Lithium – not only for improved well-being

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 [1].

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 [2].

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

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5-HT1A receptors, while not negatively affecting the autoregulation of 5-HT receptors, which would result in the abolition of the described effect [4]. 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 [5]. 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 [6].

Lithium increases the activity of NGF and GDNF [7] 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 [5]. 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 [11].

Lithium neuroprotective actions

It has an anti-NMDA receptor stimulant effect, resulting from glutamate activity [5]. To a large extent, this is the result of inhibition of the calcium inflow, which determines NMDA receptor activity [12].

Lithium effects on mood

The soothing and stabilizing mood of lithium is known.

In an animal study, lithium supply reduced aggressive behaviours [13].

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 [14].

Lithium also has a positive effect in people with obsessive compulsive disorders [22] 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 [23].

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 [30], 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 [15].

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.

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There is an increase in the production of IgG and IgM antibodies with lithium supplementation [20]. At the same time, it reduces the production of prostaglandins, preventing a decline in the efficiency of the immune system [21].

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 [29], 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 [33]

– Antipsychotics, such as clozapine [34]

– Anticonvulsants (lithium may increase the side effects of these medicines) [35]

– Hypotensive drugs (may increase the concentration of lithium in the blood) [36]

– Diuretics, such as furosemide (may increase the concentration of lithium in the blood) [37]

– 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 [40]

– 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

PROS:

  • It works in improving mental well-being
  • Antidepressant action [41]
  • Better control over emotions (aggressive behaviour)
  • May improve cognitive fitness

CONS:

  • It can negatively affect people with autoimmunisation, exacerbating it
  • It may reduce the production of thyroid hormones
  • Is a competitive magnesium inhibitor [5], which in a way is the mechanism of its action (GSK-3 inhibition)

Lithium benefits [43]:

The following side effects, though only sporadically, can occur in people who are taking lithium:

– Headaches

– Nausea

– Stomach pain

– Muscle weakness

– tiredness

– drowsiness

– 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 [42], 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!

References:

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