Low Dose of Lithium Reverses Alzheimer's Symptoms In Mice (newscientist.com) 70
An anonymous reader quotes a report from New Scientist: People withAlzheimer's disease have lower levels of lithium in their brains, and giving lithium to mice with symptoms of the condition reverses cognitive decline. Together, the findings suggest that lithium deficiency could be a driver of Alzheimer's disease and that low-dose lithium medications could help treat it. [...] [Bruce Yanknerat Harvard University] and his colleagues analyzed levels of 27 metals in the brains of 285 people after they died, 94 of whom were diagnosed with Alzheimer's disease and 58 of whom had mild cognitive impairment, a precursor of the condition. The other participants showed no signs of cognitive decline at the time of their death.
Lithium levels in the prefrontal cortex -- a brain region crucial for memory and decision-making -- were about 36 percent lower, on average, in people with Alzheimer's disease than in those without any cognitive decline. For those with mild cognitive impairment, lithium levels were about 23 percent lower. "We suspect that's due to a number of environmental factors: dietary intake, genetics and so forth," says Yankner. Yet there seemed to be another reason, too. In those with Alzheimer's disease, clumps of proteins called amyloid plaques contained nearly three times the amount of lithium as plaque-free regions of their brain. "Lithium becomes sequestered in these plaques," says Yankner. "We have two things going on. There is impaired uptake of lithium [in the brain] very early on and then, as the disease progresses, the lithium that is in the brain is further diminished by being bound to amyloid."
To understand how this influences cognition, the team genetically engineered 22 mice to develop Alzheimer's-like symptoms and reduced their lithium intake by 92 percent. After about eight months, the animals performed significantly worse on multiple memory tests compared with 16 mice on a standard diet. It took lithium-deficient mice around 10 seconds longer to find a hidden platform in a water maze, for example, even after six days of training. Their brains also contained nearly two and a half times as many amyloid plaques. Genetic analysis of brain cells from the lithium-deficient mice showed increased activity in genes related to neurodegeneration and Alzheimer's. They also had more brain inflammation and their immune cells were less able to clear away amyloid plaques, changes also seen in people with Alzheimer's disease.
The team then screened different lithium compounds for their ability to bind to amyloid and found that lithium orotate -- a naturally occurring compound in the body formed by combining lithium with orotic acid -- appeared to be the least likely to get trapped within plaques. Nine months of treatment with this compound significantly reduced plaques in mice with Alzheimer's-like symptoms, and they also performed as well on memory tests as normal mice. These results suggest lithium orotate could be a promising treatment for Alzheimer's. The findings have been published in the journal Nature.
Lithium levels in the prefrontal cortex -- a brain region crucial for memory and decision-making -- were about 36 percent lower, on average, in people with Alzheimer's disease than in those without any cognitive decline. For those with mild cognitive impairment, lithium levels were about 23 percent lower. "We suspect that's due to a number of environmental factors: dietary intake, genetics and so forth," says Yankner. Yet there seemed to be another reason, too. In those with Alzheimer's disease, clumps of proteins called amyloid plaques contained nearly three times the amount of lithium as plaque-free regions of their brain. "Lithium becomes sequestered in these plaques," says Yankner. "We have two things going on. There is impaired uptake of lithium [in the brain] very early on and then, as the disease progresses, the lithium that is in the brain is further diminished by being bound to amyloid."
To understand how this influences cognition, the team genetically engineered 22 mice to develop Alzheimer's-like symptoms and reduced their lithium intake by 92 percent. After about eight months, the animals performed significantly worse on multiple memory tests compared with 16 mice on a standard diet. It took lithium-deficient mice around 10 seconds longer to find a hidden platform in a water maze, for example, even after six days of training. Their brains also contained nearly two and a half times as many amyloid plaques. Genetic analysis of brain cells from the lithium-deficient mice showed increased activity in genes related to neurodegeneration and Alzheimer's. They also had more brain inflammation and their immune cells were less able to clear away amyloid plaques, changes also seen in people with Alzheimer's disease.
The team then screened different lithium compounds for their ability to bind to amyloid and found that lithium orotate -- a naturally occurring compound in the body formed by combining lithium with orotic acid -- appeared to be the least likely to get trapped within plaques. Nine months of treatment with this compound significantly reduced plaques in mice with Alzheimer's-like symptoms, and they also performed as well on memory tests as normal mice. These results suggest lithium orotate could be a promising treatment for Alzheimer's. The findings have been published in the journal Nature.
There should be an easy natural observation (Score:5, Insightful)
Re:There should be an easy natural observation (Score:5, Interesting)
track the population that is taking lithium for other reasons
Lithium is commonly given to those with bipolar or schizo-affective disorders. Those suffering from those disorders on average have a mortality 10 to 20 years sooner than others. While it may give insights, it's not without other causes of life issues. As Alzheimer's disease usually (though not exclusively) onsets at advanced age, a higher instance of early mortality may impact the study. I'm not enough of a statistician to know if that can be effectively filtered out and still give a useful observation but it's something to be aware of.
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Lithium is commonly given to those with bipolar or schizo-affective disorders
Which is certainly interesting ... since despite the many differences, dementia and those disorders both involve thinking and behavior that is diverging from what's appropriate for reality.
Re:There should be an easy natural observation (Score:4, Interesting)
Re:There should be an easy natural observation (Score:5, Informative)
Leafy greens, bulbs and root vegetables and fruits, more specifically cabbage, garlic, potatoes, tomatoes. And coriander (some may find chewing an 18650 cell more palatable).
So you'll be pleased to learn that a diet heavy in sauerkraut, kimchi and Mexican food should minimise your chance of developing Alzheimers, however people in your immediate vicinity might not be so pleased.
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What I could find places USA at 11%, south korea at 9.5%. Even saying that both countries use similar diagnostics, that is not that big a difference.
16% higher (Score:2)
Re:Well... (Score:3)
https://pubmed.ncbi.nlm.nih.go... [nih.gov]
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They are given a different type of lithium at a much higher dose. If I recall correctly, some of the initial insights on the benefits of lithium came from those patients. However, it has nothing to do with this study. It's easy to control from that by removing those patients. Furthermore, almost everyone gets some lithium whe
Re:There should be an easy natural observation (Score:5, Informative)
There have been quite a few studies that do just that. Well, not "taking lithium", as in the medication, because typical psychiatric doses of lithium (hundreds of milligrams per day) are like 2-3 orders of magnitude higher than typical dietary doses. But dietary doses themselves vary by orders of magnitude (some European studies put consumption in some places in Europe as low as a couple micrograms per day, while in places in northern Chile some people consume ~10mg per day), because lithium is so widely varied from place to place. One study found for example that one Slovakian bottled water product had 10 milligrams per litre, while the mean European bottled water had less than a microgram per litre. In most places, peoples' dietary consumption is closer to the lower end than the upper end. And the studies strongly suggest that people who naturally consume the higher amounts of lithium have lower rates dementia (there's also positive, though weaker, evidence for lower rates of violent crime and suicide). In general, it seems to be neuroprotective.
It's been argued that we should probably be lithiating water, e.g. that there should be minimum and maximum standards for lithium in drinking water the same way that there are minimums and maximums for numerous other minerals, with a provisional recommended daily intake of 1mg per day based on the evidence. But given the huge backlash to fluoride in water, I can't even imagine how harsh the backlash to lithium would be, given that people associate it with being a psychiatric medication (even though that's at doses orders of magnitude higher). It's just not going to happen.
I personally take 1mg of lithium a day. Which is well within the normal dietary range (in some places in northern Chile people naturally consume ~10mg per day!). A common supplement form is lithium orotate, but it's a weird choice - it's chosen because it's covalently bonded into a molecule which is delivered into cells whole, to "make it more effective", but A) that's not how normal dietary lithium is delivered, and B) orotic acid isn't exactly healthy. Instead, I make my own (both concentrate and diluted solution). I start with lithium carbonate, and while it's not available in food grade (anywhere I've found), it's a very common compound available at high purity (>99,5%), with easy composition tests - crimson flame test, density tests (offset by a typically poor packing density), low solubility in water but high bubbling solubility in weak acids (with no precipitate), etc). Because it's poorly soluble & tastes like baking soda / mineral water, I also add citric acid to the solution, forming lithium citrate. Even if the impurities were pure lead, the amount would still be small when you're only taking 1mg a day. But actual impurities are mostly (A) water, (B) other lithium compounds (hydroxide, chloride, sulfate, etc etc), and (C) other similar mono- and divalent cations to lithium, such as sodium, potassium, calcium, magnesium, plus some iron, alumium and silicon due to their ubiquity in nature and presence in processing.
Re: There should be an easy natural observation (Score:2)
Thank you..
This post is worthy of a slashdot story, all by itself.
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Fascinating, thank you for posting.
Why did you choose to start supplementing with lithium?
Re:There should be an easy natural observation (Score:5, Interesting)
The least-harm principle. There's essentially universal agreement that low (dietary-range) levels of lithium are not harmful, while the research as a whole is strongly suggestive of a benefit (but has not yet met the standards of, for example. an EPA regulatory standard for lithium in drinking water). Lithium, at the doses necessary, costs basically nothing, takes seconds to take, and is orders of magnitude away from the levels where potential toxicity symptoms can arise. To me, that's an easy call. Also, Alzheimer's runs in my family, so there's an extra factor weighing on the scale.
Re:There should be an easy natural observation (Score:4, Informative)
Lithium aspartate [amazon.com], for example
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No issues with aspartate. It dissociates fully upon dissolution. L-aspartate is a building block to proteins. D-aspartate is also naturally found and used in the body.
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This is why I keep coming to SlashDot all these years.
Couple of possibilities (Score:2)
Lithium may be an essential micronutrient, needed in minute dose for vitamin b12 and folate transport and uptake https://www.jpands.org/vol20no... [jpands.org]
Lithium reacts strongly with mercury, https://pubs.rsc.org/en/conten... [rsc.org]
Wouldn't that make it react strongly with nitric oxides in the body induced by iNOS or eNOS? Not sure how it all relates to Alzheimers other than it disrupts the problem or provides something of a solution via those means, which it seems like they could precipitate fixing the root cause. Wh
Re:Couple of possibilities (Score:5, Informative)
Lithium may be an essential micronutrient, needed in minute dose for vitamin b12 and folate transport and uptake https://www.jpands.org/vol20no.... [jpands.org]
I just skipped to the exciting bit at the end:
Timothy M. Marshall, Ph.D., is a holistic neurospecialist/pharmacologist
and professor of chemistry and pharmacology in Tucson, Ariz. Contact:
tmarshall73@gmail.com.
Disclosure: Dr. Marshall willl be marketing products containing lithium as a
nutritional supplement.
Re:Couple of possibilities (Score:5, Interesting)
It always strikes me as weird that people would be shocked that a substance commonly prescribed to affect the brain... affects the brain.
Beyond increasing BDNF activity (which promotes neuron survival and new growth), one of the main therapeutic targets is Glycogen synthase kinase-3 beta [wikipedia.org], which controls a wide range of developmental parameters for neuronal development, including discouraging regeneration and promoting apoptosis, and is pro-inflammatory (CNS inflammation is itself associated with Alzheimers). Lithium reduces its activity, both with direct and indirect inhibition. While GSK-3B is essential to a degree, overactivity of GSK-3B is associated with a wide range of neurodegenerative diseases [frontiersin.org], including Alzheimer's.
Lithium also helps promote cleanup (misfolded proteins, degradation products, etc) via autophagy by reducing the activity of IMPase [wikipedia.org]... at least at low doses. At high doses, it can cause the inverse effect, due to its GSK-3B and mTOR impacts. In general, though, it seems to typically be pro-autophagy.
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Maybe I won't provide sources, this isn't a journal and people nitpick about things.
If you decide never to refer to this source again it's definitively in your favor: Journal of American Physicians and Surgeons https://en.wikipedia.org/wiki/... [wikipedia.org]
Re:Couple of possibilities (Score:4, Funny)
Supplements? Just suck on your old phone / laptop batteries a few minutes a day, and you'll get all the lithium you need, and more. Also, if you're into experimental nootropics, just stop cleaning your bathroom and take microdoses of what appears on the walls, floors, and especially ceilings - some extra good stuff is available up there.
Re:Couple of possibilities (Score:4, Insightful)
I understand the conflict of interest but I also understand that someone believing in the benefits of some product to have some compulsion to get this to people, and that likely goes double for something that could be considered a benefit to health and quality of life as well as not having some barrier to entry like some laws restricting trade and production.
Consider someone with the belief that there's psychological benefits to avoiding loud noises, that exposure to noise is more than just a matter of protecting hearing. I'd expect this person to practice what they preach by offering extra sound deadening car mufflers, hearing protection such as earmuffs and ear buds, but perhaps draw the line at firearm suppressors as that's getting into federal laws and special licenses. (Though apparently the federal laws on firearm suppressors is changing soon.) Anyone preaching of the benefits of hearing protection and not in the business of selling hearing protection, such as being a kind of celebrity spokesperson for someone selling earmuffs, then they can likely expect to be approached at some point to provide some paid endorsement by someone already in the business of hearing protection.
If this guy is speaking loudly enough on the benefits of low dose lithium then at some point he's likely to be approached by some people that make mineral supplements to endorse their product. If he's smart enough, and has some business sense, then expect him to seek those making mineral supplements to fund his efforts to get the word out.
I don't know how we can separate the honest people from the scam artists when it comes to anything that impacts health. I could go on but I hope everyone gets the point by now. There's a fine line here and given the information that this guy could see personal enrichment as a result of him spreading his message does leave questions on motivations. Maybe such fears of being a scam artist could be mitigated by him having little to no ability to monopolize the market on lithium supplements, perhaps mitigated further in that he has a livable income from an unrelated source. In this case that income from being a chemistry professor.
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Lithium may be an essential micronutrient, needed in minute dose for vitamin b12 and folate transport and uptake https://www.jpands.org/vol20no... [jpands.org]
Lithium reacts strongly with mercury, https://pubs.rsc.org/en/conten... [rsc.org]
Wouldn't that make it react strongly with nitric oxides in the body induced by iNOS or eNOS? Not sure how it all relates to Alzheimers other than it disrupts the problem or provides something of a solution via those means, which it seems like they could precipitate fixing the root cause. Which they still haven't elucidated. Seems like that'd be the first major step (how can you fix a problem that you don't know what exactly is causing it?).
Are there any trends to suggest lithium was far more present in the past? Did or do we have a significant statistical rise in mental decline attributed more to time than population growth? Seems the first major step is to look at history. Where the answer may have already been provided. Or already discovered, and were too stupid or corrupt to learn it. Again.
When realizing we’re talking about the Medicated States of America and their Medical Industrial Complex, it gets a bit difficult discerning
Re:Couple of possibilities (Score:5, Informative)
Lithium is naturally present in the diet, but it varies by orders of magnitude depending on where you get your water and where your food was grown / grazed, with most people today on the lower end of the intake. Mineral spring waters in particular tend to be much richer in lithium than river / lake water, and also the fact that municipal water supplies' range limitations on the quantities of common minerals (sodium, potassium, calcium, etc) will also tend to reduce lithium, could be argued that, on average, the average person in the past might have consumed more. But it still would be quite varied on a regional basis.
Note that drinking lithiated water used to be a popular health trend [wikipedia.org]. Indeed, 7-Up was originally called 7up Lithiated Lemon Soda [wikipedia.org] (though the claim of being lithiated was actually a lie in their case, and they ultimately had to remove it!).
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Indeed, 7-Up was originally called 7up Lithiated Lemon Soda [wikipedia.org] (though the claim of being lithiated was actually a lie in their case, and they ultimately had to remove it!).
Rather sad that the 7-Up marketing story simply confirms how much snake oil was sold in the past AND how much it’s still being sold today. Look at fish oil. Only took one study to sell a planet on the idea they should be consuming cod liver oil daily. 7-Up flat out lied about it and sold it by the case. Should we believe lithium benefits, or no?
Alternatively, what is even worse in America is finding the known and proven being shit upon and destroyed. We used to make the claim that diet and exerc
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Alternatively, what is even worse in America is finding the known and proven being shit upon and destroyed. We used to make the claim that diet and exercise was key to a healthy life. Then the obesity movement herded around the idiotic notion of body positivity at any size and poof! No more need for physical exercise programs for kids who grow into highly-profitable obesitorians instead of adults.
Not just a US issue.. DDG Body positivity Europe. https://www.psychreg.org/body-... [psychreg.org] is just one of the results. Celebration of the morbidly obese and their inevitable young deaths is a world problem.
Now I’m left wondering if lithium was ultimately removed from our food and drink in the past because it was found to be a bit too beneficial.
Probably not. Using the US lithium in water supply maps, it will be pretty hard to do that. https://www.usgs.gov/news/nati... [usgs.gov]. https://pubs.acs.org/doi/10.10... [acs.org]
Already known is it's mental attributes of treating depression and bipolar, as well as reduced suicide rate. It may have an increase in autism, so pr
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In the recent past no one tracked most of these conditions that people get in old age. Alzheimers was first named in 1901. And a lot of people died young enough from various untreated common bacterial infections to reduce the size of the population old enough to even get Alzheimer's. Historical data is fairly limited, the data we have is at best poor to non-existent (not tracked, health so poor as to make what data that existed useless to compare), and for the most part we only even have useful data from
Finally (Score:3)
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Wrong type, the lithiums all went on fire.
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Finally a use for all those old batteries that won't charge anymore.
Yeah, but is it Lithium 6 or 7? THAT is the question! (Press 7 for batteries, press 6 for thermonuclear bombs. (See: Castle Bravo Test)
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(See: Castle Bravo Test)
Castle Bravo is a somewhat odd example to bring up in the context of Lithium 6 versus 7: Lithium 7 fissioning from high energy neutrons and producing tritium was the reason that Castle Bravo was 2.5x larger than expected.
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(See: Castle Bravo Test)
Castle Bravo is a somewhat odd example to bring up in the context of Lithium 6 versus 7: Lithium 7 fissioning from high energy neutrons and producing tritium was the reason that Castle Bravo was 2.5x larger than expected.
That's because the lithium made Castle Bravo really happy.
Re: Finally (Score:2)
No, it's dirt cheap and and a medical dose is tiny. You are really paying for the processing and testing and not so much for the material.
As I recall plaque isn't necessarily bad. (Score:1, Interesting)
I'll start with something of a joke on the need to mine more lithium domestically or we could run out of medications for varied mental disorders, because battery manufacturers are sucking up all demand.
With that out of the way...
I recall reading something, or maybe it was a TED talk, perhaps both, that spelled out how plaque on the brain wasn't necessarily a bad thing. Plaque is certainly an indication something is wrong but the treatment should not be based on the presence or absence of plaque but rather
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I can confirm... but I don't want to look up a link now. It just seems like solid science to me after hearing many podcasts, that many people are very lucid despite having lots of plaque, and others seem to have alzheimer's with little. There does seem to be a correlation, but I don't believe they have established a causation yet. On a side note, I have more hope in eating a good diet, walking, and mental exercises in preventing dementia, than in Lithium... a cure apparently being promoted by what seems to be a quack doctor.
My recollection is that the amount of mis-folded amyloid isn't a strong indicator of cognitive function; rather the existence of adequate amounts of properly folded protein is. If you're producing more, then you can have more of the bad stuff and still have enough of the good stuff to feed your neurons, basically. That said, larger amounts of mis-folded amyloid probably increases the rate at which the normal amyloid protein misfolds, assuming this is a prion situation, so there's likely some correlation t
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Another poster pointed out that lithium bonded with mercury, which I believe causes neurological disorders..
Elemental lithium does, but LiC5H3N2O4 is a salt, and, as I understand it, is not particularly reactive.
My chemistry knowledge is almost nonexistent, so all of this could be wrong, but here's what I think: Mercury is less reactive than lithium, so it won't take its place in a single-replacement reaction. Mercury is insoluble, so no double replacement, either. It's a salt, so no acid-base reaction. So unless a lithium salt somehow catalyzes oxidation of the elemental mercury, I wouldn't expect any reactio
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TL/DR, it affects the enzymes that regulate these processes [slashdot.org].
Re: As I recall plaque isn't necessarily bad. (Score:2)
I agree nutrition and exercise are the most important and best solutions even if the problem is lack of lithium in our diet.
The problem is our food is less and less vitamin and mineral dense every year.
Our soils are depleted of minerals, and hydroponic fertilizers typically contain even fewer.
It is sadly possible to eat exactly the foods you should, but still be vitamin/mineral deficient because of this.
I highly recommend a book called Soil, Grass, and Cancer. It's a
Didn't we know this a decade ago? (Score:3)
I'm looking at the abstract of an article [nih.gov] in the Journal of Alzheimer's Disease from 2015 that did a meta-analysis of placebo-controlled human trials of lithium in Alzheimer's patients that showed a statistically significant reduction in cognitive decline (albeit only barely significant at the 95% CI) from lithium supplementation, with approximately zero AEs.
It's not surprising that a mouse model study would support what human studies have already demonstrated, though I guess this is interesting in that it is presumably a larger study and more controlled than any meta-analysis would be.
One neat thing about this story is that the lithium salt that they chose (chosen because of its comparatively weak amyloid binding) is lithium orotate, which is commonly available over the counter as a dietary supplement from a rather large number of companies. If you have Alzheimer's and want to try it, there's literally nothing stopping you.
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It's not surprising that a mouse model study would support what human studies have already demonstrated, though I guess this is interesting in that it is presumably a larger study and more controlled than any meta-analysis would be.
Wait a minute. I just noticed something in the abstract that I missed on the first reading. They showed a reduction in plaques. The 2015 study showed no impact on CNS biomarkers. So apparently the specific lithium salt chosen might actually be critically important (or that effect might happen only in mice, or the presence of the biomarkers may not be correlated with the amount of plaque in the way that one might assume, or...).
How is BigPharma going to patent this now? (Score:2)
If ths is such a common salt, then it will be really problematic.
Just like with those Dutch researchers who could not find a way to patent ordinary sodium for certain cancer treatments.
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USA patent laws are awful. How can EpiPens be patent protected when epinephrine is a natural human hormone and not patentable and the rest of the EpiPen is a syringe, needle and spring?
That asshat who ramped up the epipens cost has competition now. A nasal spray. I dunno what the cost is, but competition can't hurt. https://www.neffy.com/ [neffy.com]
Must be good - look at how happy everyone in the ad is! 8^)
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If ths is such a common salt, then it will be really problematic. Just like with those Dutch researchers who could not find a way to patent ordinary sodium for certain cancer treatments.
Yes, being so common reduces the profit margin when yo9u can't patent it.
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Really annoying that lithium orotate became the standard way to deliver lithium, given that orotic acid is toxic and mutagenic :P
Re: Didn't we know this a decade ago? (Score:2)
Man, you should see what they do with fluor...
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Nothing weird about sodium fluoride, fluorosilicic acid, or sodium fluorosilicate. Sodium fluoride is a simple salt, dissociates immediately upon dissolution to Na+ and F-. Fluorosilicic acid and sodium fluorisilicate result in a fluorosilicate ion (SiF-2) which rapidly hydrolyzes to Si(OH)4 + 6F- + 4H+. Si(OH)4 (orthosilicic acid) is the form of soluble silicon which plants and diatoms consume and is perfectly normal in water in the tiny amounts from fluoridation (like 6 micromolar concentration). Ocean
lithium reversing cognitive decline (Score:1)
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All of the salts you listed fully dissociate in water.
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He switched his prescription from Lithium to Lead.
Treat causes not symptoms (Score:2)
If a lithium deficiency is the cause, then find out what causes a lithium deficiency. Or is there no money to be made in that?
Re: Treat causes not symptoms (Score:3)
Science works one step at a time. I suppose if you are interested into getting to the root cause of things, then consider funding research and give out grants instead of waiting for there to be a business motive. (So like a normal country and not like the US approach to everything)
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Oh dear, I didn't realize I said that if you can't solve everything with a single solution that we should give up. If I did, I'm terribly sorry because that would be completely wrong of me to say!
so one might say (Score:2)
Just like I keep saying... (Score:2)
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Only if you are the mouse that wasn't purposely modified to get alzheimers and the one getting the palcebo. They will forget about it anyway though I guess.
One study ? Fuck off. (Score:2)
That is good science reporting, which is good for science.