Lithium and and brain health

DavidPS

This is another instance of what is old is new again. Lithium has been known to benefit the brain. Small amount of lithium found in the water table had great benefit.

Review of Lithium Effects on Brain and Blood (2009)

Recently, scientist as Harvard have found that lithum helps with Alzehimers disease. I would have thought that the using lithium would have been obivious to try. But maybe that is just the benfit of hindsight.

Lithium deficiency and the onset of Alzheimer’s disease (2025)

The earliest molecular changes in Alzheimer’s disease (AD) are poorly understood1,2,3,4,5. Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration. We explored the role of endogenous Li in the brain by depleting it from the diet of wild-type and AD mouse models. Reducing endogenous cortical Li by approximately 50% markedly increased the deposition of amyloid-β and the accumulation of phospho-tau, and led to pro-inflammatory microglial activation, the loss of synapses, axons and myelin, and accelerated cognitive decline. These effects were mediated, at least in part, through activation of the kinase GSK3β. Single-nucleus RNA-seq showed that Li deficiency gives rise to transcriptome changes in multiple brain cell types that overlap with transcriptome changes in AD. 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. These findings reveal physiological effects of endogenous Li in the brain and indicate that disruption of Li homeostasis may be an early event in the pathogenesis of AD. Li replacement with amyloid-evading salts is a potential approach to the prevention and treatment of AD.

LucH

@DavidPS

DavidPS said

Lithium has been known to benefit the brain. Small amount of lithium found in the water table had great benefit.
Excerpts from the study (main points):
Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration.
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.
These findings reveal physiological effects of endogenous Li in the brain and indicate that disruption of Li homeostasis may be an early event in the pathogenesis of AD. Li replacement with amyloid-evading salts is a potential approach to the prevention and treatment of AD.

Analyze
Yes, but …
The amount is so light that it’s hard to measure without an appropriate tool.
I’ve decided to make a search with LucH’s pendulum (1) when I saw last month an article in a medical review.
We have to make a distinction between a pathology (AD) and cognitive preservation by anticipation.
First, note that the improvement has been obtained on mice. Not only, but well in the referenced study. The improvement observed in the axons is fine / real but there is no feedback on the long term. A mouse doesn’t talk and doesn’t feel good but shows an ability to target sth (behavior to recognize, to memorize a way to get a sweat).
The mouse acts in order to obtain a reward in the form of food or a punishment when it makes a mistake.

I explain the restriction:
Synaptic reuptake is a key process for regulating neurotransmitter concentration in the synapse. Lithium acts on this process to modulate neuronal activity.
How much lithium is found in brain axons and how much is sequestered by cortical amyloid plaques has been studied. It has been done with human beings. See further details on the link beneath.
For the other readers:
Overall, lithium readjusts the balances between excitatory and inhibitory neurotransmission, as well as between catecholamines and acetylcholine. It is the adjustment of these balances, rather than the isolated effect on a single neurotransmitter, that partly allows for the improvement and stabilization of mood. End of the parenthesis.

Dose range
The effective dose range for lithium is relatively narrow, and exceeding it can lead to adverse effects. The specific mechanisms by which lithium exerts its effects on the brain are still under investigation (…). In case of supplementation, toxic effects are to be expected, such as concentration problems, but not only that.
Plasma concentration is reached within 2 to 4 hours after oral administration of a supplement. (1) The plasma half-life is approximately 24 hours. Equilibrium is reached between the 5th and 8th day. More quickly if the kidneys' elimination capacity is reduced. Be careful, apprentice chemists, especially in the case of insufficient sodium intake.

Final thought:
Yes, Li is a cofactor in the absorption of certain vitamins, helps the body produce serotonin, supports the transmission of neural messages and much more.
But I’d rather try to get my Li through food, provided you don’t suffer from intolerance, as there is a lot of Li in milk, cheese, eggs and sea food or liver (chicken or beef).
Not yet official, but lithium is gradually being considered an essential trace element, with a recommended daily intake of 1 mg for a 70 kg adult. (2)
Studies also suggest that lithium's effectiveness depends on the availability of other minerals and works synergistically with them to maximize its effectiveness on mood, longevity, and cognitive support. (3)
In another human study, a daily microdose of just 300 mcg of lithium was found to significantly reduce age-related cognitive decline just three months after starting a lithium supplement. (4)
NB1: Alzheimer is a complex pathology. We need to act in many directions.
In short: exercise (mental and physical), K2 MK4, tocos, iodine and other well-known ones. For another article.
NB2: I won’t trust a labo when they say lithium orotate could do the job. (5) Low supplementation (e.g., 5 to 20 mg/day of lithium orotate) may produce transient or subtle effects, but does not guarantee stable maintenance of brain levels.

Sources & references

My article on lithium
https://mirzoune-ciboulette.forumactif.org/t2124-le-lithium-ameliore-l-humeur-optimise-les-cellules-souches-la-longevite-et-plus-encore#30285
Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr, 2002) DOI: 10.1080/07315724.2002.10719188
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443601/
https://pubmed.ncbi.nlm.nih.gov/22746245/
Une supplémentation faible (ex : 5 à 20 mg/jour de lithium orotate) peut produire des effets transitoires ou subtils, mais ne garantit pas un maintien stable des niveaux dans le cerveau (cf. étude Human brain 7Li-MRI: 10 à 60 µM, stable après 2-4 semaines).
Human brain 7Li-MRI following low-dose lithium dietary supplementation in healthy participants - ScienceDirect 2024