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Longevity

SpermidineEvidence & Dosage

Autophagy inducer, wheat germ, lifespan data in animals and humans.

Evidence at a glance

Total studies
61
With abstract
48
Meta / Systematic / RCT
4
Highly cited
14
Publication years
2009–2026

Spermidine in the context of Longevity

This topic is part of our "Longevity" world. There you'll find methodology, evidence and the highest-impact levers — plus the order in which they sensibly build on each other.

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Top studies on Spermidine

Ranked by influential-citation count and publication year.

  1. Spermidine is essential for fasting-mediated autophagy and longevity.

    Nat Cell Biol2024n=104other174 influential citations

    Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced…

  2. Spermidine Ameliorates Colitis via Induction of Anti-Inflammatory Macrophages and Prevention of Intestinal Dysbiosis.

    Journal of Crohn's & colitis2023n=3274 influential citations

    Background and Aims Exacerbated immune activation, intestinal dysbiosis and a disrupted intestinal barrier are common features among inflammatory bowel disease [IBD] patients. The polyamine spermidine, which is naturally present in all…

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

    JAMA Netw Open2022n=100RCT65 influential citations

    <h4>Importance</h4>Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial…

  4. Spermidine protects intestinal mucosal barrier function in mice colitis via the AhR/Nrf2 and AhR/STAT3 signaling pathways.

    International immunopharmacology202355 influential citations

    <h4>Background</h4>Aryl hydrocarbon receptor (AhR) activation promotes intestinal barrier repair and enhances the gut mucosal barrier function in inflammatory bowel diseases (IBD). Spermidine is beneficial in several murine models of IBD…

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

    Cortex2018n=30RCT49 influential citations

    INTRODUCTION: Nutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine…

  6. Spermidine from arginine metabolism activates Nrf2 and inhibits kidney fibrosis.

    Communications biology2023n=1046 influential citations

    Kidney metabolism may be greatly altered in chronic kidney disease. Here we report that arginine metabolism is the most altered in unilateral ureteral obstruction (UUO)-induced fibrosis of the kidneys in metabolomic analysis. Spermidine is…

  7. Tumor cell-derived spermidine is an oncometabolite that suppresses TCR clustering for intratumoral CD8 + T cell activation.

    Proceedings of the National Academy of Sciences of the United States of America2023n=841 influential citations

    The activation and expansion of T cells that recognize cancer cells is an essential aspect to antitumor immunity. Tumors may escape destruction by the immune system through ectopic expression of inhibitory immune ligands typically…

  8. 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.

    Nutrients2023n=12RCT37 influential citations

    (1) Background: Spermidine is a biogenic polyamine that plays a crucial role in mammalian metabolism. As spermidine levels decline with age, spermidine supplementation is suggested to prevent or delay age-related diseases. However, valid…

  9. Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms.

    Frontiers in chemistry202332 influential citations

    Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically…

  10. Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury.

    Cell death &amp; disease201530 influential citations

    Spermidine acts as an endogenous free radical scavenger and inhibits the action of reactive oxygen species. In this study, we examined the effects of spermidine on retinal ganglion cell (RGC) death in a mouse model of optic nerve injury…

Frequently asked

What dosage was studied?
• Fasting/intermittent fasting, caloric restriction, spermidine supplementation, DFMO, ODC1/SPE1 inhibition or knockdown, rapamycin, GC7 (Human fasting ~250 kcal/day for 7–13 days; flies 10 mM DFMO; mice 0.25% or 0.5% DFMO; 3 mM SPD in water; yeast 100 µM or 5 mM SPD; GC7 50 mM stock, used pharmacologically; rapamycin 40 nM) • Spermidine-rich dietary supplement extracted from wheat germ (0.9 mg spermidine/d; 750 mg plant extract daily (6 capsules of 125 mg each))
Which population does the evidence apply to?
Most studies investigated: unknown.
Are there safety considerations for Spermidine?
• DFMO blunted IF benefits in flies and mice, indicating a dose/target ceiling for polyamine suppression. • In flies, DFMO generally seemed non-toxic and did not affect food consumption or acute body weight. • No major adverse events were reported for human fasting cohorts in the excerpt. • All 19 serious adverse events were judged unrelated to treatment.

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