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      Is Lithium a Micronutrient? From Biological Activity and Epidemiological Observation to Food Fortification

      review-article
      ,
      Biological Trace Element Research
      Springer US
      Lithium, Suicide, Micronutrient, Fortified food

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          Abstract

          Lithium compounds have been widely used in psychopharmacology, particularly in the treatment of bipolar disorder. Their normothymic and neuroprotective properties when used at high doses have been well established. However, a number of observations suggest that environmentally relevant lithium doses may also exert beneficial health effects, leading to a decrease in the rate of suicides and levels of violence. Despite the fact that this element is not officially considered to be a micronutrient, some authors have suggested provisional recommended intakes set at 1000 μg/day for a 70-kg adult (14.3 μg/kg body weight). The present paper reviews the biological action of lithium, its bioavailability and metabolism, and content in different foodstuffs and water. It also assesses epidemiological data on potential correlations between lithium intake and suicide rate as well as examines the concept of fortifying food with this element as a strategy in the primary prevention of mood disorders and pre-suicidal syndrome.

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          Most cited references72

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          The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2012 on the long-term treatment of bipolar disorder.

          These guidelines are based on a first edition that was published in 2004, and have been edited and updated with the available scientific evidence up to October 2012. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the long-term treatment of bipolar disorder in adults. Material used for these guidelines are based on a systematic literature search using various data bases. Their scientific rigor was categorised into six levels of evidence (A-F) and different grades of recommendation to ensure practicability were assigned. Maintenance trial designs are complex and changed fundamentally over time; thus, it is not possible to give an overall recommendation for long-term treatment. Different scenarios have to be examined separately: Prevention of mania, depression, or an episode of any polarity, both in acute responders and in patients treated de novo. Treatment might differ in Bipolar II patients or Rapid cyclers, as well as in special subpopulations. We identified several medications preventive against new manic episodes, whereas the current state of research into the prevention of new depressive episodes is less satisfactory. Lithium continues to be the substance with the broadest base of evidence across treatment scenarios. Although major advances have been made since the first edition of this guideline in 2004, there are still areas of uncertainty, especially the prevention of depressive episodes and optimal long-term treatment of Bipolar II patients.
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            Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review.

            To update and extend comparisons of rates of suicides and suicide attempts among patients with major affective disorders with versus without long-term lithium treatment. Broad searching yielded 45 studies providing rates of suicidal acts during lithium treatment, including 34 also providing rates without lithium treatment. We scored study quality, tested between-study variance, and examined suicidal rates on versus off lithium by meta-analytic methods to determine risk ratios (RRs) and 95% confidence intervals (CI). In 31 studies suitable for meta-analysis, involving a total of 85,229 person-years of risk-exposure, the overall risk of suicides and attempts was five times less among lithium-treated subjects than among those not treated with lithium (RR = 4.91, 95% CI 3.82-6.31, p < 0.0001). Similar effects were found with other meta-analytic methods, as well as for completed versus attempted suicide, and for bipolar versus major mood disorder patients. Studies with higher quality ratings, including randomized, controlled trials, involved shorter exposures with somewhat lesser lithium superiority. Omitting one very large study or those involving lithium-discontinuation had little effect on the results. The incidence-ratio of attempts-to-suicides increased 2.5 times with lithium-treatment, indicating reduced lethality of suicidal acts. There was no indication of bias toward reporting positive findings, nor were outcomes significantly influenced by publication-year or study size. Risks of completed and attempted suicide were consistently lower, by approximately 80%, during treatment of bipolar and other major affective disorder patients with lithium for an average of 18 months. These benefits were sustained in randomized as well as open clinical trials.
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              Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials.

              Observational studies suggest that long-term lithium treatment has a strong antisuicidal effect in mood disorders, but it is uncertain whether this association is a genuine therapeutic effect or is due to confounding factors in nonrandomized studies. The authors conducted a systematic review and meta-analysis of randomized trials to investigate the effect of lithium, compared to placebo and other active treatments, on the risk of suicide, deliberate self-harm, and all-cause mortality in patients with mood disorder. The data source was the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE (1966-June 2002), EMBASE (1980-June 2002), CINAHL (1982-March 2001), PsycLIT (1974-June 2002), PSYNDEX (1977-October 1999), and LILACS (1982-March 2001). The Cochrane Central Register of Controlled Trials (CENTRAL) was searched with the term "lithium" for new records entered into the database from 1999 to 2003. Studies selected included randomized, controlled trials comparing lithium with placebo or all other compounds used in long-term treatment for mood disorders (unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, and rapid cycling, diagnosed according to DSM or ICD criteria). Of 727 references identified in the search, 52 articles were marked as possibly relevant on the basis of the abstract, and 32 randomized, controlled trials were eligible for inclusion in the review. Two independent reviewers extracted the data, and disagreements were resolved by consensus with a third reviewer. Methodological quality was assessed according to the criteria of the Cochrane Collaboration. When the outcomes of interest were not reported, an attempt was made to obtain the required data from the original authors. In 32 trials, 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds. Patients who received lithium were less likely to die by suicide (data from seven trials; two versus 11 suicides; odds ratio=0.26; 95% confidence interval [CI]=0.09-0.77). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio=0.21; 95% CI=0.08-0.50). There were fewer deaths overall in patients who received lithium (data from 11 trials; nine versus 22 deaths; odds ratio=0.42, 95% CI=0.21-0.87). Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.
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                Author and article information

                Contributors
                rzymskipiotr@ump.edu.pl
                Journal
                Biol Trace Elem Res
                Biol Trace Elem Res
                Biological Trace Element Research
                Springer US (New York )
                0163-4984
                1559-0720
                31 July 2018
                31 July 2018
                2019
                : 189
                : 1
                : 18-27
                Affiliations
                ISNI 0000 0001 2205 0971, GRID grid.22254.33, Department of Environmental Medicine, , Poznan University of Medical Sciences, ; Rokietnicka 8, 60-806 Poznań, Poland
                Author information
                http://orcid.org/0000-0002-4713-0801
                Article
                1455
                10.1007/s12011-018-1455-2
                6443601
                30066063
                608eecfc-0597-4b67-825e-df20318834de
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 2 July 2018
                : 19 July 2018
                Categories
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                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2019

                Biochemistry
                lithium,suicide,micronutrient,fortified food
                Biochemistry
                lithium, suicide, micronutrient, fortified food

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