Many observational studies associate prostate cancer with markers of metabolic syndrome. Which gives us the omega3/trans fat paradox, well discussed in several places around the net.
Here's a similar prostate paradox.
How come these two exceptions buck the trend? Here's a random thought:
Let's assume prostate cancer is related to chronic hyperinsulinaemia, a reasonable idea, ie it is "metabolic syndrome of the prostate".
Conversely, castration is a component of conventional prostate cancer treatment.
Getting to the chemical-castration stage of metabolic syndrome might well be prostate cancer protective.
Omega 3 fats probably slow progression of metabolic syndrome, trans fats probably accelerate it.
If you want to get to the castration level of metabolic syndrome as fast as possible, to maximise this prostate benefit, never forget to ask for your favourite lipotoxin by name.
For metabolic castration you should always ask for Crisco.
Peter
Alternatively I have a couple of bricks available. It's an old anaesthetist's joke:
Surgeon: "I don't need to use anaesthesia for castration."
Anaesthetist: "Really, what's your technique?"
Surgeon: "I have these two bricks and I smash them together on the testicles."
Anaesthetist (aghast): "Doesn't that hurt?"
Surgeon: "Only if you get your thumbs in the way."
Saturday, April 30, 2011
Monday, April 25, 2011
Diabetic nephropathy and the lost Swede
Chris over at Conditioning Research forwarded me the link to the PLoS paper demonstrating partial reversal of diabetic nephropathy in a couple of mouse models. This isn't exactly a world shattering finding as anyone with diabetes who is not eating a mildly ketogenic diet probably has shares in dialysis machines or is being grossly mismanaged.
Anyway, the first thing to do with a paper like this is to check whether the authors cited Nielsen's 2006 case report of a human being having their diabetic renal failure halted and partially reversed. I mean, this might be relevant...
They didn't.
The Swedish group simply fixed a patient without a mouse model in sight. They got ignored for their temerity. Shocking to fix a human without the death of a single leptin deficient mouse, but there you go. And it's not so hard to do either............
As a complete aside:
It turned out to be interesting to go back and see where the mouse folks were coming from. They cited this paper.
Here is part of figure 6, the line to follow is the open triangles.
Up to day 84 a high fat diet was fed. As happens so often, the high fat diet is 31.7% sucrose/maltodextrin by weight and (gasp) 20.7% lard.
From day 84 onwards these lazy, greedy porkers of mice were switched to a diet which was 47.5% lard and, utter horror, 19.95% butter. Of course this is not really a high fat diet as it has no sucrose or maltodextrin...
Look at the weight drop to below (ns) that of the mice fed crapinabag throughout........
Obviously this must be the satiating effect of protein, so often cited by idiots as the reason for weight loss of LC diets. Except it's not, the ketogenic mice had the lowest protein intake, 9.5% by weight cf 24% in the crapinabag and HF diets. That is very low in protein.
Here are the actual diets in Table 1:
A far more plausible explanation is that ketosis induces dissatisfaction in these mice concerning their body image due to their obese state so they then started to cut calories and go to the gym every night. Duh.
Now please don't make me put up the fasting insulin levels. Aw, okay, you twisted my arm.
Edit: I noticed that these are the FED insulin levels, we don't get fasting levels in the paper...
No comment.
Peter
Anyway, the first thing to do with a paper like this is to check whether the authors cited Nielsen's 2006 case report of a human being having their diabetic renal failure halted and partially reversed. I mean, this might be relevant...
They didn't.
The Swedish group simply fixed a patient without a mouse model in sight. They got ignored for their temerity. Shocking to fix a human without the death of a single leptin deficient mouse, but there you go. And it's not so hard to do either............
As a complete aside:
It turned out to be interesting to go back and see where the mouse folks were coming from. They cited this paper.
Here is part of figure 6, the line to follow is the open triangles.
Up to day 84 a high fat diet was fed. As happens so often, the high fat diet is 31.7% sucrose/maltodextrin by weight and (gasp) 20.7% lard.
From day 84 onwards these lazy, greedy porkers of mice were switched to a diet which was 47.5% lard and, utter horror, 19.95% butter. Of course this is not really a high fat diet as it has no sucrose or maltodextrin...
Look at the weight drop to below (ns) that of the mice fed crapinabag throughout........
Obviously this must be the satiating effect of protein, so often cited by idiots as the reason for weight loss of LC diets. Except it's not, the ketogenic mice had the lowest protein intake, 9.5% by weight cf 24% in the crapinabag and HF diets. That is very low in protein.
Here are the actual diets in Table 1:
A far more plausible explanation is that ketosis induces dissatisfaction in these mice concerning their body image due to their obese state so they then started to cut calories and go to the gym every night. Duh.
Now please don't make me put up the fasting insulin levels. Aw, okay, you twisted my arm.
Edit: I noticed that these are the FED insulin levels, we don't get fasting levels in the paper...
No comment.
Peter
Yesterdayday was first meat day
Edit: Today was fillet steak, OK so long as the piece is big enough to be sucked on without getting it all in her mouth at once...
Apparently babies are revolted by meat, just ask any vegan idiot
Peter
Apparently babies are revolted by meat, just ask any vegan idiot
Peter
Sunday, April 17, 2011
Palmitic acid: the horror never ends speculation
Back in her PhD days my wife attended a seminar presented by a visiting researcher on some aspect of the inflammatory cascade. It was very technical and focused around the interaction of a certain ligand with its receptor at some critical juncture in whatever process they had devoted the last n years of their life to studying.
The ligand was all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid. No one in the room had any idea what this stuff was, certainly not the extremely intelligent presenter, other than as a molecular key to a molecular lock. It's a stock lab reagent purchased in research grade purity from any one of a number of suppliers. You could equally order cervonic acid.
At the level of reductionism these people can work at there is no need to be aware that all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid is available in gel caps from Holland and Barrett or is present in the nearest can of sardines as the more familiar DHA.
So imagine you are some newbie PhD student. You walk in to the lab and are handed a reading list a mile long. The lab has certain research lines you are going to slot in to, particularly focused around inflammasome activation by fatty acids. You got the post because you had picked up extensive experience with cell culture and inflammation research based around both endotoxin and asbestos, plus a track record of multiple Nature publications from your undergraduate work.
The lab you walk in to has cells in culture which go ballistic on exposure to utterly physiological concentrations of palmitic acid. At least six widely differing cell types behave in exactly the same way. This looks like a generic effect and puts palmitic acid up there with asbestos as a proinflammatory agent. You switch to Flora that very lunch time, and spread it thinly too.
The lab also has an animal house in the basement. The rats are either fed a standard lab chow or a red coloured greasy type of pellet oozing fat. The lab techs feed and water the ratties. Your job is to compare molecular aspects of white blood cell inflammasome activation as the high fat rats get fatter over the weeks. Once a fortnight someone brings you a blood sample to work with but, apart from that, you will never see the rats again...
What do you question? EVERYONE knows that eating fat makes you fat. Fat is fat. Do you give a monkey's about EXACTLY what is in the pellets which stain the tech's hands red when they do the feeding? It's a standard obesogenic high fat diet from www.testdiets.com. All obesity research uses it or something similar...
Would you sit down and work out whether the hydrogen atoms on either side of the central double bond of one type of fatty acid in one constituent of the 5TJN are aligned on the same side or on opposite sides of the bond? You know, cis vs trans configuration...
It's sloppy. It's possible. People will really be able stand up and say, as Ting does:
"The simple message is to avoid fatty foods as much as possible."
They probably have no doubts. They believe. It's complete bollocks of course. But I have this concept of how things work...
Peter
The ligand was all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid. No one in the room had any idea what this stuff was, certainly not the extremely intelligent presenter, other than as a molecular key to a molecular lock. It's a stock lab reagent purchased in research grade purity from any one of a number of suppliers. You could equally order cervonic acid.
At the level of reductionism these people can work at there is no need to be aware that all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid is available in gel caps from Holland and Barrett or is present in the nearest can of sardines as the more familiar DHA.
So imagine you are some newbie PhD student. You walk in to the lab and are handed a reading list a mile long. The lab has certain research lines you are going to slot in to, particularly focused around inflammasome activation by fatty acids. You got the post because you had picked up extensive experience with cell culture and inflammation research based around both endotoxin and asbestos, plus a track record of multiple Nature publications from your undergraduate work.
The lab you walk in to has cells in culture which go ballistic on exposure to utterly physiological concentrations of palmitic acid. At least six widely differing cell types behave in exactly the same way. This looks like a generic effect and puts palmitic acid up there with asbestos as a proinflammatory agent. You switch to Flora that very lunch time, and spread it thinly too.
The lab also has an animal house in the basement. The rats are either fed a standard lab chow or a red coloured greasy type of pellet oozing fat. The lab techs feed and water the ratties. Your job is to compare molecular aspects of white blood cell inflammasome activation as the high fat rats get fatter over the weeks. Once a fortnight someone brings you a blood sample to work with but, apart from that, you will never see the rats again...
What do you question? EVERYONE knows that eating fat makes you fat. Fat is fat. Do you give a monkey's about EXACTLY what is in the pellets which stain the tech's hands red when they do the feeding? It's a standard obesogenic high fat diet from www.testdiets.com. All obesity research uses it or something similar...
Would you sit down and work out whether the hydrogen atoms on either side of the central double bond of one type of fatty acid in one constituent of the 5TJN are aligned on the same side or on opposite sides of the bond? You know, cis vs trans configuration...
It's sloppy. It's possible. People will really be able stand up and say, as Ting does:
"The simple message is to avoid fatty foods as much as possible."
They probably have no doubts. They believe. It's complete bollocks of course. But I have this concept of how things work...
Peter
Thursday, April 14, 2011
Palmitic acid: the horror never ends addendum
Okay, Victoria sent me the full pdf.
This group used 0.2mmol/l or 0.5mmol/l palmitate conjugated to bovine serum albumin. All other fatty acids were completely excluded. No semblance of physiological mixtures were involved.
But guess what, they had a living mouse model too!
Now you have to be wondering exactly how they managed to get a mouse to have 0.5mmol/l of palmitate in its bloodstream, to the exclusion of all other fatty acids, during a glucose tolerance test. After all, their test tube model used pure palmitate, surely they used the same conditions in their mice? This is a Nature paper after all.
How did they perform this near miracle? Well the methods section (when you finally find it tacked on to the end of the paper, an afterthought down beyond the references) doesn't mention any attempt to measure live mouse fatty acids at all. They didn't. WTF, this got published in Nature!
The diet used was good old commercial 5TJN. When I downloaded the composition pdf from the Test Diet website to my laptop it said I'd already downloaded it some time before..... It's popular!
Here's the link, it won't embed:
www.testdiet.com/PDF/5TJN.pdf
How much sugar would you like with your Crisco? Remember, always ask for your favourite lipotoxin by name...
NO NO NO.
JUST SAY NO.
Say no to Crisco.
As so often happens, this paper details feats of molecular and cellular manipulation of breathtaking complexity. How can anyone be capable of doing this and yet be so stupid? Awesome!
Peter
And it gets worse. The stats were done on "Prism 5.0 for Macintosh". OMG they're Mac users. It shouldn't be allowed. Their laptops should be confiscated forthwith. Now. I'll have them please.
This group used 0.2mmol/l or 0.5mmol/l palmitate conjugated to bovine serum albumin. All other fatty acids were completely excluded. No semblance of physiological mixtures were involved.
But guess what, they had a living mouse model too!
Now you have to be wondering exactly how they managed to get a mouse to have 0.5mmol/l of palmitate in its bloodstream, to the exclusion of all other fatty acids, during a glucose tolerance test. After all, their test tube model used pure palmitate, surely they used the same conditions in their mice? This is a Nature paper after all.
How did they perform this near miracle? Well the methods section (when you finally find it tacked on to the end of the paper, an afterthought down beyond the references) doesn't mention any attempt to measure live mouse fatty acids at all. They didn't. WTF, this got published in Nature!
The diet used was good old commercial 5TJN. When I downloaded the composition pdf from the Test Diet website to my laptop it said I'd already downloaded it some time before..... It's popular!
Here's the link, it won't embed:
www.testdiet.com/PDF/5TJN.pdf
How much sugar would you like with your Crisco? Remember, always ask for your favourite lipotoxin by name...
NO NO NO.
JUST SAY NO.
Say no to Crisco.
As so often happens, this paper details feats of molecular and cellular manipulation of breathtaking complexity. How can anyone be capable of doing this and yet be so stupid? Awesome!
Peter
And it gets worse. The stats were done on "Prism 5.0 for Macintosh". OMG they're Mac users. It shouldn't be allowed. Their laptops should be confiscated forthwith. Now. I'll have them please.
Wednesday, April 13, 2011
Palmitic acid: the horror never ends
Chris forwarded me a link to this study. Read about inflammasones in tissue culture and quake. Here is the relevant line:
"These findings provide insights into the association of inflammation, diet and T2D."
It gets even better. Here is the best line from the press release:
"These results support the idea that inflammation plays a role in chronic disease," says Ting. "The simple message is to avoid fatty foods as much as possible."
OK, you take isolated cells, bathe them in 2mmol palmitic acid and they become unhappy. This is supposed to have something to do with eating a high fat diet?????
Just for fun I'm going, in my head, to eat some (gasp, horror) palmitic acid. Please don't do this at home, you probably don't want to inflame your inflammasomes.
I'm looking through my refrigerator for some palmitic acid but I notice that all there is in my fridge is Food. Bugger. What comes closest? Maybe butter??? Butter is undoubtedly Food, but it does have rather a lot of palmitic acid. Let's give it a try.
Half a pound of butter, here I come. Mmmmmmm. Nice. Yummie.
Now let's measure my blood palmitic acid levels . OOOOOh, post prandial triglycerides are up! Right on, I'm gonna die, some time soon. But what about the acid, the pamitic acid?
Ah, FFAs are also up up up. Success! 500, 600, 700, yes, 800micromol/l. If I really am in luck I might make that 2000micomol/l hit and drop right in to the inflammasome mediated diabetes zone. You know, that palmitic acid trip to nowhere.
Oh, but except for feeling a bit nauseous from all that butter in one go, I feel fine. Perhaps because I don't really have 2mmol/l palmitate in my blood stream after all. Double bugger. It seems like there is major, like MAJOR, contamination of my blood palmitate with oleate. Some is from the butter, some is from my own bloody liver cocking up the experiment. Using delta 9 desaturase to drop the occasional double bond in to long chain saturated fats ensures normal physiology.
Now, if I wasn't such a cheapskate I'd shell out the ackers to see if Ting et al used mixes of palmitate and oleate as well as either fatty acid in isolation. We know from the abstract that oleate does not inflame your inflammasomes... But I am a cheapskate, so I won't. Instead I'll go to this study:
"Low concentrations of oleate (0.1mM) completely inhibited palmitate-induced oxidative stress, SAPK activation, and apoptosis."
That's it, one tenth of one millimole of oleate completely negates the adverse effects of isolated palmitate.
Maybe check this one:
"Oleate alone did not cause mtROS generation and mtDNA damage, and its addition to palmitate prevented palmitate-induced mtDNA damage, increased total ATP levels and cell viability, and prevented palmitate-induced apoptosis and inhibition of insulin-stimulated Akt (Ser(473)) phosphorylation."
I could go on. No one, ever, at any time, has 2mmol/l of isolated palmitate in their bloodstream. A whiff of oleate is completely protective against the evil intentions of a researcher with a block of palmitate when viewed from the bottom of a test tube. It's called physiology. We are evolved to work this way. Knock out delta 9 desaturase and things become quite fun, but that's another story!
Citing the existing literature doesn't get you a Nature publication. Nor does it allow you to write press releases of utter stupidity to support low fat eating while simultaneously keeping yourself off the dole.
Peter
"These findings provide insights into the association of inflammation, diet and T2D."
It gets even better. Here is the best line from the press release:
"These results support the idea that inflammation plays a role in chronic disease," says Ting. "The simple message is to avoid fatty foods as much as possible."
OK, you take isolated cells, bathe them in 2mmol palmitic acid and they become unhappy. This is supposed to have something to do with eating a high fat diet?????
Just for fun I'm going, in my head, to eat some (gasp, horror) palmitic acid. Please don't do this at home, you probably don't want to inflame your inflammasomes.
I'm looking through my refrigerator for some palmitic acid but I notice that all there is in my fridge is Food. Bugger. What comes closest? Maybe butter??? Butter is undoubtedly Food, but it does have rather a lot of palmitic acid. Let's give it a try.
Half a pound of butter, here I come. Mmmmmmm. Nice. Yummie.
Now let's measure my blood palmitic acid levels . OOOOOh, post prandial triglycerides are up! Right on, I'm gonna die, some time soon. But what about the acid, the pamitic acid?
Ah, FFAs are also up up up. Success! 500, 600, 700, yes, 800micromol/l. If I really am in luck I might make that 2000micomol/l hit and drop right in to the inflammasome mediated diabetes zone. You know, that palmitic acid trip to nowhere.
Oh, but except for feeling a bit nauseous from all that butter in one go, I feel fine. Perhaps because I don't really have 2mmol/l palmitate in my blood stream after all. Double bugger. It seems like there is major, like MAJOR, contamination of my blood palmitate with oleate. Some is from the butter, some is from my own bloody liver cocking up the experiment. Using delta 9 desaturase to drop the occasional double bond in to long chain saturated fats ensures normal physiology.
Now, if I wasn't such a cheapskate I'd shell out the ackers to see if Ting et al used mixes of palmitate and oleate as well as either fatty acid in isolation. We know from the abstract that oleate does not inflame your inflammasomes... But I am a cheapskate, so I won't. Instead I'll go to this study:
"Low concentrations of oleate (0.1mM) completely inhibited palmitate-induced oxidative stress, SAPK activation, and apoptosis."
That's it, one tenth of one millimole of oleate completely negates the adverse effects of isolated palmitate.
Maybe check this one:
"Oleate alone did not cause mtROS generation and mtDNA damage, and its addition to palmitate prevented palmitate-induced mtDNA damage, increased total ATP levels and cell viability, and prevented palmitate-induced apoptosis and inhibition of insulin-stimulated Akt (Ser(473)) phosphorylation."
I could go on. No one, ever, at any time, has 2mmol/l of isolated palmitate in their bloodstream. A whiff of oleate is completely protective against the evil intentions of a researcher with a block of palmitate when viewed from the bottom of a test tube. It's called physiology. We are evolved to work this way. Knock out delta 9 desaturase and things become quite fun, but that's another story!
Citing the existing literature doesn't get you a Nature publication. Nor does it allow you to write press releases of utter stupidity to support low fat eating while simultaneously keeping yourself off the dole.
Peter
Saturday, April 02, 2011
Fasting insulin and weight loss and calories-in vs calories-out
I had this exchange in the comments on a previous post:
Frank said...
Hi Peter. I'd say that I pretty much agree with your post. Insulin and caloric deficit are not mutually exclusive, ie, low-insulin could enhance fat loss on a caloric deficit or, looked from another perspective, a caloric deficit could enhance fat loss if someone has low insulin level. I have only one question for you. For the sake of it lets make thing black and white. What do you believe is the most important thing to do, in order to achieve weight/fat loss a) be in a caloric deficit (your insulin level does not matter much) b) having a low-insulin level (it does not matter much if you're in a caloric deficit or not). Again, in real life, I don't believe they exclude each other, but if you could fix only one to have a weight loss, which one would you fix? Calories or insulin? The way I see it is that, as you stated, insulin inhibits lipolysis, but more lipolysis does not equal more oxidation. It still has to be matched to energy expenditure. In that case, calories would be the most important factor. That's my point of view and it could be wrong. I'm just wondering if you agree to some degree with it, because reading your post, I get the idea that you do. Thanks for your time.
Peter said...
Ah Frank, now there is a question. Without caloric deficit (and I want uncoupling proteins, sleeping metabolic rate, spontaneous movements, etc, etc, etc, everything, accounted for) there will be no weight loss. But, in real life, if I could only alter just one, it would be insulin. I would expect no weight loss but I would expect improved health. What else matters?
There is a flaw in the answer I gave to this question. It's working at the Noddy level of calories-in vs calories-out.
The Noddy approach is perfectly adequate to explain the findings of GnK's paper (PR's weight loss excepted, if she genuinely ate all she was asked to), but embarrassingly stupid in the real world.
Let's look at calories-in vs calories-out in the fixed caloric phase of the Abredeen study.
Calories-in is total calories in to metabolism. There are two sources. Those from the diet, let's assume (incorrectly) these are genuinely all of the 2000kcal/d on offer. Then there is the supply of free fatty acids metered out from adipocytes under the regulation of insulin. Maybe a little glycogen, but I'll ignore that for the discussion.
Under LCHF conditions more FFAs are accessible due to lower insulin levels. More get used and, from Table 1, only 1930kcal of food are needed to supplement those calories-in from adipocytes in order to meet total metabolic needs. Hunger is low. Calories supplied are clearly able to meet voluntary calories out. Demand is within the limits of supply. Some food is refused.
Under MCMF conditions the higher insulin level allows less calories to be supplied from fat in to metabolism (adipose derived calories-in fall), so calories-in accepted from food spontaneously increase to the full 2000kcal/d. Under the study conditions we cannot tell if 2000kcal plus reduced adipose FFA supply is enough for as much metabolic activity as was possible under low insulin conditions. What if it is not? Now the real question is: Does lipolysis automatically increase to supply all needs for calories out? Why should it? Lipolysis is controlled by insulin. Insulin is high, lipolysis restrained.
If there is any shortfall in the calories from fat plus 2000kcal, there are only limited calories available to burn. You can't burn what you don't have. Calories-out would drop because they simply cannot exceed the supply available. I would expect the participants to automatically reduce their calories-out. There is no free lunch. Calories-out = calories-in. All need to be accounted for.
Is it be possible to force lipolysis in the face of hyperinsulinaemia to increase FFAs from fat to a higher level without lowering insulin?
Of course it is. There are other hormones in addition to insulin. You can throw around adrenaline, growth hormone, glucagon and probably a truckload of others I've not thought about. You can add in direct sympathetic nervous system innervation of adipocytes to effect lipolysis if you like. But these mechanisms come with a price. The price is hunger.
I think it's called working up an appetite.
In the Aberdeen study the attempt to maintain caloric intake failed during the LCHF phase because low insulin increased caloric supply from fat. Higher insulin in the MCMF phase limited calories-in derived from adipose tissue and may well have set a cap on total calories available for use during this higher insulin phase.
In Frank's thought experiment it might be easy to fix dietary calories-in, but people might refuse some of them if insulin was low enough for adipose tissue derived FFAs to be available.... If they ate all of their calories but wriggled in their chair a bit more because they had more calories available then the concept of calories-out being fixed is lost....
I'll just finish with a clarification of this phrase from another commenter:
"lipolysis is not beta oxidation"
This is, ultimately, accurate. That doesn't stop it being bollocks.
A rather more perceptive view is the situation comes from, of all places, the lipophobic cardiologists who published on FFAs and myocardial ischaemia:
"The rate of fatty-acid uptake and oxidation by the heart is controlled by their availability [33]"
Oh, interesting. Availability. A supply led system. Hmmmmmm. I would guess most FFA burning tissue would follow cardiac muscle. Now I can't quite remember what effect insulin has on lipolysis and FFA availability. Silly me.
Peter
Frank said...
Hi Peter. I'd say that I pretty much agree with your post. Insulin and caloric deficit are not mutually exclusive, ie, low-insulin could enhance fat loss on a caloric deficit or, looked from another perspective, a caloric deficit could enhance fat loss if someone has low insulin level. I have only one question for you. For the sake of it lets make thing black and white. What do you believe is the most important thing to do, in order to achieve weight/fat loss a) be in a caloric deficit (your insulin level does not matter much) b) having a low-insulin level (it does not matter much if you're in a caloric deficit or not). Again, in real life, I don't believe they exclude each other, but if you could fix only one to have a weight loss, which one would you fix? Calories or insulin? The way I see it is that, as you stated, insulin inhibits lipolysis, but more lipolysis does not equal more oxidation. It still has to be matched to energy expenditure. In that case, calories would be the most important factor. That's my point of view and it could be wrong. I'm just wondering if you agree to some degree with it, because reading your post, I get the idea that you do. Thanks for your time.
Peter said...
Ah Frank, now there is a question. Without caloric deficit (and I want uncoupling proteins, sleeping metabolic rate, spontaneous movements, etc, etc, etc, everything, accounted for) there will be no weight loss. But, in real life, if I could only alter just one, it would be insulin. I would expect no weight loss but I would expect improved health. What else matters?
There is a flaw in the answer I gave to this question. It's working at the Noddy level of calories-in vs calories-out.
The Noddy approach is perfectly adequate to explain the findings of GnK's paper (PR's weight loss excepted, if she genuinely ate all she was asked to), but embarrassingly stupid in the real world.
Let's look at calories-in vs calories-out in the fixed caloric phase of the Abredeen study.
Calories-in is total calories in to metabolism. There are two sources. Those from the diet, let's assume (incorrectly) these are genuinely all of the 2000kcal/d on offer. Then there is the supply of free fatty acids metered out from adipocytes under the regulation of insulin. Maybe a little glycogen, but I'll ignore that for the discussion.
Under LCHF conditions more FFAs are accessible due to lower insulin levels. More get used and, from Table 1, only 1930kcal of food are needed to supplement those calories-in from adipocytes in order to meet total metabolic needs. Hunger is low. Calories supplied are clearly able to meet voluntary calories out. Demand is within the limits of supply. Some food is refused.
Under MCMF conditions the higher insulin level allows less calories to be supplied from fat in to metabolism (adipose derived calories-in fall), so calories-in accepted from food spontaneously increase to the full 2000kcal/d. Under the study conditions we cannot tell if 2000kcal plus reduced adipose FFA supply is enough for as much metabolic activity as was possible under low insulin conditions. What if it is not? Now the real question is: Does lipolysis automatically increase to supply all needs for calories out? Why should it? Lipolysis is controlled by insulin. Insulin is high, lipolysis restrained.
If there is any shortfall in the calories from fat plus 2000kcal, there are only limited calories available to burn. You can't burn what you don't have. Calories-out would drop because they simply cannot exceed the supply available. I would expect the participants to automatically reduce their calories-out. There is no free lunch. Calories-out = calories-in. All need to be accounted for.
Is it be possible to force lipolysis in the face of hyperinsulinaemia to increase FFAs from fat to a higher level without lowering insulin?
Of course it is. There are other hormones in addition to insulin. You can throw around adrenaline, growth hormone, glucagon and probably a truckload of others I've not thought about. You can add in direct sympathetic nervous system innervation of adipocytes to effect lipolysis if you like. But these mechanisms come with a price. The price is hunger.
I think it's called working up an appetite.
In the Aberdeen study the attempt to maintain caloric intake failed during the LCHF phase because low insulin increased caloric supply from fat. Higher insulin in the MCMF phase limited calories-in derived from adipose tissue and may well have set a cap on total calories available for use during this higher insulin phase.
In Frank's thought experiment it might be easy to fix dietary calories-in, but people might refuse some of them if insulin was low enough for adipose tissue derived FFAs to be available.... If they ate all of their calories but wriggled in their chair a bit more because they had more calories available then the concept of calories-out being fixed is lost....
I'll just finish with a clarification of this phrase from another commenter:
"lipolysis is not beta oxidation"
This is, ultimately, accurate. That doesn't stop it being bollocks.
A rather more perceptive view is the situation comes from, of all places, the lipophobic cardiologists who published on FFAs and myocardial ischaemia:
"The rate of fatty-acid uptake and oxidation by the heart is controlled by their availability [33]"
Oh, interesting. Availability. A supply led system. Hmmmmmm. I would guess most FFA burning tissue would follow cardiac muscle. Now I can't quite remember what effect insulin has on lipolysis and FFA availability. Silly me.
Peter