What is Spermidine?

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Last updated: May 28, 2025View editorial policy

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From the Guidelines

Spermidine is a naturally occurring polyamine that has been shown to induce macroautophagy, potentially leading to improved cellular function and lifespan, and its administration has been found to increase lifespan and healthspan of multicellular model organisms, at least in part through TORC1 inhibition and enhancement of autophagy 1. When considering spermidine, it is essential to note that it works by activating cellular maintenance processes that remove damaged components, potentially slowing aging and improving cellular function. Key points to consider about spermidine include:

  • It is found in various foods, including wheat germ, soybeans, aged cheese, mushrooms, and certain fruits
  • Typical supplemental doses range from 1-5 mg daily, although no official dosage recommendations exist
  • Research suggests it may support heart health, cognitive function, and immune system regulation
  • Spermidine supplements are not FDA-approved for treating any condition, and most evidence comes from laboratory and animal studies rather than extensive human trials
  • If considering supplementation, it is recommended to start with lower doses and consult a healthcare provider, especially if you have existing health conditions or take medications
  • For most people, focusing on spermidine-rich foods represents a safer approach than supplements, as evidenced by the fact that tissue levels of spermidine decline with age in model organisms and in humans, although they are unusually high in healthy nona/centenarians 1. It is also worth noting that other compounds that modulate autophagy, such as resveratrol and urolithin A, have shown anti-aging properties, and the combination of spermidine and resveratrol has been found to have synergistic effects on autophagy induction 1. However, developing assays for autophagy in humans is challenging, and further development and validation of assessment methods are needed before these assays can be used in clinical studies 1. In terms of safety, while spermidine has been found to have potential health benefits, its long-term effects in humans are not yet fully understood, and more research is needed to determine its safety and efficacy as a supplement 1.

From the Research

Spermidine Mechanisms and Effects

  • Spermidine has been shown to exhibit anti-aging properties, increasing lifespan and resistance to stress, and decreasing age-related pathology and loss of locomotor ability 2.
  • The main mechanism of action of spermidine is autophagy, but it can also act through other mechanisms such as inflammation reduction, lipid metabolism, and regulation of cell growth, proliferation, and death 2.
  • Spermidine can interact with many molecules, affecting aging via several mechanisms, and may be a strong regulator of aging 2.

Spermidine Supplementation and Pharmacokinetics

  • External supplementation of spermidine has been shown to extend lifespan and health span across species, including yeast, nematodes, flies, and mice 3.
  • However, a study found that high-dose spermidine supplementation did not increase spermidine levels in blood plasma and saliva of healthy adults, suggesting that dietary spermidine is presystemically converted into spermine 4.
  • Spermidine supplementation significantly increased spermine levels in plasma, but did not affect spermidine or putrescine levels, and had no effect on salivary polyamine concentrations 4.

Spermidine and Aging-Related Diseases

  • Spermidine has been shown to modulate aging, suppress the occurrence and severity of age-related diseases, and prolong lifespan 5.
  • The precise mechanisms through which spermidine exerts its anti-aging effects have not been established, but it is thought to play a critical role in molecular and cellular interactions involved in various physiological and functional processes 5.
  • Spermidine insufficiency is associated with various physio-pathological processes, such as aging and cancers, and recent advances in immuno-metabolism and immunotherapy have shed new light on the role of spermidine in immune cell regulation and anticancer responses 6.

Spermidine and Immune Function

  • Spermidine is produced by collective metabolic pathways of gut bacteria, bacteria-host co-metabolism, and by the host cells, including activated immune cells 6.
  • Spermidine has been shown to enhance antitumor responses in aged animals and may be used to enhance the efficacy of anti-PD-1 treatment 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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