What is lithium?
Lithium is a lightweight soft mineral that when taken in high doses acts as a potent pharmaceutical with serious potential side effects; however, in low doses, it is a nutrient required for many important functions in the human body. (6) The medicinal use of lithium dates back to the mid-1800s, but it wasn’t until 1970 that the Federal Food and Drug Administration approved the use of lithium carbonate in psychiatry, making the United States the 50th country to approve the prescription. (10) Over the past several decades, research evaluating the brain and mental health effects of low-dose nutritional lithium has led to a growing interest among integrative health practitioners. The terms nutritional lithium and lithium orotate are often used interchangeably.Mechanisms of action
Much of the research that has taken place over the past 40 years has focused on the multiple mechanisms of action that lithium has on the brain. Lithium may exert its health effects along the following pathways: (3)(11)- Angiogenesis: stimulates cerebral blood flow
- Anti-inflammatory: increases anti-inflammatory immunoregulatory cytokines and other compounds
- Circadian rhythm: resynchronizes clock genes and can help normalize hypothalamus-pituitary-adrenal axis function
- Neurogenesis: stimulates growth factors, increases synaptic plasticity, and positively regulates cell survival
- Neuroprotective: preserves grey matter and influences cell division, metabolism, and apoptosis
- Neurotransmitters: modifies and synthesizes the release of key neurotransmitters, such as the promotion of GABA-mediated neurotransmission to calm, and inhibits excitatory neurotransmitters such as dopamine and glutamine
- Stem cell production: enhances stem cells so they can become neurons
What is lithium used for?
Given the mechanisms of action identified, it’s not surprising that lithium has been shown to benefit the brain from a mental and cognitive health standpoint.Lithium orotate for mental health
Scientific evidence demonstrates that people who live in lithium-deficient regions of the world, compared to higher lithium areas, are at increased risk of mood instability, including depression, drug dependence, hyper-aggression, and suicide. (7) A 2020 systematic review and meta-analysis looked at 15 different ecological studies and identified a consistent direct protective effect between lithium in drinking water and suicide when compared to communities with little or no lithium in the water. The data was so compelling that the researchers recommended that trials be conducted in which drinking water was supplemented with lithium in communities with high rates of crime, substance abuse, and suicide risk. (8) Another systematic review published in 2020 looked at 18 prospective, 10 retrospective, and 16 ecological studies, which also found that low levels of nutritional lithium provided protection against suicide and had a mood-stabilizing effect. (2) It’s important to note that there is no research demonstrating the efficacy of low-dose lithium orotate for the treatment of bipolar disorder or severe depression with a suicidal tendency. These are serious conditions and require the care of a trained professional who may prescribe pharmaceutical lithium carbonate. Interestingly, while pharmaceutical lithium carbonate can lead to cognitive ramifications including brain fog, poor concentration, and confusion, the opposite is true with low-dose nutritional lithium orotate. (12)
Lithium orotate has been shown to benefit mental and cognitive health.
Lithium orotate improves brain function
The neuroprotective mechanisms of lithium indicate that it may be important for several neurological applications. Researchers first looked at reducing the risk of cognitive decline and Alzheimer’s disease, and research conducted in 2011 and 2019 confirmed that patients with mild cognitive impairment who were given low-dose nutritional lithium treatment experienced enhanced cognitive performance and attention compared to a placebo. Both of these randomized clinical trials also showed that low-dose lithium treatment was associated with a reduction in cognitive deterioration and enhanced brain function. (4)(5) These results are supported by further research showing that low-dose lithium can help prevent cognitive decline, particularly in high-risk patients who are showing signs of mild cognitive impairment. (9)The bottom line
As a human race, we have been ingesting small amounts of lithium from food and water since the dawn of time. Scientific evidence now shows that these small amounts of this trace mineral are incorporated into biological systems that can impact health, specifically brain health. Low-dose nutritional lithium may help enhance mental health and also improve cognition and reduce the risk of cognitive decline.References
- Brown, E. E., Gerretsen, P., Pollock, B., & Graff-Guerrero, A. (2018). Psychiatric benefits of lithium in water supplies may be due to protection from neurotoxicity of lead exposure. Med Hypothesis, 115, 94-102.
- Del Matto, L., Muscas, M., Murru, A., Verdolini, N., Anmella, G., Fico, G., Corponi, F., Carvalho, A. F., Samalin, L., Carpiniello, B., Fagiolini., A., Vieta, E., Pacchiarotti, I. (2020). Lithium and suicide prevention in mood disorders and in the general population: a systematic review. Neuroscience and Biobehavioral Reviews, 116,142-153.
- Forlenza, O. V., De-Paula, V. J., & Diniz, B. S. (2014). Neuroprotective effects of lithium: implications for the treatment of Alzheimer’s disease and related neurodegenerative disorders. ACS Chem Neurosci, 5(6), 443-450.
- Forlenza, A. V., Diniz, B. S., Radanovic, M., Santos, F. S., Talib, L. L, & Gattaz, W. F. (2011). Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomized controlled trial. Br J Psychiatry, 198(5), 351-6.
- Forlenza, O. V., Radanovic, M., Talib, L. L., & Gattaz, W. F. (2019). Clinical and biological effects of long-term treatment in older adults with amnestic mild cognitive impairment: randomized clinical trial. BJ Psych, 215(5), 668-674.
- Marshall, T. M. (2015). Lithium as a nutrient. Journal of American Physicians and Surgeons, 20(4).
- Martone, G. (2018). Nutritional lithium. J Clin Psychiatry Neurosci, 1(1), 3-4.
- Memon, A., Rogers, I., Fitzsimmons, S., Carter, B., Strawbridge, R., Hidalgo-Mazzei, D, & Young, A. H. (2020). Association between naturally occurring lithium in drinking water and suicide rates: systematic review and meta-analysis of ecological studies. BJ Psych, 217, 667-678.
- Nunes, M., Viel, T., & Buck, H. (2013). Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s. Curr Alzheimer Res, 10(1), 104-7.
- Shorter E. (2009). The history of lithium therapy. Bipolar disorders, 11 Suppl 2(Suppl 2), 4–9.
- Szklarska, D., & Rzymski, P. (2019). Is Lithium a Micronutrient? From Biological Activity and Epidemiological Observation to Food Fortification. Biological trace element research, 189(1), 18–27.
- Volkmann, C., Bschor, T., & Kohler, S. (2020). Lithium treatment over the lifespan in bipolar disorders. Frontiers in Psychiatry, 11(377).
