Singh · European journal of clinical nutrition 2022 · randomized controlled trial · n=100

Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population.

Cited 119 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial measuring plasma bioavailability and microbiome profiles.

PubMed 34117375 · doi:10.1038/s41430-021-00950-1 · record verified 2026-08-26

What was done

In a randomized trial of 100 healthy adults, participants were evaluated for urolithin A (UA) producer status using dietary pomegranate juice (PJ) and randomized 1:1 to receive either PJ or a food product containing 500 mg of UA. Fecal samples, diet questionnaires, and serial plasma samples were analyzed to assess gut microbiome composition and circulating levels of UA and its conjugates.

What was found

At baseline, 12% of subjects had detectable UA. Following PJ intake, approximately 40% of subjects converted precursor compounds into UA. UA producers had significantly higher gut microbiome diversity and a higher ratio of Firmicutes to Bacteroides than non-producers. Direct supplementation with 500 mg UA provided a >6-fold higher plasma exposure compared to PJ (p < 0.0001).

Why it matters

Most healthy adults lack the microbiome capacity to convert dietary ellagitannins into urolithin A, demonstrating that direct supplementation provides consistent plasma levels across a population.

Limits

The abstract does not report downstream clinical, functional, or mitochondrial health outcomes, focusing solely on pharmacokinetic exposure and microbiome markers. Exact numerical plasma concentrations, dispersion measures, and demographics beyond healthy adults are not detailed.

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