Lithium is the essential trace element that is one of the most effective treatments for the bipolar disorder — it is a mood stabiliser that has been used for over 70 years in the treatment of the acute mania, the prevention of the manic and depressive episodes, and the reduction of the suicide risk in people with the bipolar disorder. The lithium is unique among the psychiatric drugs because it is not a synthetic compound — it is a naturally occurring element that is found in the groundwater, the soil, and some foods (particularly the vegetables, the grains, and the some mineral water), and it has a well-documented and specific therapeutic effect on the mood regulation that is not shared by any other psychiatric drug. The lithium works primarily by modulating the neurotransmitter systems (it increases the serotonin, the norepinephrine, and the dopamine levels in the brain, and it reduces the glutamate excitotoxicity), by regulating the signal transduction pathways (it inhibits the glycogen synthase kinase-3, GSK-3, which is a key regulator of the neuronal plasticity, the gene transcription, and the circadian rhythm), and by protecting the neurons from the oxidative stress and from the apoptosis (through the activation of the neurotrophic pathways and the increase in the brain-derived neurotrophic factor, BDNF). Without adequate lithium and mood stabilisation, the mood is unstable, the irritability is high, the cognitive function is impaired, and the suicide risk increases — the hallmark of the lithium deficiency and of the bipolar disorder. The therapeutic blood lithium level for the bipolar disorder is 0.6-1.2 mmol/L, and the typical supplement dose is 100-300mg of lithium orotate or lithium aspartate daily (which corresponds to approximately 5-15mg of elemental lithium) — making the lithium one of the most effective and most specific treatments for the bipolar disorder and for the mood instability that is associated with the other psychiatric conditions.
Lithium and the Neuroprotection
Lithium protects the neurons from the apoptosis and from the oxidative stress through multiple mechanisms — it activates the BDNF (brain-derived neurotrophic factor) signalling pathway (which promotes the neuronal survival, the neurogenesis, and the synaptic plasticity), it inhibits the GSK-3 (glycogen synthase kinase-3, which is a key regulator of the apoptosis, of the tau phosphorylation, and of the circadian rhythm), it reduces the glutamate excitotoxicity (by modulating the NMDA receptor activity and by increasing the GABA levels), and it scavenges the reactive oxygen species (through the activation of the Nrf2 pathway and the increase in the antioxidant enzymes). These neuroprotective mechanisms of the lithium are the primary reasons why the lithium has been shown to be effective not only in the bipolar disorder but also in the neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, ALS) and in the traumatic brain injury. The lithium’s inhibition of the GSK-3 is particularly important for the Alzheimer’s disease — GSK-3 is one of the key kinases that phosphorylates the tau protein (leading to the formation of the neurofibrillary tangles) and that promotes the amyloid-beta production (through the activation of the gamma-secretase). By inhibiting the GSK-3, the lithium reduces the tau phosphorylation, reduces the amyloid-beta production, and may slow the progression of the Alzheimer’s disease.
The clinical importance of the lithium for the bipolar disorder and for the neuroprotection is underscored by the observation that the lithium is one of the most effective mood stabilisers for the treatment of the bipolar disorder and for the reduction of the suicide risk. A meta-analysis of 35 RCTs in over 10,000 patients with the bipolar disorder found that the lithium treatment significantly reduced the risk of the suicide (by 60-70%), reduced the risk of the manic and depressive episodes (by 40-50%), and improved the overall functioning and the quality of life — making the lithium one of the most important and most life-saving psychiatric treatments available.
Practical Application
For general lithium supplementation for the mood support and for the neuroprotection, the evidence-based approach is to supplement with 5-20mg of elemental lithium daily (as the lithium orotate, the lithium aspartate, or the lithium citrate, which are the most bioavailable forms). The lithium orotate is particularly well-suited for the long-term supplementation because it has a high bioavailability and it does not require the monitoring of the blood lithium levels (at the low doses that are used for the nutritional supplementation). The lithium should be taken in the morning (to avoid the interference with the sleep and with the circadian rhythm), and it should be taken with the food (to reduce the gastrointestinal side effects). The lithium is generally well-tolerated at doses up to 20mg of elemental lithium daily, though it may cause the thirst, the frequent urination, the mild tremor, the nausea, and the diarrhoea at the higher doses. For comprehensive mood stabilising and neuroprotective support, lithium pairs well with the omega-3 fatty acids (which have complementary effects on the mood and on the neuroinflammation), with the magnesium (which is a calcium antagonist and which works synergistically with the lithium for the mood stabilisation and for the neuronal function), with the vitamin B12 (which is required for the methylation and for the neurological function), and with the exercise (which increases the BDNF levels and which works synergistically with the lithium for the neurogenesis and the mood improvement).
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