Spermidine Supplement Shows Promise in Boosting COVID-19 Vaccine Response in Older Adults
Key Insights
A pilot trial found that daily spermidine supplementation improved antibody responses to COVID-19 (search) vaccination in older adults who previously responded poorly.
About one quarter of participants aged 65 and older showed weak antibody responses despite three vaccine doses, with immune cells displaying signs of biological aging.
Spermidine reduced markers of immunosenescence (search) and stimulated autophagy, the cellular recycling process that declines with age.
A naturally occurring compound found in aged cheeses, mushrooms, and wheat germ may help restore waning vaccine responses in older adults, according to a pilot study published in Aging Cell. Researchers led by Dr. Katja Simon at the Max Delbrück Center (search) and Dr. Ghada Alsaleh at the University of Oxford demonstrated that a daily supplement of spermidine improved immune responses to COVID-19 (search) vaccination in healthy individuals aged 65 and older, particularly among those who had failed to mount adequate protection after repeated immunization.
The findings address a persistent challenge in vaccinology: immunosenescence (search), the gradual deterioration of the immune system with age. This biological aging process leaves older adults more vulnerable to infections and can render vaccines less effective, a problem underscored during the COVID-19 (search) pandemic and previously documented with influenza vaccines.
A targeted approach for vaccine non-responders
The study enrolled 40 healthy adults aged 65 and older. Following their third COVID-19 (search) vaccination, participants received either six milligrams of spermidine daily or a placebo for 13 weeks. The researchers identified that approximately one quarter of participants produced very weak antibody responses despite three vaccine doses. Their immune cells carried clear signs of biological aging, including increased DNA damage and markers of cellular senescence—a state in which damaged or aging cells stop functioning properly and begin to accumulate.
Among these vaccine non-responders who took spermidine, several measures of vaccine-induced immunity improved substantially. They tended to have higher levels of antibodies against SARS-CoV-2 (search) and stronger neutralizing activity against multiple viral variants, meaning their antibodies were better able to block the virus in laboratory tests.
“Many older adults respond well to vaccines,” said Dr. Ghada Alsaleh, Associate Professor at the Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences at the University of Oxford. “But some do not develop strong protection, even after repeated vaccination. Biological aging of immune cells may be one reason why this happens. Our findings suggest that spermidine could help restore aspects of immune function in this group.”
Mechanism rooted in cellular housekeeping
Spermidine is a natural polyamine produced by the body and also present in foods such as wheat germ, mushrooms, and aged cheeses including parmesan and cheddar. Previous research has linked the molecule to cellular maintenance processes that tend to decline with age, particularly autophagy—the cell's internal recycling system that breaks down damaged components and reuses useful materials to sustain healthy function.
The research team found that spermidine supplementation reduced markers of immunosenescence (search) and stimulated autophagy. The supplement appeared safe and well tolerated, with no adverse effects linked to the treatment.
Cautious optimism and next steps
Despite the encouraging results, the researchers emphasized the preliminary nature of the findings. “This study was designed as a pilot trial and involved a relatively small number of participants,” said Dr. Katja Simon, Group Leader of the Cell Biology of Immunity lab at the Max Delbrück Center (search). “Larger studies will be needed to determine whether spermidine can consistently improve vaccine responses and whether similar effects are seen with other vaccines, such as those used against seasonal influenza.”
The study also involved collaborators from the Oxford Vaccine Group, including Drs. Paul Klenerman, Teresa Lambe, and Lucy Jones, as well as Owen B. Spiller from Cardiff University. The full reference is: “Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults—A Pilot Study” by Ghada Alsaleh et al., published 22 May 2026 in Aging Cell (DOI: 10.1111/acel.70545).