Malonyldialdehyde (MDA) is a small molecule formed by the random oxidation of a polyunsaturated fatty acid. The exact chemistry seems quite complex but needs, as an absolute minimum, two double bonds in the fat molecule, three omega numbers apart. But a feature of organic chemistry makes the free radical attack much more successful if there is a third double bond, located three omega numbers away from that bare minimum pair. So linoleic acid, that good old omega 6 fatty acid, can form some MDA because it has a double bond at the omega 9 position and at the omega 6 position, but it struggles to do it. Alpha linolenic acid, with its third double bond down at the omega 3 position, really allows MDA production to get going. That's chemistry. There's the briefest of summaries here.
So omega three fatty acid supplementation will increase MDA production. Adding vitamin E will largely eliminate this effect in the short term and the theory is that the vitamin E protects the omega 3 fatty acids in the chylomicrons en route to the liver. So more undamaged PUFA reach the liver, which has a greater impact on fasting triglycerides (VLDLs). This much comes from this paper.
But what I found really interesting is what happens within the liver itself. This paper comes up with some answers. The VLDL particles are manufactured as per normal, but if there is enough lipid peroxidation, the particle is degraded and never released. The liver appears to use iron to generate MDA from PUFA as a decider as to whether to release the VLDL particle or degrade it. The more MDA generated within the liver cell, the lower the plasma VLDL levels drop.
Why should that be? The liver makes a VLDL particle, tests how stable it is in terms of lipid peroxidation, and refuses to release any VLDLs deemed too unstable. This peroxidation is what omega 3 fats do, far better than omega 6 fats do it. The message I get from this is that our liver does not want lipid peroxidation prone VLDLs being released in to the circulation. So, if we accept that VLDLs from carbohydrate are stable (palmitic acid based) lots can be safely released. Render then unstable with fish oil and they, and their components, stay in the liver. Is this good or bad?
Well, taking fish oil makes your fasting triglyceride value look like it belongs to a LC eating person, even though you may not be a LC eating person. Does your cardiac risk belong to the the LC person or the mixed diet person? Draw the comparison with torcetrapib. Fantastic lipids, increased death risk. Now look at atrovasatain, quite "good" lipids and permission to trade in your heart attack death certificate for a cancer one, with the same date. Then look at LC eating and wonder about the blank cause of death and date.
Where do fish oils fit in to this spectrum? Dropping your triglycerides is treating a number. Fine for cardiologists. Eating like a Greenland eskimo requires strict LC in addition to 15g/d of EPA+DHA. This is a double triglyceride lowering approach but one which, in addition, dramatically minimises the glycation of apoB containing lipoproteins too. Is it the LC, the low trigs or the changes in tissue lipids which helps reduce CV risk? The mixed diet eating person with fish oil induced LC style triglycerides may well be munching lots of fruit as healthy low fat snacks to stave off hunger pangs between mixed meals. VLDL gycation?
If you have already lived your way to a heart attack, just "doing" EPA+DHA at 3.5g/d is as effective as 4g/d of corn oil for prevention of that second heart attack within the next 12 months! It's okay, unless you are one of the 25% of heart attack victims in each group re infarcting. Of course the fasting triglycerides were MUCH lower in the omega 3 group...
So do I think fish oils are useless? Not at all, but I think that using them as a tool to manipulate a number is, well, not a good idea. I do know that low dose EPA+DHA seems to benefit me, at around 1g/day. Whether this is "treating" the amount of omega 6 fatty acids I get from chicken and pork, I wouldn't like to say. But there's a lot more to omega 3 supplements than meets the eye.
What does seem lacking to me is convincing evidence of toxicity. The Greenlanders (back in the 1950s) were at low CV risk on high omega three intakes and I think it's reasonable to assume they were at the same low cancer risk as the Inuit described by Stefansson, see Stephan's post here. So I don't rate omega 3 as coming with the same toxicity as omega 6s.
There's another post on hepatic VLDL stability testing, but I'll call it a day on this rambling entry...
Peter
Tuesday, August 19, 2008
Sunday, August 17, 2008
Helicobacter and hydrogen
This one just has to jump the queue of posts, it had me cracked up. Thanks to Marco for the abstract and press release, the full text doesn't say anything much you can't get from those two sources.
Here's the gist of it:
If you are eating to one of those complex carb high fiber diets beloved of Ornish and his ilk, your flatuses (flati?) may be room clearing, but you're probably healthier if you just drop them and run. Clamping tight to save embarrassment could seriously damage your health, as could eating the high fiber diet in the first place of course. The only significant source of hydrogen in your body is colonic fermentation of carbohydrate by bacteria.
Helicobacter is a harmless or potentially beneficial commensal in your stomach, unless you feed and feed and feed it with, guess what? Hydrogen. This carbohydrate derivative may be more important than sugar for H pylori gastritis, though perhaps not in the gastric carcinogenesis aspect. Looks like it might also be a preferred energy source for assorted serious nasties, here's the speculation from the press release:
"Though unstudied, it's possible that this hydrogen could serve as an energy source for pathogens in other areas of the body, including the lungs and internal organs.
Since the amount of hydrogen produced in the colon varies based on diet, and since the researchers have shown that H. pylori uses this hydrogen as an energy source, something as simple as a diet change could affect virulence and persistence of this and other pathogens"
I don't think it's practical to eliminate all fiber from your diet. The absolutely indigestible fiber from grains can go very easily as cereal avoidance is a major step towards health, but getting rid of all remaining vegetable fiber is more difficult. I suspect having some hydrogen in your blood stream is probably normal. I've heard in various places on the net that LC eaters do still produce some flatus (but it's usually odourless) so must be making some hydrogen and methane, but the amount is low. So too will be the molecular hydrogen in their gastric mucosa.
So be tolerant if a whole grain fiber derived room clearer gets you. It's there for health purposes. Better out than in.
Peter
Here's the gist of it:
If you are eating to one of those complex carb high fiber diets beloved of Ornish and his ilk, your flatuses (flati?) may be room clearing, but you're probably healthier if you just drop them and run. Clamping tight to save embarrassment could seriously damage your health, as could eating the high fiber diet in the first place of course. The only significant source of hydrogen in your body is colonic fermentation of carbohydrate by bacteria.
Helicobacter is a harmless or potentially beneficial commensal in your stomach, unless you feed and feed and feed it with, guess what? Hydrogen. This carbohydrate derivative may be more important than sugar for H pylori gastritis, though perhaps not in the gastric carcinogenesis aspect. Looks like it might also be a preferred energy source for assorted serious nasties, here's the speculation from the press release:
"Though unstudied, it's possible that this hydrogen could serve as an energy source for pathogens in other areas of the body, including the lungs and internal organs.
Since the amount of hydrogen produced in the colon varies based on diet, and since the researchers have shown that H. pylori uses this hydrogen as an energy source, something as simple as a diet change could affect virulence and persistence of this and other pathogens"
I don't think it's practical to eliminate all fiber from your diet. The absolutely indigestible fiber from grains can go very easily as cereal avoidance is a major step towards health, but getting rid of all remaining vegetable fiber is more difficult. I suspect having some hydrogen in your blood stream is probably normal. I've heard in various places on the net that LC eaters do still produce some flatus (but it's usually odourless) so must be making some hydrogen and methane, but the amount is low. So too will be the molecular hydrogen in their gastric mucosa.
So be tolerant if a whole grain fiber derived room clearer gets you. It's there for health purposes. Better out than in.
Peter
Monday, August 11, 2008
Food: steak and kidney casserole
One pound diced beef, two pig's kidneys, one onion, one carrot, tin of tomatoes, few mushrooms, garlic, salt, pepper plus a little water to just cover. Simmer for three hours (I like my meat to melt in the mouth).
OK, spot the hidden mistake?
This is what I cooked and I only realised when I was turning it off to let it stand over night: There's NO BUTTER or DRIPPING in the pot!!!! I'm out of dripping at the moment so, as a matter of some urgency, I threw in the remains of a part used 250g block of butter. Probably about 100g. This stew will probably do three portions, might freeze some and take it to work. There is no way to cook eggs at work, so usually I have cream and chocolate for lunch but the occasional cold serving of casserole is nice. People seem shocked to see me eat "ordinary" food.
Hee hee. I always explain that the meat is for show, the fat is what I'm eating.
Peter
OK, spot the hidden mistake?
This is what I cooked and I only realised when I was turning it off to let it stand over night: There's NO BUTTER or DRIPPING in the pot!!!! I'm out of dripping at the moment so, as a matter of some urgency, I threw in the remains of a part used 250g block of butter. Probably about 100g. This stew will probably do three portions, might freeze some and take it to work. There is no way to cook eggs at work, so usually I have cream and chocolate for lunch but the occasional cold serving of casserole is nice. People seem shocked to see me eat "ordinary" food.
Hee hee. I always explain that the meat is for show, the fat is what I'm eating.
Peter
Food: Optimal ice cream
One pint of double cream, six egg yolks, about 10 drops of vanilla and sweetener to taste.
JK uses about 60g (100g to a litre) of sucrose. This is wayyyyyy too sweet for me, 20g is usually plenty. I also like it made with honey, about 20ml of liquid honey is fine. Sweetener users can adjust stevia/saccharin etc to taste. I just use some of my carbs to sweeten it.
Blend it up in a food processor and transfer to an ice cream maker. I can manage quite a lot of this before I hit fat overload and it's always tempting to push my fat tolerance limits with it... Just in a spirit of exploration of course!
Peter
JK uses about 60g (100g to a litre) of sucrose. This is wayyyyyy too sweet for me, 20g is usually plenty. I also like it made with honey, about 20ml of liquid honey is fine. Sweetener users can adjust stevia/saccharin etc to taste. I just use some of my carbs to sweeten it.
Blend it up in a food processor and transfer to an ice cream maker. I can manage quite a lot of this before I hit fat overload and it's always tempting to push my fat tolerance limits with it... Just in a spirit of exploration of course!
Peter
Sunday, August 10, 2008
Pork in green salsa and random dessert
Last night we made Optimal ice cream because, well, no reason. You need a reason to make ice cream????? Anyway, breakfast was a little informal today...
After that nutritious start we had some rubbish to finish off. Squiggs discovered the raspberry canes and though we expected the birds to get most of the berries this year (first crop) he beat them to it. Every morning. He likes raspberries so much that occasional shop bought ones are allowed. Though he only likes certain types...
Tonight's meal was belly pork in green salsa. Our own tomatillos, green peppers and chillis are all eatable at the moment, so the salsa was almost home made. The belly pork was prepared as for carnitas but then fried in the salsa sauce.
Salsa sauce: Tomatillos, green peppers, green chillis, garlic. Coarse blend, fry in butter, add the pre cooked belly pork and simmer for 20 minutes. Quantities are basically what you feel like! Just before serving add cream. Lots, just adjust your calories to your needs. Salt and pepper help.
We've never had tomatillos before this year, but the flavour is so good we can understand why the Mexican post docs we know (a) rave about them and (b) take whatever supply we can spare!
Even Squiggs was defeated by the left over ice cream so we used it this evening as a base for a few raspberries and poured hot chocolate sauce over it (melted 85% cocoa solids chocolate diluted with double cream). This dessert was totally, utterly and completely unnecessary. But yummy!
Low fat vegan anyone?
Peter.
OK, tomorrow's steak and kidney casserole is simmering and Nirvana is on the CD player. Time to make a start on omega 3s, Krauss and VLDLs. And a glass of wine.
After that nutritious start we had some rubbish to finish off. Squiggs discovered the raspberry canes and though we expected the birds to get most of the berries this year (first crop) he beat them to it. Every morning. He likes raspberries so much that occasional shop bought ones are allowed. Though he only likes certain types...
Tonight's meal was belly pork in green salsa. Our own tomatillos, green peppers and chillis are all eatable at the moment, so the salsa was almost home made. The belly pork was prepared as for carnitas but then fried in the salsa sauce.
Salsa sauce: Tomatillos, green peppers, green chillis, garlic. Coarse blend, fry in butter, add the pre cooked belly pork and simmer for 20 minutes. Quantities are basically what you feel like! Just before serving add cream. Lots, just adjust your calories to your needs. Salt and pepper help.
We've never had tomatillos before this year, but the flavour is so good we can understand why the Mexican post docs we know (a) rave about them and (b) take whatever supply we can spare!
Even Squiggs was defeated by the left over ice cream so we used it this evening as a base for a few raspberries and poured hot chocolate sauce over it (melted 85% cocoa solids chocolate diluted with double cream). This dessert was totally, utterly and completely unnecessary. But yummy!
Low fat vegan anyone?
Peter.
OK, tomorrow's steak and kidney casserole is simmering and Nirvana is on the CD player. Time to make a start on omega 3s, Krauss and VLDLs. And a glass of wine.
Tuesday, August 05, 2008
AGE RAGE and ALE: low fat!
Just to finish on glycation before moving on to signaling molecules, I'd like to add to Dave Dixon's comments about meal timing and chylomicron peaks after the segragation post. Let's just have a quick think about a serious low fat diet, using real food, say as eaten on Kitava or by the non vegetarian Bantu. These people are up at 70% of calories from carbohydrate. They tend to have the typical elevated fasting triglycerides of carbohydrate based diets, but not the heart disease associated with similarly elevated triglycerides in Western populations. Fasting triglycerides are VLDL particles released from the liver to move carbohydrate derived lipid to adipose tissue or muscle. They may have some PUFA from chylomicrons which have been taken up by the liver. They're certainly not chylomicrons in healthy people.
What's happening on the glycation front here? Post prandially there will be a marked glycation hot spot in the portal vein. This is unavoidable on a high carbohydrate diet. Insulin will rise and insulin promptly inhibits the release of VLDL particles from the liver. Same principle as we went through in this post, using all night glucose bingeing to "treat" hypertiglyceridaemia.
So, post prandially there are minimal chylomicrons due to the low fat content of the diet and VLDL secretion is inhibited. This is a neat way of separating glycation after a carb load from contact with any apoB containing lipids. As glucose uptake tails off, insulin falls and the processed glucose beyond acute needs can be shipped out as VLDLs, primarily as saturated fat which won't generate lipid peroxides anyway.
So there is some scope for genuine low fat diets to avoid glycation problems. You can have your fasting VLDLs up at 3.0mmol/l, just so long as they are full of palmitic acid and don't have sugar all over their apoB100 tags. You'll barely have a chylomicron anywhere to be seen at any stage, so who cares about that apoB48 tag?
It's the three times daily mix of sugar and soy oil (with fridge raid at 3am) which sets the scene for vascular catastrophe. The apoB counts might be the same in Kitava as in the USA, but the sugar coating and rancid fatty acid contents on and in those apoB tagged particles may be very different.
Peter
What's happening on the glycation front here? Post prandially there will be a marked glycation hot spot in the portal vein. This is unavoidable on a high carbohydrate diet. Insulin will rise and insulin promptly inhibits the release of VLDL particles from the liver. Same principle as we went through in this post, using all night glucose bingeing to "treat" hypertiglyceridaemia.
So, post prandially there are minimal chylomicrons due to the low fat content of the diet and VLDL secretion is inhibited. This is a neat way of separating glycation after a carb load from contact with any apoB containing lipids. As glucose uptake tails off, insulin falls and the processed glucose beyond acute needs can be shipped out as VLDLs, primarily as saturated fat which won't generate lipid peroxides anyway.
So there is some scope for genuine low fat diets to avoid glycation problems. You can have your fasting VLDLs up at 3.0mmol/l, just so long as they are full of palmitic acid and don't have sugar all over their apoB100 tags. You'll barely have a chylomicron anywhere to be seen at any stage, so who cares about that apoB48 tag?
It's the three times daily mix of sugar and soy oil (with fridge raid at 3am) which sets the scene for vascular catastrophe. The apoB counts might be the same in Kitava as in the USA, but the sugar coating and rancid fatty acid contents on and in those apoB tagged particles may be very different.
Peter
AGE RAGE and ALE: fasting
Jan Kwasniewski hates fasting. I'm not so sure it's as simple as this, there are some aspects which might be beneficial.
I started thinking about fasting when Dr Davis put up this post.
I'd just like to put this in to the perspective of glycoxidation. Let's look at glucose and lipid metabolism under a fast. There is no glucose uptake from the gut. The portal vein is no longer a glycation hot spot, the systemic circulation has only basal glucose too. Arterial endothelial cells are not undergoing hyperglycaemia induced apoptosis. This minimises the need for foam cell formation as there is essentially no damage needing repair.
Chylomicrons are not being produced at all, the liver is depleted of carbohydrate and so puts out a minimum of VLDLs. However many VLDLs and subsequent LDLs are actually produced, they will not be exposed to aggressive glycation conditions. If the liver does continue to produce significant levels of VLDL, they will be based either on fats synthesised from residual glycogen stores or free fatty acids derived from adipose tissue. That is, mostly saturated with some monounsaturated. So VLDLs will be deficient in PUFA and not prone to glycoxidation. PUFA supply will be limited to hepatic stores and whatever is present in adipose tissue, ie not a lot.
Bulk lipid for energy supply will be derived from adipose tissue lipolysis and be (a) mostly saturated fatty acids and (b) in free fatty acid form. You cannot glycate free fatty acids without direct free radical attack. No amino group on a FFA to form that horrible Schiff base.
From the perspective of someone who regards arteriosclerosis as a repair process gone horribly wrong, fasting has a lot to offer in the short term, with death in the long term. LC high saturated fat diets mimic fasting in several ways: There's never a lot of glucose in the portal vein and the chylomicrons based on saturated fats are pretty well glycoxidation proof. Fat gets stored as adipose tissue after each meal and is released as free fatty acids on demand. Metabolism mostly runs on free fatty acids. The big difference is that there is no (premature!) death if the diet is sustained for more than a few months!
Peter
I started thinking about fasting when Dr Davis put up this post.
I'd just like to put this in to the perspective of glycoxidation. Let's look at glucose and lipid metabolism under a fast. There is no glucose uptake from the gut. The portal vein is no longer a glycation hot spot, the systemic circulation has only basal glucose too. Arterial endothelial cells are not undergoing hyperglycaemia induced apoptosis. This minimises the need for foam cell formation as there is essentially no damage needing repair.
Chylomicrons are not being produced at all, the liver is depleted of carbohydrate and so puts out a minimum of VLDLs. However many VLDLs and subsequent LDLs are actually produced, they will not be exposed to aggressive glycation conditions. If the liver does continue to produce significant levels of VLDL, they will be based either on fats synthesised from residual glycogen stores or free fatty acids derived from adipose tissue. That is, mostly saturated with some monounsaturated. So VLDLs will be deficient in PUFA and not prone to glycoxidation. PUFA supply will be limited to hepatic stores and whatever is present in adipose tissue, ie not a lot.
Bulk lipid for energy supply will be derived from adipose tissue lipolysis and be (a) mostly saturated fatty acids and (b) in free fatty acid form. You cannot glycate free fatty acids without direct free radical attack. No amino group on a FFA to form that horrible Schiff base.
From the perspective of someone who regards arteriosclerosis as a repair process gone horribly wrong, fasting has a lot to offer in the short term, with death in the long term. LC high saturated fat diets mimic fasting in several ways: There's never a lot of glucose in the portal vein and the chylomicrons based on saturated fats are pretty well glycoxidation proof. Fat gets stored as adipose tissue after each meal and is released as free fatty acids on demand. Metabolism mostly runs on free fatty acids. The big difference is that there is no (premature!) death if the diet is sustained for more than a few months!
Peter
AGE RAGE and ALE: segregation
Both glucose and fructose are transported from the gut to the liver via the portal vein. I've never seen papers which have measured the concentration of either of these sugars in the portal vein, but the determinants must be rate of uptake from the gut, strongly influenced by dietary load, and splanchic blood flow, a high flow carrying the sugars at lower concentration per unit uptake. Ultimately this blood flow must carry the highest plasma glucose concentration and absolutely the highest plasma fructose concentration in the body, especially in the aftermath of drinking a giant Pepsi. Or maybe after a detox dose of Kiwi fruits.
Fatty acids come as mixtures. Even beef dripping carries a small load of PUFA. Nuts more so, seeds like those from Sunflowers much more so. Humans eat all of these in variable quantities. They are broken down by lipase, absorbed in to intestinal cells and reassembled in to triglycerides to be secreted as chylomicrons. Chylomicrons are the bulk transport system used to get lipid, including the PUFA, from the diet to the muscles, fat and the liver. A chylomicron is labled with a marker protein. It's a truncated form of that good old apoB100 used by the liver to mark the VLDLs destined to become LDL particles. The truncated protein is called apoB48. It starts life as an apoB100 but gets a socking great chunk cut off between transcription and particle assembly. It looses the LDL receptor interacting section but keeps the AGE triggered switch. No one seems to have looked at how glycation of chylomicrons acts in terms of receptor attachment to deliver lipid to muscles, or it's interaction with the "LDL-like" receptor which allows it to be recycled by the liver. I'll bet both actions get mangled by glycation. It does seem reasonable to assume that glycation allows chylomicrons to interact with RAGE, the receptor for glycated lipoproteins on mesothelial cells, in particular macrophages. These are the cells which make foam cells as part of atherosclerotic lesions.
This seems to be a feature of all apoB containing lipoproteins which have been glycoxidised. Obviously you would expect this to be a problem in the chronic hyperglycaemia of diabetes.
If your dietary carbohydrate intake stays within the capability of your liver to handle effectively, avoiding systemic hyperglycaemia, there is no need for foam cell formation. Avoiding chylomicron glycation under these physiologically normal circumstances, ie when you don't need foam cells, is likely to be beneficial. That's what happens.
The body actually puts chylomicrons in to the lymphatics which drain the gut, not in to the portal vein. They then pass down the thoracic duct and directly in to the venous circulation, avoiding the portal vein and its glycating environment. Mixing bulk lipids with bulk sugars gives bulk glycoxidation. Evolution has segregated them.
I'd always wondered why the digestive system was arranged this way. Now at least I have some idea.
Peter
Fatty acids come as mixtures. Even beef dripping carries a small load of PUFA. Nuts more so, seeds like those from Sunflowers much more so. Humans eat all of these in variable quantities. They are broken down by lipase, absorbed in to intestinal cells and reassembled in to triglycerides to be secreted as chylomicrons. Chylomicrons are the bulk transport system used to get lipid, including the PUFA, from the diet to the muscles, fat and the liver. A chylomicron is labled with a marker protein. It's a truncated form of that good old apoB100 used by the liver to mark the VLDLs destined to become LDL particles. The truncated protein is called apoB48. It starts life as an apoB100 but gets a socking great chunk cut off between transcription and particle assembly. It looses the LDL receptor interacting section but keeps the AGE triggered switch. No one seems to have looked at how glycation of chylomicrons acts in terms of receptor attachment to deliver lipid to muscles, or it's interaction with the "LDL-like" receptor which allows it to be recycled by the liver. I'll bet both actions get mangled by glycation. It does seem reasonable to assume that glycation allows chylomicrons to interact with RAGE, the receptor for glycated lipoproteins on mesothelial cells, in particular macrophages. These are the cells which make foam cells as part of atherosclerotic lesions.
This seems to be a feature of all apoB containing lipoproteins which have been glycoxidised. Obviously you would expect this to be a problem in the chronic hyperglycaemia of diabetes.
If your dietary carbohydrate intake stays within the capability of your liver to handle effectively, avoiding systemic hyperglycaemia, there is no need for foam cell formation. Avoiding chylomicron glycation under these physiologically normal circumstances, ie when you don't need foam cells, is likely to be beneficial. That's what happens.
The body actually puts chylomicrons in to the lymphatics which drain the gut, not in to the portal vein. They then pass down the thoracic duct and directly in to the venous circulation, avoiding the portal vein and its glycating environment. Mixing bulk lipids with bulk sugars gives bulk glycoxidation. Evolution has segregated them.
I'd always wondered why the digestive system was arranged this way. Now at least I have some idea.
Peter
When is a high fat diet not a high fat diet? Masai part 2
Many many thanks to Dave and Hege for the text of the paper. What does it say?
OK, they did a single 24h dietary recall and they ain't telling us anything about the results except for diet "type" predominant in each group. So they have discovered the Masai eat low carb high fat, the Bantu subsistence farmers eat high carb, low fat and urban Bantu probably eat junk. I simplify.
They also noticed the Masai walk a long way everyday and the urban Bantu don't. Cracking stuff this.
They took random bloods and found exactly what you would expect, deteriorating lipids from the "excellent" values from the high fat/LC Masai down to the "worst" lipids of the urban Bantu. If you believe the sort of lipids they're measuring are "good" or "bad" per se. They forgot to check HbA1c.
After that it's an ad hoc hypothesis that walking makes a lethal dose of saturated fat give you the "best" lipids in Africa. A bit like saying the French are protected from heart disease by all that red wine they drink.
The job of observational studies is to generate hypothesises. This one generates an ad hoc hypothesis to explain a non existing paradox. The well known effects of high fat low carb diets on blood lipids have been documented in the obesity and diabetes literature so many times now that you wonder why Mbalilaki has not been sacked on publication of this study for ignorance of the current intervention studies. Just pubmed Volek or Westman to catch a few.
How do you sum up this paper? Line one of their introduction:
"Despite overwhelming evidence for a link between intake of saturated fat and coronary heart disease... blah blah blah"
Translation: Haven't read the literature.
The Norwegian Centre for International University Co-operation and the Swedish Council for Working Life and Social Research funded her jaunt to Africa. I hope she enjoyed it as much as we did our walking safari in Kwazulu Natal in pre Squiggs days.
She wins hands down over Gibney.
This girl will go far.
Peter
In the Drankensbergs, nice hill walking.
OK, they did a single 24h dietary recall and they ain't telling us anything about the results except for diet "type" predominant in each group. So they have discovered the Masai eat low carb high fat, the Bantu subsistence farmers eat high carb, low fat and urban Bantu probably eat junk. I simplify.
They also noticed the Masai walk a long way everyday and the urban Bantu don't. Cracking stuff this.
They took random bloods and found exactly what you would expect, deteriorating lipids from the "excellent" values from the high fat/LC Masai down to the "worst" lipids of the urban Bantu. If you believe the sort of lipids they're measuring are "good" or "bad" per se. They forgot to check HbA1c.
After that it's an ad hoc hypothesis that walking makes a lethal dose of saturated fat give you the "best" lipids in Africa. A bit like saying the French are protected from heart disease by all that red wine they drink.
The job of observational studies is to generate hypothesises. This one generates an ad hoc hypothesis to explain a non existing paradox. The well known effects of high fat low carb diets on blood lipids have been documented in the obesity and diabetes literature so many times now that you wonder why Mbalilaki has not been sacked on publication of this study for ignorance of the current intervention studies. Just pubmed Volek or Westman to catch a few.
How do you sum up this paper? Line one of their introduction:
"Despite overwhelming evidence for a link between intake of saturated fat and coronary heart disease... blah blah blah"
Translation: Haven't read the literature.
The Norwegian Centre for International University Co-operation and the Swedish Council for Working Life and Social Research funded her jaunt to Africa. I hope she enjoyed it as much as we did our walking safari in Kwazulu Natal in pre Squiggs days.
She wins hands down over Gibney.
This girl will go far.
Peter
In the Drankensbergs, nice hill walking.
Monday, August 04, 2008
When is a high fat diet not a high fat diet? Masai
Just a quick post to comment on this paper from a link emailed to me by Dave Lull.
It turns out that eating saturated fat is fine if you burn 2500kcal above basal metabolic requirements. Phew. That must be an awful lot of saturated fat being burned off to make it safe.
I only have the abstract of this paper, so can't get much of an idea of the size of the blinkers worn by the authors. They look pretty enormous from the here. In fact my window faces East and from Berkshire (far inland in southern England) I think I can see the tops of their blinkers way over there on the other side the North Sea (can't see any surf, must be flat, it is August).
If we go back to 1980 and another of my favourite idiots, we have Gibney's abstract here. He's now a major noise in Irish obesity promotion. He explains that it was the Masai's, and I quote:
"variable and generally low energy intakes"
that kept them healthy.
Now does 2500kcal over BMR count as a generally low intake? Why would variation in intake protect against IHD and the demon hypercholesterolaemia?
It's competition time. Who is the bigger idiot, Gibney or Mbalilaki? I know, I know, it's impossible to decide. You can stop trying now.
Equally difficult is to decide if Mbalilaki will do as well in influencing nutrition policy as Gibney seems to have done. Just pubmed him to see how well he has done for himself since 1980. They probably both know how to get on pretty well as dietitians. But as scientists? The biggest mistake I can see in the press release is to describe Mbalilaki et al as scientists.
Peter
PS if anyone has access to the full text of Mbalilaki's paper I'd be interested to see if she "forgot" to check sugar intake of the "high fat" urban Bantu. I would expect her to have skipped it and so to snatch the idiot's crown from Gibney by a gnat's whisker. Please don't let her disappoint me.
It turns out that eating saturated fat is fine if you burn 2500kcal above basal metabolic requirements. Phew. That must be an awful lot of saturated fat being burned off to make it safe.
I only have the abstract of this paper, so can't get much of an idea of the size of the blinkers worn by the authors. They look pretty enormous from the here. In fact my window faces East and from Berkshire (far inland in southern England) I think I can see the tops of their blinkers way over there on the other side the North Sea (can't see any surf, must be flat, it is August).
If we go back to 1980 and another of my favourite idiots, we have Gibney's abstract here. He's now a major noise in Irish obesity promotion. He explains that it was the Masai's, and I quote:
"variable and generally low energy intakes"
that kept them healthy.
Now does 2500kcal over BMR count as a generally low intake? Why would variation in intake protect against IHD and the demon hypercholesterolaemia?
It's competition time. Who is the bigger idiot, Gibney or Mbalilaki? I know, I know, it's impossible to decide. You can stop trying now.
Equally difficult is to decide if Mbalilaki will do as well in influencing nutrition policy as Gibney seems to have done. Just pubmed him to see how well he has done for himself since 1980. They probably both know how to get on pretty well as dietitians. But as scientists? The biggest mistake I can see in the press release is to describe Mbalilaki et al as scientists.
Peter
PS if anyone has access to the full text of Mbalilaki's paper I'd be interested to see if she "forgot" to check sugar intake of the "high fat" urban Bantu. I would expect her to have skipped it and so to snatch the idiot's crown from Gibney by a gnat's whisker. Please don't let her disappoint me.
Wednesday, July 23, 2008
Playing with salt and water
While we're talking about the risks of low salt and high water intakes, this hit the news today: You want to try a "detox" diet?
Don't!
It's arguable whether a detox diet is more or less likely to precipitate a hyponatraemic crisis than either Ecstasy or psychogenic polydipsia (a psychosis). Never forget the massive press misinformation about Leah Betts. This is what really happened to her:
"Hyponatraemia is an uncommon complication of MDMA ingestion. Only a few cases have been reported. The death of Leah Betts achieved wide publicity in the popular press, and it became clear that fatal water intoxication can be precipitated by excessive water drinking in ecstasy users. Fifteen cases were identified between August 1994 and December 1995 by the National Poisons Information Service (London), with serum Na+ concentrations of <130 mmol litre–1. The clinical pattern was remarkably uniform, with initial vomiting and disturbed behaviour, followed by drowsiness and agitation and, in seven cases, epileptiform convulsions. Drowsiness, a mute state and disorientation were observed for up to 3 days (Hartung TK, Schofield E, Short AI, Parr MJA, Henry JA, unpublished)"
Detox time or too much water after taking E at a party? Neither is beneficial and both can be fatal. Play safely!
Peter
Don't!
It's arguable whether a detox diet is more or less likely to precipitate a hyponatraemic crisis than either Ecstasy or psychogenic polydipsia (a psychosis). Never forget the massive press misinformation about Leah Betts. This is what really happened to her:
"Hyponatraemia is an uncommon complication of MDMA ingestion. Only a few cases have been reported. The death of Leah Betts achieved wide publicity in the popular press, and it became clear that fatal water intoxication can be precipitated by excessive water drinking in ecstasy users. Fifteen cases were identified between August 1994 and December 1995 by the National Poisons Information Service (London), with serum Na+ concentrations of <130 mmol litre–1. The clinical pattern was remarkably uniform, with initial vomiting and disturbed behaviour, followed by drowsiness and agitation and, in seven cases, epileptiform convulsions. Drowsiness, a mute state and disorientation were observed for up to 3 days (Hartung TK, Schofield E, Short AI, Parr MJA, Henry JA, unpublished)"
Detox time or too much water after taking E at a party? Neither is beneficial and both can be fatal. Play safely!
Peter
Thursday, July 17, 2008
Update
Well, here I am briefly. Things have pretty much ground to a halt on Hyperlipid. What has happened is that my boss has broken his little finger, in to lots of little pieces (pushbiking is pretty dangerous!). The steel pin, support dressing and full time sling don't seem to be doing much good so he's off work for 6 weeks and I've gone from working one day a week to working full time. Then our other primary surgeon is on study leave for his surgery ticket and our full time internal medicine slanted vet is off sick... So this is the first time I've logged on to do anything other than check work emails.
I'm just finishing week four out of six... By the time I get to answer comments people will probably will probably have forgotten they posted them! Still, it pays off a chunk of the mortgage.
So apologies for the lack of activity and replies.
BTW the off sick vet is really interesting. Anaemia to the point of hyperventilation after climbing the stairs and recurrent major infections. Ah, Weight Watchers and wholemeal bread! People love these wacky diets, play at your own risk!
Peter
I'm just finishing week four out of six... By the time I get to answer comments people will probably will probably have forgotten they posted them! Still, it pays off a chunk of the mortgage.
So apologies for the lack of activity and replies.
BTW the off sick vet is really interesting. Anaemia to the point of hyperventilation after climbing the stairs and recurrent major infections. Ah, Weight Watchers and wholemeal bread! People love these wacky diets, play at your own risk!
Peter
Thursday, July 10, 2008
AGE, RAGE and ALE; oxLDL
This is the abstract from a discussion paper, it's not in pubmed for some reason but I have the pdf lying around my hard drive. It's just an opinion piece but quite well referenced.
Oxidized Low-Density Lipoproteins and Atherosclerosis
S. Ylä-Herttuala1,2, T. Pakkanen1, P. Leppänen1, T. Häkkinen1
Basic research has provided strong evidence that LDL oxidation plays an important role in atherogenesis. Several mechanisms have been identified which can lead to LDL oxidation in vivo. Clinical and epidemiological studies have provided circumstancial evidence that oxidized LDL may be involved in the progression of atherosclerotic vascular disease. Better understanding of mechanisms that lead to LDL oxidation or protect LDL against oxidative damages shouldhelp the development of new strategies for the prevention of cardiovascular diseases. J Clin Basic Cardiol 2000; 3: 87–8.
Just look at this table of comparison between LDL lipoproteins and oxLDL lipoproteins.
If you are measuring the size and numbers of your LDL particles, you might also want to look at their oxidation state too. Perhaps it matters more? Are the small dense LDL particles so associated with atherosclerosis also the most AGEd and ALEd?
Here's the table, click to enlarge
If you had the choice between lots of minimally oxidised LDL and a small amount of highly oxidised LDL which would you choose? Low fat diet anyone, or maybe just more sugar on your soya oil fried donut? Mmmmmmm, yumeeee.
Peter
Oxidized Low-Density Lipoproteins and Atherosclerosis
S. Ylä-Herttuala1,2, T. Pakkanen1, P. Leppänen1, T. Häkkinen1
Basic research has provided strong evidence that LDL oxidation plays an important role in atherogenesis. Several mechanisms have been identified which can lead to LDL oxidation in vivo. Clinical and epidemiological studies have provided circumstancial evidence that oxidized LDL may be involved in the progression of atherosclerotic vascular disease. Better understanding of mechanisms that lead to LDL oxidation or protect LDL against oxidative damages shouldhelp the development of new strategies for the prevention of cardiovascular diseases. J Clin Basic Cardiol 2000; 3: 87–8.
Just look at this table of comparison between LDL lipoproteins and oxLDL lipoproteins.
If you are measuring the size and numbers of your LDL particles, you might also want to look at their oxidation state too. Perhaps it matters more? Are the small dense LDL particles so associated with atherosclerosis also the most AGEd and ALEd?
Here's the table, click to enlarge
If you had the choice between lots of minimally oxidised LDL and a small amount of highly oxidised LDL which would you choose? Low fat diet anyone, or maybe just more sugar on your soya oil fried donut? Mmmmmmm, yumeeee.
Peter
Tuesday, July 08, 2008
AGE, RAGE and ALE: The ALE of LDL
I looked at glucose reacting with amino groups of proteins in the last post on the formation of AGEs. Apart from protein, cell membranes and the surface membrane of lipoprotein particles contain lipids. These form the classical lipid bilayer of biological membranes. The lipids of the bilayer come in a mix of saturates, mono unsaturates and PUFA. The exact mix of saturates to monounsaturates is largely determined by stearoyl-CoA desaturase, the enzyme which puts double bonds in to saturated fats to give monounsaturates.
Interestingly this enzyme appears to be under the control of insulin and activity goes up in insulin resistant states. That's another subject.
The PUFA composition is largely diet determined.
While boiling sugar with butter gives toffee, the situation in vivo seems more complicated and the initial generation of damaged lipids (ALEs, advanced lipoxidation end products) seems to involve an amino group. These are freely available from molecules like phosphatidylserine in cell (or lipoprotein) membranes. They provide the nitrogen for the formation of that horrible unstable Schiff base and its subsequent decay. The decaying base triggers oxidation/reduction reactions which hit double bonds in surrounding fatty acids, leading to ALE formation.
There's a good summary in this paper.
I just loved the chemistry in the introduction with stuff about electron spins, the pi antibonding level and other stuff that sounds really fancy. I think it means that molecular oxygen leaves PUFA alone without a transition metal or a pre formed free radical to get things going.
Until you add glucose that is.
Now I have two complaints about this paper. First is that some of the glucose concentrations used would make the ADA blanche. Not even an ADA diabetologist would suggest a blood glucose of 500mM (ie 500mmol/l). The 200mM used to oxidise the LDL particles would have had an intact human being in hyperglycaemic coma too. This is aggressive corner cutting on a time basis I guess. They did do some work down at 5mM.
Second is that they thanked Scott Grundy for helpful discussions. If you don't know who Scott Grundy is then you haven't read enough about the cholesterol con. Big black mark to the paper.
Third is that they used oleic acid for a lot of the work. They do comment that PUFA are 10-30 fold more oxidisable than oleic acid but PUFA didn't fit their protocols. They also forgot to mention that saturated fats just won't randomly oxidise at all in biological systems. No double bonds. But who would expect that sort of information from a cardiologist?
Did I say two complaints? Fourth...
So this paper is a bit rocky.
But what I do like about it is that it appears to show that glycation is what converts an LDL cholesterol particle in to an oxLDL particle. They're not the same. This is compatible with the recent study using low fat diets to (accidentally) raise the levels of oxLDL in intact humans.
Seems like sugar is what oxidises the PUFA in LDL to give oxLDL.
Avoid sugar, PUFA or both. Seems sensible to me.
Peter
Interestingly this enzyme appears to be under the control of insulin and activity goes up in insulin resistant states. That's another subject.
The PUFA composition is largely diet determined.
While boiling sugar with butter gives toffee, the situation in vivo seems more complicated and the initial generation of damaged lipids (ALEs, advanced lipoxidation end products) seems to involve an amino group. These are freely available from molecules like phosphatidylserine in cell (or lipoprotein) membranes. They provide the nitrogen for the formation of that horrible unstable Schiff base and its subsequent decay. The decaying base triggers oxidation/reduction reactions which hit double bonds in surrounding fatty acids, leading to ALE formation.
There's a good summary in this paper.
I just loved the chemistry in the introduction with stuff about electron spins, the pi antibonding level and other stuff that sounds really fancy. I think it means that molecular oxygen leaves PUFA alone without a transition metal or a pre formed free radical to get things going.
Until you add glucose that is.
Now I have two complaints about this paper. First is that some of the glucose concentrations used would make the ADA blanche. Not even an ADA diabetologist would suggest a blood glucose of 500mM (ie 500mmol/l). The 200mM used to oxidise the LDL particles would have had an intact human being in hyperglycaemic coma too. This is aggressive corner cutting on a time basis I guess. They did do some work down at 5mM.
Second is that they thanked Scott Grundy for helpful discussions. If you don't know who Scott Grundy is then you haven't read enough about the cholesterol con. Big black mark to the paper.
Third is that they used oleic acid for a lot of the work. They do comment that PUFA are 10-30 fold more oxidisable than oleic acid but PUFA didn't fit their protocols. They also forgot to mention that saturated fats just won't randomly oxidise at all in biological systems. No double bonds. But who would expect that sort of information from a cardiologist?
Did I say two complaints? Fourth...
So this paper is a bit rocky.
But what I do like about it is that it appears to show that glycation is what converts an LDL cholesterol particle in to an oxLDL particle. They're not the same. This is compatible with the recent study using low fat diets to (accidentally) raise the levels of oxLDL in intact humans.
Seems like sugar is what oxidises the PUFA in LDL to give oxLDL.
Avoid sugar, PUFA or both. Seems sensible to me.
Peter
Statin stupidity again
Read and cry.
Cure for C sections!
Perhaps a little less sugar might be a better approach!
I found this while searching for a snippet from Radio 4's Today Program announcing the recommendation from field leaders in the USA that children should start taking stains at 8 years of age, on the off chance it might eliminate all illness for ever. Happy happy happy I don't think. Couldn't find it on R4, but it'll surface soon in other places I guess.
Sigh.
Peter
Edit: You've all read Chris's post here? Never mind which end of life, you have a statin deficiency.
Cure for C sections!
Perhaps a little less sugar might be a better approach!
I found this while searching for a snippet from Radio 4's Today Program announcing the recommendation from field leaders in the USA that children should start taking stains at 8 years of age, on the off chance it might eliminate all illness for ever. Happy happy happy I don't think. Couldn't find it on R4, but it'll surface soon in other places I guess.
Sigh.
Peter
Edit: You've all read Chris's post here? Never mind which end of life, you have a statin deficiency.
Sunday, July 06, 2008
AGE, RAGE and ALE: The AGE of LDL
A glucose molecule can assume various shapes. If presented as a linear rather than a ring structure, one of the two end carbons will contain an aldehyde grouping. The C=O structure of the aldehyde can react chemically with an amino group on another organic molecule to give a Schiff base. This is a horribly complex structure where the carbon of the sugar is double bonded to the nitrogen of the amino group, which stays attached by its third bond to whatever structure it's part of. Classically this is a "free" amino group of lysine or arginine. Needless to say this structure is unstable and falls apart in various ways. The sugar can remain attached or break off taking the amino group with it. Either way there is damage to the protein and the potential for cross linkages to form. Lysine and arginine are, as I mentioned, the most susceptible amino acids. Glucose is one of the least problematic sugars, fructose is one of the worst.
The end result of this sugar driven reaction is the generation of Advanced Glycation Endproducts (AGEs). They're probably bad.
There is a section of the apolipoprotein B100 molecule (That's that sole protein on the surface of the LDL cholesterol particle) which is very prone to AGE formation. These people have looked at the process in detail. They have located, within the apoB100 protein, a distinct continuous sequence of 67 amino acids which are exquisitely prone to AGE formation. This section of apoB100 is probably not part of the binding domain for the LDL receptor, but formation of AGEs here does strongly influence the binding domain and effectively stops it working. So AGE formation in this area inhibits LDL particle attachment to its receptor, so reduces clearance from the plasma.
This is highly reminiscent of the situation in familial hypercholesterolaemia.
Why is apoB100 designed this way? Stuff doesn't just happen "accidentally" like this. Evolution has selected the sequence of apoB100 protein to provide a 67 animo acid section in which AGE formation inhibits uptake of the LDL particle in to cells which might want it.
Let's look at the logic.
During glycation conditions the LDL cholesterol particle stops sticking to its normal receptor. Why? My answer is that under these conditions it is more advantageous for the body to have the LDL cholesterol particle in the blood stream than it is to have it endocytosed by an endothelial cell.
Glycation is related to sugar concentration. Glucose is the sugar least prone to glycate anything to an AGE. Couple that with the tendency for humans, over an evolutionary time scale, to eat diets that rarely budge the blood glucose outside of a relatively narrow range, and I'm not sure hyperglycaemia is what the "switch" on LDL is evolved to look at.
No, my guess is that fructose was the original lever to develop a glycation based switch on the apoB100 molecule. Just about the only time a human ought to get a big enough load of sugar to risk any damage to themselves is during late summer or autumn in temperate regions, the source would be fruit. Possibly large amounts during a short period. If this happens in autumn it's a good source of calories to convert to fat and not to be wasted. But fructose is ten or seventeen times as good as glucose at AGE formation, depending on which AGE you look at and which model you use.
Fructose appears to be bad news, especially if any gets in to the systemic circulation. I can see some logic in taking the LDL particle away from arterial endothelial cells, which can make their own cholesterol anyway, and having it handy in the circulation for other purposes, like patching up fructose induced damage. Bear in mind that, while fructose is only present in the systemic circulation in trace amounts (which are probably bad for you) it will be present in copious amounts in the portal vein from gut to liver after each fruit meal. Lipoproteins are present throughout the circulation. Fructose will meet LDL particles with head on impact in the portal vein. AGEs on apoB100 suggest AGEs elsewhere, which mean repair is going to be needed. The LDL particle is diverted away from the endocytosis receptor. This is probably physiological.
But raising blood glucose from below 6mmol/l to above 30mmol/l would allow glucose to become the primary glycating agent. For a diabetic on the ADA diet the glycosylation of apoB100 is probably a fact of life. This is not our normal autumn carb loading pre winter. It's more of a pathological process.
Finding high levels of LDL cholesterol is one of the more logical aspects of the hyperglycaemia of type 2 diabetes. Putting these patients on to LC diets usually drops their calculated LDL cholesterol levels along with their blood glucose levels. It probably markedly reduces AGE formation throughout their physiology. LDL can then get back to supplying normal lipid to normal cells through the LDL receptor.
Peter
The end result of this sugar driven reaction is the generation of Advanced Glycation Endproducts (AGEs). They're probably bad.
There is a section of the apolipoprotein B100 molecule (That's that sole protein on the surface of the LDL cholesterol particle) which is very prone to AGE formation. These people have looked at the process in detail. They have located, within the apoB100 protein, a distinct continuous sequence of 67 amino acids which are exquisitely prone to AGE formation. This section of apoB100 is probably not part of the binding domain for the LDL receptor, but formation of AGEs here does strongly influence the binding domain and effectively stops it working. So AGE formation in this area inhibits LDL particle attachment to its receptor, so reduces clearance from the plasma.
This is highly reminiscent of the situation in familial hypercholesterolaemia.
Why is apoB100 designed this way? Stuff doesn't just happen "accidentally" like this. Evolution has selected the sequence of apoB100 protein to provide a 67 animo acid section in which AGE formation inhibits uptake of the LDL particle in to cells which might want it.
Let's look at the logic.
During glycation conditions the LDL cholesterol particle stops sticking to its normal receptor. Why? My answer is that under these conditions it is more advantageous for the body to have the LDL cholesterol particle in the blood stream than it is to have it endocytosed by an endothelial cell.
Glycation is related to sugar concentration. Glucose is the sugar least prone to glycate anything to an AGE. Couple that with the tendency for humans, over an evolutionary time scale, to eat diets that rarely budge the blood glucose outside of a relatively narrow range, and I'm not sure hyperglycaemia is what the "switch" on LDL is evolved to look at.
No, my guess is that fructose was the original lever to develop a glycation based switch on the apoB100 molecule. Just about the only time a human ought to get a big enough load of sugar to risk any damage to themselves is during late summer or autumn in temperate regions, the source would be fruit. Possibly large amounts during a short period. If this happens in autumn it's a good source of calories to convert to fat and not to be wasted. But fructose is ten or seventeen times as good as glucose at AGE formation, depending on which AGE you look at and which model you use.
Fructose appears to be bad news, especially if any gets in to the systemic circulation. I can see some logic in taking the LDL particle away from arterial endothelial cells, which can make their own cholesterol anyway, and having it handy in the circulation for other purposes, like patching up fructose induced damage. Bear in mind that, while fructose is only present in the systemic circulation in trace amounts (which are probably bad for you) it will be present in copious amounts in the portal vein from gut to liver after each fruit meal. Lipoproteins are present throughout the circulation. Fructose will meet LDL particles with head on impact in the portal vein. AGEs on apoB100 suggest AGEs elsewhere, which mean repair is going to be needed. The LDL particle is diverted away from the endocytosis receptor. This is probably physiological.
But raising blood glucose from below 6mmol/l to above 30mmol/l would allow glucose to become the primary glycating agent. For a diabetic on the ADA diet the glycosylation of apoB100 is probably a fact of life. This is not our normal autumn carb loading pre winter. It's more of a pathological process.
Finding high levels of LDL cholesterol is one of the more logical aspects of the hyperglycaemia of type 2 diabetes. Putting these patients on to LC diets usually drops their calculated LDL cholesterol levels along with their blood glucose levels. It probably markedly reduces AGE formation throughout their physiology. LDL can then get back to supplying normal lipid to normal cells through the LDL receptor.
Peter
Sunday, June 29, 2008
Food, fremented cream and 85% chocolate
OK, another non technical post. I hit a patch of work so I'm just glad to have arrived home one day while Squiggs was still up and eating.
Voices are the neighbours... Except the lip smacking from Squiggs!
Peter
Voices are the neighbours... Except the lip smacking from Squiggs!
Peter
Monday, June 23, 2008
Opioid pictures
No, it's not Afghanistan, that's the A34 in the background. The NHS had (has?) a diamorphine supply problem since our foray in to the opium fields of Afghanistan. Now we're in to grow your own!
The surrounding fields are far less recreational but could be far more damaging!
No surprise people like bread, it's acting on the same receptors as the poppy juice....
Peter
The surrounding fields are far less recreational but could be far more damaging!
No surprise people like bread, it's acting on the same receptors as the poppy juice....
Peter
Diabetes in Sweden update
Just an update from Nielson and Joensson, original comment here. Happened on it while chasing assorted lipoprotein numbers for another post.
HbA1c below 5% without meds is possible through diet. I wouldn't describe these people as cured, a pizza a week would have them in trouble, but with HbA1c this low I'd not be worrying about CVD too much.
"Of the total of 10 controls, who have switched diet, 2 persons after a weight reduction of 20 kg each are free of all signs of diabetes after 3 and 2 years respectively i.e. HbA1c below 5.0%, fasting blood glucose below 5.0 mmol/l and free of any blood glucose lowering medication"
Second comment is that, even with successful weight loss and diabetes imporvement, carb creep is real and hard to avoid.
"After 22 months 2 patients had resumed insulin treatment following an increase of carbohydrates."
I know that rye crisp bread was a feature of this diet. I wonder what would have happened in the complete absence of gluten? Or whether the problems of removing this potentially addictive carbohydrate source would just have sabotaged the initial compliance?
Peter
HbA1c below 5% without meds is possible through diet. I wouldn't describe these people as cured, a pizza a week would have them in trouble, but with HbA1c this low I'd not be worrying about CVD too much.
"Of the total of 10 controls, who have switched diet, 2 persons after a weight reduction of 20 kg each are free of all signs of diabetes after 3 and 2 years respectively i.e. HbA1c below 5.0%, fasting blood glucose below 5.0 mmol/l and free of any blood glucose lowering medication"
Second comment is that, even with successful weight loss and diabetes imporvement, carb creep is real and hard to avoid.
"After 22 months 2 patients had resumed insulin treatment following an increase of carbohydrates."
I know that rye crisp bread was a feature of this diet. I wonder what would have happened in the complete absence of gluten? Or whether the problems of removing this potentially addictive carbohydrate source would just have sabotaged the initial compliance?
Peter
Sunday, June 22, 2008
Gluten, thyroid and auto immunity
This an old press release, no longer available, sent to me by a friend from Dr Bernstein's forum. It appears to relate to this paper. Can't get the full text but the abstract and PR seems to sum up the results quite well.
There are three things of particular interest, one was the suggestion that coelaic disease patients develop other auto immune diseases. Second was that on withdrawl of gluten they not only loose both their anti endomysial antibody titers (traditional marker of coeliac disease) but they also loose their auto immune disease antibodies too. Third is that it's not overnight, 3-6 months is more like it.
From several people I get the impression that 2 weeks is often enough to see some change in an auto immune disease, a month is needed for convinving improvement and resolution needs about 6 months. There are good and bad patches in the process.
Nice to see a research group backing up the anecdote. Here's the press release:
"Dr. Tarcisio Not, of Clinica Pediatrica, I.R.C.C.S., Trieste, and colleagues, studied 172 patients with autoimmune thyroid disorders, and two control groups. The control groups comprised 498 patients with other diseases and 4,000 healthy blood donors. Screening was done with IgA-class endomysium antibody using immunofluorescence.
The findings, reported in the February issue of Digestive Diseases and Sciences, show that the prevalence of celiac disease was 3.4% in patients with autoimmune thyroiditis, and 0.6% and 0.25% among the two control groups.
Moreover, the study found an association between untreated celiac disease, gluten intake and autoimmune disorders. The researchers write, "We believe that undiagnosed celiac disease can cause other disorders by switching on some as yet unknown immunological mechanism. Untreated celiac patients produce organ-specific autoantibodies."
They add, "By following these subjects longitudinally, it has been seen that not only do the anti-gliadin antibodies and anti-endomysium antibodies disappear after 3 to 6 months of a gluten-free diet, but so do the organ-specific autoantibodies."
Given these results, Dr. Not and his team suggest that patients with autoimmune thyroiditis "may benefit from a screening for celiac disease so as to eliminate symptoms and limit the risk of developing other autoimmune disorders."
Dig Dis Sci 2000;45:403-406.(end)"
Peter
There are three things of particular interest, one was the suggestion that coelaic disease patients develop other auto immune diseases. Second was that on withdrawl of gluten they not only loose both their anti endomysial antibody titers (traditional marker of coeliac disease) but they also loose their auto immune disease antibodies too. Third is that it's not overnight, 3-6 months is more like it.
From several people I get the impression that 2 weeks is often enough to see some change in an auto immune disease, a month is needed for convinving improvement and resolution needs about 6 months. There are good and bad patches in the process.
Nice to see a research group backing up the anecdote. Here's the press release:
"Dr. Tarcisio Not, of Clinica Pediatrica, I.R.C.C.S., Trieste, and colleagues, studied 172 patients with autoimmune thyroid disorders, and two control groups. The control groups comprised 498 patients with other diseases and 4,000 healthy blood donors. Screening was done with IgA-class endomysium antibody using immunofluorescence.
The findings, reported in the February issue of Digestive Diseases and Sciences, show that the prevalence of celiac disease was 3.4% in patients with autoimmune thyroiditis, and 0.6% and 0.25% among the two control groups.
Moreover, the study found an association between untreated celiac disease, gluten intake and autoimmune disorders. The researchers write, "We believe that undiagnosed celiac disease can cause other disorders by switching on some as yet unknown immunological mechanism. Untreated celiac patients produce organ-specific autoantibodies."
They add, "By following these subjects longitudinally, it has been seen that not only do the anti-gliadin antibodies and anti-endomysium antibodies disappear after 3 to 6 months of a gluten-free diet, but so do the organ-specific autoantibodies."
Given these results, Dr. Not and his team suggest that patients with autoimmune thyroiditis "may benefit from a screening for celiac disease so as to eliminate symptoms and limit the risk of developing other autoimmune disorders."
Dig Dis Sci 2000;45:403-406.(end)"
Peter
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