Like.
Peter
Saturday, September 21, 2013
Electron Transport Chain image
Just off to bed. Wow, do I have wild Saturday nights! Had to share this lovely pic. One of the better representations of the ETC I've ever seen, lifted from here.
Like.
Peter
Like.
Peter
Wooo and the snps
There seems to be quite a bit of interest going on in the LC Hardcore at the moment and I'm sat here, under my stone, looking at UCPs as prime mediators of the insulin resistance of fasting and membrane pumps in the origin of life as relates to lactate and extracellular pH in cancer. And I should really be working on a dead-lined anaesthesia project. Wooo and Toxic ("I read your potatoes, and the news will never be good" LMAO) have both brought up 23andme and, surprise surprise, Wooo has enough snps on assorted ion channel genes to have her in a loony bin several times over. She concludes that a ketogenic diet gets her a normal life.
Obviously I have nothing to disagree with here.
What I would comment on is that a very, very large chunk of the "normal" population may not be quite as normal as she suspects. Having frank bipolar disease with severe enough presentation to give you a clear cut "label" is quite rare. Having severe depression to the point of complete loss of functionality or schizophrenia to the point of obeying the voices completely, whatever they command, are all equally rare. But shades of grey appear to be very common and I don't see that many normal people are all that normal. Undoubtedly we all have snps on all sorts of genes. That's genetic variability and is essential to provide a pool for the species to adapt through.
That many mental illnesses are essentially metabolic, and that ion channels have a great deal to do with neural energy demands, is not exactly unexpected. Sid Dishes emailed me this rather interesting review (BTW finding this in Nature is rather like reading a massive endorsement of the Atkins diet in the Sun or the Daily Mail, Sid feels paradigm shift) looking at exactly the metabolic aspect. Yet another email needing a thankyou not sent yet. Thanks Sid. Look at this quote from the abstract talking about central neurons:
"it is now clear that they [psychiatric illnesses] are associated with impairments of synaptic plasticity"
and tie that back to peripheral neuropathy, here's Chowdhury on peripheral nerves:
"The consequences of suboptimal ATP supply for the distal nerve fiber are numerous: (1) collateral sprouting and plasticity will be retarded, (2) this will lead to gradual pruning of the axonal network and shrinkage of sensory innervation fields, and (3) end organs of myelinated fibers within the dermis will lose innervation and function (see Fig. 3)"
My italics.
The parallels, to me, make it sound like we are talking about the same process. I would suggest that hyperglycaemia breaks the mitochondrial population and ketosis is an excellent sticking plaster. Which snps you have determine which neurons break first.
If you also have metabolic snps which limit your ability to avoid hyperglycaemia on the SAD in addition to neural snps which make for "upper limit of normality" energy demands within hyperglycaemia compromised neurons, you are on your way to the Funny Farm. Or a ketogenic diet.
I, for one, am very glad Wooo hit the ketogenic diet arm.
I have said that I think it is unlikely that humans are in any way adapted to a diet which regularly and severely induces hyperglycaemia. Had Wooo been born in to a normoglycaemic environment, what would the effect have been of her ion channel snps on perception?
If you think Wooo is "normal", you are crazy.
Personally, I think we need people who are three standard deviations from the population norm when it comes to insight and perception. This may well be down to ion channels and snps of the Wooo flavour... I don't see that we would get too far, species wise, if we were all Taterheads with ion channels which allowed tolerance of hyperglycaemia until Alzheimers (type 3 diabetes) kicked in, and yet only allowed as much insight in to anything as a turnip has. Of the latter, there is a lot of it about, we have more than enough.
Blog on Wooo.
Peter
Obviously I have nothing to disagree with here.
What I would comment on is that a very, very large chunk of the "normal" population may not be quite as normal as she suspects. Having frank bipolar disease with severe enough presentation to give you a clear cut "label" is quite rare. Having severe depression to the point of complete loss of functionality or schizophrenia to the point of obeying the voices completely, whatever they command, are all equally rare. But shades of grey appear to be very common and I don't see that many normal people are all that normal. Undoubtedly we all have snps on all sorts of genes. That's genetic variability and is essential to provide a pool for the species to adapt through.
That many mental illnesses are essentially metabolic, and that ion channels have a great deal to do with neural energy demands, is not exactly unexpected. Sid Dishes emailed me this rather interesting review (BTW finding this in Nature is rather like reading a massive endorsement of the Atkins diet in the Sun or the Daily Mail, Sid feels paradigm shift) looking at exactly the metabolic aspect. Yet another email needing a thankyou not sent yet. Thanks Sid. Look at this quote from the abstract talking about central neurons:
"it is now clear that they [psychiatric illnesses] are associated with impairments of synaptic plasticity"
and tie that back to peripheral neuropathy, here's Chowdhury on peripheral nerves:
"The consequences of suboptimal ATP supply for the distal nerve fiber are numerous: (1) collateral sprouting and plasticity will be retarded, (2) this will lead to gradual pruning of the axonal network and shrinkage of sensory innervation fields, and (3) end organs of myelinated fibers within the dermis will lose innervation and function (see Fig. 3)"
My italics.
The parallels, to me, make it sound like we are talking about the same process. I would suggest that hyperglycaemia breaks the mitochondrial population and ketosis is an excellent sticking plaster. Which snps you have determine which neurons break first.
If you also have metabolic snps which limit your ability to avoid hyperglycaemia on the SAD in addition to neural snps which make for "upper limit of normality" energy demands within hyperglycaemia compromised neurons, you are on your way to the Funny Farm. Or a ketogenic diet.
I, for one, am very glad Wooo hit the ketogenic diet arm.
I have said that I think it is unlikely that humans are in any way adapted to a diet which regularly and severely induces hyperglycaemia. Had Wooo been born in to a normoglycaemic environment, what would the effect have been of her ion channel snps on perception?
If you think Wooo is "normal", you are crazy.
Personally, I think we need people who are three standard deviations from the population norm when it comes to insight and perception. This may well be down to ion channels and snps of the Wooo flavour... I don't see that we would get too far, species wise, if we were all Taterheads with ion channels which allowed tolerance of hyperglycaemia until Alzheimers (type 3 diabetes) kicked in, and yet only allowed as much insight in to anything as a turnip has. Of the latter, there is a lot of it about, we have more than enough.
Blog on Wooo.
Peter
Friday, September 06, 2013
Omega 3s and G-protein coupled receptors
Let's just summarise the role of omega 6 fats in Sauer's rat model of cancer:
In the lab situation rapid hepatoma tumour growth needs either arachidonic or linoleic acids. The acids must be taken up in to the hepatoma cells, they must be acted on by lipoxygenase to produce 13-hydroxyoctadecadienoic acid, better known as 13-HODE. 13-HODE appears to be the mitogen which promotes rapid cancer growth. 13-HODE looks like a repair signal gone wrong in cancer cells. Omega 3 fatty acids block omega 6 fatty acid uptake in to hepatoma cells. That's all well and good but the reason I got in to this paper was omega 3 PUFA signalling, rather than those omega 6 issues...
OK, Sauer starts to give some pointers on the function of omega 3 fatty acids in health. That's interesting, as I'm no great lover of any sort of PUFA when I view them from the Protons perspective, yet omega 3s seem to come out pretty well, certainly at low doses. You know my fall back, omega 3 PUFA don't always behave like omega 6 PUFA because they get used as signalling molecules blah blah blah. My own inability to tie the molecular structure of omega 3s to their clinical effects is very frustrating! That they probably act are sites "above" the ETC suggest that they act as what I view as 'high level signals".
Well they do.
The signalling appears to be through a G-protein linked receptor with all of the usual cAMP cascade that follows binding of a ligand to such a receptor. What I found particularly interesting was the effect produced on fat pads of normal rats when EPA (other papers from Sauer suggest all omega 3s act on whichever receptor is involved) was added to the perfusate.
OK, here is a neat little graph taken from here:
This is from fed rats. In the fed state the FFA uptake by the inguinal fat pad of a rat is about 6 mcg/min/gram, white open squares.
Adding EPA at 0.84mmol/l (a bit supraphysiological for EPA but let's let that ride) and FFA uptake by the fat pad drops to zero, or close to zero. Or, in fact, you could argue a suggestion of fatty acid relase, shown as a negative uptake value. Black circles. Fatty acids are not taken up, they end up in the venous effluent in the experiment, plus a little extra.
Whooooah, so do FFAs go through the roof when you take fish oil IRL??
Well no. That's because of this graph from here in the same paper:
Here we have the free fatty acid release from the inguinal fat pad of a healthy rat who has been starved for 48 hours. Fatty acid release is trundling along at about 3mcg/min/gram until EPA is added, again at around 0.8mmol/l. The release of FFAs, in the fasted state, is eliminated. Table 1 in the same paper shows you can get this effect of halting lipolysis in starved rats with under 0.3mmol/l EPA.
Both effects are mediated through a G-protein coupled receptor, ie high level signalling compared to electrons and superoxide in the electron transport chain.
Obviously there are a number of serious problems with this paper but, as a proof of concept, I buy it. I doubt DHA or alpha linolenic acid would work as well (or the group would have used them for this proof of point exercise!) and I think the levels of EPA used produce a very artefactual "switch-like" effect which is probably a graded response. I doubt 0.8mmol/l or even 0.3mmol/l of EPA is exactly physiological but...
Let's suggest that there is a progressive removal of the influence of adipocytes from the FFA flux in/out of plasma as the level of omega 3s in arterial blood increases. Omega 3 fatty acids render adipocytes irrelevant to free fatty acid levels in the plasma.
That is one hell of an idea.
Next we need a brief look at hepatoma cells, again the graph is provided by Sauer and it shows that omega 3 fatty acids, in a G-protein coupled receptor manner, completely turn off the uptake of ALL fatty acids in to hepatoma cells.
If, and it's quite a big "if", the same effects apply to hepatocytes as well as hepatoma cells, we then have a very straightforward mechanism for the protective effects of omega 3 fish oils on hepatic lipidosis. From my point of view this is quite real as there are pretty convincing papers showing that cats, in real life, can be largely protected against the potentially fatal hepatic lipidosis of rapid weight loss by modest doses of omega 3 fatty acids.
Soooo while omega 3s stop the release of all FFAs from adipocytes, they simultaneously stop the uptake of all fatty acids in to the two primary storage organs for fatty acids, adipocytes and liver.
Do plasma FFAs go up or down?
They do, of course, go down. A paradox? Next paper.
Health warning: This paper is so steeped in VLDL and ApoB lipophobia that it makes difficult reading. But there is so little published on FFAs and omega 3 supplementation that it's worth the ondansetron to read it. It's looking at how omega 3 supplements might lower fasting triglycerides, which are the devil incarnate for CVD risk. A huge chunk of VLDL comes from FFAs released from adipocytes and their subsequent repackaging by the liver. Apparently, and I quote from the abstract:
"FO [fish oil] counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation"
A bit like insulin resistance is caused by "inflammation". Well, maybe it's that simple. They have taken the concept of high level signalling to its 2013 pedestal without looking for basic mechanisms. They have placed the G-protein coupled receptor on to macrophages in the fat pads, which subsequently control the adipocyte lipolysis using cytokines. I haven't checked how good this concept is. Sauer never looked that deeply. Looks a bit modern to me.
Personally I would guess that there are similar receptors on both adipocytes and hepatocytes, but the review does not seem to cover the ability of omega 3s to inhibit general fatty acid uptake by these two tissues. Ah well.
What they do argue is that omega 3 fatty acids upregulate lipoprotein lipase, pretty well whole body. Of course liver and adipocytes ignore this fatty acid bonanza, as above. LPL upregulation is what I needed to know from this paper.
So where do "spare" fatty acids go to? They go to muscles. Upregulated lipoprotein lipase (heralded as the saviour from elevated fasting triglycerides) allows increased lipid release from VLDL to lower those fasting triglycerides. But it's worth bearing in mind that cells do not "see" VLDL, the LPL is on the vascular endothelium and the cells behind the vessel wall only ever receive "free" fatty acids. These are not labelled as from albumin, VLDL or chylomicrons.
Slight aside for later: It seems likely that chylomicrons are going spill their lipids via that same LPL, worth remembering.
The story in the review can be sumarised as omega 3 fatty acids block the release of FFAs from adipocytes and increase the activity of lipoprotein lipase pretty well whole body. VLDL drops, FFAs drop. All is happy in the cardiovascular system. If you believe.
Various "bits" of omega 3s, especially the lipid peroxides of DHA, are signals for mitochondrial biogenesis. I had a paper which specified which lipoxide was most effective but must have missed the "save" button. Mea culpa yet again. There are hints here.
That's a very neat story, which has more than a grain of truth to it.
Why is it like this? What does it mean, physiologcally? Speculation time:
Omega 3 fats come from plants. Mostly from chloroplasts. Where do humans get their omega 3s from? Certainly not from plants. If we did then the rabid Dr Furhman would not be (correctly) recommending DHA supplementation (along with B12) to avoid brain collapse on veg*n diets. Actually, this link is quite funny when cited by Mc-Starch-Dougall:
"There is no evidence of adverse effects on health or cognitive function with lower DHA intake in vegetarians"
Well, I found it amusing. It's almost the converse of the neurological truism which states that being concerned about having a neurodegenerative disease probably means you don't actually have one.
Anyhoo. Away from the coast we have to get our DHA from animals (or buy algae derived supplements). They get it from grass. There is DHA present in adipose tissue of herbivores just as much as it is present in lipid membranes of their cells. My suspicion is that DHA is a signal to your metabolism that you have just eaten animal fat, from an animal who's food chain starts with grass [or algae]. The more fat you eat, the stronger the signal. We do not need much DHA overall for our brains as it is well protected in this site, but we might well be using it at low levels as a [G-protein coupled receptor sensed] signal to target metabolic adaptation to process fat. So is McDougall correct that veg*n "brain" tissue is OK, despite their periphery being depleted? Shrug.
Fish oil supplements? Well, using our "dietary fat is here" marker to pharmacologically modify some perceived CVD risk factor, without the appropriate change in source of metabolic fuel supply, looks to me to be of very limited value. Large intervention trials do show some benefit from omega 3s provided you do your stats well enough, you have a large enough population to pick up a very small effect and you give a high enough dose. But they do not seem to be any sort of panacea. Especially of you are avoiding dietary fat while "faking" the signal that you have eaten dietary fat...
This is not exactly surprising when you try to pick the likely physiology apart. I like the concept of DHA as an animal fat signal.
Peter
Final thought: Do we need omega 3 PUFA at anything above the most minimal levels if we are in saturated fat based ketosis? Of course I don't know. But the signal to cope with starvation is palmitic acid (physiological insulin resistance), not DHA. I live in starvation mode, not on a mixed diet with only intermittent access to healthy ruminant fat. I have long wanted to look at the selective release of FFAs from adipocytes in extended starvation. My suspicion is that in the early days after glycogen depletion palmitic acid is preferentially released over other lipids, PUFA are not needed/wanted. By a few weeks all the palmitate is gone and whatever is left then gets released. People like David Blaine suddenly start to feel weak, wobbly and are probably hypoglycaemic once they run out of palmitate and have to release less saturated fats. Two to four weeks if you carry some spare weight. Sauer's rats had only ever been fed a low fat omega 6 based diet and had no serious palmitate reserves, PUFA release came early for these.
In the lab situation rapid hepatoma tumour growth needs either arachidonic or linoleic acids. The acids must be taken up in to the hepatoma cells, they must be acted on by lipoxygenase to produce 13-hydroxyoctadecadienoic acid, better known as 13-HODE. 13-HODE appears to be the mitogen which promotes rapid cancer growth. 13-HODE looks like a repair signal gone wrong in cancer cells. Omega 3 fatty acids block omega 6 fatty acid uptake in to hepatoma cells. That's all well and good but the reason I got in to this paper was omega 3 PUFA signalling, rather than those omega 6 issues...
OK, Sauer starts to give some pointers on the function of omega 3 fatty acids in health. That's interesting, as I'm no great lover of any sort of PUFA when I view them from the Protons perspective, yet omega 3s seem to come out pretty well, certainly at low doses. You know my fall back, omega 3 PUFA don't always behave like omega 6 PUFA because they get used as signalling molecules blah blah blah. My own inability to tie the molecular structure of omega 3s to their clinical effects is very frustrating! That they probably act are sites "above" the ETC suggest that they act as what I view as 'high level signals".
Well they do.
The signalling appears to be through a G-protein linked receptor with all of the usual cAMP cascade that follows binding of a ligand to such a receptor. What I found particularly interesting was the effect produced on fat pads of normal rats when EPA (other papers from Sauer suggest all omega 3s act on whichever receptor is involved) was added to the perfusate.
OK, here is a neat little graph taken from here:
This is from fed rats. In the fed state the FFA uptake by the inguinal fat pad of a rat is about 6 mcg/min/gram, white open squares.
Adding EPA at 0.84mmol/l (a bit supraphysiological for EPA but let's let that ride) and FFA uptake by the fat pad drops to zero, or close to zero. Or, in fact, you could argue a suggestion of fatty acid relase, shown as a negative uptake value. Black circles. Fatty acids are not taken up, they end up in the venous effluent in the experiment, plus a little extra.
Whooooah, so do FFAs go through the roof when you take fish oil IRL??
Well no. That's because of this graph from here in the same paper:
Here we have the free fatty acid release from the inguinal fat pad of a healthy rat who has been starved for 48 hours. Fatty acid release is trundling along at about 3mcg/min/gram until EPA is added, again at around 0.8mmol/l. The release of FFAs, in the fasted state, is eliminated. Table 1 in the same paper shows you can get this effect of halting lipolysis in starved rats with under 0.3mmol/l EPA.
Both effects are mediated through a G-protein coupled receptor, ie high level signalling compared to electrons and superoxide in the electron transport chain.
Obviously there are a number of serious problems with this paper but, as a proof of concept, I buy it. I doubt DHA or alpha linolenic acid would work as well (or the group would have used them for this proof of point exercise!) and I think the levels of EPA used produce a very artefactual "switch-like" effect which is probably a graded response. I doubt 0.8mmol/l or even 0.3mmol/l of EPA is exactly physiological but...
Let's suggest that there is a progressive removal of the influence of adipocytes from the FFA flux in/out of plasma as the level of omega 3s in arterial blood increases. Omega 3 fatty acids render adipocytes irrelevant to free fatty acid levels in the plasma.
That is one hell of an idea.
Next we need a brief look at hepatoma cells, again the graph is provided by Sauer and it shows that omega 3 fatty acids, in a G-protein coupled receptor manner, completely turn off the uptake of ALL fatty acids in to hepatoma cells.
If, and it's quite a big "if", the same effects apply to hepatocytes as well as hepatoma cells, we then have a very straightforward mechanism for the protective effects of omega 3 fish oils on hepatic lipidosis. From my point of view this is quite real as there are pretty convincing papers showing that cats, in real life, can be largely protected against the potentially fatal hepatic lipidosis of rapid weight loss by modest doses of omega 3 fatty acids.
Soooo while omega 3s stop the release of all FFAs from adipocytes, they simultaneously stop the uptake of all fatty acids in to the two primary storage organs for fatty acids, adipocytes and liver.
Do plasma FFAs go up or down?
They do, of course, go down. A paradox? Next paper.
Health warning: This paper is so steeped in VLDL and ApoB lipophobia that it makes difficult reading. But there is so little published on FFAs and omega 3 supplementation that it's worth the ondansetron to read it. It's looking at how omega 3 supplements might lower fasting triglycerides, which are the devil incarnate for CVD risk. A huge chunk of VLDL comes from FFAs released from adipocytes and their subsequent repackaging by the liver. Apparently, and I quote from the abstract:
"FO [fish oil] counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation"
A bit like insulin resistance is caused by "inflammation". Well, maybe it's that simple. They have taken the concept of high level signalling to its 2013 pedestal without looking for basic mechanisms. They have placed the G-protein coupled receptor on to macrophages in the fat pads, which subsequently control the adipocyte lipolysis using cytokines. I haven't checked how good this concept is. Sauer never looked that deeply. Looks a bit modern to me.
Personally I would guess that there are similar receptors on both adipocytes and hepatocytes, but the review does not seem to cover the ability of omega 3s to inhibit general fatty acid uptake by these two tissues. Ah well.
What they do argue is that omega 3 fatty acids upregulate lipoprotein lipase, pretty well whole body. Of course liver and adipocytes ignore this fatty acid bonanza, as above. LPL upregulation is what I needed to know from this paper.
So where do "spare" fatty acids go to? They go to muscles. Upregulated lipoprotein lipase (heralded as the saviour from elevated fasting triglycerides) allows increased lipid release from VLDL to lower those fasting triglycerides. But it's worth bearing in mind that cells do not "see" VLDL, the LPL is on the vascular endothelium and the cells behind the vessel wall only ever receive "free" fatty acids. These are not labelled as from albumin, VLDL or chylomicrons.
Slight aside for later: It seems likely that chylomicrons are going spill their lipids via that same LPL, worth remembering.
The story in the review can be sumarised as omega 3 fatty acids block the release of FFAs from adipocytes and increase the activity of lipoprotein lipase pretty well whole body. VLDL drops, FFAs drop. All is happy in the cardiovascular system. If you believe.
Various "bits" of omega 3s, especially the lipid peroxides of DHA, are signals for mitochondrial biogenesis. I had a paper which specified which lipoxide was most effective but must have missed the "save" button. Mea culpa yet again. There are hints here.
That's a very neat story, which has more than a grain of truth to it.
Why is it like this? What does it mean, physiologcally? Speculation time:
Omega 3 fats come from plants. Mostly from chloroplasts. Where do humans get their omega 3s from? Certainly not from plants. If we did then the rabid Dr Furhman would not be (correctly) recommending DHA supplementation (along with B12) to avoid brain collapse on veg*n diets. Actually, this link is quite funny when cited by Mc-Starch-Dougall:
"There is no evidence of adverse effects on health or cognitive function with lower DHA intake in vegetarians"
Well, I found it amusing. It's almost the converse of the neurological truism which states that being concerned about having a neurodegenerative disease probably means you don't actually have one.
Anyhoo. Away from the coast we have to get our DHA from animals (or buy algae derived supplements). They get it from grass. There is DHA present in adipose tissue of herbivores just as much as it is present in lipid membranes of their cells. My suspicion is that DHA is a signal to your metabolism that you have just eaten animal fat, from an animal who's food chain starts with grass [or algae]. The more fat you eat, the stronger the signal. We do not need much DHA overall for our brains as it is well protected in this site, but we might well be using it at low levels as a [G-protein coupled receptor sensed] signal to target metabolic adaptation to process fat. So is McDougall correct that veg*n "brain" tissue is OK, despite their periphery being depleted? Shrug.
Fish oil supplements? Well, using our "dietary fat is here" marker to pharmacologically modify some perceived CVD risk factor, without the appropriate change in source of metabolic fuel supply, looks to me to be of very limited value. Large intervention trials do show some benefit from omega 3s provided you do your stats well enough, you have a large enough population to pick up a very small effect and you give a high enough dose. But they do not seem to be any sort of panacea. Especially of you are avoiding dietary fat while "faking" the signal that you have eaten dietary fat...
This is not exactly surprising when you try to pick the likely physiology apart. I like the concept of DHA as an animal fat signal.
Peter
Final thought: Do we need omega 3 PUFA at anything above the most minimal levels if we are in saturated fat based ketosis? Of course I don't know. But the signal to cope with starvation is palmitic acid (physiological insulin resistance), not DHA. I live in starvation mode, not on a mixed diet with only intermittent access to healthy ruminant fat. I have long wanted to look at the selective release of FFAs from adipocytes in extended starvation. My suspicion is that in the early days after glycogen depletion palmitic acid is preferentially released over other lipids, PUFA are not needed/wanted. By a few weeks all the palmitate is gone and whatever is left then gets released. People like David Blaine suddenly start to feel weak, wobbly and are probably hypoglycaemic once they run out of palmitate and have to release less saturated fats. Two to four weeks if you carry some spare weight. Sauer's rats had only ever been fed a low fat omega 6 based diet and had no serious palmitate reserves, PUFA release came early for these.
Tuesday, September 03, 2013
Axen and Axen: The tradition continues
Another superb abstract, hot off the press, on LCHF diets. The data are suggested to be utterly clear cut, solid, and supportive of the physiology of LC eating which I have been espousing for many years now.
The conclusions are criminal. There are 13 authors. None seems to have read Kinzig et al's 2010 paper showing not only this very effect but also showing its complete reversal by a few carbohydrate based meals.
That omission, by 13 people on the author list, is what is criminal. The lack of understanding of the basic physiology of carbohydrate restriction even without Kinzig, by people in what claims to be nutrition research, is criminal. The blood on their hands, from dialysis patients, is criminal.
If even one of the authors has read Kinzig it leaves you wondering about the ethics in the group. If they haven't read the literature...
Disclosure: I haven't seen the full text.
Peter
BTW I just Pubmeded "ketogenic" + "insulin" + "resistance" and Kinzig was hit 24, primarily because 2010 is ancient history and the hits come in date order.
Hat tip to Liv for the link.
EDIT
Laura gave us this in the comments: "They actually cite the Kinzig 2010 paper in their discussion saying that their results match and that the results "could" be reversible... and then they leave it at that".
You have to ask what the lead in time to a study like this is. It strikes me as possible that Kinzig pipped them at the post by 3 years but they went on with the study as they had the funding but couldn't add a re feeding arm because they had no study ethics approval for this. Just trying to be kind, probably a mistake. Or perhaps they are just LC bashers as per usual. The cardinal sign, of using the name "Atkins" in the abstract, is not a good marker for an ethical group. But Kinzig is correct. Reversal is absolutely nothing a newbie LCer wouldn't pick up in 10 minutes on the internet.
END EDIT
The conclusions are criminal. There are 13 authors. None seems to have read Kinzig et al's 2010 paper showing not only this very effect but also showing its complete reversal by a few carbohydrate based meals.
That omission, by 13 people on the author list, is what is criminal. The lack of understanding of the basic physiology of carbohydrate restriction even without Kinzig, by people in what claims to be nutrition research, is criminal. The blood on their hands, from dialysis patients, is criminal.
If even one of the authors has read Kinzig it leaves you wondering about the ethics in the group. If they haven't read the literature...
Disclosure: I haven't seen the full text.
Peter
BTW I just Pubmeded "ketogenic" + "insulin" + "resistance" and Kinzig was hit 24, primarily because 2010 is ancient history and the hits come in date order.
Hat tip to Liv for the link.
EDIT
Laura gave us this in the comments: "They actually cite the Kinzig 2010 paper in their discussion saying that their results match and that the results "could" be reversible... and then they leave it at that".
You have to ask what the lead in time to a study like this is. It strikes me as possible that Kinzig pipped them at the post by 3 years but they went on with the study as they had the funding but couldn't add a re feeding arm because they had no study ethics approval for this. Just trying to be kind, probably a mistake. Or perhaps they are just LC bashers as per usual. The cardinal sign, of using the name "Atkins" in the abstract, is not a good marker for an ethical group. But Kinzig is correct. Reversal is absolutely nothing a newbie LCer wouldn't pick up in 10 minutes on the internet.
END EDIT