The Anti-AGEing Diet

Advanced Glycation End-products, AGEs, are a diverse collection of compounds that have been associated with endothelial dysfunction, cataracts, kidney disease, and atherosclerosis in both animal models and human studies. Not all involve glycation nor glucose, but the catch-all name has stuck.

There are a number of actively-held theories of aging, such as the idea that aging is the result of accumulated products of oxidative injury; a genetically pre-programmed script of declining hormones and other phenomena; genetic "mis-reading" that results in disordered gene expression, debris, and uncontrolled cell proliferation (e.g., cancer); among others.

One of the fascinating theories of aging is, cutely, the AGEing theory of aging, i.e., the accumulation of AGE debris in various tissues. Such AGEs have been recovered in lenses from the eyes, atherosclerotic plaque in arteries, kidney and liver tissue, even brain tissue of people with Alzheimer's dementia. AGEs perform no known useful physiologic function: They are relatively inert once formed (especially polymeric AGEs), they do not participate in communication, they make no contribution of significance. They simply gum up the works--debris. (AGEs are to health as the USDA food pyramid is to dietary advice: material for the junkyard.)

There are two general ways to develop AGEs:

1) Endogenous--High blood glucose (any blood sugar above 100 mg/dl) will permit glycation of the various proteins of the body. The higher the blood glucose, the more glycation will proceed. Glycation also occurs at low velocity at blood glucose levels below 100 mg/dl, though this would therefore represent the "normal," expected rate of glycation. Endogenous glycation explains why people with diabetes appear to age and develop all the phenomena of aging faster than non-diabetics (kidney disease, eye diseases, atherosclerosis, dementia, etc.). Hemoglobin A1c, HbA1c, is a readily-obtainable blood test that can show how enthusiastically you have been glycating proteins (hemoglobin, in this case) over the last 2 to 3 months.

A low-carbohydrate diet is the nutritional path that limits endogenous glycation leading to AGE formation. Restricting the most obnoxious carbohydrates, the ones that increase blood sugar the most, such as wheat, cornstarch, rice starch, potato starch, tapioca starch, and sucrose, will limit endogenous AGE formation.

2) Exogenous--AGEs (here especially is where the "AGE" label is misleading, since many other reactions besides glycation lead to such compounds) are formed with cooking at high temperatures, especially meats and animal products. Therefore, a rare steak will have far less than a well-done steak. A thoroughly baked piece of salmon will have greater AGE content than sashimi.

The forms of cooking that increase AGE content the most: roasting,deep-frying, and barbecuing. Temperatures of 350 degrees Fahrenheit and greater increase AGE formation.

Therefore, cooking foods at lower temperature (e.g., baking, sauteeing, or boiling), eating meats rare whenever possible (not chicken or pork, of course), eating raw foods whenever possible (e.g., nuts) are all strategies that limit exogenous AGE exposure. And minimize or avoid butter use, if we are to believe the data that suggest that it contains the highest exogenous AGE content of any known food.

If we connect the dots and limit exposure to both endogenous and exogenous AGEs, we will therefore not trigger this collection of debris that is likely associated with disease and aging. So following a low-AGE diet may also be an anti-aging strategy.

The New Track Your Plaque Diet, soon to be released on the Track Your Plaque website, has incorporated strategies to limit both endogenous as well as exogenous AGEs.

Comments (36) -

  • August

    10/22/2010 4:04:38 PM |

    I could see this might be a problem if gut health was compromised; exogenous AGEs would then have a pathway to get into our tissues.  Assuming someone is on a low carbohydrate paleolithic style diet, what evidence is there that the exogenous AGEs do anything other than merely pass through the digestive system?

  • Tyler

    10/22/2010 5:02:07 PM |

    Hi August, I echo the same question. Is there any research on exogenous AGE's absorbing in to our bodies?

  • Davide

    10/22/2010 5:21:48 PM |

    Dr. Davis,

    Are palm oils/hydrogenated oils a significant source of AGE's like butter?

  • Anonymous

    10/22/2010 5:55:23 PM |

    What about clarified butter (ghee)?

  • Martin Levac

    10/22/2010 6:36:40 PM |

    Dr. Davis, now you're delving into the unknown with your suggestion of an anti-AGE diet. You don't know. You're suggesting we eat that diet but you haven't any data to support such a suggestion. Don't do like they did with saturated fat. Think of the alternative we adopted then that brought us here. Think of the alternative we will adopt now that will bring us who knows where.

    If the advice of the day is to avoid AGEs in food, what kind of food will we eat then? Since meat contains a boatload of AGEs, that's out but what will replace it, soy? See how your advice is already turning on itself?

    Stick to what works on the TYP program as a good doctor should and leave the speculation to the speculators.

  • Anonymous

    10/22/2010 7:11:25 PM |

    Martin, there have been numerous studies connecting the association of AGEs with various health issues. There is nothing novel or or new about this.

    Avoiding AGEs doesn't mean you can't eat meat. All you have to do is eat good fresh meat and don't over cook it until it is well done or overbrowned. If you like your meat chared and well done, then you may have to make a sacrifice.

    Yes even properly prepared meat has some AGEs in it. But no one food or diet is perfect. You just do the best you can and try to avoid the big mistakes. Just my opinion for what it is worth.

  • Anonymous

    10/22/2010 7:49:52 PM |

    Doc - with regards to exogenous AGEs, it sounds like this could be the new cholesterol-is-bad-for-you theory. My apologies if I have overlooked something in your post, but I don't see any logical argument leading to the conclusion that exogenous AGEs affect your health. Your previous post on butter also makes you sound like an alarmist. Of course, if you have a diet coming up, this is understandable.

    Frown

  • Anonymous

    10/22/2010 8:02:14 PM |

    what do stomach acid and bile do to ingested ages?? ...and the rest of the digestive process? sss

  • Joel

    10/22/2010 9:46:44 PM |

    One of the primary AGE components of milk products is pyrraline:

    Glycation in food and metabolic transit of dietary
    AGEs


    Here are some quotes from this study:

    "Given the data for pyrraline excretion, it
    can be concluded that dietary pyrraline is nearly completely
    released and resorbed during digestion, followed by rapid
    elimination via the kidneys, thus leading to nearly complete
    recovery of dietary pyrraline in the urine. This indicates that,
    in contrast with Amadori products, of which only up to 5%
    are recovered in the urine [24,25], pyrraline obviously is not
    metabolized within the body."

    "Above all, however,
    it has to be realized that the term ‘AGE’ comprises a large
    number of individual amino acid derivatives, of which only a
    minority have been identified and quantified either in foods
    or in vivo."

  • Joel

    10/22/2010 9:56:29 PM |

    Now that everyone is speculating in the last two posts, is it possible that some AGEs are much more harmful than others? (As the previous study indicates?)

    Are we distinguishing the types of AGEs when we measure them? (Or are we lumping them all together like what was done with cholesterol?)

    Are food derived AGEs eaten as part of a meal less harmful then analogues produced in a lab and fed in isolation? (Like most AGE studies I've read?)

    Again, if butter is as bad as these measurements indicate, why hasn't it been identified epidemiologically as such a bad food? Those with the highest butter consumption tend to be the healthiest (although I suppose because it displaces margarine).

    I can understand why all AGEs might be harmful to someone with compromised kidneys, but I agree with Martin Levac that we're really delving into the unknown.

    "Martin, there have been numerous studies connecting the association of AGEs with various health issues. There is nothing novel or or new about this."

    Please give us a study. This sort of broad statement is hard to counter argue otherwise!

  • Nancy

    10/22/2010 10:35:39 PM |

    I'm not really convinced AGEs you eat are a problem. But if you're enamored of low temperature cooking, looking into Sous Vide cooking. It yields delicious results by cooking at much lower temperatures than normal.

  • Ned Kock

    10/23/2010 12:26:20 AM |

    Speaking of endogenous AGEs, caused by high blood glucose levels, here is an interesting factoid - blood glucose levels in birds are very high yet their HbA1c levels are low:

    http://healthcorrelator.blogspot.com/2010/10/blood-glucose-levels-in-birds-are-high.html

    There are a few possible reasons for this. One of the most interesting mechanisms is vitamin C synthesis. Not only is vitamin C a powerful antioxidant, but it also has the ability to reversibly bind to proteins at the sites where glycation would occur.

  • Michael Barker

    10/23/2010 2:30:23 PM |

    All humans cook food and have done so for thousands of years. This is natural for us. If you've ever cooked meat on a camp fire, you know that the some of the meat becomes very crisp. Paleo people didn't have temperature gauges so I'm very sure there were plenty of exogenous AGE's. In fact, I would suggest, since these pieces of foods tend to taste very good to humans that they are an important piece of our nutrition not the opposite.

  • Geoffrey Levens

    10/24/2010 1:17:10 AM |

    "High blood glucose (any blood sugar above 100 mg/dl) will permit glycation"

    I would love to know some research that backs this claim. I have seen it numerous times but have not been able to find any research that specifically deals with it.  Also, just guessing, but I would bet that damage occurs at considerably lower blood sugar levels for those eating a conventional, nutrient sparse diet as compared to those replete w/ vitamins, minerals, phyto-nutrients etc who eat a diet containing very large amounts of "real food" particularly non-starchy vegetables

  • Jonathan

    10/24/2010 1:19:54 PM |

    Has anyone ever taken an A1C of a grain-feed cow?  Maybe that high AGE butter was from a diabetic cow!

  • Lori Miller

    10/24/2010 2:48:42 PM |

    I don't know if AGEs are harmful either, but a pressure cooker is great for low-temperature cooking. It's also much faster and keeps in the juices better than oven roasting.

  • Lori Miller

    10/24/2010 4:32:39 PM |

    Re: sausage (from the last post), the list of ingredients from the chorizo I eat is pork, water, salt, paprika, spices and garlic powder. "No nitrates, MSG, preservatives, sugar or soy," reads the label. I don't understand why this is worse than any other meat.

  • Anonymous

    10/25/2010 1:09:48 AM |

    Sausage could be a problem because,

    1)The meat is ground up so more of the surface area was exposed to oxygen. More of the meat is oxidized.

    2)Sausage unlike unground cuts of meat must be cooked through because of bacterial contamination. The more you cook meat the more you get AGEs.

    3)Some sausages as with hot dogs are pre cooked. Then you cook them again. This should also increase AGEs.

  • Dr. William Davis

    10/25/2010 2:42:03 AM |

    There are indeed studies that 1) measure serum levels of AGEs in humans after consumption of exogenous sources, and 2) relate AGE levels to biologic effect, e.g., endothelial response.

    There is no question that the exogenous AGE conversation requires more exploration. I've followed this conversation for some years, but I believe it is gathering real momentum and looks and feels like a genuinely meaningful issue.

    We need more info, no doubt. The notion of endogenous AGEs already fits quite nicely into our observations of the benefits of a low-carb diet. But  exogenous AGEs have potential for taking us one step farther in crafting an ideal diet. Recall that the "Paleo" approach is one reconstructed to mimic ancient behaviors, not necessarily one to achieve a new set of modern goals, such as reversal of coronary disease or osteoporosis.

  • Peter

    10/25/2010 11:25:03 AM |

    It's clear that in the US we eat lots of carbs and get lots of heart disease and diabetes.  But there are lots of traditional cultures that eat even higher percentages of carbs (cassava, beans, rice and others) but that don't get those diseases.  How does the AGE theory explain that?

  • LeenaS

    10/25/2010 12:58:51 PM |

    Dear Dr Davis,

    I know your opinion against butter, but disagree, based on a lifelong experience, as a skin chronic healed by milkfats and (land)animal fats.

    For the first 40 years of my life I was never free of allergic reactions and imflammated skin symptoms. Raw food helped not, vegetables and salads helped not, and the official healthy lifestyle helped not either. 10 years ago, when the stsart of Zonish lowcarb (much like your style) finally helped me incredibly much... Yet my skin has healed fully only after I switched to very, very buttery and egg-yolky diet close to Jan Kwasniewski.

    I live far up North, but have no symptoms of vitamin D deficiency, in spite of not eating the pills and not having much sun for the better part of the year. Furthermore, I cannot eat fish, and do no longer supplement with fish oil either, due to problems induced by it. Yet my skin has never been as good as now, fully without irritation or other symptoms. And unlike my frends and colleagues, I no longer seem to catch seasonal colds, either.

    So far the only thing I can blame for the last few years of well-being is increased use of milkfat and non-muscle parts of animals (fat, marrow, liver and skin collagen). Of these the milkfats make up a major part of the daily calories, often more than 50 E%.

    I'm interested to hear your thought on possible causes, which make this butter strategy work the best of all that we've ever tried; both for myself and for others in our family Smile

    With regards,
    LeenaS

  • Steve Cooksey

    10/25/2010 2:50:34 PM |

    I am a Type 2 Diabetic with normal blood sugar who takes -0- drugs and -0- insulin.

    I experienced tremendous benefits from going low carb primal. I won't detail them here but I have not been sick in 20 mos.

    This summer I performed a one week dairy fast (I'd been off milk for almost a year) and then added back butter.

    Butter was very inflammatory. I no longer eat it. Clarified butter or Ghee and Cheese are not inflammatory and I eat it occasionally.

    So for me, I agree with butter.

  • Lori Miller

    10/25/2010 9:47:14 PM |

    Anonymous, thanks for the info on sausage. I buy raw sausage and I'm careful to avoid over-cooking any meat, mostly because it gets like shoe leather.

    Another question: is cream high in AGEs? Does the churning action required for butter contribute to oxidation or AGEs?

  • Anonymous

    10/25/2010 11:43:50 PM |

    What's the consensus on carnosine ? I've read some articles claiming it helps with AGE factors.

  • Martin Levac

    10/26/2010 8:47:46 AM |

    Dr. Davis, it's fine to have data on a diet that contains AGEs, but where's the data on a diet that avoids AGEs? Where is the justification for adopting such a diet? Avoiding something leads to adopting something else. What will that be? You can't predict. Nobody can predict. This is the danger of advising to avoid something just like that was the danger of advising to avoid saturated fat and pretty much all animal fat altogether in one big swoop.

    If we can't eat fat, we must eat sugar. There's no other alternative. If we can't eat meat, we must eat some other form of protein. What will that be, soy, wheat, any other grain, legumes? If we can't eat meat, we must eat some other form of those essential nutrients like B12 and EFAs. But where can we get such a high quality source of those nutrients but in animal flesh? The quick answer is nowhere.

    When you advise to avoid AGEs without giving us a safety threshold, the safe course is to avoid all AGEs, not just a little bit. When you give a safety threshold, it doesn't matter because the substance has been declared bad entirely anyway so the safe course is the same.

    We can see this with animal fat and pretty much any kind of fat. Fat is bad, so any fat is bad, so less fat is good or better, but no fat is best. That's how it works in spite of having some form of safety threshold we can abide by like say 10g of saturated fat per day maximum. Why is that? The safety threshold is declared as a maximum with no minimum.

    So tell us Dr. Davis, what is the maximum and the minimum amount of AGEs you advise we eat? But more relevant to the discussion, how can we find out exactly how much AGEs is in the food we eat every day so that we can make an informed decision on exactly how much AGEs we eat every day? Is there a tool that will allow me to find that out? The point is that even if you give us a precise number on how much AGEs we can and cannot eat, we can't even control how much AGEs we eat. Accordingly, the best course of action is to avoid all AGEs and not just a little bit just to be safe because the contention is that lots of AGEs is worse than none.

    With endogenous AGEs production due to high blood glucose and other simple sugars like fructose, the problem is much simpler. That's because this AGEs aspect of sugars is merely the last installment of How Sugars Kill Us Slowly. We already know that sugars kill us slowly and we already know just how much of it will do it and how long it will take and etc. But until you find out exactly how much exogenous AGEs we must avoid and exactly how much we can get away with and how to measure the AGEs in the food we eat, this problem will remain unresolved and unresolvable.

    In other words, the best course of action with exogenous AGEs is to just ignore them outright. After all, we've been ignoring them outright for the past couple million years without so much trouble.

  • Fred Hahn

    10/26/2010 4:52:57 PM |

    Bill,

    Butter is high in AGEs? Wow - why? What about Ghee?

    Do you know what the AGEs are in smoked meats like smoked trout?

    Does the canning process increases ages as in canned wild caught salmon?

  • Dr. William Davis

    10/27/2010 1:47:27 AM |

    Hi, Fred-

    I believe that smoked fish tend to be moderately high in exogenous AGEs.

    One of the difficulties with quantification of AGEs in foods is we have limited data on the AGE content of various foods. It's not like grams fats or carbohydrates listed in plain sight on the label.

    I find the AGE conversation a fascinating new potential insight into helping us decide how to best manage food choices, as well as food preparation.

    As with all new ideas, it will cause upheaval in preconceived notions.

  • Poisonguy

    10/27/2010 7:34:44 AM |

    Given some of the previous blog posts, the largest preconceived notion might be yours toward butter. So, it's no big deal if you aren't up to the challenge of defending what you posted. That's okay. Trying to be coy about it, not so much.

  • Anna

    10/28/2010 7:28:18 PM |

    Count me as a skeptic on this one.

  • Anonymous

    10/29/2010 3:54:56 PM |

    Very good review on AGEs. Dr. Davis is 100% right to be concerned.

    http://biomedgerontology.oxfordjournals.org/content/65A/9/963.full#ref-109

  • blogblog

    10/30/2010 12:31:18 PM |

    People are confusing exogeneous AGEs which are generally harmless compared to the dangerous endogenous AGEs.

    Endogenous AGEs are created by proteins in our bodies reacting with reducing sugars.  Practically the only sources of dietary reducing sugars are fructose (table sugar, HFCS) and  cooked starches. The obvious solution is to eat far more meat and butter and drastically reduce carbohydrates.

    Humans have been eating cooked food for 1.8 million years and are very well adapted to them. The novel foods in the human diet are large quantities of plant proteins, starches and sugars.

    I'm surprised you think kale and spinach are so wonderful. Renowned toxicologist Dr Bruce Ames says that there are considerable amounts of natural toxins and carcinogens present in all food plants.
    http://www.fortfreedom.org/n16.htm

    Any potential benefits from eating kale is likely to be due to hormesis.

    In fact there is absolutely nil direct scientific evidence that eating fruit and vegetable has any health benefits whatseover. The benefits of vegetables have only been found in a few poorly designed population studies. Any observed 'benefits' of eating vegetables are probably just due to confounding variables - people who eat vegetables smoke less, drink less alcohol, are more active and eat less sugar and junk foods.

  • Apra -- The Shaman

    10/30/2010 4:35:41 PM |

    Gary Taubes is skeptical of the claims about exogenous AGES

    http://www.healthcentral.com/diabetes/c/36758/17729/gary-taubes

  • blogblog

    10/31/2010 8:12:44 AM |

    Hi Apra,

    In 'The Diet Delusion' Gary Taubes says that the natural diet of humans is almost purely carnivore with a few berries. Taubes studied physics at Harvard and aerospace engineering at Stanford before becoming a journalist. Because he was properly trained in using rigorous scientific methods he can readily see the flaws in nutrition research.

  • Ed

    11/16/2010 3:06:38 AM |

    I've read the sole paper that lists butter as a high-AGE food: "Advanced Glycoxidation End Products in Commonly Consumed Foods" (2004, Journal of the American Dietetic Association, via Google Scholar cache).

    The data is in Table 1, which refers to "foods prepared by standard cooking methods" (these include frying), but the table says nothing specific about how the butter was processed. I am willing to bet that the butter in question had been treated at high temperature (maybe used in frying).

    Consider these values:

    Milk, cow, whole .... 0.05 kU/mL
    Butter .............. 265 kU/g

    Expecting high AGEs in uncooked butter -- over 5000 times the level in milk! -- would make little sense.

    Would you consider revising your post in light of this?

  • Mary McNeill

    8/5/2012 4:10:37 PM |

    The data table lists butter as 100 gm serving, or over 3 ounces (23,000 - 26,000).  In the serving size database, the amount of AGEs normalize a bit, at 1100 - 1300.  I wish they had done organic vs commercial butters, but maybe next time we can see that data.  No surprise on pan fried bacon at 91,577 for 3 ounces and 11,905 for the serving size (2 slices is the norm).   As with all foods, moderation.  And thank you for your blog - it is very informative!

Loading