Evidence Level
Evidence for low-dose lithium is primarily epidemiological and mechanistic rather than from clinical supplement trials. The most compelling data comes from ecological studies: a 2011 meta-analysis by Vita et al. (British Journal of Psychiatry) analyzing 9 studies found a consistent inverse association between natural lithium in drinking water and suicide rates across multiple countries. Fajardo et al. (2018) extended this finding to dementia, showing lower Alzheimer mortality in regions with higher water lithium. Mechanistically, lithium is a potent GSK-3 beta inhibitor and BDNF inducer — both are validated therapeutic targets for mood disorders and neurodegeneration. However, direct RCTs of lithium orotate supplements are lacking; most clinical lithium research uses prescription lithium carbonate at much higher doses.