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Supplement

Spermidine

Supports broad cellular function with category-specific mechanisms.[2926,3141,3813, etc.]

Superscript reference numbers link to the Sources bibliography.

Strong Evidence
LongevityMetabolic HealthEnergy

Composite Rating

3.8/5

Blends evidence depth, community direction, safety friction, and completeness.

Evidence Intensity

100/100

High depth from human/RCT/meta counts

Community Direction

21

Positive Lean • confidence Moderate

Safety Friction

100/100

High signal from adverse/interaction markers

Data Completeness

100%

Studies 12 • mentions 10 • links 23

Not medical advice. This product is for educational and informational purposes only. It does not diagnose, treat, cure, or prevent any disease and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions regarding a medical condition.

FDA disclaimer: These statements have not been evaluated by the Food and Drug Administration. Dietary supplements are not intended to diagnose, treat, cure, or prevent any disease. Results may vary. Not intended for use by pregnant or nursing women, individuals under 18, or those with known medical conditions without physician consultation.

If you are experiencing a medical emergency, call 911 or your local emergency number immediately.

Implementation Blueprint

Goal alignment: Longevity, Metabolic Health, Energy.[31,96,289, etc.]

Dose guide: Human-study daily dose: 15 mg-40 mg/day (higher-confidence extraction from PubMed abstracts)..[31,96,289, etc.]

Category: other.[31,96,289, etc.]

Category

Other

Evidence Tier

HIGH

Daily Guide

Human-study daily dose: 15 mg-40 mg/day (higher-confidence extraction from PubMed abstracts).

Dosing Guide

Human-study daily dose: 15 mg-40 mg/day (higher-confidence extraction from PubMed abstracts).[2926,, etc.]

At-A-Glance Evidence Architecture[2926,3141,3813, etc.]

Clinical Depth

Humans: 206 • RCTs: 14 • Meta: 0

Cohort / Real-World

Cohort signals: 0

Safety Markers

Adverse signals: 490 • Interactions: 1,010

Evidence Tracking

Freshness, trend, and study timeline for this item

Evidence Tracking

Status

New Evidence

Trend

→ Stable evidence base

Depth

629 total studies · 3 recent

Timeline

20182024

Top Signal Metrics[2926,3141,3813, etc.]

Animal-only studies

4,607

In vitro / tissue

1,672

Interaction signals

1,010

Total indexed

629

Safety adverse signals

490

Human studies

206

Community Direction Mix[31,96,289, etc.]

Weighted direction score: 21 (Positive Lean)

Evidence Quality Summary[2926,3141,3813, etc.]

High when >=2 human meta-analyses, or >=5 human RCTs with substantial human literature volume.

Animal-only studies

4,607

In vitro / tissue

1,672

Interaction signals

1,010

Total indexed

629

Safety adverse signals

490

Human studies

206

Randomized trials

14

Meta-analyses

0

Study Type Breakdown

Distribution of evidence by study design strength

Randomized TrialsLevel 1b14
Human Studies (other)Level 3-4192
All IndexedAll levels629
100

Evidence Strength: High

Composite of study volume, RCTs, and meta-analyses

Top Human Studies[2926,3141,3813, etc.]

PMID 35616942 • 2022 May 2

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

JAMA Netw Open

Open PubMed

PMID 39405978 • 2024 Dec

Supplementation of spermidine at 40 mg/day has minimal effects on circulating polyamines: An exploratory double-blind randomized controlled trial in older men.

Nutr Res

Open PubMed

PMID 39549554 • 2024 Dec

Community Report Frequency[31,96,289, etc.]

Benefit reports: 5

Adverse reports: 2

No-effect reports: 0

Mixed reports: 3

Unclear reports: 0

Signal confidence: 0.41

Top Reported Effects[31,96,289, etc.]

Benefits

  • energy: 3
  • reduced: 2
  • sleep: 2
  • recovery: 2
  • improved: 2
  • focus: 1
  • better: 1

Adverse

  • side effects: 3
  • nausea: 2

No Effect

  • hard to tell: 1

Insufficient empirical signal for a directional adjustment.

Reddit evidence: 7 mentions (confidence 0.41) across Biohackers, Supplements.

Amazon signal: 0 products scanned (confidence 0.00).

GNC signal: 0 products scanned (confidence 0.00) [BLOCKED].

PerimeterX / captcha block encountered.

Use adverse/interactions PubMed signal counts for screening; perform clinician review before high-dose or multi-drug stack use.

Community Evidence Examples[31,96,289, etc.]

post • r/Biohackers • unclear

Distinct Roles of Urolithin A and Spermidine in Mitophagy and Autophagy: Implications for Dietary Supplementation | Nutrition Research Reviews (2025)

Open mention

post • r/Supplements • mixed

Confused about spermidine: side effects and dosage For those who don't know, spermidine is a longevity supplement that increases autophagy. TL;DR: Spermidine seems to give me nausea and increase my saliva production AND give me a lot of en…

Open mention

post • r/Biohackers • benefit

A study tracked 146 nutrients in 829 people across 15 years to see their effects on mortality and longevity. Guess which nutrient out of those 146 was easily ranked as the most beneficial? **Spermidine!** In a study of 146 nutrients, sperm…

Retail Signal Examples

amazon

Amazon search for Spermidine

Rating: n/a | Reviews: n/a

Open product

Primary Source Links

Evidence Sources

  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22spermidine%22)%20AND%20(supplement*%5BTitle%2FAbstract%5D%20OR%20supplementation%5BTitle%2FAbstract%5D%20OR%20intake%5BTitle%2FAbstract%5D%20OR%20dietary%20supplements%5BMeSH%20Terms%5D)
  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22spermidine%22)%20AND%20humans%5BMeSH%20Terms%5D%20AND%20(supplement*%5BTitle%2FAbstract%5D%20OR%20supplementation%5BTitle%2FAbstract%5D%20OR%20intake%5BTitle%2FAbstract%5D%20OR%20dietary%20supplements%5BMeSH%20Terms%5D)
  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22spermidine%22)%20AND%20animals%5BMeSH%20Terms%5D%20NOT%20humans%5BMeSH%20Terms%5D

Scientific Evidence Notes[2926,3141,3813, etc.]

1. PubMed evidence summary: Spermidine

PUBMED • Humans + preclinical triage

Counts aggregated from automated literature sweep and tiering rules.

Outcome: Tier HIGH; humans 206, RCTs 14, meta-analyses 0.[2926,3141,3813, etc.]

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

PUBMED • 2022 • Human evidence curation set

PMID 35616942 from JAMA Netw Open.

Outcome: See linked PubMed abstract for methods and outcomes.[, etc.]

3141,
3813

Safety and Pitfalls

  • Elevated adverse/interactions signal in literature; review medications and conditions before use.[31,96,289, etc.]
  • High interaction-signal count detected in literature search.[31,96,289, etc.]
  • Potential side effect: side effects[31,96,289, etc.]
  • Potential side effect: nausea[31,96,289, etc.]
  • Legacy caution group: Active cancer[31,96,289, etc.]
  • Legacy caution group: Those with wheat/gluten allergies (wheat germ source)[31,96,289, etc.]
Benefit
5 (50%)
Adverse2 (20%)
No Effect0 (0%)
Mixed3 (30%)

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.

Nutr Res

Open PubMed

PMID 37111071 • 2023 Apr 12

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.

Nutrients

Open PubMed

PMID 30388439 • 2018 Dec

The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.

Cortex

Open PubMed

PMID 33211152 • 2021 May

The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial.

Wien Klin Wochenschr

Open PubMed

PMID 29371440 • 2018 Jan 26

Spermidine in health and disease.

Science

Open PubMed

PMID 37845508 • 2023 Nov

Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging.

Nat Aging

Open PubMed

PMID 33151120 • 2020 Nov 9

Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice.

Gut Microbes

Open PubMed

PMID 33852843 • 2021 Apr 13

Dietary spermidine improves cognitive function.

Cell Rep

Open PubMed

PMID 34105442 • 2021 Aug

Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging.

Autophagy

Open PubMed

PMID 37723019 • 2024 May

Spermidine - an old molecule with a new age-defying immune function.

Trends Cell Biol

Open PubMed

Human-study daily dose signal: 15 mg-40 mg/day (confidence HIGH).

Extracted from 7 dosing mentions across 3 PubMed studies (mg/day).

Imported legacy community score: 8.0/10 (heuristic mapping confidence 1.00).

Imported legacy monthly cost signal: ~$30.00.

Legacy community note: Growing rapidly in longevity community. Users appreciate the fasting-mimicking autophagy benefit without actually fasting. Wheat germ extract is the most common delivery form. Often part of advanced longevity stacks.

Open mention

post • r/Supplements • mixed

What Are the Best Anti Aging Supplements to Take in Your 30s for Long-Term Health? hey i’m in my 30s and been getting more into anti aging stuff lately. i already eat decent, stay active, try to sleep enough but i figured why not start doi…

Open mention

post • r/Biohackers • unclear

What are your top longevity supplements in 2025? I'm trying to build a solid longevity stack and would love to hear from people who are already experimenting with supplements for healthy aging. What are your top picks right now? Think NMN,…

Open mention

post • r/Supplements • unclear

Bryan Johnson's Supplement Lis # Bryan Johnson's Supplement List I just finished a writeup on Bryan Johnson's Supplement stack and figured I would share here for anyone interested. [**This full list with more information**](https://jakesjo…

Open mention

post • r/Biohackers • unclear

22M: My Personalized Longevity Stack for Health, Hormonal Balance & Vascular Function Hi friends, I’m a 22 year old who has been experimenting with a structured longevity stack. My goals are not only healthy aging but also hormonal balance…

Open mention

post • r/Biohackers • benefit

Longevity protocol - Thoughts ? Greetings all Long time lurker- first time posting. Been working on my Vitagenix longevity protocol for the past 5 years experimenting, optimizing and updating when needed. I'd like some push back though it …

Open mention

comment • r/Biohackers • benefit

# Abstract The increasing focus on longevity and cellular health has brought into the spotlight two key compounds, urolithin A (UroA) and spermidine, for their promising roles in autophagy and mitophagy. Urolithin A, a natural metabolite d…

Open mention

comment • r/Supplements • mixed

Spermidine’s mostly marketed for its possible “cell cleanup” effects, but in practice people usually stick to much smaller amounts than 10 mg/day—more like 1–6 mg from wheat-germ extracts. Some have more energy or appetite changes, but nau…

Open mention
https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22spermidine%22)%20AND%20humans%5BMeSH%20Terms%5D%20AND%20(supplement*%5BTitle%2FAbstract%5D%20OR%20supplementation%5BTitle%2FAbstract%5D%20OR%20intake%5BTitle%2FAbstract%5D%20OR%20dietary%20supplements%5BMeSH%20Terms%5D)%20AND%20randomized%20controlled%20trial%5BPublication%20Type%5D
  • https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=pubmed&term=(%22spermidine%22)%20AND%20humans%5BMeSH%20Terms%5D%20AND%20(supplement*%5BTitle%2FAbstract%5D%20OR%20supplementation%5BTitle%2FAbstract%5D%20OR%20intake%5BTitle%2FAbstract%5D%20OR%20dietary%20supplements%5BMeSH%20Terms%5D)%20AND%20meta-analysis%5BPublication%20Type%5D
  • https://pubmed.ncbi.nlm.nih.gov/35616942/
  • https://pubmed.ncbi.nlm.nih.gov/39405978/
  • https://pubmed.ncbi.nlm.nih.gov/39549554/
  • https://pubmed.ncbi.nlm.nih.gov/37111071/
  • https://pubmed.ncbi.nlm.nih.gov/30388439/
  • https://pubmed.ncbi.nlm.nih.gov/33211152/
  • https://pubmed.ncbi.nlm.nih.gov/29371440/
  • https://pubmed.ncbi.nlm.nih.gov/37845508/
  • https://pubmed.ncbi.nlm.nih.gov/33151120/
  • https://pubmed.ncbi.nlm.nih.gov/33852843/
  • https://pubmed.ncbi.nlm.nih.gov/34105442/
  • https://pubmed.ncbi.nlm.nih.gov/37723019/
  • https://pubmed.ncbi.nlm.nih.gov/?term=Spermidine
  • Community Sources

    • https://old.reddit.com/search.json?raw_json=1&sort=relevance&t=year&limit=12&q=%22spermidine%22%20(supplement%20OR%20dosage%20OR%20stack%20OR%20side%20effects%20OR%20review)%20(subreddit%3ASupplements%20OR%20subreddit%3ANootropics%20OR%20subreddit%3ABiohackers%20OR%20subreddit%3Alongevity%20OR%20subreddit%3ANutrition%20OR%20subreddit%3AHubermanLab%20OR%20subreddit%3ASleep%20OR%20subreddit%3AFitness%20OR%20subreddit%3Aketoscience%20OR%20subreddit%3AStackAdvice)
    • https://old.reddit.com/r/Biohackers/comments/1psfcl6/distinct_roles_of_urolithin_a_and_spermidine_in/.json?raw_json=1&sort=top&limit=25
    • https://old.reddit.com/r/Supplements/comments/1p21ijq/confused_about_spermidine_side_effects_and_dosage/.json?raw_json=1&sort=top&limit=25
    • https://old.reddit.com/r/Biohackers/comments/1lahzlv/a_study_tracked_146_nutrients_in_829_people/.json?raw_json=1&sort=top&limit=25
    • https://www.reddit.com/search/?q=Spermidine
    2926,
    3141,
    3813
    Open source
    3. Supplementation of spermidine at 40 mg/day has minimal effects on circulating polyamines: An exploratory double-blind randomized controlled trial in older men.

    PUBMED • 2024 • Human evidence curation set

    PMID 39405978 from Nutr Res.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    4. 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.

    PUBMED • 2024 • Human evidence curation set

    PMID 39549554 from Nutr Res.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    5. 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.

    PUBMED • 2023 • Human evidence curation set

    PMID 37111071 from Nutrients.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    6. The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.

    PUBMED • 2018 • Human evidence curation set

    PMID 30388439 from Cortex.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    7. The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial.

    PUBMED • 2021 • Human evidence curation set

    PMID 33211152 from Wien Klin Wochenschr.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    8. Spermidine in health and disease.

    PUBMED • 2018 • Human evidence curation set

    PMID 29371440 from Science.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    9. Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging.

    PUBMED • 2023 • Human evidence curation set

    PMID 37845508 from Nat Aging.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    10. Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice.

    PUBMED • 2020 • Human evidence curation set

    PMID 33151120 from Gut Microbes.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    11. Dietary spermidine improves cognitive function.

    PUBMED • 2021 • Human evidence curation set

    PMID 33852843 from Cell Rep.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    12. Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging.

    PUBMED • 2021 • Human evidence curation set

    PMID 34105442 from Autophagy.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source
    13. Spermidine - an old molecule with a new age-defying immune function.

    PUBMED • 2024 • Human evidence curation set

    PMID 37723019 from Trends Cell Biol.

    Outcome: See linked PubMed abstract for methods and outcomes.[2926,3141,3813, etc.]

    Open source