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.
Respectfully,
DGM
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: //thepaleodiet.com/ancestral-fire-production-implications-contemporary-paleo-diets/ ).
Cordially,
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).
- 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.
- 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
- 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.
- 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
- 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:
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
