Key findings from detailed records
Human spermidine research now reaches immune-cell biology. A 2026 pilot using 6 mg/day reported autophagy-related and antibody-response changes, particularly in a small subgroup with low vaccine responses. This exploratory immune finding is distinct from the earlier memory trials. PMID 42169618
KNOWLEDGE RECORD
- Category
- Ingredients and research
- Last Reviewed
OUTCOME-SPECIFIC EVIDENCE
Scientific Evidence Profile
Assessment pending
An outcome-specific assessment has not yet been completed. This is not a finding that the ingredient is ineffective. The study records below remain available.
This profile concerns the stated outcome and population, not the ingredient as a whole. It is not a probability of benefit, a safety rating, a product efficacy rating or an indication of product adoption.
How we assess evidenceIngredient Profile
- What is it?
- Spermidine is a polyamine with three amino groups. Its name describes a molecule; a spermidine-rich food extract also contains other substances. [1]
Sources for this profile
Compound properties and formulation properties are different. These sources do not establish the efficacy of a finished supplement.
- PubChem — Spermidine (CID 1102) Chemical identity reference. Maintained by NCBI, U.S. National Library of Medicine. Database record; not a clinical trial.
Profile sources checked:
Read the evidence in context
- Evidence: what was measured in the stated population or experimental model.
- Inference: an interpretation connecting findings; its applicability depends on the study conditions.
- Hypothesis: a proposed explanation or effect that remains to be tested.
Why immune-cell maintenance matters #
Cellular maintenance becomes a testable human question when researchers measure autophagy, immune-cell behavior and functional responses together. The 2026 pilot connects these levels in older adults after vaccination. PMID 42169618
What the 2026 pilot found #
The trial used 6 mg/day for 13 weeks. Exploratory improvements in antibody responses and B-cell autophagy were especially apparent among eight initially low responders. Because the placebo arm had only two low responders, the study cannot provide a balanced confirmatory comparison for that subgroup. PMID 42169618
How this relates to memory research #
Immune responses and memory are different questions. The 2018 memory pilot suggested a favorable signal, while the larger 12-month SmartAge trial did not confirm a primary memory benefit. Read these trials alongside, rather than as tests of the same endpoint or preparation. PMID 35616942
What we can learn and what comes next #
The next step is a larger trial with balanced baseline immune responses and predefined outcomes. Tracking cellular mechanisms alongside function can clarify biological relevance; a cell-level change alone is not a measure of slower whole-body ageing. PMID 42169618
LITERATURE MAP / 11 PAPERS
Compare papers by conditions and findings.
A literature map covering different populations, outcomes and formulations. Read alongside detailed records to avoid treating one trial as the conclusion for an entire ingredient.
Initial selection: 2026-09-21; human-study additions: 2026-10-11. Editorial selection spans populations and research questions. The source-review scope is recorded per study; this is not a systematic review.
11 RECORDS
A dash marks fields outside the bibliographic record. Use detailed records to compare findings and design records to connect mechanisms.
| Paper and topic | Study conditions | Findings and scope |
|---|---|---|
| Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults—A Pilot Study. | 40 older adults recruited; baseline analyses: 38, aged 65–81, after a third SARS-CoV-2 vaccine dose. · Spermidine 6 mg/day versus placebo · 13 weeks of intake; immune follow-up to week 37 · Safety, vaccine-specific antibodies, B-cell recall, cellular senescence and autophagy | Exploratory analyses found improved antibody/B-cell responses and autophagy-related changes, particularly in eight initially low responders receiving spermidine. Explore the research |
| Mechanism and designCardioprotection and lifespan extension by the natural polyamine spermidinePMID 27841876 # | Study conditions Mice and other models / Mitophagy and respiration — | Findings and scope Animal experiments reported effects on cardiac autophagy, mitophagy and mitochondrial respiration. These findings inform the focus on quality control through cellular renewal. The main mechanistic findings are from animals, not proof of quality-control effects in humans at 6 mg/day. |
| Cognition and neurologyEffects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.PMID 35616942 # | Study conditions SmartAge: single-center, double-blind, placebo-controlled RCT (phase 2b)
| Findings and scope Between-group difference: −0.03 (95% CI −0.11 to 0.05, p=0.47). No significant improvement in primary or secondary outcomes; some signals in exploratory analyses. View findings and limitations |
| High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study.PMID 37111071 # | Study conditions — | Findings and scope — Open original paper |
| Supplementation of spermidine at 40 mg/day has minimal effects on circulating polyamines: An exploratory double-blind randomized controlled trial in older men.PMID 39405978 # | Study conditions — | Findings and scope — Open original paper |
| Human Supplementation with AM3, Spermidine, and Hesperidin Enhances Immune Function, Decreases Biological Age, and Improves Oxidative-Inflammatory State: A Randomized Controlled Trial.PMID 39594533 # | Study conditions — | Findings and scope — Open original paper |
| Longitudinal association of dietary spermidine with hepatic function indexes and cardiometabolic traits in older adults with metabolic syndrome.PMID 42455181 # | Study conditions — | Findings and scope — Open original paper |
| Cognition and neurologyThe effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.PMID 30388439 # | 30 adults aged 60–80 with subjective cognitive decline · Spermidine-rich wheat-germ extract, providing 1.2 mg/day spermidine. The related safety report specifies 750 mg/day extract, also containing spermine and putrescine. · 3 months · Memory discrimination using the Mnemonic Similarity Task | The memory contrast favored supplementation: 0.17 (95% CI −0.01 to 0.35). The interval included zero. Explore the research |
| A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study.PMID 29214104 # | Study conditions — | Findings and scope — Open original paper |
| Absorption, anti-inflammatory, antioxidant, and cardioprotective impacts of a novel fasting mimetic containing spermidine, nicotinamide, palmitoylethanolamide, and oleoylethanolamide: A pilot dose-escalation study in healthy young adult men.PMID 39549554 # | Study conditions — | Findings and scope — Open original paper |
| The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial.PMID 33211152 # | Study conditions — | Findings and scope — Open original paper |
No papers match. Change the search conditions.
The literature map is an index of research questions and references. Individual assessment of results, doses, funding and COI is limited to the detailed study records. Related reports from the same trial may be included; paper counts are not counts of independent trials.
Explore the research Study Records
Listed doses describe study conditions, not recommended intake.
Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults—A Pilot Study.
PMID 42169618DOI: 10.1111/acel.70545
- Authors
- Alsaleh G, Ali M, Kayvanjoo AH, et al.
- Journal
- Aging Cell
- Publication year
- 2026
- Study design
- Randomized, double-blind, placebo-controlled mechanistic pilot
- Participants
- 40 older adults recruited; baseline analyses: 38, aged 65–81, after a third SARS-CoV-2 vaccine dose.
- Dose and intervention
- Spermidine 6 mg/day versus placebo
- Duration
- 13 weeks of intake; immune follow-up to week 37
- Outcomes and their role in the study
- Safety, vaccine-specific antibodies, B-cell recall, cellular senescence and autophagy
- Findings
- Exploratory analyses found improved antibody/B-cell responses and autophagy-related changes, particularly in eight initially low responders receiving spermidine.
- Limitations
- Low responders were imbalanced (8 treated versus 2 placebo). Small subgroups and exploratory comparisons do not establish protection from infection or general rejuvenation.
- Funding
- Arthritis UK, Wellcome, UK SPINE, TLL/The Longevity Labs, Helmholtz, University of Graz and FWF.
- Conflict of Interest
- Consultancy relationships with TLL and/or Oxford Healthspan were disclosed by A.K.S., G.A. and T.E. TLL reportedly had no role in design, results, analysis or manuscript.
- Scope of source review
- Methods, results and funding/COI sections of the public full text reviewed on 2026-10-11.
The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.
PubMed 30388439DOI: 10.1016/j.cortex.2018.09.014
- Authors
- Wirth M, Benson G, Schwarz C, Köbe T, Grittner U, Schmitz D, Sigrist SJ, Bohlken J, Stekovic S, Madeo F, Flöel A.
- Journal
- Cortex
- Publication year
- 2018
- Study design
- Randomized double-blind placebo-controlled phase IIa pilot
- Participants
- 30 adults aged 60–80 with subjective cognitive decline
- Dose and intervention
- Spermidine-rich wheat-germ extract, providing 1.2 mg/day spermidine. The related safety report specifies 750 mg/day extract, also containing spermine and putrescine.
- Duration
- 3 months
- Outcomes and their role in the study
- Memory discrimination using the Mnemonic Similarity Task
- Findings
- The memory contrast favored supplementation: 0.17 (95% CI −0.01 to 0.35). The interval included zero.
- Limitations
- Exploratory signal, not confirmation. The larger 2022 trial below found no primary memory benefit.
- Funding
- Not verified in the abstract reviewed.
- Conflict of Interest
- Not verified in the abstract reviewed.
- Scope of source review
- Memory results checked against the original abstract; formulation cross-checked against the related trial safety report (doi:10.18632/aging.101354). These reports are not independent replications. Final Cortex disclosures remain unverified.
Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.
PubMed 35616942DOI: 10.1001/jamanetworkopen.2022.13875
- Authors
- Schwarz C, Benson GS, Horn N, Wurdack K, Grittner U, Schilling R, Märschenz S, Köbe T, Hofer SJ, Magnes C, Stekovic S, Eisenberg T, Sigrist SJ, Schmitz D, Wirth M, Madeo F, Flöel A.
- Journal
- JAMA network open
- Publication year
- 2022
- Study design
- SmartAge: single-center, double-blind, placebo-controlled RCT (phase 2b)
- Participants
- 100 adults aged 60–90 with subjective cognitive decline; 89 completed the trial
- Dose and intervention
- Spermidine-containing wheat germ extract, supplying 0.9 mg/day of spermidine.
- Duration
- 12 months
- Outcomes and their role in the study
- Primary: memory discrimination measured by the Mnemonic Similarity Task
- Findings
- Between-group difference: −0.03 (95% CI −0.11 to 0.05, p=0.47). No significant improvement in primary or secondary outcomes; some signals in exploratory analyses.
- Limitations
- Distinguish spermidine itself from the weight of a spermidine-rich extract. Compare the actual intervention and population; exploratory findings require confirmation.
- Funding
- German Federal Ministry of Education and Research and others. The Longevity Labs supported development of the study ingredient.
- Conflict of Interest
- Some authors disclosed equity, advisory or employment relationships with The Longevity Labs and other interests. See the original paper.
- Scope of source review
- Bibliographic information and abstract checked, along with relevant funding and conflict-of-interest sections in the public full text. This is not a comprehensive critical appraisal of the full paper.
Cite this page
LÍFSVARÐA. Spermidine: autophagy, immune cells and human research / Updated 2026-10-24
https://lifsvarda.com/knowledge/spermidine/Edited by LÍFSVARÐA (product brand).Editorial policy
Sources and updates
- Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults—A Pilot Study.
- Wirth M, Benson G, Schwarz C, Köbe T, Grittner U, Schmitz D, Sigrist SJ, Bohlken J, Stekovic S, Madeo F, Flöel A. (2018). The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.
- SmartAge trial (2022): spermidine supplementation, cognition and biomarkersBibliographic information and abstract checked, along with relevant funding and conflict-of-interest sections in the public full text. This is not a comprehensive critical appraisal of the full paper.
2026-10-11: Human-study coverage, findings and comparisons reviewed. Source-review scope is stated for each study.