While I was looking through some of the references cited by Krauss in his discussion paper about the roll of omega 3 fatty acids in the lowering of triglycerides, I came across this paper from 1999 on the effects of high and low fat diets on LDL subclasses. I read the abstract, re read it and read it again, scratching my head. Then I slogged through the whole paper. I just couldn't make out whether Krauss considered saturated fats to produce atherogenic changes in plasma lipids or not. After reading the paper I still couldn't decide what his conclusions were! Here are some quotes from the discussion:
"Change in dietary saturated fat was associated positively with mass of larger LDL particles and with peak LDL particle diameter and LDL flotation rate. These results suggest, therefore, that feeding saturated fat is associated with increased mass of larger LDL"
I think this means that saturated fats make "good" bad cholesterol. What do you think? What do you think Krauss thinks? Can you tell?
"In the present study, correlation analyses revealed significant positive relations of change in intake of the long-chain saturated fatty acids myristic and palmitic acids with change in plasma concentrations of large LDL particles. These findings are consistent with studies showing that, of the long-chain saturated fatty acids, myristic and palmitic are the most hypercholesterolemic"
Gasp, saturated fats are hypercholesterolaemic. Good or bad? Surely hypercholesterolaemis is bad? Keys said so. But large LDLs... atherogenic or benign????
"In summary, the present study showed that changes in dietary saturated fat are associated with changes in LDL subclasses in healthy men. An increase in saturated fat, and in particular, myristic acid, was associated with increases in larger LDL particles (and decreases in smaller LDL particles [did you spot this inset???? It matters]). LDL particle diameter and peak flotation rate were also positively associated with saturated fat, indicating shifts in LDL-particle distribution toward larger, cholesterol-enriched LDL"
Now, would you eat something which produced "cholesterol enriched" particles?
"Although there is a possibility that a subset of large LDL particles may be atherogenic (46), earlier results (37) point to a differential benefit of low-saturated-fat diets on LDL concentrations in individuals who have an atherogenic lipoprotein profile denoted by a predominance of small LDL particles"
What on earth does "a differential benefit of low-saturated-fat diets" mean? Your guess is as good as mine on that one. Answers on a postcard to Hyperlipid.
From the results, from whence it didn't seem to make it to the discussion, except in that little inset in brackets I highlighted:
"During the high-fat diet, saturated fat was correlated negatively with mass of smaller LDL particles"
What does this mean? Isn't that good? Does this mean the small dense LDLs are less dense?
As far as I can see, saturated fats improve every lipid marker they looked at BUT just look at this comment, again from the discussion:
"An increase in dietary saturated fat has been associated with the progression of CAD independent of LDL-cholesterol concentrations (56), and in cross-cultural studies, higher intakes of dietary saturated fat are associated with higher prevalence rates of CAD (57)"
Translates as: Never mind the lipid paramenetrs, saturated fats are BAD. Full stop. I think it's called nailing your colours to the mast.
BTW Ref 57 is Keys. Scraping the barrel a bit there!
So what did I do? I was beginning to doubt anything I'd read about lipid particle sub types, so I googled something along the lines of "LDL particle size CAD" or the like.
This was the first hit. Really, no kidding.
It's clear cut, cutting edge science from 1994:
"The lowest quintile--those with the smallest and most dense LDL particles--had more than three times the risk of heart attack as the quintile with the largest LDL particles"
Classic quote from: Ronald M Krauss, circa 1994.
Hmmmmmmmmm
Peter
Wednesday, August 27, 2008
Tuesday, August 26, 2008
Familial Hypercholesterolaemia and glucose
Just as an aside from hepatic lipids. This study is about heart disease within a group of people with heterozygous FH. The full text doesn't say much more than the abstract. Here are the two punch lines:
"The combination of DM [diabetes mellitus] or IGT [impaired glucose tolerance] with FH was associated with a further increase in the prevalence of CAD"
and
"total cholesterol levels were not significantly different [ie between normal, IGT or DM affected people with FH]"
The basic conclusion I get from the study is that if you take a group of statin naive FH "victims", it's not the variation of LDL cholesterol level in their bloodstream which determines CV disease, it's the degree of glucose dysregulation which seems to matter within the group.
Now what I want to know is if a heterozygous FH person maintained chronic and rigid normoglycaemic, 24/7 and so kept their blood glucose always below, say 5.0mmol/l, would they have ANY CVD above that of a non FH person under the same circumstances. Especially if they were omega 6 fatty acid restricted....
Mutations of the gene for the LDL receptor seem to be common and to come in an enormous number of flavours. If it was so very important to have two fully functional copies of the gene I would expect it to be much more highly conserved.
Peter
"The combination of DM [diabetes mellitus] or IGT [impaired glucose tolerance] with FH was associated with a further increase in the prevalence of CAD"
and
"total cholesterol levels were not significantly different [ie between normal, IGT or DM affected people with FH]"
The basic conclusion I get from the study is that if you take a group of statin naive FH "victims", it's not the variation of LDL cholesterol level in their bloodstream which determines CV disease, it's the degree of glucose dysregulation which seems to matter within the group.
Now what I want to know is if a heterozygous FH person maintained chronic and rigid normoglycaemic, 24/7 and so kept their blood glucose always below, say 5.0mmol/l, would they have ANY CVD above that of a non FH person under the same circumstances. Especially if they were omega 6 fatty acid restricted....
Mutations of the gene for the LDL receptor seem to be common and to come in an enormous number of flavours. If it was so very important to have two fully functional copies of the gene I would expect it to be much more highly conserved.
Peter
Monday, August 25, 2008
AGE RAGE and ALE: VLDL degradation and Fish Oil
OK, this is the direct link to figure 1 of Krauss' commentary paper. I just want to run through what seems to be happening and some of the consequences. Best to have the picture open alongside Hyperlipid.
Top left is the nucleus, then there's the stack of endoplasmic reticulum, then a newly synthesised lipid particle stuck on the outer surface of the ER. There is an interesting initial particle labelled I receiving "lipids" (another post there) which goes on to become that unlabelled particle on the outer surface of the ER (call it a nascent lipoprotein). The nascent lipoprotein has two arrows leading away from it representing two metabolic options. The upper arrow goes to a particle labeled III. On this pathway the particle receives saturated fatty acids which, at step V, stop it being destroyed. Destruction is termed PERPP, and the line from PERPP has a flat end meaning its blocked, and the legend "+SFAs" is shown as doing the blocking (by the little curved arrow). Got it? This SFA loaded particle is exported as an IDL (bad) or a large LDL (good). Luckily the IDL appears, on this diagram, to convert to the large form of LDL. But IDL may only be bad if secreted post prandially, I don't know, life is so complex in the ad hoc world of the lipid hypothesis!
Summary so far: Basic particle plus SFA gives the "good" version of "bad" cholesterol. Don't you just love these terms.
Now go back to that nascent lipoprotein and follow the alternative pathway shown by the downwards arrow. This leads to particle labeled IV, having accepted a lipid droplet via the curved arrow. Remember the lipid droplet. It might matter later. Anyway, there is then a dashed arrow showing possible secretion of this particle. If secreted it becomes a large VLDL particle.
While large LDL particles are good guys, large VLDLs are not. In fact they are the precursor to the evil incarnate particle, the small dense LDL. Like Darth Vader, only without the pre death conversion to the good side. Secrete and die.
Fish oils to the rescue! There is an arrow from the PERPP "destructaparticle" system pointing straight to this evil particle, joined by a little "n-3 PUFA-ox" which destroys the evil large VLDL before it ever gets secreted. Less of the large VLDL means less of the small dense LDL. More joy on blood results. Not only do triglycerides drop, it's the evil fraction of triglycerides which drop.
To summarise this pathway: Basic particle plus lipid droplet gives you bad VLDLs and small dense LDLs, unless aborted by omega 3 lipoxidation product (malondialdehyde is claimed but I'll get on to signaling molecules eventually).
All of that is pretty straight forward but it doesn't give us any insight in to anything except how to improve lab numbers.
Here are the nitty gritty questions.
1. Where did the SFAs come from? This is easy. Just follow Krauss' refs and you will find it's diet. Another post there needs writing.
2. Where did the lipid droplet come from? Well, lipid droplets in the liver vary from normal physiological amounts through to hepatic lipidosis. Hepatic lipidosis is a routine feature of the metabolic syndrome. We know that fructose is converted to lipid as rapidly as possible in the liver. We know that insulin inhibits the release of all VLDLs from the liver. Combining fructose with a glucose source (to raise insulin) seems a good way to generate hepatic lipid and block it's release. The bigger the dose and particularly the more continuous the ingestion, the more lipid droplets are likely to form. Sucrose or HFCS would do the job nicely. So might alcohol. Alcohol is interesting. Low doses improve insulin sensitivity and high doses do the opposite. The histpathology of non alcoholic hepatic steatosis is indistinguishable from alcoholic steatosis. They are the same condition. Keeping those lipid droplets in your liver seems a good way to get hepatic lipidosis and subsequent cirrhosis.
3. Where are the lipid droplets going? Well, if you dose up on fish oils the answer is nowhere! Lipid droplets should be off-loaded as small dense LDL precursor particles, the large VLDLs. You're not going to release them if you're on high dose fish oils! So you are trading the drop in "bad" LDLs for a rise in hepatic lipidosis. Are you going to mangle your liver to make Krauss happy? Yes?
Now let's go back and look at the high dose fish oil study from back in 1991.
Here are the triglyceride effects of 30ml fish oil a day for three weeks. Without vitamin E some omega 3s still get to the liver and trigs (probably large VLDLs in this case) drop from 2.6 to 2.0mg/dl. Modest and not statistically significant. Have a wash out period and do it again, but this time preserve the omega 3s with vitamin E. The drop is 48% this time, p<0.01, enough to warm the cockles of a cardiologist's heart.
Remember, these absent triglycerides should have contained lipid droplets which the liver wants rid of. I find it fascinating to see that, in the post washout/pre omega 3+vitamin E session, that the trigs were up at 3.4mg/dl, quite a bit higher than the 2.6 at the start of the study. Is this the liver off loading lipid droplets retained during the first section of the study? With trigs down at 1.8mg/dl by the end of the high dose vitamin E section, how much hepatic steatosis is going on?
Now look at this table, especially insulin and glucose. You'll have to click to enlarge.
All of these FBG values are scarily high, so these volunteers are on the edge of diabetes. What happens when you load up on fish oils? Insulin: No significant change at any time. FBG; both fish oil sessions show increased FBG! For low dose vitamin E section the change had p<0.05, for the vitamin E protected phase it had p<0.001.
That smells of insulin resistance to me and hepatic lipid overload is the easiest explanation.
Aha! So the Greenland eskimo, who refuse to die of cancer on 15g/d of EPA+DHA, must all have been dropping like flies from hepatic cirrhosis. Or type 2 diabetes. Apparently not. This dose of fish oil appears to be fine, just so long as you are not making lipid droplets in the first place. That means no sugar and no excessive alcohol. Remember modest dose alcohol improves insulin sensitivity, so zero alcohol is not needed. The Greenland eskimo were VERY low carb.
So where does that leave fish oil supplements? I think if you have a problem with alcohol they are very bad news and you should be absolutely minimising all forms of PUFA, unless you really want cirrhosis. If you are eating to the ADA or AHA sucrose ladened guidelines and already have "mysterious" raised liver enzymes, you will make an already appalling job worse.
If you are LC and low PUFA in the first place, or even just eating a diet which doesn't generate hepatic lipidosis (minimal sucrose), I think there are advantages to modest dose fish oils for long term changes in insulin sensitivity (another post needed). Dropping your triglycerides in the short term is not one of them, unless you are in to treating numbers, in which case; come back torcetrapib, all is forgiven!
Peter
PS Let's just clarify: There is no "good" or "bad" bad cholesterol. You can fuel your metabolism with saturated fat, and the "good" bad cholesterol goes up as a marker. It's the saturated fat which is really good. Or you fuel your metabolism on sucrose, which raises "bad" bad cholesterol. Stuff the cholesterol. It's a marker you are being evil to your metabolism by eating sucrose, which is what does the damage.
Top left is the nucleus, then there's the stack of endoplasmic reticulum, then a newly synthesised lipid particle stuck on the outer surface of the ER. There is an interesting initial particle labelled I receiving "lipids" (another post there) which goes on to become that unlabelled particle on the outer surface of the ER (call it a nascent lipoprotein). The nascent lipoprotein has two arrows leading away from it representing two metabolic options. The upper arrow goes to a particle labeled III. On this pathway the particle receives saturated fatty acids which, at step V, stop it being destroyed. Destruction is termed PERPP, and the line from PERPP has a flat end meaning its blocked, and the legend "+SFAs" is shown as doing the blocking (by the little curved arrow). Got it? This SFA loaded particle is exported as an IDL (bad) or a large LDL (good). Luckily the IDL appears, on this diagram, to convert to the large form of LDL. But IDL may only be bad if secreted post prandially, I don't know, life is so complex in the ad hoc world of the lipid hypothesis!
Summary so far: Basic particle plus SFA gives the "good" version of "bad" cholesterol. Don't you just love these terms.
Now go back to that nascent lipoprotein and follow the alternative pathway shown by the downwards arrow. This leads to particle labeled IV, having accepted a lipid droplet via the curved arrow. Remember the lipid droplet. It might matter later. Anyway, there is then a dashed arrow showing possible secretion of this particle. If secreted it becomes a large VLDL particle.
While large LDL particles are good guys, large VLDLs are not. In fact they are the precursor to the evil incarnate particle, the small dense LDL. Like Darth Vader, only without the pre death conversion to the good side. Secrete and die.
Fish oils to the rescue! There is an arrow from the PERPP "destructaparticle" system pointing straight to this evil particle, joined by a little "n-3 PUFA-ox" which destroys the evil large VLDL before it ever gets secreted. Less of the large VLDL means less of the small dense LDL. More joy on blood results. Not only do triglycerides drop, it's the evil fraction of triglycerides which drop.
To summarise this pathway: Basic particle plus lipid droplet gives you bad VLDLs and small dense LDLs, unless aborted by omega 3 lipoxidation product (malondialdehyde is claimed but I'll get on to signaling molecules eventually).
All of that is pretty straight forward but it doesn't give us any insight in to anything except how to improve lab numbers.
Here are the nitty gritty questions.
1. Where did the SFAs come from? This is easy. Just follow Krauss' refs and you will find it's diet. Another post there needs writing.
2. Where did the lipid droplet come from? Well, lipid droplets in the liver vary from normal physiological amounts through to hepatic lipidosis. Hepatic lipidosis is a routine feature of the metabolic syndrome. We know that fructose is converted to lipid as rapidly as possible in the liver. We know that insulin inhibits the release of all VLDLs from the liver. Combining fructose with a glucose source (to raise insulin) seems a good way to generate hepatic lipid and block it's release. The bigger the dose and particularly the more continuous the ingestion, the more lipid droplets are likely to form. Sucrose or HFCS would do the job nicely. So might alcohol. Alcohol is interesting. Low doses improve insulin sensitivity and high doses do the opposite. The histpathology of non alcoholic hepatic steatosis is indistinguishable from alcoholic steatosis. They are the same condition. Keeping those lipid droplets in your liver seems a good way to get hepatic lipidosis and subsequent cirrhosis.
3. Where are the lipid droplets going? Well, if you dose up on fish oils the answer is nowhere! Lipid droplets should be off-loaded as small dense LDL precursor particles, the large VLDLs. You're not going to release them if you're on high dose fish oils! So you are trading the drop in "bad" LDLs for a rise in hepatic lipidosis. Are you going to mangle your liver to make Krauss happy? Yes?
Now let's go back and look at the high dose fish oil study from back in 1991.
Here are the triglyceride effects of 30ml fish oil a day for three weeks. Without vitamin E some omega 3s still get to the liver and trigs (probably large VLDLs in this case) drop from 2.6 to 2.0mg/dl. Modest and not statistically significant. Have a wash out period and do it again, but this time preserve the omega 3s with vitamin E. The drop is 48% this time, p<0.01, enough to warm the cockles of a cardiologist's heart.
Remember, these absent triglycerides should have contained lipid droplets which the liver wants rid of. I find it fascinating to see that, in the post washout/pre omega 3+vitamin E session, that the trigs were up at 3.4mg/dl, quite a bit higher than the 2.6 at the start of the study. Is this the liver off loading lipid droplets retained during the first section of the study? With trigs down at 1.8mg/dl by the end of the high dose vitamin E section, how much hepatic steatosis is going on?
Now look at this table, especially insulin and glucose. You'll have to click to enlarge.
All of these FBG values are scarily high, so these volunteers are on the edge of diabetes. What happens when you load up on fish oils? Insulin: No significant change at any time. FBG; both fish oil sessions show increased FBG! For low dose vitamin E section the change had p<0.05, for the vitamin E protected phase it had p<0.001.
That smells of insulin resistance to me and hepatic lipid overload is the easiest explanation.
Aha! So the Greenland eskimo, who refuse to die of cancer on 15g/d of EPA+DHA, must all have been dropping like flies from hepatic cirrhosis. Or type 2 diabetes. Apparently not. This dose of fish oil appears to be fine, just so long as you are not making lipid droplets in the first place. That means no sugar and no excessive alcohol. Remember modest dose alcohol improves insulin sensitivity, so zero alcohol is not needed. The Greenland eskimo were VERY low carb.
So where does that leave fish oil supplements? I think if you have a problem with alcohol they are very bad news and you should be absolutely minimising all forms of PUFA, unless you really want cirrhosis. If you are eating to the ADA or AHA sucrose ladened guidelines and already have "mysterious" raised liver enzymes, you will make an already appalling job worse.
If you are LC and low PUFA in the first place, or even just eating a diet which doesn't generate hepatic lipidosis (minimal sucrose), I think there are advantages to modest dose fish oils for long term changes in insulin sensitivity (another post needed). Dropping your triglycerides in the short term is not one of them, unless you are in to treating numbers, in which case; come back torcetrapib, all is forgiven!
Peter
PS Let's just clarify: There is no "good" or "bad" bad cholesterol. You can fuel your metabolism with saturated fat, and the "good" bad cholesterol goes up as a marker. It's the saturated fat which is really good. Or you fuel your metabolism on sucrose, which raises "bad" bad cholesterol. Stuff the cholesterol. It's a marker you are being evil to your metabolism by eating sucrose, which is what does the damage.
Friday, August 22, 2008
Conditioning Research on bad carbs
Just a 10 second post:
Chris over at Conditioning Research just emailed this link to me. You're all reading Conditioning Research I hope. There'll be a full post over there on it some time soon.
Enjoy.
Peter
OK, now back to the incredible publications from Krauss. He's really getting in the way of signalling molecules for vascular disease.
Chris over at Conditioning Research just emailed this link to me. You're all reading Conditioning Research I hope. There'll be a full post over there on it some time soon.
Enjoy.
Peter
OK, now back to the incredible publications from Krauss. He's really getting in the way of signalling molecules for vascular disease.
Wednesday, August 20, 2008
Rheumatoid arthritis and fasting
Many moons ago (it seems) Bloggeier sent me a pdf of a paper in which a group of researchers made a serious attempt to look at the roll of food allergies in rheumatoid arthritis. They went deeper than simple food challenges, antibody counts and skin prick allergy testing. They looked in to the small intestine, I won't go in to how, and found that people with rheumatoid arthritis have food allergies. Lots of food allergies. Never mind the levels of antibody in the blood, local reaction in the gut picked up far more allergies than it seems fair for anyone to have. Food seems to be important in RA.
I've had this paper lying around for ages but pretty well ignored it due to its vegan/vegetarian stance. I really shouldn't let my biases stop me thinking about interesting stuff. Before I get on to the main jist of this post I'd just like to point out that this group also looked at antibody counts against Proteus mirabilis during their intervention diet and the antibody counts dropped in some subjects. This is important if you have followed Ebringer's work on bacterial mimicry as a trigger for auto immune diseases. There is a protein sequence on the surface of P. mirabilis that is remarkably similar to certain sequences on the HLA molecules associated with RA in humans. The diet changes, used over a year, ONLY helped those people in whom the antibody titre to P. mirabilis dropped. Look at it this way, you could eat a totally allergy free diet, say a cocktail of amino acids and glucose, and P. mirabilis could assemble those amino acids in to an allergenic protein.... Neat hey? RA is associated with antibodies to P. mirabilis and this holds true in various countries around Europe. I'll come back to this later.
Back to the study. They starved their subjects for the first 7 days. As far as I can see they used a water fast. It produced dramatic improvement.
The same group looked at ketosis without calorie deficit and it didn't work, though I don't know what components were used in the less than 40g of carbs per day which were allowed. This may be important, especially if gluten was included in the carbs. In a separate study they looked at various cells in the immune system after a 7 day fast and found that CD4+ lymphocytes, the ones I chatted about here, went sleepeebyes after a fast.
What's happening during a fast? Well, you're not getting any food! So for food allergens it's an absolute, total and complete elimination diet. Then your GUT BACTERIA aren't getting any food either. In fact, your gut bacterial count is likely top drop like a stone when you fast. If you are remotely lucky your P. mirabilis count will also drop and your CD4+ cells might start ignoring both proteus and your HLA DR1 and DR4 molecules.
So fasting is good news. Personally I've only ever played with fasting for 48 hours, in a spirit of companionship with a friend who was fasting for non specific arthritis. We both did 48 hours and, because we were both already in full ketosis, it was easy. That included cooking carbs for my children over that 48 hours. I don't know how easy it would be to extend this to 7 days, and my willpower might be markedly influenced by the size of the RA gorilla sitting on my shoulders. It worked for the non specific arthritis BTW (which has never been worked up and could be rheumatoid).
But no one can fast for ever and expect to stay healthy.
Assuming the improvement occurred, as it really should, anecdote and Kjeldsen-Kragh's work supported, how should you break the fast?
I'd suggest with a single food substance of absolutely no allergenic potential and of no use to P. mirabilis. Beef dripping comes to mind. I discussed long chain fatty acids and starving your gut bacteria in the fiaf posts. The colon, home to P. mirabilis, is anaerobic. Nothing can be done here with a fatty acid. Fatty acids only do oxidation, never fermentation. Aesthetically I guess clarified butter might taste better but watch the casein and lactose. Next would be to add some protein. Not much, say 40 grams as a maximum. You want it all absorbed and none to get through to the colon. Egg yolks first, whole eggs next. If you are still ok you are set up. You can live on eggs and clarified butter. How big is the gorilla?
After that it's a matter of introductions and seeing what happens. In general animal protein won't make it to the colon, cereal protein will always and pulse protein is not worth the risk.
Unless you want to stay in frank raging ketosis some carbs are going to be needed. That's a tricky one. Obviously any fiber will feed colonic bacteria. No fiber. Simple sugars with absorption slowed by a high fat meal might do the job. Optimal icecream comes to mind. A peeled potato might do a reasonable job too, as chips if you like.
It feels a bit odd sitting here musing about a disease as nasty as RA when I don't have it. Having read a little about RA, it seems that musing without the disease is infinitely preferable to musing with the disease.
Peter
I've had this paper lying around for ages but pretty well ignored it due to its vegan/vegetarian stance. I really shouldn't let my biases stop me thinking about interesting stuff. Before I get on to the main jist of this post I'd just like to point out that this group also looked at antibody counts against Proteus mirabilis during their intervention diet and the antibody counts dropped in some subjects. This is important if you have followed Ebringer's work on bacterial mimicry as a trigger for auto immune diseases. There is a protein sequence on the surface of P. mirabilis that is remarkably similar to certain sequences on the HLA molecules associated with RA in humans. The diet changes, used over a year, ONLY helped those people in whom the antibody titre to P. mirabilis dropped. Look at it this way, you could eat a totally allergy free diet, say a cocktail of amino acids and glucose, and P. mirabilis could assemble those amino acids in to an allergenic protein.... Neat hey? RA is associated with antibodies to P. mirabilis and this holds true in various countries around Europe. I'll come back to this later.
Back to the study. They starved their subjects for the first 7 days. As far as I can see they used a water fast. It produced dramatic improvement.
The same group looked at ketosis without calorie deficit and it didn't work, though I don't know what components were used in the less than 40g of carbs per day which were allowed. This may be important, especially if gluten was included in the carbs. In a separate study they looked at various cells in the immune system after a 7 day fast and found that CD4+ lymphocytes, the ones I chatted about here, went sleepeebyes after a fast.
What's happening during a fast? Well, you're not getting any food! So for food allergens it's an absolute, total and complete elimination diet. Then your GUT BACTERIA aren't getting any food either. In fact, your gut bacterial count is likely top drop like a stone when you fast. If you are remotely lucky your P. mirabilis count will also drop and your CD4+ cells might start ignoring both proteus and your HLA DR1 and DR4 molecules.
So fasting is good news. Personally I've only ever played with fasting for 48 hours, in a spirit of companionship with a friend who was fasting for non specific arthritis. We both did 48 hours and, because we were both already in full ketosis, it was easy. That included cooking carbs for my children over that 48 hours. I don't know how easy it would be to extend this to 7 days, and my willpower might be markedly influenced by the size of the RA gorilla sitting on my shoulders. It worked for the non specific arthritis BTW (which has never been worked up and could be rheumatoid).
But no one can fast for ever and expect to stay healthy.
Assuming the improvement occurred, as it really should, anecdote and Kjeldsen-Kragh's work supported, how should you break the fast?
I'd suggest with a single food substance of absolutely no allergenic potential and of no use to P. mirabilis. Beef dripping comes to mind. I discussed long chain fatty acids and starving your gut bacteria in the fiaf posts. The colon, home to P. mirabilis, is anaerobic. Nothing can be done here with a fatty acid. Fatty acids only do oxidation, never fermentation. Aesthetically I guess clarified butter might taste better but watch the casein and lactose. Next would be to add some protein. Not much, say 40 grams as a maximum. You want it all absorbed and none to get through to the colon. Egg yolks first, whole eggs next. If you are still ok you are set up. You can live on eggs and clarified butter. How big is the gorilla?
After that it's a matter of introductions and seeing what happens. In general animal protein won't make it to the colon, cereal protein will always and pulse protein is not worth the risk.
Unless you want to stay in frank raging ketosis some carbs are going to be needed. That's a tricky one. Obviously any fiber will feed colonic bacteria. No fiber. Simple sugars with absorption slowed by a high fat meal might do the job. Optimal icecream comes to mind. A peeled potato might do a reasonable job too, as chips if you like.
It feels a bit odd sitting here musing about a disease as nasty as RA when I don't have it. Having read a little about RA, it seems that musing without the disease is infinitely preferable to musing with the disease.
Peter
Tuesday, August 19, 2008
AGE RAGE and ALE: VLDL degradation and Krauss
When you are waiting for a paradigm shift, you look at the old school dinosaurs with incredulity. One such dinosaur is Krauss. Who is Krauss? Well, you know that time worn phase of Churchill's:
"Man will occasionally stumble over the truth, but most of the time he will pick himself up and continue on"
That man is not really Krauss. Krauss is more like a little kitten, just beginning to use a litter tray and making such a mess trying to bury the truth that it doesn't manage to cover it effectively... The smell is pretty much a give away and someone has to empty the litter tray anyway.
This is Krauss burying the unsavoury truth about low carbohydrate diets as best he can, taken from the abstract.
"Moreover, beneficial lipid changes resulting from a reduced carbohydrate intake were not significant after weight loss"
The kitten's litter tray had to be emptied by Feinman and Volek, who know the truth when they smell it. You can read the full text here but this is the summary:
"Although some effort is required to disentangle the data and interpretation, the recent publication from Krauss et al. [1] should be recognized as a breakthrough. Their findings, presented in Figures 1-5, make it clear that the salutary effects of CR [carbohydrate restriction] on dyslipidemia do not require weight loss, a benefit that is not a feature of strategies based on fat reduction. As such, Krauss et al. [1] provides one of the strongest arguments to date for CR as a fundamental approach to diet, especially for treating atherogenic dyslipidemia"
Don't you just love that first phrase! So that's Krauss, just an introduction. Bearing in mind that all of these people live within the lipid hypothesis.
Why focus on Krauss? Well he wrote this commentary on the paper teasing apart the mechanism of the fasting triglyceride lowering effect of fish oils.
Here is the title of his commentary:
Hold the antioxidants and improve plasma lipids?
It never ceases to amaze me how someone who knows so much about the detail of VLDL production can be so stupid. The first thing is that back in the 1990s the original fish oil work showed that adding vitamin E actually increased the hypolipidaemic effect of fish oils. Maybe Krauss doesn't read old stuff from the wilds of scandinavia. Giving vitamin E by mouth is not remotely the same as dropping some vitamin E or desferroxamine on to cultured liver cells in a petri dish. Ancient practical work makes that crystal clear.
The other bizarre lack of perception is that it is BECAUSE saturated fats are not prone to peroxidation that they don't drop VLDL counts. He actually says this. For goodness sake. The man knows so much. He almost understands, but never quite. Saturated fats don't drop VLDLs, specifically because there is no need for the body to panic about saturated fat based VLDLs entering the blood stream. They don't peroxidise. Maybe Krauss has never heard of Kitava, unless he sees it as a potential market for mass stain medication...Sugar coated VLDLs may be another matter, whatever their lipid content.
And then of course you have to ask whether lowering triglycerides with fish oil does any good at all. The answer to that seems to depend on which study you cite. In some they help, in some they don't. But Krauss can't see beyond a lab number.
Peter
"Man will occasionally stumble over the truth, but most of the time he will pick himself up and continue on"
That man is not really Krauss. Krauss is more like a little kitten, just beginning to use a litter tray and making such a mess trying to bury the truth that it doesn't manage to cover it effectively... The smell is pretty much a give away and someone has to empty the litter tray anyway.
This is Krauss burying the unsavoury truth about low carbohydrate diets as best he can, taken from the abstract.
"Moreover, beneficial lipid changes resulting from a reduced carbohydrate intake were not significant after weight loss"
The kitten's litter tray had to be emptied by Feinman and Volek, who know the truth when they smell it. You can read the full text here but this is the summary:
"Although some effort is required to disentangle the data and interpretation, the recent publication from Krauss et al. [1] should be recognized as a breakthrough. Their findings, presented in Figures 1-5, make it clear that the salutary effects of CR [carbohydrate restriction] on dyslipidemia do not require weight loss, a benefit that is not a feature of strategies based on fat reduction. As such, Krauss et al. [1] provides one of the strongest arguments to date for CR as a fundamental approach to diet, especially for treating atherogenic dyslipidemia"
Don't you just love that first phrase! So that's Krauss, just an introduction. Bearing in mind that all of these people live within the lipid hypothesis.
Why focus on Krauss? Well he wrote this commentary on the paper teasing apart the mechanism of the fasting triglyceride lowering effect of fish oils.
Here is the title of his commentary:
Hold the antioxidants and improve plasma lipids?
It never ceases to amaze me how someone who knows so much about the detail of VLDL production can be so stupid. The first thing is that back in the 1990s the original fish oil work showed that adding vitamin E actually increased the hypolipidaemic effect of fish oils. Maybe Krauss doesn't read old stuff from the wilds of scandinavia. Giving vitamin E by mouth is not remotely the same as dropping some vitamin E or desferroxamine on to cultured liver cells in a petri dish. Ancient practical work makes that crystal clear.
The other bizarre lack of perception is that it is BECAUSE saturated fats are not prone to peroxidation that they don't drop VLDL counts. He actually says this. For goodness sake. The man knows so much. He almost understands, but never quite. Saturated fats don't drop VLDLs, specifically because there is no need for the body to panic about saturated fat based VLDLs entering the blood stream. They don't peroxidise. Maybe Krauss has never heard of Kitava, unless he sees it as a potential market for mass stain medication...Sugar coated VLDLs may be another matter, whatever their lipid content.
And then of course you have to ask whether lowering triglycerides with fish oil does any good at all. The answer to that seems to depend on which study you cite. In some they help, in some they don't. But Krauss can't see beyond a lab number.
Peter
Physiological insulin resistance: Clarification of FBG
This is a cheat "copy-paste" entry trying to clarify the difference between a fasting blood glucose of 5.5mmol/l in an insulin resistant SAD eater and a FBG of 5.5mmol/l in a LC very high fat eater running their metabolism on free fatty acids. The original exchange is in the comments section of this post. Here we go:
Peter,
I've read again you post "Helicobacter and glucose" and yes, the Hisayama study suggested an increase in Fasting Plasma Glucose (FPG) to be a risk factor for gastric cancer (Helicobacter Pylori positive).
A modest increase in the FPG, but not a "modest increase" in the incidence of gastric cancer.
7.2 gastric cancers per 1000 person/years in the high FPG (> 5.8 mmol/l) vs. 2.2 per 1000 person/years in the low FPG (< 5.3 nmol/l) in men.
In women 2.5 per 1000 person/year in the high FPG vs. 0.8 per 1000 person/years in the low FPG.
More than three times higher incidence?!?
Good if you have a low FPG. Ok, but do you have a low FBG if you're on a LC diet?
I don't want to spoil the party to many LCers here, but I read on this Blog that "LC eating rapidly induces insulin resistance" and that "elevated non esterified fatty acids induce physiological insulin resistance and a higher than expected FBG level.".
Uhmm... Bad news for LCers who carry their "beast"?
p.s. - Peter, you said: "This carbohydrate derivative may be more important than sugar for H pylori gastritis, though perhaps NOT IN THE GASTRIC CARCINOGENESIS ASPECT".
I don't understand. Why "not in the carcinogenesis aspect"? Could you explain?
Thanks again.
Marco
Reply
OK, here we go.
A LC eater has a FBG of 5.5mmol/l, technically pre diabetic, but blood insulin is 3.5 IU/ml. This is VERY low. Glucose is in very short supply but blood glucose is maintained by physiological insulin resistance, ie the muscles are full of triglycerides assembled from free fatty acids (NEFA) from lipolysis. The LC eater has breakfast, with enough protein from his eggs or particularly casein from his yoghurt to raise insulin from 3.5 IU/ml to 5.0IU/ml. This inhibits lipolysis enough to reduce NEFA in the bloodstream, intramuscular triglycerides fall and muscle insulin sensitivity returns. There's minimal glucose coming from the gut and so plasma glucose drops to between 4.0 and 5.0mmol/l, probably nearer 4.0mmol/l. It fluctuates between 4.0 and 5.0 after and between each LC meal. In the early hours of the morning there is a growth hormone surge and NEFA from lipolysis peak early morning to give insulin resistant muscles and an elevated FBG.
MEAN glucose over 24h will be in 4 point somethingish, HbA1c will be between 4 and 5%. INSULIN will probably average out around 5-10 IU/ml, averaged out over 24h.
A SAD eater has a FBG of 5.5, prediabetic, because he is prediabetic. His muscles and liver are permanently and pathologically insulin resistant. His pancreas is cranking out 50 IU/ml of insulin to just keep that FBG in the 5.5mmol/l range. He eats bagels, jam and a large mocha for breakfast and his blood glucose hits 15mmol/l. His pancreas ups the insulin output as high as it can get it, perhaps to 150 IU/ml and just manages to to get blood glucose back down to 5.5mmol/l before lunch. Lunch is pasta and the cycle repeats.
Mean glucose over 24 hours will be between 7 and 12mmol/l. HbA1c might just hover around 7%. INSULIN will average 100 IU/ml over the 24 hours.
Helicobacter lives on the hydrogen from flatus, so is present in far too high a number for health in our flatulent carb eater and chronically irritates the gastric lining. Insulin-like Growth Factor-1 (IGF-1) receptor is over expressed and converts disorderly proliferation of gastric mucosa in to gastric cancer. See here.
Insulin acts on IGF-1 receptor to achieve this transformation.
A high carb eater with FBG of 5.5mmol/l implies chronic hyperinsulinaemia, 24/7 and is looking for something to die from.
A LC, very high fat eater with a FBG of 5.5mmol/l implies they haven't had breakfast yet. They are not going to be hyperinsulinaemic at any stage. Unless they eat a bagel instead of their normal bacon and eggs that is. If they do this their blood glucose will hit 10mmol/l before insulin can shut down lipolysis and get the muscle accepting glucose.
It's NOT the FBG of 5.5mmol/l that matters. It's what that means about insulinaemia if you are eating a rice based diet. It's bad. The Kitavans eat a sweet potato based diet, are not insulin resistant and have FBG of 3 point something.
Does that clarify matters? Did I screw up in terms of clarity in the posts on physiological insulin resistance and H. pylori? If so, I'd better get a new post up!
Thinking in terms of FBG = 5.5mmol/l = huge cancer risk is thinking like a cardiologist. Don't go there. Think why, think holistically.
Peter
Peter,
I've read again you post "Helicobacter and glucose" and yes, the Hisayama study suggested an increase in Fasting Plasma Glucose (FPG) to be a risk factor for gastric cancer (Helicobacter Pylori positive).
A modest increase in the FPG, but not a "modest increase" in the incidence of gastric cancer.
7.2 gastric cancers per 1000 person/years in the high FPG (> 5.8 mmol/l) vs. 2.2 per 1000 person/years in the low FPG (< 5.3 nmol/l) in men.
In women 2.5 per 1000 person/year in the high FPG vs. 0.8 per 1000 person/years in the low FPG.
More than three times higher incidence?!?
Good if you have a low FPG. Ok, but do you have a low FBG if you're on a LC diet?
I don't want to spoil the party to many LCers here, but I read on this Blog that "LC eating rapidly induces insulin resistance" and that "elevated non esterified fatty acids induce physiological insulin resistance and a higher than expected FBG level.".
Uhmm... Bad news for LCers who carry their "beast"?
p.s. - Peter, you said: "This carbohydrate derivative may be more important than sugar for H pylori gastritis, though perhaps NOT IN THE GASTRIC CARCINOGENESIS ASPECT".
I don't understand. Why "not in the carcinogenesis aspect"? Could you explain?
Thanks again.
Marco
Reply
OK, here we go.
A LC eater has a FBG of 5.5mmol/l, technically pre diabetic, but blood insulin is 3.5 IU/ml. This is VERY low. Glucose is in very short supply but blood glucose is maintained by physiological insulin resistance, ie the muscles are full of triglycerides assembled from free fatty acids (NEFA) from lipolysis. The LC eater has breakfast, with enough protein from his eggs or particularly casein from his yoghurt to raise insulin from 3.5 IU/ml to 5.0IU/ml. This inhibits lipolysis enough to reduce NEFA in the bloodstream, intramuscular triglycerides fall and muscle insulin sensitivity returns. There's minimal glucose coming from the gut and so plasma glucose drops to between 4.0 and 5.0mmol/l, probably nearer 4.0mmol/l. It fluctuates between 4.0 and 5.0 after and between each LC meal. In the early hours of the morning there is a growth hormone surge and NEFA from lipolysis peak early morning to give insulin resistant muscles and an elevated FBG.
MEAN glucose over 24h will be in 4 point somethingish, HbA1c will be between 4 and 5%. INSULIN will probably average out around 5-10 IU/ml, averaged out over 24h.
A SAD eater has a FBG of 5.5, prediabetic, because he is prediabetic. His muscles and liver are permanently and pathologically insulin resistant. His pancreas is cranking out 50 IU/ml of insulin to just keep that FBG in the 5.5mmol/l range. He eats bagels, jam and a large mocha for breakfast and his blood glucose hits 15mmol/l. His pancreas ups the insulin output as high as it can get it, perhaps to 150 IU/ml and just manages to to get blood glucose back down to 5.5mmol/l before lunch. Lunch is pasta and the cycle repeats.
Mean glucose over 24 hours will be between 7 and 12mmol/l. HbA1c might just hover around 7%. INSULIN will average 100 IU/ml over the 24 hours.
Helicobacter lives on the hydrogen from flatus, so is present in far too high a number for health in our flatulent carb eater and chronically irritates the gastric lining. Insulin-like Growth Factor-1 (IGF-1) receptor is over expressed and converts disorderly proliferation of gastric mucosa in to gastric cancer. See here.
Insulin acts on IGF-1 receptor to achieve this transformation.
A high carb eater with FBG of 5.5mmol/l implies chronic hyperinsulinaemia, 24/7 and is looking for something to die from.
A LC, very high fat eater with a FBG of 5.5mmol/l implies they haven't had breakfast yet. They are not going to be hyperinsulinaemic at any stage. Unless they eat a bagel instead of their normal bacon and eggs that is. If they do this their blood glucose will hit 10mmol/l before insulin can shut down lipolysis and get the muscle accepting glucose.
It's NOT the FBG of 5.5mmol/l that matters. It's what that means about insulinaemia if you are eating a rice based diet. It's bad. The Kitavans eat a sweet potato based diet, are not insulin resistant and have FBG of 3 point something.
Does that clarify matters? Did I screw up in terms of clarity in the posts on physiological insulin resistance and H. pylori? If so, I'd better get a new post up!
Thinking in terms of FBG = 5.5mmol/l = huge cancer risk is thinking like a cardiologist. Don't go there. Think why, think holistically.
Peter
AGE RAGE and ALE: VLDL degradation
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
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
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.
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