Glycation Accelerates Whole-Body AgingJanuary 2019
By Amy Rosen
Diabetics suffer premature illnesses related to uncontrolled blood sugar.
A common diabetic complication happens when glucose binds to the body's proteins through a process called glycation.
The result is formation of damaged structures that are hallmarks of accelerated aging.
Glycation's effect on living tissue is similar to the process by which meat is browned when cooked at high temperatures. Our body's living proteins also turn brown in the presence of excess glucose and are rendered functionally impaired.
Glycation occurs in all aging adults, not just diabetics, and affects tissues throughout the body.
Fortunately, there are documented ways to help block and even reverse toxic glycation reactions in our bodies.
What you need to know
- Glucose (blood sugar) can form toxic compounds that damage cells and tissues through a process called glycation.
- Advanced glycation end-products or AGEs are implicated in accelerated aging, as well as age-related loss of function and chronic diseases of aging.
- Several compounds have the ability to prevent, and potentially reverse, glycation and its deleterious effects.
- Benfotiamine and carnosine have demonstrated anti-glycation activity that may help slow the aging process.
- Glycation damage is not limited to diabetics. Scientists have found it in healthy individuals whose blood levels of fasting glucose are over 85 mg/dL. Most aging people have glucose levels above 85 mg/dL, even though they are not clinically recognized as being diabetic.32
- Eating foods cooked at high temperatures also causes and accelerates glycation damage.31
The Development of Glycation
Glucose in the body is a double-edged sword.
On one hand, glucose serves as a critical source of cellular energy.
On the other, the accumulation of glucose-derived (glycation) byproducts damages delicate cellular structures. The pathologic impact is chronic inflammation, premature diseases, and accelerated aging.1-5
These harmful byproducts are called advanced glycation end-products (AGEs). They accelerate aging in a number of ways including:6
- Interfering with the normal function of our body's proteins;
- Cross-linking proteins to cause tissue stiffening, skin-wrinkling, and impaired heart and blood vessel function;
- Inducing chronic inflammatory reactions;
- Making cells more susceptible to oxidative damage.
Glycation's Impact on Aging
Everyone is at risk for the age-accelerating effects of glycation. However, diabetics' tissues undergo rapid aging and deterioration due to poor glucose control.
The life expectancy of an individual whose diabetes is not adequately controlled is significantly shortened, and quality of life suffers from this accelerated aging process.7
In diabetics and non-diabetics, glycation has been implicated in disorders such as:2-6,8-13
- Kidney failure,
- Alzheimer's and Parkinson's disease,
- Skin cancer,
- Spinal disease,
- Visual loss,
- Atherosclerosis, and
- Heart disease.
Glycation has been identified as an important contributor to atherosclerosis and direct damage to the heart muscle.6,9
New human studies demonstrate that higher accumulations of advanced glycation end-products (AGEs) are associated with lower levels of physical activity and decreased reaction time.14,15
The good news is that glycation, and its harmful effects on health, can be greatly reduced.
Preventing damage due to glycation can be accomplished by two general means:
- Preventing the formation of AGEs in the first place, and
- Minimizing the impact of AGEs that are already in the body.
Many of the compounds that can help combat glycation can contribute to both the prevention of AGEs formation and a reduction in the harmful inflammation they trigger.
Benfotiamine is a fat-soluble derivative of thiamine that has greater bioavailability that makes it capable of delivering increased clinical benefits.
Benfotiamine blocks several tissue-damaging mechanisms, one of them being the advanced glycation end-products (AGEs) formation pathway.16,17 It is also able to limit effects of AGEs by reducing inflammation and harmful AGE-triggered changes.17
Most human studies have evaluated the ability of benfotiamine to prevent or reverse complications of diabetes caused by glycation. Clinical markers of diabetic nerve disease, kidney failure, blood vessel dysfunction, and oxidative stress have all been improved with benfotiamine.16-18
In one study, those supplementing with benfotiamine saw improvements in diabetic nerve disease symptoms, including pain and loss of sensation. 19
Carnosine is a naturally occurring amino acid derivative that is found in high levels in muscle tissues and the nervous system.
It has been shown to deliver potent anti-glycation activity by preventing the cross-linking of proteins, which is associated with tissue stiffening in the skin, blood vessels, and heart.20,21
In animal models, carnosine supplementation provided a stabilizing effect on atherosclerotic plaques in blood vessels, reducing the risk of stroke or heart attack.22,23
Cross-linking of proteins might also contribute to the structural changes in the brain that leads to Alzheimer's. Studies show that carnosine can prevent these cross-links as well, potentially preventing cognitive decline in the elderly.24,25
Carnosine Improves Skin Appearance
Carnosine is notable in that it is able to stop and remove damaged proteins.20
Glycation of the skin tissues is unique in that its effects can be seen externally in the form of fine lines and wrinkles.
Scientists designed a randomized, double-blind, placebo-controlled study that evaluated a carnosine-based supplement for its ability to improve age-related skin changes, many of which are caused by cross-linking of skin collagen by glycation. The test formula contained 210 mg of carnosine and was taken every other day.26
Healthy adult females were divided into two groups, one taking carnosine and one serving as the control group. Their skin was assessed by a dermatologist using both objective and subjective parameters.
In the carnosine group, there were significant improvements in all parameters, including the skin firmness, smoothness, and reductions of fine lines
Using objective measures, there was as much as a 23% improvement in skin appearance in the carnosine group.26
What's interesting about this study showing improved outward appearance of aged skin is the modest dose of carnosine used.
A dose 210 mg of carnosine only lasts about 5 hours in the blood before being degraded by carnosinase enzymes. That's why many readers of this magazine take 500 mg of carnosine twice a day, to ensure continuous protection against glycation.
Yet in this study revealing overall improvements in skin appearance, just 210 mg of carnosine taken every other day resulted in these outward reversals of skin aging.
This indicates lower dose carnosine may provide greater benefits than originally postulated back in 2001.
The Benefits of Higher Doses
A study of 18 people sought to determine carnosine concentrations in blood plasma after eating beef.27 Each 7.1-ounce serving of ground beef used in this study naturally contained 248 mg of carnosine.
In the study's first phase, meat foods were removed from the diet for 48 hours. When fasting blood levels were measured, no carnosine was present.
After the subjects ate 7.1 ounces of ground beef, carnosine was detected in the blood within 15 minutes and continued to increase for several hours. After 5.5 hours, there was again no carnosine in the blood.
This study showed that 248 mg of carnosine does not provide the body with all-day protection against glycation reactions.
The reason carnosine disappears so quickly from the blood is the presence of an enzyme (carnosinase) that naturally degrades carnosine in the body. This study helps confirm what Life Extension published 18 years ago about the virtues of taking higher-dose carnosine every day.28,29
Avoid Foods Cooked at High Temperature
Although glycation forms AGEs inside the body, the diet has also been found to be a significant source of AGEs.33,34 Certain methods of food preparation increase the AGEs content in foods.
Highly processed foods contain high levels of AGEs, as do protein- and fat-rich foods cooked by dry heat methods such as frying, grilling, and roasting. The browning of food, in addition to adding flavor, produces glycated compounds in the food.
Although only about 10% of these AGEs consumed in the diet make it into the bloodstream, they are believed to contribute to the overall burden of AGEs and may significantly contribute to aging and chronic disease.33
Small changes in cooking methods and diet can dramatically slow glycation damage.
Researchers have determined that advanced glycation end products (AGEs) are found in foods that are overheated or cooked at very high temperatures.30 This includes foods that have been fried, barbecued, grilled, or broiled.
The worst culprits are overcooked animal products that speed up glycation, but any food that is exposed to extreme high heat can scorch the sugars/fats in food and accelerate formation of advanced glycation end products in the body.
AGEs can also be found in many pre-packed foods that have been preserved, pasteurized, homogenized or refined, such as white flour, cake mixes, dried milk, dried eggs, dairy products including pasteurized milk, and canned or frozen pre-cooked meals.
Consider steaming, boiling, poaching, stewing, stir-frying or using a slow cooker. These methods not only cook foods with a lower amount of heat, they create more moisture during the cooking process.
According to a study Life Extension® reported on in 2003, water or moisture can help delay the reactions that lead to toxic glycation byproducts.
Marinating foods in olive oil, cider vinegar, garlic, mustard, lemon juice and dry wines can also help.
In addition, avoiding foods cooked at high temperatures can assist in weight loss.31
Glucose produces glycation compounds that cause significant damage to fats and proteins.
Glycation occurs in diabetics and non-diabetics and has been implicated as a major mechanism of accelerated aging, development of chronic disease and loss of function.
Benfotiamine and carnosine help prevent glycation and even reverse some of this damaging process, as observed in the skin of females supplementing with a modest dose carnosine.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Davis KE, Prasad C, Vijayagopal P, et al. Advanced Glycation End Products, Inflammation, and Chronic Metabolic Diseases: Links in a Chain? Crit Rev Food Sci Nutr. 2016;56(6):989-98.
- Hipkiss AR. Aging risk factors and Parkinson's disease: contrasting roles of common dietary constituents. Neurobiol Aging. 2014 Jun;35(6):1469-72.
- Kim CS, Park S, Kim J. The role of glycation in the pathogenesis of aging and its prevention through herbal products and physical exercise. J Exerc Nutrition Biochem. 2017 Sep 30;21(3):55-61.
- Qu D, Venzon D, Murray M, et al. Noninvasive measurement of advanced glycation end-products in the facial skin: New data for skin aging studies. J Cosmet Sci. 2017 May/Jun;68(3):195-204.
- Rabbani N, Thornalley PJ. Advanced glycation end products in the pathogenesis of chronic kidney disease. Kidney Int. 2018 Apr;93(4):803-13.
- Simm A. Protein glycation during aging and in cardiovascular disease. J Proteomics. 2013 Oct 30;92:248-59.
- Caspersen CJ, Thomas GD, Boseman LA, et al. Aging, diabetes, and the public health system in the United States. Am J Public Health. 2012 Aug;102(8):1482-97.
- Younus H, Anwar S. Prevention of non-enzymatic glycosylation (glycation): Implication in the treatment of diabetic complication. Int J Health Sci (Qassim). 2016 Apr;10(2):261-77.
- Ward MS, Fortheringham AK, Cooper ME, et al. Targeting advanced glycation endproducts and mitochondrial dysfunction in cardiovascular disease. Curr Opin Pharmacol. 2013 Aug;13(4):654-61.
- Burd J, Lum S, Cahn F, et al. Simultaneous noninvasive clinical measurement of lens autofluorescence and rayleigh scattering using a fluorescence biomicroscope. J Diabetes Sci Technol. 2012 Nov 1;6(6):1251-9.
- Li J, Liu D, Sun L, et al. Advanced glycation end products and neurodegenerative diseases: mechanisms and perspective. J Neurol Sci. 2012 Jun 15;317(1-2):1-5.
- Tsuru M, Nagata K, Jimi A, et al. Effect of AGEs on human disc herniation: intervertebral disc hernia is also effected by AGEs. Kurume Med J. 2002;49(1-2):7-13.
- Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. 2002 Jan;46(1):114-23.
- Arnold P, Njemini R, Vantieghem S, et al. Reaction time in healthy elderly is associated with chronic low-grade inflammation and advanced glycation end product. Exp Gerontol. 2018 Jul 15;108:118-24.
- Drenth H, Zuidema SU, Krijnen WP, et al. Advanced Glycation End Products Are Associated With Physical Activity and Physical Functioning in the Older Population. J Gerontol A Biol Sci Med Sci. 2018 Oct 8;73(11):1545-51.
- Balakumar P, Rohilla A, Krishan P, et al. The multifaceted therapeutic potential of benfotiamine. Pharmacol Res. 2010 Jun;61(6):482-8.
- Raj V, Ojha S, Howarth FC, et al. Therapeutic potential of benfotiamine and its molecular targets. Eur Rev Med Pharmacol Sci. 2018 May;22(10):3261-73.
- Stirban A, Negrean M, Stratmann B, et al. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care. 2006 Sep;29(9):2064-71.
- Winkler G, Pal B, Nagybeganyi E, et al. Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy. Arzneimittelforschung. 1999 Mar;49(3):220-4.
- Brownson C, Hipkiss AR. Carnosine reacts with a glycated protein. Free Radic Biol Med. 2000 May 15;28(10):1564-70.
- Hobart LJ, Seibel I, Yeargans GS, et al. Anti-crosslinking properties of carnosine: significance of histidine. Life Sci. 2004 Jul 30;75(11):1379-89.
- Brown BE, Kim CH, Torpy FR, et al. Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice. Atherosclerosis. 2014 Feb;232(2):403-9.
- Stegen S, Stegen B, Aldini G, et al. Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress. Appl Physiol Nutr Metab. 2015 Sep;40(9):868-76.
- Babizhayev MA, Deyev AI, Yegorov YE. Olfactory dysfunction and cognitive impairment in age-related neurodegeneration: prevalence related to patient selection, diagnostic criteria and therapeutic treatment of aged clients receiving clinical neurology and community-based care. Curr Clin Pharmacol. 2011 Nov;6(4):236-59.
- Hipkiss AR. Could carnosine or related structures suppress Alzheimer's disease? J Alzheimers Dis. 2007 May;11(2):229-40.
- Babizhayev MA, Deyev AI, Savel'yeva EL, et al. Skin beautification with oral non-hydrolized versions of carnosine and carcinine: Effective therapeutic management and cosmetic skincare solutions against oxidative glycation and free-radical production as a causal mechanism of diabetic complications and skin aging. J Dermatolog Treat. 2012 Oct;23(5):345-84.
- Park YJ, Volpe SL, Decker EA. Quantitation of carnosine in humans plasma after dietary consumption of beef. J Agric Food Chem. 2005 Jun 15;53(12):4736-9.
- Available at: https://www.lifeextension.com/Magazine/2001/1/report_carnosine/Page-01. Accessed November 5, 2018.
- Quinn PJ, Boldyrev AA, Formazuyk VE. Carnosine: its properties, functions and potential therapeutic applications. Mol Aspects Med. 1992;13(5):379-444.
- Vlassara H, Cai W, Crandall J, et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15596-601.
- Available at: https://www.lifeextension.com/Magazine/2003/5/awsi/Page-01. Accessed October 25, 2018.
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- Sharma C, Kaur A, Thind SS, et al. Advanced glycation End-products (AGEs): an emerging concern for processed food industries. J Food Sci Technol. 2015 Dec;52(12):7561-76.
- Uribarri J, del Castillo MD, de la Maza MP, et al. Dietary advanced glycation end products and their role in health and disease. Adv Nutr. 2015 Jul;6(4):461-73.