Comparison
Berberine vs Urolithin A
Side-by-side of Berberine and Urolithin A. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Berberine
Berberine supplement guide: 1500 mg/day lowers fasting glucose and HbA1c, AMPK activation, metformin parity in RCTs, dihydroberberine absorption.
Urolithin A
Urolithin A supplement guide: pomegranate-derived metabolite, 500-1000 mg Mitopure dosing, mitophagy and muscle endurance evidence.
Effects at a glance
Berberine
- •Lowers HbA1c by ~0.7% versus placebo at 1500 mg/day across 27-trial meta-analysis (Lan 2015)
- •Roughly comparable to metformin on fasting glucose and HbA1c in small head-to-head RCTs (Yin 2008)
- •Reduces LDL cholesterol 10-20% and triglycerides 15-25% via PCSK9 inhibition
- •Activates AMPK, the cellular energy sensor that drives insulin-independent glucose uptake
- •Oral bioavailability under 1%; dihydroberberine is the higher-absorption alternative at lower doses
- •GI side effects affect 10-30% at 1500 mg/day; split dosing with meals reduces incidence
Urolithin A
- •Gut-microbiome-derived metabolite of pomegranate and walnut ellagitannins
- •Roughly 40% of adults are 'urolithin producers' from dietary intake; ~60% are non-producers
- •Ryu 2016 (Nature Medicine) reported lifespan extension in C. elegans and muscle benefits in aged rodents
- •Andreux 2019 first-in-human trial (n=60) established safety and mitochondrial gene-expression upregulation
- •Singh 2022 (n=66, 4 months, 1000 mg/day) reported improved muscle endurance in older adults
- •Most human trial portfolio is Amazentis-funded; independent replication is thin
Side-by-side
| Attribute | Berberine | Urolithin A |
|---|---|---|
| Category | natural | supplement |
| Also known as | berberine HCl, berberine hydrochloride | UA, Mitopure, ellagitannin metabolite |
| Half-life (hr) ↗ | 3 | 17 |
| Typical dose (mg) ↗ | 1500 | 500 |
| Dosing frequency | 3x daily with meals | daily, morning with food |
| Routes | oral | oral |
| Onset (hr) | 2 | 2 |
| Peak (hr) | 3 | 4 |
| Molecular weight | 336.36 | 228.2 |
| Molecular formula | C20H18NO4+ | C13H8O4 |
| Mechanism | Activates AMP-activated protein kinase (AMPK), suppressing hepatic gluconeogenesis and lipogenesis while increasing peripheral glucose uptake. Inhibits PCSK9 transcription, modulates bile acid signaling, and shifts gut microbiome composition. | Induces mitophagy via potentiation of PINK1/Parkin signaling, leading to selective degradation of damaged mitochondria. Secondary anti-inflammatory effects via NF-kB modulation. |
| Legal status | Dietary supplement (US, EU, UK, Canada); Rx in some Asian jurisdictions | OTC dietary supplement (US GRAS 2018; EFSA Novel Food 2021) |
| WADA status | allowed | allowed |
| DEA / Rx | Not scheduled | OTC supplement (not scheduled) |
| Pregnancy | Contraindicated (kernicterus risk in neonates) | Insufficient data; not routinely recommended |
| CAS | 2086-83-1 | 1143-70-0 |
| PubChem CID | 2353 | 5488186 |
| Wikidata | Q411435 | Q27101321 |
Safety profile
Berberine
Common side effects
- constipation
- diarrhea
- abdominal cramping
- flatulence
- nausea
Contraindications
- pregnancy
- lactation
- neonatal jaundice
- severe liver disease
Interactions
- metformin: additive HbA1c reduction; additive GI side effects(moderate)
- insulin or sulfonylureas: additive hypoglycemia risk; dose adjustment may be required(major)
- statins (simvastatin, atorvastatin): CYP3A4 inhibition raises statin plasma levels(moderate)
- cyclosporine: raises cyclosporine levels through CYP3A4 and P-gp inhibition(major)
- calcium channel blockers (amlodipine): elevated plasma levels via CYP3A4 inhibition(moderate)
Urolithin A
Common side effects
- mild GI upset (rare)
- soft stools (rare)
Contraindications
- pregnancy and lactation (insufficient data)
- active chemotherapy (consult oncology)
Interactions
- chemotherapy agents: theoretical interaction with mitochondrial-targeting agents; consult oncologist(moderate)
Which Should You Take?
Urolithin A comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-A outcome catalogued. Berberine is the right call when one of the conditionals below applies.
- → If your priority is metabolic health and glucose control, pick Berberine.
- → If your priority is cardiovascular health, pick Berberine.
- → If your priority is muscle hypertrophy, pick Urolithin A.
- → If your priority is mitochondrial function, pick Urolithin A.
Edge case: Berberine is contraindicated in pregnancy; Urolithin A is the safer pick if that applies.
Default choice: Urolithin A. Lower friction to source, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for Berberine only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Berberine and Urolithin A?
Berberine and Urolithin A differ in category (natural vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Berberine or Urolithin A?
Berberine half-life is 3 hours; Urolithin A half-life is 17 hours.
Can you stack Berberine with Urolithin A?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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