Lithium is an alkali metal that occurs mainly in water, but in very small amounts. It gained interest thanks to its nootropic properties, demonstrating the effect on brain functions. It found application in the treatment of depression, bipolar disorder and schizophrenia.
For healthy people, lithium offers other benefits, such as multispecific neuroprotective effects, for example by inhibiting the influence of proteins that result in neurodegeneration .
In medicine, it’s used in the form of carbonate and due to the side effects of this form, it’s available on prescription. No less, lithium is also available in the form of orotate, which can be purchased as a dietary supplement. At the same time, lithium orotate has a much greater safety of use than carbonate and has a higher bioavailability, which allows it to be used in lower doses .
But let’s start with how the lithium affects the well-being.
Lithium and depression
Lithium shows anti-depressant effects by affecting the serotonin metabolism (the neurotransmitter responsible for overall happiness). This is done by increasing the activity of postsynaptic serotonin
5-HT1A receptors, while not negatively affecting the autoregulation of 5-HT receptors, which would result in the abolition of the described effect . The study in which such a mechanism was recorded was of short-term nature.
But this is not the only mechanism that lithium affects the improvement of well-being.
Lithium and neurogenesis
With the use of lithium, the activity of BDNF protein increases . BDNF is a factor affecting cognitive functions, synaptic plasticity, as well as protecting neurons from damage and having antidepressant and anxiolytic effect, which, combined with a positive effect on serotonin activity in the brain, makes lithium multi-phase affect the improvement of well-being.
Most likely, the above mechanism results from lytic inhibition of the GSK-3 protein kinase enzyme (glycogen synthase kinase-3), which is a mediator in the attachment of a phosphate molecule to the amino acid residues of serine and threonine. This enzyme in its activity is associated with bipolar disorder, Alzheimer’s disease, as well as many cancers .
Lithium increases the activity of NGF and GDNF  proteins in parts of the brain such as the hippocampus, frontal cortex, occipital cortex and striatum. These proteins increase the ability of neurons to regenerate and form new connections in the central nervous system.
Long-term lithium supplementation results in improved memory by stimulation of progenitor and stem cells in the hippocampus . Lithium also prevents the reduction of cellular capacity for proliferation caused by glutamate or cortisol. Thus, it can be suspected that lithium supplementation may reduce the degree of decline in cognition caused by chronic stress [8, 9].
Lithium also increases the activity of N-acetyl aspartate (NAA), which positively correlates with creativity and intelligence [10, 11]. NAA affects the activity of the corpus callosum, which is largely responsible for the communication between the hemispheres of the brain and the rate of information processing .
Lithium neuroprotective actions
It has an anti-NMDA receptor stimulant effect, resulting from glutamate activity . To a large extent, this is the result of inhibition of the calcium inflow, which determines NMDA receptor activity .
Lithium effects on mood
The soothing and stabilizing mood of lithium is known.
In an animal study, lithium supply reduced aggressive behaviours .
It seems interesting to study people with known ADHD who have been supplemented with methylphenidate or lithium. Factors such as the tendency to irritability, learning problems, tendency to aggression, anti-social behaviour and the tendency to depression were taken into account. Both groups reported improvement in these parameters and the result was comparable between both groups .
Lithium also has a positive effect in people with obsessive compulsive disorders  who are resistant to the standard therapy model.
The reduction of obsessive compulsive behaviours is also observed in compulsive gamblers who have been subjected to lithium therapy .
To a certain extent, the effect of improving self-control is due to the fact that lithium reduces the sensitivity of the post-synaptic noradrenaline receptor , which can cause emotional shaking.
Lithium and immune system
Lithium has the ability to reduce inflammation, mainly due to inhibition of GSK-3 activity. In animal studies with an autoimmune model, lithium inhibited the activity of the arm of the Th1 immune system, including interferon γ, but not Th17 arm activity .
Lithium reduces the production of proinflammatory IL-1β and TNF-α, while stimulating the secretion of IL-2, TGF, IL-1RA and IL-10, which have properties regulating inflammation [16, 17]. At the same time, studies have reported that under certain conditions lithium may increase the production of proinflammatory cytokines IL-4, IL-6, TNF-α [18, 19], hence its use in autoimmunity is debatable.
There is an increase in the production of IgG and IgM antibodies with lithium supplementation . At the same time, it reduces the production of prostaglandins, preventing a decline in the efficiency of the immune system .
Lithium and thyroid
Lithium may negatively affect the production of thyroid hormones [24-28]. In studies, lithium supplementation resulted in a decrease in fT4 production and an increase in TSH level.
Moreover, lithium may exacerbate thyroid autoimmune , but it’s not a direct mechanism, but indirect, as lithium stimulates the immune system to produce specific cytokines that are mediators of inflammation.
Lithium and Vitamin B12
Lithium shows the feature of being a co-factor in the metabolism of vitamin B12, supporting its transport to cells [31, 32]. Although early studies have shown that lithium supplementation leads to a decrease in B12 levels in the blood, subsequent experiments have shown that lithium causes a higher concentration of vitamin B12 in the cells.
Lithium interactions. Lithium side effects. Is Lithium safe?
– Antidepressants from the SSRI genus 
– Antipsychotics, such as clozapine 
– Anticonvulsants (lithium may increase the side effects of these medicines) 
– Hypotensive drugs (may increase the concentration of lithium in the blood) 
– Diuretics, such as furosemide (may increase the concentration of lithium in the blood) 
– Non-steroidal anti-inflammatory drugs (may increase the concentration of lithium in the blood) [38, 39]
– Medicines for muscle relaxation (lithium may prolong their action time 
– Other: it’s not recommended to use lithium by pregnant women and breastfeeding women; people with kidney dysfunction; people with heart disease, as lithium can cause arrhythmia in these people.
Lithium benefits and side effects
- It works in improving mental well-being
- Antidepressant action 
- Better control over emotions (aggressive behaviour)
- May improve cognitive fitness
- It can negatively affect people with autoimmunisation, exacerbating it
- It may reduce the production of thyroid hormones
- Is a competitive magnesium inhibitor , which in a way is the mechanism of its action (GSK-3 inhibition)
Lithium benefits :
The following side effects, though only sporadically, can occur in people who are taking lithium:
– Stomach pain
– Muscle weakness
– shaking hands
Lithium dosage. How to take lithium? How much lithium to take?
The beneficial effects of lithium have been demonstrated at doses of 1-2mg , but many people prefer slightly higher doses of 5 mg daily, and this concentration can usually be found in dietary supplements.
Where to buy lithium? Which lithium to buy? Which lithium to choose? Which form of lithium to choose?
Lithium in form of Lithium orotate is definitely the best one. We suggest checking Lithium Orotate from Seeking Health – well known, and reputable brand straight from USA. For us – it is the best lithium on the market!
- Vo TM, Perry P, Ellerby M, Bohnert K. Is lithium a neuroprotective agent? Ann Clin Psychiatry. 2015 Feb;27(1):49-54.
- Shaheen E Lakhan and Karen F Vieira. Nutritional therapies for mental disorders. Nutr J. 2008; 7: 2. Published online 2008 Jan 21. doi: 10.1186/1475-2891-7-2
- Alevizos B, Alevizos E, Leonardou A, Zervas I. Low dosage lithium augmentation in venlafaxine resistant depression: an open-label study. Psychiatriki. 2012 Apr-Jun;23(2):143-8.
- Pierre Blier , Claude De Montigny, Danielle Tardif. Short‐term lithium treatment enhances responsiveness of postsynaptic 5‐HT1A receptors without altering 5‐HT autoreceptor sensitivity: An electrophysiological study in the rat brain.
- Chi-Tso CHIU and De-Maw CHUANG. Neuroprotective action of lithium in disorders of the central nervous system. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Jun; 36(6): 461–476.
- Jope RS, Johnson GV (February 2004). The glamour and gloom of glycogen synthase kinase-3. Trends in Biochemical Sciences. 29 (2): 95–102.
- Angelucci F, Aloe L, Jiménez-Vasquez P, Mathé AA. Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression. Int J Neuropsychopharmacol. 2003 Sep;6(3):225-31.
- Born J, Wagner U. Memory consolidation during sleep: role of cortisol feedback. Ann N Y Acad Sci. 2004 Dec;1032:198-201.
- Eun Joo Kim, Blake Pellman, and Jeansok J. Kim. Stress effects on the hippocampus: a critical review. Learn Mem. 2015 Sep; 22(9): 411–416. Published online 2015 Sep. doi: 10.1101/lm.037291.114
- Gregory J Moore, Gregory J Moore, Joseph M Bebchuk, Khondakar Hasanat, Guang Chen, Navid Seraji-Bozorgzad, Ian B Wilds, Michael W Faulk, Susanne Koch, Debra A Glitz, Libby Jolkovsky, Husseini K ManjiLithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects? July 1, 2000Volume 48, Issue 1, Pages 1–8
- Aydin K, Uysal S, Yakut A, Emiroglu B, Yılmaz F. N-acetylaspartate concentration in corpus callosum is positively correlated with intelligence in adolescents. Neuroimage. 2012 Jan 16;59(2):1058-64. doi: 10.1016/j.neuroimage.2011.08.114. Epub 2011 Oct 1.
- Ghasemi M, Dehpour AR. The NMDA receptor/nitric oxide pathway: a target for the therapeutic and toxic effects of lithium. Trends Pharmacol Sci. 2011 Jul;32(7):420-34. doi: 10.1016/j.tips.2011.03.006. Epub 2011 Apr 13.
- Kelley C. O’Donnell and Todd D. Gould. The Behavioral Actions of Lithium in Rodent Models. Neurosci Biobehav Rev. 2007; 31(6): 932–962. Published online 2007 Apr 13. doi: 10.1016/j.neubiorev.2007.04.002
- Dorrego MF, Canevaro L, Kuzis G, Sabe L, Starkstein SE. A randomized, double-blind, crossover study of methylphenidate and lithium in adults with attention-deficit/hyperactivity disorder: preliminary findings. J Neuropsychiatry Clin Neurosci. 2002 Summer;14(3):289-95.
- Amber L. Rowse, Rodrigo Naves , Kevin S. Cashman, Donald J. McGuire, Tethia Mbana, 3 Chander Raman and Patrizia De Sarno. Lithium Controls Central Nervous System Autoimmunity through Modulation of IFN-γ Signaling. PLoS One. 2012; 7(12): e52658. Published online 2012 Dec 28. doi: 10.1371/journal.pone.0052658
- Olga Stępień-Wyrobiec , Antoni Hrycek , Grzegorz Wyrobiec. Transforming growth factor beta (TGF-beta): Its structure, function, and role in the pathogenesis of systemic lupus erythematosus. Postepy Hig Med Dosw. (online), 2008; 62: 688-693.
- Agnieszka Szuster-Ciesielska, Anna Tustanowska-Stachura, Maria Słotwińska, Halina Marmurowska-Michałowska, Martyna Kandefer-Szerszeń. IN VITRO IMMUNOREGULATORY EFFECTS OF ANTIDEPRESSANTS IN HEALTHY VOLUNTEERS. Polish Journal of Pharmacology. Pol. J. Pharmacol., 2003, 55, 3530362. ISSN 1230-6002
- Maes M, Song C, Lin AH, Pioli R, Kenis G, Kubera M, Bosmans E. In vitro immunoregulatory effects of lithium in healthy volunteers. Psychopharmacology (Berl). 1999 Apr;143(4):401-7.
- Ahmad Nassar and Abed N. Azab. Effects of Lithium on Inflammation. ACS Chem Neurosci. 2014 Jun 18; 5(6): 451–458. Published online 2014 Apr 25. doi: 10.1021/cn500038f
- Weetman, A.M.McGregor, J.H.Lazarus, B.ReesSmith, R.Hall. The enhancement of immunoglobulin synthesis by human lymphocytes with lithium. Clinical Immunology and Immunopathology Volume 22, Issue 3, March 1982, Pages 400-407
- Yao-Chun, Wang, Ghanshyam N.Pandey, JoeMendels, AlanFrazer. Effect of lithium on prostaglandin E1− stimulated adenylate cyclase activity of human platelets. Biochemical Pharmacology Volume 23, Issue 4, 15 February 1974, Pages 845-855
- Rasmussen SA. Lithium and tryptophan augmentation in clomipramine-resistant obsessive-compulsive disorder. Am J Psychiatry. 1984 Oct;141(10):1283-5.
- Pallanti S, Haznedar MM, Hollander E, Licalzi EM, Bernardi S, Newmark R, Buchsbaum MS. Basal Ganglia activity in pathological gambling: a fluorodeoxyglucose-positron emission tomography study. Neuropsychobiology. 2010;62(2):132-8. doi: 10.1159/000317286. Epub 2010 Jun 30.
- Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):723-33. doi: 10.1016/j.beem.2009.06.002.
- Johnston AM, Eagles JM. Lithium-associated clinical hypothyroidism. Prevalence and risk factors. Br J Psychiatry. 1999 Oct;175:336-9.
- Andrea Fagiolini, David J. Kupfer, John Scott, Holly A. Swartz, David Cook, Danielle M. Novick and Ellen Frank. Hypothyroidism in patients with Bipolar I Disorder treated primarily with lithium. Epidemiology and Psychiatric Sciences Volume 15, Issue 2 June 2006 , pp. 123-127
- Davis Kibirige, Kenneth Luzinda and Richard Ssekitoleko. Spectrum of lithium induced thyroid abnormalities: a current perspective. Thyroid Research2013 6:3 https://doi.org/10.1186/1756-6614-6-3
- Ozpoyraz N, Tamam L, Kulan E. Thyroid abnormalities in lithium-treated patients. Adv Ther. 2002 Jul-Aug;19(4):176-84.
- Wilson J. H. McKlllop G. T. Crocket C. Pearson C. Jenkins F. Burns A. K. Burnett J. A. Thomson. The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease. https://doi.org/10.1111/j.1365-2265.1991.tb00305.x
- Swann AC. Norepinephrine and (Na+, K+)-ATPase: evidence for stabilization by lithium or imipramine. Neuropharmacology. 1988 Mar;27(3):261-7.
- Schrauzer GN, Shrestha KP, Flores-Arce MF. Lithium in scalp hair of adults, students, and violent criminals. Effects of supplementation and evidence for interactions of lithium with vitamin B12 and with other trace elements. Biol Trace Elem Res. 1992 Aug;34(2):161-76.
- Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005 Jan;19(1):59-65.
- Austin LS, Arana GW, Melvin JA. Toxicity resulting from lithium augmentation of antidepressant treatment in elderly patients. J Clin Psychiatry. 1990 Aug;51(8):344-5.
- Rudra Prakash, SurendraKelwala, Thomas A.Ban. Neurotoxicity with combined administration of lithium and a neuroleptic. Comprehensive Psychiatry Volume 23, Issue 6, November–December 1982, Pages 567-571
- Finley PR, Warner MD, Peabody CA. Clinical relevance of drug interactions with lithium. Clin Pharmacokinet. 1995 Sep;29(3):172-91.
- Finley PR, O’Brien JG, Coleman RW. Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction. J Clin Psychopharmacol. 1996 Feb;16(1):68-71.
- Crabtree BL, Mack JE, Johnson CD, Amyx BC. Crabtree BL1, Mack JE, Johnson CD, Amyx BC. Am J Psychiatry. 1991 Aug;148(8):1060-3.
- J C Frölich, R Leftwich, M Ragheb, J A Oates, I Reimann, and D Buchanan. Indomethacin increases plasma lithium. Br Med J. 1979 Apr 28; 1(6171): 1115–1116.
- Reimann IW, Frölich JC. Effects of diclofenac on lithium kinetics. Clin Pharmacol Ther. 1981 Sep;30(3):348-52.
- Herman BordenMaxine T. Clarke Herzl Katz. The use of pancuronium bromide in patients receiving lithium carbonate. Canadian Anaesthetists’ Society Journal. January 1974, Volume 21, Issue 1, pp 79–82
- Fabrice Jollant. Add-on lithium for the treatment of unipolar depression: Too often forgotten? J Psychiatry Neurosci. 2015 Jan; 40(1): E23–E24. doi: 10.1503/jpn.140162
- Zarse K, Terao T, Tian J, Iwata N, Ishii N, Ristow M. Low-dose lithium uptake promotes longevity in humans and metazoans. Eur J Nutr. 2011 Aug;50(5):387-9. doi: 10.1007/s00394-011-0171-x. Epub 2011 Feb 8.
- RICHARD T. TIMMER and JEFF M. SANDS. Lithium Intoxication. JASN March 1999, 10 (3) 666-674