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.
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.
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.
Exactly. An "exquisitely low dose" should be safe. And Alzheimer's also kills you, after making life no longer worth living. For people who already have it, I don't see any reason why they shouldn't try an appropriate dose.
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.
Oh, it’s rational for them! That’s the problem - it’s always rational to treat anything you write as the highest level of liability. No one loses money by adding more disclaimers. Observe:
Drinking water is a good idea.
*check with your doctor if you are allergic to water, have a history of drowning, or are unable to distinguish water from ethanol. Do not consume water while intubated. People with rabies may have adverse reactions to water. Use caution when drinking water if you cannot swallow or are currently vomiting. Water from some sources may be contaminated. Salt water may contain jellyfish.
—-
My legal exposure from the initial statement went down with every little stupid disclaimer I added there, and there’s no penalty for each one. But you probably didn’t even read the full thing. We’ve created a culture of everyone feeling like they need to cover their ass, and the real important things get drowned out.
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.
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.
12 to 24 months is old in mouse years. And the article offers a plausible explanation for both why plaques could cause the disease and why clearing them alone might not fix it without lithium supplementation.
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?
The literature search identified 415 articles; of these, 15 ecological studies were included in the synthesis. The random-effects meta-analysis showed a consistent protective (or inverse) association between lithium levels/concentration in publicly available drinking water and total (pooled β = −0.27, 95% CI −0.47 to −0.08; P = 0.006, I2 = 83.3%), male (pooled β = −0.26, 95% CI −0.56 to 0.03; P = 0.08, I2 = 91.9%) and female (pooled β = −0.13, 95% CI −0.24 to −0.02; P = 0.03, I2 = 28.5%) suicide mortality rates. A similar protective association was observed in the six studies included in the narrative synthesis, and subgroup meta-analyses based on the higher/lower suicide mortality rates and lithium levels/concentration.
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.
"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).
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.
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 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.
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'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.
> 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?
And if it actually makes Alzheimer's worse?
We are talking about a mouse model of a disease that very famously doesn't work the same way in mice and humans. The most likely scenario is it does nothing. With this level of evidence you might as well just eat random garbage off the ground in the off chance it helps.
"Conclusion: Individuals with BD [Bi Polar Disorder] 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."
It's called evidence-based medicine and it's useful for answering questions such such as 'with taking Lithium prevent Alzheimer's by ensuring you die of kidney disease first.
Taking a bunch of unnecessary supplements isn't inherently "safe".
Low dose lithium is not going to cause kidney failure.
I was also responding specifically to OP advocating for people to intentionally not to take it so there is a ready supply of people to test it on who are not already on it for a long period of time (decades). They are advocating for self sacrifice.
This by default means there must be a large supply of people not on it for a long period of time who will suffer and die from Alzheimer's instead of just taking the supplement. That was my issue. It seemed to call for the self sacrifice of many in order to allow for a long term study. But I think you already know that if you read my response and just chose to focus on a single sentence.
The alternative to a clinical trial would be that there continues to be much less certainty whether lithium orotate actually works and is safe. Which would result in less or more usage than optimal.
Well I was the OP. It might be a tragedy of the commons situation. For each individual it may be better to ignore trials and just self medicate, but on the whole this could lead to an overall worse outcome in the long run.
Although that means you avoided answering my question directly multiple times although I think you strongly alluded that the answer would be no in your last response.
I look at my life and those of my family as precious and more valuable than all other lives (their lives over mine). I expect others to operate in a similar manner and that is why I am always taken aback at posts that seem to advocate for the sacrifice of one's self for the benefit of strangers. This is different of course from in the moment actions such as running into a burning building to save someone or stepping up to protect a woman you have never met from an aggressive man.
Your response while vague appears to indicate that you would not sacrifice yourself for this experiment either. Which is what I would expect from everyone.
I understand your general advocation for the clinical study and I agree with the need overall but not at the cost of intentionally sacrificing oneself.
So I'll pop a low dose lithium tablet along with a baby aspirin each night and hope you do the same. Wishing you a long life my friend.
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?
> 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.
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.
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.
"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
Lithium is a strange drug. It also cures bipolar disorder and nobody knows why. It also fucks up the liver over time and basically people on lithium eventually have to make a choice between dying or being insane.
It's mostly the kidneys that get damaged, not so much the liver. It also has a massive amount of benign or merely annoying side effects. Lithium might even be the drug with the largest overall amount of side effects. It's certainly a weird one.
High-dose lithium is extremely hard on your kidneys and may well lead to kidney failure in a decade or so. Medium-dose lithium is a lot more gentle but still requires monitoring. Many people can go down in dose after initial treatment, and good psych prescribers will attempt to do this after a while. (Or patients will request it, after the other side effects of lithium become noticable after the bipolar has settled down.) Low-dose lithium is much harder to study and may well be pretty safe. May.
It is not quite true that people have no idea how it cures bipolar disorder. It's definitely affecting the ion channels (sodium, potassium, etc), just like many other anticonvulsant drugs also used for treating bipolar. So the mechanism for action is not totally insane and unique. Now, why the ion channels are the place to go for certain people, that's an open question....
I have to say that I think the current popular idea of "we know how X drug works in the body because it does Y to Z" is patently insane. It may be useful information, sure, but it's not really _why_ it works, because we don't understand how the body works. It would be like Toyota saying: "the Corolla works on gasoline because it burns inside the engine, but we have no idea why the engine breaks when you put acetone in it." It would be obvious that Toyota had no goddamn clue what was going on in the engine! And yet, that's exactly where we are with most drugs including lithium; most of these so-called mechanisms would work on rubidium, so why does rubidium have different effects? Who knows!
If you read a literature review for lithium's mechanism of action, it's a wild ride [0] that clearly demonstrates exactly how little we know. More importantly, though, is that all of this is made up ex post facto. Nobody can take a _new_ drug and tell you anything concrete about what it will do or how it will work: instead, we look at what happens and _then_ we make crude guesses. It is essentially modern miasma theory. For those who have forgotten, the application of miasma theory built our first sanitation systems, which eliminated more deaths from disease than the entirety of vaccines. That is to say: just because we are groping in the dark does not make the work useless, and indeed, our first vaccines were also constructed with very primitive methods.
I think that a more concrete understanding of the human body can only come when we start to understand all the many pathways of life in/on/around the body. Right now, our technology constrains us to investigate only individual points in mostly static ways. Give it a few decades of advancement and I bet we'll have some fascinating insights. I would also bet that, as with any complex system, there will be no simple answers to how things work.
-----------
For what it's worth, in the specific case of lithium, the American Society of Health-System Pharmacists would agree with me that the mechanism of action is unknown: https://www.drugs.com/monograph/lithium.html
That monograph is not appropriate to this discussion because it is written for practitioners, not researchers. There is plenty of information on some of the things lithium is doing. My point was not "we have a complete understanding", but "we have some idea what is going on here, but there is still a lot we don't know".
Lithium is one of a large class of drugs that modulate the chemical potentials of the body's voltage-gated ion channels. There are a lot of drugs in this class, and most have been used with at least some degree of success to treat bipolar disorder. This class is also first-line treatment for many forms of epilepsy. The GABA system is directly tied in here too, and GABAergic agents are generally considered part of this class... and, guess what, they often help in bipolar as well. Lithium is a unique member of this class, and it is completely obvious (to a biochemist) that adding another species of alkali metal in sufficient concentration will disrupt the chemical potentials of sodium and potassium ion transport in the ion channels.
My point is: the first-level effect of lithium is well understood, and it affects an area that is well known to be affected by other drugs that have similar effects. So it is not total voodoo. However, you are also very correct that our understanding starts to break down after this. We can come up with new ion channel modulating drugs, and can reasonably expect them to be effective candidates for helping bipolar patients. What we cannot do is predict other targets or classes of drugs that might be interesting. That is where our understanding breaks down.
I'm not sure why the relevant portion of the monograph isn't appropriate simply because of the target audience. "Alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown" is the general consensus on lithium whether you're reading it as you, me, or Donald Duck.
Here is where we can both agree: we know a few things about the mechanism, which allow us to make some useful judgments in a few limited cases. We can also both agree that we know so little that, if a new, similar drug were proposed, with only a small change to its chemical structure, neither of us would dare make any confident statements about its action. We also cannot accurately predict what would happen if given to a patient with a well-studied but different disorder. In other words: most of the useful judgments about lithium - those that would be economically or socially interesting, for example - cannot be made from the model, because our understanding of the mechanism of action is too crude.
All of that is also, however, true about my hypothetical Corolla from my first example: we can say a few things, but most of the useful judgments that could be made from a full understanding cannot be made. It would be obvious to anyone that we do not understand the Corolla. So why, then, would we claim to understand lithium?
Personal theory: these things are like "global constants" for the brain's GPU. Somewhat similar to the temperature constant in an LLM. There is no real "explanation" for why they work, they just have an effect. Various chemicals have various effects, often depending on the patient (because other constants vary, training data varies...) and we pick the chemical we like the effect of most.
Surely the minimal dosage they're studying here won't have such dramatic impacts on the liver? It's basically what's available in some water sources. It's also available in food sources like leafy greens, nuts, and legumes.
That's quite a stretch. Lithium does not cure bipolar disorder nor is it effective in many afflicted. Also, Lithium is not the only medication for Bipolar Disorder, there are a double-digit number of alternative options.
Also, to my knowledge, we are not entirely sure why most, if not all, of the psychiatric drugs work. Plenty of hypotheses though.
I have (had?) a chronic skin condition called seborrheic dermatitis. It manifested as dry cracks over my lips and cheekbones exuding an orange/yellow liquid. It was itchy and looked absolutely disgusting. It would stay there for a few weeks and then come back in a few months. Treatment was cortisone which reduced the time it would but it would always reappear a couple of months later, it'd also lose effectiveness. Then my dermatologist prescribed a new lithium based treatment (Lithioderm) and after a first treatment, I got a couple of progressively smaller outbreaks, and it's never reappeared since then, it's been 20 years. I don't think we know how or why it works but I'm glad it did.
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.
Yes, but not only did they improve the memory of mouse models of Alzheimer's, they also improved the memory of older wild-type mice, which seems impressive to me. https://www.nature.com/articles/s41586-025-09335-x/figures/1...
> 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
Could you share some sources that show this to be true?
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...
Not a source, but the fact that we can treat AD in mice but not humans should demonstrate OPs point sufficiently.
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.
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 reject this kind of blind safetyism.
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.
The kidney damage, etc, are consequences of the very high doses of lithium needed to control bipolar disorder.
Most experts who have been recommending lithium supplementation to support general health recommend doses about 100 or 300 times lower.
Exactly. An "exquisitely low dose" should be safe. And Alzheimer's also kills you, after making life no longer worth living. For people who already have it, I don't see any reason why they shouldn't try an appropriate dose.
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.
> The former just fades into the modern world’s background noise of unchecked ass-covering.
The missing piece of this argument is just what the probability of different legal risks is here.
Wether or not their ass-covering is reasonable hinges on that and on their risk tolerance.
Oh, it’s rational for them! That’s the problem - it’s always rational to treat anything you write as the highest level of liability. No one loses money by adding more disclaimers. Observe:
Drinking water is a good idea.
*check with your doctor if you are allergic to water, have a history of drowning, or are unable to distinguish water from ethanol. Do not consume water while intubated. People with rabies may have adverse reactions to water. Use caution when drinking water if you cannot swallow or are currently vomiting. Water from some sources may be contaminated. Salt water may contain jellyfish.
—-
My legal exposure from the initial statement went down with every little stupid disclaimer I added there, and there’s no penalty for each one. But you probably didn’t even read the full thing. We’ve created a culture of everyone feeling like they need to cover their ass, and the real important things get drowned out.
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.
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.
12 to 24 months is old in mouse years. And the article offers a plausible explanation for both why plaques could cause the disease and why clearing them alone might not fix it without lithium supplementation.
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.
People use it in much smaller dosages then it's usually prescribed to apparently beneficial effect.
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...
Yes, it's already thought that there's an association between naturally occurring lithium in drinking water and decreased suicide rates:
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?
(for others like myself)
Results
The literature search identified 415 articles; of these, 15 ecological studies were included in the synthesis. The random-effects meta-analysis showed a consistent protective (or inverse) association between lithium levels/concentration in publicly available drinking water and total (pooled β = −0.27, 95% CI −0.47 to −0.08; P = 0.006, I2 = 83.3%), male (pooled β = −0.26, 95% CI −0.56 to 0.03; P = 0.08, I2 = 91.9%) and female (pooled β = −0.13, 95% CI −0.24 to −0.02; P = 0.03, I2 = 28.5%) suicide mortality rates. A similar protective association was observed in the six studies included in the narrative synthesis, and subgroup meta-analyses based on the higher/lower suicide mortality rates and lithium levels/concentration.
And crime in general.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7576670/
The addition of flouride to tap water supply likely affects brain development. Let's not go adding lithium too.
These things are simple enough to advise the populace to use on their own. The government should never play nanny, ever.
This is fascinating, thank you.
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.
Not for you, then, right? Pretty normal for many medicines, supplements, etc. I think it’s cool we can try things (even if they don’t always work).
"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).
Indeed!
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.
My spouse was prescribed lithium by doctors and it messed up her thyroid, it's not a drug to be taken lightly.
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.
yup, because this could not be a scam.
You are free to try it, it's over the counter, no one is oppressing you here, Darwin is your friend.
I've heard of suggestions that it should be added to water(in low doses of course) to see it reduces suicide rates.
I like the idea but can only imagine the anti-flouride crowd would freak out.
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 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.
That's exactly what the Lizard overlords are doing! /s - wouldn't be surprised there's a few conspiracy theorists who believe this...
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'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.
> 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?
And if it actually makes Alzheimer's worse?
We are talking about a mouse model of a disease that very famously doesn't work the same way in mice and humans. The most likely scenario is it does nothing. With this level of evidence you might as well just eat random garbage off the ground in the off chance it helps.
Probably nothing
https://pubmed.ncbi.nlm.nih.gov/31954065/
"Conclusion: Individuals with BD [Bi Polar Disorder] 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."
> I don't really understand this mindset.
It's called evidence-based medicine and it's useful for answering questions such such as 'with taking Lithium prevent Alzheimer's by ensuring you die of kidney disease first.
Taking a bunch of unnecessary supplements isn't inherently "safe".
Low dose lithium is not going to cause kidney failure. I was also responding specifically to OP advocating for people to intentionally not to take it so there is a ready supply of people to test it on who are not already on it for a long period of time (decades). They are advocating for self sacrifice.
This by default means there must be a large supply of people not on it for a long period of time who will suffer and die from Alzheimer's instead of just taking the supplement. That was my issue. It seemed to call for the self sacrifice of many in order to allow for a long term study. But I think you already know that if you read my response and just chose to focus on a single sentence.
The alternative to a clinical trial would be that there continues to be much less certainty whether lithium orotate actually works and is safe. Which would result in less or more usage than optimal.
I will ask you the same question I asked OP
"Would you be willing to die of Alzheimer's in order to serve as a placebo for the control group? What about your parents?"
Since that is essentially what you are asking the people that would have ordered low dose lithium based on this article to do.
Well I was the OP. It might be a tragedy of the commons situation. For each individual it may be better to ignore trials and just self medicate, but on the whole this could lead to an overall worse outcome in the long run.
Ha! you were op, my fault :)
Although that means you avoided answering my question directly multiple times although I think you strongly alluded that the answer would be no in your last response.
I look at my life and those of my family as precious and more valuable than all other lives (their lives over mine). I expect others to operate in a similar manner and that is why I am always taken aback at posts that seem to advocate for the sacrifice of one's self for the benefit of strangers. This is different of course from in the moment actions such as running into a burning building to save someone or stepping up to protect a woman you have never met from an aggressive man.
Your response while vague appears to indicate that you would not sacrifice yourself for this experiment either. Which is what I would expect from everyone.
I understand your general advocation for the clinical study and I agree with the need overall but not at the cost of intentionally sacrificing oneself.
So I'll pop a low dose lithium tablet along with a baby aspirin each night and hope you do the same. Wishing you a long life my friend.
I ordered 5mg tablets of Lithium Orate 5 minutes after reading this article on X. I take EGCG as well due to a similar article.
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?
From the abstract of the paper:
https://www.nature.com/articles/s41586-025-09335-xAnother source on lithium orotate:
https://pmc.ncbi.nlm.nih.gov/articles/PMC8413749/Definitely, good point
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.
Watch out, there's no reliable Alzheimer's mouse model.
Things I love to read.
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.
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.
It's a terrible disease. You cease to be you.
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
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.
worse than familial insomnia?
> 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.
Lithium-6 if I recall correctly was the preferred isotope (for the brain, not this study). I don't recall why.
I was curious if there was any correlation, inverse or other between people with Bi-polar disease treated with lithium and dementia.
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
Lithium is a strange drug. It also cures bipolar disorder and nobody knows why. It also fucks up the liver over time and basically people on lithium eventually have to make a choice between dying or being insane.
It's mostly the kidneys that get damaged, not so much the liver. It also has a massive amount of benign or merely annoying side effects. Lithium might even be the drug with the largest overall amount of side effects. It's certainly a weird one.
High-dose lithium is extremely hard on your kidneys and may well lead to kidney failure in a decade or so. Medium-dose lithium is a lot more gentle but still requires monitoring. Many people can go down in dose after initial treatment, and good psych prescribers will attempt to do this after a while. (Or patients will request it, after the other side effects of lithium become noticable after the bipolar has settled down.) Low-dose lithium is much harder to study and may well be pretty safe. May.
It is not quite true that people have no idea how it cures bipolar disorder. It's definitely affecting the ion channels (sodium, potassium, etc), just like many other anticonvulsant drugs also used for treating bipolar. So the mechanism for action is not totally insane and unique. Now, why the ion channels are the place to go for certain people, that's an open question....
I have to say that I think the current popular idea of "we know how X drug works in the body because it does Y to Z" is patently insane. It may be useful information, sure, but it's not really _why_ it works, because we don't understand how the body works. It would be like Toyota saying: "the Corolla works on gasoline because it burns inside the engine, but we have no idea why the engine breaks when you put acetone in it." It would be obvious that Toyota had no goddamn clue what was going on in the engine! And yet, that's exactly where we are with most drugs including lithium; most of these so-called mechanisms would work on rubidium, so why does rubidium have different effects? Who knows!
If you read a literature review for lithium's mechanism of action, it's a wild ride [0] that clearly demonstrates exactly how little we know. More importantly, though, is that all of this is made up ex post facto. Nobody can take a _new_ drug and tell you anything concrete about what it will do or how it will work: instead, we look at what happens and _then_ we make crude guesses. It is essentially modern miasma theory. For those who have forgotten, the application of miasma theory built our first sanitation systems, which eliminated more deaths from disease than the entirety of vaccines. That is to say: just because we are groping in the dark does not make the work useless, and indeed, our first vaccines were also constructed with very primitive methods.
I think that a more concrete understanding of the human body can only come when we start to understand all the many pathways of life in/on/around the body. Right now, our technology constrains us to investigate only individual points in mostly static ways. Give it a few decades of advancement and I bet we'll have some fascinating insights. I would also bet that, as with any complex system, there will be no simple answers to how things work.
-----------
For what it's worth, in the specific case of lithium, the American Society of Health-System Pharmacists would agree with me that the mechanism of action is unknown: https://www.drugs.com/monograph/lithium.html
[0] https://link.springer.com/article/10.1007/s40263-013-0039-0
That monograph is not appropriate to this discussion because it is written for practitioners, not researchers. There is plenty of information on some of the things lithium is doing. My point was not "we have a complete understanding", but "we have some idea what is going on here, but there is still a lot we don't know".
Lithium is one of a large class of drugs that modulate the chemical potentials of the body's voltage-gated ion channels. There are a lot of drugs in this class, and most have been used with at least some degree of success to treat bipolar disorder. This class is also first-line treatment for many forms of epilepsy. The GABA system is directly tied in here too, and GABAergic agents are generally considered part of this class... and, guess what, they often help in bipolar as well. Lithium is a unique member of this class, and it is completely obvious (to a biochemist) that adding another species of alkali metal in sufficient concentration will disrupt the chemical potentials of sodium and potassium ion transport in the ion channels.
My point is: the first-level effect of lithium is well understood, and it affects an area that is well known to be affected by other drugs that have similar effects. So it is not total voodoo. However, you are also very correct that our understanding starts to break down after this. We can come up with new ion channel modulating drugs, and can reasonably expect them to be effective candidates for helping bipolar patients. What we cannot do is predict other targets or classes of drugs that might be interesting. That is where our understanding breaks down.
I'm not sure why the relevant portion of the monograph isn't appropriate simply because of the target audience. "Alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown" is the general consensus on lithium whether you're reading it as you, me, or Donald Duck.
Here is where we can both agree: we know a few things about the mechanism, which allow us to make some useful judgments in a few limited cases. We can also both agree that we know so little that, if a new, similar drug were proposed, with only a small change to its chemical structure, neither of us would dare make any confident statements about its action. We also cannot accurately predict what would happen if given to a patient with a well-studied but different disorder. In other words: most of the useful judgments about lithium - those that would be economically or socially interesting, for example - cannot be made from the model, because our understanding of the mechanism of action is too crude.
All of that is also, however, true about my hypothetical Corolla from my first example: we can say a few things, but most of the useful judgments that could be made from a full understanding cannot be made. It would be obvious to anyone that we do not understand the Corolla. So why, then, would we claim to understand lithium?
> Now, why the ion channels are the place to go
Personal theory: these things are like "global constants" for the brain's GPU. Somewhat similar to the temperature constant in an LLM. There is no real "explanation" for why they work, they just have an effect. Various chemicals have various effects, often depending on the patient (because other constants vary, training data varies...) and we pick the chemical we like the effect of most.
Surely the minimal dosage they're studying here won't have such dramatic impacts on the liver? It's basically what's available in some water sources. It's also available in food sources like leafy greens, nuts, and legumes.
That's quite a stretch. Lithium does not cure bipolar disorder nor is it effective in many afflicted. Also, Lithium is not the only medication for Bipolar Disorder, there are a double-digit number of alternative options.
Also, to my knowledge, we are not entirely sure why most, if not all, of the psychiatric drugs work. Plenty of hypotheses though.
I have (had?) a chronic skin condition called seborrheic dermatitis. It manifested as dry cracks over my lips and cheekbones exuding an orange/yellow liquid. It was itchy and looked absolutely disgusting. It would stay there for a few weeks and then come back in a few months. Treatment was cortisone which reduced the time it would but it would always reappear a couple of months later, it'd also lose effectiveness. Then my dermatologist prescribed a new lithium based treatment (Lithioderm) and after a first treatment, I got a couple of progressively smaller outbreaks, and it's never reappeared since then, it's been 20 years. I don't think we know how or why it works but I'm glad it did.
guess I'll add phone batteries to my diet