3 ms·

Thanks for posting this, neurodegenrative diseases are horrible but at the same time this is a review of the literature. They are reporting about feeding mice

Thanks for posting this, neurodegenrative diseases are horrible but at the same time this is a review of the literature. They are reporting about feeding mice with 400 mg/kg/day during 6 to 8 weeks. For humans, this is equivalent to 33mg/kg/day. So for a 80kg body: 2.6g, half a sugar cube every day. If you feed an animal (including us) with unreasonable levels of most anything you will observe weird stuff. For example feeding mice with high fat diets gives them a kind of Alzheimer disease.

Gordonjcp 4y ago
That's a lot of anything to dose with. It reminds me a bit of the datasheet for sodium chloride - common table salt - that describes the skin contact LD50 (the amount that is a lethal dose for 50% of a population of test rabbits) as ">25kg". So what do we read from that? If you drop a sack of salt weighing as much as an eight-year-old child on a series of rabbits, roughly half of them will die? I can't say I'm *very* surprised...
- eshack94 4y ago
  The last part of your comment feels like it should be the punchline for an xkcd comic.
  - JPLeRouzic 4y ago
    Ha, ha, sorry if it looks odd, English is not my native tongue.
- DuckFeathers 4y ago
  Not very different from study designs used by pharmaceuticals to show that their new patent-pending drug outperforms the generic one. They deliberately design it so that the competing drug isn't the right dose or somehow not administered correctly... and if someone tries to fight them, their license is taken away.
- thaumasiotes 4y ago
  > So what do we read from that? If you drop a sack of salt weighing as much as an eight-year-old child on a series of rabbits, roughly half of them will die? No, you should read exactly what it says. If you put a series of rabbits in skin contact with 25kg of salt each, less than half of them will die. That's how we know the LD50 is greater than 25 kilograms. I assume 25 kilograms was the limit of testing, and that's why the result is reported the way it is. I'm also willing to go out on a limb and assume the number of test rabbits that died from being put in skin contact with 25kg of salt was zero, which is less than half of the test pool as long as it contained a positive number of rabbits.
  - deleted 4y ago
    [deleted]
  - misja111 4y ago
    > ... as long as it contained a positive number of rabbits. That seems a pretty safe assumption.
  - Gordonjcp 4y ago
    > I'm also willing to go out on a limb and assume the number of test rabbits that died from being put in skin contact with 25kg of salt was zero, Depending on what height it was applied from > less than half of the test pool as long as it contained a positive number of rabbits. Positive integer number of rabbits, with any luck, although I suspect in this instance imaginary rabbits may have been used. Definitely not complex ones though.
  - jodrellblank 4y ago
    I'd be surprised if a rabbit has enough skin surface area to be in contact with more than about 1Kg of salt. How could the skin contact test continue past the point where extra salt wasn't in skin contact?
    - Gordonjcp 4y ago
      Put the rabbit and the salt in a sealed container and pump the air out to expand the rabbit?
- phkahler 4y ago
  It's different if dropping the salt crushes the animals, gets eaten and causes a heart attack, burns off their fur, causes bleeding, or causes Parkinson disease. That last one is so odd you'd take note of any high dose of anything causing it. Like TFA suggests, this is reason for further investigation.
bschne 4y ago
> They are reporting about feeding mice with 400 mg/kg/day during 6 to 8 weeks. For humans, this is equivalent to 33mg/kg/day. How does one convert that? It makes sense that this isn't necessarily linear, but I have no idea how to turn one of those numbers into the other
- A_D_E_P_T 4y ago
  Here, "Dose Translation from Animals to Humans": https://pubmed.ncbi.nlm.nih.gov/17942826/ https://pubmed.ncbi.nlm.nih.gov/17942826/ Generally, from mice, it's ([mouse dose in mg/kg] * (3/37)) = human equivalent dose in mg/kg.
misja111 4y ago
> 400 mg/kg/day during 6 to 8 weeks. For humans, this is equivalent to 33mg/kg/day. So for a 80kg body: 2.6g, half a sugar cube every day. But humans have much more time to ingest it. Parkinson develops during decades, not weeks.
devb 4y ago
So? That doesn't preclude low doses over a long period from causing harm. High doses are used to prove a conclusive link, not establish a lower limit of toxic effects.
throwaway12245 4y ago
> feeding mice with high fat diets gives them a kind of Alzheimer disease. Do you have a link for this. I found this: "However, some of these diets contain levels of dietary fat that are much higher than the levels that humans routinely consume. The question has been raised as to whether experimental use of these diets with very high levels of fat adequately models the situation of human obesity." https://www.nature.com/articles/s41366-019-0363-7 https://www.nature.com/articles/s41366-019-0363-7
adrianN 4y ago
If you're unsure whether there is an effect you probably want to start with a very high dose to justify funding for follow-up studies that determine which dose is safe.

Gordonjcp 4y ago

That's a lot of anything to dose with. It reminds me a bit of the datasheet for sodium chloride - common table salt - that describes the skin contact LD50 (the amount that is a lethal dose for 50% of a population of test rabbits) as ">25kg". So what do we read from that? If you drop a sack of salt weighing as much as an eight-year-old child on a series of rabbits, roughly half of them will die? I can't say I'm *very* surprised...

eshack94 4y ago
The last part of your comment feels like it should be the punchline for an xkcd comic.
- JPLeRouzic 4y ago
  Ha, ha, sorry if it looks odd, English is not my native tongue.
DuckFeathers 4y ago
Not very different from study designs used by pharmaceuticals to show that their new patent-pending drug outperforms the generic one. They deliberately design it so that the competing drug isn't the right dose or somehow not administered correctly... and if someone tries to fight them, their license is taken away.
thaumasiotes 4y ago
> So what do we read from that? If you drop a sack of salt weighing as much as an eight-year-old child on a series of rabbits, roughly half of them will die? No, you should read exactly what it says. If you put a series of rabbits in skin contact with 25kg of salt each, less than half of them will die. That's how we know the LD50 is greater than 25 kilograms. I assume 25 kilograms was the limit of testing, and that's why the result is reported the way it is. I'm also willing to go out on a limb and assume the number of test rabbits that died from being put in skin contact with 25kg of salt was zero, which is less than half of the test pool as long as it contained a positive number of rabbits.
- deleted 4y ago
  [deleted]
- misja111 4y ago
  > ... as long as it contained a positive number of rabbits. That seems a pretty safe assumption.
- Gordonjcp 4y ago
  > I'm also willing to go out on a limb and assume the number of test rabbits that died from being put in skin contact with 25kg of salt was zero, Depending on what height it was applied from > less than half of the test pool as long as it contained a positive number of rabbits. Positive integer number of rabbits, with any luck, although I suspect in this instance imaginary rabbits may have been used. Definitely not complex ones though.
- jodrellblank 4y ago
  I'd be surprised if a rabbit has enough skin surface area to be in contact with more than about 1Kg of salt. How could the skin contact test continue past the point where extra salt wasn't in skin contact?
  - Gordonjcp 4y ago
    Put the rabbit and the salt in a sealed container and pump the air out to expand the rabbit?
phkahler 4y ago
It's different if dropping the salt crushes the animals, gets eaten and causes a heart attack, burns off their fur, causes bleeding, or causes Parkinson disease. That last one is so odd you'd take note of any high dose of anything causing it. Like TFA suggests, this is reason for further investigation.

bschne 4y ago

> They are reporting about feeding mice with 400 mg/kg/day during 6 to 8 weeks. For humans, this is equivalent to 33mg/kg/day. How does one convert that? It makes sense that this isn't necessarily linear, but I have no idea how to turn one of those numbers into the other

A_D_E_P_T 4y ago
Here, "Dose Translation from Animals to Humans": https://pubmed.ncbi.nlm.nih.gov/17942826/ https://pubmed.ncbi.nlm.nih.gov/17942826/ Generally, from mice, it's ([mouse dose in mg/kg] * (3/37)) = human equivalent dose in mg/kg.

misja111 4y ago

> 400 mg/kg/day during 6 to 8 weeks. For humans, this is equivalent to 33mg/kg/day. So for a 80kg body: 2.6g, half a sugar cube every day. But humans have much more time to ingest it. Parkinson develops during decades, not weeks.

devb 4y ago

So? That doesn't preclude low doses over a long period from causing harm. High doses are used to prove a conclusive link, not establish a lower limit of toxic effects.

throwaway12245 4y ago

> feeding mice with high fat diets gives them a kind of Alzheimer disease. Do you have a link for this. I found this: "However, some of these diets contain levels of dietary fat that are much higher than the levels that humans routinely consume. The question has been raised as to whether experimental use of these diets with very high levels of fat adequately models the situation of human obesity." https://www.nature.com/articles/s41366-019-0363-7 https://www.nature.com/articles/s41366-019-0363-7

adrianN 4y ago

If you're unsure whether there is an effect you probably want to start with a very high dose to justify funding for follow-up studies that determine which dose is safe.