Introduction: Lithium is a medication used to treat bipolar disorder and may also prevent cognitive decline and suicide. Lithium is also found naturally, in levels well below clinical doses, in drinking water worldwide, and levels have been inversely associated with rates of psychiatric disorders. Lead (Pb) is another element in the environment but is a toxin of public health concern. Negative effects of chronic lead exposure and possible benefits of environmental lithium exposure appear complementary.
Hypothesis: Exposure to environmental lithium has associated benefits, which may be due to the mitigation of lead toxicity by lithium.
Methods: A series of reviews tested each element of the hypothesis. A systematic review clarified the psychiatric and medical correlates of lithium in drinking water. Non-systematic reviews clarified the harms of environmental lead, summarized experimental studies of lithium used to prevent lead toxicity, and explored overlapping biological mechanisms in lithium and lead exposure.
Results: Higher levels of lithium in drinking water were associated with lower suicide rates in 13 of 15 identified studies. While fewer studies were available for other outcomes, lithium was associated with lower rates of homicide, crime, dementia, and mortality. Lead was reported to be ubiquitous in the environment, and chronic low-level exposure has been associated with adverse effects, including effects opposite to the outcomes associated with lithium. Animal studies demonstrated that lithium pre-treatment mitigates lead toxicity. Neurophysiological correlates of lead and lithium exposure overlap.
Conclusions: Microdose lithium is associated with better psychiatric and medical outcomes, which are complementary to harms of environmental lead exposure. Experimental animal evidence is supportive, and lead and lithium impact overlapping neurophysiologic pathways. Therefore, several lines of circumstantial evidence suggest that lithium protects against the neurotoxic effects of lead. Further studies are required to clarify the benefits and mechanisms of low-dose lithium. There are significant public health implications if this paper's hypothesis is true.
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