Fisetin vs Quercetin: The Senolytic Showdown Most People Get Wrong

Here's something that drives me crazy: people are spending hundreds on "senolytic" supplements without understanding which flavonoid actually matches their health goals. The supplement industry loves to lump fisetin and quercetin together as "antioxidants," but as a physician, I have to say—the clinical picture is more nuanced, and choosing wrong means you're probably wasting your money.

I had a patient last year—a 62-year-old former marathon runner with persistent joint stiffness—who came in taking high-dose quercetin because a blog told him it was "anti-aging." His labs showed elevated liver enzymes. When we switched him to a pulsed fisetin protocol? The stiffness improved within 8 weeks, and his ALT normalized. That's not anecdotal—it's biochemistry meeting clinical practice.

What the Research Actually Shows (Not What Blogs Claim)

Let's start with fisetin. A 2018 study in EBioMedicine (PMID: 30279143) really changed my perspective. Researchers gave aged mice fisetin and found it reduced senescent cell burden by about 35% and extended median lifespan by 10%. The human equivalent dose? Roughly 100-200mg daily for a pulsed protocol. But—and this is important—the senolytic effect seems dose-dependent and intermittent. You don't take it daily like a vitamin.

Quercetin's story is different. Published in the American Journal of Clinical Nutrition (2021;113(4):924-933), a meta-analysis of 15 RCTs (n=2,187 total) found quercetin supplementation reduced CRP levels by 0.67 mg/L compared to placebo. That's statistically significant (p=0.01) but clinically modest. Where quercetin shines is in allergy research: a 2020 randomized trial (doi: 10.3390/nu12072076) with 50 seasonal allergy sufferers found 500mg quercetin daily reduced symptom scores by 32% versus placebo.

Here's where it gets interesting—and where most people get confused. The famous "senolytic cocktail" study from the Mayo Clinic used dasatinib plus quercetin. But that research (Aging Cell, 2019;18(1):e12877) specifically noted quercetin alone had minimal senolytic effect. The combination worked, but quercetin was the supporting actor, not the star. Fisetin, in contrast, appears to work solo.

Dr. James Kirkland's team at Mayo—they're the senolytic pioneers—published a 2022 paper (Nature Aging, 2:1150-1160) comparing several flavonoids. Fisetin came out ahead for senolytic potency, with an EC50 (that's half-maximal effective concentration) about 3 times lower than quercetin's. Translation: you need less fisetin to get the cellular cleanup effect.

Dosing & Recommendations: Stop Taking These Wrong

Okay, this is where I see the most mistakes. Patients come in taking 500mg of quercetin daily year-round because they read it's "anti-inflammatory." That's not necessarily wrong, but it's expensive and probably overkill for general health. And fisetin? Most people take too little, too often.

Fisetin Protocol:
For senolytic purposes: 100-200mg daily for 2 consecutive days, then stop for 2-4 weeks. Repeat. The pulsed approach mimics the mouse study protocols that showed benefit. Taking it daily might actually reduce effectiveness—your cells need time to respond and regenerate.
Form matters: Look for "Novusetin" or liposomal formulations. Regular fisetin has terrible bioavailability—like 5-10% absorption. The enhanced forms boost that to 30-40%.
Timing: With a fatty meal. Fisetin is fat-soluble.

Quercetin Protocol:
For allergy/immune support: 250-500mg daily during allergy season or immune challenge.
For general inflammation: 250mg daily is probably sufficient based on the CRP data.
Form matters even more here: Quercetin phytosome (like Thorne uses) increases bioavailability 20-fold compared to plain quercetin. Don't waste money on the basic form.
Timing: Away from iron supplements or iron-rich meals—it chelates iron.

I'll admit—five years ago I was skeptical of both. But the aging research has gotten too compelling to ignore. I actually take fisetin myself (the pulsed protocol) because at 52, I'm more interested in cellular health than allergy control. My husband, who has seasonal allergies? He gets the quercetin.

Who Should Avoid (This Isn't Optional)

Fisetin precautions: If you're on blood thinners (warfarin, Eliquis, etc.), fisetin can potentiate effects—I've seen INR increases of 0.5-1.0 in patients on combined therapy. Also, pregnancy/breastfeeding: no human safety data. Liver issues: while generally safe, we monitor enzymes with high-dose use.

Quercetin precautions: This one interacts with more medications. It inhibits CYP3A4—that's the liver enzyme pathway that metabolizes about 50% of prescription drugs. Statins, blood pressure meds, antidepressants? Potential interactions. I had a patient on simvastatin whose cholesterol levels dropped too low when she added quercetin. Also, kidney stones: quercetin is high in oxalates.

Both flavonoids can affect thyroid medication absorption. Take them at least 4 hours apart from levothyroxine. This isn't theoretical—I've had to adjust doses for three patients this year because of this interaction.

FAQs: What My Patients Actually Ask

Can I take fisetin and quercetin together?
You can, but I'm not sure why you would. They compete for absorption pathways. If you want senolytic action, pick fisetin. If you want allergy support, pick quercetin. Combining them doesn't give you "double benefits"—it gives you expensive urine.

Which is better for brain health?
The evidence is honestly mixed. Fisetin crosses the blood-brain barrier better in animal studies. A 2021 mouse study (PMID: 33632224) showed fisetin improved memory in aging models. Quercetin has more general anti-inflammatory brain benefits. For cognitive concerns, I'd lean fisetin.

How long until I see results?
For quercetin allergy relief: 1-2 weeks. For fisetin's senolytic effects? You won't "feel" cellular cleanup. We track biomarkers like CRP, fasting glucose, and sometimes epigenetic aging clocks. Give it 3-6 months of pulsed cycles.

Are foods enough?
Fisetin is in strawberries (about 160μg per gram) and persimmons. You'd need to eat 5 pounds of strawberries daily to get a therapeutic dose. Quercetin is in onions, apples, capers—more feasible but still not therapeutic levels for specific conditions.

Bottom Line: Stop Guessing, Start Matching

• Choose Fisetin If: You're over 50, focused on cellular aging, have metabolic concerns, or want targeted senolytic action. Use pulsed dosing, not daily.
• Choose Quercetin If: You have allergies, need immune support during travel/season, or want general anti-inflammatory benefits without specific senolytic goals.
• Skip Both If: You're on multiple medications without checking interactions, pregnant/breastfeeding, or expecting miracle results overnight.
• Quality Matters: Don't buy cheap Amazon brands. Life Extension for fisetin, Thorne for quercetin. Third-party testing isn't optional—it's medical-grade supplementation.

Disclaimer: This information is for educational purposes and doesn't replace personalized medical advice. Talk to your doctor before starting any new supplement, especially if you have health conditions or take medications.