Does longer-term spermidine supplementation affect memory performance and biomarkers in older adults with subjective cognitive decline?
Spermidine, a randomized controlled trial (JAMA Netw Open 2022, PMID 35616942) — longer-term spermidine supplementation (0.9 mg/d) did not significantly improve memory or biomarkers in older adults with subjective cognitive decline compared to placebo. Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P =.47) or secondary outcomes.
Source: JAMA Netw Open 2022, PMID 35616942 ↗ · Research map · How Magellan grades evidence · evidence confidence: high
JAMA Netw Open · 2022 · PMID 35616942 · DOI 10.1001/jamanetworkopen.2022.13875
A 12-month daily spermidine supplement did not improve memory or biomarkers in older adults with subjective cognitive decline, though exploratory findings suggest possible benefits for verbal memory and inflammation.
The question
Does longer-term spermidine supplementation affect memory performance and biomarkers in older adults with subjective cognitive decline?
What they tested
Spermidine supplementation will show beneficial effects on memory performance and biomarkers in older adults with subjective cognitive decline, based on prior animal studies and preliminary human evidence.
How they did it
This was a 12-month randomized, double-masked, placebo-controlled phase 2b trial (SmartAge trial) conducted at a single academic clinical research center in Germany. One hundred participants aged 60 to 90 years with subjective cognitive decline were randomly assigned (1:1) to receive either 0.9 mg/d of a spermidine-rich wheat germ extract or placebo (microcrystalline cellulose). The primary outcome was the change in mnemonic discrimination performance from baseline to 12 months, assessed by the Mnemonic Similarity Task. Secondary outcomes included other neuropsychological, behavioral, and physiological parameters, with safety also assessed.
What they found
A total of 100 participants (51 in the spermidine group, 49 in the placebo group; mean age 69 years; 49% female) were included in the analysis. Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) or secondary outcomes. Exploratory analyses suggested possible beneficial effects on inflammation and verbal memory. Adverse events were balanced between the groups.
What it means
Longer-term spermidine supplementation (0.9 mg/d) did not significantly improve memory or biomarkers in older adults with subjective cognitive decline compared to placebo. Exploratory findings on verbal memory and inflammation require validation in future studies, potentially with higher dosages.
Limitations
The study was a monocenter trial, and the dosage of spermidine (0.9 mg/d) might have been insufficient to elicit significant effects. The observed beneficial effects on verbal memory and inflammation were exploratory and require further validation.
The paper at a glance
| Title | Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial |
|---|---|
| Journal | JAMA Netw Open |
| Year | 2022 |
| PMID | 35616942 ↗ |
| DOI | 10.1001/jamanetworkopen.2022.13875 ↗ |
| Topic | Brain, cognition & mood |
Read the source: PubMed record (authors, abstract, full citation) ↗ · Publisher via doi.org ↗
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Spermidine (Wheat-Germ Extract)
In model organisms (yeast, worms, flies and mice) spermidine induces autophagy and extends lifespan, and in rodents it reduces age-related cardiac dysfunction and blood pressure and improves memory. Human evidence is earlier-stage and genuinely mixed.
Spermidine is a naturally occurring polyamine present in all human cells and obtained from the diet…
Research describes the compound or intervention studied. It is not a claim about any specific product.
Molecules & mechanisms in this paper
Each of these is named in the paper’s own words above. Open the monograph for the full mechanism and its other citations.
Cite this page
These citations point at this summary. To cite the original paper with its full author list, use the PubMed record or doi.org.
Magellan Longevity. (2026). Does longer-term spermidine supplementation affect memory performance and biomarkers in older adults with subjective cognitive decline? [Plain-English summary of JAMA Netw Open 2022, PMID 35616942, DOI 10.1001/jamanetworkopen.2022.13875]. Magellan Longevity. https://magellanlongevity.com/study/x3.html@misc{magellan_x3,
title = {Does longer-term spermidine supplementation affect memory performance and biomarkers in older adults with subjective cognitive decline?},
author = {{Magellan Longevity}},
year = {2026},
howpublished = {\url{https://magellanlongevity.com/study/x3.html}},
note = {Plain-English summary of PubMed PMID 35616942; DOI 10.1001/jamanetworkopen.2022.13875; JAMA Netw Open 2022. Reviewed by Gabriel Radu, DO},
urldate = {2026-08-11}
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