Different tissues "prefer" or are able to utilize different fuels. While the brain "prefers" glucose if you will, the heart "prefers" fats. Most skeletal muscle does just fine on fats is my understanding. So it's not that your entire metabolism will run exclusively on sugar in the "optimal state" and keto is a global "backup state." The shift seems to be more on the margin, and in individual organs/tissues, with the biggest change maybe appearing in the brain since it cannot take up fats (they are too big to pass the blood brain barrier).
The "optimal" state (if there is such a thing) probably has different tissues burning individual mixes of different fuels, maybe even including ketones, but definitely glucose and fats. The body can make nearly everything out of nearly everything else, so even a 90% carb eating peasant or rice farmer will actually run on a large % of fatty acids in various tissues.
I disagree with the whole idea of "prefers." Does your engine "prefer" gasoline or diesel? That's not how it works. Prefer seems like a bad analogy for a system that can deal with both. For every "prefers glucose" I can say "tries to get rid of glucose because excess glucose is toxic" (true). It seems like an intuition pump to reinforce which side you're on (Peat carbs/ketard). It's kind of like saying that water prefers flowing downhill because altitude is bad. No, it's just a bunch of mechanistic shit happening that will lead to certain outcomes. (if glucose? (burn :glucose) (burn :fatty-acids)) doesn't have a "prefer" anywhere in there.
I largely agree with the "keto circumvents a breakage" idea. Keto is like showering at the gym; it's great and you can shower at the gym all the time, but it's still a good idea to call the plumber and have him fix the shower in your house. That doesn't mean you should stop showering at the gym when you're at the gym. Ok end of metaphor now.
Overall great post; pretty much exactly my current mental model. Something something protein is in there, but possibly (likely?) downstream from "PUFAs mess up the Krebs cycle." BCAAs go into the Krebs cycle too, so it wouldn't be a surprise if that part of it gets mucked up in some people as well.
Weirdly and uncharacteristically old boy, I agree with everything you just said! I must be getting old.
Forgive my imprecision.
I do think that although glucose may not be the "optimal fuel", the "preferred state" of the body is to have a glycogen reserve to deal with short term energy requirements. (And that does pretty much preclude ketosis, but it doesn't imply that the brain prefers glucose. In fact my brain seems to prefer ketones. But that's probably because it's broken.)
Yea, not sure if the ketone-preferring brain is broken, or some people are just like this, or what... I had non-24 when I was a toddler. So it must've broken very early.
Only read the summary of this one, but they seem to be saying that fat people burn less of the fat they ate *that morning*. That seems believable, the fat people have got vast reserves of stored fat to draw on as well.
Like if you stick a load of red diesel into a full fuel tank, you'll burn less of the red dye than if you put it into an empty tank?
They were trying to prove that the fat people didn't burn fat so well, and yet their conclusion is:
> Contrary to our hypothesis, obese and reduced-obese individuals oxidized as much dietary and total fat as lean individuals over 24-hr.
i.e. they think fat people work in the same way as thin people.
I must say, I don't see how they get that conclusion, I think I read their graphs the same way you do (fatties burn less fat). I'll print it off and see if I can get it to make sense.
Oops, sorry, you're right. They saw higher carb use and lower fat use. But because they couldn't fiddle the p-value below 0.05 they've decided that they've disproved their hypothesis even though they've seen what they were expecting just not terribly convincingly.
The probability can be debated, but what seems obvious is that this generalization that broken metabolism does not oxidize carbs does not hold.
Glucose-induced thermogenesis is actually reduced in obese people, so in the post-meal period they oxidize fewer carbs, but in any case they seem to compensate throughout the day.
I am a bit freaked out by this. (Which is great! Thank you!)
As far as I can tell 'PUFAs block glycolysis' is an established fact. That should sure cause a problem with burning carbs! So I think I'd predict that people with high PUFAs in their system would be bad at carb metabolism. And I wonder why that hasn't shown up in some study somewhere.
Maybe the problem is that *everyone's* full of PUFAs these days, so it's difficult to measure the effect? Even so, more PUFAs should make for worse carb metabolism.
Whether more PUFAs is strongly correlated with obesity I don't know. I'd certainly bet that way....
On the other hand, more PUFAs might be causing type-2 diabetes / insulin resistance (because of the blocked glycolysis), and obesity might be what you get if you are somehow bad at burning glucose but still capable of storing the glucose as fat (although that makes no sense, if you can't do glycolysis you can't make fat out of glucose either) ??
I have no clue.
*I* think obesity is caused by a broken homeostasis mechanism, but as to how it's actually broken, I don't even have a hypothesis!
Maybe if the homeostasis is broken you don't release fat when you need energy? And so you don't burn as much as you should?
A few comments as I'm reading along:
Different tissues "prefer" or are able to utilize different fuels. While the brain "prefers" glucose if you will, the heart "prefers" fats. Most skeletal muscle does just fine on fats is my understanding. So it's not that your entire metabolism will run exclusively on sugar in the "optimal state" and keto is a global "backup state." The shift seems to be more on the margin, and in individual organs/tissues, with the biggest change maybe appearing in the brain since it cannot take up fats (they are too big to pass the blood brain barrier).
The "optimal" state (if there is such a thing) probably has different tissues burning individual mixes of different fuels, maybe even including ketones, but definitely glucose and fats. The body can make nearly everything out of nearly everything else, so even a 90% carb eating peasant or rice farmer will actually run on a large % of fatty acids in various tissues.
I disagree with the whole idea of "prefers." Does your engine "prefer" gasoline or diesel? That's not how it works. Prefer seems like a bad analogy for a system that can deal with both. For every "prefers glucose" I can say "tries to get rid of glucose because excess glucose is toxic" (true). It seems like an intuition pump to reinforce which side you're on (Peat carbs/ketard). It's kind of like saying that water prefers flowing downhill because altitude is bad. No, it's just a bunch of mechanistic shit happening that will lead to certain outcomes. (if glucose? (burn :glucose) (burn :fatty-acids)) doesn't have a "prefer" anywhere in there.
I largely agree with the "keto circumvents a breakage" idea. Keto is like showering at the gym; it's great and you can shower at the gym all the time, but it's still a good idea to call the plumber and have him fix the shower in your house. That doesn't mean you should stop showering at the gym when you're at the gym. Ok end of metaphor now.
Overall great post; pretty much exactly my current mental model. Something something protein is in there, but possibly (likely?) downstream from "PUFAs mess up the Krebs cycle." BCAAs go into the Krebs cycle too, so it wouldn't be a surprise if that part of it gets mucked up in some people as well.
Weirdly and uncharacteristically old boy, I agree with everything you just said! I must be getting old.
Forgive my imprecision.
I do think that although glucose may not be the "optimal fuel", the "preferred state" of the body is to have a glycogen reserve to deal with short term energy requirements. (And that does pretty much preclude ketosis, but it doesn't imply that the brain prefers glucose. In fact my brain seems to prefer ketones. But that's probably because it's broken.)
Yea, not sure if the ketone-preferring brain is broken, or some people are just like this, or what... I had non-24 when I was a toddler. So it must've broken very early.
Oh that is interesting. Do toddlers have much access to PUFAs?
https://www.walmart.com/ip/Parent-s-Choice-Gentle-Premium-Baby-Formula-for-Fussiness-Gas-and-Crying-34-Ounces/1452252458?athbdg=L1102&from=/search
Oh no. Poor babies. Oh well with any luck we're totally wrong and PUFAs are great. The alternative is too horrible to think about.
Just out of interest did you get to eat a lot of this sort of thing as a baby?
I'd have to ask my mom.
Obese people burn more carbs in a 24-hour period than lean people.
I wonder why this notion of a broken metabolism doesn't burn carbs, when in fact it doesn't burn enough fat.
Oh nice, thank you, can you cite? Is it that they burn more carbs in total or is it that they burn more as a percentage?
No comparison between fat and carbs, but also pertinent:
https://pubmed.ncbi.nlm.nih.gov/18175746/
Only read the summary of this one, but they seem to be saying that fat people burn less of the fat they ate *that morning*. That seems believable, the fat people have got vast reserves of stored fat to draw on as well.
Like if you stick a load of red diesel into a full fuel tank, you'll burn less of the red dye than if you put it into an empty tank?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979741/figure/pone-0094181-g003/
They were trying to prove that the fat people didn't burn fat so well, and yet their conclusion is:
> Contrary to our hypothesis, obese and reduced-obese individuals oxidized as much dietary and total fat as lean individuals over 24-hr.
i.e. they think fat people work in the same way as thin people.
I must say, I don't see how they get that conclusion, I think I read their graphs the same way you do (fatties burn less fat). I'll print it off and see if I can get it to make sense.
Fat oxidation in obese individuals, although lower, may not have reached the level of significance, but carbohydrate oxidation was significant.
Obese people oxidize more carbohydrates in a 24-hour period.
"Twenty-four hour carbohydrate oxidation was significantly higher in the Obese as compared to the Lean group (p = 0.039, Table 2)"
Oops, sorry, you're right. They saw higher carb use and lower fat use. But because they couldn't fiddle the p-value below 0.05 they've decided that they've disproved their hypothesis even though they've seen what they were expecting just not terribly convincingly.
Interesting!
The probability can be debated, but what seems obvious is that this generalization that broken metabolism does not oxidize carbs does not hold.
Glucose-induced thermogenesis is actually reduced in obese people, so in the post-meal period they oxidize fewer carbs, but in any case they seem to compensate throughout the day.
I am a bit freaked out by this. (Which is great! Thank you!)
As far as I can tell 'PUFAs block glycolysis' is an established fact. That should sure cause a problem with burning carbs! So I think I'd predict that people with high PUFAs in their system would be bad at carb metabolism. And I wonder why that hasn't shown up in some study somewhere.
Maybe the problem is that *everyone's* full of PUFAs these days, so it's difficult to measure the effect? Even so, more PUFAs should make for worse carb metabolism.
Whether more PUFAs is strongly correlated with obesity I don't know. I'd certainly bet that way....
On the other hand, more PUFAs might be causing type-2 diabetes / insulin resistance (because of the blocked glycolysis), and obesity might be what you get if you are somehow bad at burning glucose but still capable of storing the glucose as fat (although that makes no sense, if you can't do glycolysis you can't make fat out of glucose either) ??
I have no clue.
*I* think obesity is caused by a broken homeostasis mechanism, but as to how it's actually broken, I don't even have a hypothesis!
Maybe if the homeostasis is broken you don't release fat when you need energy? And so you don't burn as much as you should?