Watch out, there is no reliable Mouse Model for Alzheimer's. I was deeply involved with mouse models at some point before quitting my phd in neuroscience and I quite remember that.
> Lithium was the only metal that differed significantly between people with and without mild cognitive impairment, often a precursor to Alzheimer’s disease.
Not a causative finding in humans but darn interesting
Wild mice do not get AD. Even if you let them achieve old age they do not develop the same brain plaques or tangles that are linked to Alzheimers.
Even if they did you'd have to run huge samples then do post testing necropsies to see which mice had AD which which didn't, then filter your data, then try to find results in what remains.
Otherwise you can inject the mice with a chemical known to cause AD, which is not reliable on it's own, so you can get genetically modified mice which express _some_ of the known plaques and misfolds that are associated with human AD.
Animal testing is still, largely, a very unethical and cruel affair. AD testing in mice is especially fraught with hazard.
It's like kind of challenging to prove this kind of negative, and the supposed proof here comprises no more than pedigreed words on a page, but here consider the section "What constitutes a good model for AD?": https://sci-hub.se/https://www.nature.com/articles/s41583-01...
Lithium orotate is available over the counter. People could try it today.
> Since lithium has not yet been shown to be safe or effective in protecting against neurodegeneration in humans, Yankner emphasizes that people should not take lithium compounds on their own
I reject this kind of blind safetyism. A cursory search suggests that lithium orotate has been used for decades, and the article suggests that "profound effects" were seen at an "exquisitely low dose" which should be safe. They're going to need a much better explanation of why people shouldn't try it.
You said you searched to learn more about lithium, but somehow missed that it's highly recommended to be administered by doctors due to side effects after long term use. Anything that damages your kidneys or thyroids can kill you, so calling it "blind safetyism" is silly.
It’s blind safetyism when an article writes “don’t do this because no one has proven it is safe”. Most people will read that as “you can probably do this but in the off chance something bad happens, I wrote these words so you have a harder time suing me”.
It would be more useful and effective for the article to say “don’t do this to yourself because it can damage your guts, see these links, there’s tradeoffs here”
The former just fades into the modern world’s background noise of unchecked ass-covering.
When I started giving injections to a family member, I learned many things can cause problems that I didn't know about, such as that very tiny bits can break loose from the bottle top and cause issues. "Blind safetyism" is a point of view that can be more popular with certain personality types, but I think it's often a good starting point for research.
>it's highly recommended to be administered by doctors due to side effects after long term use
This is at a clinical dose which is somewhat high. It is the dosage fund reliable as treatment for bipolar type 1. As long as you get your kidney numbers checked twice a year, at that dose, its mostly unproblematic as issues show themselves in the numbers before major damage.
Lithium orotate has been available as a supplement for decades and hasn't shown adverse effects. Here is a study from a few years ago that also showed no harmful effects from lithium orotate: https://www.sciencedirect.com/science/article/pii/S027323002...
Especially since mice are not really perfect models for humans. For starters: these mice were "12 to 24 months of age", whereas your typical Alzheimer patient is well over 30 times that. The article also links it to amyloid plaques, which is a contested hypothesis that may well have held back Alzheimer research for decades. To be fair, the article seems to look at more mechanisms, but that's well beyond my expertise.
To add to what the parent comment said - Lithium is also prescribed for some mood disorders. So if you are thinking of self-medicating with it please be aware that it can mess with your brain chemistry too.
The error in "safteyism" isn't that the conventional wisdom will incorrectly identify safe things as dangerous. It's that risk and reward always exists on a spectrum, and the people best incentivized to get that tradeoff right are patients and caretakers, not concerned 3rd parties.
The error of the concerned 3rd party is particularly egregious with a disease like Alzheimer's, which presents a significant risk of ruin in the form of information death. It is totally rational to use an intervention that will cause you significant harm if it preserves your mind another few years.
I would think naturally occurring lithium in some people's water would give pretty good control conditions to do a wide study of this effect on Alzheimers as well?
Completely agree. The other thing that was very encouraging about the study is that it actually reversed memory decline - it's not like you needed to take it for years/decades in advance to prevent that decline in the first place, so you can make the choice when the risk/reward tradeoff is much clearer.
Having seen a few family members succumb to dementia, it's not a path I want to take. Fuck up my kidneys and give me an early death, fine, but if I start showing the signs of that type of mental decline, I'm taking the lithium orotate.
My related biggest concern about this is that since it's a cheap supplement that can't be patented, it won't be a priority for the drug industry to study. Another reason to not necessarily trust the "Just slowly die by Alzheimers until we find the perfectly safe (patentable) antidote" crowd.
I tried Lithium Orotate at the typical supplement dose. After the first week it left me feeling rather blah. Discontinuing it reversed the feeling after a few days.
I repeated this a couple more times with a repeatable outcome.
It’s very hyped in supplement communities with claims that it’s perfectly safe and side effect free. I didn’t get any kidney damage or anything, but I also didn’t get a positive benefit from it. Only subtle negatives that built up over a week.
I've played with it on and off for years from 1mg up to 10mg a day. It's a drug I definitely 'feel' when I'm not saturated. I initially became interested in it due to this -> "Since vitamin B12 and folate also affect mood-associated parameters, the stimulation of the transport of these vitamins into brain cells by lithium may be cited as yet another mechanism of the anti-depressive, mood-elevating and anti-aggressive actions of lithium at nutritional dosage levels.” (https://pubmed.ncbi.nlm.nih.gov/11838882/)
It does reach a point of diminishing returns for me and I become too sedated. I now take it irregularly.
"They" are just some people who did an experiment on mice. They don't know the effects on humans. It sounds like you think you know more than they do. Ok.
A paper is not like a religious commandment or something. It's, best case, some mortals honestly trying to learn something. Scolding them for admitting the limits of their knowledge is not reasonable.
The comment I see right above yours says "there is no reliable Mouse Model for Alzheimer's." So it's certainly not a slam dunk that taking OTC lithium orotate is going to prevent Alzheimer's. Maybe it'll work? (but you won't know for decades) And maybe it's safe as long as you don't exceed the recommended dose, but there can be interactions with other meds you might be taking (some diuretics will cause you to concentrate lithium, for example).
I tried the low-dose lithium orotate supplements and the net effect was apathy and reduced motivation. Not everyone experiences this but from searching I’m not alone.
Definitely not something to start pouring into the water supply.
Pulling this out of my ass, but lithium is associated with weight gain, and has been suggested to be a possible causative agent on the obesity epidemic. (Extremely low confidence on this one)
I can no longer sit back and allow Communist infiltration, Communist indoctrination, Communist subversion, and the international Communist conspiracy to sap and impurify all of our precious bodily fluids.
Sure, but the amount and form of the lithium matters. 5mg of lithium orotate (as a supplement) versus 600mg lithium carbonate (as a mood stabilizer) will have vastly different acute and chronic health effects.
> They're going to need a much better explanation of why people shouldn't try it.
Clinical trials need many participants and take a long time, and they require a control group which doesn't take lithium orotate. Finding these people might be hard if everyone is taking it anyway.
So if after a long time its proven that it does prevent Alzheimer's, was the deaths of everyone that would have been taking lithium to prevent it due to this anecdotal article worth it?
Would you be willing to die of Alzheimer's in order to serve as a placebo for the control group? What about your parents?
I don't really understand this mindset.
I already ordered 5mg tablets of lithium orate as soon as I read this. I'll just add them to the handfuls of other supplements I take each day just in case they may protect against common degenerative ailments.
I very much adhere to the better safe than sorry or yolo approach to supplementation.
I went to visit my aunt one day, and my favourite uncle couldn't recognize me.
It made me think that Alzheimer's is probably the worst thing that could happen to a person. I mean, what's worse than not being able to recognize those closest to you?
You work a lifetime, and then you go out in such an undignified manner.
It's worse. Not recognizing people close to you is really hard on everyone else(including people taking care of you), but since you don't remember, it's not as bad for you.
You won't even remember whether or not you had lunch. I met a grandma that was distraught that nobody was feeding her and she was hungry. Except she had had lunch already but couldn't remember. You forget where you live so if you get out of the house you can't get back. And many have 'sundowning', they get scared if they are outside and the night falls. It's not just the forgetting either, you start losing fundamental functions and eventually die. Not to mention the aggression and mood swings, which are aggravated if you try to point out that they are forgetting things.
What most people don't realize is that Alzheimer's - and its friend FTD - are terminal diseases with life expectancy just as bad as many cancers. Hardly anyone makes it to 5 years after diagnosis. The bodily degeneration that eventually results in the patient being utterly unable to function is heartbreaking. Forgetting things is a relatively minor symptom. It's also terrible on the family members of the patient whose mental health also suffers along the way.
> It made me think that Alzheimer's is probably the worst thing that could happen to a person.
Alzheimer's is slowly destroying the person, but this might in some cases be not as bad as diseases which leave the person in place but make them suffer intensely, e.g. from pain or depression. Though it's hard to compare.
I'll take pain over slowly reversing to fetal brain development. My grandma had it, and it was freaking sad to watch her lose all body functions. I've already made a decision that when I spot first symptoms, and there won't be a cure, I'll finish all my earthly stuff, and will buy some good morphine.
Given that tens of millions people have been treated for bipolar disorder with Lithium Carbonate, shouldn't researchers have already seen a correlation with Alzheimer's in patients?
Lithium carbonate was tested and didn't help the mice at all because it was just absorbed by the plaques. The exciting thing is they found a form of lithium (already commonly available as a supplement) which is not absorbed by the plaques and showed a reversal of symptoms with P=0.00007. That's the kind of statistical significance I like to see in my medical papers.
> Replacement therapy with lithium orotate, which is a Li salt with reduced amyloid binding, prevents pathological changes and memory loss in AD mouse models and ageing wild-type mice.
> LiOr is proposed to cross the blood–brain barrier and enter cells more readily than Li2CO3, which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns.
The important part is this: “a Li salt with reduced amyloid binding”
If cells in the brain are being deprived of lithium due to sequestration by amyloid beta plaques, then a bioavailable form of lithium that is resistant to sequestration may treat the pathology.
"Conclusion: Individuals with BD are at higher risk of dementia than both the general population or those with MDD. Lithium appears to reduce the risk of developing dementia in BD."
Overall people with Bi-Polar have a much higher rate of dementia but lithium treatment appears to reduce that.
People treated with valproate instead (a mood stabilizer) do not enjoy the same benefit.
So I'll commit to adding low dose lithium to my daily supplements
If you don't rewrite the headline to include 'in mice', we have to scroll past pages of people throwing shade on the study by repeating 'in mice', as if this is something new or insightful about how medical research works. Until many readers add the 'therefore not humans' fallacy in their minds.
A spring near where I grew up used to be considered a notable watersource, and was actively bottled and sold, with the marketing proclaiming the benefits of "Lithia Water" --- always wondered how trace minerals from wells and springs affects health, and how consistent the elemental content is from year-to-year.
Readit News
Not a causative finding in humans but darn interesting
Even if they did you'd have to run huge samples then do post testing necropsies to see which mice had AD which which didn't, then filter your data, then try to find results in what remains.
Otherwise you can inject the mice with a chemical known to cause AD, which is not reliable on it's own, so you can get genetically modified mice which express _some_ of the known plaques and misfolds that are associated with human AD.
Animal testing is still, largely, a very unethical and cruel affair. AD testing in mice is especially fraught with hazard.
> Since lithium has not yet been shown to be safe or effective in protecting against neurodegeneration in humans, Yankner emphasizes that people should not take lithium compounds on their own
I reject this kind of blind safetyism. A cursory search suggests that lithium orotate has been used for decades, and the article suggests that "profound effects" were seen at an "exquisitely low dose" which should be safe. They're going to need a much better explanation of why people shouldn't try it.
You said you searched to learn more about lithium, but somehow missed that it's highly recommended to be administered by doctors due to side effects after long term use. Anything that damages your kidneys or thyroids can kill you, so calling it "blind safetyism" is silly.
Most experts who have been recommending lithium supplementation to support general health recommend doses about 100 or 300 times lower.
It would be more useful and effective for the article to say “don’t do this to yourself because it can damage your guts, see these links, there’s tradeoffs here”
The former just fades into the modern world’s background noise of unchecked ass-covering.
This is at a clinical dose which is somewhat high. It is the dosage fund reliable as treatment for bipolar type 1. As long as you get your kidney numbers checked twice a year, at that dose, its mostly unproblematic as issues show themselves in the numbers before major damage.
The error of the concerned 3rd party is particularly egregious with a disease like Alzheimer's, which presents a significant risk of ruin in the form of information death. It is totally rational to use an intervention that will cause you significant harm if it preserves your mind another few years.
I believe its also in the water supply in certain places, so if it works for dementia there are natural experiments already running on this.
https://www.psychiatrictimes.com/view/low-dose-lithium-a-new...
https://www.cambridge.org/core/journals/the-british-journal-...
I would think naturally occurring lithium in some people's water would give pretty good control conditions to do a wide study of this effect on Alzheimers as well?
Having seen a few family members succumb to dementia, it's not a path I want to take. Fuck up my kidneys and give me an early death, fine, but if I start showing the signs of that type of mental decline, I'm taking the lithium orotate.
My related biggest concern about this is that since it's a cheap supplement that can't be patented, it won't be a priority for the drug industry to study. Another reason to not necessarily trust the "Just slowly die by Alzheimers until we find the perfectly safe (patentable) antidote" crowd.
I repeated this a couple more times with a repeatable outcome.
It’s very hyped in supplement communities with claims that it’s perfectly safe and side effect free. I didn’t get any kidney damage or anything, but I also didn’t get a positive benefit from it. Only subtle negatives that built up over a week.
It does reach a point of diminishing returns for me and I become too sedated. I now take it irregularly.
A paper is not like a religious commandment or something. It's, best case, some mortals honestly trying to learn something. Scolding them for admitting the limits of their knowledge is not reasonable.
Sure, maybe lithium orotate can be bad in high doses.
You know what's super-bad for sure? Alzheimer's!
If I have Alzheimer's, please let me try whatever long-shot you have. I'll be your gunnie pig.
I like the idea but can only imagine the anti-flouride crowd would freak out.
Definitely not something to start pouring into the water supply.
Clinical trials need many participants and take a long time, and they require a control group which doesn't take lithium orotate. Finding these people might be hard if everyone is taking it anyway.
Would you be willing to die of Alzheimer's in order to serve as a placebo for the control group? What about your parents?
I don't really understand this mindset.
I already ordered 5mg tablets of lithium orate as soon as I read this. I'll just add them to the handfuls of other supplements I take each day just in case they may protect against common degenerative ailments.
I very much adhere to the better safe than sorry or yolo approach to supplementation.
You are free to try it, it's over the counter, no one is oppressing you here, Darwin is your friend.
I went to visit my aunt one day, and my favourite uncle couldn't recognize me. It made me think that Alzheimer's is probably the worst thing that could happen to a person. I mean, what's worse than not being able to recognize those closest to you? You work a lifetime, and then you go out in such an undignified manner.
I pray for a cure in my lifetime.
You won't even remember whether or not you had lunch. I met a grandma that was distraught that nobody was feeding her and she was hungry. Except she had had lunch already but couldn't remember. You forget where you live so if you get out of the house you can't get back. And many have 'sundowning', they get scared if they are outside and the night falls. It's not just the forgetting either, you start losing fundamental functions and eventually die. Not to mention the aggression and mood swings, which are aggravated if you try to point out that they are forgetting things.
It's a terrible disease. You cease to be you.
Alzheimer's is slowly destroying the person, but this might in some cases be not as bad as diseases which leave the person in place but make them suffer intensely, e.g. from pain or depression. Though it's hard to compare.
I've had relatives die of Alzheimer's, and others die from other causes. Let me assure you that there are worse fates than the one you describe.
Another source on lithium orotate:
https://pmc.ncbi.nlm.nih.gov/articles/PMC8413749/If cells in the brain are being deprived of lithium due to sequestration by amyloid beta plaques, then a bioavailable form of lithium that is resistant to sequestration may treat the pathology.
Seems like a good real world example that should prove out if lithium works as we know people with BD take it.
Turns out there is a study that says there is.
https://pubmed.ncbi.nlm.nih.gov/31954065/
"Conclusion: Individuals with BD are at higher risk of dementia than both the general population or those with MDD. Lithium appears to reduce the risk of developing dementia in BD."
Overall people with Bi-Polar have a much higher rate of dementia but lithium treatment appears to reduce that.
People treated with valproate instead (a mood stabilizer) do not enjoy the same benefit.
So I'll commit to adding low dose lithium to my daily supplements
The headline right now "Lithium Reverses Alzheimer's in Mice"
Those are two quite different statements. Someone should fix that.