Urolithin A

What it is

Urolithin A is a so-called postbiotic: a substance that is not supplied by the plant but is first produced by our gut bacteria. Pomegranate and, to a lesser extent, walnuts and some berries contain ellagitannins, complex tannins. The body cannot use them on its own. In the large intestine, certain bacteria convert them via ellagic acid and intermediate stages into urolithin A, which then enters the blood and the tissues.

The catch: only some people have the right bacteria. In a study with 100 participants, only 12 percent had any measurable urolithin A in their blood at baseline; after a glass of pomegranate juice, around 40 percent formed appreciable amounts. You cannot tell this about your own microbiome from the outside. Taking the pure substance directly bypasses this lottery; it is best known under the name Mitopure from the Swiss company Amazentis, which also funds most of the research.

The natural route remains possible: pomegranate, pure pomegranate juice and walnuts supply the precursors. But it works only for the minority with a suitable microbiome, and even then the levels remain much lower. In the same study, direct intake of the pure substance brought more than six times as much urolithin A into the blood as the juice.

The name sounds unappetizing, and so is its origin: chemists first found this class of substances in urinary stones of grazing animals.

How it is supposed to work

Mitophagy is the cell's quality control. It detects damaged mitochondria, dismantles them and recycles the components. With age this process declines, and defective power plants keep running, delivering less energy and more oxidative by-products. In muscle in particular, this is considered a core mechanism of aging.

In 2016, the team led by Johan Auwerx at EPFL in Lausanne showed that urolithin A triggers mitophagy in animals, extends the lifespan of the roundworm and improves the endurance of old mice. Mechanistically, this is elegant: urolithin A does not mimic energy, but maintenance. Exercise, incidentally, works through the same pathway and is the strongest known stimulus for mitophagy.

What is being discussed beyond muscle

Advertising now also promises effects on skin, the immune system and the brain. For skin there are first small studies, for the immune system animal data on rejuvenated T cells, for the brain mouse models of Alzheimer's disease. This is an active field of research, but not yet a basis for statements about humans. So far, the robust data concern muscle.

Who the data fit

The studies examined people from midlife onward and older people whose muscle function is declining. For this group, urolithin A is most plausible as an experiment, in addition to strength training and adequate protein intake, not instead of them. The idea is also interesting for phases without training, for example after injuries. For trained young people, the added benefit is small: in a study with runners, urolithin A did not improve race performance.

Anyone who tries it can set a simple reference point beforehand, such as grip strength, the number of repetitions of a standard exercise or stair climbing, and compare after three to four months. This does not replace a study, but it makes one's own impression easier to check.

What the studies show

Older adults (JAMA Network Open 2022)

Liu and colleagues randomized 66 people between 65 and 90 years of age to 1,000 milligrams of urolithin A or placebo for 4 months. Muscle endurance in the hand and lower leg, measured as the number of contractions until fatigue, improved more than under placebo; CRP and some acylcarnitines and ceramides fell. The two primary endpoints, 6-minute walking distance and maximal ATP production in the hand muscle, did not differ significantly. Funded by Amazentis.

Middle-aged adults (Cell Reports Medicine 2022)

Singh and colleagues randomized 88 overweight, healthy middle-aged people to 500 milligrams, 1,000 milligrams or placebo for 4 months. The strength of the hamstring muscles rose by around 12 percent with urolithin A; the authors also describe improvements in oxygen uptake and in a walking test. The primary endpoint, maximal power output, did not improve significantly. Funded by Amazentis.

Endurance runners (Sports Medicine 2025)

Whitfield and colleagues gave 42 high-performing runners 1,000 milligrams or placebo for 4 weeks during an altitude training camp. Performance over 3,000 meters, measured in 22 of the 42 runners, did not improve, but perceived exertion and markers of muscle damage after exercise were lower.

Where the data stop

First, the funding: almost all human research was paid for by Amazentis or produced with company employees as authors. That does not make the data wrong, but independent replication is largely missing. Second, the endpoints: in both large muscle studies the primary endpoint was missed; the positive findings come from secondary endpoints. The effects are moderate and concern muscle measurements; whether less frailty, more healthy years or a longer life follow from them, nobody knows.

Third, an obvious comparison is missing: urolithin A was never tested against systematic strength training or in combination with it. Fourth, the controlled data end after 4 months. And the findings on skin, the immune system and the brain are so far animal or pilot data.

Status, approval and legal

In Germany, urolithin A is not a medicinal product. In the EU it is considered a novel food; Amazentis applied for authorization as a novel food in 2018. In the US, the food authority FDA responded to the manufacturer's GRAS notice in 2018 with no objections, for use levels of up to 500 or 1,000 milligrams per serving in foods. There are no authorized health claims. Urolithin A is not on the doping list. The studies used 500 to 1,000 milligrams daily, the muscle studies in older people 1,000 milligrams. Products with pomegranate extract or ellagic acid are something else: they shift the conversion back into the gut.

Safety

In the human studies of up to 4 months, urolithin A caused no more side effects than placebo, and no serious events were observed. In the animal study of the authorization application, the amount without adverse effects after 90 days was far above the study amounts. Long-term data in humans are lacking. There are no data for pregnant or breastfeeding women, children, or people with serious illnesses. Anyone who takes medication or is chronically ill should discuss intake with a physician.

Sources

• Ryu et al., Nat Med 2016
• Andreux et al., Nat Metab 2019
• Liu et al., JAMA Netw Open 2022
• Singh et al., Cell Rep Med 2022
• Singh et al., Eur J Clin Nutr 2022
• Whitfield et al., Sports Med 2025
• FDA, GRAS Notice GRN 791 Urolithin A
• European Commission, novel food application for urolithin A (summary, Amazentis 2018)