The Metabolisms Mortal Enemy: Advanced Glycation End Products

Date: 2020-05-01 22:35:12

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What Are AGEs & Why Are They Bad?

Advanced Glycation End Products (AGEs) are proteins or lipids that get chemically modified by the attachment of sugars. Inside the body, this chemical modification by sugar can both impair the normal healthy function of certain proteins and lipids and bestow upon those proteins or lipids new harmful functions.

AGEs, as their name cleverly implies, contribute to all manner of chronic diseases, including diabetes, heart disease, and neurodegenerative diseases, like Alzheimer’s. They do so by:

Cross-linking collagen proteins, the main structural protein of the body and of blood vessels, impairing the function of blood vessels and trapping oxLDL inside arterial plaques.
Speaking of LDL, the glycation of LDL increases its propensity to become oxidized and, thus, become atherogenic.

AGEs also have their own receptors on many cells, named Receptor for AGEs (RAGE). Activation of the RAGE receptor causes oxidative stress within cells and causes the activation of NFkB within cells, a master transcription factor regulator of inflammation. Therefore, AGEs cause both oxidative stress and inflammation, the two foundations of chronic disease!

Three examples include:

HbA1c — Glycated haemoglobin protein in red blood cells is a primary marker for diabetes. (You want your HbA1c less than 5.7%.)

Beta-Amyloid — Beta-Amyloid is the preeminent Alzheimer’s protein. More accurately, (Beta-Amyloid is the neurotoxic fragment of the amyloid precursor protein (APP)) it is the oligomers (not the plaques) of Beta-Amyloid that are neurotoxic. To the point, glycated Beta-Amyloid oligomers are the most neurotoxic of all!

Endogenous vs. Exogenous AGEs?

Endogenous AGEs are those produced within your body. For example, imagine you eat a bagel. That bagel is converted into sugar and those sugars attach to hemoglobin and LDL, making HbA1c and glycation LDL, which becomes atherogenic oxLDL.

Exogenous AGEs are those produced outside the body, i.e. are already present in food. Unfortunately, the foods containing the most AGEs include a lot of keto-approved (albeit dirty keto) foods, such as pan-seared meat. A pan-seared steak contains a whopping 9,000 kilounits (kU) per 100 grams of AGEs, as opposed to the bagel, which contains only 100 kU per 100 grams. However,…

Most of the AGEs in food come, not for the actual food product itself, but from the cooking process! Whereas that pan-seared steak contains 9,000 kU of AGEs per 100 grams, the raw version only contains 700 kU per 100 grams.

Reducing Endogenous AGEs

Easy… consume less sugar… go low-carb.

Reducing Exogenous AGEs

Here are three key tips for reducing your exogenous AGE intake:

Low temperature; moist heat; minimal time. Cooking at higher temperatures, dryer conditions, or for longer periods of time increases AGE production.

Marinate in an acid. Marinating your protein (meat, fish, etc.) in lemon juice or vinegar before cooking will reduce exogenous AGE production by 50% by blocking the Maillard reaction.

Journal of the American Dietetic Association, 2013 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704564/

Cook with turmeric and black pepper, which also inhibit AGE formation.

Critical Reviews in Food Science and Nutrition, 2019 https://www.ncbi.nlm.nih.gov/pubmed/29185795
Masters Thesis, Kansas State University, 2013
https://pdfs.semanticscholar.org/9c0c/2af47d0e943bbe025a24b4ba0c437d7b7aee.pdf

Nicholas Norwitz – Oxford PhD Researcher and Harvard Med Student:
https://www.dpag.ox.ac.uk/team/nicholas-norwitz

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