No, it's an accounting tautology. Is double-entry bookkeeping a "law of physics?" Same thing.
I like your way of thinking. We should debug this like any other system. Scientists just don't seem to have the practical experience debugging somewhat complex systems!
Related to the blood/brain thing, I remember a lipid scientist (on Nick Jackomes' podcast I think?) mentioning that while PUFA levels in the body normalize somewhat quickly, that it takes MUCH longer in the brain. Since the brain is such a controlled environment, what gets in and out is very controlled, and IIRC the level changes there are significantly lower.
It might be something like "leptin receptors built with faulty cell membranes due to PUFA" and you just gotta rebuild your leptin receptors over the years.
Tbh I don't think leptin alone can explain it though. If it was just leptin, then we should be able to explain everything about obesity with increased food intake. But my food intake now, if I measure it, doesn't jive well with that theory. By any measure (and I've done pretty much all of them), my calories out is normal or high, and I don't lose weight sustainably even if eating significantly less.
If excess CI due to broken leptin receptors were at fault, wouldn't we expect me to eat 4,000kcal/day on average?
This theory I have just come up with is too complicated for my tastes but bear with me...
We've got considerable stores of PUFAs that are continually being released into the blood. Not much that can be done about that except long-term PUFA avoidance.
In ketosis, a lot of that PUFA is getting burned for fuel along with the other fat. So blood PUFAs go down relative to what they would be.
Without excess protein competing for the PUFA-destruction pathway, a lot of it just gets destroyed and excreted. So blood PUFAs go even further down.
Whatever PUFAs remain in the blood are interfering with leptin reception somehow, interfering with leptin production maybe, but also damaging the leptin receptors or interfering with BBB transport.
But at least *some* of that interference is medium term. Some effects are seen quickly, but it takes a few weeks or a few months for the receptors or the structure of the BBB to recover from the PUFA damage. Maybe whole cells need to be replaced.
That means we should see a lag effect. So when I go home to visit Mum, and she feeds me a no-PUFAs but very high protein fatted-calf based diet, my blood levels of PUFA rise, they do damage to receptors and transport for all that time, raise my set point as a result, and it takes a long time to recover.
We were wondering if there was some sort of time-lag effect to lack of/excess of protein, and maybe that lag is coming from PUFA damage to the leptin system taking a long time to heal?
This theory is complicated enough to not be obvious, at least without our obsession with PUFAs-bad, so we don't need to worry about the fact that no-one's spotted it.
Can you think of any observation that either of us has made that it doesn't explain?
I will say, the "spookily precise satiety" vs " ravenous until bloated to the point of pain" thing comes and goes within a day or less. When I do a protein refeed, my first meal of the day still gives me satiety, even if it's yogurt or lots of meat or something else "high-protein."
That evening, or the next morning, the same meal will give me zero satiety.
When I go back on ex150, it typically is back within 1 day as well, so that I feel pretty good satiety the first evening and am definitely back by the 2nd day.
So that part of the satiety can't be a long term cell process, it must be very fast acting. Which makes your "protein somehow fucks up the satiety system, maybe via outcompeting PUFAs" very compelling.
Unfortunately (for science), even 1 significant buffer/reservoir can make scientific experimentation extremely difficult. If we introduce another, or 2-3 more... pretty soon it's chaotic af :)
Which doesn't mean it's not true, just that it's really hard to test.
I'd say we kinda do know that there is such a buffer/lag effect with cell walls. We know cell walls are important to cells. We know some cells have YEARS in turnover.
I'm actually thinking that 'leptin based homeostat affected by PUFAs and protein' explains *your* experiences pretty well, it's *mine* I'm having trouble with.
In your case, I figure that your zero-PUFA low protein diet has restored a lot of your normal functioning (as long as you keep it up at least).
At the moment, you're generating higher-than-normal leptin levels (because you're still a bit fat, and your leptin production is relatively undamaged). You've actually measured blood leptin and it's quite high, isn't it?
And then either the transport into the brain, or the receptors it acts on are somewhat impeded, so your brain is thinking your fat reserves are correct and acting to keep them there. That's why you can feel satiety. If you just go with your appetite you'll eat exactly enough calories to balance your expenditure and your weight will stay the same.
Your high leptin blood leptin levels might be stimulating your metabolism, (maybe the only bit of you that can't see the signal is your brain, and there are leptin receptors in other tissues too), so you might be running hotter than you should be as a result of being overweight.
As you noticed, you seem to be very good at detecting the calorie density of cream, and the time you tried a different brand with less fat in it your intake went up in a spookily accurate way to compensate.
When you tried starving yourself (the short fasts), that made your weight fall, presumably some fat loss at least, and so your leptin levels fell, your brain got the idea that you were underweight, and increased your hunger to compensate, and you went quickly back to precisely your pre-fasting weight.
Yea my fasted (not sure if that makes a difference) blood leptin is somewhat high but not super high, coming down. Pretty much what you'd expect from somebody with my body fat.
My doctor has seen people who lost a bunch of weight and their leptin levels absolutely tanked which is a "bad" adaptation because it means your body now wants to make you fat again cause it thinks you're starving. So far, that is not a problem I have. But I'm also not yet at "lean people" levels of leptin.
Well unfortunately the entire part about leptin is speculation. This model could explain things, but it could also be something completely different. Suppose I could've tested leptin at the end of a fast. But if it's leptin in the brain (not blood), or leptin receptors, we couldn't even tell that. I.e. maybe my leptin didn't go down but my receptors got messed up again.
> Well unfortunately the entire part about leptin is speculation.
Oh totally, I'm wondering about how I would have designed this thing, if I was operating under the sorts of constraints evolution was operating under, and then wondering what might go wrong in that design if you suddenly stick odd substances in there.
Sometimes the best way to debug things is just to sit around thinking for a bit, and try to explain the problem to other people. So I really appreciate you telling me where I'm not being convincing. Thanks!
It would be amazing if we could get real time readouts of things in the blood, but even then, as you say, it wouldn't tell us everything that's going on, although it should be full of clues.
Maybe the problem is excessively logging in the success case, which wouldn't be a problem if the intern writing the deploy config for the logging server hadn't typo'd the unit, causing it to be misinterpreted by the system for the last 4 years.
And in another 2 years we'll have a full disk taking the system down.
> CICO is a law of physics
No, it's an accounting tautology. Is double-entry bookkeeping a "law of physics?" Same thing.
I like your way of thinking. We should debug this like any other system. Scientists just don't seem to have the practical experience debugging somewhat complex systems!
Related to the blood/brain thing, I remember a lipid scientist (on Nick Jackomes' podcast I think?) mentioning that while PUFA levels in the body normalize somewhat quickly, that it takes MUCH longer in the brain. Since the brain is such a controlled environment, what gets in and out is very controlled, and IIRC the level changes there are significantly lower.
It might be something like "leptin receptors built with faulty cell membranes due to PUFA" and you just gotta rebuild your leptin receptors over the years.
Tbh I don't think leptin alone can explain it though. If it was just leptin, then we should be able to explain everything about obesity with increased food intake. But my food intake now, if I measure it, doesn't jive well with that theory. By any measure (and I've done pretty much all of them), my calories out is normal or high, and I don't lose weight sustainably even if eating significantly less.
If excess CI due to broken leptin receptors were at fault, wouldn't we expect me to eat 4,000kcal/day on average?
This theory I have just come up with is too complicated for my tastes but bear with me...
We've got considerable stores of PUFAs that are continually being released into the blood. Not much that can be done about that except long-term PUFA avoidance.
In ketosis, a lot of that PUFA is getting burned for fuel along with the other fat. So blood PUFAs go down relative to what they would be.
Without excess protein competing for the PUFA-destruction pathway, a lot of it just gets destroyed and excreted. So blood PUFAs go even further down.
Whatever PUFAs remain in the blood are interfering with leptin reception somehow, interfering with leptin production maybe, but also damaging the leptin receptors or interfering with BBB transport.
But at least *some* of that interference is medium term. Some effects are seen quickly, but it takes a few weeks or a few months for the receptors or the structure of the BBB to recover from the PUFA damage. Maybe whole cells need to be replaced.
That means we should see a lag effect. So when I go home to visit Mum, and she feeds me a no-PUFAs but very high protein fatted-calf based diet, my blood levels of PUFA rise, they do damage to receptors and transport for all that time, raise my set point as a result, and it takes a long time to recover.
We were wondering if there was some sort of time-lag effect to lack of/excess of protein, and maybe that lag is coming from PUFA damage to the leptin system taking a long time to heal?
This theory is complicated enough to not be obvious, at least without our obsession with PUFAs-bad, so we don't need to worry about the fact that no-one's spotted it.
Can you think of any observation that either of us has made that it doesn't explain?
I will say, the "spookily precise satiety" vs " ravenous until bloated to the point of pain" thing comes and goes within a day or less. When I do a protein refeed, my first meal of the day still gives me satiety, even if it's yogurt or lots of meat or something else "high-protein."
That evening, or the next morning, the same meal will give me zero satiety.
When I go back on ex150, it typically is back within 1 day as well, so that I feel pretty good satiety the first evening and am definitely back by the 2nd day.
So that part of the satiety can't be a long term cell process, it must be very fast acting. Which makes your "protein somehow fucks up the satiety system, maybe via outcompeting PUFAs" very compelling.
Interesting. Scumbag systems theory!
Unfortunately (for science), even 1 significant buffer/reservoir can make scientific experimentation extremely difficult. If we introduce another, or 2-3 more... pretty soon it's chaotic af :)
Which doesn't mean it's not true, just that it's really hard to test.
I'd say we kinda do know that there is such a buffer/lag effect with cell walls. We know cell walls are important to cells. We know some cells have YEARS in turnover.
So the effects are just super unpredictable :(
I'm actually thinking that 'leptin based homeostat affected by PUFAs and protein' explains *your* experiences pretty well, it's *mine* I'm having trouble with.
In your case, I figure that your zero-PUFA low protein diet has restored a lot of your normal functioning (as long as you keep it up at least).
At the moment, you're generating higher-than-normal leptin levels (because you're still a bit fat, and your leptin production is relatively undamaged). You've actually measured blood leptin and it's quite high, isn't it?
And then either the transport into the brain, or the receptors it acts on are somewhat impeded, so your brain is thinking your fat reserves are correct and acting to keep them there. That's why you can feel satiety. If you just go with your appetite you'll eat exactly enough calories to balance your expenditure and your weight will stay the same.
Your high leptin blood leptin levels might be stimulating your metabolism, (maybe the only bit of you that can't see the signal is your brain, and there are leptin receptors in other tissues too), so you might be running hotter than you should be as a result of being overweight.
As you noticed, you seem to be very good at detecting the calorie density of cream, and the time you tried a different brand with less fat in it your intake went up in a spookily accurate way to compensate.
When you tried starving yourself (the short fasts), that made your weight fall, presumably some fat loss at least, and so your leptin levels fell, your brain got the idea that you were underweight, and increased your hunger to compensate, and you went quickly back to precisely your pre-fasting weight.
Yea my fasted (not sure if that makes a difference) blood leptin is somewhat high but not super high, coming down. Pretty much what you'd expect from somebody with my body fat.
My doctor has seen people who lost a bunch of weight and their leptin levels absolutely tanked which is a "bad" adaptation because it means your body now wants to make you fat again cause it thinks you're starving. So far, that is not a problem I have. But I'm also not yet at "lean people" levels of leptin.
Well unfortunately the entire part about leptin is speculation. This model could explain things, but it could also be something completely different. Suppose I could've tested leptin at the end of a fast. But if it's leptin in the brain (not blood), or leptin receptors, we couldn't even tell that. I.e. maybe my leptin didn't go down but my receptors got messed up again.
> Well unfortunately the entire part about leptin is speculation.
Oh totally, I'm wondering about how I would have designed this thing, if I was operating under the sorts of constraints evolution was operating under, and then wondering what might go wrong in that design if you suddenly stick odd substances in there.
Sometimes the best way to debug things is just to sit around thinking for a bit, and try to explain the problem to other people. So I really appreciate you telling me where I'm not being convincing. Thanks!
It would be amazing if we could get real time readouts of things in the blood, but even then, as you say, it wouldn't tell us everything that's going on, although it should be full of clues.
Debugging is a pain sometimes.
Maybe the problem is excessively logging in the success case, which wouldn't be a problem if the intern writing the deploy config for the logging server hadn't typo'd the unit, causing it to be misinterpreted by the system for the last 4 years.
And in another 2 years we'll have a full disk taking the system down.