Why would this be worth investigating and discussing for neuroprotection? The answer will become clearer, below, but low dose lithium appears to have the potential to not only prevent disease, but also to be disease modifying for both Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). It is important to differentiate between high dose lithium and the low doses we are discussing here.
Isn’t lithium a dangerous drug requiring monitoring of blood levels? Yes, when used in doses for bipolar disease (mostly manic phase) at 300-600 mg/dose 2-3 times daily. The doses reviewed here are a fraction of this, typically 15-45 mg per day for those who have disease, and 1-10 mg per day for those who are at risk of disease, which generally would not require blood level monitoring. The rationale for this dose, for those who have disease, is at least partially detailed here: https://clinicaltrials.gov/study/NCT06099886
Isn’t lithium a prescription drug? Yes, but it is widely sold as a supplement in these doses without need for a prescription (some countries like the U.K. and Switzerland require a prescription). I prefer Lithium Orotate as the form to use as it has a long metabolic half-life, allowing daily dosing, and seems to cross into the brain significantly better than lithium carbonate, the standard prescription formulation.
A good article on this is available here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413749/ This article’s section 3.3, details the science behind lithium decreasing neuroinflammation and normalizing a whole host of inflammatory markers including interleukin‐4, interleukin‐6, interleukin‐1β and tumor necrosis factor‐α (TNFα). It appears that some anti-inflammatory effects of lithium relate to GSK3β antagonism, which is involved in pro‐inflammatory microglial (this is the primary immune cell in the central nervous system) responses.
1. Lithium promotes benefits in cognitive and pathophysiological aspects of AD and PD.
2. Lithium might represent a valid option for AD and PD treatments.
3. Human studies are still lacking to clarify the beneficial effects of lithium.
Dosing is speculative, but based on some rationale as noted in the reference below. It is important to noted that patients on mental health doses aren’t what should be reviewed, as the dosing here is from <0.1% up to 5% of those doses. https://clinicaltrials.gov/study/NCT06099886
Alzheimer's Disease and Lithium:
This article https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003941 looked at individuals exposed or not exposed to lithium and concluded “We observed an association between lithium use and a decreased risk of developing dementia. This lends further support to the idea that lithium may be a disease-modifying treatment for dementia and that this is a promising treatment to take forwards to larger randomised controlled trials (RCTs) for this indication.” Their adjusted likelihood of being diagnosed with AD was 0.55 (45% less likely than expected) and for Vascular Dementia was 0.36 (64% less likely than expected).
This article https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1408462/full gives a solid summary with the introduction stating “Several studies indicate that lithium may be a disease-modifying agent in the treatment of AD. Lithium’s neuroprotective properties in AD by acting on multiple neuropathological targets, such as reducing amyloid deposition and tau
phosphorylation, enhancing autophagy, neurogenesis, and synaptic plasticity, regulating cholinergic and glucose metabolism, inhibiting neuroinflammation, oxidative stress, and apoptosis, while preserving mitochondrial function.”
This 2016 discussion, written by a psychiatrist on use of Lithium for AD is a worthwhile read. It has multiple additional reference articles. https://www.psychiatrictimes.com/view/lithium-alzheimer-prevention-what-are-we-waiting He discussed a 2013 study where as little as 1.5 mg daily of lithium stabilized cognitive impairment in AD patients (his reference #1).
This study https://pubmed.ncbi.nlm.nih.gov/21525519/ discussed how lithium use led to a significant decrease in tau protein and better performance on the cognitive part of the AD Assessment scale and in attention tasks.
There are also findings in patients with high dose lithium (often confounded by lifestyle issues relating to underlying mental illness) of increased rates of Dementia. Another look at very low dose exposures in drinking water in Japan indicated benefit in Women, but not in Men. https://gwern.net/doc/psychiatry/lithium/2022-muronaga.pdf
This study, looked at those on mental health dosing of lithium (much higher than what we are discussing) and didn’t see any benefit for dementia, but did see lower cardiovascular and cerebrovascular disorders. https://pubmed.ncbi.nlm.nih.gov/36651280/
Here is another upcoming clinical trial which will examine lithium 20 mg/day in 20 early-stage PD patients. https://clinicaltrials.gov/study/NCT06339034 Among their description and rationale, is a 77% reduced risk of developing PD in observational studies with small doses of lithium.
This interesting 2023 review of patients who have PD, disease progression, and supplements taken concluded: Nutraceuticals associated with improved outcomes were Ginkgo biloba (GB), NAD+ or its precursors, 5-methyltetrahydrofolate, glutathione, mucuna, CoQ10, low dose lithium, curcumin, homocysteine factors, DHEA, coconut oil, vitamin C, and omega-3 fatty acids (fish oil). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966010/
What have we learned here?
We’ve got an association with lithium use, primarily in low dose, and the potential to decrease rates of PD and AD, and possibly disease modification of these conditions. We need prospective trials. We at least see a couple, listed above for PD, but not for AD .. ahh but we do https://www.clinicaltrials.gov/study/NCT03185208 and it has estimated completion 8/31/24!
It’s a relatively benign supplement for most people, but a poison at high doses.
Would I take it myself if I had early PD or high risk of developing AD or early cognitive decline? It would seem very low risk.
Are there some better drugs in this space for PD and AD that have better data? Yes, but a multipronged approach is probably sensible, as some of the items chosen won’t end up working out (this seems low risk for harm) and others will.
Another caution – which is why it is worth looking at mechanisms, is to consider not having all attempted treatment/preventive medications and supplements only addressing a single pathway. Lithium seems to be working on somewhat different pathways than other drugs discussed thus far.
Disclaimer:
This blog provides general education only and should not be used to diagnose or replace the advice of a qualified medical professional.
This content is not intended to be a substitute for consultation with a qualified and licensed physician or another medical provider.
Readers should consult a medical professional for advice, diagnosis and treatment relating to their individual case.
You should discuss any supplement/medication being considered with your medical professional before starting it.
This post could contain affiliate links. I may receive a small commission if you click on the links of the products and make a purchase.
Credit:
Special thanks to Antoine Dusséaux of www.adssx.com for his assistance with research and authoring of this blog.
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