Two studies giving current hope for Alzheimer's
Creatine for fast brain changes, and lithium as a micronutrient
Two new studies on Alzheimer’s prevention and treatment bring me a lot of hope. The first study looks at using creatine for improving cognition, while the second explains how and why lithium is a key micronutrient for the prevention of Alzheimer's disease.
Creatine for cognitive function
The brain uses a lot of energy, and one theory is that impaired brain energy metabolism contributes to Alzheimer’s disease. A new study in the Alzheimer’s Association Journal1 directly looks at an inexpensive and easy solution.
The clinical trial involved 20 patients with Alzheimer’s diagnosis, 65% of whom carried the APOE4 allele. The trial looked at the effects of creatine supplementation.
Study participants took 20 g of creatine daily for 8 weeks. Researchers tracked the changes in brain metabolism and cognitive function.
By four weeks, there were significant increases in total creatine in the brain, and at 8 weeks, there were statistically significant improvements in multiple cognitive tests.
Creatine supplements have a good safety profile, and the most common complaint in this study was muscle pain, which resolved in the first weeks.
Creatine HCL supplements are readily available as a powder on Amazon, in health food stores, or even at Walmart. Here’s one2 that I’ve used.
Lithium for preventing Alzheimer’s
While low-dose lithium for Alzheimer’s disease isn’t a new topic (read about prior studies here), a new study published in Nature3 by Harvard researchers explains why and how lithium is important for brain health as we age.
The mechanism identified is really interesting (and not what I expected), so stick with me here as I explain parts of the study.
The researchers used mass spectrometry to determine the trace metal content both in the brain and blood of older people with either no cognitive impairment, mild cognitive impairment, or Alzheimer’s disease.
Metals have long been suspected of playing a role in Alzheimer’s disease. (Way back when I was young, I remember my grandma telling me not to use aluminum foil when baking because it would cause Alzheimer’s.)
In the study, the researchers looked at 27 different trace metals and found that only one, lithium, differed in the brains of people with mild cognitive impairment (MCI) or Alzheimer’s.
Lithium levels were significantly lower in the brain, but only in the prefrontal cortex, in the areas where amyloid beta plaque tends to accumulate. Blood levels of lithium were similar among all participants, suggesting that everyone was getting a similar amount through their diets.
The researchers then looked at how lithium interacts with amyloid plaques. They found that lithium was concentrated in the amyloid plaques, and that its level increased from mild cognitive impairment (MCI) to an Alzheimer’s diagnosis.
However, low levels of lithium were found in the amyloid plaque-free areas of the brain in individuals with AD and MCI - lower than were found in the brains without cognitive impairment.
Next up, the researchers used several mouse experiments to tease out what is going on. They found:
Lithium is sequestered in the amyloid-beta deposits, reducing its bioavailability in the rest of the brain.
Feeding mice an almost lithium-free diet (92% reduction) caused “a significant elevation in Aβ deposition” and at an earlier age.
Lithium deficiency also causes a 3 to 4-fold increase in tau tangles.
A lithium-deficient diet also impairs learning and long-term memory.
A lack of lithium in the brain causes changes in gene expression, upregulating the pathways seen in neurodegeneration and Alzheimer’s.
Lithium deficiency in the brain activates microglia, the brain’s immune cells, increases inflammatory cytokines (IL-6, TNF-alpha), and blocks the clearance of amyloid-beta.
The researchers also showed that lithium deficiency elevates GSK3β levels. (This finding is also backed up by decades of research on bipolar disorder and prescription levels of lithium carbonate.) Elevated GSK3β then directly increases the phosphorylation of tau, resulting in the neurofibril tangles.
Taking it to the final step, the researchers gave normal mice a low dose of lithium orotate (LiO) in their water from middle age on. The result showed that the low-dose lithium orotate almost completely prevented the age-related activation of microglia that causes inflammation in the brain. The low-dose lithium orotate also reversed the normal age-related decrease in the ability to degrade amyloid-beta plaque.
Thus, LiO reduces age-related neuroinflammatory changes and restores the ability of microglia to clear Aβ.
To me, this study beautifully explains why previous studies show positive results for low-dose lithium as a preventative strategy and for reversing the beginning stages of cognitive decline. It explains the epidemiological studies showing that areas with higher lithium in the water have a lower Alzheimer’s rate. Lithium is an essential micronutrient needed for amyloid beta clearance, prevention of tau tangles, and moderation of neuroinflammation.
What can you do with this information?
The Nature study then goes on to look at the possible solutions. There are multiple forms of lithium available, and the researchers determined that lithium orotate is the best form of lithium for elevating lithium in the non-plaque regions of the brain.
When it comes to lithium, the average amount that we get per day from food and water is estimated to be around 3 mg. In areas where lithium levels are naturally higher in the drinking water, there are lower rates of Alzheimer’s.4 I can’t help but think that many of us are eating food grown in micronutrient-depleted soil and drinking water that has the minerals stripped out.
Lithium orotate is readily available as a supplement online and in health food stores. You can get it in capsules, drops, or fastmelt. It’s inexpensive. For a 5mg supplement, you are looking at less than $3/month, and if you want to go with a lower dose than 5mg, you could easily do that with the liquid drops at an even lower monthly cost.
Which brand to use? ConsumerLab.com tested lithium supplements and found that all the brands they tested (KAL, Weyland, Advanced Research, Swanson, PureEncapsulation, Solaray, and Vital Nutrients) contained approximately the amount on the label and had no heavy metal contamination.
Talk with your doctor if you have any questions on whether a supplement is right for you.
Conclusion:
I love studies that give me practical, easy-to-implement solutions for the prevention of neurodegeneration and for improving cognitive function in aging.
Lithium orotate has been on my radar for about 10 years for Alzheimer’s prevention, but this study explaining the mechanisms going on with relative lithium deficiency in the brain is exactly what I needed to be consistent with it. I tend to need to know and understand the reason behind an intervention in order to truly buy into it and make it a habit.
Let me know in the comments if you have any experience with either creatine or lithium orotate in someone with MCI. I’m curious!
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Lithium deficiency and the onset of Alzheimer’s disease, Aron, et al. 2025
Thank you, Great piece!
Great info.