Urolithin A

Overview

Urolithin A (UA) is a natural metabolite produced by gut bacteria from ellagitannins and ellagic acid found in foods like pomegranates, strawberries, raspberries, and walnuts¹⁵. Classified as a postbiotic and benzo-coumarin (dibenzo-α-pyrone), it belongs to coumarins with a 1-benzopyran moiety and ketone at C2³⁴. UA is not directly in foods; its production depends on individual microbiota, with only certain bacteria converting precursors⁵. It exhibits anti-inflammatory, antioxidant, and antiproliferative properties, notably inducing mitophagy—the selective removal of damaged mitochondria—to recycle defective ones and support cellular health¹². Traditionally linked to pomegranate consumption for health benefits, UA has gained attention as a geroprotector in aging research, improving muscle health in preclinical models¹³.

Forms and Variations

Urolithin A is primarily available as a synthetic supplement in pure powder or solid form for research and therapeutic use, with purity levels exceeding 97-98% via HPLC²⁶⁸. It appears as a white to beige, pale yellow, or yellow-green powder/crystal, soluble in DMSO (slightly to 50 mg/ml) and methanol (very slightly)¹²⁸. In the body, it metabolizes into conjugates like urolithin A glucuronide, sulfate, or methylated forms via enterocytes and hepatocytes before circulation and urinary excretion⁵. Choose high-purity synthetic forms (>97% HPLC) for consistent dosing, as dietary production varies by gut microbiome; research-grade ensures reliability for mitophagy induction². Capsules or formulations may emerge for bioavailability, stored at 2-8°C to maintain stability¹.

Dosage and Administration

Specific human dosages are not standardized due to its research status, but preclinical studies suggest oral administration induces mitophagy in vivo². Typical research doses range from 250-1000 mg/day in emerging supplements, taken once daily with food to aid gut absorption, though bioavailability depends on microbiota⁵. For optimal effect, pair with ellagitannin-rich foods like pomegranate, but direct supplementation bypasses microbiome variability¹. Take in the morning to align with circadian mitochondrial activity; divide higher doses if needed. Best practices include starting low (250 mg) to assess tolerance, hydrating well due to slight DMSO solubility aiding formulations, and cycling (e.g., 5 days on/2 off) to prevent adaptation⁸. Consult professionals for personalized dosing, as no official RDA exists³.

Scientific Research and Mechanism of Action

Urolithin A stimulates mitophagy, an evolutionarily conserved process removing dysfunctional mitochondria, via pathways like PINK1/Parkin activation, improving muscle endurance and mitochondrial health in aged animals and preclinical aging models¹²³. It acts as an antioxidant by its phenolic hydroxyl groups scavenging free radicals, reduces inflammation by modulating NF-κB, and shows antiproliferative effects⁶⁷. Key studies demonstrate oral UA enhances autophagy in vitro and in vivo, recycling mitochondria for better energy production². As a geroprotector, it supports longevity by maintaining cellular quality control³. Research is promising but mostly preclinical; human trials are emerging for muscle and metabolic health. Current state: strong mechanistic evidence, with ongoing clinical validation needed for dosing and long-term safety¹⁵.

Benefits and Potential Uses

Urolithin A promotes mitochondrial health via mitophagy, enhancing muscle strength, endurance, and recovery in aging models, potentially countering sarcopenia¹³. Its antioxidant properties combat oxidative stress, while anti-inflammatory effects may alleviate chronic conditions²⁶. Proven in preclinical research for improving muscle function in old animals and antiproliferative activity². Potential uses include aging support, exercise performance, metabolic health, and neuroprotection via better mitochondrial quality. It addresses mitochondrial dysfunction in conditions like muscle wasting, neurodegeneration, and metabolic syndrome¹. As a postbiotic, it may benefit gut-related health indirectly. Human studies are limited but show promise for vitality in older adults⁷.

Side Effects and Risks

Urolithin A is generally well-tolerated in research settings with no major common side effects reported at studied doses². Potential mild gastrointestinal upset may occur due to gut metabolism⁵. Risks include unknown long-term effects, as human safety data is emerging; those with poor microbiota converters may see less benefit¹. Contraindications for pregnancy, lactation, or hormone-sensitive conditions due to coumarin structure, though less potent than warfarin-like coumarins⁴. Use caution in liver/kidney impairment, as it undergoes conjugation there⁵. Groups like children, pregnant individuals, or those on multiple supplements should avoid without medical advice³.

Interactions and Precautions

No specific drug interactions are well-documented, but its metabolism via glucuronidation/sulfation may compete with drugs using UGT enzymes⁵. Potential mild anticoagulant caution due to coumarin class, though UA lacks strong vitamin K antagonism⁴. Precautions for elderly with mitochondrial issues, monitoring liver enzymes; avoid pre-surgery due to possible anti-inflammatory effects on clotting². Specific populations: not recommended for pregnant/lactating women or children lacking safety data. Those with gut dysbiosis may need probiotics to enhance conversion. Always consult physicians, especially with mitochondrial disorders or polypharmacy¹⁷.

Impact on Biomarkers

Urolithin A may lower inflammation markers like CRP and cytokines via NF-κB inhibition². It improves mitochondrial biomarkers such as ATP production, oxygen consumption, and reduces ROS levels in cells¹. Muscle health metrics like endurance and strength rise in models; potential to normalize CK-MB or LDH in damage contexts. Blood tests may show conjugated metabolites in plasma/urine⁵. Monitor liver enzymes (ALT/AST) for safety³.

Overdose and Toxicity

No established toxicity data; preclinical studies show safety at high oral doses with no acute toxicity². Over-supplementation risks unknown but may include GI distress or microbiome disruption⁵. Symptoms could mimic excess phenolics: nausea, diarrhea. Safe upper limits unestablished; stay below 1000 mg/day pending research. LD50 not reported; treat as research compound¹.

Disclaimer

The information provided in this document is for educational purposes only and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.