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. However, another study in 1978 study showed that eight hours after intraperitoneal injections brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2·0 m equiv kg−1 lithium carbonate, two‐thirds of the 2 h serum lithium concentration was present 24 h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations. This study was refuted a year later by another study that repeated the experiment and found that the higher concentrations in the brain could be possibly accounted for by decreased renal function in rats treated with lithium orotate. The proponents of lithium orotate have since criticized the results by citing the fact that the dose of lithium orotate used in the study was in the toxic range. The pharmacokinetics of lithium orotate in human brains is poorly documented, and there is no known mechanism by which orotate ions could alter the pharmacokinetics of dissociated lithium ions. Major medical research has not been conducted on lithium orotate since the 1980s due to its patent status and the abundant availability of lithium carbonate. As previously stated, lithium intake appears to be effective even at low doses, and this may account for lithium orotates claimed effectiveness.
Safety
Lithium orotate's safety remains in question. Concerns have been raised in medical literature after a case report of a patient who required medical attention after taking an overdose of lithium orotate supplement. Orotic acid can be mutagenic in very high doses of 50 mg/kg in mammalian somatic cells. It is also mutagenic for bacteria and yeast.
