Fisetin - The Mayo Clinic Senolytics Protocol?

Can anyone tell me the actually protocol used in the landmark Mayo Study involving Human skeletal health? And what type/brand of Fisetin?

“Subjects will receive Fisetin (F; ~20 mg/kg/day for three consecutive days) taken orally on an intermittent schedule (starting every 28 days) with no-therapy periods in between dosing regimens, repeated every 28 days over 20 weeks, resulting in five total dosing periods throughout the entire intervention”

No fisetin brand is mentioned.

I have seen this dosing before, but only for two days, which is what I do monthly.

Reddit and alivebyscience.com have discussions of this.

https://alivebyscience.com/forums/viewtopic.php?t=2432

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Thank you. So you take it for three consecutive days, then wait 28 days, then do it again four more times? Then you restart again when?

Some people are using this band - only because its higher dose - can’t recommend it personally, I have no experience with it:

https://www.revgenetics.com/senolytics-500-fisetin-500-mg-for-your-mind-lifespan/

But the Amazon Choice is $0.51 per 100mg:

This was the length of the clinical study - so that was all they did. So - if you want to know how many times you keep repeating a cycle like this, you’ll have to look for other studies.

Here is another Kirkland / Mayo Center clinical study using senolytics. Their dosing plan is:

Subjects with MCI or Alzheimer’s disease will take Dasatinib and Quercetin by mouth at the same times for 2 days out of every 15 days for 6 cycles lasting for a total of 77 days (12 concurrent doses of each agent).

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I’m curious about the cost of this type of senolytics protocol that I see more and more people incorporating into their lives.

So let me tally up what I see, and perhaps people can chime in with corrections or their own experiences.

From the Mayo Center Clinical Study - The interventions are:

  • Drug: Dasatinib, Dasatinib will be supplied as 100 mg tablet white to off-white, biconvex, oval, film- coated. Other Name: Sprycel
  • Drug: Quercetin: Quercetin will be supplied as quercetin phytosome (sophora japonica concentrate (leaf) / phosphatidylcholine complex from Sunflower) 250 mg
  • Drug: Fisetin: Fisetin will be supplied in 100 mg capsules to be administered orally

The Protocols:

  • Dasatinib plus Quercetin Treatment Goup
    Subjects will receive Dasatinib (D; 100 mg for two days) plus Quercetin (Q; 1000 mg total daily for three consecutive days taken orally on an intermittent schedule (starting every 28 days) with no-therapy periods in between dosing regimens, repeated every 28 days over 20 weeks, resulting in five total dosing periods throughout the entire intervention.

Amount of Dasatinib needed: 100mg daily, for 2 days, every 28 days.
Amount of Quercetin needed: 1000mg for 3 consecutive days every 28 days.

Assume a yearly course of treatment:
Total: 24 X 100mg tablets of Dasatinib: Cost Approx. $12,400 at Goodrx, or $24 to $800 India product

Dasatinib Prices:

Quercetin prices: insignificant

Experimental: Fisetin Treatment Group

Subjects will receive Fisetin (F; ~20 mg/kg/day for three consecutive days) taken orally on an intermittent schedule (starting every 28 days) with no-therapy periods in between dosing regimens, repeated every 28 days over 20 weeks, resulting in five total dosing periods throughout the entire intervention

Fisetin Dosing (assume 70kg male for example purposes)
Fisetin Dosing: 70*20mg= 1400mg/day for 3 consecutive days, repeated every 28 days.
Fisetin Total: 1400mg x 3 x 12 = 50,400 mg of Fisetin.
Cost of popular Fisetin brands on Amazon are around $0.51 per 100mg
Fisetin Cost: Approx. $250/year given the Mayo Clinic protocol.

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How are people scheduling their senolytic protocol with their rapamycin? Does it matter?

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I don’t think there is any firm research on this - but I did see that Dr. Green has a strategy on this topic - how to phase in the Senolytics with rapamycin. Here is the video (or if not this one - check the others in this series:

Here is Dr. Green’s current (August, 2021) rapamycin and senolytics schedule: My Longevity Protocol | Dr Alan Green Episode 6 - YouTube

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I didn’t really understand Dr. Green’s line of thinking here. But I do believe that alternating them is beneficial.

My reasoning is this: ideally and in younger folks, senescent cells are cleared by the immune system. When it comes to rapamycin and the immune system, it seems like there is potentially a temporary suppression of the immune system during rapa ON, and a boost during rapa OFF. It makes me feel that taking senolytics and rapamycin apart from each other might help.

But then again, I wonder if it shouldn’t really matter. Any senescent cell damaged by senolytics would eventually be cleared by the immune system (irrespective of rapa ON or OFF) ? If Blaggosklony’s hypothesis that is no such thing as senolytics, and the current senolytic candidates are just weak mTOR inhibitors, is taken seriously then maybe administering it along with rapamycin would be helpful.

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I started taking Rapamycin (1 mg a week) about two weeks ago. I have been taking Fisetin + Quercetin Monthly at the start of each month. This week they lined up on the same day. I have been having a bout of extreme excess energy. It’s almost as if I can’t sit down. I need to stand and I feel as energetic as a 9-year-old kid who can’t sit in his seat. Has anyone else experienced this? Is it from the Fisetin + Quercetin + Rapamycin, or is it just what happens after using Rapamycin for a while? Not sure how I feel about all this excess energy. Is it good or bad? (I think it’s good?) Hopefully, I can sleep tonight???

So - what dose did you take of each today? What time did you take each?

I took 1 mg of Rapamycin with GFJ along with 3g of Fisetin and 1.5g Quercetin yesterday. Today I took another 3g of Fisetin and 1.5g of Quercetin. I noticed a little energy spike yesterday and a big one today. In addition to this, I took my normal supplement stack which has not produced an energy spike in the past. I took everything in the morning at around 6 am. I did stop my Astaxanthin today as I think it is causing me dull pain issues. Other than those changes, everything has been routine.

@EnrQay I do a senolytics course every 3-4 months, 100mg Dasatinib + 2000 Q/Fisetin 2 days in a row.

On that week I skip my rapa dose.

cheers
Sonia

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Hyper energy is now gone. I’m still energetic but not hyper. Peak energy was about 3 hours after morning supplements. Probably just an anomaly?

I think most people doing rapamycin and the Mayo Clinic senolytics protocol schedule it such that they are not taken in the same week to reduce risk of side effects. Perhaps people who do this can add their comments.

What’s the reason for doing them a week apart? Do they conflict with each other? I wasn’t aware of any conflicts, but I may have missed a post that explained it. Thank you for your help.

Are there any other supplements or medications that cause problems with Rapamycin?

Supplements - see this post: Rapamycin Interactions with Other Food, Drinks, Supplements and Drugs

Drugs, etc. - see this resource: https://www.drugs.com/drug-interactions/sirolimus.html

and

https://www.pfizermedicalinformation.com/en-us/rapamune/drug-interactions

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Thanks for that. Good to know that finesteride and acarbose have drug interactions with Rapamycin!