New Hope for Alzheimer’s: Study Says Lithium May Reverse Aging Brain

In terms of genetics, a variant of the apolipoprotein E (Apo E) gene, called ApoE4, is the number-one risk factor for late-onset Alzheimer’s disease, but having it does not necessarily mean an individual will develop AD.

When it comes to lifestyle factors, diet, exercise, sleep, social isolation, and a lack of new learning all have an influence on AD risk. Other contributors to memory loss include exposure to environmental toxins, head trauma, inflammation, low blood flow, infections, neurohormone imbalances, and mental health issues.

Related: Alzheimer’s Is a Lifestyle Disease

Research shows that treating these risk factors can improve memory and cognitive function. A study performed at Amen Clinics on 30 retired NFL players with cognitive impairment and brain damage found that following a brain-healthy protocol resulted in improvements in memory, attention, and reasoning.

Brain scans showed that the former players also benefited from improved blood flow and activity in several key regions of the brain, including:

• Prefrontal cortex
• Parietal lobes
• Occipital lobes
• Anterior cingulate gyrus
• Cerebellum

In recent years, scientists have also studied the environmental impact of trace metals on Alzheimer’s, which, in part, led to the new study examining lithium deficiency.

WHAT IS THE CONNECTION BETWEEN LITHIUM AND HEALTH?

Lithium is a natural trace element found in the environment and present in certain foods and water. In the nineteenth and early twentieth centuries, lithium was valued for its various health and mood benefits.

Natural springs with higher lithium content became destinations for health as “lithia water” was thought to be a curative for many ailments. Lithia water was bottled and sold as a health beverage. In fact, an early formulation for 7-Up contained lithium with a lemon-lime flavoring and was marketed as a health tonic.

However, the US Food and Drug Administration (FDA) banned it due to its potential negative side effects in the 1950s.

In the field of psychiatry, the first successful clinical trial on lithium treatment for manic-depression (now referred to as bipolar disorder) was published in 1954, and by 1970, the FDA had approved the use of lithium carbonate as a mood stabilizer, according to published documentation.

Today, carefully prescribed levels of lithium carbonate—a pharmaceutical form of the element—is considered the gold standard treatment for bipolar disorder. Yet, this prescribed lithium can have serious negative side effects, including risk of toxicity, if not monitored properly.

LITHIUM AND ALZHEIMER’S DISEASE RESEARCH

A number of key studies in recent years have pointed to lithium’s protective action against dementia and, specifically, Alzheimer’s disease.

One study, published in the British Journal of Psychiatry in 2007, examined risk of Alzheimer’s disease in elderly patients with bipolar disorder. Based on an established association between bipolar disorder and higher risk of dementia, Brazilian researchers compared bipolar patients treated with chronic lithium therapy and those without recent lithium therapy.

It turned out that the bipolar patients who had lithium treatment showed reduced prevalence of Alzheimer’s disease to levels in the general elderly population.

The findings appeared to provide further evidence that lithium inhibits processes that factor into the pathogenesis of Alzheimer’s disease.

Other significant epidemiological research examined the effects of trace lithium in drinking water and how very low doses of lithium, over time, might help to prevent dementia.

A large 2017 Danish study published in JAMA Psychiatry noted an association between long-term increased lithium exposure in drinking water and lower incidence of dementia.

More recently, in 2024, Brazilian researchers examined five studies that reported a link between trace lithium in water and dementia and mortality from dementia. The published review study found associations between trace lithium levels and a lower risk of dementia or mortality from dementia.

The study concluded that evidence shows that trace lithium levels in drinking water are sufficient to lower the incidence or mortality from dementia and recommended future clinical trials focusing on long-term use of low or even microdoses of lithium for dementia treatment and prevention. 

THE BREAKTHROUGH STUDY ON LITHIUM AND ALZHEIMER’S DISEASE

As mentioned, the overall grand-arching finding of the new study published in Nature suggests that replenishing the brain’s natural stores of lithium can protect against and even reverse Alzheimer’s disease.

The research results presented in the published study offer many significant discoveries, serving to advance the scientific community’s understanding of lithium’s role in both the pathogenesis and potential treatment of AD.

Here’s a look at some of those discoveries.

1. Human Research Findings

Scientists have been looking closely at metals in the brain, since imbalances may play a role in Alzheimer’s disease (AD). In one study, researchers measured 27 different metals in the brain and blood of older adults—some healthy, some with mild cognitive impairment (MCI), and some with Alzheimer’s.

Here’s what they discovered:

• Lithium Is Naturally in the Brain: Healthy brains naturally contain small amounts of lithium.
• Much Lower Lithium in Alzheimer’s: In both MCI and Alzheimer’s patients, brain lithium levels were about 50% lower than in healthy people.
• Lower Where Damage Is Worst: Areas of the brain most affected by Alzheimer’s had the lowest lithium levels. Some lithium was trapped inside amyloid plaques, making less available for normal brain function.
• Other Metal Changes: People with Alzheimer’s also had higher zinc levels and lower copper levels compared to healthy individuals.

2. Animal Research Findings

Researchers have tested lithium in mice with Alzheimer’s disease (AD), and the results are promising—though they still need to be confirmed in human studies. Here’s what they found:

• Protects Brain Connections: Lithium helps maintain healthy connections between brain cells as mice age. When mice with Alzheimer’s ate a diet low in lithium, their thinking and memory worsened faster. Their brains also showed more of the harmful protein buildup (amyloid plaques and tau tangles) seen in Alzheimer’s, more inflammation, and gene changes linked to the disease.
• How It Works: One way lithium deficiency may cause harm is by overactivating a brain protein called GSK3β, which is involved in Alzheimer’s development.
• Best Form for the Brain: Out of 16 types of lithium tested, lithium orotate was the least likely to stick to amyloid plaques (which are toxic to brain cells).
• Better Than the Standard Form: In mice with Alzheimer’s, lithium orotate in drinking water worked better than the more common lithium carbonate at preventing memory loss, reducing harmful protein buildup, lowering brain inflammation, and even helping immune cells in the brain (microglia) “clean up” plaques.
• Helps Healthy Brains, Too: In healthy mice, lithium orotate also protected brain structure from the normal wear and tear of aging.
• Safer for the Body: Unlike lithium carbonate, lithium orotate didn’t show the same harmful effects on the kidneys or thyroid.
• Restores Memory: In Alzheimer’s mice, lithium orotate—given in the right dose—restored memory performance to normal levels, something lithium carbonate did not achieve.

These are truly extraordinary results. Treatment for Alzheimer’s disease has previously only targeted the reduction of plaques and tau tangles, but never so many pathologies underlying AD. If these findings are confirmed in clinical trials, it could have substantial implications for AD treatment and prevention.

LITHIUM OROTATE VS LITHIUM CARBONATE

You may be wondering how lithium orotate differs from high-dose, pharmaceutical lithium carbonate commonly used in the treatment of bipolar disorder.

Related: Understanding the Differences Between Lithium and Lithium Orotate

For starters, lithium orotate is a low-dose, over-the-counter nutritional supplement that consists of orotic acid (a compound produced naturally in the body) and lithium. It is not a medicine. Some people refer to lithium orotate as “nutritional lithium.”

There are no official guidelines for lithium orotate dosage levels but they are much closer to the generally safe amounts of lithium found in foods such as grains and vegetables. (The average human consumption of lithium from food sources and water has been estimated to be approximately 0.5 to 3 mg/day, according to research.)

Supplemental suggested dosages are usually between 5 to 10mg, and sometimes up to 20mg with little to no adverse effects noted. By comparison, lithium carbonate may be prescribed at 1,800 mg therapeutically with significant risk of side effects unless monitored closely.

Some research has been conducted using lithium orotate in the treatment of alcoholism, migraines, and depression associated with bipolar disorder. However, experts suggest that more research is needed.

Until now, the potential benefits of low-dose lithium have been underappreciated largely due the stigma linked to lithium carbonate. Thanks to the new research, however, the tides may now be turning for low-dose lithium orotate.

If future clinical research confirms these findings, lithium orotate may become a common strategy for the prevention and treatment of Alzheimer’s disease.