The Rage of AGE (Advanced Glycation End Products) and Your Pet's Fight Against It

advanced glycation end products acrylamide and hmf are loaded in kibble and canned pet foods due to starch and they cause disease in pets

AGEs have you, your dog and your cat surrounded. But you can fight your way out.

Nutritionists agree that dogs and cats have no biologic need for starch. Yet, the average bag of grain-based dog food is over 50% carbs, largely from insulin-raising, pesticide-laden corn.  Grain-free dog food is not much better. It averages 40% sugars and starches.  Despite cats being obligate carnivores, the average cat food contains 1.3x more starch than protein.

Advanced Glycation End Products Increase Likelihood of Cancer Diabetes Dementia Cardiovascular Disease Allergies and Obesity in Dogs

Many pet parents understand what their bodies would look like if 50% of their daily diets came from pasta.  Making healthy choices for pets is lightyears harder, though. 

Here’s why: 

  1. Carbs are not printed on the nutritional labels of pet food.
  2. The pretty pictures on pet food packaging are allowed to mislead consumers.
  3. Comparing a kibble to a canned to a freeze dried to a frozen requires a calculator.
  4. The legal definition of an ingredient (e.g. “corn” or "chicken") on a pet food label is not the same legal definition as it is for human food. Personal opinion: that’s crazy.

It’s the job of AAFCO, the FDA and the state agricultural regulators to protect parents and pets, yet they consistently (and often overwhelmingly) fail them.

There's another problem with all that starch beyond its association to blood sugar and insulin.  Here comes the Good the Bad and the Ugly.

First the Bad: Glycotoxins

Advanced glycation end products (“AGEs”), also known as glycotoxins, are a diverse group of highly oxidant compounds with pathogenic significance in aged-chronic disease, including cancer, diabetes, cardiovascular disease, neurodegenerative disease, and others.  AGEs are tightly tied to chronic low-level inflammation, metabolic syndrome, and diet-related pathologies.  

AGEs are produced by chemical reactions that happen inside the body when we eat certain foods.  AGEs are also produced outside then body and then ingested in the foods we eat.  

Dogs, cats, humans, you name it, produce AGEs endogenously (i.e. inside the body) when a reducing sugar binds to a free amino acid group of macromolecules.  This happens when you digest starch.  The amino acid, asparagine found largely in corn, potatoes, rice, soy, beans, peas, and other legumes and whole grains for example, produces AGEs when it is digested. 

What is the difference between Oxidants, Reactive Oxygen Species, and Oxidative Stress

Health conditions such as hyperglycemia and oxidative stress can increase AGE formation, contribute to the aging processes, and exacerbate disease.

Outside the body (“exogenously”), AGEs are formed when you cook certain foods a certain way.   When you bake or fry sugars and amino acids at high temperatures AGEs are formed.  We recognize this as a change in color and flavor that occurs during caramelization. In food processing, it’s called the Maillard reaction.   AGEs can also be formed at normal room temperatures during storage.  (More on that in a moment.)

There are many types of AGEs.  Acrylamide and HMF (hydroxymethylfurfural) are two types. 

Acrylamide is a well-recognized genotoxin and classified by IARC as a probable carcinogen. Several animal studies have shown it to be a multi-organ carcinogen. 

HMF has been shown to be cytotoxic, genotoxic, mutagenic and carcinogenic in animals, and the toxic effects of HMF can be metabolically enhanced via some of its metabolites - namely SMF (sulfuric acid esther 5-sulfo-oxymethylfurfural).  Moreover, evidence shows that the more HMF one consumes, the higher the absorption rate.

Acrylamide and HMF can be regarded as the most important heat-induced contaminants in food and another reason why starch is pet food enemy #1.

So how are eating, cooking and storing starchy foods tied to AGE formation and disease?

When the Maillard reaction occurs during cooking, acrylamide forms mostly from a reduction of asparagine – the amino acid found richly in potatoes, corn, and other crops noted earlier – or of wheat gluten.    

HMF is formed in many ways.  HMF occurs during the Maillard reaction.  HMF can also be formed at low temperatures in a low pH (acidic) environment. It occurs when you dehydrate fruits and starchy vegetables (i.e. via sugar dehydration in an acid medium).  Dehydrated is how big pet food manufacturers buy most plant-based ingredients. 

HMF an Advanced Glycation End Product Is Formed In Cooking Dry Storage Dehydration and in Digestion of Starchy Foods

HMF is clearly and efficiently generated under dry storage of materials containing fruits, starchy vegetables, and nuts (or more specifically their sugars sucrose and fructose) just like that big bag of kibble that sits on a store shelf or in a pantry.  High moisture foods in metallic containers cause HMF formation too – just like that can of cat food. 

The formation of HMF is an indicator of storage conditions, food quality and the occurrence of contamination during Maillard reactions or dehydration. In fact, human toothpaste can be recalled for improper temperature storage because of the formation of contaminants like HMF, but pet food cannot and is not.

There also appears to be a high correlation between HMF levels and oil concentration -- meaning higher fat foods exposed to heat have generated more HMF than their defatted counterparts.

So how do AGE's cause aging?

STEP 1:  Protein-bound and free AGEs can be released in the gut by digestive enzymes and intestinal microbiota.  

STEP 2:  Once released, these AGEs interact with the gut’s mucosal immune system by binding to several receptors expressed on immune cells. Appropriately named RAGE (Receptor of AGEs) being one of these receptors.

Metabolism of Advanced Glycation End Products and how they trigger the immune system to cause cancer diabetes allergies cardiovascular disease dementia cognitive dysfunction

STEP 3:  Innate immune cells become activated through a pathway (known as NF-kB) and produce reactive oxygen species (ROS), and cytokines. (Cytokines are cell-signaling molecules released by innate immune cells that help communicate and modulate cellular response to inflammation, infection, trauma, and toxins.)

STEP 4: Together these activities may skew T-cell activation and contribute to oxidative stress, systemic inflammation, premature aging, and a broad array of diseases.

Is your dog allergic to chicken?  Maybe it’s the AGEs that’s causing the allergy and not the chicken.

There are a lot of interesting human and animal studies on the effects of AGEs.  Some studies that stand out show how these Maillard reaction products:

  1. Cross-link proteins contributing to a range of problems like digestibility, immunogenicity and allergenicity issues in the general population. When proteins are cross-linked, the body does not recognize them.  This can cause GI distress, allergic reactions and immune system dysfunction.  Maybe resolution of your dog’s food allergy can be achieved by eliminating the AGEs in her diet.  Elimination of AGEs may be one reason why dogs can eat a protein (like chicken) in a minimally processed, gently cooked, or raw diet that would otherwise cause an inflammatory response in a kibble or canned feed.
  2. Cause collagen-related vascular complications in diabetics through cross-linking of proteins too. This is a mechanism through which AGEs contribute to poor circulation in diabetics.
  3. Increase gut permeability. Leaky gut initiates and perpetuates disease everywhere in the body, so it is definitely a condition that all beings want to defend against.
  4. Affect bioavailability of minerals – decreasing absorption of calcium, phosphorous and iron in particular.

Good news: reducing AGEs promotes healing.

Metabolic Syndrome is a cluster of conditions that increase the risk of heart disease, stroke, and diabetes. Metabolic syndrome includes high blood pressure high blood sugar excess body fat around the waist and abnormal cholesterol levels

Multiple studies on aging dogs have shown increased tissue levels of AGEs in dogs with diabetes, cataracts, osteoarthritis, neurodegenerative canine cognitive dysfunction syndrome, vascular dysfunction, and atherosclerosis. Improvements in these conditions are shown to occur when dietary AGEs are restricted. 

This is the flash of Good News.  Reducing AGE formation leads to healing. 

So how much AGEs do pets consume?  Sorry, that's the Ugly part.

A 2021 study out of Japan looked at 51 dog foods and calculated that the daily intake of acrylamide of dogs eating kibble is approximately four times higher than that of humans on a μg/kg basis. 

The Glycotoxin AGE HMF levels in canned dog food are 169 times greater than human food and kibble is 122 times greater

A 2018 study out of the Netherlands (by MARS Petcare) analyzed 67 kibble and canned dog and cat foods for growth and adult maintenance.  They found that the average daily intake of HMF in dogs eating canned food was 169 times higher than humans, and kibble-eating dogs were exposed to 122x more HMF than humans. 

The average daily intake for cats eating a canned food was 56x greater than human.  Cats eating kibble had exposures 39x greater than humans.

Why are AGEs in pet food so much worse than human food?

Ultra-processed carbs is the short answer. 

The MARS Petcare study says:

  1. HMF was higher in pet foods that were higher in carbs and lower in protein.
  2. HMF also occurs in a certain ratio with CML (carboxymethyllysine). CML is another AGE that is formed in numerous ways including metal-catalyzed oxidation of polyunsaturated fatty acids in the presence of protein.  (Note to self: don’t eat canned food.)
  3. Pre-processing of ingredients with heat increases AGEs. Most ingredients that go into kibble and canned products are heat treated.  Proteins and fats are rendered with heat; starches are gelatinized with heat; and fruits, vegetables, proteins and dairy are dehydrated with heat. 
  4. Processing plays a huge role. Once all those rendered, gelatinized, and dehydrated ingredients are put into the kibble extrusion or canning process, they are subject to MORE heat and pressure. Canned foods are heated until sterilized -- until the center of the can reaches 250 degrees F.  Kibble is processed at up to 400 degrees under pressure, then extruded and dried under heat, and then sprayed with a heated fat to make it palatable. 

The ingredients in the average bag of kibble are heated four to six times.  With all this processing comes AGEs and nutrient destruction. 

So how do you reduce your dog's or cat’s exposure to AGEs and promote a healthier, longer life?

Replacing as little as 10% to 20% of a kibble, canned, or sausage/roll-packed diet with fresh, whole non-starchy foods has a positive impact on a pet’s body.

You can swap out 10% of that diet for some lightly steamed dark leafy or cruciferous greens like broccoli, spinach, kale or Swiss chard.

Or you can replace 10% or more of that diet with a low glycemic, human grade, gently cooked pet food that’s complete and balanced.   You would want to pick a food that’s high protein, low starch, and moderate fat. 

Replacing as little as 10% of an ultra-processed pet food like kibble or canned with gently cooked human grade whole foods has a positive impact on a dog's body

You also want a pet food where the gentle cooking uses a method like steam that does not generate AGEs, where the ingredients are added to the recipe fresh and whole (not preprocessed). and where the fat additions (like fish oil) are not heated.

Goodness Gracious makes five recipes for dogs just like this.  They’re high protein, rich in healthy greens, low starch, and with a glycemic load of 1.