Trace amounts of lithium make people more peaceful and friendly. Lithium also supports the immune system, protects the brain, and helps people with anxiety and depression. Lithium orotate and other lithium salts have a shocking number of benefits at low doses – most of which have been downplayed. Should you start supplementing? Read on to find out.

What is Lithium Orotate?

Lithium is an alkali metal, naturally present in trace amounts in minerals, water, soil, fruits, vegetables, and other plants that are grown in lithium-rich soil [1].

Lithium is classified as an essential micronutrient, which means that all humans require it in small doses for good health [1].

This comes as a surprise to some people. Lithium is an unfairly overlooked nutrient, mostly because it is associated with high-dose prescription formulations for bipolar disorder. At high doses, lithium can cause a long list of side effects [1].

The shocking truth is that lithium has a number of benefits unrelated to its use as a high-dose pharmaceutical. We humans have adapted to getting trace amounts of lithium from food and water, and it seems that getting a bit more might make people more friendly and peaceful.

Many enzymes, hormones, vitamins, and growth factors require lithium to work. Lithium also supports the immune and nervous systems. It promotes the regeneration of cells, and it might even increase telomeres and prolong lifespan [2].

The modern boom of lithium supplements started with lithium orotate. Some supplements contain lithium citrate or aspartate salts. What makes them different mostly comes down to dosage. Lithium supplements are used in much lower doses than prescription lithium.

In this post, I’ll focus on lithium orotate and the benefits of low-dose lithium in general, as opposed to prescription lithium (lithium carbonate).

How Is it Different from Prescription Lithium?

Dosage

The most important distinction between lithium orotate and lithium carbonate (the prescription form of lithium) is their dosage differences.

Lithium orotate contains about 4 mg of actual or elemental lithium per 100 mg dose [3].

This is in contrast to lithium carbonate, which contains about 19 mg of lithium per 100 mg [3].

Also, keep in mind how they are taken:

  • Lithium carbonate is typically prescribed at doses of 900-1800 mg/day. This would give you about 170-340 mg of elemental lithium.
  • Lithium orotate usually contains only 5 mg of elemental lithium per dose.

This means that prescription lithium drugs are over 30 times stronger than lithium orotate, making toxicity from supplements far less likely.

Although lithium orotate contains only a fraction of the lithium that prescription drugs do, studies show that trace amounts of lithium may still offer health benefits [2].

Each person needs about 1 mg of lithium per day. Only a bit more than that – well below the prescription dose – has been linked to most of the benefits I’ll discuss below [4].

Plus, the lower amount of lithium in supplements make them very unlikely to cause the same side effects and toxicity as prescription medications.

Lithium orotate likely causes fewer side effects because it contains much less lithium than its prescription counterparts.

Availability in the Brain

Some early studies on lithium orotate suggest that this form of lithium may be better at penetrating the blood-brain barrier, allowing it to reach higher levels in the brain [5, 6].

Other studies have challenged these claims. All in all, we’re still in serious need of more research about lithium orotate to get answers about its safety and effectiveness [7, 8].

Snapshot

PROs

  • Protects the brain and may prevent mental disorders
  • May reduce aggression and impulsiveness
  • Promotes cell development and repair
  • May extend lifespan
  • May help combat depression
  • May help treat alcoholism

CONs

  • Lack of research on safety and effectiveness
  • May cause mild side effects

Joe’s Words

“The usual dosage is 5 mg of elemental lithium (100 mg of lithium orotate), but I decided to take 15 mg to see what would happen. I can say that there’s definitely a subtle cognitive effect. It’s anti-depressant and anti-anxiety, and it seemed to lengthen the period of my circadian rhythm, as I started to feel tired later on.

On the negative side, it made me more zoned out. It also made me feel less attached to everything. The fact that I felt acute effects at 15 mg suggests to me that lithium orotate passes the brain barrier efficiently.

Anyway, I’m glad I did the experiment. Now I now know lithium orotate definitely has an effect and I can use it in my coaching practice.

I also think that at least some of the benefits of other lithium salts prescribed by doctors can be achieved through the orotate version by adapting the dosage.”

Benefits of Lithium Orotate (& Low-Dose Lithium)

1) Protects the Brain

Lithium protects the brain at the low doses that supplements provide.

For example, animal studies show that subtherapeutic lithium blocks NMDA receptors, which prevents damage caused by excess glutamate [9, 10, 11].

Lithium also inhibits GSK-3, an enzyme that plays a role in metabolism, cell growth, and the immune system. Overactivity of GSK-3 is linked to a number of diseases, including bipolar disorder and Alzheimer’s disease. By blocking GSK-3, lithium can prevent the death of brain cells (apoptosis) and potentially prevent these psychiatric disorders, according to animal and cell studies [12, 13].

Animal research suggests that low doses of lithium may protect against the toxic effects of lead exposure as well [14, 15].

Small doses of lithium can protect the brain from toxicity and psychiatric disorders.

2) Promotes Cell Growth and Repair

Many cells depend on lithium for proper development and repair.

For example, a rat study found that lithium supplementation increases the concentration of growth factors in the brain, such as BDNF, NGF, and GDNF. These factors are neurotrophic, which means that they are brain food. The term comes from the Greek words neuro for brain and trophic for food or nourishment [16].

Neurotrophic factors increase the birth of new neurons to help “regrow” the brain and repair brain damage. The birth of new brain cells is called neurogenesis, and it’s especially important for recovering from mental illness [17].

These factors also increase neuroplasticity, which is the brain’s ability to make new connections and adapt throughout life [18].

According to research on human cells, subtherapeutic levels of lithium (0.2 mmol/L) increase VEGF, another type of growth factor that affects blood vessels. This could potentially help with blood vessel repair after a stroke [19].

Growth factors aren’t the only ones affected. Several studies show that lithium stimulates stem cells in the blood, brain, and bones, potentially improving tissue repair after injury [20, 21].

There is also some evidence that lithium causes autophagy [22].

Autophagy translates to “self-eating” and it’s equivalent to a “detox” from a cellular perspective. Autophagy takes old cell material, recycles it, and re-uses the components. This process regenerates aging cells, prevents diseases, and it’s key to lifespan extension [23, 24].

Lithium increases growth factors and stem cells in the body, which gives birth to new cells and enhances the repair of damaged tissues.

3) May Reduce Risk of Suicide

Lithium has unique effects on suicidal behavior. Prescription lithium reduces suicide risk in people with mood disorders much better than most antidepressant and antipsychotic medications [25, 26].

Low doses of lithium may also reduce suicides. Studies show that even trace amounts of lithium found in groundwater may reduce suicide rates [27].

Higher lithium levels in public drinking water are strongly linked to lower suicide rates, according to a study looking at water samples from 226 counties in Texas [27].

In fact, the same association between lithium levels and suicide rates can be found in multiple countries, including Japan, Italy, Lithuania, and Greece [28, 29, 30, 31].

However, a 22-year long study of close to 4 million adults in Denmark did not find this same link. This may be explained by Denmark’s low average level of lithium in drinking water, which was about 12 micrograms per liter [32].

People living in areas with higher concentrations of lithium in the drinking water tend to have lower suicide rates.

4) May Reduce Criminal Behavior

Here’s the most intriguing part: lithium seems to make people more mellow and easygoing – that is, it makes people less likely to engage in behavior that might put them in jail. Lithium deficiency, on the other hand, has been linked to aggression and violence [33, 34].

I’ve been wondering whether communities of more peaceful, less aggressive, less impulsive, and happier people around the world all have more lithium in their water and food. Of course, it can’t be as simple, but lithium might be a part of the equation [33, 34].

It may sound silly to some people, but studies show a very real connection between lithium and criminal behavior.

Areas with higher concentrations of lithium in the drinking water have lower rates of homicide, rape, and theft. This is according to a study looking at 9 years worth of data from 27 counties in Texas [35].

A study performed in Greece found similar results. Cities with higher lithium levels in the public water supply have lower incidences of homicide, rape, and drug abuse [36].

Why does this happen?

The connection between low lithium and criminal behavior is not totally understood, but lithium’s ability to improve impulse control likely plays a major role [33].

Lithium improves impulse control and may lower crime rates by making people less aggressive and more peaceful.

5) Improves Cognition

A massive study performed in Denmark compared drinking water samples from over 800k people. They found that people drinking water with higher amounts of lithium had lower rates of dementia [37].

In a study of 45 people with mild cognitive impairment, subtherapeutic lithium delayed the progression into dementia [38].

One study found that a microdose of lithium (300 micrograms) prevents cognitive loss in Alzheimer’s patients [39].

Higher lithium levels in drinking water also lowered the risk of death in Alzheimer’s patients, according to a study looking at water samples from 234 counties in Texas [40].

Small doses of lithium may improve cognition and slow mental decline.

6) May Extend Lifespan

Research into lithium’s effect on lifespan has revealed intriguing results.

A study in Texas found that higher trace levels of lithium in tap water are linked to lower rates of death by any cause [41].

According to several studies, this life-extending effect may be due to lithium’s ability to increase the length of telomeres – small proteins that cap your DNA-holding chromosomes [42, 43, 44].

The longer telomeres are, the more leeway your cells have to divide. The length of telomeres is something like the sand in the top part of your lifespan hourglass – the more you have, the better 45].

Lithium’s effects on lifespan may also be due to its ability to improve mitochondrial turnover, which maintains healthy mitochondria [46].

For example, a study in roundworms found that lithium increases lifespan by improving mitochondrial function [46].

Lithium may extend the length of telomeres, which potentially increases lifespan.

7) May Help Treat Alcoholism

One study treated 42 alcoholic patients with 150 mg lithium orotate daily for at least 6 months. About a third of the patients went 1 to 3 years without relapse and a quarter went 3 to 10 years without any form of relapse [47].

The same study reported some mild side effects, including muscle weakness, loss of appetite, and mild apathy. However, these disappeared when the supplement was given less frequently [47].

8) May Prevent Mental Disorders

As a prescription medication, lithium is used to treat several psychiatric conditions, including bipolar disorder, depression, and schizophrenia [48, 49, 50].

As a supplement, lithium has even more interesting benefits to mental health. Old reports suggest it might not only treat but also prevent certain mental disorders [14].

One curious phenomenon dates over a hundred years back. It’s known as the “crazy waters” of Texas.

Many mineral springs contain lithium, but the Mineral Wells in Texas became famous as “crazy waters.” Texas had many mineral water resorts back in the 19th century. Thousands of “crazy” people and those with various chronic health problems used to gush to these springs to get the healing benefits of lithium. Others reported good health just from living nearby [51].

There’s also one anecdotal case from the 1930s France. French physician Dr. Reyss-Brion remembers that a preparation called “Dr. Gustin’s Lithium” was popular in the south of France around that time. “It’s quite simply for that reason that you don’t have a lot of manic-depressives in Marseilles,” he said [51].

Only one recent study provides us with additional clues. In over 3k students in Japan, those with higher levels of lithium in tap water had fewer symptoms of depression [52].

Despite all the anecdotes, we’re still missing hard evidence about lithium for preventing mental disorders like depression and bipolar at low doses.

The evidence is limited, but getting a bit more lithium might help prevent depression.

9) May Help Treat Depression

Prescription lithium is used to treat depression in people who don’t respond to conventional antidepressants [49].

But even low doses of lithium may offer some benefit.

One study examined 51 patients with depression who did not respond to treatment with venlafaxine (a commonly prescribed antidepressant). When low dose lithium was added to their normal venlafaxine treatment, about half of the patients saw an immediate improvement [53].

10) May Help in Huntington’s Disease

Low doses of lithium may be beneficial in those with Huntington’s disease.

A case series including 3 patients with Huntington’s describes how low dose lithium (150 mg) improved movement and behavioral symptoms [54].

In fact, there is currently a low-dose lithium formulation in development for the treatment of Huntington’s. Preliminary animal studies show that this new drug improves motor function and prevents brain cell death [55].

11) May Decrease Insulin Resistance

Lithium improves glucose transport and glycogen synthesis in insulin-resistant rats, according to one study [56].

The researchers of the study suggest that lithium enhances the effect of insulin, which could potentially help patients with diabetes and insulin resistance [57].

12) May Support Bone Health

Research in animals shows that lithium may decrease the risk of bone fractures and promote bone growth [58, 59].

Human studies have revealed similar benefits to bone health, but only prescription doses of lithium have been tested [60, 61].

13) May Reduce Autoimmunity and Inflammation

Lithium may interact with the immune system through several mechanisms.

By inhibiting GSK-3, lithium may prevent autoimmunity (conditions where the immune system attacks its own body), according to animal studies [62].

Lithium also suppresses Th1 cells and interferon-gamma (but not Th17 cells), which cause autoimmune inflammation [62].

Other immune system effects include increasing the production of IgG and IgM antibodies while decreasing the activity of inflammatory prostaglandins [63, 64].

14) May Help Improve Sleep

According to animal and cell studies, lithium has a few interesting effects on the circadian rhythm.

It can lengthen the circadian rhythm period, which can help you if you are desynchronized from a normal 24-hour cycle [65, 66].

Lithium may also help activate the genes and proteins involved in the sleep-wake cycle, which can help the body be in better sync with day and night cycles. This makes lithium a sort of sensitizer to zeitgebers – biological cues for the time of day [65, 66].

Clinical trials show that lithium medications can improve sleep in bipolar patients. However, it’s unknown if lower doses of lithium provide the same benefit [67, 68].

15) May Relieve Headaches

A review of multiple studies reveals that lithium may reduce the severity of cluster headaches, a rare, but severe type of headache. Even subtherapeutic levels of lithium (0.4 to 1.0 mmol/L in the blood) could improve symptoms in many patients [69].

Lithium may also help in hypnic headache (sometimes called “alarm clock headache”). This rare type of headache usually affects the elderly, waking them from sleep at around the same time each night [70].

Low-dose lithium carbonate (200 mg/day) completely resolves hypnic headaches within two days, according to a case report of an elderly man [70].

Side Effects of Lithium Orotate (& Low-Dose Lithium)

Typical Side Effects

Prescription doses of lithium can cause a number of side effects and can be toxic at high levels [71].

Luckily, the relatively small amounts of lithium contained in supplements make side effects less likely.

Based on anecdotal evidence, some people taking lithium orotate experience headaches, nausea, and diarrhea. Some people also report feeling slightly disconnected. Reducing your dose may improve these side effects.

There is also a case report of a woman experiencing nausea and vomiting after taking 18 tablets of lithium orotate at once. Even after this large amount, her level of lithium in the blood was only 0.4 mmol/L, a long way from levels normally considered toxic (>1.5 mmol/L) [72].

However, there is very little information about the side effects or toxicity of lithium orotate outside of a few case reports. Lithium orotate (at normal doses) likely causes far fewer side effects as prescription lithium, but more studies are needed to say for sure.

For reference, some common side effects of prescription lithium include [71, 73]:

  • Increased thirst
  • Increased urination
  • Dry mouth
  • Nausea
  • Diarrhea
  • Tremors (usually in the hands)
  • Weight gain
  • Stomach discomfort
  • Drowsiness
  • Constipation
  • Acne

Take a look at my article on the side effects of lithium carbonate for more information.

Other Risks

Those who take prescription lithium are constantly monitored for signs and symptoms of toxicity.

One important concern is lithium’s effect on the kidneys. Lithium medications can reduce kidney function, which can potentially lead to kidney failure (although the risk is fairly low) [74].

Lithium may also cause damage to the thyroid and parathyroid glands, which can result in hypothyroidism or hyperparathyroidism [74].

However, these toxicities are usually associated with high lithium levels (>1.5 mmol/L) [75].

The big question is if lower doses of lithium (like those in lithium orotate) can cause these same toxicities. It’s probably unlikely. But unfortunately, no safety studies look specifically at lithium orotate.

Overall, the available evidence suggests that low-dose lithium is safe.

A 2-year-long clinical trial of 61 patients found that long-term, low-dose lithium does not affect kidney function. However, they did find elevations in TSH and the number of side effects [76].

Low-dose prescription lithium contains significantly more lithium than supplements do. It’s unlikely that normal doses of lithium orotate cause these same toxicities, but more research is needed.

Also, be aware that lithium can have toxic effects during pregnancy. If you are pregnant or plan to become pregnant, consult your doctor before taking any kind of lithium [77].

Check out my article on lithium toxicity to learn more.

Lithium orotate is less likely to cause the side effects and toxicities that are normally associated with prescription doses of lithium.

Limitations

Research on lithium orotate is very limited and most studies are decades old.

Many of the benefits of lithium orotate are inferred from studies that look at low-dose prescription lithium (also known as subtherapeutic or microdose lithium).

Studies examining the trace amounts of lithium found in drinking water also offer some insight into the potential benefits of lithium supplements.

Lithium in Food

Many of the foods we commonly eat contain some lithium. According to some estimates, grains and vegetables contribute about 66% to 90% of your total lithium intake [3].

Some examples of lithium-rich foods include [3]:

  • Nuts (8.8 micrograms/g)
  • Cereals (4.4 micrograms/g)
  • Fish (3.1 micrograms/g)
  • Vegetables (2.3 micrograms/g)
  • Dairy products (0.5 micrograms/g)

This means that a cup of cereal will give you 0.4 mg of lithium, while half a cup of nuts or 200g of fish will have about 0.6 mg of lithium [78].

Certain types of tea may also be a good source of lithium.

A quarter liter of black tea provides about 0.58-1.35 micrograms/g of lithium, while the same volume of red tea contains 0.72-1.70 micrograms/g [3].

Remember that the amount of lithium in these foods depends on the soil they were grown in. Foods grown in low-lithium areas will be lower in lithium. Most dry areas, such as Texas, are higher in lithium [79, 35].

It can even come down to your specific city – neighboring cities or counties can have much different lithium levels in their water sources. For example, water supplies in Los Angeles County average around 0.5 micrograms/L of lithium while drinking water in nearby Orange County contains as much as 10 micrograms/L [79, 35, 28].

If you do live in a lithium-poor area and buy local foods, it might be better to supplement.

Lithium Orotate Dosage

Dosage

Lithium orotate supplements are available in several strengths, all of which are meant to be taken once a day.

The most common dose contains 5 mg of elemental lithium (elemental lithium refers to the actual amount of lithium found inside each pill). This is just a bit over the amount most people get from food and water, which is 1mg. If you live in a low-lithium area, this is probably a good maintenance dose.

Other products contain as much as 10 to 20 mg of elemental lithium, which may be appropriate for those who see no beneficial effects with lower doses.

Anecdotally, some people are sensitive to lithium. People who experience side effects may benefit more from taking lower doses (1 to 2.5 mg of elemental lithium).

Let your doctor know if you do take lithium supplements, especially if you’re taking other medications. Lithium has many potential drug interactions.

Low-Dose Lithium

Some studies have explored the benefits of “low-dose lithium”, also called subtherapeutic or microdose lithium. Low-dose lithium refers to the use of prescription lithium (lithium carbonate) at lower-than-normal dosages.

The exact dose of low-dose lithium varies between studies, but typically ranges from 150 to 300 mg per day. Some microdose studies go as low as using 300 micrograms (equivalent to 0.3 mg) [39, 54, 70, 47].

These subtherapeutic doses of lithium are over 3 times lower than normal doses of prescription lithium (which is typically prescribed at 900-1800 mg/day), but typically much higher than doses provided by lithium orotate.

This would usually only be an option if you’re working with a practitioner who is prescribing low-dose lithium “off-label,” as the carbonate form requires a prescription. “Off label” means a drug is being used outside the official indications (as is the case with low-dose naltrexone).

Most people prefer to go with lithium orotate or citrate, since they’re available as supplements.

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Want More Targeted Ways to Enhance Brain Function and Mood?

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SelfDecode is a sister company of SelfHacked. This post contains sponsored links, which means that we may receive a small percentage of profit from your purchase, while the price remains the same to you. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thanks for your support.

Takeaway

Your body needs tiny amounts of lithium to function properly. People who get a bit more lithium might be less suicidal and more peaceful.

Supplemental doses support brain health, cell regeneration, and might even extend lifespan. At low doses, lithium might also improve cognition and reduce autoimmunity.

Based on anecdotal reports, side effects are generally mild. Very low doses (about 5mg/day of elemental lithium) are likely the best option for people who live in lithium-deprived areas.

About the Author

Mathew Eng, PharmD

PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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