Metabolism
Glycation
The attachment of a sugar to a protein.
Glycation is the attachment of sugar molecules to proteins, but Ray Peat argued that most of the damage attributed to it is actually caused by lipid peroxidation of polyunsaturated fatty acids (PUFA), not by glucose itself. In controlled experiments, lipid peroxidation products damage proteins roughly 23 times faster than simple sugars do, and the fragments of deteriorating PUFA combine with proteins to produce immunogenic substances often misidentified as "advanced glycation end products." Peat stated plainly that "most of the things that are called glycation are really fat-breakdown products," with the glycerol liberated by lipolysis being metabolized to methylglyoxal, a potent glycating agent.
The process is intimately tied to the failure of oxidative glucose metabolism. When cells cannot oxidize glucose, they shift toward fat oxidation, producing less carbon dioxide and more lactate. Carbon dioxide has a spontaneous ability to attach to the same reactive amino groups on proteins that sugars would otherwise occupy, meaning that when carbon dioxide is abundant, glycation is directly blocked by this protective carbamylation. The failure of glucose consumption and carbon dioxide production, as seen in Alzheimer's disease, therefore predisposes tissues to glycation, which imitates mutated forms of proteins and promotes amyloid formation. Glycation of collagen in the extracellular matrix alters its properties, making it a preferred site for glycated prion-like proteins, and is considered the major mechanism in the cross-linking characteristic of aging.
The primary drivers of this pathological glycation are the PUFA and the hormonal stress state they induce. PUFA block glucose metabolism for energy, suppress thyroid function, and increase the liberation of free fatty acids, creating a vicious cycle where more glucose is produced adaptively but cannot be oxidized. The oxidative breakdown products of PUFA—including malondialdehyde, acrolein, and glyoxal—damage mitochondria directly, further reducing the ability to oxidize sugar and produce protective carbon dioxide. Peat noted that sugar often gets the blame for what PUFA do, citing the example of hemoglobin A1c (HbA1c), where most of the so-called glycation is really from oxidative breakdown fragments of PUFA.
Therapeutic intervention against glycation centers on restoring oxidative metabolism and blocking the underlying mediators of damage. Aminoguanidine, a recognized blocker of glycation, was found to achieve its effect by inhibiting nitric oxide, which leads to oxidative damage in blood vessels. Peat emphasized that shifting away from PUFA toward saturated fats, while eating frequently with sugar to avoid stress-induced lipolysis, allows the slow disposition of unsaturated toxic fats over a period of years, progressively restoring efficient metabolism and the protective production of carbon dioxide.
People also ask
- What does Ray Peat identify as the true cause of damage usually blamed on glycation?Peat argued that most damage attributed to glycation is actually caused by lipid peroxidation of polyunsaturated fatty acids (PUFA), with their breakdown fragments damaging proteins far faster than sugars and creating substances mistaken for advanced glycation end products.
- How does carbon dioxide protect against glycation?The entry describes carbon dioxide spontaneously attaching to the same amino groups on proteins that sugars would target, so when oxidative glucose metabolism is strong and CO2 is abundant, this protective carbamylation directly blocks glycation.
- Why did Peat consider polyunsaturated fats central to glycation-related aging?PUFA block glucose oxidation, suppress thyroid function, and their breakdown products damage mitochondria, creating a cycle where less protective carbon dioxide is produced and more pathological glycation occurs, driving the cross-linking characteristic of aging.