By Matt Worthy, founder of ScienceBod.com

The harm caused by sugar does not stop with all the many ways it wrecks our bodies that we are already aware of. Here’s a term you may not have heard before: glycation. What is glycation? Glycation is a process that occurs when sugar bonds to protein resulting in Advanced Glycation End-products, or AGE’s for short. AGE’s are also known within the scientific community as “glycotoxins.” [i] The dictionary defines a “toxin” as a poisonous substance.

AGE’s can form outside the body during the manufacturing of processed foods, as well as when cooking, frying, searing, baking, or barbequing food at home or at restaurants, especially when foods are exposed to high temperatures. High heat causes sugars in the food being cooked to bond with protein molecules also present, forming AGE’s. AGE’s produced in these ways can cause damage when we eat them.

AGE’s can also form internally when sugar molecules attach to proteins inside the body. Consuming excessive amounts of sugars, resulting in elevated blood sugar levels, contributes to AGE formation in our tissues, organs, and blood vessels. [ii] Ingesting sugars with a higher proportion of fructose results in the creation of more AGE’s inside the body than from other sugars. Fructose has ten times more affinity for AGE formation than does glucose. [iii] AGE intake is directly linked to overall oxidative stress levels in the body, regardless of age or sex. [iv] Oxidative stress is a known major accelerator of aging.

The big picture is that AGE’s are bad, bad, bad. We can think of them as stiffening tissues that need to be flexible, tangling the function of organs, and hastening the clogging of arteries, veins, and capillaries. It is sort of akin to injecting ourselves with sticky glue. They assail nearly every bit of our bodies. To put it in simple terms, they gum up and stiffen tissues throughout our body from the lining of blood vessels to the gray matter of our brains. When cells or tissues are invaded by AGE’s, an inflammatory response is also initiated which exacerbates the negative effects of AGE’s.

AGE’s form as a result of a chemical reaction called the Maillard Process. A telltale sign of AGE formation via the Maillard Process is browning – whether it is a piece of steak or a loaf of bread. If you see browning, you are seeing AGE’s forming. Browning via the Maillard Process can also occur inside the body. Cataracts, especially in diabetics, often take on a brownish color that is caused by the clouding of the eye’s lens with AGE’s. [v] Autopsies of diabetic patients have revealed that tissues inside their bodies had taken on a brownish color as the result of AGE accumulation. [vi] Diabetes is the result of elevated blood sugar levels. High blood sugar levels accelerate the formation of AGE’s.

AGE’s have been linked to cardiovascular disease, diabetes, several cancers, Alzheimer’s, and skin aging. In 2017, European researchers described AGE’s as significant contributors to heart aging, which subsequently leads to the shortening of telomeres. [vii] Short telomeres are strongly associated with advanced aging. In another study, scientists exposed young human endothelial cells (cells that line the interior of blood vessels) to glycation. The young cells quickly aged and went into senescence. [viii] A 2010 study conducted by Dr. Richard Semba of Johns Hopkins Medical School, found that AGE’s were shown to cause “widespread” damage affecting “virtually all cells, tissues, and organ systems,” and that the evidence strongly indicates “that AGE’s contribute to the multisystem decline that occurs with aging.” [ix] In a 2007 evaluation of a group of older and younger people of both sexes, AGE’s were shown to correlate directly with a higher body mass index, inflammation, and oxidative stress: all significant contributors to the development of age-related disease. [x]

Not good. And it gets worse.

AGE’s also age our skin. Glycation in the skin means glucose and fructose are linking together the amino acids found in collagen and elastin. Collagen and elastin are two of the most important proteins that give our skin its youthful look. Glycated forms of them have a much more difficult time regenerating. [xi] The rate of skin glycation is accelerated with ultraviolet light exposure. [xii] The dermis, or second layer of skin, is constantly producing new skin cells to replace old ones so that our skin can maintain its smooth quality. When this process is impeded by glycated proteins, our skin begins to look old, saggy and wrinkly.

Like stepping out of the restroom stall and not realizing that a length of toilet paper has stuck to your heel, the effects of enjoying too much sugar leave clear indications on our faces. They are not pretty. Dentists claim to be able to diagnose a methamphetamine addiction by simply looking at the teeth of a patient and observing the telltale signs. They call it “meth mouth.” [xiii] Similarly, dermatologists and beauty industry professionals can look at our faces and recognize a sugar addiction. They call it “sugar face.” Some of the giveaways are lines and wrinkles on the forehead, thinning skin, especially on the cheeks and under the eyes, the loss of youthful luminosity, blotchy spots, and acne. [xiv]

This process of “sugar-ification” of your face is significantly hastened with an increase in glucose concentration in the blood. That happens as a result of eating high-carbohydrate and high-sugar foods (ultimately all carbohydrates break down into sugar). In addition to wrinkling and sugar face, AGE’s and glycation have also been shown to cause age spots, hyperpigmentation, hardness of skin, dull skin, uneven skin tone, sagging and bagging, inflammation, skin tags, and even tumors. “Because it is almost impossible to repair glycated collagen cross-links, prevention is the prime defense, and the earlier preventive activity is begun, the better.” [xv]

Eating “clean” is one method of prevention. A 2017 analysis evaluated nearly 3,000 people from the Netherlands and found that women who ate an unhealthy diet characterized by meat, grains, snacks, soft drinks, coffee and other alcoholic drinks showed more facial wrinkling than women who ate a healthy diet characterized by, among other things, low sugar consumption. [xvi] Additionally, “among lifestyle-related factors, drinking, smoking and lack of sleep are known to increase skin AGE content.” [xvii] So, if you would prefer to avoid looking prematurely old or if you would like to maintain a youthful appearance as long as possible, here is some advice: avoid sugar (especially fructose), minimize drinking and smoking, get plenty of sleep, and protect yourself from the sun. It’s that simple.

Worse than aging skin and sugar face, AGE’s have been strongly implicated in diabetes. Since diabetes is characterized by high blood sugar levels, diabetics have a particularly difficult time with AGE’s. A tragic, downward spiraling process can ensue in the case of diabetics. High blood sugar levels fuel the creation of an extraordinarily high number of AGE’s, which amplifies their destructive power throughout the body. In turn, that creates additional complications for the victim of diabetes. AGE’s exacerbate diabetic complications in the kidneys, eyes, nerves, vascular system, and heart. [xviii]

AGE’s are also thought to play a key role in Alzheimer’s. Two of the proteins that are central to the disease process of Alzheimer’s are beta-amyloid and tau. Both are subject to glycation which accelerates their cross-linking and formation of fibrils within the brain. Both processes are central to the dysfunction caused by Alzheimer’s. They gum up the brain. AGE’s in the brain can also bind to microglia cells. When AGE’s bind to microglia, they cause the microglia to express an immune response and to release free radicals into the brain. [xix] Microglia cells are key components of the brain’s defense system. When they begin to lose function, it quickens the progress of the disease.

If you want to age well, AGE’s are bad news. By far the easiest way to avoid problems with AGE’s is to cut back on our sugar intake, and avoid foods cooked with high heat. Animal studies have shown a low-AGE diet has the ability “to reverse insulin resistance and chronic inflammation, inhibit the progression of atherosclerosis” and prevent kidney disease. [xx] Other studies, including some human studies, “show that the restriction of dietary AGE’s has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGE intake has been reported to increase the lifespan in animal models.” [xxi]

So, did you know about AGE’s already? Did you know how damaging they are? Does knowing about AGE’s change anything about the way you approach your own health and wellness?

Works Cited

[i] J. Uribarri et al., “Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet,” J Am Diet Assoc 110, no. 6 (2010).

[ii] Marco Malavolta and Eugenio Mocchegiani, Molecular Basis of Nutrition and Aging, Molecular Nutrition Series (Amsterdam ; Boston: Elsevier, AP, 2016).

[iii] Victor Katch, “Can Foods Cause Chronic Disease?,” Michigan Today, http://michigantoday.umich.edu/can-foods-cause-chronic-disease/.

[iv] J. Uribarri et al., “Circulating Glycotoxins and Dietary Advanced Glycation Endproducts: Two Links to Inflammatory Response, Oxidative Stress, and Aging,” J Gerontol A Biol Sci Med Sci 62, no. 4 (2007).

[v] Atef M. Mahmoud Lequaa A. Moemen, et al, “The Relation between Advanced Glycation End Products and Cataractogensis in Diabetics,” World Journal of Medical Sciences 10, no. 4 (2014).

[vi] V. M. Monnier, R. R. Kohn, and A. Cerami, “Accelerated Age-Related Browning of Human Collagen in Diabetes Mellitus,” Proc Natl Acad Sci U S A 81, no. 2 (1984).

[vii] O.N. Tkacheva E.V. Plokhova, et al, “Advanced Glycation End-Products and Telomere Shortening Contribute to Cardiac Aging: The Relationship with Myocardial Strain,” European Heart Journal 38, no. Suppl 1 (2017).

[viii] J. Chen et al., “Glycated Collagen I Induces Premature Senescence-Like Phenotypic Changes in Endothelial Cells,” Circ Res 90, no. 12 (2002).

[ix] R. D. Semba, E. J. Nicklett, and L. Ferrucci, “Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype?,” J Gerontol A Biol Sci Med Sci 65, no. 9 (2010).

[x] Uribarri et al., “Circulating Glycotoxins and Dietary Advanced Glycation Endproducts: Two Links to Inflammatory Response, Oxidative Stress, and Aging.”

[xi] Masamitsu Ichihashi et al., “Glycation Stress and Photo-Aging in Skin,” ANTI-AGING MEDICINE 8, no. 3 (2011).

[xii] Z. D. Draelos, “Aging Skin: The Role of Diet: Facts and Controversies,” Clin Dermatol 31, no. 6 (2013).

[xiii] Palmer Holton, “Meet the Dentist Who Will Fix Your Mouth after Meth Ruins It,” Vice, Meet the Dentist Who Will Fix Your Mouth After Meth Ruins It.

[xiv] Nigma Talib, Younger Skin Starts in the Gut : 4-Week Program to Identify and Eliminate Your Skin-Aging Triggers–Gluten, Wine, Dairy, and Sugar (Berkeley, CA: Ulysses Press, 2016).

[xv] F. W. Danby, “Nutrition and Aging Skin: Sugar and Glycation,” Clin Dermatol 28, no. 4 (2010).

[xvi] S. Mekic et al., “A Healthy Diet in Women Is Associated with Less Facial Wrinkles in a Large Dutch Population-Based Cohort,” J Am Acad Dermatol  (2018).

[xvii] Yoshikazu Yonei, Wakako Takabe, and Masayuki Yagi, “Photoaging and Glycation of Elastin : Effect on Skin,” Glycative stress research : official journal 2, no. 1 (2015).

[xviii] S. Y. Goh and M. E. Cooper, “Clinical Review: The Role of Advanced Glycation End Products in Progression and Complications of Diabetes,” J Clin Endocrinol Metab 93, no. 4 (2008).

[xix] Patrick R. Hof and Charles V. Mobbs, Functional Neurobiology of Aging (San Diego, CA: Academic Press, 2001).

[xx] N. J. Kellow and G. S. Savige, “Dietary Advanced Glycation End-Product Restriction for the Attenuation of Insulin Resistance, Oxidative Stress and Endothelial Dysfunction: A Systematic Review,” Eur J Clin Nutr 67, no. 3 (2013).

[xxi] C. Luevano-Contreras and K. Chapman-Novakofski, “Dietary Advanced Glycation End Products and Aging,” Nutrients 2, no. 12 (2010).