While lithium orotate is capable of providing lithium to the body, like lithium carbonate and other lithium salts, there are no systematic reviews supporting the efficacy of lithium orotate and it is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition. A 1979 study drew the mistaken conclusion that its use may in fact be harmful to kidney function compared to lithium carbonate. According to researcher Vickie Gunther, the study failed to take into account that much less lithium orotate is needed because of its higher efficacy verses lithium carbonate. Dr. John Gray has pointed out that this is because the orotate form is the one the body's defenses, the ion-selective protein gates in the blood-brain barrier is matched to, so the orotate molecule passes unhindered through the barrier, while the carbonate form is largely blocked. A fairer comparison would have been to administer eight times less lithium orotate than lithium carbonate, thereby lessening concerns of potential impaired kidney function. Lithium orotate has been promoted as an alternative to lithium carbonate, which because it must be used in high doses, is potentially toxic.
In 1973, Nieper reported that lithium orotate contained 3.83 mg of elemental lithium per 100 mg and lithium carbonate contained 18.8 mg of elemental lithium per 100 mg. Nieper went on to claim that lithium did not dissolve from the orotate carrier until it passed through the blood brain barrier, however a 1976 study documented that lithium concentrations within the brains of rats were not statistically different between equivalent dosages of lithium from lithium orotate, lithium carbonate, or lithium chloride. While this study was conducted with rats, it directly contradicts the aforementioned assumptions made by Nieper and others. The pharmacokinetics of lithium orotate in human brains is poorly documented and further inquiry is needed to affirm that lithium concentrations in the brain are higher with lithium orotate. Major medical research has not been conducted on lithium orotate since the 1980s due to its patent status and the abundant availability lithium carbonate. As previously stated, lithium intake appears to be effective even at low doses, and this may account for lithium orotates claimed effectiveness.
It is heavily touted by Dr. John Gray, among others, as a low toxicity alternative. Although a few psychiatrists prescribe lithium orotate to their patients mostly for bipolar disorder, it is most often naturopaths and other alternative health practitioners who recommend this lithium compound to their patients.
^Smith DF, Schou M (March 1979). "Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate". J. Pharm. Pharmacol.31 (3): 161–3. PMID34690.
^Nieper HA. (1973). "The clinical applications of lithium orotate. A two years study". Agressologie.14 (6): 407–11. PMID4607169.
^Smith DF (April 1976). "Lithium orotate, carbonate, and chloride: pharmacokinetics, polydipsia and polyuria in rats". Br J Pharmacol.56 (4): 399–402. PMID1260219.
^Alevizos B, Alevizos E, Leonardou A, Zervas I (2012). "Low dosage lithium augmentation in venlafaxine resistant depression: An open-label study". Psychiatrike.23 (2): 143–8. PMID22796912.
^Nunes MA, Viel TA, Buck HS I (2013). "Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease". Curr Alzheimer Res.10 (1): 104–7. PMID22746245.
^Berger GE, Wood SJ, Ross M, Hamer CA, Wellard RM, Pell G, Phillips L, Nelson B, Amminger GP, Yung AR, Jackson G, Velakoulis D, Pantelis C, Manji H,McGorry PD I (2012). "Neuroprotective effects of low-dose lithium in individuals at ultra-high risk for psychosis. A longitudinal MRI/MRS study". Curr Pharm Des.18 (4): 570–5. PMID22239590.