Urolithin A
Urolithin A
Urolithin A is a gut microbiome-derived metabolite produced from ellagitannins found in pomegranates, walnuts, and berries, now available as a direct oral supplement. It is primarily used to support mitochondrial health, muscle function, and longevity by activating mitophagy — the selective removal of damaged mitochondria. Clinical interest has grown significantly due to its ability to improve cellular energy production and slow age-related muscle decline (sarcopenia).
Mechanism of Action
Urolithin A activates mitophagy by upregulating PINK1/Parkin signaling pathways, enabling cells to selectively clear dysfunctional mitochondria and replace them with healthy ones. It also modulates the AMPK pathway to enhance mitochondrial biogenesis and has been shown to reduce inflammatory markers including NF-κB activity. These combined effects improve mitochondrial quality control, ATP production efficiency, and skeletal muscle endurance.
Evidence by Health Goal(18 goals)
Dosing Protocols
With or without food, preferably in the morning
500mg/day showed efficacy in human clinical trials for muscle endurance; 1000mg/day used in studies targeting mitochondrial gene expression. Higher doses up to 2000mg appear safe but offer diminishing additional benefit. Not all individuals produce Urolithin A from dietary sources due to gut microbiome variability, making direct supplementation beneficial.
Safety & Side Effects
Urolithin A has a well-characterized and favorable safety profile based on Phase I and Phase II clinical trials; doses up to 2000mg/day have been well tolerated in healthy adults and older individuals. It is not a controlled substance, is widely available over the counter, and no serious adverse events have been reported in human studies to date, though long-term data beyond 4 months remain limited.
Possible Side Effects
- !Mild gastrointestinal discomfort including bloating or loose stools, particularly at doses above 1000mg
- !Nausea, typically transient during the first 1-2 weeks of use
- !Mild headache reported in a minority of users during initial supplementation
- !Temporary fatigue or energy fluctuation during adaptation phase
- !Elevated liver enzymes in rare cases at very high doses (above 2000mg) in preclinical data
Interactions
- -May additively support mitochondrial function when combined with NAD+ precursors (NMN, NR) — not harmful but monitor for excessive fatigue modulation
- -Theoretical interaction with immunosuppressants due to autophagy-modulating effects — use caution in transplant patients
- -May enhance the effects of metformin via overlapping AMPK activation — monitor blood glucose in diabetic patients
- -Combined use with other polyphenols (resveratrol, quercetin) is generally synergistic but unstudied for formal interactions
- -Anticoagulant medications — ellagitannin-rich dietary sources have mild antiplatelet properties; direct supplemental Urolithin A interaction is not well established but warrants monitoring
Cost & Where to Buy
Cost varies substantially by brand and formulation — Mitopure (Timeline Nutrition), the clinically validated branded form, is at the higher end (~$90-120/month). Generic Urolithin A supplements are available at lower price points but may vary in purity and bioavailability. At 500mg/day dosing, monthly cost is on the lower end of the range.
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