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That is an interesting interview with William Cromwell. When he says insulin resistance goes with lots of small LDL, why does it? I don't know how cells turning

That is an interesting interview with William Cromwell. When he says insulin resistance goes with lots of small LDL, why does it? I don't know how cells turning down their insulin sensitivity has a connection to fat in the blood, particularly. What's causing what to happen/not happen, there? That Twitter exchange; separate from the lipid hypothesis bit, are you saying in summary that Avi is not contesting the claim that the reduced fat group had a higher heart attack risk, only contesting which fat was reduced? They intervention group reduced dietary cholesterol by 30% and that didn't change their serum cholesterol at all and they had higher heart attack risk?? How does that track with your comments about you reducing your dietary fat, why are you if doing that doesn't change serum levels or death risk? That seems to track what Dr Davis says about CAC scores and reducing dietary fat not helping them. From out here in layman's view, what people on many different sides are saying is about insulin resistance and metabolic syndrome being more important (and more modifiable). Say as a layman chain of reasoning: if most cholesterol in the blood is made by the liver rather than by diet, if one use for cholesterol is to shuttle repair materials to damaged sites around the body, if chronic inflammation is a sign of widespread low grade damage which needs lots of repair, if some of that damage is caused by glycation, if insulin resistance means more free blood glucose not being taken into cells so there's more in the blood to cause more damage, if damage is also caused by oxidised and rancid fats, if unsaturated fats oxidise more easily... then reducing (sugars, simple carbs, unsaturated fats) in the diet should result in reduced insulin resistance, in less damage, in lower levels of chronic inflammation, therefore in less cholesterol produced by the liver, in lower blood LDL of any size, in less cholesterol to be damaged and less free glucose to damage it, therefore in less plaque buildup, lower heart disease risk. (At no point here am I saying "more fat is better" in absolute terms; I don't think that adding butter onto a takeaway makes it healthier).

KempyKolibri 2y ago
My understanding is that insulin resistance leads to increase DNL in the liver, so you end up with a greater production rate of LDL particles, but each one contains less cholesterol. I’m not woke on the mechanisms, but there’s a review paper here if you’re interested: https://www.sciencedirect.com/science/article/abs/pii/S1050173801000846?via%3Dihub https://www.sciencedirect.com/science/article/abs/pii/S10501... Re: the twitter conversation: the diet heart hypothesis is specifically about replacing saturated fat with polyunsaturated fat. If you just reduce overall fat, you may even be making that P:S ratio worse. In the case of the WHI it means that the study is essentially null by default on that issue. Dietary cholesterol is an interesting one - basically there is a significant effect of dietary cholesterol on serum cholesterol, but only when you go from very low to low levels. After that, the effect tails off dramatically. So in the general population you might not expect a 30% reduction to make a significant difference. Additionally, you have to consider the overall picture. Maybe the reduction in dietary cholesterol did have a small beneficial effect, but the fact that the intervention group ended up with lower PUFA consumption than the control group meant this reduction was overshadowed by that effect. There’s no evidence that oxidised fats in unsaturated fats are a cause for concern for health. Aside from that I don’t think stringing together a bunch of mechanisms and speculating about them is a particularly useful way to carry out science. What we care about is actual outcomes from actual interventions. So yes, I agree that in those with metabolic disease and insulin resistance, we should address this issue. The evidence seems to suggest this is best done by losing weight. If there’s a certain dietary pattern that helps someone do that, great. If it’s a GLP-1 agonist, go for it. Whatever works. But we also know that fat quality affects CVD risk too, and by a decent amount. So within whatever dietary pattern one settles on, replacing SFA with PUFA would also be a good idea. We can do both!
- jodrellblank 2y ago
  > "If you just reduce overall fat, you may even be making that P:S ratio worse." Ugh. > "There’s no evidence that oxidised fats in unsaturated fats are a cause for concern for health." https://openheart.bmj.com/content/5/2/e000898 https://openheart.bmj.com/content/5/2/e000898 says: "The low-density lipoprotein (LDL) oxidation hypothesis gained traction during the 1980s because it was noted that in general, native unoxidised LDL does not cause foam cell formation. In other words, LDL had to become oxidised first in order for atherosclerosis to develop [..] what causes LDL to become oxidised in the first place? It was later discovered that the oxidation of LDL was initiated by the oxidation of linoleic acid contained within the LDL particles [..] a more comprehensive theory, the ‘oxidised linoleic acid theory of coronary heart disease’, is as follows: dietary linoleic acid, especially when consumed from refined omega-6 vegetable oils, gets incorporated into all blood lipoproteins (such as LDL, VLDL and HDL) increasing the susceptibility of all lipoproteins to oxidise and hence increases cardiovascular risk [..] cholesterol was protected from oxidation if bound to saturated fat but susceptible to oxidation when bound to linoleic acid" That is condeming oxidised serum fats, not oxidised dietary fats, but it appears to be condemning "omega-6-rich vegetable oils" in the diet because they are more likely to oxidise in the body(?). I'm guessing if they are already oxidised when eaten that matters, because the only way it couldn't matter is if we deconstructed fats we eat and rebuilt them completely from scratch and if we did that completely then none of any of this would matter. The link's Box 1 has 29 points criticising those fats, Box 2 has 1 point in their favour "reduces total cholesterol and LDL". > "Aside from that I don’t think stringing together a bunch of mechanisms and speculating about them is a particularly useful way to carry out science." Well I'm not gonna understand biology, chemistry, lipid science to the level of a PhD researcher, PhD statistician, medical doctor, or an interested smart amateur biologist/chemist, myself. If I also can't have a bro-science chain of layperson reasoning, then your position boils down to "Science is only for experts, and only the experts I choose, not those they believe the wrong things so they're quacks, trust me" which is .. disagreeable. > "What we care about is actual outcomes from actual interventions." We can't see those until people don't die of heart disease fourty years later. This is why I'm so on the side of Dr William Davis because the CAC score seems to be the only good non-invasive measure of plaque available, something which can show an almost direct outcome of intervention on plaque. Whereas "serum LDL went down" is easily measurable but doesn't show if plaque formation is slowed, stopped, reversed, or unchanged. I also think that if low-fat did avoid or reverse heart disease, the massive international push over the last 50 years for low-fat foods would have made it absolutely clear, and instead heart disease is up up up. Doubling down on "people simply didn't eat low-fat yoghurt hard enough, do that harder" is just so unconvincing. > "But we also know that fat quality affects CVD risk too" When you say fat quality, do you mean PUFA vs SFA? Or do you mean things like presense of Glyphosate, trans-fats, contaminations in the food chain, things ordinary people mean by quality? > "and by a decent amount. So within whatever dietary pattern one settles on, replacing SFA with PUFA would also be a good idea. We can do both!" You've made a strong case that reducing serum cholesterol would be a good idea. Not such a strong case that reducing dietary fat would be a good idea. And not much case at all that replacing SFA with PUFA is a good idea. Let's be clear that I'm lost in the details of SFA, PUFA, linoleics, Omegas, LDLs/HDLs, triglycerides, cholesterols, which ones are more important, which ones are a tiny effect but easier to study or more interesting to study. When someone is 150lbs overweight and insulin resistant and never does an exercise it can't possibly come down to wibbling over whether they ate two slices of bacon vs half an avocado, or whether they put butter or margarine on a scone that one time. On the other hand if someone is Mark Sisson[1] a lean former ironman runner and paleo/low-carb enthusiast who got famous for eating a "big-ass salad" everyday, who does intermittent fasting, eats salmon and leaves with avocado oil dressing for lunch, then a ribeye stake with asparagus and avocado for dinner, no snacks, no desert, who cares about health, is he at risk of heart disease because he put heavy cream in his one coffee of the day and has red meat on his plate instead of nutloaf? I guess you're suggesting to remove a daily Starbucks coffee with whipped dairy cream and sugar, right? No-brainer, I would agree. But telling Mark Sisson to replace that steak with tofu? He has solved or avoided so many other problems people have with food - no food cravings or hunger, he's not overweight, he's not fatigued or big swings of energy, he's unusually healthy for someone in a Western country at his age (50s IIRC) that he's gotta be doing a lot right, not a lot wrong. He's gotta be somewhere close to a good human diet even if that is too much meat to eat every day for other reasons. [1] https://www.youtube.com/watch?v=knbo9Tw2b9g https://www.youtube.com/watch?v=knbo9Tw2b9g

KempyKolibri 2y ago

My understanding is that insulin resistance leads to increase DNL in the liver, so you end up with a greater production rate of LDL particles, but each one contains less cholesterol. I’m not woke on the mechanisms, but there’s a review paper here if you’re interested: https://www.sciencedirect.com/science/article/abs/pii/S1050173801000846?via%3Dihub https://www.sciencedirect.com/science/article/abs/pii/S10501... Re: the twitter conversation: the diet heart hypothesis is specifically about replacing saturated fat with polyunsaturated fat. If you just reduce overall fat, you may even be making that P:S ratio worse. In the case of the WHI it means that the study is essentially null by default on that issue. Dietary cholesterol is an interesting one - basically there is a significant effect of dietary cholesterol on serum cholesterol, but only when you go from very low to low levels. After that, the effect tails off dramatically. So in the general population you might not expect a 30% reduction to make a significant difference. Additionally, you have to consider the overall picture. Maybe the reduction in dietary cholesterol did have a small beneficial effect, but the fact that the intervention group ended up with lower PUFA consumption than the control group meant this reduction was overshadowed by that effect. There’s no evidence that oxidised fats in unsaturated fats are a cause for concern for health. Aside from that I don’t think stringing together a bunch of mechanisms and speculating about them is a particularly useful way to carry out science. What we care about is actual outcomes from actual interventions. So yes, I agree that in those with metabolic disease and insulin resistance, we should address this issue. The evidence seems to suggest this is best done by losing weight. If there’s a certain dietary pattern that helps someone do that, great. If it’s a GLP-1 agonist, go for it. Whatever works. But we also know that fat quality affects CVD risk too, and by a decent amount. So within whatever dietary pattern one settles on, replacing SFA with PUFA would also be a good idea. We can do both!

jodrellblank 2y ago
> "If you just reduce overall fat, you may even be making that P:S ratio worse." Ugh. > "There’s no evidence that oxidised fats in unsaturated fats are a cause for concern for health." https://openheart.bmj.com/content/5/2/e000898 https://openheart.bmj.com/content/5/2/e000898 says: "The low-density lipoprotein (LDL) oxidation hypothesis gained traction during the 1980s because it was noted that in general, native unoxidised LDL does not cause foam cell formation. In other words, LDL had to become oxidised first in order for atherosclerosis to develop [..] what causes LDL to become oxidised in the first place? It was later discovered that the oxidation of LDL was initiated by the oxidation of linoleic acid contained within the LDL particles [..] a more comprehensive theory, the ‘oxidised linoleic acid theory of coronary heart disease’, is as follows: dietary linoleic acid, especially when consumed from refined omega-6 vegetable oils, gets incorporated into all blood lipoproteins (such as LDL, VLDL and HDL) increasing the susceptibility of all lipoproteins to oxidise and hence increases cardiovascular risk [..] cholesterol was protected from oxidation if bound to saturated fat but susceptible to oxidation when bound to linoleic acid" That is condeming oxidised serum fats, not oxidised dietary fats, but it appears to be condemning "omega-6-rich vegetable oils" in the diet because they are more likely to oxidise in the body(?). I'm guessing if they are already oxidised when eaten that matters, because the only way it couldn't matter is if we deconstructed fats we eat and rebuilt them completely from scratch and if we did that completely then none of any of this would matter. The link's Box 1 has 29 points criticising those fats, Box 2 has 1 point in their favour "reduces total cholesterol and LDL". > "Aside from that I don’t think stringing together a bunch of mechanisms and speculating about them is a particularly useful way to carry out science." Well I'm not gonna understand biology, chemistry, lipid science to the level of a PhD researcher, PhD statistician, medical doctor, or an interested smart amateur biologist/chemist, myself. If I also can't have a bro-science chain of layperson reasoning, then your position boils down to "Science is only for experts, and only the experts I choose, not those they believe the wrong things so they're quacks, trust me" which is .. disagreeable. > "What we care about is actual outcomes from actual interventions." We can't see those until people don't die of heart disease fourty years later. This is why I'm so on the side of Dr William Davis because the CAC score seems to be the only good non-invasive measure of plaque available, something which can show an almost direct outcome of intervention on plaque. Whereas "serum LDL went down" is easily measurable but doesn't show if plaque formation is slowed, stopped, reversed, or unchanged. I also think that if low-fat did avoid or reverse heart disease, the massive international push over the last 50 years for low-fat foods would have made it absolutely clear, and instead heart disease is up up up. Doubling down on "people simply didn't eat low-fat yoghurt hard enough, do that harder" is just so unconvincing. > "But we also know that fat quality affects CVD risk too" When you say fat quality, do you mean PUFA vs SFA? Or do you mean things like presense of Glyphosate, trans-fats, contaminations in the food chain, things ordinary people mean by quality? > "and by a decent amount. So within whatever dietary pattern one settles on, replacing SFA with PUFA would also be a good idea. We can do both!" You've made a strong case that reducing serum cholesterol would be a good idea. Not such a strong case that reducing dietary fat would be a good idea. And not much case at all that replacing SFA with PUFA is a good idea. Let's be clear that I'm lost in the details of SFA, PUFA, linoleics, Omegas, LDLs/HDLs, triglycerides, cholesterols, which ones are more important, which ones are a tiny effect but easier to study or more interesting to study. When someone is 150lbs overweight and insulin resistant and never does an exercise it can't possibly come down to wibbling over whether they ate two slices of bacon vs half an avocado, or whether they put butter or margarine on a scone that one time. On the other hand if someone is Mark Sisson[1] a lean former ironman runner and paleo/low-carb enthusiast who got famous for eating a "big-ass salad" everyday, who does intermittent fasting, eats salmon and leaves with avocado oil dressing for lunch, then a ribeye stake with asparagus and avocado for dinner, no snacks, no desert, who cares about health, is he at risk of heart disease because he put heavy cream in his one coffee of the day and has red meat on his plate instead of nutloaf? I guess you're suggesting to remove a daily Starbucks coffee with whipped dairy cream and sugar, right? No-brainer, I would agree. But telling Mark Sisson to replace that steak with tofu? He has solved or avoided so many other problems people have with food - no food cravings or hunger, he's not overweight, he's not fatigued or big swings of energy, he's unusually healthy for someone in a Western country at his age (50s IIRC) that he's gotta be doing a lot right, not a lot wrong. He's gotta be somewhere close to a good human diet even if that is too much meat to eat every day for other reasons. [1] https://www.youtube.com/watch?v=knbo9Tw2b9g https://www.youtube.com/watch?v=knbo9Tw2b9g