Lithium orotate (C₅H₃LiN₂O₄) is a

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...

orotic acid Orotic acid is a pyrimidinedione and a carboxylic acid. Historically, it was believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin. The compound is synthesized in the body via a mi ...

and

lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid el ...

. It is available as the monohydrate, LiC₅H₃N₂O₄·H₂O. In this compound, lithium is non-covalently bound to an

orotate Orotic acid is a pyrimidinedione and a carboxylic acid. Historically, it was believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin. The compound is synthesized in the body via a m ...

ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

, rather than to a

carbonate A carbonate is a salt of carbonic acid (H2CO3), characterized by the presence of the carbonate ion, a polyatomic ion with the formula . The word ''carbonate'' may also refer to a carbonate ester, an organic compound containing the carbonate g ...

or other ion, and like other salts, dissociates in solution to produce free lithium ions. It is marketed as a

dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

, though it has been researched minimally between 1973–1986 to treat certain medical conditions, such as

alcoholism Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...

and

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

. While lithium orotate is capable of providing lithium to the body, like lithium carbonate and other lithium salts, there are no

systematic reviews A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...

supporting the efficacy of lithium orotate and it is not approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) for the treatment of any medical condition.

Effectiveness

In 1973, Hans 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 The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

; 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. A year later, Smith and Schou repeated the experiment at a higher dose (2 mM Li+) 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. In 2022, Pacholko redid the experiment and showed lithium orotate to have a safer kidney profile than lithium carbonate, it also showed that both had an increased TSH only in females, but the increase was lower in the orotate group. 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. As previously stated, lithium intake appears to be effective even at low doses, and this may account for lithium orotates claimed effectiveness.

Safety

Preliminary studies seem to indicate that lithium orotate is safe; a 6 month alcoholism cessation study led to only minor adverse effects in 8 out of 42 patients. However, the lack of safety studies and the OTC status raises concerns. Attention to it was specially raised in medical literature after a case report of an 18 year old woman who required medical attention after taking an overdose of a lithium orotate supplement. She was discharged after treatment. Orotic acid can be

mutagen In genetics, a mutagen is a physical or chemical agent that permanently changes nucleic acid, genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can ca ...

ic in very high doses of 50 mg/kg in mammalian somatic cells. It is also mutagenic for bacteria and yeast. Although lithium orotate was not shown to be genotoxic, short and long term studies must be performed to guarantee public safety.

References

External links

* {{DEFAULTSORT:Lithium Orotate Alternative medical treatments Lithium compounds Mood stabilizers Organolithium compounds

Effectiveness

Safety

See also

References

External links