Does Urolithin A Actually Work? What the Research Shows

Short answer: In scientific studies, urolithin A does something measurable, and researchers are now exploring what that means for how we feel and perform. Here’s what the research shows so far.

First, what is urolithin A?

Urolithin A is a natural compound made by your gut bacteria. They make it from compounds called ellagitannins, found in pomegranates, walnuts, and berries.1 So you don’t eat urolithin A itself: it starts with eating those foods, and even then not every gut is up to the job. Some people make plenty, others make little or none.2 In one trial of 100 people, only about 12% had detectable urolithin A in their blood to begin with, and after a glass of pomegranate juice, only about 40% turned it into urolithin A.3

That’s where a supplement comes in. It hands you the finished compound, so you don’t have to rely on what you eat or on your gut bacteria. In that same trial, a product containing 500 mg of urolithin A gave more than six times as much exposure to it as the pomegranate juice did.3 Another trial found that after four months of daily doses, blood levels of urolithin A and the forms your body turns it into were high, when most people had none to start with.1

One reality check: researchers employed by a urolithin A manufacturer were involved in both trials. The first measured how much urolithin A reached the blood, not what it does once it gets there. The later one also tested strength and fitness, covered below.

Why the fuss?

Mitochondria are the tiny power plants inside your cells, and they wear out. Healthy cells clear out the worn ones and recycle them in a process called mitophagy, which is thought to slow with age. In animal studies, urolithin A kicked that recycling into gear: the worms lived longer and the rodents’ muscles worked better.4 The big question is whether people get the same treatment.

What happened in people?

Researchers have now run a handful of placebo-controlled trials, typically lasting four weeks to four months at 250 to 1,000 mg a day. The first human trial, in older adults, mostly checked safety, and it passed. It also spotted changes in muscle gene activity and blood markers linked to mitochondrial health.5 Since that first trial, researchers have tested whether the changes translate into real-world effects. Here’s what they found:

• Muscle strength: promising. In a trial of 88 inactive, overweight adults aged 40 to 64, strength in the back of the thigh (hamstrings) rose by about 10 to 12% over four months, while the placebo group’s fell by about 10%.¹ The catch: it was an early-stage trial, its main goal (peak power) wasn’t met, and strength in the front of the thigh wasn’t clearly different from placebo.¹
  

• Muscle endurance in older adults: encouraging. In 66 adults aged 65 to 90, muscles in the hand and leg held out longer before tiring after two months of urolithin A than after placebo. The trial’s main goals, walking distance and muscle energy output, didn’t differ significantly.⁶
  

• Athletes: mixed. Trained runners didn’t get faster over a 3,000 m time trial, though they said the effort felt easier and blood markers of muscle damage were lower.⁷ In a small trial of 20 strength-trained men, some strength and endurance measures improved.⁸
  

• Immune cells: interesting, but too early to say. In 50 healthy middle-aged adults, four weeks of urolithin A nudged the mix of T cells (white blood cells that help your immune system spot and respond to threats) toward fresher, less worn-out ones. The shift was small, and whether it matters for everyday health is an open question.9
  

• Blood vessels: no clear benefit. In 50 adults with obesity, four weeks of urolithin A didn’t improve how well blood vessels work, the trial’s main goal. One secondary measure, the brain’s blood-flow response during a memory task, did increase, though performance on the task didn’t change. The authors think it deserves a closer look.¹⁰

The bigger picture

One 2026 review pooled five trials (236 people in total). Only two used the same test, a six-minute walk, so that was the only result it could combine. On average, people taking urolithin A walked about 17 meters further, but the true difference could be anywhere from about 5 meters less to about 39 meters more, so chance can’t be ruled out. The authors rated their confidence in that result as low. The other trials reported some gains, mainly in muscle endurance, plus a few strength results and lower levels of some blood markers, including one linked to inflammation. Because the trials measured different things in different people, the authors treated these as early signals, not proven effects.¹¹

Also worth knowing: several of the bigger trials involved researchers who work for a urolithin A manufacturer. That’s common in supplement research and isn’t a reason to dismiss the results, but it is a reason to want independent studies to confirm them.

So, does urolithin A work?

It’s promising, not proven. The most encouraging signals are in muscle strength and endurance, and urolithin A was well tolerated in the trials that reported on safety.1, 5, 6, 10 But the studies are small and short, results vary by who is studied, and some trials found nothing. That’s where many promising ingredients start: worth watching, not yet worth bold claims.

Where does urolithin A fit into Protocol X?

The human trials we reviewed used 250 to 1,000 mg a day. The Protocol X formula update contains 200 mg, below every dose tested, so we won’t claim it matches these results. What urolithin A brings is one angle on cellular repair: recycling worn-out mitochondria, the part the research above looks at.

In Protocol X it sits alongside glycine, spermidine, and ergothioneine, which are there to support cellular housekeeping from other angles. The idea is that together they cover more ground than any one alone, though so far that’s our reasoning rather than something trials have confirmed. We’ll keep updating the formula as the research does.

Also in this series

→ Can you take Urolithin A and NMN together?

→ We’ve refined Protocol X: here’s what changed, and why

Frequently asked questions

What is urolithin A?

A compound your gut bacteria make from ellagitannins, which are found in pomegranates, walnuts, and berries.1 In lab and animal studies, it nudges cells to recycle worn-out mitochondria, a process called mitophagy.4

Can’t I just eat more pomegranates and walnuts?

They supply the raw material, so eating them is the starting point, but turning it into urolithin A is up to your gut bacteria, and that varies from person to person. In one trial of 100 people, only about 40% turned a glass of pomegranate juice into urolithin A, while a product containing 500 mg of urolithin A gave more than six times the exposure (the trial involved researchers employed by a urolithin A manufacturer).3 Gut bacteria can shift, though: in one small study, some non-producers began making urolithin A after taking a pomegranate extract.2

How much did the studies use, and how much is in Protocol X?

The human trials we reviewed used 250 to 1,000 mg a day.1, 5, 6, 11 Protocol X contains 200 mg, below every dose tested, so we don’t claim it will match those results. At 200 mg, urolithin A plays a supporting role, mainly in the cellular repair pathway, aimed at the recycling of worn-out mitochondria, alongside glycine, spermidine, and ergothioneine.

Is urolithin A safe?

In human trials lasting up to four months, at doses up to 1,000 mg a day, it was well tolerated and no safety concerns were reported.1, 5, 6, 10 Longer-term data is still limited. If you’re pregnant, nursing, have a medical condition, or take medication, check with a healthcare professional first.

How long did the trials take to show anything?

Most ran four weeks to four months. Changes in lab measures, such as muscle gene activity and immune cell profiles, showed up within four weeks.5, 9 Muscle endurance in older adults improved at the two-month check, and strength was measured after four months.6, 1 Not every trial found a change in what it set out to measure.

If the evidence is early, why is it in Protocol X?

Because the biology is interesting, the early human results are encouraging, and we’d rather be upfront about the dose than leave it out. It sits in the cellular repair pillar alongside glycine, spermidine, and ergothioneine, and we’ll update the formula as the research does.

Can I take urolithin A with NMN?

Protocol X contains both: 200 mg of urolithin A and 400 mg of NMN. For the detail, see our post Can You Take Urolithin A and NMN Together?

This article is for general educational purposes and is not intended as medical advice. This product is a health supplement and is not intended to diagnose, treat, cure or prevent any disease. Consult a qualified health professional if you’re pregnant, nursing, have a medical condition, or take medications.

References

1. Singh A, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022;3(5):100633. DOI: 10.1016/j.xcrm.2022.100633

2. González-Sarrías A, et al. Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate: a randomized clinical trial. Mol Nutr Food Res. 2017;61(5). DOI: 10.1002/mnfr.201600830

3. Singh A, D’Amico D, Andreux PA, et al. Direct supplementation with urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr. 2022;76(2):297–308. DOI: 10.1038/s41430-021-00950-1

4. Ryu D, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med. 2016;22(8):879–888. DOI: 10.1038/nm.4132

5. Andreux PA, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab. 2019;1(6):595–603. DOI: 10.1038/s42255-019-0073-4

6. Liu S, et al. Effect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults: a randomized clinical trial. JAMA Netw Open. 2022;5(1):e2144279. DOI: 10.1001/jamanetworkopen.2021.44279

7. Whitfield J, et al. Evaluating the impact of urolithin A supplementation on running performance, recovery, and mitochondrial biomarkers in highly trained male distance runners. Sports Med. 2025;55(12):3183–3200. DOI: 10.1007/s40279-025-02292-5

8. Zhao 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. J Int Soc Sports Nutr. 2024;21(1):2419388. DOI: 10.1080/15502783.2024.2419388

9. Denk D, et al. Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. Nat Aging. 2025;5(11):2309–2322. DOI: 10.1038/s43587-025-00996-x

10. da Costa Pinaffi-Langley AC, et al. Urolithin A and endothelial and cerebrovascular function in middle-aged adults with obesity: a randomized clinical trial. JAMA Netw Open. 2026;9(10):e2638047. DOI: 10.1001/jamanetworkopen.2026.38047

11. Dao T, et al. Effects of urolithin A supplementation on muscle health outcomes in humans from randomized controlled trials. Front Nutr. 2026;13:1834344. DOI: 10.3389/fnut.2026.1834344