Fisetin to Clear Senescent Cells

Robert Olin 

Robert Olin said:
I just heard

 Er, and where did you hear this?

Robert Olin said:
quercetin with a bio-available zinc does the same as HCQ in that it escorts the zinc into the cell to kill viruses.

 Since HCQ doesn't kill viruses except at crazy doses in test tubes, I don't think that's a very interesting claim.

Jimmy2 Did you notice any changes? Why not do it monthly like the mayo protocol and other users here?

Fred Cloud I figured I am still young so I don't have senescent cells.  But, now that you mention it maybe I will do it again next month.

I didn't feel any major effects with fisetin this time around with the 1500mg/day dosage.  However, the first time I did it six months ago I took 600mg/day for five days.  On day two or so I felt slightly weak, just barely.  I attributed this weakness to cells being destroyed.  I did not feel weakness this time, even with the larger dose.  I am going to get some Dasatinib and try it out.

Arizona Kid 

Arizona Kid 

GEdwards As far as rapamycin, mTOR1 is said to be exquisitely sensitive to Rapamycin while mTOR2 (associated primarily with the innate immune system) is far less so affected. Rapamycin taken daily at only 2mgs build up over a week enough to suppress mTOR2, not desirable unless you want to suppress a kidney transplant.  Taken only weekly, 5-12mgs of rapamycin largely reduces mTOR1 without impacting mTOR2.... Suppressing inflammation, encouraging autophagy, clearing many senescent cells.

I am not aware of dose toxicity for Fisetin. But it is not thought to affect mTOR2

GEdwards Have you ever heard of increased blood sugar from taking Rapamycin or Fisetin? 

GEdwards GEdwards thank you for the info! I just wonder the maximum dose of Rapa, I tend to believe everyone is conservative with dosing, we may be missing out on the optimal dose.  

Arizona Kid I've read that a single 20mg dose is enough to stop mTOR1 for almost a full week but I don't believe that's thought to be ideal..... As mild to moderate suppression is sufficient to provide benefits.  Certainly mTOR1 should not be suppressed after surgery of any kind requiring wound healing!  

Remember that male dosing of the same amount as a female results on~30% less bioavailable Rapamycin. Also taking with high fat food results in higher absorbtion. And taking with GF juice also leads to a ~3x increase in absorbtion.  I take 3-4mgs weekly with GF juice.

Aka Loo yes and it can spike lipids a bit....https://www.nature.com/articles/s41419-019-1822-8#:~:text=Rapamycin%20(Sirolimus)%20slows%20aging%2C,glucose%20intolerance%20without%20insulin%20resistance.

Arizona Kid It may depend on if you have issues.....I heard from Dr. Attia that the son of the discoverer of Rapamycin that got it to novartis was beset with cancer and took 1mg a day.....but we know that daily comes with issues.... I can tell you that my doc, Dr. Allen Green (RapamycinTherapy.com) is the best way to find out.....I went to NYC through La Guardia and had a regular appt with him in his home.....he will want blood work....he can show you how to get the tests. Dr. Green is an older gent, not chatty or terribly social but sharp sharp! He advises my close friend with an aggressive cancer.....and notes that if you already have a chronic disease, rapamycin is more a preventative than a treatment at weekly doses.
Anecdotally, I am taking the equivalent of 10-12mg once a week....eg 3-4mgs with GF Juice and I am shortly going to be 68 and have a somewhat less aggressive prostate cancer......Dr. Green asked that I up from 9mgs to 12mgs.....or 3mg to 4mg w/ GF Juice.  If your C Reactive Protein blood test is high or high normal.....tend to take more....suppressing systemic inflammation if a major major benefit.  I had mild gout, and virtually none, I have painful hand arthritis, and now that's 70-80% gone......Do not buy from Biocon of India.....go through Dr. Green who has a compounding pharmacy that sells 3mg pills for about $10.  I also take 500mg ER metformin on days I do not work out....two pills.  That is also helpful....remember, there is no single magic bullet but Rapamycin is pretty close.

GEdwards thank you for the reply! I am sorry that your going through cancer. With your attitude and measures I am sure it will be gone soon!

 

I have a good source of Rapa hear. I am, actually 31… but I am obsessed with anti aging because I have a nuerodegenrative like disorder. Best way to describe it is, like Parkinson’s and dementia combined. I have lost all of my twenties to this and want them back. Out of the 30 people who have this condition, I am only one of two that has never had a suicide attempt. I have to thank my faith in Jesus Christ for that… knowing I would always get better, but also being able to accept if I don’t I don’t. 
 

So my goal is to stay and look as young as possible!  Especially because my dating life has taken a back seat, will need to date younger if I want a family ;)

Arizona Kid I'm sure the lady is giving her honest opinion, but I looked at her profile on Amazon.  She currently has 13 reviews and rates every product she reviewed with 5 stars.  I rate products on Amazon sometimes, but my ratings are across the board from 1 to 5 stars.  I suppose I'm just more critical.

Jay Orman That’s valid, but she could also only be leaving reviews in products she really believes in!  At the least, it’s worth trying for a month if someone has the funds, no?

Logged in under wrong address. Please ignore above post from Antoniag. I can't seem to delete it.

Age 69 and no known health problems other than chronic migraine for which I take a triptan more days than not. This is an inherited trait as my mother had them and my daughter also suffers daily.  So I took my first dose of fisetin and Q two days in a row. 1200 mg F and 600 mg Q. Mixed them in EVOO. So far, absolutely no reactions. I was a little negligent in that I also had antioxidant supplements (C,D, NAC and astaxanthin). So will repeat in a month sans those and maybe take some black pepper beforehand. I used 500mg caps of F from Austin Nootropics.

Moonlitnight I get a different experience (placebo?) if I take fisetin with black pepper or if I take fisetin with piper longum (long pepper). Piper longum contains both piperlongumines and piperine. Black pepper contains only piperine. I get a stronger respons with piper longum. 

Staffan Olsson   Thank you Staffan. I will use the Piper longum and keep it all crossed. I am wondering if I should try again in a week rather than a month.

Moonlitnight Doctor's Best Fisetin featuring Novusetin is the brand that I have used. Others have used Swanson's fisetin and gotten positive results. 

 

The fact is that we don't know which brands that are high quaity and which brands that are poorly produced.

 

Besides Doctor's Best Fisetin   have also bought bulk Fisetin, but that was a terrible experince. That fisetin had a taste of an undefined chemical solvent. 

Staffan Olsson  Austin Nootropics has third party certification on their NMN supplement and has this to say on the fisetin: Every batch of FISETIN is independently verified to have a purity of at least 99%, with no dangerous levels of heavy metals or micro-organisms.  Of course, anyone can say anything, but there is nothing in the taste to indicate the presence of an unnatural substance. I will try it once more, then switch to Swanson to see if there is a difference.  Thanks for your input! @robert_weinhardt I would like to know this too. I use their face serum with NAD, NMN and apocynin, and their NAD+

RAW Good question.  With no way to estimate the dose and no real way to tell if it did anything, it seems like all you could do is take a wild guess. 

Paul D Wolf   Since lipid "encapsulation" has been shown to significantly increase absorption I'm surprised that more experimenters apparently haven't tried or haven't commented on the recently  released "micro encapsulated" gel formula.   Any significant improvement over the estimated 2% absorption of Fisetin seems like a potential game changer in getting effective doses into the blood stream.   In the absence of other comments, I guess I'll have to try a wild guess at an effective dose and adjust according to results. 

    I keep hoping some researchers will come up with a practical method of monitoring Fisetin levels in blood or urine in real time.    Urine test strips could provide easy, periodic tests.    Perhaps some transdermal sensor reacting to a chemical change related to Fisetin?

karl kuffner What do you mean last time she tried this approach with out fisetin? In what ways did she look 18 years younger?

Arizona Kid Arizona Kid the original life extension formula of "senolytics activator" was made without fisetin.  She took on a much healthier,  much younger ," look" that was kind of shocking for me...  then she reverted to normal appearance within a few days.   Shes planning  to take ," 2 LE senolytics caps ,( again), tomorrow and Thursday morning... ask me Friday morning what results we experience, if you'd like.     *note*  the correct dose is "3 caps"      my wife only takes 2.

karl kuffner sure. But my memory is worse than yours. I do think there is an opportunity to megadose these. Or at least 3 days a week. 

karl kuffner I have had similar feelings of high spirit and a very good mood after taken the original senolytic activator + increased capacity for endurance exercise the next day. 

karl kuffner Thats an impressive reaction. Fairy8i8 had a similar response, she is female similar age. But the effect lasted 3-4 weeks and so she repeats every 3-4 weeks. She was taking just straight fisetin like the mayo protocol. You can do a search and find her experience.

hi fred;  my wife, Marilou, would benefit from ," chatting " w the young woman who reported similar experiences,  to my wife's.  I'm not sure how they might ," touch base" with each other.. Any suggestions would be helpful.   Thankyou.

karl kuffner 

Hi to all,

I am a 47 year old female pharmacist (retired to run an education business) in Australia weighing 59kg. No current health problems. Latest bloods - all within normal limits.

I have just finished my 4th fisetin trial over 5 days.

I do a fisetin trial every 4-6 months using fisetin from Vitaspace (powder form). Vitaspace provide a spoon which measures 620mg.

 

Latest dosing as follows:

 

Day 1: 3100mg (620mg x 5 Vitaspace spoonfuls) - dissolve and mix thoroughly in equal parts of Polysorbate 80, extra virgin olive oil and hot water with a dissolved 1/2 Equal artificial sweetener tablet. It becomes a very smooth toothpaste consistency. Eat with a spoon. Rinse with strong coffee with real cream (this is the cream you get from the dairy section and might whip to put on top of a meringue cake).

Do not eat anything for 30 minutes.

 

Day 2: 3100mg (620mg x 5 Vitaspace spoonfuls)

Day 3: 3720mg (620mg x 6 Vitaspace spoonfuls)

Day 4: 4340mg (620mg x 7 Vitaspace spoonfuls)

Day 5: 4960mg (620mg x 8 Vitaspace spoonfuls)

 

Results:

Day 1: nothing, had a nap after lunch

Day 2: 90% reversal of chronic nasal congestion, 50 - 60% more energy, faster urination.

Day 3: woke with more than normal amount of energy

Day 4: nothing of note

Day 5: Got COVID-19. Runny nose lasted for three days. Used my Ventolin puffer a few times for a dry cough which became a wet cough for 1-2 days after the runny nose finished.

 

One week later:

Feeling sharp and clear today on 10/01/22

 

I import the fisetin in powder form from Peter at Vitaspace in New York State. You can order direct from the website.

 

https://www.vitaspace.com

PHONE = 631-342-1883.

 

Email Peter direct if required:

vitaspace@mindspring.com

 

Fisetin 98% (PURE) (Light Yellow Powder):

Reiterating: Peter provides a 1.7ml Vitaspace spoon which measures 620mg assuming that the powder is tightly packed and levelled.

 

I get the Polysorbate 80 (food-grade) from a cooking store in the US: https://modernistpantry.com/

Moonlitnight 

Dale Piggott To Moonlitnight and all others who have mentioned (or take) quercetin. www.Mountsinai.org states in part that: " Anticoagulants (blood thinners). Quercetin may enhance the effect of these drugs, increasing your risk for bleeding. Anticoagulants include:."  So, consider it as well..

Dale Piggott  Thank you so much. I personally don't take anticoagulants (except for the occasional aspirin) but this is good to know.

ripeideas The truth is that the researchers at the Mayo Clinic are guessing!  The two consecutive days is based on limited murine studies, but in a longer lived mammal like humans, one could argue for a longer period.  The researchers at the Life Extension Foundation are suggesting chronic use of senolytics on a once weekly basis.  

ripeideas I read a study on Quercitin showing that it does not directly induce apoptosis but opens several pathways for apoptosis, presumably ripe for a senolytic like fisetin.  Seems like it should be considered, esp liposomal.

ripeideas I don't think anyone really knows yet what frequency is best.  One idea is to base it on how long it takes for senescent cells to accumulate after a treatment.  A month or so I think, but will depend on age and health.

Rob8311 I wish I didn't get so damned depressed on the choline content of liposomal supplements. I actually made my own liposomal Vitamin C and resveratrol but I was depressed as all get out. Strange. Melatonin does the same thing. I'm not a depressive person! 

Rob8311 I'm 60 and in poor health due to severe insomnia and ME/CFS. Maybe i'll do it every few months. Thanks.

Rob8311  Lack of a practical means for measuring the percentage or volume of senescent cells in the body seems to be the biggest problem with determining the effectiveness of any senolytic treatment.    Autopsy seems to be the only reliable method and has been used in tests involving lab mice but is obviously impractical for human testing.    I keep hoping someone will come up with a blood or urine test which will provide a relative indication of the volume or percentage of senescent cells in a human body or an indication of cells being destroyed by in vivo following a senolytic treatment.    Perhaps some residue from ruptured senescent cells released into the bloodstream or excreted in urine.....

ripeideas Swanson has quercitin anhydrous (out of stock right now) and there's also quercitin EMIQ.

ripeideas That sucks.  I have my own insomnia problem, not the same as yours I know.  THC/CBN gummies worked great, for a while.  Sounds like you are using an overall health approach instead of playing whack-a-mole with symptoms.  Having said that, have you tried LDN? 

Rob8311 Just ordered a test from The DNA Company (damn webinars!).  Maybe I'll be able to see if I am somehow triggering the wrong gene.  Not an endorsement because I haven't tried it yet, just brainstorming.  I didn't react to LDN, but I have tried that and other interventions through AgelessRX.

RAW My "peptide guy" at the anti-aging institute I use said they are working on it!  Stay tuned.

Chris M I got this one. https://www.amazon.com/Fisetin-Capsules-Bioflavonoid-Polyphenols-Supplements/dp/B082WLT5V2/ref=sr_1_6?keywords=fisetin&qid=1639963119&sr=8-6

Denise Shugerman Have you tried high dose fish oil? Over the counter is cheap and you can get analysis of various brands if you are member of Consumer Labs. To get about 5 grams of EPA/DHA costs about $15/month at Costco.  

A quick check on Google will document the many benefits of high dose fish oil for most of your issues ( and many more). You might want to check out one of Barry Sears books.

Good luck!!!!

Peter H. Howe I use to be a member of Consumer Labs.  The big problem they have is you as a supplement manufacture/distributor must pay them to test your product.  They will not test anyone/s product that does not pay.  So they charge the consumer and the supplier. Many best products are never tested. 

  In my mind a BAD WAY TO DO BUSINESS.  I do not trust them

Van Thank you for the information. I was not aware of the conflict and it is a conflict. May be the reason why my fish oil is no longer on the list and earlier tests are no longer mentioned. I have, however,  seen occasions when they have reported different conclusions on two different products from the same supplier. 

Peter H. Howe I know it is disappointing in that we need an honest supplement reviewer.  Best thing we can do is buy supplements from well know and trusted retailers like Costco, and be sure to be educated enough to read the labels. 

Van If I do not get from Costco, I get from LEF. Note that Consumers Lab found Costco's green tea inferior as it had little or no EGGC but found Costco's   Kirkland fish oil one of the better brands. Consumers Lab also get into arguments with some manufactorers about some of the products it evaluates. I will still check Consumer Labs but with skepticism.

Denise Shugerman This may be a bit of a different approach from what you have tried, but you mention OA which I assume is osteoarthritis, and joint pain.  The first thing I would do is supplement with Borax.  (Yes, 20 Mule Team Borax...)  Borax is a clean and excellent source of Boron.  Boron has been shown to be a necessary trace element and low levels in the water and diet has been shown to correlate with higher levels of arthritis in both people and animals.  I have used this myself with excellent results and have recommended it to about 15 or so people and every one of them has experienced some level of improvement in their joint pain. 

You need to take at least 100mg of Borax (which contains about 10mg of Boron) a day, and if you take more initially it is not a problem.  The daily maintenance dose of 3mg a day is definitely not enough to get ahead of the curve on this.  You can think of it like table salt and take a fair pinch of it, as much as you would use for a good salting of ones eggs at breakfast.  I would recommend taking it like this for about 3 weeks.  I usually get results in a week and then forget to continue as I don't continue to have pain...  After this, you can supplement at 3mg if you like.

Dan Nave that is quite unconventional!  But I will try anything.  Thank you!

Denise Shugerman I'm hearing that fasting is an excellent way to cause autophagy.  It starts at 17 hours and if long enough you get stem cells released.   Google or duckduckgo fasting+autophagy.   

Robert Olin Yes, I know about fasting for autophagy...just waiting to get inspired to do it!

Denise Shugerman    I just had a big chocolate milkshake before starting my 1st 48 hour fast.   Autophagy is supposed to start at 17 hours.     Wish me luck.  

https://www.youtube.com/watch?v=5RT4qIO27uw

Robert Olin I find a nice approach to fasting is to eat my last meal on the afternoon of a Friday (2-3pm as work allows). Go through Saturday on green tea or black coffee -> add a little salt for electrolyte balance. Gently refeed on Sunday morning starting with a small amount of bone broth or protein. Should get you into the autophagy space. Frequency once a month for me. As long as your insulin levels are already tamed by having avoided snacking and the like for a while this degree of fasting is almost effortless, in fact it's pleasurable.

Jack Black Thanks for the advice.  I would prefer to snack all the time, but realize that I probably have insulin resistance and am also a hyper responder to carbs.   My wife is serious about feeding everything around her and can eat all the potatoes and rice she wants and never gains a pound and her HDL is 88.  

Robert Olin wow, if I had a chocolate milkshake before fasting, I'd be starving due to the sugar. Actually I am on the Peptide Semaglutide which controls sugar levels really well and makes you not hungry so i do not have an excuse to avoid fasting. I am just not disciplined, I want my coffee and I want it with milk every morning. The longevity institute I work with says 16 hours of fasting is good so I've done that here and there but yeah, 48 hours I'm sure is better.

Denise Shugerman Dr. Mindy say autophagy starts at 17 hour and slowly ramps up.   I'm like an alcoholic with food.   I'm either on the wagon or I'm not.   It's a lot easier once the decision is made.  No food today period.   Of course, I still have 1.5 days to go.   Talk is cheap.   Stem cell production is another interesting effect of fasting.   We'll see if my back stops aching so much.

Robert Olin I'd just like to clarify that autophagy does NOT "start" at the 17 hour mark, which is by no means a definitive dividing line in any case.  Actually, autophagy is happening ALL the time, but does increase with fasting. On different pages of her website (which also seems geared towards product sales), Dr. Mindy Pelz also cites Dr. Ohsumi's 13-15 hours and Naomi Whittel's 16 hours, but peer reviewed academic research has demonstrated that depending on the size and composition of the last full meal, the liver may use the last of its glucose reserves in as few as 8 to 12 hours, hence the popularity not only of the 18/6, but also the 16/8 and even 14/10 time restricted eating protocols.  My best wishes for your aching back!   

Brian Valerie Thanks for the information.  At 71 I can use all the autophagy I can get.   I understand some people also take fisetin and Quertcetin while fasting.   Others say go easy as your body starts detoxing when you are new to fasting and there might be a lot of toxins to deal with.   I'm at 18 hours.  Last night while in bed I fantasied eating a large BabyRuth candy bar.   Last thing I remembered as I fell asleep.  Better than counting sheep...grin.

Robert Olin At 40 hours into my fast I took my blood sugar and it was 99.   I've had lower when not fasting.   I assume my liver is dumping stored sugar?   I never got really hungry.   What I missed is the pleasure I get from eating.    This is the 1st time I've said no to my stomach, in my entire 71 years.    Hope to do it at least once a months.

Perhaps I'll take some fisetin  next time.

Denise Shugerman I was searching another topic, but saw your post.  20 years ago I also had L4-L5 issues with herniated disc.  Pain can radiate to all different areas.  I investigated various approaches, & decided on protocol which was 100% effective:  spinal decompression.

Likely you could find MRIs online, showing how the disc is actually inflated by the decompression.

In those days there was 1-2 high-end units, available only at MDs.  These days there are several computer controlled machines, with cost to MD / chiro for equipment from $13,000 = $150,000.

Individual treatments are generally about $70 - $120 per 40 minute session.  I think protocol is for 21 consecutive days.  When I started it was covered by insurance, but not sure these days.  I was unable to walk without a walker (about age 50 then,) but after session 10, about 50% improved; by session 17-18, fully recovered.

Every 3-4 years I get about 5 sessions to prevent possible back problems.  Very successful.

Related, but vits/supplements with decompression is helpful.  One I did not know then is CMO (Cetyl Myristoleate,) available both in capsules & topically.  It helps to shuttle various nutrients into the discs.  I assume F+Q etc. to remove senescent cells would be helpful too.

Denise Shugerman Yes, I have had a good experience. Been using high dose ( 5.5 grams of EPA/DHA from 6, 1.4 gram Natures Bounty capsules. )  for more than 25 years with low dose statin as part of a  preventative cardiac problem  after a bypass.  At 81 I have no joint  issues or arthritis.  My inflammatory cytokines  ( IL-6) are below detection limit. It also inhibits the brain shrinkage and cognitive  decline that are part of the aging process. 

The Barry Sears books will describe the chemistry and multiple benefits, and he recommends at least 5 grams if you have a chronic inflammatory condition.

Again, wish you luck in correcting the problems you have. 

Peter H. Howe What do you mean by: " 5.5 grams of EPA/DHA from 6, 1.4 gram Natures Bounty capsules"? 

Thanks

Denise Shugerman I purchase my Nature's Bounty fish oil from Costco. Each capsule weighs 1.4 grams ( 1400 mg) and contains 0.88 grams of EPA/DHA total. I rounded it off to 0.9 grams of EPA/DHA /capsule. I take 6 capsules/day ( 3 in am and 3 in pm ).  6 capsules x 0.9 grams/capsule = 5.4 grams of EPA/DHA.

There are 130 capsules/bottle and each bottle costs~ $16.00 when they go on sale every other month. Not on sale cost is ~$21.00 at my Costco. 

I suggest you may want to read one of Barry Sears books as he goes into detail about the numerous benefits of fish oil for multiple systems which include cardiac, inflammation (arthritis),  neurological and vision.   He recommends ~2.5 grams /day for maintenance, ~5.0 gams/day for chronic conditions and higher levels for acute conditions.  There are over 7,000 peer reviewed publications on fish oil. 

As I indicated, I started on fish oil almost 30 years ago after an emergency bypass. It came to my attention from articles in LEF 's magazine and the author  ( Dr. William Davis) was a cardiac physician who also  published a book entitled "Track Your Plaque" . I visited him in Wisconsin and over a period of about 1.5 years he balanced my cholesterol with  high dose  fish oil and low dose statin to lower several critical factors to a non threatening condition. Basically fish oil lowers triglycerides which in turn lowers LDL-P and particle size to an acceptable level.

At the time, I was using LEF's oil but switched as Natures Bounty was it somewhat less expensive and more convenient. I also made the switch at the time based on Consumer Labs findings. Since that time, Consumer Lab no longer tests Natures Bounty and the historical record has been removed. Consumer Labs most recent analyses indicate the Kirkland Brand ( Costco) and LEF's straight fish oil are OK as well several other brands.  As regards Consumers Lab, please note Vans' ealier comment in that Consumer Lab's only test if they are paid. This is a conflict but I do not know what else to tell you as pharmaceutical grade fish oil will cost you orders of magnitude more  than the 3 over the counter brands I mentioned above.

Wish you the best on your efforts

Denise Shugerman In my case, it is a correlation issue in that I started high dose fish oil due to cardiac issues almost 30 years ago and have never developed any arthritic type issues. The literature documents extensively the benefits of high dose fish oil in preventing joint pain and some of my brothers and sisters have joint pain as did my mother. 

Note  I just doubled my dogs  (12 year old Aussie) fish oil and his stiffness has disappeared. My previous dog was a lab who made it to 15 without any noticeable joint pain and she got at least 2 grams/day.

Denise Shugerman Please make sure you do the calculation based on the EPA/DHA content of the capsule. My capsules ( Nature Bounty) are 1.4 grams but the EPA/DHA fraction is 0.9 grams which gives me 5.5 grams of EPA/DHA if I take 6 capsules. Note that Consumer Labs identified Costco's Kirkland brand and Life Extensions straight fish oil as  two of the better brands in terms of quality based on testing.  I selected Nature Bounty based on Consumer Labs testing several years ago but they have not tested Nature Bounty lately.

Good Luck 

Michael Fast sometimes anyway. Everything I find about our metabolism seems to scream that we're highly adapted to survive famines. Fast and feast seems very agreeable to the human body. Feast all the time poisons us.

Juan Daw Thanks Juan  Metformin inhibits glucose production in liver thus dropping glucose levels in the body.  Lower glucose = less inflammation = less plaque buildup in arteries in brain, heart and kidneys = reduced risk for heart attack, stroke and kidney disease + glucose stores calories as fat = weight gain.  There is a reason they are doing the TAME trial with Metformin. 

Van If it ever gets launched...7+ yrs and running. 

Additional info on fisetin:

https://www.frontiersin.org/articles/10.3389/fchem.2019.00697/full

• Recent in vitro studies have given a mechanistic insight into how fisetin inhibits the target of the rapamycin pathway in various cell models and therefore influences cellular pathways that are known to affect aging (Syed et al., 2013; Pallauf et al., 2016).

• It has also been found that fisetin in combination with other epigenetically active molecules which are able to cross the blood-aqueous and blood-retina barriers exhibit synergistic beneficial effects. This applies for a low dose red wine polyphenols, as well as for vitamin D3 and some other compounds of small molecular weight, synergistically improving visual acuity in patients with advanced atrophic age-related muscular degeneration, including the older ones with advanced stages of the disease for whom very few options remained (Ivanova et al., 2017).
• The anticancer activity of fisetin can be enhanced by some auxiliary substances. For example, fisetin significantly impairs carcinoma cell growth in the presence of ascorbic acid, which results in a 61% inhibition of cell growth, in 72 h; the treatment with ascorbic acid alone had no effect on cellular proliferation (Kandaswami et al., 1993). 

JGC Remember the ITP has three test sites.  From what I remember in previous experiments there are 100 control mice and 50 experiment mice at each location.  So the ITP is actually reporting the results in culmination from all three sites.  That’s why any conclusion they come up with has weight.  They also tested the fisetin at two different doses.  So let’s wait and see.  However, they also reported fisetin doesn’t hurt.  So while we wait we can still take it without harm.

Chris M You apear to be confusing the nugatory life extension the ITP reported with massive levels of glycine alone, with the recent report on GlyNAC, which was not from the ITP and was a BS study. All the animals were short-lived; it's just that the GlyNAC animals were less short-lived than the controls.

Iðunn Yes, sorry I confused those two.  So, do you think that GlyNAC will improve lifespan?

Chris M No.

Moonlitnight 

Waiting for the paper to be published. 

https://www.youtube.com/watch?v=42PzfNs9egA&t=0s

Dr. Miller talks about two substances (minute 1:12:13) he is excited about, but the study is incomplete - astaxanthin and meclizine (dramamine - anti-motion sickness drug); also given to pregnant women for morning sickness).

Juan Daw The best results come from Rapamycin and Acarbose (alpha gluosidase inhibitor). I am not ready to try drugs yet, so I will try a combination of Ashwaghandha with some natural alpha glucosidase inhibitor (maybe grape seed extract). 

There is a whole bunch of alpha glucosidase inhibitors from food, to experiment with, but grape seed extract has the added benefit of its own study. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020213/

• Morus alba (White mulberry) is another plant species for which AG inhibitory activity has been well-studied [44], and its leaf extracts exhibited AG inhibition activity with an IC50 value of 91.63 µg/mL compared to that of acarbose (IC50: 402.33 µg/mL) [45]. A range of bioactive compounds isolated from the leaves of Mango (Mangifera indica L.) were screened for their inhibitory effect against AG and among them arjunolic acid and actinidic acid exhibited inhibitory activity with IC50 values of 239.60 ± 25.00 and 297.37 ± 8.12 μM, respectively [46]. Similarly, extracts from the peel of fruits of Jackfruit (Artocarpus heterophyllus) displayed the strongest inhibitory activity (IC50: 0.05 mg/mL) followed by its seed (IC50: 1.79 ± 0.15 mg/mL), pulp (IC50: 6.81 ± 0.52 mg/mL), and flake (IC50: 10.52 ± 0.73 mg/mL) extracts [47]. Grape seed and green tea extracts were also found to have strong inhibitory activity against AG with an IC50 values of 1.2 ± 0.2 and 0.5 ± 0.1 µg/mL, respectively. These inhibition potencies were much stronger than the inhibitory effect obtained from acarbose (IC50: 91.0 ± 10.8 µg/mL) [48].

Juan Daw  Juan, isn't dramamine dimenhydrinate?  That's a powerful anticholinergic. I used to take Gravol (Canadian brand name) to help me sleep. I stopped when I heard the study suggesting a link between anticholinergics and Alzheimer's. I take astaxanthin daily.

Moonlitnight Yes. I stand corrected. My fault, not the keyboard's.

Juan Daw Dr. Miller has yet to publish his study about fisetin. Yet, people are already concluding fisetin's benefits have been discredited. I would want to read the study and compare with the study below.

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(18)30373-6/fulltext

• Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism.

Juan Daw   Thanks for posting that!

Juan Daw The Dramamine used in the experiment is the non drowsy formula using meclizine.  It is not the original formula!

Chris M Agreed. I stood corrected by Moonlitnight.

Juan Daw I think it is relevant to mention that Maqui Berry - Delphinidine has shown some distinct effects on fasting and Postprandial Glycemia and Insulinemia. 

 

Delphinidin-Rich Maqui Berry Extract (Delphinol®) Lowers Fasting and Postprandial Glycemia and Insulinemia in Prediabetic Individuals during Oral Glucose Tolerance Tests (hindawi.com)

Staffan Olsson Thank you.

There seem to be many natural substitutes for metformin or acarbose, for the calorie-restriction mimetic effect. Berries are more palatable; but leaf powder is cheaper.

Below is another study on mulberry twigs, and a direct comparison with acarbose, on HbA1c levels.

https://www.healio.com/news/endocrinology/20210517/mulberry-twig-alkaloids-lower-hba1c-with-fewer-gastrointestinal-effects-vs-acarbose.

 

• Qu and colleagues analyzed data from 600 adults who met 1999 WHO diagnostic criteria for type 2 diabetes and had not been treated for diabetes for more than 3 months. Participants were randomly assigned mulberry twig alkaloids (n = 360; 48.6% men; mean age, 55 years) or acarbose (n = 240; 53.2% men; mean age, 54 years) for 24 weeks. Primary endpoint was change in HbA1c compared with baseline. Researchers also assessed adverse events and gastrointestinal disorders.
• At 24 weeks, change in HbA1c was –0.93% (95% CI, –1.03 to –0.83) and –0.87% (95% CI, –0.99 to –0.76) in the mulberry twig alkaloids and acarbose groups, respectively. The least squares mean difference was –0.05% (95% CI, –0.18 to 0.07) between the two groups, with no significant difference on the basis of covariance analysis.

Now to find a rapamycin mimetic, in addition to withaferin, so I can pair them for  self-experimentation. Would help if Dr. Miller publishes his study, so dosage can be determined. 

Juan Daw Agreed! To me, while new research such as that conducted by ITP carries some weight, to me it's just another data point. Fisetin still holds other benefits. Plus if you look at ITP's other studies like rapamycin, most people aren't going to run out and buy it. They conduct the study in a controlled environment, and we know it's not ready for prime time until further research is done.

JOHN Agree with you. I saw immediate, quantifiable  increase in my exercise performance  and qualitative improvement in color vision. Those improvements continue after 1.5 years of continuing Mayo Protocol.

Note that several others on this thread reported similar results. 

JOHN Agreed, I am not convinced either.

There have been so many positive reports from taking fisetin as a senolytic and people are just going to ignore those and listen to the ITP instead? Bizarre. Sure, you could say some of those are possibly placebo effect, but are you saying all of them are placebo? No way. What kind of person rejects every single report of benefits of fisetin that is out there and instead just blindly believes some guy saying their study said it didnt work without even reading the study or anything else? Are people that easily persuaded?

Peter H. Howe Agreed Peter, there are many reports of positive effects from fisetin out there like yours. It really makes me wonder how people do research on substances. Do they just read a study and reject all other evidence and thats it?

If there is an abundance of positive feedback, then that should be a huge red flag that maybe the study was done incorrectly instead.

Fred Cloud Forgot to mention that I am 81 yo male. My age ( lots of senescent cells ???)  may have contributed to the positive effects that I noticed. I was somewhat impressed as the positive effects were almost immediate--next day after my first treatment. My chinups/pullups increased by 25 % from 20 to 25. My exercise regime had been about the same for the past several years. What I perceived to be increased color vision was also immediate.

Peter H. Howe Twenty five pullups at any age is impressive. At age 81 its scary!

Peter H. Howe Great to hear. But even younger people using fisetin on this forum have been getting great results, like fairy8i8 who is 38 years old. I guess I should tell her to ignore all her great results and stop using fisetin because Dr Richard Miller from ITP said so.  

fairy8i8 wrote: "I have been taking 1200mg/day of fisetin in a single dose for 2 days (I am 56.8kg). I started doing this monthly over 18 months ago. After about 6 months, I started taking this dose twice a month because I noticed clearance of facial fine lines, which would return after a few weeks. Doing the dose every 2 weeks has kept visible skin indicators of aging decreasing. 

At first, I did not think anything of the treatment. I am young (started treatment at age 38), and didn't figure I would see much effect. However, my mother, age 70, has had a nickel sized flat mole on her cheek since her mid 50s. She took 1 round for 2 days, and when I saw her a few months later, the mole was gone, and there were just a few small freckles there. I asked her about it, and she said it disappeared after taking the fisetin. After that, I started to track my own moles. The ones that have appeared over the years have all lightened significantly and diminished in size, and the few I've had since childhood have all lightened to almost skin color. 

I have injury onset arthritis in my big toe, and that reduced to nothing (before walking 13 miles, running for 30 minutes on the Great Wall, not having run in almost 10 years, and then getting on a plane 3 hours later made it hurt again). I am recovering from that, but the pain is consistently decreasing again...."

more at: https://forum.age-reversal.net/t/36dhmw?r=35h3qdq

Fred Cloud What brand are you taking and how much? Thanks, Fred.

Peter H. Howe will you be my adopted grandfather? You sound awesome

Michael Look for a brand that uses Novusetin fisetin ingredient. Lately, I have been using Wellness resources brand on amazon because they were offering 250mg caps so you dont have to take as many capsules.

Fred Cloud 

I am among those who have had distinct improvements from fisetin. I have  noticed different effects from different formulas. When I (orally) take the fisetin labelled as novousetin from  Dr’s best, after a few days I notice distinct  physical improvements on muscular strength and when it comes to joint health. When I (orally) take the more bioavailable formula from life extension “bio-fisetin” (a formula created for better absorption in the digestive tract) I notice mental effects - like clarity of mind and an uplifted mood.

 

I have made my own suppositories based on the Dr’s best brand. But when using those suppositories I do not experience the same effects as I do from orally taken fisetin from Dr’s best.

 

When it comes to homemade suppositiries I am of course a novice. So that experience does not say much. Just out of curiosity I will make suppositories from the life extension's brand as well.

 

Ps. In my case I am sure the experience from the Dr’s best formula is not placebo.