Supplement: Spermidine

What It Is

Spermidine is a polyamine, a small molecule that your own cells make, that gut bacteria also make, and that you get from food. It was first found in semen, the source of its name, but it sits in tissues throughout the body. It turns up in almost everything you eat, most richly in wheat germ, then whole grains, legumes, mushrooms, aged cheese and fermented soy foods such as natto. Your tissue levels of it fall as you age. The reason it draws attention is one well-studied action: it switches on autophagy. In laboratory organisms, that action extends life.

What It Does

In worms, flies, yeast and mice, spermidine turns on autophagy and lengthens life. The same experiments show the life extension depends on that autophagy: block the recycling and the benefit disappears. In aged mice it also keeps the heart from stiffening. These results hold across species, and they are why spermidine moved from a biochemical curiosity to a longevity candidate. The key papers appeared in 2009 and 2016.

People with more spermidine in their diet live modestly longer. That is an observational pattern in people who tend to eat and live well in other ways, so it cannot prove the molecule did anything. When the compound was given as a supplement and tested directly, the one adequately sized trial found no effect on memory, its main measure. The dietary cohort was published in 2018, the supplement trials after that.

Taking spermidine in the hope of slowing your own aging is an experiment with an effect no human trial has measured.

The Research & Studies

Everything here is based on the research we have collected and checked, sorted into groups and ordered with the strongest evidence first. Click any claim to open the studies behind it.

How it works

La spermidine active l'autophagie, et le blocage de l'autophagie supprime son bénéfice sur la durée de vieModerate · mixed

In plain terms

La spermidine active l'autophagie, le processus par lequel une cellule élimine et recycle ses propres composants usés, et c'est cette activation qui lui permet de prolonger la vie chez des organismes de laboratoire simples. Lorsque les chercheurs bloquent l'autophagie, l'effet de prolongation de la vie disparaît.

In detail

Eisenberg et al. (2009, Nature Cell Biology) ont montré que la spermidine inhibe l'activité de l'histone acétyltransférase, déclenche l'autophagie et prolonge la durée de vie chez la levure, la drosophile, le ver et les cellules immunitaires humaines en culture. Le blocage génétique ou pharmacologique de l'autophagie a supprimé le bénéfice sur la durée de vie, établissant l'autophagie comme mécanisme médiateur, et non comme simple corrélat. C'est la base mécanistique bien caractérisée de l'intérêt porté à la spermidine.

The study · 1

Eisenberg et al., Induction of autophagy by spermidine promotes longevity · Nat Cell Biol 2009;11(11):1305-1314

Counts once: this finding and 1 other here come from the same source, so they are one body of evidence, not separate confirmations.

Cognition

Aucun bénéfice sur la mémoire avec 0.9 mg/jour de spermidine sur un an chez 100 adultes plus âgésModerate · no effect

In plain terms

Dans le plus grand essai à ce jour, des adultes plus âgés se plaignant de troubles de la mémoire ayant pris un complément quotidien de spermidine de germe de blé pendant un an n'ont pas obtenu de meilleurs résultats au test de mémoire principal que ceux prenant un placebo.

In detail

L'essai SmartAge (Schwarz et al. 2022, JAMA Network Open) a randomisé 100 adultes âgés de 60 à 90 ans (49 % de femmes) pour recevoir 0.9 mg/jour de spermidine de germe de blé ou un placebo pendant 12 mois. Le critère principal, la discrimination mnémonique évaluée par le Mnemonic Similarity Task, n'a montré aucune différence entre les groupes (-0.03; IC à 95 % -0.11 à 0.05; P = 0.47), et les critères secondaires étaient inchangés. Des analyses exploratoires ont suggéré des effets possibles sur la mémoire verbale et l'inflammation, que les auteurs ont dit devoir confirmer à des doses plus élevées.

The study · 1

Schwarz et al., Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline (SmartAge trial) · JAMA Netw Open 2022;5(5):e2213875

Une étude pilote de 30 personnes a laissé entrevoir un gain de mémoire (d de Cohen de 0.77) que l'essai plus large n'a pas confirméPreliminary

In plain terms

Un petit essai de trois mois portant sur 30 adultes plus âgés a laissé entrevoir qu'un complément de spermidine améliorait légèrement la mémoire. L'étude était trop petite pour être fiable et un suivi de plus grande ampleur ne l'a pas confirmé.

In detail

Wirth et al. (2018, Cortex) ont mené une étude pilote de phase IIa sur 30 adultes plus âgés cognitivement intacts présentant un déclin cognitif subjectif, utilisant un extrait végétal riche en spermidine pendant trois mois. La discrimination mnémonique s'est améliorée dans le groupe spermidine avec une taille d'effet moyenne (d de Cohen d'environ 0.77), bien que les intervalles de confiance soient larges et atteignent zéro. Les auteurs l'ont présenté comme un signal à valider, que l'essai SmartAge plus large n'a ensuite pas confirmé sur son critère principal.

The study · 1

Wirth et al., The effect of spermidine on memory performance in older adults at risk for dementia: a randomized controlled trial · Cortex 2018;109:181-188

Longevity And Mortality

La spermidine prolonge la durée de vie chez la levure, la drosophile, le ver et la sourisPreliminary

In plain terms

Nourrir la levure, la drosophile, le ver et la souris avec de la spermidine les aide à vivre plus longtemps. Il s'agit d'un résultat animal qui n'a pas montré que cela fait vivre les humains plus longtemps.

In detail

La prolongation de la durée de vie par la spermidine a d'abord été rapportée chez la levure, la drosophile et le ver (Eisenberg et al. 2009), puis étendue aux mammifères par Eisenberg et al. (2016, Nature Medicine), où la spermidine orale a augmenté la survie chez la souris et a été associée à une autophagie et une mitophagie accrues. De nombreuses interventions prolongent la durée de vie des rongeurs et des invertébrés sans jamais être reproduites chez l'humain.

The studies · 2

Eisenberg et al., Induction of autophagy by spermidine promotes longevity · Nat Cell Biol 2009;11(11):1305-1314

Eisenberg et al., Cardioprotection and lifespan extension by the natural polyamine spermidine · Nat Med 2016;22(12):1428-1438

Counts once: this finding and 1 other here come from the same source, so they are one body of evidence, not separate confirmations.

Un apport alimentaire plus élevé en spermidine est associé à une mortalité plus faible, rapport de risque de 0.76 par écart-type (observationnel)Preliminary

In plain terms

Les adultes qui consommaient davantage d'aliments riches en spermidine sont morts à des taux plus faibles sur 20 ans, et l'écart entre les apports les plus élevés et les plus faibles était à peu près aussi important qu'être plus jeune de plusieurs années. Il s'agit d'un schéma observé, pas d'une preuve que la spermidine en soit la cause.

In detail

Kiechl et al. (2018, American Journal of Clinical Nutrition) ont suivi 829 participants de l'étude Bruneck (âgés de 45 à 84 ans, 49.9 % d'hommes) à l'aide de questionnaires de fréquence alimentaire validés et répétés; 341 décès sont survenus sur 20 ans. Le rapport de risque ajusté sur l'âge, le sexe et les calories pour le décès toutes causes pour un apport en spermidine plus élevé de 1 écart-type était de 0.74 (IC à 95 % 0.66-0.83), et de 0.76 (0.67-0.86) après ajustement supplémentaire sur le mode de vie et d'autres facteurs alimentaires. Le résultat a été reproduit indépendamment dans la cohorte SAPHIR.

The study · 1

Kiechl et al., Higher spermidine intake is linked to lower mortality: a prospective population-based study · Am J Clin Nutr 2018;108(2):371-380

Heart And Vascular

Chez les souris âgées, la spermidine réduit la rigidité cardiaque et améliore la fonction diastoliquePreliminary

In plain terms

Chez les souris âgées, la spermidine a empêché le cœur de se rigidifier et l'a aidé à se relâcher correctement entre les battements. Il s'agit d'une observation animale, pas d'un effet démontré sur les cœurs humains.

In detail

Eisenberg et al. (2016, Nature Medicine) ont rapporté que la spermidine orale chez des souris âgées réduisait l'hypertrophie ventriculaire gauche et la rigidité myocardique et améliorait la fonction diastolique, avec des améliorations parallèles de la fonction mitochondriale et de l'autophagie. L'article incluait également des données observationnelles humaines associant une consommation alimentaire plus élevée de spermidine à une pression artérielle plus basse et à moins d'événements cardiovasculaires, ce qui est générateur d'hypothèses, non confirmatoire.

The study · 1

Eisenberg et al., Cardioprotection and lifespan extension by the natural polyamine spermidine · Nat Med 2016;22(12):1428-1438

Counts once: this finding and 1 other here come from the same source, so they are one body of evidence, not separate confirmations.

How It Works

Anatomy of the Practice

1Inside the cell

Spermidine blocks an enzyme that adds acetyl tags to proteins. That block, plus a few related effects, switches on autophagy, the process a cell uses to break down and recycle its own worn-out proteins and organelles. Fasting and calorie restriction switch on the same process. Spermidine reproduces part of that effect.

2What autophagy clears

Worn-out mitochondria, misfolded proteins and other debris build up inside cells as the body ages. Autophagy clears them. Turning up autophagy is the mechanism behind every laboratory result for spermidine.

3From cell to person

A compound can switch on a good process in a dish and in a mouse and still not change how long or how well a person lives. Human aging is slow and has many causes. That gap is why the mechanism is settled while the human benefit is not.

The supplements tested in people deliver about 1 mg a day. An ordinary mixed diet supplies several times that, so the trials may have added little. You can read more about the autophagy process and the wider science of biological aging in the science library. The food-first case sits on the whole foods page, alongside autophagy itself.

Getting It Right

Ways to Do It

The mortality signal comes from food, and food supplies more spermidine than the trial supplements did.

1

Eat the foods that carry itFreeEasy

Wheat germ is the richest common source. Whole grains, legumes and peas add more, as do mushrooms, aged cheese and fermented foods such as natto. This is the food pattern that tracked with lower mortality in the observational data, and it overlaps almost entirely with a plain whole-food diet worth eating for many other reasons.

2

A spoon of wheat germ$Easy

If you want to raise intake deliberately, a tablespoon or two of plain wheat germ stirred into yogurt, oatmeal or a smoothie is the cheapest concentrated food source there is. It keeps in the fridge once opened and delivers spermidine alongside fiber, B vitamins and vitamin E.

3

A standardized wheat germ extract supplement$ to $$Easy

The supplements studied in people are wheat germ extracts standardized for spermidine, at roughly 1 to 6 mg a day. The one larger trial of such a product found no effect on its primary memory measure. Check for an independent testing mark, since supplements are loosely regulated.

Go Deeper

• Autophagy: what spermidine switches on, why it matters in aging, and what does and does not raise it.
• Biological aging: the wider science of how the body ages, and the levers with human evidence behind them.
• Whole foods: the food-first case; the spermidine-rich grains and legumes here are one part of it.

Cautions For This Practice

Extra restraint

Everything to be aware of is here, in one place. This practice suits most healthy people; a few situations call for real care.

A three-month trial found the wheat germ supplement well tolerated, side effects like placebo

Schwarz et al. (2018, Aging) tested the safety and tolerability of a wheat germ spermidine supplement in mice and in older adults with subjective cognitive decline over three months. In the human arm, the supplement was well tolerated, adverse events were balanced against placebo, and there were no clinically relevant changes in safety laboratory measures. The trials to date are short and modestly sized, so long-term safety of chronic supplementation is not established.Schwarz et al., Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline

The longevity claim is animal and observational, so treat anti-aging use as experimental

The lifespan results are in animals. The human mortality link is observational, drawn from food records in people who also ate and lived well. Anyone taking the compound to slow their own aging is running a personal experiment whose effect no human trial has measured. Exercise, sleep and diet have stronger human evidence for aging than any supplement.

The larger memory trial found no effect on its main measure

The SmartAge trial gave 100 older adults a wheat germ spermidine supplement for a year and found no change in memory.

Weigh who ran the trials

Several of the human supplement studies were designed or funded with involvement from a company that sells spermidine products, and some authors hold related patents or equity. That does not make the results wrong, and the studies disclosed it. But it is a reason to read the supplement claims with the source in mind, and to lean on the independent dietary and mechanistic work.

The usual source is wheat germ, which contains gluten

Most spermidine supplements are extracted from wheat germ, and wheat germ contains gluten. If you have celiac disease or a wheat allergy, a wheat germ product is not for you; look for a certified gluten-free source or get spermidine from tolerated foods instead. This is easy to miss because spermidine itself is marketed as a pure compound.

Pregnancy, breastfeeding, active cancer, and children: check first

Supplemental spermidine above food levels has not been studied in pregnancy, breastfeeding or childhood, so food-level intake is the sensible ceiling there. Polyamines including spermidine support cell growth, and levels run high in some tumors, so anyone with an active cancer should raise supplemental use with their oncology team before starting. Food intake as part of a normal diet is a separate matter and is not the concern here.

Start slow, be smart, read the research, and consult a professional if you have any concerns. This is here to inform your choice, not make it for you.

Common Questions

Does spermidine actually slow aging or extend life?

Not that any human trial has shown. In animals, spermidine switches on autophagy and extends lifespan, and that mechanism is well characterized. In people, the strongest signal is observational. In a cohort of 829 adults followed twenty years, higher dietary spermidine tracked with lower mortality. That worked out to a hazard ratio near 0.76 per standard deviation of intake, and a gap between the highest and lowest intakes comparable to being 5.7 years younger. It is an association in people who also tend to eat well and take care of themselves, so the healthier diet may explain the lower mortality on its own.

Should I eat spermidine foods or take a supplement?

For most people, eat the foods. The observational link to lower mortality comes from diet, and a normal diet already provides more spermidine than the supplement trials added. Wheat germ carries the most, with legumes, mushrooms, aged cheese and natto behind it. A wheat germ extract supplement delivers the isolated compound.

Does spermidine improve memory?

The only adequately powered trial found no benefit at the dose it used. A small pilot in 30 older adults hinted at a memory benefit earlier. That pilot also provided the short-term safety data, so both signals came from one small group. The SmartAge trial then gave 100 older adults with memory complaints a wheat germ spermidine supplement at 0.9 mg a day for a year. It showed no benefit on the primary memory outcome. Exploratory analyses raised the possibility of effects on verbal memory and inflammation. The authors said those would need a higher dose and a further trial to confirm.

Is spermidine safe to take?

In short trials at these doses it was well tolerated, with side effects no different from placebo. Pregnancy and breastfeeding, active cancer, and the gluten in wheat-germ products are the exceptions covered in the cautions above. For other adults at food levels or the 1-to-6-mg supplement doses studied, spermidine's short-term safety record is reassuring.