6 ms·

What is the current state of understanding on high cholesterol as a leading or trailing indicator of poor health? I vaguely remember reading one theory that ch

What is the current state of understanding on high cholesterol as a leading or trailing indicator of poor health? I vaguely remember reading one theory that cholesterol was used by the body to mitigate arterial damage from other causes?

shlant 3mo ago
the literature is very clear about the relationship between high LDL and Atherosclerosis. Are you referring to poor health in general, separate from Cardiovascular Disease?
_kidlike 3mo ago
cholesterol is one of the most crucial molecules for survival. It's used to create and maintain cell membranes, and other critical functions. The vast majority is created by the liver, and there are a lot of regulating signals for how much, which is where usually things go off. Low cholesterol production is an extremely serious condition. The "only" problem with high cholesterol is that it builds up inside artery walls, which eventually may or may not dislodge and may or may not cause a heart attack or an embolic stroke. (I'm not a doctor. I just get medication for high cholesterol and have done some research)
- cthalupa 3mo ago
  > Low cholesterol production is an extremely serious condition. This is correct, but not in the way you mean it. We know people can effectively produce no LDL cholesterol in their liver and have positive health impacts - these MR studies are a big part of what drove this entire class of cholesterol medications. And the monoclonal antibody versions of PCSK9 inhibitors have shown basically the same results. Virtually all human cells can produce cholesterol locally de novo, including your brain.
  - _kidlike 3mo ago
    o_O
eternauta3k 3mo ago
Peter Attia had a great series of blog posts on this before his fall from grace: https://peterattiamd.com/the-straight-dope-on-cholesterol-part-i/ https://peterattiamd.com/the-straight-dope-on-cholesterol-pa... He also had a series of podcast interviews about this with Tom Dayspring. I believe his explanations are all mainstream, except he favors treating LDL and LP(a) more aggressively than normal doctors
- stavros 3mo ago
  Wait, why did he fall from grace?
  - messel 3mo ago
    I didn't know either, not sure of veracity but https://share.gemini.google/0YDt55yyfITs https://share.gemini.google/0YDt55yyfITs
  - hammock 3mo ago
    1700 mentions of his name in the Epstein files that Trump released.
  - eternauta3k 3mo ago
    Epstein files showed he neglected to visit his seriously sick son because he was hanging out with Epstein. He still knows his stuff, asshole or not.
- leopoldj 3mo ago
  Wow the guy did Mechanical Engineering and Applied Math before going into medicine and surgery.
barnacs 3mo ago
It turns out LDL has different subfractions based on size. Normally, the liver produces large ones which shuttle fat around the bloodstream, lose their payload and shrink then the liver reabsorbs them and the cycle continues. The problem appears to begin when these LDL molecules hang around for too long. They are damaged by external factors in the bloodstream (eg. glycation due to high blood glucose, oxidation due to fragile polyunsaturated fats) and not recognized anymore for recycling. That's when they can start forming macrophages. tl;dr LDL by itself is an incorrect measure of cardiovascular risk. Big pharma still profits by selling everyone LDL reducing drugs. one authentic source: https://www.youtube.com/watch?v=fVLZA0qp-wc https://www.youtube.com/watch?v=fVLZA0qp-wc
- grep_name 3mo ago
  I have heard this too, and that cholesterol measurements are flawed because they don't account for particle size. That you can actually have better 'numbers' but worse results, if you reduce particulate size but also overall volume. It's frustrating that the science behind cholesterol is constantly in wild flux, but at any discrete moment you're expected to accept whatever the momentary consensus is. Interestingly, my dentist, who also has a bit of a fixation on cholesterol on a personal level and is educated on the matter, has said that a heart calcium scan is the best way to determine what someone's target cholesterol number should actually be, and that it should not be the same from person to person. This was after I voiced my frustration to him at having made lifestyle changes to get my cholesterol down in order to avoid getting put on statins (not wanting yet another daily drug if I can avoid it), getting the my number below the target of 110, only to shortly after that find out that they'd lowered it to 70. I talked to my endocrinologist about it, and she basically said "yeah, those numbers are more-or-less unachievable. But we want to be extra careful for type 1 diabetics, so we hold them to a higher standard. Either way, everyone gets put on statins at some point anyway, so who cares?" I'm absolutely allergic to "everyone goes on x medication, so stop whining and go on x medication" as a medical argument, and will probably just deal with being labelled non-compliant over this one unless my cholesterol reaches a level I actually personally find to be too high at this point. Which sucks to have to do, but hey, it's my body after all, and so far doctors have failed to make a convincing case for me personally here.
dev_l1x_be 3mo ago
You should check which part of your body has the most cholesterol.
- shermantanktop 3mo ago
  How would I check the parts of my body for that?
  - amanaplanacanal 3mo ago
    I think they meant ask Google. It's the brain.
  - dev_l1x_be 3mo ago
    The brain is the most cholesterol-rich organ in the body. While accounting for only 2% of body weight, it contains roughly 20% of the body's cholesterol. It is essential for nerve cell communication, learning, and memory.
cthalupa 3mo ago
It (Particularly ApoB/Combining LDL-C and Lp(a) is one of the single largest leading indicators of health risk we have. If anything, the data we have is suggesting we've gotten wrong what the upper limits should be for what is considered OK. https://www.lipidjournal.com/article/S1933-2874(25)00317-4/fulltext https://www.lipidjournal.com/article/S1933-2874(25)00317-4/f...
- guerby 3mo ago
  Isn't diabete and metabolic syndrome way more predictive than ldl or apob? Do you have a reference comparing the various factors?
BiteCode_dev 3mo ago
All the answers are smart sounding and completely avoid to address your main point. Same with most doctors I asked it to.
Eddy_Viscosity2 3mo ago
We've been testing for cholesterol for a long time now and have had other meds to lower it. It should be possible to see if lowering cholesterol via medication results in improved life expectancy or reducing cardiac events. I would think this study has been done a few times already. As someone who does not have much medical knowledge, I'm not even sure how to look this up or be able to assess what I see if I did.
- cthalupa 3mo ago
  Just google 'mortality data statins' and there's a mountain of it. 5 years studies show minimal or no benefit for people in low-risk groups. High-risk groups see significant benefit Follow up/longer term studies show increased benefit in low-risk groups but obviously not matching the high risk groups.
sn9 3mo ago
There isn't a conflict between cholesterol having a useful role in the body and too much being harmful. There are mountains of evidence establishing a causal relationship between elevated cholesterol levels and heart disease.

shlant 3mo ago

the literature is very clear about the relationship between high LDL and Atherosclerosis. Are you referring to poor health in general, separate from Cardiovascular Disease?

_kidlike 3mo ago

cholesterol is one of the most crucial molecules for survival. It's used to create and maintain cell membranes, and other critical functions. The vast majority is created by the liver, and there are a lot of regulating signals for how much, which is where usually things go off. Low cholesterol production is an extremely serious condition. The "only" problem with high cholesterol is that it builds up inside artery walls, which eventually may or may not dislodge and may or may not cause a heart attack or an embolic stroke. (I'm not a doctor. I just get medication for high cholesterol and have done some research)

cthalupa 3mo ago
> Low cholesterol production is an extremely serious condition. This is correct, but not in the way you mean it. We know people can effectively produce no LDL cholesterol in their liver and have positive health impacts - these MR studies are a big part of what drove this entire class of cholesterol medications. And the monoclonal antibody versions of PCSK9 inhibitors have shown basically the same results. Virtually all human cells can produce cholesterol locally de novo, including your brain.
- _kidlike 3mo ago
  o_O

eternauta3k 3mo ago

Peter Attia had a great series of blog posts on this before his fall from grace: https://peterattiamd.com/the-straight-dope-on-cholesterol-part-i/ https://peterattiamd.com/the-straight-dope-on-cholesterol-pa... He also had a series of podcast interviews about this with Tom Dayspring. I believe his explanations are all mainstream, except he favors treating LDL and LP(a) more aggressively than normal doctors

stavros 3mo ago
Wait, why did he fall from grace?
- messel 3mo ago
  I didn't know either, not sure of veracity but https://share.gemini.google/0YDt55yyfITs https://share.gemini.google/0YDt55yyfITs
- hammock 3mo ago
  1700 mentions of his name in the Epstein files that Trump released.
- eternauta3k 3mo ago
  Epstein files showed he neglected to visit his seriously sick son because he was hanging out with Epstein. He still knows his stuff, asshole or not.
leopoldj 3mo ago
Wow the guy did Mechanical Engineering and Applied Math before going into medicine and surgery.

barnacs 3mo ago

It turns out LDL has different subfractions based on size. Normally, the liver produces large ones which shuttle fat around the bloodstream, lose their payload and shrink then the liver reabsorbs them and the cycle continues. The problem appears to begin when these LDL molecules hang around for too long. They are damaged by external factors in the bloodstream (eg. glycation due to high blood glucose, oxidation due to fragile polyunsaturated fats) and not recognized anymore for recycling. That's when they can start forming macrophages. tl;dr LDL by itself is an incorrect measure of cardiovascular risk. Big pharma still profits by selling everyone LDL reducing drugs. one authentic source: https://www.youtube.com/watch?v=fVLZA0qp-wc https://www.youtube.com/watch?v=fVLZA0qp-wc

grep_name 3mo ago
I have heard this too, and that cholesterol measurements are flawed because they don't account for particle size. That you can actually have better 'numbers' but worse results, if you reduce particulate size but also overall volume. It's frustrating that the science behind cholesterol is constantly in wild flux, but at any discrete moment you're expected to accept whatever the momentary consensus is. Interestingly, my dentist, who also has a bit of a fixation on cholesterol on a personal level and is educated on the matter, has said that a heart calcium scan is the best way to determine what someone's target cholesterol number should actually be, and that it should not be the same from person to person. This was after I voiced my frustration to him at having made lifestyle changes to get my cholesterol down in order to avoid getting put on statins (not wanting yet another daily drug if I can avoid it), getting the my number below the target of 110, only to shortly after that find out that they'd lowered it to 70. I talked to my endocrinologist about it, and she basically said "yeah, those numbers are more-or-less unachievable. But we want to be extra careful for type 1 diabetics, so we hold them to a higher standard. Either way, everyone gets put on statins at some point anyway, so who cares?" I'm absolutely allergic to "everyone goes on x medication, so stop whining and go on x medication" as a medical argument, and will probably just deal with being labelled non-compliant over this one unless my cholesterol reaches a level I actually personally find to be too high at this point. Which sucks to have to do, but hey, it's my body after all, and so far doctors have failed to make a convincing case for me personally here.

dev_l1x_be 3mo ago

You should check which part of your body has the most cholesterol.

shermantanktop 3mo ago
How would I check the parts of my body for that?
- amanaplanacanal 3mo ago
  I think they meant ask Google. It's the brain.
- dev_l1x_be 3mo ago
  The brain is the most cholesterol-rich organ in the body. While accounting for only 2% of body weight, it contains roughly 20% of the body's cholesterol. It is essential for nerve cell communication, learning, and memory.

cthalupa 3mo ago

It (Particularly ApoB/Combining LDL-C and Lp(a) is one of the single largest leading indicators of health risk we have. If anything, the data we have is suggesting we've gotten wrong what the upper limits should be for what is considered OK. https://www.lipidjournal.com/article/S1933-2874(25)00317-4/fulltext https://www.lipidjournal.com/article/S1933-2874(25)00317-4/f...

guerby 3mo ago
Isn't diabete and metabolic syndrome way more predictive than ldl or apob? Do you have a reference comparing the various factors?

BiteCode_dev 3mo ago

All the answers are smart sounding and completely avoid to address your main point. Same with most doctors I asked it to.

Eddy_Viscosity2 3mo ago

We've been testing for cholesterol for a long time now and have had other meds to lower it. It should be possible to see if lowering cholesterol via medication results in improved life expectancy or reducing cardiac events. I would think this study has been done a few times already. As someone who does not have much medical knowledge, I'm not even sure how to look this up or be able to assess what I see if I did.

cthalupa 3mo ago
Just google 'mortality data statins' and there's a mountain of it. 5 years studies show minimal or no benefit for people in low-risk groups. High-risk groups see significant benefit Follow up/longer term studies show increased benefit in low-risk groups but obviously not matching the high risk groups.

sn9 3mo ago

There isn't a conflict between cholesterol having a useful role in the body and too much being harmful. There are mountains of evidence establishing a causal relationship between elevated cholesterol levels and heart disease.