Lithium in Water and Neuroprotection
Essential in medicine as lithium salts (e.g., lithium carbonate, lithium citrate). Naturally present in many groundwater sources.
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Methods
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Search strategy
Packed with essential trace minerals for The initial search for the present review was conducted on May 12th, 2024. The terms used to gather the studies from PubMed for this review included: (Lithium) AND (Drinking Water) AND (Dementia) AND (Humans). This primary search yielded 13 studies which were saved and subsequently uploaded into Covidence, a systematic review tool for abstract screening. Two screeners were involved in this procedure to ensure the studies included were appropriate for the present review (JFP, TH).
Eligibility criteria
The exclusion and inclusion criteria for this review were determined a priori using the “eligibility criteria” tab in Covidence. These eligibility criteria were pre-established to increase the consistency and reliability of the identified sample, while potentially controlling for bias.
Inclusion criteria
The inclusionary criteria for the population included studies on human adults (18 +) focusing on dementia outcomes in relation to trace or low-Li levels in drinking water. Finally, only papers published in the English language were considered in this review.
Screening process
13 studies were uploaded into Covidence for screening. Upon reviewing the 13 abstracts, 3 studies were deemed irrelevant. Two of those studies were excluded as their target population did not meet the a priori-determined eligibility criteria (one focusing on mice and another on adolescents) and one due to being altogether unrelated to the topic of review.
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Trace Lithium in Drinking Water and Its Association with Dementia Risk: A Systematic Review
Lithium is a naturally occurring mineral found in soil, rocks, and, in trace amounts, drinking water. While best known for its use in psychiatric medicine to treat bipolar disorder and depression, research has uncovered intriguing evidence that even low levels of lithium in drinking water may provide potential neuroprotective benefits.
Results
We conducted a systematic review of five studies examining the relationship between trace lithium (Li) in drinking water and dementia incidence or mortality. Associations between trace Li exposure and a reduced risk of dementia were reported at concentrations as low as 0.002 mg/L to 0.056 mg/L, whereas levels below 0.002 mg/L showed no protective effect. While three of the five studies indicated neuroprotective benefits of lithium in both men and women, one study—including lower concentrations (0.002 mg/L)—found such an effect only among women.
Advantages
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SPRING WATER’S LIFECYCLE THAT GIVES IT CRITICAL NUTRIENTS
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Neuroprotective Effects of Lithium
Lithium (Li) was first introduced to psychiatry in 1949 (Cade, 1949) and has since remained the gold standard for treating mood disorders. Even after 75 years of clinical use, lithium continues to reveal novel pharmacodynamic properties that may broaden its therapeutic applications. For instance, preclinical research demonstrates that lithium protects neurons against a variety of toxins and models of neurodegenerative disease (Lauterbach & Mendez, 2011; Qu et al., 2011; Dou et al., 2005; Nunes et al., 2015). Human brain imaging studies—across cross-sectional, longitudinal, and even randomized controlled trial designs—have likewise suggested neuroprotective effects of lithium (Lyoo et al., 2010). These findings raise the possibility that lithium may have utility in the treatment of neurodegenerative disorders.
Despite encouraging preclinical and imaging evidence, clinical trials specifically examining lithium’s neuroprotective potential remain limited. Concerns about toxicity, which is dose-dependent and can be more pronounced in older adults (Arnaoudova, 2014; Adityanjee & Thampy, 2005; Mecê et al., 2022), may partly explain this gap. However, such concerns may be overstated. Controlled studies show lithium can be used safely even in cognitively impaired older adults (Aprahamian et al., 2014), and lithium-treated elderly patients often demonstrate better overall and mental health outcomes than their untreated counterparts with bipolar disorder (Forlenza et al., 2022). Importantly, the doses required for neuroprotection may be substantially lower than those needed for mood stabilization.
Similarly, randomized controlled studies using subtherapeutic doses (0.25–0.5 mmol/L) found reduced cerebrospinal fluid P-tau levels and improvements in functional preservation (Forlenza et al., 2011; Forlenza et al., 2019). These findings have positioned nano-lithium as a promising candidate in drug-repurposing efforts for neurodegenerative diseases (Cummings et al., 2023). Collectively, they indicate that lithium doses far below those used in psychiatry may exert meaningful effects in preventing cognitive decline and dementia.
Moreover, epidemiological studies suggest that even trace lithium exposure from drinking water may confer long-term protection against dementia (Kessing et al., 2017; Parker et al., 2018; Fajardo et al., 2017; Muronaga et al., 2022; Duthie et al., 2023). Despite these promising findings, the evidence has not yet been comprehensively synthesized. The present manuscript aims to review the literature on trace lithium exposure and dementia risk, providing an evidence base to inform future trials on the use of low-dose lithium to prevent or delay the onset of dementia.