What is the difference between urolithin A and urolithin B?

Urolithin A vs. Urolithin B: Key Structural and Biological Differences

Urolithin A and urolithin B are distinct gut microbiota-derived metabolites of ellagic acid that differ in their hydroxyl group positioning, with urolithin A (3,8-dihydroxy-urolithin) demonstrating superior antiproliferative activity compared to urolithin B (3-hydroxy-urolithin), though both compounds exhibit beneficial health effects through mitochondrial enhancement and anti-inflammatory mechanisms. 1, 2

Structural and Chemical Differences

• Urolithin A contains two hydroxyl groups at positions 3 and 8 on the urolithin backbone, while urolithin B has only one hydroxyl group at position 3 3, 4
• The additional hydroxyl group at position 8 in urolithin A appears critical for its enhanced biological activity compared to urolithin B 4
• Both compounds are produced through sequential gut bacterial metabolism of ellagic acid, with urolithin B representing a more extensively metabolized (less hydroxylated) form 3

Biological Activity Differences

Antiproliferative and Anticancer Effects

• Urolithin A demonstrates significantly stronger antiproliferative activity against leukemic cell lines (Jurkat and K562) compared to urolithin B 2
• In colon cancer cells (Caco-2), urolithin A shows an IC50 of 49.2 ± 3.8 μM at 48 hours, establishing it as the more potent anticancer agent 4
• Both urolithins induce apoptosis in leukemic cells equally, but urolithin A achieves this at lower concentrations 2
• Both compounds alter cellular metabolism, affecting glutamine metabolism, one-carbon metabolism, and lipid metabolism pathways 2

Mitochondrial and Anti-Aging Properties

• Urolithin A has been extensively studied for mitochondrial enhancement, inducing mitophagy in cell cultures, increasing longevity in nematodes, and preventing age-related muscle impairment in mouse models 5, 1
• Urolithin A administration in healthy, sedentary elderly individuals produces changes in muscle mitochondrial gene expression suggestive of improved mitochondrial and cellular health 5
• No comparable human clinical trial data exists for urolithin B regarding mitochondrial function or anti-aging effects 1

Metabolic Production and Individual Variability

Metabotype Classification

• Three distinct urolithin metabotypes exist in humans: metabotype 0 (non-producers), metabotype A (produces only urolithin A), and metabotype B (produces urolithin B and/or isourolithin A in addition to urolithin A) 3
• The ability to produce urolithin B depends entirely on individual gut microbiota composition, with only 10-50% of humans capable of producing this metabolite 4
• Bifidobacterium species (B. longum, B. adolescentis, B. bifidum) are involved in the conversion pathway leading to urolithin A production 6

Cellular Metabolism Considerations

• Urolithin A undergoes approximately 20% glucuronidation in colon cancer cells after 48 hours, while its isomer isourolithin A undergoes ~50% conversion 4
• Glucuronidated forms of both urolithins do not exert antiproliferative effects, making the extent of glucuronidation clinically relevant 4
• Both urolithins show higher growth inhibition in cancer cells compared to normal cells, suggesting some degree of selectivity 4

Clinical Implications

Therapeutic Potential

• Urolithin A has established clinical evidence in elderly populations for muscle health and should be considered the primary urolithin for supplementation strategies 5, 1
• For patients with established cardiovascular disease, urolithin A should not replace guideline-directed medical therapy including antiplatelet agents, statins, ACE inhibitors, and revascularization when indicated 5
• Urolithin B lacks human clinical trial data and remains primarily a research compound without established therapeutic applications 1

Important Caveats

• The sequential bacterial metabolism pathway means urolithin B production requires passage through urolithin A as an intermediate, making isolated urolithin B production unlikely 3
• Individual metabotype determines which urolithins will be produced from dietary ellagitannin consumption (pomegranate, walnuts, berries), affecting the clinical relevance of urolithin B in any given patient 3, 4
• Metabotype 0 individuals (non-producers) may benefit from direct urolithin A supplementation rather than dietary ellagitannin sources, bypassing the need for gut bacterial conversion entirely 3