Comparison
Berberine vs Fisetin
Side-by-side of Berberine and Fisetin. 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.
Fisetin
Fisetin is a flavonoid found in strawberries with senolytic activity in mouse models. Hickson 2019 confirmed senescent-cell clearance in human adipose tissue.
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
Fisetin
- •Flavonoid found in strawberries; most potent natural senolytic in screening assays (Yousefzadeh 2018)
- •Hickson 2019 confirmed reduced senescent-cell burden in human adipose tissue at 20 mg/kg pulsed for 2 days
- •Pulsed Mayo protocol (20 mg/kg/day x 2 days monthly) is the only dose with human biomarker evidence
- •Daily low-dose (100-500 mg) is mechanistically weaker but commonly used
- •Low oral bioavailability; with-fat dosing modestly improves absorption
- •Active cancer is a relative contraindication pending clearer polyphenol-treatment data
Side-by-side
| Attribute | Berberine | Fisetin |
|---|---|---|
| Category | natural | supplement |
| Also known as | berberine HCl, berberine hydrochloride | 3,7,3',4'-tetrahydroxyflavone |
| Half-life (hr) ↗ | 3 | 2 |
| Typical dose (mg) ↗ | 1500 | 500 |
| Dosing frequency | 3x daily with meals | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) |
| Routes | oral | oral |
| Onset (hr) | 2 | 1 |
| Peak (hr) | 3 | 4 |
| Molecular weight | 336.36 | 286.24 |
| Molecular formula | C20H18NO4+ | C15H10O6 |
| 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. | Senolytic via Bcl-2 family inhibition (Bcl-xL, Bcl-w); broad polyphenol with Nrf2 activation, mTOR inhibition at high concentrations, and antioxidant effects. |
| Legal status | Dietary supplement (US, EU, UK, Canada); Rx in some Asian jurisdictions | OTC dietary supplement |
| WADA status | allowed | allowed |
| DEA / Rx | Not scheduled | OTC supplement |
| Pregnancy | Contraindicated (kernicterus risk in neonates) | Insufficient data |
| CAS | 2086-83-1 | 528-48-3 |
| PubChem CID | 2353 | 5281614 |
| Wikidata | Q411435 | Q230614 |
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)
Fisetin
Common side effects
- mild GI upset
- headache (rare)
Contraindications
- active cancer (theoretical, polyphenol interactions)
- pregnancy and lactation (insufficient data)
- concurrent CYP3A4-sensitive medications
Interactions
- statins (CYP3A4 substrates): theoretical reduction in statin clearance at high fisetin doses(minor)
- warfarin: theoretical CYP-mediated interaction; monitor INR if combining(moderate)
- other senolytics (rapamycin, dasatinib + quercetin): additive senolytic effect; pairing is investigational(minor)
Which Should You Take?
Berberine comes out ahead for most readers on the criteria we weight: 3 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-B outcome catalogued. Fisetin 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 focus or working memory, pick Fisetin.
Edge case: Berberine is contraindicated in pregnancy; Fisetin is the safer pick if that applies.
Default choice: Berberine. Lower friction to source, and broader goal coverage. Reach for Fisetin 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 Fisetin?
Berberine and Fisetin 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 Fisetin?
Berberine half-life is 3 hours; Fisetin half-life is 2 hours.
Can you stack Berberine with Fisetin?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper