Lithium in drinking water and suicide prevention: The largest nationwide epidemiological study from Japan

Kugimiya, Tsuyoshi; Ishii, Nobuyoshi; Kohno, Kentaro; Kanehisa, Masayuki; Hatano, Koji; Terao, Takeshi

doi:10.1111/bdi.12983

Cited by 31 publications

(20 citation statements)

References 22 publications

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“…Additionally, this necessitates further clinical studies to confirm the aforementioned findings. For example, in the association between suicide rate and lithium in drinking water, we performed clinical studies [2,3] to directly confirm the indirect evidence from epidemiological studies [27][28][29][30] although we could not perform RCTs for that field.…”

Section: Discussionmentioning

confidence: 99%

The Present State of Lithium for the Prevention of Dementia Related to Alzheimer’s Dementia in Clinical and Epidemiological Studies: A Critical Review

Ishii

Terao

2021

IJERPH

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Despite the unavailability of essential anti-dementia drugs, lithium may inhibit glycogen synthase kinase-3 (GSK-3) and decrease beta-amyloid and hyper-phosphorylated tau. In this review, we hypothesized that trace to standard levels of lithium (i.e., corresponding to the therapeutic levels for bipolar disorder) may be effective for dementia prevention. Excluding three insufficient level studies, we obtained two and one excellent clinical studies on standard and trace lithium levels, respectively, all of which supported the effects of lithium for dementia prevention. In addition, we identified good clinical and epidemiological studies (four each) on standard lithium levels, of which six studies supported the effects of lithium. Moreover, of three good epidemiological studies on trace lithium levels, two supported the aforementioned effects of lithium. The number of studies were substantially small, particularly those on trace lithium levels. Moreover, studies on standard lithium levels were insufficient to establish the efficacy of lithium for dementia prevention. This necessitates accumulating good or excellent clinical evidence for the effects of trace to standard lithium levels on dementia prevention.

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Section: Discussionmentioning

confidence: 99%

The Present State of Lithium for the Prevention of Dementia Related to Alzheimer’s Dementia in Clinical and Epidemiological Studies: A Critical Review

Ishii

Terao

2021

IJERPH

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“…Most of natural bodies of water have higher Na content, which alleviates toxic Li effects (Kszos & Stewart, 2003;. Kugimiya et al (2020) reviewed the literature data and concluded that Li content in drinking water ranges from 0 to 219 µg/L depending on the location and environmental conditions. Li found in drinking water is completely bioavailable.…”

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confidence: 99%

Lithium in the Environment and its Effects on Higher Plants

Kastori

Maksimović

Putnik-Delić

2022

Contemporary Agriculture

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Summary Lithium (Li) is present in low concentrations in all parts of the biosphere, including living organisms. It reaches the terrestrial environment primarily through natural processes to which parent substrate was subjected during pedogenesis, and due to anthropogenic activities. Individual soil types differ regarding Li content; for example saline and loamy soils have higher Li content. It is found in low concentrations primarily in ionic form in aquatic environments in surface and groundwater. It is mobile in the soil and thus soil contamination with Li can lead to its higher concentration in groundwater. In the environment, Li reaches the atmosphere from Li-emitting sources. It is widely used in many industries, lately in the Li-ion batteries in electronic goods, due to which it may be a potential risk for the environment. Terrestrial plants take up Li largely via roots from the soil, but also via shoots from the atmosphere. In the soil, Li is mostly bound by clay fraction and organic matter. During the uptake, transport and distribution in plants it behaves like an alkaline earth ion, not like an alkali ion. The fact that Li is immobile in the phloem supports this claim. Its ascendent transport mainly depends upon the transpiration intensity. More Li is taken up by plants from acid soils than from alkaline soils. Li is non-essential for plant growth and development. In low concentrations it can be stimulative and affect chemical composition and organic production of plants. Li plays an important role in the metabolism of halophyte species. It is increasingly regarded as an essential trace element for animals and humans, and used in human medication to treat dementia, suicidal ideation, aggression and violence. High levels of Li are toxic to all plants, but uptake and sensitivity to Li are species-dependent. Some representatives of the Ranunculaceae, Solanaceae and Asteraceae families are characterized by increased Li accumulation, while Poaceae, Liliaceae, Brassicaceae, Caprifoliaceae show low accumulation. High concentrations of Li have adverse effects on many physiological and biochemical processes in plants (DNA, RNA and protein pathways, water relations, content of photosynthetic pigments, photosynthesis, production of reactive oxygen species, lipid peroxidation of the cell membranes etc.), which is further manifested as stunted growth, developmental disorder, visual symptoms, interveinal necrosis and necrosis along the leaf margins. Hyperaccumulator plants extract significant amounts of Li and are therefore used in phytoremediation. Better understanding of the effects of beneficial and phytotoxic concentrations of Li on metabolism and plant growth and development remains vital for the improvement of the knowledge about biological activity of Li in higher plants.

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“…The potential minimum effective dose of lithium in preventing suicide should be examined. As a previous study showed that 30 µg/L or more lithium concentration in drinking water is associated with lower suicide rate [ 36 ], a certain minimum dose of lithium may be required to achieve anti-suicidal properties. Although several studies have examined the effect of micro-dose lithium on mood or cognitive impairment [ 26 , 27 , 37 ], no clinical trial has investigated the effect of micro-dose lithium on suicide.…”

Section: Discussionmentioning

confidence: 99%

Comparison of lithium levels between suicide and non-suicide fatalities: Cross-sectional study

et al. 2022

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Ecological studies have suggested the protective effect of micro-dose lithium in drinking water against suicide, however, the association between body lithium level and suicide is unknown. We aimed to compare body lithium levels between suicide and non-suicide fatalities. This cross-sectional study included 12 suicides and 16 non-suicides who were examined or dissected at the Tokyo Medical Examiner’s Office from March 2018 to June 2021. The aqueous humor lithium concentration was measured twice using inductively coupled plasma mass spectrometry. Analysis of covariance (ANCOVA) was used to compare the lithium concentration between suicides and non-suicides. Mixed-effects model was conducted to account for all lithium concentration data. The aqueous humor lithium concentration did not change after death (t(7) = −0.70, $$\bar v = - 0.02$$ v ¯ = − 0.02 , SE = 0.03, 95% CI = [−0.09, 0.05], P = 0.51, Cohen’s d = 0.01). The aqueous humor lithium concentration was lower in suicides (mean 0.50 μg/L (variance s2 0.04)) than in non-suicides (mean 0.92 μg/L (s2 0.07)) (t(26) = 4.47, $$\bar v = 0.42$$ v ¯ = 0.42 , SE = 0.09, 95% CI = [0.22 to 0.61], P < 0.001, Cohen’s d = 1.71). The ANCOVA showed that death by suicide was significantly associated with lower lithium concentration (F(1, 24) = 8.57, P = 0.007), and the effect size was large (ηp2 = 0.26). The random intercept model showed a significant effect of suicide on aqueous humor lithium concentration (b = −0.261, SE = 0.102, 95% CI = [−0.471 to −0.051], t(24) = −2.568, P = 0.017). The results of this study demonstrate that even micro-dose lithium is associated with suicide death. Clinical studies are warranted to examine the effects of micro-dose lithium on suicide prevention.

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Lithium in drinking water and suicide prevention: The largest nationwide epidemiological study from Japan

Cited by 31 publications

References 22 publications

The Present State of Lithium for the Prevention of Dementia Related to Alzheimer’s Dementia in Clinical and Epidemiological Studies: A Critical Review

The Present State of Lithium for the Prevention of Dementia Related to Alzheimer’s Dementia in Clinical and Epidemiological Studies: A Critical Review

Lithium in the Environment and its Effects on Higher Plants

Comparison of lithium levels between suicide and non-suicide fatalities: Cross-sectional study

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