Spermidine supplement may improve some older adults’ vaccine response
An Oxford-led pilot trial found the compound was linked to stronger COVID-19 vaccine immunity in older adults with weak responses.
By Priya Raghavan · Science Reporter
3 min read
A small Oxford-led clinical trial has found that daily spermidine supplements may strengthen vaccine responses in some older adults whose immune cells show signs of aging. The finding could help researchers identify why a subset of older people remains poorly protected after repeated vaccination.
Researchers at the University of Oxford’s Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, or NDORMS, reported the results in the journal Aging Cell. The team was led by Professor Katja Simon and Associate Professor Ghada Alsaleh, according to the university.
Spermidine is a molecule produced naturally by human cells and also found in foods including wheat germ, mushrooms, some cheeses, lentils, chickpeas and broccoli, according to Oxford. Previous research cited by the team has suggested the compound may support cell maintenance processes that weaken with age.
The study focused on immunosenescence, the gradual decline in immune function that occurs as people get older. Oxford said that process can reduce the body’s ability to respond to infections and vaccines, contributing to poorer protection in later life.
Oxford noted that more than 92% of COVID-related deaths during the pandemic occurred in people older than 60. Vaccination reduces severe illness and death, but older adults can generate lower protective antibody and T-cell responses than younger people, including after influenza vaccination, the university said.
How the trial was run
The pilot trial enrolled 40 healthy adults older than 65 who had already received three doses of a COVID-19 vaccine, according to the Aging Cell paper. The study was double-blind, randomized and placebo-controlled.
Participants received either a daily spermidine supplement or a placebo for 13 weeks after their third COVID-19 vaccination. Oxford said the supplement was safe and well tolerated, with no treatment-linked adverse effects reported.
The researchers found that about one-quarter of participants had very weak antibody responses despite three vaccine doses. Those participants’ immune cells showed signs of biological aging, including higher DNA damage and markers tied to cellular senescence, according to the study.
In that group of vaccine nonresponders, spermidine use was associated with stronger measures of vaccine immunity. Oxford said participants showed higher antibody levels against SARS-CoV-2, stronger B-cell responses and improved neutralizing activity against multiple viral variants.
The research team also reported that spermidine appeared to reduce markers of immune-system aging and stimulate autophagy. Autophagy is a cellular recycling process that helps cells clear damaged components and maintain normal function, according to the university.
Researchers urge larger studies
Alsaleh said the findings suggest that biological aging in immune cells may help explain why some older adults fail to build strong protection even after repeat vaccination. She said the work could help identify people at risk of weak vaccine responses and point to interventions aimed at aging-related immune changes.
Simon cautioned that the study was designed as a pilot and included a relatively small number of people. She said larger trials will be needed to test whether spermidine reliably improves vaccine responses and whether similar effects occur with other vaccines, including seasonal influenza shots.
The paper, “Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults—A Pilot Study,” was published in Aging Cell in 2026. The reported DOI is 10.1111/acel.70545.
This story draws on original reporting from Medical Xpress.