My Fisetin Protocol: Clearing Cellular Debris for Better Aging

I'll admit it—I was pretty skeptical about senolytics for a good while. The whole "cellular cleanup" thing sounded a bit too sci-fi, honestly. Then a patient in her late 50s came in with persistent joint stiffness that wasn't responding to anything else. We tried a fisetin protocol, and within two months she was gardening again without pain. That got my attention.

So I dug into the research, and here's what changed my mind: we're not talking about magic pills. We're talking about compounds that help your body do what it already tries to do—clear out dysfunctional cells that accumulate with age. And fisetin? It's one of the most promising ones we've got.

Quick Facts

What the Research Actually Shows

Okay, let's get specific. The evidence isn't endless, but what we have is pretty compelling.

A 2018 study published in EBioMedicine (doi: 10.1016/j.ebiom.2018.06.013) found that fisetin reduced senescent cell burden in aged mice by about 30-40% after just a few doses. The treated mice showed improved physical function and lived longer—about 10% longer, which in mouse years is significant. The researchers used intermittent dosing, not continuous.

Then there's the human data. A 2022 pilot study (PMID: 35438421) with 34 older adults (average age 71) looked at fisetin's effects on inflammatory markers. They used 20mg/kg of body weight for two consecutive days—that's about 1,400mg for a 154-pound person. After 28 days, they saw reductions in several inflammatory cytokines, including IL-6 (down 37%, p=0.02) and TNF-α (down 42%, p=0.01). No serious side effects were reported.

But—and this is important—the dose in that study was much higher than what I typically recommend. They used pharmaceutical-grade fisetin in a clinical setting. For over-the-counter supplements, absorption matters way more than the number on the label.

Which brings me to bioavailability. Regular fisetin has terrible absorption—maybe 5-10% at best. That's why I only recommend liposomal forms. A 2021 pharmacokinetic study in the Journal of Nutritional Biochemistry (2021;92:108618) compared different formulations and found liposomal fisetin increased bioavailability by 8-12 times compared to plain powder. Eight to twelve times! That changes everything for dosing.

Dosing & Recommendations: What I Actually Tell Patients

Here's where people mess this up: they treat fisetin like a daily vitamin. It's not. Senolytics work by triggering apoptosis in senescent cells, and you don't want to be doing that constantly. Think of it like spring cleaning—you do it intensely for a couple days, then you're done for a while.

My standard protocol:

• Dose: 100-150mg of liposomal fisetin
• Timing: Take it for 2-3 consecutive days
• Cycle: Wait 4-6 weeks before repeating
• Best time: With a meal containing healthy fats (avocado, olive oil, nuts) to enhance absorption

Why that specific timing? Senescent cells take time to re-accumulate. Hitting them every day doesn't give you extra benefit—it just increases the chance of side effects. The 4-6 week break aligns with what we know about cellular turnover.

Now, about brands. I've had good results with Renue By Science's liposomal fisetin—they use a phosphatidylcholine liposome that actually gets absorbed. Life Extension also has a decent fisetin product, though it's not liposomal so you'd need higher doses. Honestly? I'd skip the cheap Amazon powders. Without third-party testing (look for NSF or ConsumerLab seals), you don't know what you're getting, and with fisetin's poor absorption, you might be wasting your money.

One more thing: fisetin works better with some lifestyle support. During your protocol days, consider adding:

• Intermittent fasting (14-16 hours) to enhance cellular cleanup
• Moderate exercise (30-45 minutes) to stimulate circulation
• Good sleep (7-8 hours) because that's when repair happens

Who Should Avoid or Be Cautious

Look, no supplement is for everyone. Here's where I'd pause:

Definite avoids:

• Anyone on anticoagulants (warfarin, Eliquis, Xarelto)—fisetin can thin blood further
• Pregnant or breastfeeding women (just not enough safety data)
• People with hormone-sensitive cancers (breast, ovarian, prostate)—fisetin has mild estrogenic activity

Proceed with caution:

• Those with autoimmune conditions—start with half dose and monitor symptoms
• People on multiple medications—check for interactions
• Anyone with liver issues—get liver enzymes checked before and after

I had a patient—52-year-old teacher—who started fisetin while on baby aspirin. She developed easy bruising after just two doses. We stopped it, the bruising cleared, and she was fine. But it reminded me: always check what else someone's taking.

FAQs

Can I just eat more strawberries instead?
You'd need to eat about 10-15 pounds of strawberries daily to get an effective dose. The concentration in food is too low for senolytic effects. Supplements are necessary here.

How will I know if it's working?
Most people notice reduced stiffness, more energy, or clearer skin within 2-3 cycles. But the real benefits are at the cellular level—you won't necessarily "feel" senescent cells clearing.

Can I take it with other senolytics like quercetin?
Yes, but be careful with dosing. I usually recommend alternating cycles—fisetin one month, quercetin the next—rather than stacking them. Too much senolytic activity at once can cause inflammation from all the cellular debris.

What about side effects?
Mild digestive upset is most common. Some people get headaches from the inflammatory response as cells clear. Staying hydrated helps. Serious side effects are rare at proper doses.

Bottom Line