Lithium Orotate, the Great Protector
A few years back I learned about Lithium Orotate from Jonathan Wright’s newsletter which disclosed he personally takes lithium for neuro-protection. I was very impressed by this, so I started lithium myself, and incorporated the mineral into our treatment program at the office.
Houston, We Have a Problem
I quickly discovered a problem. Every time I mentioned the word lithium to anyone at the office, they make an unpleasant face, wrinkle up their nose and start heading for the exit door. Why? Perhaps it’s because most people associate Lithium with mental illness, and a prescription drug called Lithium Carbonate used for bipolar disorder. That is the great mistake. We don’t use that form of lithium.
Dr Wright is not taking prescription lithium carbonate. He is taking lithium orotate, a non-prescription nutritional supplement. A big difference between the two types of lithium is the disparity in dosage. Prescription lithium carbonate comes in 300 mg tablets, and dosage is 3-6 tablets a day equal to 900 to 1800 mg per day. Non-prescription Lithium orotate comes from the health food store in 5 mg capsules, and people usually take one or two caps, one to three times a day depending on how they are feeling.
Another difference is prescription lithium dosage is high, requiring periodic blood testing for lithium toxicity. However, for the low dose lithium orotate, no toxicity or blood testing is required. That’s one of the reasons it is so safe. We use the safer, non-prescription Lithium Orotate, sold as a nutritional supplement.
Lithium Carbonate, Carrie Matheson (Claire Dane) in Homeland
We are all familiar with lithium carbonate as a psych med thanks to the popular TV series, Homeland, staring Clare Dane as Carries Matheson, the “Bipolar Super-Hero”. The TV series sensationalizes Bipolar Disorder in which Carrie Matheson, a CIA operative, alternates between a “manic state” and a “depressed state”, taking Lithium Carbonate to stabilize her moods. At certain times, she will “go off” her medication to induce a “manic state”, during which she experiences almost superhuman mental abilities to solve spy plots and intrigues, beyond the abilities of “normal” people.(1-6) This is lithium carbonate the psych med. We don’t use this. We use the vitamin form called lithium orotate, a safe nutritional supplement sold at the health food store.
Lithium Carbonate the First and Best Psych Drug that Actually Works
Regular readers will know I am not a fan of psychiatric medications, as most of them are ineffective, useless and produce horrific adverse side effects. Although current day anti-psychotic drugs such as Haldol, Prolixin, Resperdol, Seroquel, Zyprexa etc. may serve as chemical lobotomy or chemical straight-jacket for the criminally insane, they are inappropriate for children and other victims of the medical system who make the mistake of expecting help with mood or emotional problems.
Instead of receiving an understanding word and a compassionate pat on the back, these patients are transformed into victims of medical iatrogenesis, caused by adverse effects of psych drugs such as tardive dykinesia, akasthesia, and generalized brain damage.
The Origins of Psychiatry 1949
However, Lithium Carbonate is the exception here. Although overdose can lead to toxicity, when used properly, lithium carbonate is remarkably safe, and effective. The origin of modern psychiatry can be traced back to John Cade’s 1949 Lancet article, in which he recognized Lithium as an effective treatment for manic psychosis. Lithium Carbonate has a long track record as effective treatment for bipolar disorder and serves as mood stabilizer. The take home message here is that if you have a friend or loved one with bipolar disorder, lithium carbonate is the drug of choice.(10-21) Although lithium carbonate is an old drug, it is far superior to modern day psych meds.
Reduction in Suicides, and Violent Crime with Lithium in Water Supply
Lithium is a naturally occurring mineral found in our water supply. If high dose lithium is useful as a psych med, what about low dose lithium in our water supply. Does that have any effect on the population?
This question was answered by Dr Schrauzer in a 1990 report.(27) Using public data for 27 Texas counties from 1978-1987, Dr Schrauzer showed the incidence rates of suicide, homicide, and rape are significantly higher in counties whose drinking water have little or no lithium, compared to counties with higher lithium levels in the drinking water (70-170 mcg/L) . (27) Dr Schrauzer even proposed adding lithium, “lithiation” of the drinking water, as a public health measure: (27)
These results suggest that lithium at low dosage levels has a generally beneficial effect on human behavior, which may be associated with the functions of lithium as a nutritionally-essential trace element. Subject to confirmation by controlled experiments with high-risk populations, increasing the human lithium intakes by supplementation, or the lithiation of drinking water is suggested as a possible means of crime, suicide, and drug-dependency reduction at the individual and community level.
Dr. Schrauzer performed another low dose lithium 1994 study. This time, twenty Four subjects were randomly divided into two groups receiving either placebo or a 400 micro-gram lithium tab daily for 4 wk. (26). The author concluded that “lithium at the dosages chosen had a mood-improving and -stabilizing effect.”(26)
Additional study from Japan showed higher lithium levels in the water supply were associated with less suicide risk, and reduced over-all mortality in that population.(28-30)
If there were any doubts, a repeat study done by Dr districts correlated with suicide rates. The study was published in the April 2011 British journal of Psychiatry showing suicide rates vary inversely with lithium levels in local drinking water. (33)
Finally, confirmation of the original Texas study was done by Dr Bluml in 2013 with state-wide sampling of lithium levels in the drinking water relative to suicide rates in 226 Texas counties. Again the authors found an inverse correlation between lithium levels and suicide rate indicating benefit of lithium in drinking water. (34)
This is the end of part one. In part two we examine the neuro-protective and anti-aging effects of low dose lithium.
Lithium Orotate: Buy on Amazon.
Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Fl 33314
Above Images are Clare Danes, Carrie Matheson in Homeland courtesy of the mass media.
Links and references
Jonathan V Wright Lithium Articles:
Lithium – The Misunderstood Mineral Part 1 by Dr. Jonathan V. Wright.
Lithium – The Misunderstood Mineral Part 2 by Dr. Jonathan V. Wright.
1) Jeffrey Lieberman M.D.Shrink Speak. Homeland: A True Portrayal of Mental Illness The TV series accurately depicts mental illness.
2) Homeland: The Case Against Calling Carrie a Bipolar ‘Superhero’
Sunday’s episode challenged the idea that the CIA agent’s disorder is the source of her talents.
3) Stanton Peele Addiction in Society
Three Things I’ve Learned About Mental Illness from Homeland
The inspiration for Carrie Mathison shows that Carrie’s disorder is all wrong
Posted Oct 08, 2013
4) A Not-So-Brief History Of Carrie Mathison’s Career At The CIA (So Far) Her so-called life of espionage hurts our heads. Entertainment Editor, The Huffington Post
5) Does Homeland sensationalise Carrie Mathison’s bipolar disorder? Hannah Jane Parkinson
6) The Unreal World: ‘Homeland’ and bipolar disorder
Claire Danes’ character hides her condition from her CIA co-workers and is medically treated by her psychiatrist sister. Is this legit?
December 19, 2011|Marc Siegel | The Unreal World
Age related decline in glucose utilization detected by PET scan with FDG
7) Mosconi, L., and P. F. McHugh. “FDG-and amyloid-PET in Alzheimer’s disease: is the whole greater than the sum of the parts?.” The Quarterly Journal of Nuclear Medicine and Molecular Imaging 55.3 (2011): 250.
Neuroprotection of Lithium inhibition of GSK-3β
8) Lithium Neuropsychiatric Neuroplasticity Glycogen Synthase Kinase3_Wada_2009. Wada, Akihiko. “Lithium and Neuropsychiatric Therapeutics: Neuroplasticity via Glycogen Synthase Kinase-3. BETA.,. BETA.-Catenin, and Neurotrophin Cascades.” Journal of pharmacological sciences 110.1 (2009): 14-28.
Since 2004, it has been documented that among the multiple direct target molecules of lithium identified so far (e.g., inositol monophosphatase),
the beneficial effects of lithium, such as mood stabilization, behavioral amelioration, and neurogenesis, are due to the inhibition of glycogen synthase kinase-3β (GSK-3β) by lithium, which promotes β-catenin–dependent transcriptional events (see reviews 1
new trends in the last five years have revealed that insulin-like growth factor-I (IGF-I), IGFII, and insulin enhance mood (9 – 12), memory (13, 14),
neurogenesis (13, 14), and angiogenesis (15); antidepressants up-regulate expression of IGF-I (16 – 18) and IGF-II (19), while IGF-I up-regulates brain-derived neurotrophic factor and its receptor TrkB
GSK-3, a serine/threonine protein kinase, controls multiple aspects of physiological events (e.g., cell membrane signal-to-gene transcription/protein translation, cytoskeletal organization, neuronal polarity, and
cell survival /apoptosis)
Dysregulated hyperactivity of GSK-3β is associated with insulin resistance, diabetes mellitus, tumorigenesis, inflammation, and neuropsychiatric and
inhibition of GSK-3β by various therapeutics (e.g.,lithium) allows β-catenin–induced de novo synthesis of IGF-I, IGF-II, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF).
Lithium: mood stabilization via GSK-3β inhibition and β-catenin activation
Therefore, therapeutic serum range (0.5 to 1.2 mM) of lithium inhibits GSK-3β in vivo
Prickaerts et al. (47) documented that transgenic mice overexpressing GSK-3β mimicked hyperactivity as observed in the manic phase of bipolar disorder (e.g., increased locomotor activity), with reduction in brain weight;
Neurogenesis via GSK-3β inhibition and β-catenin activation.
Neural stem cells give rise to new hippocampal neurons throughout adulthood; conversely, defective neurogenesis may predispose an individual to mood disorders
In Caenorhabditis elegans, McColl et al. (52) documented that lithium elongated the life-span of the nematode; lithium down-regulated expression of histone
demethylase via mechanisms including GSK-3β inhibition by lithium.
Lithium treatment in Alzheimer’s patients: prevention of dementia
In a study of 1423 outpatients at a university psychiatric clinic, Terao et al. (63) reported that lithium therapy prevented the dementia in Alzheimer’s disease,
when their cognition and memory capacity were evaluated by Mini-Mental State Examination.
In mice, Li et al. (56) showed that intraperitoneal injection of d-fenfluramine
(to stimulate serotonin secretion and block its reuptake) rapidly increased Ser9-phosphorylation of GSK-3β by up to 500% at 1 h in the prefrontal cortex, hippocampus, and striatum.
There is to date compelling evidence indicating that the GSK-3β/β-catenin pathway is the convergent therapeutic target of lithium and various classical neuropsychiatric drugs, ameliorating behavior, mood, anxiety,
cognition, and neurogenesis. brain-derived neurotrophic factor and vascular endothelial growth factor),
IGF-I has proved to be a crucial factor in mood disorders. Antidepressants up-regulate IGF-I and IGF-II levels in the brain, and physical exercise and a healthy diet increases IGF-I synthesis in the brain and transport
of peripheral circulating IGF-I to the brain via the bloodbrain barrier. Importantly, IGF-I up-regulates the levels of brain-derived neurotrophic factor and its receptor TrkB, increasing synthesis of its downstream synaptic proteins.
9) Nciri, Riadh, et al. “Chronic neuroprotective effects of low concentration lithium on SH-SY5Y cells: possible involvement of stress proteins and gene expression.” Neural regeneration research 9.7 (2014): 735.
chronic exposure to lithium induces adaptive changes in metabolism of SH-SY5Y cells including a higher cell growth rate and a better resistance to oxidative stress
10) Chi-Tso, C. H. I. U., and De-Maw CHUANG. “Neuroprotective action of lithium in disorders of the central nervous system.” Zhong nan da xue xue bao. Yi xue ban= Journal of Central South University. Medical sciences 36.6 (2011): 461.
This article reviews recent findings regarding potential target involved in lithium’s neuroprotective effects and their implications fo the treatment of human disorders of the CNS.
Lithium’s main mechanisms of action appear to stem from its ability to inhibit glycogen synthase kinase-3 activity and also to induce signaling mediated by brain-derived neurotrophic factor.
Lithium in Parkinson’s and other NeuroDegenerative
11) full pdf free
Lazzara Kim Lithium in Parkinsons Neurodegenerative Dis Front Neurosci 2015
Lazzara, C. A., and Y. H. Kim. “Potential application of lithium in Parkinson’s and other neurodegenerative diseases. Front. Neurosci. 9: 403. doi: 10.3389/fnins. 2015.00403 Potential application of lithium in Parkinson’s and other neurodegenerative diseases Carol A. Lazzar a and Yong-Hwan Kim* Department of Biological Sciences, Delaware State University.” (2015).
Lithium inhibits apoptosis in brain and increases grey matter
12) Shimomura, Atsushi, Ryuji Nomura, and Takao Senda. “Lithium inhibits apoptosis of mouse neural progenitor cells.” Neuroreport 14.14 (2003): 1779-1782.
Lithium given to humans with bipolar – MRI imaging
13) Moore, Gregory J., et al. “Lithium-induced increase in human brain grey matter.” The Lancet 356.9237 (2000): 1241-1242.
Rodent studies have shown that lithium exerts neurotrophic or neuroprotective effects. We used three-dimensional magnetic resonance imaging and brain segmentation to study pharmacologically-induced increases in grey matter volume with chronic lithium use in patients with bipolar mood disorder. Grey-matter volume increased after 4 weeks of treatment. The increases in grey matter probably occurred because of neurotrophic effects.
Human bipolar study-
Lithium increases Hippocampus size and Verbal Memory
14) Psychopharmacology (Berl). 2007 Dec;195(3):357-67. Epub 2007 Aug 20.
Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Yucel K1, McKinnon MC, Taylor VH, Macdonald K, Alda M, Young LT, MacQueen GM.
1Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th Street, Hamilton, ON, L8N 3K7, Canada,
OBJECTIVES:To our knowledge, no longitudinal volumetric study has been performed in patients with BD, which would allow for an examination of whether lithium therapy used to treat BD can exert a long-term effect on hippocampal volume.
MATERIALS AND METHODS:We examined the effects of lithium on hippocampal volumes and recollective memory performance over a period of 2 to 4 years in 12 patients with BD who had never received pharmacotherapy before lithium initiation.
RESULTS:We found bilateral increases in volume of the hippocampus over time. We also found some evidence of improvement in verbal memory performance over the 4-year measurement period as assessed by the California Verbal Learning Test.
CONCLUSIONS:Consistent with preclinical literature supporting the neuroprotective effects of lithium, long-term treatment is associated with preservation of recollective memory function and increased hippocampal size in vivo.
Lithium given to aged mice
15) Riadh, Nciri, et al. “Neuroprotective and neurotrophic effects of long term lithium treatment in mouse brain.” Biometals 24.4 (2011): 747-757.
Since the worldwide approval of lithium therapy in 1970, lithium has been used for its anti-manic, antidepressant, and anti-suicidal effects. The last decade has witnessed the following discoveries about its neuroprotective and neurotrophic properties, yet the therapeutic mechanisms at the cellular level remain not-fully defined. We have undertaken the present study to determine if chronic lithium treatment, at therapeutically relevant concentrations, exerts neurotrophic/neuroprotective effects in the mouse brain in vivo. For this purpose, 10 months aged mice were fed for 3 months on food pellets contained 1 g (L1 group) or 2 g (L2 group) lithium carbonate/kg, resulting in serum concentrations of 0.4 and 0.8 mM, respectively. The evaluation of lipid peroxidation level and the activities of catalase, superoxide-dismutase and glutathione-peroxidase showed that chronic Li administration, at therapeutic doses doesn’t induce oxidative stress in brain tissue. No changes in the expression levels of molecular chaperones, namely, the HSP70, and HSP90 heat shock proteins and the GRP94 glucose-regulated protein were detected. Moreover, this treatment has caused
(1) an increase in the relative brain weight
(2) a delay in the age induced cerebral glucose impairment
(3) an enhancement of the neurogenesis in hippocampus and enthorinal cortex highlighted by silver impregnation.
Under these experimental conditions, no modifications were observed in expression levels of GSK3 and of its downstream target β-catenin proteins. These results suggested that chronic Li administration, at therapeutic doses, has a neuroprotective/neurotrophic properties and its therapeutic mechanism doesn’t implicate GSK3 inactivation.
Treatment of Bipolar
first report of Lithium for Bipolar John Cade 1949
16) CADE, JFJ. “Lithium salts in the treatment of psychotic excitement.” The Med. J. Australia 2 (1949): 518-520. Lithium treatment of psychotic excitement Bipolar Disorder John Cade 1949
17) Bipolar Disord. 2008 Mar;10(2):231-7.
What is the optimal serum lithium level in the long-term treatment of bipolar disorder–a review? Severus WE1, Kleindienst N, Seemüller F, Frangou S, Möller HJ, Greil W.
There is substantial uncertainty about the most efficacious serum lithium level for the long-term treatment of bipolar disorder (BD). This review focuses on the available evidence taking into consideration the effects of previous lithium history, changes in lithium level and polarity of relapse or recurrence.
METHODS: We conducted a MEDLINE search, using the MeSH Terms ‘bipolar disorder’ and ‘lithium’ together with ‘randomized controlled trial’ or ‘controlled clinical trial’ covering the time span from 1966 to March 2006. We only included studies reporting on the long-term treatment of mood disorders where patients with BD were examined as a separate group and were assigned to precisely specified target ranges of lithium level.
RESULTS:The minimum efficacious serum lithium level in the long-term treatment of bipolar disorder was 0.4 mmol/L with optimal response achieved at serum levels between 0.6-0.75 mmol/L. Lithium levels >0.75 mmol/L may not confer additional protection against overall morbidity but may further improve control of inter-episode manic symptoms. Abrupt reduction of serum levels of more than 0.2 mmol/L was associated with increased risk of relapse.
CONCLUSIONS:In the long-term treatment of bipolar disorder clinicians should initially aim for serum lithium levels of 0.6-0.75 mmol/L, while higher levels may benefit patients with predominantly manic symptoms.
Tondo, Leonardo, et al. “Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders.” (2014). Am J Psychiatry. 1998 May;155(5):638-45.
Clinical research records of 317 patients with DSM-IV-defined bipolar disorder (188 with type I and 129 with type II) were analyzed for frequency and duration of affective episodes and hospitalizations before (mean = 8.38 years) versus during (mean = 6.35 years) lithium maintenance treatment. Treatment effects were also assessed by survival analysis of interepisode intervals and by multivariate regression testing for factors associated with response to treatment.
RESULTS: Bipolar I and bipolar II patients were ill before treatment a similar percentage of time, but the subtype distinction was supported descriptively. Lithium had superior benefits in type II patients, with significantly greater reduction of episodes per year and of the percentage of time ill. Reduction of depressive morbidity was similarly strong in both diagnostic types. During treatment, bipolar II patients had 5.9-fold longer interepisode intervals and were twice as likely as type I patients to have no new episodes. Starting lithium maintenance earlier predicted greater improvement.
CONCLUSIONS: Lithium maintenance yielded striking long-term reductions of depressive as well as manic morbidity in both bipolar disorder subtypes, with greater overall benefits in type II patients and with earlier treatment.
19) Machado‐Vieira, Rodrigo, Husseini K. Manji, and Carlos A. Zarate Jr. “The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis.” Bipolar disorders 11.s2 (2009): 92-109.
The present article: (i) reviews what has been learned regarding lithium’s neurotrophic effects since Cade’s original studies with this compound; (ii) presents human data supporting the presence of cellular atrophy and death in BD as well as neurotrophic effects associated with lithium in human studies; (iii) describes key direct targets of lithium involved in these neurotrophic effects, including neurotrophins, glycogen synthase kinase 3 (GSK-3), and mitochondrial/endoplasmic reticulum key proteins; and (iv) discusses lithium’s neurotrophic effects in models of apoptosis and excitotoxicity as well as its potential neurotrophic effects in models of neurological disorders.
First, human studies showing evidence for neural cell atrophy and loss in BD are described, as well as lithium’s ability to reverse these pathological findings.
Second, the potential roles of intracellular cascade systems in BD are described; these have been shown to directly regulate cell survival/death pathways and are directly targeted by lithium.
Yucel et al. showed increased bilateral hippocampal volume after 2–4 years of lithium treatment in previously drug-naïve BD subjects (10).
Also, a recent study using high-resolution volumetric MRI showed a direct therapeutic relevance of lithium neurotrophic effects in BD. It was observed that only lithium-responders showed increases in gray matter in the prefrontal areas (11).
Third, the neurotrophic effects of lithium are described in preclinical models in vivo and in vitro and in clinical studies, demonstrating lithium’s clinical relevance not only in BD, but as a potential neurotrophic agent for use in several neurological disorders.
The most replicated finding from structural neuroimaging studies is an association between lithium treatment and increased gray matter volume in brain areas implicated in emotional processing and cognitive control, such as the anterior cingulate gyrus, amygdala, and hippocampus, which suggests that lithium has considerable neurotrophic effects (24, 25).
human postmortem and imaging studies in BD suggest that neurotrophic effects play a critical role in lithium’s therapeutic effects.
Glycogen synthase kinase 3 (GSK-3) polymorphism in the GSK-3 gene was associated with earlier onset of BD.
GSK-3 was shown to be downregulated by lithium in diverse studies, inducing direct neuronal protection against different injuries (40) and providing new insights into lithium’s neurotrophic effects [reviewed in (41)]. Indeed, GSK-3 is potently inhibited by chronic administration of lithium (42–44);
20) Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12;32(8):1761-71.
Lithium: bipolar disorder and neurodegenerative diseases Possible cellular mechanisms of the therapeutic effects of lithium. Marmol F1.
Bipolar illness is a major psychiatric disorder that affects 1-3% of the worldwide population. Epidemiological studies have demonstrated that this illness is substantially heritable. However, the genetic characteristics remain unknown and a clear personality has not been identified for these patients.
The clinical history of lithium began in mid-19th century when it was used to treat gout. In 1940, it was used as a substitute for sodium chloride in hypertensive patients. However, it was then banned, as it had major side effects.
In 1949, Cade reported that lithium could be used as an effective treatment for bipolar disorder and subsequent studies confirmed this effect. Over the years, different authors have proposed many biochemical and biological effects of lithium in the brain. In this review, the main mechanisms of lithium action are summarised, including ion dysregulation; effects on neurotransmitter signalling; the interaction of lithium with the adenylyl cyclase system; inositol phosphate and protein kinase C signalling; and possible effects on arachidonic acid metabolism. However, none of the above mechanisms are definitive, and sometimes results have been contradictory. Recent advances in cellular and molecular biology have reported that lithium may represent an effective therapeutic strategy for treating neurodegenerative disorders like Alzheimer’s disease, due to its effects on neuroprotective proteins like Bcl-2 and its actions on regulators of apoptosis and cellular resilience, such as GSK-3. However, results are contradictory and more specific studies into the use of lithium in therapeutic approaches for neurodegenerative diseases are required.
SCience and Practice of Lithium therapy
21) Aust N Z J Psychiatry. 2012 Mar;46(3):192-211. The science and practice of lithium therapy. Malhi GS1, Tanious M, Das P, Berk M.
INTRODUCTION: Despite more that 60 years of clinical experience, the effective use of lithium for the treatment of mood disorder, in particular bipolarity, is in danger of becoming obsolete. In part, this is because of exaggerated fears surrounding lithium toxicity, acute and long-term tolerability and the encumbrance of life-long plasma monitoring. Recent research has once again positioned lithium centre stage and amplified the importance of understanding its science and how this translates to clinical practice.
OBJECTIVE: The aim of this paper is to provide a sound knowledge base as regards the science and practice of lithium therapy.
METHOD: A comprehensive literature search using electronic databases was conducted along with a detailed review of articles known to the authors pertaining to the use of lithium. Studies were limited to English publications and those dealing with the management of psychiatric disorders in humans. The literature was synthesized and organized according to relevance to clinical practice and understanding.
RESULTS: Lithium has simple pharmacokinetics that require regular dosing and monitoring. Its mechanisms of action are complex and its effects are multi-faceted, extending beyond mood stability to neuroprotective and anti-suicidal properties.
Its use in bipolar disorder is under-appreciated, particularly as it has the best evidence for prophylaxis, qualifying it perhaps as the only true mood stabilizer currently available.
In practice, its risks and tolerability are exaggerated and can be readily minimized with knowledge of its clinical profile and judicious application.
CONCLUSION: Lithium is a safe and effective agent that should, whenever indicated, be used first-line for the treatment of bipolar disorder. A better understanding of its science alongside strategic management of its plasma levels will ensure both wider utility and improved outcomes.
22) Malhi, Gin S., et al. “Potential mechanisms of action of lithium in bipolar disorder.” CNS drugs 27.2 (2013): 135-153.
Licht, Rasmus W. “Lithium: still a major option in the management of bipolar disorder.” CNS neuroscience & therapeutics 18.3 (2012): 219-226.
24) Cruceanu, Cristiana, Martin Alda, and Gustavo Turecki. “Lithium: a key to the genetics of bipolar disorder.” Genome Med 1.8 (2009): 79. Lithium key to genetics bipolar disorder.Cruceanu Turecki 2009
In spite of any side-effects, lithium is still recognized as the most effective prophylactic agent for BD. Moreover, continued treatment with lithium has been associated with a significantly reduced risk of suicide in patients with
mood disorders , which appears to be unique to this line of treatment. While lithium’s positive effect on BD symptoms is well accepted, the mechanisms leading to this response are only partially understood.
25) Malhi, Gin S., and Michael Berk. “Is the safety of lithium no longer in the balance?.” The Lancet 379.9817 (2012): 690-692. safety of lithium in the balance lancet 2012 Gin S Malhi Michael Berk
Nutritional supplement levels of lithium- benefit for mood
26) Biol Trace Elem Res. 1994 Jan;40(1):89-101.
Effects of nutritional lithium supplementation on mood. A placebo-controlled study with former drug users. Schrauzer GN1, de Vroey E.
A total of 24 subjects, 16 males and 8 females, average age 29.4 +/- 6.5 y, were randomly divided into two groups. Group A received 400 micrograms/d of lithium orally, in tablets composed of a naturally lithium-rich brewer’s yeast, for 4 wk. Group B was given normal, lithium-free brewer’s yeast as a placebo. All the subjects of the study were former drug users (mostly heroin and crystal methamphetamine). Some of the subjects were violent offenders or had a history of domestic violence. The subjects completed weekly self-administered mood test questionnaires, which contained 29 items covering parameters measuring mental and physical activity, ability to think and work, mood, and emotionality. In the lithium group, the total mood test scores increased steadily and significantly during the period of supplementation. The 29 items were furthermore placed into three subcategories reflecting happiness, friendliness, and energy, as well as their negative counterparts. In Group A, the scores increased consistently for all subcategories until wk 4 and remained essentially the same in wk 5. Based on these results and the analysis of voluntary written comments of study participants, it is concluded that lithium at the dosages chosen had a mood-improving and -stabilizing effect.
Crime/suicide rate lower with higher lithium levels
27 Texas counties from 1978-1987 , incidence rates of suicide, homicide, and rape, incidence rates of robbery, burglary, and theft were statistically significant
lithiation of drinking water is suggested as a possible means of crime, suicide, and drug-dependency reduction at the individual and community level.
27) Biol Trace Elem Res. 1990 May;25(2):105-13.
Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Schrauzer GN1, Shrestha KP.
Using data for 27 Texas counties from 1978-1987, it is shown that the incidence rates of suicide, homicide, and rape are significantly higher in counties whose drinking water supplies contain little or no lithium than in counties with water lithium levels ranging from 70-170 micrograms/L; the differences remain statistically significant (p less than 0.01) after corrections for population density.
The corresponding associations with the incidence rates of robbery, burglary, and theft were statistically significant with p less than 0.05. These results suggest that lithium has moderating effects on suicidal and violent criminal behavior at levels that may be encountered in municipal water supplies. Comparisons of drinking water lithium levels, in the respective Texas counties, with the incidences of arrests for possession of opium, cocaine, and their derivatives (morphine, heroin, and codeine) from 1981-1986 also produced statistically significant inverse associations, whereas no significant or consistent associations were observed with the reported arrest rates for possession of marijuana, driving under the influence of alcohol, and drunkenness.
These results suggest that lithium at low dosage levels has a generally beneficial effect on human behavior, which may be associated with the functions of lithium as a nutritionally-essential trace element.
Subject to confirmation by controlled experiments with high-risk populations, increasing the human lithium intakes by supplementation, or the lithiation of drinking water is suggested as a possible means of crime, suicide, and drug-dependency reduction at the individual and community level.
Lithium Reduces Suicide Risk
28) Ohgami, H., et al. “Lithium levels in drinking water and risk of suicide.” The British journal of psychiatry: the journal of mental science 194.5 (2009): 464.
Br J Psychiatry. 2009 May;194(5):464-5; discussion 446.
Although lithium is known to prevent suicide in people with mood disorders, it is uncertain whether lithium in drinking water could also help lower the risk in the general population. To investigate this, we examined lithium levels in tap water in the 18 municipalities of Oita prefecture in Japan in relation to the suicide standardised mortality ratio (SMR) in each municipality. We found that lithium levels were significantly and negatively associated with SMR averages for 2002-2006.
These findings suggest that even very low levels of lithium in drinking water may play a role in reducing suicide risk within the general population.
29) Int Clin Psychopharmacol. 2015 Jan;30(1):1-5. Lithium in drinking water and suicide prevention: a review of the evidence. Vita A1, De Peri L, Sacchetti E.
Suicide is a serious public health problem worldwide, and many nations are committed to developing prevention programmes to reduce the incidence of suicide. To date, several strategies have been proposed for suicide prevention, both at the population and at the individual level, some of which may be pharmacological. In particular, a substantial amount of data show that lithium significantly reduces mortality in patients with mood disorders. Initiating from this evidence, some recent studies have investigated whether a relationship might exist between levels of lithium in drinking water and mortality rates for suicide in the general population. We have systematically reviewed all the articles published on this issue to date.
The available literature indicates that higher lithium levels in drinking water may be associated with reduced risk of suicide in the general population.
30) Am J Psychiatry. 2005 Oct;162(10):1805-19.
Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials.
Cipriani A1, Pretty H, Hawton K, Geddes JR.
Observational studies suggest that long-term lithium treatment has a strong antisuicidal effect in mood disorders, but it is uncertain whether this association is a genuine therapeutic effect or is due to confounding factors in nonrandomized studies. The authors conducted a systematic review and meta-analysis of randomized trials to investigate the effect of lithium, compared to placebo and other active treatments, on the risk of suicide, deliberate self-harm, and all-cause mortality in patients with mood disorder.
METHOD:The data source was the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE (1966-June 2002), EMBASE (1980-June 2002), CINAHL (1982-March 2001), PsycLIT (1974-June 2002), PSYNDEX (1977-October 1999), and LILACS (1982-March 2001). The Cochrane Central Register of Controlled Trials (CENTRAL) was searched with the term “lithium” for new records entered into the database from 1999 to 2003. Studies selected included randomized, controlled trials comparing lithium with placebo or all other compounds used in long-term treatment for mood disorders (unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, and rapid cycling, diagnosed according to DSM or ICD criteria). Of 727 references identified in the search, 52 articles were marked as possibly relevant on the basis of the abstract, and 32 randomized, controlled trials were eligible for inclusion in the review. Two independent reviewers extracted the data, and disagreements were resolved by consensus with a third reviewer. Methodological quality was assessed according to the criteria of the Cochrane Collaboration. When the outcomes of interest were not reported, an attempt was made to obtain the required data from the original authors.
RESULTS:In 32 trials, 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds. Patients who received lithium were less likely to die by suicide (data from seven trials; two versus 11 suicides; odds ratio=0.26; 95% confidence interval [CI]=0.09-0.77). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio=0.21; 95% CI=0.08-0.50). There were fewer deaths overall in patients who received lithium (data from 11 trials; nine versus 22 deaths; odds ratio=0.42, 95% CI=0.21-0.87).
CONCLUSIONS:Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.
Longevity – Life Span extension
Japanese Community drinking water Lithium and Mortality
31) Zarse, Kim, et al. “Low-dose lithium uptake promotes longevity in humans and metazoans.” European Journal of Nutrition 50.5 (2011): 387.
Based on a large Japanese observational cohort, we identify effects of tap water-derived lithium on overall mortality. Independently, we have exposed Caenorhabditis elegans, a small roundworm commonly used for anti-aging studies, to comparable concentrations of lithium, and have quantified mortality during this intervention.
Results: In humans, we find here an inverse correlation between drinking water lithium concentrations and all-cause mortality in 18 neighboring Japanese municipalities with a total of 1,206,174 individuals (β = −0.661, p = 0.003). Consistently, we find that exposure to a comparably low concentration of lithium chloride extends life span of C. elegans (p = 0.047).
Conclusions: Taken together, these findings indicate that
long-term low-dose exposure to lithium may exert anti-aging capabilities and unambiguously decreases mortality in evolutionary distinct species.
Study Nematode Worms
McColl, Gawain, et al. “Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans.” Journal of Biological Chemistry 283.1 (2008): 350-357.
A dose-response relationship was observed with an optimal lifespan increase seen at 10 mm LiCl where median wild-type lifespan was increased by 46%
Lithium in drinking water
33) Kapusta, Nestor D., et al. “Lithium in drinking water and suicide mortality.” The British Journal of Psychiatry 198.5 (2011): 346-350.
34) Blüml, Victor, et al. “Lithium in the public water supply and suicide mortality in Texas.” Journal of Psychiatric Research 30 (2013): 1e5. Lithium water supply suicide mortality Texas Blüml 2013
Methods and compositions for the treatment of the skin
US 5594031 A
The invention relates to a method of skin treatment comprising the step of topically applying to skin affected by seborrheic dermatitis an amount of a composition comprising an excipient and from about 1% to 30% lithium ion, said amount being sufficient to reduce sebum production by said skin. The invention also relates to a method of skin treatment, which comprises the step of topically applying to skin affected by seborrheic dermatitis an amount of a composition comprising a topically acceptable excipient and an effective amount of a lithium salt.
I have now found that a variety of topically acceptable lithium salts will reduce the oiliness of the skin surface, apparently due to a reduction in sebum formation.
Nutritional supplement containing lithium CA 1332358 C
Thus in healthy sub~ects lithium plasma levels may generally be in excess of 0.04 mM/l, whereas in sub~ects suffering from atopic eczema or seborrheic dermatitis mean plasma levels of below 0.025 mM/l are found.
Lithium containing medicament for combatting papilloma virus infections – HPV
WO 1998017288 A1
While lithium is known to be effective in the treatment of depression, alcoholism, herpes infections, and seborrhoeic dermatitis, its utility in the treatment of HPV disease is surprising and hitherto has not been suggested.
The precise concentrations of lithium in the topical compositions of the invention will depend of course on a number of factors including, for example, the severity of the condition to be treated, the form of lithium used and the physical nature of the pharmaceutical composition. Generally, however, an effective lithium concentration in the composition is 0.001 to 10% by weight lithium ion, preferably 0.005 to 5%, and most especially preferably 0.3 to 2%. Thus for example where the active agent is lithium succinate, topical compositions may contain 1 to 20% by weight, preferably 4 to 12% and especially 5 to 9% of the lithium compound.
Treatment duration will generally be for a period of weeks, e.g. 1 to 14 weeks, e.g. 10 days to 12 weeks, preferably 2 to 10 weeks, more preferably about 8 weeks or less, for example 3 to 5 weeks.
Anti-viral compositions US 4886670 A
The anti-viral effectiveness of conventional anti-viral agents such as acylovir, idoxuridine, vidarabine etc. is enhanced by formulation or administration with a physiologically acceptable lithium salt.
Patent – Low- dose lithium for the treatment of neurodegenerative disorders WO 2012007387 A1
Low dose lithium in the treatment or prophylaxis of parkinson’s disease
US 20130017274 A1
Targeting gsk-3beta for the treatment of parkinson’s disease
WO 2012170657 A1
A method for treating Parkinson’s Disease (PD) uses Lithium (Li) to inhibit GSK-3 beta and simultaneously stimulate autophagy to clear protein aggregates of a-synuclein (a-Syn) and nyperphosphorylated Tau. The method reverses synucleinopathy and tauopathy associated with neurodegenerative diseases, especially Parkinson’s disease. Lithium is useful in the treatment of Alzheimer’s disease, multiple system atrophy and Lewy body disease with dementia, which are all characterized by high levels of a-Syn, p-Tau and activated GSK-3 beta.
Migraine treatment medicaments – contg. lithium orotate, ergotamine tartrate, caffeine and quinine dihydrochloride
DE 2462312 A1
Lithium orotate is a particularly advantageous compound for administration of lithium because it is highly specifically absorbed into glial regions of the brain and permits much lower lithium doses to be used than is the case with conventional lithium salts. This in turn means that control of serum lithium levels is not necessary when lithium orotate is used.
Lithium Orotate 130 mg (providing 4.8 mg elemental lithium)
The misunderstood mineral, References Part 1:
Think young into your 90s with this anti-aging secret for your brain
 Moore GJ, et al. Lithium-induced increase in human brain grey matter. Lancet 2000; 356: 1,241-1,242
2 Chuang D, Hashimoto R, Kanai H, Leeds P, Senatorov V. Lithium stimulates progenitor proliferation in cultured brain neurons. Neuroscience 2003; 117(1): 55-61
3 Chuang D, Christ L, Fujimaki K, Hashimoto R, Jeong MR. Lithium-induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: A role in neuroprotection against N-methyl-D-aspartate receptor-mediated excitotoxicity. FEBS Letters 2003; 538(1-3): 45-148
4 Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002; 43: 1,173-1,179
5 Ren M, Kanai H, Chuang DM, Chen RW, Chalecka-Franaszek E, Qin ZH. Regulation of c-Jun n-terminal kinase (JNK) and p38 kinase in cultured brain neurons: Roles of glutamate and lithium. Society for Neuroscience Abstracts 2001; 27(1): 259
6 Chuang D. Lithium exerts robust neuroprotective effects in vitro and in the CNS in vivo: Therapeutic implications. Neuropsychopharmacology 2000; 23(S2): S39
7 Nonaka S, Hough CJ, Chuang DM. Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx. Proceedings of the National Academy of Sciences of the United States of America 1998; 95(5): 2,642-2,647
8 Chuang D, Christ L, Fujimaki K, Hashimoto R, Jeong MR. Lithium-induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: A role in neuroprotection against N-methyl-D-aspartate receptor-mediated excitotoxicity. FEBS Letters 2003; 538(1-3): 45-148
9 Manji HK, Chen G, Moore GJ. Lithium at 50: Have the neuroprotective effects of this unique cation been overlooked? Biological Psychiatry 1999; 46(7): 929-940
10 Williams R, Harwood AJ. Lithium therapy and signal transduction. Trends in Pharmacological Sciences 2000; 21(2): 61-64
11 Lenox RH, Hahn CG. Overview of the mechanism of action of lithium in the brain: Fifty-year update. Journal of Clinical Psychiatry 2000; 61 (Supplement 9): 5-15
12 Nonaka S, Chuang DM. Neuroprotective effects of chronic lithium on focal cererbral ischemia in rats. Neuroreport 1998; 9(9): 2,081-2,084
13 Nonaka S, Katsube N, Chuang D. Lithium protects rat cerebellar granule cells against apoptosis induced by anticonvulsants, phenytoin and carbamazepine. Journal of Pharmacology and Experimental Therapeutics 1998; 286(1): 539-547
14 Manji, HK; Chen G; Moore GJ. Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: A role for neurotropic and neuroprotective effects in manic depressive illness. Journal of Clinical Psychiatry 2000; 61(9): 82-96
15 Tsai G, Coyle JT. N-acetyl aspartate in neuropsychiatric disorders. Prog Neurobiol 1995; 46: 531-540
16 Moore GJ et al. Lithium Increases N-acetyl aspartate in the human brain: in vivo evidence in support of bcl-2s neurotrophic effects? Biol Psych 2000; 48:1-8
17 Williams R, Harwood AJ. Lithium therapy and signal transduction. Trends in Pharmacological Sciences 2000; 21(2); 61-64
18 Lenox R, Hahn C. Overview of the mechanism of action of lithium in the brain: Fifty-year update. Journal of Clinical Psychiatry 2000; 61(Supplement 9): 5-15
19 Weeks O, Volmar CH. Lithium and spatial memory: A new pathway? Society for Neuroscience Abstracts 2001; 27(1): 845
20 Takashima A, Murayama M, Murayama O, Park J, Sato S, Sun X, Yamaguchi H. Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100. Neuroscience Letters 2002; 321(1-2): 61-64
21 Chuang D, Chen R, Leeds P, Qian Y, Wei H, Wei W. beta-Amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment. European Journal of Pharmacology 2000; 392(3): 117-123
22 Diaz-Nido J, Alvarez G, Avila J, Bogonez E, Munoz-Montano JR, Satrustegui J. Lithium protects cultured neurons against beta-amyloid-induced neurodegeneration. FEBS Letters 1999; 453(3): 260-264
24 Munoz-Montano JR, Moreno FJ, Avila J, Diaz-Nido J. Lithium inhibits Alzheimer’s disease-like tau protein phosphorylation in neurons FEBS Letters 1997; 411(2-3): 183-188
25 Radesater A, Peterson E, Nilsson Y, Luthman J, Leonov S, Budd SL, Bhat RV, Backstrom A. Inhibition of GSK3beta by lithium attenuates tau phosphorylation and degeneration. Society for Neuroscience Abstracts 2001; 27(1): 1,437
26 Bjorksten J. athways to the decisive extenesion of the human lifespan J Am Ger Soc 1977; 25: 396-399
The misunderstood mineral, References Part 2:
Lithium fights crime and your most nagging health concerns
 Schrauzer GN, Shreshta KP. Lithium in drinking water and the incidence of crims, suicides, and arrests related to drug addiction. Biological Trace Elements Research 1990; 25: 105-113.
2 McMillan TM. Lithium and the treatment of alcoholism: a critical review. British Journal of Addiction 1981; 76: 245-258
3 Tyber MA. Can Med Assoc J 1990; 143: 902-904
4 Bsrcai A. Lithium in adult anorexia nervosa. Acta Psychiat Scand 1977; 55: 97-101
5 Ekborn K. Lithium for cluster headache: review of the literature and preliminary results of long-term treatment. Headache 1981; 21: 132-139
6 Klimek A, Szulc-Kuberska J, Kawiorski S. Lithium therapy in cluster headache. Eur Neurol 1979; 18: 267-268
7 Randall S et al. Effect of lithium on viral replication. In Birch NJ (editor) Lithium and the Cell: Pharmacology and Biochemistry, Academic Press, New York, 1991, pp. 99-112
8 Amsterdam JD, Maislin G, Hooper MB. Suppression of herpes simplex virus infections with oral lithium carbonatea possible antiviral activity. Pharmacotherapy 1996; 16(6): 1,070-1,075
9 Temple R et al. The use of lithium in Graves disease. Mayo Clin Proc 1972; 47: 872-872
10 Benbasset CA, Molitch ME. The use of lithiumin the treatment of hyperthyroidism. The Endocrinologist 1998; 8: 383-387
When I was a medical student many years ago, Lithium Carbonate was a popular prescription anti-depressant medication. Lithium is a naturally occurring mineral found in the water supply. The observation has been made that in the Texas counties with the highest lithium content in the water supply, you will find the lowest rates for homicide, suicide and violent crimes.
Lithium carbonate works really well as an anti-depressant. The problem with Lithium Carbonate is that the dosage needed is very high, and it requires blood monitoring to avoid toxicity. Lithium Orotate, on the other hand, is more bio-available, and safer than the Lithium Carbonate. The reason for this is that Lithium Orotate can be used at very low doses and is still effective.
Dr. Jonathon Wright, who incidentally takes Lithium Orotate himself, recommends 10 to 20 milligrams of Lithium Orotate daily as a preventive measure. Dr. Wright thinks that lithium may be useful in treating Alzheimer’s disease, senile dementia, and possibly Parkinson’s disease. Lithium protects brain cells from a whole variety of toxic molecules, including patent medications. It can also promote brain cell regeneration and increase brain cell mass. In essence, the research suggests that lithium is a brain anti-aging nutrient. Dr. Wright feels that unlike the 5HTP and St Johns Wort which should not be combined with SSRI drugs, Lithium can and should be used along with any patent medicine being used for depression, anxiety, or any other “mood-altering” reason, since it will protect brain cells against their unwanted toxic effects.
No adverse side effects have been reported from Lithium Orotate in recommended dosages and it is approved for sale as a nutritional supplement without a prescription.
Dr. Wright’s advice on lithium supplementation
Q: I remember reading about lithium supplementation in your newsletter, and noticed you recommend 5 mg doses. When I started doing some online shopping, though, I found that there are several options, like Lithium Aspartate (5 mg) and Lithium Orotate (120 mg). Which is the right type and amount?
Dr. Wright: Either form of lithium is fine: What you want to look for on the labels of the lithium supplements you’re choosing between is the amount of “elemental lithium” each one contains. Research indicates that taking 10 to 20 milligrams of elemental lithium per day can help keep your brain functioning at peak performance. Many lithium supplements contain 5 milligrams of elemental lithium (though, again, you should read labels carefully to be sure), so you would need two to four tablets or capsules to achieve the brain-protecting dose.
Lithium aspartate supplements containing 20 milligrams elemental lithium per capsule (manufactured by Bio-Tech Pharmacal) are also available at many compounding pharmacies.
Even at a quantity of two low-dose tablets three times daily (for a total 30 milligrams of elemental lithium), patients’ serum lithium usually stay in the “non-detectable” or range, which means that they’re very safe. In my 30 years of practice, I’ve never had a patient report symptoms of lithium excess. But just to be on the safe side, I always recommend taking extra quantities of essential fatty acids to prevent any possibility of lithium toxicity.
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Jeffrey Dach MD
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