---
title: "Effects of Spermidine Supplementation on Cognition and…"
description: "A 12-month daily spermidine supplement did not improve memory or biomarkers in older adults with subjective cognitive decline, though exploratory…"
url: "https://magellanlongevity.com/study/x3.md"
canonical: "https://magellanlongevity.com/study/x3.html"
html: "https://magellanlongevity.com/study/x3.html"
type: "study"
study_key: "x3"
journal: "JAMA Netw Open"
year: 2022
pmid: "35616942"
doi: "10.1001/jamanetworkopen.2022.13875"
citations: 1
updated: 2026-09-02
author: "Gabriel Radu, DO"
author_credentials: "Physiatrist (PM&R). NY medical license 275110. NPI 1376861765."
publisher: "Magellan Longevity"
content_format: "markdown"
---

# Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial

[Home](https://magellanlongevity.com/) › [Research map](https://magellanlongevity.com/longevity-research-map.html) › Effects of Spermidine Supplementation on Cognition and…

**HTML version:** https://magellanlongevity.com/study/x3.html · **In the Magellan app:** https://magellanlongevity.com/#/study/x3

## Citation

| Field | Value |
| --- | --- |
| Journal | JAMA Netw Open |
| Year | 2022 |
| PMID | [35616942](https://pubmed.ncbi.nlm.nih.gov/35616942/) |
| DOI | [10.1001/jamanetworkopen.2022.13875](https://doi.org/10.1001/jamanetworkopen.2022.13875) |
| Study key | x3 |

## Takeaway

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?

## Hypothesis

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.

## Methods

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.

## Results

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.

## Conclusion

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.

## Verbatim from the abstract

> exploratory analyses indicated possible beneficial effects on verbal memory and inflammation

## Where this study is used on Magellan

This paper is one of the citations behind the evidence grade on the pages below. Grades are assigned from the published research and are independent of affiliate commissions.

| Compound or device | Evidence grade | Graded pages |
| --- | --- | --- |
| Spermidine (Wheat-Germ Extract) | Moderate evidence | [Spermidine (Wheat-Germ Extract)](https://magellanlongevity.com/p/7.md) |

## Reference

1. **Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial**
   JAMA Netw Open 2022 · [PMID 35616942](https://pubmed.ncbi.nlm.nih.gov/35616942/) · [DOI 10.1001/jamanetworkopen.2022.13875](https://doi.org/10.1001/jamanetworkopen.2022.13875)

   > exploratory analyses indicated possible beneficial effects on verbal memory and inflammation

## Structured data

```json
{"@context":"https://schema.org","@graph":[{"@type":"MedicalWebPage","@id":"https://magellanlongevity.com/study/x3.html#page","url":"https://magellanlongevity.com/study/x3.html","name":"Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive…","description":"A 12-month daily spermidine supplement did not improve memory or biomarkers in older adults with subjective cognitive decline, though exploratory…","inLanguage":"en","isPartOf":{"@type":"WebSite","name":"Magellan Longevity","url":"https://magellanlongevity.com/"},"author":{"@type":"Person","name":"Gabriel Radu, DO","jobTitle":"Physiatrist (PM&R)","identifier":[{"@type":"PropertyValue","name":"NPI","value":"1376861765"},{"@type":"PropertyValue","name":"NY medical license","value":"275110"}]},"publisher":{"@type":"Organization","name":"Magellan Longevity","url":"https://magellanlongevity.com/"},"encoding":{"@type":"MediaObject","encodingFormat":"text/markdown","contentUrl":"https://magellanlongevity.com/study/x3.md"},"dateModified":"2026-09-02"},{"@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https://magellanlongevity.com/"},{"@type":"ListItem","position":2,"name":"Research map","item":"https://magellanlongevity.com/longevity-research-map.html"},{"@type":"ListItem","position":3,"name":"Effects of Spermidine Supplementation on Cognition and…","item":"https://magellanlongevity.com/study/x3.html"}]},{"@type":"ScholarlyArticle","@id":"https://magellanlongevity.com/study/x3.html#study","name":"Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial","headline":"Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive…","datePublished":"2022","isPartOf":{"@type":"Periodical","name":"JAMA Netw Open"},"identifier":"PMID:35616942","url":"https://pubmed.ncbi.nlm.nih.gov/35616942/","sameAs":"https://doi.org/10.1001/jamanetworkopen.2022.13875","abstract":"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."}]}
```

## Related on Magellan Longevity

- [Spermidine (Wheat-Germ Extract)](https://magellanlongevity.com/p/7.md) — product graded on this and related evidence
- [Higher spermidine intake is linked to lower mortality: a prospective population-based…](https://magellanlongevity.com/study/sperm_mort.md)
- [Induction of autophagy by spermidine promotes longevity.](https://magellanlongevity.com/study/spermidine_autophagy.md)
- [Cardioprotection and lifespan extension by the natural polyamine spermidine.](https://magellanlongevity.com/study/spermidine_cardio.md)
- [Longevity research map](https://magellanlongevity.com/longevity-research-map.html)
- [Evidence-based longevity supplements](https://magellanlongevity.com/longevity-supplements.md)

## Scope and disclosures

Educational information, not medical advice. Nothing here is intended to diagnose, treat, cure, or prevent any disease. Talk to your physician before starting any supplement or device, especially if you are pregnant, nursing, or taking medication.

Editorial firewall: evidence grades are assigned from the published research and are independent of any affiliate commission. As an Amazon Associate, Magellan Longevity earns from qualifying purchases.

Reviewed for accuracy by a board-certified physician (DO).