In This article

• Lithium orotate is an over-the-counter lithium salt marketed for “brain health,” but it is not FDA-approved for any medical or psychiatric indication.
  
• Unlike prescription lithium carbonate, lithium orotate is taken at very low doses with unknown efficacy for mood stabilization or cognitive enhancement.
  
• Current evidence does not support using lithium orotate to treat bipolar disorder, depression, anxiety, or to improve cognition or prevent dementia.
  
• Lithium orotate is still lithium and may carry similar risks to kidney and thyroid function, with the added concern of variable dosing and purity in supplement form.
  
• In pregnancy, clinicians should rely on evidence-based treatments like lithium carbonate, which has a defined reproductive safety profile, rather than unregulated lithium orotate.

A few weeks ago was the first time I heard somebody talking about lithium orotate. It was a social gathering, and a friend mentioned lithium orotate, wondering if it was a “natural” way to support mood and cognition. It’s not clear where all the buzz is coming from, but over the next few weeks, people kept mentioning lithium orotate. Eventually, one of my patients asked if lithium orotate would be a safe option during pregnancy. So here is what we know.

What is Lithium Orotate?

Lithium is a naturally occurring element that exists in the environment, typically in trace amounts in rocks, soil, and drinking water. It occurs as a salt, and for the treatment of bipolar disorder, we typically use lithium as lithium carbonate, and less commonly as lithium citrate, at doses yielding therapeutic serum levels in the range of about 0.6 to 1.0 mEq/L. Lower doses of lithium carbonate may be used in combination with antidepressants or other mood stabilizers, when the primary goal is augmentation rather than full mood stabilization.

Lithium orotate is another type of lithium salt. It has not been approved by the FDA for the treatment of any psychiatric or medical disorder; however, you can buy lithium orotate over the counter, where it is advertised as a supplement that can boost mood, cognition, or brain health. In animal models, lithium orotate may reach the brain somewhat more readily than lithium carbonate, but all lithium salts cross the blood-brain barrier, and these pharmacokinetic differences may not be clinically meaningful. In humans, there is no evidence that lithium orotate is safer or more effective.

While lithium carbonate is prescribed in doses of about 300 to 1200 mg per day, corresponding to therapeutic serum levels, lithium orotate is typically sold in formulations that contain about 5 mg of elemental lithium per tablet or capsule. These very low doses are unlikely to produce measurable serum lithium levels. 

Exploring the Benefits of Lower-Dose Lithium

In patients treated with therapeutic doses of lithium carbonate, lithium stabilizes mood and decreases suicidality, with robust evidence supporting its role in preventing both depressive and manic episodes as well as suicide attempts in individuals with mood disorders. More recently, researchers have been interested in the potential benefits of low-dose lithium, in part based on ecological studies suggesting lower suicide rates in regions with higher levels of naturally occurring lithium in drinking water. The levels of lithium in drinking water are far below those used in clinical treatment, which has understandably led to questions about whether very low doses of lithium might confer some anti-suicidal or neuroprotective benefit without the side effects associated with standard dosing.

There has also been interest in “microdosing” lithium as a means of capturing some of its neuroprotective effects, particularly in relation to neurodegenerative disorders such as Alzheimer’s disease. Preclinical work suggests that lithium may exert neuroprotective, anti-inflammatory, and pro-neurotrophic effects at concentrations below those required for full mood stabilization, although this research is still evolving and largely based on animal models or early-phase studies. 

While the research on the use of low-dose lithium in humans is sparse, prominent biohackers and longevity enthusiasts like Kevin Rose and Tim Ferriss have touted the use of low-dose lithium, often in the form of lithium orotate, to promote cognitive functioning or emotional resilience, despite the absence of rigorous clinical data to support these claims.

What the Research Tells Us About Lithium Orotate

While these are interesting observations, there is no data in the peer-reviewed medical literature to support the use of lithium orotate for the treatment of bipolar disorder, major depressive disorder, or anxiety disorders. There are also no controlled clinical trials demonstrating that lithium orotate improves cognitive function, prevents dementia, or enhances overall brain health in humans.

Given the sparse data on this product, patients with mood and anxiety disorders who require mood stabilization or augmentation should use traditional formulations and doses of lithium, with medical supervision. If lithium is not tolerated or is contraindicated, there are multiple other evidence-based options to consider, including other mood stabilizers, atypical antipsychotics, antidepressants, and psychotherapies, depending on the specific diagnosis and clinical context. In other words, lithium orotate should not be viewed as a “gentler” or “safer” form of lithium that can replace standard treatments, particularly in individuals with a history of bipolar disorder or severe mood episodes.

There is, however, robust data indicating that subtherapeutic doses of lithium are not effective for the treatment or prevention of depressive or manic episodes in bipolar disorder. While Manchia and colleagues highlight data suggesting that some anti-suicidal and neuroprotective effects of lithium may occur at lower doses, the optimal dosing and clinical relevance of these findings require further study. 

Safety Considerations and Pregnancy

Although lowering the dose of lithium may reduce the risk of certain side effects, such as tremor or gastrointestinal symptoms, lithium orotate is still lithium. Lithium’s potential to affect kidney and thyroid function is related to cumulative exposure and individual susceptibility, not just the specific salt formulation, and we have no evidence that lithium orotate is exempt from these risks. An additional concern is that, because lithium orotate is marketed as a dietary supplement, products are not regulated by the FDA to the same degree as prescription medications, and there may be variability in dose, purity, and labeling accuracy across brands.

When it comes to pregnancy, our goal is to use medications that are effective and, ideally, those with a well-characterized reproductive safety profile. For lithium carbonate, we now have a large body of data suggesting that first-trimester exposure is associated with a modest increase in the risk of cardiac malformations, but that the absolute risk remains relatively low. Several studies and reviews support the continued use of lithium during pregnancy in women with bipolar disorder, with careful monitoring and targeted fetal echocardiography, because the risk of relapse and severe mood episodes can also be substantial if lithium is discontinued.

In contrast, we have essentially no reproductive safety data for lithium orotate. It would be inadvisable to assume that lithium orotate is safer than lithium carbonate during pregnancy. It would also be risky to presume that microdosed lithium orotate is adequately effective as a mood stabilizer for someone with bipolar disorder who is at risk for relapse during pregnancy and the postpartum period.

For women planning pregnancy or already pregnant who require mood stabilization, the safest course is to work with a clinician to use treatments with demonstrated efficacy and a defined reproductive safety profile, such as lithium carbonate or other standard mood stabilizers, rather than unregulated supplements. For now, lithium orotate remains an unproven product with unknown safety in pregnancy, and it should not be used as a substitute for established, evidence-based treatments.

—Ruta Nonacs, MD PhD