The other thing cholesterol is used to make, also quite nice to have, is bile. Used for fat digestion and such. A lot of bile. From a lot of cholesterol. Seems like a waste though, to excrete all that finely synthesized bodily chemical. BUt aha, the body realizes this and so resorbs it. THus there is a cycle and recycle of cholesterol and bile. Aha! What if we can trick the body to not resorb it and just release it. Such a drug has been developed. Well, hard to call it a drug. There is no fanciness, no elegant molecular binding to an esoteric receptor, no, nothing of the sort. It's called metamucil, and as the name tells us, it mostly works by being a big chonky mucinous blob of very impressively thick goop. The "magic" of how it works is literally the bile gets trapped in the thick goop and excreted. And thus we've bled off some bile from the cholesterol recycling loop, and thus, cholesterol. And that's why this weird blobby old person fiber supplement is cholesterol magic.
Certain famous men in the past smoked pipe all day and lived very long lives. E.g. Winston Churchill and Bertrand Russell. Do you have any theories on why smoking didn't harm them as much. Do you think back then there might not have been some interaction factor that's prevalent today, etc.?
Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. — https://en.m.wikipedia.org/wiki/Cholesterol
I thought it was obvious, hence the original broad quote, but the bizarre Wikipedia response made me think that perhaps I wasn’t clear enough. Hence the clarification with my follow up.
What’s the evidence for the claim “cholesterol by itself isn’t harmful?”
I thought it was obvious, hence the original broad quote, but the bizarre Wikipedia response made me think that perhaps I wasn’t clear enough. Hence the clarification with my follow up.
So for clarification on your view - do you think that high levels of LDL-C (proxying for ApoB) increase risk of CVD?
What I think is that your behavior is quite strange, to create a fake profile just to post a link "debunking" the author. Do you have something personal against her?
And then when you got corrected, in place of recognizing you said something wrong, you double-down your irrational behavior: "shadow boxing against an imaginary interlocutor". Yeah because the original interlocutor makes stupid questions.
By "imaginary interlocutor" I was referring to a misreading of the parent reply, not mine. This was the person who said: "Anyone else have alternative takes on cholesterol based on personal experience?"
The question is then whether when that person said "alternative takes on cholesterol" they meant "alternative takes on the function of an individual molecule of cholesterol" and not "alternative takes on the significance of high serum cholesterol". Considering their next two bullet points refer to high and low levels of serum cholesterol, I thought it was fairly obvious.
Apparently it wasn't for some people, and those same people are then claiming that making this clear is some sort of dodge/goalpost shift/deceptive behaviour. But it clearly isn't. If you read the above, where someone was obviously referring to high serum cholesterol, and in response someone says "cholesterol by itself isn’t harmful", is it reasonable to quote that claim and ask for evidence, by which you mean "I want evidence that high serum cholesterol isn't harmful"? If it is reasonable, which I believe it is, then no deception, goalpost shifting or correcting has actually taken place here.
The full pathway and supporting evidence can be found here: https://academic.oup.com/eurheartj/article/41/24/2313/573522...
If a patient is already accumulating arterial wall damage then it might be necessary to limit serum cholesterol through dietary changes or statins or something. But I would claim that those interventions usually come too late, and that most of the damage can be prevented through other interventions thus making serum cholesterol levels less relevant.
It's like if you have a truck driving around full of toxic waste. Maybe that's cause for concern, but if you can take other measures to ensure it won't crash and spill the cargo then maybe it's fine.
These factors may increase the effect of high LDL-c on CVD, but I’m not sure on what basis we should assume that those without them aren’t at risk from high LDL-c.
Some people live a long time with high(er) fat diets and no heart disease; Cardiologist Dr William Davis[1] selling his heart-scan plan using non-invasive CT scan / calcium measuring as a proxy for atherosclerotic plaque buildup claims that cholesterol is "virtually worthless" for predicting heart disease, and that taking statins or cutting the fat in your diet measurably "does nothing" to affect that measure of plaque buildup. Your suggestion is that cutting fat should do something. He claims his plan of removing wheat, grains, using fish oil, fixing inflammation and insulin resistance, various vitamins and minerals, can measurably stop plaque developing and it can reduce. That seems like it should be a very testable claim.
I haven't read his books, don't know the details of his plan, but if calcium is a solid proxy for plaque buildup, and a CT scan can measure it stay the same in people who switch to low-fat diets, and measure it drop in some people who don't but instead remove grains, that suggests plaque buildup from LDL only takes place in some individuals who eat fat, not all. Arterial wall injury or inability to repair damage are they possible reasons? Or the inflammation and insulin resistance he mentions?
[1] https://drdavisinfinitehealth.com/2019/03/why-you-should-get...
CAC scores (which it sounds like what you’re referring to) only look at calcified plaque, but not soft plaques. So there’s a whole category of risk that is missed by them. People’s CAC only tends to go up when they’re in a very late stage of atherosclerosis, and calcified plaques also tend to be more stable than soft plaques, so if two individuals had the same mass of plaque, but one’s was soft and the other’s one’s hard (sorry for the “carry on cardiology”) then we’d actually expect the individual with the CAC score of zero to be at greater risk of a CVD event.
It’s my interlocutor’s burden to show that arterial wall damage and/or an individual’s inability to repair damage is required for ASCVD to take hold, and so far they’ve yet to meet it. That’s what I’m looking for, basically.
From what I could gain in the paper you linked in another comment, they write that apoB with less LDL in it goes more easily into the arterial wall, apoB with more LDL in it causes more damage once in the arterial wall, and those two effects cancel out, so overal more LDL is worse.
These things don't add up to a coherent picture. If eating less fat reduced LDL, that should reduces plaque buildup (by your claims and your study's claims) and that should reduces heart disease risk, and that should show up in the CAC scans. And apparently it doesn't. If eating more fat increases LDL and that increases heart disease risk, that should show up in Dr Davis' CAC scans and he should think that worsens heart disease risk, and he doesn't.
> "But this being the case does not serve as evidence that arterial wall injury or an inability to repair damage is required in order for high serum cholesterol to be a risk."
It doesn't, and I don't make that claim. So I have no more comment. Agree that it's multifactorial (or appears that way).
[1] https://myheart.net/articles/ct-coronary-artery-calcium-hear...
Your Dr Davis just appears to be one person saying something is the case, without providing any evidence for it. I don’t see why we should believe his claims that serum cholesterol is irrelevant over the incredibly robust evidence I’ve brought to the table.
I agree that the two things don’t add up, but why wouldn’t we then just favour the higher quality evidence? Seems like Davis is a quack with historical form for just making things up without any evidence in order to sell a product: https://www.healthyeating.org/blog/detail/rdn-s-book-review-...
I don't think Dr Davis has said serum cholesterol is irrelevant, the statement I linked is that dietary fat removal doesn't stop CAC score increasing.
Why we should believe him is that he's got a feedback loop with a measuring machine. Science is about settling abstract arguments by testing them against the real world, right? So you can dismiss Paul Mason by saying he's an idiot, he can't read, he's looking at old studies, and he's a sports medicine doctor so he's not treating heart disease anyway, but Dr Davis is actually a cardiologist and he gets a patient with a heart problem, he takes actual measurements (CAC score) then gives advice to change their life, then sees them again for followup over years and years, measures again and sees the results. The measurement is not based on whether he is smart or stupid, it's not affected by which studies he's citing.
He's a quack selling a book? The US Bureau of Labour says Cardiologist is the highest paying job in the USA[2]. He could just as easily be shilling low-fat books instead of low-carb books so that makes no sense that he would be shilling a book which goes against his findings instead of one which goes with his findings. Why does he need to shill any product - his financial incentive is do do more treatments, more stents, more bypass surgery, prescribe more statins for pharma kickbacks.
Could he be totally wrong, and his patients are dying en-masse, and others are leaving him to go to another cardiologist for bypasses, and other patients are eating something different and lying to him - I'd actually believe it, yes, but who knows. If we go with that he appears to have found something which reduces his patients' need for surgical intervention over years and decades, then it seems that the biggest things to affect heart disease risk are metabolic syndrome et al, and they appear to have far more effect on serum fats than dietary fat intake does, and far more effect on fats-causing-plaque-buildup than dietary fat does. Less fat in the blood is better, is something your links claimed, and that can also be something Dr Davis would agree with through insulin resistance improvements; as I asked in my other comment, I have no idea what the link there actually is.
At this point serum LDL seems important, dietary fat intake might be but it seems less important/effective as a way to modulate serum levels than fixing other diesease processes does?
[1] It says: "Results A total of 23 759 symptomatic patients, of whom 12 771 (54%) had a CAC score of 0, were included. Overall, the prevalence of obstructive CAD was relatively low across all age groups, ranging from 3% (39 of 1278 patients) in those who were younger than 40 years [..] In patients with obstructive CAD, 14% (725 of 5043) had a CAC score of 0, and the prevalence varied across age groups from 58% (39 of 68) among those who were younger than 40 years" - how can there be 39 people with CAD under fourty in total and also (__ of 68) under fourty with CAD and zero score? Where did the 68 come from?
[2] https://cardiovascularbusiness.com/topics/healthcare-managem... (I don't know why they don't say "CEO" but whatever, it's a high paying job, he doesn't need to be shilling anything).
Your response was "Some people live a long time with high(er) fat diets and no heart disease". But this is not evidence that atherosclerosis only takes place in individuals with arterial wall injury or without the ability to repair damage. That could equally be evidence that some people are genetically less predisposed to arterial retention, regardless of arterial wall injury, for example. There are plenty of hypotheses that negate your proposed one that are equally likely on the evidence you've provided. So this whole thread is just a tangent that doesn't engage with the core question. That said, here goes:
My point on CAC was that your entire argument hinges on being able to look at a CAC score and say "this score is a reliable indicator of whether a person has coronary artery disease". But if you're under 40 and actually have CAD, there's a 58% chance that when you get your test results back, it will show 0 CAC (even though you have CAD!). So demonstrably, CAC is a poor proxy for CAD, and so a lynchpin proposition in your argument is clearly false. Whether the numbers look different when read a different way is irrelevant. The above is true, and demonstrates how CAC is not a reliable metric.
> I don't think Dr Davis has said serum cholesterol is irrelevant, the statement I linked is that dietary fat removal doesn't stop CAC score increasing.
Literally from the article you linked: "Can you look at your cholesterol and say “Oh, my cholesterol is 240. I must have heart disease.”? No, of course not — cholesterol is virtually worthless when it comes to predicting heart disease"
So he says exactly that, unless you're willing to quibble over a semantic difference between "virtually worthless" and "irrelevant".
> Why we should believe him is that he's got a feedback loop with a measuring machine
It's not just "why should we believe him", it's "why should we believe him over meta-analyses of RCTs, and other high quality data?" Look at where "expert opinion" and "case reports" (which is the evidence you're citing, if we're being generous) sits relative to the MAs of RCTs that I'm bringing to the table on the hierarchy of evidence (https://en.wikipedia.org/wiki/Hierarchy_of_evidence). It's not clear to me why you're throwing out robust evidence with comparatively low risk of systematic bias and relying on bottom-tier evidence instead. Can you please explain to me why this is a superior epistemic framework?
> He's a quack selling a book?
Yes. I'd take a quack to be anyone wearing the coat of science while violating the standards of modern science. Whether or not he stands to gain (or cares about) the money his book makes isn't relevant to that claim, it's based entirely on the nature of what he has to say/publish.
Indeed, going back to the previous point, dismissing the enormous body of high quality evidence showing LDL cholesterol is a causal agent in atherosclerosis by referring to serum cholesterol measurement as "virtually worthless" merely because of his own personal experience, with the plethora of biases that entails, is textbook quackery. The fact that he's published a pop science book that blames many of the ills of the world on wheat with no evidence to back up such an assertion is just the cherry on top.
So I don't need to speculate why he's a quack, and his salary doesn't alter my point. Maybe he does it because being a number one bestseller satisfies his ego in a way nothing else can. Maybe having that accolade means he can charge more for his cardiology services, so there's an indirect financial benefit. Maybe he genuinely believes wheat is the devil's food? I don't really care, my point is that his output suggests he's not a sound practitioner of the scientific method.
Your entire argument here seems to boil down to "there's this guy who sees patients and he says they're not leaving his practice and they're getting better, how would he have patients if everything he says about heart disease wasn't true?" This is wild, the kind of arguments I see from homeopathy advocates. We should always aim for the evidence base most likely to be free from bias. That is not one clinician's account of how they do things.
From your study link: "Introduction .. Coronary artery calcium (CAC) that is assessed by computed tomography is reliable in evaluating the future risk in both asymptomatic and symptomatic patients with stable coronary artery disease (CAD)".
They call it "unmatched".
OK it isn't perfect, that doesn't make it poor. Still instead of "can it miss something", the other way around - if the CAC score measures something is it always definitely plaque buildup? Because then repeated CAC scores have the potential to be good for telling if plaque buildup is changing over time in response to dietary changes in people with non-zero scores and CAD.
Fine with him saying cholesterol is worthless, yes.
> ""why should we believe him over meta-analyses of RCTs, and other high quality data?""
Because when someone you don't like cites multiple meta-analyses of RCTs you handwave it away with a Twitter thread where he "runs away from an argument chef's kiss". I know of Ben Goldacre's Bad Science, I see plenty of HN links about the reproducibility crises in science about the ways of p-hacking and manipulating data, about the broken incentives to publish and get funding, about the complexities of statistical analysis, things I can't argue through. Medical experts are incentivised to push treatments, academic experts are incentivised to push dodgy results, it's not easy for people who like and care about this stuff to say what's "high quality data" or isn't, let alone me. One can't handwave away measuring the amount of plaque buildup in the heart and say "that's not a measure of the amount of plaque buildup in the heart" as easily. If people change X and their heart health measurably improves, and X isn't reducing dietary fat, that should mean something.
> "Your entire argument here seems to boil down to"
My argument was less about Dr Davis himself and more as a way to bring the CAC score in and to say Dr Davis says the CAC score isn't affected by removing dietary fat. That's a testable claim. That's much nicer than "this expert says that expert is wrong" or "this paper says that paper is wrong". You don't believe Dr Davis, well, presumably somewhere is a researcher or practitioner who has done many CAC measurements and has studied whether cutting dietary fat changes the score or not, at this point I am not going to look for it.
I am interested in the things you've said and linked, and my opinions have changed, but I think I'm well past what I am able to follow or interested to continue.
Ok, that's unfortunate but obviously your prerogative! I will try to post some more lay-friendly links in this response that may convey my points more straightforwardly.
> if the CAC score measures something is it always definitely plaque buildup? Because then repeated CAC scores have the potential to be good for telling if plaque buildup is changing over time in response to dietary changes in people with non-zero scores and CAD.
No, it can measure plaque density. Additionally, since calcified plaques are more stable than soft plaques, it can actually go up while risk goes down. We see this occur on some statin regimes, where we have boatloads of data showing statins reduce risk, yet we can see CAC scores go up as soft plaque is stabilised into calcified plaque.
I'm not saying CAC is without its merits, but you are stretching credulity beyond breaking point to suggest that because one cardiologist claims that reducing dietary fats doesn't show a reduction in CAC scores, it therefore disproves the lipid hypothesis. CAC has too many caveats to use it to make such bold inferences, even if we get to the wild epistemic standards required to think one cardiologist's claims are sufficient to overturn decades of well-conducted research. Additionally, as I've stated elsewhere, it still wouldn't be evidence that arterial wall damage or inability to repair damage is required for ASCVD, which, let's remember, is the reason we're even talking about this in the first place.
There's quite an interesting discussion about the pros and cons of the CAC here. Suffice to say, it's not suitable to stand up the kind of arguments you're making: https://www.youtube.com/watch?v=gxIeRUbHauw
> Because when someone you don't like cites multiple meta-analyses of RCTs you handwave it away with a Twitter thread where he "runs away from an argument chef's kiss"
No, that's not why I dismiss Mason's claims. I dismiss Mason's claims because he says "this meta analysis says this" and then when you look at the MA it says nothing of the sort. It's false to claim that I'm handwaving away the evidence itself.
> I know of Ben Goldacre's Bad Science, I see plenty of HN links about the reproducibility crises in science about the ways of p-hacking and manipulating data, about the broken incentives to publish and get funding, about the complexities of statistical analysis, things I can't argue through. Medical experts are incentivised to push treatments, academic experts are incentivised to push dodgy results, it's not easy for people who like and care about this stuff to say what's "high quality data" or isn't, let alone me. One can't handwave away measuring the amount of plaque buildup in the heart and say "that's not a measure of the amount of plaque buildup in the heart" as easily. If people change X and their heart health measurably improves, and X isn't reducing dietary fat, that should mean something.
I think it's really worth taking a second to think about what you're saying here. Some points of order first:
- The reproducibility crisis is about some fields of science re-running individual studies and finding that when they do so, they cannot reproduce the original findings.
- p-hacking is about altering the methodology of a study post-hoc to generate statistically significant findings when such findings were not present under the original methodology.
- the objection of the complexities of statistical analyses, I presume, is an objection based on the fact that when using statistical analyses to try to account for confounders and systematic bias, sometimes these analyses are poorly conducted and thus fail to mitigate these biases.
- "Medical experts are incentivised to push treatments" is presumably an objection that individuals publishing papers may have an implicit or explicit bias that causes them to over or understate the significance of a given finding, or record data incorrectly.
So your argument appears to be: "Ok, so you've provided evidence that LDL is a risk for CVD based on over 200 prospective cohort studies (that is, the results have been successfully produced literally hundreds of times), mendelian randomisation studies, and randomised controlled trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events. However, I believe it's likely that if we were to re-run those studies again, we would not be able to reproduce those results.
“I'm also concerned that p-hacking and systematic bias is so consistently prevalent within all of these studies that it affects the summated findings so profoundly, and consistently in the same direction, that we cannot trust the findings to be accurate. Additionally, the individuals conducting these studies are all incentivised to push treatments and therefore we should believe it to be more likely than not, without any evidence to actually demonstrate this, that these individuals are biasing the results because of these incentives.
“It's not easy for lay people like me to ascertain whether these data from the top of the evidence hierarchy (that is, the evidence least likely to be affected by bias) are high quality, so we have to find a source of evidence that is less likely to be affected by such bias. To achieve this, I propose that we throw all the above data out, and instead trust the claims of a single cardiologist, who's written a blog post on his website about how serum cholesterol is irrelevant when it comes to cardiovascular disease risk.
“After all, p-hacking can't take place when the evidence is so poor that there are no p-values, calculations of statistical significance, or even recorded data from which one could calculate p-values.
“After all, you can't make errors in your statistical analyses if you don't perform any statistical analyses.
“After all, your attempts to control for bias can't go wrong if you don't attempt to control for bias.
“After all, 'One can't handwave away measuring the amount of plaque buildup in the heart and say "that's not a measure of the amount of plaque buildup in the heart" as easily. If people change X and their heart health measurably improves, and X isn't reducing dietary fat, that should mean something,' despite the fact that there are studies that do measure plaque buildup in the heart and show that it is affected by serum cholesterol. I believe that we can handwave it away when it's published in a peer reviewed journal, but we can't do so when it's a blog post on a cardiologist's website. This is the most reliable way to make sound scientific inferences.”
I don't even understand how one can reach these conclusions. I've tried my absolute best to interpret what you've said generously, but there's only so much I can do given material like this.
This whole line of reasoning is also far closer to what you’re accusing me of - instead of discussing what the data show, we should just “trust the experts”. We can’t analyse Dr Davis’ data because he doesn’t even provide any, but we should just assume he’s telling the truth because he’s a cardiologist and therefore so well paid that he has no motivation to be wrong. We should ignore the evidence I’ve provided because it’s harder for laypeople to understand than this supposed expert just saying “trust me, I ran some CAC tests”.
> presumably somewhere is a researcher or practitioner who has done many CAC measurements and has studied whether cutting dietary fat changes the score or not, at this point I am not going to look for it.
I've already provided you even better evidence than that: a pooled analysis of studies where SFA is replaced with PUFA and cardiovascular events and coronary deaths are reduced. You don't need to go looking, I gave it to you: https://pubmed.ncbi.nlm.nih.gov/19211817/. If you want a more consumable version, here's an excellent podcast on it (all their stuff is good, you should see if there's anything else there of interest to you: https://sigmanutrition.com/episode481/).
It's a shame, but not entirely surprising that you no longer desire to continue the discussion. Fundamentally, I think you will always run into issues until you re-assess your underlying epistemic framework when it comes to assessing evidence. Until you do so, reading studies will be largely pointless as you have no reliable tools to interpret those studies. You're running before you can walk.
If you're interested, the Cut Through Nutrition podcast is quite a nice primer on how to think about nutrition science research, I'd highly recommend working through the episodes. Once you've internalised the concepts, it becomes a lot easier to see how quacks like Mason and Davis are operating, even without a great deal of domain-specific knowledge. Podcast is here: https://podcasts.apple.com/gb/podcast/cut-through-nutrition/...
Have a good week!
> "If there are any other causes of obstructive CAD other than fats getting into the artery walls, those cause would all have to be in that group as well (I don't know of any but I can speculate several)."
Here's one speculation of lay-person reasoning:
- Cosmetics people like Retinol skin creams because it makes skin look better. That's a fact that people recommend it.
- One way it does this by making it plumper, which smooths out wrinkles. I think that's a fact.
- It does this by increasing skin cell "turnover", i.e. what it does at the epithelial layer is trigger stem cells to split, making more skin cells, making thicker skin. That's a claim I've seen and am not sure if it's a fact, but it's a plausible mechanism of action.
- We eat retinol in our food, in the form of Vitamin A, that's a fact.
- Vitamin A gets through the guts into the body, that's a fact - it couldn't be a vitamin if it passed straight through us and out.
- Vitamin A gets into the blood stream; fact, there are lab tests of serum retinol levels.
- Vitamin A in the blood is supposed to be wrapped in Retinol Binding Protein to carry it through the blood, but it isn't always. It's normally captured by the liver, and released from the liver wrapped in RBP, but not all of it is captured by the liver and is free in the blood stream. The more of it in the diet, the more gets past the liver, the more of it is free in the blood stream. I've seen it claimed, have no sources to back it up.
- Blood vessels have an epithelial layer on the inside, an internal skin. Claim.
- Retinol in the diet -> retinol in the blood -> triggers stem cell split in the blood vessel walls -> thickening of the walls ("youthful!") -> narrowed blood vessels. Speculation.
(What do we have in this random link[1] I haven't read? "Until recently, it was thought that the sole important retinoid delivery pathway to tissues involved retinol bound to retinol-binding protein (RBP4). More recent findings, however, indicate that retinoids can be delivered to tissues through multiple overlapping delivery pathways, involving chylomicrons, very low density lipoprotein (VLDL) and low density lipoprotein (LDL)" - retinol is not only able to split stem cells, it's a pretty potent molecule in various forms; "Retinoids and immunotherapy may be used to treat high-risk or recurrent neuroblastoma" says Canadian Cancer Society; there's one bro-science connection for increased total LDL -> increased blood vessel damage which is nothing to do with the LDL per-se, but something it carries along with it. Something we eat a lot of as Vitamin A and carotenoids, something the US and Canada fortify flour and low-fat dairy and margarine with, which is another tie-in to both low-wheat and low-fat diet).
[Edit: it isn't relebant; thickened walls would be non-obstructive CAD].