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Can foods cause chronic disease?

By Victor Katch
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Beware of ‘advanced glycation end’ products (AGEs)

Most chronic diseases incubate over years, not overtly expressing until reaching a critical horizon, often in mid-to-late adulthood. Only after years of incubating do the invading forces unleash their devastation. Whether it’s diabetes, heart disease, Alzheimer’s, sarcopenia, arthritis, or any of the other chronic diseases, we are shocked when we “suddenly” become afflicted. With surprise and fear we cry, “How did this happen to me?”

Guess what? Precursors for most chronic diseases have been there for years, just waiting to erupt.

Inflammation

Blocked artery, stock

Inflamed arteries are common in heart disease. When fats build up in coronary artery walls, the body produces inflammatory chemicals which can, over time, trigger a blood clot that can cause a heart attack or stroke.

We now understand that various inflammatory processes – part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, irritants, and toxins – commonly represent the “silent” markers of chronic disease.

The word “inflammation” traces back to the Latin for “set afire.” In some conditions, like rheumatoid arthritis, there are expressions of heat, pain, redness, and swelling. In other cases, like early-onset aging, heart disease, Alzheimer’s, and type 2 diabetes, inflammatory signs are not so obvious. Without sophisticated medical tests, it’s difficult or impossible to know the full extent of inflammatory processes that eventually lead to expressions of a chronic disease.

As these long-term inflammatory processes incubate in the body, waiting to be vented, they may begin to reveal themselves as diabetic-induced shock, signs of early onset Alzheimer’s, or symptoms of inflammatory bowel disease (ulcerative colitis and/or Crohn’s disease). Or, they could manifest as joint pain.

Toxins as inflammatory agents

Toxicity represents the degree to which a substance, usually a chemical or a mixture of substances, can damage an organism (animal, bacterium, or plant), or a substructure of an organism, such as a cell (cytotoxicity) or an organ like the liver (hepatotoxicity).

Effects of a toxin are dose-dependent. Thus, even water can lead to water intoxication (hyponatremia) when taken in too high a dose. Toxicity is species-specific, making cross-species analyses problematic.

There are four types of recognized toxins: chemical, biological, physical, and radiation.

  • Chemical toxins include nonliving substances such as lead, mercury, and chlorine gas, and such living compounds as methyl alcohol (Methanol — CH₃OH), most medications, and poisons from living species (like snakes).
  • Biological toxins include disease-causing microorganisms and parasites (termed pathogens) that are difficult to measure because their “threshold dose” differs wildly among individuals.
  • Physical toxins include physical substances that interfere with biological processes. These include substances like coal dust, asbestos fibers, or silicon dioxide. Asphyxiant gases, like smog, also are considered physical toxicants.
  • Radiation toxins include some weakly radioactive substances, such as uranium. These are classified as chemical toxicants.

Advanced glycation end products (AGEs) are inflammatory toxins

Advanced glycation end products, or AGEs, represent an assorted group of large molecules formed by the process of glycation, which involves bonding of a sugar molecule, such as glucose or fructose, to a protein or fat molecule without help from enzymes. The resulting macromolecules (AGEs) are considered biologic toxins that associate with such issues as diabetes, aging, chronic kidney disease (CKD), anemia, poor skeletal muscle strength and performance, cardiovascular disease, and brain and bone disorders, just to name a few. The figure below shows the many AGEs-induced chronic-disease conditions that reduce longevity.

Glycation

Humans are exposed to two main sources of AGEs: endogenous AGEs formed within the body, and exogenous AGEs ingested from foods.

Endogenous AGEs

There is not much we can do about endogenous AGEs that generate mainly in the bloodstream from small proportions of the absorbed dietary simple sugars glucose, fructose, and galactose. Since fructose has about 10 times the glycation activity of glucose, it is believed to contribute more than glucose to endogenous AGEs’ inflammatory processes. Some endogenous AGEs are benign, but others are more reactive than the sugars from which they are derived, and thus are implicated in many age-related chronic diseases. For example, elevated endogenous AGEs have been implicated in cardiovascular diseases (where endothelium, fibrinogen, and collagen are damaged); Alzheimer’s disease (where amyloid proteins are side-products of reactions progressing to AGEs); cancer (where acrylamide and other AGE side-products release); peripheral neuropathy (where myelin – a fatty white substance that surrounds the axon of some nerve cells is attacked); and other sensory losses such as deafness (due to demyelination).

Exogenous AGEs

Grilling sausages, stockA diet consisting of high levels of animal meats, sugar, and fat represents the major source of exogenous AGEs. Some AGEs are formed when food cooks at elevated temperatures, i.e., during deep-frying, broiling, roasting, or grilling. AGEs also form during high-temperature processing of certain foods such as pasteurized dairy products, cheeses, sausages, and processed meats, as well as commercial breakfast cereals. Glycation processes also may contribute to formation of acrylamide, a potential carcinogen formed during deep-fried cooking of certain foods, particularly potatoes (think french fries).

Until recently, it was thought that exogenous glycation-derived AGEs were negligible contributors to inflammation and disease development. This conclusion was almost entirely based on animal research. Recent research on humans, however, has shown this not to be the case.

Moreover, food manufacturers have added AGEs to foods in the form of flavor enhancers and colorants to improve appearance. Foods with significant browning, caramelization, or directly added preformed AGEs can be high in these compounds. Foods with very high exogenous AGEs include donuts, barbecued meats, cake, and dark-colored soda pop.

Reducing AGEs promotes healthy aging and longevity

Try to reduce or eliminate foods and cooking methods that associate with the highest levels of AGEs. In this respect, a plant-based diet appears optimal.
The number of scientific publications on AGEs has increased astronomically in the past decade. There is now convincing human evidence from in vitro studies, animal models, clinical and pathological studies, epidemiological human cohort studies of aging, and human clinical trials that limiting AGEs promotes reduction in inflammation and oxidative stress, and thus improves health and longevity.

The table below is sourced from an article in the Journal of the American Dietetic Assn. It presents examples of the AGE enzyme activity for different foods. AGE enzyme activity expresses as kilounits (kU) per 100 grams of a food (column 1) or as AGE enzyme activity in kU units per food serving (column 2). The serving size expresses as grams (g) for solids; millileters (mL) for liquids. (A more comprehensive list can be found at the Journal of the American Dietetic Assn.Not surprisingly, on a comparative basis, animal-based foods contain the most exogenous AGE activity.

FATS AGEs per 100g Serving Size (g) AGEs per serving
Almonds, roasted 6,650 30 1,995
Avocado 1,577 30 473
Butter, sweet cream, unsalted (Land O’ Lakes) 23,340 5 1,167
Margarine (tub) 17,520 5 876
Mayonnaise 9,400 5 470
Oil, sesame 21,680 5 1,084
BEEF AGEs per 100g Serving Size  AGEs per serving
Frankfurter, broiled 450 degrees, 5 min 11,270 90 10,143
Hamburger (McDonald’s) 5,418 90 4,876
Steak, broiled 7,479 90 6,731
Steak, (pan-fried w/olive oil) 10,058 90 9,052
CHICKEN AGEs per 100g Serving Size  AGEs per serving
Breast with skin, 450 degrees, 45 min. 8,244 90 7,420
Back/thigh w/skin, roasted, BBQ 18,520 90 16,668
Leg w/skin, roasted 10,997 90 9,897
Thigh, w/skin, roasted 11,149 90 10,034
TURKEY AGEs per 100g Serving Size  AGEs per serving
Burger, pan-fried with cooking spray 7,968 90 7,171
Burger, pan-fried with 5ml Canola oil 8,251 90 7,426
PORK AGEs per 100g Serving Size AGEs per serving
Bacon, fried, 5 mins, no added oil 91,577 13 11,905
Bacon, microwaved, 2 slices, 3 min 9,023 13 1,173
Sausage, beef/pork links, pan-fried 5,426 90 4,883
SEAFOOD AGEs per 100g Serving Size AGEs per serving
Salmon, filet, broiled 3,347 90 3,012
Salmon, filet, poached 2,292 90 2,063
Shrimp, marinated, raw 1,003 90 903
Shrimp, marinated, grilled on BBQ 2,089 90 1,880
Trout, baked, 25 min 2,138 90 1,924
CHEESE AGEs per 100g Serving Size  AGEs per serving
American, white, processed 8,677 30 2,603
Feta, Greek, soft 8,423 30 2,527
Parmesan, grated (Kraft) 16,900 15 2,535
Swiss, processed 4,470 30 1,341
SOY AGEs per 100g Serving Size  AGEs per serving
Burger (Boka burger) microwaved, 1.5 min 67 30 20
Burger (Boka burger) skillet, spray, 5 min 100 30 30
Tofu, broiled 4,107 90 3,696
Tofu, sauteed 5,877 90 5,289
EGGS AGEs per 100g Serving Size  AGEs per serving
Fried, one large 2,749 45 1,237
Scrambled, one large, pan, high, w/cooking spray, 1 min 117 30 35
Scrambled, pan, high, w/margarine, 1 min 123 30 37
Scrambled, pan, medium-low, w/butter, 2 min 167 30 50
BREADS AGEs per 100g Serving Size  AGEs per serving
Bagel, toasted 167 30 50
Biscuit (McDonald’s) 1,470 30 441
100% whole wheat 53 30 16
White, Italian 23 30 7
Croissant, w/butter, (Starbucks) 1,113 30 334
Dinner roll 77 30 23
BREAKFAST CEREALS AGEs per 100g Serving Size  AGEs per serving
Cinnamon Toast Crunch (General Mills) 1,100 30 330
Corn Flakes (Kellogg’s) 233 30 70
Corn Flakes, Honey Nut (Kellogg’s) 320 30 96
Corn Flakes, Sugar Frosted (Kellogg’s) 427 30 128
Cream of Wheat, instant/prepared (Nabisco) 108 175 189
Fiber One (General Mills) 1,403 30 421
Rice Krispies (Kellogg’s) 2,000 30 600
Oatmeal, instant, dry (Quaker Oats) 13 30 4
BREAKFAST FOODS AGEs per 100g Serving Size  AGEs per serving
French toast, frozen, microwaved (Aunt Jemima) 603 30 181
Hot cakes (McDonald’s) 243 30 73
Pancake from mix 823 30 247
Pancake, frozen, toasted (General Mills) 2,263 30 679
Waffle, frozen, toasted (Kellogg’s) 2,870 30 861
GRAINS & LEGUMES AGEs per 100g Serving Size AGEs per serving
Beans, red kidney, raw 116 100 116
Pasta, cooked, 12 min 242 100 242
Pasta, spiral 245 100 245
Rice, white, quick-cooking, 10 min 9 100 9
STARCHY VEGETABLES AGEs per 100g Serving Size  AGEs per serving
Corn, canned 20 100 20
Potato, sweet, roasted, one hour 72 100 72
Potato, white, boiled, 25 min 17 100 17
Potato, white, roasted 45 min, 5ml oil per svg 218 100 218
Potato, white, french fries (McDonald’s) 1,522 100 1,522
SNACKS AGEs per 100g Serving Size  AGEs per serving
Corn chips (Dorito’s) 503 30 151
Potato chips, baked (FritoLay) 450 30 135
Nacho cheese pretzel Combos (M&M Mars) 1,680 30 504
Chocolate Teddy Grahams (Nabisco) 1,647 30 494
Goldfish crackers (Pepperidge Farms) 2,177 30 653
Air-popped popcorn w/butter 133 30 40
Microwave popcorn, fat free (PopSecret/General Mills) 33 30 10
COOKIES, CAKES, PASTRIES AGEs per 100g Serving Size  AGEs per serving
Granola bar, chocolate chunk, soft (Quaker) 507 30 152
Rice Krispies Treat (Kellogg’s) 1,920 30 576
Cookie, biscotti, vanilla almond (Starbuck’s) 3,220 30 966
Cookie, chocolate chip (Nabisco) 1,683 30 505
Cookie, Oreo (Nabisco) 1,770 30 531
Donut, glazed, devil’s food cake (Krispy Kreme) 1,407 30 422
Donut, chocolate-iced, cream-filled (Krispy Kreme) 1,803 30 541
Fruit rollup, “Sizzlin’ red” (General Mills) 980 30 294
Apple pie, individual, baked (McDonald’s) 637 30 191
Pop tart, microwave, 3 secs, high (Kellogg’s) 243 30 73
FRUITS AGEs per 100g Serving Size  AGEs per serving
Apple, baked 45 100 45
Banana 9 100 9
Cantaloupe 20 100 20
Fig, dried 2,663 30 799
Plums, dried, pitted prunes (Sun-Maid) 167 30 50
Raisin from Post Raisin Brain (Kellogg’s) 120 30 36
VEGETABLES AGEs per 100g Serving Size  AGEs per serving
Carrots, canned 10 100 10
Celery 43 100 43
Cucumber 31 100 31
Eggplant, grilled, marinated w balsamic vinegar 256 100 256
Eggplant, raw, marinated w balsamic vinegar 116 100 116
Green beans, canned 18 100 18
Portabella mushroom, raw, marinated w balsamic 129 100 129
Onion 36 100 36
Tomato 23 100 23
Tomato sauce (Del Monte Foods) 11 100 11
Grilled broccoli, carrots and celery 226 100 226
Grilled peppers and mushrooms 261 100 261
MILK and MILK PRODUCTS AGEs per 100g Serving Size (mL)  AGEs per serving
Swiss Miss hot cocoa packet, prepared 262 250 656
Swiss Miss hot cocoa packet, prepared, sugar-free 204 250 511
Milk, fat-free 1 250 2
Milk, whole, 4% fat 5 250 12
Pudding, instant, chocolate, skim milk 1 120 1
Yogurt, cherry (Dannon) 4 250 10
FRUIT JUICES AGEs per 100g Serving Size (mL) AGEs per serving
Apple 2 250 5
Orange 6 250 14
Orange, from fresh fruit 0 250 1
Orange, with calcium 3 250 8
Fruit pop, frozen (Dole) 18 60 11
Honey 7 15 1
Sherbet, strawberry (Edy’s) 2 125 3
COMBINATION FOODS AGEs per 100g Serving Size  AGEs per serving
Bacon/egg/cheese biscuit (McDonald’s) 2,289 100 2,289
Big Mac (McDonald’s) 7,801 100 7,801
Cheeseburger (McDonald’s) 3,402 100 3,402
Chicken McGrill (McDonald’s) 5,171 100 5,171
Double quarter pounder w/cheese (McDonald’s) 6,283 100 6,283
Filet-o-fish (McDonald’s) 6,027 100 6,027
Hummus w/garlic and scallions 884 100 884
Hummus w/vegetables 487 100 487
Veggie burger, 400 degrees F (Amy’s Kitchen) 198 100 198
CHOCOLATE AGEs per 100g Serving Size AGEs per serving
Hershey’s Special Dark Chocolate (Hershey Co.) 1,777 30 533
M&Ms, milk chocolate (Mars) 1,500 30 450
Reese’s Peanut Butter Cup (Hershey Co.) 3,440 30 1,032
Snickers (Nestle) 263 30 79
CONDIMENTS AGEs per 100g Serving Size AGEs per serving
Pickle, bread and butter 10 30 3
Ketchup 13.33 15 2
Mustard 0 15 0
Soy sauce 60 15 9
BEVERAGES AGEs per 100g Serving Size (mL) AGEs per serving
Budweiser beer, (Anheuser Busch) 1.2 250 3
Breast milk, fresh 6.67 30 2
Breast milk, frozen 10 30 3
Coca-Cola Classic 2.8 250 7
Coffee w/milk and sugar 2.4 250 6
Coffee, drip method 1.6 250 4
Pepsi, diet (PepsiCo) 2.8 250 7
Pepsi, diet, caffeine-free (PepsiCo) 2.4 250 6
Pepsi, regular (PepsiCo) 2.4 250 6
Rum, Baccardi Superior (80 proof) 0 250 0
Sprite (Coca-Cola Co.) 1.6 250 4
Tea, teabag (Lipton) 2 250 5
Vodka, Smirnoff (80 proof) 0 250 0
Whiskey, Dewars, white label .4 250 1
Wine, Pinot Grigio 32.8 250 82
Wine, Pinot Noir 11.2 250 28

References

    • Clarke, R.E., et al. “Dietary advanced glycation end products and risk factors for chronic disease: A systematic review of randomised controlled trials.” Nutrients, 2016; 8(3):125.
    • DeChristopher, L.R., et al. “Perspective: The paradox in dietary advanced glycation end products research — The source of the serum and urinary advanced glycation end Products is the intestines, not the food.” Advances in Nutrition, 2017 Sept. 15; 8(5):679.
    • Di Pino, A., et al. “High intake of dietary advanced glycation end products is associated with increased arterial stiffness and inflammation in subjects with type 2 diabetes.” Nutrition, Metabolism, and Cardiovasc Diseases. 2017; Epub; Jul 8.
    • Uribarri, J., et al. “Dietary advanced glycation end products and their role in health and disease.” Advances in Nutrition. 2015; 15:6(4):461.
    • Uribarri, J., et al. “Advanced glycation end products in foods and a practical guide to their reduction in the diet.” Journal of the American Dietetic Association. 2010; 110(6):911–16.e12.
    • Vlassara, H. “Identifying advanced glycation end products as a major source of oxidants in aging: Implications for the management and/or prevention of reduced renal function in elderly persons.” Seminars in Nephrology  .2009;29(6):594-603.
    • www.nutritionfacts.org/video/glycotoxins/
    • Yacoub, R., et al. “Advanced glycation end products dietary restriction effects on bacterial gut microbiota in peritoneal dialysis patients: A randomized open-label controlled trial.” PLoS One. 2017; 12(9):e0184789.
    • Yang X. et al. CD36 in chronic kidney disease: novel insights and therapeutic opportunities. Nat Rev Nephrol.2017 Sep 18. doi: 10.1038/nrneph. 2017.126. [Epub ahead of print].

Editor’s Note: This article was edited after publication to clarify the contents of the chart about the ways AGEs present in foods. In addition, the term for ‘water intoxication’ has been corrected.

Victor Katch

Victor Katch

VICTOR KATCH has been active in the exercise, nutrition, and weight control arena for more than 40 years at the University of Michigan. He earned his undergraduate degrees in international relations (political science) and physical education (kinesiology) from California State University at Northridge. He also did undergraduate work in international relations at the prestigious University of Uppsala in Sweden. Katch's graduate degrees are from the University of California, Berkeley. He is a professor in movement science in the School of Kinesiology. He has three children and five grandchildren, and is an avid exerciser who enjoys year-round walking and jogging with his wife, Heather, and playing golf whenever possible, weather permitting.

COMMENTS

  • Larry Gagnon - 1976 1968

    Is there any data on how many AGEs on a daily or yearly or life-time basis cause any specific disease or show a statistic correlation with any specific disease?

    The more that I read about food, the more that I think the best alternative is to stop eating. It seems that every food is named in some article as potentially toxic.

    I am not sure that attempting to minimize ingestion of all such potentially toxic foods will result in living 100 years, but I am rather sure that any such attempt will make life feel that long.

    Reply

  • Kara Lynn - 1989

    Thank you for this eye-opening article. Could you please explain or direct me to further information about eggs. The huge difference in AGEs between fried and scrambled eggs is difficult to make sense of. It would also be interesting to know about microwaved scrambled eggs – my preferred method of cooking. What about hard-boiled, a regular lunch-box item for many children. Thank you.

    Reply

  • Ruth Blackburn - 1993

    Please note that the correct association that published the article with the table is The American Dietetic Association now called The Academy of Nutrition and Dietetics. Thank you.

    Reply

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