Lithium for Alzheimer’s Disease Prevention

Lithium for Alzheimer’s Disease Prevention

Project Topics

Lithium and the brain

Lithium is a trace element that is found in the cells of most plants and animals. Lithium compounds are naturally present in the environment, including drinking water. Lithium is often considered a mood stabilizer. It has been used to treat psychiatric illness since the 1870’s and is now best known for the treatment of bipolar disorder.

Recent studies indicate that even trace amounts of lithium salts may have positive effects on the brain. For example, a 2020 review found evidence for a protective effect of lithium from public drinking water and lower suicide mortality at the population level. Evidence is mounting for lithium’s antisuicidal, antiviral, immunomodulary, and neuroprotective effects, including for Alzheimer’s disease prevention.

Lithium and Alzheimer’s disease

Lithium protects the brain from injury and neurodegeneration. In experimental studies in animals, lithium appears to limit some of the key pathological processes related to Alzheimer’s disease. In epidemiological studies in humans, therapeutic doses as well as trace amounts of lithium in drinking water were related to lower rates of dementia. A study in Texas reported that trace levels of lithium in drinking water was related to reduced deaths from Alzheimer’s disease, as well as lower levels of obesity and type 2 diabetes due to lithium’s effects on insulin activity. Research on lithium and Alzheimer’s disease is at an early stage. There is some evidence for a slowing of cognitive decline in clinical trials of lithium treatment, although it may be more relevant as a preventative than treatment of Alzheimer’s. 

Lithium may protect against Alzheimer’s disease by reducing apoptosis, inflammation, and oxidative stress; activating neuroprotective cellular processes; and inhibiting glycogen synthase kinase 3 (GSK3) which is related to Alzheimer’s pathology. But much more research is needed to clarify the potential benefit of lithium for cognition.

Senior woman playing chess as a cognitive rehabilitation activity.

Lithium orotate – a better choice than lithium carbonate?

Lithium carbonate is a lithium salt that has been used to treat bipolar disorder and depression. It appears to have neuroprotective properties and has been the subject of studies on the prevention and treatment of diseases like Alzheimer’s. Unfortunately, lithium carbonate has a narrow therapeutic range and a number of serious side effects – including toxic impacts on the thyroid and kidneys. 

Another lithium salt – lithium orotate – may provide an alternative with fewer side effects. Lithium orotate studies in the 1970s found that it was superior to lithium carbonate in crossing the blood-brain barrier and in entering cells. However, a 1976 study raised the potential for increased renal toxicity of high-dose lithium orotate, which limited continued study.

Research is now underway to determine if lithium orotate can be used to treat bipolar disorder at a lower – and less toxic – dose than lithium carbonate. Lithium orotate is also widely available now as a supplement, which appears to be effective, safe, and well tolerated. Lithium orotate has only recently been fully characterized, and more research – especially clinical trials – will be needed to determine its long-term safety.

An experimental study of lithium orotate for Alzheimer’s disease prevention

We know that diet and lifestyle factors are related to the development of Alzheimer’s disease. Stress, lack of exercise, a typical Western diet and decreased lithium levels are all factors likely contributing to the pathology of Alzheimer’s disease. For example, scientists have found that high levels of sugar in the diet are related to elevated glucocorticoids (such as cortisol). This results in processes that can damage the brain, including inflmamation and an insulin-resistant brain state. 

To best understand how lithium salts may impact Alzheimer’s disease, Dr. Lane Bekar of Saskatchewan University has developed a mouse model with a genetic predisposition to the disease. The mice are provided a high sugar diet to mimic the human condition.  Lithium orotate is being evaluated to determine if it has a protective effect on the brain. Positive results will support the proposition that lithium may be considered as an essential mineral to add to multivitamin and mineral complexes.

The Parsemus Foundation is supporting research on the ability of lithium to prevent neurodegeration, memory loss, and Alzheimer’s disease.

Young woman rejecting sugary food and choosing healthy food such as fresh fruit.

Take Action on Lithium for Alzheimer’s Disease Prevention

Learn more about dementia and Alzheimer’s disease – and what you can do to lower your risk. Prevention is key, and there are modifiable risk factors that you can do something about today, such as diet, exercise, and appropriate supplements. General information as well as scientific publications are listed below.

For general information, research trials, and prevention information regarding Alzheimer’s disease, see: Alzheimer’s Association, Alzheimer’s Research and Prevention Foundation, list of Alzheimer’s Research Centers and Organizations.

  • Devadason P. Is there a role for lithium orotate in psychiatry? (2018). Australian & New Zealand J Psychiatry. 52(12):1107-1108.
  • Fajardo VA, Fajardo VA, LeBlanc PJ, MacPherson REK. (2018). Examining the relationship between trace lithium in drinking water and the rising rates of age-adjusted Alzheimer’s disease mortality in Texas. J  Alzheimer’s Dis 61(1): 425–434. (Free full text).
  • Kessing LV, Gerds TA, Knudsen NN. (2017). Association of lithium in drinking water with the incidence of dementia. JAMA 74(10):1005-1010. (Free full text).
  • Memon A, Rogers I, Fitzsimmons SMDD, et al. (2020). Association between naturally occurring lithium in drinking water and suicide rates: systematic review and meta-analysis of ecological studies. BJ Psych, 217(6), 667-678. (Free full text).
  • Pacholko AG, Bekar LK. (2021). Lithium orotate: A superior option for lithium therapy? Brain Beh 11(8):e2262. (Free full text).
  • Pacholko AG,  Wooton CA, Bekar LK. (2019). Poor diet, stress, and inactivity converge to form a “Perfect Storm” that drives Alzheimer’s disease pathogenesis. Neurodegener Dis 2019;19:60–77. (Free full text).
  • Rybakowski JK (2022). Antiviral, immunomodulatory, and neuroprotective effect of lithium. J. Integr. Neurosci. 2022, 21(2), 68. (Free full text).
  • Vlachos GS, Scarmeas N. (2019). Dietary interventions in mild cognitive impairment and dementia. Dialogues Clin Neurosci 21(1):69-82. (Free full text).

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