Does oral urolithin A supplementation improve 6-minute walk distance, muscle endurance, and biomarkers of mitochondrial and cellular health in older adults?
Urolithin A, a double-blind, placebo-controlled trial in 66 adults (JAMA Netw Open 2022, PMID 35050355) — urolithin A significantly improved muscle endurance in the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles at 2 months compared to placebo. While it did not significantly improve 6-minute walk distance or maximal ATP production, it did improve muscle endurance and plasma biomarkers, suggesting a potential to counteract age-associated muscle decline.
Source: JAMA Netw Open 2022, PMID 35050355 ↗ · Research map · How Magellan grades evidence · evidence confidence: high
JAMA Netw Open · 2022 · PMID 35050355 · DOI 10.1001/jamanetworkopen.2021.44279
Daily urolithin A supplementation improved muscle endurance and certain cellular health biomarkers in older adults, but did not significantly impact walking distance or maximal ATP production.
The question
Does oral urolithin A supplementation improve 6-minute walk distance, muscle endurance, and biomarkers of mitochondrial and cellular health in older adults?
What they tested
Urolithin A, a natural gut microbiome-derived metabolite, will improve muscle function and mitochondrial health in older adults, based on its known effects in animals and its ability to induce mitochondrial gene expression in humans.
How they did it
This was a double-blind, placebo-controlled randomized clinical trial involving 66 adults aged 65 to 90 years. Participants were randomized to receive either 1000 mg daily oral urolithin A or placebo for 4 months. Muscle fatigue tests and plasma biomarker analysis were conducted at baseline, 2 months, and 4 months. Six-minute walk distance and maximal ATP production were assessed at baseline and 4 months. An intention-to-treat approach was used for analysis.
What they found
Urolithin A significantly improved muscle endurance in the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles at 2 months compared to placebo. Plasma levels of several acylcarnitines, ceramides, and C-reactive protein decreased with urolithin A at 4 months compared to placebo. There was no significant improvement in the 6-minute walk distance or maximal ATP production in the hand muscle with urolithin A supplementation compared to placebo. No statistical differences in adverse events were observed between the groups.
| Urolithin A (FDI) | 95.3 | |
|---|---|---|
| Placebo (FDI) | 11.6 | |
| Urolithin A (TA) | 41.4 | |
| Placebo (TA) | 5.7 |
Urolithin A significantly increased the number of muscle contractions until fatigue in both the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles at 2 months compared to placebo.
What it means
Urolithin A supplementation was safe and well tolerated. While it did not significantly improve 6-minute walk distance or maximal ATP production, it did improve muscle endurance and plasma biomarkers, suggesting a potential to counteract age-associated muscle decline. Further research is needed to confirm these findings.
Limitations
The study did not find significant improvements in primary endpoints like 6-minute walk distance and maximal ATP production, indicating that the observed benefits might be limited or require further investigation.
The paper at a glance
| Title | Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial |
|---|---|
| Journal | JAMA Netw Open |
| Year | 2022 |
| PMID | 35050355 ↗ |
| DOI | 10.1001/jamanetworkopen.2021.44279 ↗ |
| Topic | NAD⁺, sirtuins & cellular energy |
Read the source: PubMed record (authors, abstract, full citation) ↗ · Publisher via doi.org ↗
Where Magellan uses this paper
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Urolithin A (Mitopure)
In human research, urolithin A supplementation is safe and bioavailable and improves markers of mitochondrial health. Randomized trials report better muscle endurance in adults 65-90, roughly 12% strength gains with improved aerobic endurance in middle-aged adults, lower inflammatory markers (C-reactive protein…
Pomegranate Ellagitannin Extract
In human research, the ellagitannin-derived metabolite urolithin A has improved muscle strength, endurance, and biomarkers of mitochondrial function and inflammation in randomized trials of middle-aged and older adults, and a small 2025 trial found more youthful immune-cell profiles after four weeks, although several…
Urolithin A is a natural compound produced by gut bacteria from ellagitannins and ellagic acid, dietary…
Pomegranate ellagitannin extract is a concentrated source of ellagitannins (such as punicalagins) and…
Research describes the compound or intervention studied. It is not a claim about any specific product.
Molecules & mechanisms in this paper
Each of these is named in the paper’s own words above. Open the monograph for the full mechanism and its other citations.
Cite this page
These citations point at this summary. To cite the original paper with its full author list, use the PubMed record or doi.org.
Magellan Longevity. (2026). Does oral urolithin A supplementation improve 6-minute walk distance, muscle endurance, and biomarkers of mitochondrial and cellular health in older adults? [Plain-English summary of JAMA Netw Open 2022, PMID 35050355, DOI 10.1001/jamanetworkopen.2021.44279]. Magellan Longevity. https://magellanlongevity.com/study/d35050355.html@misc{magellan_d35050355,
title = {Does oral urolithin A supplementation improve 6-minute walk distance, muscle endurance, and biomarkers of mitochondrial and cellular health in older adults?},
author = {{Magellan Longevity}},
year = {2026},
howpublished = {\url{https://magellanlongevity.com/study/d35050355.html}},
note = {Plain-English summary of PubMed PMID 35050355; DOI 10.1001/jamanetworkopen.2021.44279; JAMA Netw Open 2022. Reviewed by Gabriel Radu, DO},
urldate = {2026-08-11}
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