August 12, 2025 • 12 mins
What if one of the brain’s most important defenses was hiding in plain sight? In this episode, we take a look at lithium, a trace element found in water, food, and the brain itself. Long before brain scans, people made pilgrimages to lithium-rich springs, swearing the waters restored their health. A century later, it became a psychiatric drug. But new research from Harvard Medical School has uncovered something unique: lithium is a master regulator in the brain, and one of the earliest changes in Alzheimer’s disease is that it disappears. We follow the evidence from historical clues to modern lab discoveries, revealing how amyloid plaques trap lithium, how that loss accelerates neurodegeneration, and how restoring it at nutritional doses could help preserve memory (without the risks of high-dose therapy).
00:00 Introduction: The Mystery of Aging and Dementia
00:42 The History and Discovery of Lithium
01:31 Lithium's Role in Mental Health
01:53 Lithium and Cognitive Decline
03:18 Harvard's Breakthrough Research
05:01 Mechanisms of Lithium in the Brain
07:34 Clinical Studies and Trials
09:13 Nutritional Lithium: Dosage and Sources
11:22 Conclusion: implying the brain is exquisitely sensitive to Li levels.
PMID: 40770094
PMID: 17401045
PMID: 20148870
PMID: 18981345
PMID: 39212809
PMID: 22746245
PMID: 30066063
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
Across the globe there are pockets of people who
seem different, not in how theylive, but in how they age.
Decade after decade.
Their minds stay sharper, theirmemories clearer.
Rates of dementia aremysteriously lower here, and no
one could quite explain why,until someone tested the water.
Hidden in every glass was atrace of something unexpected.
(00:22):
Not a vitamin, not an exoticherb, a metal, one that most
people only associate withpsychiatric drugs.
But what if I told you it mightbe the brain's forgotten
nutrient.
(00:43):
The story of this element startsnot in a laboratory, but in
stone.
Lithium, from the Greek lithos,meaning stone, is the lightest
metal on earth and the thirdelement on the periodic table.
It scattered in trace amountsacross seawater, soil and rock
and seeps quietly into our foodand water.
In the 19th century, mineralsprings rich in lithium became
(01:06):
destinations for the sick andthe curious.
Visitors believed these waterscould soothe melancholy, calm
mania and heal inflamed joints.
Even soft drinks once carriedit.
The original 7-Up, launched in1929, contained lithium citrate,
marketed as a mood lifter andhangover cure.
That all ended when thegovernment banned lithium in
(01:29):
beverages in the late 1940s.
But its medical story was justbeginning.
In 1947, australianpsychiatrist John Cade stumbled
on lithium's calming effects inguinea pigs, a finding that
would lead to its adoption as agold standard treatment.
Or bipolar disorder.
By the 1970s, lithium had FDAapproval for psychiatric use.
(01:50):
Then came an unexpected cluePsychiatrists began noticing
that bipolar patients takinglithium long-term seemed to have
lower rates of cognitivedecline.
Early studies backed this up.
In one group of elderly bipolarpatients, just 5% of those on
lithium had Alzheimer's disease,compared to 33% of those not
(02:11):
taking lithium.
Large registry studies inDenmark and observational work
in Japan and Texas pointed thesame way.
The higher the lithium in thelocal water supply, the lower
the rates of dementia.
In fact, a 2024 systematicreview pulling five separate
observational studies found thateven trace lithium, between
(02:32):
just 2 and 56 micrograms perliter in drinking water, was
associated with lower incidenceand mortality from dementia.
These aren't therapeutic doses.
These are environmentalwhispers of lithium present in
the background of daily life,and yet somehow they seem to tip
the odds in favor of a longer,sharper model.
(02:54):
For decades these findings saton the fringe, intriguing but
without clear explanation untilrecently.
What is the earliest spark thatignites the memory-robbing
march of Alzheimer's disease?
Why do some people withAlzheimer's-like changes in
their brains never developdementia, while others decline
rapidly.
(03:15):
For decades that trail ran cold.
Now, after 10 years of work, ateam at Harvard Medical School
believes they've found themissing link Lithium, not as a
drug, but as a naturallyoccurring brain nutrient.
In a series of studiespublished in the journal Nature,
they showed for the first timethat lithium exists in the human
(03:36):
brain at biologicallymeaningful levels, shields it
from neurodegeneration and helpsmaintain the health of every
major brain cell type.
And here's the twist One of thevery first changes in
Alzheimer's disease is thatlithium disappears In brain
tissue.
From healthy donors, lithium wasabundant, but in people with
mild cognitive impairment, oftenthe earliest stage of
(03:59):
Alzheimer's, levels had alreadyplummeted.
In advanced Alzheimer's theywere even lower.
The culprit Amyloid betaplaques, acting like molecular
sponges trapping lithium androbbing surrounding cells of its
protective functions.
In mice, the same patternemerged.
When researchers fed healthymice a lithium-restricted diet,
(04:22):
their brain lithium fell toAlzheimer's-like levels.
The results were striking Moreamyloid plaques, more tau
tangles, myelin thinning,synapse loss, inflammation and
faster memory decline.
Gene activity shifted acrossthe entire brain In microglia
neurons, oligodendrocytes,astrocytes, even blood vessel
(04:44):
cells, to resemble theAlzheimer's disease profile At
doses one in a dozen correlatedwith disease.
It drove no toxicity over ayear.
So how does lithium actuallykeep the plaque chain resilient?
What goes wrong when it's gone?
Unlike standard lithium, corelithium acts as a massive
amyloid inside the brain,restoring lithium to the brain's
(05:07):
important jaw and protectingthe reactivity of an aging
wild-type and Alzheimer's modelIn mice.
Lithium-portrait-basedinflammation reactivated
microbreed.
A clear amyloid deservessynapses and restored memory,
even in older animals withlithium-1 disease, as they do in
the earliest stages ofAlzheimer's.
Glycogen synthase kinase 3 betaruns unchecked.
(05:30):
The result it accelerates theproduction of amyloid.
Beta, drives tau proteins intotheir toxic tangle-forming state
and disrupts the molecularprograms that keep synapses,
axons and myelin intact.
Lithium's influence is broaderthan one enzyme.
It alters the transcriptome,that's the full set of genes
being switched on and off acrossevery major brain cell type.
(05:53):
It keeps microglia, the brain'simmune cells, in a balanced
state where they can clearamyloid without triggering
chronic inflammation.
Without lithium, those samemicroglia become overactive and
ineffective, releasing damagingcytokines while letting amyloid
pile up.
In humans without Alzheimer's,higher cortical lithium levels
(06:14):
correlate with greaterexpression of presynaptic
proteins like complexin 1 and 2,important for maintaining
healthy synaptic communication,and with stronger performance on
working memory tests.
That's a clue that lithiumhomeostasis isn't just chemistry
.
It's tied directly to cognitiveresilience.
If that still feels abstract,picture a city.
(06:36):
Lithium is the combination ofthe power grid manager, traffic
controller and the sanitationdepartment.
It keeps the lights on, ensurestraffic flows and makes sure
the garbage gets picked upbefore it causes problems.
When amyloid plaques traplithium, it's like locking the
control room and cutting thepower.
The lights flicker, trafficsnarls and trash piles up in the
(06:59):
streets.
Traffic snarls and trash pilesup in the streets.
Restoring lithium is likeflipping the breakers and
sending out the cleanup crews,allowing the city, or in this
case the brain, to functionsmoothly.
This wasn't the first timelithium had left a trail of
clues.
Decades earlier, a largepopulation study in Denmark
found a clear patternCommunities with more lithium in
their drinking water had lowerrates of dementia.
(07:21):
Other work in Japan, texas andScotland hinted at the same
relationship.
At the time no one couldexplain why, but the Harvard
team's findings now fit thatpuzzle piece exactly.
Clinical studies also had beensending up flares.
In some trials, lithiumprevented or even reversed
cognitive decline in Alzheimer'spatients, though not every
(07:43):
study was successful.
One limitation we now know mayhave been the type of lithium
salt.
Standard forms, like lithiumcarbonate, can be trapped by
amyloid plaques, never reachingthe parts of the brain where
they're needed.
Even so, the signals were there.
In 2013, a randomized controltrial showed that taking just
(08:04):
300 micrograms a day of lithiumorotate a true microdose
stabilized cognition inAlzheimer's patients for 15
months, while the placebo groupcontinued to decline In mild
cognitive impairment.
Higher dose trials lasting oneto two years not only improved
cognitive performance andattention, but also reduced
(08:25):
levels of hyperphosphorylatedtau in the cerebral spinal fluid
, important Alzheimer's marker.
Remarkably, participants onlithium stayed stable even after
the study ended, while those onplacebo continued to
deteriorate.
Ended, while those on placebocontinued to deteriorate.
A meta-analysis of eightclinical trials later found that
(08:47):
lithium treatment might even besafer than newer monoclonal
antibody drugs for Alzheimer's,which often come with serious
side effects.
Looking back, the pattern isobvious.
Population studies, smallclinical trials and now the
Harvard team's mechanistic workall point to the same conclusion
Lithium isn't just a moodstabilizer.
It may be a fundamental piece ofthe brain's defense system, one
(09:07):
that's been hiding in plainsight.
If lithium is part of thebrain's defense system, how do
we make sure we're gettingenough and safe?
The answer starts withunderstanding that the body
handles lithium very differently, at low and high doses.
In psychiatry, lithium isprescribed at doses 50 to 300
(09:27):
times higher than what wenaturally get from food or water
.
At those levels, it acts like adrug powerful, but with the
potential for side effects thatrequire careful monitoring.
Nutritional lithium operates ina different range.
Entirely Based on decades oftrace element research, gerhard
Schrauser, one of the pioneersin this field, proposed a
(09:50):
provisional recommended dailyallowance of about 1 milligram
or 1,000 micrograms of elementallithium.
This figure wasn't plucked fromthin air.
It comes from comparing intakesin regions with robust mental
and cognitive health to thosewith deficiency.
In the US, typical dietaryintake is estimated to be
(10:10):
between 600 micrograms to 3.1milligrams per day, with some
populations, like those in theAndes, consuming up to 30
milligrams a day without signsof harm.
Schrauser's 1 milligram targetwas meant as a safe,
conservative baseline that stillsupports lithium's known roles
in human biology.
At these levels, lithiumassists with vitamin B12 and
(10:32):
folate transport into cells.
It modulates neurotrophicfactors and helps maintain the
brain's chemical balance, allwithout the risks associated
with pharmacological dosing.
In over 40 years of use inEurope and the US, low-dose
forms like lithium orotate havenot been linked to serious side
effects.
Natural sources include foodstraditionally regarded as
(10:56):
neurotonics cacao, oats, seafood, seaweed, goji berries, various
fruits and vegetables,depending on the soil they were
grown in, and egg yolks, withlocal drinking water often
contributing a significant share.
The main takeaway is that thedose makes the difference Too
little and the brain'sprotective systems weaken Too
(11:17):
much, and you're in drugterritory.
In between lies a possiblesweet spot, one that ongoing
research is now trying to define.
The clues were scatteredPopulation studies, small
clinical trials, unexplainedresilience in certain patients
but together they point to asimple truth Lithium isn't just
(11:37):
a psychiatric drug.
It may be an essential brainmicronutrient, one that helps
keep machinery of memory running.
The Harvard team's work doesn'tjust explain decades of curious
observation.
It opens the door to newstrategies for prevention
observation.
It opens the door to newstrategies for prevention, early
detection and maybe evenreversal of Alzheimer's disease.
(11:58):
The challenge now istranslating this into human
clinical trials, defining theright dose and learning how to
protect lithium's place in thebrain before it's lost, because
if lithium is part of thebrain's operating system, then
maintaining it isn't justchemistry, it's maintenance for
the mind itself.
Until next time, stay sharp andstay healthy.
Across the globe there are pockets of people who
seem different, not in how theylive, but in how they age.
Decade after decade.
Their minds stay sharper, theirmemories clearer.
Rates of dementia aremysteriously lower here, and no
one could quite explain why,until someone tested the water.
Hidden in every glass was atrace of something unexpected.
(00:22):
Not a vitamin, not an exoticherb, a metal, one that most
people only associate withpsychiatric drugs.
But what if I told you it mightbe the brain's forgotten
nutrient.
(00:43):
The story of this element startsnot in a laboratory, but in
stone.
Lithium, from the Greek lithos,meaning stone, is the lightest
metal on earth and the thirdelement on the periodic table.
It scattered in trace amountsacross seawater, soil and rock
and seeps quietly into our foodand water.
In the 19th century, mineralsprings rich in lithium became
(01:06):
destinations for the sick andthe curious.
Visitors believed these waterscould soothe melancholy, calm
mania and heal inflamed joints.
Even soft drinks once carriedit.
The original 7-Up, launched in1929, contained lithium citrate,
marketed as a mood lifter andhangover cure.
That all ended when thegovernment banned lithium in
(01:29):
beverages in the late 1940s.
But its medical story was justbeginning.
In 1947, australianpsychiatrist John Cade stumbled
on lithium's calming effects inguinea pigs, a finding that
would lead to its adoption as agold standard treatment.
Or bipolar disorder.
By the 1970s, lithium had FDAapproval for psychiatric use.
(01:50):
Then came an unexpected cluePsychiatrists began noticing
that bipolar patients takinglithium long-term seemed to have
lower rates of cognitivedecline.
Early studies backed this up.
In one group of elderly bipolarpatients, just 5% of those on
lithium had Alzheimer's disease,compared to 33% of those not
(02:11):
taking lithium.
Large registry studies inDenmark and observational work
in Japan and Texas pointed thesame way.
The higher the lithium in thelocal water supply, the lower
the rates of dementia.
In fact, a 2024 systematicreview pulling five separate
observational studies found thateven trace lithium, between
(02:32):
just 2 and 56 micrograms perliter in drinking water, was
associated with lower incidenceand mortality from dementia.
These aren't therapeutic doses.
These are environmentalwhispers of lithium present in
the background of daily life,and yet somehow they seem to tip
the odds in favor of a longer,sharper model.
(02:54):
For decades these findings saton the fringe, intriguing but
without clear explanation untilrecently.
What is the earliest spark thatignites the memory-robbing
march of Alzheimer's disease?
Why do some people withAlzheimer's-like changes in
their brains never developdementia, while others decline
rapidly.
(03:15):
For decades that trail ran cold.
Now, after 10 years of work, ateam at Harvard Medical School
believes they've found themissing link Lithium, not as a
drug, but as a naturallyoccurring brain nutrient.
In a series of studiespublished in the journal Nature,
they showed for the first timethat lithium exists in the human
(03:36):
brain at biologicallymeaningful levels, shields it
from neurodegeneration and helpsmaintain the health of every
major brain cell type.
And here's the twist One of thevery first changes in
Alzheimer's disease is thatlithium disappears In brain
tissue.
From healthy donors, lithium wasabundant, but in people with
mild cognitive impairment, oftenthe earliest stage of
(03:59):
Alzheimer's, levels had alreadyplummeted.
In advanced Alzheimer's theywere even lower.
The culprit Amyloid betaplaques, acting like molecular
sponges trapping lithium androbbing surrounding cells of its
protective functions.
In mice, the same patternemerged.
When researchers fed healthymice a lithium-restricted diet,
(04:22):
their brain lithium fell toAlzheimer's-like levels.
The results were striking Moreamyloid plaques, more tau
tangles, myelin thinning,synapse loss, inflammation and
faster memory decline.
Gene activity shifted acrossthe entire brain In microglia
neurons, oligodendrocytes,astrocytes, even blood vessel
(04:44):
cells, to resemble theAlzheimer's disease profile At
doses one in a dozen correlatedwith disease.
It drove no toxicity over ayear.
So how does lithium actuallykeep the plaque chain resilient?
What goes wrong when it's gone?
Unlike standard lithium, corelithium acts as a massive
amyloid inside the brain,restoring lithium to the brain's
(05:07):
important jaw and protectingthe reactivity of an aging
wild-type and Alzheimer's modelIn mice.
Lithium-portrait-basedinflammation reactivated
microbreed.
A clear amyloid deservessynapses and restored memory,
even in older animals withlithium-1 disease, as they do in
the earliest stages ofAlzheimer's.
Glycogen synthase kinase 3 betaruns unchecked.
(05:30):
The result it accelerates theproduction of amyloid.
Beta, drives tau proteins intotheir toxic tangle-forming state
and disrupts the molecularprograms that keep synapses,
axons and myelin intact.
Lithium's influence is broaderthan one enzyme.
It alters the transcriptome,that's the full set of genes
being switched on and off acrossevery major brain cell type.
(05:53):
It keeps microglia, the brain'simmune cells, in a balanced
state where they can clearamyloid without triggering
chronic inflammation.
Without lithium, those samemicroglia become overactive and
ineffective, releasing damagingcytokines while letting amyloid
pile up.
In humans without Alzheimer's,higher cortical lithium levels
(06:14):
correlate with greaterexpression of presynaptic
proteins like complexin 1 and 2,important for maintaining
healthy synaptic communication,and with stronger performance on
working memory tests.
That's a clue that lithiumhomeostasis isn't just chemistry
.
It's tied directly to cognitiveresilience.
If that still feels abstract,picture a city.
(06:36):
Lithium is the combination ofthe power grid manager, traffic
controller and the sanitationdepartment.
It keeps the lights on, ensurestraffic flows and makes sure
the garbage gets picked upbefore it causes problems.
When amyloid plaques traplithium, it's like locking the
control room and cutting thepower.
The lights flicker, trafficsnarls and trash piles up in the
(06:59):
streets.
Traffic snarls and trash pilesup in the streets.
Restoring lithium is likeflipping the breakers and
sending out the cleanup crews,allowing the city, or in this
case the brain, to functionsmoothly.
This wasn't the first timelithium had left a trail of
clues.
Decades earlier, a largepopulation study in Denmark
found a clear patternCommunities with more lithium in
their drinking water had lowerrates of dementia.
(07:21):
Other work in Japan, texas andScotland hinted at the same
relationship.
At the time no one couldexplain why, but the Harvard
team's findings now fit thatpuzzle piece exactly.
Clinical studies also had beensending up flares.
In some trials, lithiumprevented or even reversed
cognitive decline in Alzheimer'spatients, though not every
(07:43):
study was successful.
One limitation we now know mayhave been the type of lithium
salt.
Standard forms, like lithiumcarbonate, can be trapped by
amyloid plaques, never reachingthe parts of the brain where
they're needed.
Even so, the signals were there.
In 2013, a randomized controltrial showed that taking just
(08:04):
300 micrograms a day of lithiumorotate a true microdose
stabilized cognition inAlzheimer's patients for 15
months, while the placebo groupcontinued to decline In mild
cognitive impairment.
Higher dose trials lasting oneto two years not only improved
cognitive performance andattention, but also reduced
(08:25):
levels of hyperphosphorylatedtau in the cerebral spinal fluid
, important Alzheimer's marker.
Remarkably, participants onlithium stayed stable even after
the study ended, while those onplacebo continued to
deteriorate.
Ended, while those on placebocontinued to deteriorate.
A meta-analysis of eightclinical trials later found that
(08:47):
lithium treatment might even besafer than newer monoclonal
antibody drugs for Alzheimer's,which often come with serious
side effects.
Looking back, the pattern isobvious.
Population studies, smallclinical trials and now the
Harvard team's mechanistic workall point to the same conclusion
Lithium isn't just a moodstabilizer.
It may be a fundamental piece ofthe brain's defense system, one
(09:07):
that's been hiding in plainsight.
If lithium is part of thebrain's defense system, how do
we make sure we're gettingenough and safe?
The answer starts withunderstanding that the body
handles lithium very differently, at low and high doses.
In psychiatry, lithium isprescribed at doses 50 to 300
(09:27):
times higher than what wenaturally get from food or water
.
At those levels, it acts like adrug powerful, but with the
potential for side effects thatrequire careful monitoring.
Nutritional lithium operates ina different range.
Entirely Based on decades oftrace element research, gerhard
Schrauser, one of the pioneersin this field, proposed a
(09:50):
provisional recommended dailyallowance of about 1 milligram
or 1,000 micrograms of elementallithium.
This figure wasn't plucked fromthin air.
It comes from comparing intakesin regions with robust mental
and cognitive health to thosewith deficiency.
In the US, typical dietaryintake is estimated to be
(10:10):
between 600 micrograms to 3.1milligrams per day, with some
populations, like those in theAndes, consuming up to 30
milligrams a day without signsof harm.
Schrauser's 1 milligram targetwas meant as a safe,
conservative baseline that stillsupports lithium's known roles
in human biology.
At these levels, lithiumassists with vitamin B12 and
(10:32):
folate transport into cells.
It modulates neurotrophicfactors and helps maintain the
brain's chemical balance, allwithout the risks associated
with pharmacological dosing.
In over 40 years of use inEurope and the US, low-dose
forms like lithium orotate havenot been linked to serious side
effects.
Natural sources include foodstraditionally regarded as
(10:56):
neurotonics cacao, oats, seafood, seaweed, goji berries, various
fruits and vegetables,depending on the soil they were
grown in, and egg yolks, withlocal drinking water often
contributing a significant share.
The main takeaway is that thedose makes the difference Too
little and the brain'sprotective systems weaken Too
(11:17):
much, and you're in drugterritory.
In between lies a possiblesweet spot, one that ongoing
research is now trying to define.
The clues were scatteredPopulation studies, small
clinical trials, unexplainedresilience in certain patients
but together they point to asimple truth Lithium isn't just
(11:37):
a psychiatric drug.
It may be an essential brainmicronutrient, one that helps
keep machinery of memory running.
The Harvard team's work doesn'tjust explain decades of curious
observation.
It opens the door to newstrategies for prevention
observation.
It opens the door to newstrategies for prevention, early
detection and maybe evenreversal of Alzheimer's disease.
(11:58):
The challenge now istranslating this into human
clinical trials, defining theright dose and learning how to
protect lithium's place in thebrain before it's lost, because
if lithium is part of thebrain's operating system, then
maintaining it isn't justchemistry, it's maintenance for
the mind itself.
Until next time, stay sharp andstay healthy.
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