Lithium and Brain Health: Could a Deficiency Raise Alzheimer’s Risk?

 A big warning buried in here: Lithium Is NOT Benign! Read all of this and grill your doctor on it.

Lithium and Brain Health: Could a Deficiency Raise Alzheimer’s Risk?

Here's a fascinating question: could lithium deficiency contribute to cognitive impairment? Is there a link between lithium and brain health?

Most healthcare professionals think about lithium, if they think about it at all, as the stuff in rechargeable batteries or as a powerful prescription drug for bipolar disorder. They probably do not think about lithium and brain health or imagine that too little of this natural mineral might have anything to do with Alzheimer’s disease. New research suggests it may be time to reconsider that assumption.

That idea is especially surprising because lithium is not officially recognized as an essential nutrient. There is no Recommended Dietary Allowance for lithium. Doctors do not routinely measure lithium levels in healthy people. There is no recognized “lithium deficiency disease” comparable to iron-deficiency anemia or vitamin D deficiency.

And yet a remarkable study published in Nature (August 6, 2025), raised a provocative possibility: tiny amounts of naturally occurring lithium may play an important role in keeping the aging brain healthy.

The title alone should have attracted enormous attention:

“Lithium deficiency and the onset of Alzheimer’s disease“

This was not a casual experiment carried out by investigators in a small lab in a foreign country. The research involved investigators from Harvard Medical School, Boston Children’s Hospital and the Rush Alzheimer’s Disease Center. They examined human brains as well as sophisticated mouse models of Alzheimer’s disease.

Lithium and Brain Health: A Mineral Hiding in Plain Sight?

Lithium is a naturally occurring element. It is found in rocks and soil. As a result, lithium gets into groundwater, drinking water, food and us. Unlike calcium, magnesium, iron or zinc, however, lithium has never achieved membership in the official essential-nutrient club.

Perhaps that is because the amounts normally present in the body are extraordinarily small. The lithium concentrations used to treat bipolar disorder, on the other hand, are vastly greater than the trace amounts normally circulating in people. The dose of lithium found in the prescription drug LITHOBID® prescribed for “manic episodes of Bipolar Disorder” is:

“3 tabs (900 mg) Morning” and “3 tabs (900 mg) Nighttime”

That’s a whopping 1,800 mg of lithium carbonate (or roughly 340 mg of pure lithium). There is considerable toxicity associated with this high dose of lithium and the boxed warning that comes with LITHOBID® (lithium carbonate) states:

WARNING

“Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy.”

For decades, most medical interest in lithium has revolved around lithium the medication, not lithium the nutrient-like trace element.

If you would like to get a thorough background about the history of lithium dating back to the 19th century, you will want to read my prior article titled:

“Rediscovering Low-Dose Lithium for Mood Disorders“

You may be surprised to learn that the original soft drink “Seven Up” was once called 7UP Lithiated Lemon Soda. It has been estimated that the original formula contained 5 mg of lithium citrate. One marketing slogan was: “It takes the ouch out of the grouch.”

There is no lithium in the current 7UP!

Fast forward to Harvard researchers and their article a year ago in Nature (August 6, 2025).

What Did the Researchers Find in Human Brains?

The scientists measured 27 metals in the blood and brains of older people who had normal cognition, mild cognitive impairment (MCI) or Alzheimer’s disease. MCI is important because it can represent an early stage on the road toward dementia.

Of all the metals measured, lithium stood out. It was the only metal significantly reduced in the prefrontal cortex in both MCI and Alzheimer’s disease. That is intriguing enough. But there was another surprise.

Blood levels of lithium were not significantly lower in people with MCI or Alzheimer’s disease.

In other words, this was not simply a matter of people having less lithium circulating throughout their bodies. Something seemed to be happening specifically inside vulnerable parts of the brain. The investigators discovered a possible explanation: amyloid plaques appeared to trap lithium.

Amyloid beta is the sticky protein that accumulates in the brains of people with Alzheimer’s disease. The researchers found lithium concentrated in those deposits, leaving less lithium available to surrounding brain tissue. That raises the possibility of a nasty feedback loop:

Alzheimer’s pathology begins → amyloid traps lithium → less lithium remains available to brain cells → the shortage may make Alzheimer’s pathology worse → still more amyloid accumulates.

That is a hypothesis, not established medical fact. But it is a fascinating one.

Lithium and Brain Health: What Happens When the Brain Doesn’t Get Enough Lithium?

Here is where the research becomes quite intriguing. The investigators deliberately reduced lithium in the diets of mice. This lowered lithium levels in the cerebral cortex by roughly half. The consequences were dramatic.

Lithium depletion increased two hallmarks of Alzheimer’s disease:

• Amyloid beta, which forms plaques
• Phosphorylated tau, which contributes to the tangles found inside nerve cells

That was only part of the story. Lithium deficiency also activated inflammatory cells in the brain called microglia. I have to be honest with you. I am totally fascinated by microglia. Think of these cells as part of the brain’s housekeeping and immune system.

This is not a perfect analogy, but for our purposes you could imagine microglia as minute vacuum cleaners, sucking up debris, old cellular brain fragments and even infectious agents. In other words, they are part of the brain’s immune defense against pathogens. They also help dispose of the brain’s cellular debris, including amyloid.

When lithium became deficient, these cells shifted toward a more inflammatory state and became less effective at clearing amyloid. The lithium-depleted animals also lost synapses, axons and myelin. Synapses allow brain cells to communicate. Axons carry electrical messages. Myelin is the insulation surrounding many of those nerve fibers.

Here’s the key piece to the puzzle. The mice experienced accelerated memory and cognitive problems. That is a remarkable collection of results from reducing one trace element that most nutrition experts think is unimportant.

A Possible Culprit: GSK-3 Beta

Now we must take a brief foray into neuroscience. Please don’t let the alphabet soup scare you away. An enzyme called glycogen synthase kinase-3 beta, thankfully abbreviated GSK-3β, appears to play a key role in several processes associated with Alzheimer’s disease.

Among other things, excessive GSK-3β activity can contribute to abnormal phosphorylation of tau. Along with amyloid beta, phosphorylated tau is considered an important marker of Alzheimer’s disease. Consider this: The FDA has approved blood tests that measure phosphorylated tau. In its May 16, 2025 announcement the agency offered this headline:

“FDA Clears First Blood Test Used in Diagnosing Alzheimer’s Disease”

New Test Provides Less Invasive Option, Reduces Reliance on PET Scans and Increases Diagnosis Accessibility

Lithium and Brain Health

Lithium has been known to affect the enzyme GSK-3β. The Harvard investigators found that lithium deficiency increased GSK-3β activity in brain cells. When they blocked GSK-3β experimentally, they reversed many of the harmful effects produced by lithium deficiency. This included improvements in amyloid accumulation, tau abnormalities, inflammation and myelin problems.

That provides something scientists always want: a plausible biological mechanism. It does not, however, prove that taking lithium will prevent Alzheimer’s disease in human beings. That distinction is crucial.

Then Came Lithium Orotate

Perhaps the most intriguing part of the Nature experiment involved different forms of lithium.

The prescription form most people know is lithium carbonate. It is the form of lithium that is used by psychiatrists to treat people with bipolar disorder.

The Harvard scientists used lithium orotate.

Here is how they described their findings with regard to Alzheimer’s disease (AD):

“Replacement therapy with lithium orotate, which is a Li [lithium] 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.”

Their experiments suggested that lithium carbonate was more readily trapped by amyloid deposits. Lithium orotate appeared less likely to become sequestered in plaques and consequently delivered more lithium to the surrounding brain tissue.

When researchers gave extremely small amounts of lithium orotate to Alzheimer’s-prone mice, the results were impressive. In one model, lithium orotate nearly prevented the accumulation of amyloid and abnormal tau when given before substantial disease developed. In older animals that already had extensive pathology, treatment reduced amyloid deposits substantially.

In aging mice without genetically engineered Alzheimer’s disease, lithium orotate also helped preserve synapses and memory. Even more surprising, the doses were designed to keep lithium concentrations in the range naturally found in the body rather than the much higher blood concentrations used to treat bipolar disorder.

Long-term treatment at these tiny doses did not produce detectable changes in the kidney and thyroid laboratory tests the investigators monitored in the mice. Please notice the last three words in that sentence: “in the mice.”

We cannot automatically assume that the same dose, safety or brain benefits would apply to people. That is why clinical trials matter!

What About Human Evidence Re: Lithium and Brain Health?

Fortunately, the lithium story does not depend entirely upon laboratory animals. There have been some intriguing human clues for years. One of the largest comes from Denmark (JAMA Psychiatry, Oct. 1, 2017).

Investigators compared lithium concentrations in drinking water with dementia diagnoses in 73,731 people with dementia and 733,653 controls.

People exposed over the long term to the highest category of lithium in drinking water had a lower rate of dementia than people in the lowest category:

“Long-term increased lithium exposure in drinking water may be associated with a lower incidence of dementia in a nonlinear way…”

But there was a wrinkle. The relationship was not linear. An intermediate exposure group actually had a higher rate of dementia than the lowest group. The investigators therefore appropriately warned that geography, socioeconomic factors or other unmeasured differences might have influenced the results.

That study should prevent anyone from making the simplistic argument that “more lithium in the water equals less dementia.” It isn’t that straightforward.

Another observational study from England found that people exposed to prescription lithium had a lower incidence of dementia (PLoS Medicine, March 17, 2022).

The conclusions:

“We observed an association between lithium use and a decreased risk of developing dementia. This lends further support to the idea that lithium may be a disease-modifying treatment for dementia and that this is a promising treatment to take forwards to larger randomised controlled trials (RCTs) for this indication.”

A “systematic review” of “Trace lithium levels in drinking water and risk of dementia” published in the International Journal of Bipolar Disorders (Aug. 30, 2024) concluded:

“The reviewed evidence shows that trace-Li levels in the water are sufficient to lower the incidence or mortality from dementia. Considering the lack of options for the prevention or treatment of dementia, we should not ignore these findings. Future trials of Li should focus on long term use of low or even micro doses of Li in the prevention or treatment of dementia.”

Again, however, observational research can identify an association. It cannot prove cause and effect. It can encourage investigators to perform large-scale, long-term randomized clinical trials.

One relatively small “pilot” clinical trial produced disappointing results (JAMA Neurology, April 1, 2026). There were 41 people getting lithium carbonate (150 or 300 mg of lithium carbonate) and 39 getting placebo. There was no meaningful benefit for those getting lithium.

Were Researchers Studying the Wrong Dose…and the Wrong Lithium?

The Harvard 2025 Nature experiment was not testing conventional psychiatric doses of lithium carbonate. It was investigating something fundamentally different: restoration of lithium concentrations toward the extraordinarily low levels normally present in brain tissue. It also found that lithium orotate behaved differently from lithium carbonate in the presence of amyloid.

That raises a question worth answering:

Would truly tiny doses of lithium orotate protect the human brain without producing the adverse effects associated with much larger doses of lithium carbonate?

We don’t know. Nobody should pretend that we do. But in June 2026, a review in JAMA Psychiatry made almost exactly that point:

“The 25-Year Evolution of Lithium as a Disease-Modifying Agent in Dementia”

The authors introduce their review this way:

“Lithium, a long-established cornerstone therapy for bipolar disorder, is a biologically plausible disease-modifying agent for neurodegenerative disorders, including mild cognitive impairment (MCI) and Alzheimer disease (AD).”

The authors have pulled together a wealth of information in this article. We highly recommend that all neuroscientists interested in dementia and Alzheimer disease read this article in its entirety. If you know such researchers, please pass it along!

They conclude:

“Across molecular, cellular, imaging, epidemiologic, and early clinical domains, lithium displays remarkable convergence across translational domains. Yet compelling biology alone is insufficient. Definitive, adequately powered randomized clinical trials are required to determine whether lithium meaningfully slows cognitive decline.”

“If validated, lithium could represent a rare example of a low-cost, mechanistically grounded, disease-modifying therapy for neurodegeneration. In short, 75 years after transforming psychiatric care, lithium is now at the forefront of a new frontier: the fight against dementia.”

Why Hasn’t the Link Between Lithium and Brain Health Received More Attention?

Imagine if a pharmaceutical company announced a new molecular compound that:

• influenced amyloid and tau;
• calmed inflammatory brain cells;
• helped preserve synapses and myelin;
• affected an enzyme implicated in Alzheimer disease;
• restored memory in animal experiments;
• and might cost pennies rather than thousands of dollars.

We suspect Wall Street analysts, biotech investors and Alzheimer’s researchers would be paying very close attention. They might be competing to invest in the company developing such a drug.

Lithium presents an awkward economic problem. It is an element. You cannot patent lithium itself. Companies can potentially patent new formulations, delivery systems or particular uses, so saying there is no commercial opportunity would go too far. Nevertheless, the financial incentive for enormous clinical trials may be considerably weaker than it is for a proprietary new drug that could sell for tens of thousands of dollars a year.

That is precisely why public and philanthropic funding could be so important. A cheap treatment should not become scientifically uninteresting simply because it is cheap. We believe the Alzheimer’s research community should pursue this question aggressively, precisely because the answer might turn out to be either very important or completely disappointing. Both outcomes would be valuable.

Lithium Is NOT Benign!

Before anyone rushes to the Internet to order lithium orotate, we need to wave a large red flag.

Lithium can be toxic.

Prescription lithium carries a boxed warning because toxic blood concentrations can occur surprisingly close to therapeutic concentrations. Kidney function, thyroid function, electrolytes and lithium blood concentrations require monitoring when conventional lithium therapy is prescribed.

Lithium as a drug for bipolar disorder can cause:

• tremor
• nausea and diarrhea
• thirst and excessive urination
• fatigue and muscle weakness
• thyroid problems
• kidney problems
• neurological toxicity at excessive blood concentrations

Dehydration and changes in salt intake can alter lithium concentrations.

Drug interactions are another concern. Diuretics, ACE inhibitors and NSAID-type pain relievers can increase the risk of lithium accumulation and toxicity.

That is why experimenting on your own with prescription lithium is a terrible idea.

And we would not recommend taking even a low-dose, over-the-counter lithium supplement for the prevention or treatment of dementia without discussing it with a very knowledgeable health professional.

“Natural” and “low dose” do not automatically mean “risk free.”

Don’t Confuse Milligrams of a Salt With Milligrams of Lithium

Here is another source of enormous confusion.

A bottle may list the weight of lithium orotate, while another product or prescription lists lithium carbonate. Those numbers do not necessarily represent the same amount of elemental lithium.

It is rather like comparing the weight of sodium chloride with the amount of sodium it contains.

Anyone designing a clinical trial—or contemplating supplementation—needs to distinguish carefully between:

1. the weight of the lithium compound,
2. the amount of elemental lithium it supplies,
3. and the blood or tissue lithium concentration it ultimately produces.

This is one more reason amateur home compounding is a bad idea.

What We Know and What We Don’t

Here is what the science suggests today.

• Naturally occurring lithium is present in the human brain.
• The Harvard-led investigators found significantly less available lithium in vulnerable brain tissue from people with mild cognitive impairment (MCI) and Alzheimer’s disease.
• Reducing lithium in mice aggravated amyloid, tau, inflammation, structural brain damage and memory loss.
• Very-low-dose lithium orotate prevented or reversed many of those abnormalities in mouse models.
• Several epidemiological studies and some small human trials have produced intriguing signals suggesting that lithium exposure might be associated with less dementia or slower cognitive decline.

But…

• We do not know whether lithium deficiency causes Alzheimer disease in humans.
• It is not clear that low-dose lithium orotate can prevent MCI or Alzheimer disease.
• The ideal dose remains a mystery.
• We do not know whether long-term, very-low-dose lithium would be safe.
• And we do not know if measuring lithium in blood tells us anything useful about lithium availability inside the human brain. The Nature study suggests it may not.

Those are not minor unanswered questions. They are precisely the questions a well-designed randomized clinical trial should answer.

Our Bottom Line on Lithium and Brain Health

For over 75 years, medicine has viewed lithium primarily as a psychiatric drug for bipolar disorder. Perhaps that focus has been too narrow. The 2025 Nature study raises the startling possibility that lithium also has a normal physiological role in the aging brain and that disruption of lithium balance could contribute to the processes that eventually produce Alzheimer disease. The finding that lithium orotate protected aging and Alzheimer-prone mice is provocative.

But mice are not people! We are not recommending lithium orotate to prevent or treat Alzheimer’s disease. The human evidence is nowhere near strong enough to justify such a recommendation.

What we are recommending is research. Lots of it.

The appropriate response to this research is neither breathless enthusiasm nor a dismissive shrug. It is a large, carefully designed, long-term randomized trial testing very-low-dose lithium orotate against placebo, with careful monitoring of cognition, Alzheimer biomarkers, kidney function, thyroid function and adverse effects.

If lithium fails, we need to know that. If an inexpensive trace element can help preserve the aging human brain, we desperately need to know that too.

For a disease as devastating as Alzheimer’s, this is one stone that should not be left unturned.

Final Words:

We know there were a lot of technical terms in this article and we are grateful that you hung in there with us for this complicated story. We sincerely hope you found the research we described intriguing. There are a number of references at the bottom of this post that you could share with healthcare providers who are interested. We hope you will pass this article on to friends, family members, physicians and neuroscientists.

Should you wish to learn more about lithium and Alzheimer disease, you might want to listen to our podcast on this topic:

Show 1451: Rethinking Dementia: Is What We Believed about Alzheimer’s Wrong?
Instead of focusing only on amyloid plaque in the brain, should we be rethinking dementia? Multiple interventions could protect cognition.

Here are links to the podcast on Apple podcasts and Spotify.

These long analyses take many hours to create and your support is invaluable. Should you wish to support our work, here is a link.

Citations

• Moore, G.J., et al, "The 25-Year Evolution of Lithium as a Disease-Modifying Agent in Dementia: A Narrative Review," JAMA Psychiatry, June 10, 2026, doi: 10.1001/jamapsychiatry.2026.1296
• Aron, L., et al, "Lithium deficiency and the onset of Alzheimer’s disease," Nature, Aug. 6, 2025, doi: 10.1038/s41586-025-09335-x
• Kessing, L.V., et al, "Association of Lithium in Drinking Water With the Incidence of Dementia," JAMA Psychiatry, Oct. 1, 2017, doi: 10.1001/jamapsychiatry.2017.2362
• Chen, S., et al, "Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study," PLoS Medicine, March 17, 2022, doi: 10.1371/journal.pmed.1003941
• Fraiha-Pegado, J., et al, "Trace lithium levels in drinking water and risk of dementia: a systematic review," International Journal of Bipolar Disorders, Aug. 30, 2024, doi: 10.1186/s40345-024-00348-5
• Gildengers, A.G., et al, "Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial," JAMA Neurology, April 1, 2026, doi: 10.1001/jamaneurol.2026.0072

Lithium Beyond Bipolar: A New Role in Brain Health

 

Your incompetent? doctor already has protocols on uses of lithium for your stroke or TBI, and Alzheimers' prevention, right? Oh no, you DON'T have a functioning stroke doctor, do you?

lithium (21 post to September 2011) So, well over a decade of incompetence! Shooting for a world record, huh!

Lithium Beyond Bipolar: A New Role in Brain Health

In recent years, psychiatry has undergone a paradigm shift: Researchers are increasingly examining how metabolism, inflammation, micronutrients, and mitochondrial function influence brain health and resilience.

One compound drawing renewed attention in this context is lithium. Long recognized as a cornerstone treatment for bipolar disorder at pharmacologic doses, lithium is now being reconsidered as a trace element with broader physiologic roles in neuroprotection, neuroplasticity, and systemic regulation.

This evolving perspective was accelerated by a landmark study published in Nature last August. Aron and colleagues demonstrated that lithium is present in the human brain at trace concentrations and proposed that insufficient lithium in the brain may contribute to neuronal vulnerability and cognitive decline. These findings suggest that lithium may function not only as a therapeutic agent at higher doses but also as a biologically relevant micronutrient involved in maintaining neural stability.

At the same time, interest in lithium has expanded within functional and integrative psychiatry. Some clinicians are exploring low-dose lithium compounds, including lithium orotate, as potential tools to support mood regulation, cognitive resilience, and neuroprotection. Controlled clinical trials evaluating these approaches, however, remain limited.

Taken together, emerging research from neuroscience, nutritional psychiatry, and metabolic medicine suggests that lithium may play a broader and more foundational role in brain biology than previously appreciated. As the field continues to evolve, understanding lithium’s physiologic functions may help reshape how clinicians think about resilience, neurodegeneration, and the biological foundations of mental health.

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The 2025 Nature Findings: Lithium Deficiency and Alzheimer’s Disease 

The Nature study constitutes a major development in lithium research, as the researchers examined the relationship between lithium availability and neurodegenerative disease.

Liviu Aron, PhD, from Harvard Medical School, and colleagues demonstrated that lithium is naturally present in the human brain and that individuals with mild cognitive impairment and Alzheimer’s disease exhibit significantly lower concentrations of lithium in brain tissue compared with healthy controls.

Intriguingly, the study also found that amyloid plaques — the protein aggregates characteristic of Alzheimer’s pathology — appear to sequester lithium, functioning as molecular “sponges” that trap the mineral and potentially deprive surrounding neurons of its biological effects.

Experimental findings suggested that lithium depletion in neural systems was associated with:

• Accelerated memory decline
• Increased neuroinflammation
• Synaptic disruption
• Widespread neuronal vulnerability

When lithium was restored at trace nutritional doses, researchers observed notable improvements in experimental models. Memory performance stabilized, inflammatory signaling decreased, and structural integrity of neuronal and glial networks — including neurons, astrocytes, and oligodendrocytes — was preserved.

These findings raise an important systems-level question: Lithium depletion may not simply be a consequence of neurodegeneration but could represent a previously underrecognized contributor to neuronal vulnerability.

From a functional medicine perspective, this reframes lithium insufficiency as a potentially modifiable risk factor in cognitive aging.

Lithium as a Natural Element in the Human Environment  

Lithium is the third element on the periodic table and occurs naturally throughout the Earth’s crust. It is present in trace amounts in groundwater, soil, plant foods, and mineral springs. Historically, lithium-rich waters were associated with calming and mood-stabilizing effects, long before the development of modern psychopharmacology.

The name “lithium” derives from the Greek word lithos, meaning stone — reflecting its natural geological origins.

Small quantities of lithium are detectable in foods such as:

• Leafy greens
• Legumes
• Grains
• Root vegetables

While concentrations are extremely small, ecologic research suggests they may carry biological significance.

A meta-analysis published in the British Journal of Psychiatry found that regions with higher naturally occurring lithium concentrations in drinking water tend to exhibit significantly lower suicide rates. Although ecologic studies cannot establish causality, the consistency of these associations across multiple geographic regions suggests that environmental lithium exposure may influence population-level mental health outcomes.

These observations have contributed to growing scientific interest in lithium as a trace mineral with neuromodulatory benefits.

Mechanisms of Low-Dose Lithium: A Systems Biology Perspective 

Lithium’s biological effects extend far beyond a single neurotransmitter pathway. It influences a broad network of cellular processes that intersect with modern models of metabolic and inflammatory psychiatry.

Mitochondrial support. Mitochondria play a central role in neuronal energy production and cellular resilience. Dysfunction in mitochondrial metabolism has been increasingly implicated in depression, bipolar disorder, neurodegeneration, and cognitive decline.

Experimental research indicates that lithium may enhance mitochondrial efficiency, improve ATP production, and reduce oxidative burden within neurons. By supporting cellular energy metabolism, lithium may contribute to improved neural stability and stress resilience.

Anti-inflammatory modulation. Chronic low-grade inflammation is increasingly recognized as a shared biological driver across numerous psychiatric and neurologic conditions.

Lithium has been shown to modulate inflammatory signaling pathways and reduce overactivation of microglial cells, the immune cells of the central nervous system. Dysregulated microglial activity contributes to neuroinflammation implicated in disorders ranging from depression to Alzheimer’s disease. 

Through these mechanisms, lithium may help dampen inflammatory cascades that disrupt neural circuitry.

Oxidative stress regulation. Oxidative stress occurs when reactive oxygen species accumulate faster than antioxidant defenses can neutralize them. This imbalance contributes to neuronal damage, aging, and psychiatric vulnerability.

Lithium has demonstrated antioxidant effects in experimental systems, reducing oxidative damage and supporting neuronal survival under chronic stress conditions.

Neurotransmitter stabilization. Lithium influences multiple neurotransmitter systems involved in emotional regulation. Research suggests that lithium can modulate serotonin signaling, enhance inhibitory GABAergic (gamma-aminobutyric acid) activity, and regulate dopamine and glutamate dynamics.

Rather than acting as a sedative, low-dose lithium appears to buffer excessive neural excitability, promoting emotional stability and cognitive clarity.

Neurotrophic and synaptic effects. Lithium has also been shown to increase expression of brain-derived neurotrophic factor (BDNF), a key molecule involved in neuronal survival, synaptic plasticity, and learning. Increased neurotrophic signaling supports the formation and maintenance of healthy neural networks.

Inflammation, Metabolism, and Mental Health 

Modern psychiatric research increasingly recognizes that mental illness often reflects systemic biological dysregulation. 

Chronic inflammation contributes to:

• Synaptic dysfunction
• Abnormal neural pruning
• Amyloid and tau pathology
• Insulin resistance
• Vascular impairment

Simultaneously, mitochondrial dysfunction reduces neuronal energy production while promoting oxidative and metabolic stress.

Lithium appears to act at this intersection of metabolism, inflammation, and neuroplasticity, helping regulate inflammatory cascades while supporting mitochondrial function. These overlapping effects align closely with the principles of functional and metabolic psychiatry. 

Cognitive support and neuroprotection. Patients with family histories of neurodegenerative disease or early cognitive concerns may benefit from broader neuroprotective strategies that include nutrition, metabolic health optimization, sleep regulation, and physical activity. Trace lithium may be considered as one component of these comprehensive approaches.

Mood instability and impulsivity. In individuals experiencing mood lability, irritability, or impulsivity, low-dose lithium may help stabilize neural signaling without requiring the serum monitoring associated with pharmacologic lithium therapy.

Supporting antidepressant tapering. Discontinuation of antidepressants can be accompanied by neurochemical fluctuations, inflammatory rebound, and mitochondrial stress.

Functional psychiatry approaches to tapering may include:

• Mitochondrial nutrients such as CoQ10 or acetyl-L-carnitine
• Magnesium and B-vitamin repletion
• Anti-inflammatory nutrition
• Trace mineral support

Lithium’s potential to stabilize neurotransmitter systems and buffer excitotoxic signaling may provide supportive regulation during carefully supervised taper protocols.

Vitamin D, Lithium, and Neuroimmune Regulation 

Emerging research continues to highlight the importance of vitamin D in brain and immune function. Vitamin D influences inflammatory cytokine signaling, mitochondrial gene expression, and neurotrophic pathways involved in mood regulation. These biological pathways overlap substantially with lithium’s mechanistic profile.

Both lithium and vitamin D influence:

• Neuroinflammatory signaling
• Mitochondrial resilience
• Neuroplasticity pathways

Within nutritional psychiatry frameworks, optimizing vitamin D status alongside trace mineral sufficiency represents a practical strategy for supporting neuroimmune balance and mental health resilience.

Metabolic Psychiatry: A Broader Framework 

The emerging field of metabolic psychiatry proposes that mood and cognition are deeply intertwined with cellular energy metabolism, insulin sensitivity, circadian rhythm integrity, and inflammatory balance.

Within this framework, low-dose lithium aligns with several key biological targets:

• Mitochondrial ATP production
• Neuroinflammatory modulation
• Synaptic stability
• Metabolic signaling pathways

Lifestyle interventions remain foundational. Nutrient-dense foods, physical activity, exposure to nature, circadian rhythm balance, restorative sleep, and stress-modulating practices (eg, yoga, tai chi) support the biological systems that maintain psychiatric stability.

Lithium complements these interventions by supporting the cellular infrastructure upon which mental health depends.

Reframing Lithium in Psychiatric Practice 

Lithium’s scientific identity is evolving. Once viewed primarily as a high-dose mood stabilizer used in severe psychiatric illness, lithium is increasingly being examined within a broader biological context. At trace nutritional levels, lithium functions as an integral resilience-supporting micronutrient influencing inflammation, metabolism, and neuroplasticity.

The findings reported in the 2025 Nature study provide a compelling biological rationale for continued investigation: If lithium depletion contributes to neurodegenerative vulnerability, restoring physiologic levels may represent a preventive strategy rather than a purely therapeutic intervention.

Lithium in Context: Dose, Form, and Neurobiological Resilience

It is encouraging to see research continuing to evolve in support of lithium’s potential to confer benefits across multiple dose ranges and formulations. A recent pilot randomized clinical trial in JAMA Neurology in individuals with mild cognitive impairment found that low-dose lithium was associated with slower decline in verbal memory, with signals of greater benefit in amyloid-positive individuals — findings that are directionally consistent with lithium’s effects on neuroinflammation, synaptic integrity, and GSK-3 beta signaling.

It is important to note that this study utilized lithium carbonate, whereas lithium orotate — more commonly used in integrative practice — may differ in brain transport and intracellular retention, with implications for greater neural bioavailability and downstream neuroprotective effects. From a functional and metabolic perspective, these distinctions are meaningful: Form, dose, and individual biology are likely to shape clinical response. The modest effects observed with carbonate may therefore reflect pharmacokinetic constraints rather than limitations of lithium’s underlying mechanisms.

Taken together with emerging evidence linking lithium homeostasis to neurodegenerative vulnerability — including the 2025 Nature findings — lithium can be more fully understood not simply as a pharmacologic agent, but as a biologically relevant regulator of the neuroimmune and metabolic systems that underpin cognitive stability and long-term brain resilience.

James M. Greenblatt, MD, is a dual board-certified psychiatrist and internationally recognized leader in functional and integrative psychiatry. He has spent more than 30 years advancing precision-based approaches to mental health and is the founder of Psychiatry Redefined, an educational platform for clinicians worldwide.

Can Lithium in Water or a Supplement Prevent Alzheimer Disease or Dementia?

 Have your competent? doctor wade through this and GIVE YOU AN EXACT ANSWER!

• lithium (20 posts to September 2011)

Can Lithium in Water or a Supplement Prevent Alzheimer Disease or Dementia?

Could lithium in water fend off Alzheimer's disease? A new study throws the low-dose lithium vs. dementia controversy into confusion.

ATTENTION DEFICIT DISORDER (ADD)The chances are good that you are exposed to some lithium almost every day of your life. That’s because this natural element is plentiful in nature. It is found in rocks and soil all over the earth. That means it ends up in our food and water supply. Trace amounts can be found in tomatoes, cucumbers, eggs, milk and mushrooms, to name just a few common food sources. Because levels of lithium in water are highly variable, researchers have been studying long-term exposure to this element and its impact on the brain. Is it possible that relatively small amounts of lithium could help prevent dementia? A study in Nature (August 6, 2025) suggests that “Lithium Replacement Therapy” might be beneficial for the brain. We have been writing our syndicated newspaper column since 1978. King Features distributes it to scores of newspapers around the country. One reason that we have appreciated this opportunity is the feedback we get from readers. This website also allows people to ask questions and/or share stories in the comment section below each post. Visitors also send us email at this address: questions@peoplespharmacy.com. Sometimes we don’t know the answers—or even if there are answers. But we often find that a search of the medical literature offers fascinating insights. We received just such a question about lithium and dementia. It surprised us, because we had never considered this possibility before: Q. What’s your assessment of the value of lithium to prevent dementia? We did some digging, and to our surprise there was research. We answered this person this way: There have long been hints that lithium might be valuable to reduce the risk for dementia (Progress in Neuro-Psychopharmacology & Biological Psychiatry, Aug. 30, 2006).  However, most research has focused on anti-amyloid drugs such as donanemab (Kisunla) or lecanemab (Leqembi). A systematic review turned up a number of animal studies but only a few clinical trials of lithium for preventing dementia (Ageing Research Reviews, March 2024).

Doses studied vary widely. When lithium is prescribed for bipolar disorder, doses range from 600 to 1,800 mg daily. Adverse effects may include diarrhea, muscle weakness, drowsiness, changes in thyroid function and kidney damage.

Much lower doses (10 to 20 mg of lithium orotate or citrate) have been used experimentally against depression and dementia. The risks may be reduced at such doses. Much more research is needed on this possible treatment.

New Research on Lithium vs. Alzheimer Disease Is Disappointing

A study published this week in JAMA Neurology (March 2, 2026) produced disappointing results. Researchers at the University of Pittsburgh recruited 80 older participants with mild cognitive impairment. They were randomly assigned to receive either a 150 mg or a 300 mg dose of lithium carbonate or a placebo.

The authors categorized this as a “low dose lithium,” but it is dramatically different from the 10 to 20 mg used to treat dementia or depression in other studies.

Keep in mind that the elemental lithium content in a lithium carbonate pill is about 19% of the total. The amount of elemental lithium in lithium orotate is about 4%.  So comparing lithium from 10 mg of lithium orotate to 300 mg of lithium carbonate is a little like comparing a Toyota Prius to an 18 wheel Mack Truck. The doses are vastly different.

Serious adverse events occurred in 29% of those getting lithium. Side effects included creatine elevations (a measure of kidney problems), diarrhea, tiredness and tremor.

As far as cognitive improvement went, after two years there was no statistically significant improvement in the lithium carbonate group compared to placebo:

“Scores declined 1.42 points annually in the placebo group vs. 0.73 points in the lithium group (difference, 0.69 points per year).”In other words, not enough to write home about.

But the authors conclude:

“Together with findings from prior independent longer-term trials, these results support further investigation of lithium in adequately powered trials to assess its potential neuroprotective properties in MCI [mild cognitive impairment].”

Several Months Ago, These Were the Headlines:

“Research on reversing Alzheimer’s reveals lithium as potential key” (Washington Post, Aug. 6, 2025)

“Could Lithium Explain — and Treat — Alzheimer’s Disease?” (Harvard Medical School News & Research, Aug. 6, 2025)

“Scientists say it may be possible to protect aging brains from Alzheimer’s with an old remedy — lithium” (CNN, Aug. 7, 2025)They were all based on a study published in Nature on August 6, 2025. This is mouse research. We know; mice and humans are different! Before you hold your nose and ignore the results, let us assure you that this is incredibly sophisticated work! These investigators are heavy hitters at Harvard Medical School, Boston Children’s Hospital and Rush Alzheimer’s Disease Center, Rush University Medical Center in Chicago, Illinois.

They start their paper this way:

“The earliest molecular changes in Alzheimer’s disease (AD) are poorly understood. 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.”

“Endogenous” lithium means the lithium that we would normally have in our brains/bodies. “Exogenous” lithium would be that which we take in from our environment, either from water, food or a supplement. These researchers “depleted” lithium levels in mice. Doing so dramatically increased two very worrisome compounds associated with Alzheimer’s disease: amyloid-beta (β) and phospho-tau. Doing so led to inflammation in the brain and the:loss of synapses, axons and myelin, and accelerated cognitive decline.”

The authors conclude:

“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.”

OK, I get that the above paragraph is a bit technical. But even if you are not familiar with some of those terms, you probably got the gist of the message. Lithium replacement therapy just might be helpful against Alzheimer’s disease!

We need randomized controlled trials to demonstrate whether low doses of lithium orotate will be helpful for humans. The dose that the researchers were using in mice was comparable to “natural” levels in humans. It was not massive, like the doses used to treat the “manic episodes of manic-depressive illness.” That’s old FDA language for bipolar disorder.Matt Kaeberlein is the former director of the Healthy Aging and Longevity Research Institute at the University of Washington.

He told the Washington Post:

“The obvious impact is that because lithium orotate is dirt cheap, hopefully we will get rigorous, randomized trials testing this very, very quickly. And I would say that it will be an embarrassment to the Alzheimer’s clinical community if that doesn’t happen right away.”

Another Reader Asks About Lithium vs. Alzheimer Disease:

“My late mother suffered from dementia for ten years. I helped care for her, and it was utter hell as it progressed. My sister is about to turn 70, and of course, she’s concerned about dementia.

“I have bipolar disorder, so I’ve been taking lithium to treat it for over 35 years now. A few years ago, I began seeing research on using lithium against dementia. The results from various researchers are impressive, including double-blind trials.

“I have learned that a micro-dose of lithium is all that is required, and not the usual dose necessary to treat bipolar disorder. On average, researchers found that 1.5 mg daily drastically reduced the formation of amyloid-B and plaques in the brain.

“What saddens me most is that I might have helped my mom avoid dementia entirely from my own bottle of lithium! But I didn’t stumble on the research until after she passed away in 2020.

“Now I figure that just one of my lithium tablets (300 mg) would supply my sister with nearly a year’s supply. I am tempted to order a micro scale, some gelatin capsules, and compound my own for her. She’s on a limited budget, and her doctor is not supportive at all. Although I’ve encouraged her to get a new doctor, that doesn’t seem likely.

Lithium in Water?

“Is there a form of lithium water she could drink? I’ve heard that others use it. I doubt there would be any need for blood work at such a low dose, but I would insist she get tested anyway, just to be safe.

“My apologies for sounding like Dr. Frankenstein, but I’m totally serious. I don’t want to wait several more years, then discover she’s got dementia like my mom if I could have prevented it!”Our Answer:

We don’t know how to help your sister find a sympathetic physician. However, we agree with you that there are a number of intriguing studies hinting that low-dose lithium might be protective.

Research on Low-Dose Lithium vs. Dementia:

In one study from England, scientists found that people exposed to lithium were about 40 percent less likely to be diagnosed with dementia (PLOS Medicine, March 17, 2022).  These populations were similar in other respects.The authors conclude:

“We observed an association between lithium use and a decreased risk of developing dementia. This lends further support to the idea that lithium may be a disease-modifying treatment for dementia and that this is a promising treatment to take forwards to larger randomised controlled trials (RCTs) for this indication.”

An analysis of three trials found that all supported the results of lithium for dementia prevention (International Journal of Environmental Research and Public Health, July 22, 2021). Tissue culture studies hint at a possible mechanism (Scientific Reports, Dec. 4, 2019).

Basic research indicates that lithium chloride can reduce beta-amyloid toxicity in the brain (Journal of Alzheimer’s Disease, 2019).  In addition, it helps prevent the buildup of tau found in tangles in the brain.

Microdoses of Lithium?

Could microdoses of lithium delay the development of Alzheimer’s disease? A study from Canada suggests that may indeed be the case (Journal of Alzheimer’s Disease, Jan. 21, 2020). Before we share the additional research on lithium and the brain, please stay with us while we present a brief historical perspective on lithium in water.

Research on Lithium in Water:

People who drink water with higher levels of lithium may be less likely to develop dementia. That’s the conclusion of a large epidemiological study from Denmark (JAMA Psychiatry, online, Aug. 23, 2017). Investigators compared 73,731 patients with dementia to 733,653 people without dementia. The subjects ranged in age from 75 to 85 years of age.

Measuring Lithium in Water:

The researchers measured lithium in drinking water from 151 communities around the Denmark and mapped where patients and controls had lived from 1986 to through 2013. Those exposed to naturally higher levels of lithium in their drinking water were less likely to have a diagnosis of dementia.

Prior research has linked lithium treatment to better learning and memory in laboratory animals. In addition, people with bipolar disorder undergoing long-term lithium treatment appear to have a reduced risk for dementia. This study seems to confirm these previous observations.

Lithium vs. Alzheimer’s Disease:

There are currently no effective treatments against Alzheimer’s disease. But researchers at McGill University in Canada have published an intriguing rodent study that goes beyond lithium in water (Journal of Alzheimer’s Disease, Jan. 21, 2020).Previous research by this team led them to believe that a special very low dose lithium preparation (NP03) could interrupt “…early amyloid pathology stages in the Alzheimer’s-like transgenic rat” (Translational Psychiatry, Aug. 1, 2017).

They concluded that:

“These findings thus suggest that NP03 reverses key AD [Alzheimer’s disease] pathologies in an in vivo AD model, and that it may have therapeutic value in the early stages of the disease.”

The Canadian research involved administering microdoses of lithium to rats bred to develop an Alzheimer’s-like brain disorder. This time, though, the brain pathology was more advanced.

This would be roughly equivalent to when amyloid plaque would be present in the brain and cognitive decline would begin to be detected. In the rodent study, the pathology was diminished and cognition improved.Lithium vs. Bipolar Disorder, Depression and ADHD:

Over the last several years, evidence has been accumulating that low levels of lithium may be beneficial against a wide range of mental problems. If you would like to learn more about this history of lithium for what used to be called manic depression (now bipolar disorder), here is a link.

Did you know that Mineral Wells, Texas, was renowned for its lithium-rich water? People found the water helpful for a variety of mental disorders. The original 7 Up soda had lithium in it. Learn all about this history of lithium here:

Rediscovering Lithium for Mood Disorders
Lithium is a mainstay for treating bipolar disorder. Side effects are scary, but could low-dose supplements be safer and more effective for mood disorders?

You will also find out about low-dose lithium in water as a potential preventive against suicide. There is also interest in low doses of this element for treating depression and possibly even ADHD. Here is a link to our free podcast about this intriguing application.

Lithium Is Not Benign:

Lithium is also found in medications. One of my early mentors was Dr. Carl Pfeiffer. He was head of the Neuropharmacology Laboratory at the NJ Neuropsychiatric Institute. He did some of the early research on the use of lithium for what was then called manic-depressive disorder.In the high doses used to treat what is now called bipolar disorder, lithium can cause several serious side effects. Not only can it disrupt the digestive system (nausea, vomiting and diarrhea), it can cause an unpleasant taste in the mouth.

Weight gain is another potential problem. More worrisome is kidney damage. Kidney function must be monitored regularly! Other adverse reactions include tremor, excessive urination, thirst, fatigue, muscle weakness, drowsiness,  thyroid problems and visual changes. Drug interactions are common and problematical. Anyone taking lithium must have regular pharmacy interaction reviews. These complications are related to high doses of lithium used therapeutically. The FDA’s dosing schedule for lithium carbonate is 600 mg taken three times daily (1,800 mg).

Low to Micro Doses of Lithium Orotate:

The doses of lithium orotate given to the mice in the Harvard study were, according to the primary author, about 1,000 times lower than the FDA-approved doses for manic-depression. While low or microdoses of lithium are unlikely to cause toxic complications, anyone contemplating such a program must be under medical supervision! Regular kidney function tests are advisable.

If you have taken lithium in low or standard doses, please share your experience in the comment section below. Do you drink lithium water? What’s that like? Has anyone taking micro doses of lithium noticed any benefits against Alzheimer’s disease or dementia?

We are not recommending such a program until well-controlled clinical trials are conducted. Sadly, it is unlikely that any drug company will sponsor such research, as there is no profit to be made. And medical research funding has been dramatically curtailed in recent months. Nevertheless, we remain hopeful that some some wealthy donors will fund this research so we can get solid scientific answers to these critical questions in a timely fashion.

Final Words:

The new study in JAMA Neurology, March 2, 2026 was titled “Low-Dose Lithium for Mild Cognitive Impairment.” But 150 to 300 mg of lithium carbonate does not seem low to us. It is certainly not a microdose. Perhaps that is why so many people in the study complained of classic lithium side effects.

Rather than 300 mg of lithium carbonate, we would like to see a study using doses of 5 to 10 mg of lithium orotate. It is entirely possible that they would work no better, but they should certainly be a lot safer.

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Citations

• Wilson, E. N., et al, "BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology," Translational Psychiatry, Aug. 1, 2017, doi: 10.1038/tp.2017.169.
• Wilson, E. N., et al, "NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats," Journal of Alzheimer's Disease, Jan. 21, 2020, doi: 10.3233/JAD-190862.
• Chenm, S., et al, "Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study," PLoS Medicine, March 17, 2022, doi: 10.1371/journal.pmed.1003941
• Singulani, M. P., et al, "Lithium and disease modification: A systematic review and meta-analysis in Alzheimer's and Parkinson's disease," Ageing Research Reviews, March, 2024, doi: 10.1016/j.arr.2024.102231
• Aron, L., et al, "Lithium deficiency and the onset of Alzheimer’s disease," Nature, Aug. 6, 2025, DOI: 10.1038/s41586-025-09335-x
• Gildengers, A.G., et al, "Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial," JAMA Neurology, March 2, 2026, doi: 10.1001/jamaneurol.2026.0072