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Medically reviewed by Holevn.org. Last updated on Nov 21, 2019.
Common Name(s): C5H3LiN2O4, Lithium orotate
Over-the-counter lithium orotate is promoted as a health supplement for use as a low-dose source of lithium; however, very limited clinical evidence exists to support use. Noncontrolled studies have examined the use of low-dose lithium orotate in the treatment of alcoholism, migraines, and depression associated with bipolar disorder.
Adequate clinical studies are lacking to support dosage recommendations.
Avoid use in patients with significant renal disease.
Avoid use. Information regarding use of the orotate salt form of lithium in pregnancy and lactation is lacking. Adverse effects have been observed with use of lithium carbonate or citrate. Lithium is excreted in breast milk; adverse events have been reported in breastfeeding infants.
Reports are lacking. A drug interaction checker tool for standard pharmaceutical lithium preparations should be consulted.
Adverse effects have not been reported for low doses; however, at higher doses, adverse effects associated with lithium pharmaceutical preparations (lithium carbonate, lithium citrate) should be expected.
Information is limited. Nephrotoxicity is associated with high doses and long-term consumption of lithium. Short-term use of lithium orotate at low doses may not be associated with these toxicity concerns.
Lithium orotate is available as an over-the-counter product in the United States, and is not approved by the Food and Drug Administration (FDA) for any indication.Balon 2013, Lakhan 2008 Pharmaceutical lithium is more common as the carbonate or citrate salt forms. Lithium is found to some extent in tomatoes, mushrooms, thyme, pistachios, egg yolks, kelp, and sardines, depending on its presence in the soil or food source. Lithium has been identified in the salt flats of Argentina and Chile as well as China.Marshall 2015 The average US consumption from food sources and water has been estimated to be approximately 0.5 to 3 mg/day.Barkins 2016
Lithium (not specifically the orotate salt) has been associated with curative properties in Greek literature for centuries, while visits to natural lithium-enriched waters were reportedly undertaken by Mark Twain, Grover Cleveland, and Theodore Roosevelt, among others, in the 19th century. A lithium citrate–containing beverage was marketed as “lithiated lemon soda” in the mid 1900s, apparently to make it seem healthier. Lithium has been associated with longevity in Japanese literature, and historically was considered beneficial in treating hepatitis.Barkins 2016
Lithium orotate is the commercially available monohydrate salt of the metal lithium and orotic acid. Based on the degree of ionization of the different salt forms, with an orotate salt in general being less ionisable and more bioavailable than a gluconate salt, earlier studies suggest that the orotate form is able to cross the blood-brain barrier more easily than the carbonate form.Barkins 2016, Kling 1978, Lakhan 2008, Marshall 2015
Studies claiming differences in the pharmacokinetics of lithium orotate salt versus the carbonate and chloride forms have been disputed. No differences were found in the uptake, distribution, and clearance of the lithium ion in rat studies,Smith 1976 despite early research suggesting lithium orotate achieved higher concentrations in the brain.Kling 1978, Nieper 1973
Uses and Pharmacology
Small amounts of lithium are required for folate and vitamin B12 transport in the human body.Marshall 2015 Clinical applications of lithium carbonate and citrate are well documented in medical references (ie, acute treatment of manic episodes and maintenance therapy for patients with a diagnosis of bipolar disorder).Lithobid 2016, Lithium 2015, Lithium 2016 Limited quality clinical studies have been conducted on the orotate salt form.
Lithium has demonstrated a decrease in amyloid and tau protein–induced neurotoxicity in experimental studies.Barkins 2016 Lithium may also upregulate neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve-growth factor (NGF), which are important in neuronal function.Marshall 2015
An open study in 42 alcoholic patients evaluated the effect of lithium orotate 150 mg/day taken over 6 months. Lithium orotate intervention demonstrated benefit in treating alcoholism, and was also associated with improvements in migraines and depression.Sartori 1986 Other studies show lithium orotate may reduce the frequency and severity of migraine attacks and improve depression associated with bipolar disorder.Lakhan 2008, Nieper 1973, Peatfield 1981 Extrapolation of reported findings is limited by poor methodology of the limited studies.
Limited studies have reported increased longevity in Caenorhabditis elegans worms with low-dose lithium (ie, 45% increase in median lifespan and a 16% increase in maximal lifespan).
Suggestions of enhanced stem-cell production and longevity appear in the literature, but clinical studies are lacking.
Over-the-counter lithium orotate is promoted as a health supplement for use as a low-dose source of lithium. The recommended daily allowance (RDA) of lithium is 1 mg/dayMarshall 2015; supplemental lithium orotate doses up to 20 mg/day have been suggested.Marshall 2015 However, adequate clinical studies are lacking to support dosage recommendations. Case reports exist of consumption of higher dosages (up to 240 mg of lithium orotate per day), with no apparent signs of toxicity.Balon 2013
Higher dosages are associated with adverse effects; see Adverse Reactions section.
Approximately 3.83 mg of elemental lithium is obtained from 100 mg of organic lithium orotatePauzé 2007; however, quality of over-the-counter preparations may vary.Heim 1994 An older study evaluated the rate of absorption and maximal concentrations of commercially available sustained-release lithium preparations, including lithium orotate, and reported that the release of lithium was largely complete within 4 hours, similar to that of immediate-release preparations.Heim 1994
Pregnancy / Lactation
Avoid use. Information regarding use of the orotate salt form of lithium in pregnancy and lactation is lacking. Lithium crosses the placenta in concentrations similar to those in maternal plasmaNewport 2005; adverse effects have been observed with use of lithium carbonate or citrate (eg, cardiac malformations in the infant, including Ebstein anomaly [with use during the first trimester]; polyhydramnios, fetal/neonatal cardiac arrhythmias, hypoglycemia, diabetes insipidus, changes in thyroid function, premature delivery, floppy infant syndrome, neonatal lithium toxicity [with use later in pregnancy].ACOG 2008 Lithium is excreted in breast milk; adverse events (eg, hypotonia, hypothermia, cyanosis, electrocardiogram [ECG] changes, lethargy) have been reported in breastfeeding infants.ACOG 2008
A report exists of suboptimal therapy with antibiotics due to the potential for an interaction with lithium. The authors emphasize the need to assess the risk of interactions, despite lithium orotate being a low-risk dietary supplement.VanWeringh 2017
A drug interaction-checker tool for standard pharmaceutical lithium preparations should be consulted.
Adverse effects have not been reported for low doses (lithium orotate 5 to 20 mg)Marshall 2015, Smith 1976; however, at higher doses, adverse effects associated with lithium pharmaceutical preparations (lithium carbonate, lithium citrate) should be expected.Gong 2016 Lithium should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation, or dehydration or sodium depletion, due to risk of lithium toxicity; if use is unavoidable, lithium may be undertaken with extreme caution, including frequent serum lithium determinations and possibly hospitalization. Discontinue therapy if clinical signs of lithium toxicity occur (eg, diarrhea, vomiting, tremor, mild ataxia, drowsiness or muscular weakness).Lithobid 2016, Lithium 2015, Lithium 2016
A small, open-label study reported mild symptoms of muscle weakness, loss of appetite, mild apathy, and listlessness among some patients taking lithium orotate 150 mg/day. The symptoms resolved following reductions in dosage.Sartori 1986
A case report exists of an 18-year-old woman ingesting 18 lithium orotate tablets, each containing 120 mg of lithium orotate. Nausea and one episode of emesis were reported, vital signs were normal on presentation, and the only other finding was a mild tremor without rigidity. ECG showed a normal sinus rhythm.Pauzé 2007
In another case report, no signs of toxicity were observed following consumption of lithium orotate 240 mg/day for self-diagnosed bipolar disorder.Balon 2013
Nephrotoxicity is associated with high-doses and long-term consumption of lithium, and a narrow therapeutic index associated with lithium limits its clinical use. Short-term use of low-dose lithium (as the orotate salt) may not be associated with these toxicity concernsGong 2016, Smith 1979, Smith 1976; some experimental data in rats suggests a nephroprotective effect with short-term use of low-dose lithium.Gong 2016
Orotic acid (also known as pyrimidinecarboxylic acid or the misnomer vitamin B13) has been shown to be mutagenic in genetically manipulated strains of Candida albicans.Wellington 2006
ACOG Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111:1001-1020.18378767Balon R. Possible dangers of a “nutritional supplement” lithium orotate. Ann Clin Psychiatry. 2013;25(1):71.23376874Barkins R. Low-dose lithium and its health supporting effects. Nutr Perspect. 2016;39(3):32-34.Gong R, Wang P, Dworkin L. What we need to know about the effect of lithium on the kidney. Am J Physiol Renal Physiol. 2016;311(6):F1168-F1171.27122541Heim W, Oelschläger H, Kreuter J, Müller-Oerlinghausen B. Liberation of lithium from sustained release preparations. A comparison of seven registered brands. Pharmacopsychiatry. 1994;27(1):27-31.8159780Kling MA, Manowitz P, Pollack IW. Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate. J Pharm Pharmacol. 1978;30(6):368-370.26768Lakhan SE, Vieira KF. Nutritional therapies for mental disorders. Nutr J. 2008;7:2.18208598Lithobid (lithium carbonate) [prescribing information]. Baudette, MN: Ani Pharmaceuticals; May 2016.Lithium extended-release tablets [prescribing information]. Morgantown, WV: Mylan Pharmaceuticals Inc; July 2015.Lithium capsules [prescribing information]. Eatontown, NJ: West-Ward Pharmaceuticals Corp; February 2016.Marshall TM. Lithium as a nutrient. J American Physicians Surgeons. 2015;20(4):104-109.Newport DJ, Viguera AC, Beach AJ, Ritchie JC, Cohen LS, Stowe ZN. Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy. Am J Psychiatry. 2005;162:2162-2170.16263858Nieper HA. The clinical applications of lithium orotate. A two years study. Agressologie. 1973;14(6):407-411.4607169Pauzé DK, Brooks DE. Lithium toxicity from an Internet dietary supplement. J Med Toxicol. 2007;3(2):61-62.18072162Peatfield RC. Lithium in migraine and cluster headache: a review. J R Soc Med. 1981;74(6):432-436.7252959Sartori HE. Lithium orotate in the treatment of alcoholism and related conditions. Alcohol. 1986;3(2):97-100.3718672Smith DF, Schou M. Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. J Pharm Pharmacol. 1979;31(3):161-163.34690Smith DF. Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats. Br J Pharmacol. 1976;56(4):399-402.1260219van Weringh G, Uitvlugt EB, Ponjee GHM, M Jalink G. Confusion caused by dietary supplement lithium orotate [in Dutch]. Tijdschr Psychiatr. 2017;59(4):234-237.28421576Wellington M, Kabir MA, Rustchenko E. 5-fluoro-orotic acid induces chromosome alterations in genetically manipulated strains of Candida albicans. Mycologia. 2006;98(3):393-398.17040068
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