Some problems are more difficult to influence than others. I have this mental image of nutrition as comparable to having your car serviced. Treat your car with respect and you will have to be unlucky for it to break down. If you ignore servicing, say you never top up the brake fluid, eventually the brakes will fail. If you end up writing the car off, say by being unable to stop at a roundabout, there is no point going back to the wreck, pouring some brake fluid in to the master cylinder and expecting the car to become functional again. It won't.
Some people get broken, I suppose all of us do eventually. But it seems improbable that diet could reverse the degree of "broken-ness" represented by cancer, one of the most serious of metabolic train wrecks. But there are reports of remission. Spontaneous remission is one thing. Engineering that spontaneity is quite another.
Can it be done?
Kasha Mikoda has left a comment on the Praise the Lard post. It's a personal account of the management of her father's non-small cell carcinoma of the lung, with mets. By Kwasniewski. It's there for the reading. Non-small cell cancer includes squamous cell, large cell and adenocarcinoma, prognosis guarded.
Her comment brought to mind an old article I read some time ago about the nutritional management of lung cancer, here.
And of course there are always the two children described by Nebeling.
In terms of an evidence base, case reports in peer reviewed publications carry little weight and non published case reports are just off the radar. But then getting a prospective trial set up to provide an evidence base, even a pilot study, is fraught with difficulties. For a flavour of the current state of difficulty anyone can browse the article which started Kasha off on her journey to Kwasniewski. Attempts at collaboration with mainstream medicine by Kwasniewski never got off the ground.
After that there is patient compliance! Look at this quote from Dr Schmidt in the article cited by Kasha:
Four of the patients were so ill, they died within the first week of the study. Others, says Schmidt, dropped out because they found it hard to stick to the no-sweets diet: "We didn't expect this to be such a big problem, but a considerable number of patients left the study because they were unable or unwilling to renounce soft drinks, chocolate and so on."
Of course these people were end stage and probably considered themselves beyond hope, so why not enjoy whatever food they could manage... But for the life of me I can't see why one has to be absolutely at the end stage of cancer before it is considered ethical to advise that you should stop eating sweets, especially when a PET scan confirms that the cancer lights up like a... Well, like a cancer feasting on glucose in a PET scanner.
Peter
Tuesday, April 15, 2008
Monday, April 14, 2008
Metabolism; mitochondria and uncoupling
Just a final couple of aspects of Nick Lane's ideas about mitochondria, diet and aging before I finally leave them alone. There are some factors which he suggests might be associated with longevity.
The first is high numbers of mitochondria per unit basal metabolism. This is the approach taken by birds and bats (which live far longer than similar sized non flight mammals). The metabolic rate needed for flight is such that resting metabolic rate can be met by the copious mitochondria running at tickover. This is effective at supplying energy without free radical leakage, especially with factor two taken on board. I don't think we'll ever get near to bird numbers of mitochondria, but upping the numbers doesn't seem like a bad idea. How about a few ketones to help?
The second is uncoupling proteins. These allow the hydrogen ion gradient in the mitochondria to be dissipated as heat. This in turn allows through flow of electrons down the electron transport chain, even if there are buckets of unused ATP hanging around. Through flow without obstruction means minimal sewer leakage, less free radicals, less apoptosis...
From this abstract, note that:
"Fatty acids are known to enhance mitochondrial uncoupling protein (UCP) activity"
No mention of glucose doing this! The point of the paper is that ketones do exactly the same thing. I don't see the need for frank ketonuria, but I do like to have ketones on tap for whenever they might be needed!
Peter
The first is high numbers of mitochondria per unit basal metabolism. This is the approach taken by birds and bats (which live far longer than similar sized non flight mammals). The metabolic rate needed for flight is such that resting metabolic rate can be met by the copious mitochondria running at tickover. This is effective at supplying energy without free radical leakage, especially with factor two taken on board. I don't think we'll ever get near to bird numbers of mitochondria, but upping the numbers doesn't seem like a bad idea. How about a few ketones to help?
The second is uncoupling proteins. These allow the hydrogen ion gradient in the mitochondria to be dissipated as heat. This in turn allows through flow of electrons down the electron transport chain, even if there are buckets of unused ATP hanging around. Through flow without obstruction means minimal sewer leakage, less free radicals, less apoptosis...
From this abstract, note that:
"Fatty acids are known to enhance mitochondrial uncoupling protein (UCP) activity"
No mention of glucose doing this! The point of the paper is that ketones do exactly the same thing. I don't see the need for frank ketonuria, but I do like to have ketones on tap for whenever they might be needed!
Peter
Sunday, April 13, 2008
Cynthia Kenyon link
Here is a link to an interview with Cynthia Kenyon, published in New Scientitst back in 2003. It's subscription only now and though I've got a copy on my hard drive it might be better if I just direct you to a site where someone called James Hughes will provide the text!
She is heavily committed to finding a life extending drug. To me, personally, this will run smack bang in to the Law of Unintended Consequences head on. Lowering insulin by diet choices, as she currently practices, seems to be the best plan for a reduction in the diseases old age. (Peter crosses fingers).
Peter
She is heavily committed to finding a life extending drug. To me, personally, this will run smack bang in to the Law of Unintended Consequences head on. Lowering insulin by diet choices, as she currently practices, seems to be the best plan for a reduction in the diseases old age. (Peter crosses fingers).
Peter
Tuesday, April 08, 2008
Cholesterol, MESA and EBCT
Thanks to Dave Lull for a copy of the latest MESA paper. I guess you could just say EBCT looks like a good predictor of heart attack risk, irrespective of age or ethnicity and leave it at that. It looks to be true.
I was just browsing through table one of the results and a few strange things came out. First is that it doesn't include LDL cholesterol at baseline! Most people with any shred of intelligence will realise that calculated LDL cholesterol is garbage, but it's not typical of the average cardiologist to get that far.... These guys must be good!
The second gem was that HDL was lower in the coronary event group, as happens in Framingham. But the difference between the means was 51.0 minus 47.3, I make that 3.7mg/dl. The standard deviation was 15 ish in both groups. If they had a Normal Distribution, which they should have, the range to include most participants is about three standard deviations around the mean. The overlap is phenomenal between heart attack and non heart attack groups. On a personal basis having an HDL of 20 could easily put you in either group, as could an HDL of 60. I guess cardiologists just get used to this.
Taking lipid lowering medication appears to be as bad as being a current of former smoker. Must be a message there but I can't work it out...
Anyone tempted to crash diet might be disappointed by the BMI in the coronary event group being .2 units lower than the spared group. Good job this has neither biological or statistical significance, or participants might have to be encouraged to gain a few pounds. Or get shorter!
I know all of these things need to be factored in to correct for know interactions as it's likely that all of the diabetics were on statins while being encouraged to eat healthy starches and shoot up with insulin, but the raw data still give me a chuckle.
So Detrano et al provide more evidence that coronary calcium, the physical evidence of on going disease, is a better marker of a physical on going disease process than a surrogate of any sort. They also seem less wedded to conventional risk factors. But I guess that's why they're doing the study...
Peter
I was just browsing through table one of the results and a few strange things came out. First is that it doesn't include LDL cholesterol at baseline! Most people with any shred of intelligence will realise that calculated LDL cholesterol is garbage, but it's not typical of the average cardiologist to get that far.... These guys must be good!
The second gem was that HDL was lower in the coronary event group, as happens in Framingham. But the difference between the means was 51.0 minus 47.3, I make that 3.7mg/dl. The standard deviation was 15 ish in both groups. If they had a Normal Distribution, which they should have, the range to include most participants is about three standard deviations around the mean. The overlap is phenomenal between heart attack and non heart attack groups. On a personal basis having an HDL of 20 could easily put you in either group, as could an HDL of 60. I guess cardiologists just get used to this.
Taking lipid lowering medication appears to be as bad as being a current of former smoker. Must be a message there but I can't work it out...
Anyone tempted to crash diet might be disappointed by the BMI in the coronary event group being .2 units lower than the spared group. Good job this has neither biological or statistical significance, or participants might have to be encouraged to gain a few pounds. Or get shorter!
I know all of these things need to be factored in to correct for know interactions as it's likely that all of the diabetics were on statins while being encouraged to eat healthy starches and shoot up with insulin, but the raw data still give me a chuckle.
So Detrano et al provide more evidence that coronary calcium, the physical evidence of on going disease, is a better marker of a physical on going disease process than a surrogate of any sort. They also seem less wedded to conventional risk factors. But I guess that's why they're doing the study...
Peter
Gluten and cardiomyopathy
Again, just a brief note. You want cardiomyopathy? Eat your healthy whole grains and start saving for that heart transplant! Or crossing your fingers if you're in the NHS.
Bear in mind that antibody production is far from necessary for gluten damage, so there is no reason why the two antibody negative patients might not have gluten related damage. Also many "non" coeliac people could equally have gluten damage without gut signs.
Peter
Bear in mind that antibody production is far from necessary for gluten damage, so there is no reason why the two antibody negative patients might not have gluten related damage. Also many "non" coeliac people could equally have gluten damage without gut signs.
Peter
Metabolism nuts and bolts
Nick Lane has produced an interesting book in Power, Sex, Suicide. When it gets down to basics, the electron transport chain of the mitochondria is a bit like a cracked sewage pipe. If that supplies all the information you wanted to know about aging, stop reading now.
What he means is that it leaks unpleasant stuff but usually only in small amounts unless there is a blockage, which fills the pipe and increases leakage pressure. Otherwise just a little of the nasty stuff escapes.
Just to leave sewer analogies aside for a while, what is the electron transport chain? It's a set of very complex molecular structures embedded in the innermost membrane of the mitochondria. It takes an electron (from where, later) and passes it through a series of "mills" and "conduits" until eventually it off loads it on to an oxygen molecule (this is why we breathe, oxygen isn't needed for much else). As it goes through the "mills" its energy is used to pump hydrogen ions from the innermost recesses of the mitochondria in to the outer zones. The more electrons through the mill, the more pumping. The hydrogen ions want to get back in. The only route back in is through a turnstyle. As the turnstyle turns, rotated by a returning hydrogen ion, a mechanism pushes an extra phosphate group on to an ADP molecule to form an ATP molecule. ATP is exported and used as the energy currency of the cell. Most, but not all, ATP is made this way. There are other routes back for hydrogen ions too, but that's another story.
Back to the sewer metaphor. The electron transfer chain leaks. It leaks raw electrons. Electrons react with anything and everything. Many things affect the rate of leakage and the consequences of leakage, but ultimately the knock on effect of this is damage to the mitochondrial DNA, which codes for certain essential components of the electron transport chain... As the DNA degrades over the years the electron chain components become more leaky and more damage is done and we age.
So much comes from PSS. There are very detailed and mostly convincing arguments for this view of aging and a number of other aspects of Life the Universe and Everything. The answer does not appear to be 42.
That got me thinking. Back to Moseby's Crash Course in Metabolism and Nutrition. A quick comparison of the break down of glucose and palmitic acid comes out with this: Glucose goes through glycolysis to pyruvate. Pyruvate enters the mitochondria, gets converted to acetyl CoA and drops in to the ubiquitous tricarboxylic acid cycle (unless your metabolism is VERY strange, like H. pylori). Palmitic acid, my favourite calorie source, gets an executive ticket straight in to the mitochondria where it undergoes beta oxidation to acetyl CoA and after that it could have been sugar (ie acetyl CoA from any source goes down the same cyclical plug hole).
So the difference in metabolism is between glycolysis and beta oxidation. These provide electrons for the electron sewer in different forms. You can't shift electrons around "neat" unless you are using some copper wire or the like. Neat electrons are what do all of the damage. No, electrons are shifted about as chemical electron equivalents. One is NADH, the other is FADH2. Doesn't matter what these stand for. Converting glucose to Acetyl CoA provides a little NADH and that's it. Converting palmitic acid to acetyl CoA provides a whole load of "electrons", in the form of an equal amount of NADH and FADH2. After that it's all acetyl CoA and the same as glucose. But for every calorie of glucose you burn, you generate a higher proportion of NADH to FADH2 than by burning palmitic acid. So what?
NADH puts its electron in to the start of the electron transport chain at complex I. Complex I is leaky. FADH2 puts its pair of electrons in to complex II, which isn't. There is some leakage at complexes III and IV, but complex I one is the worst and fatty acids partially bypass it. I'd like to keep my mitochondria as happy as possible, as they decide when my cells are going to age and die. The later the better. Minimising leakage seems like a good idea (although some is necessary for health, read PSS).
The biochemistry suggests that running your metabolism on fat may release less free radicals than running it on glucose. As I am hopelessly biased in favour of fat metabolism and I enjoy the nuts and bolts of biochemistry, this makes me happy.
It also puts some logic and a mechanism on to Cynthia Kenyon's comment (in reply to being asked why she restricts her carbohydrate intake, ie is it to extend her life expectancy):
"That's not necessarily why I do it. I do it because it makes me feel great and keeps me slender. And I don't feel really tired after a meal. But I think if I wanted to eat in a way that extended lifespan this is how I would do it. In fact, I stopped eating carbohydrates the day we found that putting sugar on the worms' food shortened their lifespans."
I know what she means about feeling good and staying awake after a meal.
Personally I think old age is a not the problem, it's getting there without those diseases normally associated with it that would be nice. If you can become aged and stay disease free, the longer it goes on for the better.
Peter
What he means is that it leaks unpleasant stuff but usually only in small amounts unless there is a blockage, which fills the pipe and increases leakage pressure. Otherwise just a little of the nasty stuff escapes.
Just to leave sewer analogies aside for a while, what is the electron transport chain? It's a set of very complex molecular structures embedded in the innermost membrane of the mitochondria. It takes an electron (from where, later) and passes it through a series of "mills" and "conduits" until eventually it off loads it on to an oxygen molecule (this is why we breathe, oxygen isn't needed for much else). As it goes through the "mills" its energy is used to pump hydrogen ions from the innermost recesses of the mitochondria in to the outer zones. The more electrons through the mill, the more pumping. The hydrogen ions want to get back in. The only route back in is through a turnstyle. As the turnstyle turns, rotated by a returning hydrogen ion, a mechanism pushes an extra phosphate group on to an ADP molecule to form an ATP molecule. ATP is exported and used as the energy currency of the cell. Most, but not all, ATP is made this way. There are other routes back for hydrogen ions too, but that's another story.
Back to the sewer metaphor. The electron transfer chain leaks. It leaks raw electrons. Electrons react with anything and everything. Many things affect the rate of leakage and the consequences of leakage, but ultimately the knock on effect of this is damage to the mitochondrial DNA, which codes for certain essential components of the electron transport chain... As the DNA degrades over the years the electron chain components become more leaky and more damage is done and we age.
So much comes from PSS. There are very detailed and mostly convincing arguments for this view of aging and a number of other aspects of Life the Universe and Everything. The answer does not appear to be 42.
That got me thinking. Back to Moseby's Crash Course in Metabolism and Nutrition. A quick comparison of the break down of glucose and palmitic acid comes out with this: Glucose goes through glycolysis to pyruvate. Pyruvate enters the mitochondria, gets converted to acetyl CoA and drops in to the ubiquitous tricarboxylic acid cycle (unless your metabolism is VERY strange, like H. pylori). Palmitic acid, my favourite calorie source, gets an executive ticket straight in to the mitochondria where it undergoes beta oxidation to acetyl CoA and after that it could have been sugar (ie acetyl CoA from any source goes down the same cyclical plug hole).
So the difference in metabolism is between glycolysis and beta oxidation. These provide electrons for the electron sewer in different forms. You can't shift electrons around "neat" unless you are using some copper wire or the like. Neat electrons are what do all of the damage. No, electrons are shifted about as chemical electron equivalents. One is NADH, the other is FADH2. Doesn't matter what these stand for. Converting glucose to Acetyl CoA provides a little NADH and that's it. Converting palmitic acid to acetyl CoA provides a whole load of "electrons", in the form of an equal amount of NADH and FADH2. After that it's all acetyl CoA and the same as glucose. But for every calorie of glucose you burn, you generate a higher proportion of NADH to FADH2 than by burning palmitic acid. So what?
NADH puts its electron in to the start of the electron transport chain at complex I. Complex I is leaky. FADH2 puts its pair of electrons in to complex II, which isn't. There is some leakage at complexes III and IV, but complex I one is the worst and fatty acids partially bypass it. I'd like to keep my mitochondria as happy as possible, as they decide when my cells are going to age and die. The later the better. Minimising leakage seems like a good idea (although some is necessary for health, read PSS).
The biochemistry suggests that running your metabolism on fat may release less free radicals than running it on glucose. As I am hopelessly biased in favour of fat metabolism and I enjoy the nuts and bolts of biochemistry, this makes me happy.
It also puts some logic and a mechanism on to Cynthia Kenyon's comment (in reply to being asked why she restricts her carbohydrate intake, ie is it to extend her life expectancy):
"That's not necessarily why I do it. I do it because it makes me feel great and keeps me slender. And I don't feel really tired after a meal. But I think if I wanted to eat in a way that extended lifespan this is how I would do it. In fact, I stopped eating carbohydrates the day we found that putting sugar on the worms' food shortened their lifespans."
I know what she means about feeling good and staying awake after a meal.
Personally I think old age is a not the problem, it's getting there without those diseases normally associated with it that would be nice. If you can become aged and stay disease free, the longer it goes on for the better.
Peter
Tuesday, April 01, 2008
Athletic acid reflux
If you work on the basis that gastroesophageal reflux is carbohydrate poisoning, you would expect a LC diet to provide remission of symptoms. Just reading through the abstract of this paper from g, that would appear to be the case. Six days is a pretty short period to sort our GERD and no doubt there would be further improvement with time. The other tweak would be gluten elimination, not that much would be coming through at 20g of carbs per day.
This goes nicely back-to-back with another paper which has been lying around on my hard drive for some time. There is a fairly large literature as to why exercise results in an omprazole deficiency in athletes, with lots of ideas floated around about pressure changes, hormones etc. I think it's reasonable to describe many endurance athletes, the ones worst affected, as indulging in "carb loading". Apart from furring up their coronary arteries with sugar, GERD would seem be (yet) another price that must be paid by athletes for this practice. I'm glad so say that I have no personal experience of GERD, though my wife could write a book bout it.
Peter
BTW Nice to see Grete Waitz doing well.
This goes nicely back-to-back with another paper which has been lying around on my hard drive for some time. There is a fairly large literature as to why exercise results in an omprazole deficiency in athletes, with lots of ideas floated around about pressure changes, hormones etc. I think it's reasonable to describe many endurance athletes, the ones worst affected, as indulging in "carb loading". Apart from furring up their coronary arteries with sugar, GERD would seem be (yet) another price that must be paid by athletes for this practice. I'm glad so say that I have no personal experience of GERD, though my wife could write a book bout it.
Peter
BTW Nice to see Grete Waitz doing well.
Fiber, sucrose and ulcers
Thanks to g for this paper. It's a little observational study looking sucrose vs fiber and their possible association with peptic ulcer. Cleave suggested refined carbohydrate caused duodenal ulcers. The carbophillic nature of post-Keys medicine suggested that fiber could redeem carbohydrate as a source of nutrition. This group from Nottingham (my place of origin) appear to be dubious about this. This phrase comes from the discussion:
"Despite the current healthy diet lobby there were no claims of increased (or decreased) fibre intake by patients or control subjects"
The clear association of ulcers with sucrose was interesting. The total lack of protection from cereal fiber was too (sorry, lack of negative association). But the best bit was vegetable fiber. This was slightly "protective". Until you corrected for social class (and a few other things), at which point the association was lost. Looks a bit suggestive that vegetable fiber intake might just be a surrogate for being more well off.
Another throw away comment from Nottingham in the late 1980s was that Crohn's disease is consistently associated with high refined sugar intake. I think I've seen quite a number of studies coming to that conclusion. But surely sucrose (or HFCS for that matter) can form part of a healthy balanced diet...
Peter
"Despite the current healthy diet lobby there were no claims of increased (or decreased) fibre intake by patients or control subjects"
The clear association of ulcers with sucrose was interesting. The total lack of protection from cereal fiber was too (sorry, lack of negative association). But the best bit was vegetable fiber. This was slightly "protective". Until you corrected for social class (and a few other things), at which point the association was lost. Looks a bit suggestive that vegetable fiber intake might just be a surrogate for being more well off.
Another throw away comment from Nottingham in the late 1980s was that Crohn's disease is consistently associated with high refined sugar intake. I think I've seen quite a number of studies coming to that conclusion. But surely sucrose (or HFCS for that matter) can form part of a healthy balanced diet...
Peter
Monday, March 31, 2008
Cholesterol; statins kill?
Just a quickie.
Go read Dr Eades' blog here. For anyone who has read the J-litt study, or more especially line one of table 6 on page 1092, none of this will come as a surprise. There is a level of LDL below which repair cells just won't get enough cholesterol and lipid to patch the hole in the intima left by the apoptosis of an endothelial cell. The repair will then be botched with a next best like Lp(a).
Interesting development.
Peter
Go read Dr Eades' blog here. For anyone who has read the J-litt study, or more especially line one of table 6 on page 1092, none of this will come as a surprise. There is a level of LDL below which repair cells just won't get enough cholesterol and lipid to patch the hole in the intima left by the apoptosis of an endothelial cell. The repair will then be botched with a next best like Lp(a).
Interesting development.
Peter
Sunday, March 30, 2008
Helicobacter and glucose
Helicobacter is a bad bug. Really bad. So bad that in the recent consensus conferences, like this one, the plan is clear. Hunt, find, kill. Sounds like the cholesterol consensus to me. The only good cholesterol molecule is a dead cholesterol molecule. Oops, getting a bit random there. Back to reality:
"The consensus conference boldly recommended population-based screening and treatment for H. pylori in particularly high-risk population settings"
Anyway, some time around 60,000 years ago humans walked out of Africa in to what is now the Middle East and kept going. Taking their Helicobacter pylori with them. Yes, H pylori has been around the human gut for a long time. There is a nice neat diagram and discussion of human/helicobacter co-expansion on this person's blog. The basic idea is that you can get some idea of the spread of humans by looking at the genes of their H pylori. Presumably the hunter-gatherers were dying like flies from gastric carcinoma along the way.
So, the consensus plan is to eliminate a bug which has been with us on a timescale of up to 100,000 years, and this will stop gastric cancer. Truly a bold recommendation.
If you go back to the early accounts of the missionary hospitals tending to native populations before the introduction of Western lifestyles, cancer was very very very rare. Stefansson summarises it rather well in his 1960 book Cancer: Disease of Civilisation. It's hard to get hold of a copy and rather expensive too, but it makes an interesting read. Cancer searches came back negative. I'm willing to accept that H. pylori wasn't causing cancer in human hunter gatherers, although they were all "infected", if that's the right word for a gastric commensal.
So why does helicobacter cause cancer in humans nowadays? Some light was shed on the problem by the Japanese who noticed that elevated fasting plasma glucose levels are associated with gastric cancer, but only in those patients who carry helicobacter.
Helicobacter is quite a specialised bug. This paper has some interesting snippets. H pylori appears to love glucose. It will do both aerobic and anaerobic metabolism with it, but look at this:
"Under aerobic conditions acetate was the major oxidation product from pyruvate; no evidence was obtained for tricarboxylic acid cycle activity"
H. pylori doesn't appear to use the tricaboxylic acid cycle! Certainly not in this set up. Pyruvate is converted to acetate without acetyl CoA entering the TCA. This looks to me as if fermentation might be producing the bulk of its ATP. In fact if you look further you find that helicobacter does actually run a TCA cycle of sorts, but it runs it in reverse, and it's non cyclical and it runs as a reducing system, non oxidative... I'm not sure how much this set up could do with a fatty acid! I get the impression that glucose might just be the preferred fuel...
Back in the big world there is a mass of anecdotal evidence that LC eating "sorts out" many cases of dyspepsia. I can't find any specific studies since Yudkin's open cross over diet trial detailed in chapter 12 of Pure, White and Deadly, where LC eating worked for many, but not all, dyspepsia patients.
I think it's a reasonable speculation that anything which increases blood glucose might just encourage helicobacter to have a field day and do some cancer generating. Dropping blood glucose might just do the opposite. Actually, maybe just eating the glucose non-stop is a bad idea! Certainly a LC diet might have a better long term outcome for those people currently dependent on ranitidine or omeprazole for control of the extremely unpleasant effects of dyspepsia.
Or of course we could just kill all the Helicobacter pylori in people at risk of gastric cancer, and stop them ever getting infected again. That's the consensus.
Ha ha ha.
Peter
"The consensus conference boldly recommended population-based screening and treatment for H. pylori in particularly high-risk population settings"
Anyway, some time around 60,000 years ago humans walked out of Africa in to what is now the Middle East and kept going. Taking their Helicobacter pylori with them. Yes, H pylori has been around the human gut for a long time. There is a nice neat diagram and discussion of human/helicobacter co-expansion on this person's blog. The basic idea is that you can get some idea of the spread of humans by looking at the genes of their H pylori. Presumably the hunter-gatherers were dying like flies from gastric carcinoma along the way.
So, the consensus plan is to eliminate a bug which has been with us on a timescale of up to 100,000 years, and this will stop gastric cancer. Truly a bold recommendation.
If you go back to the early accounts of the missionary hospitals tending to native populations before the introduction of Western lifestyles, cancer was very very very rare. Stefansson summarises it rather well in his 1960 book Cancer: Disease of Civilisation. It's hard to get hold of a copy and rather expensive too, but it makes an interesting read. Cancer searches came back negative. I'm willing to accept that H. pylori wasn't causing cancer in human hunter gatherers, although they were all "infected", if that's the right word for a gastric commensal.
So why does helicobacter cause cancer in humans nowadays? Some light was shed on the problem by the Japanese who noticed that elevated fasting plasma glucose levels are associated with gastric cancer, but only in those patients who carry helicobacter.
Helicobacter is quite a specialised bug. This paper has some interesting snippets. H pylori appears to love glucose. It will do both aerobic and anaerobic metabolism with it, but look at this:
"Under aerobic conditions acetate was the major oxidation product from pyruvate; no evidence was obtained for tricarboxylic acid cycle activity"
H. pylori doesn't appear to use the tricaboxylic acid cycle! Certainly not in this set up. Pyruvate is converted to acetate without acetyl CoA entering the TCA. This looks to me as if fermentation might be producing the bulk of its ATP. In fact if you look further you find that helicobacter does actually run a TCA cycle of sorts, but it runs it in reverse, and it's non cyclical and it runs as a reducing system, non oxidative... I'm not sure how much this set up could do with a fatty acid! I get the impression that glucose might just be the preferred fuel...
Back in the big world there is a mass of anecdotal evidence that LC eating "sorts out" many cases of dyspepsia. I can't find any specific studies since Yudkin's open cross over diet trial detailed in chapter 12 of Pure, White and Deadly, where LC eating worked for many, but not all, dyspepsia patients.
I think it's a reasonable speculation that anything which increases blood glucose might just encourage helicobacter to have a field day and do some cancer generating. Dropping blood glucose might just do the opposite. Actually, maybe just eating the glucose non-stop is a bad idea! Certainly a LC diet might have a better long term outcome for those people currently dependent on ranitidine or omeprazole for control of the extremely unpleasant effects of dyspepsia.
Or of course we could just kill all the Helicobacter pylori in people at risk of gastric cancer, and stop them ever getting infected again. That's the consensus.
Ha ha ha.
Peter
Friday, March 28, 2008
Food; sausages
Tonight was sausages. First buy some Norfolk pork sausages from these people.
I asked them what filler they used in their wide range of gluten free sausages. The answer was that if you buy a sausage making machine which costs as much as a small Mercedes car you don't need any filler. No filler.
If you're not in the UK just hunt down some all meat sausages if you can get them.
We had about half a pound each. Fry them gently until lightly browned but not cooked through using butter/oilve oil as prefered. Stick them in a bowl to one side and fry a small onion and two red peppers (all chopped) in the fat. Put the sausages back in, add a tin of tomatoes, some pepper, crushed garlic and generous red wine plus lots of oregano. Simmer for as long as you can wait. About half an hour is needed, longer blends the flavours better. Tastes best with olive oil but I suspect lard would be healthier....
Peter
I asked them what filler they used in their wide range of gluten free sausages. The answer was that if you buy a sausage making machine which costs as much as a small Mercedes car you don't need any filler. No filler.
If you're not in the UK just hunt down some all meat sausages if you can get them.
We had about half a pound each. Fry them gently until lightly browned but not cooked through using butter/oilve oil as prefered. Stick them in a bowl to one side and fry a small onion and two red peppers (all chopped) in the fat. Put the sausages back in, add a tin of tomatoes, some pepper, crushed garlic and generous red wine plus lots of oregano. Simmer for as long as you can wait. About half an hour is needed, longer blends the flavours better. Tastes best with olive oil but I suspect lard would be healthier....
Peter
Thursday, March 27, 2008
Kwasniewski; praise the lard
This article was originally published in 2004 in the Chicago Tribune. It's still knocking around on the web in various places but the original seems to have disappeared. You can't have too much of a good thing. Obviously Stephan's recent posts on lard prompted me to put this one up. The imported nutritionist doesn't seem quite as dismissive as you might expect! But notice in the last paragraph that the big bogeyman is protein overload damaging the kidneys! On 60g/d of protein??? Sobor clearly knows nothing about high fat diets, certainly not the one he is commenting so authoritatively about in this case!
Peter
Praise the LARD
By Monica Eng
Chicago Tribune
CHICAGO -- Vinka Peschak starts each day by knocking back a full cup of heavy whipping cream.
That's at 8 a.m.
"At around 11 o'clock I take three or four egg yolks and make some kind of omelet with lard for breakfast," the Portage Park resident explains. Peschak, a native of Poland, eats her omelet with a cup of buttery boiled vegetables and a slender piece of almond toast slathered in more butter or lard.
Dinner is usually a fatty piece of pork or some kind of organ meat with lard-cooked french fries and more butter-soaked vegetables.
In the middle of the day she might have a cup of coffee, "but only with a lot of heavy whipping cream in it."
Peschak has been eating like this for more than five years. She is slim, energetic, and says, "I feel wonderful, never tired and never hungry."
She is not on Atkins. She is not on South Beach.
Peschak, along with an estimated 2 million folks worldwide is on the Optimal Diet, a Polish eating plan that requires the consumption of prodigious amounts of animal fat -- preferably lard.
The diet was hatched in Poland some 40 years ago by Dr. Jan Kwasniewski, who started developing it while working as a dietician for a military sanitarium in Ciechocinek, Poland. There he observed that many of his patients were sick, "not because of any pathogenic factors ... but the result of one underlying cause -- bad nutrition," according to his English language "Optimal Nutrition" book. After experimenting on his family and himself, Kwasniewski concluded that the ideal nutritional combo came from eating three grams of fat for every one gram of protein and half a gram of carbohydrates.
After a couple of decades of refining this theory, Kwasniewski published his first book in Poland in 1990. But it wasn't until converts came forward with their stories of weight loss and recovery from disease in the mid-'90s that the diet really took off it its native land and Kwasniewski's books went into wide circulation. Today there are at least two magazines devoted to the Optimal lifestyle and Kwasniewski writes a twice weekly column for the regional Polish newspaper Dziennik Zachodni.
It wasn't until 2001, though, that Chicago would become the North American capital for this eating plan. That's when Tomasz Zielinski bought a little storefront on Milwaukee Avenue and opened Calma Optimal Foods. The first and only one of its kind in the nation, it operates as a deli, meeting center and, as of this spring, a restaurant for those on the lard-laden plan. Peschak serves as its manager.
Sometimes called the Polish Atkins, the Optimal Diet severely restricts the intake of carbohydrates and sugars, but differs from Atkins by de-emphasizing protein and beefing up, or more accurately porking up, the fat to a level that would have even made the late Robert Atkins reach for his heart.
On average, the diet recommends a whopping 250 grams of fat per day, about four times what the FDA recommended for the average person to maintain his/her weight and about 10 times the amount of saturated fat allowed.
So despite its popularity in Poland -- Lech Walesa is reported to have lost 44 pounds and cured his diabetes on it recently -- the mainstream medical establishment there and here is skeptical.
"I am very against diets like this," says Jadwiga Roguska, a practicing internist at the Feinberg School of Medicine at Northwestern University. "All high-fat diets are unhealthy in the long term and there is absolutely no benefit to weight reduction of this sort because it is threatening to health. ... Of course, high-fat diets will give you the benefits of energy and weight loss, but they are just not good for you."
Roguska based her comments on a brief overview of its principles, but Chicago physician Mark Sobor has seen it up close and has watched an increasing number of his patients in the Polish community embrace it.
"Kwasniewski is pure fat," says Sobor who practices in Jefferson Park and is also a licensed acupuncturist. "Eat fat non-stop. Everything is pure fat. The more fat you can take in the better and these people are fanatics about it. But the thing is they're all skinny."
On a recent Sunday morning at the Optimal deli/center in Portage Park, Ill., about 30 mature, fairly slim followers of the Kwasniewski plan gathered for a weekly meeting and shared their stories.
There was the ginger-haired firecracker Irena Kozlowicz, 78, who went on the diet five years ago after Kwasniewski came to speak at the Copernicus Center in 1999. At the time she was suffering from chronic eye problems, asthma and pain in her knees.
"Now I can walk better than a young person," she chirps. "I can run up six floors of stairs and my grandson can't catch me. He's 17 years old. I meet young ladies and they are always tired and sweating, but I never am. I didn't need to lose weight, but I lost 8 pounds. I am 78, but I feel like I am 50. I thank God for the diet."
Then there is Jozef Michael Ostrowski, 71, who says he has been on a variation of the diet his whole life.
"Since the occupation of Poland my parents could only afford pork meat and liver and blood sausage and lard," Ostrowski says through an interpreter. "It is not like I was following this diet precisely but generally. At that time I didn't know this kind of natural food was good for me. I just knew that I could eat scrambled eggs with a thin piece of bread and lard and I would be full all day. I started eating regular food like McDonald's and I could not handle the pain and so I went back to the diet and have felt better and better every day."
Zofia Pawlik, 56, started the diet last year when she went on an Optimal vacation, a retreat to the Wisconsin Dells to learn about the program and eat its foods. Over the course of a year, she says she has lost 10 pounds while improving her energy and overall health.
IMPRESSIVE RESULTS
Chicago physician Christopher Kubik wasn't at the meeting, but in a phone interview he said that four and a half years ago he was overweight and suffering from fatigue and stones in the bladder. But within a couple of months of embarking on this high-fat journey he saw results.
"I was losing weigh gradually (he lost about 25 pounds in six weeks) but I felt fine. Since then, I didn't have any more problems with stones, my skin complexion improved and I am still feeling a lot of energy," says Kubik, 57, who reports that he breakfasts on fried eggs, bacon and string cheese seven days a week. "So I experienced myself significant detectable improvement even though I generally had good health to begin with. While I was losing the weight I could feel the ketones as a metallic tasted on the mouth, but after I reached my optimal weight, (the ketosis) stopped. Now my weight has remained steady at about 185, which is in the upper limit of normal for my height."
Kubik, who also has degrees in public health and health law, says he does not actively promote the diet, "because it is not considered a standard of care and the medical community still recommends low-fat diets and it is not something I could support if I were sued." But if patients ask, "I tell them that I am on it and have seen positive results."
Dr. Sobor has also seen a growing number of Kwasniewski converts who claim weight loss is only one of the benefits they've reaped.
Chester Matuszewski, 46, for instance says that four years ago he was diagnosed with rheumatoid arthritis and was told that there was no way he could be totally cured.
"Every single joint imaginable in my hips, elbows, knees and hands hurt," Matuszewski recalled. Remembering something he had read in a Polish newspaper about the Optimal diet, he decided to check it out even though it seemed unappetizing.
"For years I thought that pork is not good for you and I didn't like the smell, but I forced myself. ... After two months I started to feel better and I didn't want to attribute it to the diet. But my friends also saw a difference in me and I had so much energy. Today after four years, I have no pain and no swelling and I am totally cured."
Sobor hears these stories all the time, but still has his reservations.
"I'm sure you've heard their claims that their joint pain is gone and diabetes is gone," he says. "And they say it because it's true. You can apparently get a lot of benefits if you decrease your carbohydrate intake, and stop taking in all the white flour and stop taking in all the refined foods because you are not stressing your body out all the time with all of the insulin spikes and becoming hyperglycemic and hypoglycemic."
"But do I recommend the diet? I don't know," he says. "I don't think Kwasniewski is as good as Atkins or that it is something you should go on for a long time. Now the South Beach Diet that is a nice diet with more flexibility. But this Optimal diet is the most radical of the low-carb diets."
Despite the popularity of the diet in its country of origin, it remains controversial there among traditional Polish nutritionists who oppose its high cholesterol and fat recommendations.
"They don't like it because they see it endangers their own positions as nutritional authorities," says Peschak.
NO POSITION FROM THE AMA
In the U.S. the Optimal Diet hasn't yet caught the attention of the medical establishment. The American Medical Association doesn't have a position on Atkins, much less Optimal. And Lisa Dorfman, spokeswoman for the American Dietetic Association, had not heard of it either.
Still, based on a quick description of the diet, she didn't condemn it outright.
"I can see how this would be a very attractive program, certainly in the senior citizen community because these are nutrient dense foods and seniors don't need to eat a lot of food," says Dorfman, a licensed nutritionist.
"And some of the foods are very nutritious albeit very high in fat and cholesterol. Liver is very high in iron and B vitamins, which would be lovely for senior citizens because they need those vitamins and are usually on a budget in that time of life.
"But for the general public I see where there could be potential problems. We just know that long-term high-fat diets leave one with a heightened risk of heart disease, stroke and hypertension. This is certainly not for children, teenagers or pregnant women.
Most Americans are getting too much fat as it is and they are not getting enough activity and they have incredible risk for heart disease because of a whole multiple list of factors including genetics and stress. And so I can't imagine that adding fat and lard and cholesterol into the mix would be beneficial to that."
"But for this group of Polish seniors I think it's adorable, especially if it was developed by someone from the old country. As a psychotherapist, I can see where they must feel like you've got to be healthy eating this because there is a psychological connection to eating these foods. It's old country eating."
Going back to the basics. It is different from the commercial processing chemical laden foods. I certainly believe these people are benefiting in some way, but it may be more than one way and it may be for certain groups and not for others is my gut hunch. It might not be appropriate for three-quarters of the population but maybe they've hit the nail on the head and this is perfect for them."
WHAT WILL IT DO LONGTERM
Although there is general agreement in the health community that lots of refined flours and sugars and their accompanying insulin spikes are not healthful, most conventional nutritionists are still not ready to embrace low-carb, high-protein and high-fat diets because of their perceived effects on the organs.
But could wear and tear on the liver, kidneys and heart be worth it for an older person to be free of the health risks of obesity?
"That I don't know," Sobor says. "No one on Atkins has died of kidney failure yet, but you can probably find a nephrologist (kidney specialist) who says it's good, one who says its bad and one who is in between. Because the truth is no one really knows yet."
"The final question is who dies faster, the people who are obese or the people who go on these diets. You would have to take 2,000 people on the diet and then 2,000 controls to see what is going to kill them first, the extra pounds or the extra protein load on the kidneys or whatever this diet will do to you. The pounds are going to do it in the short and medium term. There's no question about that. But the jury is out on the long term. The final arbiter is death. If they live longer than you do, then they won."
Peter
Praise the LARD
By Monica Eng
Chicago Tribune
CHICAGO -- Vinka Peschak starts each day by knocking back a full cup of heavy whipping cream.
That's at 8 a.m.
"At around 11 o'clock I take three or four egg yolks and make some kind of omelet with lard for breakfast," the Portage Park resident explains. Peschak, a native of Poland, eats her omelet with a cup of buttery boiled vegetables and a slender piece of almond toast slathered in more butter or lard.
Dinner is usually a fatty piece of pork or some kind of organ meat with lard-cooked french fries and more butter-soaked vegetables.
In the middle of the day she might have a cup of coffee, "but only with a lot of heavy whipping cream in it."
Peschak has been eating like this for more than five years. She is slim, energetic, and says, "I feel wonderful, never tired and never hungry."
She is not on Atkins. She is not on South Beach.
Peschak, along with an estimated 2 million folks worldwide is on the Optimal Diet, a Polish eating plan that requires the consumption of prodigious amounts of animal fat -- preferably lard.
The diet was hatched in Poland some 40 years ago by Dr. Jan Kwasniewski, who started developing it while working as a dietician for a military sanitarium in Ciechocinek, Poland. There he observed that many of his patients were sick, "not because of any pathogenic factors ... but the result of one underlying cause -- bad nutrition," according to his English language "Optimal Nutrition" book. After experimenting on his family and himself, Kwasniewski concluded that the ideal nutritional combo came from eating three grams of fat for every one gram of protein and half a gram of carbohydrates.
After a couple of decades of refining this theory, Kwasniewski published his first book in Poland in 1990. But it wasn't until converts came forward with their stories of weight loss and recovery from disease in the mid-'90s that the diet really took off it its native land and Kwasniewski's books went into wide circulation. Today there are at least two magazines devoted to the Optimal lifestyle and Kwasniewski writes a twice weekly column for the regional Polish newspaper Dziennik Zachodni.
It wasn't until 2001, though, that Chicago would become the North American capital for this eating plan. That's when Tomasz Zielinski bought a little storefront on Milwaukee Avenue and opened Calma Optimal Foods. The first and only one of its kind in the nation, it operates as a deli, meeting center and, as of this spring, a restaurant for those on the lard-laden plan. Peschak serves as its manager.
Sometimes called the Polish Atkins, the Optimal Diet severely restricts the intake of carbohydrates and sugars, but differs from Atkins by de-emphasizing protein and beefing up, or more accurately porking up, the fat to a level that would have even made the late Robert Atkins reach for his heart.
On average, the diet recommends a whopping 250 grams of fat per day, about four times what the FDA recommended for the average person to maintain his/her weight and about 10 times the amount of saturated fat allowed.
So despite its popularity in Poland -- Lech Walesa is reported to have lost 44 pounds and cured his diabetes on it recently -- the mainstream medical establishment there and here is skeptical.
"I am very against diets like this," says Jadwiga Roguska, a practicing internist at the Feinberg School of Medicine at Northwestern University. "All high-fat diets are unhealthy in the long term and there is absolutely no benefit to weight reduction of this sort because it is threatening to health. ... Of course, high-fat diets will give you the benefits of energy and weight loss, but they are just not good for you."
Roguska based her comments on a brief overview of its principles, but Chicago physician Mark Sobor has seen it up close and has watched an increasing number of his patients in the Polish community embrace it.
"Kwasniewski is pure fat," says Sobor who practices in Jefferson Park and is also a licensed acupuncturist. "Eat fat non-stop. Everything is pure fat. The more fat you can take in the better and these people are fanatics about it. But the thing is they're all skinny."
On a recent Sunday morning at the Optimal deli/center in Portage Park, Ill., about 30 mature, fairly slim followers of the Kwasniewski plan gathered for a weekly meeting and shared their stories.
There was the ginger-haired firecracker Irena Kozlowicz, 78, who went on the diet five years ago after Kwasniewski came to speak at the Copernicus Center in 1999. At the time she was suffering from chronic eye problems, asthma and pain in her knees.
"Now I can walk better than a young person," she chirps. "I can run up six floors of stairs and my grandson can't catch me. He's 17 years old. I meet young ladies and they are always tired and sweating, but I never am. I didn't need to lose weight, but I lost 8 pounds. I am 78, but I feel like I am 50. I thank God for the diet."
Then there is Jozef Michael Ostrowski, 71, who says he has been on a variation of the diet his whole life.
"Since the occupation of Poland my parents could only afford pork meat and liver and blood sausage and lard," Ostrowski says through an interpreter. "It is not like I was following this diet precisely but generally. At that time I didn't know this kind of natural food was good for me. I just knew that I could eat scrambled eggs with a thin piece of bread and lard and I would be full all day. I started eating regular food like McDonald's and I could not handle the pain and so I went back to the diet and have felt better and better every day."
Zofia Pawlik, 56, started the diet last year when she went on an Optimal vacation, a retreat to the Wisconsin Dells to learn about the program and eat its foods. Over the course of a year, she says she has lost 10 pounds while improving her energy and overall health.
IMPRESSIVE RESULTS
Chicago physician Christopher Kubik wasn't at the meeting, but in a phone interview he said that four and a half years ago he was overweight and suffering from fatigue and stones in the bladder. But within a couple of months of embarking on this high-fat journey he saw results.
"I was losing weigh gradually (he lost about 25 pounds in six weeks) but I felt fine. Since then, I didn't have any more problems with stones, my skin complexion improved and I am still feeling a lot of energy," says Kubik, 57, who reports that he breakfasts on fried eggs, bacon and string cheese seven days a week. "So I experienced myself significant detectable improvement even though I generally had good health to begin with. While I was losing the weight I could feel the ketones as a metallic tasted on the mouth, but after I reached my optimal weight, (the ketosis) stopped. Now my weight has remained steady at about 185, which is in the upper limit of normal for my height."
Kubik, who also has degrees in public health and health law, says he does not actively promote the diet, "because it is not considered a standard of care and the medical community still recommends low-fat diets and it is not something I could support if I were sued." But if patients ask, "I tell them that I am on it and have seen positive results."
Dr. Sobor has also seen a growing number of Kwasniewski converts who claim weight loss is only one of the benefits they've reaped.
Chester Matuszewski, 46, for instance says that four years ago he was diagnosed with rheumatoid arthritis and was told that there was no way he could be totally cured.
"Every single joint imaginable in my hips, elbows, knees and hands hurt," Matuszewski recalled. Remembering something he had read in a Polish newspaper about the Optimal diet, he decided to check it out even though it seemed unappetizing.
"For years I thought that pork is not good for you and I didn't like the smell, but I forced myself. ... After two months I started to feel better and I didn't want to attribute it to the diet. But my friends also saw a difference in me and I had so much energy. Today after four years, I have no pain and no swelling and I am totally cured."
Sobor hears these stories all the time, but still has his reservations.
"I'm sure you've heard their claims that their joint pain is gone and diabetes is gone," he says. "And they say it because it's true. You can apparently get a lot of benefits if you decrease your carbohydrate intake, and stop taking in all the white flour and stop taking in all the refined foods because you are not stressing your body out all the time with all of the insulin spikes and becoming hyperglycemic and hypoglycemic."
"But do I recommend the diet? I don't know," he says. "I don't think Kwasniewski is as good as Atkins or that it is something you should go on for a long time. Now the South Beach Diet that is a nice diet with more flexibility. But this Optimal diet is the most radical of the low-carb diets."
Despite the popularity of the diet in its country of origin, it remains controversial there among traditional Polish nutritionists who oppose its high cholesterol and fat recommendations.
"They don't like it because they see it endangers their own positions as nutritional authorities," says Peschak.
NO POSITION FROM THE AMA
In the U.S. the Optimal Diet hasn't yet caught the attention of the medical establishment. The American Medical Association doesn't have a position on Atkins, much less Optimal. And Lisa Dorfman, spokeswoman for the American Dietetic Association, had not heard of it either.
Still, based on a quick description of the diet, she didn't condemn it outright.
"I can see how this would be a very attractive program, certainly in the senior citizen community because these are nutrient dense foods and seniors don't need to eat a lot of food," says Dorfman, a licensed nutritionist.
"And some of the foods are very nutritious albeit very high in fat and cholesterol. Liver is very high in iron and B vitamins, which would be lovely for senior citizens because they need those vitamins and are usually on a budget in that time of life.
"But for the general public I see where there could be potential problems. We just know that long-term high-fat diets leave one with a heightened risk of heart disease, stroke and hypertension. This is certainly not for children, teenagers or pregnant women.
Most Americans are getting too much fat as it is and they are not getting enough activity and they have incredible risk for heart disease because of a whole multiple list of factors including genetics and stress. And so I can't imagine that adding fat and lard and cholesterol into the mix would be beneficial to that."
"But for this group of Polish seniors I think it's adorable, especially if it was developed by someone from the old country. As a psychotherapist, I can see where they must feel like you've got to be healthy eating this because there is a psychological connection to eating these foods. It's old country eating."
Going back to the basics. It is different from the commercial processing chemical laden foods. I certainly believe these people are benefiting in some way, but it may be more than one way and it may be for certain groups and not for others is my gut hunch. It might not be appropriate for three-quarters of the population but maybe they've hit the nail on the head and this is perfect for them."
WHAT WILL IT DO LONGTERM
Although there is general agreement in the health community that lots of refined flours and sugars and their accompanying insulin spikes are not healthful, most conventional nutritionists are still not ready to embrace low-carb, high-protein and high-fat diets because of their perceived effects on the organs.
But could wear and tear on the liver, kidneys and heart be worth it for an older person to be free of the health risks of obesity?
"That I don't know," Sobor says. "No one on Atkins has died of kidney failure yet, but you can probably find a nephrologist (kidney specialist) who says it's good, one who says its bad and one who is in between. Because the truth is no one really knows yet."
"The final question is who dies faster, the people who are obese or the people who go on these diets. You would have to take 2,000 people on the diet and then 2,000 controls to see what is going to kill them first, the extra pounds or the extra protein load on the kidneys or whatever this diet will do to you. The pounds are going to do it in the short and medium term. There's no question about that. But the jury is out on the long term. The final arbiter is death. If they live longer than you do, then they won."
Wednesday, March 26, 2008
Back home
Got to paddle on Easter Sunday as soon as the wind dropped, four foot and clean. I kept most of the wet snow out of my dry suit, and the sun even came out when the snow stopped.
About the only Hyperlipidy aspect was that there doesn't appear to be a fall off in endurance ability with lack of practice. Paddled for about two and a half hours and could have carried on but the surf was dropping with the rising tide. The reflexes and muscles still work after what must be two years off of the surf...
What do you do with five days off line? Well, Nick Lane's "Power, Sex, Suicide" has been a very interesting read. Well over half way through it and it makes a great deal of sense.
Lots of catching up to do!
Peter
About the only Hyperlipidy aspect was that there doesn't appear to be a fall off in endurance ability with lack of practice. Paddled for about two and a half hours and could have carried on but the surf was dropping with the rising tide. The reflexes and muscles still work after what must be two years off of the surf...
What do you do with five days off line? Well, Nick Lane's "Power, Sex, Suicide" has been a very interesting read. Well over half way through it and it makes a great deal of sense.
Lots of catching up to do!
Peter
Thursday, March 20, 2008
Monday, March 17, 2008
Food; carnitas
Tonight was carnitas.
Buy some strips of belly pork. Be sure to pick over the selection for the fattiest if you're in a supermarket. Any time from lunch time onwards stick them in a large sauce pan and just cover with water. Add salt and pepper, a chopped onion and a whole root of garlic, cut in half horizontally. Two bay leaves are essential. Buy a bay tree if necessary. Dried might be okay, dunno, I've got the tree.
Cover tightly, bring to boil, turn heat very low and forget about for at least 3 hours. Five hours is fine. You can do this the night before, but the smell is so good I prefer to eat them on the day.
Pick out the strips (gently, they tend to break up) and cut up in to chunks about 2 inches long. I don't use the stock for anything. Transfer the meat pieces to a non stick heavy frying pan and cook them slowly in their own fat. Sprinkle with salt, pepper, chili powder, some cumin and some more chili powder. Flip the pieces once. You're aiming to have a crispy outside and the fat within fully softened. If you over-fry them all the fat runs out and you end up with hard meat in lard. Avoid!
That's it. We had them with sweet potatoes. They should absolutely melt in the mouth. They did.
Peter
Buy some strips of belly pork. Be sure to pick over the selection for the fattiest if you're in a supermarket. Any time from lunch time onwards stick them in a large sauce pan and just cover with water. Add salt and pepper, a chopped onion and a whole root of garlic, cut in half horizontally. Two bay leaves are essential. Buy a bay tree if necessary. Dried might be okay, dunno, I've got the tree.
Cover tightly, bring to boil, turn heat very low and forget about for at least 3 hours. Five hours is fine. You can do this the night before, but the smell is so good I prefer to eat them on the day.
Pick out the strips (gently, they tend to break up) and cut up in to chunks about 2 inches long. I don't use the stock for anything. Transfer the meat pieces to a non stick heavy frying pan and cook them slowly in their own fat. Sprinkle with salt, pepper, chili powder, some cumin and some more chili powder. Flip the pieces once. You're aiming to have a crispy outside and the fat within fully softened. If you over-fry them all the fat runs out and you end up with hard meat in lard. Avoid!
That's it. We had them with sweet potatoes. They should absolutely melt in the mouth. They did.
Peter
Sunday, March 16, 2008
Diabetes and hunger
I can vaguely remember being hungry, way back before LC eating. The sort of day when you would get home at 5.30 and you HAD to have to have two doorsteps of wholemeal bread, spread with peanut butter (to avoid the saturated fats) and filled with a sliced banana, because there was NO WAY you could wait the hour it was going to take you to get supper ready. In the door, slice the bread. I remember hopping on the scales at work once and thinking that skipping a meal here and there might drop that pound or two around my tummy. Then trying it!
At the time my need to eat didn't seem like greed.
We all know that if you are a type 2 diabetic you must have been greedy for years before getting your just comuppance (thinks your GP). It's self evident that fat people get fat by eating too much food and obviously it's the dietary fat which is the main factor. Obesity is clearly the cause of type 2 diabetes (except in skinny type 2s and those naughty extremely skinny people with lipodystrophy, duhh). It's also self evident that once you have a serious blood sugar regulation problem you should eat as much sugar as possible and avoid fat like the plague because otherwise you might get even fatter, which gives you more blood sugar problems (ADA advice).
So a type 2 diabetic should eat a diet which is as carbohydrate based as practical and make sure they loose weight, lots of it. I think it's reasonable to say that that's current diabetes advice.
One day I found this paper on diabetic rats. I'm not really sure how similar streptozotocin induced diabetes in lab rats is to type 2 diabetes in humans. Insulin production is blunted but not eliminated, so perhaps it is the equivalent to fairly late type 2, when the pancreas has finally started to give up under the strain of the ADA carbohydrate based diet. The paper was quite interesting from the point of view of hunger.
Lab rats don't generally get described as being lazy glutttons. Sitting in a cage all day limits your trips to the gym. You eat what the investigator gives you. It seems quite reasonable that rats eat to satiety and no more. Beyond that would be gluttony. But if you make a rat diabetic, then feed it a carbohydrate based diet, it exhibits "hyperphagia". It eats a LOT. And it becomes fat. Perhaps a little bit of streptozotocin and some lab chow equals gluttony.
Obviously no self respecting rat wants to be either diabetic or hyperphagic. Luckily rats are not stupid and, given a choice of macronutrients after its streptozotocin, a lab rat will automatically dump the carbs, eat the fat and keep both its waistline slim and its blood glucose within acceptable limits. Given the ADA diet they don't, or rather they can't. Why can't they?
Because they're hungry. Very, very hungry.
This looks to be what is happening, from the abstract:
"When maintained on a HC [high carbohydrate] diet, diabetic rats also exhibit increased gene expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamic arcuate nucleus, and reduced expression of the anorectic peptide corticotropin-releasing hormone (CRH) in the paraventricular nucleus, and these changes are hypothesized to contribute to diabetic hyperphagia"
Orexigenic means hunger generating. Anorectic is the opposite.
Diabetic rats on the ADA diet are RAVENOUS. Oops, sorry, gluttenous. Diabetic rats on a genuine high fat diet are not. They're not very diabetic either.
Now take that to humans. I don't think humans are particularly different to rats. Telling a human diabetic to eat a carbohydrate based diet will bump up their neuropeptide Y levels and will drop their corticotropic releasing hormone levels. They'll be ravenous. Bit of a cruel trick really.
But here's the really funny bit.
You then tell them they MUST lose weight. When they fail to lose weight, you underline the bit in their case notes where it says glutton/failed to comply.
Don't laugh too much, it's not funny really.
Peter
At the time my need to eat didn't seem like greed.
We all know that if you are a type 2 diabetic you must have been greedy for years before getting your just comuppance (thinks your GP). It's self evident that fat people get fat by eating too much food and obviously it's the dietary fat which is the main factor. Obesity is clearly the cause of type 2 diabetes (except in skinny type 2s and those naughty extremely skinny people with lipodystrophy, duhh). It's also self evident that once you have a serious blood sugar regulation problem you should eat as much sugar as possible and avoid fat like the plague because otherwise you might get even fatter, which gives you more blood sugar problems (ADA advice).
So a type 2 diabetic should eat a diet which is as carbohydrate based as practical and make sure they loose weight, lots of it. I think it's reasonable to say that that's current diabetes advice.
One day I found this paper on diabetic rats. I'm not really sure how similar streptozotocin induced diabetes in lab rats is to type 2 diabetes in humans. Insulin production is blunted but not eliminated, so perhaps it is the equivalent to fairly late type 2, when the pancreas has finally started to give up under the strain of the ADA carbohydrate based diet. The paper was quite interesting from the point of view of hunger.
Lab rats don't generally get described as being lazy glutttons. Sitting in a cage all day limits your trips to the gym. You eat what the investigator gives you. It seems quite reasonable that rats eat to satiety and no more. Beyond that would be gluttony. But if you make a rat diabetic, then feed it a carbohydrate based diet, it exhibits "hyperphagia". It eats a LOT. And it becomes fat. Perhaps a little bit of streptozotocin and some lab chow equals gluttony.
Obviously no self respecting rat wants to be either diabetic or hyperphagic. Luckily rats are not stupid and, given a choice of macronutrients after its streptozotocin, a lab rat will automatically dump the carbs, eat the fat and keep both its waistline slim and its blood glucose within acceptable limits. Given the ADA diet they don't, or rather they can't. Why can't they?
Because they're hungry. Very, very hungry.
This looks to be what is happening, from the abstract:
"When maintained on a HC [high carbohydrate] diet, diabetic rats also exhibit increased gene expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamic arcuate nucleus, and reduced expression of the anorectic peptide corticotropin-releasing hormone (CRH) in the paraventricular nucleus, and these changes are hypothesized to contribute to diabetic hyperphagia"
Orexigenic means hunger generating. Anorectic is the opposite.
Diabetic rats on the ADA diet are RAVENOUS. Oops, sorry, gluttenous. Diabetic rats on a genuine high fat diet are not. They're not very diabetic either.
Now take that to humans. I don't think humans are particularly different to rats. Telling a human diabetic to eat a carbohydrate based diet will bump up their neuropeptide Y levels and will drop their corticotropic releasing hormone levels. They'll be ravenous. Bit of a cruel trick really.
But here's the really funny bit.
You then tell them they MUST lose weight. When they fail to lose weight, you underline the bit in their case notes where it says glutton/failed to comply.
Don't laugh too much, it's not funny really.
Peter
Thursday, March 13, 2008
Food; chicken salsa
Tonight was chicken salsa. Melt lots of butter in a heavy wok. OK, a frying pan will do. We had a mix of cheap chicken drumsticks and thighs. Fry the chicken a bit to get it started but don't try to cook it through. When it's brown on the surface scoop it out and stick it in a bowl. The salsa sauce got a bit improvised. We used a red pepper, two cloves of garlic and an onion, all finely chopped. Add as much cumin as you like. We like lots. Some cayenne pepper was needed as we are out of chillies. Salt and pepper too. Ingredients got fried for a few minutes before pouring in a can of tomatoes. Once it's back to boiling put the chicken back in, turn the heat down, put a lid on and simmer for 20 minutes so the chicken cooks through. And takes up the flavour.
You can eat it just like that, but we like to lift the chicken out once it's had its time and let it cool a bit. We turn up the heat to reduce the sauce until it's really thick and tasty. Pour it over the chicken. There should be enough butter in the sauce that eating it with a spoon is still the only way to finish it. Use a bowl, not a plate!
If you have any fresh coriander chop some leaves over it as you dish up. We're out. It was great without.
Peter
I think we're a bit low on carbs as there was no time for added veg. Might have chips later.
You can eat it just like that, but we like to lift the chicken out once it's had its time and let it cool a bit. We turn up the heat to reduce the sauce until it's really thick and tasty. Pour it over the chicken. There should be enough butter in the sauce that eating it with a spoon is still the only way to finish it. Use a bowl, not a plate!
If you have any fresh coriander chop some leaves over it as you dish up. We're out. It was great without.
Peter
I think we're a bit low on carbs as there was no time for added veg. Might have chips later.
Food; steak and kidney casserole
My wife has already sorted tomorrow night's supper as I'm working a late shift and neither of us will get time to cook on the day. I'd pulled two containers of steak and kidney mix from the freezer earlier. She put a can of tomatoes in a casserole, put in the meat and kidneys, followed by a couple of small chopped onions, a chopped orange pepper and a small parsnip. Salt, pepper and a bouquet garni. Splash of red wine of course. Oh and butter. Lean meat equals lots of butter, add whatever you feel like. If it seems a bit random that's because it's made up of pretty well what was left in the fridge....
Oh, bring it to the boil, simmer for a couple of hours then take the lid off to let it reduce down to a thick stew. Stir occasionally.
Looking forward to my portion when I get home at 10 tomorrow night. Smells great already.
Peter
PS a day at work usually means nothing but cream and chocolate through the day. Might get my eggs before I go if I'm organised... It always seems to me that these are pretty ordinary meals, just no huge amount of added carbs when served and usually no carbs for the rest of the day. That's just how it seems to work out most days.
Oh, bring it to the boil, simmer for a couple of hours then take the lid off to let it reduce down to a thick stew. Stir occasionally.
Looking forward to my portion when I get home at 10 tomorrow night. Smells great already.
Peter
PS a day at work usually means nothing but cream and chocolate through the day. Might get my eggs before I go if I'm organised... It always seems to me that these are pretty ordinary meals, just no huge amount of added carbs when served and usually no carbs for the rest of the day. That's just how it seems to work out most days.
Glucose as a cure for hypertriglyceridaemia?
This is a very interesting paper, cited in one of Bruce's comments. It's interesting enough that it really had me thinking, so here are the thoughts. Eating 80% carbs continuously through the day cranks up your triglycerides, but they only go up overnight when you stop eating the carbs. Inhibiting overnight lipolysis with either a B3 infusion or by maintaining insulin levels at 30-50microIU/ml, by drinking 60g of sugar solution every two hours (gulp), sorts the rise in trigs out. Sort of. No, it does sort it out.
This is a cracker.
We know that B3 and insulin both inhibit hormone senstitive lipase in adipose tissue, so they limit FFA delivery to the plasma and so to the liver. The presumption, in this fascinating 1973 paper, is that this is what drops the triglycerides. But is this what is happening? In addition to inhibiting hormone sensitive lipase does insulin have a roll in inhibiting VLDL secretion? Can't be bothered chasing this at the moment, but I'll bet it does. After all, failure of the liver to listen to insulin is "associated" with massive elevations of triglycerides in some unlucky people. Niacin acts through the beta hydroxy butyrate receptor. Does activation of this receptor do anything in the liver? Like drop tryglycerides maybe?
There's a bit about B3 and trigs here.
"A second mechanism has been postulated. The second mechanism by which it’s postulated that there’s a decrease in triglyceride synthesis involves a pathway of triglyceride synthesis in which the last step in triglyceride synthesis is catalyzed by an enzyme called DGAT2. It is postulated that niacin may also act through inhibiting DGAT2".
If we look at the dutch study, comparing a group of type 2 diabetics who were crossed over between 89% carbohydrate calories and 89% fat calories we see that there was essentially no difference in fasting free fatty acids, yet the fasting triglycerides in the high fat period were half those of the high carb period. Not only that but the ability of insulin to suppress free fatty acids during a clamp (elevate plasma insulin and then give a glucose infusion to maintain a constant non fatal blood glucose level) was markedly reduced in the high fat group, yet still trigs were low during this phase. See table 2.
The whole premise of the 1973 paper, that FFAs induce hypertriglyceridaemia looks wrong to me, or at least simplistic. Insulin and B3 (which is a pharmacological mimic of beta hydroxybutyrate) suppress VLDL production (fasting trigs) from the liver. Never mind what they do to FFAs.
That all night oral glucose drinking dropped the morning trigs at the cost of an all night combined hyperglycaemia and hyperinsulinaemia. This isn't treating a problem, this is correcting a lab number at the cost of glucose poisoning. Fatty liver anyone?
Aside: The type IV hyperlipoproteinaemia patients spent 24 hours with blood glucose levels between 130 and 150mg/dl in the study, and insulin levels at over 100microIU/ml for most of that 24 hour period. And their cardiovascular problems will get blamed on the triglycerides!!!!!!
Enthralling paper, but I don't think I'd take it as an endorsement of drinking 60g of glucose every 2h through the night to lower my "fasting" triglycerides. If I had elevated triglycerides, which I don't!
Peter
This is a cracker.
We know that B3 and insulin both inhibit hormone senstitive lipase in adipose tissue, so they limit FFA delivery to the plasma and so to the liver. The presumption, in this fascinating 1973 paper, is that this is what drops the triglycerides. But is this what is happening? In addition to inhibiting hormone sensitive lipase does insulin have a roll in inhibiting VLDL secretion? Can't be bothered chasing this at the moment, but I'll bet it does. After all, failure of the liver to listen to insulin is "associated" with massive elevations of triglycerides in some unlucky people. Niacin acts through the beta hydroxy butyrate receptor. Does activation of this receptor do anything in the liver? Like drop tryglycerides maybe?
There's a bit about B3 and trigs here.
"A second mechanism has been postulated. The second mechanism by which it’s postulated that there’s a decrease in triglyceride synthesis involves a pathway of triglyceride synthesis in which the last step in triglyceride synthesis is catalyzed by an enzyme called DGAT2. It is postulated that niacin may also act through inhibiting DGAT2".
If we look at the dutch study, comparing a group of type 2 diabetics who were crossed over between 89% carbohydrate calories and 89% fat calories we see that there was essentially no difference in fasting free fatty acids, yet the fasting triglycerides in the high fat period were half those of the high carb period. Not only that but the ability of insulin to suppress free fatty acids during a clamp (elevate plasma insulin and then give a glucose infusion to maintain a constant non fatal blood glucose level) was markedly reduced in the high fat group, yet still trigs were low during this phase. See table 2.
The whole premise of the 1973 paper, that FFAs induce hypertriglyceridaemia looks wrong to me, or at least simplistic. Insulin and B3 (which is a pharmacological mimic of beta hydroxybutyrate) suppress VLDL production (fasting trigs) from the liver. Never mind what they do to FFAs.
That all night oral glucose drinking dropped the morning trigs at the cost of an all night combined hyperglycaemia and hyperinsulinaemia. This isn't treating a problem, this is correcting a lab number at the cost of glucose poisoning. Fatty liver anyone?
Aside: The type IV hyperlipoproteinaemia patients spent 24 hours with blood glucose levels between 130 and 150mg/dl in the study, and insulin levels at over 100microIU/ml for most of that 24 hour period. And their cardiovascular problems will get blamed on the triglycerides!!!!!!
Enthralling paper, but I don't think I'd take it as an endorsement of drinking 60g of glucose every 2h through the night to lower my "fasting" triglycerides. If I had elevated triglycerides, which I don't!
Peter
Tuesday, March 11, 2008
Diabetes; endothelial damage
Just in case anyone thought that it was only your myocardial cells which die as a result of hyperglycaemia, those lining your aorta are queueing up at the same time.
The people doing this research are extremely clever. The molecular mechanism looks complex and finding a drug to block the effect is certainly going to need people who are very bright to do it.
Of course you could cop out and do the simple thing, which is to avoid the hyperglycaemia in the first place. Unless you're a Kitavan that looks like LC eating to me. Where ever you live, the secret appears to be to live within the limits of carbohydrate intake dictated by your ability to maintain normoglycaemia. Of course eating less carbs than this shouldn't be a problem. More just might be.
Once the endothelial cells are dead they will leave a cell sized open wound on the lining of the aorta. This will be repaired by the endothelial cells adjoining the wound dividing or by endothelial progenitor cells from the blood stream settling down on the wound (or both). These cells need energy and cholesterol to grow or divide. Sugar caused the problem in the first place so I vote energy from lipid. Any sensible system would be set up to provide lipid and cholesterol. Perhaps the surrounding cells should up regulate their LDL receptor numbers? Note especially that a loss of glycosoaminoglycans from the endothelial surface also markedly up regulates LDL particle internalisation. These endothelial cells are not taking in LDL cholesterol particles to kill themselves. Glucose does that.
Peter
The people doing this research are extremely clever. The molecular mechanism looks complex and finding a drug to block the effect is certainly going to need people who are very bright to do it.
Of course you could cop out and do the simple thing, which is to avoid the hyperglycaemia in the first place. Unless you're a Kitavan that looks like LC eating to me. Where ever you live, the secret appears to be to live within the limits of carbohydrate intake dictated by your ability to maintain normoglycaemia. Of course eating less carbs than this shouldn't be a problem. More just might be.
Once the endothelial cells are dead they will leave a cell sized open wound on the lining of the aorta. This will be repaired by the endothelial cells adjoining the wound dividing or by endothelial progenitor cells from the blood stream settling down on the wound (or both). These cells need energy and cholesterol to grow or divide. Sugar caused the problem in the first place so I vote energy from lipid. Any sensible system would be set up to provide lipid and cholesterol. Perhaps the surrounding cells should up regulate their LDL receptor numbers? Note especially that a loss of glycosoaminoglycans from the endothelial surface also markedly up regulates LDL particle internalisation. These endothelial cells are not taking in LDL cholesterol particles to kill themselves. Glucose does that.
Peter
Diabetes and cardiac apotosis
There is nothing wrong with eating carbohydrate per se. What is completely unacceptable is the development of hyperglycaemia. There may well be people who can live on a diet of yams and sweet potatoes without cardiovascular problems. I would suspect that the pre requisite is that insulin sensitivity must be such that they avoid hyperglycaemia. If they don't you end up back in to the realms of apoptosis, with your myocardial cells deciding they've had so much sugar they'd rather die than have more. They then vote with their "cytochrome c-activated caspase-3 pathway" (whatever that is: EDIT, okay I've read PSS now and have more of a clue!) and take this to its logical conclusion. Blood glucose levels of 22 mmol/l and 33 mmol/l are well within the reach of any diabetic taking the ADA dietary advice.
One of the best quotes I've ever heard was very second hand. It came from a poster on Dr Bernstein's forum who had tried to convert another type 2 diabetic to LC eating. The quote was from the LC refusenik:
"I'd rather die than eat bacon and eggs without hash browns"
So be it.
Peter
One of the best quotes I've ever heard was very second hand. It came from a poster on Dr Bernstein's forum who had tried to convert another type 2 diabetic to LC eating. The quote was from the LC refusenik:
"I'd rather die than eat bacon and eggs without hash browns"
So be it.
Peter
Food: Liver and bacon
This is what we usually do with liver. Melt lots of butter in a fryingpan (You choose how much!). Finely chop an onion or two. Turn the heat down low and allow the onion to cook slowly until it's just brown around the edges and tastes of sugar. Chop up a piece of streaky bacon per person and fry this in the middle of the onion, usually I've scraped the onion to the edges of the fryingpan at this stage. Pull the cooked bacon in to a heap with the onions at the edge of the pan and fry the liver in the space they leave. I like lamb's liver. Turn it about twice so its nicely browned on the outside. We like it cooked through so I then mix the whole lot together, cover with it over with the lid from the stockpot and let it cook on a very low heat for about another 5 minutes. Dish it up and eat. Pepper is nice somewhere along the way but for me there is enough salt in the bacon.
I don't really do sophisticated cooking!
Peter
I don't really do sophisticated cooking!
Peter
Awful offal
Your kidneys convert about 5% of your cardiac output in to primitive urine. That's a lot urine per minute. They do it day in, day out until there is no cardiac output left, hopefully >100 years down the road. Then they stop. This is hard work. Primitive urine cannot be peed down the loo. It is absolutely loaded with stuff you need to stay alive. Water for a start. And sodium. You go on a zero salt diet and your kidneys will go in to overdrive to keep you alive despite your attentiveness to the AHA. You pour glucose in to this filtrate. You waste magnesium, potassium, bicarbonate, loads of stuff you can't do without. Then you claw it all back again. Back comes the glucose, back comes the sodium, back comes the water. Your kidneys pump 180 litres of water alone back in to your bloodstream every 24 hours. All of this is done against a concentration gradient. This takes energy. Lots of it.
While you are snoozing, your muscles are snoozing too. Same for a cow. Your kidneys are continuously working their cotton socks off, 24/7. So they must have the metabolic tools to generate serious amounts of ATP. Eating muscle tissue is a massive improvement on eating a Marsbar. Eating kidneys is the next level up. Liver (with the tubes) is the most phenomenally active organ for biochemical transformation you can imagine. You want a precursor molecule for something? Look in the liver. Or an egg yolk.
Aside: It's that age old question. Why is there so much cholesterol in an egg yolk? Because that's how much it takes to make a healthy chick. Anon (unless you know better).
Anyway, you want folate? Try some liver. B12? There too. Quite a lot of cholesterol too.
What about lung tissue? Lungs are special. Oxygen is amongst the most damaging and corrosive molecules that we all depend on to stay alive. The environment in the lung is harsh for alveolar epithelial cells. So alveolar cells know all about antioxidant defences. Staying alive in the lungs needs energy. You want useful metabolic molecules? You won't get them by eating tofu! I love haggis but can't eat the barley or oats it's made with. Now, gluten free haggis maybe. Add mashed neaps with tons of butter and just enough mashed potatoes, also with tons of butter, to stay within my carb limit. And a wee dram if I'm willing to damage my joints for the pleasure. Anyway...
I won't mention brain as it's essentially unavailable in the UK. But guess where you find a number of interesting lipids in addition to cholesterol?
I could go on. I'll shut up now. I like offal.
Peter
While you are snoozing, your muscles are snoozing too. Same for a cow. Your kidneys are continuously working their cotton socks off, 24/7. So they must have the metabolic tools to generate serious amounts of ATP. Eating muscle tissue is a massive improvement on eating a Marsbar. Eating kidneys is the next level up. Liver (with the tubes) is the most phenomenally active organ for biochemical transformation you can imagine. You want a precursor molecule for something? Look in the liver. Or an egg yolk.
Aside: It's that age old question. Why is there so much cholesterol in an egg yolk? Because that's how much it takes to make a healthy chick. Anon (unless you know better).
Anyway, you want folate? Try some liver. B12? There too. Quite a lot of cholesterol too.
What about lung tissue? Lungs are special. Oxygen is amongst the most damaging and corrosive molecules that we all depend on to stay alive. The environment in the lung is harsh for alveolar epithelial cells. So alveolar cells know all about antioxidant defences. Staying alive in the lungs needs energy. You want useful metabolic molecules? You won't get them by eating tofu! I love haggis but can't eat the barley or oats it's made with. Now, gluten free haggis maybe. Add mashed neaps with tons of butter and just enough mashed potatoes, also with tons of butter, to stay within my carb limit. And a wee dram if I'm willing to damage my joints for the pleasure. Anyway...
I won't mention brain as it's essentially unavailable in the UK. But guess where you find a number of interesting lipids in addition to cholesterol?
I could go on. I'll shut up now. I like offal.
Peter
Monday, March 10, 2008
Brain on a statin
Apoptosis is an essential component of the maintenance process of our bodies. It is a highly controlled and organised technique for removing unwanted cells from any organ by the process of induced metabolic suicide.
Tinkering with this process is a potentially catastrophic game, that good old law of unintended consequences could have a field day here.
Statins promote apoptosis. They do it in diseased tissues, including cancer cells; hooray for Lipitor. Unfortunately they also do it in normal tissues too; boo for Lipitor.
Statins promote apoptosis in heart muscle. You just have to imagine what having heart muscle cells commit suicide does for your pumping ability. Most of the work on statins and myopathy focuses on coenzyme Q10 depletion. This looks to be an additional problem.
Statins promote apoptosis in the vascular epithelium. Again you just have to wonder what the death of vascular lining cells does for your circulation. Brings to mind those folks in Japan who were highly susceptible to simvastatin. This is the effect on mortality from cardiac causes when you really respond to a statin.
Statins also promote apoptosis in brain cells, or at least do so in a lab prep designed to mimic brain cells. This is your brain on a statin. Last sentence of the paper:
"These findings could contribute to elucidate the molecular mechanisms by which statins induce growth suppression and/or apoptosis in neuronal cells, and may also help to explain the CNS side effects associated with statin therapy."
Just going back to that J-Litt paper, the death rate from accidents/suicides were increased just under three fold in the TC <160mg/dl group. Seems like low cholesterol causes you to throw punches at a well armed wide boy in a down town bar.
However all is not doom and gloom. Here is your brain on chocolate!
OK, that's a complete cheat. I've absolutely no idea how much of the stearic acid in the topping of a dessert cheesecake ever gets remotely near a human brain neurone in real life. Much less activate PPAR gamma there. But I'd prefer (real) chocolate to a statin any day if I was looking to avoid Alzheimer's (or anything else for that matter).
Peter
Tinkering with this process is a potentially catastrophic game, that good old law of unintended consequences could have a field day here.
Statins promote apoptosis. They do it in diseased tissues, including cancer cells; hooray for Lipitor. Unfortunately they also do it in normal tissues too; boo for Lipitor.
Statins promote apoptosis in heart muscle. You just have to imagine what having heart muscle cells commit suicide does for your pumping ability. Most of the work on statins and myopathy focuses on coenzyme Q10 depletion. This looks to be an additional problem.
Statins promote apoptosis in the vascular epithelium. Again you just have to wonder what the death of vascular lining cells does for your circulation. Brings to mind those folks in Japan who were highly susceptible to simvastatin. This is the effect on mortality from cardiac causes when you really respond to a statin.
Statins also promote apoptosis in brain cells, or at least do so in a lab prep designed to mimic brain cells. This is your brain on a statin. Last sentence of the paper:
"These findings could contribute to elucidate the molecular mechanisms by which statins induce growth suppression and/or apoptosis in neuronal cells, and may also help to explain the CNS side effects associated with statin therapy."
Just going back to that J-Litt paper, the death rate from accidents/suicides were increased just under three fold in the TC <160mg/dl group. Seems like low cholesterol causes you to throw punches at a well armed wide boy in a down town bar.
However all is not doom and gloom. Here is your brain on chocolate!
OK, that's a complete cheat. I've absolutely no idea how much of the stearic acid in the topping of a dessert cheesecake ever gets remotely near a human brain neurone in real life. Much less activate PPAR gamma there. But I'd prefer (real) chocolate to a statin any day if I was looking to avoid Alzheimer's (or anything else for that matter).
Peter
Food; Mutton or lamb in orange sauce
This is the plan for the left over mutton tonight:
Spicy Orange Lamb adapted from Ken Hom.
You can use fresh lamb, briefly stir fried, if you have it to hand. I've got cold mutton!
Melt lots of butter in a wok. Throw in as much garlic as you like (say four cloves, finely sliced), about a cubic inch of fresh root ginger, peeled and finely chopped and the thinly peeled rind of an orange (no pith), also finely chopped. And some pepper, plenty of salt will come from the soy sauce.
After a few seconds of stir frying throw in the cubed lamb/mutton and cook until the fat is soft. Add two tablespoons of fresh orange juice from the orange that provided the peel and as much soy sauce (gluten free, we use Tamari) as you feel is safe on an excitotoxin basis. I have been known to throw in a little cooking sherry or white wine. Cook it a bit longer, maybe 5 mins. Add a little sesame oil just before serving.
It will probably go with chips tonight, might use sweet potatoes, but any other carb source would do. You know how you need something to soak up the butter sauce...
Spicy Orange Lamb adapted from Ken Hom.
You can use fresh lamb, briefly stir fried, if you have it to hand. I've got cold mutton!
Melt lots of butter in a wok. Throw in as much garlic as you like (say four cloves, finely sliced), about a cubic inch of fresh root ginger, peeled and finely chopped and the thinly peeled rind of an orange (no pith), also finely chopped. And some pepper, plenty of salt will come from the soy sauce.
After a few seconds of stir frying throw in the cubed lamb/mutton and cook until the fat is soft. Add two tablespoons of fresh orange juice from the orange that provided the peel and as much soy sauce (gluten free, we use Tamari) as you feel is safe on an excitotoxin basis. I have been known to throw in a little cooking sherry or white wine. Cook it a bit longer, maybe 5 mins. Add a little sesame oil just before serving.
It will probably go with chips tonight, might use sweet potatoes, but any other carb source would do. You know how you need something to soak up the butter sauce...
Ah well, another night without raw cabbage.
Peter
Peter
Food; Mutton followed by cheesecake
Last weekend we happened on the Farmer's Market in Newbury, completely by chance. Some serious meat and free bones. Happy!
Yesterday's supper, a 1.3kg breast of mutton. I just stuck it in the Chicken Brick with two small potatoes and two small parsnips (chopped and posted in to the space around the meat). I added some beef dripping to get the veggies started before enough fat melted out of the mutton to start them roasting properly. Sprinkled salt over the lot. Stuck the whole thing in to a fan assisted oven at 150 deg C for 2 and a quarter hours. It was good. The junkfood was the cauliflower we ate with it.
The Chicken Brick.
For afters we had cheesecake. The cake base was 200g nuts chopped in a blender, solidified with 50g butter and sweetened with 25g honey. Junk food; a layer of blueberries. Cheese part was a 50:50 mix of Mascarpone and creme fraiche, a capful of vanilla and 25g honey. Topping was a 100g bar of 70% cocoa chocolate melted. Boil 100ml of cream, mix with the chocolate and throw in 25g butter. Stir until even, allow to cool slightly and pour on while still liquid enough to be self leveling. Stick it in the fridge and wait while the mutton digests enough to leave some room, then eat.
It's quite nice. You can always adjust sweetness to taste/carb limits. I didn't count anything with this!
Peter
Yesterday's supper, a 1.3kg breast of mutton. I just stuck it in the Chicken Brick with two small potatoes and two small parsnips (chopped and posted in to the space around the meat). I added some beef dripping to get the veggies started before enough fat melted out of the mutton to start them roasting properly. Sprinkled salt over the lot. Stuck the whole thing in to a fan assisted oven at 150 deg C for 2 and a quarter hours. It was good. The junkfood was the cauliflower we ate with it.
The Chicken Brick.
For afters we had cheesecake. The cake base was 200g nuts chopped in a blender, solidified with 50g butter and sweetened with 25g honey. Junk food; a layer of blueberries. Cheese part was a 50:50 mix of Mascarpone and creme fraiche, a capful of vanilla and 25g honey. Topping was a 100g bar of 70% cocoa chocolate melted. Boil 100ml of cream, mix with the chocolate and throw in 25g butter. Stir until even, allow to cool slightly and pour on while still liquid enough to be self leveling. Stick it in the fridge and wait while the mutton digests enough to leave some room, then eat.
It's quite nice. You can always adjust sweetness to taste/carb limits. I didn't count anything with this!
Peter
Saturday, March 08, 2008
Gluten and rheumatoid arthritis
The quote below comes from Dr Freed, written in an editorial for the British Medical Journal, to commemorate the public sacrifice of Dr Arpad Pusztai on the altar of GM agribusiness (see the last line of the editorial). Dr Freed:
"Lectins stimulate class II HLA antigens on cells that do not normally display them"
Wheat germ agglutinin is a lectin and sections of gliadin (in gluten) are "lectin like". If you have an auto immune disease the quote is quite important. What is a class II HLA antigen?
If you really really want to know you can have a look here, which explains what MHC class I and class II molecules are. It's the simplified version, including the sausage in a hot dog metaphor which made my wife laugh. Sort of. EDIT: You probably need to know she's an immunologist to understand that last comment.
Here's a rough translation.
Class II molecules sit on the surface of cells, holding out a fragment of foreign protein (in this case a short fragment of gluten). Only certain sub families of immune cells should do this, certainly it should never be done by tissue cells of organs like the pancreas or thyroid as cited by Freed. I would add joint cells in the case of rheumatoid arthritis.
Class II expression is different from MIC expression but just as bad, if not worse.
Waving around a class II molecule on your cell surface is a direct invitation to a subset of white blood cells (in particular a sub group of lymphocytes, ie those with a certain molecule called the CD4 molecule on their surface) to come and interact with the cell displaying the Class II marker. CD4 molecules generally "talk to" class II molecules.
The class II marker molecule has to be holding out a gluten fragment and the CD4+ cell has to be able to recognise that fragment for them to interact. Given this situation, things happen. The CD4 positive cell does several things, one of which is that it starts producing lymphokines. That is it causes inflammation. Note that antibody production is not needed for this to occur.
Of course once the CD4+ cell has seen gluten it may well trot off to get antibodies produced. Or it may not. The immune system is frighteningly complex. If the CD4+ cell does interact with an antibody producing lymphocyte you get this.
Avoiding gluten helps. Forget the vegan bit, it's a failure to control variables in the study and not remotely needed. The gluten avoidance is essential.
LC is very helpful too. I'll post the refs some time but basic premise is that the inflammatory soup production in response to class II/CD4 interaction is controlled to a large extent by NF kappa B, which is controlled by insulin which is controlled by carbohydrate in the diet. Insulin per se is anti inflammatory, chronic hyperinsulinaemia is pro inflammatory.
There are also non specific effects of PUFA in propagating the free radicals generated by the inflammatory response. Suet and dripping contain far more stable fats than vegetable oil does and these highly saturated fatty acids are almost immune to free radical attack in an inflammatory soup.
Vitamin D modulates the irritablity of most cells in the immune system so supplementation or serious sun bathing, without sun burn, probably has an effect to diminish all auto immune problems.
If you read the whole vegan paper you will see there was no radiographic improvement, though patients felt better. Too much carbohyrate, too many PUFA and there are several other plant sources of lectins beyond gluten. Anecdotally nightshade lectins (also mentioned by Freed) can be a potent trigger for rheumatoid arthritis in much the same way as gluten.
That's without going on to Ebringer's work on bacterial proteins and rheumatoid disease....
This aspect is probably also amenable to LC eating. Anyone with a degree of insulin resistance may well be transiently glucosuric on occasions while eating a normal diet. Bacteria love glucose. LC eating should starve any Proteus in the urinary tract because it stops any glycosuria. Proteus also lives in our gut and starving it here too, this time by fiber avoidance, would probably help.
So there are a few factors involved in rheumatoid arthritis. A serious LC, high saturated fat and minimal lectin diet should help.
As would an all over tan.
Peter
"Lectins stimulate class II HLA antigens on cells that do not normally display them"
Wheat germ agglutinin is a lectin and sections of gliadin (in gluten) are "lectin like". If you have an auto immune disease the quote is quite important. What is a class II HLA antigen?
If you really really want to know you can have a look here, which explains what MHC class I and class II molecules are. It's the simplified version, including the sausage in a hot dog metaphor which made my wife laugh. Sort of. EDIT: You probably need to know she's an immunologist to understand that last comment.
Here's a rough translation.
Class II molecules sit on the surface of cells, holding out a fragment of foreign protein (in this case a short fragment of gluten). Only certain sub families of immune cells should do this, certainly it should never be done by tissue cells of organs like the pancreas or thyroid as cited by Freed. I would add joint cells in the case of rheumatoid arthritis.
Class II expression is different from MIC expression but just as bad, if not worse.
Waving around a class II molecule on your cell surface is a direct invitation to a subset of white blood cells (in particular a sub group of lymphocytes, ie those with a certain molecule called the CD4 molecule on their surface) to come and interact with the cell displaying the Class II marker. CD4 molecules generally "talk to" class II molecules.
The class II marker molecule has to be holding out a gluten fragment and the CD4+ cell has to be able to recognise that fragment for them to interact. Given this situation, things happen. The CD4 positive cell does several things, one of which is that it starts producing lymphokines. That is it causes inflammation. Note that antibody production is not needed for this to occur.
Of course once the CD4+ cell has seen gluten it may well trot off to get antibodies produced. Or it may not. The immune system is frighteningly complex. If the CD4+ cell does interact with an antibody producing lymphocyte you get this.
Avoiding gluten helps. Forget the vegan bit, it's a failure to control variables in the study and not remotely needed. The gluten avoidance is essential.
LC is very helpful too. I'll post the refs some time but basic premise is that the inflammatory soup production in response to class II/CD4 interaction is controlled to a large extent by NF kappa B, which is controlled by insulin which is controlled by carbohydrate in the diet. Insulin per se is anti inflammatory, chronic hyperinsulinaemia is pro inflammatory.
There are also non specific effects of PUFA in propagating the free radicals generated by the inflammatory response. Suet and dripping contain far more stable fats than vegetable oil does and these highly saturated fatty acids are almost immune to free radical attack in an inflammatory soup.
Vitamin D modulates the irritablity of most cells in the immune system so supplementation or serious sun bathing, without sun burn, probably has an effect to diminish all auto immune problems.
If you read the whole vegan paper you will see there was no radiographic improvement, though patients felt better. Too much carbohyrate, too many PUFA and there are several other plant sources of lectins beyond gluten. Anecdotally nightshade lectins (also mentioned by Freed) can be a potent trigger for rheumatoid arthritis in much the same way as gluten.
That's without going on to Ebringer's work on bacterial proteins and rheumatoid disease....
This aspect is probably also amenable to LC eating. Anyone with a degree of insulin resistance may well be transiently glucosuric on occasions while eating a normal diet. Bacteria love glucose. LC eating should starve any Proteus in the urinary tract because it stops any glycosuria. Proteus also lives in our gut and starving it here too, this time by fiber avoidance, would probably help.
So there are a few factors involved in rheumatoid arthritis. A serious LC, high saturated fat and minimal lectin diet should help.
As would an all over tan.
Peter
Wednesday, March 05, 2008
Familial Hypercholesterolaemia and porcelain
What IS an LDL particle? There is a very neat picture here. Perhaps the most striking thing about it is that there is only one single protein molecule embedded in the particle surface, the apo-B100 protein molecule. It wraps neatly around the sphere of lipid to give support and identity. Identity is very important.
Of course the LDL particle has to come from somewhere. It is derived from IDL (Intermediate Density Lipoprotein) and before that from VLDL (Very Low Density Lipoprotein), which was secreted by the liver. All of these precursors also have the apo-B100 protein molecule, plus a whole load of other proteins too, apo-C1, apo-C2, apo-C3, and apo E. VLDLs are big (relatively), they need to be to fit all those proteins on to their surface! Most of these proteins are there to either turn on or turn of lipoprotein lipase, in order to get fatty acids from the lipid particle in to cells. That's how lipids get bulk transported. Apo-E gets the particle back in to the liver, should the liver want it back.
Quite where all of these proteins disappear to as LDL is formed is a bit of a mystery to me. Certainly it looks like LDL, derived from IDL/VLDL, has only apo-B100 and none of the other surface proteins of VLDL/IDL particles. Probably they hop on to HDL particles. Some of them came from there in the first place, rather than the liver directly, so that would be appropriate.
So there is this bag of lipid with just one identification tag on its surface, looking for a home. There is a receptor which exactly fits the apo-B100 id tag. The LDL cholesterol receptor. This is the archetypal, best studied endocytosis receptor of all time. LDL attaches to this receptor and the whole lipoprotein is engulfed by the cell sporting the receptor. The particle gets stripped of the engulfing apparatus, eventually fused with a lysosome and the cell is in clover with a supply of both lipid and cholesterol. It recycles the LDL receptor to the cell surface and does it all again. Cells appear to need both lipid and cholesterol.
But here's the interesting bit. The LDL receptor is a statin as in:
"Consistent with this hypothesis, they found that addition of LDL to the culture medium of normal human fibroblasts inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme in the cholesterol biosynthetic pathway
EDIT: When you go to the original authors it becomes obvious that it is the cholesterol itself which inhibits HMG-CoA, a classic negative feed back mechanism. Have to do some more thinking about xanthomata. End edit.
The LDL receptor inhibits the intracellular synthesis of cholesterol, at the HMG-CoA step, when activated by an LDL particle. There is impeccable logic to this. Cholesterol is a complex molecule, synthesised in a stupendously intricate and energy demanding process. Usually the liver does this for cells of the body, shipping it out in lipoprotein particles. After all the liver is a biosynthetic powerhouse with lots of energy to play with. It's not some poor smooth muscle cell or fibroblast struggling to make metabolic ends meet in the arterial media. If, as a cell, you have just swallowed a big ball of cholesterol you can afford to switch off the production apparatus. It would be wasteful not to.
Cells need cholesterol. Homozygous familial hypercholesterolaemia means that a patient's cells have zero functional LDL receptors. If they can't get cholesterol by swallowing whole LDL particles they really do have to make it themselves. But the other feature of a non functional LDL receptor (remember, it's a statin) is that it doesn't give the ability to limit local cholesterol synthesis, so there might be quite a lot of cholesterol made. Enough to generate tendon xanthomas. These xanthomas should be composed of cholesterol synthesised from acetate in local cells, not from sticky LDL particles. I don't suppose anyone has checked this.
The synthesis of one molecule of cholesterol requires 14 NADPH molecules and 18 ATPs. It yields 6 phosphate (Pi) molecules and 4 pyrophosphate (PPi) molecules. While PPi appears to be an inhibitor of soft tissue calcification Pi is a promoter. Alkaline phosphatase, an enzyme whose production is upregulated by hyperglycaemia, converts PPi (calcification inhibitor) to Pi (calcification promoter). Hyperglycaemia is a feature of refined carbohydrate diets. Did I say low fat?
So there is the potential for an awful lot of inorganic phosphate ions, possibly 14 per molecule, being produced as a spin off from cholesterol synthesis on low fat diets. One LDL particle provides about 2000 molecules of cholesterol.
We know that insulin converts smooth muscle cells to bone secreting cells. Local cholesterol synthesis provides a supply of inorganic phosphate. A low fat (high sugar) diet raises insulin.
Perhaps it should come as no surprise that there is the phenomenon of "porcelain aorta", seen in patients with homozygous familial hyprecholesterolaemia. Aortic cells manufacturing cholesterol, which they can't get from LDL, produce inorganic phosphate and pyrophosphate as a spin off from the synthesis. A modern low fat diet, based on sugar, elevates blood glucose which increases alkaline phosphatase production and so the conversion of pyrophosphate to inorganic phosphate. A modern low fat diet elevates insulin too, which makes smooth muscle cells secrete bone matrix proteins.
Add calcium to phosphate in soft tissues and you have bone.
How good is the evidence base for current dietary recommendations in Familial Hypercholesterolaemia, particularly in children, who don't seem to get put on a pharmaceutical statin (yet)?
The Cochrane Review seems to think they are completely unsubstantiated.
Should all homozygous FH people be on a pharmaceutical statin? Another post there.
Peter
NB I didn't see any calcium or phosphate in that picture of the LDL particle. Soddy: "Rutherford, this is transmutation!" Rutherford snapped back, "For Christ's sake, Soddy, don't call it transmutation. They'll have our heads off as alchemists." Or cardiologists.
Of course the LDL particle has to come from somewhere. It is derived from IDL (Intermediate Density Lipoprotein) and before that from VLDL (Very Low Density Lipoprotein), which was secreted by the liver. All of these precursors also have the apo-B100 protein molecule, plus a whole load of other proteins too, apo-C1, apo-C2, apo-C3, and apo E. VLDLs are big (relatively), they need to be to fit all those proteins on to their surface! Most of these proteins are there to either turn on or turn of lipoprotein lipase, in order to get fatty acids from the lipid particle in to cells. That's how lipids get bulk transported. Apo-E gets the particle back in to the liver, should the liver want it back.
Quite where all of these proteins disappear to as LDL is formed is a bit of a mystery to me. Certainly it looks like LDL, derived from IDL/VLDL, has only apo-B100 and none of the other surface proteins of VLDL/IDL particles. Probably they hop on to HDL particles. Some of them came from there in the first place, rather than the liver directly, so that would be appropriate.
So there is this bag of lipid with just one identification tag on its surface, looking for a home. There is a receptor which exactly fits the apo-B100 id tag. The LDL cholesterol receptor. This is the archetypal, best studied endocytosis receptor of all time. LDL attaches to this receptor and the whole lipoprotein is engulfed by the cell sporting the receptor. The particle gets stripped of the engulfing apparatus, eventually fused with a lysosome and the cell is in clover with a supply of both lipid and cholesterol. It recycles the LDL receptor to the cell surface and does it all again. Cells appear to need both lipid and cholesterol.
But here's the interesting bit. The LDL receptor is a statin as in:
"Consistent with this hypothesis, they found that addition of LDL to the culture medium of normal human fibroblasts inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme in the cholesterol biosynthetic pathway
EDIT: When you go to the original authors it becomes obvious that it is the cholesterol itself which inhibits HMG-CoA, a classic negative feed back mechanism. Have to do some more thinking about xanthomata. End edit.
The LDL receptor inhibits the intracellular synthesis of cholesterol, at the HMG-CoA step, when activated by an LDL particle. There is impeccable logic to this. Cholesterol is a complex molecule, synthesised in a stupendously intricate and energy demanding process. Usually the liver does this for cells of the body, shipping it out in lipoprotein particles. After all the liver is a biosynthetic powerhouse with lots of energy to play with. It's not some poor smooth muscle cell or fibroblast struggling to make metabolic ends meet in the arterial media. If, as a cell, you have just swallowed a big ball of cholesterol you can afford to switch off the production apparatus. It would be wasteful not to.
Cells need cholesterol. Homozygous familial hypercholesterolaemia means that a patient's cells have zero functional LDL receptors. If they can't get cholesterol by swallowing whole LDL particles they really do have to make it themselves. But the other feature of a non functional LDL receptor (remember, it's a statin) is that it doesn't give the ability to limit local cholesterol synthesis, so there might be quite a lot of cholesterol made. Enough to generate tendon xanthomas. These xanthomas should be composed of cholesterol synthesised from acetate in local cells, not from sticky LDL particles. I don't suppose anyone has checked this.
The synthesis of one molecule of cholesterol requires 14 NADPH molecules and 18 ATPs. It yields 6 phosphate (Pi) molecules and 4 pyrophosphate (PPi) molecules. While PPi appears to be an inhibitor of soft tissue calcification Pi is a promoter. Alkaline phosphatase, an enzyme whose production is upregulated by hyperglycaemia, converts PPi (calcification inhibitor) to Pi (calcification promoter). Hyperglycaemia is a feature of refined carbohydrate diets. Did I say low fat?
So there is the potential for an awful lot of inorganic phosphate ions, possibly 14 per molecule, being produced as a spin off from cholesterol synthesis on low fat diets. One LDL particle provides about 2000 molecules of cholesterol.
We know that insulin converts smooth muscle cells to bone secreting cells. Local cholesterol synthesis provides a supply of inorganic phosphate. A low fat (high sugar) diet raises insulin.
Perhaps it should come as no surprise that there is the phenomenon of "porcelain aorta", seen in patients with homozygous familial hyprecholesterolaemia. Aortic cells manufacturing cholesterol, which they can't get from LDL, produce inorganic phosphate and pyrophosphate as a spin off from the synthesis. A modern low fat diet, based on sugar, elevates blood glucose which increases alkaline phosphatase production and so the conversion of pyrophosphate to inorganic phosphate. A modern low fat diet elevates insulin too, which makes smooth muscle cells secrete bone matrix proteins.
Add calcium to phosphate in soft tissues and you have bone.
How good is the evidence base for current dietary recommendations in Familial Hypercholesterolaemia, particularly in children, who don't seem to get put on a pharmaceutical statin (yet)?
The Cochrane Review seems to think they are completely unsubstantiated.
Should all homozygous FH people be on a pharmaceutical statin? Another post there.
Peter
NB I didn't see any calcium or phosphate in that picture of the LDL particle. Soddy: "Rutherford, this is transmutation!" Rutherford snapped back, "For Christ's sake, Soddy, don't call it transmutation. They'll have our heads off as alchemists." Or cardiologists.
Thursday, February 28, 2008
Cholesterol (the HDL sort) kills?
This article was picked up by GinnyL, a prolific reader of diabetes news and a poster on Dr Bernstein's site. There are no links to anywhere from the article, so I pubmeded the guy who got a mention by name, Dr Genest, for 2008, and came up with this ref, which I can get at the full text of.
BTW there are some interesting papers of FH he's published, maybe another day.
There's a lot of waffle but you do get the fact he is talking about EPIC-Norfolk and IDEAL. This appears to be a reasonable summary of their findings:
The more HDL particles you have the better, the less cholesterol in the particles the better. ie you want to have a high HDL-C particle count with not too much cholesterol in each particle.
Your lab work merely picks out any HDL it can find, measures the total cholesterol in this fraction and gives you that number. Compare this to the accepted wisdom re LDL-C, typically from Dr Davis:
Your lab work just picks out the LDL, measures the cholesterol and guesses (sorry, calculates) an approximate number. Actually that's completely wrong. The lab measures the TC, subtracts a few numbers, adds VAT, subtracts the first number you thought of and that's the best guess of your LDL-C concentration. Maybe.
Anyway, if your really do measure particle sizes/numbers, the fewer LDL particles you have better, the more cholesterol in each particle the better.
Are you seeing a pattern here? It all comes down to particle numbers, sizes, contents. What controls all of these? Not statin deficiencies, as in IDEAL.
Forget your cholesterol. What marker predicts heart attacks and total mortality without all of the paradoxes?
Follow EPIC and HbA1c (yes, same that same EPIC study as this one) to get some sort of clue. Control what you are doing wrong diet/lifestyle-wise to glycosylate your haemoglobin and your liver will sort out whatever cholesterol particles sizes/numbers it needs for health.
The EPIC/IDEAL paper is quite amusing for the shock horror throughout the discussion that high HDL could be killing people via heart attacks, but you get used this sort of rhetoric from cardiologists. It sort of gets summed up by Dr Genest's comments about torcetrapib:
"The second such compound, torcetrapib, proved toxic despite causing a large increase in HDL-C levels and was withdrawn from clinical use"
No, Dr Genest, think again. Perhaps it's not "despite", perhaps it's "because". Perhaps it is the artificial packing of cholesterol in to HDL particles which was toxic, not the drug per se. Treating a lab number is all torcetrapib did, it's for idiots. Sort out your diet so as to live within the limits of your own personal level of insulin resistance and leave your lipids alone. On Kitava and for the fishing Bantu this can involve 70% of calories from carbohydrate producing an HDL <1.0mmol/l with excellent cardiovascular health. For an insulin resistant Norfolk diabetic it might mean 5% of calories from carbs and the rest from saturated fat giving an HDL of 2.0mmol/l.
It's not the labels on the lipids that do the damage.
Peter
PS Also from Dr Genest
"Mutations that impair the function of cholesteryl ester transfer protein (CETP) are associated with marked elevations in HDL-C levels but not necessarily with protection against coronary heart disease (8)"
Ref (8) does not quite say that the mutation (the one which torectrapib mimicked) was neutral, it said it was bad. Naughty mis-citation. He must be a cardiologist. And people are surprised at torcetrapib killing people, using heart attacks? Torcetrapib was a success, it did exactly what it should do! The Zhong et al paper was published in 1996. It was the basis for the development of torcetrapib. You can't say Pfizer didn't know what they were doing. You can't understand why they did it either.
BTW there are some interesting papers of FH he's published, maybe another day.
There's a lot of waffle but you do get the fact he is talking about EPIC-Norfolk and IDEAL. This appears to be a reasonable summary of their findings:
The more HDL particles you have the better, the less cholesterol in the particles the better. ie you want to have a high HDL-C particle count with not too much cholesterol in each particle.
Your lab work merely picks out any HDL it can find, measures the total cholesterol in this fraction and gives you that number. Compare this to the accepted wisdom re LDL-C, typically from Dr Davis:
Your lab work just picks out the LDL, measures the cholesterol and guesses (sorry, calculates) an approximate number. Actually that's completely wrong. The lab measures the TC, subtracts a few numbers, adds VAT, subtracts the first number you thought of and that's the best guess of your LDL-C concentration. Maybe.
Anyway, if your really do measure particle sizes/numbers, the fewer LDL particles you have better, the more cholesterol in each particle the better.
Are you seeing a pattern here? It all comes down to particle numbers, sizes, contents. What controls all of these? Not statin deficiencies, as in IDEAL.
Forget your cholesterol. What marker predicts heart attacks and total mortality without all of the paradoxes?
Follow EPIC and HbA1c (yes, same that same EPIC study as this one) to get some sort of clue. Control what you are doing wrong diet/lifestyle-wise to glycosylate your haemoglobin and your liver will sort out whatever cholesterol particles sizes/numbers it needs for health.
The EPIC/IDEAL paper is quite amusing for the shock horror throughout the discussion that high HDL could be killing people via heart attacks, but you get used this sort of rhetoric from cardiologists. It sort of gets summed up by Dr Genest's comments about torcetrapib:
"The second such compound, torcetrapib, proved toxic despite causing a large increase in HDL-C levels and was withdrawn from clinical use"
No, Dr Genest, think again. Perhaps it's not "despite", perhaps it's "because". Perhaps it is the artificial packing of cholesterol in to HDL particles which was toxic, not the drug per se. Treating a lab number is all torcetrapib did, it's for idiots. Sort out your diet so as to live within the limits of your own personal level of insulin resistance and leave your lipids alone. On Kitava and for the fishing Bantu this can involve 70% of calories from carbohydrate producing an HDL <1.0mmol/l with excellent cardiovascular health. For an insulin resistant Norfolk diabetic it might mean 5% of calories from carbs and the rest from saturated fat giving an HDL of 2.0mmol/l.
It's not the labels on the lipids that do the damage.
Peter
PS Also from Dr Genest
"Mutations that impair the function of cholesteryl ester transfer protein (CETP) are associated with marked elevations in HDL-C levels but not necessarily with protection against coronary heart disease (8)"
Ref (8) does not quite say that the mutation (the one which torectrapib mimicked) was neutral, it said it was bad. Naughty mis-citation. He must be a cardiologist. And people are surprised at torcetrapib killing people, using heart attacks? Torcetrapib was a success, it did exactly what it should do! The Zhong et al paper was published in 1996. It was the basis for the development of torcetrapib. You can't say Pfizer didn't know what they were doing. You can't understand why they did it either.
Wednesday, February 27, 2008
Gluten and NK cells (forget the antibodies)
I just thought I'd stick this down as it's minor and it will get forgotten if I don't say something. There are grades/types of inflammatory bowel disease. The really easy one to treat is coeliac disease, where gluten avoidance is all that is required. There are also a host of problems which are responsive to gluten avoidance which do not come up positive on antibody test or have "typical" coeliac gut biopsy results.
I stumbled across this paper which grabbed me because my wife works with Natural Killer (NK) cells and has pointed out their relevance to surviving diseases before antibodies kick in. I was lucky to get the full text.
This is from the introduction, before it discusses coeliac disease, which is the second disease it covers (rheumatoid arthritis is the first):
"MIC A/B are stress-induced molecules acting as danger signals to alert NK cells and CD8 T lymphocytes through engagement of the NKG2D activating receptor [2]. At variance with classical MHC class I molecules, MIC are specialized for reporting stress without the requirement for peptide (or other ligand) binding and can direct NK and T cells to kill transformed or infected cells."
This translates as:
Gluten stresses your gut cells. They scream on the molecular level. NK cells cells get in there and put them out of their misery. This is (auto) immunity. It does NOT REQUIRE antibody production.
Background
Antibody production appears to be an add on to the immune system, a memory storage facility for preventing future re infection with a previous encountered bug. The acute survival of an infection, like influenza, relies on the innate immune system, based around NK cells. If you had to wait 10 days for your lymphocytes to get around to antibody production before you recovered, all viruses would be lethal. NK cells are non specific and use molecules like MIC as markers that something is seriously wrong with a cell and it's time to get killin'. MIC is a like a large target sign painted on a cell and NK cells are equipped an AK47 looking for that target. Usually a cell expressing MIC is infected, but gluten appears to do as much "stressing" as a viral infection.
Relevance:
Gluten reactions do not need antibody production. It is perfectly possible to have serious on going gut damage without a positive antibody test. Statistically it is quite probable that you WILL get a positve antibody test. There is so much damage going in that battlefield which is your gut under the influence of gluten that there is a trauma "soup". All you need is for an "antigen presenting cell" (APC) to collect some gluten from this soup, give it to your lymphocytes and tell them "we want this stuff recognised by an antibody, get producing". Of course the APC may pick up tissue transaminase, endomysial protein or any of a host of other proteins to push at the lymphocytes (which make the antibodies). But there is a chance you may not get either gluten or transaminase etc presented (ie no antibodies in our current lab tests), so you continue with "psychosomatic" gut problems or get labeled as inflammatory bowel disease, which is not regarded as gluten responsive. Severe IBD requires more than gluten avoidance but this basic step is probably essential.
Antibodies are a consequence, and an amplifier, of gluten toxicity, not a cause. That's intrinsic to gluten, MIC and NK cells. What brought this on?
Speculation time.
Did I have psoriasis or Dermatitis Herpetiformis (essentially coeliac disease of the skin)?
Answer: Maybe it's the same parallel as gut problems. WGA certainly gets in to the systemic circulation. I think it's a reasonable assumption gluten does too. It will be landing on vascular and/or dermal cells in the skin. Gluten induced stress here results in MIC expression. NK cells have that AK47, an itchy trigger finger and are seriously looking for MIC. Sometimes there is antibody production, sometimes there isn't. This could easily be the result of receptor subtypes (genetic) on your antigen presenting cells. Different labels, different lab results (if it ever gets that far) but a similar approach is needed. Perhaps there are a host of immune mediated problems triggered by gluten that are not antibody producing.
Peter
I stumbled across this paper which grabbed me because my wife works with Natural Killer (NK) cells and has pointed out their relevance to surviving diseases before antibodies kick in. I was lucky to get the full text.
This is from the introduction, before it discusses coeliac disease, which is the second disease it covers (rheumatoid arthritis is the first):
"MIC A/B are stress-induced molecules acting as danger signals to alert NK cells and CD8 T lymphocytes through engagement of the NKG2D activating receptor [2]. At variance with classical MHC class I molecules, MIC are specialized for reporting stress without the requirement for peptide (or other ligand) binding and can direct NK and T cells to kill transformed or infected cells."
This translates as:
Gluten stresses your gut cells. They scream on the molecular level. NK cells cells get in there and put them out of their misery. This is (auto) immunity. It does NOT REQUIRE antibody production.
Background
Antibody production appears to be an add on to the immune system, a memory storage facility for preventing future re infection with a previous encountered bug. The acute survival of an infection, like influenza, relies on the innate immune system, based around NK cells. If you had to wait 10 days for your lymphocytes to get around to antibody production before you recovered, all viruses would be lethal. NK cells are non specific and use molecules like MIC as markers that something is seriously wrong with a cell and it's time to get killin'. MIC is a like a large target sign painted on a cell and NK cells are equipped an AK47 looking for that target. Usually a cell expressing MIC is infected, but gluten appears to do as much "stressing" as a viral infection.
Relevance:
Gluten reactions do not need antibody production. It is perfectly possible to have serious on going gut damage without a positive antibody test. Statistically it is quite probable that you WILL get a positve antibody test. There is so much damage going in that battlefield which is your gut under the influence of gluten that there is a trauma "soup". All you need is for an "antigen presenting cell" (APC) to collect some gluten from this soup, give it to your lymphocytes and tell them "we want this stuff recognised by an antibody, get producing". Of course the APC may pick up tissue transaminase, endomysial protein or any of a host of other proteins to push at the lymphocytes (which make the antibodies). But there is a chance you may not get either gluten or transaminase etc presented (ie no antibodies in our current lab tests), so you continue with "psychosomatic" gut problems or get labeled as inflammatory bowel disease, which is not regarded as gluten responsive. Severe IBD requires more than gluten avoidance but this basic step is probably essential.
Antibodies are a consequence, and an amplifier, of gluten toxicity, not a cause. That's intrinsic to gluten, MIC and NK cells. What brought this on?
Speculation time.
Did I have psoriasis or Dermatitis Herpetiformis (essentially coeliac disease of the skin)?
Answer: Maybe it's the same parallel as gut problems. WGA certainly gets in to the systemic circulation. I think it's a reasonable assumption gluten does too. It will be landing on vascular and/or dermal cells in the skin. Gluten induced stress here results in MIC expression. NK cells have that AK47, an itchy trigger finger and are seriously looking for MIC. Sometimes there is antibody production, sometimes there isn't. This could easily be the result of receptor subtypes (genetic) on your antigen presenting cells. Different labels, different lab results (if it ever gets that far) but a similar approach is needed. Perhaps there are a host of immune mediated problems triggered by gluten that are not antibody producing.
Peter
Saturday, February 23, 2008
What, Sweden again?
I've had this paper kicking around since it was published. There are a few things which grabbed me about it. I was initially a bit dubious; a diet containing 20% of calories as carbohydrate didn't really seem low enough to be seriously useful for a diabetic. But then I twigged that these people were using a calorie restricted diet, so the absolute amounts of carbs were actually down at 80-90g/d. That's just above Dr Lutz's suggestion of 72g/d and not hugely above Kwasniewski's recommendations. Of course it's WAY above Dr Bernstein's recommendations (30g/d), but he really is a perfectionist, a good one too. The 50% of calories from dietary fat under weight loss conditions was obviously being supplemented from stored adipose tissue (quite highly saturated I believe), hence the weight loss.
These are some of the sections of text I particularly enjoyed.
From the introduction:
"The objective of the present study, therefore, was to determine to what degree the changes among the 16 patients in the low-carbohydrate diet group at 6-months were preserved or changed 22 months after start, even without close follow-up. In addition, we report that, after the 6 month observation period, two thirds of the patients in the high-carbohydrate changed their diet. This group also showed improvement in bodyweight and glycemic control."
OK, it's a short study. A couple of years is way too quick to see changes in heart attack rate from eating all that fat. Isn't it? You know, fatty streaks to soft plaque to... (yawn)
The other feature here was the comment about "changed their diet" applied to the control group (low fat, ADA style diet). It's made clearer in the methods:
"Seven of the controls switched to a 20 % carbohydrate diet immediately after the follow-up period. For those we have data 12–14 months after the change. Three more have later sought information and have changed diet. We have no long-term data for those. Five of the original controls have not changed diet."
This was an open study by the look of it. You can't spend hours sitting in a diabetes clinic chatting to someone who is loosing weight, dropping HbA1c and binning their insulin without realising that the LC intervention diet works. Only an ADA diabetologist is stupid enough to miss this. Given the option to change, you change. Unless you really are as stupid as...
But of course, all of that fat will have the LC diet group dropping like flies from heart attacks. We all know that. We've been told.
So, from the discussion:
"We have examined the medical charts for both the original high-carbohydrate group and the low-carbohydrate group from 3 months after the initiation of the diet therapy – when an effect might be detected – and forward for episodes of cardiovascular disease. Three episodes of cardiovascular disease have occurred among the 5 patients that never changed diet. The 16 patients in the low-carbohydrate diet group (19 months observation time) and the 7 from the high-carbohydrate diet group that changed diet (10 months observation time) – totalling 23 patients – have been free of cardiovascular disease during the follow-up period (p < 0.03. Fischer Exact)."
So we have three out of five people with episodes of CV disease during about a year of ADA style low fat diet and zero out of 23 patients on Lutz style high fat.
Must be a paradox. Ha! (now think of the Queen launching a new ship) I name this paradox "The Swedish Paradox".
What, again? Ok, there are only a limited number of countries in the world and so many paradoxes looking for names...
Peter
These are some of the sections of text I particularly enjoyed.
From the introduction:
"The objective of the present study, therefore, was to determine to what degree the changes among the 16 patients in the low-carbohydrate diet group at 6-months were preserved or changed 22 months after start, even without close follow-up. In addition, we report that, after the 6 month observation period, two thirds of the patients in the high-carbohydrate changed their diet. This group also showed improvement in bodyweight and glycemic control."
OK, it's a short study. A couple of years is way too quick to see changes in heart attack rate from eating all that fat. Isn't it? You know, fatty streaks to soft plaque to... (yawn)
The other feature here was the comment about "changed their diet" applied to the control group (low fat, ADA style diet). It's made clearer in the methods:
"Seven of the controls switched to a 20 % carbohydrate diet immediately after the follow-up period. For those we have data 12–14 months after the change. Three more have later sought information and have changed diet. We have no long-term data for those. Five of the original controls have not changed diet."
This was an open study by the look of it. You can't spend hours sitting in a diabetes clinic chatting to someone who is loosing weight, dropping HbA1c and binning their insulin without realising that the LC intervention diet works. Only an ADA diabetologist is stupid enough to miss this. Given the option to change, you change. Unless you really are as stupid as...
But of course, all of that fat will have the LC diet group dropping like flies from heart attacks. We all know that. We've been told.
So, from the discussion:
"We have examined the medical charts for both the original high-carbohydrate group and the low-carbohydrate group from 3 months after the initiation of the diet therapy – when an effect might be detected – and forward for episodes of cardiovascular disease. Three episodes of cardiovascular disease have occurred among the 5 patients that never changed diet. The 16 patients in the low-carbohydrate diet group (19 months observation time) and the 7 from the high-carbohydrate diet group that changed diet (10 months observation time) – totalling 23 patients – have been free of cardiovascular disease during the follow-up period (p < 0.03. Fischer Exact)."
So we have three out of five people with episodes of CV disease during about a year of ADA style low fat diet and zero out of 23 patients on Lutz style high fat.
Must be a paradox. Ha! (now think of the Queen launching a new ship) I name this paradox "The Swedish Paradox".
What, again? Ok, there are only a limited number of countries in the world and so many paradoxes looking for names...
Peter
Wednesday, February 20, 2008
Bantu Lp(a) and Swedish Lp(a)
Lipoprotein (a) is interesting enough that I might put up some more thoughts about it, but this post is based on the Bantu cross sectional study cited, as all the best cardiac studies are, by Dr Davis of Track Your Plaque.
The initial link is to this paper which explains quite a lot about Lp(a) and its genetics.
I wanted to compare values of the Bantu with an intervention trial in some Swedes, and to think about eating fish and taking fish oil, to reduce that "risk factor" for heart disease. And yes, Lp(a) is a "risk factor" for all forms of vascular disease; ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and abdominal aortic aneurism.
First the Bantu. That first paper covered the Bantu genetics, apoprotein (a) sizes and Lp(a) blood levels. Basically, if you match individual gene types, the fish eating Bantu always have lower Lp(a) than their matched apo(a) size vegetarian Bantu equivalents. You get nothing about diet in this initial paper, for that you need to go to a previous publication from the same group.
Fish eaters and vegetarians were pretty well matched for calorie intake at around 2100kcal/d. The fish eaters ate 18% of calories from protein, 12% from fat and 70% from complex carbohydrate. The values for the vegetarians were 11% from protein, 7% from fat and 82% from complex carbohydrate. Dean "Mcdonalds" Ornish would be proud of the vegetarians. BTW, both groups ate 4g/day of salt, worth remembering that.
On a fully vegetarian, completely home grown, ultra low fat, low salt, complex carbohydrate diet these Bantu natives show exactly the same rise in blood pressure with age as Westeners do. Their systolic pressure approximates quite closely to that "age plus 100" rule of thumb which used to be considered normal in the UK and diastolic pressure followed systolic as you would expect. Fish eaters stuck with a systolic around 120-130mmHg and a diastolic around 70mmHg, life long. Remember both groups only ate 4g/d of salt. Now what does that tell you about salt and hypertension? Anyway, the politically correctest Bantu had significant markers of CV deterioration with age, not so the fish eaters.
BTW, as an aside, HDL figures were abysmal with both groups at under 1.0mmol/l, exactly as you'd expect on a low fat diet. They were slightly higher in the vegetarian group, presumable because they drank more alcohol. Triglycerides were higher in the veggie group, again pretty much as you'd expect from their carb intake.
The theory was/is that it was the omega three fats which were saving the fish eaters from hypertension and Lp(a) elevation. They undoubtedly did eat more omega three fats, and less omega six fats, and we know from the Lyon Heart Study that this is probably a Good Thing.
The Bantu fishermen were getting roughly 5% of calories from fish derived fat, that's 105kcal, equivalent of about 12ml of fish oil per day, as fish. This intake of fish oil is associated with a Lp(a) concentration of 201mg/dl as opposed to 321mg/dl in the vegetarians.
So what happens if we take a group of Swedes and give them more than twice that dose of fish derived lipid, as 30ml of fish oil per day, then track their Lp(a) level? Initially the subjects were on a typical Swedish diet (no information given) and were advised not to change it throughout the study. The fish oil was added at 30ml plus some vitamin E per day for three weeks, then there were two weeks off of fish oil, then three more weeks on fish oil, but without the vitamin E (for Bruce; yes, lipid peroxides rocketed on the later protocol).
Lp(a) before fish oil plus vit E: 128mg/dl, after three weeks supplemented: 125mg/dl. Back on Swedish diet for 2 weeks: 124mg/dl, after fish oil without E for three weeks: 128mg/dl.
All of these figures are essentially identical. Fish oil at 30ml per day does nothing to Lp(a) levels on a Swedish diet. It's also worth noting that, although we don't know the Swedish geneotypes for apoprotein (a) size, these values are all much lower than either of the Bantu groups. Maybe 35% of calories from fat in Sweden?
So is it really the fish oil which is saving the carnivorous Bantu from the hypertension and elevated Lp(a) which are prevalent in their vegetarian cousins?
Somehow I doubt it, based on the Swedish data and the behaviour of Lp(a).
Intervention studies show us that low fat diets increase Lp(a) and high fat diets decrease it, I put the studies here.
The fish eating Bantu got through more than half a kilo of fish on a good day. If your average calorie in take stays unchanged, that's an awful lot of complex carbohydrate you didn't eat. If I assume causality, not eating complex carbohydrate appears to be extremely good for your cardiovascular system. And your Lp(a) levels.
You don't need any "magic" fats to drop Lp(a), unless those magic fats are saturated fats, which seem to do the job best (just turn the DELTA study on its head).
Peter
BTW: No, I don't believe our liver manufactures Lp(a) to kill us. Again, more thoughts on Lp(a) to come. I might even talk hedgehogs if I can get my head around what they were doing with their lipids!
Another BTW, the Kitava studies showed these islanders ran at 70% calories from carbs but with Swedish levels of Lp(a). Kitava was lowish in fat at 20% of calories, but their dietary fats were almost all saturated (from coconut), with just a little omega 3s from fish. So it looks to be arguable whether you need to consume saturated fats to keep you Lp(a) levels down or keep carbs below the vegetarian Bantu levels. Ignoring genetics. Open to discussion on that one.
EDIT 28th Feb: Just been back to the Kitava papers for something else and noticed Lipoprotein(a) was around 300mg/dl, ie Bantu levels, bad Bantu levels. No heart disease. Bear in mind Lp(a) is notoriously variable from lab to lab. But still needs slotting in to Lp(a) and heart disease.
The initial link is to this paper which explains quite a lot about Lp(a) and its genetics.
I wanted to compare values of the Bantu with an intervention trial in some Swedes, and to think about eating fish and taking fish oil, to reduce that "risk factor" for heart disease. And yes, Lp(a) is a "risk factor" for all forms of vascular disease; ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and abdominal aortic aneurism.
First the Bantu. That first paper covered the Bantu genetics, apoprotein (a) sizes and Lp(a) blood levels. Basically, if you match individual gene types, the fish eating Bantu always have lower Lp(a) than their matched apo(a) size vegetarian Bantu equivalents. You get nothing about diet in this initial paper, for that you need to go to a previous publication from the same group.
Fish eaters and vegetarians were pretty well matched for calorie intake at around 2100kcal/d. The fish eaters ate 18% of calories from protein, 12% from fat and 70% from complex carbohydrate. The values for the vegetarians were 11% from protein, 7% from fat and 82% from complex carbohydrate. Dean "Mcdonalds" Ornish would be proud of the vegetarians. BTW, both groups ate 4g/day of salt, worth remembering that.
On a fully vegetarian, completely home grown, ultra low fat, low salt, complex carbohydrate diet these Bantu natives show exactly the same rise in blood pressure with age as Westeners do. Their systolic pressure approximates quite closely to that "age plus 100" rule of thumb which used to be considered normal in the UK and diastolic pressure followed systolic as you would expect. Fish eaters stuck with a systolic around 120-130mmHg and a diastolic around 70mmHg, life long. Remember both groups only ate 4g/d of salt. Now what does that tell you about salt and hypertension? Anyway, the politically correctest Bantu had significant markers of CV deterioration with age, not so the fish eaters.
BTW, as an aside, HDL figures were abysmal with both groups at under 1.0mmol/l, exactly as you'd expect on a low fat diet. They were slightly higher in the vegetarian group, presumable because they drank more alcohol. Triglycerides were higher in the veggie group, again pretty much as you'd expect from their carb intake.
The theory was/is that it was the omega three fats which were saving the fish eaters from hypertension and Lp(a) elevation. They undoubtedly did eat more omega three fats, and less omega six fats, and we know from the Lyon Heart Study that this is probably a Good Thing.
The Bantu fishermen were getting roughly 5% of calories from fish derived fat, that's 105kcal, equivalent of about 12ml of fish oil per day, as fish. This intake of fish oil is associated with a Lp(a) concentration of 201mg/dl as opposed to 321mg/dl in the vegetarians.
So what happens if we take a group of Swedes and give them more than twice that dose of fish derived lipid, as 30ml of fish oil per day, then track their Lp(a) level? Initially the subjects were on a typical Swedish diet (no information given) and were advised not to change it throughout the study. The fish oil was added at 30ml plus some vitamin E per day for three weeks, then there were two weeks off of fish oil, then three more weeks on fish oil, but without the vitamin E (for Bruce; yes, lipid peroxides rocketed on the later protocol).
Lp(a) before fish oil plus vit E: 128mg/dl, after three weeks supplemented: 125mg/dl. Back on Swedish diet for 2 weeks: 124mg/dl, after fish oil without E for three weeks: 128mg/dl.
All of these figures are essentially identical. Fish oil at 30ml per day does nothing to Lp(a) levels on a Swedish diet. It's also worth noting that, although we don't know the Swedish geneotypes for apoprotein (a) size, these values are all much lower than either of the Bantu groups. Maybe 35% of calories from fat in Sweden?
So is it really the fish oil which is saving the carnivorous Bantu from the hypertension and elevated Lp(a) which are prevalent in their vegetarian cousins?
Somehow I doubt it, based on the Swedish data and the behaviour of Lp(a).
Intervention studies show us that low fat diets increase Lp(a) and high fat diets decrease it, I put the studies here.
The fish eating Bantu got through more than half a kilo of fish on a good day. If your average calorie in take stays unchanged, that's an awful lot of complex carbohydrate you didn't eat. If I assume causality, not eating complex carbohydrate appears to be extremely good for your cardiovascular system. And your Lp(a) levels.
You don't need any "magic" fats to drop Lp(a), unless those magic fats are saturated fats, which seem to do the job best (just turn the DELTA study on its head).
Peter
BTW: No, I don't believe our liver manufactures Lp(a) to kill us. Again, more thoughts on Lp(a) to come. I might even talk hedgehogs if I can get my head around what they were doing with their lipids!
Another BTW, the Kitava studies showed these islanders ran at 70% calories from carbs but with Swedish levels of Lp(a). Kitava was lowish in fat at 20% of calories, but their dietary fats were almost all saturated (from coconut), with just a little omega 3s from fish. So it looks to be arguable whether you need to consume saturated fats to keep you Lp(a) levels down or keep carbs below the vegetarian Bantu levels. Ignoring genetics. Open to discussion on that one.
EDIT 28th Feb: Just been back to the Kitava papers for something else and noticed Lipoprotein(a) was around 300mg/dl, ie Bantu levels, bad Bantu levels. No heart disease. Bear in mind Lp(a) is notoriously variable from lab to lab. But still needs slotting in to Lp(a) and heart disease.
Fiber, inulin and cancer
Just a quickie,
It has come up off blog on a number of occasions that inulin, a fructose polymer completely indigestible to humans but edible by bacteria, is a potential carcinogen. Couple of refs here and here. I was a bit dubious of this model as it showed beef to be carcinogenic too. That upsets my biases!!!! And slightly odd as this different model showed bacon, yes you read that correctly as bacon, to be protective. Beef and chicken were neutral in this chemical carcinogen based model. I decided that playing with mice, especially bowel cancer prone mice like ApcMin/+ engineered mice, might say relatively little about humans. Still not sure.
Now this dropped out of Pubcrawler today. If you are a ApcMin/+ mouse you can choose you carcinogen from wheat bran or apple pulp (that's the healthy fiber from healthy fruit, apples):
"In conclusion, both types of resistant carbohydrates increased polyp number and tumour burden and this was associated with elevated epithelial cell proliferation and crypt fission."
Because my access account doesn't allow me the full text I can't see what the fiber did to the wild type control mice. Always the most interesting bit and not in the abstract.
Crypt fission is bad, it's what wheat germ agglutinin and insulin do. Looks like all sorts of fiber do too. Just an extreme mouse model, but next time someone extolls their belief in the benefits of resistant starches or fiber, maybe they should read and think!
Peter
It has come up off blog on a number of occasions that inulin, a fructose polymer completely indigestible to humans but edible by bacteria, is a potential carcinogen. Couple of refs here and here. I was a bit dubious of this model as it showed beef to be carcinogenic too. That upsets my biases!!!! And slightly odd as this different model showed bacon, yes you read that correctly as bacon, to be protective. Beef and chicken were neutral in this chemical carcinogen based model. I decided that playing with mice, especially bowel cancer prone mice like ApcMin/+ engineered mice, might say relatively little about humans. Still not sure.
Now this dropped out of Pubcrawler today. If you are a ApcMin/+ mouse you can choose you carcinogen from wheat bran or apple pulp (that's the healthy fiber from healthy fruit, apples):
"In conclusion, both types of resistant carbohydrates increased polyp number and tumour burden and this was associated with elevated epithelial cell proliferation and crypt fission."
Because my access account doesn't allow me the full text I can't see what the fiber did to the wild type control mice. Always the most interesting bit and not in the abstract.
Crypt fission is bad, it's what wheat germ agglutinin and insulin do. Looks like all sorts of fiber do too. Just an extreme mouse model, but next time someone extolls their belief in the benefits of resistant starches or fiber, maybe they should read and think!
Peter
Tuesday, February 19, 2008
Cat rawfeeding; scroll down the comments
Just like to say thanks to everyone who posted comments on the last blog entry.
Thanks, they're appreciated.
Peter
Thanks, they're appreciated.
Peter
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