Narrative review of spermidine, fisetin, berberine and urolithin A as functional food ingredients
This narrative review describes four natural compounds that act on different aging-associated pathways and suggests potential for combined functional food formulations, while noting limited direct evidence for combined use. [1]
Automatic summary · not editorially reviewed
The key findings
Spermidine induces autophagy through EP300 inhibition and is associated with reduced all-cause mortality in prospective studies. [1]
Berberine has the most extensive clinical dataset of the four compounds, and fisetin has emerging clinical evidence. [1]
The review notes limited direct evidence for combined use and the need for dedicated co-administration studies. [1]
The source at a glance
- Study type / format
- Narrative review (abstract only)
- Population / context
- Four natural bioactive compounds (spermidine, fisetin, berberine, urolithin A) discussed in relation to human aging
- Summary based on
- Study abstract
- Original publication
- August 3, 2026
Four compounds and their proposed aging pathways
The review covers spermidine, fisetin, berberine and urolithin A as emerging functional food ingredients. Spermidine, a dietary polyamine from wheat germ and fermented foods, induces autophagy through EP300 inhibition. Fisetin, a flavonoid from strawberries and apples, shows senolytic activity by selectively eliminating senescent cells via PI3K/AKT and Bcl-2/Bcl-xL inhibition. Berberine, an isoquinoline alkaloid from Berberis species, modulates metabolic dysfunction via AMPK activation and reshapes gut microbiota. Urolithin A, a gut microbiome-derived postbiotic from ellagitannins in pomegranates and nuts, induces mitophagy via PINK1/Parkin.
Supporting source [1]
Reported human evidence differs across the four compounds
The review reports different levels of human evidence. Spermidine is associated with reduced all-cause mortality in prospective studies. Fisetin has emerging clinical evidence. Berberine has the most extensive clinical dataset of the four compounds. Urolithin A has been evaluated in a growing number of registered human clinical trials. These are associations and evidence descriptions, not proof that the compounds extend human lifespan.
Supporting source [1]
Combined use remains untested in dedicated studies
The four compounds primarily target distinct but complementary aging-associated pathways: autophagy, senolysis, metabolic regulation and mitophagy. The review suggests rational potential for combined functional food formulations. However, it notes limited direct evidence for their combined use and the need for dedicated co-administration studies, alongside bioavailability, safety and regulatory considerations.
Supporting source [1]
How to interpret this
This is an abstract of a narrative review; the full text was not reviewed. The abstract reports no sample sizes, follow-up durations or effect estimates, and the evidence levels described differ by compound. Combined use is not supported by dedicated studies according to the abstract.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Rzeski W, Rzeska W. · europepmc.org · August 3, 2026