advanced glycation endproducts and your poor health

ADVANCED GLYCATION ENDPRODUCTS
A BIG REASON YOUR HEALTH ISN’T WHAT IT SHOULD BE

“Dietary AGEs do not tell the whole story, because they can also form through various metabolic pathways in the body. One study showed that while omnivores generally have higher dietary intakes of AGEs than vegetarians, vegetarians actually end up with higher concentrations of AGEs in their plasma.  The authors hypothesized that their results were due to the increased fructose intake of vegetarians…..    Overall, there’s no good evidence that red meat is more inflammatory than other meats, and some evidence indicating that it’s less inflammatory. Just like any other food, it’s certainly possible for people to have individual intolerances to red meat that might induce inflammation, but there’s no reason for most people to restrict red meat on the basis of inflammation. Additionally, AGEs from meat are probably not a concern, and meat eaters might even be better off when it comes to plasma levels of AGEs.”     Chris Kresser from Does Red Meat Cause Inflammation?
Over the past several years, I have mentioned something called Advanced Glycation Endproducts, also known as AGES, several different times.  According to the Journal of the American Dietetics Association (Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet), AGES…..

“are a diverse group of highly oxidant compounds with pathogenic significance in diabetes and in several other chronic diseases. AGEs are created through a nonenzymatic reaction between reducing sugars and free amino groups of proteins, lipids, or nucleic acids [DNA & RNA]. This reaction is also known as the Maillard or browning reaction. The formation of AGEs is a part of normal metabolism, but if excessively high levels of AGEs are reached in tissues and the circulation they can become pathogenic. The pathologic effects of AGEs are related to their ability to promote oxidative stress and inflammation by binding with cell surface receptors or cross-linking with body proteins, altering their structure and function…..   Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs)….   Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking.”

The first thing we should notice here is that AGES are bad news.  In fact, a quick tour through PubMed reveals slews of studies that have been done in the last two years linking AGES to any number of health-related problems — not surprising considering that DIABETES is heavily associated with AGES, and most health problems start with (or at least have a major relation to) UNCONTROLLED BLOOD SUGAR.   Dr. Loren Cordain, Professor Emeritus of the Department of Health and Exercise Science at Colorado State University in Fort Collins, says on his blog that….

“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, high blood pressure), cardiovascular disease, kidney failure, Alzheimer’s disease, allergy and autoimmune diseases, cancers, cataracts, retinal degeneration, and gastrointestinal diseases. Additionally, excessive AGEs are known to speed the aging process.”

The second thing that catches my eye has to do with the sorts of foods that contain large amounts of AGES.  If it’s true that, “animal-derived foods” (can anyone say RED MEAT or SATURATED FAT?) are high in AGES and that, “whole grains and milk contain relatively few,” it would appear that a LOW CARB or PALEO DIET —- the way of eating that I recommend to nearly all my CHRONICALLY INFLAMED patients — could backfire; actually making them worse.   As is often the case, there is more to this issue than meets the eye.

HOW AGES FORM

WHAT AGES DO TO YOU

One of the biggest factors that increases the AGE content in meat and poultry is the cooking method used.  Meat that has been blackened, fried, seared, broiled, or grilled, has a tendency to be very high in AGES.  This has to do with the Maillard Reaction mentioned earlier — a “carmelization” sort of thing that occurs with the darkening of meats or other food products via heat (Video #1).   As far as AGES are concerned, meat is better off slow-cooked in fluids at a lower temp, like you would do in a crock pot.  Interestingly enough, The AGE Foundation tells us that, “acidic marinades [think lemon or vinegar here] can suppress AGE formation by up to 50 percent when cooking meat.”  Cooking, however, is not the biggest factor in our exposure to AGES —- not by a long shot.  Meet Chris Masterjohn.

Dr. Masterjohn earned his Ph.D in Nutritional Sciences from UConn, and currently works as an Assistant Professor of Health and Nutrition Sciences and researcher at City University of New York, Brooklyn campus.  He runs the website CHOLESTEROL AND HEALTH (his blog is called ‘The Daily Lipid‘).   Allow me to summarize his post, ‘Where Do Most AGEs Come From? O Glycation, How Thy Name Hast Deceived Me!

Remember that there are two different ways that AGES get into our bodies.  Firstly, and most importantly, is the Maillard Reaction — an internal reaction that is directly related to the amount of HIGH GLYCEMIC INDEX CARBOHYDRATE / SUGAR that we consume (endogenous — it’s made by our bodies in response to sugar).  Secondly, are the AGES that come directly from our diet (exogenous — not made by our body, but consumed).  Listen to what Dr. Masterjohn says about exogenous AGES.  

The available evidence suggests that we do absorb certain AGEs from the intestinal tract, but almost immediately begin peeing them out.  As a result, dietary AGEs are unlikely to contribute meaningfully to the pool of AGEs circulating in our bodies at any given moment.

What does this sound like?  Although the mechanism for clearing the body is certainly different, this reminds me of what we know about CHOLESTEROL.   For years we were told not to eat any fat (HERE), all the while being lectured that carbs and sugar can’t make us fat since they don’t contain any fat.  Hence, we endured forty years of stupid BS like, DON’T EAT EGGS or DON’T EAT RED MEAT OR FAT (but eat all the carbs you want) — positions that have been turned on their heads by several decades of research (not to mention the fact that we are the sickest and fattest society in the history of the world). 

In other words, the Cholesterol you consume does not cause your blood cholesterol levels to increase (see first link in this paragraph) — and neither does dietary consumption of AGES cause blood levels to rise like you would assume they would.  It’s kind of akin to people going on the Atkins Diet and not only losing a ton of weight, but getting their blood work in order as well — even though they are probably consuming more fat than they ever have before.   Masterjohn then says something that I myself have said in the past, “Diabetes is not so much a sugar problem, as it is an Inflammation problem” (my quote, not his).   Dr. Masterjohn reveals that…..

Diabetes involves a lot more than high blood sugar.  Most likely, increased concentrations of glucose and ketones, defective energy metabolism, defective insulin signaling, and oxidative stress lead to the increased production of and decreased detoxification of dicarbonyls.  These dicarbonyls then form AGEs, defective degradation of AGE-modified proteins elevates their concentration further, and if the diabetes damages the kidneys, even the free AGEs released from degraded proteins will not be efficiently excreted.  High blood sugar is a part of this, but only a part.

Interesting, but this brings up a whole other issue for those using a Low Carb or Paleo approach — ketones.   WebMD says this about having lots of ketones in your bloodstream. “Ketosis is a normal metabolic process, something your body does to keep working. When it doesn’t have enough carbohydrates from food for your cells to burn for energy, it burns fat instead. As part of this process, it makes ketones.  If you’re healthy and eating a balanced diet, your body controls how much fat it burns, and you don’t normally make or use ketones. But when you cut way back on your calories or carbs, your body will switch to ketosis for energy.  For people with uncontrolled diabetes, ketosis is a sign of not using enough insulin.”  Did you catch that?  Ketosis is “normal” when you burn fat for energy.  Unfortunately, many people confuse Ketosis with Keto-acidosis.

According to the American Diabetes Association, Ketoacidosis (aka Diabetic Ketoactidosis or DKA) occurs, “When your cells don’t get the glucose they need for energy, your body begins to burn fat for energy, which produces ketones.  Ketones are chemicals that the body creates when it breaks down fat to use for energy. The body does this when it doesn’t have enough insulin to use glucose, the body’s normal source of energy.  When ketones build up in the blood, they make it more acidic. They are a warning sign that your diabetes is out of control or that you are getting sick.  High levels of ketones can poison the body. When levels get too high, you can develop DKA. DKA may happen to anyone with diabetes, though it is rare in people with type 2.”   While true, is this definition completely accurate?  After all, the purpose of the ‘Induction Phase’ of Dr. Atkins’ diet was to put people into Ketosis.  According to the website Ketogenic Diet Resource, never confuse the two.

Ketosis is NOT Ketoacidosis.   The difference between the two conditions is a matter of volume and flow rate.  Benign dietary ketosis is a controlled, insulin regulated process which results in a mild release of fatty acids and ketone body production in response to low carbohydrate intake, and higher fat consumption.  Nutrional ketosis associated with a properly formulated ketogenic diet is not dangerous because it is regulated by insulin within the body.  It’s simply the metabolic process of burning your own body fat for fuel, and unless you are diabetic and lacking insulin, or you are a raging alcoholic, it is perfectly safe. Ketoacidosis is a condition in which abnormal quantities of ketones are produced in an unregulated biochemical situation. In order to reach a state of ketoacidosis, the body has to be in a state of not producing enough insulin to regulate the flow of fatty acids and the creation of ketone bodies.  If left untreated, acidosis can result in a coma and death.” 

All of this brings me to another interesting point concerning the KETOGENIC DIET.  Despite the negative reviews by people in the (Ornish camp), not only is a state of Ketosis an excellent way for the VERY OBESE to lose weight in a hurry, but for those with severe neurological conditions to help get them under control as well.   Almost a century ago, Dr Russell Wilder of the Mayo Clinic designed a diet specifically used to treat Epilepsy, which was based on consuming large quantities of cream (unlike milk, cream has no sugar or carbs) and other protein-based foods.  Although, not surprisingly, it has fallen out of favor due to the advent of anti-seizure drugs, this begs the question of whether or not it was / is effective?  A 2012 Cochrane Review (Ketogenic Diet and Other Dietary Treatments for Epilepsy) helps answer this question.

“Several large observational studies investigated the effect of ketogenic diets in epilepsy and reported a beneficial effect. Recently, this view has been strengthened by the publication of four randomized controlled trials including one study which looked specifically at the Atkins diet, a related diet.These studies suggest that in children, the ketogenic diet results in short to medium term benefits in seizure control, the effects of which are comparable to modern antiepileptic drugs. We found one randomized study of reasonable quality of the Atkins diet.  This study showed similar benefits in seizure control with a less restrictive diet.  For those with medically intractable epilepsy or those in whom surgery is unsuitable, a ketogenic diet could improve seizure control, but tolerability is poor (dislike for the diet).   All studies showed 30-40% reduction in seizures compared to comparative controls.”

Did you catch that?  The effects of the KETOGENIC DIET are comparable to drugs.  But enough of this; let’s get back to AGES.  Although there is a huge debate about whether or not dietary AGES are bad for you (or at least as bad for you as some say they are), there is no debate as to whether the AGES created by your body in response to sugar / carb consumption are bad.  I went over to PubMed and cruised through studies on AGES published just in the past few months.   AGES have been tied to Diabetes, OSTEOARTHRITIS, problems with the eye, hearing problems, liver problems, any number of cardiovascular problems, AUTOIMMUNITY, CANCER, SYSTEMIC INFLAMMATION, PCOS, MS, HASHIMOTO’S THYROIDITIS, periodontal disease, mutations of DNA, cellular apoptosis (death), ULCERATIVE COLITIS, wrinkles (premature aging), kidney problems, OSTEOPOROSIS, OXIDATIVE STRESS, pregnancy complications / preterm labor, inability to heal bone fractures, and all-cause mortality (death by any and all causes) —- and this was only going back to July.

In a study published in the August issue of Molecular Aspects of Medicine (Dietary Glycemia as a Determinant of Health and Longevity), the authors looked at what it takes to live for a very long time, by specifically studying the link between visual health and dietary carbohydrate consumption.  “Extending healthful life is a millennia-old dream and objective. During the intervening centuries a multitude of concoctions and remedies have been offered, usually with few substantiated results.  Loss of vision due to age-related cataracts or age-related macular degeneration is widely prevalent, affecting about 85% and 15% of the elderly respectively.  With centenarians among the fastest growing segments of societies, and with loss of vision a very costly personal and societal burden, there is keen interest in extending vision – that is, delaying age-related macular degeneration and cataract – or diminishing risk for these debilities.  Using extensive epidemiologic and nutritional information from the Nurses’ Health Study and Age-Related Eye Disease Study we determined that measures of total carbohydrate, and even more so, glycemic index, are associated with visual health.

I’m not surprised.   I have shown you repeatedly that LIVING A HIGH CARB LIFESTYLE will not only kill you, it can make your life a living hell (just look at the list of diseases above).  And as for the whole don’t-eat-meat-because-it-causes-AGES thing, lets take one last look at what DR ART AYERS of Cooling Inflammation has to say about this in his post called Diabetic Hypertension, Browning of the Arteries.  “Should we fear browned foods as inflammatory.  I don’t think that AGE in foods is any more of a hazard than all of the toxic phytochemicals that are touted as plant antioxidants.  I think that the gut and liver provide protection.  I brown the sugar on my flans and sear my steaks, even as I relish eating my veggies.  The body can detox these natural products in the gut better than it can handle the AGE made by high blood sugars.”  To see precisely what Ayers is talking about, you can read THIS POST

The truth is that we have to be worried about dietary AGE consumption causing the high blood levels of AGES that lead to all sorts of sickness, pain, and disease, about as much as we have to worry about eggs or dietary fat making us fat.  In a blog comment on Diabetes Forecast (Foods High in AGES), commenter Rehun says it nicely when he states……

“Wow! talk about misinformation!  The proof that exogenous AGE’s make it into the bloodstream is very dicey. Just like the idea that eggs have cholesterol, therefore we shouldn’t eat eggs. Show me the proof that meat, which is protein contributes to AGE’s in our bodies. Sugar contributes to AGE’s. The AGE’s we need to be concerned with are endogenous AGE’s, that are created in our bodies when a glucose molecule binds with a protein/lipid molecule without a controlling enzyme. Those AGE’s (glycation) become “ugly” molecules sticking to cells throughout our bodies and, with time, create a great deal of damage and disease. Want to lower blood sugar and AGE’s? Reduce the carbs and increase protein. Then exercise and look for anti glycation products….they’re out there.  The idea that AGE’s attached to the food we eat causes damage is just like the ridiculous idea that eating fat creates fat in our bodies.”

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