Lithium isn’t Only for Mental Health Problems 

 
Besides its use for mental health problems most notably bipolar syndrome you may be interested in lithiums many other positive effects our health.  
 
Low-dose lithium supplementation can be considered by anyone with PTSD, OCD, alcoholism, bipolar depression, unipolar depression, migraine/cluster headaches, improving low white blood cell count, juvenile convulsive disease, liver disorders, recovery from stroke, traumatic brain injury, mild cognitive impairment, Alzheimer's disease, histamine  reactions contracting the airways in the lungs, metal toxicity, inflammatory bowel disease and hyperthyroidism.
 
Lithium Grows and Regenerates Brain Cells
 
Lithium is involved in the repair, regeneration and maintenance of brain cells.  You can consider supplementing low-dose lithium to help to maintain the long term health of your brain, just as little as 0.5 to 1 mg (elemental lithium from lithium-orotate) could be added to your food or drinking water to achieve this.  Alternatively you can consider supplementing higher but still low-doses say 2 to 5 or even up to 10 mg to stimulate more intensive period of brain repair and regeneration.
 
Shrinkage of the brain is observed in many conditions including Alzheimer's disease, mild cognitive impairment, bipolar and chronic depression, for simplicity you can think of there being two things happening, there can be an increased net loss of brain cells and the branches (dendrites) on the remaining cells wither away.  
 
The good news is that we now know at least some parts of the brain actually grow new brain cells, the current estimate is that the region of the brain called the hippocampus produces perhaps 7000 new brain cells per day which means that by the time you're 50 you've actually produce enough new brain cells to regrow the hippocampus which is a pretty large structure within the brain, when the process of growing new brain cells is inhibited as it is for example when people take anti-cancer drugs designed to stop new cell growth people often experience depression and it’s believed that it's the inhibition of the brain's ability to grow new cells but actually causes the depression, if this is true and I believe it is it has quite big implications, it's saying that depression is not due to a lack of chemicals such as serotonin within the synapses but rather due to a lack of actual synapses themselves.  
 
Furthermore the withered dendritic branches are very capable of regrowing when we create the right healthy conditions in the brain.  the growth of new cells is called neurogenesis and the growth of dendritic branches is called neuroplasticity.  I'm not sure that lithium increases  neurogenesis -the growth of new cells- (does anyone know of any evidence for this?) however there is evidence that it slows down the death of brain cells, incidentally the best thing known for increasing, neurogenesis is exercise particularly short burst of vigourous exercise.  when it comes to neuroplasticity -the ability of brain cells to grow new connections- however lithium is fantastic stuff.
 
So whether you've had shrinkage of your dendrites due to prolonged stress and mental illness or damage to a part of the brain due to a stroke and you want to stimulate your existing brain cells to grow new connection you want to  supplement lithium. ,   oOhe did the right nutrition such as omega-3 oils and 
 
 
supplementation stimulates repair and regeneration of  brain cells, it also
Lithium supplementation can have a powerful effect on repairing and protecting the brain it combats the brain shrinkage is seen in cognitive decline, Alzheimer's disease, bipolar syndrome and chronic depression; it also promotes repair and regeneration in the brain following strokes or traumatic brain injury. 
 
 
Lithium supplementation protects against shrinkage of the brain and can even regenerate the grey and white matter in the brain, improve cognitive function and assist recovery from not only brain injury but also the shrinkage in parts of brain observed in people with chronic stress, depression, bipolar, OCD and PTSD. 
 
I believe supplementing lithium is one of the most powerful things you can do to not only to maintain memory and cognitive function but also regenerate an unhealthy brain. 
ADD
 
Lithium attenuate excessive glutamate
Research explains lithium’s dual anti-manic/ anti-depressive effect July 1, 1998 Researchers at the UW Medical School have solved the puzzle of how one drug — lithium — can effectively stabilize both the wild euphoria and the crushing melancholy that are the hallmark of manic depression, or bipolar disorder. As reported in the July 7 Proceedings of the National Academy of Sciences, the researchers found that in mice brains, lithium exerts a push/pull effect on the neurotransmitter glutamate, eventually causing it to level off in a stable zone where it can control both extremes. “Glutamate is the primary excitatory neurotransmitter, carrying messages instantaneously from one nerve cell to another in 85 percent of the brain,” said UW Medical School professor of pharmacology Dr. Lowell Hokin, who directed the research. Other neurotransmitters include serotonin, dopamine, norepinephrine and acetylcholine. Under normal circumstances, an impulse from a nerve cell releases a flood of message-bearing glutamate aimed at a neighboring neuron across the synapse. A structure on the end of the releasing nerve cell, called a reuptake transporter, then shuts off the signal by reabsorbing the glutamate, pumping it back into the cell for reuse. If the reuptake mechanism malfunctions, inappropriate concentrations of neurotransmitter remain in the synapse. Hokin postulates abnormally low glutamate levels are involved in depression, while elevated levels are responsible for mania. Nearly a half century ago, Australian psychiatrist John F. Cade discovered lithium’s mood-stabilizing effect. It has long been the drug of choice in treating bipolar disorder, which affects approximately 2.5 million Americans. Despite some side effects, lithium usually successfully dampens the mood swings that in the most severe cases end in suicide, the dire result for one in five untreated or unresponsive bipolar patients. In an earlier study (reported in PNAS, Aug. 30, 1994), Hokin and his colleague showed that lithium causes glutamate to accumulate in synapses of mice and monkey brain slices, but exactly how it worked remained unclear until now. In the current study, functioning slices of mice brain were examined following exposure to lithium, while control slices were not exposed to the drug. The researchers observed that lithium raised the glutamate level by slowing its reuptake. The higher the lithium dose, the greater the inhibition, they found. To study the chronic effect of the lithium, the UW team administered it to live mice for two weeks. To their surprise, they saw that glutamate reuptake increased. This “up-regulation” resulted in less neurotransmitter in the synapse, which would produce an anti-manic effect. “We were especially interested to find that the reuptake mechanism in the 18 lithium-treated mice was stabilized in a very narrow range, compared to the 18 controls,” he said. Hokin speculates a compensatory mechanism in the reuptake system strives over time to reset raised glutamate levels down into a fixed range. When the levels are too low, as postulated in depression, lithium brings them up into the stable region. The research findings support clinical observations, he noted. “It takes a few weeks before lithium begins to relieve depression and mania in bipolar patients,” he said. “It’s now apparent an adaptive reuptake mechanism that brings glutamate within a ‘normal’ range works over time to curb both the highs and lows.” What’s more, he added, lithium doesn’t change the moods of people who aren’t bipolar, suggesting that their glutamate levels may be positioned consistently within the set zone, and therefore would not be affected by the drug. - See more at: http://news.wisc.edu/research-explains-lithiums-dual-anti-manic-anti-depressive-effect/#sthash.DQ6C2WLI.dpuf
 
Neuropharmacology. 2002 Dec;43(7):1173-9.
Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity.
Hashimoto R1, Takei N, Shimazu K, Christ L, Lu B, Chuang DM.
Author information
 

  • 1Molecular Neurobiology Section, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1363, USA.
Abstract
Mechanisms underlying the therapeutic effects of lithium for bipolar mood disorder remain poorly understood. Recent studies demonstrate that lithium has neuroprotective actions against a variety of insults in vitro and in vivo. This study was undertaken to investigate the role of the brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway in mediating neuroprotection of lithium against glutamate excitotoxicity in cortical neurons. Pretreatment with either lithium or BDNF protected rat cerebral cortical neurons from glutamate excitotoxicity. The duration of treatment required to elicit maximal neuroprotection by BDNF (1 day) was much shorter than that by lithium (6 days). K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody suppressed the neuroprotective effect of lithium. Treatment of cortical neurons with lithium increased the cellular BDNF content in 3 days and the phosphorylation of TrkB at Tyr490 in 5 days, suggesting that long-term lithium administration enhances BDNF expression/secretion, leading to the activation of TrkB receptor. Lithium failed to protect against glutamate excitotoxicity in cortical neurons derived from homozygous and heterozygous BDNF knockout mice, although lithium fully protected cortical neurons prepared from wild type mice littermates. Taken together, these data suggest that the BDNF/TrkB pathway plays an essential role in mediating the neuroprotective effect of lithium.
PMID:
12504924
[PubMed - indexed for MEDLINE]
 
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Reduced Violent Crime and Suicide
 
There’s evidence that when people have a higher intake of lithium from their diet and water they are less likely to commit suicide {The British Journal of Psychiatry Apr 2011, 198 (5) 346-350; DOI: 10.1192/bjp.bp.110.091041} and violent crimes, so just tiny amounts of this little mineral can have remarkable life saving effects on improving mental health.  
See How to use low-dose lithium for more on suicide.
 
There is also some evidence that an increased dietary intake of lithium increases life expectancy and the increasing life expectancy is not just because of the reduced rate of suicide. {doi:10.1007/s00394-011-0171-x}
 
Lithium and Longevity 
A new paper was published this week - Low-dose lithium uptake promotes longevity in humans and metazoans.  Now, as a psychiatrist, I'm a lithium fan.  Apparently, it is an essential trace micronutrient (who knew) aside from the uses for decreasing suicide and helping mood stabilization. Want a primer - look at my blog post here.  (Here is the original lithium for treating mania paper by John Cade if you are interested.)

Decreasing suicide?  Yes, well lithium is actually very good at keeping people alive.  Even those with bipolar disorder or major depression who have no real symptomatic improvement seem to have less suicidal thoughts and suicides while on lithium.  Very interesting.  But why?

Let's start with some observational studies.  Back in 1989, Schrauzer and Shrestha published a paper called "Lithium in Drinking Water and the Incidences of Crimes, Suicides, and Arrests Related to Drug Addictions."  They took information about the lithium level in the water of  27 counties in the Great State of Texas.  Seems that counties with higher lithium levels in the water had a statistically significant decrease in the incidence of homicide, suicide, arrests for opiates and cocaine, and violent criminal behavior.  Now to put things into perspective, a high lithium water content translates to about 2mg of lithium a day.  Psychiatric doses start at 300mg daily.
 
 
Reduced GSK3
Lithium reduces an enzyme called GSK3B which is a good thing.  Elevated GSK3b promotes inflammation and chronic degeneration, its associated with the development of TAU proteins in the brain involved in the development of Alzheimer's disease, elevated GSK3B increases the risk of developing type II diabetes and abnormal expression of the GSK3B gene looks like it's involved in causing disturbances in the timing of the biological clock/sleep cycles common in bipolar syndrome and in possibly causing bipolar syndrome itself.  (references for all of this are so easy to find I'll let you look yourself).
 
I think it would be useful in the future if we could test for GSK3B levels like we test for high cholesterol today.
 
 
lithium and cognitive decline
 
 
Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder
Paula V. Nunes, Orestes V. Forlenza, Wagner F. Gattaz
DOI: 10.1192/bjp.bp.106.029868 Published 30 March 2007 
  Abstract
Bipolar disorder is associated with increased risk for dementia. We compared the prevalence of Alzheimer's disease between 66 elderly euthymic patients with bipolar disorder who were on chronic lithium therapy and 48 similar patients without recent lithium therapy. The prevalence of dementia in the whole sample was19% v. 7% in an age-comparable population. Alzheimer's disease was diagnosed in 3 patients (5%) on lithium and in 16 patients (33%) who were not on lithium (P<0.001). Our case–control data suggest that lithium treatment reduced the prevalence of Alzheimer's disease in patients with bipolar disorder to levels in the general elderly population. This is in accordance with reports that lithium inhibits crucial processes in the pathogenesis of Alzheimer's disease.
 
  • © 2007 Royal College of Psychiatrists
 
 
Curr Alzheimer Res. 2013 Jan;10(1):104-7.
Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease.
Nunes MA1, Viel TA, Buck HS.
Author information
Abstract
A lower incidence of dementia in bipolar patients treated with lithium has been described. This metal inhibits the phosphorylation of glycogen-synthase-kinase 3-α and β, which are related to amyloid precursor protein processing and tau hyperphosphorylation in pathological conditions, respectively. Following the same rationale, a group just found that lithium has disease-modifying properties in amnestic mild cognitive impairment with potential clinical implications for the prevention of Alzheimer's Disease (AD) when a dose ranging from 150 to 600 mg is used. As lithium is highly toxic in regular doses, our group evaluated the effect of a microdose of 300 μg, administered once daily on AD patients for 15 months. In the evaluation phase, the treated group showed no decreased performance in the mini-mental state examination test, in opposition to the lower scores observed for the control group during the treatment, with significant differences starting three months after the beginning of the treatment, and increasing progressively. This data suggests the efficacy of a microdose lithium treatment in preventing cognitive loss, reinforcing its therapeutic potential to treat AD using very low doses.
J Clin Psychiatry. 2009 Jun;70(6):922-31.
Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.
Hampel H1, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J, Schönknecht P, Riepe MW, Kraft I, Gasser T, Leyhe T, Möller HJ, Kurz A, Basun H.
Author information
Abstract
OBJECTIVE: 
Lithium, a first-line drug for the treatment of bipolar depression, has recently been shown to regulate glycogen synthase kinase-3 (GSK-3), a kinase that is involved in the phosphorylation of the tau protein. Since hyperphosphorylation of tau is a core pathological feature in Alzheimer's disease, lithium-induced inhibition of GSK-3 activity may have therapeutic effects in Alzheimer's disease. In the current study, we tested the effect of short-term lithium treatment in patients with Alzheimer's disease.
METHOD: 
A total of 71 patients with mild Alzheimer's disease (Mini-Mental State Examination score > or = 21 and < or = 26) were successfully randomly assigned to placebo (N = 38) or lithium treatment (N = 33) at 6 academic expert memory clinics. The 10-week treatment included a 6-week titration phase to reach the target serum level of lithium (0.5-0.8 mmol/L). The primary outcome measures were cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) and GSK-3 activity in lymphocytes. Secondary outcome measures were CSF concentration of total tau and beta-amyloid(1-42) (Abeta(1-42)), plasma levels of Abeta(1-42), Alzheimer's Disease Assessment Scale (ADAS)-Cognitive summary scores, MMSE, and Neuropsychiatric Inventory (NPI). Patients were enrolled in the study from November 2004 to July 2005.
RESULTS: 
No treatment effect on GSK-3 activity or CSF-based biomarker concentrations (P > .05) was observed. Lithium treatment did not lead to change in global cognitive performance as measured by the ADAS-Cog subscale (P = .11) or in depressive symptoms.
CONCLUSIONS: 
The current results do not support the notion that lithium treatment may lead to reduced hyperphosphorylation of tau protein after a short 10-week treatment in the Alzheimer's disease target population.
TRIAL REGISTRATION: 
(Controlled-Trials.com) Identifier: ISRCTN72046462.
Drugs Aging. 2012 May 1;29(5):335-42. doi: 10.2165/11599180-000000000-00000.
Does lithium prevent Alzheimer's disease?
Forlenza OV1, de Paula VJ, Machado-Vieira R, Diniz BS, Gattaz WF.
Author information
Abstract
Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly.
 
lithium and cognitive decline
 
 
HOW TO ENLARGE YOUR BRAIN AND IMPROVE BRAIN PERFORMANCE
 
 
 
By Dr. James Howenstine, MD.
May 5, 2004
NewsWithViews.com
Conventional medical thinking concerning the brain have always believed that the brain steadily decreased in size with aging and that when brain neurones (nerve cells) died they were lost forever. This explains why elderly persons generally have slightly smaller brains than younger individuals.
Preserving And Renewing Brain Cells With Lithium
Medical students are taught that there is a slow steady loss of brain cells with aging culminating in gradual shrinkage of the brain. Lithium has long been known to be an effective therapy for Bipolar Disorder (manic depression) when taken in high doses. However, recent research has shown that low doses of lithium preserve and renew[1] brain cells. Eight of ten persons given lithium showed an increase in brain grey matter of 3 % after only 4 weeks. By promoting brain cell regeneration and increasing brain size lithium can function as an anti-aging nutrient for the brain.
Lithium also accomplishes the following benefits for brain cells:
 
  • Lithium enhances DNA replication which is the first step to formation of new cells.
  • The damaging effects of excitotoxins. (monosodium glutamate (MSG), aspartame (Nutrasweet) etc. can be blocked by lithium.[2]
  • Animal research shows that lithium can decrease the areas of cell death after induced strokes by 56 %.
  • Lithium protects rat brain cells from the. increased levels of brain cell death caused by anti-convulsant drugs (Dilantin phenytoin , Tegretol, carbamazepine etc.)
  • Lithium may protect against adverse effects from mood altering drugs, alcohol, tobacco, caffeine, 'uppers"and "downers", and marihuana all of which cause brain damage with long term use.
  • Abnormally functioning signaling pathways may become repaired by lithium.
  • The aluminum felt to be a possible cause of Alzheimer's Disease (AD). is chelated[3] by lithium so it can be more easily removed from the body.
Research has suggested that lithium blocks the secretion of beta-amyloid in Alzheimer's disease and prevents damage from pre-existing beta amyloid. Overactivity of the brain cell protein tau contributes to death of neurones in Alzheimer's Disease. Lithium inhibits this tau protein damage and the formation of the neurofibrillary tangles seen in AD.
Ten years of research by 27 counties in Texas disclosed that the incidence of homicide, rape, robbery, burglary, arrests for drug possession, and suicide[4] were higher in counties whose drinking water contained little or no lithium. Counties whose drinking water naturally contained higher amounts of lithium had significantly lower rates of all these crimes. These counties with higher levels of lithium in their tap water experienced fewer hospitalizations for homicides, mental illness[5], psychosis, neurosis, schizophrenia, and personality disorder. Low dosage lithium benefits alcoholism and mood disorders seen in heavy users of alcohol and their relatives. This therapy is often obvious to family members[6] when depression, premenstrual tension, temper flareups and irritability cease affecting the individual. Lithium has been helpful in reducing aggressive[7] behavior in children. High dosages of lithium helped two adult women with severe anorexia nervosa[8] regain 26 and 20 pounds in six weeks. Both women experienced improvement in behavioral problems.
Low dosages of lithium have been found to be safe.[9] Dr. Jonathan Wright suggests 20 to 30 mg. of lithium aspartate or lithium-orotate daily as an appropriate dose to stop brain aging. This is 1/3 to 1/6 the dosage of lithium-carbonate used to treat manic depressive disorder. Dr. Hans Nieper of Germany has learned that lithium-orotate or lithium aspartate penetrate cells more effectively than lithium-carbonate so smaller doses can be used. One tablespoon of flaxseed oil daily along with 400 I.U. of vitamin E ensures that no lithium toxicity can develop. These lithium products can be obtained from Tehama Clinic 425-264-0059.
Should Lithium Be Added To The Water Supply In The U.S.?
The answer is yes, particularly for parts of the country where lithium water levels are low. Placing lithium in the water supply would almost certainly lower crime rates and would also improve the productivity of many emotionally troubled persons.
Is this likely to occur? Probably not because there is no large corporation that would profit from the placing of lithium in water. To understand the political environment surrounding an issue like this it is important to have an awareness of how fluoride was placed in U.S. water supplies.
Why did fluoride get placed in U.S. community water supplies? A politically important industry (aluminum manufacture) had an enormous problem disposing of the very toxic sodium fluoride created as a byproduct of the production of aluminum. Other than use as a rat poison, sodium fluoride had no economic value.
Was there any evidence that fluoride decreases the incidence of cavities? No, not then or since then.
Were any studies conducted to verify if the placing of fluoride in the water was safe for the American public? No.
Did anyone know how much fluoride should be added to water? No. The dose selected one part per million[10] was selected arbitrarily. When the legislation to place fluoride into U.S. water supplies was passed every congressman had bottled water placed in their offices. A prominent senator always carried a flask of spring water in his coat pocket when he dined in a fashionable Washington restaurant. He stated to his dinner companions " Not one drop of fluoridated water will ever pass my lips." Such are the guardians of our nation. Since placing lithium in our water could improve general health and decrease the need for pharmaceutical drugs there is little possibility this will occur.
Preserving Brain Function
An interesting study was done in elderly nuns living in a convent to try to ascertain what factors seem to contribute to declining brain function in the elderly (dementia). What was discovered was that those who were involved in activities that challenged the brain (learning new skills, working crossword puzzles, playing chess, etc.) were less likely to become demented than those who had no interests and were simply vegetating. This fits with "use it or lose it concept regarding brain function in the elderly" which appears to be valid.
Footnotes:
1, Moore G.L. et al Lithium-induced increase in human grey matter. Lancet 2000; 356: 1, 241-1, 242
2, Nanaka S., Chronic lithium treatment robustly protects neurones in the central nervous system against neuro excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx. Proceedings of the National Academy of Sciences of U.S.A. 1998; 95: 2,642-2,647
3, Radesater A., et al, Inhibition of GSK 3 beta by lithium attenuates tau phosphoralation and degeneration. Society for Neuroscience Abstracts 2001: 1, 437
4, Schrauzer,GN et al Lithium in drinking water and the incidence of crimes, suicides, and arrests related to drug addiction. Biological Trace Element Research 1990;105-113
5, Dawson E. B. The relationship of tap water and physiological levels of lithium levels of lithium to mental hospital admission and homicide in Texas. In Schrauzeer GN, Klippel KF (editors) Lithium in Biology and Medicine VCH Publishers, New York, 1991, pp. 170-187
6, Wright Jonathan Lithium Part 2 Other Effects Townsend Letter for Doctors & Patients April 2004 pg.59-60
7, Wright J. Lithium, Part 2: Other Effects Townsend Letter for Doctors & Patients April 2004 pp. 59
8, Bsreai A. Lithium id adult anorexia nervosa. Acta Psychiat Scand 1977; 55:97-101
9, Wright, J., Nutrition & Healing Vol. 10, Issue 7 Augiust 2003 pg.1-4
10, Mullins Eustace Murder By Injection The story of the Medical Conspiracy Against America pp 158 The National Council for Medical Research, P.O. Box 1105, Staunton, Virginia 24401
© 2004 Dr. James Howenstine - All Rights Reserved
Is Lithium Good for Depression
 
 
 
lithium bipolar 2
Biochemical and Physiological Effects of Lithium
Cellular Transport and the Inorganic Biochemistry of Lithium (N.J. Birch)
The chemistry of lithium is unusual. Lithium atoms are very small, highly polarized, and have a high charge density. The chemical and biochemical properties of lithium are similar to those of magnesium, with which it shares a “diagonal relationship” in the periodic table. Because magnesium plays a crucial role in the regulation of biochemical systems, it has been theorized that lithium influences magnesium-dependent processes
Lithium can be transported across membranes in five different ways. Of these, passive flux is important for the entry of lithium into cells, and sodium-lithium countertransport for the extrusion of lithium from cells. Lithium can presumably replace sodium in the sodium-sodium countertransport system, although the biological significance of the latter process is still unclear.
It appears that the concentration of lithium in cells does not reach the levels predicted by the Nernst equation. Rather, the intracellular lithium concentration is considerably lower than its concentration in blood or extracellular fluid. This is important for the models which have been proposed for its mechanism of action, as these must be able to explain the effects of lithium at intracellular concentrations of 0.1 mmol/l (i.e. similar to those seen in patients on lithium prophylaxis).
One hypothesis suggests that the biological effects of lithium are due to the role it plays at the cell periphery, where, for example, it may influence cell recognition, cell signaling mechanisms at the cell membrane, and certain immunological processes.

Position of lithium in the Periodic System
Lithium as a Trace Element (K. Lehmann)
In humans endogenous serum lithium levels normally range from 0.14-8.6 micromol/l, with a maximum level of 15.8 micromol/l.
These lithium serum levels are 3 orders of magnitude lower than those necessary for therapeutic/prophylactic treatment.
Scientists suspect that endogenous lithium in the human body has a physiological function, although sufficient evidence of this is still lacking.
Daily lithium intake in humans is dependent on both diet and the use of medications that contain lithium. With the latter, a total of 15 micromol to 0.66 mmol of lithium may be administered per day.
Effects of Lithium on Neurotransmitters and Second Messenger Systems (D. van Calker)
Studies examining the effect of lithium ions on the synthesis and metabolism of neurotransmitters have, thus far, yielded inconsistent results, failing to shed any light on the mechanism of action of lithium in vivo.
Lithium ions prevent the development of functional supersensitivity to dopamine and acetylcholine receptor stimulation, most likely by influencing second messenger systems.
Lithium ions increase basal cAMP levels and inhibit the neurotransmitter-stimulated accumulation of cAMP in the brain and other tissues.
Acute administration of lithium inhibits the stimulation of adenylyl cyclase, most likely through direct competition with magnesium, whose hydrated ionic radius is similar to that of lithium. The effects of chronic lithium treatment, however, probably result from (a) the modification of gene expression among components of the adenylyl cyclase system, especially G protein subunits (G_i, G_s), as well as from (b) a stabilization of the inactive trimeric form of the Gi protein. Lithium has been found to increase basal cAMP levels, which is most likely due to attenuation of the Gi protein and an increase – probably resulting from the effects of lithium on gene transcription – in the levels of adenylyl cyclase type I and type II mRNA.
At therapeutically relevant concentrations, lithium ions inhibit the hydrolysis of inositol mono-phosphatase to inositol. This leads to a depletion of inositol and a strong increase in diacylglycerol (DAG) in susceptible cells and tissues, depending on species and tissue type. Susceptibility is determined by the activity of a high-affinity inositol transport system, as well as by the degree to which the inositolphospholipid (IP) second messenger system is hormonally stimulated. Pronounced inositol depletion can lead to an inhibition of the IP system in affected cells, which is probably a result of attenuated IP synthesis and/or the activation of protein kinase C (PKC) through the accumulation of DAG.
Lithium exposure facilitates the activation of certain PKC isozymes, chronic activation of which can result in a downregulation of PKC activity (i.e. a constitutive activation and redistribution in the cell nucleus). This process is probably responsible for the diverse effects of lithium on the release of neurotransmitters, the inhibition of receptor sensitization and certain membrane transport processes. By influencing transcription factors such as c-fos, this process could also be responsible for the lithium-induced changes in gene transcription which have been observed.
The inhibitory effects of chronic lithium treatment on the PI system have also been demonstrated in humans. Peripheral cells from manic-depressive patients show increased hormonal sensitivity in the phosphoinositide (PI) system. Thus, it appears that lithium ions might compensate for the hyperactivity of the PI system which is associated with illness in these patients.
The Effect of Lithium on Serotoninergic Function (B. Müller-Oerlinghausen)
In animal experiments, lithium administration results in a net rise in 5-HT activity, which is probably caused presynaptically by an increase in the release and transformation of 5-HT precursors, an increase in the release of 5-HT, and by the functional antagonism between lithium and inhibitory presynaptic 5-HT1A receptors.
However, there are considerable differences in the amount of time which elapses before each of the different effects occurs.
An increase in 5-HT uptake in the thrombocytes of depressive patients, but not in those of healthy test subjects, has been observed.
In several studies of patients and healthy volunteers on short-term lithium therapy, neuroendocrine stimulation (e.g. with fenfluramine or tryptophan) led to increased prolactine or cortisol responses via serotoninergic transmission.
The presumably adaptive mechanisms which tend to emerge after chronic lithium administration (e.g. a decrease in the number and sensitivity of postsynaptic 5-HT receptors) probably result in a stabilization of serotoninergic neurotransmission rather than a unidirectional increase in 5-HT activity.
Specifically, there is a growing body of evidence that suggests that lithium increases the effect of antidepressants by acting at the presynaptic serotoninergic receptor to up-regulate 5-HT (serotonin) release. The effect may also be linked to a decrease in the sensitivity of presynaptic 5-HT receptors, which results in an increase in the amount of serotonin absorbed at the post-synaptic level.
Serotonin is a hormone and a neurotransmitter, acting as a chemical messenger which regulates many diverse aspects of the nervous system (roles in sleep, memory, appetite, mood, sex, endocrine function, among others) . Altered serotonin levels have been found in many different kinds of nervous disorders, from depression to anorexia to Parkinson’s to schizophrenia. A depletion of serotonin through either drugs or mis-aligned neurochemistry can be a powerful trigger for depression, and has been suggested to play a role in many other disorders. Correcting this serotonin depletion is the target of drugs such as Paxil.
It takes time for lithium to exert a meaningful ans therapeutic change in the brain. Interestingly, when lithium is administered chronically (3 weeks +) , this increase in serotonin is focused in the hippocampus, rather than globally. Conversely, when lithium is administered for only a short time (1 week), an increase in serotonin is seen more globally, throughout the cortex. The therapeutic effects of lithium are only evidenced after a few weeks, suggesting that it is the increase of serotonin in the hippocampus which is the target for anti-depressive treatment. This may also explain one of the side effects of lithium use: memory loss. The hippocampus is crucial in the formation of new memories and the maintenance of old ones, so memory loss can occur when the activity in this region changes.
Lithium also enhances the effect of selective serotonin reuptake inhibitors (SSRIs), a type of drug commonly prescribed to treat depression:
Muraki et al. (2001), investigated the effect of citalopram (SSRI) on median prefrontal cortex (mPFC) 5-HT levels
following a subchronic (1 week) lithium diet treatment. The subchronic lithium treatment group showed a significantly higher basal levels of extracellular 5-HT compared to control group; thus this indicates that lithium potentiates the neurobiochemical effect of an acute dose of SSRI on the mPFC.
Furthermore, it has been hypothesized that lithium blocks presynaptic 5-HT (1B) receptors only (partial agonist)—-which prevents the presynaptic terminal from taking released serotonin back. The serotonin must instead stay in the synaptic cleft, and therefore more likely to act on the un-blocked post-synaptic end. This in effect reverses the pre-existing “depletion” of serotonin at the nerve terminal, which could have been responsible for depression etc.
Source: Franck Chenu and Michel Bourin. 2006. Potentiation of Antidepressant-Like Activity with Lithium: Mechanism
Involved. Current Drug Targets, 7, 159-163 159.
 
 
The Effects of Lithium on the Hematopoietic System (V.S. Gallicchio)
Lithium increases the number of neutrophil and eosinophil granulocytes, but probably not that of monocytes, basophil granulocytes, thrombocytes or erythrocytes/reticulocytes in peripheral blood.
Whereas lithium increases the number of pluripotent stem cells in bone marrow, as well as of granulocyte-macrophage and megakaryocyte precursors, it probably reduces the number of erythrocyte progenitor cells.
Researchers suspect that these phenomena result from both the direct and indirect effects of lithium on cells, including an increase in the number of macrophages that produce growth factors and cytokines. A lithium-induced increase in bone marrow activity also appears to play a role in this context. A decline in erythropoiesis during lithium therapy may be due to inhibition of cAMP which, in turn, inhibits prostaglandin E production.
Thus, lithium can be used to treat toxic impairment of the hematopoietic system, whether this damage be caused by chemotherapy, radiation, antiviral medication, or granulocytopenia induced by carbamazepine or neuroleptics.
To date there has been no scientific evidence that lithium can cause leukemia.
The Effects of Lithium on the Immune System (V.S. Gallicchio)
In humans lithium therapy may lead to an increase in immunoglobulin synthesis by B-lymphocytes. However, the results of in vitro experiments and animal testing are contradictory.
Lithium stimulates the proliferation of T-lymphocytes and appears to increase the phagocytic activity of macrophages, but only at doses higher than those prescribed for medical treatment.
Experimental evidence suggests that lithium can increase cytokine production. This has been confirmed in the case of interleukin-2. Moreover, lithium potentiates tumor necrosis factor-mediated cytotoxicity. In high doses, lithium inhibits cyclic AMP (cAMP), which leads to an increase in the synthesis of interferon products.
It appears that lithium influences the immune system in part by reducing intracellular concentrations of cAMP and inositol phosphate.
Because of the high doses involved, the potential usefulness of lithium in the treatment of inflammatory and auto-immune diseases is still unclear. However, because it can increase interleukin-2 production, as well as potentiate killer cell activity, high-dose lithium has been used in the treatment of various cancers. Recent evidence also indicates that, by inhibiting T-suppressor cells lithium can reduce the severity of graft-versus-host reactions following transplants.
Of great importance is the potential use of lithium in the treatment of immune deficiency syndromes such as AIDS. In vitro experiments have shown that lithium can lead to a more robust immune response in patients with AIDS. The direct antiviral effects of lithium, e.g. in herpes virus infections, are already being utilized in clinical practice.
Chronobiological Aspects of Lithium Prophylaxis (B. Pflug)
Repetitive variations with a periodicity of approximately 24 hours are part of the circadian system. This system can be found among single-celled organisms, plants, animals, and humans.
In humans the circadian system is based on a number of oscillators of varying strengths which exert mutual influence on one another. The main pacemaker of this multi-oscillatory system is the nucleus suprachiasmaticus.
Lithium ions are chronobiologically active. They influence the circardian system by modifying phase relationships and lengthening the free-running period.
During manic-depressive episodes a variety of circadian rhythm dysfunctions have been observed.
The chronobiological effects of lithium salts help explain their efficacy in the treatment of manic-depressive disorders.
The Psychological Approach to the Effects of Lithium Prophylaxis (W. Classen)
The main effect of long-term lithium treatment is based on the modification of behavior and perception. These effects can be explained within psychological models and need not be reduced to other, lower levels of explanation.
Over the last 25 years, animal studies, psychophysiological investigations in humans, and routine clinical observation have led to the development of models which help explain the psychological effects of lithium salts. The phenomenological model developed by Kropf integrates concepts of genetic disease, aspects of the illness described in psychological terms, as well as the acute and chronic effects of lithium.
Among healthy test subjects lithium can cause fatigue, apathy, irritability, alternation between increased and decreased susceptibility to external stimuli, and general feelings of illness along with negative thinking, dysphoria, and lethargy.
Depressive patients exhibit a rigid and non-regulable behavioral repertoire, both during acute episodes and over the long term. This indicates a change in mental functions, such as cognition, perception, emotions, and the ability to structure thoughts and process information. Lithium most likely modulates these processes by raising the perception threshold for various stimuli and improving information processing structures.
The aggression-dampening effect of lithium which has been observed in human and animal studies is probably due to changes in the perception of aggression-inducing stimuli, as well as to improved control over aggressive impulses accompanied by a reduction in the number of aggressive behavioral patterns.
The Pharmacokinetics of Lithium Salts (K. Lehmann)
The kinetics of lithium are determined by the fact that it is a simple, monovalent cation.
The anion and/or the galenic formulation chosen for the final drug product primarily influence the resorption phase. This needs to be taken into account when initiating lithium treatment or changing a patient’s prescription.
The primary route of lithium elimination is renal (via glomerular filtration). Between 70-80% is reabsorbed in the proximal tubule. The overall elimination half-life of lithium is approximately 24 hours.
The exogenous clearance of lithium (ca. 19-20%) is approximately equal to the endogenous clearance of the drug in patients with normal renal function.
The renal clearance of lithium is subject to manifold influences, the most significant of which are (a) changes in electrolyte levels and (b) the secretion of aldosterone.
Impaired kidney function and age-related decreases in renal clearance can lead to a dramatic rise in serum lithium levels.
Lithium is distributed slowly and unevenly in the human body. Distribution is usually complete within 12 hours of first ingestion. During lithium therapy, steady state concentrations are generally reached within 4-7 days of repeated oral application in patients with normal renal function.


 
 
Could You Have a Lithium Deficiency?
Shocking but true. Lithium is an essential trace element.
Post published by Emily Deans M.D. on Jan 29, 2012 in Evolutionary Psychiatry
 
Source: http://www.flickr.com/photos/28761527@N06/3115190048/sizes/m/in/photostream/
When one mentions lithium, most people have a negative reaction. They think of One Flew Over the Cuckoo's Nest (link is external), drooling, and lobotomies. And lithium in pharmacologic doses has some terrible downsides. However, lithium is, in fact, an essential trace mineral, present in many water systems with some very beneficial effects in the brain.
Scientists first figured out lithium could help stabilize mood in bipolar disorder in the late 1800s when the mineral salt was also used to treat gout. Lithium was the original "up" ingredient in 7-UP soda (link is external), though I'm certain it is not in the modern recipe. The first research paper on lithium (link is external) didn't appear until 1949, when Australian psychiatrist John Cade (link is external) made his mark on psychiatric history. However, Greek physicians thousands of years earlier were treating mental disorders with mineral water now thought to be high in lithium.
Before John Cade, mania was treated with sequestration in darkness, electroshock therapy or lobotomy, so lithium was a terrific option—in fact it was the first successful pharmaceutical treatment for mental illness. It has huge side effects: lithium is toxic to the thyroid and kidneys (and heart in high amounts), causes weight gain, is fatal in overdose, and a lot of the time it simply doesn't work. But when lithium does work, it is a wonderful thing. Suicidal depression and mood swings relieved within the week. To this day, lithium is one of the few medications proven to decrease the risk of suicide.
Despite the fame and long term, widespread use, no one really knew what lithium actually did. In medical school, I was taught that it had some effect on the regulation of second messenger systems within the neurons (1 (link is external)). Meaning, like every other psychotropic medication, it changes something about the communication in the brain, for good or ill.
A recent article (link is external) sheds some light on lithium's actual mechanism of action. In bipolar disorder, there has been shown to be an increase in inflammatory markers of the frontal cortex of the brain. There is also an increase in the enzymes that regulate the expression of the omega 6 fatty acid derived arachidonic acid. When rats are given lithium-laced or lithium-free food for 6 weeks, the lithium-dosed rats had less arachidonic acid, and more 17-OH DHA, which is an anti-inflammatory metabolite of the fish oil, DHA. 17-OH DHA seems to inhibit all sorts of inflammatory proteins in the brain.
Interestingly enough, lithium has been shown to be the only effective drug (at least to slow the progression down) in another inflammatory, progressive, and invariably fatal neurotoxic disease, ALS, which is also known as Lou Gerhig's disease (2 (link is external)), and lithium is being studied in HIV, dementia and Alzheimer's disease.
Now that we've seen some of the good side of lithium, let's look at what happens in populations who get a steady trace amount of it in the water. Back in 1989, Schrauzer and Shrestha published a paper called "Lithium in Drinking Water and the Incidences of Crimes, Suicides, and Arrests Related to Drug Addictions (link is external)."  They took information about the lithium level in the water of  27 counties in Texas.  Seems that counties with higher lithium levels in the water had a statistically significant decrease in the incidence of homicide, suicide, arrests for opiates and cocaine, and violent criminal behavior.  Now to put things into perspective, a high lithium water content translates to about 2mg of lithium a day.  Pharmacologic psychiatric doses typically start at 300mg daily. 
From the 1989 paper:
Lithium has previously been used to control episodic outbreaks of rage among prisoners and in the management of drug abusers.  Animal experiments have demonstrated that lithium suppresses cocaine-induced super sensitivity...the kindling phenomenon following the chronic application of...a central nervous system stimulant, and head-twitching in response to the administration of mescaline.  Furthermore, lithium has been found to [improve] distractibility... and produce improvement of selective attention to stimuli... it prevents behavioral alterations owing to social isolation, lowers [aggressive behavior] owing to confinement...and causes a normalization of spontaneous motor activity.
That's a lot for one little trace mineral.  But what happens outside of Texas? Observational studies from Japan seem to correlate - back in 2009, researchers there noted that suicide rates decreased with higher amounts of lithium in the water (3 (link is external)). In Japan, rates of suicide have been distressingly high for the past 15 years. Japan has a suicide rate of 21 per 100,000 individuals per year vs. the US rate of 11 per 100,000. 
In another paper (link is external) studying lithium in the Japanese water supply, human longevity increased with the amount of trace lithium in the water. The same trace amounts of lithium in a controlled experiment (equivalent to about 2mg of lithium daily) increased the lifespan of the C elegans worms.  Trace amounts of lithium could improve human behavior and increase longevity. Perhaps it is the anti-inflammatory mechanism discussed above. But lithium is an interesting salt and could change brain communication in other ways.
Basic science time: Lithium looks a lot like sodium (link is external).  It has the same number of electrons in the outer shell—the molecule itself is a bit smaller, but the kidneys don't seem to be able to tell the difference.  And, perhaps, neither do the neurons.  So the addition of a bit of lithium to the matrix will decrease the overall sodium gradient in the brain, decreasing neuroxicity, and increasing the efficiency of brain energetics. From the Japanese drinking water, lithium, and suicide study:
It can be speculated that very low but very long lithium exposure can enhance neurotrophic factors, neuroprotective factors and/or neurogenesis, which may account for a reduced risk of suicide.
The authors of the two Japanese studies get rather enthusiastic, recommending supplementation at a level of about 2mg per day for human populations with the proposed effect to control behavior, increase longevity, and reduce suicide.
On the negative side, Swedish researchers (link is external) tested thyroid effects of trace lithium in the water in some villages in the Peruvian Andes. Some of these villages had some 10-20X the natural lithium in the food and water of the Japanese subjects, up to a maximum of 30mg daily (which is, of course, within an order of magnitude of the pharmacologic dose of 300mg).  They found that lithium in the water seemed to decrease active thyroid hormone levels and increase thyroid stimulating levels—lithium as a medicine will tend to cause hypothyroidism.
So, all told, lithium is a natural component of drinking water, and observationally decreases suicide and general naughtiness, and increases longevity, but perhaps also decreases thyroid function. I think it is quite plausible that since we evolved drinking fresh mineral water from the ground, our brains are designed to have a little bit of lithium on board, and its presence in trace amounts could credibly improve our behavior and reduce suicide.
 
 
Curr Alzheimer Res. 2013 Jan;10(1):104-7.
Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease.
Nunes MA1, Viel TA, Buck HS.
Author information
Abstract
A lower incidence of dementia in bipolar patients treated with lithium has been described. This metal inhibits the phosphorylation of glycogen-synthase-kinase 3-α and β, which are related to amyloid precursor protein processing and tau hyperphosphorylation in pathological conditions, respectively. Following the same rationale, a group just found that lithium has disease-modifying properties in amnestic mild cognitive impairment with potential clinical implications for the prevention of Alzheimer's Disease (AD) when a dose ranging from 150 to 600 mg is used. As lithium is highly toxic in regular doses, our group evaluated the effect of a microdose of 300 μg, administered once daily on AD patients for 15 months. In the evaluation phase, the treated group showed no decreased performance in the mini-mental state examination test, in opposition to the lower scores observed for the control group during the treatment, with significant differences starting three months after the beginning of the treatment, and increasing progressively. This data suggests the efficacy of a microdose lithium treatment in preventing cognitive loss, reinforcing its therapeutic potential to treat AD using very low doses.
J Clin Psychiatry. 2009 Jun;70(6):922-31.
Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.
Hampel H1, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J, Schönknecht P, Riepe MW, Kraft I, Gasser T, Leyhe T, Möller HJ, Kurz A, Basun H.
Author information
Abstract
OBJECTIVE:
Lithium, a first-line drug for the treatment of bipolar depression, has recently been shown to regulate glycogen synthase kinase-3 (GSK-3), a kinase that is involved in the phosphorylation of the tau protein. Since hyperphosphorylation of tau is a core pathological feature in Alzheimer's disease, lithium-induced inhibition of GSK-3 activity may have therapeutic effects in Alzheimer's disease. In the current study, we tested the effect of short-term lithium treatment in patients with Alzheimer's disease.
METHOD:
A total of 71 patients with mild Alzheimer's disease (Mini-Mental State Examination score > or = 21 and < or = 26) were successfully randomly assigned to placebo (N = 38) or lithium treatment (N = 33) at 6 academic expert memory clinics. The 10-week treatment included a 6-week titration phase to reach the target serum level of lithium (0.5-0.8 mmol/L). The primary outcome measures were cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) and GSK-3 activity in lymphocytes. Secondary outcome measures were CSF concentration of total tau and beta-amyloid(1-42) (Abeta(1-42)), plasma levels of Abeta(1-42), Alzheimer's Disease Assessment Scale (ADAS)-Cognitive summary scores, MMSE, and Neuropsychiatric Inventory (NPI). Patients were enrolled in the study from November 2004 to July 2005.
RESULTS:
No treatment effect on GSK-3 activity or CSF-based biomarker concentrations (P > .05) was observed. Lithium treatment did not lead to change in global cognitive performance as measured by the ADAS-Cog subscale (P = .11) or in depressive symptoms.
CONCLUSIONS:
The current results do not support the notion that lithium treatment may lead to reduced hyperphosphorylation of tau protein after a short 10-week treatment in the Alzheimer's disease target population.
TRIAL REGISTRATION:
(Controlled-Trials.com) Identifier: ISRCTN72046462.
Drugs Aging. 2012 May 1;29(5):335-42. doi: 10.2165/11599180-000000000-00000.
Does lithium prevent Alzheimer's disease?
Forlenza OV1, de Paula VJ, Machado-Vieira R, Diniz BS, Gattaz WF.
Author information
Abstract
Lithium salts have a well-established role in the treatment of major affective disorders. More recently, experimental and clinical studies have provided evidence that lithium may also exert neuroprotective effects. In animal and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. Recent studies addressing the inhibition of glycogen synthase kinase-3 beta (GSK3B) by lithium have further suggested the modification of biological cascades that pertain to the pathophysiology of Alzheimer's disease (AD). A recent placebo-controlled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in AD, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support. Although the clinical evidence available so far is promising, further experimentation and replication of the evidence in large scale clinical trials is still required to assess the benefit of lithium in the treatment or prevention of cognitive decline in the elderly.
Lithium and Longevity
A new paper was published this week - Low-dose lithium uptake promotes longevity in humans and metazoans.  Now, as a psychiatrist, I'm a lithium fan.  Apparently, it is an essential trace micronutrient (who knew) aside from the uses for decreasing suicide and helping mood stabilization. Want a primer - look at my blog post here.  (Here is the original lithium for treating mania paper by John Cade if you are interested.)

Decreasing suicide?  Yes, well lithium is actually very good at keeping people alive.  Even those with bipolar disorder or major depression who have no real symptomatic improvement seem to have less suicidal thoughts and suicides while on lithium.  Very interesting.  But why?

Let's start with some observational studies.  Back in 1989, Schrauzer and Shrestha published a paper called "Lithium in Drinking Water and the Incidences of Crimes, Suicides, and Arrests Related to Drug Addictions."  They took information about the lithium level in the water of  27 counties in the Great State of Texas.  Seems that counties with higher lithium levels in the water had a statistically significant decrease in the incidence of homicide, suicide, arrests for opiates and cocaine, and violent criminal behavior.  Now to put things into perspective, a high lithium water content translates to about 2mg of lithium a day.  Psychiatric doses start at 300mg daily. 

From the 1989 paper:
Lithium has previously been used to control episodic outbreaks of rage among prisoners and in the management of drug abusers.  Animal experiments have demonstrated that lithium suppresses cocaine-induced super sensitivity... the kindling phenomenon following the chronic application of ... a central nervous system stimulant, and head-twitching in response to the administration of mescaline.  Furthermore, lithium has been found to [improve] distractability... and produce improvement of selective attention to stimuli... it prevents behavioral alterations owing to social isolation, lowers aggressivity owing to confinement... and causes a normalization of spontaneous motor activity.

 Wow!  That's a lot for one little trace mineral.  And observational studies from Japan seem to correlate - back in 2009, researchers there noted that suicide rates decreased with higher amounts of lithium in the water (1)(In Japan, rates of suicide have been distressingly high for the past 15 years - Japan has a suicide rate of 21 per 100,000 individuals per year vs. the US rate of 11 per 100,000 (3)).  And, with the newest paper, longevity in Japan increased with the amount of trace lithium in the water in humans, and the same trace amounts of lithium in a controlled experiment (equivalent to about 2mg of lithium daily) increased the lifespan of the C elegans worms (2)(due to the increased suicide rates in Japan, suicide was controlled for in the numbers, and lithium still seemed to increase longevity in the observational studies.).

So, all old, that is rather interesting.  Trace amounts of lithium seem to improve human behavior in general, and no one knows why. 

Basic science time - lithium looks a lot like sodium.  It has the same number of electrons in the outer shell - the molecule itself is a bit smaller, but the kidneys don't seem to be able to tell the difference.  And, perhaps, neither do the neurons.  So the addition of a bit of lithium to the matrix will decrease the overall sodium gradient in the brain, decreasing neuroxicity, and increasing the efficiency of brain energetics. From the Japanese drinking water, lithium, and suicide study:
It can be speculated that very low but very long lithium exposure can enhance neurotrophic factors, neuroprotective factors and/or neurogenesis, which may account for a reduced risk of suicide.

In addition, lithium is thought to modulate the system of second messengers in the brain, meaning they enhance certain signaling processes.

The authors of these studies get rather enthusiastic, recommending supplementation at a level of about 2mg per day for human populations with the proposed effect to control behavior, increase longevity, and reduce suicide.

On the negative side, some Swedish researchers tested thyroid effects of trace lithium in the water in some villages in the Peruvian Andes (3).  Some of these villages had some 10-20X the natural lithium in the food and water of the Japanese subjects, up to a maximum of 30mg daily (which is, of course, within an order of magnitude of the pharmacologic dose of 300mg).  They found that lithium in the water seemed to decrease active thyroid hormone levels and increase thyroid stimulating levels - lithium as a medicine will tend to cause hypothyroidism.

In another interesting tidbit, they found that natural selenium levels in the water correlated with free T4 thyroid levels.  Only, thing is, selenium is supposed to act to help T4 become active thryoid hormone, T3.  So one would expect selenium levels to correlate with T3 levels and inversely correlate with T4. 

So, all told, lithium is a natural component of drinking water, and observationally decreases suicide and general naughtiness, and increases longevity, but perhaps also decreases thyroid function. 
 
 
Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder
Paula V. Nunes, Orestes V. Forlenza, Wagner F. Gattaz
DOI: 10.1192/bjp.bp.106.029868 Published 30 March 2007
  Abstract
Bipolar disorder is associated with increased risk for dementia. We compared the prevalence of Alzheimer's disease between 66 elderly euthymic patients with bipolar disorder who were on chronic lithium therapy and 48 similar patients without recent lithium therapy. The prevalence of dementia in the whole sample was19% v. 7% in an age-comparable population. Alzheimer's disease was diagnosed in 3 patients (5%) on lithium and in 16 patients (33%) who were not on lithium (P<0.001). Our case–control data suggest that lithium treatment reduced the prevalence of Alzheimer's disease in patients with bipolar disorder to levels in the general elderly population. This is in accordance with reports that lithium inhibits crucial processes in the pathogenesis of Alzheimer's disease.
 
  • © 2007 Royal College of Psychiatrists

 
 
 
 

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