A Little Lithium + B12 may make the world a happier place - depending on your #genetic snps. It is funny sometimes, looking back on the journey you take to discover something new and personal to your health. Of all the lessons that I’ve learned from reading through thousands of research studies on genes, the most important lessons sometimes come from stumbling across a nugget of information that hits a chord. For me, seeing first hand the power of supplementing with a little mineral (lithium orotate) was eye-opening as to the power of combining genetics with nutrients.  

Let me cut to the chase (since no one reads to the end of the article): for some people, supplementing with lithium orotate helps with anxiety, mood, and anger issues, while for other people, lithium orotate supplements will have little or no noticeable effect on mood. Genes play a role in this.

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 actually a naturally occurring mineral that is found in foods at concentrations dependent upon the mineral content of the soil. We naturally get about 3 -4 mg in our food each day.  Supplemental lithium orotate comes in 5mg and 10 mg dosages.

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] [ref] Why is vitamin B12 so darn 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]

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.

Genes involved:
Here is a list of the MTR and MTRR SNPs involved in vitamin B12 and the alleles to look for:

Check your 23andMe results: (v.4 and v.5)

Dr. Yasko also has an excellent 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. She now also checks the COMT status in regards to lithium supplementation.

Check your 23andMe results: (v.4 and v.5)


Lithium Supplements

Lithium orotate and lithium aspartate are both available in health food stores and online in 5 mg doses. Amazon carries several brands including Seeking Health’s Lithium Orotate (5mg) and Weyland’s Lithium Orotate (5mg or 10mg)*.

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.  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.

Studies on lithium levels found naturally in drinking water:

  • Lithium in the Public Water Supply and Suicide Mortality in Greece 2013 – “The purpose of the present study was to evaluate the association between lithium levels in the public water supply and prefecture-based suicide rates in Greece. Analyses were conducted with respect to lithium levels in 149 samples from 34 prefectures of Greece. The average lithium level was 11.10 [mu]g/l (range 0.1 to 121 [mu]g/l). The results indicate that there is a tendency for lower suicide rates in the prefectures with high levels of lithium in drinking water.”
  • A Negative Association Between Lithium in Drinking Water and the Incidences of Homicides, in Greece, 2015 – “total of 149 samples of drinking water were collected from 34 out of 52 prefectures, and data for homicides were taken from National Statistic Service of Greece (Hellenic Statistical Authority – EL.STAT). The average lithium level was 11.10 [mu]g/l (SD=21.16). The results indicate that there is a tendency for a lower mean number of homicides in the prefectures with high levels of lithium in drinking water (R ^sup 2^=0.054, [beta]=-0.38, p=.004).”

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 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 in the News:
There have been a couple of really good articles recently explaining the benefits of a little lithium.

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.

Studies on lithium (pharmacological doses for mood disorders) and genetic polymorphisms:

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 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.
  • 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 overall risk being 0.5%.

Updated on 2/4/2017


Emily · January 24, 2018 at 10:46 pm

What type of b 12 is best to pair with lithium? I believe there are two kinds. And is liquid or pill form better.

    Debbie Moon · January 26, 2018 at 11:12 am

    Hi Emily,
    What type of B12 is best depends on your genes :-) A lot of people with the slow version of COMT rs4680 (http://www.geneticlifehacks.com/comt-genetic-connections-to-neurotransmitter-levels/) find adenosylB12 or hydroxyB12 work best. Otherwise, most do well with methylB12. From different things that I’ve read online (haven’t seen any studies on it), a sublingual form that you keep in your mouth for a while is the best for absorption.

EJCH · April 30, 2018 at 5:52 pm

Wondering what doses of lithium orotate and B12 to give my young son, who has many of the mutations you mentioned. Need to balance them properly.

    Debbie Moon · April 30, 2018 at 7:42 pm

    Check out Dr. Amy Yasko’s website – http://www.ch3nutrigenomics.com/phpBB3/welcome.html. She has a forum there for parents, and she is an expert on methylation, lithium, children with autism, etc.

      CJ · November 8, 2018 at 7:09 pm

      Dr. Amy Yasko confuses me. She has, what appears to be, a web 1.0 website even though she claims to be an expert on all of this. When you upload your genetic testing raw data the site processes results for you that are tied directly to her supplements line. She doesn’t talk about food at all. Instead, she wants you to spend several hundred dollars to supplement EVERYTHING and of course… links to each of the products on her site. I find it hard to “trust” what she’s saying when she so heavily promotes buying all of her products at every turn.
      Debbie, you seem to be very involved with her forums and invested in what she says. Care to comment on this?

Michael Robinson · August 17, 2018 at 12:00 pm

Amazon says their vendor does not ship Weyland’s Lithium Orotate to France. While I’m trying to sort that one out, have you any thoughts on the following:
I sometimes read that Li and Mg can be in competition for sites, see for example:

Does this mean one should not take them together (or perhaps take them together), separate taking them by a day or more, take them at different times, stop Mg for a period while taking Li, or what? Can SNPs influence this?

Difficult question! Thank you

    Debbie Moon · August 20, 2018 at 2:18 pm

    You do ask difficult questions :-)

    The full paper that is referenced in the first article that you link to indicates that Li and Mg shouldn’t be competing for binding with ATP. “This observation provides direct evidence that under conditions of saturating, stoichiometric binding of Mg2+, Li+ does not displace Mg2+ from ATP, but rather cobinds in proximity to the divalent cation (Mg2+/Mn2+)”
    I readily admit, though, that the chemistry in that paper is over my head.

    Not sure if you found it or not, but I do have another article with more information on lithium: http://www.geneticlifehacks.com/lithium-a-mineral-that-affects-mood-alzheimers-disease-obesity-and-telomeres/ If you read through the references in the section on circadian rhythm, there are studies showing that one mechanism of action for lithium in bipolar disorder is through inhibiting GSK3 which changes the amplitude of rhythm of a core circadian gene. This makes sense for bipolar disorder since genetically it is tied to several SNPs in the clock genes — as well as being tied to sleep and circadian disruptions.

      Michael Robinson · August 26, 2018 at 9:39 am

      Thanks for replying to the above. I have to say I felt a bit guilty after posting it, particularly as the links were perhaps not the best to illustrate my point. Questions like that don’t usually attract replies!
      I took you down an arduous path there, but there won’t be any of the heavy stuff below.

      Interested in the use of lithium orotate for long-term and particularly very long-term use in view of its well-documented neuroprotective properties, I reviewed a certain amount of the very voluminous literature on the subject, including yours. I had looked at your article you directed me to but what I hadn’t done was click on the link https://www.ncbi.nlm.nih.gov/pubmed/22746245/ This says a microdose of 300 μg, lithium administered once daily to AD patients for 15 months appeared to halt their decline. This is surprising, and potentially revolutionary, as the common wisdom says that once Alzheimers has got a hold, there is practically nothing you can do to halt its ineluctable progression. The microdose used is also interesting as all we can get OTC in France is Lithium gluconate to be taken under the tongue and containing 279.6 µg elemental lithium, intended for calming anxious/unruly children. The adult dose is 2 to four times this. People have sometimes wondered whether such a low dose could have any effect at all, but it seems it can.

      My concern was how lithium which has some remarkable properties, taken as a supplement, would get along with magnesium, which also has some very important properties. There are articles that suggest that lithium can inhibit the action of magnesium (I won’t give my better link here) and I think my concern was genuine.

      It seems that I am not the only one wondering about this. This addresses my concern but doesn’t arrive at any conclusion: https://www.reddit.com/r/StackAdvice/comments/3e6u4x/magnesium_and_lithium_interaction/

      However, this article says Mg and Li might in fact cooperate: https://www.nist.gov/news-events/news/2016/07/new-model-may-help-solve-mystery-how-lithium-stabilizes-moods

      So my provisional conclusion is that 1 mg of lithium as orotate three or four times a week, together with magnesium and vitamin B6, occasional zinc picolonate and possibly inositol (inositol is apparently depleted by lithium), all these latter not taken at the same time as the lithium would be safe and effective as a neuroprotective agent for long or very long-term use.

Victoria · September 13, 2018 at 6:01 am

Hi, when you say “Here is a list of the MTR and MTRR SNPs involved and the allele to look for”, are the alleles listed indicating that you SHOULD or SHOULDN’t supplement with the lithium/b12? Thank you

    Siegfried Verheijke · October 8, 2018 at 6:35 pm

    I have the same question as Victoria: when we are looking for these alleles, what do we do when we find them in our data?

Leave a Reply

Your email address will not be published. Required fields are marked *

Related Posts


BDNF: Genetic variants for introversion, stress resilience, and more…

Brain-derived neurotrophic factor (BDNF) is a protein that works in the central and peripheral nervous system to promote nerve function and growth. It works in the neurons of the brain both in forming neurons and Read more…

Circadian Rhythm

Circadian Rhythm Connections: Part 1 – Mood Disorders

Roosters crowing at the first crack of daylight. Morning glories unfurling their blooms as the sun rises in the sky. Lightning bugs flickering just as dusk falls. Most people intuitively understand that plants respond to Read more…


Serotonin: How your genes affect this neurotransmitter

Serotonin… most of us think of the commercials with happy brain neurons bouncing the serotonin molecule between them. Turns out that there is a lot more to this molecule than most of us realize. About Read more…