Spermidine Supplement Boosts Vaccine Response in Older Adults

As people age, their immune systems become progressively less effective — a process called immunosenescence. This decline means older adults often mount weaker responses to vaccines, leaving them more vulnerable to infections like COVID-19 and influenza even after repeated doses. Finding safe, accessible interventions to reverse this trend is a priority in longevity medicine.

Researchers at the Max Delbrück Center and University of Oxford investigated whether spermidine, a naturally occurring polyamine compound, could improve vaccine responses in older adults. In a small randomized pilot trial, 40 healthy adults aged 65 and older received either 6mg of spermidine or a placebo daily for 13 weeks after their third COVID-19 vaccination. The study was published in the journal Aging Cell.

The most striking results emerged in a subset of participants — roughly one quarter — who were classified as vaccine nonresponders due to persistently weak antibody production. In this group, those who received spermidine showed meaningfully higher antibody levels against SARS-CoV-2 and stronger neutralizing activity across several viral variants. Their immune cells also showed reduced markers of cellular senescence and DNA damage, suggesting spermidine may help rejuvenate aging immune machinery.

Spermidine is produced naturally by human cells and is present in foods including wheat germ, mushrooms, parmesan, and cheddar. Prior research suggests it activates autophagy — a cellular cleanup process that declines with age — which may explain its immune-supportive effects. The compound's food-based availability and established safety profile make it an attractive candidate for further investigation.

Important caveats apply. This was a small pilot trial, and results should be considered preliminary until confirmed in larger, adequately powered studies. Effects were most pronounced in the weakest immune responders, so benefits may not generalize broadly. Optimal dosing, timing relative to vaccination, and long-term safety also remain to be established.