Lithium's Role in Alzheimer's: From Repeated Eulogies to a Renewed Hope

Alzheimer’s

Alzheimer's is a progressive brain disorder that affects millions of older adults across the world. In the USA itself, Alzheimer’s causes a loss of more than $300bn in America, over $1tn all over the world.

Alzheimer’s has been understood through the buildup of two harmful proteins: amyloid-beta and tau. Amyloid-beta appears as a clump and sticky material that starts eating up the brain and keeps growing in size. While Tau proteins are naturally occurring proteins that start assembling disorderly, destroying natural cells and causing brain damage.

For the past several decades, billions of research studies have focused on the causeway and pathway of these proteins. Recent Alzheimer's drug research has focused precisely on the progress of these proteins. The decade-long research is pivotal because this is the first time lithium and normal brain function have been correlated. They also show how amyloid plaques can bind Lithium, causing sudden depletion of Lithium

The scientists are the first ever to show that Alzheimer's is directly related to Lithium depletion. They also show how a new class of lithium-based salts can reverse plaque progression by avoiding the bindings

History of Lithium Therapy

In the early 1900s, carbonated beverage industry veteran Charles Leiper Grigg was already burned by his unsuccessful attempt to overthrow established beverage brands via his new, albeit another orange drink. At the cusp of dwindling finances, Charles decided to instead focus on the lemon and lime market that was much more fragmented. This time he wagered on a new differentiator! - Lithium Citrate

7Up's citrusy, juicy flavor was a hit. Users vouched for its energizing and fresh taste. Lithium was then known as a mood enhancer in the medical world.

Man's first Serendipity with Lithium

It was in mid-1800s that Alfred Baring was trying to treat gout patients. He theorized that the accumulated uric acid can be easily dissolved by Lithium, thus he started prescribing Lithium salt to patients. While that did not work, he did start to observe improved mental conditions among depression patients. His published work was widely adopted and expiremented.

Alfred Baring was trying to dissolve uric acid via Lithium salts and accidentally found its mood enhancing effects

By 1870s, several practitioners across Copenhagen, New York, and Philadelphia started to meticulously study the effect of Lithium salts and saw it as a versatile treatment for various nervous conditions.

Moreover, natural lithium-rich springs, such as Lithia Springs in Georgia, had long been associated with therapeutic benefits for visitors seeking treatment for nervous conditions. The presence of lithium in these mineral waters was later identified as a potential contributing factor to their purported mental health benefits, lending credence to the growing medical interest in lithium compounds.

Alfred's Brain Grout dissolution theory will remain at the centre of the Lithium mechanism for several decades before it will be discarded, and the scientific community will call for more evidence.

The Overhype-Backlash Effect

Throughout human history, numerous technological and scientific breakthroughs have suffered dramatic reversals due to overselling and hype. During peak enthusiasm, these innovations are promoted as revolutionary game-changers, but when promised benefits fail to materialize, governments and institutions tend to completely abandon them—overlooking even their modest, genuine benefits—causing funding and support to immediately dry up.

CBD oil, 3D printing, plant-based meat, cold fusion, and countless others have followed this pattern. Since public regulatory authorities are answerable to the public, they tend to respond to excessive public backlash with equally excessive restrictions. Nuclear power serves as a classic example of this phenomenon. After disasters like Chernobyl and Fukushima, many governments completely abandoned expansion plans and existing programs. It has taken almost three decades for nuclear researchers to regain public attention regarding the possibilities of safer technologies, with only recently the US and UK governments beginning to fund next-generation small modular reactors.

Lithium became another victim of the hype cycle. From pharmaceutical preparations to consumer products, lithium appeared in everything: "Lithium Water," "Lithium Soap," and "Lithium Drinks" flooded the market with little oversight.

Most dangerously, lithium salts were marketed as a table salt substitute for patients requiring low-sodium diets

The overuse quickly spiraled out of control. Lithium prescriptions expanded far beyond nervous system conditions to include cardiac issues and hypertension. Most dangerously, lithium salts were marketed as a table salt substitute for patients requiring low-sodium diets. Reports of severe toxicity and adverse effects began surfacing throughout the medical community, including numerous fatal incidents directly linked to lithium salt consumption.

Leading scientists began warning against lithium use, and research documenting the severe toxicity of lithium compounds flooded medical journals. The mounting scientific evidence, combined with regulatory pressure, gradually forced lithium products off consumer shelves. In February 1949, the FDA banned both the practice of using lithium salts as table salt substitutes and the sale of lithium itself, following reports detailing severe side effects and deaths. It would take 21 years before the FDA reconsidered lithium for any therapeutic application

The Rise of Underground Therapy

While opposition to lithium peaked in the United States due to fatal incidents, groundbreaking research was underway in Melbourne, Australia. John Cade was meticulously studying the effects of lithium carbonate and lithium citrate on mental health patients. His 1949 paper "Lithium salts in the treatment of psychotic excitement" became one of the most cited works in psychiatric literature. While his seminal research demonstrated once again that lithium salts had profound effects on patients, one of his patients later died from lithium toxicity. However, by then, European researchers had already begun adopting and expanding upon his work with lithium salts.

The breakthrough came in 1958 when technology for precise blood level monitoring was finally invented. Over the next decade, European psychiatrists could safely test lithium dosages while keeping patients below toxic levels, witnessing remarkable effects especially in treating bipolar disorders.

By the late 1960s, this "lithium underground" had grown bold enough that some physicians publicly declared they would prescribe it regardless of FDA approval

However, skepticism persisted in North America, where many dismissed lithium as "dangerous nonsense" due to concerns about its narrow safety margin. Despite this resistance, controlled studies continued proving lithium's effectiveness. Meanwhile, an underground network of American physicians began prescribing lithium without official approval, driven by desperation to help patients with severe manic conditions.

By the late 1960s, this "lithium underground" had grown bold enough that some physicians publicly declared they would prescribe it regardless of FDA approval. In 1970, the United States became the 50th country to approve lithium for medical use, specifically for bipolar disorder treatment.

Economic Paradox

But as lithium experienced its revival, a new obstacle emerged: economics. Pharmaceutical companies had little interest in promoting a treatment they couldn't patent. While lithium salts cost patients $20-$30 per month in 2025, newer patentable alternatives command over $1,000 monthly—with patent protection lasting up to 20 years.

The economic incentives were clear. Pharmaceutical giants systematically directed research funds toward developing patentable alternatives rather than studying lithium further. Abbott's valproate became a blockbuster drug, marketed for everything from epilepsy to bipolar disorder. Medical conferences, sponsorships, and clinical adoption efforts deliberately steered away from lithium.

This created a healthcare paradox: systems were paying exponentially more for treatments that were often less effective than the cheaper, proven alternative. Today, while lithium remains widely recommended for bipolar disorder, the shadow of its early toxicity scandals still haunts public perception. Additionally, the requirement for regular blood monitoring continues to deter both patients and physicians from choosing this remarkably effective treatment.

Pharmaceutical giants systematically directed research funds toward developing patentable alternatives rather than studying lithium further.

Not Just a Mood Enhancer but a Brain Protector

The lithium story has now taken an extraordinary turn in 2025 when Harvard Medical School published groundbreaking research that could rewrite our understanding of Alzheimer's disease. After nearly a decade of investigation, Dr. Bruce Yankner's team discovered that lithium deficiency may be the earliest detectable molecular change in Alzheimer's—potentially occurring decades before symptoms appear.

The research revealed lithium's crucial role as a brain protector, maintaining healthy amyloid clearance and preventing tau protein damage. But Harvard scientists uncovered a devastating trap: amyloid plaques actively sequester lithium from brain tissue, creating a vicious cycle where falling lithium levels lead to more plaques, which trap even more lithium. This discovery explains why standard lithium treatments often fail—they get caught in the very plaques they're meant to combat.

Amyloid Plaques were found to be notorious in absorbing common forms of Lithium such as in Lithium Citrate and Lithium Nitrate. That's why researchers used Lithium Orotate

The breakthrough came with lithium orotate, a formulation that bypasses this amyloid trap entirely. In animal studies, this approach achieved remarkable results: 70% reduction in amyloid plaques, complete memory restoration, and full reversal of neuroinflammation—all at doses 1,000 times lower than traditional lithium therapy. Perhaps most striking, aging mice treated with lithium orotate performed memory tasks at the level of young adults.

What makes this discovery revolutionary is that falling brain lithium levels can now serve as an early warning system, potentially identifying Alzheimer's risk decades before cognitive decline begins. This shifts the entire approach from treating advanced disease to preventing it altogether—transforming Alzheimer's from an inevitable fate into a potentially preventable condition.

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