T Nation 🔥 Conquer Glycation and Slow Down Aging

Conquer Glycation and Slow Down Aging

TC Luoma

We're All Slowly Cooking Ourselves

You know how meat turns brown when you cook it? Your diet is likely causing the same thing to happen to tissues in your body.

So you're cooking meat on the barbie. Got some chicken on one side and some steaks on the other. The grill is sizzling, and the meat is starting to turn a delectable shade of brown that's somewhere on the spectrum between a brand-new catcher's mitt and Lupita Nyong'o's thigh.

Little do most barbecuers know (or care) that the color change they're witnessing results from the Maillard reaction, a process by which high heat rearranges the amino acids and certain simple sugars into rings and collections of rings to reflect brown wavelengths of light. The reaction is also responsible for much of the flavor and smell of food.

But it doesn't just happen with meat; the reaction occurs when cooking/baking almost any kind of food, although the affected amino acids and simple sugars in the food produce distinctly different smells. Oven-baked pizza, of course, or bread, smells very different than fried fish or grilled burgers.

The Maillard reaction has a dark side, though. Early in the reaction, something called glycation occurs. It's when heat causes carbohydrates and proteins to form a covalent bond. This process results in the formation of a heterogenous group of molecules called "advanced glycation end products" (AGEs), of which there are at least 20 different types.

When you inadvertently consume these AGEs over the years through the food you eat, they accumulate in the body where they can cause all kinds of trouble.

Of course, you could go to heroic lengths to avoid foods that contain high(er) levels of AGEs, but unfortunately, the Maillard reaction/glycation also occurs inside the human body all on its own (in certain circumstances, which I'll get to later).

Now, before you chalk this glycation thing up as just another case of nutritional paranoia and add it to the already long list of things that are meant to scare the hell out of us (pesticides, plastics, phytoestrogens, carcinogens), consider that this one might just deserve a little more scrutiny because AGEs are likely a primary cause of many of the biological indignities associated with aging, including the cosmetic ones.

So, What Exactly Do these AGEs Things Do?

At their most basic level, AGEs cause cross-linking of proteins. You know how a raw egg dramatically changes when you drop it into a hot frying pan? The change is caused by protein cross-linking.

Now imagine what protein cross-linking, albeit at a less dramatic level than the frying of an egg, might do to various body tissues like collagen, skin, tendons, blood vessels, eyes, and the organs of the body.

Cross-linked proteins don't function like they're supposed to. Cross-linked proteins don't look like they're supposed to (e.g., collagen and wrinkled skin). They often lead to various diseases often associated with aging.

The Effects of AGEs on Various Body Tissues

Most proteins in the body have a lifespan of a day or two, but certain proteins have extremely long lives. For instance, certain proteins that live on the surface of the nucleus of neurons might be as old as the organism that houses them.

It's these long-lived proteins that are especially vulnerable to AGEs because their age makes it more probable that they've accumulated higher levels of AGEs, but shorter-lived proteins are also susceptible.

Here are just a few organs/tissues that are affected by AGEs:

Skin

Glycation and the resulting AGEs damage collagen and elastin, two proteins responsible for youthful-looking skin. Once these proteins are damaged, the cells of the epidermis get disordered. Eventually, the integrity of the stratum corneum (the outermost layer of the skin) that contains keratinocytes, is reduced. Skin becomes thin, wrinkled, and less elastic, i.e., Yoda-esque.

In short, glycation speeds up the aging process, or at least the cosmetic side of the aging process.

Eyes

Maybe the most easily "visible" effects of long-term accumulation of AGEs concern lens proteins, i.e., those found in the eyes. AGEs cause protein cross-links in the lens of the eye, causing opacification, aka cataracts.

Cardiovascular Disease

This protein cross-linking can also occur in the collagen found in arteries. High plasma levels of carboxymethyl-lysine (CML), a type of AGE, have been found to be positively correlated with an increase in cardiovascular disease.

Additionally, a study of 559 older women found that those with the highest levels of AGEs were twice as likely to die from heart disease than those with the lowest levels. It seems higher levels of AGEs and the resultant protein cross-linking likely cause blood vessels to brittle up like a plastic garden hose that's been left in the Arizona sun for an entire summer.

Cancer

AGEs bind to cellular receptors for advanced glycation end products (RAGE), which cause a multitude of signaling cascades associated with oxidative stress and oxidation. These, in turn, seem to be intrinsically linked with cancer. Many researchers believe the contribution of AGEs to malignant cell transformation and subsequent development (and progression) of cancer is conclusive.

Metabolism

AMP-activated protein kinase (AMPK) is known as a cellular "master switch" as it plays a critical role in the maintenance of energy balance. When things are running smoothly, it prompts cells to switch from ATP consumption to ATP production.

Accordingly, glucose transport increases, as does glycolysis (the breakdown of sugar) and beta-oxidation (breaking down fatty acids for energy), while lipogenesis (the formation of new fat cells) and cholesterol production are inhibited.

However, it appears that the presence of methylglyoxal (MGO), an AGE, can hamstring AMPK, thereby favoring lipogenesis, insulin resistance, and hyperglycemia, all of which are hallmarks of metabolic syndrome and diabetes.

And All the Rest

AGEs have also been implicated in causing or worsening neurological problems like Alzheimer's and Parkinson's, along with possibly causing or hastening kidney failure. (Samples of Alzheimer's afflicted brains show more than three times the levels of AGEs than age-matched healthy brains.)

AGEs probably play a role in practically any condition or disease you can think of, but there's one disease, or one aspect of that disease, that's kind of the Rosetta Stone that ties all of them together, and that disease is diabetes.

Diabetes is not only exacerbated by AGEs, but it also leads to the production of AGEs that can cause or worsen any of the well-documented diabetes-related diseases, many of which are listed above. It also gives us a clue as to how people who don't have diabetes might be churning out AGEs at a Chinese-factory rate and setting themselves up for any of those same diseases.

What Diabetes Tells Us About AGEs

The hyperglycemic conditions associated with diabetes accelerate the production and accumulation of AGEs. High sugar in the blood equals high rates of protein glycation, leading to many of the complications seen in diabetics.

However, it doesn't take diabetic-levels of blood sugar for glycation to occur. In fact, "normal" people who eat a typical highly processed Western diet usually have wild fluctuations in blood sugar. Many Americans spend a good deal of time walking around with blood glucose levels in pre-diabetic or even diabetic ranges, i.e., over 100 mg/dl or higher than 126 mg/dl (the diabetic "redline"). All this time spent in a high-sugar zone leads to the high-scale production of AGEs.

Don't forget, though, that we also inadvertently expose ourselves to AGEs through our diets, high-blood sugar non-withstanding, but there are several things that can be done about reducing AGEs in general. First off are dietary/lifestyle modifications.

Turn Down the Heat

As I mentioned earlier, the Maillard reaction is what causes cooked foods to turn brown. It's also responsible for glycation – the binding of sugars to proteins – which also leads to the production of AGEs. When these foods are consumed, they accumulate in the human body.

However, there's wide disparity of AGE content in food, based mostly on cooking methods. For instance, cooking methods that involve high heat, like barbecuing, grilling, roasting, baking, frying, broiling, sauteing, and toasting can increase the AGE content of foods by 10 to 100 times that of uncooked food. I'll give you some examples:

• 1 fried egg: 1,240 kilounits per liter (kU/l)
• 1 scrambled egg: 75 kU/l
• 3 ounces of grilled chicken: 5,200 kU/l
• 3 ounces of poached chicken: 1,000 kU/l
• 3 ounces of broiled steak: 6,600 kU/l
• 3 ounces of braised beef: 2,200 kU/l

Animal foods in general tend to be higher in AGEs, but they appear in almost any type of food that's been exposed to high heat, be they proteins, carbohydrates, or fats.

There's a lot you can do to reduce the level of AGEs in food. Most, I'll readily admit, are things few people will adopt because they involve too much effort or result in foods that taste kind of blah. Duty, however, requires me to describe them.

First off, you can use "wet" cooking methods like boiling, poaching, stewing, and steaming instead of the high-heat methods listed above.

Wet cooking, of course, involves water, and subsequently the temperature is never going to exceed 212 degrees, far below the 300-plus degrees necessary for significant levels of glycation to occur. Using lower temperatures in general will help, as well as cooking for shorter periods of time.

Slow cookers, popular in yesteryear but displaced by quicker cooking methods, are likely one of the healthiest ways to cook food, while the Instant Pot and air fryers are among the worst. At the very least, though, each of those two quick-cooking methods is still better than barbecuing because the food is only exposed to high heat for a relatively short time.

You can, however, ameliorate the damage caused by these high-heat cooking methods by using acidic ingredients like citrus fruits, vinegar, or tomato juice in their preparation.

Okay, I've done my nutritional duty by suggesting these AGE-fighting strategies, most of which will likely be ignored or, if attempted, quickly cast aside simply because "wet foods" don't taste as good at their counterparts. As such, let me offer some more pragmatic strategies instead.

The Polyphenol Strategy to Squash AGEs

I've droned on about phytochemicals in a whole lot of articles, but for those of you who were spared, phytochemicals are natural compounds found in plants that are responsible for their color, taste, and aroma.

They're mainly comprised of classes of chemicals known as terpenoids, thiols, and polyphenols, the latter probably being the largest of the groups, comprising around 8,000 (and probably more) different phytochemicals. The average total intake of polyphenols by human-types is reported to be over 1 gram a day, which is about ten times that of all the other classes of phytochemicals.

Their assigned task in plants is to play chemical bodyguard. They defend against excess UV light, insects, fungi, and various diseases. The beautiful thing? They appear to do much of the same for the humans that ingest them.

Most of the beneficial effects were first attributed back in the 1990s to their antioxidant effect, but the reality is much more complex. Their biological effects involve detailed biochemical interactions that we've only just started to understand.

Regardless of the exact mechanism, polyphenols can both hinder the formation of AGEs and reduce their negative health effects. As such, you should eat substantive amounts of them each day, preferably partaking of foods from each of the "polyphenolic categories" I've identified:

1. Vegetables: Artichokes, potatoes, rhubarb, yellow onions, red cabbage, cherry tomatoes, leeks, broccoli, celery.
2. Fruits: Berries, apples, apricots, plums, pears, grapes, cherries. The darker the fruit, the higher the polyphenol content.
3. Whole Grains: Buckwheat, rye, oats, barley, corn, wheat, rice.
4. Nuts, Seeds, Legumes: Black beans, white beans, pecans, almonds, walnuts, flaxseed, chestnuts, hazelnuts.
5. Fats: Extra virgin olive oil, sesame seed oil, dark chocolate.
6. Beverages: Coffee, tea, red wine, cocoa. (Obviously, these are all liquid forms of foods from some of the other groupings, but it's more convenient to think of them as a separate group.)
7. Spices: Oregano, rosemary, soy sauce, cloves, peppermint, anise, celery seed, saffron, spearmint, thyme, basil, curry powder, ginger, cumin, cinnamon, garlic.

Following this strategy could really help prevent premature aging/dying. However, the best way to fight the formation of AGEs involves avoiding another dietary habit, one that bodybuilders and many physique-conscious people practice habitually.

Also, Stop with the Multiple Small Meals

The average bodybuilder eats several small meals a day and never allows themselves to get hungry. Because of this, despite their best dietary efforts, many bodybuilders end up walking around with high blood sugar most of the day, much like the average junk-food-eating American. Because blood sugar is high most of the day, it makes for the perfect environment for production of AGEs.

But maybe you don't do that. You eat fewer meals, and you're thinking that since your last fasting blood glucose was a fairly admirable 95 mg/dl, you're safe from glycation. No, not necessarily. Glycation – what I call "cooking your meat" – still occurs at that level of blood sugar, albeit at a much slower rate than what might be seen in type 2 or full-blown diabetics. (An ideal blood sugar level would be about 80 mg/dl.)

You have a few lifestyle/supplement/drug options on how to keep your blood sugar as low as possible and help prevent AGE production, though. For those that eat multiple meals, you could, obviously, simply reduce the number of times you eat a day, but that might prove counterproductive to your muscle-building efforts.

A compromise might be to use a "sugar-eating" supplement or drug. Supplement options include cyanin 3-glucoside (Indigo-3G Buy at Amazon) or berberine. Both are polyphenols and each has been shown to compete favorably with blood-sugar-reducing drugs.

Another option is to convince your doctor to prescribe metformin, a blood-sugar drug that's been used to treat type 2 diabetes for over 65 years.

Logically, metformin's sugar-eating properties should equate to lowered rates of glycation and subsequently lower levels of AGEs, and several research studies with mice, in vitro human cells, and even some involving real humans appear to have confirmed it. (This may well explain many of metformin's alleged life-extending properties.)

There's also a drug that was purported to directly break the crosslinks caused by AGEs. Unfortunately, clinical trials of alagebrium were suspended in 2009. You can, however, obtain the chemical from various chemical supply companies, but most people might find that daunting.

Alternately, aminoguanidine, once an investigational drug for the treatment of diabetic neuropathy, also reduces glycation directly, even having been found to prevent AGE cross-linking in the walls of arteries. The substance, while somewhat hard to find, is available as an over-the-counter supplement.

Another option is a flavonoid/polyphenol combo that appears to have AGE-destroying properties: hesperedin and resveratrol (Buy at Amazon). Both are available in supplement form.

All these options would also work for the people who don't eat multiple times a day but still face the production of AGEs because their fasting blood sugar level is above 80.

Let's Make This Simple

Okay, by now I've bombarded you with info, so let me condense most of what I've told you and just give you some easily digestible take-home strategies to help you whack away at AGE production and accumulation. Adopting even one of them might go a long way in keeping your skin, eyes, tendons, blood vessels, heart, brain, and other organs youthful and free from disease and disorder:

• Try to avoid high-heat cooking and instead choose "wet" cooking.
• If high-heat cooking is unavoidable, marinate foods in acidic substances like vinegar, citrus, or tomato juice prior to cooking.
• Accordingly, avoid fried foods.
• Reduce consumption of processed foods in general.
• Partake of polyphenols (particularly hesperedin and resveratrol) liberally.
• Keep blood sugar low by eating fewer meals and eating less sugar and simple carbohydrates in general.
• Consider taking the drug metformin or supplements like cyanidin 3-glucoside or berberine to increase insulin sensitivity and lower blood sugar levels in general.

References

1. George L. Bakris, et al. Advanced glycation end-product cross-link breakers: A novel approach to cardiovascular pathologies related to the aging process, Am Jour Hypertension, 01 December 2004.
2. Jyotiska Chaudhuri, et al. The role of advanced glycation end products in aging and metabolic diseases; bridging association with causality, Cell Metabolism Review, 28, September 4, 2018.
3. Chun-yu Chen, et al. Advanced glycation end products in the skin: Molecular mechanisms, methods of measurement, and inhibitory pathways, Front Med, 2022 May 11.
4. Alison Goldin, et al. Advanced glycation end products, Circulation, 8 Aug 2006.
5. David Schroter and Annika Hohn, Role of advanced glycation end products in carcinogenesis and their therapeutic implications, Curr Pharm Des, 2019 Dec; 24(44): 261-266.
6. FJ Tessier, The Maillard reaction in the human body. The main discovery and factors that affect glycation, Pathol Biol (Paris), 2010 Jun;58(3):214-9.
7. Cigdem Toprak and Semra Yigitasian, Alagebrium and complications of diabetes mellitus, Eur Jour Med, 2019, Oct; 51 (3): 285-292.
8. Zhong'e Zhou, et al. Metformin inhibits advanced glycation end products-induced inflammatory response in murine macrophages partly through AMPK activation and RAGE/NFkB pathway suppression, Journal of Diabetes Research, 2016, Sep 28.