Figure 3. Effect of Spermidine Supplementation on Primary and Selected Secondary Outcomes in Intention-to-Treat Analysis ALT indicates alanine aminotransferase; AST, aspartate…
The largest trial gave 100 older adults with memory complaints 0.9 mg of spermidine or a dummy pill (placebo A dummy treatment that looks like the real one, so people can't tell which they got.) daily for 12 months. Memory did not change, and the gap between groups could easily be chance1Randomized trial · 2022 · 100 peopleEffects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future…JAMA Netw Open. Exploratory checks hinted at gains in verbal memory and inflammation, which need confirming1Randomized trial · 2022 · 100 peopleEffects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future…JAMA Netw Open.
A 3-month pilot of 30 similar adults (1.2 mg a day) found a moderate memory gain with spermidine. The uncertainty range was wide, and the trial was small3Randomized trial · 2018 · 30 peopleThe effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.TRIAL REGISTRATION: Registered in ClinicalTrials. gov with the Identifier NCT02755246.Cortex. It was designed mainly to test safety, and blood tests and vital signs matched placebo2Randomized trial · 2018 · 30 peopleSafety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.The data demonstrate that spermidine supplementation using a spermidine-rich plant extract is safe and well-tolerated in mice and older adults. These findings allow for longer-term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.Aging (Albany NY).
A trial of 85 nursing home residents with dementia over 3 months linked higher spermidine doses to better memory scores in mild dementia. Results differed across dose groups, and the report was preliminary4Randomized trial · 2021 · 85 peopleThe positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial.47) in phonematic fluidity. By comparison, the group which had a lower spermidine intake showed consistent or declining cognitive performance.Wien Klin Wochenschr.
A pilot of 40 healthy adults over 65 gave 6 mg daily for 13 weeks after a COVID vaccine dose. In people who responded poorly to the vaccine, antibody and immune-cell measures improved. The study was small and measured immune markers, not aging5Randomized trial · 2026 · 40 peopleSpermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults-A Pilot Study.Single-cell RNA-seq after treatment revealed increased expression of TFEB targets and autophagy-related genes in B cells, in line with elevated autophagic flux. These findings suggest that targeting immune cell senescence with Spermidine may improve vaccine responsiveness in older adults and highlight…Aging Cell.
A 56-day pilot of 12 healthy adults, single-blinded, found that 3.3 mg a day (not 1.5 mg) was linked to small rises in autophagy and brain markers and to lower inflammation and triglycerides compared with their own starting values8Randomized trial · 2025 · 12 peopleEffects of Spermidine-Rich Rice Germ Extract Supplement on Biomarkers of Healthy Aging and Autophagy-Proof-of-Concept Pilot Study.This pilot study found that 3.3 mg/day of spermidine from Miricell® rice germ extract tends to improve biomarkers of autophagy, neuroprotection, and cardiometabolic health. Appropriate follow-up studies are warranted to confirm these findings.Altern Ther Health Med. It had no placebo group.
Spermidine from food was associated with better liver and metabolic readings over a year in 2,664 older adults with metabolic syndrome. This was an observational Studies that watch what happens to people rather than assigning a treatment. They can show links, not cause and effect. analysis, so it can't show cause10Randomized trial · 2026 · 2,664 peopleLongitudinal association of dietary spermidine with hepatic function indexes and cardiometabolic traits in older adults with metabolic syndrome.A 1-year increase in dietary spermidine intake was associated with improvements in hepatic function indexes and cardiometabolic traits in overweight and obese older adults with metabolic syndrome.Eur J Nutr.
Lab and animal work, plus reviews of it, links spermidine to longer life in yeast, worms, flies and mice. This hasn't been shown in people7Review · 2018Spermidine in health and disease.Mechanistically, it shares the molecular pathways engaged by other caloric restriction mimetics: It induces protein deacetylation and depends on functional autophagy. Because spermidine is already present in daily human nutrition, clinical trials aiming at increasing the uptake of this polyamine appear feasible.Science,9Study · 2024Spermidine is essential for fasting-mediated autophagy and longevity.Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.Nat Cell Biol.
Key studies
Study
Who
What it found
Trial, 20221Randomized trial · 2022 · 100 peopleEffects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future…JAMA Netw Open
100 older adults, memory complaints
No memory change after 12 months
Pilot trial, 20183Randomized trial · 2018 · 30 peopleThe effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.TRIAL REGISTRATION: Registered in ClinicalTrials. gov with the Identifier NCT02755246.Cortex
30 older adults, memory complaints
Moderate memory gain at 3 months
Pilot trial, 20265Randomized trial · 2026 · 40 peopleSpermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults-A Pilot Study.Single-cell RNA-seq after treatment revealed increased expression of TFEB targets and autophagy-related genes in B cells, in line with elevated autophagic flux. These findings suggest that targeting immune cell senescence with Spermidine may improve vaccine responsiveness in older adults and highlight…Aging Cell
40 healthy adults over 65
Better vaccine response in poor responders
Pilot trial, 20258Randomized trial · 2025 · 12 peopleEffects of Spermidine-Rich Rice Germ Extract Supplement on Biomarkers of Healthy Aging and Autophagy-Proof-of-Concept Pilot Study.This pilot study found that 3.3 mg/day of spermidine from Miricell® rice germ extract tends to improve biomarkers of autophagy, neuroprotection, and cardiometabolic health. Appropriate follow-up studies are warranted to confirm these findings.Altern Ther Health Med
12 healthy adults
Marker changes at 3.3 mg only
Study following people, 202610Randomized trial · 2026 · 2,664 peopleLongitudinal association of dietary spermidine with hepatic function indexes and cardiometabolic traits in older adults with metabolic syndrome.A 1-year increase in dietary spermidine intake was associated with improvements in hepatic function indexes and cardiometabolic traits in overweight and obese older adults with metabolic syndrome.Eur J Nutr
2,664 older adults, metabolic syndrome
Higher intake linked to better liver readings
Safety
Trials reported spermidine as well tolerated, with compliance above 85%2Randomized trial · 2018 · 30 peopleSafety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.The data demonstrate that spermidine supplementation using a spermidine-rich plant extract is safe and well-tolerated in mice and older adults. These findings allow for longer-term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.Aging (Albany NY). In the 12-month trial, side effects were balanced overall, but bone and joint problems such as arthritis and gout attacks were more common with spermidine (11 people versus 4)1Randomized trial · 2022 · 100 peopleEffects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future…JAMA Netw Open. One dementia report saw lower vitamin B12 in one group, which may be chance4Randomized trial · 2021 · 85 peopleThe positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial.47) in phonematic fluidity. By comparison, the group which had a lower spermidine intake showed consistent or declining cognitive performance.Wien Klin Wochenschr.
What we don't know
Whether spermidine affects lifespan, healthspan or disease in people; no trial tracked these.
Which dose works, if any. Trials used about 0.9 to 6 mg a day, and the largest used the lowest dose1Randomized trial · 2022 · 100 peopleEffects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial.In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future…JAMA Netw Open,5Randomized trial · 2026 · 40 peopleSpermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults-A Pilot Study.Single-cell RNA-seq after treatment revealed increased expression of TFEB targets and autophagy-related genes in B cells, in line with elevated autophagic flux. These findings suggest that targeting immune cell senescence with Spermidine may improve vaccine responsiveness in older adults and highlight…Aging Cell.
Written by AI from the studies listed, without review by a clinician, and graded with the GRADE method. It can be wrong, so check the studies it cites. Education, not medical advice.