In a small, recent human trial, a naturally occurring compound called urolithin A has yielded positive results and appears to slow down part of the aging process that is related to the production of energy in our cells.
What is urolithin A?
Urolithin A is the end product created when bacteria in the gut break down ellagitannins, which are polyphenols found in fruits such as pomegranates, strawberries, walnuts, and raspberries. The substance does not appear naturally in its end form, so we normally rely on the beneficial bacteria in the microbiome, our internal ecology of gut bacteria, to convert the polyphenols into urolithin A.
Because this compound needs a particular bacterium to create it, the bioavailability of urolithin A could vary considerably from person to person, having a greater or lesser effect depending on individual gut bacteria diversity.
Urolithin A has been a subject of interest to researchers for a while, as there have been promising early results in mice and flatworms, in which the compound increased lifespan. It appears to have geroprotective, meaning age-delaying, properties.
The geroprotective effect of urolithin A appears to be focused on improving the function of the mitochondria, the power plants of our cells, which are responsible for turning nutrient-derived molecules into a form of cellular energy called adenosine triphosphate (ATP).
The results of a human trial are positive
Recently, the details of a small human trial have been published, and they show some positive results. The purpose of this trial was to determine both the safety and efficacy of urolithin A.
For the study, the team synthesized urolithin A and gave it to a test group of 60 older people in various dosages. The participants had generally sedentary lifestyles but were healthy at the time of the study.
For the first part of the study, the research team gave some of the participants a single dose of between 250 and 2000 mg of urolithin A. There were no side effects reported from this test group compared to the control group, suggesting that the compound is well tolerated.
The following step saw the team move to a longer study of the safety and efficacy of urolithin A over a 28-day period. The 60 participants were divided into four groups and given either 250 mg, 500 mg, 1000 mg, or a placebo as a control group. After 28 days, the results showed that, once again, there were no serious side effects following sustained use. The 500 mg and 1000 mg dosage groups also had an increased level of mitochondrial gene expression, which is known to stimulate biogenesis in the same way that exercise does.
Urolithin A (UA) is a natural dietary, microflora-derived metabolite shown to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging. Here, we report the results of a first-in-human clinical trial in which we administered UA, either as a single dose or as multiple doses over a 4-week period, to healthy, sedentary elderly individuals. We show that UA has a favourable safety profile (primary outcome). UA was bioavailable in plasma at all doses tested, and 4 weeks of treatment with UA at doses of 500 mg and 1,000 mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elderly individuals (secondary outcomes). These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.
The researchers plan to develop urolithin A products for market as soon as possible, pending the results of additional research and human trials. Their hope is that urolithin A may be able to slow down the loss of skeletal muscle that happens with age and reduces mobility and independence.
Given that mitochondrial dysfunction is a hallmark of aging, the use of urolithin A may have merit as a geroprotector while more robust solutions to mitochondrial decline are developed, such as the MitoSENS mitochondrial repair approach from SRF.
 Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., … & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism, 1(6), 595.