Lithium and Memory
Lithium is a mineral present in foods like potatoes, cabbage, nuts, tomatoes and cereals as well as in our drinking water. The average person ingests around 0.4-3 mg per day through their diet and many experts agree this mineral plays a key role in supporting brain and mood health. Lithium is believed to relieve anxiety, support a positive mood and support long-term cognitive health (1)(2)(3).
Lithium inhibits GSK3.
One study followed 113 participants with mild memory loss for 15 months. Participants were divided into two groups and were to receive either lithium or placebo. Over the 15-month period, the placebo group continued to experience cognitive decline while the group receiving lithium showed no decreased cognitive performance (4).
Researchers of this study believe lithium’s potential benefits comes from its ability to inhibit the enzyme, GSK3. GSK3 is well-known to be associated with memory loss while lithium’s ability to inhibit GSK is also very well-established (4-10).
Lithium boosts BDNF.
Lithium’s neuroprotective properties are believed to come from its ability to boost levels of Brain-derived neurotrophic factor (BDNF). In a study, those with mild memory loss experienced a significant increase in BDNF levels while taking lithium (11).
BDNF is a special protein called a "neurotrophin" and helps the brain develop new connections, repair failing brain cells and protect healthy brain cells. It plays an important role in neuronal survival, growth and function (12). Studies have shown BDNF is lower as we age and in those with memory loss (13).
Lithium is associated with better memory outcomes.
A study published in 2022 screened almost 30,000 electronic medical records and found an association with lithium use and a decreased risk of developing memory loss. Researchers say this supports the idea lithium (14).
An additional study separated 45 adults with mild memory loss into a lithium and a placebo group. After one year, the group using lithium had a nearly 50% lower rate of worsening memory than those in the placebo group (15).
Between the two groups, this study also found a significant difference in CSF (cerebrospinal fluid) levels of the protein “P-tau.” After one year, the P-tau levels decreased in the lithium group whereas the placebo group recorded elevated P-tau levels. Increasing CSF levels of P-tau are associated with worsening memory (15).
References:
1) Al-Achi, A. (2019). Lithium as a dietary supplement. Journal of Pharmacy Practice and Pharmaceutical Sciences, 2019(01). https://doi.org/10.33513/ppps/1901-16
2) Lithium Orotate for Brain Health, mood and anxiety. Calgary Age Management. (2018, November 25). Retrieved July 13, 2022, from https://www.calgaryagemanagement.com/lithium-orotate/
3) Lanphier, L. (2019, October 11). Benefits of lithium orotate. OAWHealth. Retrieved July 13, 2022, from https://oawhealth.com/2016/07/11/benefits-of-lithium-orotate/
4) Andrade Nunes, M., Araujo Viel, T., & Sousa Buck, H. (2013). Microdose lithium treatment stabilized cognitive impairment in patients with alzheimer’s disease. Current Alzheimer Research, 10(1), 104–107. https://doi.org/10.2174/1567205011310010014
5) DaRocha-Souto, B., Coma, M., Pérez-Nievas, B. G., Scotton, T. C., Siao, M., Sánchez-Ferrer, P., Hashimoto, T., Fan, Z., Hudry, E., Barroeta, I., Serenó, L., Rodríguez, M., Sánchez, M. B., Hyman, B. T., & Gómez-Isla, T. (2012). Activation of glycogen synthase kinase-3 beta mediates β-amyloid induced neuritic damage in alzheimer’s disease. Neurobiology of Disease, 45(1), 425–437. https://doi.org/10.1016/j.nbd.2011.09.002
6) Takashima, A. (2006). GSK-3 is essential in the pathogenesis of alzheimer’s disease. Journal of Alzheimer’s Disease, 9(s3), 309–317. https://doi.org/10.3233/jad-2006-9s335
7) Aplin AE, et al. Effect of increased glycogen synthase kinase-3 activity upon the maturation of the amyloid precursor protein in transfected cells. Neuroreport. 1997;8:639–643.
8) Patel, S., & Woodgett, J. (2008). Glycogen synthase kinase-3 and cancer: Good cop, bad cop? Cancer Cell, 14(5), 351–353. https://doi.org/10.1016/j.ccr.2008.10.013
9) Ryves, W. J., & Harwood, A. J. (2001). Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochemical and Biophysical Research Communications, 280(3), 720–725. https://doi.org/10.1006/bbrc.2000.4169
10) Snitow, M. E., Bhansali, R. S., & Klein, P. S. (2021). Lithium and therapeutic targeting of GSK-3. Cells, 10(2), 255. https://doi.org/10.3390/cells10020255
11) Leyhe, T., Eschweiler, G. W., Stransky, E., Gasser, T., Annas, P., Basun, H., & Laske, C. (2009). Increase of BDNF serum concentration in lithium treated patients with early alzheimer’s disease. Journal of Alzheimer’s Disease, 16(3), 649–656. https://doi.org/10.3233/jad-2009-1004
12) Bathina, S., & Das, U. N. (2015). Brain-derived neurotrophic factor and its clinical implications. Archives of Medical Science, 6, 1164–1178. https://doi.org/10.5114/aoms.2015.56342
13) Tanila, H. (2017). The role of BDNF in alzheimer’s disease. Neurobiology of Disease, 97, 114–118. https://doi.org/10.1016/j.nbd.2016.05.008
14) Chen, S., Underwood, B. R., Jones, P. B., Lewis, J. R., & Cardinal, R. N. (2022). Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study. PLOS Medicine, 19(3). https://doi.org/10.1371/journal.pmed.1003941
15) Forlenza, O. 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: Randomised controlled trial. British Journal of Psychiatry, 198(5), 351–356. https://doi.org/10.1192/bjp.bp.110.080044