[HN Gopher] Lithium compound can reverse Alzheimer's in mice: study
       ___________________________________________________________________
        
       Lithium compound can reverse Alzheimer's in mice: study
        
       Author : highfrequency
       Score  : 126 points
       Date   : 2025-08-07 14:56 UTC (8 hours ago)
        
 (HTM) web link (hms.harvard.edu)
 (TXT) w3m dump (hms.harvard.edu)
        
       | MaxPock wrote:
       | 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.
        
         | outworlder wrote:
         | 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.
        
           | groos wrote:
           | 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.
        
         | cubefox wrote:
         | > 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.
        
           | a5c11 wrote:
           | 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.
        
         | switchbak wrote:
         | > 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.
        
         | prmph wrote:
         | worse than familial insomnia?
        
       | chevalier_1222 wrote:
       | guess I'll add phone batteries to my diet
        
       | modeless wrote:
       | 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.
        
         | adamgordonbell wrote:
         | 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...
        
           | cypherpunks01 wrote:
           | 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?
        
             | Mistletoe wrote:
             | This is fascinating, thank you.
        
             | valianteffort wrote:
             | 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.
        
             | victorbjorklund wrote:
             | And crime in general.
             | 
             | https://pmc.ncbi.nlm.nih.gov/articles/PMC7576670/
        
             | twojacobtwo wrote:
             | (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 b = -0.27, 95% CI -0.47 to -0.08; P =
             | 0.006, I2 = 83.3%), male (pooled b = -0.26, 95% CI -0.56 to
             | 0.03; P = 0.08, I2 = 91.9%) and female (pooled b = -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.
        
         | cubefox wrote:
         | > 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.
        
           | wonderwonder wrote:
           | 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.
        
             | Angostura wrote:
             | > 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".
        
               | wonderwonder wrote:
               | 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.
        
             | cubefox wrote:
             | 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.
        
               | wonderwonder wrote:
               | 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.
        
               | cubefox wrote:
               | 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.
        
               | wonderwonder wrote:
               | 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.
        
             | bawolff wrote:
             | > 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.
        
               | wonderwonder wrote:
               | 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."
        
         | jsbisviewtiful wrote:
         | > 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.
        
           | rogerrogerr wrote:
           | 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.
        
             | CoastalCoder wrote:
             | > 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.
        
               | rogerrogerr wrote:
               | 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.
        
           | tgv wrote:
           | 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.
        
             | modeless wrote:
             | 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.
        
           | hollerith wrote:
           | 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.
        
             | modeless wrote:
             | 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.
        
           | tokai wrote:
           | >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.
        
           | QuantumGood wrote:
           | 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.
        
         | wonderwonder wrote:
         | 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.
        
         | alphazard wrote:
         | 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.
        
         | lawlessone wrote:
         | 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.
        
           | Aurornis wrote:
           | 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.
        
             | ianmcgowan wrote:
             | That's exactly what the Lizard overlords are doing! /s -
             | wouldn't be surprised there's a few conspiracy theorists
             | who believe this...
        
           | amanaplanacanal wrote:
           | 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)
        
         | zingababba wrote:
         | 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.
        
         | connicpu wrote:
         | My spouse was prescribed lithium by doctors and it messed up
         | her thyroid, it's not a drug to be taken lightly.
        
           | vczf wrote:
           | 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.
        
         | renecito wrote:
         | 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.
        
         | nyeah wrote:
         | "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.
        
         | UncleOxidant wrote:
         | 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).
        
         | Aurornis wrote:
         | 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.
        
           | leoh wrote:
           | 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).
        
         | Nifty3929 wrote:
         | 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.
        
         | hn_throwaway_99 wrote:
         | 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.
        
       | phkahler wrote:
       | Lithium-6 if I recall correctly was the preferred isotope (for
       | the brain, not this study). I don't recall why.
        
       | ninetyninenine wrote:
       | 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.
        
         | bink wrote:
         | 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.
        
         | exmadscientist wrote:
         | 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....
        
           | dboreham wrote:
           | > 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.
        
           | owenversteeg wrote:
           | 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
        
             | exmadscientist wrote:
             | 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.
        
               | owenversteeg wrote:
               | 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?
        
           | funnym0nk3y wrote:
           | Lithium is far from the drug with the highest amount of side
           | effects among psych meds. Take the first generation
           | antipsychotics for example. They are nasty.
           | 
           | As a matter of fact, lithium patients aren't much worse off
           | when it comes to kidney function. Especially with modern
           | levels of around 0.6 to 0.8 mmols.
           | 
           | Lithium has many modes of action, ion channels like you said,
           | but also GSK3 function, BDNF changes and many more. It even
           | changes the DNA methylation.
        
         | hirvi74 wrote:
         | 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.
        
           | funnym0nk3y wrote:
           | Lithium cures Bipolar the same way all the other psych meds
           | do. They don't. They just manage symptoms. Like insulin does,
           | or antihistamines, etc. A propper cure is rare in medicine.
        
         | nartho wrote:
         | 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.
        
       | stivatron wrote:
       | Watch out, there's no reliable Alzheimer's mouse model.
        
       | stivatron wrote:
       | 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.
        
         | kovek wrote:
         | Could you share some sources that show this to be true?
        
           | j_bum wrote:
           | Not a source, but the fact that we can treat AD in mice but
           | not humans should demonstrate OPs point sufficiently.
        
           | themafia wrote:
           | 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.
        
           | xkcd-sucks wrote:
           | 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...
        
         | csaid81 wrote:
         | 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...
        
         | leoh wrote:
         | > 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
        
       | WillAdams wrote:
       | 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.
        
       | nahikoa wrote:
       | 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?
        
         | vczf wrote:
         | From the abstract of the paper:                 > 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.
         | 
         | https://www.nature.com/articles/s41586-025-09335-x
         | 
         | Another source on lithium orotate:                 > 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.
         | 
         | https://pmc.ncbi.nlm.nih.gov/articles/PMC8413749/
        
         | leoh wrote:
         | Definitely, good point
        
       | wonderwonder wrote:
       | 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
        
       | amluto wrote:
       | Interestingly, the proposed mechanism seems consistent with the
       | apparent small benefit of anti-amyloid antibody therapy: if
       | amyloid deposits interfere with lithium uptake, then removing
       | them could restore some lithium availability without doing
       | anything about the underlying initial cause of insufficient
       | lithium.
        
       | funnym0nk3y wrote:
       | There are so many misconceptions about lithium wrt to the human
       | body.
       | 
       | I don't know why so many people differentiate between lithium
       | orotate and the lithium carbonate in psychiatry. Although they
       | differ in absorption the active component is the lithium ion in
       | both cases. Dosage is done according to lithium content, there
       | are tables for converting from orotate to carbonate and back.
       | 
       | Then the effects of lithium orotate and carbonate can't be that
       | different. And thus, above a particular dose blood monitoring is
       | mandatory.
       | 
       | There are benefits of low dose lithium for sure. And the dosages
       | in psychiatry have been on a steady decline. With lower doses
       | come less side effects. It is definitly not the hammer of
       | psychiatry that turns people into zombies or messes. It feels
       | quite natural.
       | 
       | In addition the reduction of Alzheimers cases is not unique to
       | lithium. Many meds cause Alzheimers rates in mentally ill people
       | to decline to general population levels.
        
       | ThinkBeat wrote:
       | The headline in the article from Harvard says "Could Lithium
       | Explain -- and Treat -- Alzheimer's Disease?"
       | 
       | The headline right now "Lithium Reverses Alzheimer's in Mice"
       | 
       | Those are two quite different statements. Someone should fix
       | that.
        
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