A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

  • Triggers autophagy and extends life

    Not studied

    Longevity · healthy · Animal study

    Life extension and autophagy-dependent cardioprotection have been shown only in mice [2]. In humans, there is one cohort in which dietary spermidine was associated with lower mortality; this is an association and does not concern a supplement [3]. Autophagy in humans was measured only exploratorily in B cells of a pilot study [9]. Lifespan in humans has not been studied.

  • Improves memory in old age

    No benefit

    Cognition & focus · Patients: subjective cognitive decline (60 to 90 years) · Human, randomised

    In SmartAge (100 participants, 12 months, wheat germ extract), neither the primary memory endpoint (−0.03; 95% CI −0.11 to 0.05; p = 0.47) nor the secondary endpoints changed; positive indications come only from exploratory analyses [8]. The preceding pilot study (30 participants, 3 months) found only a nonsignificant benefit in the group comparison (contrast 0.17; 95% CI −0.01 to 0.35), an improvement only within the spermidine group [7]. Several authors are involved in the manufacturer [6][8].[6]

  • Rejuvenates the immune system and improves the vaccine response in old age

    Single unconfirmed finding

    Immune system & infections · healthy (over 65 years) · Human, randomised small studiesEvery study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    Pilot study with 40 participants, primary endpoint safety; better antibody and B cell responses only in people without a sufficient vaccine response, with unevenly distributed groups at baseline and explicitly exploratory efficacy findings. Three authors advise spermidine providers (TLL, Oxford Healthspan), and TLL co-funded the study and supplied extract and placebo [9].

  • Protects heart and blood vessels

    Not studied

    Heart & blood vessels · healthy · Animal study

    Cardioprotection in old mice and blood pressure reduction in salt-sensitive rats [2]. In humans, only associations between dietary spermidine and blood pressure or cardiovascular disease [2]; an intervention study with a cardiovascular endpoint was not found.

  • Replenishes the spermidine level that declines with age (marker only)

    No benefit

    Longevity · healthy · Human, randomised small studiesEvery study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

    Marker only: in a randomized crossover study with 12 people, only spermine rose in plasma, not spermidine [4]; synthetic spermidine trihydrochloride hardly changed polyamines in serum and urine (manufacturer study with 37 men) [5]. No kinetic data were found for the wheat germ extract from SmartAge.

small studies: Every study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

manufacturer-funded: According to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

Mechanism of action

Evidence map: Spermidine

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

Spermidine, together with putrescine and spermine, belongs to the polyamines, which occur in all cells and decline with age. A review by the Graz research group describes it as a caloric restriction mimetic: in animal and cell models, it triggers protein deacetylation and autophagy, and its protective effects depend on functioning autophagy [1].

The most important finding comes from animal experiments. Spermidine given in the feed extended the lifespan of mice, reduced cardiac hypertrophy and preserved diastolic function in old animals; in the heart, autophagy, mitophagy and mitochondrial respiration rose. In mice lacking the autophagy protein Atg5 in cardiac muscle cells, the cardioprotection was absent. In salt-sensitive rats, spermidine lowered blood pressure and delayed heart failure (level 2) [2]. In humans, there are only observational data on this: in the same paper, a high spermidine intake according to a dietary questionnaire was associated with lower blood pressure and fewer cardiovascular diseases [2], and in the Bruneck cohort (829 participants, 341 deaths in 20 years), an intake one standard deviation higher was associated with about one quarter lower mortality (HR 0.76) [3]. These are associations with diet, not evidence for a supplement.

Whether ingested spermidine reaches the body at all is questionable. In a triple-blind crossover study with twelve healthy people, after five days of taking a spermidine-rich preparation based on chlorella and soy extract, only spermine rose in plasma, not spermidine; the authors suspect a conversion before passage into the blood [4]. Even high-dose synthetic spermidine trihydrochloride hardly changed polyamines in serum and urine in 37 older men; this study comes from the manufacturer [5].

The clinical studies mostly used a wheat germ extract. After a three-month safety study with 30 older people without differences from placebo [6], whose memory analysis (same study, NCT02755246) found at the end only a nonsignificant group difference (contrast 0.17; 95% CI −0.01 to 0.35) and an improvement only within the spermidine group [7], the SmartAge study in 100 people aged 60 to 90 with subjective cognitive decline tested memory for twelve months: the primary endpoint did not change (difference −0.03; 95% CI −0.11 to 0.05), nor did any of the secondary ones; indications of effects on inflammation and verbal memory come from exploratory analyses [8]. Several authors of these studies are involved in the manufacturer The Longevity Labs (TLL) [6][8]. A pilot study with 40 people over 65 years after the third COVID vaccination had safety as its primary endpoint; only in people without a sufficient vaccine response did antibody and memory B cell responses improve, and the expression of autophagy-related genes rose in B cells. The groups were unevenly distributed at baseline (eight of 20 versus two of 18 without vaccine response), and the efficacy findings are explicitly exploratory. TLL supplied extract and placebo and co-funded the study; three authors advise TLL or Oxford Healthspan [9].

Synaptik serves solely to explain biochemistry and pharmacology and is not medical advice or a recommendation to take anything.

Mechanism of action only. Schematic cutaway, not to scale: on the left a body cell with the nutrient switches AMPK and mTORC1, on the right two senescent cells. Particles, speeds and switch positions are illustrative and only show the direction of a finding; the switch bar says where it comes from (cell culture, animal or human). Lifespan findings come from worms and mice; human lifespan has not been studied with any of these drugs.

Autophagy and mitophagy increased (mouse heart) · AMPK and mTORC1: not measured

AMPK
not measured
mTORC1
not measured
Autophagy
increasedmouse heart
Senescent cells
not measured
Drug
View

ATP  AMP  amino acids  SASP  mTORC1 inhibitors  AMPK activators  Autophagy  Senolytics  particles illustrative

Spermidine, an endogenous polyamine, given in the diet extended the lifespan of mice and preserved heart function in old animals; autophagy, mitophagy and mitochondrial respiration rose in the heart. In mice lacking the autophagy protein Atg5 in cardiomyocytes, the heart protection was lost [28]. These are animal data. In humans, a spermidine-rich wheat germ extract did not change memory in the SmartAge trial (100 people aged 60 to 90, twelve months) [29].

Tap or focus a labelled part for a one-line explanation.

Also acting here, not drawn

What the figure shows, and how sure we are

Mechanism-of-action explainer only. Not medical advice, and no statement about benefit, risk, amount or use. Sirolimus, everolimus, metformin, canagliflozin and dasatinib are prescription medicines; none of them is approved for use against ageing.

What was simplified. One cell stands for many cell types; the findings come from liver, muscle, fat and heart cells of different species, and the figure only shows where each drug acts. Sizes, numbers of organelles, particles and speeds are illustrative; glucose output applies to liver cells only. The signal lines stand for several intermediate steps (for example AMPK via TSC2 and Raptor). Switches marked “not measured” do not follow the textbook pathway: whether metformin, for instance, increases autophagy in these cells is not stated in the profile's sources. Drugs are drawn as markers, not as skeletal formulas. Calcium alpha-ketoglutarate, pentadecanoic acid, sulforaphane, TUDCA and further substances are listed at this site in the figure catalogue but are not drawn; the reasons are given in the list below the figure. The γ subunit is drawn with four CBS domains, with nucleotides only at the three binding sites from [3]. The numbers in [5], [6], [8] to [15] and [17] to [35] come from the Synaptik profiles of the drugs, where they were checked against the sources. [1] and [2] were checked against the full text, [3], [4], [7] and [16] against the PubMed abstract (25 Oct 2026).

Targets

TargetTypeActionKey dataEvidence
Autophagy and mitophagySignaling pathwayActivatorincreased in the mouse heart; cardioprotection abolished in Atg5 deficiency Animal study[1][2]
Autophagy-related genes in B cells (TFEB target genes)Signaling pathwayExpression ↑single-cell sequencing in a pilot study, exploratory Human, randomised[9]
Spermine in plasmaOtherLevels ↑Spermine rose, spermidine and putrescine did not (n = 12) Human, randomised[4]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineno data
  • Noradrenalineno data
  • Serotoninno data
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowmodulated · Blood pressure lowered in salt-sensitive rats; in humans only an association with dietary spermidine[2]
  • Nitric oxideno data
  • Energy metabolismno data
  • Insulin · glucoseno data
  • Inflammation · oxidativeno data
  • Stress axisno data
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescence↑ · Autophagy and mitophagy in the heart of mice, effect dependent on Atg5; in humans only exploratory gene findings in B cells[1][2][9]
  • Immune systemmodulated · Vaccine response improved only in older people without a sufficient response; pilot study with unequal groups[9]
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Oral (swallowed) · spermidine-rich preparation (chlorella and soy extract)

    Plasma spermidine unchanged, spermine increased (human)

    The authors suspect a conversion to spermine before entry into the circulation; salivary polyamines remained unchanged [4].

    Human, randomised

  • Oral (swallowed) · synthetic spermidine trihydrochloride

    hardly any change in polyamines in serum and urine (human)

    Manufacturer study in 37 older men over up to 28 days [5].

    Human, randomised

Human studies

  • Bruneck cohort: dietary spermidine and mortality

    prospective cohort with validation in a second cohort · healthy (45 to 84 years) · n = 829 · 20 years

    Measured: All-cause mortality

    Result: HR 0.76 (95% CI 0.67–0.86) per standard deviation of higher intake after adjustment; association, not a supplement.[3]

    Human, non-randomised

  • Safety of a wheat germ extract

    RCT, double-blind, placebo-controlled, phase 2 · Patients: subjective cognitive decline (60 to 80 years) · n = 30 · 3 months

    Measured: Vital signs, laboratory values, self-reported health

    Result: No differences from placebo; capsules from the manufacturer, authors financially involved.[6]

    Human, randomised

  • Memory in the pilot study (same study as the safety study)

    RCT, double-blind, placebo-controlled, phase 2a · Patients: subjective cognitive decline (60 to 80 years) · n = 30 · 3 months

    Measured: Memory performance (Mnemonic Similarity Task)

    Result: Group difference at the end not significant (contrast 0.17; 95% CI −0.01 to 0.35; Cohen’s d 0.77); improvement only within the spermidine group; analysis by effect sizes. Authors with TLL involvement.[7]

    Human, randomised

  • SmartAge: memory in subjective cognitive decline

    RCT, double-blind, placebo-controlled, phase 2b · Patients: subjective cognitive decline (60 to 90 years) · n = 100 · 12 months

    Measured: Mnemonic discrimination (primary); further neuropsychological and physiological measures

    Result: No difference in the primary (p = 0.47) and in the secondary endpoints; adverse events balanced. Several authors involved in the manufacturer.[8]

    Human, randomised

  • Kinetics of a spermidine-rich preparation

    RCT, triple-blind, placebo-controlled, crossover · healthy · n = 12 · 2 × 5 days

    Measured: Polyamines in plasma and saliva, plasma metabolome

    Result: Spermine in plasma increased, spermidine and putrescine unchanged; no conflicts of interest, no external funding.[4]

    Human, randomised

  • Synthetic spermidine trihydrochloride

    RCT, double-blind, placebo-controlled, within-subject · healthy (men, 50 to 70 years) · n = 37 · 7 and 28 days

    Measured: Safety, polyamines in serum and urine

    Result: No differences in safety parameters; polyamines hardly changed. Study by employees and with funding from the manufacturer.[5]

    Human, randomised

  • Vaccine response in old age

    RCT, double-blind, placebo-controlled, pilot study · healthy (over 65 years, after third COVID vaccination) · n = 40 · 13 weeks

    Measured: Safety (primary); antibodies, B and T cell responses, senescence and autophagy markers (exploratory)

    Result: Well tolerated; antibody and B cell responses improved only in people without a sufficient vaccine response; unequal baseline groups (8/20 vs. 2/18 without response).[9]

    Human, randomised

Risks and warnings

  • Short-term safety unremarkable, long-term data lacking

    In studies lasting 4 weeks to 12 months, there were no differences from placebo in adverse events or laboratory values [5][6][8][9]. The Union list permits the wheat germ extract only for adults, excluding pregnant and lactating women [10]. Data over several years are lacking.

    Human, randomised

  • Manufacturer involvement

    Several authors of the wheat germ extract studies hold shares in The Longevity Labs (TLL) or advise the company; the manufacturer supplied the capsules or funds for the extract development [6][8]. In the vaccination study, three authors advise TLL or Oxford Healthspan, and TLL supplied extract and placebo and was among the funders, according to the statement without influence on design and analysis [9]. In the mouse study, five authors of the Graz research group held shares in TLL [2]; two of them are also involved in the Bruneck analysis [3]. The study on synthetic spermidine comes from employees of the manufacturer Chrysea Labs [5]. Without declared conflicts of interest and without external funding is the kinetic study [4].

    Human, randomised

Fact check: common claims

  • not supported

    “Spermidine works like fasting in capsule form (caloric restriction mimetic)”

    The concept comes from animal and cell models [1]. In humans, neither a fasting-like metabolic effect nor an increase in autophagy in tissue has been shown; only exploratory gene findings in B cells were measured [9].

  • partly supported

    “Anyone who eats a lot of spermidine lives longer”

    In the Bruneck cohort, a higher intake was associated with lower mortality, confirmed in a second cohort [3]. This is an association; cause and effect are not documented by it, and it cannot be transferred to supplements.

  • not supported

    “Spermidine supplements raise spermidine in blood plasma in the short term”

    In two controlled studies with preparations other than the wheat germ extract (chlorella-soy preparation and synthetic spermidine trihydrochloride, respectively), plasma spermidine remained unchanged or hardly changed; only spermine rose [4][5]. Kinetic data of its own are lacking for the wheat germ extract; hence “not documented” instead of “refuted” (Tilman, October 25, 2026). For [5], only the abstract was checked.

  • not supported

    “Spermidine demonstrably improves memory”

    Tested only in older people with subjective cognitive decline: the twelve-month RCT SmartAge found no effect on the primary and secondary memory endpoints [8], the small pilot study only a nonsignificant group difference [7]. For other groups, such as healthy people without complaints, there are no studies; a “no benefit” cannot be transferred to them.

Pharmacokinetics

Absorption
In two controlled studies, spermidine in plasma did not rise appreciably after intake; after a preparation from chlorella and soy, spermine rose [4][5].
Half-life
Not verified.
Metabolism
Presumably conversion to spermine before entry into the circulation (interpretation of the authors) [4].
Entry into the brain
Not studied in humans.

Legal status

Germany
Not verified; for the EU regulation, see below.
EU
The consolidated Union list of novel foods (as of August 10, 2026) lists “wheat germ extract (Triticum aestivum) with high spermidine content”, authorized only for food supplements for adults, excluding pregnant and lactating women; the specification applies in the version of Implementing Regulation (EU) 2020/443 [10]. Synthetic spermidine or spermidine trihydrochloride has no entry of its own; the specification of the wheat germ extract allows spermidine trichloride only in traces. Other spermidine-rich preparations (e.g., from algae or soy) were not checked individually. Via Cellar, no EU legal act with “spermidine” in the English title can be found other than Implementing Regulation (EU) 2020/443 (October 24, 2026). Maximum amounts are not reproduced.
USA
Not verified.

Related compounds

Urolithin Asame class

Open questions

  • Does ingested spermidine from wheat germ extract reach blood and tissue at all, or does it act, if at all, via spermine or the gut?
  • Can the better vaccine response be confirmed in a sufficiently large study with balanced groups?
  • Do high polyamine levels over years promote the growth of existing tumors? No human data were found on this.
  • What is behind the widespread claim about hair growth? Not researched.

References

  1. Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018;359(6374):eaan2788. doi:10.1126/science.aan2788 · PubMed
  2. Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22(12):1428–1438. doi:10.1038/nm.4222 · PubMed
  3. Kiechl S, Pechlaner R, Willeit P, Notdurfter M, Paulweber B, Willeit K, et al. Higher spermidine intake is linked to lower mortality: a prospective population-based study. Am J Clin Nutr. 2018;108(2):371–380. doi:10.1093/ajcn/nqy102 · PubMed
  4. Senekowitsch S, Wietkamp E, Grimm M, Schmelter F, Schick P, Kordowski A, et al. High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study. Nutrients. 2023;15(8):1852. doi:10.3390/nu15081852 · PubMed
  5. Keohane P, Everett JR, Pereira R, Cook CM, Blonquist TM, Mah E. Supplementation of spermidine at 40 mg/day has minimal effects on circulating polyamines: An exploratory double-blind randomized controlled trial in older men. Nutr Res. 2024;132:1–14. doi:10.1016/j.nutres.2024.09.012 · PubMed
  6. Schwarz C, Stekovic S, Wirth M, Benson G, Royer P, Sigrist SJ, et al. Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline. Aging (Albany NY). 2018;10(1):19–33. doi:10.18632/aging.101354 · PubMed
  7. Wirth M, Benson G, Schwarz C, Köbe T, Grittner U, Schmitz D, 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. doi:10.1016/j.cortex.2018.09.014 · PubMed
  8. Schwarz C, Benson GS, Horn N, Wurdack K, Grittner U, Schilling R, et al. Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(5):e2213875. doi:10.1001/jamanetworkopen.2022.13875 · PubMed
  9. Alsaleh G, Ali M, Kayvanjoo AH, Liu F, Moreau T, Bibi S, et al. Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults-A Pilot Study. Aging Cell. 2026;25(6):e70545. doi:10.1111/acel.70545 · PubMed
  10. Durchführungsverordnung (EU) 2017/2470 der Kommission vom 20. Dezember 2017 zur Erstellung der Unionsliste der neuartigen Lebensmittel gemäß der Verordnung (EU) 2015/2283. ABl. L 351 vom 30.12.2017, S. 72. Konsolidierte Fassung vom 10.08.2026 (CELEX 02017R2470-20260810).
How this profile was checked

Last reviewed: 2026-10-25. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-25); translation checked on 2026-10-26.

Checked

  • DOIs checked via Crossref and PMIDs via PubMed (checking script); Vancouver references generated from the PubMed records.
  • Checked against the abstract: caloric restriction mimetic, deacetylation, autophagy-dependent [1]; life extension in mice, hypertrophy, diastolic function, Atg5 knockout, salt-sensitive rats, questionnaire association in humans [2]; n = 829, 341 deaths, HR 0.76 (0.67–0.86), validation in SAPHIR [3]; n = 12, crossover, spermine ↑, spermidine and putrescine unchanged [4]; n = 37, hardly any change in polyamines, employees and funding Chrysea Labs [5]; n = 30, 3 months, no differences [6]; n = 100, primary endpoint −0.03 (−0.11 to 0.05), p = 0.47 [8]; n = 40, non-responders, consulting relationships with TLL and Oxford Healthspan [9].
  • Checked in the full text: [4] (PMC10143675) preparation based on chlorella and soy extract, no conflicts of interest, no external funding; [6] (PMC5807086) capsules from TLL The Longevity Labs, four authors (Stekovic, Sigrist, Eisenberg, Madeo) with a financial interest in TLL; [8] (PMC9136623) shares and consulting roles at TLL (Madeo, Sigrist, Eisenberg), one author CEO of TLL during the study, TLL funded the extract development, study itself funded by the BMBF; [9] (PMC13240347) wheat germ extract, primary endpoint safety, efficacy exploratory, 8 of 20 versus 2 of 18 without vaccine response at baseline.
  • Legal status (October 24, 2026): consolidated Union list 02017R2470-20260810 (German and English) read: entry “wheat germ extract (Triticum aestivum) with high spermidine content”, food supplements for adults excluding pregnant and lactating women, specification with amendment note M43 = Implementing Regulation (EU) 2020/443 [10]; no further entry on spermidine. Cellar SPARQL over English titles: only 32020R0443.
  • PubChem: Spermidine CID 1102.
  • Cross-check on October 24, 2026: [7] against the abstract: n = 30, 60–80 years, phase IIa, contrast 0.17 (CI −0.01 to 0.35), d = 0.77, registration NCT02755246, identical to the registration of [6] (full text PMC5807086). [9] COI in the PubMed record: A.K.S. advises TLL and Oxford Healthspan, G.A. Oxford Healthspan, T.E. TLL; full text PMC13240347, funding: among others “TLL The Longevity Labs GmbH”, extract and placebo from TLL. [2] COI in the PubMed record: F.M., T.E., D.C-G., S.J.S. and S. Stekovic with shares in TLL; freely available in PMC (PMC5806691). [3] Author list with Eisenberg T and Madeo F; COI statement of [3] not checked. [5] Abstract: “minimal effects on circulating polyamines”.
  • October 25, 2026: decision q066 (Tilman): claim “Spermidine supplements raise spermidine in blood plasma in the short term” refuted → not documented (both kinetic studies with preparations other than the wheat germ extract; rationale adjusted). The marker second promise remains 4 · no benefit (marker unchanged in both studies, K3). q012: full texts read [4], [6], [8], [9]; all other study findings checked against the abstract only.
  • October 26, 2026, precision flags (m004; rules in the guideline under “number rule and precision flags”, implementation by Claude pending confirmation by Tilman): “Rejuvenates the immune system and improves the vaccine response in old age”: “kleine_studien”, “herstellerfinanziert” – [9] 40 participants (abstract); funding statement in PubMed among others “TLL The Longevity Labs GmbH”, according to the rationale, TLL supplied extract and placebo (co-funding by the manufacturer, pending confirmation by Tilman). “Replenishes the spermidine level that declines with age (marker only)”: “kleine_studien” – [4] 12 people (crossover), [5] 37 men (abstracts). Cross-check on October 26, 2026: evidence for the flags (participant numbers, direction, funding) transferred into the rationale and checked again against abstracts and full texts.

Not verified

  • Status in Germany and the USA; novel food status of spermidine-rich preparations from algae, soy or buckwheat and of synthetic spermidine (catalogue not checked). The ECJ ruling C-141/22 on buckwheat sprout flour from the scope notes was not read personally and therefore not included.
  • Kinetic data on the wheat germ extract itself.
  • Half-life of spermidine in humans.
  • COI statement of the Bruneck analysis [3].

No dosages, no sources of supply. This information does not replace medical advice.

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