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"...there are no strong theories for the diseases caused by low cholesterol..." Well, the body has a whole mechanism for manufacturing cholesterol, so it must

"...there are no strong theories for the diseases caused by low cholesterol..." Well, the body has a whole mechanism for manufacturing cholesterol, so it must be good for something. It seems obvious that there's some level at which low cholesterol must cause death. A U-shaped cholesterol-mortality curve is pretty much guaranteed to exist. The only question is where the minimum is.

c54 5y ago
Cell membranes (remember the “lipid bilayer”?) include cholesterol molecules floating around within the phospholipid matrix to help the cell membrane stay flexible and flowy. This is the case for all cell membranes in the body, afaik.
staticassertion 5y ago
> Well, the body has a whole mechanism for manufacturing cholesterol, so it must be good for something. It's good for all sorts of things, for example building cells - cell membranes are made of cholesterol, which is why our body produces a shitload of it.
sooheon 5y ago
Yeah good point. The point is not that lower serum cholesterol must be monotonically better down to 0, just that observational studies like this overestimate the the minimum due to confounders like underlying disease.
thaumasiotes 5y ago
> Well, the body has a whole mechanism for manufacturing cholesterol, so it must be good for something. It seems obvious that there's some level at which low cholesterol must cause death. Agreed. > A U-shaped cholesterol-mortality curve is pretty much guaranteed to exist. Yes, this is a necessary consequence of the first observation. Mortality will go to 100% if cholesterol is too low or too high. > The only question is where the minimum is. But I don't think this is right. You can calculate a mortality-by-cholesterol-level curve for the population, and it will have a minimum somewhere. But it doesn't follow that it would be good for you, even in a sense restricted to all-cause mortality, if you moved your personal cholesterol level closer to the minimum value on that curve. Most people in the population aren't like you.
- amelius 5y ago
  > Yes, this is a necessary consequence of the first observation. Not necessarily. The cholesterol could be redundant.
  - thaumasiotes 5y ago
    No, that's not the case. If your natural weight is 150 pounds, but you've gotten to the point where you contain 700 pounds of cholesterol, you'll die.
    - amelius 5y ago
      I was referring to the lower bound.
      - thaumasiotes 5y ago
        You think we have a working system producing a substance that is only ever harmful? If it's ever helpful, that's already guaranteed to produce a U-shaped curve. Just like I say in the quote you pull. (It's theoretically possible that mortality won't go to 100% at zero cholesterol. But that's not the quote you pulled.)
        amelius 5y ago
        If substance X produces Z and substance Y produces Z, then removing X still gives you Z. Or, removing a substance that is produced by the body does not necessarily leads to mortality. I'm not saying that Y exists, just that the argument is either incomplete or the logic unsound.
        radford-neal 5y ago
        Well, the body can utilize energy by either an aerobic or anaerobic pathway, but that doesn't mean we'd be fine if either of these pathways were disabled. We'd die without the aerobic pathway and have much reduced capabilities (probably fatal too, I'd guess - certainly if a tiger is chasing you) without the anaerobic pathway. If a mechanism has been produced/preserved by natural selection, it's hard to believe that disabling it wouldn't lead to death (or infertility), or to serious debilitation (also likely to lead to death, in a non-benign environment).
Gatsky 5y ago
Hemorrhagic stroke is a leading candidate for the mechanism of low cholesterol induced mortality. It is a known side effect of statins, albeit rare.
refurb 5y ago
Right, but this is blood cholesterol concentration, not total body cholesterol.

c54 5y ago

Cell membranes (remember the “lipid bilayer”?) include cholesterol molecules floating around within the phospholipid matrix to help the cell membrane stay flexible and flowy. This is the case for all cell membranes in the body, afaik.

staticassertion 5y ago

> Well, the body has a whole mechanism for manufacturing cholesterol, so it must be good for something. It's good for all sorts of things, for example building cells - cell membranes are made of cholesterol, which is why our body produces a shitload of it.

sooheon 5y ago

Yeah good point. The point is not that lower serum cholesterol must be monotonically better down to 0, just that observational studies like this overestimate the the minimum due to confounders like underlying disease.

thaumasiotes 5y ago

> Well, the body has a whole mechanism for manufacturing cholesterol, so it must be good for something. It seems obvious that there's some level at which low cholesterol must cause death. Agreed. > A U-shaped cholesterol-mortality curve is pretty much guaranteed to exist. Yes, this is a necessary consequence of the first observation. Mortality will go to 100% if cholesterol is too low or too high. > The only question is where the minimum is. But I don't think this is right. You can calculate a mortality-by-cholesterol-level curve for the population, and it will have a minimum somewhere. But it doesn't follow that it would be good for you, even in a sense restricted to all-cause mortality, if you moved your personal cholesterol level closer to the minimum value on that curve. Most people in the population aren't like you.

amelius 5y ago
> Yes, this is a necessary consequence of the first observation. Not necessarily. The cholesterol could be redundant.
- thaumasiotes 5y ago
  No, that's not the case. If your natural weight is 150 pounds, but you've gotten to the point where you contain 700 pounds of cholesterol, you'll die.
  - amelius 5y ago
    I was referring to the lower bound.
    - thaumasiotes 5y ago
      You think we have a working system producing a substance that is only ever harmful? If it's ever helpful, that's already guaranteed to produce a U-shaped curve. Just like I say in the quote you pull. (It's theoretically possible that mortality won't go to 100% at zero cholesterol. But that's not the quote you pulled.)
      - amelius 5y ago
        If substance X produces Z and substance Y produces Z, then removing X still gives you Z. Or, removing a substance that is produced by the body does not necessarily leads to mortality. I'm not saying that Y exists, just that the argument is either incomplete or the logic unsound.
        radford-neal 5y ago
        Well, the body can utilize energy by either an aerobic or anaerobic pathway, but that doesn't mean we'd be fine if either of these pathways were disabled. We'd die without the aerobic pathway and have much reduced capabilities (probably fatal too, I'd guess - certainly if a tiger is chasing you) without the anaerobic pathway. If a mechanism has been produced/preserved by natural selection, it's hard to believe that disabling it wouldn't lead to death (or infertility), or to serious debilitation (also likely to lead to death, in a non-benign environment).

Gatsky 5y ago

Hemorrhagic stroke is a leading candidate for the mechanism of low cholesterol induced mortality. It is a known side effect of statins, albeit rare.

refurb 5y ago

Right, but this is blood cholesterol concentration, not total body cholesterol.