One of our patients had some interesting questions about lithium orotate. He said he had come across a couple of research papers that suggested that lithium orotate might have a unique pharmacologic profile, one that reduces adverse effects from lithium while preserving its therapeutic benefit.
Lithium orotate is a compound formed from lithium and orotic acid. It is available for purchase without a a prescription, although at doses of lithium that are not usually thought of as therapeutic.
Lithium orotate does not dissociate into Li2+ and orotate– as readily as lithium carbonate does. In our blood lithium carbonate exists almost entirely as a solution of two ions: Li2+ and CO32- whereas lithium orotate in the body exists mostly as a stable lithium orotate or lithium orotate hydride molecules.
It has been suggested that lithium orotate is actively transported by nucleotide transporters such as the uracil transporter. According to this theory, lithium orotate gets actively transported to places in the body and brain where nucleotide synthesis is taking place (glia, vascular endothelium, and neurons).
Lithium is not released from the compound until orotate is being used in nucleotide synthesis via action of the enzyme dihydroorotate dehydrogenase which is located on mitochondrial membranes.
The result of this process of active transport and then release at certain sites in the body and brain, is that lithium orotate may be effective at much lower doses and blood levels than is lithium carbonate. This might reduce the toxic effects of lithium on the kidney and thyroid gland.
The attentive reader may notice that much of what I have cited so far is theoretical. It may be the case that lithium orotate is effective with less toxicity. This is a long way from saying that one should be using lithium orotate to treat a potentially serious condition such as bipolar disorder.
There are many potential treatments with a similarly interesting story, treatments which have not turned out to work. When I was an intern in training on the cardiac ICU we often used antiarrhythmic medications to normalize cardiac rhythm in people with cardiac disorders (for example, after a heart attack). You could show that the medications did indeed result in more normal EKG findings. However, at the time, it had not been shown that they prolonged life. When the results from those studies started to get published it turned out that the medications actually shortened life, rather than prolonging it.
In other words, we await research that shows that lithium orotate is reasonably safe and effective (and that clarifies what the dose should be), and until those studies get published I do not recommend using these “supplements.”
References
Bach, Ina, Otto Kumberger, and Hubert Schmidbaur. “Orotate Complexes. Synthesis and Crystal Structure of Lithium Orotate(-I) Monohydrate and Magnesium Bis[ Orotate(-I)] Octahydrate.” Chemische Berichte 123.12 (1990): 2267–2271. Web.
Forester, Brent P. et al. “Brain Lithium Levels and Effects on Cognition and Mood in Geriatric Bipolar Disorder: A Lithium-7 Magnetic Resonance Spectroscopy Study.” The American journal of geriatric psychiatry 17.1 (2009): 13–23. Web.
Nieper,H.-A. (1973). The clinical applications of lithium orotate. A two years study. Agressologie: revue internationale de physio-biologie et de pharmacologie appliquées aux effets de l’agression, 14(6), 407–411.
Pacholko, Anthony G., and Lane K. Bekar. “Different Pharmacokinetics of Lithium Orotate Inform Why It Is More Potent, Effective, and Less Toxic than Lithium Carbonate in a Mouse Model of Mania.” Journal of psychiatric research 164 (2023): 192–201. Web.
Pacholko, Anthony G., and Lane K. Bekar. “Lithium Orotate: A Superior Option for Lithium Therapy?” Brain and behavior 11.8 (2021): n. pag. Web.
SMITH, DONALD F., and MOGENS SCHOU. “Kidney Function and Lithium Concentrations of Rats given an Injection of Lithium Orotate or Lithium Carbonate.” Journal of pharmacy and pharmacology 31.1 (1979): 161–163. Web.