Lithium orotate: A superior option for lithium therapy?

Abstract

Bipolar disorder (BD) poses a significant public health concern, with roughly onequarter of sufferers attempting suicide. BD is characterized by manic and depressive mood cycles, the recurrence of which can be effectively curtailed through lithium therapy. Unfortunately, the most frequently employed lithium salt, lithium carbonate (Li 2 CO 3 ), is associated with a host of adverse health outcomes following chronic use: these unwanted effects range from relatively minor inconveniences (e.g., polydipsia and polyuria) to potentially major complications (e.g., hypothyroidism and/or renal impairment). As these undesirable effects can limit patient compliance, an alternative lithium compound with a lesser toxicity profile would dramatically improve treatment efficacy and outcomes. Lithium orotate (LiC 5 H 3 N 2 O 4 ; henceforth referred to as LiOr), a compound largely abandoned since the late 1970s, may represent such an alternative. LiOr is proposed to cross the blood-brain barrier and enter cells more readily than Li 2 CO 3 , which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns. This review addresses the controversial history of LiOr, complete with discussions of experimental and clinical efficacy, putative mechanisms of action, adverse effects, and its potential future in therapy.

Lithium: balancing mental and renal health

“…A 'microdose' of lithium orotate can be purchased without prescription as a nutritional supplement. Despite a distinct lack of human scientific studies, recent commentaries have extolled lithium orotate's potential: 9 Advocates highlight its use over several decades in the community without safety concerns, and safety is also supported by evidence from studies of low-dose lithium (other formulations), 10 and established knowledge of this mineral's pharmacodynamics. It has also been claimed that lithium orotate formulations impart benefits at lower doses than carbonate forms, and that the orotate anion itself could have biosynthetic advantages.…”

“…It has also been claimed that lithium orotate formulations impart benefits at lower doses than carbonate forms, and that the orotate anion itself could have biosynthetic advantages. 9 The biological and clinical potential of trace (<~5mg/day) and micro (~5-20mg/day elemental lithium) doses require systematic investigation to verify the above claims in human studies. Prolonged exposure to low dose lithium could be one of several routes towards identifying how this environmental, bioavailable mineral could impart its magic effectively while averting chronic renal problems.…”

Identifying the neuropsychiatric health effects of low-dose lithium interventions: A systematic review

“…Lithium consumed in the diet appears to be bioavailable, based on biochemical mechanistic theory, (Szklarska and Rzymski, 2019) preclinical data, (Seidel et al, 2020) and preliminary pharmacokinetic data (Seidel et al, 2019). The bioavailability, potential benefits and safety profile of alternative lithium formulations, such as lithium orotate (which is not regulated and available from health food outlets), therefore, requires consideration and further investigation (Pacholko and Bekar, 2021;Murbach et al, 2021).…”

What affects chronic lithium poisoning in psychiatric patients? - a case report

“…[1] Lithium is the most commonly prescribed and least expensive mood stabilizer for the abovementioned indications [4,5], and of its salts, lithium carbonate is the most commonly used. [6] Despite this drug's long history of use, its mechanism of action is not fully understood.…”

“…[7] It acts on glycogen synthase kinase-3β (GSK3β), serine/retreonin protein kinase, exhibits anti-inflammatory abilities (attenuation of neuroinflammation), and transiently increases serotonin release by decreasing norepinephrine and dopamine release from nerve endings which contributes to its properties. [6,8,9] Renal function, thyroid function, calcium, body weight should be checked, and electrocardiography may be performed before starting treatment with this product. These tests should be repeated every 6 weeks, 3 months, every 6 months, then annually, depending on the source.…”