A toxicological evaluation of lithium orotate

Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have...

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Bibliographic Details
Published in:Regulatory toxicology and pharmacology Vol. 124; p. 104973
Main Authors: Murbach, Timothy S., Glávits, Róbert, Endres, John R., Hirka, Gábor, Vértesi, Adél, Béres, Erzsébet, Szakonyiné, Ilona Pasics
Format: Journal Article
Language:English
Published: Elsevier Inc 01.08.2021
Subjects:
Genotoxicity
Lithium orotate
NOAEL
Repeated-dose toxicity
Safety
Toxicity
Lithium orotate
MPCE
LO
Repeated-dose toxicity
Toxicity
Genotoxicity
SPF
ALT
GLP
ICH
2AA
NDI
OA
OECD
TG
SCE
ANOVA
TBIL
NOAEL
LC
FOB
Safety
ISSN:0273-2300, 1096-0295, 1096-0295
Online Access:Get full text
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Summary:Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5–67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption. •This is the first preclinical toxicologic evaluation of lithium orotate.•No in vitro or in vivo genotoxic effects were observed in a standard test battery.•No treatment related adverse effects were observed in Wistar rats.•No target organs were identified in Wistar rats.•The NOAEL was 400 mg/kg bw/day, the highest dose tested.
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ISSN:0273-2300
1096-0295
1096-0295
DOI:10.1016/j.yrtph.2021.104973