I've lost a study. It's really annoying when that happens, you flick through a patient characteristics table and think, hmmmm, I'll keep that. Then you don't. This was another colorectal cancer and/or polyp study. Probably looking at fiber. It was another of those splits, people who got cancer vs those who didn't. I was reading the baseline patient characteristics. The eye catching parameter was financial income. Below so many thousand dollars (possibly Aussie dollars) of income per year was bad news for colorectal cancer. Higher income improved prognosis. Sorry, higher income was "associated" with a better prognosis.
Another of those missed opportunities to try throwing money at a problem.
While I was hunting said paper I hit on the PPT (Polyp Prevention Trial). This was another mega intervention trial along the lines of WHEL in breast cancer. I had the temerity to click on the "related articles" link and all of the papers poured out. Significant increases in all of the politically correct stuff, sustained with INCREASING compliance over 4 years. Fat was down at close to 20% of calories with at least 7 servings of plants a day. Enough fiber you wouldn't want to share an enclosed space with an intervention participant for too long. Obviously produced diddly squat improvement compared to no intervention by four years, so they followed for eight years. You can't say that this belief structure doesn't engender persistance! More diddly squat at eight years.
However people in the intervention group felt very positive about the whole thing. That's nice. But nobody seemed to care about the control group...
Overall, not a lot to show for eight years of work. But of course it needed doing to disprove the hypothesis that fruit 'n' fiber is good for you, which it did, nicely. No one seems to have been overjoyed. Or noticed for that matter.
Somewhat hysterically they did a data trawl and came up with this gem.
Again, please be cautious about getting in to a lift with someone eating enough dry beans to make a difference. If it really was beans which made the difference, which I doubt.
Peter
Thursday, January 31, 2008
Tuesday, January 29, 2008
Colorectal cancer and cholesterol
Because I'm quite interested in colorectal cancer I've had this abstract lying around on my desktop for some time, awaiting full reading before "drag and drop" in to that enormous and chaotic folder labeled "Diet stuff".
OK, the usual caveats apply; it's observational and it's a bit of a data trawl from the Cardiovascular Health Study. Hmmm, this means that cardiologists are involved in the data acquisition. Bad.
On the plus side it's prospective and no drug company is involved. US government funded. It's also available in full text, which is nice because it means I can work through their results and see if their conclusions are derived from their findings.
You know how it is, you browse down these tables slotting yourself in to the various groups and... Ooooh, they measured cholesterol levels! Now there's a surprise. Did you notice any mention of cholesterol levels in the abstract? Particularly that killer LDL cholesterol?
No, neither did I.
LDL-C got its little section as the penultimate parameter in table 2. Let's read the table, the bit we want is down at the bottom. And the risk of colorectal cancer is:
LDL-C quartile and risk of colorectal cancer:
Lowest.......1.0 (reference value)
2nd............0.8
3rd.............0.6
Highest.......0.5
The absolute numbers were, from lowest to highest, 35/1447, 26/1416, 23/1467 and 16/1386 incident cancers.
The relationship is remarkably linear, p = 0.01
None of the other parameters (fasting glucose or glucose 2h post OGTT) did any better than p = 0.02. But they got in to the abstract. And in to the title too!
The LDL-C association did get a brief mention in the discussion:
"Surprisingly, a strong association between increased LDL levels and decreased risk of colorectal cancer was identified. The explanation for this finding is unclear."
That's it.
That's the total discussion of their most statistically significant finding. Possibly their most biologically significant finding.
The lowest quartile for men had LDL-C below 100mg/dl, women below 110mg/dl. Those were the ones most likely to get bowel cancer. I think it's worth pointing out that the average cardiologist would consider an LDL-C of 100mg/dl or above as a peracute statin deficiency. That lowest quartile is where your cardiologist wants you to be.
BTW I'm in the highest LDL-C group. Just as well, with my family history.
Just assuming, for a split second, that there is causality between low LDL-C and colorectal cancer, would you expect statins to trade heart attacks for cancer? Pravastatin perhaps? I posted the body counts here.
Anyone chosen between heart attack and bowel cancer yet?
The last author on this paper is Savage. He's surprised at the association. Why should he be? He helped write the guide to treating metabolic syndrome for the US government. He would be expected to have read the literature. Maybe.
Obviously he wouldn't read an Irish paper:
"A group of 114 Irish patients with primary adenocarcinoma of the large bowel had significantly lower serum cholesterol concentrations than an age and sex matched group drawn from the general population"
or a Brazilian paper:
"Our study suggests an association between low blood cholesterol and colorectal cancer"
or an Austrian paper:
"low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases"
or a Japanese paper:
"The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin"
or even stuff from Honalulu:
"Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION: We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L, 181mg/dl) in elderly people"
But, for crying out loud, you would have thought he would have memorised chunks of Keys as part of his cardiology training!
Keys:
"Among 477 cancer deaths five years after cholesterol measurement, there was a significant excess of lung cancer deaths in the bottom 20% of the cholesterol distributions in the populations"
How about NHANES1:
"The inverse cholesterol-cancer relation in men was present for cholesterol determinations made 6 or more years before diagnosis of cancer"
or even Framingham:
"Although the Framingham data are not conclusive, they do suggest that in some cancer cases where the serum cholesterol level was lower than that expected at as much as 16--18 years before cancer diagnosis, the depressed level was likely to be a precursor to the tumor growth"
Surprised is he?
That's enough. I was looking for information about glucose and cancer and yet again ended up grinding my teeth on the stupid cholesterol hypothesis and its followers.
I'll calm down now.
Peter
OK, the usual caveats apply; it's observational and it's a bit of a data trawl from the Cardiovascular Health Study. Hmmm, this means that cardiologists are involved in the data acquisition. Bad.
On the plus side it's prospective and no drug company is involved. US government funded. It's also available in full text, which is nice because it means I can work through their results and see if their conclusions are derived from their findings.
You know how it is, you browse down these tables slotting yourself in to the various groups and... Ooooh, they measured cholesterol levels! Now there's a surprise. Did you notice any mention of cholesterol levels in the abstract? Particularly that killer LDL cholesterol?
No, neither did I.
LDL-C got its little section as the penultimate parameter in table 2. Let's read the table, the bit we want is down at the bottom. And the risk of colorectal cancer is:
LDL-C quartile and risk of colorectal cancer:
Lowest.......1.0 (reference value)
2nd............0.8
3rd.............0.6
Highest.......0.5
The absolute numbers were, from lowest to highest, 35/1447, 26/1416, 23/1467 and 16/1386 incident cancers.
The relationship is remarkably linear, p = 0.01
None of the other parameters (fasting glucose or glucose 2h post OGTT) did any better than p = 0.02. But they got in to the abstract. And in to the title too!
The LDL-C association did get a brief mention in the discussion:
"Surprisingly, a strong association between increased LDL levels and decreased risk of colorectal cancer was identified. The explanation for this finding is unclear."
That's it.
That's the total discussion of their most statistically significant finding. Possibly their most biologically significant finding.
The lowest quartile for men had LDL-C below 100mg/dl, women below 110mg/dl. Those were the ones most likely to get bowel cancer. I think it's worth pointing out that the average cardiologist would consider an LDL-C of 100mg/dl or above as a peracute statin deficiency. That lowest quartile is where your cardiologist wants you to be.
BTW I'm in the highest LDL-C group. Just as well, with my family history.
Just assuming, for a split second, that there is causality between low LDL-C and colorectal cancer, would you expect statins to trade heart attacks for cancer? Pravastatin perhaps? I posted the body counts here.
Anyone chosen between heart attack and bowel cancer yet?
The last author on this paper is Savage. He's surprised at the association. Why should he be? He helped write the guide to treating metabolic syndrome for the US government. He would be expected to have read the literature. Maybe.
Obviously he wouldn't read an Irish paper:
"A group of 114 Irish patients with primary adenocarcinoma of the large bowel had significantly lower serum cholesterol concentrations than an age and sex matched group drawn from the general population"
or a Brazilian paper:
"Our study suggests an association between low blood cholesterol and colorectal cancer"
or an Austrian paper:
"low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases"
or a Japanese paper:
"The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin"
or even stuff from Honalulu:
"Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION: We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L, 181mg/dl) in elderly people"
But, for crying out loud, you would have thought he would have memorised chunks of Keys as part of his cardiology training!
Keys:
"Among 477 cancer deaths five years after cholesterol measurement, there was a significant excess of lung cancer deaths in the bottom 20% of the cholesterol distributions in the populations"
How about NHANES1:
"The inverse cholesterol-cancer relation in men was present for cholesterol determinations made 6 or more years before diagnosis of cancer"
or even Framingham:
"Although the Framingham data are not conclusive, they do suggest that in some cancer cases where the serum cholesterol level was lower than that expected at as much as 16--18 years before cancer diagnosis, the depressed level was likely to be a precursor to the tumor growth"
Surprised is he?
That's enough. I was looking for information about glucose and cancer and yet again ended up grinding my teeth on the stupid cholesterol hypothesis and its followers.
I'll calm down now.
Peter
Monday, January 28, 2008
Hunger
I'm about half way through Marina Lwycka's multiple prize wining novel "A Short History of Tractors in Ukrainian". It's quite funny in places, although the stereotypes are laid on with a trowel. The narrator is Nadia (Nadezhda), a first generation English woman with Ukrainian parents. After her mother's funeral she describes the state of the house. It's full of food. The understairs pantry, the freezers, the drawers under the beds. All full of food. This is fiction.
Lwycka herself was born to Ukrainian parents in a refugee camp in Germany, at the end of the second World War. Her parents may well have had the same history as my father. I'll bet they were the source of the snippets of history involving food.
The only book my father owned was Victor Kravchenko's "I Chose Freedom". This is factual autobiography. You can pick up a copy for under £3.00 second hand through Amazon. Kravchenko was a young and enthusiastic Soviet official at the time when Stalin discovered that famine could be used to solve what was then known as the "Agrarian Problem". If you starved the peasant populace to death in their millions, the survivors would accept the collectivisation of agriculture. The policy required between 7 and 10 million Ukrainians dead of starvation in just over one year, but it worked. Kravchenko was there and was aghast at the suffering he witnessed in the Western Ukraine. His account makes harrowing reading. My father, a peasant from the Western Ukraine, would have been about 10 years old when the famine was engineered. He never, ever alluded to any of this beyond owning Kravchenko's book. And mentioning, just once, that Kravchenko painted an accurate picture.
As a youngster it never struck me as odd that we had a large part of our garden down to vegetables (mind you, as a youngster I didn't think my father had an accent!). Or a big greenhouse full of tomatoes and cucumbers. Or multiple fruit trees. Or TWO local council allotments. Each with a greenhouse packed with tomatoes. Big potato patches, spuds in clamps for the winter. We never much ate New Potatoes. Bulk main crop was preferred. Masses of bulk yield soft fruit. Peas. Peas were harvested late, because Dad had no interest in petit pois when two weeks later you could have a crop of serious bulk food. Apples in drawers and boxes in the basement, wrapped in newspaper. Bottled fruit. Freezers full of runner beans. Pickled cabbage.
No one else's family did this, as far as I can remember, but Lwycka's character of the mother in her novel could have been based on my father.
Anyway, there is a fascinating passage in "Tractors". It's a disastrous argumentative tea party and one of the interchanges goes like this. Nadia, the narrator, is skinny. The elderly Ukrainians (the Zadchucks) are not. They're arguing about weight.
Mrs Zadchuck (heavy Ukranian accent, broken english) says to her husband:
'Better fatty than skinny. Look Nadezhda. She starving Bangladesh-lady.'
I (Nadia) take this as a slight. Righteously, I draw in my stomach. 'Thin is good. Thin is healthy. Thin people live longer.'
All of them turn on me with howls of derisive laughter.
'Thin is hunger! Thin is famine! Everyone thin drop over dead! Ha ha.'
It's fiction, but these characters are based on people who were there in the Ukraine in 1932. Humans don't get fat to get metabolic syndrome. Those of us (me included) who are a bit smug with a BMI around 20 maybe ought to remember that a BMI of 25-30 appears to give best longevity in Western culture, even without a famine. I don't rate my own chances living off my fat during any period of famine and I only own one greenhouse and a small freezer...
Peter
Lwycka herself was born to Ukrainian parents in a refugee camp in Germany, at the end of the second World War. Her parents may well have had the same history as my father. I'll bet they were the source of the snippets of history involving food.
The only book my father owned was Victor Kravchenko's "I Chose Freedom". This is factual autobiography. You can pick up a copy for under £3.00 second hand through Amazon. Kravchenko was a young and enthusiastic Soviet official at the time when Stalin discovered that famine could be used to solve what was then known as the "Agrarian Problem". If you starved the peasant populace to death in their millions, the survivors would accept the collectivisation of agriculture. The policy required between 7 and 10 million Ukrainians dead of starvation in just over one year, but it worked. Kravchenko was there and was aghast at the suffering he witnessed in the Western Ukraine. His account makes harrowing reading. My father, a peasant from the Western Ukraine, would have been about 10 years old when the famine was engineered. He never, ever alluded to any of this beyond owning Kravchenko's book. And mentioning, just once, that Kravchenko painted an accurate picture.
As a youngster it never struck me as odd that we had a large part of our garden down to vegetables (mind you, as a youngster I didn't think my father had an accent!). Or a big greenhouse full of tomatoes and cucumbers. Or multiple fruit trees. Or TWO local council allotments. Each with a greenhouse packed with tomatoes. Big potato patches, spuds in clamps for the winter. We never much ate New Potatoes. Bulk main crop was preferred. Masses of bulk yield soft fruit. Peas. Peas were harvested late, because Dad had no interest in petit pois when two weeks later you could have a crop of serious bulk food. Apples in drawers and boxes in the basement, wrapped in newspaper. Bottled fruit. Freezers full of runner beans. Pickled cabbage.
No one else's family did this, as far as I can remember, but Lwycka's character of the mother in her novel could have been based on my father.
Anyway, there is a fascinating passage in "Tractors". It's a disastrous argumentative tea party and one of the interchanges goes like this. Nadia, the narrator, is skinny. The elderly Ukrainians (the Zadchucks) are not. They're arguing about weight.
Mrs Zadchuck (heavy Ukranian accent, broken english) says to her husband:
'Better fatty than skinny. Look Nadezhda. She starving Bangladesh-lady.'
I (Nadia) take this as a slight. Righteously, I draw in my stomach. 'Thin is good. Thin is healthy. Thin people live longer.'
All of them turn on me with howls of derisive laughter.
'Thin is hunger! Thin is famine! Everyone thin drop over dead! Ha ha.'
It's fiction, but these characters are based on people who were there in the Ukraine in 1932. Humans don't get fat to get metabolic syndrome. Those of us (me included) who are a bit smug with a BMI around 20 maybe ought to remember that a BMI of 25-30 appears to give best longevity in Western culture, even without a famine. I don't rate my own chances living off my fat during any period of famine and I only own one greenhouse and a small freezer...
Peter
Sunday, January 27, 2008
Wheat and lactose and Cordain
In the comments thread of another post "g" pointed me to this ref. It's very interesting about WGA (Wheat Germ Agglutinin) hitting the nuclear pore, so stopping all sorts of cell signaling traffic. But this business about lactase is very dubious.
From here on down the inverted coma bits are direct quotes from Cordain, the other bits are me. EGF-R is epidermal growth factor receptor, a cell signaling and growth regulating receptor.
"Once in gut cells (enterocytes) WGA gains access to the circulation via the lymph and is not removed from circulation by the liver or by gamma globulins. Hence, within an hour of consumption WGA is found in plasma in physiological meaningful concentrations (as high as 5ug/ml). Because EGF-R are found on virtually all cells in the body, WGA now can enter the cellular compartment of all cells in the body. Once within cells, WGA wreaks more havoc by binding a structure called the nuclear pore and thereby impedes or prevents the cytosolic transport of the vitamin D receptor and its ligand (1,25 hydroxyvitamin D3) to the nucleus which results in impaired vitamin D utilization and systemically will result in rickets if high dietary levels of whole wheat are chronically consumed."
This is very interesting, it looks like Cordain follows Pusztai's line of thinking on systemic absorption of WGA and is citing a new toxicity. This time via the vitamin D receptor and rickets. Nice.
However Cordain always seems to blot his copybook. Let's try and make head or tail of the next paragraph. It goes like this:
"Lactase is an enzyme technically known as lactase phorizin hydrolase or LPH. LPH [lactase] is a carbohydrate enzyme (glycosidase) belonging to the beta galactosidase family and it catalyzes the sugar beta-galactosidase in addition to catalyzing lactose, the sugar in milk."
What does this mean? Beta-galactosidase is not a sugar, it's the enzyme family to which lactase belongs, as Cordain has just told us. So this has to be a typo, which leaves us in the dark as to exactly what Cordain intended to say. Was it beta galactosamine he was talking about, as in the next sentence? Is he suggesting that lactase either breaks down or synthesises beta galactosamine?
"Beta galactosamine is a key structural sugar in the EGF-R."
I'll take that on trust.
"Hence the adult retention of LPH [lactase] was strongly selected in Neolithic N. European populations because it could compete with WGA for the EGF-R and thereby, in effect, displace WGA from the EGF-R."
Now what does this mean? Is he saying lactase binds directly to the EGF-R on the gut to stop the ingress of WGA in to enterocytes and thus in to the lymphatics and systemic circulation?
"WGA preferentially binds the sugar n-acetylglucosamine which is also present in the EGF-R."
This is true (taking on trust that n-acetylglucosamine is present on EGF-R).
"Consequently, the evolutionary selection for LPH [lactase] occurred as direct competition for the EGF-R rather than LPH binding WGA directly."
The implication from this is that lactase is binding to beta galactosamine on EGF-R of enterocytes and this binding is stopping WGA from binding to the n-acetylglucosamine of same EGF-R molecule. Cordain doesn't mention the gut cell surface as the site of interaction but never suggests that lactase ever reaches significant concentrations in the systemic circulation, so let's stick with gut. He finishes:
"In summary then, the simulataneous selection for LPH [lactase] and dermal de-pigmentation were two changes in the genome of Northern Europeans that were a direct evolutionary response to increased consumption of whole wheat"
I can buy the need for pale skin on a Vitamin D deficient diet in Northern climates. Grains are the pits for deficiency diseases. The nuclear pore blockade should actually predict that WGA consuming people need a higher absolute level of vitamin D for health. I wonder if this is true?
But I don't buy the lactase part.
Lactase is part of a family of enzymes for cleaving terminal sugar moieties. Why should it just sit on the EGF-R to keep WGA off? I can believe it might visit EGF-R briefly to chop up the beta galactosamine (but why?) whenever it's not actively chopping up lactose, but would it sit there attached to beta galactosamine (without cleaving it?) when it should really be getting on with its next lactose cleavage job? Also, would a mammal put in to its infant food a sugar which induces lactase production if that lactase was then going to slip away and sit on the glycation moiety of one of its growth factor receptors? EGF-R is there for cell signaling and the beta galactosamine is a "key structural sugar", not decoration. Maybe it actually needs its beta galactosamine component to work.
On the other hand wheat is looking for a free ride for its seeds. WGA is its lectin, which uses n-acetylglucosamine moieties on cell surfaces specifically to become endocytosed. Once inside the cell all WGA needs to do is produce as much damage as possible, so disrupting digestion, which will maximise the chances of any still undamaged wheat seeds being passed through the gut in tact. Then these can seed the next piece of clear ground which the herbivore poops on.
I notice the email comment is dated Feb 2006. It's now late Jan 2008 and the publication has not hit Pubmed yet. Maybe that one final experiment didn't work?
What's wrong with WGA damaging everyone, full stop? And that lactase persistence is rapidly selected for in people who keep cows for milk, otherwise they get gut rot? Do the Maasai loose lactase when weaned from their mothers because they don't eat wheat? They would no more eat wheat than Cordain would live on sour cow's milk, bulked up when necessary with fresh cow's blood!
Yummie.
Peter
PS I'm surprised Cordain didn't suggest a statin to raise vitamin D levels!
From here on down the inverted coma bits are direct quotes from Cordain, the other bits are me. EGF-R is epidermal growth factor receptor, a cell signaling and growth regulating receptor.
"Once in gut cells (enterocytes) WGA gains access to the circulation via the lymph and is not removed from circulation by the liver or by gamma globulins. Hence, within an hour of consumption WGA is found in plasma in physiological meaningful concentrations (as high as 5ug/ml). Because EGF-R are found on virtually all cells in the body, WGA now can enter the cellular compartment of all cells in the body. Once within cells, WGA wreaks more havoc by binding a structure called the nuclear pore and thereby impedes or prevents the cytosolic transport of the vitamin D receptor and its ligand (1,25 hydroxyvitamin D3) to the nucleus which results in impaired vitamin D utilization and systemically will result in rickets if high dietary levels of whole wheat are chronically consumed."
This is very interesting, it looks like Cordain follows Pusztai's line of thinking on systemic absorption of WGA and is citing a new toxicity. This time via the vitamin D receptor and rickets. Nice.
However Cordain always seems to blot his copybook. Let's try and make head or tail of the next paragraph. It goes like this:
"Lactase is an enzyme technically known as lactase phorizin hydrolase or LPH. LPH [lactase] is a carbohydrate enzyme (glycosidase) belonging to the beta galactosidase family and it catalyzes the sugar beta-galactosidase in addition to catalyzing lactose, the sugar in milk."
What does this mean? Beta-galactosidase is not a sugar, it's the enzyme family to which lactase belongs, as Cordain has just told us. So this has to be a typo, which leaves us in the dark as to exactly what Cordain intended to say. Was it beta galactosamine he was talking about, as in the next sentence? Is he suggesting that lactase either breaks down or synthesises beta galactosamine?
"Beta galactosamine is a key structural sugar in the EGF-R."
I'll take that on trust.
"Hence the adult retention of LPH [lactase] was strongly selected in Neolithic N. European populations because it could compete with WGA for the EGF-R and thereby, in effect, displace WGA from the EGF-R."
Now what does this mean? Is he saying lactase binds directly to the EGF-R on the gut to stop the ingress of WGA in to enterocytes and thus in to the lymphatics and systemic circulation?
"WGA preferentially binds the sugar n-acetylglucosamine which is also present in the EGF-R."
This is true (taking on trust that n-acetylglucosamine is present on EGF-R).
"Consequently, the evolutionary selection for LPH [lactase] occurred as direct competition for the EGF-R rather than LPH binding WGA directly."
The implication from this is that lactase is binding to beta galactosamine on EGF-R of enterocytes and this binding is stopping WGA from binding to the n-acetylglucosamine of same EGF-R molecule. Cordain doesn't mention the gut cell surface as the site of interaction but never suggests that lactase ever reaches significant concentrations in the systemic circulation, so let's stick with gut. He finishes:
"In summary then, the simulataneous selection for LPH [lactase] and dermal de-pigmentation were two changes in the genome of Northern Europeans that were a direct evolutionary response to increased consumption of whole wheat"
I can buy the need for pale skin on a Vitamin D deficient diet in Northern climates. Grains are the pits for deficiency diseases. The nuclear pore blockade should actually predict that WGA consuming people need a higher absolute level of vitamin D for health. I wonder if this is true?
But I don't buy the lactase part.
Lactase is part of a family of enzymes for cleaving terminal sugar moieties. Why should it just sit on the EGF-R to keep WGA off? I can believe it might visit EGF-R briefly to chop up the beta galactosamine (but why?) whenever it's not actively chopping up lactose, but would it sit there attached to beta galactosamine (without cleaving it?) when it should really be getting on with its next lactose cleavage job? Also, would a mammal put in to its infant food a sugar which induces lactase production if that lactase was then going to slip away and sit on the glycation moiety of one of its growth factor receptors? EGF-R is there for cell signaling and the beta galactosamine is a "key structural sugar", not decoration. Maybe it actually needs its beta galactosamine component to work.
On the other hand wheat is looking for a free ride for its seeds. WGA is its lectin, which uses n-acetylglucosamine moieties on cell surfaces specifically to become endocytosed. Once inside the cell all WGA needs to do is produce as much damage as possible, so disrupting digestion, which will maximise the chances of any still undamaged wheat seeds being passed through the gut in tact. Then these can seed the next piece of clear ground which the herbivore poops on.
I notice the email comment is dated Feb 2006. It's now late Jan 2008 and the publication has not hit Pubmed yet. Maybe that one final experiment didn't work?
What's wrong with WGA damaging everyone, full stop? And that lactase persistence is rapidly selected for in people who keep cows for milk, otherwise they get gut rot? Do the Maasai loose lactase when weaned from their mothers because they don't eat wheat? They would no more eat wheat than Cordain would live on sour cow's milk, bulked up when necessary with fresh cow's blood!
Yummie.
Peter
PS I'm surprised Cordain didn't suggest a statin to raise vitamin D levels!
Saturday, January 26, 2008
Breast cancer and starch
Validated food frequency questionnaires strike me as a particularly blunt instrument for assessing nutrient intakes. Generating "dietary patterns" to slot people in to appears to allow the most appalling biases of the investigators to be embedded in to the study design. Couple that with the observational nature and you can see that this recent study by Edefonti does not have a great deal going for it in terms of usefulness, but it does have one plus factor. The research group appear to be able to countenance the possibility that factors other than fat intake may influence disease. This has not always been the case.
To requote Merchant's press release describing the intrinsic biases of "usual" dietary research:
"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"
When Edefonti did actually look at starch based diets and cancer he observed this sort of thing:
"In conclusion, the starch-rich pattern is potentially an unfavorable indicator of risk for both breast and ovarian cancers, while the animal products and the vitamins and fiber patterns may be associated with a reduced risk of breast and ovarian cancers, respectively"
Mind you, the same group has been saying the same thing since 1996!
Now, from where do low fat diets derive their calories?
Peter
To requote Merchant's press release describing the intrinsic biases of "usual" dietary research:
"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"
When Edefonti did actually look at starch based diets and cancer he observed this sort of thing:
"In conclusion, the starch-rich pattern is potentially an unfavorable indicator of risk for both breast and ovarian cancers, while the animal products and the vitamins and fiber patterns may be associated with a reduced risk of breast and ovarian cancers, respectively"
Mind you, the same group has been saying the same thing since 1996!
Now, from where do low fat diets derive their calories?
Peter
Wednesday, January 23, 2008
Monday, January 21, 2008
Prof Yudkin on ascorbate
Top of page 76, 1972 hardback copy of Pure, White and Deadly. Prof Yudkin is talking about mistakes in interpreting data when attributing effect to cause:
"Many older people who suffer from a variety of diseases, gradually develop a degree of heart failure, and one of the effects is swollen legs due to dropsy (oedema). This can be relieved if large amounts of vitamin C are taken, for the vitamin acts as a diuretic and increases the loss of fluid through the kidneys. Though this cures the symptoms of heart failure, the condition was clearly not due to a deficiency of vitamin C."
These have got to be perhaps three of the most intriguing sentences which I have ever read. I have great respect for Prof Yudkin, but some bits of this paragraph are completely wrong. I am fully aware that 5000mg of sodium ascorbate, taken by mouth, produces no discernible diuresis. During periods of self experimentation I have taken 20,000mg by mouth on at least 4 occasions during a single day. Although an occasionally spectacular laxative effect can be produced, and a positive urine test for glucose (due to the urinary ascorbate), frank diuresis has never been a notable effect.
So I look at Prof Yudkin's observation with interest. It is innocently made as an illustration, so I see absolutely no reason to think it is untrue. I think his explanation is incorrect. I'm not an ascorbate megadoser, Optimal Diet and its derivatives shouldn't need that. But I'm fascinated by this snippet, and what it might mean about ascorbate and heart failure in a carbohydrate eater.
Makes you think.
Peter
"Many older people who suffer from a variety of diseases, gradually develop a degree of heart failure, and one of the effects is swollen legs due to dropsy (oedema). This can be relieved if large amounts of vitamin C are taken, for the vitamin acts as a diuretic and increases the loss of fluid through the kidneys. Though this cures the symptoms of heart failure, the condition was clearly not due to a deficiency of vitamin C."
These have got to be perhaps three of the most intriguing sentences which I have ever read. I have great respect for Prof Yudkin, but some bits of this paragraph are completely wrong. I am fully aware that 5000mg of sodium ascorbate, taken by mouth, produces no discernible diuresis. During periods of self experimentation I have taken 20,000mg by mouth on at least 4 occasions during a single day. Although an occasionally spectacular laxative effect can be produced, and a positive urine test for glucose (due to the urinary ascorbate), frank diuresis has never been a notable effect.
So I look at Prof Yudkin's observation with interest. It is innocently made as an illustration, so I see absolutely no reason to think it is untrue. I think his explanation is incorrect. I'm not an ascorbate megadoser, Optimal Diet and its derivatives shouldn't need that. But I'm fascinated by this snippet, and what it might mean about ascorbate and heart failure in a carbohydrate eater.
Makes you think.
Peter
Saturday, January 19, 2008
Casein vs gluten
Milk production is a demand driven process. I was thinking at the biological level, rather than at the economy level.
When a newborn baby drops water weight, which he does as he uses up his glycogen before starting to feed properly, there comes a "tick box" percentage drop in weight at which your UK midwife will start asking if you'd like to give a formula feed, "just while his mother's milk comes in". But it's a demand and supply system. How can demand possibly work to increase supply if the baby is full of denatured cow casein and fast asleep?
The shut down of milk production at the end (or start!) of lactation is not something that just happens. On the biological basis, any mammary gland which is not being asked to produce milk will "assume" there is no infant to feed. Continued lactation then needs to be stopped. Casein, the primary protein in milk, is the signal to cease lactation!
If the casein is not removed from the mammary gland it starts sending signals that nothing is feeding. Milk is actively secreted in to the mammary gland. It's kept sealed in to to ductal system by the "tight junctions" between the cells lining the secretory system. It's worth noting that the first sentence of this abstract is generic, ie tight junctions are probably the same throughout the body, they're not limited to mammary glands.
Tight junctions become leaky when there is milk stasis.
It's important that casein per se does not do this as there is always some in the milk glands, it's hydrolysed casein that does it. This is logical as fresh casein should leave lactation in tact, provided it's removed promptly. If it hangs around for any period of time it gets broken down by plasmin, a proteolytic enzyme also present in milk.
So it's quite convincing that casein hydrosylates open up tight junctions. Then the leakage of milk in to the tissue spaces of the mammary gland produce an inflammatory reaction which shuts down milk production.
There is quite good evidence that it is amino acids 1-28 of beta casein that do the tight junction opening, maybe 2-28.
That's the basics of mammary gland involution at the end of lactation.
Fascinating, but so what?
There are tight junctions in the gut too, the ones that gluten opens up to cause auto immune diseases. Does casein open those junctions up as well as gluten does? There is no hard science here, so I'll speculate.
No.
Why not? Because a cow does not intend to maim the digestive system of her calf, any more than a mother does that of her baby.
The tight junction opening peptide from casein needs to be 27 or 28 amino acids long to work. This is what is produced by the action of plasmin in the udder/breast. Milk is normally delivered directly from mother to offspring, being deposited immediately in to the stomach. The enzyme here is pepsin. There is nothing gentle about pepsin. It's an industrial grade hydrolysing agent working best in a strong hydrochloric acid solution, pH around 2. If it just manages to cleave that initial amino acid sequence in even one place it will deactivate the tight junction opening ability. Ditto if the sequence is repeated elsewhere in the protein. How much in the way of active peptides are left after churning beta casein with acid pepsin for two hours at pH 2? Not a lot if you believe this report. No biological activity is left. Not much anyway.
So does that mean that casein is problem free? Of course not. How many people maintain that ideal pH of 2 for their pepsin to work in? Just take a swig of Gaviscon and your pepsin is not going to do its job. A pH of 7 is not the one at which it was designed to work. Even worse, take a ranitidine (H2 antagonist) tablet and the gastric pH is raised for 12 hours. Yet even worse (worser?) pop an omeprazole tablet, a proton pump inhibitor, and you simply are not going to pump any protons for 24 hours. Take one a day and forget your pepsin is ever going to do much protein digestion.
Once you've eliminated a functional stomach all bulk protein digestion is down to pancreatic trypsin. This is one of the better enzymes for making the casein hydrosylates used to open up the tight junctions in the mammary glands of experimental cows and goats. It's acting in your small intestine to manufacture a tight junction disruptor from milk.
That doesn't sound good to me.
Omeprazole is a market leader. Gaviscon and ranitidne are available OTC. I know at least one baby which has acid reflux so badly that she has spent (and still spends) most of her life on the latter two drugs. What's happening to her gut?
I think there is a case to be made for both the pasteurisation of liquid milk and the drying of powdered milk altering the shape of the protein structure of casein to render the 1-28 amino acid sequence protected from digestion in the stomach. This is absolute speculation, there's no data to support this. Except the world is full of anecdotes about people tolerating raw milk but not pasteurised milk. I'm also willing to speculate that bacteria used to ferment milk to yogurt or kefir may cleave this amino acid sequence, making fermented dairy products far less problematical, even if they are derived from pateurised milk. More speculation.
Bear in mind that once tight junctions in your gut are open, it does not have to be the casein which triggers the allergy, exactly as in the case of wheat gluten. Any intestinal protein can freeload through the opened epithelium.
BTW: Why on earth should a baby have acid reflux so badly she needs to live on ranitidine? It can all start from that suggestion, made with the best intentions by the midwife (ignoring box ticking), to give "just one" formula feed as baby is being slow to regain birth weight..... Considering formula milk appears to be made of sucrose and dried casein, with loads of omega 6 fatty acids (partly oxidised?), I think there are a host of suspects as to why it happens. But an unlucky baby can end up needing antacids as a lifesaver if she regurgitates repeatedly and projectilely on formula milk. I don't much like formula milk.
I also really don't like the idea of removing the functional ability of anyone's stomach either, at any age.
It's just asking for trouble.
Peter
When a newborn baby drops water weight, which he does as he uses up his glycogen before starting to feed properly, there comes a "tick box" percentage drop in weight at which your UK midwife will start asking if you'd like to give a formula feed, "just while his mother's milk comes in". But it's a demand and supply system. How can demand possibly work to increase supply if the baby is full of denatured cow casein and fast asleep?
The shut down of milk production at the end (or start!) of lactation is not something that just happens. On the biological basis, any mammary gland which is not being asked to produce milk will "assume" there is no infant to feed. Continued lactation then needs to be stopped. Casein, the primary protein in milk, is the signal to cease lactation!
If the casein is not removed from the mammary gland it starts sending signals that nothing is feeding. Milk is actively secreted in to the mammary gland. It's kept sealed in to to ductal system by the "tight junctions" between the cells lining the secretory system. It's worth noting that the first sentence of this abstract is generic, ie tight junctions are probably the same throughout the body, they're not limited to mammary glands.
Tight junctions become leaky when there is milk stasis.
It's important that casein per se does not do this as there is always some in the milk glands, it's hydrolysed casein that does it. This is logical as fresh casein should leave lactation in tact, provided it's removed promptly. If it hangs around for any period of time it gets broken down by plasmin, a proteolytic enzyme also present in milk.
So it's quite convincing that casein hydrosylates open up tight junctions. Then the leakage of milk in to the tissue spaces of the mammary gland produce an inflammatory reaction which shuts down milk production.
There is quite good evidence that it is amino acids 1-28 of beta casein that do the tight junction opening, maybe 2-28.
That's the basics of mammary gland involution at the end of lactation.
Fascinating, but so what?
There are tight junctions in the gut too, the ones that gluten opens up to cause auto immune diseases. Does casein open those junctions up as well as gluten does? There is no hard science here, so I'll speculate.
No.
Why not? Because a cow does not intend to maim the digestive system of her calf, any more than a mother does that of her baby.
The tight junction opening peptide from casein needs to be 27 or 28 amino acids long to work. This is what is produced by the action of plasmin in the udder/breast. Milk is normally delivered directly from mother to offspring, being deposited immediately in to the stomach. The enzyme here is pepsin. There is nothing gentle about pepsin. It's an industrial grade hydrolysing agent working best in a strong hydrochloric acid solution, pH around 2. If it just manages to cleave that initial amino acid sequence in even one place it will deactivate the tight junction opening ability. Ditto if the sequence is repeated elsewhere in the protein. How much in the way of active peptides are left after churning beta casein with acid pepsin for two hours at pH 2? Not a lot if you believe this report. No biological activity is left. Not much anyway.
So does that mean that casein is problem free? Of course not. How many people maintain that ideal pH of 2 for their pepsin to work in? Just take a swig of Gaviscon and your pepsin is not going to do its job. A pH of 7 is not the one at which it was designed to work. Even worse, take a ranitidine (H2 antagonist) tablet and the gastric pH is raised for 12 hours. Yet even worse (worser?) pop an omeprazole tablet, a proton pump inhibitor, and you simply are not going to pump any protons for 24 hours. Take one a day and forget your pepsin is ever going to do much protein digestion.
Once you've eliminated a functional stomach all bulk protein digestion is down to pancreatic trypsin. This is one of the better enzymes for making the casein hydrosylates used to open up the tight junctions in the mammary glands of experimental cows and goats. It's acting in your small intestine to manufacture a tight junction disruptor from milk.
That doesn't sound good to me.
Omeprazole is a market leader. Gaviscon and ranitidne are available OTC. I know at least one baby which has acid reflux so badly that she has spent (and still spends) most of her life on the latter two drugs. What's happening to her gut?
I think there is a case to be made for both the pasteurisation of liquid milk and the drying of powdered milk altering the shape of the protein structure of casein to render the 1-28 amino acid sequence protected from digestion in the stomach. This is absolute speculation, there's no data to support this. Except the world is full of anecdotes about people tolerating raw milk but not pasteurised milk. I'm also willing to speculate that bacteria used to ferment milk to yogurt or kefir may cleave this amino acid sequence, making fermented dairy products far less problematical, even if they are derived from pateurised milk. More speculation.
Bear in mind that once tight junctions in your gut are open, it does not have to be the casein which triggers the allergy, exactly as in the case of wheat gluten. Any intestinal protein can freeload through the opened epithelium.
BTW: Why on earth should a baby have acid reflux so badly she needs to live on ranitidine? It can all start from that suggestion, made with the best intentions by the midwife (ignoring box ticking), to give "just one" formula feed as baby is being slow to regain birth weight..... Considering formula milk appears to be made of sucrose and dried casein, with loads of omega 6 fatty acids (partly oxidised?), I think there are a host of suspects as to why it happens. But an unlucky baby can end up needing antacids as a lifesaver if she regurgitates repeatedly and projectilely on formula milk. I don't much like formula milk.
I also really don't like the idea of removing the functional ability of anyone's stomach either, at any age.
It's just asking for trouble.
Peter
Friday, January 18, 2008
Zetia, are things getting better?
I like zetia.
It had a lot going for it. No bungling in the advertising department this time. They must have learned their lesson from the crash and burn of torcetrapib, the standard fate of drugs without an X, Y or Z in their name. So it was the big Z for Zetia. Even the drug name, ezetimbe, has that cool z... It has overtones of relaxing, good times, not in the least difficult, eze in fact.
And it's turned to be one of the best cholesterol lowering drugs ever. I don't have the full study (does anyone?) I'm just looking at the press reports and Dr Nissen's squirming featured on Dr Eades' blog. But the best thing is:
I don't think they killed anyone with Zetia.
This is a big improvement on both torcetrapib and clofibrate. I've no idea about the actual fatalities, and I doubt the Zetia study was powered to detect changes in overall death rate anyway. Total mortality always seems something of a gamble in cholesterol lowering trials. Mind you, just thinking aloud, there seems to be no talk of "a trend towards improved survival", so perhaps there was an non significant increase in fatalities, I hope not. As I say, I don't have the numbers. But it seems impossible to spin this study to be pro Zetia. Tragic.
Apart from the bankruptcy of the lipid hypothesis, why did Zetia fail?
That's pretty obvious. Have a look at this paper. Those poor hyper responders to dietary cholesterol were fed eggs. Their cholesterol went up. Oh no. Except it was the "good" lipoproteins which increased.
"These findings suggest that the increases in LDL-C and HDL-C due to increased egg consumption in hyper-responders are not related to an increased number of LDL or HDL particles but, to an increase in the less atherogenic lipoprotein subfractions."
Similarly in this study they found
" the LDL peak diameter was increased during the EGG period for all subjects."
I believe increased LDL particle diameter is considered to be a Good Thing.
Now if Zetia stops you absorbing your breakfast eggs, you don't have to be a genius to predict what it will to the "atherogenicity" of your lipids.... Oh, but your calculated LDL goes down with Zetia. Yawn again.
Anyway, Zetia is less frankly toxic than some the previous non statin cholesterol lowering agents, for what that's worth.
Still useless. How did a drug with such a cool name fail?
Peter
It had a lot going for it. No bungling in the advertising department this time. They must have learned their lesson from the crash and burn of torcetrapib, the standard fate of drugs without an X, Y or Z in their name. So it was the big Z for Zetia. Even the drug name, ezetimbe, has that cool z... It has overtones of relaxing, good times, not in the least difficult, eze in fact.
And it's turned to be one of the best cholesterol lowering drugs ever. I don't have the full study (does anyone?) I'm just looking at the press reports and Dr Nissen's squirming featured on Dr Eades' blog. But the best thing is:
I don't think they killed anyone with Zetia.
This is a big improvement on both torcetrapib and clofibrate. I've no idea about the actual fatalities, and I doubt the Zetia study was powered to detect changes in overall death rate anyway. Total mortality always seems something of a gamble in cholesterol lowering trials. Mind you, just thinking aloud, there seems to be no talk of "a trend towards improved survival", so perhaps there was an non significant increase in fatalities, I hope not. As I say, I don't have the numbers. But it seems impossible to spin this study to be pro Zetia. Tragic.
Apart from the bankruptcy of the lipid hypothesis, why did Zetia fail?
That's pretty obvious. Have a look at this paper. Those poor hyper responders to dietary cholesterol were fed eggs. Their cholesterol went up. Oh no. Except it was the "good" lipoproteins which increased.
"These findings suggest that the increases in LDL-C and HDL-C due to increased egg consumption in hyper-responders are not related to an increased number of LDL or HDL particles but, to an increase in the less atherogenic lipoprotein subfractions."
Similarly in this study they found
" the LDL peak diameter was increased during the EGG period for all subjects."
I believe increased LDL particle diameter is considered to be a Good Thing.
Now if Zetia stops you absorbing your breakfast eggs, you don't have to be a genius to predict what it will to the "atherogenicity" of your lipids.... Oh, but your calculated LDL goes down with Zetia. Yawn again.
Anyway, Zetia is less frankly toxic than some the previous non statin cholesterol lowering agents, for what that's worth.
Still useless. How did a drug with such a cool name fail?
Peter
Tuesday, January 15, 2008
Wheat and lactose
Apart from gluten there are a large number of other proteins in wheat. I wanted to go in to the problems of wheat germ agglutinin (WGA) in slightly more detail than I did the last time I posted on the toxicity of wheat.
WGA is a lectin. The technical definition of a lectin is a protein which attaches itself to a carbohydrate moiety on the surface of a cell and "does something" to the cell. WGA is an insulin mimic. This paper from 1973 sums it up nicely.
"wheat germ agglutinin [is] as effective as insulin in enhancing the rate of glucose transport and in inhibiting epinephrine-stimulated lipolysis in isolated adipocytes."
"The possible implications of these findings to certain biological properties (mitogenicity) of these lectins and to the mechanism of action of other growth-promoting substances are considered."
Mitogenicity is the key word. WGA causes cells to divide. Interestingly so does insulin, in pretty much the same areas of the gut as WGA...
Let's look at gut structure more closely. The surface of the gut is highly folded. The bits which stick up (villi) provide the brush border. The brush border is the area which does the actual digesting and absorbing of food. The folds between the sticky up bits are called the crypts. Deep in here active cell division occurs. As the cells divide they migrate up from deep in the crypts towards the brush border. As they migrate they mature until, as they arrive at the tips, they become typical brush border digestive cells. They do some digesting for a while, then get sloughed off to be replaced by more up and coming cells from deep in the crypts. It's tough at the top for a cell in the gut lining.
WGA, as we've noted, has "mitogenicity". The cells deep in the crypts, minding their own business, suddenly get told, by WGA, to divide. Now. Never mind biological need, complex inter-cell signaling, nutritional needs, just divide NOW. And again. Once more. Keep going.
Let's say normal gut turn over requires the cells get replaced every three or four days. It's around that. Crypt cells will divide to meet this need. Drop on WGA and they will divide irrespective of the needs of the gut. This results in rapid proliferation and migration of cells up up to the tips of the villi.
The end result, when WGA is given given to normal rats (note, these rats do not have gluten allergy), is a trashing of the gut, resembling early coeliac disease. Note the short villi.
With rapidly turning over digestive cells and minimal time for them to mature, how good will the brush border be?
Not very good!
The brush border produces all of the really interesting enzymes needed for the last stage of digestion. Most people know about lactase but the brush border also makes the enzymes to break down peptides to amino acids, all sorts of disaccharides to monosaccharides and even breaks down ingested triglycerides. Some of these enzymes are inhibited by WGA before it damages the gut, others are enhanced. Weird.
As a classic example, many many people are lactose in tolerant. They get gut rot when they drink milk. They may well avoid all dairy for the rest of their lives. However, it's pretty obvious from this thread that eating wheat trashes the brush border, where lactase is produced. This happens in NORMAL animals (and people). So it's impossible to genuinely say a human is lactose intolerant while they are eating wheat.
Humans are mammals after all, lactase is produced on demand whenever lactose is present, why should we be lactose intolerant?
If we have sub clinical coeliac disease then the loss of lactase is very straight forward. And very reversible.
My argument is that no one is likely to be tolerant of WGA. The effects on the gut lining do not require allergy, they are intrinsic to the nature of the lectin WGA and the glycosylation of the gut lining cells. Undoubtedly allergy will make matters much worse (and may give you a positive blood test, thus providing an ad lib supply of gluten free junk foods from the NHS).
Anyone unable to correctly digest fat, a specific protein or certain carbohydrates should really be thinking about wheat.
It's a metabolic poison.
I'm sounding like Dr Davis.
Peter
BTW, if WGA and insulin are so driving to mitosis, why don't they promote intestinal cancers? They do. Both of them. Though I guess omega 6 fatty acid excess and vitamin D deficiency should get a look in as partners in crime...
EDIT: see comments for an apology re reference inaccuracy on this BTW add on.
WGA is a lectin. The technical definition of a lectin is a protein which attaches itself to a carbohydrate moiety on the surface of a cell and "does something" to the cell. WGA is an insulin mimic. This paper from 1973 sums it up nicely.
"wheat germ agglutinin [is] as effective as insulin in enhancing the rate of glucose transport and in inhibiting epinephrine-stimulated lipolysis in isolated adipocytes."
"The possible implications of these findings to certain biological properties (mitogenicity) of these lectins and to the mechanism of action of other growth-promoting substances are considered."
Mitogenicity is the key word. WGA causes cells to divide. Interestingly so does insulin, in pretty much the same areas of the gut as WGA...
Let's look at gut structure more closely. The surface of the gut is highly folded. The bits which stick up (villi) provide the brush border. The brush border is the area which does the actual digesting and absorbing of food. The folds between the sticky up bits are called the crypts. Deep in here active cell division occurs. As the cells divide they migrate up from deep in the crypts towards the brush border. As they migrate they mature until, as they arrive at the tips, they become typical brush border digestive cells. They do some digesting for a while, then get sloughed off to be replaced by more up and coming cells from deep in the crypts. It's tough at the top for a cell in the gut lining.
WGA, as we've noted, has "mitogenicity". The cells deep in the crypts, minding their own business, suddenly get told, by WGA, to divide. Now. Never mind biological need, complex inter-cell signaling, nutritional needs, just divide NOW. And again. Once more. Keep going.
Let's say normal gut turn over requires the cells get replaced every three or four days. It's around that. Crypt cells will divide to meet this need. Drop on WGA and they will divide irrespective of the needs of the gut. This results in rapid proliferation and migration of cells up up to the tips of the villi.
The end result, when WGA is given given to normal rats (note, these rats do not have gluten allergy), is a trashing of the gut, resembling early coeliac disease. Note the short villi.
With rapidly turning over digestive cells and minimal time for them to mature, how good will the brush border be?
Not very good!
The brush border produces all of the really interesting enzymes needed for the last stage of digestion. Most people know about lactase but the brush border also makes the enzymes to break down peptides to amino acids, all sorts of disaccharides to monosaccharides and even breaks down ingested triglycerides. Some of these enzymes are inhibited by WGA before it damages the gut, others are enhanced. Weird.
As a classic example, many many people are lactose in tolerant. They get gut rot when they drink milk. They may well avoid all dairy for the rest of their lives. However, it's pretty obvious from this thread that eating wheat trashes the brush border, where lactase is produced. This happens in NORMAL animals (and people). So it's impossible to genuinely say a human is lactose intolerant while they are eating wheat.
Humans are mammals after all, lactase is produced on demand whenever lactose is present, why should we be lactose intolerant?
If we have sub clinical coeliac disease then the loss of lactase is very straight forward. And very reversible.
My argument is that no one is likely to be tolerant of WGA. The effects on the gut lining do not require allergy, they are intrinsic to the nature of the lectin WGA and the glycosylation of the gut lining cells. Undoubtedly allergy will make matters much worse (and may give you a positive blood test, thus providing an ad lib supply of gluten free junk foods from the NHS).
Anyone unable to correctly digest fat, a specific protein or certain carbohydrates should really be thinking about wheat.
It's a metabolic poison.
I'm sounding like Dr Davis.
Peter
BTW, if WGA and insulin are so driving to mitosis, why don't they promote intestinal cancers? They do. Both of them. Though I guess omega 6 fatty acid excess and vitamin D deficiency should get a look in as partners in crime...
EDIT: see comments for an apology re reference inaccuracy on this BTW add on.
Saturday, January 12, 2008
PUFA table
This post is for bruce. It's a copy paste of the table from:
Elgersma, A., S. Tamminga, and G. Ellen. 2003. Effect of grazing versus stall-feeding of cut grass on milk fatty acid composition of dairy cows. Proceedings of the Int. Occ. Symp. of the European Grassland Federation, Pleven, Bulgaria, May 2003. Grassland Science in Europe 8: 271-274.
I've no idea where I got the pdf from, it's just been lying around on my hard drive for ages. Not on pubmed.
The PUFA varied from 4.34 to 5.76, in the same 6 cows over a 5 month period. I don't really think of diet components in terms of accuracy to two decimal places. The figure of 5% is somewhere in the middle. My own PUFA intake estimate comes as total PUFA value from Fitday, so is USA based and probably bears little resemblance to values from parts of the world where cows are fed on grass! My estimate varies between 10 and 20g/d, depending on menu and how much I believe Fitday represents UK food. Even using http://www.nutritiondata.com/ the values in various types of cream and butter are wildly variable in their PUFA ratios. I just feel we can never really know exactly what is in a specific block of butter... Keeping it low is good, how low is low? I really dunno what I eat!
Sorry the table's a bit small, that's how it copy pasted
Peter
PS thanks for the reading pointers. Bear I've read, but not Peat.
Elgersma, A., S. Tamminga, and G. Ellen. 2003. Effect of grazing versus stall-feeding of cut grass on milk fatty acid composition of dairy cows. Proceedings of the Int. Occ. Symp. of the European Grassland Federation, Pleven, Bulgaria, May 2003. Grassland Science in Europe 8: 271-274.
I've no idea where I got the pdf from, it's just been lying around on my hard drive for ages. Not on pubmed.
The PUFA varied from 4.34 to 5.76, in the same 6 cows over a 5 month period. I don't really think of diet components in terms of accuracy to two decimal places. The figure of 5% is somewhere in the middle. My own PUFA intake estimate comes as total PUFA value from Fitday, so is USA based and probably bears little resemblance to values from parts of the world where cows are fed on grass! My estimate varies between 10 and 20g/d, depending on menu and how much I believe Fitday represents UK food. Even using http://www.nutritiondata.com/ the values in various types of cream and butter are wildly variable in their PUFA ratios. I just feel we can never really know exactly what is in a specific block of butter... Keeping it low is good, how low is low? I really dunno what I eat!
Sorry the table's a bit small, that's how it copy pasted
Peter
PS thanks for the reading pointers. Bear I've read, but not Peat.
Thursday, January 10, 2008
Prize for worst misuse of a statin
Cardiology rounds, Haydarpasa Numune Training and Research Hospital, Turkey.
Head of department, senior clinicians, residents and interns all stand around a gold plated replica of a Simvastatin package. Slowly each clinician raises their hands, palms uppermost, out to their sides, then arches them upwards to curl over and bring the tips of fingers to meet on mid line of their head, making a kind of a heart sign.
There is a deep sense of intense religious presence, a faint smell of incense and rapt attention to the reading of the simvastatin data sheet, excepting the adverse reactions page, which seems to have disappeared. All then intone:
We believe in the lipid hypothesis, the sole lipid hypothesis and nothing but the lipid hypothesis. We believe in the great saviour Simvastatin. We believe it is the answer to all ills, especially thyroid deficiency.
OK, I made all of that up.
Except the bit about thyroid deficiency.
Where did this rant come from? This paper.
Thyroid deficiency is a major driver of arteriosclerosis. Replacing the missing thyroid hormone reverses the arteriosclerosis. You would think that nothing could be simpler. Not so. You can also reverse the signs of arteriosclerosis with simvastatin WITHOUT replacing the thyroid hormone. It doesn't work quite as well as fixing the genuine problem but, hey, it's a glossy statin not a drab thyroid supplement. I don't suppose you feel much better on a statin with or without having your thyroid problem corrected.
Best quote from the abstract:
"No correlation was demonstrated between the changes in total or LDL-cholesterol concentration and IMT (degree of arteriosclerosis) in the simvastatin group."
Translation: The cholesterol hypothesis is garbage.
My thanks to Chris Masterjohn for dropping that one on me on New Year's Day. Luckily I didn't break any fillings while grinding my teeth!
You can read Chris' comments, including snippets from the full text, here at The Cholesterol Times.
You can read his whole web site here, it's good.
Peter
Head of department, senior clinicians, residents and interns all stand around a gold plated replica of a Simvastatin package. Slowly each clinician raises their hands, palms uppermost, out to their sides, then arches them upwards to curl over and bring the tips of fingers to meet on mid line of their head, making a kind of a heart sign.
There is a deep sense of intense religious presence, a faint smell of incense and rapt attention to the reading of the simvastatin data sheet, excepting the adverse reactions page, which seems to have disappeared. All then intone:
We believe in the lipid hypothesis, the sole lipid hypothesis and nothing but the lipid hypothesis. We believe in the great saviour Simvastatin. We believe it is the answer to all ills, especially thyroid deficiency.
OK, I made all of that up.
Except the bit about thyroid deficiency.
Where did this rant come from? This paper.
Thyroid deficiency is a major driver of arteriosclerosis. Replacing the missing thyroid hormone reverses the arteriosclerosis. You would think that nothing could be simpler. Not so. You can also reverse the signs of arteriosclerosis with simvastatin WITHOUT replacing the thyroid hormone. It doesn't work quite as well as fixing the genuine problem but, hey, it's a glossy statin not a drab thyroid supplement. I don't suppose you feel much better on a statin with or without having your thyroid problem corrected.
Best quote from the abstract:
"No correlation was demonstrated between the changes in total or LDL-cholesterol concentration and IMT (degree of arteriosclerosis) in the simvastatin group."
Translation: The cholesterol hypothesis is garbage.
My thanks to Chris Masterjohn for dropping that one on me on New Year's Day. Luckily I didn't break any fillings while grinding my teeth!
You can read Chris' comments, including snippets from the full text, here at The Cholesterol Times.
You can read his whole web site here, it's good.
Peter
Vitamin D
On the last post I mentioned the Kitavans and their tendency to eat fish as their primary source of protein. Fish comes bundled with omega three fatty acids and I would suggest that this is a major contributor to their overall health.
The other highly relevant substance for human health is vitamin D. This is not really a food related vitamin or even a vitamin at all, as we make it ourelves. I think it's probably impossible to improve on Vieth's early summary except to say every paper published on vitamin D shows that it is critical to avoiding heart disease, cancer, multiple autoimmune diseases plus type 2 diabetes. And anything else you care to mention I guess.
How much D is needed for health? Vieth's abstract sums it up in these terms:
"Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 µg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of 1000 µg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 µg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 µg (2000 IU)/d is too low by at least 5-fold."
So Vieth is pushing for 10,000 iu/d. Six egg yolks provide about a third of the Fitday RDA (recently increased to 10 µg or 400 iu). Half an hour's sun bathing provides Vieth amounts. But even when the sun does shine in January there is no UVB in the UK. So 10,000 iu of oil based D3 it is during the Winter.
I was curious as the the probable vitamin D status of the Kitava natives studied by Lindeberg. They maintain their insulin sensitivity throughout their lives and vitamin D is crucial for this. Lindeberg didn't measure D3, so I've had to have a guess. Kitava is just off of the equator. My guess is that there is probably about 12 hours of sunshine per day many days of the year. I wondered how pigmented the Kitavans were and how much clothing they wore. These are primary determinants of vitamin D3 synthesis.
Putting "Kitava" in to a google image search brought this up as the first hit. Humans are mammals. Please do not click on the following link if you are offended by the direct proof of this. It's to do with feeding babies.
Kitava native
I would guestimate 10,000 iu/d D3, most days of her life.
That's my Winter supplement sorted out. Summer time I'd opt for the Kitava solution.
Peter
The other highly relevant substance for human health is vitamin D. This is not really a food related vitamin or even a vitamin at all, as we make it ourelves. I think it's probably impossible to improve on Vieth's early summary except to say every paper published on vitamin D shows that it is critical to avoiding heart disease, cancer, multiple autoimmune diseases plus type 2 diabetes. And anything else you care to mention I guess.
How much D is needed for health? Vieth's abstract sums it up in these terms:
"Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 µg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of 1000 µg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 µg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 µg (2000 IU)/d is too low by at least 5-fold."
So Vieth is pushing for 10,000 iu/d. Six egg yolks provide about a third of the Fitday RDA (recently increased to 10 µg or 400 iu). Half an hour's sun bathing provides Vieth amounts. But even when the sun does shine in January there is no UVB in the UK. So 10,000 iu of oil based D3 it is during the Winter.
I was curious as the the probable vitamin D status of the Kitava natives studied by Lindeberg. They maintain their insulin sensitivity throughout their lives and vitamin D is crucial for this. Lindeberg didn't measure D3, so I've had to have a guess. Kitava is just off of the equator. My guess is that there is probably about 12 hours of sunshine per day many days of the year. I wondered how pigmented the Kitavans were and how much clothing they wore. These are primary determinants of vitamin D3 synthesis.
Putting "Kitava" in to a google image search brought this up as the first hit. Humans are mammals. Please do not click on the following link if you are offended by the direct proof of this. It's to do with feeding babies.
Kitava native
I would guestimate 10,000 iu/d D3, most days of her life.
That's my Winter supplement sorted out. Summer time I'd opt for the Kitava solution.
Peter
Wednesday, January 09, 2008
Essential fatty acids are essential
If you take a cow and feed it on grass it gets quite a lot of omega 3 fatty acids. If you feed it on a barley based concentrate feed it doesn't get nearly so many, just loaded up on omega 6s. Because cows have a rumen they actually live on a combination of volatile fatty acids produced by bacteria, which breaking down that otherwise useless fiber in grass, plus bacterial protein. Not much of the grass itself actually gets through to the cow. Most bovine fat is self assembled from things like butyric acid or acetate, so it's fully saturated or monounsaturated, ie typical mammalian produced fat. But some essential fatty acids do get through, after all they're essential to the cow just as much as they are to you and me.
How much PUFA get through the intensely reducing environment of the rumen? This paper gives some idea of the input and transformations which occur.
Table 1 shows the amounts of linoleic and linolenic acids in grass, concentrates and sliage. Grass and silage are pretty much the same, with one part omega 6 (linoleic, 18:2) to three parts omega 3 (linolenic, 18:3). That is, grass has a rather huge excess of omega three over omega six. Before it hits the rumen.
Concentrates don't. They're not quite as bad as the "prudent" diet of the Lyon Heart study (only a cardiologist could design a diet that bad) but, at roughly eight parts omega 6 to each part omega 3, this is still cardiological profit making nirvana for the AHA.
What comes out of the rumen? The paper next looks at the fatty acid composition of intramuscular fat, the results are in Table 3. Grass only fed cattle have about 2.33 times as much omega 6 as omega 3 fatty acids in their muscles.
I firmly believe that humans evolved with an excellent ability to hunt herbivores, grass fed herbivores. On the basis that hunting provided the bulk of the lipids to a hunter-gatherer, this looks like a pretty good fatty acid ratio to aim at. Eating wild herbivores seems to be what we were good at and what should provide us with a healthy diet. Plus a bit of fishing too I guess.
The concentrates-only fed cattle were actually given some hay too, because cows tend to die if you feed them on concentrates alone, and they came out with a 4.15 parts omega 6 to each part omega 3 fats in their muscles. It's worth noting that the worst quality of grain fed Irish beef still provides an omega 6 to omega 3 ratio as good as the intake in the best ever dietary intervention trial! Still, a ratio of 2:1 looks to be even better. In both groups the PUFA made up about 5% of the fat.
The other place worth looking is Kitava , full text here, keep scrolling down to find it and try to ignore the more weird papers written by Cordain. These subsistence farmers got their lipids from fish and coconuts. There are some omega 6 fats in both fish and coconuts, but the omega 3 from the fish predominate, ie they eat less than one part omega 6 to each part omega 3. No heart disease, despite smoking. PUFA made up 10% of the lipids eaten, which were low in total at 20% of calories.
Back to cattle. What comes out in the milk? Important if you are as dairy dependent as I am. I only have data for grass fed cattle. You can see from table 3 in this paper* that PUFA run at around 5% of lipids and that there is almost a 1:1 ratio. Omega 6 come out at or just above 1% of total lipids, omega 3 at just below 1%. Hang on, that's only 2%... What are the other 3% to make up the 5% PUFA? It's mostly conjugated linoleic acid, CLA. The good stuff, the anti-cancer, anti-this pro-that CLA. Non synthetic, straight from the cow. You can see why I like dairy fats. Cows intend calves to be healthy.
That's the grass fed stuff. In general grass is cheap and concentrates are expensive, certainly here in the UK. In areas where grass will grow and wheat won't, we grow cows. Via grass. It makes quite good silage for winter use too. If you are running a dairy unit you will feed the maximum possible of grass/silage and a minimum of cattle cake. Economics dictate this. It's a hard market for dairy farmers. But even the worst case lipid scenario, using a maximum of cattle cake, would be a 1:4 ratio in cream. This is as good as the Lyon investigators got with their gloop.
Obviously neither chickens nor pigs have a rumen, so their fatty acid balance will be far more affected by the high omega six content of their diet. This is the primary reason I add 5g/day of fish oil to my diet. It goes some way to getting an essential fatty acid ratio of about one part omega 3 to, at worst, 2 parts omega 6 overall. PUFA make up about 5% of my total lipid intake, which obviously is quite high in absolute terms, due to the total amount of fat I eat.
This seems to be a very reasonable approach to PUFA for me.
Obviously all vegetable oils except olive oil are banned from the house. Banning these oils is the biggest step needed to make balancing lipids straightforward. It's possibly more important than the gloop to the Lyon heart study success. Once you crack a bottle of corn oil, sunflower oil or a pot of margarine you will never get your omega 6 intake low enough to balance things out with a few grams of fish oil. I guess that's why it's impossible to show overall benefit form one or two cod liver oil capsules a day in a "normal" diet...
Olive oil gets used in our house as a flavouring, never for bulk calories. Actually, so does a small amount of sesame oil too...
The food has to taste good as well as being nutritious!
I don't regard fish oil as a supplement. I look on it as a tool for correcting the fatty acid defect ubiquitous in UK non ruminant fat. It even makes the excellent dairy lipids better.
Peter
*Oh, I just found that the milk-lipids paper is on my hard drive as a pdf and it's not on pubmed. No idea where I got it from! It's:
Elgersma, A., S. Tamminga, and G. Ellen. 2003. Effect of grazing versus stall-feeding of cut grass on milk fatty acid composition of dairy cows. Proceedings of the Int. Occ. Symp. of the European Grassland Federation, Pleven, Bulgaria, May 2003. Grassland Science in Europe 8: 271-274.
if anyone want's to chase it!
How much PUFA get through the intensely reducing environment of the rumen? This paper gives some idea of the input and transformations which occur.
Table 1 shows the amounts of linoleic and linolenic acids in grass, concentrates and sliage. Grass and silage are pretty much the same, with one part omega 6 (linoleic, 18:2) to three parts omega 3 (linolenic, 18:3). That is, grass has a rather huge excess of omega three over omega six. Before it hits the rumen.
Concentrates don't. They're not quite as bad as the "prudent" diet of the Lyon Heart study (only a cardiologist could design a diet that bad) but, at roughly eight parts omega 6 to each part omega 3, this is still cardiological profit making nirvana for the AHA.
What comes out of the rumen? The paper next looks at the fatty acid composition of intramuscular fat, the results are in Table 3. Grass only fed cattle have about 2.33 times as much omega 6 as omega 3 fatty acids in their muscles.
I firmly believe that humans evolved with an excellent ability to hunt herbivores, grass fed herbivores. On the basis that hunting provided the bulk of the lipids to a hunter-gatherer, this looks like a pretty good fatty acid ratio to aim at. Eating wild herbivores seems to be what we were good at and what should provide us with a healthy diet. Plus a bit of fishing too I guess.
The concentrates-only fed cattle were actually given some hay too, because cows tend to die if you feed them on concentrates alone, and they came out with a 4.15 parts omega 6 to each part omega 3 fats in their muscles. It's worth noting that the worst quality of grain fed Irish beef still provides an omega 6 to omega 3 ratio as good as the intake in the best ever dietary intervention trial! Still, a ratio of 2:1 looks to be even better. In both groups the PUFA made up about 5% of the fat.
The other place worth looking is Kitava , full text here, keep scrolling down to find it and try to ignore the more weird papers written by Cordain. These subsistence farmers got their lipids from fish and coconuts. There are some omega 6 fats in both fish and coconuts, but the omega 3 from the fish predominate, ie they eat less than one part omega 6 to each part omega 3. No heart disease, despite smoking. PUFA made up 10% of the lipids eaten, which were low in total at 20% of calories.
Back to cattle. What comes out in the milk? Important if you are as dairy dependent as I am. I only have data for grass fed cattle. You can see from table 3 in this paper* that PUFA run at around 5% of lipids and that there is almost a 1:1 ratio. Omega 6 come out at or just above 1% of total lipids, omega 3 at just below 1%. Hang on, that's only 2%... What are the other 3% to make up the 5% PUFA? It's mostly conjugated linoleic acid, CLA. The good stuff, the anti-cancer, anti-this pro-that CLA. Non synthetic, straight from the cow. You can see why I like dairy fats. Cows intend calves to be healthy.
That's the grass fed stuff. In general grass is cheap and concentrates are expensive, certainly here in the UK. In areas where grass will grow and wheat won't, we grow cows. Via grass. It makes quite good silage for winter use too. If you are running a dairy unit you will feed the maximum possible of grass/silage and a minimum of cattle cake. Economics dictate this. It's a hard market for dairy farmers. But even the worst case lipid scenario, using a maximum of cattle cake, would be a 1:4 ratio in cream. This is as good as the Lyon investigators got with their gloop.
Obviously neither chickens nor pigs have a rumen, so their fatty acid balance will be far more affected by the high omega six content of their diet. This is the primary reason I add 5g/day of fish oil to my diet. It goes some way to getting an essential fatty acid ratio of about one part omega 3 to, at worst, 2 parts omega 6 overall. PUFA make up about 5% of my total lipid intake, which obviously is quite high in absolute terms, due to the total amount of fat I eat.
This seems to be a very reasonable approach to PUFA for me.
Obviously all vegetable oils except olive oil are banned from the house. Banning these oils is the biggest step needed to make balancing lipids straightforward. It's possibly more important than the gloop to the Lyon heart study success. Once you crack a bottle of corn oil, sunflower oil or a pot of margarine you will never get your omega 6 intake low enough to balance things out with a few grams of fish oil. I guess that's why it's impossible to show overall benefit form one or two cod liver oil capsules a day in a "normal" diet...
Olive oil gets used in our house as a flavouring, never for bulk calories. Actually, so does a small amount of sesame oil too...
The food has to taste good as well as being nutritious!
I don't regard fish oil as a supplement. I look on it as a tool for correcting the fatty acid defect ubiquitous in UK non ruminant fat. It even makes the excellent dairy lipids better.
Peter
*Oh, I just found that the milk-lipids paper is on my hard drive as a pdf and it's not on pubmed. No idea where I got it from! It's:
Elgersma, A., S. Tamminga, and G. Ellen. 2003. Effect of grazing versus stall-feeding of cut grass on milk fatty acid composition of dairy cows. Proceedings of the Int. Occ. Symp. of the European Grassland Federation, Pleven, Bulgaria, May 2003. Grassland Science in Europe 8: 271-274.
if anyone want's to chase it!
Monday, January 07, 2008
Easiyo
I bought a yogurt maker from Julian Graves, the nut shop. Brand is "Easiyo". It's a 1 litre plastic container in to which I pour a pint pot of UK double cream, the rest of the volume I fill with some milk to provide lactose for the bacteria and water to keep it fluid for pouring. About 50:50. The yogurt maker itself is a plastic insulated flask which has an internal shelf and a mark. You fill it to the mark with boiling water, put in the yogurt fermenting container, which then sits on the shelf, pop the lid on and wait. I decant it in to fully waterproof sealable food beakers after three days. Shake it first. I leave it at room temperature. I have a production line but mostly it gets eaten within 7 days. I use Total brand Greek yogurt as my starter culture. It will do about six batches before becoming contaminated and starting to produce alcohol. My kitchen is loaded with a yeast since I tried some lactofermenting of rye flour, to see if I could tolerated home fermented sourdough rye bread. I can't. But it was nice trying.
You get a layer of cheese inside the top of the lid and around the top of the yogurt container screw thread. I clean this off with a tissue and scald the lid with boiling water between batches. I don't clean out the container as this is the source of bugs for the next batch. Until a yeast gets in that is, then it's a re-start after a mega sterilisation.
I like the taste, my wife doesn't. I guess it's acquired and I have the driving need for calories. Access to raw dairy is quite difficult in the UK (though far from impossible) and fermenting the cream appears to un-pasteurise it.
Peter
You get a layer of cheese inside the top of the lid and around the top of the yogurt container screw thread. I clean this off with a tissue and scald the lid with boiling water between batches. I don't clean out the container as this is the source of bugs for the next batch. Until a yeast gets in that is, then it's a re-start after a mega sterilisation.
I like the taste, my wife doesn't. I guess it's acquired and I have the driving need for calories. Access to raw dairy is quite difficult in the UK (though far from impossible) and fermenting the cream appears to un-pasteurise it.
Peter
Sunday, January 06, 2008
What do I eat? Fitday analysis.
Breakfast is usually six egg yolks fried in 40g butter, last time I weighed it. This will just about soak in to the yolks if scrambled, but if I gently fry the yolks to keep the centers soft I usually eat the combination with a spoon. I discard the whites as they are pure protein, without any other significant nutrients. Because I limit my protein intake I tend to "spend" the rest of my "allowance" on meat. I aim for 65g/d of protein but don't stress if I run over.
Lunch is typically about one third of a pint pot of cream. Usually fermented with a yogurt starter culture (plus a little milk added to feed the bugs), occasionally just fresh cream. I threw in 50g of raspberries to Fitday. Sometimes I'll have 85% cocoa chocolate with it instead, other days I'll spread the cream out through the day in mugs of Green and Black's cocoa powder with about a gram of dextrose powder to sweeten each mug.
Supper I put in as a chili mix. Basically I fry (in butter, another 40+grams) an onion, a red pepper and some 'shrooms. Throw in a pound of Sainsbury's economy high fat beef, fry briefly then add tomatoes, garlic, red wine and a seriously hot chili. Cumin (lots) and a little coriander pretty well finishes it. Simmer it down over 45 minutes and serve. I eat about half of the total.
This day I specified parsnip chips. If you part squish them they soak up left over fat. Mmmmmmm. I usually can't be bothered to cook a green veg but do occasionally, especially in the summer when we have runner beans, french beans and spinach in the garden. Maybe a few peas too. We're waiting for the curly kale to get big enough for a winter green, but it's slow! We've got leeks at the moment still.
I put this menu through Fitday and got this:
______________ grams________kcal________%kcal
Total_______________________2636
Fat_____________245________2204 _______85
Sat_____________134________1204________46
PUFA____________12_________106_________4
Mono____________79_________707________27
Carb_____________44_________136________5
Fiber_____________10
Protein___________65_________260________10
Nutritionally it gets a number of red flags from Fitday but none of these concern me as they are based on people eating to the Food Pyramid.
Supplements: Offal should be eaten weekly but I get lazy. Liver is my usual source but kidneys are nutritional powerhouses too. There's another post there. I use fish oil (5g/d) to balance the fatty acids, another post there too. I gave up on UK cod liver oil as someone takes out the vits A and D and replaces them with homeopathic doses, and the vit A used is synthetic retinoic acid. So for D3 I sunbathe as much as practical in the Summer and take 10,000 iu/d in the Winter. I get my vit A from liver and eggs.
That's about it. We do bone broths when we get the time. Beef heart makes fantastic slow casseroles. Pork mince is a favorite.
My wife eats all of her eggs, so eats only three a day, usually with bacon. She usually has cheese for lunch and we share supper. She eats a fair bit higher in protein and lower in fat than I do, but we're both lean. Her cholesterol levels are frighteningly low but she's just a youngster, so that's probably fine. Mine are, and always have been, very high. Not record breaking, just very high.
Treats: occasional Thornton's candy bar on a lower than average carb day. Home made ice cream is not a treat, but it tastes like one. Makes an excellent breakfast if you're in a hurry. Recipe:
Pint pot of cream, six egg yolks, 5ml vanilla extract, 20-30g dextrose to sweeten, 10g honey for flavour. Mix and freeze in whatever size portions you fancy.
High cocoa solid chocolate is primarily stearic acid and magnesium, so quite a lot of this sneaks in too. If I need extra calories for a day's concrete breaking I'll up both the cream and the chocolate. Several days of sustained heavy building work and I'll up protein too. Ditto if I have an exercise patch.
We're totally gluten free and almost totally grain free. Legumes only in small amounts. Dairy doesn't seem to be a problem. Another post there too.
That's what it's like...
What do I miss? Nelson's Revenge from the Woodford's brewery and Adnam's bitter. Both gluten loaded.
After a few years eating to this type of menu becomes just a normal way of life. You tend to forget how strange you are.
Actually, the oddest feeling I have ever had was at a goth rock concert, probably VNV Nation playing last year at Rock City in Nottingham. One of the best gigs ever. Very dark, very loud, very packed. Great lighting, what there was of it. Full dress goths with fantastic clothes and body jewelry and everyone moving to the deep roaring beat. But the weirdest thing was they all had pints. Pints of beer. Not the people actually in the mosh pit of course, but almost everyone else. It's a wheat based, alcohol fueled culture that we live in and a pint of beer is a symbol of everything I've left behind. I felt VERY strange, a real odd ball amongst the hard core goths at the gig... Despite external appearances, they were far more mainstream that I'll ever be again!
Peter
Lunch is typically about one third of a pint pot of cream. Usually fermented with a yogurt starter culture (plus a little milk added to feed the bugs), occasionally just fresh cream. I threw in 50g of raspberries to Fitday. Sometimes I'll have 85% cocoa chocolate with it instead, other days I'll spread the cream out through the day in mugs of Green and Black's cocoa powder with about a gram of dextrose powder to sweeten each mug.
Supper I put in as a chili mix. Basically I fry (in butter, another 40+grams) an onion, a red pepper and some 'shrooms. Throw in a pound of Sainsbury's economy high fat beef, fry briefly then add tomatoes, garlic, red wine and a seriously hot chili. Cumin (lots) and a little coriander pretty well finishes it. Simmer it down over 45 minutes and serve. I eat about half of the total.
This day I specified parsnip chips. If you part squish them they soak up left over fat. Mmmmmmm. I usually can't be bothered to cook a green veg but do occasionally, especially in the summer when we have runner beans, french beans and spinach in the garden. Maybe a few peas too. We're waiting for the curly kale to get big enough for a winter green, but it's slow! We've got leeks at the moment still.
I put this menu through Fitday and got this:
______________ grams________kcal________%kcal
Total_______________________2636
Fat_____________245________2204 _______85
Sat_____________134________1204________46
PUFA____________12_________106_________4
Mono____________79_________707________27
Carb_____________44_________136________5
Fiber_____________10
Protein___________65_________260________10
Nutritionally it gets a number of red flags from Fitday but none of these concern me as they are based on people eating to the Food Pyramid.
Supplements: Offal should be eaten weekly but I get lazy. Liver is my usual source but kidneys are nutritional powerhouses too. There's another post there. I use fish oil (5g/d) to balance the fatty acids, another post there too. I gave up on UK cod liver oil as someone takes out the vits A and D and replaces them with homeopathic doses, and the vit A used is synthetic retinoic acid. So for D3 I sunbathe as much as practical in the Summer and take 10,000 iu/d in the Winter. I get my vit A from liver and eggs.
That's about it. We do bone broths when we get the time. Beef heart makes fantastic slow casseroles. Pork mince is a favorite.
My wife eats all of her eggs, so eats only three a day, usually with bacon. She usually has cheese for lunch and we share supper. She eats a fair bit higher in protein and lower in fat than I do, but we're both lean. Her cholesterol levels are frighteningly low but she's just a youngster, so that's probably fine. Mine are, and always have been, very high. Not record breaking, just very high.
Treats: occasional Thornton's candy bar on a lower than average carb day. Home made ice cream is not a treat, but it tastes like one. Makes an excellent breakfast if you're in a hurry. Recipe:
Pint pot of cream, six egg yolks, 5ml vanilla extract, 20-30g dextrose to sweeten, 10g honey for flavour. Mix and freeze in whatever size portions you fancy.
High cocoa solid chocolate is primarily stearic acid and magnesium, so quite a lot of this sneaks in too. If I need extra calories for a day's concrete breaking I'll up both the cream and the chocolate. Several days of sustained heavy building work and I'll up protein too. Ditto if I have an exercise patch.
We're totally gluten free and almost totally grain free. Legumes only in small amounts. Dairy doesn't seem to be a problem. Another post there too.
That's what it's like...
What do I miss? Nelson's Revenge from the Woodford's brewery and Adnam's bitter. Both gluten loaded.
After a few years eating to this type of menu becomes just a normal way of life. You tend to forget how strange you are.
Actually, the oddest feeling I have ever had was at a goth rock concert, probably VNV Nation playing last year at Rock City in Nottingham. One of the best gigs ever. Very dark, very loud, very packed. Great lighting, what there was of it. Full dress goths with fantastic clothes and body jewelry and everyone moving to the deep roaring beat. But the weirdest thing was they all had pints. Pints of beer. Not the people actually in the mosh pit of course, but almost everyone else. It's a wheat based, alcohol fueled culture that we live in and a pint of beer is a symbol of everything I've left behind. I felt VERY strange, a real odd ball amongst the hard core goths at the gig... Despite external appearances, they were far more mainstream that I'll ever be again!
Peter
Mediterranean France
There is one notable diet intervention trial which succeeded in producing marked improvement in outcome, for both cardiac and cancer mortality. This is the Lyon Diet Heart Study. The final analysis is available in full text here. The sub analysis for cancer protection is available here.
What did the Lyon group do? Well this is a little bit difficult to find out as the early publications are in the Lancet and are not available on line. But, from the subsequent rhetoric, I think we can assume the usual things about increasing fruit and vegetables, skipping fat, especially the dreaded saturated fat, and putting the maximum amount of fiber down the loo were all applied. All well and good, except most of these were done far more effectively by the WHEL study, which failed miserably.
When you look at the macronutrient ratios given in table 3 it's clear that there was a 3% replacement of calories from fat with those from carbohydrate. Not a huge change, but on the basis of the Finland study it was probably significantly deleterious. Vitamin intake? In table 4 of the cancer sub analysis paper you can see that there was minimal difference in daily intake of vitamins E and C between groups.
On the face of it there are remarkably few differences between the two groups, especially when you look at the much larger and completely ineffective changes produced by the WHEL study in nutrient intakes.
So what is so special about the Mediterranean diet in Lyon that is not present in the Mediterranean diet in San Diego?
Surely everyone (in France anyway) knows that there is a centuries long tradition of avoiding all butter and cream in an arc between Perpignan and Nice, and for 50 miles inland. Absolutement mon amis, people there have always, at least since Roman times, eaten an experimental gloop produced by Astra-Calve, a subsidiary of Unilever. Made of partially hydrogenated canola oil. Hopefully that's the low erucic acid version of rapeseed oil. The trans fats listed in table here don't look too traditional but, what the heck, it was free and people ate it, in the study anyway.
As it says in the trial design their Mediterranean/intervention diet included:
"no butter and cream, which were to be replaced with an experimental canola oil–based margarine (Astra-Calve, Paris, France) rich in oleic and alpha-linolenic acids. The oils recommended for salad and food preparation were canola and olive oils exclusively."
The exact composition of this gloop is unclear, except that it had a rather high omega 3 to omega 6 ratio. Skipping back to table 3 from the final analysis paper we can also see that dumping all corn oil and sunflower oil (not allowed for cooking or salad dressing) reduces your omega six intake, while the gloop increases your omega three intake, giving a ratio of 1:4. That's a pretty good ratio. The "prudent diet" diet group trundled along with a ratio, pleasing to any poverty stricken cardiologist who needs more business, of 1:16. Awful.
The message I get from the Lyon study is that an absolute omega three fatty acid deficiency is probably rather bad for you and that correcting the ratio of omega three to omega 6 is probably very good for you.
Want to get hold of Astra-Calve's gloop to correct your fatty acid balance?
Forget it. There are better ways.
Peter
PS The Lyon study final report begins with this sentence:
"Recent dietary trials in secondary prevention of coronary heart disease (CHD) reported impressive reduction of the recurrence rate by a range of 30% to 70%."
It cites three references for this statement.
First is the DART study. This found that reducing total fat while increasing PUFA (probably omega 6 back in the 1980s) was useless. No surprise there. Increased cereal fiber was slightly worse, this produced a small but non significant increase in the risk of being dead at the two year mark. But two or three fish meals a week, without all that fruit 'n' fiber rigmarole, was very useful. A drop of 29% in two year total mortality. Good, though hardly world shattering
Second reference is to Singh. Read more about this particular paper from Singh here in the BMJ and you will see why the WHEL trial did so badly!
Third reference is self citation.
I don't see a huge amount of support for that first statement.
What did the Lyon group do? Well this is a little bit difficult to find out as the early publications are in the Lancet and are not available on line. But, from the subsequent rhetoric, I think we can assume the usual things about increasing fruit and vegetables, skipping fat, especially the dreaded saturated fat, and putting the maximum amount of fiber down the loo were all applied. All well and good, except most of these were done far more effectively by the WHEL study, which failed miserably.
When you look at the macronutrient ratios given in table 3 it's clear that there was a 3% replacement of calories from fat with those from carbohydrate. Not a huge change, but on the basis of the Finland study it was probably significantly deleterious. Vitamin intake? In table 4 of the cancer sub analysis paper you can see that there was minimal difference in daily intake of vitamins E and C between groups.
On the face of it there are remarkably few differences between the two groups, especially when you look at the much larger and completely ineffective changes produced by the WHEL study in nutrient intakes.
So what is so special about the Mediterranean diet in Lyon that is not present in the Mediterranean diet in San Diego?
Surely everyone (in France anyway) knows that there is a centuries long tradition of avoiding all butter and cream in an arc between Perpignan and Nice, and for 50 miles inland. Absolutement mon amis, people there have always, at least since Roman times, eaten an experimental gloop produced by Astra-Calve, a subsidiary of Unilever. Made of partially hydrogenated canola oil. Hopefully that's the low erucic acid version of rapeseed oil. The trans fats listed in table here don't look too traditional but, what the heck, it was free and people ate it, in the study anyway.
As it says in the trial design their Mediterranean/intervention diet included:
"no butter and cream, which were to be replaced with an experimental canola oil–based margarine (Astra-Calve, Paris, France) rich in oleic and alpha-linolenic acids. The oils recommended for salad and food preparation were canola and olive oils exclusively."
The exact composition of this gloop is unclear, except that it had a rather high omega 3 to omega 6 ratio. Skipping back to table 3 from the final analysis paper we can also see that dumping all corn oil and sunflower oil (not allowed for cooking or salad dressing) reduces your omega six intake, while the gloop increases your omega three intake, giving a ratio of 1:4. That's a pretty good ratio. The "prudent diet" diet group trundled along with a ratio, pleasing to any poverty stricken cardiologist who needs more business, of 1:16. Awful.
The message I get from the Lyon study is that an absolute omega three fatty acid deficiency is probably rather bad for you and that correcting the ratio of omega three to omega 6 is probably very good for you.
Want to get hold of Astra-Calve's gloop to correct your fatty acid balance?
Forget it. There are better ways.
Peter
PS The Lyon study final report begins with this sentence:
"Recent dietary trials in secondary prevention of coronary heart disease (CHD) reported impressive reduction of the recurrence rate by a range of 30% to 70%."
It cites three references for this statement.
First is the DART study. This found that reducing total fat while increasing PUFA (probably omega 6 back in the 1980s) was useless. No surprise there. Increased cereal fiber was slightly worse, this produced a small but non significant increase in the risk of being dead at the two year mark. But two or three fish meals a week, without all that fruit 'n' fiber rigmarole, was very useful. A drop of 29% in two year total mortality. Good, though hardly world shattering
Second reference is to Singh. Read more about this particular paper from Singh here in the BMJ and you will see why the WHEL trial did so badly!
Third reference is self citation.
I don't see a huge amount of support for that first statement.
Tuesday, January 01, 2008
Fruit and vegetables WHEL study
There are people, like these "scientific" committee members, who believe that if "powerhouse" fruit and vegetables were eaten more often in the USA, there would be major health benefits. Don't bother getting the full text.
Here's a flavour of the outpourings of Nanney, Haire-Joshu, Hessler and Brownson:
"Epidemiological (yawn) data published from large longitudinal cohort studies such as the Women’s Health Study, Health Professionals Follow-Up Study, Physician’s Health Study, and National Health and Nutrition Examination Survey (NHANES) have helped to identify food constituents (dietary folate, vitamin C) 3, 4, 5 and 6, food patterns (cruciferous vegetables) 4, 7 and 8, and specific food outcomes (carrots, tomatoes) 6, 8, 9, 10, 11 and 12 as more directly linked to reduced risk for selected chronic diseases. For example, consumption in the highest quintiles of green leafy vegetables is associated with a risk reduced by 6% to 30% for cardiovascular disease and stroke 4, 7 and 8. High intakes of broccoli and spinach are associated with reduced risk for some cancers 11 and 12 and cataract formation 13, 14 and 15. The Netherlands Cohort Study on Diet and Cancer (1986–1992; n=62,573) further specified that women with the highest consumption of cooked cauliflower and cooked spinach were associated with 38% to 49% risk reduction in colon cancer (11)."
Oops, I fell asleep after the first word.
The first word is epidemiological. That is; only useful for generating speculation.
OK, let's speculate, I mean generate an hypothesis. I hypothesise that a massive, intensive and long duration intervention trial, to get women to eat "powerhouse" fruit and vegetables, will do nothing to prevent or reduce the recurrence of previously operated breast cancer. Someone else generated a very different hypothesis. They got mega funded to check it out.
They set up the WHEL (Women's Healthy Eating and Living) study. Nice catchy name.
How might one change women's eating habits? Let's try this:
"The Women’s Healthy Eating and Living Study’s principal strategy to promote dietary change involves a telephone-counseling protocol that facilitates one-on-one advice tailored to the needs of the individual participant. The highly-structured, computer-assisted protocol facilitates standardization of the intervention. Quality control is enhanced by providing this telephone service from a centralized location at the Study Coordinating Center, thus enabling weekly case management meetings and considerable flexibility in scheduling. Counselor performance is carefully monitored, and regular feedback comparing individual to group performance has led to considerable consistency across counselors. Additional intervention strategies include an orientation meeting, monthly cooking classes, and monthly newsletters. The intervention protocol recommends 28 to 36 intervention contacts during the first 12 months (Table 1), with the majority (54% to 64%) of these contacts made by telephone."
This will work. It did work. What did it achieve?
It achieved "5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat."
It worked for 7.3 years. This is hard core long term intervention stuff. No groups of 10 people for 8 weeks and measure a few lipid parameters. This is big research using big money to make a big point. To confirm all of the benefits of those mysterious micro-nutrients in the vegetable juice.
What did it achieve? I can't say anything. I just have to leave it to the WHEL study team 2007 report:
"CONCLUSION: Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period."
Pretty conclusive. No mincing of words.
You could say it didn't do any harm I guess.
Phew.
Peter
Here's a flavour of the outpourings of Nanney, Haire-Joshu, Hessler and Brownson:
"Epidemiological (yawn) data published from large longitudinal cohort studies such as the Women’s Health Study, Health Professionals Follow-Up Study, Physician’s Health Study, and National Health and Nutrition Examination Survey (NHANES) have helped to identify food constituents (dietary folate, vitamin C) 3, 4, 5 and 6, food patterns (cruciferous vegetables) 4, 7 and 8, and specific food outcomes (carrots, tomatoes) 6, 8, 9, 10, 11 and 12 as more directly linked to reduced risk for selected chronic diseases. For example, consumption in the highest quintiles of green leafy vegetables is associated with a risk reduced by 6% to 30% for cardiovascular disease and stroke 4, 7 and 8. High intakes of broccoli and spinach are associated with reduced risk for some cancers 11 and 12 and cataract formation 13, 14 and 15. The Netherlands Cohort Study on Diet and Cancer (1986–1992; n=62,573) further specified that women with the highest consumption of cooked cauliflower and cooked spinach were associated with 38% to 49% risk reduction in colon cancer (11)."
Oops, I fell asleep after the first word.
The first word is epidemiological. That is; only useful for generating speculation.
OK, let's speculate, I mean generate an hypothesis. I hypothesise that a massive, intensive and long duration intervention trial, to get women to eat "powerhouse" fruit and vegetables, will do nothing to prevent or reduce the recurrence of previously operated breast cancer. Someone else generated a very different hypothesis. They got mega funded to check it out.
They set up the WHEL (Women's Healthy Eating and Living) study. Nice catchy name.
How might one change women's eating habits? Let's try this:
"The Women’s Healthy Eating and Living Study’s principal strategy to promote dietary change involves a telephone-counseling protocol that facilitates one-on-one advice tailored to the needs of the individual participant. The highly-structured, computer-assisted protocol facilitates standardization of the intervention. Quality control is enhanced by providing this telephone service from a centralized location at the Study Coordinating Center, thus enabling weekly case management meetings and considerable flexibility in scheduling. Counselor performance is carefully monitored, and regular feedback comparing individual to group performance has led to considerable consistency across counselors. Additional intervention strategies include an orientation meeting, monthly cooking classes, and monthly newsletters. The intervention protocol recommends 28 to 36 intervention contacts during the first 12 months (Table 1), with the majority (54% to 64%) of these contacts made by telephone."
This will work. It did work. What did it achieve?
It achieved "5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat."
It worked for 7.3 years. This is hard core long term intervention stuff. No groups of 10 people for 8 weeks and measure a few lipid parameters. This is big research using big money to make a big point. To confirm all of the benefits of those mysterious micro-nutrients in the vegetable juice.
What did it achieve? I can't say anything. I just have to leave it to the WHEL study team 2007 report:
"CONCLUSION: Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period."
Pretty conclusive. No mincing of words.
You could say it didn't do any harm I guess.
Phew.
Peter
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