Tier 3 — preclinical

Association of spermidine plasma levels with brain aging in a population-based study

Silke M Wortha, Stefan Frenzel, Martin Bahls, Mohamad Habes, Katharina Wittfeld, Sandra Van der Auwera, Robin Bülow, Stephanie Zylla, Nele Friedrich, Matthias Nauck, Henry Völzke, Hans J Grabe, Claudia Schwarz, Agnes Flöel

Alzheimer's & Dementia 2023 19(5):1832-1840

Bibliography

PubMed: PMID 36321615
PubMed Central: PMC11246659
DOI: 10.1002/alz.12815
Funding: Supported by SHIP/German federal and state funding, Siemens Healthineers with Mecklenburg-West Pomerania, NIH grants, Deutsche Forschungsgemeinschaft grants, and ERA PerMed/BMBF support as disclosed in the paper.
Competing interests: H.J. Grabe disclosed travel grants, speaker honoraria and research funding from several medical companies; Agnes Flöel disclosed consulting fees and speaker honoraria from Biogen, Roche, Novartis and Bayer. Other authors declared no conflicts.

Study snapshot

Design	Population-based cross-sectional biomarker and brain MRI study
Model	SHIP-TREND community cohort
Sample	659
Intervention	No intervention; plasma spermidine measured
Duration	Cross-sectional
Endpoints	Hippocampal volume; Cortical thickness; Alzheimer disease pattern score; White matter hyperintensity volume; Plasma spermidine

What the study showed, in plain terms

Contrary to several dietary-intake studies, higher plasma spermidine in this population sample was associated with smaller hippocampal volume, thinner cortex and a less favorable Alzheimer-related brain-imaging pattern.

Key findings

This study is a key warning against assuming that higher circulating spermidine is automatically beneficial. Plasma concentration, dietary intake, tissue metabolism and supplementation exposure are different biological measures.

What this study can and cannot tell us

Cross-sectional design cannot establish directionality. Higher circulating spermidine could be a consequence or marker of altered metabolism rather than a cause of brain aging.

Editorial review

Reviewed by the Biohack Blueprint research team

Khaled Mahmoud