Spermidine

What is spermidine?

Spermidine is a naturally occurring polyamine found in every living cell, where it regulates cell growth, DNA stability, and gene expression. First isolated from semen in 1678 by Antonie van Leeuwenhoek (hence the name), it has since been identified as a key regulator of cellular homeostasis. Spermidine concentrations decline with age, and this decline correlates with reduced autophagy, the cellular recycling process that clears damaged proteins and organelles ^[1]. That age-related drop has made spermidine one of the most actively studied compounds in longevity research.

How spermidine triggers autophagy

The primary way spermidine protects against aging is by inducing autophagy. A landmark 2009 study by Eisenberg, Madeo and colleagues showed that spermidine supplementation extends lifespan in yeast, nematodes, and fruit flies through autophagy-dependent pathways ^[2]. Spermidine inhibits the acetyltransferase EP300, which leads to deacetylation of autophagy-related proteins and promotes autophagic flux. In 2024, a study in Nature Cell Biology revealed that spermidine is essential for fasting-mediated autophagy: fasting triggers a surge in endogenous spermidine that drives the hypusination of translation factor eIF5A, which enhances production of the autophagy master regulator TFEB ^[3]. Blocking this pathway abolished the lifespan benefits of caloric restriction in model organisms. Separately, a 2024 study confirmed that rapamycin-induced autophagy also depends on endogenous spermidine, reinforcing its position as a central mediator of cellular renewal ^[9].

Spermidine benefits for heart and brain

Spermidine supplementation has shown cardioprotective effects across multiple studies. In mice, oral spermidine reduced cardiac hypertrophy, preserved diastolic function, and lowered blood pressure ^[4]. Data from the Bruneck Study, a prospective human cohort with over 800 participants followed for 20 years, found that higher dietary spermidine intake was linked to roughly 40% lower risk of fatal heart failure and reduced overall cardiovascular mortality ^[5]. A 2021 study also showed that 6-month spermidine administration in aged mice preserved telomere length in cardiac tissue and attenuated age-related cardiac inflammation ^[10].

For cognitive health, the randomized, placebo-controlled SmartAge trial showed that 1.2 mg/day of spermidine-rich wheat germ extract for three months moderately improved memory performance in older adults with subjective cognitive decline ^[6]. Epidemiological data associate higher dietary spermidine intake with 26% lower risk of dementia and 47% lower risk of Alzheimer's disease.

Spermidine for hair and skin

Beyond internal health, spermidine has shown measurable effects on hair growth and skin function. A 2011 study published in PLOS ONE demonstrated that spermidine promotes human hair follicle growth in organ culture and modulates epithelial stem cell functions ^[11]. A follow-up randomized, placebo-controlled, double-blind study confirmed that a spermidine-based nutritional supplement taken daily for 90 days prolonged the anagen (active growth) phase of hair follicles in humans ^[12]. Research also suggests spermidine can support skin barrier integrity and may stimulate melanin production, though clinical data on skin-specific outcomes remains early-stage.

Spermidine-rich foods

Dietary spermidine intake varies widely, with average Western diets providing 7-25 mg per day. The richest natural sources include wheat germ (up to 243 mg/kg), soybeans and natto (167-291 mg/kg), aged cheeses like cheddar, parmesan, and blue cheese (up to 200 mg/kg), mushrooms (approximately 89 mg/kg), and green peas (65 mg/kg) ^[7]. Other good sources are amaranth grain, pumpkin seeds, lentils, broccoli, and cauliflower. The Mediterranean and traditional Japanese diets, both linked to exceptional longevity, are naturally high in spermidine-containing foods. Fermentation increases polyamine content, which explains why aged cheese and natto rank so high. Gut bacteria also produce spermidine, meaning a healthy microbiome contributes to your body's total supply.

Spermidine supplements and safety

Spermidine supplements, typically derived from wheat germ extract, come in doses ranging from 1 to 6 mg per day, with some clinical trials testing up to 40 mg daily. A 2024 randomized, double-blind, placebo-controlled trial found that 40 mg/day of purified spermidine trihydrochloride for 28 days was safe and well tolerated in healthy older men, with no product-related adverse events ^[8]. A 12-month Phase II trial with 100 healthy older adults reported comparable adverse event rates between spermidine and placebo groups. However, doses below 15 mg/day may not significantly raise circulating spermidine levels, which suggests dietary sources remain important.

People with histamine intolerance should be cautious, since polyamines compete with histamine for the diamine oxidase (DAO) enzyme. Those with celiac disease or wheat allergies should check the source of their supplement, as many products are wheat germ-based. Cancer patients should consult their oncologist before supplementing, because while epidemiological data links higher spermidine intake to reduced cancer mortality, polyamines can theoretically accelerate the growth of existing tumors. Current evidence supports spermidine as a promising geroprotective compound, but optimal dosing and long-term effects in humans need further study.