How lithium went from 7Up to treatment for mental illness — and maybe Alzheimer’s A new study suggests lithium may play a crucial role in developing Alzheimer’s treatments, but the substance has long been used to treat mood disorders like bipolar disorder. Today at 6:00 a.m. EDT
A study this week in the journal Nature found that the loss of lithium, a naturally occurring element in the brain, could be an early sign of Alzheimer’s and a powerful driver of the disease, which afflicts more than 7 million Americans.
The study, led by Bruce A. Yankner, a professor of genetics and neurology at Harvard Medical School, found that lithium is important to the health of all the major types of brain cells in mice. Depletion of lithium in the brain also seems to be a factor in almost all of the major deterioration that occurs with Alzheimer’s disease.
While the latest study of lithium is novel in pointing toward a potential Alzheimer’s treatment, the use of lithium to treat other conditions is not. Here’s a look at what it has worked for and how its use is being researched in new ways.
What is lithium?
Lithium, soft and silvery, is nature’s lightest metal, enabling it to store energy at high density and discharge electrons rapidly.
“This is the basis of the lithium battery that powers our phones, laptops and electric vehicles,” Yankner said.
Less well known is that the original formulation of the soft drink 7Up contained lithium; the drink was marketed under the name Bib-Label Lithiated Lemon-Lime Soda. The lithium was removed in 1948 after the Food and Drug Administration banned the use of lithium citrate in soft drinks.
As of 2024, Australia was the world’s largest producer of lithium, though Bolivia, Chile and Argentina are known as the “lithium triangle.”
How has lithium been used for mental health treatment?
A form of lithium, lithium carbonate, has been widely prescribed in the treatment of bipolar disease in the United States since it was first approved by the FDA in 1970. It is believed to be a mood stabilizer and can also be prescribed for long-term treatment of depression.
While the precise mechanism of lithium carbonate isn’t known, it is believed to suppress stress in the brain and help restore neuroplasticity — the brain’s ability to change and adapt as we get older. One of the findings of the Nature study was that our brains contain a small amount of naturally occurring lithium.
There are cases of lithium being used in psychiatry going back to the mid-19th century, but the study of lithium for mood disorders took a larger step in the late 1940s when an Australian psychiatrist, John Cade, found that it helped many bipolar patients stabilize quickly.
“It’s been around for decades, and we have a lot of research and a lot of evidence supporting its use,” said Elizabeth Hoge, a professor of psychiatry at Georgetown University School of Medicine. “The most important thing is that it does help patients. We know that it works from randomized, controlled trials.”
Hoge said the use of lithium does require monitoring of renal and thyroid function, which can decline in some cases.
Balwinder Singh, an assistant professor of psychiatry at the Mayo Clinic, said lithium remains the “gold standard” medication for bipolar disorder, though it is under-prescribed in his view. About 10 to 15 percent of Americans with bipolar disorder take lithium, compared with about 35 percent of patients in Europe.
“Lithium is the only mood stabilizer consistently shown to reduce suicidality in individuals with bipolar disorder,” according to a recent comment Singh wrote in the journal Lancet Psychiatry.
Although lithium has been widely prescribed and its use is supported in many studies, a 2022 paper argued that its effect on bipolar depression, a part of bipolar disorder, does not represent a statistically significant improvement over a placebo or antidepressants.
Why is lithium being researched for Alzheimer’s?
Lithium had been investigated previously as a potential Alzheimer’s treatment and antiaging medication. A 2017 study in Denmark found that the presence of lithium in drinking water might be linked to a lower incidence of dementia in the population.
Yankner’s lab became interested in lithium after measuring the levels of 30 different metals in the brain and blood of people who were cognitively healthy, people in a very early stage of dementia and people with full-blown Alzheimer’s disease. Of the 30 metals, only lithium changed significantly among the three groups.
Lithium maintains the connections and communication lines that allow neurons in a healthy brain to talk with one another. The metal also helps form the myelin that coats and insulates the communication lines and helps microglial cells clear cellular debris that can impede brain function. All this adds up to promoting good memory function both in mice and in humans, researchers said.
How could the research translate to treatment?
Yankner’s lab found that small amounts of the compound lithium orotate were able to reverse a mouse model of Alzheimer’s disease and restore brain function. Researchers said the discovery should be enough to spur clinical trials for testing the compound in people.
But Yankner said he could not recommend at this point that people start taking lithium because its use for Alzheimer’s has not been validated in people, and “things can change as you go from mice to humans.” Lithium can also be toxic if not regulated properly.
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