What I’m Doing to Prevent Alzheimer’s Disease After Seeing this New Harvard Study

What if one of the simplest elements in the known universe could help prevent Alzheimer's disease? It's a radical idea, but you might be surprised to learn it's not entirely novel. I'm raising this topic now because a major new paper published in Nature from researchers at Harvard has reinvigorated the scientific interest in lithium for Alzheimer's disease prevention. We will dive into these new data, and we will end with practical takeaways that could change your daily routine and protect your brain. And I promise to tell you what I'm doing personally and what I'm recommending for my parents. But first, let's lay the groundwork. Common and trace metals play critical roles in biology. Think about zinc or iron. They're essential for cell signaling, enzyme activation, and altering biochemical pathways. But one of the simplest metals of all— actually, the simplest metal of all— and one of the smallest elements on the periodic table is Lithium. But despite its simplicity, lithium is biologically potent and pretty mysterious. At very high doses, lithium is a mood stabilizer commonly prescribed for bipolar disorder. That's really fascinating when you stop to think about it. One of the simplest elements in the known universe is a frontline treatment for severe mental illness. It can alter the human mind potently. Kinda crazy. And over the years, signals have emerged in the scientific literature suggesting that lithium may protect against Alzheimer's disease. For example, population studies have found that regions with higher levels of lithium in the drinking water, trace lithium just naturally found in drinking water, tend to have lower rates of Alzheimer's disease and other dementias. Quoting from JAMA Psychiatry, "Exposure to higher long-term lithium levels in drinking water may be associated to the lower incidence of dementia. Coincidence? I doubt it. We already know that lithium inhibits a key protein involved in Alzheimer's pathology called glycogen synthase kinase 3 beta, or GSK3 beta for short. The name isn't great and doesn't exactly reveal its mischief. GSK3 beta, also called tau kinase 1, adds a phosphate group to a protein called tau in the brain, and this drives the formation of one of the core hallmarks of Alzheimer's disease: phospho-tau neurofibrillary tangles. As a matter of fact, GSK-3 beta, this tau kinase 1, actually promotes the formation of both neuropathological hallmarks of Alzheimer's disease: the infamous amyloid plaques and these phospho-tau neurofibrillary tangles. And if you want a real mind twister, you can try to read this paper, from which I took this multi-loop model figure. It's written by some weirdo when he was at Oxford. Anyway, to simplify, higher lithium levels in drinking water correlate geographically with lower Alzheimer's disease rates. And lithium inhibits a protein, GSK3 beta, in the Alzheimer's brain that is hyperactive and drives Alzheimer's disease. And we can add to this that older evidence, preliminary human trials, show that very low-dose lithium even 1,000 times lower doses than used to treat bipolar, appears to slow Alzheimer's progression in humans. Those trials already exist. The picture's already pretty intriguing. And now add onto it this new Harvard study. So let's talk about this study. The research behind this new study began with an exploratory analysis measuring 27 common and trace metals in the brain and blood of people with normal cognition, mild cognitive impairment, a precursor to Alzheimer's disease, and full-blown Alzheimer's disease. And only lithium stood out. Lithium was significantly reduced in the prefrontal cortices of individuals with mild cognitive impairment and, to a greater extent, in Alzheimer's disease. And strikingly, lithium was also concentrated in the amyloid plaques in the Alzheimer's brain, the same plaques that, along with tau tangles, represent the neuropathological hallmarks of Alzheimer's disease. So if you're paying really close attention, maybe you can see how this lithium sequestration, this lithium trapping by amyloid, could establish a vicious cycle. Lithium inhibits GSK-3 beta, which drives tau pathology. Amyloid plaques then trap and deplete lithium, diminishing its protective effects. And the result is a self-perpetuating loop of worsening disease. Less lithium, worse disease. Worse disease, trapping lithium, and so on. Pretty scary, but also hopeful. The team then confirmed that lithium deficiency does indeed exacerbate and contribute to Alzheimer's disease by feeding mice a lithium-depleted diet and comparing them to control mice. The results were dramatic. Lithium deficiency worsened neuropathology, more amyloid plaques, higher levels of toxic amyloid oligomers, Aβ40 and Aβ42, and faster phospho-tau tangle accumulation, and cognition suffered. Memory impairment appeared sooner and was more severe. The authors write, "Administration of the lithium-deficient diet to mice significantly impaired learning and long-term memory." Furthermore, molecular analyses revealed that lithium deficiency decreased the expression of genes and proteins critical for synaptic function and myelination while increasing those linked with neuroinflammation. And importantly, these transcriptomic and proteomic changes mirrored those seen in humans with Alzheimer's disease. So in short, lithium deficiency in the animal model reproduces many of the brain changes found in human Alzheimer's disease. Now comes the moment I know you've been waiting for. Can Alzheimer's disease be slowed or reversed with supplemental lithium? I'm going to give you the answer, but probably with more detail than you were expecting. You see, lithium is a positively charged element that forms salts when combined with negatively charged components, and different salts behave differently in the body. They have different conductances, and the researchers wanted to find the lithium salt that is least likely to be trapped in amyloid plaques. This maximizes its bioavailability in the brain and thereby can maximize its anti-Alzheimer's potential. So they tested 16 different lithium salts for their conductance, and one stood out: lithium orotate. And when mice were given this lithium orotate, the results were remarkable. It prevented amyloid plaque deposition and phospho-tau accumulation. And it even reversed existing pathology in a follow-up experiment when given after the disease had already progressed. In fact, memory loss was almost completely reversed even at the lowest doses tested. By contrast, lithium carbonate, another lithium salt that was used as a control, failed to produce these effects, probably because it was sequestered, trapped by the amyloid plaques. Now, I know I've gone over a lot. Hopefully you've been able to follow along. But I want to pause and summarize to ensure you've got the main points. Lithium is a trace element with multiple biological roles, including inhibition of GSK-3 beta, a protein that worsens Alzheimer's disease pathology. The data suggests that lithium levels are lower in patients with Alzheimer's disease than in controls, and higher lithium in drinking water already is known to correlate with lower Alzheimer's disease rates geographically. And a previous small human trial already found low-dose lithium can slow Alzheimer's progression, but this Harvard study rigorously confir— confirms that lithium deficiency exacerbates Alzheimer's disease and neuropathological brain changes, and it finds that specifically lithium orotate can prevent and even reverse these pathologies in animal models. Pretty cool! Now, now, I can't give medical advice via YouTube, you already know that, but I can tell you what I'm gonna do. I'm now gonna take 5mg of lithium orotate daily. Maybe for the rest of my life. For the brand I'm using, see the newsletter linked in the video notes. No affiliation, but I will disclose what I'm using. And just to put that in perspective, bipolar disorder treatment uses lithium dosed at around 600mg or more per day. So that boosts levels in the blood to about 1,000 times above what's physiologically normal. This super high-dosed lithium used for bipolar disorder can have adverse effects, But obviously 5mg is far lower than 600mg, but 5mg is still higher than the doses that are known to have biological effects in humans based on prior trials. So basically, in my view, 5mg sits in the sweet spot of being both safe and potentially effective. And for me, now disclosing, this is especially important since I'm among the 2% of people who carry two copies of the APOE4 gene variant, for Alzheimer's disease, the risk gene variant, that increases my risk for Alzheimer's disease 15-fold. But my genes aren't my fate, and neither are yours. I love data like these because they give me the opportunity to turn insight into action, and they give my neurons a little boost. Get it? Anyway, I hope you found this interesting. I hope you found it useful. Stay curious, and thank you.