Urolithin A and Statin Metabolism: No Known Interaction
Based on available evidence, urolithin A does not appear to affect the metabolism of statins through known drug-metabolizing pathways. The provided guidelines and research do not identify urolithin A as an inhibitor or inducer of the cytochrome P450 enzymes (CYP3A4, CYP2C9) or drug transporters (P-gp, OATP1B1, OATP1B3) that are critical for statin metabolism 1.
Key Metabolic Pathways for Statins
Statins are primarily metabolized through specific enzymatic pathways that determine their drug interaction potential:
- CYP3A4-metabolized statins: Simvastatin and lovastatin undergo significant CYP3A4 metabolism, while atorvastatin undergoes lesser amounts 1
- CYP2C9-metabolized statins: Fluvastatin, pitavastatin, and rosuvastatin require CYP2C9 for metabolism 1
- Non-CYP metabolism: Pravastatin is metabolized through non-CYP pathways, primarily glucuronidation 1
- Drug transporters: All statins are substrates for OATP1B1, and some are substrates for P-gp and OATP1B3 1
Urolithin A Metabolic Profile
Urolithin A undergoes metabolism distinct from statin pathways:
- Urolithin A is primarily metabolized through glucuronidation and sulfonation, producing glucuronidated and sulfonated metabolites as the predominant forms following oral administration 2
- These metabolic pathways do not overlap with the CYP450 enzymes responsible for most statin metabolism 2
- No evidence suggests urolithin A inhibits or induces CYP3A4, CYP2C9, or drug transporters relevant to statin metabolism 3, 4, 5, 2, 6
Clinical Safety Data
Multiple clinical trials have evaluated urolithin A safety without identifying statin interactions:
- A 90-day safety study in rats at doses up to 3826 mg/kg/day showed no alterations in drug-metabolizing enzyme activity or toxicity patterns that would suggest CYP450 modulation 2
- Human clinical trials administering 1000 mg daily for 4 months documented no drug interactions, though specific statin co-administration was not explicitly studied 6
- The safety profile and biomarker changes observed in elderly participants taking urolithin A did not indicate metabolic enzyme alterations 4, 6
Practical Considerations
While no direct interaction is expected, clinicians should remain aware of general principles:
- Patients on CYP3A4-metabolized statins (simvastatin, lovastatin, atorvastatin) should be monitored for muscle symptoms as standard practice, regardless of urolithin A use 1, 7
- The known drug interactions with statins involve potent CYP450 inhibitors (macrolide antibiotics, azole antifungals, cyclosporine, gemfibrozil) and inducers (rifampin, phenytoin, carbamazepine), none of which characterize urolithin A 1
- Urolithin A's anti-inflammatory and mitochondrial effects may theoretically complement statin therapy for cardiovascular protection, though this has not been formally studied 3, 5
Monitoring Recommendations
Standard statin monitoring applies when urolithin A is used concurrently:
- Baseline and follow-up assessment at 6-12 weeks after initiating either agent 7
- Immediate reporting of muscle pain, tenderness, weakness, or dark urine as these indicate potential myopathy requiring prompt evaluation 7
- No additional monitoring beyond standard statin protocols is warranted based on current evidence 7, 6