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Rage of Ages: Advanced Glycation End Products

By Loren Cordain, Ph.D., Professor Emeritus, Founder of The Paleo Diet
May 28, 2015
Rage of Ages: Advanced Glycation End Products image

If you were to walk into your local physician or general practitioner’s office and ask them about the connection between nutrition and health, most would say that a diet high in plant foods and low in animal proteins and fat is the way to go. If you were to probe more deeply and ask your doctor about the glycemic index and how it influences your health, many might stare off into space because they are unaware of this concept.

Bearing down even further, if you were to question them about RAGE’s, AGE’s and diet, they might assume you are somehow angry about your age. The meaning and implications of these terms have huge implications upon our health and well being that have only been widely recognized in the past 5 years.3

Carbs & Glycemic Index
By The Paleo Diet® Team

What does "AGE" mean?

AGE stands for “advanced glycation end-products.” These are compounds that naturally form in our bodies from the chemical reaction of sugars with proteins. If the concentration of AGEs becomes excessive in our bloodstream, they can cause damage to almost every tissue and organ in our bodies.1-3 In the past decade scientists have discovered that foods also contain AGEs that may greatly add to the AGE burden in our bodies.

The problem with AGEs is that they act like a key that permanently turns on low level inflammation1-3 in our bodies by binding to AGE receptors known as RAGEs.1, 8 They also cross link with proteins in our cells thereby altering normal structure and function.

It is now becoming clear to scientists that high tissue levels of AGEs are associated with almost all chronic diseases that afflict us in the western world. AGEs are directly involved with or accelerate the progression of numerous diseases including: The Metabolic Syndrome (type 2 diabetes,9 high blood pressure,10 cardiovascular disease2, 8, 10), kidney failure,11 Alzheimer’s disease,12 allergy and autoimmune diseases,13 cancers,14 cataracts,15 retinal degeneration,15 and gastrointestinal diseases.16 Additionally, excessive AGEs are known to speed the aging process.5, 17

In rodents, diets low in AGEs lengthen their lifespan to the same degree that caloric restriction does.4 In humans, restriction of dietary AGEs lowers markers of oxidative stress and inflammation.17 Hence, it may be possible to increase human lifespan manner similar to experimental animals4 by limiting dietary AGEs.17

How to follow a low AGE diet

The good news is that if you are already following The Paleo Diet you won’t have to tweak it much at all to convert it into a low AGE diet. In the table below I have listed the concentrations of AGEs found in many Paleo foods and in certain non-Paleo foods.

Rage of Ages: Advanced Glycation End Products image

By closely examining this table, you can get a feel for those foods which yield excessive AGEs and those that don’t. Although we don’t yet have clear guidelines regarding healthful dietary limits for AGEs, we do know that the typical American adult consumes about 14,700 kU of AGEs per day. [7] Based upon animal studies, if we can cut this number in half (7,350 kU per day), it will reduce inflammation, oxidative stress and potentially increase our lifespan. [4] You can use the table above to get an idea of the AGEs you may consume on a daily basis.

Notice that fruits and veggies – staples of The Paleo Diet are exceedingly low in AGEs, as are eggs. In contrast, most dairy products, fast and processed foods are overloaded with these deleterious compounds.

How to cook meat for a low concentrations of AGE

In their raw forms, meat, fish and seafood contain relatively little AGEs but these chemicals become increasingly concentrated in our diets depending upon the method of cooking. Am I advocating that we eat our meat and sea food raw? Almost certainly not! – as the risk for bacterial infection with E. coli and other bacterial contaminants is greatly magnified when we eat raw meat or seafood. Nevertheless, if you can find sources of untainted meats and seafoodeating these foods raw may represent a healthful alternative when it comes to AGEs. Sushi bars (raw fish and seafood) and restaurants serving “Steak Tartare” (raw beef) have been popular for decades.

Yes, raw meats and fish contain much lower concentrations of AGEs, but so do animal foods prepared using slow cooking methods. More importantly, cooked meats are generally free from bacteria which may produce disease. As a Paleo Dieter, be aware that slow cooking methods such as stewing, poaching, steaming and slow roasting reduce the AGE content of meats while simultaneously preventing bacterial contamination. Look no further than at the table above and you can see the AGE numbers for yourself. The worst way to cook your meats and seafood when it comes to AGEs is by high heat: searing, broiling, frying and high temperature roasting.

I would never be one to ruin a wonderful summer evening dinner at a close friend’s home by saying that I couldn’t eat the char encrusted London Broil that was served my way. However, by slicing off the burnt surface and eating the pink inner layers, I can reduce my AGE intake nearly to levels in raw, uncooked beef. So, the message here is simple: whenever and wherever possible, try to replace high temperature, searing techniques with long slow cooking procedures. I love tender beef stew chunks slowly cooked all day long with carrots, celery, onions and spices in a crock pot. Similarly, poached salmon with basil and tender, fresh asparagus doesn’t get much better for me.

Processed, Cured and Smoked Meats: Definitely Not Paleo!
By Loren Cordain, Ph.D.


[1] Alexiou P, Chatzopoulou M, Pegklidou K, Demopoulos VJ. RAGE: a multi-ligand receptor unveiling novel insights in health and disease. Curr Med Chem. 2010;17(21):2232-52.

[2] Barlovic DP, Thomas MC, Jandeleit-Dahm K.Cardiovascular disease: what's all the AGE/RAGE about? Cardiovasc Hematol Disord Drug Targets. 2010 Mar;10(1):7-15.

[3] Bengmark S. Advanced glycation and lipoxidation end products--amplifiers of inflammation: the role of food. JPEN J Parenter Enteral Nutr. 2007 Sep-Oct;31(5):430-40.

[4] Cai W, He JC, Zhu L, Chen X, Zheng F, Striker GE, Vlassara H.Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan. Am J Pathol. 2008 Aug;173(2):327-36.

[5] Semba RD, Nicklett EJ, Ferrucci L. Does accumulation of advanced glycation end products contribute to the aging phenotype? J Gerontol A Biol Sci Med Sci. 2010 Sep;65(9):963-75.

[6] Takeuchi M, Iwaki M, Takino J, Shirai H, Kawakami M, Bucala R, Yamagishi S. Immunological detection of fructose-derived advanced glycation end-products. Lab Invest. 2010 Jul;90(7):1117-27.

[7] Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.

[8] Yan SF, Ramasamy R, Schmidt AM. The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res. 2010 Mar 19;106(5):842-53.

[9] Nowotny K, Jung T, Höhn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules. 2015 Mar 16;5(1):194-222. doi: 10.3390/biom5010194.

[10] Baumann M. Role of advanced glycation end products in hypertension and cardiovascular risk: human studies. J Am Soc Hypertens. 2012 Nov-Dec;6(6):427-35.

[11] Mallipattu SK, Uribarri J. Advanced glycation end product accumulation: a new enemy to target in chronic kidney disease? Curr Opin Nephrol Hypertens. 2014 Nov;23(6):547-54.

[12] Rahmadi A, Steiner N, Münch G. Advanced glycation endproducts as gerontotoxins and biomarkers for carbonyl-based degenerative processes in Alzheimer's disease. Clin Chem Lab Med. 2011 Mar;49(3):385-91.

[13] Rojas A, Pérez-Castro R, González I, Delgado F, Romero J, Rojas I. The emerging role of the receptor for advanced glycation end products on innate immunity. Int Rev Immunol. 2014 Jan;33(1):67-80.

[14] Foster D, Spruill L, Walter KR, Nogueira LM, Fedarovich H, Turner RY, Ahmed M, Salley JD, Ford ME, Findlay VJ, Turner DP. AGE metabolites: a biomarker linked to cancer disparity? Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2186-91.

[15] Nagaraj RH, Linetsky M, Stitt AW. The pathogenic role of Maillard reaction in the aging eye. Amino Acids. 2012 Apr;42(4):1205-20.

[16] Ciccocioppo R, Imbesi V, Betti E, Boccaccio V, Kruzliak P, Gallia A, Cangemi GC, Maffe GC, Vanoli A, Merante S, De Amici M, Falcone C, Klersy C, Corazza GR. The Circulating Level of Soluble Receptor for Advanced Glycation End Products Displays Different Patterns in Ulcerative Colitis and Crohn's Disease: A Cross-Sectional Study. Dig Dis Sci. 2015 Mar 11. [Epub ahead of print].

[17] Van Puyvelde K1, Mets T, Njemini R, Beyer I, Bautmans I. Effect of advanced glycation end product intake on inflammation and aging: a systematic review. Nutr Rev. 2014 Oct;72(10):638-50.

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