Urolithin A

Mitophagy is the selective autophagy of mitochondria — the process by which cells identify damaged or dysfunctional mitochondria and route them for recycling. It is an essential quality-control mechanism: without effective mitophagy, cells accumulate dysfunctional mitochondria that generate excess reactive oxygen species (ROS) and fail to produce adequate ATP. In skeletal muscle and immune cells, this accumulation is strongly associated with the functional decline seen in ageing — reduced muscle endurance, impaired immune surveillance, and declining metabolic efficiency.

Urolithin A (UA) is a postbiotic metabolite produced when gut bacteria metabolise ellagitannins, a class of polyphenols found at highest concentrations in pomegranates, walnuts, and certain berries. UA induces mitophagy through inhibition of the EP300 acetyltransferase pathway and by activating the PINK1/Parkin axis — the canonical mitochondrial quality control programme. In human cell studies and animal models, UA increases mitophagy flux markers (LC3-II, p62 turnover), promotes clearance of damaged mitochondria, and is associated with downstream improvements in mitochondrial biogenesis. Critically, the production of UA from dietary sources varies enormously between individuals, depending on gut microbiome composition: roughly 40% of adults produce detectable UA after pomegranate consumption, meaning that food-derived intake cannot be relied upon without supplementation using the purified metabolite.

Six randomised controlled trials have assessed Urolithin A in human participants. The bulk of this work originates from Amazentis (now Timeline Bioscience) and EPFL, using their Mitopure formulation — a pharmaceutical-grade purified UA. The table below summarises the primary trials. Results in independent studies using different UA formulations are fewer and methodologically weaker.

Trial doses ranged from 500 to 1,000 mg/day. No universally accepted clinical protocol has been established. The studied form, Mitopure (by Amazentis/Timeline Bioscience), is pharmaceutical-grade purified UA. Food-derived UA depends entirely on an individual's gut microbiome composition and is not a reliable substitute for supplemental UA.

Urolithin A has been generally well-tolerated across the published trials. No serious adverse events attributable to UA supplementation were reported in any of the six RCTs. Mild gastrointestinal symptoms (nausea, loose stools) were reported by a small proportion of participants in the 1,000 mg/day arm and resolved without intervention. No clinically significant changes in liver enzymes, kidney function, or haematological parameters were observed across 12-week to 4-month supplementation periods.

In the UK, Urolithin A is classified as a food supplement and does not require a prescription. It carries GRAS (Generally Recognised as Safe) status in the United States. The FSA Novel Foods Register does not currently list UA as a novel food requiring pre-market authorisation in Great Britain. As with all supplements, individuals taking anticoagulants or immunosuppressants should consult a qualified practitioner before use, as interaction data in these populations is limited.