar with the blood test Hemoglobin A1c, particularly if you have developed diabetes. It is a very telling marker of metabolic wellness. It is a measure of an AGEs! Sugars interact with the hemoglobin proteins in your red blood cells. It measures your average blood sugar for about 90 days, which is the lifespan of a red blood cell. But what about the rest of your body that isn’t turned over, replaced, and regenerated? Like your heart muscle, your brain tissue, and basically the majority of all your tissues? This interaction of sugar with these tissues, termed glycation, is largely permanent. The more AGEs, the faster you age. Seriously, I can’t make this stuff up despite my freaky imagination.

Sugar is Sucrose, which is half glucose and half fructose. High-fructose corn syrup (HFCS) is a bit more fructose. Sugar-sweetened foods and drinks create a “psychological dependence” (Avena et al. Neurosci. Bioibehav. Rev. 2008). Sugar-added foods and drinks increase the risk of obesity (Schmidt et al. JAMA. 2014); cardiovascular disease (Malik et al. Circulation. 2010); fatty liver disease (Alwahsh et al. Arch. Toxicol. 2016); and cognitive decline, meaning you get un-smarterer. (Soares et al. Neuroscience 2013). I’ve written a few articles specifically about sugar, its toxic nature, and its anti-performance-enhancing effects. Re-read them because they’re just that good.

Sugar-The Antithetic Performance Enhancer

According to Aragno et al, the formation of AGEs takes place slowly and continuously throughout the lifespan, driving AGE accumulation in tissues during aging. Yamagishi et al. (Nutrition 2016) reported that the accumulation of AGE drives many age-related diseases and that elevated blood sugar (hyperglycemia) is known to induce high rates of glycation.

How does hyperglycemia develop? There are spikes in blood sugar that occur during the day related to high carbohydrate eating and sugar consumption. These blood sugar extrusions are very unhealthy and drive diabetes, hypertriglyceridemia, obesity, joint inflammation, and basically feeling like absolute crap. Depending on your genetic predilections, these blood sugar excursions ultimately lead to insulin resistance and type 2 diabetes.

Let me be clear: the pandemic disease of type 2 diabetes is one of excessive carbohydrate consumption… human animals consistently eating non-human animal food. In my experience, patients who choose to eat and drink differently than every other member of their family who have developed Type II Diabetes basically NEVER develop the disease. To restate, even with a strong family history of diabetes with different lifestyle choices, it is exceedingly rare to develop diabetes. Many other metabolic diseases are also far less, like cancer and heart disease. Think about the culture though, of eating. The event of a meal runs so deep within families that it is the rare individual who can break free of that diabetic and obesity-prone familial system. Also, in my experience, patients who have NOT developed type 2 diabetes, like all of their first-degree relatives, usually left home early and visited rarely. Sad huh.

Stay with me. Recall that sugar is half glucose and half fructose. When we’re talking about AGE formation (glycation), fructose is WAY more potent than glucose. Bunn et al. (Science 1981) found that fructose glycated 7.5 times more than glucose. Other authors found over 10 times more potency of fructose than glucose at permanently sticking to our tissues, gumming up our cellular machinery and basically creating metabolic mayhem and creating glycotoxins. Just picking an exercise fuel, and a source of sweet that doesn’t involve fructose is a huge improvement. Sugar is just so bad in so many ways. Thus, among the numerous “sugars” used for sweetening drinks and foods, fructose (in the form of sucrose or high fructose corn sugar) likely represents the most hazardous for AGE accumulation and your health in general.

Here's something interesting: we’ve developed proteins (enzymes) that help degrade (remove) AGEs. This is why I wrote largely permanent above. Of all the ways AGEs develop, from high-temperature cooking to interaction with a variety of carbohydrates, AGEs that develop from fructose are the hardest to remove (Mastrocola et al. Am. J. Physiol. Gastrointerst. Liver Physiol. 2013). Sugar then exerts a twofold contribution on glycation through both enhanced production and by reducing the bodies’ ability to detoxify them. Again, an exercise-fueling source or dietary form of sweets that isn’t sugar, is just a better long-term choice.

Brownlee et al. (Ann Intern Med. 1984), way back when I had a mullet, detailed the three-stage formation of AGEs. The first stage involves a blood sugar elevation after a meal. This sugar interacts with other tissues in a matter of hours. It represents a “shot across the bow” because it is reversible. The occasional and mindful blood sugar excursion, no problem. The second stage becomes a bit more serious. Amadori products are made. These chemicals result from actual molecular rearrangement of our normal tissues. Are you getting an idea of how potent and sinister sugar is? Yet you have another chance. These Amadori products are not permanent. But…when they accumulate, the permanent third stage occurs, with irreversible formation of AGEs. This process, depending on the degree of blood sugar abnormality and individual predilections, can occur over weeks or just in a few hours (Stirban et al. Mol Metab. 2014).

Click here to read Part 2