Urolithin A and Immune Function: What the Human Trials Measured

This is a Mt. Angel Vitamins white paper, not a peer-reviewed article. It summarizes the human urolithin A immune studies. The one randomized trial that measured immune cells gave 50 healthy middle-aged adults 1,000 mg a day or placebo for four weeks. It moved some CD8 T cell measures and their metabolism. It did not measure infections, illness, or vaccine response, so it is not evidence of a clinical immune benefit.

If you're not a researcher

The question: does urolithin A change the immune system in people? One randomized trial says it changes some immune cells. No human trial has shown fewer infections or fewer illnesses.

The main trial: 50 healthy middle-aged adults took 1,000 mg a day or placebo for four weeks. The headline T cell result was a 0.50 percentage-point difference between the groups, which is a small shift.

Strength of the evidence: preliminary. It is one randomized trial of 50 people, measured in blood cells rather than illness. The sponsoring company, Amazentis SA, is listed as an affiliation for four of the 19 authors.

The dose tested: 1,000 mg a day for 28 days. The dosage page covers the other doses the human trials used.

What to do with this: if you take urolithin A for general wellness, 1,000 mg a day is the number to compare against. If you are taking it for immune reasons, the human evidence does not support that choice yet.

Full plain-English guide: the urolithin A monograph covers forms, safety, and who should ask a clinician first.

Does urolithin A help the immune system?

No human trial has shown that urolithin A improves an immune outcome. The one randomized trial that measured immune cells found changes in some T cell groups after four weeks, and the main change was small. The trial did not measure infections, illness, or vaccine response, so those cell changes do not show a benefit to the immune system. The immune health guide covers the wider immune picture.

What did the 2025 trial measure?

Denk et al. (2025, Nature Aging) ran a randomized, double-blind, placebo-controlled trial in 50 healthy middle-aged adults. Each participant took 1,000 mg of urolithin A a day or placebo for 28 days, and immune cells were measured at baseline and day 28. The registry entry, NCT05735886, lists four 250 mg softgels a day, names the ingredient Mitopure, lists Amazentis SA as lead sponsor, and sets eligibility at ages 45 to 70 with a BMI under 35.

Primary outcomes. The primary outcomes were changes in CD8 T cell subsets and in the metabolism of those cells. Urolithin A expanded the naive-like, less exhausted CD8 group, with a treatment difference of 0.50 percentage points (95% interval 0.16 to 0.83, P = 0.0437). It also raised the fat-burning capacity of CD8 cells by 14.72 percentage points (95% interval 6.46 to 22.99, P = 0.0061). Grade: Preliminary for both. The evidence is one randomized trial of 50 people, the outcomes are cell measurements, and no other trial has repeated them.

Secondary outcomes. The abstract also reports more CD56+CD16+ NK cells and nonclassical CD14+CD16+ monocytes in the urolithin A group, more mitochondrial biogenesis in CD8 cells, better TNF release from activated T cells, and better bacterial uptake by monocytes. An exploratory single-cell analysis showed gene activity shifts across immune cell types. Grade: Preliminary for these cell-level results, since they are secondary or exploratory and come from the same 50 people.

Limits. Four weeks is a short window. These are cell measurements, not clinical outcomes. Four of the 19 authors list Amazentis SA as an affiliation. ClinicalTrials.gov shows no posted results.

What did the trial leave out?

The registry classifies the study's primary purpose as basic science, not as a test of clinical benefit. The registered outcomes include cytokine levels, an in vitro immune assay, and a count of adverse events. They do not include infections, illness, or vaccine response.

Plasma cytokines (IL-6, TNF, IL-1β, IL-10) were a secondary outcome. The abstract does not report a result for them, and this page works from the abstract and the registry record. Check the full paper before quoting cytokine data. Grade: Insufficient for any anti-inflammatory effect in this trial.

The trial excluded people taking vitamin C, zinc, CoQ10, or NAD+ supplements in the 45 days before screening, and anyone on systemic immunosuppression in the prior six months. Its results describe healthy adults, not people on immunosuppressive treatment.

What do the other human trials show?

Three other trials gave urolithin A directly, and one gave a synbiotic that raised the body's own urolithin A. A fifth study is a protocol with no results. None of the five reports infection or vaccine data, the outcomes most readers mean by immune benefit.

Singh et al. (2022, Cell Reports Medicine). A randomized trial in middle-aged adults, run for four months at two doses. The abstract reports muscle strength up about 12 percent, with gains in aerobic endurance and a six-minute walk test. Peak power output, the primary endpoint, did not improve significantly. The abstract reports lower C-reactive protein (CRP) and plasma acylcarnitines with urolithin A. Six of nine authors list Amazentis SA. Grade for CRP: Preliminary, because the CRP signal rests on a single trial and is one of several markers. The abstract describes no immune outcome beyond CRP.

Zhao et al. (2024, Journal of the International Society of Sports Nutrition). Twenty resistance-trained men took 1 g a day for eight weeks in a randomized, placebo-controlled trial. CRP rose from baseline in the urolithin A group (difference 0.71 mg/L, P = 0.001) but ended lower than placebo (difference 0.79 mg/L, P = 0.032). IL-6 did not change significantly. Superoxide dismutase fell relative to placebo (P = 0.041), which is hard to read as an improvement without more context. The authors summarize the study as reduced inflammation and oxidative stress. Grade: Insufficient. The CRP result depends on which comparison you read, and the group is small.

Whitfield et al. (2025, Sports Medicine). Forty-two trained male distance runners took 1,000 mg a day for four weeks during an altitude training camp, the same dose and length as the 2025 immune trial. The 3,000 m time trial did not improve significantly in either group, although perceived exertion was lower with urolithin A. Creatine kinase, a muscle-damage marker, was lower after the time trial than with placebo. In a biopsy subset of 20, proteomics showed mitochondrial pathways up and inflammatory pathways down. The abstract gives no CRP result. Three of 11 authors list Amazentis SA. Grade for the inflammation finding: Insufficient, because it is exploratory and comes from a subset.

Napier et al. (2025, Nutrients). Thirty-two healthy adults took a multi-strain synbiotic with 400 mg of pomegranate extract, or placebo, for 91 days. That trial did not give urolithin A. The synbiotic group made far more urolithin A from its own gut bacteria, with urinary output up 49-fold by day 91. The authors say the synbiotic was associated with reduced systemic inflammation (serum CRP). Because there was no urolithin A-only arm, the trial cannot separate urolithin A from its 24 probiotic strains. Two of the eight authors list Seed Health, Inc. as an affiliation. Grade: Insufficient for any urolithin A immune effect.

Kuerec et al. (2026, GeroScience, protocol). The PROMETHEUS protocol plans an eight-week feasibility study of 20 middle-aged to older adults. Participants were prescribed one or more of urolithin A, NMN, or a multivitamin, chosen from their baseline measures, and immune function is among the primary outcomes. The protocol reports no results. Because urolithin A is one of several interventions, its effect could not be isolated. Grade: none yet, no results.

The interactive clinical-data guide shows the muscle and biomarker results as interactive charts.

Why would urolithin A affect T cells at all?

Gut bacteria make urolithin A from ellagitannin-rich foods, and it triggers mitophagy, the clearing of damaged mitochondria (Denk et al., 2022, Immunity). In that mouse study, urolithin A-induced mitophagy expanded T memory stem cells and strengthened CD8 responses in tumor-bearing mice. The authors traced the effect to PINK1-dependent mitophagy and downstream Wnt signaling. Grade: Preliminary. The mouse data are consistent, and the 2025 trial measured a similar CD8 group in people, but the human evidence is one trial. The mitophagy paper covers the mechanism in more depth.

A second mouse and cell study (Ginefra et al., 2024, Cancer Research Communications) reports that urolithin A activated the transcription factor FOXO1 in CD8 T cells, which expanded the naive T cell pool. Grade: Insufficient for human claims, because it is animal and cell-culture work.

In cell culture, urolithin A was the most active urolithin at blunting LPS-triggered TNF-α in human and mouse macrophages, and its phase II conjugates lost that effect (Bobowska et al., 2021, European Journal of Nutrition). Cell culture is not a person. Grade: Insufficient.

What is established, what is proposed, and what would settle it

What is established

In one randomized trial (Denk et al., 2025), four weeks of 1,000 mg a day shifted the naive-like CD8 group and CD8 fatty acid oxidation capacity. Both reported 95% intervals exclude zero, and the size of the shift is small.
In mice, urolithin A-driven mitophagy expanded T memory stem cells (Denk et al., 2022).
Across the human trials reviewed here, no study reported an infection, illness, or vaccine response.

What is proposed

The 2025 authors propose that short-term supplementation could counter age-related immune decline and inflammaging. That is a hypothesis. The registry classifies the trial as basic science, and the trial measured cells, not clinical outcomes.

What would settle it

An independent replication of the naive-like CD8 result by a group with no sponsor affiliation.
A randomized trial with clinical immune endpoints, such as illness or vaccine response, run for longer than four weeks.
The full cytokine results from the 2025 trial, which the abstract does not report.

Limits of this page. It is a company white paper, not a peer-reviewed article. It summarizes peer-reviewed studies, and the secondary-outcome details come from published abstracts and the registry record. Read the full papers before quoting them.

Next reads

The urolithin A monograph covers the ingredient, its forms, and its safety. Start here for the full picture.
The urolithin A complete guide places this trial beside the muscle and dose research.
The buyer's guide checks products against the trial doses and their testing, and it includes competitor brands.

Glossary

CD8 T cell: a white blood cell that kills infected or abnormal cells.
Naive-like T cell: a T cell that has not yet encountered its target. The registry defines naive-like CD8 cells by four surface markers.
T memory stem cell: a long-lived, self-renewing memory T cell.
Mitophagy: the process cells use to clear out damaged mitochondria.
Mitochondrial biogenesis: the cell building new mitochondria.
Oxidative phosphorylation (OXPHOS): the mitochondrial process that produces most of a cell's energy.
Fatty acid oxidation: breaking down fat inside mitochondria to make energy.
NK cell: a natural killer cell, an immune cell that kills abnormal cells without prior exposure.
Nonclassical monocyte: a monocyte subset marked CD14 and CD16 positive.
C-reactive protein (CRP): a blood protein the liver makes more of during inflammation. It is a marker, not a diagnosis.
Cytokine: a signaling protein that immune cells use to communicate.
Percentage point: the arithmetic difference between two percentages (5 percent to 5.5 percent is 0.5 percentage points).
Randomized, placebo-controlled trial: participants are assigned by chance to the product or an inactive substitute.

References

Denk D, Singh A, Kasler HG, et al. Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. Nature Aging. 2025;5(11). PMID 41174221. https://pubmed.ncbi.nlm.nih.gov/41174221/ DOI: https://doi.org/10.1038/s43587-025-00996-x
ClinicalTrials.gov. NCT05735886, Urolithin A Supplementation to Boost Immune Health. Lead sponsor: Amazentis SA. https://clinicaltrials.gov/study/NCT05735886
Denk D, Petrocelli V, Conche C, et al. Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy. Immunity. 2022;55(11). PMID 36351375. https://pubmed.ncbi.nlm.nih.gov/36351375/
Ginefra P, Hope HC, Chiang YH, et al. Urolithin-A Promotes CD8+ T Cell-mediated Cancer Immunosurveillance via FOXO1 Activation. Cancer Research Communications. 2024;4(5). PMID 38626334. https://pubmed.ncbi.nlm.nih.gov/38626334/
Bobowska A, Granica S, Filipek A, et al. Comparative studies of urolithins and their phase II metabolites on macrophage and neutrophil functions. European Journal of Nutrition. 2021;60(4) (epub 2020). PMID 32960290. https://pubmed.ncbi.nlm.nih.gov/32960290/
Singh A, D'Amico D, Andreux PA, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Reports Medicine. 2022;3(5). PMID 35584623. https://pubmed.ncbi.nlm.nih.gov/35584623/
Zhao H, Zhu H, Yun H, et al. Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study. Journal of the International Society of Sports Nutrition. 2024;21(1). PMID 39487653. https://pubmed.ncbi.nlm.nih.gov/39487653/
Whitfield J, McKay AKA, Tee N, et al. Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers in Highly Trained Male Distance Runners. Sports Medicine. 2025;55(12). PMID 40839339. https://pubmed.ncbi.nlm.nih.gov/40839339/
Napier BA, Allegretti JR, Feuerstadt P, et al. Multi-Species Synbiotic Supplementation Enhances Gut Microbial Diversity, Increases Urolithin A and Butyrate Production, and Reduces Inflammation in Healthy Adults: A Randomized, Placebo-Controlled Trial. Nutrients. 2025;17(17). PMID 40944126. https://pubmed.ncbi.nlm.nih.gov/40944126/
Kuerec AH, Guan L, Wang W, et al. PROMETHEUS clinical trial protocol: tailoring healthy ageing with lifestyle and nutraceuticals. GeroScience. 2026;48(5). PMID 42393428. https://pubmed.ncbi.nlm.nih.gov/42393428/

The Bottom Line

Urolithin A has one randomized trial that measured immune cells in healthy adults, and no human trial that measured infections or illness. Four weeks of 1,000 mg a day shifted some T cell measures by small amounts. Choosing it for immune reasons is not yet supported by human evidence. If you take it for other reasons, the dose to compare against is 1,000 mg a day. The urolithin A monograph covers forms, safety, and who should ask a clinician first.

FAQ

Does urolithin A help the immune system?

No human trial has shown that urolithin A improves an immune outcome such as infections, illness, or vaccine response. One randomized trial of 50 healthy middle-aged adults (Denk et al., Nature Aging, 2025) measured immune cells after four weeks of 1,000 mg a day. It found shifts in some CD8 T cell groups and in how those cells use fat for energy. Those are cell measurements, not a demonstrated benefit to the immune system.

What did the urolithin A immune trial find?

The main result was a shift in the naive-like subset of CD8 T cells, defined by surface markers in the trial registry. The treatment difference was 0.50 percentage points (95% interval 0.16 to 0.83, P = 0.0437). That is a small difference. Fat-burning capacity in those CD8 cells rose by 14.72 percentage points (95% interval 6.46 to 22.99, P = 0.0061). Secondary results included more NK cells and nonclassical monocytes, and better TNF release from activated T cells. All figures come from the published abstract.

Does urolithin A change immune cells in people?

Yes, in one trial, and only at the cell level. The trial's primary measures were CD8 T cell subsets and their metabolism, and the naive-like subset differed between groups by 0.50 percentage points. The other human trials reviewed here measured muscle, performance, or blood markers, and none reported T cell results in its abstract. Whether those cell changes lead to fewer infections has not been tested.

Is urolithin A studied for immune aging?

Only in one trial so far. Denk et al. framed the question as age-related immune decline and enrolled healthy adults aged 45 to 70 (ClinicalTrials.gov NCT05735886). The same first author's 2022 mouse study found that urolithin A expanded T memory stem cells, a long-lived T cell group. No human trial has tested that, using illness or vaccine response as the measure.

How long was the urolithin A immune trial?

Four weeks, or 28 days of daily dosing. Participants took four 250 mg softgels a day (1,000 mg) or matching placebo, and immune cells were measured at baseline and day 28. The registry lists the study as completed, with primary completion on March 31, 2024. No results are posted on ClinicalTrials.gov, so the published paper is the only results source.

Does urolithin A reduce inflammation in people?

Not in a way anyone has shown. Small trials have measured C-reactive protein (CRP), a blood marker that rises with inflammation, and the results point in different directions. In a 2022 trial, CRP was lower with urolithin A, according to the abstract. In an 8-week trial of 20 male athletes, CRP rose from baseline in the urolithin A group but ended lower than placebo. No trial in this review measured a clinical outcome tied to inflammation.