It is not merely a coincidence that the acronym for advanced glycation endproducts spells out AGE. Research points to these molecules causing oxidative stress and inflammation, two mechanisms implicated in the aging process. Inflammation and oxidative stress have also been associated with many chronic diseases plaguing society today, including diabetes, cardiovascular disease, and cancer. As will be seen, AGEs are implicated in these diseases as well.
AGEs form during the cooking process, but you do not have to opt for a completely raw diet to avoid AGEs. There are many actions you can take to limit your exposure to AGEs. Before diving into ways in which to reduce your level of AGEs, let's first review the literature to find out what they are and how they affect your health.
What are AGEs?
Advanced glycation endproducts (AGEs) can be taken into the body through food and produced in the body. AGEs form through an interaction between protein (more specifically the free amino group) and sugars, although fat can also be a part of these reactions. You might be familiar with the "Maillard reaction" which occurs during cooking something with protein and sugar. This reaction creates the brown coloring you might associate with baked goods and caramel.
Endogenous AGEs (or those derived in your own body) typically arise due to excess blood sugar in diabetics. However, excess oxidative stress can also contribute to excess endogenous AGEs. Exogenously derived (or from outside your body) AGEs generally come from food, although smoking also contributes to the number. Only about 10 percent of dietary AGEs are absorbed, but they can still have a significant impact.
The body does not distinguish between endogenous and exogenous derived AGEs; they combine together to create one pool. When that pool overflows, problems occur. In the body, AGEs contribute to oxidative stress and inflammation in the body. There is a certain capacity that your body can handle, and if you go beyond the body's capacity to mitigate oxidative stress and inflammation, whether the AGEs are internally and externally derived, disease and dysfunction arise.
The Role in Aging and Disease
AGEs affect the body in many different ways. AGEs have the potential to alter protein structures, which in turn changes the function and properties. Additionally, AGEs impact communication between cells, generally through one of the receptors, RAGE. For example, RAGE also binds to molecules that produce inflammation.
As discussed, two of the major detrimental effects from excessive AGEs in the body are oxidative stress and inflammation. Studies have also found an association between several chronic illnesses and high levels of AGEs.
Inflammation and Oxidative Stress
Several studies have pointed to an increase in inflammatory markers upon consuming a diet high in AGEs, which is more pronounced with long-term exposure to dietary AGEs. A systematic review compared several randomized control trials looking at biomarkers of inflammation and oxidative stress. The review found three studies that detected changes in the circulating TNF-alpha levels (a marker of inflammation) in the blood of healthy individuals. Lengthier exposure had a greater effect. During an observational period of 16 weeks, a diet high in AGEs led to inflammation; however, there were no observational differences between those consuming a high and low AGEs diet in a study that took place over a period of just two weeks. However, the studies reviewed did not point to similar changes in IL-6 or CRP levels, other markers of inflammation.
The systematic review also found similar results in studies with patients who had diabetes and chronic kidney disease. Another systematic review found 17 studies, including animal, human and observational, with findings that pointed to a positive association between AGEs and inflammation.
One reason for the association might be AGEs' influence on macrophages. In one study, researchers looked at the ways in which AGEs affected macrophages, which play a key role in the development the inflammatory condition atherosclerosis. Macrophages promote several proinflammatory cytokines, including TNF-alpha and IL-6. Using mouse cells, the researchers tested the level of AGEs and the impact on macrophage production. The results pointed to a dose-dependent impact on IL-6 and TNF-alpha production. The researchers also found that AGEs upregulated the produced of RAGE on the macrophages.
AGEs also increase oxidative stress on the body. A study looked at the impact of dietary AGEs on diabetic patients. Those who had high levels of AGE also had higher levels of total cholesterol, LDL-cholesterol, glycated LDL levels and HbA1c. They also had higher levels of 8-isoprostane, IL-1 alpha, TNF-alpha, and MCP-1, along with lower activity of SOD. These markers not only demonstrate higher inflammation, but it also shows a higher oxidative stress and a lower antioxidant capacity. SOD and 8-isoprostane levels are biomarkers for oxidative stress, while MCP-1 is the chemotactic factor that initiates monocytes, which then produce inflammatory cytokines. Additionally, the interaction between AGEs and RAGE leads to the generation of reactive oxygen species (ROS), which are known to cause oxidative stress if not properly mitigated by an antioxidant defense system.
Ovarian Dysfunction
Studies have linked excess AGEs to ovarian dysfunction, especially in women with polycystic ovary syndrome (PCOS). AGEs in the ovarian tissue cause dicarbonyl stress, which alters the growth of oocytes, ultimately impacting the function of the ovaries. A dicarbonyl that has the potential to generate AGEs, methylglyoxal (MG), might also play a role in ovarian dysfunction through affecting the integrity of the genetic material. When MG passes from cumulus cells to the oocyte, it potentially damages the genetic material. It also alters mitochondrial function, which can cause dysfunction. The AGE-RAGE interaction also leads to dysfunction in LH signaling, which in turn affects oocyte development. There is also evidence pointing to an associating between high levels of AGEs and higher AMH levels, which is associated with anovulation. AGEs also negatively affect men's reproductive health, especially older men and those with diabetes. Studies have linked erectile dysfunction to higher levels of AGE, most likely due to oxidative stress and AGEs' effect on the vascular system.
Chronic Illness
Inflammation and oxidative stress are implicated in several chronic illnesses, including cancer, diabetes, obesity, metabolic syndrome, neurodegenerative conditions, and cardiovascular disease. Therefore, increasing your serum level of AGEs could increase the risk of developing these disorders due to systemic inflammation and excessive oxidative stress. Some studies have found a more direct link between AGEs and chronic disease and mental health conditions, including schizophrenia. This typically occurs due to the interaction between AGEs and RAGE receptors, which are found in tissues all over the body.
For example, RAGE might contribute to neurodegenerative disorders through increasing apoptosis in neuron cells, degeneration of cells, and neuroinflammation. Additionally, several studies have found an associated between AGEs and cancer, with RAGE interacting with different ligands to increase oxidative stress and activate certain proteins that increase cancerous cells. RAGE expression is also linked to better survival of the cancerous cells, increased proliferation, autophagy, limited apoptosis, and angiogenesis, all of which promote the spread of cancer and limits the body's own natural defenses against it.
With so much potential for damage, it is important to do what you can to limit the level of AGEs in your body. One way to do this is through limiting the amount you consume. There are also weapons to put in your arsenal that help you defend from both exogenous and endogenous AGEs.
How to Reduce Your AGEs
The first place to look when trying to reduce your AGEs level is the foods you consume. As a general rule of thumb, foods high in lipid and protein are at a greater risk of developing AGEs, especially when cooked at high temperatures. According to one study, some of the foods with the highest level of AGEs include fats such as butter, almonds, and mayonnaise, as well as cheeses. Below is a comparison table of a selection of foods with high levels of AGEs per serving:
The researchers also found that carbohydrate foods, such as whole-wheat bread, pancakes, apples, bananas, green beans, and carrots, tended to have lower levels of AGEs, regardless of preparation. However, processed foods in this group had a much higher content of AGE compared to the whole foods. Below is a comparison chart of some commonly consumed carbohydrate foods, based on the findings of the study:
In terms of food preparation, there are a few main components that determine the extent of AGE formation: nutrient composition, humidity, pH, temperature, duration of heat, and any trace metals. Therefore, the same raw ingredients have the potential to produce more or less AGEs depending on the circumstances in which they are prepared and cooked. The foods with the highest number of AGEs are typically those with a high level of protein and fat.
Out of all the variables, high temperatures seem to have the greatest impact on AGE formation. The researchers found greater changes when samples were cooked above 230 degrees Celsius, which is around 446 degrees Fahrenheit. Another study found that the cooking temperatures correlating with the higher levels of AGEs were also between 177 and 230 degrees Celsius, or 350 to 446 degrees Fahrenheit.
However, you do not have to simply eat a raw diet. Instead, you can have a delicious diet filled with cooked foods, as long as you take the following precautions to limit the formation of AGEs.
Avoid Processed Foods
There are many reasons to avoid processed foods, and you can add the high level of AGEs to it. Commercially processed foods generally incorporate thermal processing in order to prevent illness, increase shelf life, and enhance taste. The heating processes lead to Maillard reactions, which produce AGEs. For example, bakery products have the potential to have up to 3000 umol/kg of AGEs, a very high number. As you can see in the chart above, homemade pancakes had just under 300 kU per serving, while processed versions had twice that at 679 kU per serving. In many cases, foods that traditionally have low levels of AGEs are prepared in such a way that increases their AGEs when commercially processed. So, cook and prepare foods yourself from whole foods and natural ingredients, and you will already be taking a significant step towards better health -- and lower levels of AGEs.
The Best Cooking Methods
Even if you prepare all of your meals from scratch, you still could end up consuming a high number of AGEs. Therefore, you need to know the best cooking methods to limit the production of AGEs.
Generally speaking, the best option is to cook food using low heat for a longer period of time in some type of moisture. A study that compared cooking methods found that broiling beef for one hour led to just 22 kU/g of AGEs compared to 60 kU/g when the beef was broiled for 15 minutes. Per 30 g serving, that led to a 2,007 kU compared to the 5,367 kU listed above.
Therefore, frying, grilling, roasting, and broiling will lead to higher levels of AGEs in food than poaching, boiling, stewing, and steaming. If you wish to sauté or stir-fry something in a pan over heat, choose a low to medium heat rather than a high heat. It might take you longer to cook, but you will have lower levels of AGEs in the final product. The type of fat in which you cook your meat can also have an effect on the level of AGEs.
Marinating is another way to mitigate your AGEs, not to mention enhance the taste of the dish. In one study, beef was roasted in 150 degree Celsius for 15 minutes with or without being marinated in vinegar or lemon juice. Although the raw beef had the lowest AGE level, the level in both the lemon and vinegar marinated samples was roughly half of that of the beef cooked without the marinade. Cooking in spices might be another way to reduce the level of AGEs in foods. Non-human studies have presented promising results demonstrating AGEs-inhibitory effects of several common spices, including cumin, thyme, rosemary, and sage.
Antioxidants and Anti-inflammatory diet
As with any contribution to oxidative stress, consuming a diet rich in antioxidants plays a key role in mitigating the negative effects of AGEs. One in vitro study found that quercetin, a flavonoid found in many plant foods including berries, broccoli, kale, apples, capers, onions, tea, tomatoes, nuts, seeds, and grapes, reduced the effects of AGEs.
The researchers discovered a dose-dependent effect of quercetin on oxidative stress caused by AGEs. At higher doses, there was a reduction of markers of oxidative stress as well as DNA damage. Even at small doses, it still reduced markers of AGEs. Quercetin also inhibited other glycations, including that of hemoglobin, as seen in the impact of this powerful antioxidant on HbA1c levels in this study.
Another antioxidant, gallic acid, which is a polyphenol found in many plant foods with known anti-inflammatory and anti-cancer activity, has also been shown to mitigate the damaging effects of AGEs. Gallic acid can be found in any part of the plant, including the seeds, roots, fruit, leaves, and bark. Some good food sources include blueberries, plums, strawberries, and walnuts. Drinking tea is an easy way of increasing your consumption of gallic acid. A small human study found a similar bioavailability of gallic acid from drinking tea as to taking acidum gallicum tablets.
Pomegranates have amazing antioxidant potential, among other health benefits. They also have the ability to reduce AGEs. One study found that one of the polysaccharides found in pomegranates led to a 28 percent reduction of AGEs. Other foods, beverages, and herbs rich in anti-inflammatory and antioxidant activity, such as green tea and curcumin, will likely provide benefits as well.
Exercise
Exercise has been shown to diminish concentrations of AGEs. In one study using obese Zucker rats (a diabetes animal model), researchers found that 10 weeks of intermittent moderate intensity exercise led to lower plasma levels of AGE compared to the control group that did not exercise. Exercise also led to better markers for kidney health, leading to a reduction in obesity-related nephropathy. It did not affect the oxidative stress levels or inflammation levels. However, there was a difference in the levels of AOPP, which is a marker of oxidative damage. The researchers postulated that exercise modulated rather than limited the activation of macrophages.
Don't Smoke
The other major source of exogenous AGEs is tobacco. This is because the way in which tobacco is cured to prepare it for cigarettes and other sources leads itself to the Maillard reaction and similar reactions that cause AGEs. In one study, researchers found that tobacco smokers who smoked at least one pack a day had a significantly higher level of AGE in their blood than non-smokers. As part of the study, the researchers tested extracts from both cigarette smoke and tobacco and found glycotoxins, or products that can lead to AGE formation.
Thus, stay away from tobacco products, especially cigarettes and vaping. It is also wise to avoid second-hand smoke as much as possible. Although this study only looked at the serum of smokers, the glycotoxins were found in the cigarette smoke. It can be postulated that inhaling second-hand smoke would also lead to inhalation of glycotoxins, which could put you at risk of increased AGE production.
Based on the above, the best way to reduce your level of AGEs and mitigate the negative impact on your health is to follow these guidelines:
- Avoid highly processed foods
- Cook foods in low heat for a longer period of time with sufficient moisture
- Consume lots of fruits and vegetables to ensure you have copious amounts of beneficial antioxidants, especially quercetin and gallic acid
- Exercise
- Do not smoke and avoid second-hand smoke
- Drink green tea and pomegranate juice
As always, discuss any changes to your diet and lifestyle and any supplements you consider taking with your doctor before doing acting to ensure that it is the correct move for you.