Let me cut to the chase:
– for some people, supplementing with lithium orotate helps with anxiety, mood, and anger issues,
– for others, lithium orotate supplements will have little or no noticeable effect on mood.
Before going any further into this, I want to clarify that I’m referring to supplementing with an over-the-counter mineral supplement of lithium orotate or lithium aspartate. This is different than the large, prescription doses of lithium carbonate used for bipolar disorder.
Lithium is a naturally occurring mineral found in foods at concentrations dependent upon the mineral content of the soil. We typically get about 3 -4 mg in our food each day. Supplemental lithium orotate comes in 5mg and 10 mg dosages.
Studies on lithium levels found naturally in drinking water:
- A study in Greece found that lithium levels in drinking water ranged from 0.1 to 121 [mu]g/l). Areas with higher levels of lithium in the natural water supply had lower suicide rates. [ref]
- Another study found that homicide rates are lower in areas with higher levels of lithium in the water supply. [ref]
What is the connection between lithium orotate, mood, and B-vitamins?
Dr. Amy Yasko explains on her website why she thinks some of us need and use more of the mineral lithium than others. She recommends checking lithium levels for all autistic children and suggests supplementing with low levels of lithium for MTR/MTRR mutations. Dr. Yasko states that “Lithium not only plays a role in mood, glutamate control and limiting aggression but also has been shown to be involved in B12 transport.”[ref] She recommends making sure your lithium level is in balance before adding in B12.
In addition to Dr. Yasko’s clinical work associating B12 and lithium, there are several studies showing this as well.[ref]
- People who take prescription levels of lithium long-term for bipolar disorder tend to have lower serum levels of B12 (thus more B12 in cells?) than people using other medications.[ref]
- A study that analyzed lithium in hair samples in a variety of locations and populations “suggests a role of lithium in the transport and distribution of vitamin B12.”[ref]
- A recent study (Feb. 2020) finds that for animal-models of manic/depressive disorder, lithium works better in conjunction with folate (vitamin B9).[ref]
Why is vitamin B12 important to your mood?
Vitamin B12, along with folate, is essential for the production of tetrahydrobiopterin (BH4) which, in turn, is involved in the production of the neurotransmitters serotonin, melatonin, dopamine, norepinephrine, and epinephrine.[ref]
A deficiency of vitamin B12 has shown to cause symptoms which “may include agitation, irritability, negativism, confusion, disorientation, amnesia, impaired concentration and attention, and insomnia; while psychiatric disorders that may be diagnosed in patients having vitamin B12 deficiency include depression, bipolar disorder, panic disorder, psychosis, phobias, and dementia”. [ref]
Does lithium orotate work for everyone?
On a personal note, one family member (who is homozygous for several of the SNPs below) found that supplementing with lithium orotate and B12 was extremely helpful and is no longer irritated by, well, everyone and everything. The rest of the family, without the homozygous SNPs, doesn’t really notice any difference when taking lithium orotate, showing once again that everyone is different. It is truly amazing, though, the difference it makes when you hit on the right food or supplement for your body and your genes.
The MTR and MTRR genes are important in vitamin B12 usage in the methylation cycle.
Dr. Yasko also has a free video of a seminar where she lays out her research on the effects of lithium. She makes the case that lithium, through the inhibition of thioredoxin, can increase COMT, which is an enzyme that regulates and degrades dopamine, epinephrine, and norepinephrine.
Note: I want to be really clear here… This information is based on online recommendations for clinicians, such as Dr. Yasko. There are no research studies that specifically show that lithium orotate works to improve mood for people with these variants.
MTR Genetic Variants:
Check your genetic data for rs1805087 (23andMe v4, v5; AncestryDNA):
- A/A: typical
- A/G: increased enzyme activity, possibly responsive to lithium orotate supplements for irritability, anxiety
- G/G: increased enzyme activity [ref] possibly responsive to lithium orotate supplements for irritability, anxiety
Members: Your genotype for rs1805087 is —.
The rs1805087 variant is also known as A2756G. The G allele causes an increase in activity, thus possibly causing a decrease in methyl groups available for other pathways to use and also using up methylB12 more quickly than normal. [ref]
MTRR Genetic Variants:
Methionine synthase reductase has several fairly common variants that affect the production of the MTRR enzyme which regenerates vitamin B12 (methylcobalamin) for use by MTR and other enzymes. The variant rs1801394 is also known as A66G, and it decreases this enzyme’s efficiency. It is a fairly common variant carried by about half the population.
Check your genetic data for rs1801394 (23andMe v4, v5; AncestryDNA):
Members: Your genotype for rs1801394 is —.
COMT rs4680, Val158Met
One of the most studied variants of the COMT gene is rs4680, often referred to as Val158Met. In looking at research studies, the G is “Val” and the A allele is usually noted as “Met”.
- The G allele (Val) has higher COMT enzymatic activity, causing a more rapid breakdown of the neurotransmitters and thus lower levels of dopamine. In most populations, the G allele is the most common.[ref]
- The A allele (Met) has lower COMT enzyme activity and thus higher levels of dopamine. This variant of the COMT enzyme is said to have lower activity because it breaks down faster at normal body temperature.[ref]
Check your genetic data for rs4680 (23andMe v.4 and v.5; AncestryDNA):
- G/G: higher COMT activity, lower dopamine & norepinephrine, higher pain tolerance (Val)
- A/G: intermediate COMT activity (most common genotype)
- A/A: 40% lower COMT activity, higher dopamine & norepinephrine, lower pain tolerance (Met), reduced stress resiliency
Members: Your genotype for rs4680 is —.
Lithium orotate and lithium aspartate are both available in health food stores and online in 5 mg – 20mg doses.
Natural Sources of Lithium:
Lithium occurs naturally in spring water in certain areas and can range from less than 1 mcg/l to well over 100 mcg/l. Additionally, it is also found in the soil and can be taken up by plants depending on the concentration in the soil. Here is a map of a few places in the US showing lithium levels in the well water.
A study in 1989 looked at the lithium levels in the water in 27 counties in Texas. The study showed that counties that had water with higher lithium levels had significantly lower violent crime rates and suicide rates. There have been several more studies completed more recently in other countries that show the same decrease in suicide and homicide with higher levels of naturally occurring lithium.
Lithium and Polyunsaturated Fatty Acids (PUFA):
Several studies have found that lithium reduces arachidonic acid (inflammatory polyunsaturated fatty acid) production in the brain. One theory is that this reduction of neuroinflammation is a reason that prescription-strength lithium chloride works for bipolar disorder. For more information about genetics and variants that affect the fatty acid composition, check out the article on Omega-3 vs. Omega-6 fats and your genes.
These two studies are worth reading if you are interested in the link between lithium and neuroinflammation:
- Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation – 2010.
- Lithium and the Other Mood Stabilizers Effective in Bipolar Disorder Target the Rat Brain Arachidonic Acid Cascade – 2014
Uses for high dosage lithium:
For well over a century, lithium has been used in high pharmacological doses (typically 300-1200+ mg per day) to treat bipolar disorder and other mood disorders. It is also being investigated and used to slow the progress of ALS, dementia, and Alzheimer’s disease.
- Prophylactic lithium response and polymorphism of the brain-derived neurotrophic factor gene.– 2005 Those with the BDNF (brain-derived neurotrophic factor gene) variant known as Val66Met (rs6265 -T allele, Met), had a better response to lithium for bipolar mood disorder.
- Influence of an interaction between lithium salts and a functional polymorphism in SLC1A2 on the history of illness in bipolar disorder. – 2012 In looking at the SLC1A2 -181A>C variant (rs4354668) T/T homozygotes had a lower number of manic/depressive episodes while on lithium.
- Serotonin transporter gene associated with lithium prophylaxis in mood disorders. 2001. The study showed that for those with the serotonin transporter gene 5-HT/TLPR variant known as the short/short variant had a worse response to lithium for mood disorders. See the SNPedia article on 5-HT/TLPR to figure out whether you are short or long on that gene.
- There are quite a few other studies on the effects of genetic variants on lithium response for bipolar disorder. A search of PubMed will give you a lot of information.
Safety of taking lithium:
Prescription levels of lithium do come with long-term side effects including higher risks of hypothyroidism and kidney problems.
- Lithium toxicity profile: a systematic review and meta-analysis, 2012 — A meta-study on side effects from prescription dosages of lithium carbonate used for mood disorders showed that lithium increased the risk for hypothyroidism and weight gain. It also showed an increased risk of renal failure, with the overall risk being 0.5%.
Lithium orotate has one case study (of one patient):
- Lithium toxicity from an internet dietary supplement, 2007 — case study of an 18-year-old who took 18 tablets of Find Serenity Now, each of which contained 120mg of lithium orotate. She went to the emergency department with nausea and was discharged after a few hours to a psychiatric hospital.
A recent animal study showed that increasing zinc intake eliminated the deleterious thyroid effects of lithium carbonate. [ref]
Lithium in the News
There have been a couple of really good articles recently explaining the benefits of a little lithium.
- Should We All Take a Bit of Lithium – New York Times article
- Could You Have a Lithium Deficiency? – Psychology Today article
Updated on 2/4/2019