Comparison
Fisetin vs Vitamin D3 + K2
Side-by-side of Fisetin and Vitamin D3 + K2. 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.
Fisetin
Fisetin is a flavonoid found in strawberries with senolytic activity in mouse models. Hickson 2019 confirmed senescent-cell clearance in human adipose tissue.
Vitamin D3 + K2
Vitamin D3 K2 supplement profile: cholecalciferol at 1000-4000 IU/day corrects deficiency, MK-7 directs calcium to bone, away from arteries.
Effects at a glance
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
Vitamin D3 + K2
- •Reduces non-vertebral fractures 10-20% in older adults at 800 IU/day or above when combined with calcium
- •VITAL trial showed neutral results on primary CV and cancer endpoints at 2000 IU/day over 5 years
- •Vitamin D supplementation reduces respiratory infection incidence ~10-20% in deficient populations
- •K2 MK-7 has 72-hour plasma half-life vs 1-2 hours for MK-4; once-daily dosing is sufficient
- •Synergy hypothesis is largely preclinical; dedicated combination RCTs are limited
- •Daily dosing outperforms bolus dosing for immune and infection outcomes
Side-by-side
| Attribute | Fisetin | Vitamin D3 + K2 |
|---|---|---|
| Category | supplement | supplement |
| Also known as | 3,7,3',4'-tetrahydroxyflavone | cholecalciferol + menaquinone, D3/K2, vitamin D3 with MK-7 |
| Half-life (hr) ↗ | 2 | 360 |
| Typical dose (mg) ↗ | 500 | 0.05 |
| Dosing frequency | pulsed 2 days/month (Mayo protocol) or daily continuous (empirical) | daily with a fat-containing meal |
| Routes | oral | oral |
| Onset (hr) | 1 | 24 |
| Peak (hr) | 4 | 168 |
| Molecular weight | 286.24 | 384.64 |
| Molecular formula | C15H10O6 | C27H44O (D3); C46H64O2 (MK-7) |
| Mechanism | Senolytic via Bcl-2 family inhibition (Bcl-xL, Bcl-w); broad polyphenol with Nrf2 activation, mTOR inhibition at high concentrations, and antioxidant effects. | D3 converts to calcidiol then calcitriol, activating the vitamin D receptor (VDR) to increase intestinal calcium absorption and modulate immune and bone gene transcription. K2 carboxylates osteocalcin and matrix Gla protein, directing calcium toward bone and inhibiting vascular calcification. |
| Legal status | OTC dietary supplement | Dietary supplement (global) |
| WADA status | allowed | allowed |
| DEA / Rx | OTC supplement | Not scheduled |
| Pregnancy | Insufficient data | Recommended at standard doses for fetal bone development; consult clinician at higher doses |
| CAS | 528-48-3 | 67-97-0 |
| PubChem CID | 5281614 | 5280795 |
| Wikidata | Q230614 | Q139347 |
Safety profile
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)
Vitamin D3 + K2
Common side effects
- GI upset at high doses
- headache (rare)
- hypercalcemia (only at sustained very high D3 doses)
Contraindications
- hypercalcemia
- sarcoidosis
- active hyperparathyroidism
- warfarin therapy (K2 component requires stable intake)
Interactions
- warfarin: K2 component can affect anticoagulation; maintain stable intake and inform anticoagulation clinic(moderate)
- thiazide diuretics: additive calcium retention; hypercalcemia risk with high-dose D3(moderate)
- digoxin and calcium channel blockers: additive effects from D3-induced hypercalcemia(moderate)
- glucocorticoids: reduced vitamin D efficacy and bone effects(moderate)
- cholestyramine and orlistat: bind fat-soluble vitamins; separate dosing by 2 to 4 hours(moderate)
Which Should You Take?
Vitamin D3 + K2 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. Fisetin is the right call when one of the conditionals below applies.
- → If your priority is focus or working memory, pick Fisetin.
- → If your priority is bone density, pick Vitamin D3 + K2.
- → If your priority is cardiovascular health, pick Vitamin D3 + K2.
Edge case: Half-lives differ materially (Fisetin ~2 hr vs Vitamin D3 + K2 ~360 hr). Vitamin D3 + K2 reaches steady state faster; Fisetin is easier to dial in if tolerability is uncertain.
Default choice: Vitamin D3 + K2. Lower friction to source, a Tier-A evidence outcome catalogued, 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 Fisetin and Vitamin D3 + K2?
Fisetin and Vitamin D3 + K2 differ in category (supplement vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Fisetin or Vitamin D3 + K2?
Fisetin half-life is 2 hours; Vitamin D3 + K2 half-life is 360 hours.
Can you stack Fisetin with Vitamin D3 + K2?
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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