What is the effect of lithium orotate?

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Last updated: April 12, 2025View editorial policy

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From the Guidelines

Lithium orotate should not be used as a substitute for FDA-approved lithium treatments for bipolar disorder due to the lack of substantial clinical research supporting its efficacy and safety claims. When considering treatment for bipolar disorder, it is essential to prioritize FDA-approved medications, such as lithium carbonate or lithium citrate, which have been extensively studied and proven to be effective in managing the condition 1. Lithium orotate, a dietary supplement, contains lithium bound to orotic acid, but its use is not supported by robust clinical evidence, and its safety profile is not well established.

Some key points to consider when evaluating lithium orotate include:

  • The typical dosage of lithium orotate ranges from 5-20 mg of elemental lithium per day, but no standardized dosing exists 1.
  • Proponents of lithium orotate claim it can improve mood, reduce anxiety, and support brain health at lower doses than prescription lithium, with fewer side effects.
  • However, the theoretical advantage of lithium orotate, that the orotate carrier may allow lithium to cross the blood-brain barrier more efficiently, is not supported by substantial clinical research 1.
  • Without proper medical supervision, using any lithium product carries risks of toxicity, including tremors, confusion, kidney problems, and dangerous interactions with other medications 1.

In contrast, FDA-approved lithium treatments, such as lithium carbonate or lithium citrate, have been extensively studied and proven to be effective in managing bipolar disorder 1. The American Academy of Child and Adolescent Psychiatry recommends lithium as a first-line treatment for bipolar disorder in children and adolescents, with FDA approval down to age 12 years for acute mania and maintenance therapy 1. Therefore, it is crucial to consult with a healthcare provider before considering lithium orotate or any other treatment for bipolar disorder.

From the Research

Lithium Orotate Overview

  • Lithium orotate is a compound that has been proposed as an alternative to lithium carbonate for the treatment of bipolar disorder 2.
  • It is suggested to have a lesser toxicity profile and may allow for reduced dosage requirements due to its ability to cross the blood-brain barrier and enter cells more readily than lithium carbonate 2, 3.

Efficacy and Potency

  • Studies have shown that lithium orotate is more potent and effective than lithium carbonate in a mouse model of mania, with a near complete blockade of amphetamine-induced hyperlocomotion at concentrations of just 1.5 mg/kg 3.
  • Lithium orotate has also been shown to have improved efficacy and potency in both male and female mice, with a superior therapeutic index compared to lithium carbonate 3.

Toxicity and Safety

  • A toxicological evaluation of lithium orotate found that it was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively 4.
  • An oral repeated-dose toxicity study in rats found no toxicity or target organs, with a no observed adverse effect level determined as 400 mg/kg body weight/day 4.
  • Lithium orotate has been marketed for decades as a supplemental source of lithium with few recorded adverse events, and its potential toxicity has not been investigated in preclinical studies until recently 4.

Comparison to Lithium Carbonate and Valproate

  • Lithium orotate may be a better treatment choice than lithium carbonate due to its improved efficacy, potency, and tolerability 3.
  • Valproate may be more effective as an antimanic rather than prophylactic agent, and may be a better choice in patients with many previous affective episodes/hospitalizations and psychiatric comorbidities 5.
  • Lithium may be effective in treating acute mania, and its efficacy is maximized when used to prevent both manic and depressive episodes 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

A toxicological evaluation of lithium orotate.

Regulatory toxicology and pharmacology : RTP, 2021

Research

Lithium and Valproate in Bipolar Disorder: From International Evidence-based Guidelines to Clinical Predictors.

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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