In a new study, a team of researchers has shown that, when given in a formulation that facilitates passage to the brain, lithium in doses up to 400 times lower than what is currently being prescribed for mood disorders is capable of both halting signs of advanced Alzheimer’s pathology and of recovering lost cognitive abilities.
The above snippet is from a press release published in January 2020 on Science Daily: Can lithium halt progression of Alzheimer’s disease? Keep in mind that this is an animal study but the results are so promising. I’m also very intrigued by the delivery method (more on that below).
In order to give this microdosing context, a typical adult prescription is 900-1800mg lithium carbonate/day. I reached out to the lead author for clarification about the dosing of this new formulation and lead researcher Dr. Cuello shared this with me:
I calculate that our lithium dosage is 285 times lower concentration than the 900 mg dose (based on 70 kg of body weight) and 570 times lower than the 1800 mg dose.
This translates to around 3.2 mg to 6.4 mg NP03 based on 70kg of body weight (which is around 154.3 lbs).
NP03 is a disease-modifying nano dose formulation of lithium citrate which is used sublingually. I assume it’s not yet commercially available.
Also from the press release: “our findings show that microdoses of lithium in formulations such as the one we used, which facilitates passage to the brain through the brain-blood barrier while minimizing levels of lithium in the blood, sparing individuals from adverse effects, should find immediate therapeutic applications.”
Here is a link to the actual paper: NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats
Can we compare NP03 to low dose lithium orotate?
What is really interesting is that low dose lithium in the form of lithium orotate is commonly recommended by integrative practitioners for anxiety, mild mood swings, brain fog, ADHD and insomnia. I have found it to be extremely beneficial for many of my clients and have used it personally with success (for brain fog and insomnia).
Just how much lithium orotate is low dose? Typical doses are 5-10 mg per day, increasing to 20mg per day.
Can we compare NP03 to low dose lithium orotate? It’s too early to know for sure but we I believe we can start to make extrapolations, especially given that both are very low doses.
Integrative psychiatrist, Dr. James Greenblatt, MD has written extensively about low dose lithium orotate for the above purposes and for Alzheimer’s too. In this article, Lithium: The Cinderella Story About a Mineral That May Prevent Alzheimer’s Disease, he shares that
Scientists first became interested in the use of lithium for treating neurodegenerative disorders when they observed that bipolar patients using lithium therapy seemed to have lower rates of cognitive decline than peers on other medications.
He writes how an enzyme called Glycogen Synthase Kinase-3 (GSK-3) – a serine/threonine protein kinase – normally plays a major role in neural growth and development and how lithium
works as a direct GSK-3 inhibitor… halting inappropriate amyloid production and the hyper-phosphoryation of tau proteins before they become problematic.
If all this fascinates you as much as it does me, Dr. Greenblatt writes more about lithium orotate in his excellent book: “Nutritional Lithium: A Cinderella Story: The Untold Tale of a Mineral That Transforms Lives and Heals the Brain” (my Amazon link).
Lithium deficiency and the onset of Alzheimer’s disease: a 2025 study
Update August 8, 2025:
A new animal study, Lithium deficiency and the onset of Alzheimer’s disease (and published Aug 2025), supports the above, concluding that lithium orotate is “a potential approach to the prevention and treatment of Alzheimer’s disease.” The authors share this about lithium in the brain:
endogenous lithium is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, lithium was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to Alzheimer’s disease. Lithium bioavailability was further reduced in Alzheimer’s disease by amyloid sequestration.
The authors explored the role of endogenous lithium in the brain (i.e. lithium within the brain) by depleting it from the diet of wild-type and Alzheimer’s disease mouse models and found that:
Reducing endogenous cortical lithium by approximately 50% markedly increased the deposition of amyloid-β and the accumulation of phospho-tau, and led to pro-inflammatory microglial activation, the loss of synapses, axons and myelin, and accelerated cognitive decline.
It’s exciting that they found that lithium orotate, “a lithium salt with reduced amyloid binding, prevents pathological changes and memory loss in Alzheimer’s disease mouse models and ageing wild-type mice.” And this paper also mentions the fact that these “effects were mediated, at least in part, through activation of the kinase GSK3β.”
They conclude that:
These findings reveal physiological effects of endogenous lithium in the brain and indicate that disruption of lithium homeostasis may be an early event in the pathogenesis (cause) of Alzheimer’s disease. Lithium replacement with amyloid-evading salts [such as lithium orotate] is a potential approach to the prevention and treatment of Alzheimer’s disease.
Given the concerns with the toxicity of high dose prescription lithium carbonate, I appreciate that this was addressed:
An important limitation in the treatment of aged individuals with pharmacological doses of lithium [i.e. lithium carbonate] is kidney and thyroid toxicity. It is encouraging that toxicity could not be detected following long-term treatment of ageing mice with a low dose of lithium orotate.
Alzheimer’s and cognitive decline have many root causes
Keep in mind that Alzheimer’s and cognitive decline have many root causes that must be considered. This may include inflammation, stress and candida, and even insecticide exposure.
The best Alzheimer’s book is “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline” by Dr. Dale Bredeson (my Amazon link). He doesn’t mention lithium orotate so I look forward to hearing his thoughts on this new research. [I’ll come and update the blog when I do]
You can read about some of Dr. Bredesen’s work here: Alzheimer’s disease, mercury and mycotoxins.
Benzodiazepines have also been linked to increased Alzheimer’s risk which is why a nutritional approach for anxiety is the best approach. Let’s use the amino acids like GABA (for physical anxiety), and tryptophan (for worry and fears), as well as dietary changes and improving gut health instead of anti-anxiety medications (more on these below).
Additional resources when you are new to using tryptophan and other amino acids as supplements
As always, I use the symptoms questionnaire to figure out if low serotonin or other neurotransmitter imbalances may be an issue.
If you suspect low levels of any of the neurotransmitters and do not yet have my book, The Antianxiety Food Solution – How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood, and End Cravings, I highly recommend getting it and reading it before jumping in and using amino acids on your own so you are knowledgeable. And be sure to share it with the practitioner/health team you or your loved one is working with.
There is an entire chapter on the amino acids and they are discussed throughout the book in the sections on gut health, gluten, blood sugar control (this is covered in an entire chapter too), sugar cravings, anxiety and mood issues.
The book doesn’t include product names (per the publisher’s request) so this blog, The Antianxiety Food Solution Amino Acid and Pyroluria Supplements, lists the amino acids that I use with my individual clients and those in my group programs.
If, after reading this blog and my book, you don’t feel comfortable figuring things out on your own (i.e. doing the symptoms questionnaire and respective amino acids trials), a good place to get help is the GABA QuickStart Program (if you have low GABA symptoms). This is a paid online/virtual group program where you get my guidance and community support. You can sign up to be notified when the next live launch is happening.
If you need serotonin support, the Serotonin QuickStart Program is a good place to get help. This is also a paid online/virtual group program where you get my guidance on using tryptophan and 5-HTP safely, and community support during 5 LIVE Q&A calls. You can sign up to be notified when the next live launch of this program is happening.
If you are a practitioner, join us in The Balancing Neurotransmitters: the Fundamentals program. This is also a paid online/virtual program with an opportunity to interact with me and other practitioners who are also using the amino acids.
Wrapping up and your feedback
I look forward to human clinical trials of NP03. Dr. Cuello “ believes that there is an excellent opportunity to launch initial clinical trials of this formulation with populations with detectable preclinical Alzheimer’s pathology or with populations genetically predisposed to Alzheimer’s, such as adult individuals with Down Syndrome.”
I also look forward to human clinical trials of lithium orotate for Alzheimer’s disease. And I would love to see lithium orotate compared to NP03 in future research.
In the meantime I feel this research is exciting because it supports so much of what is being seen clinically with lithium orotate.
Have you used lithium orotate with success? How much has helped you and have you seen cognitive benefits? What about a more even mood, better sleep and less anxiety?
And have you or a family member seen improvements with the Bredesen protocol?