Spermidine-Rich Foods and Their Anti-Aging Benefits

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.

Introduction
What is spermidine?
Dietary sources
Evidence for anti-aging effects
Therapeutic potential and supplements
Conclusions
References
Further reading

Spermidine, a natural polyamine abundant in plant-based and fermented foods, promotes longevity by activating autophagy and supporting cardiovascular and cognitive health. Research in humans and animals shows its dietary intake is linked to reduced mortality and improved cellular function

Wheat germ is a dietary source of spermidine. Image Credit: xpixel / Shutterstock

Introduction

Spermidine preserves cellular integrity by promoting autophagy, as well as enhancing antioxidant, anti-inflammatory, and mitochondrial functions. These actions are mediated primarily through activation of autophagy-related genes (Atg), modulation of histone acetylation, and regulation of signaling cascades such as AMPK–FOXO3a and SIRT1/PGC-1α, which collectively improve mitochondrial turnover and energy metabolism. Spermidine levels naturally decline with age, thus emphasizing the importance of increasing dietary intake to support longevity.^1,2

What is spermidine?

Spermidine is a naturally occurring polyamine that interacts with nucleic acids, proteins, and adenosine triphosphate (ATP). As a result, spermidine influences vital processes like cell growth, differentiation, repair, and gene expression, with emerging evidence suggesting its role in supporting cellular resilience and healthy aging.¹

Spermidine induces autophagy by inhibiting the enzyme E1A-associated protein p300 (EP300), in addition to activating Atg genes and translation initiation factor eukaryotic translation initiation factor 5A (eIF5A). By reducing acetyl-CoA availability and EP300-dependent acetylation, spermidine facilitates deacetylation of essential autophagy proteins and promotes lysosomal turnover. Spermidine also reduces the secretion of inflammatory cytokines like interleukin-1 β (IL-1β) and IL-18, both of which regulate cell turnover, reduce inflammation, and prevent age-related decline.^1,2

As a positively charged molecule, spermidine binds to negatively charged nucleic acids like ribonucleic acid (RNA) and DNA. This reaction protects nucleic acids from oxidative damage and preserves genomic integrity, which subsequently prevents genetic mutations and cellular dysfunction.¹

In cellular models, spermidine counteracts oxidative DNA damage and promotes proteostasis through enhanced transcription factor EB (TFEB) synthesis and inhibition of ROS-mediated stress signaling^1,12.

Spermidine enhances mitochondrial biogenesis and energy metabolism through the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1/PGC-1α) pathway. These anti-inflammatory and anti-oxidant properties promote cardiac and neuronal health while delaying the onset of chronic diseases like atherosclerosis and Parkinson’s disease.¹ Additional mechanisms include modulation of insulin/IGF signaling and suppression of NF-κB–dependent cytokine release, further contributing to cellular longevity^1,2.

Dietary sources

Plant and fungal foods are the richest dietary sources of spermidine, with wheat germ, soybeans, and legumes containing concentrations of up to 35 mg/100 g, 18 mg/100 g, and 10 mg/100 g, respectively. Certain mushrooms, including shiitake and king trumpet varieties, contain up to 16 mg/100 g, whereas nuts and seeds offer 5–6 mg/100 g. Vegetables like broccoli, cauliflower, and green pepper, as well as grains like amaranth, are other notable sources of spermidine.³

Among fruits, citrus varieties and pears contain moderate levels (2–3 mg/100 g), while fermented soy products such as natto can reach 20 mg/100 g due to microbial biosynthesis³.

Spermidine levels are typically lower in animal-based products. However, organ meats like cow liver contain up to 16 mg/100 g, whereas aged cheeses can contain up to 20 mg/100 g, particularly in varieties like aged cheddar. Dry-cured ham and fermented sausages also display elevated polyamine levels because of microbial enzymatic activity during curing³.

The fermentation process in cheese and soy-based products enhances polyamine content through the activity of polyamine-producing microbes. Thus, consuming foods like wheat germ, soy, mushrooms, and aged cheese could increase polyamine intake through natural diet.³

Dietary spermidine is rapidly absorbed in the small intestine, particularly the duodenum and proximal jejunum, without extensive degradation. In vivo studies conducted in mice suggest that 60–75% of ingested spermidine may enter circulation within minutes. Human studies show that systemic spermidine bioavailability correlates with habitual intake and gut microbial composition, suggesting a contribution from endogenous intestinal synthesis^3,8.

Evidence for anti-aging effects

In mice, oral spermidine supplementation increased lifespan by approximately 10% and mitigated age-related cardiovascular decline. Treated mice also exhibited reduced cardiac hypertrophy, preserved diastolic function, enhanced autophagy and mitophagy, as well as improved mitochondrial respiration.²

Following spermidine treatment, hypertensive salt-sensitive rats exhibited lower blood pressure levels, delayed progression of heart failure, and maintained cardiac elasticity, all of which are effects associated with increased titin phosphorylation and reduced inflammation.² Spermidine also supports brain health by improving cognition, delaying neurodegeneration, and ameliorating memory deficits in aging mice.^4,5 Mechanistically, these neuroprotective effects are linked to restoration of autophagic flux, reduced accumulation of misfolded proteins, and maintenance of synaptic integrity^5,9.

Similar results have been observed in humans, including a randomized controlled trial in older adults between 60 and 80 years of age who reported improved memory performance and mnemonic discrimination after three months of spermidine supplementation.⁶ Subsequent open-label and follow-up analyses confirmed maintenance of cognitive function without adverse hematologic or metabolic effects¹¹. Higher spermidine levels have also been associated with lower risks of hypertension and improved lipid profiles, with reduced low-density lipoprotein (LDL) and increased high-density lipoprotein (HDL) levels.⁷

A recent analysis of 23,894 United States National Health and Nutrition Examination Survey (NHANES) participants revealed that higher dietary spermidine intake from vegetables, cereals, legumes, nuts, and cheese significantly reduced the risk of cardiovascular disease-related and all-cause mortality, regardless of the presence of hypertension or hyperlipidemia.⁸ These findings align with earlier European cohort data demonstrating inverse associations between dietary spermidine and mortality, independent of socioeconomic and dietary confounders¹⁰. Taken together, these studies indicate that spermidine supports cardiovascular, cognitive, and cellular longevity.

Therapeutic potential and supplements

The landmark Bruneck study, a 15-year prospective cohort study of 829 adults between 45 and 84 years of age, reported a 26% lower all-cause mortality risk that is equivalent to a biological age difference of nearly six years. Study participants with higher spermidine consumption, primarily from whole grains, fruits, vegetables, and potatoes, had significantly lower mortality from cardiovascular disease and cancer, regardless of lifestyle or socioeconomic factors. The Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study confirmed these findings, as spermidine emerged as the nutrient most strongly associated with increased survival.¹⁰

Spermidine supplementation appears to be safe and well-tolerated in both preclinical and human studies. In a 28-day repeated-dose tolerance study in mice, a spermidine-enriched wheat germ extract did not affect behavior, morbidity, or organ pathology, including tumorigenic or fibrotic events. In long-term murine studies, supplementation up to 50 μmol/kg/day extended median lifespan without affecting fertility, hematopoiesis, or neoplastic transformation^2,11.

In a Phase II randomized, double-blinded, placebo-controlled trial in 30 older adults with subjective cognitive decline, daily supplementation of 1.2 mg spermidine for three months did not affect vital signs, weight, hematological or clinical chemistry parameters, or self-reported health, with compliance rates exceeding 85%, indicating excellent tolerability.¹¹

Although epidemiological data suggest spermidine may have cancer-protective effects, some studies have linked elevated polyamine levels to the development of tumors. However, current evidence from dietary supplementation does not indicate an increased risk of cancer, which supports the feasibility of longer-term human studies.¹² Experimental data indicate that endogenous polyamine homeostasis, rather than dietary spermidine intake, determines oncogenic potential through regulation of cell proliferation and apoptosis^1,12.

Conclusions

Spermidine, a naturally occurring polyamine abundant in plant-based and fermented foods, has been shown to extend lifespan, protect cardiovascular function, and support cognitive health in both animal and human studies. Through mechanisms involving autophagy induction, suppression of chronic inflammation, stabilization of DNA, modulation of lipid metabolism, and improved mitochondrial biogenesis, spermidine represents a promising dietary factor for healthspan extension^1,2,10.

References

1. Ni, Q., & Liu, S. (2021). New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases. Aging and Disease 12(8);1948-1963. DOI:10.14336/AD.2021.0603, https://www.aginganddisease.org/EN/10.14336/AD.2021.0603.
2. Eisenberg, T., Abdellatif, M., Schroeder, S., et al. (2016). Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine 22;1428-1438. DOI:10.1038/nm.4222, https://www.nature.com/articles/nm.4222.
3. Madeo, F., Hofer, S. J., Pendl, T., et al. (2020). Nutritional Aspects of Spermidine, Annual Review of Nutrition 40;135-159. DOI:10.1146/annurev-nutr-120419-015419, https://www.annualreviews.org/doi/10.1146/annurev-nutr-120419-015419.
4. Ricke, K. M., Cruz, S. A., Qin, Z., et al. (2020). Neuronal Protein Tyrosine Phosphatase 1B Hastens Amyloid β-Associated Alzheimer's Disease in Mice. Journal of Neuroscience, 40(7):1581-1593. DOI:10.1523/JNEUROSCI.2120-19.2019, https://www.jneurosci.org/content/40/7/1581.
5. Xu, T., Li, H., Dai, Z., et al. (2020). Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice. Aging 12(7);6401-6414. DOI:10.18632/aging.103035, https://www.aging-us.com/article/103035.
6. Wirth, M., Benson, G., Schwarz, C., et al. (2018). The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial. Cortex 109;181-188. DOI:10.1016/j.cortex.2018.09.014, https://www.sciencedirect.com/science/article/pii/S0010945218303137.
7. Wang, T., Li, N., & Zeng, Y. (2024). Protective effects of spermidine levels against cardiovascular risk factors: An exploration of causality based on a bi-directional Mendelian randomization analysis. Nutrition, 127, 112549. DOI:10.1016/j.nut.2024.112549, https://www.sciencedirect.com/science/article/pii/S0899900724001989.
8. Wu, H., Wang, J., Jiang, H., et al. (2022). The association of dietary spermidine with all-cause mortality and CVD mortality: The U.S. National Health and Nutrition Examination Survey, 2003 to 2014. Frontiers in Public Health, 10, 949170. DOI:10.3389/fpubh.2022.949170, https://www.frontiersin.org/articles/10.3389/fpubh.2022.949170.
9. Gruendler, R., Hippe, B., Sendula Jengic, V., et al. (2019). Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer’s Disease: A Systematic Review. Molecules 25(24); 6018. DOI:10.3390/molecules25246018, https://www.mdpi.com/1420-3049/25/24/6018.
10. Kiechl, S., Pechlaner, R., Wileit, P., et al. (2018). Higher spermidine intake is linked to lower mortality: a prospective population-based study. The American Journal of Clinical Nutrition 108(2);371-380. DOI:10.1093/ajcn/nqy102, https://academic.oup.com/ajcn/article/108/2/371/5038227.
11. Schwarz, C., Stekovic, S., Wirth, M., et al. (2018). Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline. Aging 10;19-33. DOI:10.18632/aging.101354, https://www.aging-us.com/article/101354.
12. Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018). Spermidine in health and disease. Science 359, 6374. DOI:10.1126/science.aan2788, https://www.science.org/doi/10.1126/science.aan2788.

Further Reading

• All Aging Content
• Age-Related Changes in Immune Function: Immunosenescence and Immune Modulation
• Unlocking the Secrets of Blue Zones: A Blueprint for Longevity and Health
• How does the Brain Change as we Age?
• The Truth About Biohacking

Last Updated: Nov 10, 2025