AGEs: Where do You Find (>500 Foods), How do You Avoid (a Dozen Tips) Them? And Why Should You Even Care?
|100g fried bacon contains record-breaking 91,677 kU of AGEs. If you microwave it instead, you reduce the AGE concentration (and its taste) by ~90%! Learn more about the complex relationship between food, type, processing, AGEs and your health…|
“AGEs kill!” That’s the message many headlines of mainstream science-news outlets have been sending over the last 2-3 decades – headlines that are usually based on observational studies.
Most of them will then discuss epidemiological data, commonly ignoring that the very same food groups that are most likely to contain significant amounts of advanced glycation end products will also contribute to metabolic disturbances, which, in turn, increase the endogenous production of AGEs…
So, is the answer your usual “just eat healthily”? Don’t worry I am going to go beyond that recommendation in today’s SuppVersity article, but I would say: eating a minimally processed whole foods diet, should be the basis of everything you do for cardio-metabolic health, anyway.
Back to the AGEs, though. The first question we have to answer is a very similar one: Do dietary AGEs even matter? If you look at the (earlier) research on AGEs in foods, there have been a number of researchers who acknowledged the ill effects of glycation on the cells of your body (just think of HbA1c, for example). More recently, though, the interaction circulating dietary AGEs with AGE-receptors has gained significant attention, so that the overview of the mechanism of ill health effects of AGEs from the 2016 review “Pathologic role of dietary advanced glycation end products in cardiometabolic disorders, and therapeutic intervention” in the peer-reviewed scientific journal “Nutrition” (Yamagishi 2016) is probably right when it signifies that dietary AGEs matter:
|Figure 1: Pathologic role of dietary AGEs in various cardiometabolic disorders and
aging (Yamagishi 2016) | Plus: Random selection of the low, medium and high AGE foods from the >500 item list at the bottom of the article.
Apart from their interaction with RAGE (review of RAGE and cancer, RAGE in health & disease, RAGE in aging), AGEs, and their highly reactive intermediates, such as methylglyoxal (MG), glyoxal, and 3-deoxyglucosone, bind to proteins, DNA, and other molecules and disrupt their structures and functions, which leads to different diseases such as vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer’s disease, and aging. In that, they are yet still only “more or less undebated”.
|Figure 2: Absolution for coffee? Not exactly: While it does contain only very low amounts of pentosidine and no detectable fructoselysine or pyrraline, the larger part (75%) of its pentosidine content is free and appears to be absorbed much easier than the higher, but largely bound (<1% free) amounts of this biomarker for AGEs (Förster 2006).|
What is still debated is the general validity of the first arrow in Figure 1, which signifies that dietary AGEs make (physiologically significant) contribution to the AGE concentration in our circulating and tissues, which is, in turn, driving the previously referenced organ damage (especially in the heart and endothelium), metabolic syndrome, cancer (not shown in Figure 1, but unquestionably an issue | Yamagishi 2005 & 2015; Sparvero 2009 | depending on one’s microbiome they may also have protective effects, though, Aljahdali 2019) and even seem to accelerate the general aging process (Chaudhuri 2018).
The link between dietary AGEs and the formation of a “sugar-coating” on your cells is not as obvious and self-evident as you’d think.
In fact, studies investigating the contribution of the health effects of dietary AGEs are of rather low(ish) quality. As Nowotny et al. point out in their 2018 review, studies investigating the methodological quality of such studies with the Heyland Methodological Quality Score identified a low methodological quality for 58% of the trials”, in general. Puyvelde et al. (2014) who, analyzing observation studies with the STROBE (strengthening the reporting of observational studies in epidemiology) statement and intervention studies with the National Institute for Health and Clinical Excellence (NICE) checklist, report a generally reasonable quality for observational studies. Good? Well, not really. As previously stated, …
…observational studies cannot tell us whether dietary AGEs are the actual culprit or just come alongside other pro-carcinogenic, pro-diabesity molecules in our favorite cookies and pastries; …
and if we turn to those studies that could provide the information we’re looking for, we have to read that the few actual intervention studies that exist are of generally low quality (van Puyvelde 2014). Even worse, most of the trials were conducted in patients with chronic kidney disease or diabetes, so that the authors of the 2014 systematic review ar right to demand that “additional studies in healthy individuals are needed” (van Puyvelde 2014).
|Roasted and BBQ-ed chicken skin doesn’t just look like the worst offenders. With a whopping 18,520 kU/100g it is also the worst chicken choice you can make… quite healthy, though compared to fried (w/out oil) bacon which contains the crazy amount of 91,577 kU/100g when it was fried (Uribarri’s | data of AGEs in 549 commonly consumed foods. You can find my compilation of all >500 values by clicking on the table in the bottom line.|
Hence, a switch from a diet with plenty of grilled or roasted meats, fats, and highly processed foods, which is associated with more than 50% increased AGE-intakes over the certainly suboptimal standard diet of the average New Yorker (Uribarri 2010), to a diet that is rich in virtually AGE-free foods such as legumes, vegetables, fruits, and dairy (all three were among the lowest dAGE items in Uribarri 2010), may promote your health or, at least, reduce your risk of consuming enough AGEs to actually do harm.
By the way, the study by Uribarri et al. (2010) has a list of the AGE content of 549 commonly consumed foods ranging from “A” as in almonds (1600-1900 kU/serving, depending on whether the almonds were roasted (higher end of the AGE range) or not (lower end of the AGE range), to “T” as in Tofu (sautéed on the outside 5,289 kU/serving) – check out all the data!
Moreover, the previously cited study by Nowotny et al. reminds us that even meta-analyses can be misleading. How’s that? Well in some cases their results are dominated by a single study. As an example the researchers refer to Baye et al. (2017), where the significant effect on blood lipids the scientists detected was driven by a single study that was weighted up to 99% – “this means that this one study (out of 6) mainly influenced the result of the meta-analysis” (Nowotny 2018).
|Table 1: While certain foods may be more prone to AGE formation than others, it’s eventually what you do to your foods in your (or commercial) kitchens that is the #1 determinant of their AGE content; here, expressed in arbitrary AGE kilounits per 90 g serving for meats and 100 g serving for potatoes (Uribari 2015).|
Things are further complicated by the way(s) in which individual differences in food preparation affect the content and type of AGEs in foods; an effect that I’ve illustrated for a couple of examples in Table 1. In short, proving the “causality of dietary AGEs on health outcomes due to different diets is challenging” (Nowotny 2018) – to say the least:
“Intervention studies examining the effect of dietary AGEs are predominantly based on diets in which the cooking method was changed. To achieve differences in dietary AGE intake, diets are based on raw and steam-cooked foods on one side and on the other side on foods prepared with high cooking techniques such as grilling, roasting or frying. The latter is often associated with the normal diet. Different cooking techniques not only influence levels of dietary AGEs but also other Maillard products such as acrylamide and hydroxy-methylfurfural” (Nowotny 2018).
So, if you start paying attention to your AGE intake, your efforts to reduce your intake of the glycated proteins and fats will lead to several changes regarding the diet composition (Pouillart 2008). The latter include, but are not limited to…
Table 1: The high vs. low AGE diets were rarely as similar as reported by Pouillart et al, and even here the complex effect of their heat-reduced preparation precludes making definite statements about the contribution of AGEs to the final outcomes feasible.
decreasing kcal-density, as avoiding high-temperature cooking techniques nullifies the decrease in water content of foods so that the caloric intake of food decreases;
- increasing nutrient density, as the corresponding cooking methods such as low heat cooking or steaming preserve micro-nutrients that would be lost during regular high heat treatment; and
- limiting ‘trash fats’, i.e. those low quality, often partially oxidized oils and fats that are used during the frying process and thus inflammation and total caloric intake.
In other words: While we do have evidence that interventions that reduce our intake of dietary AGEs will lead to significant improvements in markers of overall and metabolic health, …
… we do not know how much of the beneficial effects of low-AGE diets are actually mediated by lowering the intake of AGEs and no collateral effect on food quality and quantity…
which are almost inevitable when you switch from an AGE-laden Western to a low-AGE diet, because the latter happens to be based on exactly those dietary principles of which the current evidence suggests that they have general benefits for your metabolic and cardiovascular health.
And if you feel that things aren’t complicated enough, yet, I suggest you revisit Figure 2 and remember the putative role of bioavailability and hence downstream (ill) health effects also seem to depend on the form (protein-bound vs. free) of AGEs in your food.
|Figure 3: The dAGE content of milk increases 2.7- and 3.5-fold when it’s pasteurized or sterilized (Ahmed 2005).|
Are there patterns that emerge when you look at the AGE-content of foods? Yes, you can! Here’s how: fats tend to contain more dietary AGEs (dAGE) per gram of weight,  meats will likely contribute more to overall dAGE intake because meats are served in larger portions than are fats.
“[…it] is noteworthy that even lean red meats and poultry contain high levels of dAGEs when cooked under dry heat[, which] is attributable to the fact that among the intracellular components of lean muscle there exist highly reactive amino-lipids, as well as reducing sugars, such as fructose or glucose-6-phosphate, the combination of which in the presence of heat rapidly accelerates new dAGE formation” (Uribarri 2010)
Speaking of heat,  low-heat processing is one of the keys to reducing your dAGE exposure. On the other hand, t is interesting to note that  even uncooked, animal-derived foods such as cheeses can contain large amounts of dAGEs. This is likely due to pasteurization (see Figure 3) and/or holding times at ambient room temperatures (eg, as in curing or aging processes).
|Figure 4: If you want to protect your meat from AGE-formation, vinegar or lemon juice containing marinades may limit the formation of AGEs – 1=raw beef. 2=roasted beef with no vinegar or lemon. 3=roasted beef after marinating with either vinegar or lemon for 1 hour (Uribarri 2015).|
Not all means of processing are bad, though:  Marinades, for example, can protect your steak (and other meats) from ‘AGE-ing’. Uribarri et al. (2010) observed a >50% reduction in AGE formation when beef (25 g) was roasted for 15 minutes at 150°C after pre-marinating in 10 mL vinegar (A) or lemon juice (B) for 1 hour. Moreover,  not all processed (fake) food are worse than the original: regular mayonnaise has ~50-fold more AGEs than mayonnaise imitation, for example.
When you’re cooking your foods, the  oil/fat you choose may easily make a ~50-70% difference, as it has been observed for scrambled eggs prepared with a cooking spray, margarine, or oil versus cooked with butter (details see tabular overview linked in the bottom line).
Lastly, you should remember that their name (“glycation end products”) may falsely mislead you to conclude that high carbohydrate foods contain generally more AGEs than your beloved keto-foods – often, the opposite is the case, though:  high(er) carbohydrate foods generally contain lower amounts of AGEs. As Uribarri et al. (2010) explain, this may be due to the often higher water- and/or higher antioxidant- & vitamin-content and in these foods, which may diminish new AGE formation, as well as the high prevalence of polysaccharides consisting of non-reducing sugars, which are less likely to give rise to AGEs – needless to say that they lose their protection when they are mixed and processed as potatoes in chips, crackers, cookies, and other popular snacks (e.g. biscuits had more than 10 times the amount of dAGEs found in low-fat breads, rolls, or bagels).
Why don’t we have AGE-tables or even an AGE label on the packaging? While there is no “this is why”-answer to this question, there are at least four limits to our ability to produce, verify, and use tables to calculate our personal (dietary) AGE exposure, Nowotny et al. summarize as follows:
Relative contribution of food items to dietary intake of a CML, b HMF, c AP and d acrylamide in the ICARE study on healthy adults. (Tessier 2012). Bacon is high in AGEs, but the “healthy” breakfast cereals (imho the worst food on the market, ’cause it’s AGE-loaden candy in disguise with an incredibly unwarranted health halo) and plain bread contribute much more to your AGE load.
the data analyzed the AGE content in food items with validated instrumental methods is restricted;
the current data on different AGEs in a great number of foods is limited; …
similar food items differ often in their nutritional profile so that the comparability with existing database is difficult; and …
the AGE content in food might depend on small variations of food processing making it difficult to generalize measured AGE levels
You can find some information about the worst and least offenders, as well as the influence of processing techniques in the red box above. Until corresponding data is included in commonly used calorie counting software, it will yet be difficult to monitor your individual exposure on a daily basis.
- Ahmed, Naila, et al. “Assay of advanced glycation endproducts in selected beverages and food by liquid chromatography with tandem mass spectrometric detection.” Molecular nutrition & food research 49.7 (2005): 691-699.
- Aljahdali, Nesreen, and Franck Carbonero. “Impact of Maillard reaction products on nutrition and health: Current knowledge and need to understand their fate in the human digestive system.” Critical reviews in food science and nutrition 59.3 (2019): 474-487.
- Baye, Estifanos, et al. “Consumption of diets with low advanced glycation end products improves cardiometabolic parameters: Meta-analysis of randomized controlled trials.” Scientific reports 7.1 (2017): 2266.
- Chaudhuri, Jyotiska, et al. “The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality.” Cell metabolism 28.3 (2018): 337-352.
- Clarke, Rachel, et al. “Dietary advanced glycation end products and risk factors for chronic disease: a systematic review of randomised controlled trials.” Nutrients 8.3 (2016): 125.
- Fleming, Thomas H., et al. “Reactive metabolites and AGE/RAGE-mediated cellular dysfunction affect the aging process–a mini-review.” Gerontology 57.5 (2011): 435-443.
- Förster, Anke, Yvonne Kühne, and Henle, Thomas. “Studies on absorption and elimination of dietary maillard reaction products.” Annals of the New York Academy of Sciences 1043.1 (2005): 474-481.
- Nowotny, Kerstin, et al. “Dietary advanced glycation end products and their relevance for human health.” Ageing research reviews (2018).
- Palanissami, Gowri, and Solomon FD Paul. “RAGE and Its Ligands: Molecular Interplay Between Glycation, Inflammation, and Hallmarks of Cancer—a Review.” Hormones and Cancer 9.5 (2018): 295-325.
- Peyroux, J., and M. Sternberg. “Advanced glycation endproducts (AGEs): pharmacological inhibition in diabetes.” Pathologie Biologie 54.7 (2006): 405-419.
- Pouillart, Philippe, et al. “Strategy for the study of the health impact of dietary Maillard products in clinical studies: the example of the ICARE clinical study on healthy adults.” Annals of the New York Academy of Sciences 1126.1 (2008): 173-176.
- Prasad, Kailash, and Manish Mishra. “AGE–RAGE Stress, Stressors, and Antistressors in Health and Disease.” International Journal of Angiology 27.01 (2018): 001-012.
- Scheijen, Jean LJM, et al. “Dietary intake of advanced glycation endproducts is associated with higher levels of advanced glycation endproducts in plasma and urine: The CODAM study.” Clinical Nutrition 37.3 (2018): 919-925.
- Shahab, Uzma, et al. “The receptor for advanced glycation end products: A fuel to pancreatic cancer.” Seminars in cancer biology. Vol. 49. Academic Press, 2018.
- Sparvero, Louis J., et al. “RAGE (Receptor for Advanced Glycation Endproducts), RAGE ligands, and their role in cancer and inflammation.” Journal of translational medicine 7.1 (2009): 17.
- Uribarri, Jaime, et al. “Advanced glycation end products in foods and a practical guide to their reduction in the diet.” Journal of the American Dietetic Association 110.6 (2010): 911-916.
- Uribarri, Jaime, et al. “Dietary advanced glycation end products and their role in health and disease.” Advances in nutrition 6.4 (2015): 461-473.
- Tessier, Frédéric J., and Ines Birlouez-Aragon. “Health effects of dietary Maillard reaction products: the results of ICARE and other studies.” Amino acids 42.4 (2012): 1119-1131.
- Yamagishi, S., et al. “Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients.” Medical hypotheses 64.6 (2005): 1208-1210.
- Yamagishi, Sho-ichi, Takanori Matsui, and Kei Fukami. “Role of receptor for advanced glycation end products (RAGE) and its ligands in cancer risk.” Rejuvenation research 18.1 (2015): 48-56.
- Yamagishi, Sho-ichi, and Takanori Matsui. “Pathologic role of dietary advanced glycation end products in cardiometabolic disorders, and therapeutic intervention.” Nutrition 32.2 (2016): 157-165.