What Are Advanced Glycation End Products?
A reader sent in a question about Advanced Glycation End-Products, or AGEs. He basically wanted to know what they are, how they’re formed, and how the body deals with them. In this post, I’ll attempt to answer that question to see what this tells us about what to eat and how to prepare it.
What Are AGEs?
AGEs are the end-products of glycation reactions, in which a sugar molecule bonds to either a protein or lipid molecule without an enzyme to control the reaction. A similar reaction, known as glycosylation, uses an enzyme to control the reaction, targeting specific receptor sites on cells. Glycation, on the other hand, “is a haphazard process that impairs the functioning of biomolecules”.
Where Do AGEs Come From?
Advanced Glycation End products can come from two sources: the food we eat and internal production in the body. Let’s look at each of them.
AGE Formation In Food
When proteins are cooked with sugars in the absense of water, AGEs are formed. Water, however, prevents these sugars from binding to the protein molecules. Now, I know what you’re thinking when you hear the word “protein”: flesh. I was too, until I got to reading. However, grains, vegetables, fruits, and such all have protein in them as well, with browning being an indication of AGEs:
According to these new findings, brown foods, such as brown cookies, brown bread crust, brown basted meats and brown beans, and even brown coffee beans may increase nerve damage, particularly in diabetics who are unusually susceptible to nerve damage.
These are the very reactions that give certain foods their flavors after cooking. Food-borne AGEs are absorbed with about 30% efficiency when ingested.
AGE Formation In The Body
Once you’ve eaten, the body can still glycate the simple sugars in your food. A small proportion of the sugar in your bloodstream is glycated, while the rest goes to running your metabolic machinery. Consider what happens in the bloodstream of a diabetic with chronically elevated blood sugar. There are many opportunities for this circulating sugar to be glycated, which helps explain why diabetics have such high incidences of the issues discussed in the next section.
Fructose and galactose undergo glycation at about 10 times the rate as does glucose. Considering the dramatic increase in sugar consumption over the past several decades, and the subsequent increase in fructose consumption (recall that most sweeteners are approximately 50% fructose), is there any question why we’re seeing rising rates of heart disease, arthritis, and other inflammatory “diseases of aging”?
What Do AGEs Do In The Body?
The body is able to handle AGEs, though very slowly. The half-life of AGEs is about double that of the average cell life, meaning that damage can persist for quite some time, especially in long-lived cells like nerve and brain cells, eye and collagen proteins, and DNA. Not good!
Here’s a run-down of a few effects of AGEs:
…and are implicated in many age-related chronic diseases such as: type II diabetes mellitus (beta cell damage), cardiovascular diseases (the endothelium, fibrinogen, and collagen are damaged), Alzheimer’s disease (amyloid proteins are side-products of the reactions progressing to AGEs), cancer (acrylamide and other side-products are released), peripheral neuropathy (the myelin is attacked), and other sensory losses such as deafness (due to demyelination) and blindness (mostly due to microvascular damage in the retina).
….
The endothelial cells of the blood vessels are damaged directly by glycations, which are implicated in atherosclerosis, for example. Atherosclerotic plaque tends to accumulate at areas of high blood flow (such as the entrance to the coronary arteries) due to the increased presentation of sugar molecules, glycations and glycation end-products at these points. Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure. Glycations also cause weakening of the collagen in the blood vessel walls, which may lead to micro- or macro-aneurisms; this may cause strokes if in the brain.
How Do I Protect Myself?
There are a few steps you can take to keep yourself safe from a toxic load of these compounds.
- Keep blood sugar low with a Real Foods diet – This will reduce sugar supplies available for glycation.
- Eat vegetables and fruits raw, boiled, or steamed – When eating raw, there is no formation of these compounds because there is no cooking, while boiling and steaming introduce water to the cooking process.
- Avoid processed carbohydrates and browned foods – Food manufacturers take steps to increase caramelization and browning in their foods, directly increasing the levels of AGEs in the foods.
- Cook meats low and slow – Higher temperatures produce more AGEs than lower temperature, longer cooking times. Rare and medium-rare meats will have fewer AGEs than fully cooked meats, like barbeque or well-done steak.
In the end, if you’re not eating well-done meats often and are sticking to vegetables, tubers, and fruits for your carbs, you’re unlikely to be taking in dangerous level of AGEs. The body can deal with these substances so long as it isn’t overrun with them.
And now a question for the science geniuses: Do AGEs serve any valuable purpose in the body or are they strictly waste products of metabolic functions?
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23 Reader Comments
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Hey Scott,
Nice post. I’ve been doing some reading on AGEs lately myself.
One question though. You say in your post:
“Food-borne AGEs are absorbed with about 30% efficiency when ingested”
Do you have a reference for this? So far, I’ve been unable to find a reliable estimate of how much AGEs we actually absorb from food.
Eating fruit raw is very likely a better choice than cooking it, but eating the fructose in fruit might still cause internal AGE production; studies show that vegetarians have higher AGE concentrations than omnivores, which may be explained by their higher fruit consumption.
By the way, drinking green tea reduces AGE formation:
http://inhumanexperiment.blogspot.com/2008/11/green-tea-reduces-formation-of-ages.html
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I’ve sent your last question off to a glycobiologist friend of ours. Will let you know what he says.
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Here’s the response from our glycobiology researcher friend:
Never thought about that, but my impression is that its waste. Glycosylation you need, glycation you don’t. In fact you have ways to get rid of it. Now you can ask, do you need just a little? I see it only as a danger sign, and if you say its a fire alarm and you want to put the fire out…well, OK. I don’t call that a metabolic benefit.
Would like to hear arguments to the contrary.
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It seems that crock pot cooking and other methods that retain water are best for avoiding AGE formation in meat, but I was wondering if you knew anything about AGE production concerning food dehydrators. I’d like to get one to make jerky and other portable foods, but I’m not sure about the AGE factor. My intuition is that dehydrators are either really beneficial or somewhere on the opposite extreme. I suppose this is because they cook long and slow but dry the food out at the same time. I’d be interested in any information you might have on this. Any opinion on food dehydrators in general for that matter would be appreciated as I admittedly know little about them.
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Craig,
Food dehydrators don’t really cook, they dry out the moisture. The temps when drying should be quite low, far below temps used for cooking. Drying food to preserve it has a *very* long tradition.
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[...] If you’re worried about the harmful effects of browning your meats and veggies read Modern Forager’s informative article on advanced glycation end-products. [...]
[...] If you’re worried about the harmful effects of browning your meats and veggies read Modern Forager’s informative article on advanced glycation end-products. [...]
One question that I recall being asked before I lost the comments was regarding how many AGEs are in specific foods and how much is too much? I don’t think this question can truly be answered….there’s no “RDA” for AGEs and I don’t think anybody can quantify that “this is too much.” I think the key is just avoiding as much of the foods that are very high in AGEs, like breads and cookies, and sticking to the meats and vegetables that are going to have very few.
It’s also worth noting that meat isn’t going to produce many AGEs because it has relatively little in the way of reducing sugars in it. It’s 100% fat and protein.
JLL, that number came from the Glycation article on Wikipedia. Good info on green tea!
Craig, I think Anna got it. Dehydrators shouldn’t be cooking the food.
Anna, Thanks for getting an answer on that. It was the way I was leaning too, but nice to get confirmation from someone far smarter.
Cheers
Scott
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i need some example regardind advanced glycation end products . like sorbitrate
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Scott, aren’t you confusing AGEs in food with AGEs in living body tissues? You advocate avoiding browned foods due to high AGE content. Yet doesn’t the digestive process break down AGE’s long before the blood stream could transport them to tissues where they could do damage?
I’ll entertain the notion that high blood sugar levels might lead to attachment of sugar molecules to existing proteins and lipids (in the blood stream and tissues), i.e., glycation. But this would be in an aqueous environment, which you say doesn’t happen (at least with proteins).
I’m not sure this issue is ready for prime time.
-Steve
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Hi Scott, Dr. Parker and all,
First, Scott- great actionable advice on avoiding these nasty compounds!
Dr. Parker, I must set the record straight here. Aren’t there endogenous (created inside of the body) and exogenous (consumed) AGEs? And by what method would you postulate the body breaks these exogenous AGEs down into innocuous compounds? Actually, there is direct evidence against that notion, and quite a bit of it, actually.
A recent study administered an AGE-rich meal (heat processed, probably a brown meat & gravy type) to diabetics. Researchers measured the endothelial dysfunction and oxidative stress before the meal and after the meal. After the meal, the diabetics’ capilllary blood flow was reduced by 60%, while the ability of larger vessels to dilate was diminished by 35%. Not good.
In the same study, researchers administered a lipid-soluble type of thiamine called benfotiamine. The benfotiamine completely prevented the detrimental effects on blood vessels. Pretty amazing. You can check out the research listed below.
But it doesn’t end there. Dr. Peppa, MD, Dr. Uribarri, MD and Dr. Vlassara, MD in the Clinical Diabetes Councils Voice, 2003 state: “This new evidence suggests that modulation of food-AGE content could become an important ingredient of the therapeutic armamentarium in the management of diabetic patients. Until effective and safe drugs become available, physicians and dieticians can, for instance, advise increased reliance on fresh foods, cooked by brief applications of heat, in the presence of ample water or humidity. A diet designed to be low in AGEs is apparently not lacking in taste, while not requiring compromises in important nutrients. Such a regimen can decrease AGE intake by more than 50%; this in turn was shown to reduce circulating AGEs by 30%..”
Dr. Parker- I think they are talking to you!!
Something else everyone may find of interest pertains to testing your levels of AGEs. The A1C test for diabetes actually measures the presence of glucose molecules that join hemoglobin in the destructive process of glycation. For optimal longevity, we want an A1C lower than 5% which equates to a blood sugar level of about 90 mg/dl.
I hope my post was helpful and would love to hear more ideas on the topic.
REFERENCES
Stadler RH, Blank I, Varga N, Robert F, Hau J, Guy PA, Robert MC, Riediker S. “Acrylamide from Maillard reaction products.” Nature 2002;419:449-50. PMID 12368845
Negrean M, Stirban A, Stratmann B, et al. Effects of low- and high-advanced glycation endproduct meals on macro- and microvascular endothelial function and oxidative stress in patients with type 2 diabetes mellitus. Am J Clin Nutr. 2007 May;85(5):1236-43.
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.
Playford DA, Watts GF. Special article: non-invasive measurement of endothelial function. Clin Exp Pharmacol Physiol. 1998 Jul;25
(7-8):640-3.
Bonetti PO, Pumper GM, Higano ST, et al. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004 Dec 7;44(11):2137-41.
Shimbo D, Grahame-Clarke C, Miyake Y, et al. The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis. 2007 May;192(1):197-203.
Vu V, Riddell MC, Sweeney G. Circulating adiponectin and adiponectin receptor expression in skeletal muscle: effects of exercise. Diabetes Metab Res Rev. 2007 Nov;23(8):600-11.
Stirban A, Negrean M, Stratmann B, et al. Adiponectin decreases postprandially following a heat-processed meal in individuals with type 2 diabetes: an effect prevented by benfotiamine and cooking method. Diabetes Care. 2007 Oct;30(10):2514-6.
Melpomeni Peppa, MD, Jaime Uribarri, MD and Helen Vlassara, MD. Glucose, Advanced Glycation End Products, and Diabetes Complications: What Is New and What Works. Clinical Diabetes 21:186-187, 2003
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Is there any information about this subject in other languages?
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Hi
Would this mean that soy suace, which is seriously ‘brown’ contains loads of AGE’s? Don’t think it has any sugars in it, although maybe in the soya beans, yes….?
Thanks
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Delia,
Y’know, I hadn’t thought about soy sauce, but your question sent me on a quick Google Quest. Here’s what I found: (page 2)
Condiments – AGE u/15 ml (~1 tbsp)
Maple sirup – 795
Brown rice vinegar – 2,100
Soy sauce – 8,700
It looks like AGEs are quite high in soy sauce (as well as duck skin!). Glad I don’t use it very often.
Cheers
Scott
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A browned meat shouldn’t be a major source of AGEs, I believe, since among other reasons, meat contains carnosine, which prevents absorption of AGEs. You can also supplement with other AGE blockers like turmeric (lather your meat in mustard), quercetin, lipoic acid, benfotiamine and so on. But I’m not sure that’s even necessary. Regarding endogenous and exogenous AGEs, I quote Dr Eades:
“I agree that there are vastly more AGEs in cooked foods, especially meats. What I’m not so sure about is whether or not the AGEs we eat end up as AGEs in us. The transit through the extreme acidity of the stomach would, I imagine, reduce the AGEs to their components, which we would absorb. The healthy human GI tract doesn’t have the ability to absorb large molecules. Even diglycerides (sugars composed of two other sugars, sucrose, for example) must be broken down to monoglycerides before being absorbed, so I seriously doubt that complex molecules such as AGEs could be absorbed in there native state. As a consequence, I’m not particularly worried about the AGEs I eat – I much more worried about the AGEs I create within.”
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Well, it seems green tea much less effective for reducing AGEs than yerba mate:
http://inhumanexperiment.blogspot.com/2009/05/yerba-mate-inhibits-age-formation.html
That’s not to say green tea isn’t the drink of gods in many ways, but for this particular purpose, I think yerba mate might be the way to go.
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[...] a frutose não! A frutose forma 7 vezes mais AGE (Advanced Glycation End-Products) que a glucose, não suprime a hormona grelina (que sinaliza que o estômago que [...]
What im wanting to resolve is if eating meat to get rid of glycation due to its carnosine is a valid idea.
Gene
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Gene, not sure what you’re asking.
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Skutes
Since vegetarians have greater incidence of AGEs, there are some who think that eating meat helps to get rid of AGEs due to its carnosin content and that therfore it is ultimately unhealthy to not eat meat. due to glycation.
Gene
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Ahh, I see what you mean Gene. I have no clue about that. I’d say just stick to unprocessed foods and the rest will probably handle itself. It’s mainly processed foods with high levels of AGEs.
Cheers
Scott
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I actually did my Masters thesis on AGE’s and their effect on gum tissue (I am a periodontist). I have read about 20 papers on AGE, and yes, they do get absorbed.
I strongly believe AGE have a significant impact on cardiovascular disease, Alzhiemers disease, cancer, periodontal disease, and possibly other chronic diseases.
Did you know tobacco smoke is a significant source of AGE? Smokers have similar CV complications to diabetics, coincidence?
As for the question, do AGE’s have a useful purpose, the answer is no; but the Receptor for AGe (RAGE) does play a part in the innate immune system.
AGE’s exert their effect in 2 ways; firstly by causing irreversible cross linking of body proteins (leading to hardening of the arteries –>high blood pressure); secondly, by binding with RAGE. RAGE is a unique receptor in that binding leads to upregulation of itself. Most receptors when they are ligated (bound) downregulate themselves. This means that repeated intake of AGE leads to greater and greater effects due to increased RAGE. Binding of RAGE leads to production of proinflammatory cytokines (molecules that tell the body to turn up inflammation). We see increased expression (amount of) RAGE in gum tissues of smokers, diabetics, and periodontal disease. It is all related.
Knowledge of AGE is critical in prevention of disease. The above advice to only cook meat in broths and soups is spot on. There is decreased formation of AGE is meat is only cooked to this temperature.
Pizza = bad
Macaroni cheese = bad
Burgers = bad
Fries = bad
Coffee = bad
Colas = bad
Green tea = Good!
Turmeric = good
Enough rambling from me!
Jamie Amir
(Diet-Derived Advanced Glycation End Products Are Major Contributors to the Body’s
AGE Pool and Induce Inflammation in Healthy Subjects Ann. N.Y. Acad. Sci. 1043: 461–466 (2005). © 2005 New York Academy of Sciences. doi:10.1196/annals.1333.052)
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Have you heard of MEG 21 with Supplamine? I’ve been using it for 4 years and absolutely love it!
MEG 21 was unexpectedly discovered through diabetes research.
The company offers free samples to skin care bloggers.
Great post!
xoxo
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