This post is pure fiction. Any semblance to currently living bloggers is probably totally libelous, so you'd better stop reading now.
Here we go. First, let's set the scene. We're looking at the Magdalenian period, 18,000-10,000 years ago, the end of the last ice age. Wiki gives a nice overview here. These HGs are fully developed homo sapiens, a great deal more sophisticated, in all probability, than many of us around today. They're not loaded with omega 6 PUFA for a start.
A few more pieces of fairly hard data come from the UK Archeological Data Service, in particular a paper which is split in to two pdfs, here and here. For those who don't want to slog through the archeology-speak, these quotes give the flavour:
We're talking about reindeer hunting btw.
"In the autumn in particular, the herd [reindeer] is at its nutritional and weight peak, and can supply substantial quantities of a high-quality, fat-rich, storable resource for over-wintering"
"The toothwear for the one and two year old individuals [reindeer] indicates that the [mass] kill took place during the autumn at both sites, within a few weeks and a little later at Verberie than at Pincevent. The large size of the kill and the season point towards a hunt related to the autumn migration (at least at Verberie) (David, in press)"
"The primary use made of reindeer was, of course, nutritional. The autumn hunts indicated by the dental eruption sequences at Pincevent and Verberie would be designed to exploit the prey in its best condition of the entire year. The summer forage would have fattened up the herd to its maximum annual weight, and even more importantly, to its highest fat content. Both meat and marrow are important for the diets of reindeer hunters. Speth and Spielmann’s arguments (1983) about the desirability of fat in the diet are particularly pertinent for cold climate hunter/gatherers in the winter. The fat in marrow can supply twice as many calories per gram as protein can, and can allow efficient metabolism of the protein from meat. There are no whole bones in the faunal assemblages from Pincevent or Verberie. There are abundant impact fractures, systematically placed to open the medullary cavities for the extraction of marrow"
Not sure what Cordain would think of this. I believe we are supposed to eat the skinny ones in the spring, not store the fat ones from autumn. Pesky facts!
Anyway, that's the end of the facts. It might also be useful to know who Fanatic Cook is and to have watched at least one of the Terminator movies (Terminator I does the job nicely and I think it has that chase scene down the dry floodwater channel). Here we go:
The wind is moaning over the autumn landscape of northern France at the tail end of the last ice age. It's October and the snow has been over a foot deep for weeks. The reindeer have fed well through the short subarctic summer and are loaded with fat for the winter. Gatherable foodstuffs are sandwiched between the snow cover and the permafrost. No one is digging. There has been a slaughter of reindeer and the tribe has divided up in to groups to butcher them. There is work for the present and food for the winter in plenty. The sound of shattering bones means marrow fat for all.
Away from the encampment there is a smell of ozone in the air and the Terminator style electric blue globe flickers and crackles to deposit a human form in to the frozen landscape. Luckily for everyone, the new time machine transports clothes as well as Terminators. And a crucial bag of white powder.
The Terminator approaches the butchery site through the heaps of reindeer bones from many previous harvests on this spot. Literally thousands of bones, all shattered to allow removal of the marrow. She approaches the main decision maker of the tribe and his shaman, both busily engaged in extracting the solid saturated fat from around the kidneys of a recently killed reindeer. Small cubes of the still warm delicacy are given to the children who scamper around, these are real treats. The rest will be frozen in a matter of minutes and be available for winter feasting later in the year.
The babel fish in the Terminator's ear does its best.
"ohmygoddon'tyouknowyouwillhardenthearteriesofthatpoor-childwithallofthatsaturatedperirenalfatandshewillget-canceranddiabetesandendherlifeinmiserywithouthospitals-tocareforherandhaven'tyoureadCordainwhereisyourflaxoil-andyoumusttrimallofthefatoffandthrowitaway"
Decision Maker (Chief, if you must), "Who's she?"
Shaman, "Looks like the angel of death to me. Wonder what the white powder in the bag is"
Terminator, "ifyoueatallofthatfatyouwillbecomeso-insulinresistantyouwillallgetdiabetesIhaveproof-
ofithereinthispowder"
Decision Maker, "What's this diabetes she keeps going on about?"
Shaman, "High blood sugar"
Decision Maker, "Waddayamean, high blood sugar? My blood sugar has been 4.6mmol/l for the last 45 years and I don't see it budging any time soon. Can you change it?"
Shaman, "Watch the powder, it ain't crack or angel dust"
Terminator, "Youmusteat100gramsofthispowderbefore-everymealofsaturatedfatandyouwillendupassickasa-labratonahighfatdietanditwillbethefatwhichisthe-
causeofallofyoursuffering"
Decision Maker, "But I'm already on a high fat diet! I live on not much else every winter and the few leaves we get in the summer give me the gripes. Why do I need to eat her white powder to be on a high fat diet?"
Shaman, "Buggered if I know. Want to humour her? It might be like the Special K that last Terminator brought. Cracking trip, if you're a shaman"
Decision Maker, "I'm no shaman, I might get lost on a trip like that and never find my way back to reality, your call"
The shaman licks his finger, dips it in the powder, touches it to his tongue. The grimace and spitting are extreme. "Dextrose mono bloody hydrate! You lend me your spear mate, I was right about the angel of death!"
The shaman promptly saves mankind from hyperglycaemia for another 10,000 years, minimum. But not for ever. The next Terminator will drop in to Egypt, about 12,000 years later. The ground will be more fertile and whole grains will sow death far more successfully in the now warmer climate. No need for the white powder.
End of fiction. Now you can go read the abstract of the paper cited by Bix here if you feel like it, but please try to apply a little more comprehension than she does. Not difficult.
Peter
Tuesday, September 30, 2008
Sunday, September 28, 2008
Physiological insulin resistance: The devil in the Prada.
On the surfing trip to Devon we watched The Devil Wears Prada on DVD. The best line for me was the fashion waif screaming at the heroine, with the deepest insulting angst:
"and you eat CARBS"
Well, it made me laugh. What made me think a little more was the same character talking about her latest diet, I paraphrase only slightly:
"My new diet doesn't of course include any food. I simply don't eat until I am about to pass out from hypoglycaemia and then swallow a small cube of cheese"
This was used to maintain the skeletal look so prized in the world of high fashion. Assuming the whole of the film is utterly true to life (except perhaps the too good then fashion corrupted heroine), I started to think about the physiology here, and about the physiology of that life threatening illness, anorexia nervosa.
Now, anyone of us relatively normal people on a lowish carb diet will never become hypoglycaemic. If we don't eat we just convert the stored triglycerides in our adipose tissue to non esterified fatty acids in our blood stream and use these to fuel our muscles. The glycerol from the triglycerides is half a glucose molecule, we can join two of them together to make glucose. Filling muscles with palmitic or stearic acid makes them insulin resistant enough to spare glucose and so maintain an adequate plasma glucose concentration to keep our brains working. Brain tissue cannot suck glucose out of plasma. It gets it by diffusion down a concentration gradient. You need at least 3.0mmol/l in your plasma unless you are in deep ketosis, when you can get by on a shade less.
But fashion waifs clearly can get hypoglycaemic if the script of the film is true. They are comparable to, or thinner than, anorexic patients. Here are the patient details of a group of ten anorexic patients. Note the % body fat in the anorexics is 4.1%, but we don't get the range. Some of these women will have body fat percentages well below 4%. Blood glucose averages below 4.0mmol/l and insulin is low. Click to enlarge.
They are not insulin resistant by HOMA-R guesstimate. They are starving yet they are exquisitely insulin sensitive. No one thought to measure their non esterified fatty acids.
What would happen if a healthy human being, such as the women in the control group with a body fat around 20%, were to eat nothing until they needed that cube of cheese? They would release NEFA from their fat, become insulin resistant and keep their blood glucose at physiological levels. They might LIKE some cheese (me too), but eating it to raise blood glucose is not needed.
Fashion models and anorexics do fast. But they have no significant body fat and their silicone implants (you have to put something in the bust of the clothes) will not release NEFA. So they can't release enough palmitic acid from their non existent adipose tissue to induce insulin resistance, so will be hypoglycaemic enough to faint if they were to move their residual muscles enough to soak up their blood glucose.
They have similar body fat % to patients with lipodystrophies such as Berardinelli-Seip syndrome which deprives people of all adipose tissue, but there the similarity ends. BS patients eat but can't store energy in fat cells so dump it in their muscles (plus anywhere else they can put it!) and become so intensely insulin resistant they become diabetic. Anorexia patients have no fat but lots of empty adipocytes and empty muscle cells, all aching for calories of any sort, glucose included.
The fashion waifs have no glycogen in their liver and no protein in their muscles (you know the look, where upper arm is thinner than the elbow, lovely). Dropping in some saturated fat from the cheese will allow transient NEFA production and the protein will allow a spike of gluconeogenesis. Blood glucose under these circumstances then rises to a level which transiently restores a semblance of brain function.
So there ARE situations where saturated fat (plus some protein) can be used to raise blood sugar. I would strongly suggest no one ever gets in to such dire straits!
Peter
"and you eat CARBS"
Well, it made me laugh. What made me think a little more was the same character talking about her latest diet, I paraphrase only slightly:
"My new diet doesn't of course include any food. I simply don't eat until I am about to pass out from hypoglycaemia and then swallow a small cube of cheese"
This was used to maintain the skeletal look so prized in the world of high fashion. Assuming the whole of the film is utterly true to life (except perhaps the too good then fashion corrupted heroine), I started to think about the physiology here, and about the physiology of that life threatening illness, anorexia nervosa.
Now, anyone of us relatively normal people on a lowish carb diet will never become hypoglycaemic. If we don't eat we just convert the stored triglycerides in our adipose tissue to non esterified fatty acids in our blood stream and use these to fuel our muscles. The glycerol from the triglycerides is half a glucose molecule, we can join two of them together to make glucose. Filling muscles with palmitic or stearic acid makes them insulin resistant enough to spare glucose and so maintain an adequate plasma glucose concentration to keep our brains working. Brain tissue cannot suck glucose out of plasma. It gets it by diffusion down a concentration gradient. You need at least 3.0mmol/l in your plasma unless you are in deep ketosis, when you can get by on a shade less.
But fashion waifs clearly can get hypoglycaemic if the script of the film is true. They are comparable to, or thinner than, anorexic patients. Here are the patient details of a group of ten anorexic patients. Note the % body fat in the anorexics is 4.1%, but we don't get the range. Some of these women will have body fat percentages well below 4%. Blood glucose averages below 4.0mmol/l and insulin is low. Click to enlarge.
They are not insulin resistant by HOMA-R guesstimate. They are starving yet they are exquisitely insulin sensitive. No one thought to measure their non esterified fatty acids.
What would happen if a healthy human being, such as the women in the control group with a body fat around 20%, were to eat nothing until they needed that cube of cheese? They would release NEFA from their fat, become insulin resistant and keep their blood glucose at physiological levels. They might LIKE some cheese (me too), but eating it to raise blood glucose is not needed.
Fashion models and anorexics do fast. But they have no significant body fat and their silicone implants (you have to put something in the bust of the clothes) will not release NEFA. So they can't release enough palmitic acid from their non existent adipose tissue to induce insulin resistance, so will be hypoglycaemic enough to faint if they were to move their residual muscles enough to soak up their blood glucose.
They have similar body fat % to patients with lipodystrophies such as Berardinelli-Seip syndrome which deprives people of all adipose tissue, but there the similarity ends. BS patients eat but can't store energy in fat cells so dump it in their muscles (plus anywhere else they can put it!) and become so intensely insulin resistant they become diabetic. Anorexia patients have no fat but lots of empty adipocytes and empty muscle cells, all aching for calories of any sort, glucose included.
The fashion waifs have no glycogen in their liver and no protein in their muscles (you know the look, where upper arm is thinner than the elbow, lovely). Dropping in some saturated fat from the cheese will allow transient NEFA production and the protein will allow a spike of gluconeogenesis. Blood glucose under these circumstances then rises to a level which transiently restores a semblance of brain function.
So there ARE situations where saturated fat (plus some protein) can be used to raise blood sugar. I would strongly suggest no one ever gets in to such dire straits!
Peter
Wednesday, September 24, 2008
EBCT scan
Well, I finally got an EBCT scan last week and the Agatston score came out as seven.
This is a bummer of a result for several reasons. The most obvious is that it's not zero, however inconclusive you might consider zero to be!
Second is that it's an isolated score, so there is no way I can tell if it's the start of an exponential rise to serious problems in 5 years time or the tail end of a fall from a higher number 5 years ago...
Third, I'm going to have to get another scan done in 12 months time to get a trend analysis. It makes me a little envious of Stephan and checking out his HbA1c reading of 5.8%. Measuring you post prandial glucose is a lot less expensive and a lot quicker than waiting a year for another EBCT scan!
While I wait, am I going to do anything different diet/exercise wise?
Probably not. Just about the only changes I'm thinking of will be to make sure I get my egg yolks every morning and not skip them on work days (which are now three days a week plus the weekend rota). I might get to paddle my kayak a little more frequently and I'll certainly continue my relaxed driving style. Apart from those, there are not a lot of changes to make. If I did alter much it would leave me wondering which alteration had affected the number in either direction in a year's time.
On the plus side the scan has dropped in price from £450 to £400. Still not cheap, but then when I think of how much our practice charges for me to do a canine dental the cost drops in to perspective!
The other plus is that if you are going to have a non zero score, having one below 10 is probably better than having one over 100...
Peter
Another up side to life is that our chicken house is about finished (been my main free time occupation for this last week) and just needs waterproofing, so it's time to start on the enclosure at the bottom of the garden! Chickens arrive in about 2 weeks time.
Oh, and the senior cardiologist in the imaging department was waaaaaay in to metabolic syndrome and the junior chap, who chatted to me after the scan, was well on his way. I had a coffee in their canteen and it's not hard to see why. Just imagine the worst possible aisles in the supermarket transported to a hospital basement! The coffee was as OK as coffee ever is.
This is a bummer of a result for several reasons. The most obvious is that it's not zero, however inconclusive you might consider zero to be!
Second is that it's an isolated score, so there is no way I can tell if it's the start of an exponential rise to serious problems in 5 years time or the tail end of a fall from a higher number 5 years ago...
Third, I'm going to have to get another scan done in 12 months time to get a trend analysis. It makes me a little envious of Stephan and checking out his HbA1c reading of 5.8%. Measuring you post prandial glucose is a lot less expensive and a lot quicker than waiting a year for another EBCT scan!
While I wait, am I going to do anything different diet/exercise wise?
Probably not. Just about the only changes I'm thinking of will be to make sure I get my egg yolks every morning and not skip them on work days (which are now three days a week plus the weekend rota). I might get to paddle my kayak a little more frequently and I'll certainly continue my relaxed driving style. Apart from those, there are not a lot of changes to make. If I did alter much it would leave me wondering which alteration had affected the number in either direction in a year's time.
On the plus side the scan has dropped in price from £450 to £400. Still not cheap, but then when I think of how much our practice charges for me to do a canine dental the cost drops in to perspective!
The other plus is that if you are going to have a non zero score, having one below 10 is probably better than having one over 100...
Peter
Another up side to life is that our chicken house is about finished (been my main free time occupation for this last week) and just needs waterproofing, so it's time to start on the enclosure at the bottom of the garden! Chickens arrive in about 2 weeks time.
Oh, and the senior cardiologist in the imaging department was waaaaaay in to metabolic syndrome and the junior chap, who chatted to me after the scan, was well on his way. I had a coffee in their canteen and it's not hard to see why. Just imagine the worst possible aisles in the supermarket transported to a hospital basement! The coffee was as OK as coffee ever is.
Monday, September 15, 2008
Physiological insulin resistance: The wild type mice
I've just got an afternoon to blog so I thought I'd put up something new before the daunting task of going through comments which have built up with the surf/work/weekend session that has (very pleasantly) limited net time.
I wanted to go through the data from the mice in this paper.
It's a Nature paper so I'm not sure how I got the full text, but there it is on the hard drive! The brown fat ablated mice are interesting enough for a post in their own right eventually, so it's the control groups that I'm looking at today. Ortmann does discuss the macronutrient preferences of mice, strain being one factor, and she does discuss in particular the role of early exposure to grains in future food choices, no surprises in what happens there! But any sensible mouse which has not been permanently broken by early exposure to lab chow loves fat. How much fat? Well, you have to let the mice choose for themselves. No lab chow for these mice. They got three separate food blocks, one lard/coconut oil, one casein and one of that sucrose/cornstarch poison so beloved of rodent researchers. Here's the composition of the blocks:
What did the mice choose? Here's the cumulative food intake from 4 weeks to 17 weeks of age. Look at the column WT (ignore the UCP-DTA column for today), these are wild type (WT) mice without any genetic engineering. They're lab mice.
Okay.... casein. It seems mice eat enough protein to grow, about 12% of their calories. How about that scrummie sugared cornstarch? I was thinking they might not have touched this junk with a barge pole, but those clever mice ate just under 6% of their calories from sucrose/starch. Very close to what I eat! And the rest? FAT!
These macronutrient ratios are pretty close to those of the Optimal Diet. It is a genuine high fat diet. There is nothing Western or Cafeteria about it. It's JK all the way.
The lab chow is unspecified but was probably Purina 5008, low fat, high starch, minimal sucrose. A bit Ornish like...
So what happened to the mice?
As you can see the free choice mice (WT 3CD, black triangles) grew indistinguishably from mice on lab chow (WT SD, black circles) re bodyweight.
Now look at energy intake, again it's only the WT SD black circles of the lab chow normal mice we are comparing to the WT 3CD black triangles of the normal type mice eating to the Optimal Diet (by choice).
Would you rather eat 90kj/d or 70kj/d to maintain your growth rate under unlimited food conditions?
Finally it's pretty obvious that eating all that saturated fat will make you instantly insulin resistant and diabetic. Well, interestingly, the fasting glucose is actually higher in the high fat eating mice.
The hatched bar is the high fat eating mice, again its the WT groups we're looking at.
Aha, the AHA was right all along. No! Insulin sensitivity is the same in high fat or lab chow mice. Each mouse was injected with insulin and their fall in blood glucose in response to this tracked. The bigger the fall, the more sensitive you are to insulin. Don't play this at home, an OGTT is much safer!
Again it's the black triangles eating to the OD. Although there is no statistical testing of the difference from the black circle lab chowers, the glucose fall in response to exogenous insulin is GREATER in the high fat group and eyeballing the Standard Error bars suggests that the difference is probably significant.
So does a high fat diet cause insulin resistance? Only in so far as there is a higher fasting glucose level in this group, of which I'm an honorary member. In terms of shifting glucose when I need to, it's effortless. But if I'm shifting free fatty acids because I'm exercising without having eaten I can still use NEFA to fuel muscle, have that muscle reject glucose and so leave that glucose for my brain, if I'm using it at the time that is...
Peter
I wanted to go through the data from the mice in this paper.
It's a Nature paper so I'm not sure how I got the full text, but there it is on the hard drive! The brown fat ablated mice are interesting enough for a post in their own right eventually, so it's the control groups that I'm looking at today. Ortmann does discuss the macronutrient preferences of mice, strain being one factor, and she does discuss in particular the role of early exposure to grains in future food choices, no surprises in what happens there! But any sensible mouse which has not been permanently broken by early exposure to lab chow loves fat. How much fat? Well, you have to let the mice choose for themselves. No lab chow for these mice. They got three separate food blocks, one lard/coconut oil, one casein and one of that sucrose/cornstarch poison so beloved of rodent researchers. Here's the composition of the blocks:
What did the mice choose? Here's the cumulative food intake from 4 weeks to 17 weeks of age. Look at the column WT (ignore the UCP-DTA column for today), these are wild type (WT) mice without any genetic engineering. They're lab mice.
Okay.... casein. It seems mice eat enough protein to grow, about 12% of their calories. How about that scrummie sugared cornstarch? I was thinking they might not have touched this junk with a barge pole, but those clever mice ate just under 6% of their calories from sucrose/starch. Very close to what I eat! And the rest? FAT!
These macronutrient ratios are pretty close to those of the Optimal Diet. It is a genuine high fat diet. There is nothing Western or Cafeteria about it. It's JK all the way.
The lab chow is unspecified but was probably Purina 5008, low fat, high starch, minimal sucrose. A bit Ornish like...
So what happened to the mice?
As you can see the free choice mice (WT 3CD, black triangles) grew indistinguishably from mice on lab chow (WT SD, black circles) re bodyweight.
Now look at energy intake, again it's only the WT SD black circles of the lab chow normal mice we are comparing to the WT 3CD black triangles of the normal type mice eating to the Optimal Diet (by choice).
Would you rather eat 90kj/d or 70kj/d to maintain your growth rate under unlimited food conditions?
Finally it's pretty obvious that eating all that saturated fat will make you instantly insulin resistant and diabetic. Well, interestingly, the fasting glucose is actually higher in the high fat eating mice.
The hatched bar is the high fat eating mice, again its the WT groups we're looking at.
Aha, the AHA was right all along. No! Insulin sensitivity is the same in high fat or lab chow mice. Each mouse was injected with insulin and their fall in blood glucose in response to this tracked. The bigger the fall, the more sensitive you are to insulin. Don't play this at home, an OGTT is much safer!
Again it's the black triangles eating to the OD. Although there is no statistical testing of the difference from the black circle lab chowers, the glucose fall in response to exogenous insulin is GREATER in the high fat group and eyeballing the Standard Error bars suggests that the difference is probably significant.
So does a high fat diet cause insulin resistance? Only in so far as there is a higher fasting glucose level in this group, of which I'm an honorary member. In terms of shifting glucose when I need to, it's effortless. But if I'm shifting free fatty acids because I'm exercising without having eaten I can still use NEFA to fuel muscle, have that muscle reject glucose and so leave that glucose for my brain, if I'm using it at the time that is...
Peter
Friday, September 05, 2008
Gone surfin'
Hoping for warmer waves in Devon. Hoping for ANY waves in Devon! The pic was around 2004 or 2005, probably January on the North Sea. Not cool, more like COLD. But adrenalin assisted lipolysis to fuel thermogenesis saves all but the fingers! Oh, and keeping your head out of the water helps.
Peter
Back middle of next week but straight on to a late shift...
On the plus side for fish (oils?)
This paper from Chris makes a nice counterbalance to the fish oil and hepatic lipidosis posts. Long term the omega 3s have benefits. Avoiding omega 6s and avoiding "food" which comes in a plastic wrap does even more in combination. I love interventions which improve insulin sensitivity. If you're not going to mainline leptin I'd suggest fish might be a good idea (or maybe the oils)... I love stuff which increases insulin sensitivity.
Peter
BTW The link in this one is interesting too!
Peter
BTW The link in this one is interesting too!
Jan Kwasniewski comment
Just a few quickies as time on the net has vanished again!
This came by email from Agata, who I guess is Polish speaking and reads one of the several web sites in Polish for OD eaters.
"Hello, I can't comment on your blog as it's only allowed for blog
owners, but:
- to augment some information from previous posts about JK:
He allows (in publicised answers to patients' letters) fasting one day a
week, if someone has trouble losing weight. Also, as a last resort, he
advises to eat 80% of the daily carb allowance in the evening - separately.
He says coconut oil is ok, however his son Tomasz Kwasniewski once wrote
on the website's forum that any oil (including CO) has zero 'biological
value' for humans and contains no enzymes for its digestion.
His son is an admin on the forum, from his posts I presume he's
background is in food technology. From time to time on a whim he
explains a bit more than his father, yet it's all full of biochemical
jargon and chains of chemical formulas - indigestible for myself.
Anecdotally, he dubs JK The Master of Simplification.
I started OD only recently, thanks to your blog, and loving it.
Thank you and good luck"
I love the idea of JK as the master of simplification. The biochemistry after eating is so complex, the choices so simple. The knock on effects of wrong choices so far reaching...
Thanks to Agata for the comment.
Peter
This came by email from Agata, who I guess is Polish speaking and reads one of the several web sites in Polish for OD eaters.
"Hello, I can't comment on your blog as it's only allowed for blog
owners, but:
- to augment some information from previous posts about JK:
He allows (in publicised answers to patients' letters) fasting one day a
week, if someone has trouble losing weight. Also, as a last resort, he
advises to eat 80% of the daily carb allowance in the evening - separately.
He says coconut oil is ok, however his son Tomasz Kwasniewski once wrote
on the website's forum that any oil (including CO) has zero 'biological
value' for humans and contains no enzymes for its digestion.
His son is an admin on the forum, from his posts I presume he's
background is in food technology. From time to time on a whim he
explains a bit more than his father, yet it's all full of biochemical
jargon and chains of chemical formulas - indigestible for myself.
Anecdotally, he dubs JK The Master of Simplification.
I started OD only recently, thanks to your blog, and loving it.
Thank you and good luck"
I love the idea of JK as the master of simplification. The biochemistry after eating is so complex, the choices so simple. The knock on effects of wrong choices so far reaching...
Thanks to Agata for the comment.
Peter
Tuesday, September 02, 2008
Physiological insulin resistance; Alzheimers
I'd just like to run through the effects of saturated fat vs unsaturated fat on the development of Alzheimers disease in a mouse model genetically engineered to be AD prone. Here is the opening sentence of the paper (thanks to Gary for the pdf):
"In Western Society, diets have gradually changed since World War II, with an increase in total caloric intake, saturated fat, and hydrogenated fat, leading to a decrease in the healthier, unsaturated fats."
This statement is frankly wrong. Good start. BTW There's accurate information on changes in fat intake in the American diet here on Stephan's blog.
Next is the methods. They added 2% by weight of chemical grade cholesterol to the diet of the saturated fat group only, none to the PUFA group. This is called failing to control your variables. If I was scrutineering this paper I would have thrown it out at this point. BTW I roughly translated this amount of cholesterol to mean >50 eggs per day for an adult human, but not as eggs, as chemical grade cholesterol. Anyone fancy trying this?
If you look through the table you will see that just under 24% of the "food" by weight was Alphacel. I think this is cotton wool, near enough.
So the "food" components of the diet are 27% by weight fat, 26% by weight starch and 32% by weight, err, sugar (dextrinised starch=sugar). Yummie. So any mouse eating any food must eat LOTS of sugar.
Why is this a problem if you mix it with saturated fat but not with soya oil? Because saturated fat induces insulin resistance.
Why should this be? Because palmitic acid is the primary NEFA released from human adipose tissue during fasting. Think of palmitic as a signal molecule to tell the muscles that inhibition of glucose uptake is needed and to tell the liver that increased gluconeogenesis is required because there is no food coming in.
Because linoleic acid comprises only a small portion of adipose tissue in humans there is no reason why an increase in this fatty acid should signal the need for physiological insulin resistance. Over an evolutionary time scale elevated linoleic acid levels mean nothing except perhaps you found a few nuts. This is not starvation and insulin resistance doesn't need to happen. Other saturated fats seem to do the same as palmitic, certainly coconut oil, fully hydrogenated, seems to do this in these mice. Lipoprotein lipase certainly spills some of the NEFA it releases from chylomicrons in to the general circulation, especially in muscle beds.
So these poor mice are being made insulin resistant, while being fed sugar. Each mouthful combines saturated fat and sugar. Non stop. Whenever they eat anything. Almost as much sugar as someone on the upper end of the sugar intake in the SAD, but with more fat (27% by weight is 54% of calories). Combining insulin resistance with sugar when you are genetically engineered to get Alzheimers does not embody bad luck. Dementia is guaranteed. For a human sugar junkie there is more genetic chance involved and you might just get lucky enough to have a heart attack sooner rather than dementia later...
Peter
"In Western Society, diets have gradually changed since World War II, with an increase in total caloric intake, saturated fat, and hydrogenated fat, leading to a decrease in the healthier, unsaturated fats."
This statement is frankly wrong. Good start. BTW There's accurate information on changes in fat intake in the American diet here on Stephan's blog.
Next is the methods. They added 2% by weight of chemical grade cholesterol to the diet of the saturated fat group only, none to the PUFA group. This is called failing to control your variables. If I was scrutineering this paper I would have thrown it out at this point. BTW I roughly translated this amount of cholesterol to mean >50 eggs per day for an adult human, but not as eggs, as chemical grade cholesterol. Anyone fancy trying this?
If you look through the table you will see that just under 24% of the "food" by weight was Alphacel. I think this is cotton wool, near enough.
So the "food" components of the diet are 27% by weight fat, 26% by weight starch and 32% by weight, err, sugar (dextrinised starch=sugar). Yummie. So any mouse eating any food must eat LOTS of sugar.
Why is this a problem if you mix it with saturated fat but not with soya oil? Because saturated fat induces insulin resistance.
Why should this be? Because palmitic acid is the primary NEFA released from human adipose tissue during fasting. Think of palmitic as a signal molecule to tell the muscles that inhibition of glucose uptake is needed and to tell the liver that increased gluconeogenesis is required because there is no food coming in.
Because linoleic acid comprises only a small portion of adipose tissue in humans there is no reason why an increase in this fatty acid should signal the need for physiological insulin resistance. Over an evolutionary time scale elevated linoleic acid levels mean nothing except perhaps you found a few nuts. This is not starvation and insulin resistance doesn't need to happen. Other saturated fats seem to do the same as palmitic, certainly coconut oil, fully hydrogenated, seems to do this in these mice. Lipoprotein lipase certainly spills some of the NEFA it releases from chylomicrons in to the general circulation, especially in muscle beds.
So these poor mice are being made insulin resistant, while being fed sugar. Each mouthful combines saturated fat and sugar. Non stop. Whenever they eat anything. Almost as much sugar as someone on the upper end of the sugar intake in the SAD, but with more fat (27% by weight is 54% of calories). Combining insulin resistance with sugar when you are genetically engineered to get Alzheimers does not embody bad luck. Dementia is guaranteed. For a human sugar junkie there is more genetic chance involved and you might just get lucky enough to have a heart attack sooner rather than dementia later...
Peter
Fruit and Vegetables; Potato fruits
On the left are some potato fruits, on the right are cherry tomatoes. If you think plants love you, just try eating those lovely fruits on the left. See you in A and E (that's the UK equivalent of the ER for those over the Pond). Please don't do this.
Potatoes forgot to put toxin in their tubers, evolution never expects... a fork or a digging stick is bad news to a potato. The tomato is just a failed toxin producer, unless you are salicylate intolerant. In which case it did a reasonable job and you'll leave it alone.
Peter
Cholesterol and memory
Some bad news if your cholesterol "normalises" on a LC diet. Before you contemplate avoiding old age, just consider that these people were on the SAD diet and high TC might not be needed if you eat LC/HF. Or perhaps your TC might rise with age the way mine seems to. Whichever, this was only a cross sectional study. The full text says very little the abstract doesn't. My favourite line from the abstract:
"In contrast to our expectations, high total cholesterol and high LDL cholesterol were associated with higher memory scores for noncarriers of the APOE4 allele" [Comment: that's most of us]
APOE4 is a bad news lipoprotein subtype gene for Alzheimers disease, you could say it fails to stop your brain rotting under the onslaught of the sugar content of the SAD.
Now if I could just remember where I left my kayak...
Peter
"In contrast to our expectations, high total cholesterol and high LDL cholesterol were associated with higher memory scores for noncarriers of the APOE4 allele" [Comment: that's most of us]
APOE4 is a bad news lipoprotein subtype gene for Alzheimers disease, you could say it fails to stop your brain rotting under the onslaught of the sugar content of the SAD.
Now if I could just remember where I left my kayak...
Peter
AGE RAGE and ALE: linoleic acid
I'm really sorry about this but I haven't quite finished with figure 1 of the engrossing commentary by Krauss. Let's open it up again here.
Now the first question we have to ask is "What is the most abundant polyunsaturated fatty acid in human LDL particles?"
OK, that's a give away at linoleic acid, our least favourite omega 6 fatty acid. This is pretty obviously the case as we've just discussed how, if you get enough omega 3 fatty acid in to a nascent LDL particle, it becomes a stillborn VLDL particle and leaves it's lipid, along with its apoB protein, in the liver. Linoleic acid based VLDLs get secreted.
So here's the tricky question. Where, in Krauss' diagram, is the linoleic acid? Well it has to be in the liver cell somewhere to get put in to the LDL particles. Clearly some lipid is added to the initial assembly of the nascent LDL, over on the left hand side of the diagram. The rest comes from that lipid droplet in the middle. You would expect that lipid droplet to be mostly saturated fat if it was fructose or alcohol derived, but with the amount of linoleic acid in the modern diet there could easily be plenty of this throughout the liver cell lipid stores.
Why is there linoleic acid throughout the liver? The liver likes linoleic acid! In an utterly artificial model, the cholesterol fed hamster (you'd better believe it!) on moderate fat diets (45% of calories from fat) show an upregulation of the LDL receptor as the proportion of fat from linoleic acid rises. Dietary saturated fat down regulates the receptor. It seems that this holds true across species and it certainly seems to work in humans, diets high in omega 6 PUFA were the classical cholesterol lowering approach pre statins. You can see why the liver should ignore an LDL particle full of saturated fat. This is Krauss' large fluffy non atherogenic lipid, used for delivering calories and cholesterol to wherever they are needed. It came from the liver, why should it go back? But why is the liver so keen to uptake LDL particles when the diet is high in linoleic acid? My guess is that linoleic acid loaded anything is a novel phenomenon and in pre agriculture times linoleic acid was probably very useful and in very short supply, so it got recycled. It is the preferred fatty acid for LDL cholesterol because, in small amounts, it has significant uses and benefits which are not provided by the omega 3 fats. So there is some logic to aborting an LDL particle over-endowed with omega 3 fats. But what were positive benefits when linoleic acid was in short supply have gone awry as the amount in the diet has skyrocketed over the last 10,000 years, especially the last hundred years or so. The knock on effects of a high linoleic acid diet are interesting for atheroma formation.
Stephan also has some interesting thoughts on linoleic acid and violence up on his blog at the moment. The two problems are interesting as while CVD mortality is currently dropping in the USA and UK, the incidence of CV disease is probably static, and might be increasing if it weren't for the decline in smoking. The fact that mortality from gunshots is rising while mortality from heart disease is falling, despite the rise in incidence for both, is a plus mark for cardiologists managing established heart problems. Trauma management has some catching up to do. Or maybe we could just give up eating 10% or so of our calories from those omega 6 fats!
Peter
Now the first question we have to ask is "What is the most abundant polyunsaturated fatty acid in human LDL particles?"
OK, that's a give away at linoleic acid, our least favourite omega 6 fatty acid. This is pretty obviously the case as we've just discussed how, if you get enough omega 3 fatty acid in to a nascent LDL particle, it becomes a stillborn VLDL particle and leaves it's lipid, along with its apoB protein, in the liver. Linoleic acid based VLDLs get secreted.
So here's the tricky question. Where, in Krauss' diagram, is the linoleic acid? Well it has to be in the liver cell somewhere to get put in to the LDL particles. Clearly some lipid is added to the initial assembly of the nascent LDL, over on the left hand side of the diagram. The rest comes from that lipid droplet in the middle. You would expect that lipid droplet to be mostly saturated fat if it was fructose or alcohol derived, but with the amount of linoleic acid in the modern diet there could easily be plenty of this throughout the liver cell lipid stores.
Why is there linoleic acid throughout the liver? The liver likes linoleic acid! In an utterly artificial model, the cholesterol fed hamster (you'd better believe it!) on moderate fat diets (45% of calories from fat) show an upregulation of the LDL receptor as the proportion of fat from linoleic acid rises. Dietary saturated fat down regulates the receptor. It seems that this holds true across species and it certainly seems to work in humans, diets high in omega 6 PUFA were the classical cholesterol lowering approach pre statins. You can see why the liver should ignore an LDL particle full of saturated fat. This is Krauss' large fluffy non atherogenic lipid, used for delivering calories and cholesterol to wherever they are needed. It came from the liver, why should it go back? But why is the liver so keen to uptake LDL particles when the diet is high in linoleic acid? My guess is that linoleic acid loaded anything is a novel phenomenon and in pre agriculture times linoleic acid was probably very useful and in very short supply, so it got recycled. It is the preferred fatty acid for LDL cholesterol because, in small amounts, it has significant uses and benefits which are not provided by the omega 3 fats. So there is some logic to aborting an LDL particle over-endowed with omega 3 fats. But what were positive benefits when linoleic acid was in short supply have gone awry as the amount in the diet has skyrocketed over the last 10,000 years, especially the last hundred years or so. The knock on effects of a high linoleic acid diet are interesting for atheroma formation.
Stephan also has some interesting thoughts on linoleic acid and violence up on his blog at the moment. The two problems are interesting as while CVD mortality is currently dropping in the USA and UK, the incidence of CV disease is probably static, and might be increasing if it weren't for the decline in smoking. The fact that mortality from gunshots is rising while mortality from heart disease is falling, despite the rise in incidence for both, is a plus mark for cardiologists managing established heart problems. Trauma management has some catching up to do. Or maybe we could just give up eating 10% or so of our calories from those omega 6 fats!
Peter
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