Spermidine (wheat-germ extract vs synthetic trihydrochloride)

Regulatory status: dietary supplement (US); authorised novel-food ingredient in the EU/UK only as spermidine-rich wheat-germ extract, not as isolated synthetic spermidine. Not a medication. Not a device

• Induces autophagy / mitophagy in humans.
• Improves memory / cognition / delays cognitive decline.
• Protects the heart / lowers blood pressure / reduces CVD events.
• Extends human lifespan / reduces all-cause mortality.
• Improves vaccine response / reduces immune senescence.
• Prolongs hair-follicle anagen / reduces hair shedding.
• Safe at common supplement doses (1–6 mg extract; 10 mg 3HCl; 40 mg 3HCl short-term).

Spermidine is a real polyamine. In yeast, worms, flies, and mice it induces autophagy and, in mice, extends median lifespan by about 10% and protects the aging and hypertensive heart — effects that disappear when autophagy genes are deleted. In humans, a spermidine-*rich diet* (Bruneck top tertile >11.6 mg/day from plants, not a pill) is associated with lower all-cause and CVD mortality and lower odds of incident cognitive impairment. That is not the same intervention as a capsule. The capsule evidence is thin and form-specific. The largest cognition RCT (SmartAge, 0.9 mg wheat-germ extract × 12 months, n = 100) was null on its primary memory endpoint and did not raise blood polyamines. The earlier n = 30 pilot is an effect-size signal whose between-group CI includes zero. Nursing-home food trials are high-bias. No supplement RCT has published a CV or mortality outcome. The 10 mg trihydrochloride serving has **zero** outcome trials. The spoken 1 g dose is a documented error for 1–2 mg active — a landmine, not a protocol. Autophagy in human *tissues that matter* (heart, brain) has not been shown; the 2026 6 mg vaccine pilot moved PBMC flux in a TLL-supplied product.