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Still feeling depressed. My husband just ordered several bottles so everyone in my family can have this valuable supplement (though my dosage will be at least four times their dosage). Uemura, N., Murakami, R., Chiba, Y., Yanase, K., Fujihara, R., Mashima, M., Matsumoto, K., Kawauchi, M., Shirakami, G., & Ueno, M. (2017). Writing: Anthony G. Pacholko. More robust evidence for the efficacy of lithium in the longterm treatment of bipolar disorder: Should lithium (again) be recommended as the single preferred firstline treatment? Neural and developmental actions of lithium: A unifying hypothesis. Luo, H., Gauthier, M., Tan, X., Landry, C., Poupon, J., Dehouck, M.P., Gosselet, F., Perrire, N., Bellivier, F., Cisternino, S., & Declves, X. Thus, studies examining the membrane transport mechanisms of LiOr, and any connections they may have to the reported elevations in serum and brain Li+ content relative to Li2CO3, are needed. Hilty, D. M., Leamon, M. H., Lim, R. F., Kelly, R. H., & Hales, R. E. (2006). A combination of probiotics and magnesium orotate attenuate depression in a small SSRI resistant cohort: An intestinal antiinflammatory response is suggested. New research is suggesting that lower doses of lithium can have the same effect without collecting in the body and overburdening the kidneys, so bipolars can have their cake and eat it too. Tondo, L., Alda, M., Bauer, M., Bergink, V., Grof, P., Hajek, T., Lewitka, U., Licht, R. W., Manchia, M., MllerOerlinghausen, B., Nielsen, R. E., Selo, M., Simhandl, C., & Baldessarini, R. J., & International Group for Studies of Lithium (IGSLi) Lithium Orotate: A superior option for lithium therapy? Key takeaways: ~For some people, supplementing with low-dose lithium orotate helps with anxiety, depression, and anger issues. If so, how does the LiOr complex accomplish this? Similar to lithium chloride, lithium sulfate is approved for use in the management of BD, but is prescribed far less frequently than Li2CO3. The underpinnings of these conditions have not been fully elucidated, though theories regarding their etiopathogenesis, such as circadian clock dysfunction (Takaesu, 2018), catecholamine excess/deficiency/dysfunction (Ashok etal., 2017; Kurita, 2016), serotonin dysregulation (Lee etal., 2012; Mahmood & Silverstone, 2001), aberrant glycogen synthase kinase3 (GSK3) (Jope & Roh, 2006; Jope, 2011; Muneer, 2017; Yu & Greenberg, 2016), inositol monophosphatase (IMPase) activity (Yu & Greenberg, 2016), neuroinflammation (Hamdani etal., 2013; Muneer, 2016; Roda etal., 2015), and loss/lack of neurotrophic factors (Li etal., 2014; Roda etal., 2015), have been proposed. Myoinositol is a substrate used for the synthesis of phosphatidylinositol phosphates (Shi etal., 2006), which are signaling molecules involved in a diverse array of processes, including cell growth, cell proliferation, apoptosis, neuronal transmission, and the actions of insulin, among others (Toker, 2002). Plasma and brain pharmacokinetics of previously unexplored lithium salts, Lithium orotate, carbonate and chloride: Pharmacokinetics, polyuria in rats, Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. if you appreciate that access to the news, opinion, humor, entertainment and cultural reporting in the Sandpoint Reader is freely available in our print newspaper as well as here on our website, we have a favor to ask. Enhanced Memory. I suffer from ADHD. Amazon.com: NCI Advanced Research Dr. Hans Nieper Lithium Orotate The benefits and drawbacks of Li2CO3 use in BD. Glucose, fructose, and urate transporters in the choroid plexus epithelium, International Journal of Molecular Sciences, Chokhawala, K., Lee, S., & Saadabadi, A. Leave your testimonial about Lithium Orotate here! To Read Lithium #4. Smile! Li2CO3 displays a relatively low volume of distribution (Mason etal., 1978), and its cellular influx and efflux appears to be driven by a combination of sodiumdependent passive and active transport mechanisms; in general, as sodium goes, so too does lithium (Luo etal., 2018; Ward etal., 1994). Antioxidant potential and angiotensinconverting enzyme (ACE) inhibitory activity of orotic acidloaded gum Arabic nanoparticles. Far more research is required before any definitive conclusions can be made regarding the inositol depletion hypothesis (Berridge etal., 1989) of lithium's therapeutic efficacy (Raghu etal., 2019). While it is now known that orotic acid is not a vitamin, its previous status as B13 provides insight into its historical importance as a dietary component. In, The science and practice of lithium therapy, The diagnosis and treatment of bipolar disorder: Decisionmaking in primary care, The Primary Care Companion for CNS Disorders. LiOr is most notable for its early use and advocacy by the controversial Hans Nieper in the 1970s, who proposed that orotic acid was a superior carrier compound that could more readily transport inorganic ions across biological membranes (Nieper, 1970, 1973). Lithium oratate. Life changer. : r/Nootropics - Reddit If you're a reader who appreciates the value of an independent, local news source, we hope you'll consider a voluntary contribution. Does LiOr truly result in higher brain and serum concentrations of lithium relative to Li2CO3, as was previously observed by Kling etal. Guelen, P. J., Janssen, T. J., De Witte, T. C., Vree, T. B., & Benson, K. (1992). Spectrum of lithium induced thyroid abnormalities: A current perspective. Lithium saved my life. Unfortunately, the most frequently employed lithium salt, lithium carbonate (Li2CO3), 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). From these humble beginnings, lithium has gone on to become the arguable gold standard for the management of the manic component of BD and the prevention of mood episode recurrences (Tondo etal., 2019). Lithium is so abundant in these areas that it frequently makes its way into both food and water supplies. I want everyone to hear the latest research on this magical mineral because I believe lithium is saving my life. Inhibition of these enzymes is mediated through the displacement of the cofactor magnesium; lithium and magnesium share similar ionic radii, allowing lithium to act as a competitive inhibitor for the binding of the magnesium ion (Mg2+) at the catalytic core of each protein (Brown & Tracy, 2013; Lu etal., 2012; Ryves & Harwood, 2001). I would like you all to know, at the end of the day, you can have so much of anything, so make the most of it and enjoy life. Abnormal phosphatidylinositol (PI)signalling in bipolar disorder. You dont have to hide being bipolar which I think you have, but you just need to stay on top of it.. If you. Petrova, T. R., Skibitskii, V. V., Grigor'ev, G. I., Vil'chinskaia, M. N., & Oleinik, N. I. Lee, K. S., Park, Y. M., & Lee, S. H. (2012). Meds have side effects. The root word of lithium means it is literally from the rock. Some communities have lithium in their water supply Hot Springs, Mont., for instance. LITHIUM Reviews and User Ratings: Effectiveness, Ease of Use, and The role of lithium in the treatment of bipolar disorder: Convergent evidence for neurotrophic effects as a unifying hypothesis. Furthermore, the sustained increase in brain Li+ over 24h may allow for a more robust and consistent control of symptoms between doses. Ennis, S. R., Ren, X. D., & Betz, A. L. (1996). So fantastic. Studies exploring its efficacy have reported a range of different outcomes, from no difference relative to Li2CO3 (Guelen etal., 1992; Shelley & Silverstone, 1986), to significant reductions in peak serum lithium levels (Tyrer etal., 1982). (1991). BENEFITS OF LITHIUM OROTATE: Reduces Excitotoxicity. (2018). The mood stabilizers lithium and valproate selectively activate the promoter IV of brainderived neurotrophic factor in neurons. Overall rating 3.3. At present, literature exploring its efficacy and/or safety is sparse. Marshall 2015 However, adequate clinical studies are lacking to support dosage . Lithium has historically been prescribed for bipolar people in large doses, but this doesn't have to be the case. Despite being the current gold standard for the control of mania and the prevention of mood episode recurrences, Li2CO3 is not without its share of issues, namely a narrow therapeutic window and a potentially severe toxic effect profile that may limit patient compliance. McCarty, M. F., & DiNicolantonio, J. J. If patients feel good at 20 mg a day, I have them stay on that dose. While complications such as hypothyroidism can be managed via thyroid supplementation, this is not a desirable outcome. Lithium was named by chemist Johan August Arfvedson, who isolated the element from petalite procured from the soils of the island of Uto. Insights into the role of magnesium triad in myoinositol monophosphatase: Metal mechanism, substrate binding, and lithium therapy, Journal of Chemical Information and Modeling. I would like you all to know, at the end of the day, you can have so much of anything, so make the most of it and enjoy life. Stout, J., Hozer, F., Coste, A., Mauconduit, F., DjebraniOussedik, N., Sarrazin, S., Poupon, J., Meyrel, M., Romanzetti, S., Etain, B., RabraitLerman, C., Houenou, J., Bellivier, F., Duchesnay, E., & Boumezbeur, F. (2020). 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. Received 2021 May 15; Accepted 2021 Jun 8. Aonuma, S., Hama, T., Tamaki, N., & Okumura, H. (1969). Intriguingly, the expression of the proinflammatory cytokines, for example, IL4, IL6, IL1, and TNF, is often rescued/normalized in previously medicationnaive BD patients following chronic treatment with lithium (Boufidou etal., 2004; Knijff etal., 2007; Rapaport etal., 1999). Furthermore, uridine itself serves many purposes outside of DNA and RNA synthesis; it is involved in the synthesis of various membrane components, participates in glycosylation reactions, and contributes to neuronal and glial communication as a signaling molecule recognized by purinergic2Y (P2Y; i.e., Gproteincoupled uridine triphosphate receptor) receptors (Dobolyi etal., 2011; von Kugelgen & Hoffmann, 2016). This antagonistic function has been proposed as a central mechanism by which lithium contributes to the alleviation of BD symptoms. Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain, Proceedings of the National Academy of Sciences of the USA, Noradrenaline plays a critical role in the switch to a manic episode and treatment of a depressive episode. They noted that both the lactate and salicylate formulations displayed reduced bioavailability relative to Li2CO3. Friedman, E., Hoau Yan, W., Levinson, D., Connell, T. A., & Singh, H. (1993). There is no shame or mania, just a peaceful detachment. "Independent" means that the Reader is locally owned, in a partnership between Publisher Ben Olson and Keokee Co. Publishing, the media company owned by Chris Bessler that also publishes Sandpoint Magazine and Sandpoint Online. Hassani, A., Hussain, S. A., Abdullah, N., Kamarudin, S., & Rosli, R. (2019). Soares, A. T., Andreazza, A. C., Rej, S., Rajji, T. K., Gildengers, A. G., Lafer, B., Young, L. T., & Mulsant, B. H. (2016). Furthermore, other studies have shown no effect of Li2CO3 on avoidance of relapse (Dorus etal., 1989), leading some to conclude that Li2CO3 is not an effective treatment for alcoholism (Lejoyeux & Ades, 1993). Bioavailability of lithium carbonate and lithium citrate: A comparison of two controlledrelease preparations. Dosing. It is therefore possible that aspects of lithium's therapeutic effects may be elicited through antiinflammatory mechanisms involving GSK3 inhibitiondependent attenuation of microglial proinflammatory responses. Liubimov, B. I., Tolmacheva, N. S., Ostrovskaia, R. U., & Mitrofanov, V. S. (1980). Holguin, S., Martinez, J., Chow, C., & Wurtman, R. (2008). LiOr received a brief surge of interest in the earlytomid 1970s in part because of advocacy from Nieper, who argued for the use of orotate as a mineral transporter (Nieper, 1970, 1973). LiOr may represent an alternative form of lithium that can enter the brain more readily than Li2CO3, which would theoretically allow for maintenance of efficacy at reduced dosages, thereby mitigating noncompliance concerns by minimizing the incidence of dosedependent side effects. Barbosa, I. G., Bauer, M. E., MachadoVieira, R., & Teixeira, A. L. (2014). Depressive states are characterized by feelings of persistent sadness, anhedonia, sleep disturbance, and fatigue, whereas mania and hypomania are noted for euphoria, loss of inhibition, impaired decisionmaking, and/or reduced need for sleep (Association AP, 2013). While these small doses are likely to be safe, the potential toxic effects of microdosing LiOr still warrants further examination. According to the National Institute of Mental Health, lithium salts were the first drugs approved by the Food and Drug Administration to treat bipolar disorder, mania and depression. A new look at an old drug: Neuroprotective effects and therapeutic potentials of lithium salts. Shi, Y., Azab, A. N., Thompson, M. N., & Greenberg, M. L. (2006). To date, these studies appear to be the only cases directly contrasting LiOr and Li2CO3. Phosphoinositides: Regulators of nervous system function in health and disease. Fiol, C. J., Williams, J. S., Chou, C. H., Wang, Q. M., Roach, P. J., & Andrisani, O. M. (1994). This is probably a healing reaction or methylation 'awakening', although it doesn't feel good sometimes. Boufidou, F., Nikolaou, C., Alevizos, B., Liappas, I. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder, Lithium: The pharmacodynamic actions of the amazing ion, Therapeutic Advances in Psychopharmacology. I love people. Canada. Furthermore, when administered at 2mmol Li+/kg as an orotate, Li+ progressively accumulated within the brain in a manner not observed for Li2CO3; Li2CO3 maintained a steady concentration of 0.5mmol Li+/kg of brain tissue, whereas LiOr increased from 0.5 to 1.3mmol Li+/kg over the course of 24h. Brain lithium concentrations were assayed via flame photometry of tissue homogenates. Dell'Osso, L., Del Grande, C., Gesi, C., Carmassi, C., & Musetti, L. (2016). By rejecting non-essential cookies, Reddit may still use certain cookies to ensure the proper functionality of our platform. In 1970, the FDA approved lithium for use in the treatment of acute mania in the United States (Shorter, 2009). Studies comparing the pharmacokinetics of lithium sulfate and Li2CO3 have found little to no difference in absorption and/or peak serum lithium concentrations (Persson, 1977), or induction of sideeffects (Edstrom & Persson, 1977). Boldyrev, A. Cytokines in bipolar disorder: Paving the way for neuroprogression. I was left with that same question that has haunted me since puberty: Couldnt I just fall asleep and not wake up to escape this pain?. Clinical use of lithium salts: Guide for users and prescribers. Reduced frontal cortex inositol levels in postmortem brain of suicide victims and patients with bipolar disorder. but apparently it helps with anxiety, depression, etc it also raises COMT enzyme activity for those who have the gene mutation Unfortunately, Li2CO3based therapy is not without issues. Laconi, E., Denda, A., Rao, P. M., Rajalakshmi, S., Pani, P., & Sarma, D. S. (1993). Olbrich, R., Watzl, H., Volter, M., & Siedow, H. (1991). Serotonergic dysfunction in patients with bipolar disorder assessed by the loudness dependence of the auditory evoked potential, Evaluation of lithium treatment in alcoholism, Sleep and circadian rhythm abnormalities in the pathophysiology of bipolar disorder, Current Topics in Behavioral Neurosciences. Transgenic mice overexpressing glycogen synthase kinase 3beta: A putative model of hyperactivity and mania, NIMH workshop report on treatment of bipolar disorder. I prescribe it for almost all of my patients in the form of lithium orotate at a dosage of 5-20 mg at bedtime. (2021). Patel, S., Yenush, L., Rodrguez, P. L., Serrano, R., & Blundell, T. L. (2002). A secondary phosphorylation of CREB341 at Ser129 is required for the cAMPmediated control of gene expression. Tyrer, S. P., Peat, M. A., Minty, P. S., Luchini, A., Glud, V., & Amdisen, A. Miura, D., Anzai, N., Jutabha, P., Chanluang, S., He, X., Fukutomi, T., & Endou, H. (2011). Is the safety of lithium no longer in the balance? Lithium User Reviews for Bipolar Disorder - Drugs.com Lieberman, I., Kornberg, A., & Simms, E. S. (1955). lithium orotate has hundreds of drug interactions. Cytokines are signaling molecules involved in either the potentiation or attenuation of inflammation, among numerous other functions. 1 She is a doctor of psychology studying suicide rates and tendencies, working to keep veterans with PTSD alive. While incredibly effective for the prevention of manic and/or depressiveepisode recurrence, Li2CO3 is not without its share of issues (Figure2). Others have found an antiarrhythmic effect in lithium oxybutyrate, which may suggest beneficial effects of the medication beyond just the control of BD symptoms (Petrova etal., 1987). hlund, L., Ott, M., Oja, S., Bergqvist, M., Lundqvist, R., Sandlund, M., Renberg, E. S., & Werneke, U. Lithium for prevention of mood episodes in bipolar disorders: Systematic review and metaanalysis, Hypercalcemia and primary hyperparathyroidism during lithium therapy. I've been depression/anxiety free for over a year. Lithium orotate may not work for everyone, but in my (consensus) experience it works for damn near everyone. Berridge, M. J., Downes, C. P., & Hanley, M. R. (1982). When coupled with the narrow therapeutic window of Li2CO3, the very existence of alternative lithium salt compounds demands further exploration of their efficacy and safety. The adverse effects on the kidneys reported by Smith etal. Gupta, V., Chitranshi, N., You, Y., Klistorner, A., & Graham, S. (2014). Allison, J. H., Blisner, M. E., Holland, W. H., Hipps, P. P., & Sherman, W. R. (1976). Padmos, R. C., Hillegers, M. H. J., Knijff, E. M., Vonk, R., Bouvy, A., Staal, F. J. T., De Ridder, D., Kupka, R. W., Nolen, W. A., & Drexhage, H. A. and transmitted securely. You can help support the Reader for as little as $1. Lithium orotate (LiC5H3N2O4; henceforth referred to as LiOr), a compound largely abandoned since the late 1970s, may represent such an alternative. Malhi, G. S., Bell, E., Porter, R. J., Boyce, P., Mulder, R., Hopwood, M., Hazell, P., Bassett, D., Bryant, R. A., Lyndon, B., Murray, G., & Berk, M. (2020). The peer review history for this article is available at https://publons.com/publon/10.1002/brb3.2262. Want to ensure that local, independent journalism survives in our town? Polter, A., Beurel, E., Yang, S., Garner, R., Song, L., Miller, C. A., Sweatt, J. D., Mcmahon, L., Bartolucci, A. Further work is not only warranted, but imperative to understanding the potential benefits of LiOr. If I could sum it up in just one word it would be this - Happy! Dobolyi, A., Juhasz, G., Kovacs, Z., & Kardos, J. I still have the ability to get upset, angry, pessimistic, overly confident, somewhat manic, etc. calm, energized, awake, not depressed. Lithium treatment of depressed and nondepressed alcoholics, Comparison of side effects with coated lithium carbonate tablets and lithium sulphate preparations giving mediumslow and slowrelease. Kato, T., Shioiri, T., Takahashi, S., & Inubushi, T. (1991). Sugawara, N., YasuiFurukori, N., Ishii, N., Iwata, N., & Terao, T. (2013). Carlezon, W. Considering the promise displayed and the overall lack of investigation into its efficacy, further exploration into lithium oxybutyrate is warranted. (1968). MachadoVieira, R., Manji, H. K., & Zarate, C. A. "I've been using lithium orotate for about a month and have had significantly better mood stability, lessened anxiety, and a sense of well-being. Mechanisms of sodium transport at the bloodbrain barrier studied with in situ perfusion of rat brain, Mammalian pyrimidine biosynthesis: Fresh insights into an ancient pathway. I woke up after a night of overstimulation (after taking 62 micrograms of Lithium orotate the morning befiore) and I feel great. Careers, Unable to load your collection due to an error. combining it with psychedelics like LSD can be deadly. More severe sideeffects, including cognitive impairment, nephrotoxicity, hypothyroidism and hyperparathyroidism (Gitlin, 2016), are typically observed during longterm treatment, that is, 10 or more years. (2) The amount of orotic acid ingested in the course of LiOr therapy by BD patients (i.e.,<1000mg or 1015mg/kg) is unlikely to contribute to the growth of cancerous cells, as stimulation of cancerous cell growth was observed at orotic acid concentrations exceeding 100mg/kg (Laconi etal., 1993).

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