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From the Townsend Letter
October 2015

Lithium: The Untold Story of the Magic Mineral That Charges Cell Phones and Preserves Memory
by James Greenblatt, MD, and Kayla Grossmann, RN
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Another interesting finding came from a study that looked at lithium levels in the hair of criminals. Trace mineral hair analysis is one of the most accurate methods for testing long-term mineral status and is therefore highly advantageous for determining where deficiencies are present. This study found that violent criminals had little to no stores of lithium when tested via hair mineral analysis, bringing forth the idea that perhaps lithium deficiency was contributing to oppositional and aggressive behaviors.
   
The most fascinating research recently, however, has been on the use of lithium for Alzheimer's disease. Given its being the only cause of death in the top 10 in America that cannot be prevented, cured, or slowed, researchers are spending billions of dollars on Alzheimer's disease. There is a fast-growing community of researchers suggesting that lithium may provide significant benefits in the treatment and prevention of Alzheimer's.
   
Lithium has been shown to disrupt the key enzyme responsible for the development of amyloid plaques and neurofibrillary tangles associated with Alzheimer's disease. This enzyme is glycogen synthase kinase-3 (GSK-3), a serine/threonine protein kinase that is important in neural growth and development. Notably, specific levels of GSK-3 are required to carry out the synaptic remodeling that drives memory formation.
   
In Alzheimer's disease, GSK-3 becomes hyperactive in the areas of the brain controlling memory and behavior, including the hippocampus and frontal cortex. This upregulation spurs GSK-3 to phosphorylate, or activate, amyloid-B and tau proteins in the neurons of these regions at an aberrantly high rate. Over time these proteins accumulate to create the signature plaques and neurofibrillary tangles that disrupt the brain tissue and result in symptoms of cognitive decline. Lithium works as a direct GSK-3 inhibitor to prevent this overexpression, halting inappropriate amyloid production and the hyperphosphorylation of tau proteins before they impair brain function.
   
In addition to protecting the brain from the development of plaques and tangles, lithium has been shown to repair existing damages brought about by Alzheimer's disease pathogenesis. Lithium ions, for example, encourage the synthesis and release of key neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), which in turn stimulate the growth and repair of neurons. Patients on lithium have been found to have significantly higher gray matter volumes in the brain. One study has even directly demonstrated that damaged nerve cells exposed to lithium respond with increases in dendritic number and length.
   
In a recent trial published in Current Alzheimer's Research, a nutritional dose of just 300 mcg of lithium was administered to Alzheimer's patients for 15 months. When compared with the control, those on low-dose lithium showed significant improvements in cognitive markers after just 3 months of treatment. Furthermore, these protective effects appeared to strengthen as the study proceeded, with many of the lithium-treated individuals showing marked cognitive improvements by the end of the trial. These results suggest that lithium could be a viable treatment for Alzheimer's disease when used at low doses over the long term.
   
Dr. Nassir Ghaemi, one of the more notable and respected advocates of lithium use in the medical community, recently published a review in 2014 in Australian and New Zealand Journal of Psychiatry summarizing the benefits of low-dose lithium therapy. Ghaemi and his colleagues performed a systematic review of 24 clinical, epidemiological, and biological reports that assessed standard or low-dose lithium for dementia along with other behavioral or medical benefits. Five of the seven epidemiological studies established a correlation with standard-dose lithium therapy and low dementia rates, while four other randomized clinical trials demonstrated that low-dose lithium yielded more benefit for patients with Alzheimer's dementia versus placebo. Based on these findings, Ghaemi stressed that "lithium is, by far, the most proven drug to keep neurons alive, in animals and in humans, consistently and with many replicated studies."

The Future of Lithium
Recognizing that nutrition is key to brain health is a fundamental premise of integrative medicine. Instead of focusing on just one type of intervention, integrative medicine tries to address all factors that may contribute to a mental disorder – bringing together nutritional supplements, medicines, psychotherapy, and lifestyle changes.
   
Lithium must be recognized as a critical component of nutritional assessments. Lithium is an underused nutritional supplement. The diverse neuroprotective mechanisms are truly remarkable. The scientific literature has shown that lithium modulates GSK-3, enhances the release of neurotrophic factors such as BDNF, and promotes epigenetic changes that resets the trajectory of mental illness. Lithium is powerful, reliable, cost effective, and, at low doses, completely safe.
   
With low-dose lithium, we have a safe nutritional supplement that is effective in treating a wide range of disabling symptoms of mental illness. Perhaps in the future, patients like Jamie Lowe, the author of the New York Times article, will not be forced to make a decision between mental and physical health. The compelling and growing scientific literature on the benefits of low-dose lithium therapy combined with over 25 years of clinical practice have convinced me that with low-dose lithium, it is entirely possible to have both.

References
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Farah R et al. Lithium's gene expression profile, a cDNA microarray study. Cell Mol Neurobiol. 2013;33:411–420.
Mauer S, Vergne D, Ghaemi NS. Standard and trace-dose lithium: a systematic review of dementia prevention and other behavioral benefits. Aust N Z J Psychiatry. 2014;48(9):809–818.
Nunes MA, Viel TA, Buck HS. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease. Curr Alzheimer Res. 2013;10(1):104–107.
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Strobasch AD, Jefferson JW. The checkered history of lithium in medicine. Pharm Hist. 1980;22(2):72–76.
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Young W. Review of lithium effects on brain and blood. Cell Transplant. 2009;18:951–975.

James M. Greenblatt, MD, currently serves as the chief medical officer and vice president of Medical Services at Walden Behavioral Care in Waltham, Massachusetts. He is assistant clinical professor of psychiatry at Tufts University School of Medicine. An acknowledged integrative medicine expert, Dr. Greenblatt has lectured throughout the US on the scientific evidence for nutritional interventions in psychiatry and mental illness. Dr. Greenblatt is on the scientific advisory board and consultant for Pure Encapsulations. He maintains an integrative psychiatric practice in the Boston area.

Kayla Grossmann, RN, works as a nurse advocate and freelance writer specializing in integrative health research and practice. She supports several large organizations in the field by contributing to their ongoing educational initiatives and clinical programming.

Find out more about their upcoming book and work on www.lowdoselithium.org.

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