Lithium orotate

Lithium orotate (C5H3LiN2O4), is a salt of orotic acid and lithium. It is available as the monohydrate, LiC5H3N2O4·H2O.[1] In this compound, lithium is non-covalently bound to an orotate ion, rather than to a carbonate or other ion, and like other salts, dissociates in solution to produce free lithium ions. It is marketed as a dietary supplement, though only barely researched between 1973–1986 to treat certain medical conditions, such as alcoholism[2] and Alzheimer's disease.

Lithium orotate
Clinical data
AHFS/Drugs.comMonograph
Routes of
administration		Oral
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.023.711
Chemical and physical data
FormulaC5H3LiN2O4
Molar mass162.03 g·mol−1
3D model (JSmol)
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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.

Effectiveness

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[3] 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.[4] 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.[5] 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.[6] 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.[7][8][9]

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.[10][11][12]

Orotic acid can be mutagenic in very high doses of 50 mg/kg in mammalian somatic cells.[13] It is also mutagenic for bacteria and yeast.[14]

See also

References
  1. Ina Bach; Otto Kumberger; Hubert Schmidbaur (1990). "Orotate complexes. Synthesis and crystal structure of lithium orotate( - I) monohydrate and magnesium bis[ orotate( - I)] octahydrate". Chemische Berichte. 123 (12): 2267–2271. doi:10.1002/cber.19901231207.
  2. Sartori HE (1986). "Lithium orotate in the treatment of alcoholism and related conditions". Alcohol. 3 (2): 97–100. doi:10.1016/0741-8329(86)90018-2. PMID 3718672.
  3. Nieper, Hans Alfred (1973), "The clinical applications of lithium orotate. A two years study", Agressologie, 14 (6): 407–11, PMID 4607169
  4. Smith DF (April 1976). "Lithium orotate, carbonate, and chloride: pharmacokinetics, polydipsia and polyuria in rats". British Journal of Pharmacology. 56 (4): 399–402. doi:10.1111/j.1476-5381.1976.tb07449.x. PMC 1666891. PMID 1260219.
  5. Kling, Mitchel A.; Manowitz, Paul; Pollack, Irwin W. (September 1978). "Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate". Journal of Pharmacy and Pharmacology. 30 (1): 368–370. doi:10.1111/j.2042-7158.1978.tb13258.x.
  6. Smith, D. F.; Schou, M. (March 1979). "Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate". The Journal of Pharmacy and Pharmacology. 31 (3): 161–163. PMID 34690.
  7. 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. PMID 22796912.
  8. Nunes MA, Viel TA, Buck HS I (2013). "Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease". Current Alzheimer Research. 10 (1): 104–7. doi:10.2174/156720513804871354. PMID 22746245.
  9. 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". Current Pharmaceutical Design. 18 (4): 570–5. doi:10.2174/138161212799316163. PMID 22239590.
  10. Balon, R (Feb 2013). "Possible dangers of a "nutritional supplement" lithium orotate". Annals of Clinical Psychiatry. 25 (1): 71. PMID 23376874.
  11. Pauzé, DK; Brooks, DE (Jun 2007). "Lithium toxicity from an Internet dietary supplement". Journal of Medical Toxicology. 3 (2): 61–2. doi:10.1007/bf03160910. PMC 3550087. PMID 18072162.
  12. Kwan, D.; Beyene, J.; Shah, P. S. (1 November 2009). "Adverse Consequences of Internet Purchase of Pharmacologic Agents or Dietary Supplements". Journal of Pharmacy Technology. 25 (6): 355–360. doi:10.1177/875512250902500602.
  13. "Vitamin B13 cannot be proven safe, says EFSA". nutraingredients.com. Retrieved 2018-10-08.
  14. Orotic acid MSDS
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