Lithium salts have been valued as a health tonic for centuries. Natural lithium springs were long regarded as sought-after health resorts and attracted numerous writers, politicians and other celebrities. Particularly in the 19th century and well into the 20th century, lithium was widely used as a mineral supplement to enrich a wide variety of foods and drinks. One well-known example is the soft drink Seven-Up, which contained lithium citrate until 1950. It was originally marketed specifically for its mood-enhancing properties and was also intended to help alleviate the effects of excessive alcohol consumption.
In recent years, the element lithium has attracted increasing attention, particularly due to the evidence of its essentiality as a trace element and its neuroprotective effects. Due to its multifactorial molecular mechanisms, microdosed lithium administration in particular appears to be a promising approach for the prevention and adjuvant therapy of Alzheimer's disease.
Molecular mechanisms of action
The molecular basis of the neuronal protection of lithium was characterized in 2025 by De Paula et al. in a review paper based on a variety of mechanisms in animal models and cell cultures [1]:
- Inhibition of glycogen synthase kinase-3β, GSK-3β for short, which leads to a reduction in tau protein hyperphosphorylation and thus reduces the formation of neurofibrillary tangles
- Reduction in the accumulation of Aβ plaque
- Inhibition of neuroinflammatory processes via NF-κB reduction and microglia activation
- Promotion of neurogenesis by increasing BDNF expression
- Protection against oxidative stress and autophagy activation (via Nrf2)
- Lengthening of telomeres, which indicates an anti-ageing effect
- Improvement of synaptic integrity and associated memory improvement
- Reduction of neuronal apoptosis (=reduced death of nerve cells)
Clinical relevance
The promising preclinical data from animal models and cell cultures have also been confirmed in human studies. In a randomized clinical study, the so-called "Lit-AD study", low-dose lithium showed good tolerability and biomarker improvements in Alzheimer's patients, such as fewer Aß plaques and higher BDNF.BDNF stands for Brain-Derived Neurotrophic Factor and is a protein that is essential for the growth, survival and differentiation of neurons [2].
In addition, meta-analyses from 2024 and 2025 show cognitive stabilization in mild cognitive impairment (MCI) and Alzheimer's disease with low-dose lithium. Lithium deficiency correlated with higher dementia risk in epidemiological studies [3].
Terao & Kodama carried out an interesting comparison in 2024: in their meta-analysis, the results of the meta-analyses with lithium were compared with those of the anti-amyloid antibody-therapy (such as aducanumab, lecanemab and donanemab) compared to monoclonal antibodies. Lithium was found to be more effective than monoclonal antibodies for cognitive function with the best tolerance and acceptance by patients and would be superior to monoclonal antibodies in the treatment of Alzheimer's disease and mild cognitive impairment (MCI) [3,4].
The following table shows a comparison of the clinical key figures [3,4]:
| Parameters | Lithium (microdose) | Aducanumab | lecanemab | donanemab |
|---|---|---|---|---|
| Primary mode of action | GSK–3β–Inhibition, ↓Tau, ↓Aβ, NF–κB–Modulation, autophagy↑ | Aβ plaque reduction | Aβ plaque reduction | Aβ plaque reduction |
| Cognitive effects (MMSE) | Significantly better than aducanumab and placebo | Low to moderate effects, partly inconsistent | No comparable data | No comparable data |
| Risk of progression (MCI/Alzheimer’s) | 45-56% reduction | 22% reduction (controversial) | 27% reduction (MCI only) | 35% reduction (MCI only) |
| Annual costs | 90-250 € | 25.000-30.000 € | 20.000-25.000 € | 25.000-30.000 € |
| Side effects | Very good safety profile | 13-37% Cerebral edema (ARIA-E) and/or cerebral hemorrhage (ARIA-H), regular MRI checks necessary | 13-37% Cerebral edema (ARIA-E) and/or cerebral hemorrhage (ARIA-H), regular MRI checks necessary | 13-37% Cerebral edema (ARIA-E) and/or cerebral hemorrhage (ARIA-H), regular MRI checks necessary |
Practical implementation
For prevention or therapy, Michael Nehls recommends low-dose lithium in the form of lithium orotate. Lithium orotate is the preferred form compared to lithium carbonate or free lithium (e.g. medicinal water), as it offers more stable levels, better brain penetration and a longer half-life. It also has few side effects in microdoses and is therefore potentially suitable for long-term use. [5,6,7]
It is primarily used for neurodegenerative diseases such as Alzheimer's, Parkinson's and multiple sclerosis. It is also used for clinical pictures and complaints such as brain fog, depression, long COVID, post-vac syndrome, chronic headaches, epilepsy and during alcohol withdrawal. It is taken on prescription from approved pharmacies, as lithium orotate is still only available on prescription. Dr. Michael Nehls is currently seeking official recognition of lithium as an essential trace element in order to obtain approval for sale as a dietary supplement. Despite petitions and publications, however, lithium is not recognized as essential in the EU and is still only available on prescription as a supplement [7].
Dosage recommendations
Preventive/essential:
1 mg elemental lithium/day (equivalent to approx. 26 mg lithium orotate) to compensate for deficiency and prevent neuroinflammation.
Therapeutic:
2-5 mg elemental lithium /day (approx. 52-130 mg lithium orotate), e.g. for depression, MCI/Alzheimer's, brain fog, long COVID, etc. until symptoms subside
Monitoring
During long-term use, it is essential to monitor the lithium levels in the whole blood. The preventive target range in whole blood is between 25 and 350 µg/L (corresponds to approx. 3 – 50 µmol/L). Compared to serum monitoring in conventional psychiatric lithium therapy, this analysis in whole blood is significantly more sensitive and is offered by specialized laboratories such as Biovis [7].
Conclusion
The essential trace element lithium has proven to be a promising candidate with proven neuroprotective properties, as it supports the prevention and adjuvant therapy of Alzheimer's disease in microdosed form.
Clinical studies and meta-analyses confirm the cognitive stabilization and superiority over expensive anti-amyloid antibody therapies with better tolerability and orders of magnitude lower costs.
In practice, microdosed lithium orotate (1-5 mg elemental lithium per day, depending on the indication) with monitoring in whole blood is suitable.
References:
- De-Paula, V. J. R., Radanovic, M., & Forlenza, O. V. (2025). Lithium and neuroprotection: a review of molecular targets and biological effects at subtherapeutic concentrations in preclinical models of Alzheimer's disease. International journal of bipolar disorders,13(1), 16. https://doi.org/10.1186/s40345-025-00386-7
- Devanand, D. P., Strickler, J. G., Huey, E. D., Crocco, E., Forester, B. P., Husain, M. M., Vahia, I. V., Andrews, H., Wall, M. M., & Pelton, G. H. (2018). Lithium Treatment for Agitation in Alzheimer's disease (Lit-AD): Clinical rationale and study design. Contemporary clinical trials,71, 33-39. https://doi.org/10.1016/j.cct.2018.05.019
- Shen, Y., Zhao, M., Zhao, P., Meng, L., Zhang, Y., Zhang, G., Taishi, Y., & Sun, L. (2024). Molecular mechanisms and therapeutic potential of lithium in Alzheimer's disease: repurposing an old class of drugs. Frontiers in pharmacology,15, 1408462. https://doi.org/10.3389/fphar.2024.1408462
- Terao, I., & Kodama, W. (2024). Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer's disease: A systematic review and network meta-analysis. Ageing research reviews,94, 102203. https://doi.org/10.1016/j.arr.2024.102203
- Pacholko, A. G., & Bekar, L. K. (2021). Lithium orotate: A superior option for lithium therapy?.Brain and behavior,11(8), e2262. https://doi.org/10.1002/brb3.2262
- Strawbridge, R., Myrtle, S., Carmellini, P., Hampsey, E., Cousins, D. A., & Young, A. H. (2025). A Survey Exploring People's Experiences With Lithium Bought as a Supplement: Une enquête sur l'expérience des personnes avec le lithium en supplément. Canadian journal of psychiatry. Revue canadienne de psychiatrie ,70(10), 782-795. https://doi.org/10.1177/07067437251328282
- Nehls, M. (2025). The lithium conspiracy: A plea for an essential trace element – The forbidden key to mental health. Mental Enterprises
Image from shutterstock by Angel Soler Gollonet
