Spermidine is gaining recognition as a powerful bioactive compound for supporting cardiovascular health and longevity. As cardiovascular disease remains one of the leading causes of morbidity and mortality worldwide, scientists are exploring novel, naturally occurring compounds that can protect the heart and extend lifespan. Spermidine—a polyamine found in many fruits, vegetables, whole grains, and even produced endogenously—is emerging as a promising candidate. Research spanning animal models and human studies has highlighted its role in promoting heart health, reducing inflammation, extending lifespan, and improving overall cardiovascular function through mechanisms such as enhanced autophagy and improved mitochondrial performance. In this review, we bring together findings from several pivotal studies to help you understand the many benefits that spermidine offers for both cardiovascular health and aging.
Extending lifespan and protecting the heart
One of the landmark pieces of research comes from a 2016 study by Eisenberg et al. in Nature Medicine. In this study, researchers demonstrated that oral supplementation with spermidine not only extended the lifespan of mice but also provided significant cardioprotective benefits. Spermidine was shown to reduce cardiac hypertrophy, preserve diastolic function, and enhance key cellular processes such as autophagy, mitophagy, and mitochondrial respiration. Importantly, the study revealed that these benefits depend on functional autophagy, as autophagy-deficient mice did not experience the same improvements. Similar benefits were observed in hypertension rat models, and human epidemiological data suggested that higher dietary spermidine intake is associated with lower blood pressure and reduced cardiovascular disease (CVD) incidence.
Dietary polyamines and cardiovascular mortality
Long before these cellular insights, a 2012 study published in the Global Journal of Health Science examined the relationship between dietary polyamines (including spermidine and its relative, spermine) and CVD mortality across 48 European and Western countries. Using food supply data and polyamine concentrations in various foods, researchers found that higher dietary intake of these polyamines was linked to lower rates of cardiovascular death. This large-scale analysis also noted that factors like higher GDP and increased consumption of fruits, vegetables, nuts, and beans were associated with better cardiovascular outcomes—while smoking and whole milk consumption had the opposite effect.
Complementing these findings, a 2018 prospective cohort study in The American Journal of Clinical Nutrition followed 829 participants aged 45–84 years over 20 years. The study reported that individuals with higher dietary spermidine intake experienced significantly lower all-cause mortality, suggesting that spermidine-rich diets may contribute to increased longevity.
A 2024 study in Nutrients utilized data from the UK Biobank (184,732 participants) to analyze the association between dietary polyamines and cardiovascular risk. The study found that moderate spermidine intake was linked to lower all-cause mortality and reduced CVD incidence. Another 2024 study in Nutrition used Mendelian randomization to confirm a causal relationship between higher spermidine levels and reduced hypertension, improved lipid profiles, and lower CVD risk, further supporting spermidine’s potential as a dietary intervention for cardiovascular health.
A closer look in the heart
Spermidine and aortic health
In 2016, a study published in Atherosclerosis investigated spermidine’s effects on atherosclerotic plaque progression in mice. The researchers found that while spermidine did not alter the size or cellular composition of plaques, it significantly reduced lipid accumulation and necrotic core formation within the plaques. These benefits were attributed to spermidine’s ability to induce autophagy in vascular smooth muscle cells (VSMCs), facilitating cholesterol efflux and stabilizing plaques. This study highlighted spermidine’s potential as a therapeutic agent for preventing cardiovascular disease by targeting plaque instability. Building on these findings, a 2020 study in Aging Cell demonstrated that spermidine reduces vascular calcification in both rat and human VSMCs under osteogenic conditions by upregulating SIRT1, a protein that inhibits endoplasmic reticulum stress. This suggests that spermidine could also help prevent arterial stiffness and vascular calcification, common issues in aging and chronic kidney disease. Together, these studies underscore spermidine’s dual role in combating atherosclerosis and vascular calcification, making it a promising candidate for cardiovascular health.
Peripheral artery disease and autophagy activation
A 2022 pilot study in Antioxidant examined a mixture of autophagy activators, including spermidine, in patients with peripheral artery disease (PAD). After 60 days, patients receiving the mixture experienced a 91% increase in maximal walking distance, alongside improvements in oxidative stress markers and autophagic activity. These results indicate spermidine’s potential in improving vascular function and reducing oxidative stress in PAD patients.
Prevention of aortic aneurysms
A 2020 study in Journal of the American Heart Association investigated spermidine’s effects on experimental abdominal aortic aneurysms (AAAs) in mice. Spermidine treatment preserved aortic structural integrity, reduced inflammation, and increased autophagy-related proteins, suggesting its promise in preventing aneurysm progression.
Spermidine and mitochondrial function
Several studies have explored spermidine’s role in mitochondrial health. A 2020 study in Aging found that spermidine supplementation in aged rats improved mitochondrial biogenesis by activating the SIRT1/PGC-1α signaling pathway, preserving myocardial structure and function. A 2021 study in Journal of Anatomy similarly demonstrated that spermidine supplementation increased mitochondrial numbers in aged mice and improved their structural alignment, suggesting that spermidine helps maintain mitochondrial integrity in aging hearts.
The role of spermidine in arterial aging and endothelial function
A 2013 study in Mechanism of Ageing and Development showed that spermidine supplementation reduced arterial stiffness and improved endothelial function in aged mice by increasing nitric oxide bioavailability and enhancing autophagy. A 2023 study in Scientific Reports further supported these findings, showing that spermidine improved angiogenesis and neovascularization in ischemic limbs of aged mice by enhancing autophagy and mitochondrial function. Similarly, a 2017 study in Oncotarget reported that both spermidine and its relative spermine reversed age-related myocardial alterations in rats, reduced fibrosis, and decreased apoptosis, further suggesting that polyamines can modulate key pathways involved in cardiac deterioration.
The gut-heart connection
Beyond direct cardiac effects, spermidine appears to influence cardiovascular health via the gut microbiota. A 2020 study in Biological & Pharmaceutical Bulletin developed an innovative hybrid putrescine biosynthesis system using Bifidobacterium animalis ssp. lactis and arginine to boost polyamine production in the gut. A clinical trial involving a specially formulated yogurt showed improved vascular endothelial function and elevated blood spermidine levels, indicating a reduced risk of atherosclerosis. Additionally, a 2019 review in the Journal of Molecular and Cellular Cardiology highlighted how polyamines synthesized by both our cells and gut bacteria contribute to improved cardiomyocyte function, enhanced nitric oxide bioavailability, and reduced systemic inflammation—factors critical in preventing aortopathy in patients with bicuspid and tricuspid aortic valves. Further supporting this gut-heart axis, a 2021 study in Frontiers in Cardiovascular Medicine demonstrated that spermidine supplementation improved cardiac function in heart failure mice while modulating gut microbiota composition, suggesting a potential mechanistic link between gut-derived polyamines and cardiovascular health.
Mechanisms underlying spermidine’s cardioprotective effects
Across these studies, several recurring mechanisms emerge:
- Enhanced Autophagy and Mitophagy: Spermidine consistently stimulates cellular recycling processes, which help clear damaged organelles and proteins, leading to improved cell survival and function.
- Improved Mitochondrial Function: Many studies show that spermidine restores mitochondrial biogenesis and quality, ensuring that cardiomyocytes maintain their energy supply and structural integrity.
- Anti-Inflammatory and Antioxidant Effects: By reducing oxidative stress and systemic inflammation, spermidine contributes to healthier blood vessels and less plaque instability.
- Gut Microbiota Interactions: The modulation of gut bacterial metabolism can increase endogenous spermidine production, offering an additional layer of cardiovascular protection.
Conclusion
Spermidine has emerged as a powerful and versatile nutraceutical with significant potential to support cardiovascular health and promote longevity. Through its ability to enhance autophagy, improve mitochondrial function, reduce oxidative stress, and modulate inflammation, spermidine addresses multiple hallmarks of cardiovascular disease. Studies spanning animal models and human populations have demonstrated its cardioprotective effects, including reducing cardiac hypertrophy, stabilizing atherosclerotic plaques, preventing vascular calcification, and improving endothelial function. Furthermore, spermidine’s interaction with the gut microbiota adds another layer of complexity to its benefits, suggesting a holistic approach to cardiovascular health.
The evidence is compelling: spermidine-rich diets are associated with lower blood pressure, reduced cardiovascular mortality, and increased lifespan. Clinical trials and mechanistic studies continue to uncover new ways in which spermidine can protect the heart, from improving peripheral artery disease symptoms to preventing aortic aneurysms. As research progresses, spermidine’s role as a dietary intervention for cardiovascular health becomes increasingly clear.
For those looking to support their heart health naturally, incorporating spermidine-rich foods—such as whole grains, legumes, aged cheeses, and mushrooms—into the diet may offer a simple yet effective strategy. Additionally, spermidine supplementation could provide a targeted approach for individuals at risk of cardiovascular disease or those seeking to optimize their longevity. While further clinical trials are needed to fully establish its therapeutic potential, the current body of evidence positions spermidine as a promising candidate for the prevention and management of cardiovascular disease.
In a world where heart health is paramount, spermidine stands out as a natural, science-backed ally in the quest for a longer, healthier life.
