How (and When) Cooking Food Causes Inflammation

By Cyrus Khambatta, PhD

You've seen it a thousand times.

A steak hits a screaming-hot grill. Bread slides into a toaster. Marshmallows turn golden over a campfire.

That deep, caramelized browning – the one that makes food smell incredible and taste even better – is the result of a well-known chemical reaction called the Maillard reaction.

Named after French chemist Louis-Camillard Maillard, who first described it in 1912, this reaction occurs when sugars react with amino acids under high heat.

It's the reason a seared steak tastes different from a boiled one.

It's the reason toast has more flavor than bread.

But here's what most people don't realize: this exact same reaction happens inside your body. And when it does, it doesn't create flavor – it creates cellular dysfunction.

The compounds produced by this reaction are called Advanced Glycation Endproducts, or AGEs. And the research suggests they're one of the most underappreciated drivers of chronic inflammation, insulin resistance, and cardiovascular disease in the modern world.

What Are AGEs?

At the molecular level, AGEs form when a sugar molecule bonds to a protein or a lipid without the help of an enzyme – a process called non-enzymatic glycation. This can happen in two ways:

1. Exogenously (in your food)

When you cook food at high temperatures with low moisture – think frying, grilling, broiling, roasting – the Maillard reaction accelerates, and AGEs form in abundance.

As I explain in Mastering Diabetes, this is what gives food its "tasty browned quality". The higher the heat and the drier the cooking environment, the more AGEs are produced.

2. Endogenously (inside your body)

AGEs also form internally when excess glucose in the bloodstream reacts with circulating proteins and lipids.

This process is remarkably similar to what happens during the formation of glycated hemoglobin (HbA1c) – the lab marker your doctor uses to assess long-term blood glucose control.

Think of it this way: your A1c test is literally measuring how much sugar has "stuck" to your hemoglobin proteins over the past 90 days.

AGEs are the result of that same sugar-coating process happening to proteins and lipids – in your blood vessels, your nerves, your kidneys, your eyes.

The mechanism is the same. The scale is just much larger.

Which Foods Contain the Most AGEs?

In 2010, researchers at the Mount Sinai School of Medicine conducted one of the most comprehensive analyses of AGE content in food ever published. They tested nearly 550 commonly consumed foods and measured their AGE levels using carboxymethyllysine (CML) as a marker.

Foods with the highest AGE content were consistently animal-derived products – beef, cheese, poultry, pork, fish, and eggs – especially when cooked using dry-heat methods.

In contrast, carbohydrate-rich plant foods – grains, legumes, vegetables, and fruits – contained the lowest AGE levels, even after cooking.

The data suggests that the primary determinants of AGE content in food are: nutrient composition (protein and fat generate more AGEs than carbohydrates), cooking temperature, duration of heat exposure, and moisture level.

As Uribarri et al. demonstrated, dry heat promotes new AGE formation by 10- to 100-fold above the uncooked state across food categories.

This has significant implications for popular dietary trends. Diets that emphasize high consumption of grilled, fried, or roasted animal products – including many ketogenic and carnivore protocols – may inadvertently expose people to very high AGE loads.

I refer to blackened, char-broiled, or heavily grilled foods as "dirty fuel." When you consume dirty fuel, you end up generating free radicals that insult the mitochondria. This is internal metabolic inflammation.

Even something as simple as nuts and seeds matters here. Most nuts on the market are toasted, which may taste better, but it's healthier to eat raw nuts and seeds to reduce our exposure to advanced glycation endproducts.

How AGEs Trigger Chronic Inflammation

What happens after AGEs accumulate in tissues?

AGEs interact with a specific cell-surface receptor called the Receptor for Advanced Glycation Endproducts (RAGE).

RAGE is a pattern-recognition receptor expressed on a wide variety of cell types including endothelial cells, immune cells, neurons, and smooth muscle cells.

When AGEs dock to RAGE receptors, they activate a downstream signaling cascade centered on NF-κB – a master transcription factor that regulates the expression of pro-inflammatory genes.

This activation leads to the production of reactive oxygen species (ROS), pro-inflammatory cytokines like TNF-α and IL-6, and adhesion molecules like VCAM-1 that promote immune cell recruitment to tissues.

What makes this pathway particularly concerning is its self-amplifying nature.

NF-κB activation doesn't just produce inflammatory mediators – it also upregulates the expression of RAGE itself. This creates a positive feedback loop: more RAGE expression leads to more AGE binding, which leads to more NF-κB activation, which leads to more RAGE expression.

The research describes this as a "vicious cycle" that perpetuates oxidative stress and chronic, low-grade inflammation.

A 2024 review published in Pharmacological Research described the AGE-RAGE axis as a central driver of chronic inflammation across multiple disease states, including diabetes, cardiovascular disease, neurodegeneration, and cancer.

The authors emphasized that strategies to inhibit this axis – including dietary AGE restriction – represent a promising therapeutic approach.

The downstream consequences are significant. As I detail in the book Mastering Diabetes, high levels of AGEs promote atherosclerosis, neuropathy, systemic inflammation, endothelial damage, and kidney disease.

AGEs and Diabetes: A Compounding Problem

For people living with diabetes, the AGE problem compounds rapidly.

Elevated blood glucose accelerates endogenous AGE formation, while oxidative stress – which is already elevated in diabetes – further promotes the glycation process.

The data shows that people living with diabetes typically have AGE levels 20–30% higher than those without diabetes, due to higher circulating glucose and increased oxidative stress.

For those with both diabetes and coronary artery disease, AGE levels may be 40–100% higher.

This creates a dangerous feedback loop: hyperglycemia drives AGE formation, AGEs activate RAGE and NF-κB, the resulting inflammation worsens insulin resistance, and insulin resistance drives further hyperglycemia.

It's a biochemical spiral that, left unchecked, accelerates the progression of diabetic complications.

A 2023 systematic review of randomized controlled trials examining dietary AGE restriction in people with diabetes found that reducing dietary AGE intake improved markers of insulin sensitivity and, in some populations, reduced circulating inflammatory markers.

A separate 2024 randomized cross-over trial by Kahleova et al. found that dietary AGEs decreased by 73% on a low-fat vegan diet compared to no change on a Mediterranean diet – and this decrease was significantly associated with weight loss, independent of total energy intake.

Evidence-Based Strategies That Reduce AGE Formation

The good news is that AGE exposure is largely modifiable. The research points to two primary strategies:

1. Change What You Eat: Prioritize Water-Rich, Whole Plant Foods

The Mount Sinai data is clear: fruits, vegetables, legumes, and whole grains contain dramatically fewer AGEs than animal-derived foods.

Plant foods are naturally higher in water content and lower in the protein and fat substrates that drive AGE formation.

The 2024 cross-over trial by Kahleova et al. demonstrated this in a clinical setting. Participants on a low-fat vegan diet saw their dietary AGE intake drop by 73%, which correlated with meaningful improvements in body weight and body composition.

A 2023 randomized clinical trial published in the Journal of the American College of Nutrition similarly found that a low-fat plant-based diet significantly decreased dietary AGEs, with associated improvements in insulin sensitivity – independent of caloric intake.

2. Change How You Cook: Use Water-Based Cooking Methods

Even if you don't change a single ingredient, simply changing your cooking method can substantially reduce AGE formation.

Frying, broiling, grilling, and roasting increase AGE production in food, while boiling, poaching, stewing, and steaming limit AGE production substantially.

A landmark 2025 randomized cross-over trial published in Cell Reports Medicine put this to the test. Researchers at KU Leuven provided healthy participants with identical ingredients but varied only the cooking methods – boiling and steaming versus grilling and baking.

The results were definitive: low-AGE-generating cooking methods (boiling, steaming) significantly decreased serum AGE levels and improved lipid profiles, while high-AGE methods (grilling, baking) increased circulating AGEs.

The study's authors concluded that "culinary techniques should be considered as an important factor in cardiometabolic preventive strategies" – a statement that challenges current dietary guidelines, which focus almost exclusively on ingredients while ignoring how those ingredients are prepared.

The Bigger Picture

AGEs aren't a fringe topic. They sit at the intersection of nutrition science, metabolic health, and chronic disease prevention.

The mechanism is clear: high-heat cooking and excess blood glucose produce AGEs. AGEs bind to RAGE receptors. RAGE activates NF-κB. NF-κB drives chronic inflammation.

And chronic inflammation is the common thread linking insulin resistance, cardiovascular disease, neuropathy, kidney disease, and accelerated aging.

The modern Western diet – built on grilled meats, fried foods, toasted snacks, and ultra-processed products – is essentially an AGE-delivery system.

And the research increasingly suggests that this isn't a minor contributor to chronic disease. It's a central one.

But here's what I always come back to: your body has a remarkable capacity to heal when you give it the right conditions.

Reducing your AGE exposure doesn't require a radical overhaul. It starts with two simple shifts – eat more whole, water-rich plant foods, and cook with water instead of dry heat.

Steam your vegetables. Stew your legumes. Poach instead of fry. Choose raw nuts over roasted.

These aren't dramatic interventions. But the biochemistry behind them is powerful. And the data supports it.

Scientific References

1. Khambatta C, Barbaro R. Mastering Diabetes. Avery/Penguin Random House, 2020.

2. Uribarri J, Woodruff S, Goodman S, et al. Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet. J Am Diet Assoc. 2010;110(6):911-16.

3. Greger, Michael. Lower LDL Cholesterol Naturally with Food: Simple Ways to Add Proven LDL Reducers to Your Everyday Routine

4. Dong H, Zhang Y, Huang Y, Deng H. Pathophysiology of RAGE in Inflammatory Diseases. Front Immunol. 2022;13:931473.

5. Peng Y, Kim JM, Park HS, et al. AGE-RAGE Signal Generates a Specific NF-κB RelA "Barcode" That Directs Collagen I Expression. Sci Rep. 2016;6:18822.

6. Saha S, et al. Activation and Modulation of the AGEs-RAGE Axis: Implications for Inflammatory Pathologies and Therapeutic Interventions. Pharmacol Res. 2024.

7. Katsarou A, et al. Dietary Restriction of Advanced Glycation End-Products (AGEs) in Patients with Diabetes: A Systematic Review of Randomized Controlled Trials. Int J Mol Sci. 2024;25(21):11407.

8. Kahleova H, Znayenko-Miller T, Motoa G, et al. Dietary Advanced Glycation End-Products and Their Associations with Body Weight on a Mediterranean Diet and Low-Fat Vegan Diet: A Randomized, Cross-Over Trial. Front Nutr. 2024;11:1426642.

9. Kahleova H, et al. A Low-Fat Plant-Based Diet Decreases Dietary AGEs and Improves Insulin Sensitivity. J Am Coll Nutr. 2023. (Referenced via PMC)

10. Wellens J, Vissers E, Dumoulin A, et al. Cooking Methods Affect Advanced Glycation End Products and Lipid Profiles: A Randomized Cross-Over Study in Healthy Subjects. Cell Rep Med. 2025;6(5):102091.

11. Zhang Y, Zhang Z, Tu C, et al.Advanced Glycation End Products in Disease Development and Potential Interventions. Antioxidants. 2025;14(4):492.