Lithium orotate: A superior option for lithium therapy?

In the scientific paper Lithium Orotate: A Superior Option for Lithium Therapy?, Pacholko et al. explore lithium orotate (LiOr) as a potential alternative to lithium carbonate (Li2CO3) in treating bipolar disorder. Lithium carbonate, while effective at stabilizing mood, has significant side effects such as kidney damage and thyroid dysfunction, which often lead to patient non-compliance. The authors suggest that LiOr may offer similar therapeutic benefits with fewer side effects, as it potentially crosses the blood-brain barrier more efficiently, allowing for lower dosages. However, concerns about renal toxicity remain, requiring more in-depth research to fully understand the safety and efficacy of LiOr compared to Li2CO3.

If LiOr crosses this barrier better, it could allow for smaller doses to be used, potentially reducing the risk of side effects. As the study notes , “LiOr is proposed to cross the blood-brain barrier and enter cells more readily than Li2CO3.” Despite this potential, research on LiOr was halted in the 1970s after concerns arose about its effects on the kidneys.

In this scientific paper, the researchers analyzed both historical and recent studies on lithium orotate and lithium carbonate. They looked at the pharmacokinetics (how the body processes the drug), safety, and efficacy of both lithium forms. The researchers also reviewed clinical trials and animal studies to compare how well each form works in the brain and body.

Special attention was given to how both forms of lithium might affect the kidneys, given that lithium can cause damage over time when taken in high doses. The study also revisited early experiments from the 1970s to see if LiOr could truly offer benefits over Li2CO3.

One key finding from early studies is that lithium orotate might cross the blood-brain barrier more efficiently than lithium carbonate. In animal studies, lithium orotate was found to increase brain lithium levels up to three times more than Li2CO3 at equivalent doses. As the study explains, "LiOr resulted in brain lithium concentrations three-fold higher than what was observed for equivalent doses of Li2CO3."

Because LiOr can potentially deliver more lithium to the brain, it could allow for smaller doses to be used in treatment. This would be a major advantage, as  smaller doses would likely result in fewer side effects . With Li2CO3, higher doses are needed to ensure enough lithium reaches the brain, which increases the risk of side effects like nausea, tremors, and kidney damage.

While lithium orotate shows promise, early studies also raised concerns about its safety, particularly its effects on the kidneys. One study noted that at high doses, LiOr caused more kidney damage than lithium carbonate . However, it’s important to note that these high doses far exceed what would be used in normal treatment.

As the study notes, “It is likely that the concentrations of LiOr used were far too high,” which could explain the kidney problems. Still, more research is needed to confirm whether lower doses of LiOr would be safer for long-term use.

Lithium orotate offers several potential advantages over lithium carbonate if further research supports these findings:

Since LiOr appears to deliver lithium to the brain more efficiently, it could be prescribed in smaller doses. This could significantly reduce the side effects associated with lithium therapy. For example, people using lithium carbonate often experience side effects like excessive thirst and frequent urination due to the higher doses needed to maintain therapeutic levels in the brain. LiOr could potentially reduce these issues. The researchers state, “LiOr may allow for reduced dosage requirements and ameliorated toxicity concerns.”

Patients often stop taking lithium because of its unpleasant side effects. If lithium orotate allows for smaller doses and fewer side effects, more people may stay on the treatment and experience fewer relapses into mania or depression. As the study points out, “an alternative lithium compound with a lesser toxicity profile would dramatically improve treatment efficacy and outcomes.”

Lithium orotate may also have antioxidant properties due to its orotic acid component, which could help protect brain cells from damage. Orotic acid itself is known to play a role in DNA and RNA synthesis, and it may help promote cellular repair and protect against oxidative stress, which damages cells. Some studies have suggested that orotic acid might even improve the heart’s function in people with heart disease. This dual benefit of mood stabilization and cellular protection could make lithium orotate particularly valuable.

Despite the potential advantages, the biggest concern with lithium orotate is its possible impact on kidney function. The kidneys are responsible for filtering lithium out of the body, and long-term lithium use can lead to kidney damage. Early studies found that high doses of lithium orotate could impair kidney function more than lithium carbonate. Specifically, a 1979 study reported that "LiOr impaired renal function to a greater extent than Li2CO3 when employed at concentrations of 2 mmol Li+/kg body weight." This has led to concerns about whether lithium orotate is safe for long-term use.

However, it’s important to note that the doses used in these early studies were far higher than what would be prescribed in a clinical setting. More recent anecdotal evidence suggests that at lower doses, lithium orotate may be safer. For instance, some people use low-dose LiOr as a nutraceutical, and there have been no reports of severe side effects from this practice. In one case, a person ingested 18 LiOr tablets, each containing 3.83 mg of lithium, and experienced only minor symptoms like nausea and tremors that resolved within hours.

Lithium orotate holds exciting potential as a treatment for bipolar disorder. It offers the possibility of better brain penetration and lower doses than lithium carbonate. This could lead to fewer side effects, making it easier for patients to stay on their medication. However, concerns about its impact on kidney health must be carefully evaluated. Although early research raised alarms about renal toxicity at high doses, more studies are needed to determine if lower doses could offer the benefits without the risks.

For now, lithium orotate remains a promising but unproven alternative to lithium carbonate. Its potential to improve brain health and mood stabilization is intriguing, but more research is needed before it can be widely recommended as a safe treatment. Anyone considering lithium orotate should consult with their healthcare provider to discuss the risks and benefits.