Spermidine for 12 months: small brain-scan differences in older adults, but no link to memory

Spermidine, a compound found naturally in the body and sold as a supplement, has attracted interest for brain health. A new analysis of brain scans from a 12-month trial, published in Aging and Disease on October 9, 2026, found some small differences in older adults who took it. The researchers describe the findings as preliminary, and the scan changes were not linked to changes in memory.

What the researchers did

The scans come from SmartAge, a randomized, double-blind, placebo-controlled trial. It tested 0.9 mg of spermidine a day for 12 months in people aged 60 to 90 with subjective cognitive decline, meaning they felt their memory or thinking had got worse, even if tests may not show it. This new paper is an exploratory secondary analysis: the researchers went back to MRI scans from 75 participants to look at “vascular brain health”, including blood flow in the brain (cerebral blood flow), the condition of the brain’s wiring (white matter microstructure), white matter damage, brain volume and cortical thickness.

What they found

• Blood flow in one area: cerebral blood flow in a region called the precuneus rose in the spermidine group compared with placebo, by a difference of 4.9 ml/100 g/min (95% CI 1.0 to 8.9; P = 0.015). A similar but weaker trend in the posterior cingulate was not statistically significant (3.7; 95% CI -0.5 to 7.8; P = 0.08).
• White matter: a measure of white matter structure (fractional anisotropy) in one bundle, the cingulate, stayed stable with spermidine but fell with placebo (difference 0.016; 95% CI 0.002 to 0.031; P = 0.029).
• Nothing else clearly changed: there were no substantial differences in overall or regional brain volume, cortical thickness or white matter damage.
• No link to how people performed: the scan changes were not associated with changes in memory performance, self-reported memory complaints or a blood marker of blood-vessel inflammation (sICAM-1). The two scan changes were also not substantially associated with each other.

The authors say these findings are “preliminary and require independent confirmation”.

What this means for you

What this means for you

• What was studied: 0.9 mg of spermidine a day for 12 months.
• Who was studied: adults aged 60 to 90 who had noticed memory decline.
• What it shows: a couple of small differences in scans of specific brain regions. It does not show better memory or healthier aging.
• Evidence strength (our simple scale: very low, low, moderate, high): very low for brain benefits. These are exploratory results from a subgroup, and several measures showed no difference.
• Read more in our beginner’s guide to spermidine.

How strong is this evidence?

The trial it comes from was randomized and placebo-controlled, which is a good design. However, this paper is a secondary analysis that looks at many scan measures in just 75 people, and only a few showed differences. When you test many measures, some small “hits” can appear by chance, which is one reason the authors call it exploratory. Importantly, the scan differences did not line up with any difference in memory. We read the abstract, the PubMed record and the publisher listing only, so we cannot report group sizes, funding or conflicts of interest, and we have not read the trial’s main memory results.

Sources

• Schwarz C, Wurdack K, Hetzer S, et al. Effects of spermidine supplementation on vascular brain health in older individuals with subjective cognitive decline: an exploratory MRI analysis. Aging and Disease, published October 9, 2026. DOI: 10.14336/AD.2026.0559 / PubMed 42858321
• Publisher listing: Max Delbrück Center (abstract and author list read)

This article is for information only and is not medical advice. Speak to a healthcare professional before changing medication or supplements.