Rage of Ages: Advanced Glycation End Products

Rage of Ages: Advanced Glycation End Products |The Paleo Diet

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 toe the party line and tell you that a diet high in plant foods and low in animal proteins and fat is the way to go – end of story!  If you were to dare to probe more deeply and ask your doctor about the glycemic index and how it influences your health, most would stare off blindly into space or ignore your question because many of them are unaware of this concept.  It is not their fault – they simply were not taught this crucial dietary/health relationship in medical school. Bearing down even further, if you were to question them about RAGE’s, AGE’s and diet, most would assume you are somehow angry (RAGE) about your (AGE). Although these terms are unknown to most physicians, their meaning and implications have huge implications upon our health and well being that have only been widely recognized in the past 5 years.3

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 disease,2, 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

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 | The Paleo Diet

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.  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.

OK. Back on topic.  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.

 

REFERENCES

[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.

About Loren Cordain, PhD, Professor Emeritus

Loren Cordain, PhD, Professor EmeritusDr. Loren Cordain is Professor Emeritus of the Department of Health and Exercise Science at Colorado State University in Fort Collins, Colorado. His research emphasis over the past 20 years has focused upon the evolutionary and anthropological basis for diet, health and well being in modern humans. Dr. Cordain’s scientific publications have examined the nutritional characteristics of worldwide hunter-gatherer diets as well as the nutrient composition of wild plant and animal foods consumed by foraging humans. He is the world’s leading expert on Paleolithic diets and has lectured extensively on the Paleolithic nutrition worldwide. Dr. Cordain is the author of six popular bestselling books including The Real Paleo Diet Cookbook, The Paleo Diet, The Paleo Answer, and The Paleo Diet Cookbook, summarizing his research findings.

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“23” Comments

  1. I guess this is part of the reason why vegans live longer. You should have mentioned some high starch/carb foods that are very low in AGEs. Boiled potatoes is 17, rice 9, oatmeal 14, white bread 23, even roasted (1h) sweet potatoes is only 72 . Sugar is 0! Maybe switch out some of that cancer-causing meat instead of suggesting to only eat the inside of the grilled meat and to throw away the rest! It’s not fair to the animal or to the environment.

  2. Hello, it’s TR again. I submitted a reply yesterday. I think I found why AGEs affect IBS. It’s the Maillard reaction.

    Metabolism of Maillard reaction products by the human gut microbiota–implications for health.

    (as quoted)

    “The Maillard reaction, involving food protein and sugar, is a complex network of reactions occurring during thermal processing. The resultant modified protein resists digestion in the small intestine but is available for colonic bacterial fermentation. Little is known about the fate of the modified protein but some Maillard reaction products (MRP) are biologically active by, e. g. altering bacterial population levels within the colon or, upon absorption, interacting with human disease mechanisms by induction of inflammatory responses.”

    So AGEs can be probiotics!

    IBS is mainly caused by bacterial overgrowth, although the underlying reasons could be a sensitivity to antinutrients generally. An exclusion diet has to limit at least temporarily all probiotic or harmful foods such as starch, sugar but also soluble fibre, and now it seems, browned meats that form a Maillard reaction. This is quite exciting find this this morning, as it helps to clear up a final puzzle for me. Why I do so much better on raw foods. I have taken your advice, and have started slowly simmered beef stews as opposed to frying meat.

    Just writing this for anyone with IBS out there who is wondering why meat, generally considered an IBS safe food, is causing symptoms.

  3. Hello, is it possible that AGEs could have an effect on the colon? I have IBS and am very thankful for your Paleo Autoimmune program. My diet is a combined low FODMAP / Paleo autoimmune and basically I just eat animal protein and mostly low FODMAP, insoluble vegetables. (These are the only foods that don’t feed bacteria much). I will gradually add FODMAP vegetables later on. I find that raw salad vegetables seem to be best for me and I was wondering why. Apparently it’s not the food enzymes as only pancreatic enzymes do the digesting. I have searched but can’t find any link between AGE’s and IBS. Is it possible AGEs could have a direct effect on peristalsis or anything else? I found when I gave up all grains and sugar the symptoms cleared up quite quickly, but it’s a very tough diet to keep to. Also could there be any link between AGEs and bacterial overgrowth – is it possible they could work together in some way? There has to be some reason why raw salad vegetables seem to work so well for me. Thanks for reading.

  4. Yeah, we’re all in trouble…

    Say looking only at dinner, if you eat a 10oz peice of beef (I think a fairly normal portion size) and you roast it you hit 13,646kU according to the above. Broil it and you’re at 16,962kU. Go for the chicken breast thinking it’s better for you and your at 13,218kU. Pan fry in olive oil and you might as well call get fitted for your body bag… Not sure how we’re going to get down to 7,000kU/day as suggested (at least practically). Especially seeing as I significantly increased my nut consumption when I shifted to Paleo.

    I love educating myself on health and nutrition, but am and will remain a pragmatist. Probably not too many of us are going to start boiling our high dollar grass-fed beef…

    Dr. Cordain, You usually are very good about integrating your research with the study of sample groups of hunter gatherer societies (229 I recall). How do these cultures, being our biologic evolutionary blue-print, compare to the 7,000kU figure? How did/do they acheive it? Fires are pretty hot.
    Respectfully,
    DGM

  5. Dietary versus Systemic Advanced Glycemic End Products
    Damage due to the unavoidable ingestion of dietary AGEs is far less significant than the damage due to systemically generated AGEs caused by high blood sugar; this was verified by testing people with high-protein high-fat diets against people with Low-fat high-carb diets. The Paleos experienced far less cardiovascular damage than the Vegans.

  6. I am highly insulted by your comments that your doctor would simply stare out into space when it comes to Glycemic index and the effects of AGEs on overall health. I am offended that you think that we are simply not taught these points in medical school, including a broad spectrum of treatment including integrative medicine. As if we are all idiots and have no clue what we are talking about. I actually came across your article while researching AGEs specifically to improve my knowledge in order to relay to patients. Just for the record, WE ARE taught these things in medical school and Glycemic LOAD is way more important than Glycemic Index. Please refrain from insulting our profession and the amount of effort we put in to provide the best care for our patients.

    Thank you for your consideration.

  7. Hi
    Am interested in where nuts fit in – they seem to be high in AGEs
    Is this because fat in all cases correlates with AGEs?
    Ted Arnold
    Paleo LC Medical Practitioner, Sydney, Australia

  8. I’m shocked at the numbers of food I thought are healthy, like Avocado, of which I eat 1/2 each day, and Olive Oil for instance. Soon I don’t know what to eat anymore.

  9. I don’t get this?
    so if you eat a piece of bacon91,000 and have a salad with virgin olive oil 10,000 and a few nuts during the day–your way over the 7,000 number
    am I missing something here?

  10. Butter, avocados, olive oil are high. Beer, diet soda and raisins are low. This goes against all my paleo understanding of what I should be eating. Oreos are lower than broiled chicken? I can’t wrap my head around this concept this early in the morning.

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