Thursday, June 9, 2016

The Daily Lipid Podcast Episode 13: Wait a Second, Is Glycation Actually GOOD For You?

Methylglyoxal regulates glycolysis in a way that prevents dangerous accumulation of glyceraldehyde, and that conserves glucose during carbohydrate restriction. Its rise on a low-carb Atkins diet makes physiological sense because it conserves glucose and even allows gluconeogenesis from fatty acids. Nevertheless, high methylglyoxal levels causally contribute to diabetes, and this seems to be a stress response that should not be chronically elevated.

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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Read on for the show notes.

Show Notes for Episode 13

This episode, while not terribly long, is pretty rich in biochemistry. If you don't want to listen to the whole thing, use this to navigate:

1:00 Follow me on Snapchat (chrismasterjohn) for sneak peaks of PUFA report and other things I’m working on
1:15 I’ll be LIVE on Facebook this Saturday, June 11, 2:00 PM Eastern time
1:50 Cliff notes
5:00 Diversify your work positions! I recorded this standing.
5:20 Like reactive oxygen species or inflammation, whether glycation contributes to health or disease depends on context
8:00 The early days of research attributed roles in cellular regulation and energy metabolism to methylglyoxal
11:05 Methylglyoxal glycates a glycolytic enzyme in a way that prevents dangerous glycolytic intermediates from accumulating.
20:00 Methylglyoxal increases when carbohydrate is limiting, and its inhibition of glycolysis helps preserve glucose for the tissues that most need it.
23:50 During carbohydrate restriction, methylglyoxal allows the conversion of fat to much-needed glucose, with the help of glutathione.
25:08 Practical strategies to boost glutathione
27:40 Back to methylglyoxal as a source of glucose.
34:00 Is the rise of methylglyoxal during carbohydrate contraction physiological, pathological, or both? Is it a stress response that is good but should not be chronically elevated?
36:40 Insulin plays too many critical roles for it to be chronically maximally suppressed, so I err on the side of believing this is a stress response that we do not want to be consistently activated. 

All of this is extensively documented in my doctoral dissertation and to a large degree in my other writings linked to in my Start Here for Glycation and AGEs post. 

Has this episode changed your view of glycation at all? What do you think of the study showing an increase in methylglyoxal on the Atkins diet? Does this episode change how you would view that study at all?


  1. I don't have time to listen to podcasts. It would be nice if they were transcribed for people like me.

    1. Someone volunteered to transcribe them so that may begin shortly if it works out.

  2. Is there a downside to using leucine as a way to trigger an insulin response on low carbohydrate diets? How would this affect glycation?

    1. Todd,

      I believe leucine is likely to stimulate glucagon in addition to insulin. Glucagon counteracts most effects of insulin, so I would not consider protein or leucine sufficient to replace carbohydrate.


  3. Chris,

    Great podcast. I just came upon your work and am enjoying...especially the biochemistry. My question, which centers on your advocacy of some insulin in the system to maintain all the positive aspects it seems to promote, how are the tribes and populations that have historically had very little access to carbohydrates able to live vibrant lives per the observations of the scientist that observed them? Is there other mechanisms that the body can use to accommodate this low carbohydrate/low insulin state?


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