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Q&A: Dr Cordain Responds to Reader’s Questions about Advanced Glycated End Products

By Loren Cordain, Ph.D., Professor Emeritus, Founder of The Paleo Diet
August 18, 2016
Q&A: Dr Cordain Responds to Reader’s Questions about Advanced Glycated End Products image

More than most sciences, the nutrition world is rife with debate and wildly different recommendations. Normally the debates center around our common knowledge of nutrition: macro- and micronutrients; glycemic index; caloric balance; etc. But sometimes it’s what we don’t know – or at least what few know - that’s important. One example is Advanced Glycated End Products or AGEs. Still new and not well understood within the nutrition world, these molecules can have a big impact on our health. And they are found in our food. Loren Cordain, PhD explained AGEs in a recent post, but you our readers asked for more. So here is a collection of Dr Cordain’s responses to your questions about RAGE of the AGES.

DGM on July 15, 2016 at 10:55 am MDT said:

Yeah, we’re all in trouble…

Say looking only at dinner, if you eat a 10 oz. piece of beef (I think a fairly normal portion size) and you roast it you hit 13,646 kU according to the above. Broil it and you’re at 16,962 kU. Go for the chicken breast thinking it’s better for you and you’re at 13,218 kU. Pan fry in olive oil and you might as well get fitted for your body bag… Not sure how we’re going to get down to 7,000 kU/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 7,000 kU figure? How did/do they achieve it? Fires are pretty hot.


Loren Cordain, PhD replied:

Dear DGM,

The study of dietary advanced glycation end products (AGE) represents a relatively new development in nutritional sciences and consequently our knowledge of the AGE/RAGE axis is incomplete. AGEs are created via a non-enzymatic reaction between sugars, free amino acids, lipids or nucleic acids and is known as the Maillard or browning reaction. The formation of AGEs is part of normal mammalian physiology including humans.

Numerous AGEs can be formed during the Maillard Reaction, including two of the best studied, N E carboxymethyllysine (CML) and methyl-glyoxal (MG). The Table of dietary AGEs I have included in my blog was derived from data in reference (7) for only dietary CML and not all known AGEs. Yet the human plasma measurement of AGEs from dietary AGEs is primarily known from measuring only two AGEs (CML and MG). Hence, the in vivo total concentration of AGEs in humans is based upon an assumed total concentration derived only from those two. Accordingly, how dietary AGEs precisely affect total human plasma concentrations of AGEs is unknown and only speculative at this point. Given this paucity of data, the suggestions for high, normal or low values based upon animal data or otherwise (7) still have considerable room for error.

My main argument for this blog was to point out general recommendations for dietary AGEs that are derived from good scientific evidence based on what is known about these compounds:

  • Cooking at high temperatures (via broiling, grilling, roasting, searing and frying) can increase the concentrations in dietary AGEs by 10 to 100 fold or more
  • Low temperature slow cooking, moist procedures (poaching, covered roasting at low heat, stewing, low temperature frying, microwave) can significantly reduce the concentrations of dietary AGEs
  • A low acidic environment (lemon juice or vinegar) can slow or arrest AGEs development in cooked meats
  • Almost all fresh fruits and vegetables (Paleo diet staples) represent low dietary sources of AGES
  • Eggs (also Paleo diet staples) contain quite low dietary AGES
  • Processed foods made with combinations of cooked fatty meats, processed meats, vegetable oils, cheese and high fructose corn syrup or sucrose contain very high concentrations of dietary AGES. For instance, fried bacon yields one of the highest values (91,577 kU) of all foods, yet some in the Paleo diet movement continue to recommend it, which I don’t.

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 AGEs intake to levels just above 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.

One final point: although we view cooking and fire as part of the human dietary repertoire for what seems like forever, this technology (fire starting) from an evolutionary time scale is quite recent. As I have pointed out in a previous blog humans have had the ability to gather fire for perhaps 300 to 400,000 years, but the ability to start fires at will is only a recent invention dating to about 75,000 to 100,000 years ago. Hence, regular cooking of any foods is a relatively recent phenomenon, and our dietary AGEs load would have always been quite low until we had the ability to start fires at will. (See: // ).

Loren Cordain, Ph.D.
Professor Emeritus

Mr. Ed on May 27, 2016 at 9:02 am MDT said:

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.

Loren Cordain, PhD replied:

Dear Mr. Ed,

You are absolutely right that elevated blood glucose brought about by consuming high-glycemic load carbohydrates and refined sugars are important contributors to endogenously produced AGEs. Although consumption of high fructose corn syrup (90 % concentration fructose) alone raises blood glucose minimally, when it is consumed with glucose as mixtures (45 or 55 % concentration fructose) it is a potent blood glucose stimulating agent.

Dietary fructose is not normally a metabolic sugar and once ingested, it is rapidly cleared by the liver. However, it remains in circulation longer when consumed on a dose related basis. Hence high concentrations of dietary fructose may temporarily bind organs and tissues before being cleared by the liver. This high consumption is not without consequence for AGEs production by indirectly raising blood glucose but also by elevating systemic fructose concentrations itself.

When fructose and protein are incubated in vitro, fluorescent and cross-linking products form, and it has been estimated that fructose produces 10 times more AGEs than glucose. Although the in vivo formation of fructose-derived AGEs has long been suspected, experimental evidence for their formation has only very recently been reported (1). A number of pathological conditions attributable to the AGE/RAGE axis have been recently reported in adults and children with consumption of high fructose corn syrup sweetened drinks including: arthritis, cardiovascular disease, bronchitis and asthma (2-5).

  1. 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.
  2. DeChristopher LR, Uribarri J, Tucker KL. Intake of high-fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent arthritis in US adults, aged 20-30 years. Nutr Diabetes. 2016 Mar 7;6:e199. doi: 10.1038/nutd.2016.7. PMID: 26950480 Free PMC Article
  3. Villegas-Rodríguez ME, Uribarri J, Solorio-Meza SE, Fajardo-Araujo ME, Cai W, Torres-Graciano S, Rangel-Salazar R, Wrobel K, Garay-Sevilla ME. The AGE-RAGE Axis and Its Relationship to Markers of Cardiovascular Disease in Newly Diagnosed Diabetic Patients. PLoS One. 2016 Jul 19;11(7):e0159175. doi: 10.1371/journal.pone.0159175. eCollection 2016.
  4. DeChristopher LR, Uribarri J, Tucker KL. Intake of high fructose corn syrup sweetened soft drinks is associated with prevalent chronic bronchitis in U.S. Adults, ages 20-55 y. Nutr J. 2015 Oct 16;14:107. doi: 10.1186/s12937-015-0097-x. PMID: 26474970
  5. DeChristopher LR, Uribarri J, Tucker KL. Intakes of apple juice, fruit drinks and soda are associated with prevalent asthma in US children aged 2-9 years. Public Health Nutr. 2016 Jan;19(1):123-30. doi: 10.1017/S1368980015000865. Epub 2015 Apr 10.PMID: 25857343

Doctor who knows more than you think on January 16, 2016 at 3:33 pm MDT said:

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.

Loren Cordain, PhD replied:

Dear Doctor (Physician),

Let me first apologize to you individually, as many highly intelligent physicians are not only aware of the GI, Glycemic Load and the AGE/RAGE axis, but are intimately working with scientists and other physicians to unravel these physiologic mechanisms as they relate to diet and disease. David Jenkins at the University of Toronto was instrumental in creating the GI in the early 1980s and my colleague Jennie Brand-Miller from the University of Sydney has done important follow-up work on the GI and GL, whereas researchers at the Harvard School of Public Health suggested the GL in 1997.

In my experience of lecturing to tens of thousands of physicians worldwide, many are quite knowledgeable about nutrition depending upon the medical school from which they graduated and the era when they graduated. But across time and space the Medical Profession could do a better job of emphasizing the importance of diet to health while emphasizing non-allopathic/evolutionary means to treating illness and disease. Biochemical pathways are frequently memorized without regard to understanding the more global evolutionary basis for these pathways and the clues they provide for unraveling the complexities of pathologies with poorly understood etiologies.

My comments were never intended as a direct insult to any single physician, or person, but rather as constructive criticism to a profession.

Loren Cordain, Ph.D.
Professor Emeritus

Carrmelita Visagio on March 10, 2016 at 1:55 pm MDT said:

You should not be offended, and look at it from OUR perspective, as most of us (patients) have this experience with doctors, as in negative impact on health and advice.

Loren Cordain, PhD replied:

I agree with Carmelita in that the Medical Profession should look to itself, academia, and its patients for direction to the future and less upon government bureaucrats who are trained neither in science or medicine.

Loren Cordain, Ph.D.
Professor Emeritus

Ted Arnold said:


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

Loren Cordain, PhD replied:

Hi Ted,

Yes, generally the higher the fat content of a food, the higher it is in dietary AGEs content. But heating and cooking also play into the equation. For instance, raw seeds and nuts contain significantly lower AGEs than do roasted or cooked seeds and nuts, as listed below:

TypeRawRoasted or Cooked
Pumpkin seeds1,853na
Sunflower seeds2,5104,693

Loren Cordain, Ph.D.
Professor Emeritus

Jeff on May 28, 2015 at 2:32 pm MDT said:

I too, am confused about seemingly Paleo friendly foods that have a very high AGE value. Some clarification would be helpful.

Loren Cordain, PhD replied:

Hi Jeff,

There are two issues here. One is that “seemingly Paleo-friendly foods” may not actually be “Paleo-friendly foods” but rather promoted as such by some in the Paleo community without scientific support. For instance, I have never recommended bacon because of its excessive salt content, but it also contains extremely high concentrations of AGEs (91,577 kU) among other nutritional shortcomings. Similar arguments can be made for honey (//, baked products made with nut flower, sea salt, honey, etc.

Secondly, some “Paleo-friendly foods” are used in much smaller quantities than the 100g (1/4 lbs) used to determine their AGEs content. For instance, 100 g of extra virgin olive oil comes in at a whopping 10,040 kU whereas an omelet cooked in olive oil at low heat only yields 337 kU.

Loren Cordain, Ph.D.
Professor Emeritus

Monika on May 28, 2015 at 10:51 am MDT said:

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.

Loren Cordain, PhD replied:

Hi Monika,

Don’t be shocked, before you cut anything out of your diet please see my comments to: DGM, Mr. Ed and Jeff. 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 AGEs diet. Bag the bacon and only use it as a treat (part of the 85:15 rule.) Keeping olive oil to a few tablespoons a day should be no problem. Finally, focus upon eating slow and low cooked meat. If you happen to eat grilled meats, cut off the blackened burned parts and eat the tender inner parts which have AGEs values similar to raw meats. Continue to eat 35 to 45 % of your fruits and veggies as fresh and continue to avoid refined sugars and carbohydrates and your Paleo Diet will also be a low AGEs diet as well.

Best wishes,
Loren Cordain, Ph.D.
Professor Emeritus.

Stuart on May 28, 2015 at 6:58 am MDT said:

I don’t get this? So if you eat a piece of bacon 91,000 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?

Loren Cordain, PhD replied:

Hi Stuart,

No, your perception of dietary AGEs is similar to many of our readers. See my responses to: DGM, Mr. Ed, Jeff and Monika and hopefully the dietary AGEs values of food will begin to make more sense in the more comprehensive picture of diet and health.

Two additional comments seem to be necessary: (1) Negative health effects of any food cannot be attributed entirely to any single dietary element (such as dietary AGEs), but rather must be evaluated globally in their contribution to the entire diet. (2) Current understanding of contemporary, modern “Paleo” diets by some in the Paleo community likely are incorrect due to AGEs and other misunderstood elements such as salt (sea salt or otherwise), natural sweetener (honey, maple sugar, date sugar, coconut sugar and others), and dairy products (ergo the Primal fractionation of the Paleo Diet).

Best wishes,
Loren Cordain, Ph.D.
Professor Emeritus

Dave Y. on May 28, 2015 at 5:37 am MDT said:

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.

Loren Cordain, PhD replied:

Hi Dave,

Yes, there is no doubt that the information on dietary AGEs can be confusing. Please see my prior comments to: DGM, Mr. Ed, Jeff and Monika and Stuart. Although butter has been promoted to be a healthful contemporary “Paleo dietary component” by some in the Paleo community (ergo the Primal fractionation of the Paleo Diet), there are nutritional problems with butter, particularly Ghee (// as I have previously pointed out. No historically studied human hunter-gatherers ate butter, and its nutritional characteristics had little or no precedence in shaping the current human genome. Having said that, note that the value for butter is reported for a 100 g portion (~1/4 pound or an entire cube). Hence, the amount of dietary AGEs in a single pat or two of butter will be much, much lower than for about ¼ pound of butter. If you enjoy butter, you can still sauté with it or put a pat or two on steamed veggies and stay within the 85:15 rule and within the confines of a low AGEs diet.

Avocados are a healthful contemporary food and shouldn’t be avoided and have a moderate to low AGEs value. Raisins are a nutritious food that shouldn’t be avoided except for obese or overweight people or those who maintain symptoms of diseases of insulin resistance because of their high glycemic load.

Beer is generally a gluten containing food and should be avoided but can be consumed occasionally because of the 85:15 rule, particularly if you can find a gluten free version. Diet soda is not a good idea and should be avoided (//, same goes for Oreos. Negative health effects of any food cannot be attributed entirely to any single dietary element (such as dietary AGEs), but rather must be evaluated globally in their contribution to the entire diet such as high glycemic, nutrient poor Oreos.

Loren Cordain, Ph.D.
Professor Emeritus

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