Lithium Mineral Deficiency: Cinderella Story for brain health

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Lithium's Billion Year Journey: A Cinderella Story for Brain Health (/blog/archive/nutritional-lithiumbrain-health-cinderella-story/) Dr. James Greenblatt (/blog/authors/dr-james-greenblatt/) Thursday, August 24, 2017

This is part one of Dr. Greenblatt's Nutritional Lithium series. Part two can be found here (/blog/archive/nutritional-lithium-deficiency-genesmental-health). As far as cosmologists can tell, there were only three elements present when the universe was first formed some 13.8 billion years ago: hydrogen, helium, and lithium. As one of the three original elements, lithium is found throughout our atmosphere. The sun, stars, and meteorites burn brightly with the gleam of this highly reactive element. On earth, lithium remains a major mineral component of granite rock, and also lingers in significant amounts in sea water, mineral springs, and soils.  Lithium has also found its way into our cell phones, electric cars, and holiday fireworks. Every organ and tissue in the human body contains the mineral lithium, with particular importance in health, specifically brain health.

Integrative Psychiatry as an Approach to Promoting Brain Health As a practitioner of integrative psychiatry, I treat individuals with a complex array of emotional, behavioral, and physical symptoms. One of the core concepts of Integrative Psychiatry is the concept of increasing the body’s nutrient reserves to promote long-term health. Lithium is one of the essential nutrients required to achieve optimal health.

History of Lithium use for Improving Mood Soft drink entrepreneur Charles Leiper Grigg understood there was something special about lithium. In 1929, he unveiled a drink called Bib-Label Lithiated Lemon-Lime Soda with the slogan: “It takes the ouch out of the grouch.” Hailed for improving mood and curing hangovers, this product was eventually rechristened 7-Up. The “7” supposedly represents the rounded-up atomic weight of the element lithium (6.9), and the “Up” suggests its power to lift spirits. Lithium remained an ingredient of 7-Up until 1950. Centuries before the advent of this celebrated soft drink, lithium was associated with calming moods. Soranus, a physician from ancient Ephesus, observed the benefits of alkaline springs for soothing the wild spirits of some of his patients. Lithium, it turned out, was abundant in these springs.

Efficacy of Low-dose Lithium as an Alternative to Pharmaceutical Dosing I consider nutritional lithium the most effective nutritional supplement I have used for neurological and psychiatric disorders in 30 years of practice. My respect and enthusiasm for lithium treatment may seem surprising considering some of the drug’s diverse applications throughout history, its association with severe mental health disorders, and its reputation for side effects. At pharmaceutical doses, lithium is an effective treatment for bipolar disorder, recurrent depression, and suicidal tendencies (Lewitzka et al., 2015) (/blog/archive/nutritional-lithium-brain-healthcinderella-story#_edn5). But today many psychiatrists, including myself, hesitate to prescribe lithium because of potential side effects at high doses. Their concerns are not unwarranted. Lithium prescribed at pharmaceutical doses can have disabling, irreversible side effects including kidney and thyroid disease.

It was not a huge leap for me in 1990 to start exploring the lowest dose of lithium possible that would alleviate my patients’ symptoms. Rather than basing my judgment on a number from a lab test, I listened to patients’ descriptions of their symptoms. I began to see that patients on lower doses of pharmaceutical lithium or nutritional lithium orotate still experienced significant clinical benefits. I have found that side effects are non-existent when lithium is used as a nutritional supplement. Nutritional lithium is a safe integrative strategy for the treatment of psychiatric and neurological disorders. In fact, it has the potential to dramatically change your clinical practice. Instead of pulling out my prescription pad, in most cases I now recommend that patients take lithium as a nutritional supplement. Not only does low-dose lithium not have any side effects, there are tremendous benefits related to many aspects of mood, behavior, and emotional health.

The Potential of Nutritional Lithium Even though lithium is among one of the oldest medications in psychiatry, large scale scientific studies of low-dose lithium are limited. Why? Because there is no profit in researching nutritional supplements. Pharmaceutical companies do not eagerly sponsor studies of inexpensive generic drugs. A prescription for lithium costs pennies, and of course, pharmaceutical companies reap no benefit from a nutritional supplement purchased at a health food store. 

I consider nutritional lithium the most effective nutritional supplement I have used for neurological and psychiatric disorders in 30 years of practice.

More recently however, small observational and interventional studies have positively associated modest concentrations of lithium with mental, emotional, and behavioral benefits. Small randomized, double-blind, placebocontrolled trials have indicated positive emotional and behavioral changes with short-term low dose supplementation with lithium. In one study, 24 participants with histories of aggression and impulsivity took a four-week course of 400 mcg of lithium daily. At the end of the month, their scores on measures of happiness, friendliness, energy, and mood had improved (Schrauzer & deVroey, 1990) (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_edn8). In another study, participants receiving low-dose lithium for 12 months experienced statistically significant increases in both memory and attention (Leyhe et al., 2009) (/blog/archive/nutritional-lithium-brain-healthcinderella-story#_edn6).

Lithium in Drinking Water  Studies of lithium in the water supply provide enlightening evidence of the benefits of low-dose lithium. Low lithium content in the water supply is correlated with higher rates of mental and emotional disorders. In 1970, one research study analyzed levels of organically derived lithium in the water of 27 Texas counties and compared them to the incidence of admissions and readmissions for psychoses, neuroses, and personality disorders at local and state psychiatric hospitals (Schrauzer & Shrestha, 1990) (/blog/archive/nutritional-lithium-brain-health-cinderellastory#_edn9). The authors noted a clear trend: the higher the lithium content in the water supply, the lower the rate of psychiatric illness in that county. This association remained significant even after possible confounding variables were accounted for. Uncertain whether these striking findings were unique to the geographical region, researchers sought to replicate the study in other areas. Lithium water studies have been conducted in Austria, England, Greece, and Japan (Giotakos et al., 2013; (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_edn2) Kabacs et al., 2011; (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_edn3) Kapusta et al., 2011; (/blog/archive/nutritionallithium-brain-health-cinderella-story#_edn4) Ohgami et al., 2009 (/blog/archive/nutritional-lithium-brain-healthcinderella-story#_edn7)). Data collection from all of these studies has confirmed a strong inverse correlation between aggressive crime and suicide, and supplemental levels of lithium in the water supply.   The potential of far-reaching use of low-dose lithium remains an exciting possibility. In 2014, Anna Fels MD proposes in her New York Times editorial:

“What if micro-dose lithium were again part of our standard nutritional fare? What if it were added back to soft drinks or popular vitamin brands or even put in the water supply? The research to date strongly suggests that suicide levels could be reduced, and even perhaps other violent acts. And maybe the dementia rate would decline. We don’t know because the research hasn’t been done.” (Fels, 2014) (/blog/archive/nutritional-lithium-brain-health-cinderellastory#_edn1)

From Plain Element to Promising Life-changer – Lithium as Cinderella  The story of lithium is a true Cinderella story. Lithium is a common and simple element, found in the rocks we walk on. Its benefits have not been heralded, as the fanfare associated with lucrative pharmaceuticals eclipses its simplicity. When newer treatments appear on the market, lithium is treated like somebody’s stepchild, often ignored and forgotten.

Nutritional lithium is a safe integrative strategy for the treatment of psychiatric and neurological disorders. In fact, it has the potential to dramatically change your clinical practice.

But also like Cinderella, lithium shows great promise. It has only to be recognized. Its ordinary nature is deceptive because it holds the power to transform lives.     

Read part two, Nutritional Lithium: Orchestrating Our Genes & Optimizing Our Moods, here. (/blog/archive/nutritional-lithium-deficiency-genesmental-health)

Adapted from Nutritional Lithium: The Cinderella Story written by James Greenblatt, MD and Kayla Grossman, RN (CreateSpace, 2016, https://www.createspace.com/5433178).

About the Authors James M. Greenblatt, MD, is chief medical officer and vice president of medical services at Walden Behavioral Care. Dr. Greenblatt is boardcertified in child and adult psychiatry. Dr. Greenblatt is a clinical faculty member in the psychiatry department at Tufts Medical School as well as the Geisel School of Medicine at Dartmouth College in New Hampshire. Dr. Greenblatt is the author of six books including those on depression, eating disorders and ADHD. He can be reached at: (781) 647-2901. For more information on Dr. Greenblatt please visit www.jamesgreenblattmd.com (http://www.jamesgreenblattmd.com).

Kayla Grossman, 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.

Related Resources Blog: Finally Focused - Mineral Imbalances & ADHD  (/blog/archive/mineral-imbalance-adhd-zinc-copper) Blog: The Distinction between DHEA and DHEA-S & Why Both are Important for a Healthy Brain (/blog/archive/difference-dhea-dheas-brainhealth) Blog: 3 Case Studies Reveal Perspectives on Mental Health & Hormones (/blog/archive/case-studies-mental-health-and-hormones)  

References [1] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref1) Fels, A. (2014). Should we all take a bit of lithium?. The New York Times. p. 6. [2] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref2) Giotakos, O., Nisianakis, P., Tsouvelas, G., & Giakalou, V.V. (2013). Lithium in the public water supply and suicide mortality in Greece. Biological Trace Elements Research, 156(1-3), 376-9. [3] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref3) Kabacs, N., Memon, A., Obinwa, T., Stochl, J., & Perez, J. (2011). Lithium in drinking water and suicide rates across the East of England. British Journal of Psychiatry, 198(5), 406-7. [4] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref4) Kapusta, N.D., Mossaheb, N., Etzersdorfer, E., et al. (2011). Lithium in drinking water and suicide mortality. British Journal of Psychiatry, 198(5), 346-50. [5] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref5) Lewitzka, U., Severus, E., Bauer, R., Ritter, P., Müller-Oerlinghausen, B., & Bauer, M. (2015). The suicide prevention effect of lithium: more than 20 years of evidence-a narrative review. International Journal Of Bipolar Disorders, 3(1), 32. [6] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref6) Leyhe, T., Eshweiler, G.W., Stansky, E. et al. (2009). Increase of BDNF serum concentration in lithium-treated patients with early Alzheimer’s disease. Journal of Alzheimer’s Disease, 16, 649-656. [7] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref7) Ohgami, H., Tetao, T., Shiotsuki, I., et al. (2009). Lithium levels in drinking water and risk of suicide. British Journal of Psychiatry, 194(5), 464-5. [8] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref8) Schrauzer, G. N., & de Vroey, E. (1994). Effects of nutritional lithium supplementation on mood. A placebo-controlled study with former drug users. Biological Trace Element Research, 40(1), 89-101. [9] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref9) Schrauzer, G.N. & Shrestha, K.P. (1990). Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biological Trace Elements Research, 25(2), 105-13. [10] (/blog/archive/nutritional-lithium-brain-health-cinderella-story#_ednref10) Zarse, K., Terao, T., Tian, J. et al. (2011). Low-dose lithium uptake promotes longevity in humans and metazoans. European Journal of Nutrition, 50(5), 387-389.

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Nutritional Lithium: Orchestrating Our Genes & Optimizing Our Moods (/blog/archive/nutritionallithium-deficiency-genes-mental-health/) Dr. James Greenblatt (/blog/authors/dr-james-greenblatt/) Friday, September 08, 2017

This is part two of Dr. Greenblatt's Nutritional Lithium series. Part one can be found here (/blog/archive/nutritional-lithium-brain-health-cinderellastory).

Epigenetics & Psychiatry The field of epigenetics has far-reaching implications for psychiatry. As acquired epigenetic alterations can be transferred to the next generations, what scientists used to label as an inherited psychiatric disease may in fact be the result of epigenetic changes in a family’s shared environment. Many psychiatric diseases are consistent with the theory of epigenetic dysregulation because of their fluctuating nature and disease course. Single gene and whole genome epigenetic analyses have shown atypical epigenetic markers in the blood and brain of individuals with psychiatric diseases including abnormalities in DNA methylation, histone modifications and microRNA expression. Among genes that potentially protect against the development of mood disorders, the brain derived neurotrophic factor (BDNF) gene has been the focus of study for the past several years, as it is associated with neural development and proliferation. BDNF is the most prevalent growth factor in the central nervous system. Because it plays a critical role in the development of plasticity of the brain, methylation of BDNF takes a toll on brain health and resilience. The BDNF gene modulates how much or how little environmental experiences become encoded within the neurons and neural circuits and thereby lead to long-lasting effects. BDNF promotes the growth and formation of new neurons, and it is responsible in part for the remarkable effect of exercise on the brain and for the increase in hippocampus size that is linked with improved memory (D’Addario et al., 2012). Mood disorders are associated with methylation of BDNF. Adverse experiences like major depression can lower BDNF levels and are linked with hippocampal shrinkage, a phenomenon that helps explain some of the cognitive impairments that are a hallmark of depression. Studies have revealed higher levels of DNA methylation at the BDNF gene promoter in patients with major depressive disorder and bipolar disorder II compared to levels in patients with bipolar I (Dell’Osso et al., 2014).

Lithium’s Influences on Genes I believe lithium deficiency is the most common mineral deficiency associated with nearly every type of psychiatric disorder. Lithium is a powerful epigenetic factor that can be used to dim the expression of genes that lead to aggression and mental illness while stimulating the expression of health-enhancing genes. Genes that are altered by lithium treatment are involved in many functions such as cell communication, immune response, protein metabolism, nucleic acid regulation/metabolism, and cell growth. A study of rat frontal cortex showed chronic treatment with lithium led to the significant up-regulation of 57 genes and down-regulation of 151 genes. Four of those genes have been specifically associated with bipolar disorder (Fatemi, Reutiman, & Folsom, 2009). Lithium changes gene expression through two basic channels: DNA methylation, and histone modification. Lithium acts by preventing the process of DNA methylation, which is critically important to improving mental health and preventing mental and emotional disorders. At least three studies have demonstrated that lithium decreases DNA methylation of the BDNF gene promoter. In other words, lithium increases the expression of the BDNF gene. The increased synthesis of BDNF contributes to robust neural growth and healthy dendritic branching. In one study of hippocampal neurons, lithium increased mRNA expression of BDNF by 67%. At a higher lithium dose there was a 100% increase. Likewise, the protein level of BDNF was increased by 53% with the lower lithium dose and by 89% with the higher lithium dose. By ensuring that the BDNF gene is left in the “on” position,

lithium promotes the consistent release of protective neurotrophins that protect and nourish the brain (Dwivedi & Zhang, 2015). BDNF levels are diminished in the brain and serum of Alzheimer’s patients. Alzheimer’s patients treated for ten weeks with lithium showed a significant increase in their BDNF serum levels. They also saw a significant decrease of cognitive impairment compared with placebo-treated Alzheimer’s patients. Reduction of cognitive impairment was inversely correlated with lithium serum concentration (Leyhe et al., 2009). BDNF also contributes to degradation of amyloid-β, a component of the amyloid plaques found in the brains of Alzheimer’s patients. In addition, BDNF is capable of inactivating GSK-3β (Leyhe et al., 2009). Abnormal regulation and expression of GSK3β is associated with an increased susceptibility towards Alzheimer’s disease and bipolar disorder. Lithium’s ability to enhance the synthesis of BDNF has far reaching implications for improving a wide range of neuropsychiatric disorders. Lithium also acts through histone modification. Histone function is particularly important for the encoding of high-level cognitive functions including learning and memory. In fact, diminished memory, as seen in patients with Alzheimer’s disease, has been linked to problems with histone metabolism. In experiments with laboratory animals, lithium has been shown to increase histone acetylation by weakening the binding of the DNA to its spool, making it more available to proteins that enhance memory (Lee et al., 2015). Although studies in humans are needed to further delineate the exact mechanism, lithium may be beneficial in preventing the genetic changes associated with the development of Alzheimer’s disease and other neurodegenerative conditions. These biological mechanisms are also important in lithium’s efficacy in bipolar disorder. Lithium affects multiple pathways in the brain which may explain its remarkable effectiveness for the treatment of bipolar disorder. BDNF has been consistently reported to be decreased in bipolar patients. One study found that bipolar patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. However, for those on lithium treatment, BDNF levels correlated positively with lithium levels (Tunca, 2014).

Lithium affects multiple pathways in the brain which may explain its remarkable effectiveness for the treatment of bipolar disorder.

Lithium has distinct and often dramatic neurotrophic effects, encouraging the survival and growth of nerve cells. Lithium ions modulate multiple biological cascades involved with nerve cell development. Lithium increases levels of key proteins such as BDNF and NT-3, which are known to be directly involved in nerve cell development. Other studies have found that lithium salts are neuroprotective, working to minimize inflammation, enhance mitochondrial function, and increase antioxidants to provide the optimal environment for neurons to thrive. Imaging studies have provided visual evidence that patients taking lithium salts experience increases in brain tissue volume over time, particularly in the gray matter of the brain, which holds the nerve cell bodies. At the cellular level lithium exerts powerful influences on neuroprotection and brain health. Lithium promotes epigenetic modifications that affect the expression of more than 50 genes, including signaling proteins, transcription factors, activators, cell adhesion proteins, oncogenes, and tumor suppressors (Farah et al., 2013). As research expands our knowledge of how to regulate gene expression and suppression, targeted use of nutritional lithium will enable us to prevent and treat psychiatric disorders that now incapacitate those who suffer from them. By acting directly on the epigenome, lithium restores neural function and improves brain health in ways that just a few years ago were not dreamed possible.

Adapted from Nutritional Lithium: The Cinderella Story written by James Greenblatt, MD and Kayla Grossman, RN (CreateSpace, 2016, https://www.createspace.com/5433178).

About the Author James M. Greenblatt, MD, is chief medical officer and vice president of medical services at Walden Behavioral Care. Dr. Greenblatt is boardcertified in child and adult psychiatry. Dr. Greenblatt is a clinical faculty member in the psychiatry department at Tufts Medical School as well as the Geisel School of Medicine at Dartmouth College in New Hampshire. Dr. Greenblatt is the author of six books including those on depression, eating disorders and ADHD. He can be reached at: (781) 647-2901. For more information on Dr. Greenblatt please visit www.jamesgreenblattmd.com (http://www.jamesgreenblattmd.com).

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References [1] D’Addario, C., Dell’Osso, B., Palazzo, M.C., et al. (2012). Selective DNA methylation of BDNF promoter in bipolar disorder: differences among patients with BDI and BDII. Neuropsychopharmacology, 37, 1647-1655. [2] Dell’Osso, B., D’Addario, C., Palazzo, M.C. et al. (2014). Epigenetic modulation of BDNF gene: differences in DNA methylation between unipolar and bipolar patients. Journal of Affective Disorders, 166, 330-333. [3] Dwivedi, T., & Zhang, H. (2015). Lithium-induced neuroprotection is associated with epigenetic modification of specific BDNF gene promoter and altered expression of apoptotic-regulatory proteins. Frontiers In Neuroscience, 8, article 457, 1-8. [4] Farah, R., Khamisy-Farah, R., Amit, T., Youdim, M. H., & Arraf, Z. (2013). Lithium’s Gene Expression Profile, Relevance to Neuroprotection A cDNA Microarray Study. Cellular And Molecular Neurobiology, 33(3), 411-420. [5] Fatemi, S. H., Reutiman, T. J., & Folsom, T. D. (2009). The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder. Biochemical Society Transactions, 37(Pt 5), 1090-1095. [6] Lee, R. S., Pirooznia, M., Guintivano, J., et al. (2015). Search for common targets of lithium and valproic acid identifies novel epigenetic effects of lithium on the rat leptin receptor gene. Translational Psychiatry, 5e600. [7] 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.

[8] Tunca, Z., Ozerdem, A., Ceylan, D., et al. (2014). Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium. Journal Of Affective Disorders, 166, 193-200.

Categories: Elements Testing (/blog/categories/elements-testing) | Neurotransmitters (/blog/categories/neurotransmitters) | Mental Health (/blog/categories/mental-health) | Mineral Imbalances (/blog/categories/mineral-imbalances)

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DeanEdward777 4 years ago

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If one is severely deficient in their serum lithium levels how much lithium orotate should they take daily? 0

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> DeanEdward777

4 years ago

The blog author notes that everyone would have undetectable serum lithium levels unless taking prescription medications. Your health care provider can advise regarding dosing of medications. Thank you! 1

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