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SpermidineEvidence & Dosage

Autophagy, polyamines, wheat germ source, and longevity studies.

Studies last updated

Evidence at a glance

Total studies
654
With abstract
47
Meta / Systematic / RCT
39
Highly cited
50
Publication years
1974–2026

Spermidine in the context of Vitamins & Minerals

This topic is part of our "Vitamins & Minerals" 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. Uncovering de novo polyamine biosynthesis in the gut microbiome and its alteration in inflammatory bowel disease.

    Gut microbes2025n=30E83 influential citations

    Polyamines are important gut microbial metabolites known to affect host physiology, yet the mechanisms behind their microbial production remain incompletely understood. In this study, we developed a stable isotope-resolved metabolomic…

  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. Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.

    Aging (Albany NY)2018n=30RCT58 influential citations

    Supplementation of spermidine, an autophagy-inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a…

  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. A review on polyamines as promising next-generation neuroprotective and anti-aging therapy.

    European journal of pharmacology2024D48 influential citations

    Neurodegenerative disorders are diseases characterized by progressive degeneration of neurons and associated structures and are a major global issue growing more widespread as the global population's average age increases. Despite several…

  7. Spermine delivered by ZIF90 nanoparticles alleviates atherosclerosis by targeted inhibition of macrophage ferroptosis in plaque.

    Journal of nanobiotechnology2025n=6E41 influential citations

    Nowadays, emerging evidence have suggested that the ferroptosis of macrophages could contribute to the progression of atherosclerosis (AS). Meanwhile, Spermine (Sp) could serve as an endogenous small molecule exhibiting a wide range of…

  8. Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.

    Alzheimers Res Ther2019n=100Clinical Trial37 influential citations

    Background Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective…

  9. 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…

  10. Mitigation of adverse effect of cadmium toxicity in lettuce (Lactuca sativa L.) through foliar application of chitosan and spermidine.

    Scientific reports2025n=50E36 influential citations

    Cadmium (Cd) stress is considered among the most harmful abiotic stresses because of its toxicity and ability to alter the ultrastructure of plants. Lettuce (Lactuca sativa L.) can readily accumulate Cd from the soil, but its elevated…

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)
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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