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What is Lithium Orotate & Is it Safe? Dosage + Side Effects

Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Matt Carland
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Matt Carland, PhD (Neuroscience) | Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Does lithium make people more friendly and peaceful?
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Trace amounts of lithium seem to make people more peaceful and friendly. There are many different types of lithium. For example, lithium carbonate is commonly used to treat mental health conditions such as bipolar disorder, anxiety, and depression. But what is lithium orotate, and is it safe? How effective are low doses and “micro-doses”? Read on to get science-based answers!

What is Lithium?

An Essential Micronutrient

Lithium is an alkali metal. Trace amounts of it are naturally present in various 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 most people. Some scientists think that lithium is an unfairly-overlooked nutrient, in large part because it is associated with high-dose prescription formulations used by doctors to treat bipolar disorder. At high doses, lithium can cause a long list of side effects [1].

We humans have adapted to getting trace amounts of lithium from food and water, and some evidence suggests that getting a bit more can make people more friendly and peaceful. Popular blogs claim that low doses of certain forms of lithium may have a number of potential benefits unrelated to its use as a high-dose pharmaceutical. But what does the science say?

Despite the hype, there is insufficient evidence to determine the effectiveness of lower lithium doses. However, early research shows some promise.

Basic biology suggests that many enzymes, hormones, vitamins, and growth factors require lithium to work. Lithium also appears to support the immune and nervous systems. Additionally, some scientists are currently investigating whether it promotes the regeneration of cells. Some suspect that it might even protect telomeres and prolong lifespan — but this hypothesis remains unproven [2].

Lithium is an essential micronutrient found in food and water. High-dose prescription lithium carbonate is used to treat bipolar disorder, while lithium orotate is a poorly-researched supplemental form of lithium.

Focus on Lithium Orotate

The modern boom of lithium supplements started with lithium orotate.

Currently, lithium orotate is poorly-researched, and its overall safety in human users has not been determined.

Additionally, lithium orotate supplements have not been officially approved by the FDA for any medical use or other health application. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them, but don’t guarantee that they’re safe or effective. Always make sure to speak with your doctor before supplementing with any new compounds.

Availability in the Brain

Some early low-quality studies on lithium orotate suggested that this form of lithium may be better at penetrating the blood-brain barrier, theoretically allowing it to reach higher levels in the brain. However, this has not yet been directly proven in any clinical trials [3, 4].

Additionally, many studies have challenged these claims about lithium orotate. All in all, we’re still in serious need of clinical research about lithium orotate in order to get solid answers about its safety and effectiveness. For now, its use is not backed up by science [5, 6].

Data are currently lacking to support claims that lithium orotate penetrates into the brain better than other lithium salts.

Other Lithium Salts

Some supplements contain lithium citrate or aspartate salts. Lithium carbonate is typically used at high doses, and requires a doctor’s prescription and careful monitoring of blood lithium levels to ensure safety.

What makes so-called “supplemental” lithium different mostly comes down to dosage: lithium supplements are used in much lower doses than prescription lithium.

In this post, we’ll focus on lithium orotate, and discuss how it’s different from high-dose and low-dose lithium carbonate. We’ll also go over the existing data about its safety and side-effects to give you an idea of what to expect from various lithium formulations on the market.

Aside from lithium orotate, supplements may also contain lithium citrate or aspartate salts.

How is Low-Dose Lithium Different from Prescription Lithium?

Dosage Matters

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

Lithium orotate contains about 4-5 mg of actual (“elemental“) lithium per 100 mg dose [7].

In contrast, prescription formulations of lithium carbonate typically contain about 19 mg of elemental lithium per 100 mg [7].

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.
  • Low-dose lithium, also known as sub-therapeutic doses, is when lithium carbonate is prescribed at about 150 mg/day (around 29 mg of elemental lithium).
  • Lithium orotate usually contains only 5 mg of elemental lithium per dose. This is the typical supplemental dosage.

This means that prescription lithium drugs are over 30 times stronger than lithium orotate. Prescription doses are also about 6-10 times stronger than “low-dose” lithium carbonate, which still requires a prescription, and is used “off-label.”

Lithium carbonate is prescribed at much higher doses than those found in lithium supplements.

Different Salts – Different Safety

Since supplements contain much lower amounts of lithium, they are less likely to cause the same side-effects and toxicity of prescription lithium.

On the other hand, the safety of orotic acid salts — including lithium orotate — has not been firmly established. Lithium carbonate has been around for decades and its use is supported by many clinical studies [8].

Limited studies suggest that these trace amounts of lithium may offer some health benefits. However, the available studies tend to be small-scale, low-quality trials, and lithium dosages vary considerably across different studies. This makes their findings unreliable and difficult to interpret [2].

All in all, there’s simply not enough good evidence to make health-related claims about supplemental or low-dose lithium.

Research suggests that the average person requires 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 controversial effects we’ll discuss below [9].

Supplemental lithium may cause fewer side effects than prescription lithium, but its effectiveness is unknown.

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

Typical Side Effects

Prescription doses of lithium can cause a number of adverse side-effects. Additionally, high lithium blood levels can be toxic: however, this can be avoided through careful monitoring by a physician [10].

The much smaller amounts of active lithium contained in supplements are believed to make negative 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 the dose may reduce or alleviate 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. Her level of lithium in the blood was 0.4 mmol/L, a long way from levels normally considered toxic (>1.5 mmol/L) [11].

However, there is very little hard clinical data regarding the potential for side-effects or toxicity from lithium orotate outside of a few case reports. More large-scale studies in human users will be needed to determine its safety and side-effect profile.

For reference, some common side-effects of prescription lithium include [10, 12]:

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

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

Lithium orotate has been reported to cause headaches, nausea, diarrhea, and a sense of emotional disconnection in some people.

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) [13].

Lithium may also cause damage to the thyroid and parathyroid glands, which can result in hypothyroidism or hyperparathyroidism [13].

However, these toxicities are usually associated with very high lithium levels (>1.5 mmol/L) [14].

The big question is if lower doses of lithium — like those commonly found in lithium orotate supplements — can cause these same toxicities. Unfortunately, no studies so far have looked specifically at the safety of lithium orotate or low-dose lithium carbonate.

The available evidence suggests that low-dose lithium carbonate may be safe when taken under the supervision of a healthcare professional.

One 2-year-long clinical trial of 61 patients has reported that long-term, low-dose lithium did not adversely affect kidney function. However, they did report elevations in TSH and a significant number of other side-effects [15].

Low-dose prescription lithium contains significantly more lithium than supplements do. It’s theoretically unlikely that normal doses of lithium orotate cause these same toxicities, but more research is needed on orotic acid salts in general. They may turn out to be less safe than lithium carbonate and lithium citrate.

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 [16].

Check out our article on lithium toxicity to learn more.

Low-dose lithium carbonate is far less likely to cause toxicities than high doses. However, the toxicity and other potential risks associated with lithium orotate are currently unknown.

Lithium in Food

Lithium-Rich Foods

Many of the foods we commonly eat contain some lithium. According to some estimates, grains and vegetables contribute about 66-90% of the average person’s total dietary lithium intake [7].

Some examples of lithium-rich foods include [7]:

  • 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 would provide roughly 0.4 mg of lithium, whereas half a cup of nuts or 200g of fish would have about 0.6 mg of lithium [17].

Certain types of tea may also be a good source of lithium. For example, 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 [7].

However, it is important to note that the amount of lithium in a given type of food will depend on the soil it was grown in. Foods grown in low-lithium areas will be lower in lithium. Most dry areas, such as Texas, are higher in lithium [18, 19].

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 [18, 19, 20].

Nuts, vegetables, and black tea are a few of the common dietary sources of lithium — especially if grown in areas with soil that is naturally rich in lithium.

Lithium Supplemental Dosage

Lithium Orotate

Evidence is currently lacking to establish official dosing guidelines for lithium orotate.

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 bio-active lithium found inside each pill).

Theoretically, this is just a bit over the amount that most people get from food and water, which is 1mg. Some manufacturers have claimed that this is a good maintenance dose, although this has not been scientifically verified.

Other products contain as much as 10 to 20 mg of elemental lithium, which is said to be appropriate for those who see no beneficial effects with lower doses. No clinical evidence supports this approach, however.

Anecdotally, some people may be particularly sensitive to lithium. For example, online reports from people who have experienced side-effects often report taking lower doses (1 to 2.5 mg of elemental lithium).

Always talk to your doctor before taking lithium supplements. This is especially important if you’re taking other medications, as lithium has many potential drug interactions that can be dangerous.

Low-Dose Lithium

Some studies have explored the benefits of “low-dose lithium”, also called “sub-therapeutic” lithium. Low-dose lithium should not be confused with so-called “micro-doses” of lithium, which are even smaller.

Low-dose lithium refers to the use of prescription lithium (lithium carbonate) at significantly lower-than-normal dosages.

The actual sizes of “sub-therapeutic” or “low” lithium doses vary between studies, but typically range from 150-300 mg of lithium carbonate per day [21, 22, 23, 24].

These sub-therapeutic doses of lithium are 3-10 times lower than normal doses of prescription lithium (which is typically prescribed at 900-1800 mg/day) — but these doses are still much higher than the doses provided by supplemental lithium orotate.

Sub-therapeutic lithium is usually only an option if you’re working with a medical practitioner who is prescribing low-dose lithium “off-label,” as the carbonate form always requires a prescription regardless of dose size. (“Off label” refers to when a drug is being used outside the official medical indications, as is the case with low-dose naltrexone, for example.)

On the other hand, lithium “micro-doses” go as low as 1.5 mg of lithium carbonate per day (300 micrograms/0.3 mg of elemental lithium) [21, 22, 23, 24].

Despite a lack of data regarding its safety and effectiveness, most supplement users appear to prefer to go with lithium orotate or lithium citrate, since they’re available as supplements.

Takeaway

The human body needs tiny amounts of lithium to function properly.

Lithium carbonate is a pharmaceutical form of lithium used to treat bipolar disorder and some forms of depression.

Lithium orotate, on the other hand, is a supplemental form of lithium that hasn’t been properly tested in clinical trials.

Controversial studies suggest that people who get higher trace amounts of lithium might be less suicidal and more peaceful, but solid data are lacking to back up this hypothesis.

Based on anecdotal reports, lithium orotate side effects are generally mild. However, the safety of lithium orotate is unknown.

Read More

About the Author

Mathew Eng

Mathew Eng

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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