In this episode, I wrap up glycation week by discussing why glycation may play essential physiological roles in the body.

In the early days of methylglyoxal research, Albert Szent-Gyorgyi, who won the 1937 Nobel prize in Physiology or Medicine for his discovery of vitamin C and critical steps in energy metabolism, saw the molecule as part of a regulatory system. In the early research into glycolysis, the system that converts methylglyoxal to pyruvate was seen as part of energy metabolism. Only later did glycation become synonymous with toxicity.

Current science can be used to make a compelling case that methylglyoxal is normally produced as part of glycolysis to prevent a dangerous buildup of glyceraldehyde and that it rises during carbohydrate restriction to help preserve much-needed glucose and to enable the conversion of fat to additional glucose. This could be seen as an elegant system of regulation and a key part of energy metabolism.

Nevertheless, it is unclear where the dividing line between physiology and pathology lies, and I see the apparent rise of methylglyoxal during carbohydrate restriction as part of a stress response that should not be chronically activated.

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