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

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.

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