Lithium Orotate – An Overview
Lithium is a mineral that may have some uses as a nootropic and mental health treatment.
Its first recorded medical use was in 1871 for the treatment of mania.
Most people associate lithium as a treatment for bipolar disorder. However, it can also have benefits for:
- Treating bipolar disorder
- Fighting depression
- Cognitive enhancement
Lithium is a trace element that your body needs in small amounts for proper health. Your body does not make this mineral on its own, you must get it from outside sources.
It’s so critical that lithium deficiency is associated with increased rates of suicides, homicides, and arrest rates for drug use and other crimes.1Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 20022Huber RS, et al. Relationship between altitude and lithium in groundwater in the United States of America: results of a 1992-2003 study Geospat Health. 20143Schrauzer GN, Shrestha KP. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions Biol Trace Elem Res. 1990
In general, diets rich in grains and vegetables provide a lot of lithium.
However, due to variations in soil concentrations of lithium, the amount of can be different depending on the source of the foods.
Tap water and beverages may also contain trace amounts of lithium.4Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality J Am Coll Nutr. 2002
According to current research, microdosing with lithium could provide many cognitive and neuroprotective benefits for the average person.
Is Lithium Orotate The Same As Lithium?
The short answer is yes. Lithium orotate is a more bioavailable form of lithium that should have essentially the same effects.
It’s important to note that much of this review of the nootropic lithium orotate is based on research done on the pharmacological research done on the prescribed drug lithium in the form of lithium carbonate.
This is due to the limited available research done on lithium orotate specifically. However, much of what is understood about lithium can be applied to lithium orotate.
The difference between these 2 types of lithium is their forms and constituents.
Orotic acid is found in milk and dairy products and is required for the regulation of genes that are important in the development of cells, tissues and organisms.6M Löffler, E A Carrey , E Zameitat. Orotate (Orotic Acid): An Essential and Versatile Molecule Nucleosides Nucleotides Nucleic Acids. 2016
Evidence shows the benefit of lithium orotate vs lithium carbonate is that you need less lithium from the orotate form vs the prescription carbonate form to achieve desired results.
The theory is that when the lithium-ion is combined with the orotate molecule, it acts as a targeted delivery system and transports the lithium-ion efficiently through the cell membrane to its various sites of action within the cell.
Compare this with lithium carbonate where you need high doses to ‘force’ lithium into the body’s cells and lithium orotate can be a great over-the-counter option for optimizing the mood.7H A Nieper. The Clinical Applications of Lithium Orotate. A Two Years Study Agressologie. 1973
What Does Lithium Orotate Do?
Lithiums most famous use is for treating bipolar disorder and “smoothing out” mood swings. There is abundant evidence that it is effective for this.
One metanalysis looking at multiple decades of research concluded that “lithium remains a fundamental tool for the treatment of BD.”
It can also boost antidepressants effects in the treatment of major depressive disorder.8Albert U, De Cori D, Blengino G, Bogetto F, Maina G. Lithium treatment and potential long-term side effects: a systematic review of the literature Riv Psichiatr. 2014
One study found that the amino acid N-acetyl-aspartate is increased in the brain of patients with bipolar disorder after lithium treatment.
NAA a diagnostic marker of neural decline, and low levels can mean that your brain is not functioning properly.9Tomas Hajek, et al. Large positive effect of lithium on prefrontal cortex N-acetylaspartate in patients with bipolar disorder: 2-centre study J Psychiatry Neurosci. 2012
Another study showed Lithium treatment is related to better brain integrity in older individuals with BD, particularly those who take lithium long-term.10Gildengers AG, et al. Longer lithium exposure is associated with better white matter integrity in older adults with bipolar disorder Bipolar Disord. 2015
Many people who microdose lithium say that it can help balance them out emotionally. They report less tendency to lash out in anger, less social anxiety, and more calm and focus.
Lithium has properties that can protect the brain and keep it healthy and running smoothly as you age.
Research shows that lithium can prevent toxicity caused by excess glutamate and N-methyl-D-aspartate (NMDA) receptor activation.
This is a major contributor to brain aging, and can be caused by prolonged stress or injury/disease.
Lithium’s neuroprotective effects have also been demonstrated with ischemic/hemorrhagic stroke, traumatic brain/spinal cord injury, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and other conditions involving cognitive degeneration. 11Chiu CT, et al. Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder Pharmacol Rev. 2013
A study of stroke patients showed lithium may be associated with gray matter volume change and verbal memory improvement.12Sun YR, et al. Lithium Carbonate in a Poststroke Population: Exploratory Analyses of Neuroanatomical and Cognitive Outcomes J Clin Psychopharmacol. 2019
There is preliminary evidence that lithium can help treat traumatic brain injury.13Peter R. Leeds, et al A New Avenue for Lithium: Intervention in Traumatic Brain Injury ACS Chem Neurosci. 2014
Neuroimaging studies show an association between long-term lithium treatment and increased gray matter volume in brain areas implicated in emotional processing and cognitive control.
This suggests that lithium has considerable neuroprotective and/or neurotrophic effect.
Taking small doses of lithium daily may be beneficial even for otherwise healthy people. It can have a holistic, long-term effect on brain health across a wide spectrum of mental functions.
Lithium For Learning and Memory
A meta analysis of 12 studies on healthy subjects revealed mixed data on lithium in regards to attention, concentration, and learning. These studies did not see any noticeable effect on cognition.14Wingo AP, et al. Effects of lithium on cognitive performance: a meta-analysis J Clin Psychiatry. 2009
There is evidence for better/improved executive functions and memory, mostly related to the activity of prefrontal cortex and medial temporal lobe in lithium-treated Bipolar Depressed patients.
Evidently, lithium can increase the volume of the hippocampus, which can have a direct effect on memory and learning ability.15Rybakowski JK, Permoda-Osip A, Borkowska A. Response to prophylactic lithium in bipolar disorder may be associated with a preservation of executive cognitive functions Eur Neuropsychopharmacol. 2009
This may point to lithium’s effectiveness for improving cognition in specifically bipolar patients versus otherwise healthy people.
Lithium For ADHD
According to current research, there is no evidence that lithium can improve attention or treat symptoms of ADHD.16Adele Quartini, et al. Lithium: from mood stabilizer to putative cognitive enhancer Neural Regen Res. 2016
That said, many users report anecdotally that microdosing with lithium orotate can have a nootropic effect on focus. This may be related to its ability to smooth out mood and emotion, allowing more relaxed calm and focus.
Lithium For Alzheimer’s Disease
In patients with Bipolar Disorder, continued lithium treatment may help prevent dementia. It seems that lithium may be able to reduce neurodegeneration associated with Alzheimers, including reducing amyloid plaques.17Nunes PV, Forlenza OV, Gattaz WF. Lithium and risk for Alzheimer’s disease in elderly patients with bipolar disorder Br J Psychiatry. 2007
Lithium may be beneficial for recovering addicts. It could help deal with the mood swings you feel as your body readjusts to sobriety.
One study of recovering substance abusers saw that lithium had a mood improving and stabilizing effect on the participants versus placebo.
Better mood may be linked to better prospects of staying clean.18Schrauzer GN, de Vroey E. Effects of nutritional lithium supplementation on mood. A placebo-controlled study with former drug users Biol Trace Elem Res. 1994
Another study looked at recovering alcoholics. They found that lithium orotate was effective at helping patients recover as part of a combination therapy.
They also noted that it was fairly side-effect free.19Sartori HE. Lithium orotate in the treatment of alcoholism and related conditions Alcohol. 1986
How Lithium Orotate Works In The Brain
Lithium orotate is a naturally occurring mineral that your body needs in small amounts to function. Once you consume it, it quickly crosses the blood brain barrier and starts working within 15-20 minutes.
It works on a number of different pathways in the brain.
Lithium stimulates the production of neural stem cells, and brain imaging shows that it increases amygdala and hippocampus volume and neurogenesis. As well as grey matter density.
One of lithium’s most important effects is inhibiting the compound GSK-3β. This inhibition results in more Brain Derived Neurotrophic Factor (BDNF), which is a major factor in creating new neurons.
GSK-3β is linked to apoptosis, or programmed cell death, so decreasing it can ensure your brain does not destroy healthy neurons. Inhibiting GSK-3β can also have an antidepressant effect.21Adele Quartini, et al. Lithium: from mood stabilizer to putative cognitive enhancer Neural Regen Res. 2016
Lithium orotate also inhibits glutamate-induced toxicity mediated by NMDA receptors. Glutamate is the main excitatory neurotransmitter in the brain, and it is necessary for many cognitive functions.
However, too much glutamate can damage neurons and cause cognitive issues. Luckily, lithium can keep glutamate levels in check, protecting the brain long-term and improving mood and mental function.22Ryota Hashimoto. 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
Lithium has been shown to induce autophagy, a sort of ‘quality control’ process believed to be particularly important in neurodegenerative disorders.
Diseases like Alzheimer’s Parkinsons, and MS are characterized by the accumulation of misfolded disease-causing proteins, which lithium can help clear out.
Lithium is the only known substance that can increase the neuroprotective protein bcl-2 in the brain.23Manji HK, Moore GJ, Chen G. Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry. 1999
How Much Lithium Orotate Should I Take?
For nootropic effects, you will be using smaller “micro-doses” than those used to treat conditions like bipolar disorder. Supplementing up to 5mg, 2 or 3 times a day seems to be well tolerated.
Lithium Orotate Potential Side Effects
For nootropic microdoses, side-effects are usually minimal or non-existent.
For larger doses, side effects include:
- Gastrointestinal issues
- Muscle tremors
Toxicity related events are seen at 1.8 mg Li/kg/day
Keep in mind this is long-term, high dose chronic usage which is not recommended, especially without a doctor’s supervision
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