Of course, some folks have already referred to this interview on the Great Barrington Declaration post.
I just want to say, in addition to the content, I greatly appreciate that the audio volume level was good. I've only heard one other interview with Peter (no video), and even with my laptop speakers turned all the way up, I could barely make out what Peter said. Partly it's the accent which is very strong to my American ears. Recorded more loudly would have helped.
I have the same problem with audio of Malcolm Kendrick. He has a soft voice to go with the Scottish accent, and without amplification it's very hard to try and listen.
The transient insulin resistance due to ROS from negative electron flow, how transient is this? Assume that this is repeated as long as the cell has extra calories to burn.
So, 4-HNE does similar thing i.e. transient insulin resistance. How does these two fit together, burning polyunstable fats does not make ROS, which does not then induce insulin resistance, however burning results in 4-HNE, which induces insulin resistance? Am I missing something in here?
Regarding the fat cell size, they found an interesting difference in Dietfits; lower carbers had smaller fat cells than higher carbers. The main finding in Dietfits was next to nill, no weight difference, but this fat cell size difference should be interesting. https://www.healio.com/news/endocrinology/20191205/despite-similar-weight-loss-lowcarbohydrate-diet-delivers-insulin-reductions-smaller-fat-cells-than
Great podcast Peter. Careful, now that people like Saladino and Marshall are taking your ideas more mainstream, you'll end up nailed to your cross. Still, on the plus side, people are hearing about your ideas and that's generally a Good Thing.
JR - I read your link and had to wonder - if the low fat dieters' fat cells are NOT shrinking significantly when they lose weight, it can only mean one of two things. Either the at cells are dying off, which sounds unlikely, or the lost body mass is coming from somewhere else. Muscle tissue perhaps? Strange that the question was never asked, at least in the article.
Lots to think about, as usual! On the reverse electron flow to indicate enough energy, it reminded me of this paper called "The Randle cycle revisited: a new head for an old hat". What they are saying is that the Randle cycle is broken under only 2 conditions: stress, which I understand is fight/flight stress, or eating high carb and high fat simultaneously. Here's a quote from the section subtitled Glucose toxicity:
"An overabundant diet rich in carbohydrates and fat (184) should force-feed electrons from glucose into the respiratory chain, in which the already prevailing high ΔΨ prevents electron flow. This excessive energy supply, not matched by energy demand, will further worsen the jamming of electrons in the respiratory chain and eventually result in massive ROS production and mitochondrial damage (Fig. 7)." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739696/
The condition of high carb plus high fat might be something to add to your analysis.
Outstanding podcast. A couple thoughts: When you say RET causes electrons to squirt back through Complex I, does that mean they do not also go back through Complex II (or any of the other inputs into the co-Q couple)? Also, I was intrigued by the contrast you talked about between overstretched adipocytes releasing saturated FFAs ( and not PUFAs) in obese people, but in people on a keto diet, they release more PUFAs. Is this the same physiological process causing a different result in the two cohorts, or are the different observations because the fat cells are doing two different things in each group? Thank you.
Hi Uknown, Yes, it’s a nice paper. The concept which is lacking is the physiological role for ROS signalling. If you accept that every single meal is hypercaloric in the absorptive phase you need to look at the physiological role for ROS to stop ingress of calories. This is not damaging… I think the paper is around 2006, people weren’t really thinking along those lines. But the mechanisms at the substrate label are nicely described.
Hi Scrivener, many thanks. There’s a follow on planned. Getting a good handle on the FFA types released under physiological vs pathological conditions is quite difficult because measuring total fatty acids is quite easy, separating them out by subtype tends to need HPLC, rather more involved than sticking plasma in a biochemistry analyser. My main push in this direction was from the Volek group’s paper https://pubmed.ncbi.nlm.nih.gov/18046594/. Mechanism is a “go read some more” subject which is still waiting.
The source of ROS is pretty well everywhere if you set up the mitochondrial model to show this. The interesting papers are those which consider what the physiological sources might be. If you use an inhibitor of complexes at or close to complex V electrons will, undoubtedly, spew out everywhere.
Excellent interview, explaining the concepts really well. With Saldaino and Brad Marshall giving you so much coverage you are going to be famous soon..... I never thought of you as a guru!
Would someone going to a high-SFA diet à la the Protons Theory (even from a “dirty keto” diet) expect an increase in dietary intake needs for electrolytes? Is there a mechanism or reason to think that switching to a high-SFA/low-PUFA substrate in mitochondria increases the demand for intracellular electrolytes Mg++ and/or K+? Does increasing the number of mitochondria generally increase intracellular electrolyte requirements?
Of course, some folks have already referred to this interview on the Great Barrington Declaration post.
ReplyDeleteI just want to say, in addition to the content, I greatly appreciate that the audio volume level was good. I've only heard one other interview with Peter (no video), and even with my laptop speakers turned all the way up, I could barely make out what Peter said. Partly it's the accent which is very strong to my American ears. Recorded more loudly would have helped.
I have the same problem with audio of Malcolm Kendrick. He has a soft voice to go with the Scottish accent, and without amplification it's very hard to try and listen.
Good job!
Hi, interesting discussion, thank you.
ReplyDeleteThe transient insulin resistance due to ROS from negative electron flow, how transient is this? Assume that this is repeated as long as the cell has extra calories to burn.
So, 4-HNE does similar thing i.e. transient insulin resistance. How does these two fit together, burning polyunstable fats does not make ROS, which does not then induce insulin resistance, however burning results in 4-HNE, which induces insulin resistance? Am I missing something in here?
rgds JR
Regarding the fat cell size, they found an interesting difference in Dietfits; lower carbers had smaller fat cells than higher carbers. The main finding in Dietfits was next to nill, no weight difference, but this fat cell size difference should be interesting. https://www.healio.com/news/endocrinology/20191205/despite-similar-weight-loss-lowcarbohydrate-diet-delivers-insulin-reductions-smaller-fat-cells-than
ReplyDeleteLooking forward further report on this...
JR
Great podcast Peter. Careful, now that people like Saladino and Marshall are taking your ideas more mainstream, you'll end up nailed to your cross. Still, on the plus side, people are hearing about your ideas and that's generally a Good Thing.
ReplyDeleteJR - I read your link and had to wonder - if the low fat dieters' fat cells are NOT shrinking significantly when they lose weight, it can only mean one of two things. Either the at cells are dying off, which sounds unlikely, or the lost body mass is coming from somewhere else. Muscle tissue perhaps? Strange that the question was never asked, at least in the article.
Lots to think about, as usual! On the reverse electron flow to indicate enough energy, it reminded me of this paper called "The Randle cycle revisited: a new head for an old hat". What they are saying is that the Randle cycle is broken under only 2 conditions: stress, which I understand is fight/flight stress, or eating high carb and high fat simultaneously. Here's a quote from the section subtitled Glucose toxicity:
ReplyDelete"An overabundant diet rich in carbohydrates and fat (184) should force-feed electrons from glucose into the respiratory chain, in which the already prevailing high ΔΨ prevents electron flow. This excessive energy supply, not matched by energy demand, will further worsen the jamming of electrons in the respiratory chain and eventually result in massive ROS production and mitochondrial damage (Fig. 7)."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739696/
The condition of high carb plus high fat might be something to add to your analysis.
Outstanding podcast. A couple thoughts:
ReplyDeleteWhen you say RET causes electrons to squirt back through Complex I, does that mean they do not also go back through Complex II (or any of the other inputs into the co-Q couple)?
Also, I was intrigued by the contrast you talked about between overstretched adipocytes releasing saturated FFAs ( and not PUFAs) in obese people, but in people on a keto diet, they release more PUFAs. Is this the same physiological process causing a different result in the two cohorts, or are the different observations because the fat cells are doing two different things in each group? Thank you.
Hi Uknown, Yes, it’s a nice paper. The concept which is lacking is the physiological role for ROS signalling. If you accept that every single meal is hypercaloric in the absorptive phase you need to look at the physiological role for ROS to stop ingress of calories. This is not damaging… I think the paper is around 2006, people weren’t really thinking along those lines. But the mechanisms at the substrate label are nicely described.
ReplyDeleteHi Scrivener, many thanks. There’s a follow on planned. Getting a good handle on the FFA types released under physiological vs pathological conditions is quite difficult because measuring total fatty acids is quite easy, separating them out by subtype tends to need HPLC, rather more involved than sticking plasma in a biochemistry analyser. My main push in this direction was from the Volek group’s paper https://pubmed.ncbi.nlm.nih.gov/18046594/. Mechanism is a “go read some more” subject which is still waiting.
The source of ROS is pretty well everywhere if you set up the mitochondrial model to show this. The interesting papers are those which consider what the physiological sources might be. If you use an inhibitor of complexes at or close to complex V electrons will, undoubtedly, spew out everywhere.
Peter
This was mind-blowingly brilliant. Thank you,Peter
ReplyDeleteI so enjoyed the interview, Peter!! Thank you for sharing your time so that more people get to hear a bit of your ideas.
ReplyDeleteExcellent interview, explaining the concepts really well. With Saldaino and Brad Marshall giving you so much coverage you are going to be famous soon..... I never thought of you as a guru!
ReplyDeleteHi Susanna, thank you, you are very welcome.
ReplyDeleteAbsolutely Chris. Neither did I. Nor do I now!!!!!
Peter
Would someone going to a high-SFA diet à la the Protons Theory (even from a “dirty keto” diet) expect an increase in dietary intake needs for electrolytes? Is there a mechanism or reason to think that switching to a high-SFA/low-PUFA substrate in mitochondria increases the demand for intracellular electrolytes Mg++ and/or K+? Does increasing the number of mitochondria generally increase intracellular electrolyte requirements?
ReplyDeleteCan't help there Scrivener, not something I've looked in to.
ReplyDeletePeter
Part 2 just got posted. https://www.youtube.com/watch?v=PQMjDtCeXlQ
ReplyDelete'Tis true
ReplyDeletePeter