Spermidine

We evaluated 30 human studies on Spermidine, including 7 randomised controlled trials and 0 meta-analyses or systematic reviews; the controlled studies include 234 participants in total. As of 13 October 2026.

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1. What Is Spermidine? Occurrence, Origin and Forms

Spermidine is a polyamine, a substance that occurs in the cells of humans, animals and plants. The body produces it itself and also takes it in through food. Spermidine is best known as a component of wheat germ, aged cheese, soy, mushrooms and legumes; in research it is studied in connection with cellular self-cleaning (autophagy) and with aging.

Spermidine occurs in almost all living cells, in the human body as well as in foods of plant and animal origin. Among the best-known sources are wheat germ, aged cheese, fermented soy products and mushrooms.

For preparations, spermidine is either obtained from wheat germ or produced chemically and supplied as spermidine trihydrochloride. Studies mainly examine wheat germ extracts, pure spermidine trihydrochloride and spermidine-rich diets.

Forms and Preparations Studied

• Wheat germ extract
• Pure spermidine trihydrochloride
• Spermidine-rich diet
• Fermented foods as a spermidine source (e.g. aged cheese, natto)
• Mixtures with further polyamines (e.g. spermine, putrescine)

Not covered on this page:

• Other polyamines such as spermine and putrescine when they are studied as substances in their own right
• Medicinal substances that influence or inhibit polyamine metabolism (e.g. eflornithine)
• Spermidine as a laboratory reagent in cell-culture experiments
• Foods and preparations in which other ingredients, not the spermidine content, are the subject

2. What Does Spermidine Do? Results by Area

How to read the table: counted are human studies whose results concern the area. “High” means at least one meta-analysis and two controlled studies showing improvement, or at least three controlled studies of which three quarters show improvement, with at least 300 participants in total. “Moderate” means at least two controlled studies showing improvement, as a majority, or one meta-analysis alongside controlled studies. “Low” means one controlled study showing improvement. Where an area has no controlled study, the strength of evidence is at most “low” (result “reviews only” or “observational data only”). Everything else is “unclear”. A study counts as showing improvement when at least half of its outcomes in this area improved. Reviews of combination products do not count as meta-analyses; results that only describe side effects or shares of users do not count as an effect. The same study is counted only once.

3. What the Studies Show in Detail

Spermidine and Biological Aging: Human Studies

In a placebo-controlled pilot study in older adults, oral spermidine lowered ageing markers in immune cells such as p16 and DNA damage, especially in those with a weak vaccine response 34. A randomised placebo-controlled study with a mixture of AM3, spermidine and hesperidin lowered the biological age measured by immune functions 2. A small pilot study without a placebo group compared two amounts of spermidine from rice germ extract; only the higher amount increased autophagy markers compared with baseline 6. The strength of evidence is low: the studies are small and short, and some of the findings come from combination preparations with AM3 and hesperidin, so the effect cannot be attributed to spermidine alone 2. Observational data on spermidine intake through the diet must be considered separately from these intervention findings and do not allow a statement about effects.

Further studies in this area: 27 28

Spermidine, Cognition and Memory: Human Studies

A pilot study in twelve healthy people compared two amounts of spermidine from rice germ extract without a placebo group; with the higher amount, the nerve growth factor BDNF increased compared with baseline 6. The strength of evidence is low: it is a single, very small study without independent confirmation, and BDNF is a laboratory value, not a measured memory test. Observational data on a spermidine-rich diet, which also includes spermine and putrescine, point in a more favorable direction, but concern overall intake through the diet and cannot be read as the effect of spermidine alone 13. A cross-sectional study with plasma spermidine levels without supplementation even reports less favorable values for hippocampal volume and cortical thickness 16; such differences in levels are not equivalent to intake through preparations. Whether spermidine intake via rice germ extract, pure spermidine or the diet actually improves memory still needs to be clarified.

Spermidine, Heart and Circulation: Human Studies

For pure spermidine, there is no placebo-controlled study in this area; the small studies available mainly tested combination preparations. A randomised controlled study with a combination preparation of spermidine, nicotinamide, palmitoylethanolamide and oleoylethanolamide showed an improvement in cholesterol levels in overweight older adults 1. A pilot study in five young men found, after taking a preparation with the same four substances, lower inflammation and radical formation by phagocytes that were treated with their blood plasma 8. A non-randomised controlled study with a mixture of trehalose, spermidine, nicotinamide and polyphenols found no difference in blood pressure, but better vascular function 10. A pilot study without a placebo group compared two amounts of spermidine from rice germ extract; with the higher amount, hs-CRP, VLDL and triglycerides fell compared with baseline 6. The strength of evidence is unclear: the studies are small, some not randomised, and three of four investigated combination preparations, so the findings cannot be attributed to spermidine alone. Observational data on the diet with the dietary polyamines spermidine, spermine and putrescine point to a lower risk of cardiovascular disease, but measure intake differently from intervention studies and do not allow proof of an effect 12. What remains open is the effect of pure spermidine, the suitable form and amount, and long-term effects.

Spermidine, Muscles and Physical Performance: Human Studies

A small crossover study in five endurance athletes found, after taking a mixture of trehalose, spermidine, nicotinamide and polyphenols, lower muscle damage markers compared with baseline 9. The strength of evidence is low: it is a single, non-randomized study with a very small number of participants, which moreover investigated a combination product of trehalose, spermidine, nicotinamide and polyphenols 9. Whether pure spermidine or a spermidine-rich diet influences muscles and performance and how longer intake acts still needs to be clarified.

Spermidine and Metabolism: Human Studies

In this area, only small studies on combination preparations are available, in which spermidine was combined with other substances. A randomised controlled study in overweight older adults with elevated HbA1c found an improvement in fasting glucose for a combination preparation of spermidine, nicotinamide, palmitoylethanolamide and oleoylethanolamide 1. A pilot study in five endurance athletes found, for a mixture of spermidine, trehalose, nicotinamide and polyphenols, less oxidative stress and more favourable autophagy markers compared with baseline 9. The strength of evidence is unclear: the participant numbers are very small, two of the three studies were not randomised, and no finding can be attributed to spermidine alone, since all the preparations investigated were mixtures. Observational data on serum spermidine concentration point to associations with insulin resistance and body weight, but are not evidence of an effect of spermidine administration 1415. What remains open is whether pure spermidine or spermidine from rice germ extract influences metabolism in humans.

Spermidine: Further Outcomes in Studies

In a placebo-controlled pilot study in older adults, oral spermidine strengthened the antibody and memory B cell response after the third SARS-CoV-2 vaccination in people with a weak vaccine response 34. A randomised controlled study with a combination preparation of spermidine, nicotinamide, palmitoylethanolamide and oleoylethanolamide found better appetite and satiety perception as well as less abdominal pain and bloating 1; another randomised controlled study with a mixture of AM3, spermidine and hesperidin reported better immune function and a more favourable oxidative-inflammatory state 2. A non-randomised controlled study with a mixture of trehalose, spermidine, nicotinamide and polyphenols showed a reduction in oxidative stress and an increase in autophagy markers in adults with grade 1 hypertension 10. High-dose pure spermidine trihydrochloride did not change clinical, blood lipid and blood count values in a randomised placebo-controlled study in older men and was well tolerated 5. In a randomised placebo-controlled crossover study, spermidine did not increase the spermidine level in plasma, but the spermine level 7. The strength of evidence is low: mainly small groups and some combination preparations, whose findings cannot be attributed to spermidine alone. Pure spermidine and combination preparations with other active substances were investigated; what remains open are effects in larger groups, over longer periods and for a spermidine-rich diet.

Further studies in this area: 26

4. How Is Spermidine Dosed? Preparation, Dose and Duration in Studies

Studies investigated pure spermidine as a dietary supplement, spermidine from rice germ extract and combination products with other active substances such as nicotinamide, trehalose or hesperidin. The amount taken differed clearly between the studies; details are shown in the table.

5. Is Spermidine Safe? Side Effects in Studies

Pure spermidine was well tolerated in two small placebo-controlled studies; in the study with high-dose spermidine trihydrochloride, no product-related adverse events occurred 35. A combination product of spermidine, nicotinamide, palmitoylethanolamide and oleoylethanolamide did not differ from placebo in side effects 1; spermidine from rice germ extract showed unremarkable safety values in a small pilot study 6.

6. What Remains Open: Limits of the Evidence

• A large part of the findings comes from combination products, so the contribution of spermidine alone remains unclear.
• The study duration is predominantly short; long-term studies are still pending.
• There are so far only a few small studies on pure spermidine and on spermidine from rice germ extract.
• Observational data on diet measure intake differently from intervention studies and do not allow proof of an effect.

7. Bottom Line: What Is Established About Spermidine

Spermidine is a polyamine that the body produces itself and takes in through the diet. Human studies mainly investigated pure spermidine, spermidine from rice germ extract and combination preparations. In a placebo-controlled pilot study, pure spermidine lowered ageing markers in immune cells and strengthened the vaccine response in poorly responding older people 34; in another study it did not change routine clinical values 5.

The overall strength of evidence is low. Many findings come from combination preparations with other active substances and cannot be attributed to spermidine alone 1. Observational data on a polyamine-rich diet point to a lower mortality and cardiovascular risk, but do not prove an effect 12. Pure spermidine was well tolerated in the small placebo-controlled studies 35.