It is remarkably widely accepted that fruit and vegetables are good for you. Three a day, five a day, nothing but fruit and vegetables all day..... The problem is that all of the evidence of benefit is epidemiological, and this never proves causation, merely association.
Where does hard science take us? This was the first study I stumbled across, about Polish cyclists.
Effects of a low carbohydrate diet and graded exercise during the follicular and luteal phases on the blood antioxidant status in healthy women.
I only have the abstract of this paper so there is no information as to exactly what comprised the 5% of energy intake which was derived from carbohydrate. Whether it was pure sucrose, apples or bananas, there wasn't a lot there in total. So minimal plant based antioxidants to speak of. End result?
"The 3 days of the L-CHO diet, which had been preceded by glycogen-depleting exercise, resulted in a stimulation of the blood antioxidant defence system in young eumenorrhoeic women both at rest and during the graded cycling exercise to maximal oxygen uptake."
Not bad for three days of dumping the fruit and veg.
The next study, which is an excellent piece of work, was this one:
Green tea extract only affects markers of oxidative status postprandially: lasting antioxidant effect of flavonoid-free diet.
Never mind the green tea bit, that turned out to be irrelevant. It's what happened when almost all fruit and vegetables were removed from the diet of the volunteers for 10 weeks that's interesting. The result being:
"The overall effect of the 10-week period without dietary fruits and vegetables was a decrease in oxidative damage to DNA, blood proteins, and plasma lipids, concomitantly with marked changes in antioxidative defence."
This later study was NOT a low carb study. Potatoes, bread and cake were all included in the sample menus provided in the full text. Please note the DECREASE in oxidative damage to your genes, your protein structure and your lipids. Great stuff fruit, when you put it in the bin.
The conclusion seems to be that there is something nasty in fruit and vegetables, something pro-oxidant. You just have to ask yourself why a plant should manufacture an antioxidant in the first place. You can bet your bottom dollar that it was not for the benefit of herbivores! No, plants hate herbivores and negotiate with substances like strychnine rather than antioxidants.
The most likely candidate for a generic pro-oxidant toxin, produced by plants, is fructose. Plants outside of domestication contain relatively little fructose and appear to use it as a lure, to get their seeds eaten, then use the fruit eater as a transport method. They protect themselves from the fructose with antioxidants. Plants in domestication have been selected, by ourselves, to produce quite unreasonable amounts of fructose (plus glucose and sucrose). Just compare the average Granny Smith to a wild crab apple. A bag of sugar.
Mammals do exactly the same when presented with fructose. They make an antioxidant, in the case of mammals it's uric acid. Uric acid improves the total plasma antioxidant capacity after fruit ingestion. The mechanism is rather well summarised here:
Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: Cause, consequence, or epiphenomenon?
"We conclude that the large increase in plasma total antioxidant capacity observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, but is likely the consequence of increased uric acid levels."
Small studies using intervention strategies show this clearly. Don't forget those marvelous fruits and vegetables in this intervention study too. Oxidised LDL cholesterol anyone?
Or the Dutch study.
So in summary plants produce fructose which is both attractive and damaging to mammals. They protect themselves as best they can with antioxidants.
I don't see any causality between fruit and vegetable consumption and improved health.
Peter
Monday, December 31, 2007
Saturday, December 29, 2007
Atrial tachycardia and fibrillation
Many moons ago I suffered alone as the sole voluntary victim of a major professional examination. My fellow co-sufferer was absent as he had been admitted, as an emergency, to his local coronary care unit. Some sort of severe atrial tachycardia on the eve of our vivas. Stress is not the word.
As he is both highly medically qualified and BUPA insured he got a full and frank discussion with an good cardiologist, who was neither pressured for time nor needing to talk down to his patient.
The summary was that the problem was idiopathic, would be recurrent, would probably get worse and eventually the medics would do some sort of radio frequency catheterisation to ablate or burn out some aberrant conducting tissue in his heart. Sounded like a lot of fun. In the mean time, until the problem had developed enough to warrant the burn, the suggestion was "Here, have some beta blockers to pop whenever the rhythm hits".
He passed the exam.
This was the state of play for several years. We then met up under rather different circumstances and got chatting about life in general, including cardiac rhythm abnormalities. I happened to have this paper on my hard drive:
Differential effects of high-fat and high-carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in lean and obese women
The crucial line is:
"After the CHO-rich meal a greater increase in LF/HF and in plasma NE levels was observed in lean... women, while no differences were observed after the fat-rich meal."
NE stands for norepinephrine, or noradrenaline as we say in the UK. The prime purpose of taking a beta blocker is to block the action of noradrenaline (and adrenaline too, if it's sloshing around). LF/HF is an ECG derived marker of sympathetic nervous system activity.
Just occasionally you are privileged to observe someone have a "eurika" moment.
His comment was:
"That's me! It's always in the evening, after a high carb meal, especially pasta."
You can guess what a "heart healthy" diet had been doing to his rhythm problem! We chatted over lunch, he ate the cheese, ham and salad but skipped the bread. I met him a year latter. He hadn't needed to take another beta blocker.
A close family member developed paroxysmal atrial fibrillation. Again she got worked up by the medics and supplied with a script for, you guessed, a beta blocker. And told to take aspirin daily to stop blood clots forming whenever the atria were fibrillating. The aspirin gave her stomach pain and the beta blocker made her feel exhausted for the 6 days she took it. Stopped the AF though.
I generally keep my mouth shut under these circumstances, but she asked for advice, point blank. It was much tougher to sort out her AF than I had expected. Even with a magnesium supplement (just finished a stint on Weight Watchers, so probably deficient in everything) it took 4 days to stop the fibrillation attacks. I had expected it to clear up after the first LC meal, but I guess it had been on going for 2 years, so some delay is acceptable...
Why don't cardiologist read these papers?
Peter
As he is both highly medically qualified and BUPA insured he got a full and frank discussion with an good cardiologist, who was neither pressured for time nor needing to talk down to his patient.
The summary was that the problem was idiopathic, would be recurrent, would probably get worse and eventually the medics would do some sort of radio frequency catheterisation to ablate or burn out some aberrant conducting tissue in his heart. Sounded like a lot of fun. In the mean time, until the problem had developed enough to warrant the burn, the suggestion was "Here, have some beta blockers to pop whenever the rhythm hits".
He passed the exam.
This was the state of play for several years. We then met up under rather different circumstances and got chatting about life in general, including cardiac rhythm abnormalities. I happened to have this paper on my hard drive:
Differential effects of high-fat and high-carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in lean and obese women
The crucial line is:
"After the CHO-rich meal a greater increase in LF/HF and in plasma NE levels was observed in lean... women, while no differences were observed after the fat-rich meal."
NE stands for norepinephrine, or noradrenaline as we say in the UK. The prime purpose of taking a beta blocker is to block the action of noradrenaline (and adrenaline too, if it's sloshing around). LF/HF is an ECG derived marker of sympathetic nervous system activity.
Just occasionally you are privileged to observe someone have a "eurika" moment.
His comment was:
"That's me! It's always in the evening, after a high carb meal, especially pasta."
You can guess what a "heart healthy" diet had been doing to his rhythm problem! We chatted over lunch, he ate the cheese, ham and salad but skipped the bread. I met him a year latter. He hadn't needed to take another beta blocker.
A close family member developed paroxysmal atrial fibrillation. Again she got worked up by the medics and supplied with a script for, you guessed, a beta blocker. And told to take aspirin daily to stop blood clots forming whenever the atria were fibrillating. The aspirin gave her stomach pain and the beta blocker made her feel exhausted for the 6 days she took it. Stopped the AF though.
I generally keep my mouth shut under these circumstances, but she asked for advice, point blank. It was much tougher to sort out her AF than I had expected. Even with a magnesium supplement (just finished a stint on Weight Watchers, so probably deficient in everything) it took 4 days to stop the fibrillation attacks. I had expected it to clear up after the first LC meal, but I guess it had been on going for 2 years, so some delay is acceptable...
Why don't cardiologist read these papers?
Peter
Meme Watching
If you go to Regina Wilshire's blog and have a look at this page you will get some idea of how a meme fights.
She includes this link, to a post by a doctor with a very simple and highly effective rule of thumb for saving the vision (and legs and kidneys and hearts too, though he doesn't claim this) of diabetic patients.
Quote from Dr Eichenbaum:
I then offer them a simple, five-finger diabetic diet saying: "There are five things you cannot eat: bread and baked goods, potatoes and root vegetables, rice, pasta and fruit except for berries."
The man is a genius. I have a mass of admiration for Dr Bernstein, but look at the simplicity and elegance of this five finger rule from Eichenbaum. It won't get the results that Dr B or Dr Kwasniewski can, but for the average early type 2 diabetic this is a lifesaver. And it's easy.
It's also not very friendly to the low fat meme.
Perhaps some heavy weight guns should be brought in for the defence. Now neither Connie B. Diekman, president, American Dietetic Association - Chicago or Lana Vukovljak, chief executive officer, American Association of Diabetes Educators - Chicago are consciously criminal in their intent. They are merely the product of their education, which is part of the structure generated by the simple idea that dietary fat is bad.
Their advice will do the opposite to that of Dr Eichenbaum. Do you want to be the blind and legless person sat in the wheelchair in the dialysis room? Following the low fat meme is your ticket there. Diekman and Vukovljak do not intend this, but the meme generates it.
As I said in my last post, the meme does not need healthy or long lived patients.
The next post from Regina documents the pro active behaviours set out by the low fat meme to expand its client base. If you can read this post and not be deeply disturbed you have eaten too many carbohydrates for too long.
To quote Regina:
"How this expert committee sleeps at night, I don't know!"
It's obvious, by eating carbs at bed time...
I would stress that these people are not acting with deliberate criminal intent. They are again simply part of the complex structure generated by the simple idea that fat is bad for you. You can bet they do not recommend the Atkins diet for teenagers! Or themselves.
Early intervention is the current UK buzz word, we'll be following along very soon...
I'm worried.
Peter
She includes this link, to a post by a doctor with a very simple and highly effective rule of thumb for saving the vision (and legs and kidneys and hearts too, though he doesn't claim this) of diabetic patients.
Quote from Dr Eichenbaum:
I then offer them a simple, five-finger diabetic diet saying: "There are five things you cannot eat: bread and baked goods, potatoes and root vegetables, rice, pasta and fruit except for berries."
The man is a genius. I have a mass of admiration for Dr Bernstein, but look at the simplicity and elegance of this five finger rule from Eichenbaum. It won't get the results that Dr B or Dr Kwasniewski can, but for the average early type 2 diabetic this is a lifesaver. And it's easy.
It's also not very friendly to the low fat meme.
Perhaps some heavy weight guns should be brought in for the defence. Now neither Connie B. Diekman, president, American Dietetic Association - Chicago or Lana Vukovljak, chief executive officer, American Association of Diabetes Educators - Chicago are consciously criminal in their intent. They are merely the product of their education, which is part of the structure generated by the simple idea that dietary fat is bad.
Their advice will do the opposite to that of Dr Eichenbaum. Do you want to be the blind and legless person sat in the wheelchair in the dialysis room? Following the low fat meme is your ticket there. Diekman and Vukovljak do not intend this, but the meme generates it.
As I said in my last post, the meme does not need healthy or long lived patients.
The next post from Regina documents the pro active behaviours set out by the low fat meme to expand its client base. If you can read this post and not be deeply disturbed you have eaten too many carbohydrates for too long.
To quote Regina:
"How this expert committee sleeps at night, I don't know!"
It's obvious, by eating carbs at bed time...
I would stress that these people are not acting with deliberate criminal intent. They are again simply part of the complex structure generated by the simple idea that fat is bad for you. You can bet they do not recommend the Atkins diet for teenagers! Or themselves.
Early intervention is the current UK buzz word, we'll be following along very soon...
I'm worried.
Peter
Friday, December 28, 2007
Memes and fat
I've gotten side tracked.
In the Fiaf post I suggested that our gut microbiota might be controlling both our metabolism and possibly our behaviour. This led to some very interesting email conversation off blog. Stan broached the subject of the ability of protozoal parasites to influence the behaviour of their hosts. My wife immediately pulled a pathology textbook off of the shelves and pointed out an interesting bug, this time a slightly larger parasite.
Look at the complexity of the ant behaviour induced by the fluke to ensure completion of it's life cycle.The ant has a few cells in a ganglion for its brain. I'm not sure what the fluke has in terms of a nervous system... Yet the ant does as the fluke needs.
The protozoal parasite which Stan pointed me towards was actually toxoplasma gondii.
I have spent many years dutifully blood testing neurological patients for evidence of active toxo infection, occasionally with some success. I never had the slightest idea that toxoplasma gondii was neurotropic for a reason, other than some quirk of misfortune on the part of the patient. But here is the reason. When the toxoplasmosis organism is in its intermediate host, which should be a mouse or rat, it wants to go home to where it belongs, which is in the digestive system of a cat. It wants the rodent to get eaten. So it pops in to the mouse's brain, removes all fear of cats, makes the smell of cat highly attractive and then lets the meeting of these two mammals allow it to complete its life cycle. But it doesn't want the mouse to die in any other way, say at the hands of a human or a fox or under the wheel of a car. So normal fears are left strictly in tact to maximise survival chances, enhancing "cat-meeting" opportunities. Not bad for a single celled organism.
That's attributing an awful lot of "intelligence" to a single celled organism. But evolution has had a lot of time to play with and this is the sort of thing that is happening in your own back garden today. Perhaps it is less subtle than the microbiota and Faif, but you can see a common drive to improve the survival chances of a particular organism(s). Not even I am suggesting that either toxoplamsa, dicrocoelium or the gut microbiota have any specific "plan" in "mind". The "plan" harks back to chaos theory and the generation of complex structures or behaviours from very simple basic rules or equations. It is clearly possible to develop very complex structures (or patterns like fractals) from what can be very simple ground rules. And this can include very specific effects on complex mammalian behaviour in the result.
From here we wandered away from microbes to ideas or "memes", in particular to the parallels between the two. Humans carry ideas which form cultures that can change and evolve with time. As best I can understand it, a meme is a unit of cultural information, in much the same way as a gene is a unit of biological information. Both generate systems which can not only evolve, but also compete. There is an obvious comparison is between groups of memes forming cultures and groups of genes forming organisms. Memes are present in and are carried by the human brain, supported by the human body. Some are highly beneficial to that human body, others less so.
Some memes are just so unpleasant that they cannot occur without severely impacting their host. An ebola virus like meme came and went with the Rwandan genocide. Too violent and too destructive to persist, yet it probably seemed like a good idea at the time (to those carrying the meme of cultural superiority that is). On a bigger scale we have the Holocaust of the last world war doing exactly the same thing. Thankfully neither has become a cultural norm.
But not all destructive ideas are so transient. Some have a low enough level of virulence that they can shape human behaviours over generations and DO become the cultural norm. I've yet to read Garry Taubes' book Good Calories, Bad Calories, but it is very obvious that there is a "low fat" meme which has infected human culture for many generations. It has so far proven to be essentially indestructable. The low fat meme has nothing to do with science, it is an idea which has found fertile ground in the human mind and is doing very well thank you very much. As with other memes (or genes for that matter) its "plan" is self perpetuation. If it can influence the physical form of humans to improve its persistence I see no reason why it shouldn't do so.
If the low fat meme produces a human behavior (eating low fat junk food) which damages the human brain in such a way as to allow the meme to spread more effectively, the scene really is truly set for persistence.
But this is looking memes down at the virus level. Think back to chaos theory and the generation of fractals. Then think about big culture. Are there any major cultural icons of the low fat meme? Obviously the national diabetes associations of the developed nations are products of the low fat meme. I can see no other explanation for their bizarre advice to diabetics. Obviously the American Heart Association competes well too. Weight Watchers.
These are all organisations generated by the low fat meme which are essentially driven by their own need for self perpetuation. The health and well being of the patients they purport to help is unimportant. Converting healthy people in to diabetics strengthens the meme. This can be surreptitiously achieved by lowering the threshold for diabetes diagnosis and more concretely by strengthening the advice to currently healthy people to eat a low fat diet. On a fixed intake of calories this essentially means a high carbohydrate diet. The rollercoaster of high and low blood glucose levels and the corresponding swings in blood insulin levels do nothing for brain function. If anyone thinks that a high carbohydrate diet helps brain function they just need to think about the classification of Alzheimer's as type three diabetes. Or have a read at my post here.
Generating a body, and particularly a brain, damaged by the low fat meme is the perfect base for further propagation of the meme.
The meme is getting more aggressive as it gets backed in to a corner by the islands of hard facts and science based common sense. Time to look at a few examples from Regina Wilshire's blog that illustrates these points.
Peter
In the Fiaf post I suggested that our gut microbiota might be controlling both our metabolism and possibly our behaviour. This led to some very interesting email conversation off blog. Stan broached the subject of the ability of protozoal parasites to influence the behaviour of their hosts. My wife immediately pulled a pathology textbook off of the shelves and pointed out an interesting bug, this time a slightly larger parasite.
Look at the complexity of the ant behaviour induced by the fluke to ensure completion of it's life cycle.The ant has a few cells in a ganglion for its brain. I'm not sure what the fluke has in terms of a nervous system... Yet the ant does as the fluke needs.
The protozoal parasite which Stan pointed me towards was actually toxoplasma gondii.
I have spent many years dutifully blood testing neurological patients for evidence of active toxo infection, occasionally with some success. I never had the slightest idea that toxoplasma gondii was neurotropic for a reason, other than some quirk of misfortune on the part of the patient. But here is the reason. When the toxoplasmosis organism is in its intermediate host, which should be a mouse or rat, it wants to go home to where it belongs, which is in the digestive system of a cat. It wants the rodent to get eaten. So it pops in to the mouse's brain, removes all fear of cats, makes the smell of cat highly attractive and then lets the meeting of these two mammals allow it to complete its life cycle. But it doesn't want the mouse to die in any other way, say at the hands of a human or a fox or under the wheel of a car. So normal fears are left strictly in tact to maximise survival chances, enhancing "cat-meeting" opportunities. Not bad for a single celled organism.
That's attributing an awful lot of "intelligence" to a single celled organism. But evolution has had a lot of time to play with and this is the sort of thing that is happening in your own back garden today. Perhaps it is less subtle than the microbiota and Faif, but you can see a common drive to improve the survival chances of a particular organism(s). Not even I am suggesting that either toxoplamsa, dicrocoelium or the gut microbiota have any specific "plan" in "mind". The "plan" harks back to chaos theory and the generation of complex structures or behaviours from very simple basic rules or equations. It is clearly possible to develop very complex structures (or patterns like fractals) from what can be very simple ground rules. And this can include very specific effects on complex mammalian behaviour in the result.
From here we wandered away from microbes to ideas or "memes", in particular to the parallels between the two. Humans carry ideas which form cultures that can change and evolve with time. As best I can understand it, a meme is a unit of cultural information, in much the same way as a gene is a unit of biological information. Both generate systems which can not only evolve, but also compete. There is an obvious comparison is between groups of memes forming cultures and groups of genes forming organisms. Memes are present in and are carried by the human brain, supported by the human body. Some are highly beneficial to that human body, others less so.
Some memes are just so unpleasant that they cannot occur without severely impacting their host. An ebola virus like meme came and went with the Rwandan genocide. Too violent and too destructive to persist, yet it probably seemed like a good idea at the time (to those carrying the meme of cultural superiority that is). On a bigger scale we have the Holocaust of the last world war doing exactly the same thing. Thankfully neither has become a cultural norm.
But not all destructive ideas are so transient. Some have a low enough level of virulence that they can shape human behaviours over generations and DO become the cultural norm. I've yet to read Garry Taubes' book Good Calories, Bad Calories, but it is very obvious that there is a "low fat" meme which has infected human culture for many generations. It has so far proven to be essentially indestructable. The low fat meme has nothing to do with science, it is an idea which has found fertile ground in the human mind and is doing very well thank you very much. As with other memes (or genes for that matter) its "plan" is self perpetuation. If it can influence the physical form of humans to improve its persistence I see no reason why it shouldn't do so.
If the low fat meme produces a human behavior (eating low fat junk food) which damages the human brain in such a way as to allow the meme to spread more effectively, the scene really is truly set for persistence.
But this is looking memes down at the virus level. Think back to chaos theory and the generation of fractals. Then think about big culture. Are there any major cultural icons of the low fat meme? Obviously the national diabetes associations of the developed nations are products of the low fat meme. I can see no other explanation for their bizarre advice to diabetics. Obviously the American Heart Association competes well too. Weight Watchers.
These are all organisations generated by the low fat meme which are essentially driven by their own need for self perpetuation. The health and well being of the patients they purport to help is unimportant. Converting healthy people in to diabetics strengthens the meme. This can be surreptitiously achieved by lowering the threshold for diabetes diagnosis and more concretely by strengthening the advice to currently healthy people to eat a low fat diet. On a fixed intake of calories this essentially means a high carbohydrate diet. The rollercoaster of high and low blood glucose levels and the corresponding swings in blood insulin levels do nothing for brain function. If anyone thinks that a high carbohydrate diet helps brain function they just need to think about the classification of Alzheimer's as type three diabetes. Or have a read at my post here.
Generating a body, and particularly a brain, damaged by the low fat meme is the perfect base for further propagation of the meme.
The meme is getting more aggressive as it gets backed in to a corner by the islands of hard facts and science based common sense. Time to look at a few examples from Regina Wilshire's blog that illustrates these points.
Peter
Monday, December 17, 2007
Who pays the piper.
This study, available in full text for free, makes some very interesting reading.
It compares the end results of two diets of identical macronutrient ratios, but differing sucrose contents, on insulin sensitivity. The subjects were moderately insulin resistant, slightly heavy volunteers. Result: Obtaining 25% of your calories from sucrose, compared to 10%, has absolutely no adverse effect on your insulin sensitivity. That's s relief to any sugar dependent young white male on the verge of type 2 diabetes. Or any researcher who's funding comes from here:
" This study was supported by an unrestricted research grant from The Sugar Bureau and Suikerstichting, the Netherlands".
But the study is very strange. It only compared the end results of the two diets. Neither diet was the volunteers' habitual diet. There was no formal comparison of the effect of the two new diets on the initial baseline parameters of health in the study participants. Oddly enough some of the changes do get mentioned in the discussion, others don't, on a rather random basis. The excess rise in LDL cholesterol (for anyone who cares) in the 25% sucrose diet compared to the 10% sucrose diet gets attributed to the higher saturated fat content of the high sucrose diet. What sort of dietician fails to control for this variable in a study reporting cholesterol levels? No need to answer that. And why not attribute it to the sucrose?
But you can look at a small number of the baseline data, selected by Dr Black and co, although not all of what was certainly measured.
So if you got to Table 2 of the results, on page 3568, line 8, you can see the fasting plasma glucose was 4.8mmol/l. Normal.
After 6 weeks on the dietician designed diet what was the fasting blood glucose? This never gets a mention anywhere in the paper. But it's there, tucked away in a table in the discussion of all places. Look at Table 7, page 3570, third variable reported.
Ooooooh, it's 5.6mmol/l. Whichever diet you look at.
A fasting plasma glucose of 4.8mmol/l for a carboholic is normal. A value of 5.6mmol/l is prediabetic.
How do you convert a slightly chunky healthy young Irish chap in to a prediabetic?
Easy, get a university nutritionist to design his diet.
Those freeliving chaps were eating 45% of calories as carbohydrate and 35% as fat before the study. Just increase the carbohydrate to 55% of calories and reduce the fat to 33% and voila, prediabetes in 6 weeks. Irrespective of sucrose content.
But don't mention this anywhere in the paper.
Why not? Re check who funded the study.
The purpose of the study was to show sucrose is harmless. It was not designed to look at the effect of carbohydrate in general on fasting blood glucose. It did that by accident.
Sometimes the truth just slips in and no one notices. Or they're not saying.
Enough of this depressing study. A much better one for the next post.
Peter
It compares the end results of two diets of identical macronutrient ratios, but differing sucrose contents, on insulin sensitivity. The subjects were moderately insulin resistant, slightly heavy volunteers. Result: Obtaining 25% of your calories from sucrose, compared to 10%, has absolutely no adverse effect on your insulin sensitivity. That's s relief to any sugar dependent young white male on the verge of type 2 diabetes. Or any researcher who's funding comes from here:
" This study was supported by an unrestricted research grant from The Sugar Bureau and Suikerstichting, the Netherlands".
But the study is very strange. It only compared the end results of the two diets. Neither diet was the volunteers' habitual diet. There was no formal comparison of the effect of the two new diets on the initial baseline parameters of health in the study participants. Oddly enough some of the changes do get mentioned in the discussion, others don't, on a rather random basis. The excess rise in LDL cholesterol (for anyone who cares) in the 25% sucrose diet compared to the 10% sucrose diet gets attributed to the higher saturated fat content of the high sucrose diet. What sort of dietician fails to control for this variable in a study reporting cholesterol levels? No need to answer that. And why not attribute it to the sucrose?
But you can look at a small number of the baseline data, selected by Dr Black and co, although not all of what was certainly measured.
So if you got to Table 2 of the results, on page 3568, line 8, you can see the fasting plasma glucose was 4.8mmol/l. Normal.
After 6 weeks on the dietician designed diet what was the fasting blood glucose? This never gets a mention anywhere in the paper. But it's there, tucked away in a table in the discussion of all places. Look at Table 7, page 3570, third variable reported.
Ooooooh, it's 5.6mmol/l. Whichever diet you look at.
A fasting plasma glucose of 4.8mmol/l for a carboholic is normal. A value of 5.6mmol/l is prediabetic.
How do you convert a slightly chunky healthy young Irish chap in to a prediabetic?
Easy, get a university nutritionist to design his diet.
Those freeliving chaps were eating 45% of calories as carbohydrate and 35% as fat before the study. Just increase the carbohydrate to 55% of calories and reduce the fat to 33% and voila, prediabetes in 6 weeks. Irrespective of sucrose content.
But don't mention this anywhere in the paper.
Why not? Re check who funded the study.
The purpose of the study was to show sucrose is harmless. It was not designed to look at the effect of carbohydrate in general on fasting blood glucose. It did that by accident.
Sometimes the truth just slips in and no one notices. Or they're not saying.
Enough of this depressing study. A much better one for the next post.
Peter
Saturday, December 15, 2007
Fiaf: Where next?
The Fiaf paper and review I've been discussing both cover high quality basic research. This is the sort of thing which gives us serious insights in to how our bodies work. They certainly give credence, with some lateral thinking, to the ability of high fat diets to assist weight loss. The germ free/high Fiaf mice also had a higher metabolic rate and were more active than their control companions (or themselves once colonised and fed the normal 10% fat, high carbohydrate rodent chow). These also seem desirable attributes which LC eaters tend to notice when they switch to fat burning.
In view of the enormous reluctance of the current health care system to accept the hard data supporting low carbohydrate eating I was curious as to how these basic scientists might take their work forward in to the clinical field. I'm slightly doubtful that the advice would be a high fat diet, if they wished to continue to obtain funding.
So here is most of the last sentence of the discussion from the 2007 review paper:
"these findings suggest that the gut microbiota contributes to mammalian adiposity by regulating more than one node within the metabolic network that controls bioenergetics. Manipulating microbial characteristics in ways that impact calorie harvest from a diet, and/or Fiaf expression, or Fiaf-mediated control of Pgc-1alpha, may represent new strategies for modifying host energy balance to promote health"
I can certainly go with the first suggestion, but my own decision to use a high fat diet, however logical, may be different to what may be tried by the mainstream medics.
Tinkering with Fiaf at the gut wall level MIGHT be safe, after all not eating for a day bumps the levels up. So perhaps here is a target for a slimming drug. But what will happen if you bump up a starvation hormone, with it's cascade of effects down stream which increase fat oxidation, yet continue to feed a diet based on glucose? I have a bad feeling about this. It is very suggestive of clofibrate, pioglitazone and rosiglitazone, none of which feature on my must-have list. You are well in to the realms of the law of Unintended Consequences with this approach.
What about that last suggestion of tinkering with Pgc-1alpha? Just have a look at the stub in wikipedia to get some idea of what this co factor does.
I'm not sure I would personally want to start tinkering with a massive metabolic control switch, many of the normal effects of which are still unknown, in the hope of improving human health.
Unintended Consequences anyone?
Eggs and butter for breakfast seems a much safer option.
Peter
In view of the enormous reluctance of the current health care system to accept the hard data supporting low carbohydrate eating I was curious as to how these basic scientists might take their work forward in to the clinical field. I'm slightly doubtful that the advice would be a high fat diet, if they wished to continue to obtain funding.
So here is most of the last sentence of the discussion from the 2007 review paper:
"these findings suggest that the gut microbiota contributes to mammalian adiposity by regulating more than one node within the metabolic network that controls bioenergetics. Manipulating microbial characteristics in ways that impact calorie harvest from a diet, and/or Fiaf expression, or Fiaf-mediated control of Pgc-1alpha, may represent new strategies for modifying host energy balance to promote health"
I can certainly go with the first suggestion, but my own decision to use a high fat diet, however logical, may be different to what may be tried by the mainstream medics.
Tinkering with Fiaf at the gut wall level MIGHT be safe, after all not eating for a day bumps the levels up. So perhaps here is a target for a slimming drug. But what will happen if you bump up a starvation hormone, with it's cascade of effects down stream which increase fat oxidation, yet continue to feed a diet based on glucose? I have a bad feeling about this. It is very suggestive of clofibrate, pioglitazone and rosiglitazone, none of which feature on my must-have list. You are well in to the realms of the law of Unintended Consequences with this approach.
What about that last suggestion of tinkering with Pgc-1alpha? Just have a look at the stub in wikipedia to get some idea of what this co factor does.
I'm not sure I would personally want to start tinkering with a massive metabolic control switch, many of the normal effects of which are still unknown, in the hope of improving human health.
Unintended Consequences anyone?
Eggs and butter for breakfast seems a much safer option.
Peter
Animal fat and cholesterol
There are a couple more posts kicking around from the Fiaf paper but as an interim here is a nice paper ref those cholesterol levels and animal fat.
Newbold appears to be one of those lone researchers who's work is a bit out on a limb. But because his data fit my preconceptions I tend to believe him!
Peter
Newbold appears to be one of those lone researchers who's work is a bit out on a limb. But because his data fit my preconceptions I tend to believe him!
Peter
Wednesday, December 12, 2007
Fiaf: Starving amidst plenty
Our gut bacteria live in our gut. OK that's obvious, but if the system is in good working order they are almost all, several trillion of them, in our colon.
Our colon is anaerobic. No oxygen.
In general oxygen is required to accept electrons at the end of the respiratory chain. As mammals we are exquisitely dependent on molecular oxygen for this. Not so the bacteria. Given a few billion years you can learn how to use other susbstances, sulphur being a favourite, to accept the respiratory chain driving electrons. In fact sulphur may have come first. Bacteria were around long before plants poisoned the planet with oxygen. Anyone who has eaten a sulphur and fiber rich meal will be well aware that hydrogen sulphide can be a highly aromatic feature of subsequent flatus. I won't translate that, let's just say roomclearing.
So bacteria are pretty sophisticated at energy extraction. I mentioned extracting sugars from fiber and extracting short chain fatty acids from sugars in my last post. So if there is some sort of electron acceptor around bacteria will extract energy. But some circumstances defeat even these metabolic wizards.
Strict anaerobic conditions impose certain limits.
Getting energy out of glucose without molecular oxygen is easy, just rearrange the molecule to free up the oxygen from those six hydroxyl groups. The end product can be anything from methane through ethanol, hydrogen or acetic acid. They all contain less oxygen than the parent glucose because the parent glucose has provided oxygen to the gut bacteria.
Given long enough bacteria will extract so much oxygen from organic molecules that all that is left is carbon and hydrogen. Bury an intact swamp with some bacteria for long enough and you end up with natural gas and crude oil.
But what I'm really driving at is that not even bacteria can extract energy from pure hydrocarbon molecules without oxygen.
Our colon is anaerobic. Eating a balanced diet feeds our gut bacteria with fiber. In return they grace us with flatulence and suppressed levels of Fiaf. At their behest we store fat under these conditions.
The bacteria never ask for the fat back directly as there is very little even the most enthusiastic bacterium can do with palmitic acid under the strict anaerobic conditions of the colon. Long chain fatty acids, especially the saturated ones, contain enormous amounts of energy per gram but we absolutely must have oxygen to liberate it.
So let's consider a normal fiber consuming rolly-polly human being carrying around 20kg of excess fat, property of their gut bacteria. Each day they consume their routine 1500kcal of food, which has failed to allow weight loss while it has been made up of a balanced fiber rich diet.
Then one day they eat 1500kcal of lard. Please don't try this at home, it's a thought experiment, strictly in your head. Under the anaerobic conditions of the colon there is no way the bacteria there can tap in to any of this energy, assuming some of the fat gets that far. It just might, which could be unpleasant.
So the gut bacteria are swimming in a sea of energy rich lipid, without any oxygen to work with. They cannot extract any of this energy. Energy deprived bacteria are hungry.
The human is not hungry!
What happens to Fiaf when our gut bacteria get hungry? As far as the gut bacteria are concerned this is starvation land and it's time to get Fiaf levels up, mobilise some host fat and get the host metabolism switched to serious fat burning. Weight loss under these circumstances becomes easy.
So with a little information it is quite possible to manipulate our gut bacteria and modify their ability to manipulate us.
High fat diets are a simple energy balance between us and our prey. Once the carbs, especially fiber rich carbs, come in there is a whole new ball game going on which includes our gut bacteria.
There is a paper out there on pubmed which I found and lost and cannot re locate. If our gut bacteria control our weight to their own advantage, wouldn't you expect them to control our food preferences to their own advantage too? They actually do this by altering peptide neurotransmitters in our brain. Anyone with a reference for this? I'd love a copy!
But it's worth noting that humans LOVE sweet things, yet there is absolutely no biological need for any carbohydrate in our diet whatsoever, except avoiding full ketosis might be benefical in terms of energy balance.
Which organisms want us to eat carbohydrate? The ones that want us to be fat! And, no, I'm not talking about the FDA of the USA here, though that organisation does seem to be acting on behalf of our gut bacteria.
You want to control your weight? Control your own energy balance.
To quote the title from one of Barry Groves' books:
Eat fat get thin.
Peter
Our colon is anaerobic. No oxygen.
In general oxygen is required to accept electrons at the end of the respiratory chain. As mammals we are exquisitely dependent on molecular oxygen for this. Not so the bacteria. Given a few billion years you can learn how to use other susbstances, sulphur being a favourite, to accept the respiratory chain driving electrons. In fact sulphur may have come first. Bacteria were around long before plants poisoned the planet with oxygen. Anyone who has eaten a sulphur and fiber rich meal will be well aware that hydrogen sulphide can be a highly aromatic feature of subsequent flatus. I won't translate that, let's just say roomclearing.
So bacteria are pretty sophisticated at energy extraction. I mentioned extracting sugars from fiber and extracting short chain fatty acids from sugars in my last post. So if there is some sort of electron acceptor around bacteria will extract energy. But some circumstances defeat even these metabolic wizards.
Strict anaerobic conditions impose certain limits.
Getting energy out of glucose without molecular oxygen is easy, just rearrange the molecule to free up the oxygen from those six hydroxyl groups. The end product can be anything from methane through ethanol, hydrogen or acetic acid. They all contain less oxygen than the parent glucose because the parent glucose has provided oxygen to the gut bacteria.
Given long enough bacteria will extract so much oxygen from organic molecules that all that is left is carbon and hydrogen. Bury an intact swamp with some bacteria for long enough and you end up with natural gas and crude oil.
But what I'm really driving at is that not even bacteria can extract energy from pure hydrocarbon molecules without oxygen.
Our colon is anaerobic. Eating a balanced diet feeds our gut bacteria with fiber. In return they grace us with flatulence and suppressed levels of Fiaf. At their behest we store fat under these conditions.
The bacteria never ask for the fat back directly as there is very little even the most enthusiastic bacterium can do with palmitic acid under the strict anaerobic conditions of the colon. Long chain fatty acids, especially the saturated ones, contain enormous amounts of energy per gram but we absolutely must have oxygen to liberate it.
So let's consider a normal fiber consuming rolly-polly human being carrying around 20kg of excess fat, property of their gut bacteria. Each day they consume their routine 1500kcal of food, which has failed to allow weight loss while it has been made up of a balanced fiber rich diet.
Then one day they eat 1500kcal of lard. Please don't try this at home, it's a thought experiment, strictly in your head. Under the anaerobic conditions of the colon there is no way the bacteria there can tap in to any of this energy, assuming some of the fat gets that far. It just might, which could be unpleasant.
So the gut bacteria are swimming in a sea of energy rich lipid, without any oxygen to work with. They cannot extract any of this energy. Energy deprived bacteria are hungry.
The human is not hungry!
What happens to Fiaf when our gut bacteria get hungry? As far as the gut bacteria are concerned this is starvation land and it's time to get Fiaf levels up, mobilise some host fat and get the host metabolism switched to serious fat burning. Weight loss under these circumstances becomes easy.
So with a little information it is quite possible to manipulate our gut bacteria and modify their ability to manipulate us.
High fat diets are a simple energy balance between us and our prey. Once the carbs, especially fiber rich carbs, come in there is a whole new ball game going on which includes our gut bacteria.
There is a paper out there on pubmed which I found and lost and cannot re locate. If our gut bacteria control our weight to their own advantage, wouldn't you expect them to control our food preferences to their own advantage too? They actually do this by altering peptide neurotransmitters in our brain. Anyone with a reference for this? I'd love a copy!
But it's worth noting that humans LOVE sweet things, yet there is absolutely no biological need for any carbohydrate in our diet whatsoever, except avoiding full ketosis might be benefical in terms of energy balance.
Which organisms want us to eat carbohydrate? The ones that want us to be fat! And, no, I'm not talking about the FDA of the USA here, though that organisation does seem to be acting on behalf of our gut bacteria.
You want to control your weight? Control your own energy balance.
To quote the title from one of Barry Groves' books:
Eat fat get thin.
Peter
Monday, December 10, 2007
Fiaf: Who's fat is it anyway?
Bacteria have been around for a long time, much longer than the eukaryotes and MUCH longer than us Johnny-come-lately multicellular organisms. They know where it's at as regards survival. Anyone who thinks of bacteria as "simple" clearly has no concept of the effect of a few billion years of selection pressure on the sophistication of survival strategies.
There is a lot of information in this paper and the current review below:
The gut microbiota as an environmental factor that regulates fat storage.
Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.
From what I can extract there are a number of things that our gut bacteria do that are very interesting. Obviously gut bacteria are both careless and careful. That is, they don't care about you or me. Their priority is to maintain an environment which is convivial to their own chances of repeated division. Keeping us alive helps.
They do this rather well. The main aspect of Bäckhed et al's research I want to talk about is Fiaf and fat storage.
Fiaf stands for Fasting induced adipose factor. Fiaf (amongst its many other actions) blocks the action of lipoprotein lipase, that enzyme which packs on the pounds of fat in humans. Fiaf is normally made by our liver, muscles and in particularly by our gut wall in times of starvation. It appears to be a signal to the body to stop storing fat, crank up blood triglycerides and start running metabolic processes on fat, but fat derived from our adipocytes (obviously, it's a starvation hormone, there is no dietary fat).
But Fiaf from the gut wall is under the control of the gut bacteria. Active bacteria stop Fiaf production, inactive (hungry) bacteria allow Fiaf to be produced. It's pretty obvious that starvation gives quiescent gut bacteria, to the point where starvation actually mimics not having any gut bacteria at all.
Germ free mice really do have no gut bacteria at all, so they produce lots of Fiaf, all of the time. This suppresses their LPL and so they are slim, whatever they eat! Bacteria added to their gut immediately suppress Fiaf production from the intestine wall and so allow recently colonised (ex germ free) mice to store fat as soon as ever they have access to food. Lots of fat.
Also the mice rapidly become insulin resistant as well as obese. That's interesting.
But under more standard laboratory conditions Fiaf is ONLY produced from the gut of normal animals in times of starvation. My presumption here is that it is the hunger of the GUT BACTERIA that allow Fiaf levels to rise, which allows the stored fat of the host to be burned, in order to keep their microbial bioreactor (our colon) alive. A dead host is of no use to a bacterium.
Why have the bacteria organised things this way?
A bacterium cannot store energy. It's got no where to put it, no storage organ. But after surviving for millenia they are hardly likley to put their furture survival down to chance. So they take any energy source that they can get, particularly those sugar moieties that mammalian digestion cannot hope to extract, those from fiber. They extract sugars, upregulate sugar transport across the intestinal wall, modify the host's liver metaboism to convert them to triglycerides and then make sure lipoprotein lipase is fully active to store the triglycerides in adipocytes. Other bacteria ferment these sugars to short chain fatty acids, then shunt these to the liver for triglyceride production too. All the same in the end. It's bacterial derived energy stored as mammalian fat.
Fiaf also controls a host of fat burning genes. So the gut microbes only allow Fiaf to rise when they, and by inference their hosts, are hungry and need stored fat to live on. By doing this they allow us to burn "our" fat to get about to find more food. But who's fat is it? Which organsims organised its storage? Which organisms are controlling access?
It's not our fat.
Hunger, of the intestinal bacteria, is needed to before it can be accessed.
There is a point to all this, beyond it being absolutely fascinating.
That'll be the next post.
Peter
There is a lot of information in this paper and the current review below:
The gut microbiota as an environmental factor that regulates fat storage.
Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.
From what I can extract there are a number of things that our gut bacteria do that are very interesting. Obviously gut bacteria are both careless and careful. That is, they don't care about you or me. Their priority is to maintain an environment which is convivial to their own chances of repeated division. Keeping us alive helps.
They do this rather well. The main aspect of Bäckhed et al's research I want to talk about is Fiaf and fat storage.
Fiaf stands for Fasting induced adipose factor. Fiaf (amongst its many other actions) blocks the action of lipoprotein lipase, that enzyme which packs on the pounds of fat in humans. Fiaf is normally made by our liver, muscles and in particularly by our gut wall in times of starvation. It appears to be a signal to the body to stop storing fat, crank up blood triglycerides and start running metabolic processes on fat, but fat derived from our adipocytes (obviously, it's a starvation hormone, there is no dietary fat).
But Fiaf from the gut wall is under the control of the gut bacteria. Active bacteria stop Fiaf production, inactive (hungry) bacteria allow Fiaf to be produced. It's pretty obvious that starvation gives quiescent gut bacteria, to the point where starvation actually mimics not having any gut bacteria at all.
Germ free mice really do have no gut bacteria at all, so they produce lots of Fiaf, all of the time. This suppresses their LPL and so they are slim, whatever they eat! Bacteria added to their gut immediately suppress Fiaf production from the intestine wall and so allow recently colonised (ex germ free) mice to store fat as soon as ever they have access to food. Lots of fat.
Also the mice rapidly become insulin resistant as well as obese. That's interesting.
But under more standard laboratory conditions Fiaf is ONLY produced from the gut of normal animals in times of starvation. My presumption here is that it is the hunger of the GUT BACTERIA that allow Fiaf levels to rise, which allows the stored fat of the host to be burned, in order to keep their microbial bioreactor (our colon) alive. A dead host is of no use to a bacterium.
Why have the bacteria organised things this way?
A bacterium cannot store energy. It's got no where to put it, no storage organ. But after surviving for millenia they are hardly likley to put their furture survival down to chance. So they take any energy source that they can get, particularly those sugar moieties that mammalian digestion cannot hope to extract, those from fiber. They extract sugars, upregulate sugar transport across the intestinal wall, modify the host's liver metaboism to convert them to triglycerides and then make sure lipoprotein lipase is fully active to store the triglycerides in adipocytes. Other bacteria ferment these sugars to short chain fatty acids, then shunt these to the liver for triglyceride production too. All the same in the end. It's bacterial derived energy stored as mammalian fat.
Fiaf also controls a host of fat burning genes. So the gut microbes only allow Fiaf to rise when they, and by inference their hosts, are hungry and need stored fat to live on. By doing this they allow us to burn "our" fat to get about to find more food. But who's fat is it? Which organsims organised its storage? Which organisms are controlling access?
It's not our fat.
Hunger, of the intestinal bacteria, is needed to before it can be accessed.
There is a point to all this, beyond it being absolutely fascinating.
That'll be the next post.
Peter
High fat meal is analgesic
Eating food in general decreases your perception of pain. A high fat meal knocks spots off of a high carbohydrate meal.
Both meals were 5.2% protein, the high fat was mediocre at 54% fat while still loaded with 42% from carbohydrate. The high carbohydrate meal really was high carbohydrate, at 88% of calories from carbohydrate and only 6.8% from fat.
More fat in the next pancakes please. And no flour, unless it's almond flour.
Peter
NB this research group, in common with the rest of the experimental world, finds that high fat meals make you sleepy. Absolutely incomprehensible to me personally!
Both meals were 5.2% protein, the high fat was mediocre at 54% fat while still loaded with 42% from carbohydrate. The high carbohydrate meal really was high carbohydrate, at 88% of calories from carbohydrate and only 6.8% from fat.
More fat in the next pancakes please. And no flour, unless it's almond flour.
Peter
NB this research group, in common with the rest of the experimental world, finds that high fat meals make you sleepy. Absolutely incomprehensible to me personally!
Sunday, December 09, 2007
Clofibrate and PUFA
It's a bit difficult not to post about the cholesterol hypothesis. I'm sheepish to admit that it is in a large part because it is such an easy target. But mostly because it also encapsulates herd stupidity beautifully. And it's wrong, yet keeps giving tricky suggestion that it might be right.
So today I want to look at clofibrate. This drug is a killer on a par with torcetrapib but does, like the statins, reduce cardiac "incidents". So the obvious conclusion is that, deep down, somewhere, anywhere, LDL cholesterol is the cause for heart disease. That's wrong.
Clofibrate is a stimulator of PPAR alpha receptors. It increases the production and activity of peroxisomes, which are cell organelles with many functions, one of which is the burning of lipids. Lowering intracellular lipids lowers insulin resistance. This is generally considered to be a Good Thing. I doubt this, if it is drug induced. Forcing your body to burn fatty acids while overloading it with glucose from your diet seems a bit odd to me. And very much in to the territory of the Law of Unintended Consequences.
Clofibrate also lowers cholesterol. So the cardiologists used to love it (until the body count got too high). But is there causality between the reduced cholesterol and reduced cardiac episodes?
Look what clofibrate does to the PUFA in the myocardium of rats.
It goes some way to correcting the appalling omega 3 to omega 6 ratio produced by the junk described as laboratory rodent "chow". I don't think anyone would object to correcting the omega 3 deficiency which is so ubiquitous in bodies of both lab rats or Food Pyramid munchers. Personally, doing this by eating 5 pence worth of fish oil capsules a day allows me to eat cheap UK beef rather than the seriously nice but expensive grass fed stuff. The latter is a weekend treat only.
No, there is a world of difference between taking a few grams of fish oil per day and putting a large spanner in your metabolic works called clofibrate. Correcting PUFA ratios would be expected to reduce cardiac incidents. Dropping your cholesterol level is probably the cause of the increased all cause mortality.
For statins the effects are about even, for clofibrate the increased mortality effect predominates.
But the message I get from both of these drug classes is that, while they were developed to reduce chloesterol, they do other things. A cholesterol lowering drug only gets out of the lab and in to clinical practice if its unknown, unsought and accidental benefits outweigh the cholesterol lowering problem it causes. It is these accidental benefits which determine whether any cholesterol lowering drug stands the test of time.
Who would have imagined clofibrate had its cardiovascular effects through going some way to correcting the fatty acid balance of the myocardium? That's not why it was developed.
BTW both Actos (pioglitazone) and Avandia (rosiglitazone) also work on PPAR receptors (PPAR gamma this time, rather than alpha) but they do similar things. They are used for their insulin resistance lowering effect. They are much less useful that putting your bagel in the bin and represent a VERY big spanner in your metabolic works. I notice that they don't seem to be too good for you, now they are in general use. Any more than clofibrate is.
Peter
So today I want to look at clofibrate. This drug is a killer on a par with torcetrapib but does, like the statins, reduce cardiac "incidents". So the obvious conclusion is that, deep down, somewhere, anywhere, LDL cholesterol is the cause for heart disease. That's wrong.
Clofibrate is a stimulator of PPAR alpha receptors. It increases the production and activity of peroxisomes, which are cell organelles with many functions, one of which is the burning of lipids. Lowering intracellular lipids lowers insulin resistance. This is generally considered to be a Good Thing. I doubt this, if it is drug induced. Forcing your body to burn fatty acids while overloading it with glucose from your diet seems a bit odd to me. And very much in to the territory of the Law of Unintended Consequences.
Clofibrate also lowers cholesterol. So the cardiologists used to love it (until the body count got too high). But is there causality between the reduced cholesterol and reduced cardiac episodes?
Look what clofibrate does to the PUFA in the myocardium of rats.
It goes some way to correcting the appalling omega 3 to omega 6 ratio produced by the junk described as laboratory rodent "chow". I don't think anyone would object to correcting the omega 3 deficiency which is so ubiquitous in bodies of both lab rats or Food Pyramid munchers. Personally, doing this by eating 5 pence worth of fish oil capsules a day allows me to eat cheap UK beef rather than the seriously nice but expensive grass fed stuff. The latter is a weekend treat only.
No, there is a world of difference between taking a few grams of fish oil per day and putting a large spanner in your metabolic works called clofibrate. Correcting PUFA ratios would be expected to reduce cardiac incidents. Dropping your cholesterol level is probably the cause of the increased all cause mortality.
For statins the effects are about even, for clofibrate the increased mortality effect predominates.
But the message I get from both of these drug classes is that, while they were developed to reduce chloesterol, they do other things. A cholesterol lowering drug only gets out of the lab and in to clinical practice if its unknown, unsought and accidental benefits outweigh the cholesterol lowering problem it causes. It is these accidental benefits which determine whether any cholesterol lowering drug stands the test of time.
Who would have imagined clofibrate had its cardiovascular effects through going some way to correcting the fatty acid balance of the myocardium? That's not why it was developed.
BTW both Actos (pioglitazone) and Avandia (rosiglitazone) also work on PPAR receptors (PPAR gamma this time, rather than alpha) but they do similar things. They are used for their insulin resistance lowering effect. They are much less useful that putting your bagel in the bin and represent a VERY big spanner in your metabolic works. I notice that they don't seem to be too good for you, now they are in general use. Any more than clofibrate is.
Peter
Wednesday, December 05, 2007
Losing the plot
I started reading Dr Dandona's work with his paper on the generation of free radicals by various white blood cells under the influence of glucose. I rather liked this, being as anti hyperglycaemia as I am. I especially liked the vitamin E depletion he found. And the rise in lipid oxidation products (TBARS).
When he went on to look at cream and protein I became a little uneasy. Protein came out quite well, despite the rather odd choice of the highly insulin provoking casein. Chicken does not do this. No evidence of an increase in lipid oxidation. But cream came out rather badly.
Cream provoked a marked increase in lipid oxidation products. As I generally live on cream this is of some interest to myself. There were a few oddities though. The TBARS peaked at 60 minutes. The cream chylomicrons peaked at 2h. This is peculiar, and Dandona says as much. It is worth noting that cream is predominantly saturated fat plus monounsaturated fat while TBARS are generated from PUFA, especially those with three or more double bonds. So I'm not quite sure what is happening here. It is worth noting that the TBARS per unit chylomicrons did not change significantly and it is hard to tell if the TBARS simply reflect the amount of lipid in the bloodstream available for oxidation. As glucose contains no lipids all TBARS produced by glucose must come from body damage.
By the time that Dandona moved on to other calorie sources he had abandoned TBARS as a marker of anything and was using NF-kappaB binding as his marker of inflammation, and eventually C reactive protein. Unfortunately he never went back to look at cream and CRP, which I would have found interesting.
More worrying was how he he trotted out a load of garbage about low fat diets and even quoted Ornish of all people (No, I refuse to reference Ornish. His yoga, relaxation and group support appear to ameliorate the worst effetcs of his awful diet. Yeugh).
We know what low fat diets do to the oxidation status of LDL cholesterol.
So I'm getting a bit uncomfortable with Dandona here.
The next substance to be checked for free radical generation and NF-kappaB binding was alcohol. This came through with flying colours on both counts. Using Dandona's approach alcohol looks like the perfect calorie source to avoid cellular damage. Hmmmmmmmm
Finally came fructose. Fructose came out of testing looking as good as alcohol, but without the intoxicant effects. Now we truly have a super food, no free radical generation, no increase in NF-kappaB binding, no increase (or even a non significant decrease) in CRP. Eurika.
And if you obtain your fructose from orange juice you get a truckload of antioxidants too. Wow. THE perfect drink for diabetics must be gin and orange! Here's what Dandona has to say:
"Our data are relevant to patients with diabetes since oxidative and inflammatory stress are markedly increased in this condition and may contribute to accelerated atherosclerosis. Clearly, the choice of foods that either do not increase or actually decrease oxidative and inflammatory stress in diabetic subjects is important"
"orange juice or fructose taken in equicaloric amounts to 75 g glucose does not cause either oxidative stress or inflammation in contrast to glucose"
Now just a minute.
If you actually measure the amount of post prandial fructose in the blood of diabetic patients it is nicely correlated with the severity of retinopathy. Whether this is a causal association cannot be determined from the Japanese study. But if you consider that fructose is much better at glycosylating proteins than glucose you can see there is a biological mechanism.
From the retinopathy abstract
"The increased prevalence of retinopathy in the high Meal Post Prandial Fructose group suggests that fructose is associated with retinopathy in patients with type 2 diabetes".
By this stage I'm off Dandona. It's a pity, I got some nice data from his studies, but he's lost the plot.
Any diabetic wanting to keep their vision would do well to pour the orange juice, with its antioxidants, down the sink. Cream would my choice, TBARS and all. Why?
No glucose spike, no insulin spike, no fructose spike.
Peter
PS Why does fructose come out so well in Dandona's assay? The liver churns out uric acid as fast as it can when it sees fructose coming, so it's not surprising that CRP trended downwards. Dandona was too busy with NF-kappaB etc to bother measuring urate. Checking urate would be a good idea before recommending fructose to people with metabolic syndrome. Also the body hates fructose so much it keeps it out of the systemic circulation as much as it can, so it never provides much fuel for white blood cells to generate reactive oxygen species.
When he went on to look at cream and protein I became a little uneasy. Protein came out quite well, despite the rather odd choice of the highly insulin provoking casein. Chicken does not do this. No evidence of an increase in lipid oxidation. But cream came out rather badly.
Cream provoked a marked increase in lipid oxidation products. As I generally live on cream this is of some interest to myself. There were a few oddities though. The TBARS peaked at 60 minutes. The cream chylomicrons peaked at 2h. This is peculiar, and Dandona says as much. It is worth noting that cream is predominantly saturated fat plus monounsaturated fat while TBARS are generated from PUFA, especially those with three or more double bonds. So I'm not quite sure what is happening here. It is worth noting that the TBARS per unit chylomicrons did not change significantly and it is hard to tell if the TBARS simply reflect the amount of lipid in the bloodstream available for oxidation. As glucose contains no lipids all TBARS produced by glucose must come from body damage.
By the time that Dandona moved on to other calorie sources he had abandoned TBARS as a marker of anything and was using NF-kappaB binding as his marker of inflammation, and eventually C reactive protein. Unfortunately he never went back to look at cream and CRP, which I would have found interesting.
More worrying was how he he trotted out a load of garbage about low fat diets and even quoted Ornish of all people (No, I refuse to reference Ornish. His yoga, relaxation and group support appear to ameliorate the worst effetcs of his awful diet. Yeugh).
We know what low fat diets do to the oxidation status of LDL cholesterol.
So I'm getting a bit uncomfortable with Dandona here.
The next substance to be checked for free radical generation and NF-kappaB binding was alcohol. This came through with flying colours on both counts. Using Dandona's approach alcohol looks like the perfect calorie source to avoid cellular damage. Hmmmmmmmm
Finally came fructose. Fructose came out of testing looking as good as alcohol, but without the intoxicant effects. Now we truly have a super food, no free radical generation, no increase in NF-kappaB binding, no increase (or even a non significant decrease) in CRP. Eurika.
And if you obtain your fructose from orange juice you get a truckload of antioxidants too. Wow. THE perfect drink for diabetics must be gin and orange! Here's what Dandona has to say:
"Our data are relevant to patients with diabetes since oxidative and inflammatory stress are markedly increased in this condition and may contribute to accelerated atherosclerosis. Clearly, the choice of foods that either do not increase or actually decrease oxidative and inflammatory stress in diabetic subjects is important"
"orange juice or fructose taken in equicaloric amounts to 75 g glucose does not cause either oxidative stress or inflammation in contrast to glucose"
Now just a minute.
If you actually measure the amount of post prandial fructose in the blood of diabetic patients it is nicely correlated with the severity of retinopathy. Whether this is a causal association cannot be determined from the Japanese study. But if you consider that fructose is much better at glycosylating proteins than glucose you can see there is a biological mechanism.
From the retinopathy abstract
"The increased prevalence of retinopathy in the high Meal Post Prandial Fructose group suggests that fructose is associated with retinopathy in patients with type 2 diabetes".
By this stage I'm off Dandona. It's a pity, I got some nice data from his studies, but he's lost the plot.
Any diabetic wanting to keep their vision would do well to pour the orange juice, with its antioxidants, down the sink. Cream would my choice, TBARS and all. Why?
No glucose spike, no insulin spike, no fructose spike.
Peter
PS Why does fructose come out so well in Dandona's assay? The liver churns out uric acid as fast as it can when it sees fructose coming, so it's not surprising that CRP trended downwards. Dandona was too busy with NF-kappaB etc to bother measuring urate. Checking urate would be a good idea before recommending fructose to people with metabolic syndrome. Also the body hates fructose so much it keeps it out of the systemic circulation as much as it can, so it never provides much fuel for white blood cells to generate reactive oxygen species.
Tuesday, December 04, 2007
Fat storage and retrieval
Human beings are adapted to live on fat. This is self evident from the way we store energy. Any average human is probably carrying around 100-200g of glucose as glycogen, stored in their liver, plus a bit more in their muscles. Let's be over generous and say 400g of glucose in all, about 1600kcal. That's enough energy to last about a day if you sit still. Assuming that same person weighs 80kg and has a body composition including 25% fat, this spare energy store of adipose tissue weighs 20kg. Containing 20,000 X 9 kcal giving 180,000kcal. At 2000kcal per day this looks like a 90 day supply to me, and allows spare energy to run around after some food.
Does any one ever use this energy? Well anyone who has ever fasted will know that energy from fat is freely available. This is completely logical. When humans were hunting and gathering, living through hard times on the fat of your bum was essential for survival. Being rendered dysfunctional by 24 hours food deprivation was non survival. Maybe 90 days without food is a bit extreme, but functioning for a week or two without food seems quite safe and is a very useful attribute.
Given your fat and some oxygen, is much else needed to extract this stored energy? Well, probably not a lot. If you are a hunter in a bad patch you don't want to be having to stop to eat a few leaves to get vitamins in order to burn your body fat. The leaves, fruits and nuts may not be that available when they buried under 6 feet of snow, while you and your mates drive some poor herbivore over a cliff to extract its stored fat from last summer's grazing.
Logically fat as an energy store is designed to be oxidised with a minimum of input, using vitamins and minerals that are available from body reserves plus a little help from muscle breakdown (which is inevitable during full fasting). Being hungry should NEVER jeopardise your ability to catch your next meal.
If you live on sugar your need for vitamins becomes crucial. One of the most important is vitamin B1, which is water soluble and not stored in the body in any amount. Certain illnesses, especially chronic alcoholism or subsisting on white rice, result in very low B1 levels. What happens when a B1 deficient person collapses and they get hooked up to an iv glucose drip? The glucose requires B1 for its metabolism, grabs it and precipitates an acute neurological catastrophe.
Sugar needs B1.
Sugar also depletes vitamin E. Taking a 75g oral glucose tolerance test, and presumably drinking a Starbucks Mocha does the same, drops your vitamin E level and it is still down at 3 hours. I wonder when it gets back to normal?
Neither eating fat nor protein deplete vitamin E levels.
I've no data on other vitamins but these snippets fit the logic of fat burning vs sugar burning on an evolutionary basis.
Now, consider burning fat which is not on your posterior but on your dinner plate. Is there any huge difference in the metabolic process of extracting the energy from dietary fat compared to adipose stored fat? I doubt it. So no desperate grubbing around for tubers and leaves to go with your fat. Somewhere along the line some protein is essential, but extracting calories from dietary fat should as be easy as extracting calories from your own adipose tisue.
It would be very interesting to see the vitamin/mineral requirements of a substantial group of people who were long term adapted to obtaining the bulk of their calories from fat, preferably saturated fat. My guess is that vitamins B1 and E would not feature at the top of the list, but I doubt we will see such a study soon.
Frankly, I'm amazed that Dandona could get ethics committee approval for the 3 floz of cream that he gave to his volunteers.
Peter
Does any one ever use this energy? Well anyone who has ever fasted will know that energy from fat is freely available. This is completely logical. When humans were hunting and gathering, living through hard times on the fat of your bum was essential for survival. Being rendered dysfunctional by 24 hours food deprivation was non survival. Maybe 90 days without food is a bit extreme, but functioning for a week or two without food seems quite safe and is a very useful attribute.
Given your fat and some oxygen, is much else needed to extract this stored energy? Well, probably not a lot. If you are a hunter in a bad patch you don't want to be having to stop to eat a few leaves to get vitamins in order to burn your body fat. The leaves, fruits and nuts may not be that available when they buried under 6 feet of snow, while you and your mates drive some poor herbivore over a cliff to extract its stored fat from last summer's grazing.
Logically fat as an energy store is designed to be oxidised with a minimum of input, using vitamins and minerals that are available from body reserves plus a little help from muscle breakdown (which is inevitable during full fasting). Being hungry should NEVER jeopardise your ability to catch your next meal.
If you live on sugar your need for vitamins becomes crucial. One of the most important is vitamin B1, which is water soluble and not stored in the body in any amount. Certain illnesses, especially chronic alcoholism or subsisting on white rice, result in very low B1 levels. What happens when a B1 deficient person collapses and they get hooked up to an iv glucose drip? The glucose requires B1 for its metabolism, grabs it and precipitates an acute neurological catastrophe.
Sugar needs B1.
Sugar also depletes vitamin E. Taking a 75g oral glucose tolerance test, and presumably drinking a Starbucks Mocha does the same, drops your vitamin E level and it is still down at 3 hours. I wonder when it gets back to normal?
Neither eating fat nor protein deplete vitamin E levels.
I've no data on other vitamins but these snippets fit the logic of fat burning vs sugar burning on an evolutionary basis.
Now, consider burning fat which is not on your posterior but on your dinner plate. Is there any huge difference in the metabolic process of extracting the energy from dietary fat compared to adipose stored fat? I doubt it. So no desperate grubbing around for tubers and leaves to go with your fat. Somewhere along the line some protein is essential, but extracting calories from dietary fat should as be easy as extracting calories from your own adipose tisue.
It would be very interesting to see the vitamin/mineral requirements of a substantial group of people who were long term adapted to obtaining the bulk of their calories from fat, preferably saturated fat. My guess is that vitamins B1 and E would not feature at the top of the list, but I doubt we will see such a study soon.
Frankly, I'm amazed that Dandona could get ethics committee approval for the 3 floz of cream that he gave to his volunteers.
Peter
Monday, December 03, 2007
Fruit and vegetables in Holland
Another nice fruit and vegetable study, this time from the Netherlands.
This is an intervention study, tightly controlled and available in full text. It looks at, amongst other things, total plasma antioxidant capacity and the resistance to oxidation of LDL cholesterol. Subjects were divided in to various groups but the two of interest either ate nearly half a kilo of vegetables per day or just over 100g per day.
The results I found most interesting were that, despite marked increases in vitamin C and assorted phyto-antioxidants, there was no increase in total plasma antioxidant capacity and no increase in resistance to oxidation of LDL cholesterol in the high vegetable vs the low vegetable group.
To a fruit and vegetable sceptic this is pretty much as expected. The one thing that did surprise me was that the total antioxidant capacity was unchanged in all groups. Looking at the variations/substitutions made between the various groups makes me suspect that the fructose concentrations in all the diets was about the same. If they had been different then uric acid production would have made the high fructose group look better than it should have done. But the study was good, tightly controlled and avoided this pitfall which is so common in this type of work.
Another intervention study to refute the causality of epidemiological associations between fruit and vegetables and health.
Peter
This is an intervention study, tightly controlled and available in full text. It looks at, amongst other things, total plasma antioxidant capacity and the resistance to oxidation of LDL cholesterol. Subjects were divided in to various groups but the two of interest either ate nearly half a kilo of vegetables per day or just over 100g per day.
The results I found most interesting were that, despite marked increases in vitamin C and assorted phyto-antioxidants, there was no increase in total plasma antioxidant capacity and no increase in resistance to oxidation of LDL cholesterol in the high vegetable vs the low vegetable group.
To a fruit and vegetable sceptic this is pretty much as expected. The one thing that did surprise me was that the total antioxidant capacity was unchanged in all groups. Looking at the variations/substitutions made between the various groups makes me suspect that the fructose concentrations in all the diets was about the same. If they had been different then uric acid production would have made the high fructose group look better than it should have done. But the study was good, tightly controlled and avoided this pitfall which is so common in this type of work.
Another intervention study to refute the causality of epidemiological associations between fruit and vegetables and health.
Peter
Sunday, December 02, 2007
PROSPER and Q10
The other day I was chatting to a work colleague about a lab result showing hypercholesterolaemia. She'd ruled out any medical problems likely to elevate blood cholesterol in a cat, so we decided it was clinically insignificant. If you are really dumb you'll add, "if you believe it's significant in human heart disease anyway".
I'm really dumb some times.
When your colleague comes back with "my father in law is on a statin and I've been meaning to find out more about them" you some times say stupid things like "does he have muscle pain?". "Yes". "Oh".
*******HEALTH WARNING*******
Next link has serious factual errors about statins. Click at your own risk.
*******HEALTH WARNING*******
It's called myalgia and even the most mis-informed hardcore true statin believers realise it's real and it's Q10 responsive. The antistatin folks have been on the ball a bit longer, they withdraw the statin as well as giving the Q10. They are well aware that the muscle pumping your blood is struggling as much as the muscles which can't get you up the stairs any more.
If you mutter something about coenzyme Q10 to most clinicians they will just look blank. Don't you get that at health food shops? Or in face cream, the anti wrinkle type?
For those with elderly relatives on a statin, especially pravastatin, the following paper deserves careful reading:
First, as I'm afraid it has to, comes the body count. This is a European study and so they give you the mortality figures. There were 2913 patients in the placebo group. A total of 306 died during their 3 years of not taking a statin. That is 10.5% died. In the treatment group there were 2891 patients and 298 died, that's 10.3%. Bear in mind that these were high risk cardiovascular patients, the sort for whom statin therapy is supposed to be effective in saving lives.
If you consider these percentage figures expressed as mortality per 1000 patients it means that 105/1000 died in placebo group and 103/1000 in the pravastatin group. That looks very much as if you had to treat 500 people for 3 years to save one life. Wow! Statistically this level of benefit is pretty certainly due to chance. That's a lot of pills for no benefit. Actually it's roughly 3 X 365 X 2891 pills, which is 3,165,645 pills. At 40mg/pill that's about 128kg of pravastatin.
They forgot to include the above information in the abstract.
They did mention the increased frequency of new cancer diagnoses. They could hardly avoid it, given the p value, which was p=0.02, well below the 0.05 needed for statistical significance. The actual cancer death rate never made statistical significance, a mere p=0.082, but in general it takes longer to die from most cancers that the three years the trial lasted, so no surprise there. Thank goodness the trial stopped when it did.
An elderly person developing cancer while on pravastatin will be pleased to hear that if you mix this study with loads of other statin studies, especially those using younger patients, this cancer increase can be made to go away. Phew. It's nice to see what meta-analysis can do. But you still have cancer.
The bottom line is that pravastatin saved some deaths due to heart disease and replaced them with deaths from other causes, the commonest of which was cancer.
Clearly no self respecting cardiologist would ever want you to die of a heart attack. Cancer, obviously, is much better and has the advantage of being an SEP (Somebody Else's Problem). Personally I'm not too certain that cancer is a good trade for a heart attack. You decide.
If you have access to The Lancet full text you want Table 2: Primary End Points of PROSPER, at the bottom of page 1625.
Best quote from the discussion:
"the most likely explanation is that the imbalance in cancer rates in PROSPER was a chance finding, which could in part have been driven by the recruitment of individuals with occult disease".
My comment?
But they mostly were recruited in to the pravastatin group, with a value of p=0.02.
Translation:
Duh, we wuz ded unlucky Guv. Ded unlucky.
Peter
I'm really dumb some times.
When your colleague comes back with "my father in law is on a statin and I've been meaning to find out more about them" you some times say stupid things like "does he have muscle pain?". "Yes". "Oh".
*******HEALTH WARNING*******
Next link has serious factual errors about statins. Click at your own risk.
*******HEALTH WARNING*******
It's called myalgia and even the most mis-informed hardcore true statin believers realise it's real and it's Q10 responsive. The antistatin folks have been on the ball a bit longer, they withdraw the statin as well as giving the Q10. They are well aware that the muscle pumping your blood is struggling as much as the muscles which can't get you up the stairs any more.
If you mutter something about coenzyme Q10 to most clinicians they will just look blank. Don't you get that at health food shops? Or in face cream, the anti wrinkle type?
For those with elderly relatives on a statin, especially pravastatin, the following paper deserves careful reading:
First, as I'm afraid it has to, comes the body count. This is a European study and so they give you the mortality figures. There were 2913 patients in the placebo group. A total of 306 died during their 3 years of not taking a statin. That is 10.5% died. In the treatment group there were 2891 patients and 298 died, that's 10.3%. Bear in mind that these were high risk cardiovascular patients, the sort for whom statin therapy is supposed to be effective in saving lives.
If you consider these percentage figures expressed as mortality per 1000 patients it means that 105/1000 died in placebo group and 103/1000 in the pravastatin group. That looks very much as if you had to treat 500 people for 3 years to save one life. Wow! Statistically this level of benefit is pretty certainly due to chance. That's a lot of pills for no benefit. Actually it's roughly 3 X 365 X 2891 pills, which is 3,165,645 pills. At 40mg/pill that's about 128kg of pravastatin.
They forgot to include the above information in the abstract.
They did mention the increased frequency of new cancer diagnoses. They could hardly avoid it, given the p value, which was p=0.02, well below the 0.05 needed for statistical significance. The actual cancer death rate never made statistical significance, a mere p=0.082, but in general it takes longer to die from most cancers that the three years the trial lasted, so no surprise there. Thank goodness the trial stopped when it did.
An elderly person developing cancer while on pravastatin will be pleased to hear that if you mix this study with loads of other statin studies, especially those using younger patients, this cancer increase can be made to go away. Phew. It's nice to see what meta-analysis can do. But you still have cancer.
The bottom line is that pravastatin saved some deaths due to heart disease and replaced them with deaths from other causes, the commonest of which was cancer.
Clearly no self respecting cardiologist would ever want you to die of a heart attack. Cancer, obviously, is much better and has the advantage of being an SEP (Somebody Else's Problem). Personally I'm not too certain that cancer is a good trade for a heart attack. You decide.
If you have access to The Lancet full text you want Table 2: Primary End Points of PROSPER, at the bottom of page 1625.
Best quote from the discussion:
"the most likely explanation is that the imbalance in cancer rates in PROSPER was a chance finding, which could in part have been driven by the recruitment of individuals with occult disease".
My comment?
But they mostly were recruited in to the pravastatin group, with a value of p=0.02.
Translation:
Duh, we wuz ded unlucky Guv. Ded unlucky.
Peter
Sugar is addictive
I glibly described sugar as addictive in my last post. Is this true?
Well, anyone who has read Mark Johnson's book Wasted will realise that a 20g sucrose load in a Thornton's chocolate bar is not quite in the same league as mixed heroin and crack cocaine injected as an iv bolus in a public lavatory on the Tottenham Court Road.
But the neuropharmacology of glucose addiction is interesting and the prospect of giving up sugar is sufficiently daunting for most people that I think it is perfectly reasonable to describe sugar as addictive. The full text of the rat paper is free and has some interesting opinion as to the hows and whys, but the bottom line is that giving up sugar should not be expected to be easy!
Is it addictive? Yes.
Peter
Well, anyone who has read Mark Johnson's book Wasted will realise that a 20g sucrose load in a Thornton's chocolate bar is not quite in the same league as mixed heroin and crack cocaine injected as an iv bolus in a public lavatory on the Tottenham Court Road.
But the neuropharmacology of glucose addiction is interesting and the prospect of giving up sugar is sufficiently daunting for most people that I think it is perfectly reasonable to describe sugar as addictive. The full text of the rat paper is free and has some interesting opinion as to the hows and whys, but the bottom line is that giving up sugar should not be expected to be easy!
Is it addictive? Yes.
Peter
When is a high fat diet not? Bang on time example!
THANK YOU Dr Bass, excellent timing.
This paper is being discussed in various nutrition fora at the moment.
It's a classic. You read the abstract and realise a high fat diet is mangling your brain. Oh no! Quick, don't bother reading the paper, get rid of the fat. Oh, you can't read the paper unless you have an account. Well, by chance, I have the full paper.
Ok, it's a "High Fat" diet alright. Up at, you guessed, 45% of calories from fat, mostly as lard. In fact it is the D12451 rodent diet. A quick Google of D12451 gives you this page. You don't get this info in the full text of the paper, you have to want to know!
You can see that the carbohydrate composition is a smidge of cornstarch (73g), a mass of maltodextrin (100g) and a huge mass of sucrose (173g) in an 858g block of food. This diet is designed to produce sugar addiction, obesity and diabetes. Adding some healthy lard will not save the poor mice from Bass et al's "High Fat" sucrose diet.
This paper does not involve a high fat diet. It's junk.
Peter
This paper is being discussed in various nutrition fora at the moment.
It's a classic. You read the abstract and realise a high fat diet is mangling your brain. Oh no! Quick, don't bother reading the paper, get rid of the fat. Oh, you can't read the paper unless you have an account. Well, by chance, I have the full paper.
Ok, it's a "High Fat" diet alright. Up at, you guessed, 45% of calories from fat, mostly as lard. In fact it is the D12451 rodent diet. A quick Google of D12451 gives you this page. You don't get this info in the full text of the paper, you have to want to know!
You can see that the carbohydrate composition is a smidge of cornstarch (73g), a mass of maltodextrin (100g) and a huge mass of sucrose (173g) in an 858g block of food. This diet is designed to produce sugar addiction, obesity and diabetes. Adding some healthy lard will not save the poor mice from Bass et al's "High Fat" sucrose diet.
This paper does not involve a high fat diet. It's junk.
Peter
When is a high fat diet not a high fat diet?
When it's a high carbohydrate diet! Preferably a high sucrose diet. The simple way to prove a high fat diet is bad for you is to use a rat or mouse, and feed it sugar, then describe this as a high fat diet in your abstract without specifying exact composition. "Normal" rat food in the USA for toxicology testing used to be NIH-07, at around 5% fat. There were so many problems with renal failure and heart failure that the diet was reformulated in the mid 1990s to the NTP-2000 diet, with just under 10% fat. The spectacular benefits were:
"The NTP-2000 diet prevented nephrocalcinosis and decreased the severity of nephropathy and cardiomyopathy, the common lesions of F344 rats in 13-week studies"
Notice it only took 13 weeks to get the problems and they certainly didn't go away on NTP-2000. Makes you wonder how they can assess drug toxicity in rats this sick from their diet! The other problem on the NIH-07 diet was cancer by 13 weeks, but that didn't seem to improve on the NTP-2000 diet at all. Still looks like chronic carbohydrate poisoning to me.
But the botttom line is that any diet with > 10% fat can theoretically be described as high fat for a lab rat. Up at 45% fat most junk science is happy to use the label "High Fat".
The comments about cardiomyopathy in the above paper are interesting as I came across this paper, only in abstract for unfortunately, but it gives the idea.
They compared the effects of 10% fat "normal" rat food with 45% fat diet, accurately described as "Western" diet, and also with a diet containing 60% of calories as fat. For a rat I would suggest 80% fat might be a better suggestion, but they got the goods at 60% anyway, so good for them. Here's the best section from the abstract
"Oleate oxidation in heart muscle ex vivo increased with high fat diet at all time points investigated. In contrast, cardiac oleate oxidation increased with western diet in the acute, short and intermediate term, but not in the long term. Consistent with fatty acid oxidation maladaptation, cardiac power decreased with long term western diet only"
When you use a genuine high fat diet there are no adverse effects on heart muscle function.
I like their introduction sentence too:
"Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal muscle insulin resistance".
If you read my post on insulin resistance you'll know why.
Just checked on who did this excellent research and it looks like Taegtmeyer, the group leader, is USA based. Very unusual for me to cite an american paper, unless from one of the few islands of common sense such as Volek et al, but here it is and it's good.
Peter
"The NTP-2000 diet prevented nephrocalcinosis and decreased the severity of nephropathy and cardiomyopathy, the common lesions of F344 rats in 13-week studies"
Notice it only took 13 weeks to get the problems and they certainly didn't go away on NTP-2000. Makes you wonder how they can assess drug toxicity in rats this sick from their diet! The other problem on the NIH-07 diet was cancer by 13 weeks, but that didn't seem to improve on the NTP-2000 diet at all. Still looks like chronic carbohydrate poisoning to me.
But the botttom line is that any diet with > 10% fat can theoretically be described as high fat for a lab rat. Up at 45% fat most junk science is happy to use the label "High Fat".
The comments about cardiomyopathy in the above paper are interesting as I came across this paper, only in abstract for unfortunately, but it gives the idea.
They compared the effects of 10% fat "normal" rat food with 45% fat diet, accurately described as "Western" diet, and also with a diet containing 60% of calories as fat. For a rat I would suggest 80% fat might be a better suggestion, but they got the goods at 60% anyway, so good for them. Here's the best section from the abstract
"Oleate oxidation in heart muscle ex vivo increased with high fat diet at all time points investigated. In contrast, cardiac oleate oxidation increased with western diet in the acute, short and intermediate term, but not in the long term. Consistent with fatty acid oxidation maladaptation, cardiac power decreased with long term western diet only"
When you use a genuine high fat diet there are no adverse effects on heart muscle function.
I like their introduction sentence too:
"Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal muscle insulin resistance".
If you read my post on insulin resistance you'll know why.
Just checked on who did this excellent research and it looks like Taegtmeyer, the group leader, is USA based. Very unusual for me to cite an american paper, unless from one of the few islands of common sense such as Volek et al, but here it is and it's good.
Peter
Thursday, November 29, 2007
Gluten ataxia
Nottingham and Sheffield are about 30 miles apart. If you have neurological problems presenting as ataxia and live in Mansfield you can either go North to Dr Hadjivassiliou's group, who will undoubtedly work you up for gluten induced problems.
Or you can go South to The Queen's Medical Centre, where you may not get worked up in the same manner. In fact, this letter to the editor of the journal Brain is about as critical as respectable doctors get of each other in public.
It is particularly notable that the main reference cited by Wills and Unsworthy for the incidence of coeliac disease only tested antibody positive patients and only accepted them as coeliac if they had intestinal signs on biopsy. Clearly depending on EMA antibodies, as used in Cook's study, missed many patients so the incidence of intestinal coeliac disease MUST be underestimated.
"The value of EMA as a screening tool is therefore limited"
Still, an incidence of 1% is massively higher than was the accepted incidence 20 years ago. This estimate will continue to increase as people realise how widespread the problems from wheat are.
Backing away from intestinal disease as a pre requisite for gluten problems:
The whole point of Hadjivassiliou's work is that there may not be ANY gut signs with neurological gluten induced disease.
We know full well that the zonulin system in the gut is disrupted by gluten. This is irrespective of the presence of intestinal coeliac disease. Once the gut is permeable to proteins you can take your pick of auto immune diseases. If you get neurological problems AND gut problems Nottingham might accept that you have gluten ataxia. If you get neurological signs without gut damage then it's time to get in your wheelchair.
Sheffield will drive you to a gluten fee diet. It might just work.
If I lived in Mansfield and had some weird neurological disease, personally I'd head North to Sheffield.
Peter (Born in Nottingham but Sheffield is good, just don't take your car)
Or you can go South to The Queen's Medical Centre, where you may not get worked up in the same manner. In fact, this letter to the editor of the journal Brain is about as critical as respectable doctors get of each other in public.
It is particularly notable that the main reference cited by Wills and Unsworthy for the incidence of coeliac disease only tested antibody positive patients and only accepted them as coeliac if they had intestinal signs on biopsy. Clearly depending on EMA antibodies, as used in Cook's study, missed many patients so the incidence of intestinal coeliac disease MUST be underestimated.
"The value of EMA as a screening tool is therefore limited"
Still, an incidence of 1% is massively higher than was the accepted incidence 20 years ago. This estimate will continue to increase as people realise how widespread the problems from wheat are.
Backing away from intestinal disease as a pre requisite for gluten problems:
The whole point of Hadjivassiliou's work is that there may not be ANY gut signs with neurological gluten induced disease.
We know full well that the zonulin system in the gut is disrupted by gluten. This is irrespective of the presence of intestinal coeliac disease. Once the gut is permeable to proteins you can take your pick of auto immune diseases. If you get neurological problems AND gut problems Nottingham might accept that you have gluten ataxia. If you get neurological signs without gut damage then it's time to get in your wheelchair.
Sheffield will drive you to a gluten fee diet. It might just work.
If I lived in Mansfield and had some weird neurological disease, personally I'd head North to Sheffield.
Peter (Born in Nottingham but Sheffield is good, just don't take your car)
Low fat moods
These two papers caught my eye. The first is observational and uses very limited in data points but clearly suggests the hypothesis that sugar is a cause of major depression. The biochemistry is supportive of this, a high carbohydrate meal increases blood insulin, which increases blood tryptophan, which increases brain serotonin.
So you fall asleep after a high carb meal.
I used to be a standing joke in our family before I went LC. One of the joys of avoiding rice and pasta was getting my evenings back. The aftermath of sleeping through a serotonon spike is that about three to six hours later your brain serotonin plummets and you can't sleep. Ah, those nights of looking at the clock every five minutes from 2am to 4.30 am. The switch to LC not only gave a good night's sleep every night but I woke feeling good each morning. That's better.
So I find it highly plausible that sugar causes depression. Kick your serotonin system often enough and it will go on strike. Or develop "serotonin resistance" comparable to "insulin resistance".
The second paper looks at the effect of a low fat diet on mood. The abstract is self explanatory and here are the important lines:
"ratings of anger-hostility significantly increased in the intervention group after 1 month on the low-fat diet"
and this
"The results suggest that a change in dietary fat content from 41 to 25% energy may have adverse effects on mood"
One month is VERY rapid for a mood disorder to emerge. Healthy volunteers are not usually prone to anger hostility episodes. This is an intervention study with the subjects acting as their own controls. It's good.
Next time you get carved up in a minor road rage episode, just ask yourself if the perpetrator will have had bacon and eggs fried in butter for breakfast. Alternatively perhaps a bowl of sugared cereals lubricated with skim milk followed by toast and jam lubricated with a low fat spread. Probably has a heart problem and is on a statin too. Anger hostility rating? Is this problem growing?
Dr Ancel Keys again?
Peter
Obviously what is missing from the second study is a period when the subjects ate 80% fat in their diet. I assure you it feels good.
So you fall asleep after a high carb meal.
I used to be a standing joke in our family before I went LC. One of the joys of avoiding rice and pasta was getting my evenings back. The aftermath of sleeping through a serotonon spike is that about three to six hours later your brain serotonin plummets and you can't sleep. Ah, those nights of looking at the clock every five minutes from 2am to 4.30 am. The switch to LC not only gave a good night's sleep every night but I woke feeling good each morning. That's better.
So I find it highly plausible that sugar causes depression. Kick your serotonin system often enough and it will go on strike. Or develop "serotonin resistance" comparable to "insulin resistance".
The second paper looks at the effect of a low fat diet on mood. The abstract is self explanatory and here are the important lines:
"ratings of anger-hostility significantly increased in the intervention group after 1 month on the low-fat diet"
and this
"The results suggest that a change in dietary fat content from 41 to 25% energy may have adverse effects on mood"
One month is VERY rapid for a mood disorder to emerge. Healthy volunteers are not usually prone to anger hostility episodes. This is an intervention study with the subjects acting as their own controls. It's good.
Next time you get carved up in a minor road rage episode, just ask yourself if the perpetrator will have had bacon and eggs fried in butter for breakfast. Alternatively perhaps a bowl of sugared cereals lubricated with skim milk followed by toast and jam lubricated with a low fat spread. Probably has a heart problem and is on a statin too. Anger hostility rating? Is this problem growing?
Dr Ancel Keys again?
Peter
Obviously what is missing from the second study is a period when the subjects ate 80% fat in their diet. I assure you it feels good.
Wednesday, November 28, 2007
Getting fat is bad when you stop
There comes a point beyond which getting fat becomes counter productive. This happens when you are too fat. What do I mean by too fat? Being fat is supposed to have survival benefits... I was thinking along the lines of type 2 diabetes, an enormously complex disease.
This problem is obviously "associated" with obesity, yet most obese people do NOT develop diabetes. Plus many thin people can and do develop type 2 diabetes.
From my perspective I think that type 2 diabetes occurs when people loose the ability to put on any more fat. This can happen at assorted body sizes, not just the seriously obese. In fact a huge person who is still gaining weight may well be safe.
We know that obesity requires just a small excess of fat per day to be locked in to adipose tissue by the insulin produced in response to dietary carbohydrate.
That's fine for a few tens of years. But there are limits on both the number of fat cells and the size to which they can be pumped. Eventually they get so full that they just say NO to any more fat. Bearing in mind that it is insulin which puts the fat in to fat cells, the easiest way to say NO is to refuse to put out any insulin receptors, the phenomenon of insulin resistance.
What happens when a fat cell refuses to listen to insulin's storage message? Well, it allows hormone-sensitive lipase freedom from insulin's restraint. This results in an outpouring of the energy set aside, over many years, for a rainy day which never came. Non esterified fatty acids (NEFA) in the plasma increase rapidly. NEFA are the high energy rival to glucose for cell power supply. The control of NEFA flow is at their release point (fat cells), not their uptake point. When the adipocytes thumb their nose at insulin, they release a flood of inappropriate energy which is taken up by just about every cell that can remotely use NEFA for fuel.
Packing NEFA in to cells beyond their wildest possible needs means that they have no logical use for glucose. Muscle tissue is the primary "sink" for glucose. Muscles love NEFA. Once they are packed with NEFA why should they accept glucose? They just say NO by becoming insulin resistant too. If there is no where for glucose to go, it builds up in the bloodstream (especially if you live on bagels and waffles) and you get the label of type 2 diabetes.
Much of this I worked out by slogging sentence by sentence through Dr Raz's article here. He gets hopelessly lost in ideas on treatment. His basic idea is that because the problem is one of excessive fat storage (it is) and the stored fat is from dietary fat (it is) then the correct approach is to reduce dietary fat (WRONG). The correct approach is to reduce the hormone which is causing the excess storage. That is insulin. The spectacular success of low carbohydrate diets for management of type 2 diabetes clearly show this is the way to go.
As soon as you drop insulin levels the fat cells, no longer over bombarded with the message to hyper-inflate themselves, start to listen to the voice of reason. Basal insulin can inhibit lipolysis to levels appropriate for energy needs of the body. Blood glucose normalises because the bagels are in the bin, not your bloodstream. Lipolysis without carbohydrate overload allows ketosis which controls appetite.
I also had some fun with this paper, which gets the prize for worst title ever on a diabetes paper.
Please Pass the Chips: Genomic Insights into Obesity and Diabetes
I guess that the chips are bits of information. I couldn't find anything in the paper about what I would call chips. It is an American paper so I guess they would have used the term French Fries if they had really meant chips... Still, an appalling suggestion for a diabetic diet.
Anyway. The paper has some interesting points. Ignore all the garbage about micro arrays and gene switching etc etc. Throwing money at a problem does not always mean that you understand it.
No, they discuss the lipodystrophies, spontaneous in humans and engineered in lab animals. The basic message is:
Total absence of fat cells equals severe type 2 diabetes, in an organism without any fat at all.
No fat cells means nothing to listen to insulin, so nowhere to store energy. The lack of adipocytes is the equivalent of being born with 100% ineffective adipocytes. If you have no storage space you have to shove your dietary fat in to whatever tissue will take it. Once the tissue, particularly muscle, has a generous supply of fat it will, as above, say no to glucose.
So, as I see it, type 2 diabetes is a condition where adipose tissue cannot accept energy, either through years of hyperinsulinaemia or because it never actually formed. The end result in both cases is muscle fatty acid build up to a level which causes glucose refusal.
You then pee the glucose down the loo. Or eat LC and fix your problem. If you have a lipodystrophy I'm not sure how effective LC eating would be, but it certainly works for standard type 2s.
Peter
This problem is obviously "associated" with obesity, yet most obese people do NOT develop diabetes. Plus many thin people can and do develop type 2 diabetes.
From my perspective I think that type 2 diabetes occurs when people loose the ability to put on any more fat. This can happen at assorted body sizes, not just the seriously obese. In fact a huge person who is still gaining weight may well be safe.
We know that obesity requires just a small excess of fat per day to be locked in to adipose tissue by the insulin produced in response to dietary carbohydrate.
That's fine for a few tens of years. But there are limits on both the number of fat cells and the size to which they can be pumped. Eventually they get so full that they just say NO to any more fat. Bearing in mind that it is insulin which puts the fat in to fat cells, the easiest way to say NO is to refuse to put out any insulin receptors, the phenomenon of insulin resistance.
What happens when a fat cell refuses to listen to insulin's storage message? Well, it allows hormone-sensitive lipase freedom from insulin's restraint. This results in an outpouring of the energy set aside, over many years, for a rainy day which never came. Non esterified fatty acids (NEFA) in the plasma increase rapidly. NEFA are the high energy rival to glucose for cell power supply. The control of NEFA flow is at their release point (fat cells), not their uptake point. When the adipocytes thumb their nose at insulin, they release a flood of inappropriate energy which is taken up by just about every cell that can remotely use NEFA for fuel.
Packing NEFA in to cells beyond their wildest possible needs means that they have no logical use for glucose. Muscle tissue is the primary "sink" for glucose. Muscles love NEFA. Once they are packed with NEFA why should they accept glucose? They just say NO by becoming insulin resistant too. If there is no where for glucose to go, it builds up in the bloodstream (especially if you live on bagels and waffles) and you get the label of type 2 diabetes.
Much of this I worked out by slogging sentence by sentence through Dr Raz's article here. He gets hopelessly lost in ideas on treatment. His basic idea is that because the problem is one of excessive fat storage (it is) and the stored fat is from dietary fat (it is) then the correct approach is to reduce dietary fat (WRONG). The correct approach is to reduce the hormone which is causing the excess storage. That is insulin. The spectacular success of low carbohydrate diets for management of type 2 diabetes clearly show this is the way to go.
As soon as you drop insulin levels the fat cells, no longer over bombarded with the message to hyper-inflate themselves, start to listen to the voice of reason. Basal insulin can inhibit lipolysis to levels appropriate for energy needs of the body. Blood glucose normalises because the bagels are in the bin, not your bloodstream. Lipolysis without carbohydrate overload allows ketosis which controls appetite.
I also had some fun with this paper, which gets the prize for worst title ever on a diabetes paper.
Please Pass the Chips: Genomic Insights into Obesity and Diabetes
I guess that the chips are bits of information. I couldn't find anything in the paper about what I would call chips. It is an American paper so I guess they would have used the term French Fries if they had really meant chips... Still, an appalling suggestion for a diabetic diet.
Anyway. The paper has some interesting points. Ignore all the garbage about micro arrays and gene switching etc etc. Throwing money at a problem does not always mean that you understand it.
No, they discuss the lipodystrophies, spontaneous in humans and engineered in lab animals. The basic message is:
Total absence of fat cells equals severe type 2 diabetes, in an organism without any fat at all.
No fat cells means nothing to listen to insulin, so nowhere to store energy. The lack of adipocytes is the equivalent of being born with 100% ineffective adipocytes. If you have no storage space you have to shove your dietary fat in to whatever tissue will take it. Once the tissue, particularly muscle, has a generous supply of fat it will, as above, say no to glucose.
So, as I see it, type 2 diabetes is a condition where adipose tissue cannot accept energy, either through years of hyperinsulinaemia or because it never actually formed. The end result in both cases is muscle fatty acid build up to a level which causes glucose refusal.
You then pee the glucose down the loo. Or eat LC and fix your problem. If you have a lipodystrophy I'm not sure how effective LC eating would be, but it certainly works for standard type 2s.
Peter
Getting fat is good
After discussing the two rat experiment and applying it to Kitava, it must be pretty obvious that getting fat in the good times improves your chances of surviving the lean times.
Being fat is good for you.
Anyone going in to the next poor harvest with a BMI of 18.5 is significantly less likely to come out alive for the next good harvest than someone of BMI 29.9. Thinking Kitava here, same applies to hunter/gatherers. But is it possible to have too much fat?
Well a BMI of 18.5-25 is considered "ideal". Looking at this paper we find that:
"Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966)"
That is BMI 25-30 has lowest all cause mortality. Lower mortality than our ideal target range. Perhaps it's time to move the goal posts. Maybe BMI <25 should be a cause for concern. I'm in trouble on that one!
My only consolation of running my own BMI at 20.5 is that being slim on a high fat diet is almost certainly not as bad for you as when you are on a carbohydrate based diet. It may be good for you. No one will ever find this out looking at USA health statistics. On their Food Pyramid everyone suffers.
Peter
PS I tried to understand this paper in depth and it is strictly for the statisticians. I'll have to take Katherine Flegal's word for the results being true.
Being fat is good for you.
Anyone going in to the next poor harvest with a BMI of 18.5 is significantly less likely to come out alive for the next good harvest than someone of BMI 29.9. Thinking Kitava here, same applies to hunter/gatherers. But is it possible to have too much fat?
Well a BMI of 18.5-25 is considered "ideal". Looking at this paper we find that:
"Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966)"
That is BMI 25-30 has lowest all cause mortality. Lower mortality than our ideal target range. Perhaps it's time to move the goal posts. Maybe BMI <25 should be a cause for concern. I'm in trouble on that one!
My only consolation of running my own BMI at 20.5 is that being slim on a high fat diet is almost certainly not as bad for you as when you are on a carbohydrate based diet. It may be good for you. No one will ever find this out looking at USA health statistics. On their Food Pyramid everyone suffers.
Peter
PS I tried to understand this paper in depth and it is strictly for the statisticians. I'll have to take Katherine Flegal's word for the results being true.
Tuesday, November 27, 2007
Professor John Yudkin and Dr Ancel Keys
Here's a page or so (p163-4) from John Yudkin's book "Pure White and Deadly", 1972 edition. Yudkin begins the chapter with an apology for talking about such uncomfortable disagreements in public. But he liked the truth.
This quote covers opinion from Prof John Yudkin and Dr Meyer Friedman. You can hear their dislike of Keys. Keys was the architect of what has become the current world obesity epidemic and never one to let the truth get in the way of a good idea, as with his six nations "fat causes heart disease" study. Unfortunately Meyer's list of those easily misled did not include gullible politicians who set food policy. Keys was a very successful politico, with intense conviction of his own correctness. Fine if he had been right, which he wasn't.
Yudkin begins:
I have already mentioned Dr Ancel Keys and his pioneer work in relation to diet and heart disease. A year or so ago he wrote a memorandum which he sent to a large number of scientists working in this field and which with very few changes has now been published in a medical journal 'Atherosclerosis'. It consists entirely of a strong criticism - I nearly said virulent criticism - of the work I have published from time to time on the theory that sugar is the main dietary factor involved in causing heart disease.
The publication contains a number of quite incorrect and unjustified statements; for instance; that we had never tested our method for measuring sugar intake; that no one eats the amounts of sugar that we and others have used in our experiments; that it was absurd of me in 1957 to use intemational statistics of 41 countries as evidence for the relationship between sugar and heart disease (exactly tbe same statistics that Dr Keys had previously used for only 6 selected countries to show the relationship between fat and heart disease).
He ends by triumphantly pointing out that both sugar and fat intakes are related to heart disease, but that the cause must be fat, not sugar, because he had just found in 1970 that fat intake and sugar intake are themselves closely linked. You will remember my own discussion of this link in Chapter 5, based on the fact that, as far back as 1964, I had shown this relationship to exist between fat intake and sugar intake. Let me therefore quote from a recently published book Pathogenesis Of Coronary Artery Disease written by Dr Meyer Friedman, another distinguished worker in this field:
"It is sad, for example, to observe that essentially honourable investigators omit published data (including some of their own data obtained earlier) which refute or call into question their contemporary data and the interpretations they have made of them. It is even sadder to observe how these same observers eagerly and indiscriminately collect studies (no matter how poorly or incompletely performed) supporting their respective hypotheses but peruse with the most "nit-picking" and distrustfuI eye other studies which tend to subvert the interpretive verity of their own. But this is not really a very important cause of our present confusion because only a few investigators indulge in these practices and their foibles are quite well known to their scientific peers. They essentially succeed in misleading only themselves and those physicians and laymen who can not be expected to know of the self-imposed enslavement of these investigators to their respective concepts"
Hmm, Friedman on Keys sounds like Ravnskov on Keys' modern followers.
Plus ça change (plus c'est la même chose)
Peter
This quote covers opinion from Prof John Yudkin and Dr Meyer Friedman. You can hear their dislike of Keys. Keys was the architect of what has become the current world obesity epidemic and never one to let the truth get in the way of a good idea, as with his six nations "fat causes heart disease" study. Unfortunately Meyer's list of those easily misled did not include gullible politicians who set food policy. Keys was a very successful politico, with intense conviction of his own correctness. Fine if he had been right, which he wasn't.
Yudkin begins:
I have already mentioned Dr Ancel Keys and his pioneer work in relation to diet and heart disease. A year or so ago he wrote a memorandum which he sent to a large number of scientists working in this field and which with very few changes has now been published in a medical journal 'Atherosclerosis'. It consists entirely of a strong criticism - I nearly said virulent criticism - of the work I have published from time to time on the theory that sugar is the main dietary factor involved in causing heart disease.
The publication contains a number of quite incorrect and unjustified statements; for instance; that we had never tested our method for measuring sugar intake; that no one eats the amounts of sugar that we and others have used in our experiments; that it was absurd of me in 1957 to use intemational statistics of 41 countries as evidence for the relationship between sugar and heart disease (exactly tbe same statistics that Dr Keys had previously used for only 6 selected countries to show the relationship between fat and heart disease).
He ends by triumphantly pointing out that both sugar and fat intakes are related to heart disease, but that the cause must be fat, not sugar, because he had just found in 1970 that fat intake and sugar intake are themselves closely linked. You will remember my own discussion of this link in Chapter 5, based on the fact that, as far back as 1964, I had shown this relationship to exist between fat intake and sugar intake. Let me therefore quote from a recently published book Pathogenesis Of Coronary Artery Disease written by Dr Meyer Friedman, another distinguished worker in this field:
"It is sad, for example, to observe that essentially honourable investigators omit published data (including some of their own data obtained earlier) which refute or call into question their contemporary data and the interpretations they have made of them. It is even sadder to observe how these same observers eagerly and indiscriminately collect studies (no matter how poorly or incompletely performed) supporting their respective hypotheses but peruse with the most "nit-picking" and distrustfuI eye other studies which tend to subvert the interpretive verity of their own. But this is not really a very important cause of our present confusion because only a few investigators indulge in these practices and their foibles are quite well known to their scientific peers. They essentially succeed in misleading only themselves and those physicians and laymen who can not be expected to know of the self-imposed enslavement of these investigators to their respective concepts"
Hmm, Friedman on Keys sounds like Ravnskov on Keys' modern followers.
Plus ça change (plus c'est la même chose)
Peter
Monday, November 26, 2007
Two rat experiment
While I'm talking about fat I ought to just run through the two rat experiment described by Daniel Quinn.
You place a breeding pair of rats in a very large cage with, let's say, 5kg of rat food. At the end of 24 hours you remove any left over food, put in a fresh 5kg and repeat the process ad infinitum. Remove the excess, never allow more than 5kg. Clean them out occasionally.
They will breed. Their children will breed. Their children's children will breed. The population will grow. Eventually there will come a day when there is no rat food spare at the end of 24 hours. The young rats will continue to grow, maybe some of the older ones will die, those in their prime may loose a little weight. That's life for rats in the cage.
Ultimately an equilibrium will be reached between 5kg of food and a dynamic population of rats. That population will not fluctuate wildly.
You cannot make new rats out of thin air. Older rats dying will free up some food supply so more youngsters will survive. It will balance out.
This was exactly the situation for the humans on Kitava when Lindeberg did his study. On an isolated island, using limited subsistence agriculture and no external power or fertiliser input, there must be a balance struck between population and food.
Back when everyone on the Earth either subsistence farmed or hunted/gathered the same situation must have applied. Hunting on the neighbouring tribe's patch might be highly unpopular and this would set limits on food availability, even with a full continent to use. People were everywhere that would support life.
I don't think that continuous hunger was ever the norm, but obesity would be unheard of. A sustained glut of food would produce extra sprogs to take up the slack. Hard times would be hard on the vulnerable. We humans did this successfully for millions of years. We are no different to rats. We can only breed to our food supply, but we always will breed to that supply.
There never was enough spare food for obesity until the Egyptians started with storable Spelt. It all went down hill from there.
Peter
You place a breeding pair of rats in a very large cage with, let's say, 5kg of rat food. At the end of 24 hours you remove any left over food, put in a fresh 5kg and repeat the process ad infinitum. Remove the excess, never allow more than 5kg. Clean them out occasionally.
They will breed. Their children will breed. Their children's children will breed. The population will grow. Eventually there will come a day when there is no rat food spare at the end of 24 hours. The young rats will continue to grow, maybe some of the older ones will die, those in their prime may loose a little weight. That's life for rats in the cage.
Ultimately an equilibrium will be reached between 5kg of food and a dynamic population of rats. That population will not fluctuate wildly.
You cannot make new rats out of thin air. Older rats dying will free up some food supply so more youngsters will survive. It will balance out.
This was exactly the situation for the humans on Kitava when Lindeberg did his study. On an isolated island, using limited subsistence agriculture and no external power or fertiliser input, there must be a balance struck between population and food.
Back when everyone on the Earth either subsistence farmed or hunted/gathered the same situation must have applied. Hunting on the neighbouring tribe's patch might be highly unpopular and this would set limits on food availability, even with a full continent to use. People were everywhere that would support life.
I don't think that continuous hunger was ever the norm, but obesity would be unheard of. A sustained glut of food would produce extra sprogs to take up the slack. Hard times would be hard on the vulnerable. We humans did this successfully for millions of years. We are no different to rats. We can only breed to our food supply, but we always will breed to that supply.
There never was enough spare food for obesity until the Egyptians started with storable Spelt. It all went down hill from there.
Peter
Getting fat, staying fat, follow on
One kilo of lard contains 9,020kcal of energy. A chunky 40kg of lard represents 360,800kcal.
In the simplistic world of calories-in versus calories-out, how many excess calories per day is this, spread over a reasonable weight gain period? Let's assume it was gained over 20 years, or 7,300 days, ignoring leap years.
That gives 49kcal/day of stored fat. If calories-in equals calories-out anyone carrying 40kg of excess weight could have stopped it by eating just one tiny spoonful less of butter per day. EASY. For goodness sake, these people must be such weak willed, greedy slobs that we should withdraw NHS medical care until they get their act together and stop pigging out on a spoonful of excess butter per day.
But just a minute, how many obese people WANT to be obese? If you believe the calories-in calories-out drivel, weight loss should be easy. Anyone can back off this much butter. Weight Watchers would go bankrupt.
But telling an overweight person to avoid eating fat (gasp, all those calories per gram) means that their diet must be based around carbohydrate. Which raises insulin. Which blocks fat loss. Just 49kcal of blocked fat loss each day over 20 years equals an obesity epidemic. It's not the calories from dry bread, spread with low fat goo, that does this but the insulinaemia that goes with it.
Most people do not read biochemistry texts for fun, they expect their nutritionist to have been paid to do that.
Peter
PS How DO people loose weight on low fat diets? They eat low everything, get hungry and dip their insulin low enough between meals to loose weight, especially in the early hours of the morning. This is hard, especially to sustain. Fat is your friend when you want to loose weight. No hunger in ketosis.
In the simplistic world of calories-in versus calories-out, how many excess calories per day is this, spread over a reasonable weight gain period? Let's assume it was gained over 20 years, or 7,300 days, ignoring leap years.
That gives 49kcal/day of stored fat. If calories-in equals calories-out anyone carrying 40kg of excess weight could have stopped it by eating just one tiny spoonful less of butter per day. EASY. For goodness sake, these people must be such weak willed, greedy slobs that we should withdraw NHS medical care until they get their act together and stop pigging out on a spoonful of excess butter per day.
But just a minute, how many obese people WANT to be obese? If you believe the calories-in calories-out drivel, weight loss should be easy. Anyone can back off this much butter. Weight Watchers would go bankrupt.
But telling an overweight person to avoid eating fat (gasp, all those calories per gram) means that their diet must be based around carbohydrate. Which raises insulin. Which blocks fat loss. Just 49kcal of blocked fat loss each day over 20 years equals an obesity epidemic. It's not the calories from dry bread, spread with low fat goo, that does this but the insulinaemia that goes with it.
Most people do not read biochemistry texts for fun, they expect their nutritionist to have been paid to do that.
Peter
PS How DO people loose weight on low fat diets? They eat low everything, get hungry and dip their insulin low enough between meals to loose weight, especially in the early hours of the morning. This is hard, especially to sustain. Fat is your friend when you want to loose weight. No hunger in ketosis.
Getting fat, staying fat
Fat gets in to fat cells from lipoproteins in the blood stream. Dietary fat is transported in chylomicrons, big fat ladened lipoproteins made by the gut wall. Their production is as random as fat consumption is variable.
Our the bodies never just move fat molecules intact. They are always broken down in to fatty acids, moved across cell membranes in this form, and then reassembled in to triglycerides for long term storage.
The enzyme which performs this break down process is called lipoprotein lipase. Lipoprotein lipase is thus essential for fat storage. That's important.
Fat breakdown, for use as an energy supply, is performed by a completely different lipase, this time it is hormone-sensitive lipase. This enzyme acts on the stored triglycerides inside fat cells and releases free fatty acids in to the blood stream. This is a highly regulated process, finely tuned to supply the energy needed by the body. It is very different from the bulk transport of dietary fat in lipoproteins. As such, the fatty acids can be transported in free form called non esterified fatty acids (attached to albumin in plasma) and simply released as they are needed. Hormone-sensitive lipase is crucial to fat breakdown. That's important too.
It is very obvious, from its name, that hormone-sensitive lipase is under hormonal control. The only hormone which turns off this lipase is insulin.
This paper (From way back in 1964, this is not new information. Physiologists asked very basic questions in those days) shows clearly that insulin, at levels way too low to do anything related to glucose, stops the release of fatty acids from fat tissue. So anything which raises insulin levels blocks fat break down. Carbohydrate raises insulin levels. Insulin blocks fat breakdown. Carbohydrate blocks fat breakdown.
Back to that other lipase, the one that puts the fat in to fat cells in the first place. Is that under any sort of control? Of course it is, our bodies control everything. Guess which hormone controls lipoprotein lipase.
Yes, insulin again.
So insulin has two effects on body fat. It puts it on and keeps it on.
But dietary fat, the primary source of the fat we store, has absolutely no effect on blood insulin levels what so ever. You can eat a block of lard and not budge your insulin levels one iota (or a cup of cream, much more enjoyable). What causes us to store dietary fat, as a big bum or tum, is dietary carbohydrate, because it elevates blood insulin level more than any other food source.
So the take home message from this post is that insulin is the key hormone for fat storage. Dietary carbohydrate makes you store dietary fat, and eating carbohydrate stops you burning stored fat.
It makes you think of those Swedish children. Eating sugar makes them fat, eating saturated fat keeps them slim. Now you know why.
If only nutritionists understood this.
Peter
PS does eating half a kilo of lard per day make you put on weight? Possibly, as there is a basal rate of lipoprotein lipase activity irrespective of insulin levels. More importantly, have you ever tried to actually eat 500g of lard in a day? Palatability apart, if you did actually succeed, you would feel dreadful and I doubt you would be tempted to repeat the experience. The vast majority of people on mildly ketogenic high fat diets seem to stabilise their food intake somewhere between 1500 and 2500kcal/day. That is appropriate for weight loss or weight stability, depending on your baseline weight and activity level.
Our the bodies never just move fat molecules intact. They are always broken down in to fatty acids, moved across cell membranes in this form, and then reassembled in to triglycerides for long term storage.
The enzyme which performs this break down process is called lipoprotein lipase. Lipoprotein lipase is thus essential for fat storage. That's important.
Fat breakdown, for use as an energy supply, is performed by a completely different lipase, this time it is hormone-sensitive lipase. This enzyme acts on the stored triglycerides inside fat cells and releases free fatty acids in to the blood stream. This is a highly regulated process, finely tuned to supply the energy needed by the body. It is very different from the bulk transport of dietary fat in lipoproteins. As such, the fatty acids can be transported in free form called non esterified fatty acids (attached to albumin in plasma) and simply released as they are needed. Hormone-sensitive lipase is crucial to fat breakdown. That's important too.
It is very obvious, from its name, that hormone-sensitive lipase is under hormonal control. The only hormone which turns off this lipase is insulin.
This paper (From way back in 1964, this is not new information. Physiologists asked very basic questions in those days) shows clearly that insulin, at levels way too low to do anything related to glucose, stops the release of fatty acids from fat tissue. So anything which raises insulin levels blocks fat break down. Carbohydrate raises insulin levels. Insulin blocks fat breakdown. Carbohydrate blocks fat breakdown.
Back to that other lipase, the one that puts the fat in to fat cells in the first place. Is that under any sort of control? Of course it is, our bodies control everything. Guess which hormone controls lipoprotein lipase.
Yes, insulin again.
So insulin has two effects on body fat. It puts it on and keeps it on.
But dietary fat, the primary source of the fat we store, has absolutely no effect on blood insulin levels what so ever. You can eat a block of lard and not budge your insulin levels one iota (or a cup of cream, much more enjoyable). What causes us to store dietary fat, as a big bum or tum, is dietary carbohydrate, because it elevates blood insulin level more than any other food source.
So the take home message from this post is that insulin is the key hormone for fat storage. Dietary carbohydrate makes you store dietary fat, and eating carbohydrate stops you burning stored fat.
It makes you think of those Swedish children. Eating sugar makes them fat, eating saturated fat keeps them slim. Now you know why.
If only nutritionists understood this.
Peter
PS does eating half a kilo of lard per day make you put on weight? Possibly, as there is a basal rate of lipoprotein lipase activity irrespective of insulin levels. More importantly, have you ever tried to actually eat 500g of lard in a day? Palatability apart, if you did actually succeed, you would feel dreadful and I doubt you would be tempted to repeat the experience. The vast majority of people on mildly ketogenic high fat diets seem to stabilise their food intake somewhere between 1500 and 2500kcal/day. That is appropriate for weight loss or weight stability, depending on your baseline weight and activity level.
Wednesday, November 21, 2007
Sugar poisoning
I don't think much of the cholesterol hypothesis. OK, it's junk.
But I do find cholesterol levels interesting, in so far as they reflect the degree of carbohydrate poisoning a population is suffering. Researchers are starting to understand this, though I guess they still think the cholesterol levels really matter, rather than looking at the primary problems with glucose and insulin. Obviously low HDL and high triglycerides are appalling things to have because, in general, they represent sugar poisoning.
A chink of light occurred with this study. It's epidemiological, observational and not available in full text without being ripped off by the American Journal of Clinical Nutrition. So not much use to anyone. But the press release by the group contains one of the best lines I've ever seen and gets 110% for deep insightful perception. Here's the line I love:
"Previous research has identified ethnic differences in cholesterol and other blood fat levels that couldn't be explained by genes, obesity, lifestyle factors or diet, Merchant and his team note, but these analyses usually looked at dietary fat, not carbohydrate consumption"
Woo hoo, now there's a surprise! People are poisoning themselves with glucose and fructose and researchers were absolutely focused on dietary fat. FAT! This is not focus, this is preconceived blinkering.
I quite like this line too:
"Reducing the frequency of intake of sugar-containing soft drinks, juices and snacks may be beneficial"
Obviously elimination is highly preferable to reduction, but these people seem to know what they are talking about, though I suspect they still think of triglycerides in terms of hot fat down a cold sewer.
Actually, the other publication from this group looks very sensible too. I'll stop being grudging and just say THANKS.
Peter
But I do find cholesterol levels interesting, in so far as they reflect the degree of carbohydrate poisoning a population is suffering. Researchers are starting to understand this, though I guess they still think the cholesterol levels really matter, rather than looking at the primary problems with glucose and insulin. Obviously low HDL and high triglycerides are appalling things to have because, in general, they represent sugar poisoning.
A chink of light occurred with this study. It's epidemiological, observational and not available in full text without being ripped off by the American Journal of Clinical Nutrition. So not much use to anyone. But the press release by the group contains one of the best lines I've ever seen and gets 110% for deep insightful perception. Here's the line I love:
"Previous research has identified ethnic differences in cholesterol and other blood fat levels that couldn't be explained by genes, obesity, lifestyle factors or diet, Merchant and his team note, but these analyses usually looked at dietary fat, not carbohydrate consumption"
Woo hoo, now there's a surprise! People are poisoning themselves with glucose and fructose and researchers were absolutely focused on dietary fat. FAT! This is not focus, this is preconceived blinkering.
I quite like this line too:
"Reducing the frequency of intake of sugar-containing soft drinks, juices and snacks may be beneficial"
Obviously elimination is highly preferable to reduction, but these people seem to know what they are talking about, though I suspect they still think of triglycerides in terms of hot fat down a cold sewer.
Actually, the other publication from this group looks very sensible too. I'll stop being grudging and just say THANKS.
Peter
Tuesday, November 20, 2007
J-LIT update
Here's a quick update on the J-LIT study using low dose simvastatin for primary prevention of heart disease.
My thanks to Stan for pointing out that I missed the six fold increase in risk of CARDIOVASCULAR mortality in the lowest cholesterol group compared to the "normal" (200-219mg/dl) cholesterol group in this study.
There it is in Table 6 on page 1092. For goodness sake, it's on the first line! I must have been asleep when I read the paper:
Cardiac mortality relative risk was 6.23 in patients who's cholesterol dropped below 160mg/dl compared to those with TC 200-219mg/dl.
That is; you are more than six times as likely to be dead of a cardiovascular problem if your TC dropped to a level to make the average cardiologist grudgingly happy.
Boy, when you need cholesterol, you need it.
Peter
My thanks to Stan for pointing out that I missed the six fold increase in risk of CARDIOVASCULAR mortality in the lowest cholesterol group compared to the "normal" (200-219mg/dl) cholesterol group in this study.
There it is in Table 6 on page 1092. For goodness sake, it's on the first line! I must have been asleep when I read the paper:
Cardiac mortality relative risk was 6.23 in patients who's cholesterol dropped below 160mg/dl compared to those with TC 200-219mg/dl.
That is; you are more than six times as likely to be dead of a cardiovascular problem if your TC dropped to a level to make the average cardiologist grudgingly happy.
Boy, when you need cholesterol, you need it.
Peter
Sunday, November 18, 2007
Best ever statin study?
I missed this landmark paper last year, full text here. Possibly because, as it continues the demolition of the cholesterol hypothesis, it received absolutely zero publicity. I posted about the J-Litt study here, but this one is even better.
The paper is from the Essen group (in Germany) and describes their study comparing normal dose atrovastatin (10mg/d) with high dose atrovastatin (80mg/d).
Same drug, different dose rates, different cholesterol levels. Follow your patients for a year and have the coronary artery calcification progress tracked by electron-beam computed tomography. This is a reasonably well designed study, except see the "phew" comment below.
How much difference does it make if you drop your LDL-cholesterol to 87mg/dl as compared to 109mg/dl?
I think the answer is technically known as "diddly squat". Or zero, zilch, nuthin, nowt.
The answer as to why is pretty clear from table 3 shown here.
Look at the falls in hsCRP and fibrinogen on low vs high dose atrovastatin. They're the same between groups. Ie the anti inflammatory effect and anti thrombotic effects are maxed out at 10mg, so no further benefit is seen at 80mg. From my point of view this is fortunate. Had these pleiotropic effects not maxed out the study might have suggested lowering cholesterol was beneficial. But 80mg of atrovastatin is no better an anti inflammatory agent than 10mg is. Phew.
The paper discussion is an amusing catalogue of excuses and references to studies "better" designed to show the benefits of aggressive statin use. The trick is to use different drugs and give the best anti inflammatory statin at the highest dose rate. Then the lowest cholesterol correlates with, but is not responsible for, the least CV problems. It is also sensible NOT to measure CRP or fibrinogen, otherwise you end up with a study like this one, where people can see what's going on.
This group strike me as genuine medics who believe in the lipid hypothesis and are genuinely surprised that they have trashed the cholesterol hypothesis by accident. Still, I'll leave them with the best line from their conclusions, ignoring the squirming in the discussion and the plea for more time to get an effect. Here it is:
"we did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis"
Peter
Thank you to Dr Davis of Track Your Plaque for citing this unheard of paper
and to
Drs Axel Schmermund, MD; Stephan Achenbach, MD; Thomas Budde, MD; Yuri Buziashvili, MD; Andreas Förster, MD; Guy Friedrich, MD; Michael Henein, MD; Gert Kerkhoff, MD; Friedrich Knollmann, MD; Valery Kukharchuk, MD; Avijit Lahiri, MD; Roman Leischik, MD; Werner Moshage, MD; Michael Schartl, MD; Winfried Siffert, MD; Elisabeth Steinhagen-Thiessen, MD; Valentin Sinitsyn, MD; Anja Vogt, MD; Burkhard Wiedeking, MD; Raimund Erbel, MD
for this excellent study, published in a full-text-for-free journal.
The paper is from the Essen group (in Germany) and describes their study comparing normal dose atrovastatin (10mg/d) with high dose atrovastatin (80mg/d).
Same drug, different dose rates, different cholesterol levels. Follow your patients for a year and have the coronary artery calcification progress tracked by electron-beam computed tomography. This is a reasonably well designed study, except see the "phew" comment below.
How much difference does it make if you drop your LDL-cholesterol to 87mg/dl as compared to 109mg/dl?
I think the answer is technically known as "diddly squat". Or zero, zilch, nuthin, nowt.
The answer as to why is pretty clear from table 3 shown here.
Look at the falls in hsCRP and fibrinogen on low vs high dose atrovastatin. They're the same between groups. Ie the anti inflammatory effect and anti thrombotic effects are maxed out at 10mg, so no further benefit is seen at 80mg. From my point of view this is fortunate. Had these pleiotropic effects not maxed out the study might have suggested lowering cholesterol was beneficial. But 80mg of atrovastatin is no better an anti inflammatory agent than 10mg is. Phew.
The paper discussion is an amusing catalogue of excuses and references to studies "better" designed to show the benefits of aggressive statin use. The trick is to use different drugs and give the best anti inflammatory statin at the highest dose rate. Then the lowest cholesterol correlates with, but is not responsible for, the least CV problems. It is also sensible NOT to measure CRP or fibrinogen, otherwise you end up with a study like this one, where people can see what's going on.
This group strike me as genuine medics who believe in the lipid hypothesis and are genuinely surprised that they have trashed the cholesterol hypothesis by accident. Still, I'll leave them with the best line from their conclusions, ignoring the squirming in the discussion and the plea for more time to get an effect. Here it is:
"we did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis"
Peter
Thank you to Dr Davis of Track Your Plaque for citing this unheard of paper
and to
Drs Axel Schmermund, MD; Stephan Achenbach, MD; Thomas Budde, MD; Yuri Buziashvili, MD; Andreas Förster, MD; Guy Friedrich, MD; Michael Henein, MD; Gert Kerkhoff, MD; Friedrich Knollmann, MD; Valery Kukharchuk, MD; Avijit Lahiri, MD; Roman Leischik, MD; Werner Moshage, MD; Michael Schartl, MD; Winfried Siffert, MD; Elisabeth Steinhagen-Thiessen, MD; Valentin Sinitsyn, MD; Anja Vogt, MD; Burkhard Wiedeking, MD; Raimund Erbel, MD
for this excellent study, published in a full-text-for-free journal.
Wednesday, November 07, 2007
Torcetrapib again
I posted on torcetrapib here but missed some information. You always miss some interesting facts when you don't have the full paper. Those nice people on the HDL forum never mentioned the increases seen in deaths from cancer and infection. Fortunately that made it in to the NY Times recently.
Quote from the NY Times article:
"Besides having more heart problems, patients taking torcetrapib were more likely to die of cancer and infection than those on a placebo. In all, 93 patients taking torcetrapib died, compared with 59 who took a placebo"
and from Dr. Daniel J. Rader of the University of Pennsylvania:
“It appears that HDL evolved as a component of the innate immune system and that its composition is critically important to its function.”
Dr Rader gets this week's prize for least well read cardiologist. It's the LDL that matters! But how many cardiologists would read Ravnskov? After all he is one of the most effective critics of the lipid hypothesis. Would you, as a cardiologist, read papers by someone convinced that yourself and the rest of the cholesterol industry is wrong?
Cholesterol and both arteriosclerosis and infection
Cholesterol and cancer
Note that Ravnskov explains all three of the problems seen in the Illuminate trials.
Again a quote from Dr Rader via the NY Times:
"But over all... it is premature to announce the death of CETP inhibitors on the basis of the torcetrapib experience alone"
My opinion?
He's wrong.
Peter
Quote from the NY Times article:
"Besides having more heart problems, patients taking torcetrapib were more likely to die of cancer and infection than those on a placebo. In all, 93 patients taking torcetrapib died, compared with 59 who took a placebo"
and from Dr. Daniel J. Rader of the University of Pennsylvania:
“It appears that HDL evolved as a component of the innate immune system and that its composition is critically important to its function.”
Dr Rader gets this week's prize for least well read cardiologist. It's the LDL that matters! But how many cardiologists would read Ravnskov? After all he is one of the most effective critics of the lipid hypothesis. Would you, as a cardiologist, read papers by someone convinced that yourself and the rest of the cholesterol industry is wrong?
Cholesterol and both arteriosclerosis and infection
Cholesterol and cancer
Note that Ravnskov explains all three of the problems seen in the Illuminate trials.
Again a quote from Dr Rader via the NY Times:
"But over all... it is premature to announce the death of CETP inhibitors on the basis of the torcetrapib experience alone"
My opinion?
He's wrong.
Peter
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