Lithium carbonate — The GSK-3 Inhibitor
Lithium is a naturally occurring trace mineral and well-established mood stabiliser that has recently gained attention for its potential anti-ageing properties. It promotes longevity and healthspan in multiple animal models, primarily by inhibiting GSK-3 and activating stress-response pathways.
Mechanism of Action
Lithium acts as a direct and indirect inhibitor of Glycogen Synthase Kinase-3 (GSK-3), a key regulatory enzyme involved in cellular ageing and neurodegeneration. By inhibiting GSK-3, lithium upregulates the NRF2 antioxidant pathway, enhancing cellular resilience against oxidative stress. It also stimulates autophagy, facilitating the clearance of damaged proteins and organelles. Additionally, lithium has been shown to modulate the Wnt/β-catenin pathway and promote neurogenesis, contributing to its neuroprotective effects.
Human Trial Evidence
Retrospective observational studies in humans have linked trace levels of lithium in drinking water to reduced all-cause mortality and increased lifespan. A recent analysis of the UK Biobank also found that clinical lithium treatment is associated with extended lifespan. However, there are currently no published prospective, randomised controlled trials specifically evaluating lithium for longevity in healthy humans.
Dosing Protocol
For longevity and neuroprotection, 'microdosing' or low-dose lithium (e.g., 1–5 mg of elemental lithium per day) is commonly discussed, though unestablished in clinical trials. Clinical doses of lithium carbonate for bipolar disorder are much higher (typically 600–1,200 mg/day) and require a prescription and strict blood level monitoring.
Safety & Contraindications
High-dose clinical lithium requires a prescription and carries risks of renal toxicity, hypothyroidism, and nephrogenic diabetes insipidus, necessitating regular blood monitoring. Low-dose or trace lithium is generally considered safe but should still be used with caution. It can interact with NSAIDs, ACE inhibitors, and diuretics, which may increase lithium blood levels and toxicity risk.