Wednesday, March 31, 2010

Limiting AGEs, Limiting Complications

Imagine a juicy piece of barbecued meat, marinated in a sweet BBQ sauce and grilled over flaming charcoal until it is a nice brown color with crispy pieces on the outside. Sounds good? Imagine your internal organs processed in the same way and you have a picture of the formation of advanced glycation end-products (AGEs), one of the most harmful processes associated with chronic inflammation. AGEs are the products of sugars and proteins binding together and, in the human cells, it is damage that cannot be undone. While all human tissue is subject to damage by AGEs, the lining of blood vessels in diabetics is especially sensitive leading to heart disease, long-lived nerve cells rapidly accumulate damage resulting in neuropathy, microvascular destruction leads to retinopathy and nephropathy, and AGEs are implicated in the destruction of beta cells in the pancreas. Where do these AGEs come from?

Exogenous AGEs come from your food and drink. Basically, any food preparation with high heat that involves browning is creating AGEs … browned meats, bread crust, caramel coloring in processed foods, and even my beloved dark roast coffee beans. Raw foods and foods cooked in the presence of water contain far less AGEs. Water prevents the proteins and sugars from binding. An example would be a raw chicken breast which contains a moderate amount of AGEs with 7686 units. If you boil it, you will increase the AGEs about 50%, microwaving increases AGEs two-fold, broiling increases AGEs eight-fold, and frying will multiply AGEs ten-fold. It’s not just about meat. Roasted nuts are one of the highest sources of AGEs. Healthy fresh butter has four times as much AGEs by weight as roasted meat. In general, processed meat and other processed foods are much higher in AGEs. See list of AGEs in common foods here.

Advocates of raw vegan diets point out that this way of eating has far less AGEs because raw fruits and vegetables have very little AGEs and cooked meat is never consumed. Makes sense in theory, but studies of long-term vegetarians have shown that they actually have similar or higher levels of plasma AGEs than people eating normal American diets. How can this be? It seems that vegans eat a relatively high carb diet with lots of fructose from fruits and zero carnisone or taurine from meat. This brings us to the other source of AGEs.

Endogenous AGEs are produced in the human body when sugars bind with proteins. Diabetics are especially susceptible to this process which is believed to be the source of most diabetic complications. The best way for diabetics to lower their plasma AGEs level is to lower their A1c which correlates highly with AGEs. As AGEs are a product of inflammation, they also correlate highly with CRP. Limiting carbohydrate in the diet is one of the best ways to minimize the production of AGEs. One sugar is especially deadly – fructose, which is far too abundant in the modern diet. According to Wikipedia:

Endogenous glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose, and galactose. It appears that fructose and galactose have approximately ten times the glycation activity of glucose, the primary body fuel.

Meat, as I have explained, can be cooked into a high-AGEs food, but it is also a source of two substances that inhibit the production of AGEs in the human body. The amino acids carnosine and taurine are only available in animal protein. For this reason, a low carb diet with little fructose and abundant animal protein may be the best diet for diabetics trying to limit damaging AGEs. Ironic, as cooked meat is one of the highest sources of exogenous AGEs.

Besides carnosine and taurine, there are several nutritional supplements which reduce the production of AGEs. The vitamins benfotiamine (lipid soluble thiamine), alpha lipoic acid (ALA) and lycopene (found in tomatoes) are well known as beneficial in preventing diabetic complications. Some phytonutrients are helpful including quercetin, EGCG (green tea extract), curcumin (turmeric extract), resveratrol (found in red wine) and others.

How to reduce AGEs? Keep your blood sugar low, eat low-carb, enjoy fresh raw veggies, cook with water, limit browned foods, avoid fructose like the plague, restrict processed foods, get enough animal protein, and consider supplements to inhibit the production of AGEs.


  1. Denny a few questions.
    Where do you think the danger from exogenous (ingested) AGEs come from? Is it really from the AGEs? Aren't they digested into their component parts like any other food we eat? AGEs are only permanent in our bodies because we lack the enzymes/processes to undo them, but the gut is pretty good at breaking things down into their component parts so we can absorb them. Do you think ingested AGEs are immune or bypass our digestive system somehow? Is this a leaky gut thing?
    Secondly, many of the anti-AGE supplements you list can fulfill that function because they are good antioxidants. Much AGE formation, but not all, can be reduced by reducing the oxidative stresses that concur with or precipitate AGE formation. Do you agree? Are those you listed the best antioxidants for the job?

    It's interesting, because as some believe fruits have high levels of fiber to "balance out" the fructose, meats also contain high levels antioxidants; perhaps to "balance out" their higher levels of AGEs.

  2. When it warms up I cook on the grill everynight. That about 3 months of grilled food everynight.

  3. You got it, Shaun. That's the key question. How do exogenous sources of AGEs affect the levels of plasma AGEs in the human body? I have opined that most AGEs in the human body are produced within the body, but I still have not found any research that speaks clearly to the affects of exogenous AGEs. Have you seen any good research on this subject?

    I believe the answer lies with Dr. K in Wyoming. I think we need to measure his plasma AGEs levels before the snows melt and then again after he has consumed his entire body weight in barbecued meat. This is one experiment where I am eagerly awaiting Dr. K's report.

    The supplements that I briefly listed are the ones believed to be most effective at inhibiting the formation of AGEs and preventing diabetic complications. Personally, I am a big believer in benfotiamine and alpha lipoic acid. Common anti-oxidants like C and E seem far less helpful. I have no personal experience with supplemental carnosine, but there is a fair amount of research supporting its efficacy. The phytonutrients are not as clear. I will be posting on supplements in the next week or two.

  4. Denny, I don't know much about AGEs, but pursuing what seems to be a logical line of thought, ingested AGEs should not harm us. AGEs harm us when our living cells are "corrupted", so to speak, by the process of forming AGEs. Ingested AGE is first of all decomposed into constituent nutrients by the digestive process. What harm can be done by the AGEs that escape disgestion and enter the blood circulation? Can these products themselves harm us? To me it appears that the process of forming AGE on living cells is harmful (because they change the cell in a harmful way) but AGEs by themselves are not harmful. I may be wrong.


  5. Rad,

    How interesting that the only vegetarian posting in this discussion suggests that dietary AGEs may not be that harmful. While I feel that endogenous AGEs are the main issue for diabetics, my reading seems to indicate that dietary AGEs do contribute to some unknown degree to diabetic complications, especially kidney disease.

    Many studies on kidney disease and dietary AGEs, but let me quote from Dr. Jaime Uribarri who has written widely on this subject.

    "Dietary AGE are linked to multiple mechanisms of disease that are associated with diabetes and CKD. Animal studies have shown that reduced consumption of dietary AGE decreased serum AGE levels and suppressed various pathophysiologic processes, including insulin resistance in db/db (+/+) mice, atherosclerosis in apolipoprotein E–deficient mice, and diabetic nephropathy in nonobese diabetic and db/db (+/+) mice. Administration of an AGE-rich diet for 6 wk in the five-sixths nephrectomized rat increased proteinuria significantly, although it did not change GFR.

    Common AGE compounds that are found in foods, such as CML or methylglyoxal derivatives, as their endogenous counterparts have been shown to have significant proinflammatory and pro-oxidative actions. LDL that was obtained from patients who had diabetes and were preexposed to a usual AGE-rich diet was shown to increase NF-B activity and vascular cell adhesion molecule-1 secretion by endothelial cells, whereas LDL from patients who had diabetes and were fed an AGE-poor diet did not have such effects. These findings support the hypothesis that exogenous reactive AGE and AGE precursors can induce pathologic transformation of endogenous macromolecules independent of hyperglycemia. Indeed, people with diabetes or kidney disease have been shown to respond to a low-AGE diet with reduced markers of inflammation.

    Although dietary AGE contribute to the internal pool, their relative importance in diabetes, kidney disease, and atherosclerotic complications remains to be elucidated. Nevertheless, the apparent deleterious nature of these compounds is a serious diet-related health concern. A new paradigm in which excessive AGE consumption as a result of a "Western lifestyle" produces chronic inflammation and oxidative stress has been proposed. Over time, excess AGE consumption likely contributes to emergence of diseases, including diabetes and CKD, that plague the developed and developing world."

    Personally, I am pro-meat. It has zero fructose which creates the most endogenous AGEs and contains significant amounts of the amino acids carnosine and taurine which inhibit the production of AGEs. Having done this research, however, I will reduce the amount of broiled, roaseted, fried and processed meat I eat.

    Vegetarian diabetics may need to pay even more attention to the amount of fructose in their diet. As a vegetarian, how do you feel about supplementing with carnosine? It is a fairly expensive supplement. Not sure if there is a vegetarian source.

  6. I am a novice in this analysis; however, I find this post by Dr. William Davis very interesting.