I already know some of these facts, but now I have details I can show.
I am talkative and ask people I meet what the have for breakfast.
I then comment politely about John Harvey's invention and why he invented it.
If they still appear interested, I go further about the food pyramid and the tobacco industry taking over the food industry and marketing snacks, to my mind the elephant in the room.
Part of the reason for the high prevalence of heart attacks during the middle decades of the 20th Century may be attributable to heavy metals toxicity. For example, "It is not unreasonable to speculate that excessive exposure to a number of toxic metals from a wide range of different sources may have been one of the main causes of the post-war epidemic of coronary heart disease both in North America and Western Europe. These include lead from car exhaust and from drinking water (especially in the British Isles), as well as mercury and silver from dental amalgam fillings and cadmium from acid rain, commercial fertilizers and tobacco smoke."
"All the above-mentioned toxic metals would be expected to bind strongly to the chelate-forming selenol and thiol groups in both thioredoxin reductase and selenoprotein P (and also, albeit not equally strongly, to chelate-forming thiol groups in thioredoxin). It is possible that their relative importance as causes of enhanced LDL oxidation and atheromatosis, both at the individual level and that of entire populations, may depend less strongly on differences in their relative binding strength to these enzymes than on differences in their abundance. If this hypothesis is correct, it means that lead, which is the most abundant of these toxic metals when considering both its average abundance in the Earth's continental crust [49] and as an environmental pollutant, could have been more important than any other toxic metal as a contributory cause of LDL oxidation, atheromatosis and coronary heart disease. This hypothesis would appear to be in reasonably good agreement with what is known about the historical curves both for coronary heart disease mortality and for the use of lead as an additive in gasoline in Western Europe, compared to North America. The use of lead as an additive in gasoline started earlier and ended earlier in the United States than it did in the countries of Western Europe. And the epidemic of coronary heart disease has followed a similar time course with both its start and its culmination occurring earlier in the United States than in Western Europe." https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-10-16
Can we have a discussion on Dr Kendrick's book The Clot Thickens.
Apparently he makes much of the idea that LDL can't go from the lumen to the back of epithelial cells. But as here, there are LDL receptors in cells and apparently LDL can enter a cell.
Thank you for that info. Do you recall off the top of your head any other things the book is wrong about? Right now, The Clot Thickens is my main source for understanding atherosclerosis, so I would greatly appreciate any other errata you could provide.
Yeah, I need to do a review. There’s a lot. It’s an interesting book, and I enjoyed reading it, but he entirely misses the boat on what is causing CVD.
In his earlier book Cholesterol Con he was ascribing CVD to stress --and giving very silly examples. Like high CVD in Finns due to stress of moving 50-100 km post surrender of territory to USSR. And high CVD in (South) Asians in UK due to stress due to (voluntary) migration. ----But no CVD in Asians in South Asia due to involuntary migration in 1947 and no CVD in survivors of WW 2 concentration camps?
“Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation.”
(Web search - adipose tissue arachidonic acid atherosclerosis) AI Overview says, "Adipose tissue arachidonic acid content is positively associated with the expression of 5-lipoxygenase in atherosclerotic plaques and is linked to a higher risk of myocardial infarction. Arachidonic acid (AA) is a precursor of pro-inflammatory eicosanoids, including leukotrienes, which play a role in the development of atherosclerosis and plaque instability. AA can be released from endothelial cells and converted into leukotriene B4 (LTB4), a potent inflammatory mediator that attracts and activates white blood cells, promoting inflammation and plaque formation."
(web search - Adipose tissue linoleic acid atherosclerosis) AI Overview says, "Linoleic acid, an omega-6 polyunsaturated fatty acid, has a complex relationship with atherosclerosis. While some studies suggest a protective effect of linoleic acid against cardiovascular disease, others indicate potential pro-inflammatory and pro-atherosclerotic effects, particularly when derived from industrial vegetable oils."
To interpret these narratives correctly requires familiarity with 'The Reverse Effect'. This narrative contains a clue. "Linoleic acid (LA), as a part of the wider debate about saturated, omega-6 and omega-3 fatty acids (FAs) and health, continues to be at the center of controversy in the world of fatty acid research. A robust evidence base, however, demonstrates that higher intakes and blood levels of LA are associated with improved cardiometabolic health outcomes...Using large prospective datasets, higher blood levels of LA were associated with lower risk of coronary heart disease, stroke and incident type-2 diabetes mellitus compared with lower levels, suggesting that, across the range of typical dietary intakes, higher LA is beneficial. Recent trials of LA-rich oils report favorable outcomes in people with common lipid disorders." https://pubmed.ncbi.nlm.nih.gov/39267068/
At the ISSFAL 2010 Dinner Debate it was decided that "a 5-year randomized controlled trial comparing the effects of historically low (2%) with currently high (7.5%) linoleic acid intakes on cardiac endpoints would address the knowledge gap about the effects of different omega-6 PUFA intakes on the risk of heart disease." https://pubmed.ncbi.nlm.nih.gov/21430375/
I've not seen any indication that a 2% energy linoleic acid trial was ever funded. The 2% energy intake of linoleic acid lies below the range of typical dietary intakes. It is important to note that the people studied who benefited from increased linoleic acid intake were already suffereing from lipid disorders. When they increased their intake of linoleic acid, they became insulin sensitive and began burning more circulating linoleic acid for energy. (web search - circulating linoleic acid insulin sensitivity) AI Overview: "Circulating linoleic acid, a common omega-6 fatty acid, has been linked to both improved and impaired insulin sensitivity, depending on the context and specific study. Some research suggests a positive association between circulating linoleic acid and insulin sensitivity, while other studies indicate a negative or neutral relationship."
The mechanistic explanation for inproved insulin sensitivity has to do with the ability of linoleic acid to displace arachidonic acid molecules from their positons in cell membranes. According to Norwegian animal science researchers, "Because arachidonic acid (AA) competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation." The Norwegian researchers suggest that "Combining reduction of the intake of AA with enhancement of the intake of oleic acid will, moreover, also be a better strategy for reducing the total extent of in vivo lipid peroxidation, rather than adding more EPA (with 5 double bonds) and DHA (with 6 double bonds) to a diet already over-abundant in arachidonic acid and linoleic acid.
In the final analysis, risk of dying from atherosclerosis is likely close to zero at 2% or less energy intake of linoleic acid. Risk of insulin resistance and early death increases for linoleic acid intakes in the lower end of the range of typical dietary intakes. Swapping unsaturated fatty acids of any sort foe dietary saturated fat increases the pool of fatty acids that serve to displace arachidonic acid from cell membranes. Displaced arachidonic acid molecules are available for beta oxidation. Once insulin sensitivity is restored, linoleic acid and arachidonic acid molecules, released from fat stores, supply some of the body's energy requirements. For example, "Weight loss could, at least in part, rebalance the fatty acid profile, because the mobilization of fatty acids does not depend on their proportion in adipose tissue, but rather on their structure (length and unsaturation number). PUFAs, such as 20:5n-3 and 20:4n-6, are more easily mobilized." https://www.mdpi.com/2227-9059/10/5/995
“When I asked Frantz [the principal investigator of the MCE] in late 2003 why the study went unpublished for sixteen years, he said, ‘We were just disappointed in the way it came out.’” (Taubes, 2008)
If it turns out to be correct that linoleic acid is the foremost cause of atherosclerosis, it's just amazing to think that these researchers could have had eternal fame as the discoverers of the top cause of heart disease, but they decided, "Nah, it's not the truth I was really hoping for, so I'll just leave it on the table."
Canola/rapeseed has good w3/w6 ratio. I suppose replacing w6 rich oils with canola/rapeseed could help a bit.
In any case, the health situation was made worse by adoption of higher fat diets worldwide. Taubes who cherry picks his data got around this by focusing on US only.
Excellent.
I already know some of these facts, but now I have details I can show.
I am talkative and ask people I meet what the have for breakfast.
I then comment politely about John Harvey's invention and why he invented it.
If they still appear interested, I go further about the food pyramid and the tobacco industry taking over the food industry and marketing snacks, to my mind the elephant in the room.
So again, thank you for showing these facts.
John Harvey’s invention?
Kellogs Corn Flakes
There was already CVD epidemic prior to widespread use of seed oil-- was it because of smoking or margarine?
Notice that corn oil was given to Eisenhower as a medical recommendation. This means corn oil was not in common use.
Part of the reason for the high prevalence of heart attacks during the middle decades of the 20th Century may be attributable to heavy metals toxicity. For example, "It is not unreasonable to speculate that excessive exposure to a number of toxic metals from a wide range of different sources may have been one of the main causes of the post-war epidemic of coronary heart disease both in North America and Western Europe. These include lead from car exhaust and from drinking water (especially in the British Isles), as well as mercury and silver from dental amalgam fillings and cadmium from acid rain, commercial fertilizers and tobacco smoke."
"All the above-mentioned toxic metals would be expected to bind strongly to the chelate-forming selenol and thiol groups in both thioredoxin reductase and selenoprotein P (and also, albeit not equally strongly, to chelate-forming thiol groups in thioredoxin). It is possible that their relative importance as causes of enhanced LDL oxidation and atheromatosis, both at the individual level and that of entire populations, may depend less strongly on differences in their relative binding strength to these enzymes than on differences in their abundance. If this hypothesis is correct, it means that lead, which is the most abundant of these toxic metals when considering both its average abundance in the Earth's continental crust [49] and as an environmental pollutant, could have been more important than any other toxic metal as a contributory cause of LDL oxidation, atheromatosis and coronary heart disease. This hypothesis would appear to be in reasonably good agreement with what is known about the historical curves both for coronary heart disease mortality and for the use of lead as an additive in gasoline in Western Europe, compared to North America. The use of lead as an additive in gasoline started earlier and ended earlier in the United States than it did in the countries of Western Europe. And the epidemic of coronary heart disease has followed a similar time course with both its start and its culmination occurring earlier in the United States than in Western Europe." https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-10-16
Yeah, one of the things I learned from Clot Thickens was the probable role of leaded gasoline. It stimulates lipid peroxidation, like smoking does.
The widespread use of seed oils started in the late 1800s. The CVD epidemic started in the early 1900s.
Can we have a discussion on Dr Kendrick's book The Clot Thickens.
Apparently he makes much of the idea that LDL can't go from the lumen to the back of epithelial cells. But as here, there are LDL receptors in cells and apparently LDL can enter a cell.
He's wrong about a number of things in that book. The notion that LDL can't be transported through the endothelial cells is one of them.
https://doi.org/10.1038/s41586-019-1140-4
Thank you for that info. Do you recall off the top of your head any other things the book is wrong about? Right now, The Clot Thickens is my main source for understanding atherosclerosis, so I would greatly appreciate any other errata you could provide.
Yeah, I need to do a review. There’s a lot. It’s an interesting book, and I enjoyed reading it, but he entirely misses the boat on what is causing CVD.
In his earlier book Cholesterol Con he was ascribing CVD to stress --and giving very silly examples. Like high CVD in Finns due to stress of moving 50-100 km post surrender of territory to USSR. And high CVD in (South) Asians in UK due to stress due to (voluntary) migration. ----But no CVD in Asians in South Asia due to involuntary migration in 1947 and no CVD in survivors of WW 2 concentration camps?
Yeah, it's a bit ridiculous.
Hyperglycemia doesn't injure epithelium ?
“Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation.”
https://doi.org/10.3945/jn.111.144592
(Web search - adipose tissue arachidonic acid atherosclerosis) AI Overview says, "Adipose tissue arachidonic acid content is positively associated with the expression of 5-lipoxygenase in atherosclerotic plaques and is linked to a higher risk of myocardial infarction. Arachidonic acid (AA) is a precursor of pro-inflammatory eicosanoids, including leukotrienes, which play a role in the development of atherosclerosis and plaque instability. AA can be released from endothelial cells and converted into leukotriene B4 (LTB4), a potent inflammatory mediator that attracts and activates white blood cells, promoting inflammation and plaque formation."
(web search - Adipose tissue linoleic acid atherosclerosis) AI Overview says, "Linoleic acid, an omega-6 polyunsaturated fatty acid, has a complex relationship with atherosclerosis. While some studies suggest a protective effect of linoleic acid against cardiovascular disease, others indicate potential pro-inflammatory and pro-atherosclerotic effects, particularly when derived from industrial vegetable oils."
To interpret these narratives correctly requires familiarity with 'The Reverse Effect'. This narrative contains a clue. "Linoleic acid (LA), as a part of the wider debate about saturated, omega-6 and omega-3 fatty acids (FAs) and health, continues to be at the center of controversy in the world of fatty acid research. A robust evidence base, however, demonstrates that higher intakes and blood levels of LA are associated with improved cardiometabolic health outcomes...Using large prospective datasets, higher blood levels of LA were associated with lower risk of coronary heart disease, stroke and incident type-2 diabetes mellitus compared with lower levels, suggesting that, across the range of typical dietary intakes, higher LA is beneficial. Recent trials of LA-rich oils report favorable outcomes in people with common lipid disorders." https://pubmed.ncbi.nlm.nih.gov/39267068/
At the ISSFAL 2010 Dinner Debate it was decided that "a 5-year randomized controlled trial comparing the effects of historically low (2%) with currently high (7.5%) linoleic acid intakes on cardiac endpoints would address the knowledge gap about the effects of different omega-6 PUFA intakes on the risk of heart disease." https://pubmed.ncbi.nlm.nih.gov/21430375/
I've not seen any indication that a 2% energy linoleic acid trial was ever funded. The 2% energy intake of linoleic acid lies below the range of typical dietary intakes. It is important to note that the people studied who benefited from increased linoleic acid intake were already suffereing from lipid disorders. When they increased their intake of linoleic acid, they became insulin sensitive and began burning more circulating linoleic acid for energy. (web search - circulating linoleic acid insulin sensitivity) AI Overview: "Circulating linoleic acid, a common omega-6 fatty acid, has been linked to both improved and impaired insulin sensitivity, depending on the context and specific study. Some research suggests a positive association between circulating linoleic acid and insulin sensitivity, while other studies indicate a negative or neutral relationship."
The mechanistic explanation for inproved insulin sensitivity has to do with the ability of linoleic acid to displace arachidonic acid molecules from their positons in cell membranes. According to Norwegian animal science researchers, "Because arachidonic acid (AA) competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation." The Norwegian researchers suggest that "Combining reduction of the intake of AA with enhancement of the intake of oleic acid will, moreover, also be a better strategy for reducing the total extent of in vivo lipid peroxidation, rather than adding more EPA (with 5 double bonds) and DHA (with 6 double bonds) to a diet already over-abundant in arachidonic acid and linoleic acid.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2875212/
In the final analysis, risk of dying from atherosclerosis is likely close to zero at 2% or less energy intake of linoleic acid. Risk of insulin resistance and early death increases for linoleic acid intakes in the lower end of the range of typical dietary intakes. Swapping unsaturated fatty acids of any sort foe dietary saturated fat increases the pool of fatty acids that serve to displace arachidonic acid from cell membranes. Displaced arachidonic acid molecules are available for beta oxidation. Once insulin sensitivity is restored, linoleic acid and arachidonic acid molecules, released from fat stores, supply some of the body's energy requirements. For example, "Weight loss could, at least in part, rebalance the fatty acid profile, because the mobilization of fatty acids does not depend on their proportion in adipose tissue, but rather on their structure (length and unsaturation number). PUFAs, such as 20:5n-3 and 20:4n-6, are more easily mobilized." https://www.mdpi.com/2227-9059/10/5/995
“When I asked Frantz [the principal investigator of the MCE] in late 2003 why the study went unpublished for sixteen years, he said, ‘We were just disappointed in the way it came out.’” (Taubes, 2008)
If it turns out to be correct that linoleic acid is the foremost cause of atherosclerosis, it's just amazing to think that these researchers could have had eternal fame as the discoverers of the top cause of heart disease, but they decided, "Nah, it's not the truth I was really hoping for, so I'll just leave it on the table."
I don't think in 1973 Frantz was in a position to understand that. Much of the work in that direction came in the 1980s and later.
Canola/rapeseed has good w3/w6 ratio. I suppose replacing w6 rich oils with canola/rapeseed could help a bit.
In any case, the health situation was made worse by adoption of higher fat diets worldwide. Taubes who cherry picks his data got around this by focusing on US only.