Question is not Rapamycin related but relates to overall longevity domain.
What protocols of Resveratrol and/or Fisetin do you follow and why?
Thanks
Hi - I suggest you avoid resveratrol - there is no good evidence that it is helpful in lifespan / healthspan improvement. See the Richard Miller Podcast / interview by Peter Attia. In the interview the following information is conveyed:
- The resveratrol story âcaught the world by stormâ
- David Sinclair published a paper suggesting longevity benefits of resveratrol in mice â showing that when resveratrol was given to metabolically-ill mice, it produced a longevity benefit in part by activating sirtuins
The problem with these studies :
- The mice in question were being given a diet consisting of 60% coconut oil â âthey were being poisoned â
- The mice were dying because their livers got so big, so filled with fat, that it compressed the chest cavity and crushed the lungs
- âSo theyâre not really studying aging, theyâre studying a bizarre pathological process where the liver gets so fat that it crushes the lungs .â
- In addition, there was a statistically significant increase in median lifespan , but only in the animals that were on this highly toxic diet
- When you look at other indices of maximum lifespan, resveratrol had no benefit
- And when you look at the lifespan affects in the mice that were not on this toxic diet, there werenât any
In short , the original Nature paper was widely misinterpreted as a demonstration of a drug that slowed aging, but in reality did not extend maximum lifespan except in mice that were dying of this extremely unusual lipid specific poisoning
Additionally - the ITP did a great lifespan study with resveratrol (and other compounds):
The ITPâs test of resveratrol
â Results : It had no effect on longevity â no change in median or maximum lifespan (see Survival Analysis of cohort 3 and cohort 4)
- The ITP studies were the first of several studies to show that resveratrol given to mice on a normal diet does not extend their lifespan
Resveratrol and Sirtuins
- Thereâs been a lot of controversy as to whether the sirtuins are important or not in the aging process
- âI donât think thereâs any evidence yet that resveratrol is good for you or that sirtuin activators slow the aging process.â says Richard Miller
As a side note - I think the same type of general comments can be said about NAD precursors right now - little evidence, with lots of hype.
Nicotinomide Riboside also failed in the ITP studies to improve lifespan in mice. So, donât waste your money until there is good data.
A good read:
FISETIN:
With regard to Fisetin - most people Iâve talked to turn to the Mayo Clinic studies are their reference point towards developing a Fisetin (and Dasatinib) protocol:
The new Mayo Clinic protocol for elimination of senescent cells using Fisetin was increased as follows: 20 mg/kg/day (this is equivalent to around 1,800mg per day for an average 180lb person) for 3 consecutive days, resting one month, then repeating this procedure of 3 days on, one month off for 5 months total.
This is a substantial increase over their previous protocol of 2 days on, one month off for only 2 months, showing Fisetin is safe and effective at even higher doses than previously known. https://clinicaltrials.gov/ct2/show/NCT04313634âŚ
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
Drug: Fisetin Fisetin will be supplied in 100 mg capsules to be administered orally
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Oh my gosh. This is an amazing forum. Thanks for the comprehensive input. Thank you for creating such a website/forum where we can all learn from each other.
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Resvertol is known to inhibit MTorc1. I take it every other day (cardio workout days). Dr Sinclair personally recommend alternating days.
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Thanks. I thought of Richard Millerâs comments with Peter Attia, almost accusing Sinclair of academic fraud, when you wrote about academics should be banned from profiting from outside companies. I was then shocked to read that Peter Attia has now gone into business with David Sinclair.
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Iâve not heard/nailed down re the above senolytic protocol; Dasa+Fisetin and not mentioned above Quercitin, is where does the every 2 week Rapa dosing come in re the timing of Dasa+Fi+Qu? Dr Greenâs later videos mention alternating weeks. Guess at his age he does Dasa (etc?) every 2 weeks⌠A guess from listening between the lines of his later Rapa youtube video.
IE Rapa NOT at the same time as Dasa ? or can be coincinding for convenience. Tnx!
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I believe Dr. Green stated in an interview that he figures that while rapamycin slows the aging of cells through autophagy and mTor inhibition, the goal of senolytics is to kill the cells, so the therapies might work at cross-purposes.
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This didnt age well lol
Can you explain why this did not age well?
The whole debacle unfolding right now about resveratrol and sirtuins with a lot of distinguished scientists calling out David Sinclair for putting out misinformation and information that has been proven wrong. Itâs been going on for a bit now, but I think there was a topic on the forum that was recently talking about it.
I was commenting more to the guy who said Dr. Sinclair personally recommending.
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part 1 and 2 (3 and 4 coming in next days/weeks)
I thing it is a great insight into resveratrol, fisetin and quercetinâŚ
the only problem I have, is that i planned starting resveratrol, fisetin and quercetin⌠now I am stocked with all three and I donât know what to doâŚ
resveratrol 500 mg capsules
fisetin 450 mg capsules
quercetin 450 mg capsules
Maybe see if you can return the Resveratrol and keep the other two 
Re the Resveratrol thing, if weâre being honest, I think most on this site would have tried it at some point (due to all the âhypeâ as @RapAdmin explained in his post above). I know I did. I think most have probably moved on now and are saving their moneyâŚâŚ
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what would be quercetin/fisetin protocol? 
I havenât actually taken these (sorry)âŚ.have looked into them but not committed currently.
Hopefully someone else can provide some guidance here 
@DMac You are very correct. Weâve probably all tried Resveratrol as the hype machine was in full force on this one. I am currently working through my Resveratrol stock. I am taking about 250 mg 3x weekly (Mon, Wed, Fri). I donât see a downside to this as itâs a sunk cost. I have heard a low dose of resveratrol (less than 500 mg) has a different effect from a high dose (~1 g). I will not purchase resveratrol again.
I am also working through my NMN stock taking 750 mg daily. I am on the fence about NMN. I feel some energy-related benefits for healthspan especially since I donât get enough sleep. The NMN seems to help with that. It also has the benefits of taking Niacin and my cholesterol levels are fantastic. I attribute that to the NMN. I will probably continue with this.
I tried the Fisetin\Quercetin senolytic therapy of 3g a day for 3 days straight once a month. Iâve stopped doing that. I think itâs better to prevent cells from going senolytic instead of removing them. Now I plan to take Rapamycin to prevent senescent cells as it is a senomorphic. I think I will do the Fisetin protocol every 6 months from now on instead of every month to clear out the senescent cells that do form. Somewhere on the forum, there was a post about heart endothelial senescent cells being a benefit and that they should not be removed, and this may do that. I am still on the fence about this though.
Good luck and if you find out any information to change our thoughts, let us know!
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I have been watching some videos on resveratrol and have a question regarding dose. The guy in the videos that I posted above is going into depth of dosage and comparing mice study with human dosage and claims that low dose will give longevity benefits (as claimed in the appendix of SInclairâs study published in 2008 Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span - PubMed) Than he goes and recalculates the human dose, but never talks about bioavailability⌠Since bioavailability is much lower in humans then mice (respectively less than 1% vs. 6-12%) wouldnât that mean that you would need to adjust the low dose with bioavailability? And wouldnât in that case be Sinclairâs 1g considered a low dose in human? just wonderingâŚ
Honestly, Iâve lost faith in resveratrol, so I havenât put much thought into it. Iâm just taking 250-350 mg every other day to use up my stock. I do mix it in EVOO to improve bioavailability and take it with black pepper. I doubt youâll find too many resveratrol enthusiasts here anymoreâŚ
totally get you, I was just wondering⌠I am also trying to move my stock
(but still I think there is a possibility that there is something in resveratrol that could help longevity⌠even after following this controversy for last few months)
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Resveratrol combats chronic diseases through enhancing mitochondrial quality
https://www.sciencedirect.com/science/article/pii/S221345302300188X
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