The most rigorous human dosing data for spermidine comes from the SmartAge trial (0.9 mg/day spermidine from wheat germ extract, 12 months in older adults with subjective cognitive decline) and the MemoriCog trial (1.2 mg/day). Both show cognitive benefits without safety concerns. Longevity practitioners typically use 2–4 mg/day for more comprehensive autophagy activation.

Should I start at 0.9 mg/day and work up?

A step-up approach (0.9 mg for month 1, 1.8 mg for month 2, then 3–4 mg for maintenance) allows assessment of individual response and tolerability. However, no adverse effects have been documented at any dose in the literature.

Does taking more than 4 mg/day add benefit?

Japanese studies have used up to 10 mg/day without reported adverse effects. Whether benefits scale linearly above 4 mg/day is not established. The marginal benefit above 4 mg/day likely diminishes relative to cost.