3 ms·

Because Mason’s making a number of flawed assumptions based on a misunderstanding of what drives atherosclerosis risk. The important factor js number of ApoB ta

Because Mason’s making a number of flawed assumptions based on a misunderstanding of what drives atherosclerosis risk. The important factor js number of ApoB tagged lipoproteins (ApoB) and not mass of cholesterol within those lipoproteins. There is significant collinearity between these two things, but in ~30% of individuals there is discordance, which can create this illusion of “lbLDL is harmless”. This is because a given individual with the same amount of lbLDL-c as someone else’s sdLDL-c (that is, mass of cholesterol in both), the person with the same mass of sdLDL-c will have more ApoB tagged lipoproteins and therefore more risk. But when we stop using LDL-c as the measure, and use ApoB, which is what lipidologists now recommend, then the risk from large and small LDL particles is more or less the same. That is, one particle of sdLDL carries about the same risk as one particle of lbLDL. If you’d like something more consumable, lipidologist William Cromwell covers the topic very well in this video: https://youtu.be/kplh30RmYo8?si=WvDMwG-Z82voxDMp https://youtu.be/kplh30RmYo8?si=WvDMwG-Z82voxDMp It’s not hard to make an X account, but ok. I can link to the individual posts so you can have a laugh: Mason said the entirety of the lipid hypothesis was challenged by the fact that those randomised to reduced fat diets had a higher risk of dying in the 2006 WHI RCT: https://x.com/drpaulmason/status/1335411781557075968?s=46 https://x.com/drpaulmason/status/1335411781557075968?s=46 It was pointed out to him that the lipid hypothesis is about P:S ratio, not total fat reduction: https://x.com/avibittmd/status/1335470882987323392?s=46 https://x.com/avibittmd/status/1335470882987323392?s=46 Avi explained the criteria a study would need to meet to challenge the LH: https://x.com/avibittmd/status/1335475024854192129?s=46 https://x.com/avibittmd/status/1335475024854192129?s=46 There’s some back and forth, eventually Mason says the rebuttal that WHI failed to significantly reduce serum cholesterol/was a failed intervention because it targeted total fat doesn’t make sense because the intervention arm of the WHI reduced their serum cholesterol by 30%,so clearly the intervention was significant according to the LH: https://x.com/drpaulmason/status/1335488114534481920?s=46 https://x.com/drpaulmason/status/1335488114534481920?s=46 Avi asks him what he’s talking about, the serum cholesterol between intervention and control was basically the same, showing the table in the study: https://x.com/avibittmd/status/1335488453417562112?s=46 https://x.com/avibittmd/status/1335488453417562112?s=46 Avi suggests he might have confused serum cholesterol with dietary cholesterol: https://x.com/avibittmd/status/1335489121486299138?s=46 https://x.com/avibittmd/status/1335489121486299138?s=46 They share the table from the study that confirms this: https://x.com/avibittmd/status/1335491375073271808?s=46 https://x.com/avibittmd/status/1335491375073271808?s=46 And then Paul, previously so headstrong and sure he was nailing everyone on this one, just peaces out from the conversation (or runs away, if you were to be less generous). His entire argument against the lipid argument was based on misreading dietary cholesterol as serum cholesterol. So good. No one should take him seriously, he’s either purposefully deceptive or completely incompetent at reading the evidence. Don’t see why anyone interested in reaching the truth should be interested in his arguments in either case.

jodrellblank 2y ago
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

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!