The researchers in the study performed several separate lines of research and published them all in one paper. First, using advanced lab techniques, they studied humans and determined the following:
That patients with Mild Cognitive Impairment (a precursor to Alzheimer’s disease) had low levels of Lithium in a part of their brain known as the pre-frontal cortex when compared to healthy controls.
That patients with Alzheimer’s have even lower levels of Lithium in their pre-frontal cortex than patients with Mild Cognitive Impairment
That patients with Mild Cognitive Impairment and Alzheimer’s do NOT have lower levels of Lithium in their bloodstream, nor in other parts of their brain, as compared to healthy controls.
The study had a “part 2”, but before I get into that, I want to note that these three points taken together paint a compelling picture. It is extremely difficult to prove cause and effect in medicine, because humans don’t live in petri dishes and can’t be studied in tightly controlled experiments that eliminate all possible confounding variables. None of the above proves beyond a doubt that Lithium plays a role in Alzheimer’s disease. However, the fact that lithium deficiency is found only in a part of the brain that is known to be affected in Alzheimer’s disease; and that lithium levels are found in a “step down” fashion in which healthy people have the highest levels, Alzheimer’s patients have the lowest, and patients with mild Mild Cognitive Impairment are in the middle, certainly suggest that this is a real possibility. Had the study found instead that Lithium levels were all over the place between the three groups of patients, or that they were reduced in many parts of the brain, it would increase the likelihood that this is just a chance finding that has no causal relationship to the development of dementia.
And now on to “part 2”. In a separate set of experiments the researchers found that:
Depriving mice of Lithium in their diet leads to degenerative changes in the brain that are consistent with Alzheimer’s disease, and
Providing those mice with Lithium supplements reverses those changes.
Again, does this prove that Lithium deficiency is the cause of Alzheimers, or that Lithium supplementation is the cure? Not at all. Mice are not humans, and the medical literature is filled with findings from animal studies that didn’t pan out once tested in humans. We still need a good randomized control study in humans (for example: give patients with early stage Alzheimer’s Lithium versus a Placebo for 24 months and follow what happens to them). But the mice findings are much more suggestive in light of the human findings from the first part of the trial, in which a plausible link was established between lithium and dementia in actual human patients.
Are there other pieces of evidence for this “Lithium hypothesis”? It turns out that there are. Consider:
Seafood, nuts, and leafy green vegetables are some of the highest lithium containing foods found in nature. And prior evidence suggests that a mediterranean style diet (which is high in – you guessed it – seafood, nuts, and green leafy vegetables) is associated with lower rates of dementia
Lithium – at high doses – has long been used to treat severe cases of bipolar disorder, which demonstrates that this mineral can have a profound effect on brain function. Moreover, while people with bipolar disorder on average have a higher risk of developing dementia as compared to the general population, some research suggests that this risk is reduced in those treated with lithium.
In sum, the jury is very much still out on what role lithium plays in the potential for developing Alzheimer’s disease and other types of dementia, but we now have multiple lines of evidence that are starting to point out a potential connection between the two.
What should we do, in the year 2025, with this information?
Let me stress that this is a blog, and no doctor-patient relationship is implied if you are reading this. In other words, please don’t make any medical decisions from reading this nor any of my other posts. Go talk to your doctor.
With that said, I would offer the following general thoughts on this topic:
There is still a lot we don’t know. If you are young and healthy with no major risk for dementia in the next decade or two, it would be very reasonable to just wait for more research in this area to develop.
If you are older and very worried about developing dementia (as many patients are), or if you are already starting to exhibit some signs of memory loss, you could talk to your doctor about trying a very low dose of lithium. It’s important to note that the type of lithium used in the new Nature study was Lithium Oronate, which is available in low doses (typically 5-10mg) over the counter without a prescription. By way of contrast, when doctors prescribe lithium for severe psychiatric conditions such as bipolar disorder, they typically are prescribing 300mg-600mg daily. So for the purposes of possible dementia protection, we are talking about doses of 1/30th or less of a prescription, which is unlikely to cause any major side effects. Even so, we get a bit nervous about patients taking prescription strength lithium due to a known risk for kidney failure, and monitor these patients closely. While the over the counter doses are not likely to cause this issue, if you are inclined to try taking Lithium I would suggest working with a licensed healthcare provider to closely monitor your kidney function and electrolyte levels just to be safe. And, please don’t exceed the dose on the bottle of your supplement.
