Tier 2 — strong

Effects of Spermidine Supplementation on Vascular Brain Health in Older Individuals with Subjective Cognitive Decline - An Exploratory MRI Analysis

Claudia Schwarz, Katharina Wurdack, Stefan Hetzer, Andrea Dell'Orco, Silke M Wortha, Daria Antonenko, Gloria S Benson, Nora Horn, Ulrike Grittner, Sebastian J Hofer, Tobias Eisenberg, Stephan J Sigrist, Dietmar Schmitz, Miranka Wirth, Frank Madeo, Agnes Flöel
Aging and Disease 2026 Online ahead of print (9 Oct 2026)

Bibliography

PubMed
PMID 42858321
DOI
10.14336/AD.2026.0559
Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.

Study snapshot

DesignExploratory secondary MRI analysis of randomized, double-blind, placebo-controlled SmartAge trial
ModelOlder adults aged 60-90 years with subjective cognitive decline
Sample75 participants in MRI analysis
InterventionSpermidine-rich wheat germ supplement providing 0.9 mg spermidine/day versus placebo
Duration12 months
EndpointsCerebral blood flow; White-matter microstructure; White-matter hyperintensities; Brain volume; Cortical thickness; Memory performance

What the study showed, in plain terms

A new 2026 secondary analysis of SmartAge found selected regional differences in cerebral blood flow and white-matter microstructure after 12 months of 0.9 mg/day spermidine, while brain volume, cortical thickness and white-matter hyperintensity outcomes were largely unchanged.

Key findings

Precuneus cerebral blood flow increased relative to placebo and cingulate white-matter fractional anisotropy was better preserved, but the MRI changes were not substantially associated with memory changes. These are exploratory neuroimaging signals, not proof of cognitive benefit.

What this study can and cannot tell us

Secondary exploratory analysis, n=75, multiple regional MRI outcomes and no clear linkage between imaging changes and memory. Independent confirmation is required, and the parent SmartAge trial was null on its primary memory endpoint.

Editorial review

Reviewed by the Biohack Blueprint research team

Khaled Mahmoud