Lithium (low-dose, longevity context)

Trace lithium exposure from drinking water (~0.01–0.1 mg/L) has been associated with lower all-cause mortality in ecological studies in Japan, Texas, and Europe; the proposed mechanism is GSK-3β inhibition and induction of autophagy, with extension of lifespan demonstrated in C. elegans. Therapeutic-dose lithium carbonate (300–1800 mg/day) is approved worldwide for bipolar disorder and has neuroprotective signals, but is constrained by renal, thyroid, and parathyroid toxicity at long-term use. Microdose lithium orotate (1–5 mg elemental lithium) is sold as a dietary supplement in the US under DSHEA and as a food supplement (Nahrungsergänzungsmittel) in Germany — it is not a licensed medicine, and BfArM has historically treated higher-strength preparations as medicinal. No adequately powered RCT supports a longevity indication. In August 2025 the Yankner group reported (Liu et al., Nature) that endogenous brain lithium is depleted in mild cognitive impairment and Alzheimer disease, with amyloid-β sequestering available lithium; a small 2026 JAMA Neurology pilot RCT (n≈80) in MCI did not meet its primary endpoint but reported a verbal-memory signal. Neither establishes a longevity indication.