JGC I don't think there's any evidence that piperine/BioPerine enhances absorption of flavonoids generally — just curcumin. Or do you know of any? And the mechanism isn't really understood, so it's hard to make strong predictions.

Dan Nave BobM nealfg deahello again;  Dan your wisdom and response to my questions,  is very useful. after 3 consecutive days of aggressive fesitin (? Spelling)  and quercetin and black tea ( help w assimilation)  I've been experiencing high energy,  more and then much less arthritis discomfort some euphoria,  I've discontinued weekly," le senolytic activator" and will do another intense fisetin, quercetin, ( probably black pepper)  and hot black tea in 30 days from now and will report on my, "experiences"  thankyou all and thankyou Dan.

nealfg 

I have read the Quercetin combination with Fisetin and I take that as well. But I'm afraid 100mg is no where near enough for humans. I have taken 800mg 1st day, 800mg 2nd and 1000 mg the 3rd. I felt fine and had no side effects. I would not take anything less then 800mg because I have recently read even those doses now seem inadequate. There was one article I read that a man took 3 grams, I believe for 3 days, he was going on and on on how incredible he felt. Though I am just now trying to find the article again to verify everything. 1 to 3 month waiting period in between doses seems to be the norm. I did read once 1 year in between doses but that seems excessive. Good luck.

Greg 

*Correction* not 1 to 3 months in between doses, but 1 to 3 months after the 3 doses.

karl kuffner 

karl kuffner         I find," writing in this forum "  to be a little challenging. , " continuing"   I feel more adventurous,  energetic,  healthier and less body/ joint pain, and am encouraged to continue once weekly lof.senolytic. Therapy.   What subjective changes have you and/or wife noticed that correlate with, " testing 8 yrs younger" wow! That's actually amazing. 

karl kuffner don’t know about effective but taking high doses of fisetin, quercitin or Danasitab on an empty stomach keeps me running to the toilet all day

Paul Beauchemin If you're taking them in oil and on an empty stomach, this can be a cause of diarrhea, as I found out the hard way 🙂 When I took senolytics in milk there were no negative side effects.

albedo 

Dose is of interest: 20mg / kg (of your weight I assume. For 2 days. This is double what I did (600mg/day). 

albedo 

Looking at the previous test #1 in the series (see the link there) the elegibilty requirements and exclusions are of interest. For example, they want you to be off statins and caffeine before and during dosing. And a long list of other things. I did not on my first dosing. Before jumping to the next round of very high dosing (1200 mg/day, 2 days), I want to get my blood tests back from the previous, and study this further. Any comments on the details of these studies as outlined? 

BobM Pretty sure this hasn't been studied so nobody knows. A 5 day water fast is what really kicks in the autophagy - more powerful than fisetin by itself FWIW. 

JGC Just FYI, caps are little (bottom one here). Taking 4 at each meal is not hard. And these are cheap. $16.26/bottle delivered. 😎. 

JGC RevGenetics offers 500 mg "senolytic" capsules which helps reduce the number of caps needed.

karl kuffner 

i bought Regular dose (100 mg) from Lucky Vitamin. Took two 3x/ day. These are branded as Doctors Best. They were out of stock for quite a while. 

karl kuffner confirm my purchase last month from responsible vender on eBay (Philly based) sells bulk only: fisiten and apocynin.  Well packaged, purity tested & extra info. Very helpful, communicative.  

karl kuffner     Try "RevGenetics" or Amazon for 500 mg capsules.   I haven't seen any analysis to verify their purity or actual content.   Wish Consumer Labs would do a test.

karl kuffner I take both. Really can perceive a gain from either. 

BobM 

this should have said “can’t” 

sorry for any confusion!

karl kuffner I am generally a fan of LEF supplements but since the Senolytic Activator is just quercitin plus some theaflavins, you're probably better off buying the quercitin by itself from a cheaper vendor.

nealfg   hello, how did you break up dosing your fisetin daily? Did you have a normal diet during that time? Do you also do a senolytics. LE program, during or before.?     Thanks

karl kuffner 

jumping in here: my recent was 1200mg/day for 2 days. Divided daily into 200mg every 2-3 hours. Some with food, some not. No adverse signs. Extra energy and alertness throughout the day with no afternoon fade, which I usually get. 

How soon are all of you thinking to repeat dosing? I’m thinking one month.... comments??

karl kuffner ........full dose 1 time in the morning on an empty stomach. No change in diet. Only other "senolytic" is 5-day, water only fast, every ~6 weeks.

JGC Ah, but would it change the flavor of a decent wine?

JGC JGC 

I’m definitely changing my delivery method! 

I have now completed 3 “dosings”. Each dosing was 1200 mg/ Day for 3 days. First 2 doses were a week apart. The 3rd a month later. I’m going to do that dosing once/month from here out. My delivery will be with good whiskey, except morning portion which might have to be a good Bloody Mary 👍

Gotta Love us self experimenters...

JPA On quality, both Swanson and Doctor's Best use Bioriginals' branded Novusetin raw material: this is a well-established company with a reliable quality reputation.

JGC 

What are the opinions about taking Fisetin with Grapefruit juice?

Its been known to increase availability of many things.

BobM Alcohol is the opposite of an anti-aging supplement.  I'd cut it back close to zero if you're actually trying to live longer.  There's some data showing that alcohol may have a very mild hormetic effect, but only at very low doses -- on the order of a few drinks a week.

Dan Nave As long as they make it into your intestines, they should work fine.

The alternative is to do what Dave Asprey and Joe Mercola discussed on the Bulletproof podcast, and put them into a suppository.  Which is gross.  But it seems to work.

JGC 

It is not clear how much fisetin is in this product.  They do not rate it or guarantee it. It may be better to buy from Alibaba if you want bulk fisetin.

JGC 

I bought my fisetin from Swansonvitamins.com. It cost $11 to $12 something for 30 100mg capsules. I have been happy with purchases from swanson.

I have never purchased from Alibaba.  I don't really know but I would try to make sure I was purchasing from a reputable manufacturer with a physical presence, and I would also be prepared to lose my payment.  

Staffan Olsson Do you plan to take the circumin with water or dissolve it in oil as some have recommended for fisetin-bioperine?

Staffan Olsson Don It's important to note that curcumin has only been shown to be senolytic in cell culture models: there is no evidence at all that taking it as a supplement kills senescent cells in vivo.

Staffan Olsson 

I decided to add curcumin to my fisetin+quercetin+black pepper dissolved in olive oil for my second trial (one month after the first one).  I decided to add it based on the paper:

https://www.mdpi.com/2077-0383/8/4/433/htm

Curcumin and o-Vanillin Exhibit Evidence of Senolytic Activity in Human IVD Cells In Vitro

o-Vanillin, apparently, is a metabolite of Curcumin.

This combo is kicking my *ss...  It may be because I was just coming off a cold that I caught from my grandson last weekend, but I had major joint pain as well as a piercing pain in my left eye and sinus all night, etc...  Feeling reasonably good at present though, but still feel a bit "off" like I did with the original formulation.  With my original dose I felt a reasonable amount of joint and bone pain mostly about the third and fourth day after starting the dosage. (I took approx. 1 gram of each substance dissolved in oil with 1/4 tsp of freshly ground black pepper, on an empty stomach, for three consecutive days.  The first time the pain was mostly in and around the joints of the knees, femurs, backbone, shoulders and elbows.

Interestingly, this time I only have the joint and bone pain in the knees and lower legs and ankles, particularly the left knee which always had the worst arthritic tendency.

I was really feeling pretty good, very good actually, just before catching the cold, so I think the initial dose had a really beneficial effect on my joints.  I still get around normally, but seem to have arthritic or rheumatic tendencies, and it runs in the family as well.  I'm hoping this protocol will reduce those tendencies, and from the way I was feeling a few weeks after the first dose, I think it has.

Don I plan to dissolve it with oil. Avaocado oil is my first choice. I try to incorporate more avacado oil in my lifestyle (mostly on salads) so it might just as well be used as a dissolvent to. 

https://www.lifeextension.com/Magazine/2015/10/Avocados-Super-Enhanced-Carotenoid-Absorption/Page-01

https://www.ncbi.nlm.nih.gov/pubmed/15735074

Iðunn Thank you for the reminder. We are in uncharterd territory here, but that the territorry where selfexperimentation usually is. 

Staffan Olsson Sure, but you want to be experimenting based on plausible preliminary data 😉. It's one thing to see something like fisetin — which has substantial senolytic effects and low toxicity in mice — and gamble that it may have similar effects in humans; it's quite another to make a similar gamble based on cells in a test tube, with none of the complex metabolism to which curcumin is subject (leading to its extremely low bioavailability). For all we know, something about curcumin or its in vivo metabolites might block the senolytic effects of fisetin — for instance, by competing for access to cellular transporters, altering membrane characteristics necessary for its uptake, or by affecting its metabolism or disposition.

Iðunn if, like its said in this thread, the structure of fisetin and quercetin is very close to each other they might just as well end up competing for transporters.

I see that Dan Nave already have tried the combo with interesting reactions. 

Curcumin in a dose of 400 mg  BCM-95 is a part of my daily program. it has wonderful effects on my body and on my mind. After 15 years of selfexperimentation I think I have  found a few substances that have a robust and excellent effect (Both short term and long term) on me. Curcumin is one of them and that might lead me into a wishful thinking that curcumin not only might be taken with fisetin but that curcumin also might increase the senolytic effect.  

I will use two protocolls. First without curcumin and then with curcumin.  

Dan Nave 

Hi Dan! How are you doing?

Regarding curcumin and its role as anti-ageing agent. Senolytic or not?

I read this article and I like to share it. There are groups promoting curcumin as a senolytic agent. But here curcumin is not seen as a primary senolytic agent but as a geroprotector. Quite a lot of in vivo studies and the salk institute chose curcumin and fisetin as the two most promising natural geroneuroprotectors. 

https://www.researchgate.net/publication/328925429_Geroneuroprotectors_Effective_Geroprotectors_for_the_Brain

https://www.genengnews.com/news/life-extending-alzheimers-disease-candidates-identified-from-diet-supplements/

Curcumin is fascinating. I read  another article and it made me think about the importance of optimum dosing. Under the section "6 conclusion" they illustrate the  importance to find the optimal dose of curcumin. To much curcumin could be detrimental. 

https://www.mdpi.com/1422-0067/20/5/1239/htm

They also write that curcumin, as anti-ageing intervention, might work through AMPK induction. 

"it is possible that positive effects of curcumin supplementation, observed on the organismal level, can be attributed to sirtuin and AMPK induction rather than the inhibition of cellular senescence"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991376/

Bottomline: Is curcumin a senolytic substance?  we don't know. But there is a growing amount of indications that it is a promising anti-ageing agent. 

Best Regards. 

Staffan Olsson Just curious what you guys think about mixing the fisetin with water and swallowing then adding an olive oil chaser.  Do you think this is the same as mixing it beforehand before consuming?

JOHN 

I have tried several ways to administer fisetin. I have mixed fiestin in the same way as they did with rats in the el mayo study, I have used home made rectal suppositories, I have mixed fisetin with oils like olive oil and avocado oil.

So far my subjective experience is that the most important (for me) has been to take fisetin with some piperine or  with some piperlungumine + piperine.

I have also taken fisetin without oil and then the experience has been approximately the same as when I take fisetin with oil.

So the jury is out there. But if you use piperine/black pepper and add some oil. And maybe also add some curcumin, then you are doing it in a way that is in line with my best self experiments.

It is very hard to find out which way is the best way to take fiestin. The most convincing study has been on animals and Intraperitoneal injections. But that I will not do.

Staffan Olsson thank you. I have been taking with olive oil and piperine. I usually would mix them altogether but this last time I drank it mixed with water and did 3 ounce shot of olive oil afterwards. The question is does it absorb differently if it doesn't all hit the stomach mixed together. It may be a stupid question since it is all going to the stomach within seconds of each other. 

JGC this is now available at Alive By Nature - liposomal Fisetin. I just ordered some. The dosing seems a bit low, but the claims is it is 3-4 x (or more) bioavailable.

https://alivebynature.com/product/lsg-fisetin-liposomal-sublingual-gel/

Simone Maher Really interesting - first I had heard of this product. If it works, the extra $ would be worth it. Please let us know your experience! Are you still using a dose of 20 mg/kg?

JGC It's 75 mg per serving, and 60 servings per bottle = 4.5 grams

Jacques Mathieu

I think JC is right. Here is the label:

• 75 mg Fisetin (98% pure) per serving
• 1 serving = 2 pumps = 2 mL
• 60 servings per bottle

I have not actually tried Fisetin yet. I have been doing a lot of research on senolytics and it seemed to me to be a better choice than D+Q due to research, cost, availability etc. My thought is to try this in addition to the powder form to get me to the 20 mg/Kg 2 day dose. There does seem to be a lot of debate over absorption and dosage. See this link ( https://alivebynature.com/forums/viewtopic.php?f=45&t=1881)

It's not that $ to use both the achieve the total, and I like that this form may be better absorbed. I plan to do this twice a year, in addition to using FOXO4-DRI peptide and anything else I can read up on/try.

My only experience thus far with senolytics is with Life Exension Senolytic Activator. Can't say I have felt any difference there, but I understand some changes happen slowly over time and there probably won't be a blockbuster effect. I am 44, and really only got into health as a way of solving my horrible insomnia. I am thinking of this as  preventative strategy to be used over time vs. trying to solve some current ailment.

Thanks to everyone for sharing your methods and sources, I'm definitely going to try the powder with the olive oil. Would never have thought of that had I not read it here!

Simone Maher 

Argh! Math/measurements is not my strong suit. Now, re looking at it I think you are right Jacques Mathieu . It does say 75 mg per serving, not 75 mg in the whole bottle.  Whew! :)

Simone Maher Jacques Mathieu That 4x bioavailability is totally unverified: they haven't actually done any testing on their product, but are pulling numbers from studies of other polyphenols, B12, and injected fisetin in rats using a different liposomal formulation.

Even at 75 mg x 60 servings, and even if we take their word for 4x bioavailability, it's still not a good deal: 60 servings at 75 mg with 4x bioavailability would be ostensibly similar to 60 servings at 300 mg powdered fisetin, or 30 servings at 600 mg, or 6 bottles of 30 x 100 mg capsules. And you can certainly do better than just suspending fisetin in water, which would close the gap on any (unproven) bioavailability advantage of their liposomal product.

Jacques Mathieu   Any way you look at it,  Fisetin is expensive because it takes a lot to make a senolytic dose and according to estimates, something like 95% is wasted by not being absorbed.   It's been suggested that taking lecithin concurrently with fisetin should increase the absorption.   Lecithin is an emulsifier which may help make fisetin more soluble.  

   As I understand it,  Fisetin does not attack cells of any kind,  it simply removes the covering or "camouflage" coating that hides senescent cells from macrophages and prevents them from being removed by normal autophagy.  Since the active time period for fisetin in the bloodstream is short and our immune systems become sluggish as we age, it seems logical to ingest a large dose of Echinacea to stimulate our immune system about a day in advance of starting a course of Fisetin + lecithin.   Reports indicate that stimulating the immune system causes it to produce more, new macrophages (or microphages in the brain) which should increase the probability of senescent cells being removed during the brief period while they're exposed.  

RAW Robert and all of you who are following this link, the following is a preliminary report on my first experience with fisetin. It was remarkable.

As background, I am a 79 year old male who has been a LEF member for the past 20  plus years after bypass surgery in 1994. I had been reading about fisetin benefits for the past year on this site and others. There was a reference to the Forever Healthy Risk Benefit aanalysis on this site and I reviewed the Risk Benefit and decided to give it a try.

 On June 6 and 7, 2020 I ingested 1.5 gram of Swanson's Fisetin ( 15, 100 mg capsules) each day on an empty stomach and did not eat for 4 hours afterword. Total cost was $10.79 for a bottle of 30, 100 mg capsules. The dosage is what Mayo Clinic  is using  in its phase 2 trials, and amounted to approximately 20mg/kg. 

The day after the second dosage, my vision in terms of color enhancement  improved significantly in that all colors became more vivid. It has remained so to this day. I realize that this is an observation and do not have any quantifiable measures, but it happened.  

I am also of the opinion that my turkey neck diminished somewhat,  but I am not positive about this observation.

However, there is no doubt that fisetin improved my strength/endurance. I have a regular exercise routine that includes chin ups and pull ups on a doorway chin up bar. I can typically do 20-21 chin ups and ~ 22 pull ups. ( As a side point my son says that I cheat.) Right after my first treatment my chin ups increased to 26 and my pull ups increased to 28.  The cheating , if any, was consistent before and after and reflects the actual fisetin effect. This increase  has remained to this day.

I repeated the doses on June 20 and June 21 and will again repeat the dose tomorrow July 4 and again on July 5. I will than go to the monthly dosage and do a chemistry profile, CBC and lipid profile in Sept. If everything looks OK  I plan to continue until Nov. when I expect to do more extensive blood work. 

Peter H. Howe   It might be prudent to remind everyone that there are 4 different types of senescent cells and each one requires a different treatment.  Fisetin treats 1 type.  Dr. Green recommends that Fisetin be taken with Dasatinib at the same time.  Some type of senergenic effect together.  Also,  Rapamycin inhibits the formation of senescent cells, but does not stop it or clear them out.  Here is Dr. Green's website which lays everything out in detail.  All backed and supported by clinical trials.  He is pathologist with many years of experience treating patients.    I personally take Fisetin and Dasatinib powder.    https://senolyticstreatment.com/

Van  Thanks Van. I am very much aware of Dr. Greens site ( have it book marked) and the fact that a large number of people have spoken well about his treatments on this site.  I do not wish to use Dasatinib as it is my "understanding" that Dr. Kirkland does not recommend it "at this time". I did not see his specific statement to that effect, however. The Forever Healthy risk assessment was also somewhat  negative in that it documented some adverse effects on patients being treated for cancer.

I personally do not agree with some of Dr. Greens other recommendations. I tried metformin several years ago, and it significantly reduced my testosterone. You can verify this side effect with a simple google.Testosterone is critical for senior men in preventing dementia, osteoporosis and sarcopenia.  I am also aware that it is probably responsible for thymus involution which is another problem, and that neutered males seem to live longer.  I am also skeptical of antibiotics as I have been trying to protect my microbiome.

I suspect that there may be more to fisetin than just its senolytic effects as many other systems were documented to benefit from fisetin in the Forever Healthy risk assessment. The effects I reported were immediate and started the day after my second dose and continue to this day. They were phenomenal which is why I decided to report it. 

Lets see what happens. 

Van you are correct. I just had a 5 hour consultation with dr green. He takes both at the same time and recommended doing a senolytic dose of each separately first to make sure you can tolerate the side effects before taking them together. He also prescribed my wife to take a zpak plus doxy, plus vitamin c for a week straight 4 times a year(so every 3 month). I wasn't prescribed this regimen because he felt she was at higher risk of cancer since she grew up next to a radioactive waste dump(he referred to it as Chernobyl but it was cold water creek in Missouri). He is a brilliant man, finished medical school at 24 and has a law degree as well. He shared some pretty cool articles with me as well. Great doctor and is in this for the benefit of human kind not just his own self interest. 

Peter H. Howe . It's true metformin can lower test. I take 100mg injected once a week of test and I'm constantly around 500 for my total test readings and that is with the metformin. The benefits are too good to pass on. If you must not take test try Berberine. Dr green thought this was just as good. 

@JOHN  Thanks  John.

 I  am hypogonadal and have always been. Use  androderm 4 mg patch, applied daily.  Metformin reduces my total t with patch from 500 to ~200. Calorie restriction does the same. I consider HRT an important part of my antiaging program.This includes DHEA and, believe it or not, making sure estradiol is in right range.

I am reluctant at this time to try dasatinib due to possible health effects. Am following those on this site who are doing what you are doing.  Will wait for Mayo to say it is OK.

If you start your program with high dose fisetin, please let us know your initial experience. Mine was fantastic in term of enhancing my color vision, strength and endurance.It was immediate and I don't think it was due to senescent cell removal.

Others have made similar positive comments about Dr. Green, and I don't mean to demean him. 

Peter H. Howe my wife and I had our two year follow up last week. Dr. Green will not prescribe metformin unless you have signs of metabolic syndrome, which I assume few of his patients have. 

Larry Thanks Larry. I had seen that position stated by others, but his web site has it towards the bottom without any caveats.

Iðunn  If your argument is that other powder forms are cheaper, then  yes, you are correct.  The cost for the liposmal for is $75. Convenient liposomal form where I don't have to mess with mixing things. I would need two bottle of Dr. Best to get to my dosage ($32)

Assuming 1 x bioavailbility = 4.5 grams. This is enough for me for the two day treament (I only weigh 100 lbs)

However - Assuming any multiple of bioavailability even just 2 = 9 grams effect that will get me through two treatments.

I think it would be very doubtful that the liposomal form doesn't increase bioavailability, that is the entire point of making an liposomal formultion (and what people are doing here with olive oil.

Personally, I prefer not to buy supplements from companies I am not familiar with or over Amazon. I trust this company (Alive by Nature) and so am willing to pay a preium for that. Also, not eager to take apart a bunch of pills and mix with olive oil.

I'm just going to experiment (today!) and see how it goes. I'm going to start with using the whole bottle over two days. Hopefully feel some difference (I'm 44 - anyone else around that age try this?) Can vary the dose a month later and compare...

Peter H. Howe I understand.  I didn't think you said anything negative about Dr. Green.  When he sees a patient he does many blood tests and takes your complete medical history to devise a plan. My wife has a different plan than I do because of some differences.  We don't take the same drugs or the same doses.

I wonder if raising your test dose would be beneficial?  Possibly 200mg injected weekly. Test does activate mtor1 so too much wouldn't be beneficial. They have done studies that show men who have higher estradiol levels do tend to live longer, and test turns into estradiol. 

I started doing senolytic doses with fisetin 12 months ago, before seeing Dr. Green. It worked great for me. I live on top of a hill with a very steep driveway. My 25 year old daughter who is a pilate instructor huffs and puffs more than I do when we walk to the top. I used to huff and puff more.  So I noticed a difference in endurance. I believe it has benefited my immune system too. I haven't been sick at all and the 2 times I started to come down with something my body fought it off. Twice where I  felt extremely tired and was running a fever of 102 degrees. This started around 2pm and I swallowed an additional 2 fisetin tablets and another zinc pill around 6pm. I went to bed at midnight still feeling very sick and with the fever. I woke up the next day with absolutely no symptoms and not sick at all. Could be a coincidence but I don't think so. Since taking Metformin and Fisetin I have noticed a big difference. Now I am on Rapa so we will see what I notice next. I can't imagine feeling any better. I would guess the feeling will just stay this way and my arthritis will probably improve. 

Simone Maher There goes my math again..

I accidentally multiplied pounds by 2.2 instead of divining to get kg. So, actually that bottle just doubled in size for me! So I only need around 900 mg per day for the two day dose.

JOHN Thank you for your kind and informative message.  I believe my My lower T levels were due to a 5:2 diet that I had been on for the past 2.5 years. The literature indicates that calorie restriction ( as well as Metformin) lowers T. I also experienced other side effects from the diet,  and I stopped the diet in mid June. I am 79 and "some" of the literature suggest that calorie restriction may not be beneficial for some seniors. I suspect that there is a negative feed back  on testosterone when AMPK is increased. 

I experienced some of the positive feedback from my first mega dose ( !.5 grams on two consecutive days) of fisetin that you also noticed. In fact I have never seen such a quick positive response from any supplement. I believe that it was due more than just its senolytic effects. 

I am concerned with possible dementia and depressed immunity as I grow older. The literature indicates that fisetin is beneficial for treatment/prevention  of both as well as as a number of other age related problems.

I will continue with my current T and fisetin treatments until mid Sept and than will do some bloodwork . Will let you know if you are interested. I do extensive bloodwork through LEF twice per year. Can't get my physicians to order what I think I need as medicare will not pay for it. I also have BC/BS and have found that Lab Corp costs with LEF are  not much different that than with insurance after co-pay.  

Take care. 

Peter H. Howe Thanks for the response Peter. I am at an increased risk of Alzheimer's myself. My father just died from it, and his sister and mother died from it. Dr Green has instructed me to get a genetic test for the APOE4 gene.  23 and me does it for around $200 but the Alzheimer's Association does it for $125. Here is the link

https://www.alzheimersorganization.org/alzheimers-test

I'm not sure if he will change my protocol if I test positive. I know my chances are 50/50 if I test positive. 

My wife and I did 5 different blood tests each before seeing Dr. Green. These were not covered but very affordable. We each paid $165 for all 5 tests. The link is below if you are interested.

https://www.health-tests-direct.com/

If you have not already considered it I would suggest getting on Rapa. That is the number 1 drug for aging health. In order of importance Dr Green said it was absolutely a miracle drug and the next big drug after antibiotics for mankind. He placed Metformin second and Fisetin third. 

the only thing I would guess Dr. Green does different for me is prescribe a higher dose of rapa if I test positive. I take 6mg now. He takes about 10mg himself. I even started my 14 year old cat on Rapa at .5 mg twice weekly!

JOHN First, note that 23andMe's test will include several hundreds of thousands of other gene variants that could be useful to have info on.

Secondly, do you know whether Dr. Green ups the rapamycin dosage for APOE-ε4/ε3s, or only APOE-ε4/ε4s? Note that the mouse studies compared transgenic 3/3s to 4/4s.

Thanks,

Brian

BrianMDelaney He didn't specify what his next steps would be. I will know more after the test. 

JOHN   Thanks John for your suggestion. My mother and one of her sisters died due to alzheimers. I have at least one younger cousin who has it.  I already had myself tested and am homozygous APOE3-- but I can still get it. 

I am following a Dr, Bredesen protocol which supposedly eliminates the risk and has been established to reverse Alzheimers and other neurological diseases. See attached.

http://www.aging-us.com/article/NjJf3fWGKw4e99CyC/text

He has also authored d a book entitled  " The End of Alzheimer's". His approach consists of three protocols. #1 is no sweets and a 12 hour period in which you do not eat - from at least 6 pm to 6 am- gives your microglia time to get rid of B amyloid and tau. His second approach, based on bloodwork, is to replace deficiencies, one of which are your steroid hormones.  The third is to test for toxics- such as metals and pestcides. Of critical importance in #2 is fish oil. 

I agree with your comment on rapamyacin and am considering it. I am constantly modifying my lifestyle, but do not want to over do it. I just finished 2.5 years of intermittent fasting based on positive results documented in a  number of peer reviewed papers. I stopped in June due to what I consider to be adverse impacts. One of the benefits to fasting is a decrease in mTOR . Without going into detail, there are some reports that fasting at a late age may not be beneficial for some. I backed off and will do bloodwork in Sept. to see if things return to normal. I "think" fasting may have adversely affected my immune system in addition to my steroid levels which I mentioned earlier. The literature indicates that this is possible.

This brings me to fisetin. It  also reduces mTOR along with a myriad of other benefits. Since our last communication, I finished my third treatment on Sunday, July 5 which consists of 1.5 grams/day for two consecutive days. I take the 15, 100 mg  Swanson capsules first thing in the morning on empty stomach and do not eat for 4 hours . The results yesterday were amazing. I did 28 chinups yesterday. Prior to starting the fisetin, , I could only do 20-21. This increased to 26 after my first treatment but is now at 28. 

Before proceeding to Rapamyasin, I will let what I am currently doing run its course, but thanks for the suggestion.

I am of the opinion that fisetin may be as beneficial as fish oil in preventing age related problems. I am a fervent believer in fish oil as it also has multiple benefits documented in over 7,000 papers.  LEF is publishing an update on fish oil in its August, 2020 magazine.

Thanks again for your suggestions. 

Dan Nave I have decided to not add curcumin to the Quercetin/Fisetin senolytic protocol.    I no longer recommend adding curcumin to the mix.

My feeling is to take Curcumin separately, if you wish, but not to add to the Q+F protocol.  Perhaps make a separate protocol with Curcumin.

I have seen several reference to Curcumin and Fisetin having counteracting effects to each other, but am not able to find any literature that clears that up in my mind.

Also, I felt really good after the Q+F, lasting for a long time, while the Q+F+C was much harsher and I didn't notice as much change for the better after taking it.

Dan Nave Hi Dave!

I am doing this step by step. 

First, I took senility activator double dose on two consecutive days. I felt good during those two days and I also felt good a few days after.

After two weeks I tried a double dose of senolytic activator again and then I also added more quercetin. That made me feel even better during the two days as well as during a few days after. 
 

Then after a few weeks I tried double dose senolytic activator with extra quercetin and I also added tocotrienols and curcumin and mixed it all in avocado oil, Then I added crushed piper longum fruits which was soaked in alcohol (piper longum has piperine as well as piperlongumines). That coktail  made feel unwell.

I don’t know if feeling unwell was good or bad. Proof of strong reaction? Or maybe I did somehting to which my body answered ”this is to much”?

Now I am aiming for fisetin experiments.

As I have read in the now famous paper, They used both chronic feeding with Fisetin as well as intermeittent and acute short term use of larger doses of Fisetin. All experiments produced positive antiaging results.

Later on I will add Fisetin to my daily supplements. But now I go for the larger senolytic doses. 

Staffan Olsson 

Hi Staffan, can you kindly share your previous dosing of each item (F, C, SA) , and your body weight?

BobM 

sorry F+ Q + C and the piperine

BobM 

Hi Bob! My body weight is 77-78 kg. 

 I have gradually incresed the dosing and along the way I have added more substances. (curcumin, tocotrienols and piperlongum)

During my most recent senolytic experiment I used:

- Double dose of senolytic activator.  That is 4 capsules. That should equal up to 2500 mg regular Quercetin. 

- 3 capsules of Quercetin. The Quercetin I use is Life extension. Bio quercetin. (the same quercetin that's in the senolytic activator). That should equal up to 1500 mg regular quercetin. 

https://www.lifeextension.com/Vitamins-Supplements/item02302/Bio-Quercetin

- 1 capsule of Life extensions Super Bio-Curcumin® Turmeric Extract. (BCM-95®)

- https://www.lifeextension.com/Vitamins-Supplements/item00407/Super-Bio-Curcumin-Turmeric-Extract

- Piperine. I have no exact dosing for the piperine. This since I used three crushed piper longum fruits which was soaked in alcohol after they were crushed.  

The best experiement so far was double dose senolytic activator + 3 capsules of Bio-quercetin. 

For my next experiment I will not use piperlongum and I will not use tocotrienols.  

 I have not yet started with Fisetin. I want to go through the selfexperimentation with the other substances first. 

Staffan Olsson 

Hi Staffan

Thank you so much for sharing all the details!

Excellent data!

Dan Nave 

So far I have learned that I get a rather strong feel good effect from senolytic activator. Especially when I take it with extra quercetin. An effect that lasts 2-3 days.

I also tend to get a minor feel good effect of a senolytic dose of fisetin. But that effect (if it’s not placebo) is definitely smaller that the effect I get from quercetin.

- Last weekend I took my first senolytic dose of Fisetin disolved in a 60% Phosalmix 50 PG, 30% PEG400. I took the same dose of fisetin on two consecutive days. I stayed at the dose used by the El Mayo researchers in their ongoing human trial, 20 mg Fisetin per kg. I was very inclined to use 35 mg/kg the second day but I  decided to stay at 20mg/kg.

Any acute feel good effect is, of course, not a sign of a working senolytic therapy. But it is a pleasant surprise. There are plenty of harmful substances that produce acute feel good effects (Refined sugar is one out of many).

So it’s wrong of me to assume a strong correlation between acute feel good effects and improved long term health. Feel good effcts are very wellcome, at least when they arise from improved health or reduced disease or inhibited ageing.

I tend to experience some negative effects when I combine fisetin, curcumin, quercetin, and tocotrienols. Even if the dose for each substance is lower than what should be used in a serious senolytic approach. And even if they are taken without piperine containing compounds.

At this stage I can only guess which substance that cause the unpleasant experience  My first wild guess is that it might be some interaction between the tocotrienols some of the other substances. This since curcumin and quercetin, when taken alone or when they are taken together give me a feel good effect.

I also have in mind that the unpleasant feeling and the reduced wellbeing that I experience from to above mentioned combination might be a pure coincidence and is not an effect of any of the substances.

Staffan Olsson 

BobM 

Great post. Thanks!

JGC that is a reasonable theory.  For now my reasoning is that high doses of quercetin reduces whole body inflammation or reduce organspecific inflammation. And might have minor senolytic effects on some tissues. My brother has morbus bechterew and since 2 years he has a very bad case of sarcoidosis in his lungs. He responds in a favourable way to high doses of quercetin. Especially when I give him senolytic activator + quercetin. A few years ago quercetin got some attention when they did some sarcoidosis research (in England I think). Only 500 mg per day. 

When my brother take large doses of quercetin he reports an immidiate and dramatic reduction in symtoms from his sarcoidosis. Now he has done three sessions and during every session he reports the same immidate and dramatic effect. I know that they have tried D+Q on idiopatisk fibrosis of the lungs. And for the first time  the results showed that it was possible to increase of the functional capacity among the researched subjects (humans). Since qualified researchers in the field of senolytic therapy chose to specifically target a lungdisease as their first human deasease it might indicate that Q theoretically has a favourable organspecific effects on lungtissue. 

Bottomline is that I think these observations is in line with what we know about Quercetin. That Q has minor senolytic effects but that Q Also has know antiinflammatory effects. And if my brother continue to report dramatic effects then I create a sarcoidosis thread here. this since he reports dramatic effects exceeding any medication. 

JGC No, I have not taken CRP test before the senolytic experiments. 

karl kuffner I used avocado oil. When I take senolytic doses of fisetin I will use the same mix as in the original research. " 100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol". Now I have recieved the substances. (From amazon). When it comes to creating a formula that increase the bioavailability of fisetin, the researchers doing the research must be  more competent than myself.

Dan Nave 

I am also a bit reluctant to use PG, PEG. But will go for it when I start my fisetin experiment. 

By the way I want to inform you about a research I read the other day. If you take Quercetin It might be a good idea to not drinkgreen tea before, during and after a senolytic session. 

When Quercetin is co-administrated with Green tea polyphenols it increase the tissue absorption of Green tea polyphenols in some tissues. Lung and kidney.

(But I have read somewhere else that Prostate tissues might have the same tendencies, that Q increase the absorption of Green tea polyphenols).

https://europepmc.org/articles/pmc3590855

"We observed a 2 to 3-fold increase of total and non-methylated EGCG in lung and kidney and a trend to increase in liver. In summary, combining quercetin with GT (Green Tea) provides a promising approach to enhance the chemo prevention of GT.

Responses of different cancers to the combination may vary by tissue depending on the intrinsic COMT and MRP activity."

"When mice were treated with quercetin alone, about 95 percent of quercetin was found in methylated form (isorhamnetin) in lung, kidney and liver tissues (Figure 5B). The combination of quercetin with GT decreased the tissue concentrations of total quercetin by 20-50% along with a decrease in isorhamnetin ratio to quercetin by 90%, 81% and 61% in lung, kidney and liver, respectively "

This indicate that when you are aiming for senolytic effects, it is reasonable to be careful with ingesting Green Tea. It looks like it takes large doses to achieve a Senolytic effects and Green tea might hold back the maximal tissue concentrations of Quercetin in some tissues. 

Dan Nave

I have to correct myself. The study that I had in mind before is not about tissue concentrations. It is about synergies, it's about how quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cells.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933702/

"Our data indicate that human prostate cancer cell lines contain a small population of CD44+CD133+ cancer stem cells and their self-renewal capacity is inhibited by EGCG. Furthermore, EGCG inhibits the self-renewal capacity of CD44+α2β1+CD133+ CSCs isolated from human primary prostate tumors, as measured by spheroid formation in suspension. EGCG induces apoptosis by activating capase-3/7 and inhibiting the expression of Bcl-2, survivin and XIAP in CSCs. Furthermore, EGCG inhibits epithelial-mesenchymal transition by inhibiting the expression of vimentin, slug, snail and nuclear β-catenin, and the activity of LEF-1/TCF responsive reporter, and also retards CSC's migration and invasion, suggesting the blockade of signaling involved in early metastasis. Interestingly, quercetin synergizes with EGCG in inhibiting the self-renewal properties of prostate CSCs, inducing apoptosis, and blocking CSC's migration and invasion. These data suggest that EGCG either alone or in combination with quercetin can eliminate cancer stem cell-characteristics."

Staffan Olsson 

This article (Linked) is very interesting. It was published in 2010. Darn it takes a long time for good data to get to the public! 

It is a tough read for non-medical folks like me. 

Has anyone figured out dosing suggested from this? 

BobM Yes this kind of articles are tough reads, Indeed very tough. 

regarding human dosing of EGCG and cancerprevention/treatment I have found this article.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824026/

"When the amount of EGCG necessary for the complete elimination of tumors in mice is converted to that for humans, it would be 6 – 9 Japanese-size-cups of green tea, i.e., 1.37 – 2.05 g EGCG/day/person." (2 g EGCG is a lot and might not be tolerated well)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384709/

"The 10-year prospective cohort study by Drs. K. Nakachi and K. Imai revealed that drinking 10 Japanese-size cups (120 mL/cup) of green tea per day delayed cancer onset in humans by 7.3 years among females and by 3.2 years among males. "

At least 1.2 liters of green tea. But keep in mind that different green tea has different amount of EGCG. So it's difficult to give specific recommendations. 

When it comes to EGCG and green tea extracts there is an issue with absorbtion.

To increase absorption of EGCG the recommendation is to drink green tea (or take supplements) on empty stomach and to have your tea with some vitamin C. Piperine, quercetin is also promoting absorption of EGCG. Most important is to avoid have green tea after a meal. At least if you want maximal absorption of EGCG. 

yes its difficult to understand and to draw conclusions from the plentyful in vitro research that is done on green tea and EGCG.

Thats why I rather trust the research made on green tea that humans actually drink. Like the 10 year prospective study mentioned above. I am not a big fan of pure EGCG supplements. Green tea is more than EGCG, For instance there is an indication that the small amount of coffein in green tea increase the absorbtion of EGCG and that the other substances in Green tea make EGCG more effective in preventing disease.  

A guess made by using the  above reasoning could be to drink 1.2 liter of green tea  on empty stomach and before meals + quercetin + c-vitamin and maybe with piperine or black pepper. (One way to reach therapeutic level in vivo in the human body could be to take a dose of green tea extracts together with the real tea )

Staffan Olsson 

very good!

thank you!

BobM  I like to give this link to you. it explains the issues surrounding green tea research. And it explains why I put more value on forwardlooking research done by tracking real people over time, drinking real tea. That reasearch indicates meaningful benefits from drinking real tea (and coffee)

https://www.nature.com/articles/d41586-019-00397-2

EGCG supplements taken on their own is more questionable. Green tea looks great for creating synergies with other substances. One example of this is the Pomi-T study. "A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer" 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020278/

A small amount of polyphenol rich whole food showed great benefit. Green tea was a part of the polyphenol-cocktail. 

The subject in this thread is fisetin. I am sorry if I fell out of line. 

Staffan Olsson 

excellent!

thank you Staffan!

BobM 

Hi!

Since I have written a bit about green tea extracts poor availability I would like to share this link to Life extensions new product.

Claiming to be 10 – 12 times mora bioavailable than regular green tea extract and has 125 mg of green tea extract.

https://www.lifeextension.com/vitamins-supplements/item02305/green-t-max

The substance is called Origene 8 Liposome and is produced by coyne healthcare.

https://coyne-healthcare.com/origine8-green-tea-extract/

 https://origine8.com/quality-science/

They claim that 125 gr extract is equal to 10-12 cups of tea. (And 250 gr origene 8 extract equals 20-24 cups of green tea).

But then again it is unspecific to talk about “cups” of tea. Serious researchers should talk about specific volumes measured in liters. A cup is sometimes referred to as 125 ml and other refer a cup of tea to  250 ml.

When it comes to EGCG content in green tea I read in that it can vary from 50 mg/cup to 125 mg/100 ml. And sometimes I see other figures as well. One statement I have seen is that a cup of tea contains a total amount of 150 – 300 mg catechins. The discussion needs to be more specific.

The bottom line is that a highly bioavailable green tea extract is very welcome. What we have to find out is if one capsule of life extensions new product is equal to the catechins in approx 1 liter of Japanese green tea.  Because that is the amount of green tea that seems to be required to receive the hoped for benefits.

And hopefully this extract is easier for the liver to handle than other extracts.

Staffan Olsson Staffan Olsson 

Staffan Olsson 

Hi Staffan

ive been taking the new Like Extensions green tea supplement for a couple months now. I like it. One (or two tabs) a day. They are very small tabs, which is very welcome. And green tea colored ( most of what I see in supplements are brown).

Staffan Olsson 

just FYI all: Life Extension has quietly withdrawn its Green T-Max product. It’s now showing “Mega Green Tea Extract”. Nothing special. 725mg of 98% polyphenols, 45% EGCG.

karl kuffner Karl, The clinical trial that is directed by James Kirkland at the Mayo Clinic uses 20 mg/kg on two consecutive days. That brings us to 2000 mg for a 100 kg person. that is four 5 mg capsules per day. 

https://clinicaltrials.gov/ct2/show/NCT03675724

(Alleviation by fisetin of frailty, inflammation and related messures in order Adults).

Since we are at the beginning of fisetin human trials nobody can be sure what the optimum human dose is. My own speculation is that an optimum dose is above 20 mg/kg. In my next experiment I will increase my dose to 30 - 35 mg/kg. 

How much fisetin that is actually absorbed is a crucial question. And I am very curious about how they handle the issues with absorption in the above mentioned human study. If we, in this forum, could get that information it would be of great help. 

Since we, in this forum, use different approachens when it comes to the issue of absorption it is a hard for us to be very specific when we discuss optimum doses. What we can do is to be transparent about what we do to handle the absorption issue. 

May I ask where you got the 500 mg capsules from? I have used 100 mg capsules and 500 mg capsules would be easier to work with.

karl kuffner  Sir, thankyou for clarification on fisetin usage.   This mayo clinic study appears to be only for 2 days total, and there posted results seem to be " only" reduction in inflammation markers. How does that relate to "frailty syndrome"?   With your knowledge and experience, would you do this treatment protocol, monthly?   What would you sum up are the most definitive benefits of your self experimentation.?  THANKYOU      karl

karl kuffner 

The dosing regimen regarding fisetin is in its infancy. There have been research done using fisetin on two consecetuive days. And then the same treatment was repeated again after 4 weeks. 

There has been senolytic research done with dasatinib och quercetin with doses taken three days consecutively then 4 days without treatment. and then another three days treatment followed by 4 day without treatment. And then they had another three days of treatment. The same substances have also been used on a biannual protocoll. 

As far as I can read from the fisetin mouse study they showed a senolytic effect also from chronic feeding with a lower dose and not only from the intermittent treatment. 

I am not a person to give recommendations based my fisetin experiments. I have recently started with fisetin. But I decided to start with a intermittent protocoll.

Senescent cells are a driver of pathologies. Senescent cells ellicit an inflammatory respons and if a senolytic experiment reduce inflammation then that can be sen as an indication of a sucessful experiment.  

John Whitling 

Thank you for your report. Based on your experience 3*700 mg is needed to get benefits. That is a useful information. I think insufficient dosing (or wrong dosing) is that factor that make quite a few products fail to help people. Nowadays I use green tea max. it is supposed to be more bioavailable and to remain longer in the body.

https://www.lifeextension.com/Vitamins-Supplements/item02305/Green-T-Max

After reading quite a few scientific reports I have found out that we might have to drink at least 1 – 1.5 liter of green tea to be sure to get its preventive and disease delaying effect (at least when it comes to the onset of many cancers).

When it comes to EGCG and dementia and other diseases of the brain there are interesting reports from japan when EGCG is used together with ferulic acid. Promising results on dementia.

https://www.sciencedaily.com/releases/2019/03/190306133414.htm

we have a section on this forum that is dedicated to Green tea extracts.

https://forum.age-reversal.net/t/m2cwax/green-tea-and-green-tea-extracts

If you like to share more information from your experience and knowledge of EGCG the above mentions forum might be a good place for future posts. Thank you for your information about the dose that is needed to achieve benefits in a AD affected brain

Staffan Olsson Thank you for the lead on ferulic acid. I will look into that. Also the forum links are quite helpful as well. Given it's effect on aging I am a little surprised that you do not have an APOE forum. I couldn't find one anyway and the site doesn't have a search tool that I could find. APOE status effects cardio as well as neuro health .. it creates advanced aging in it's APOE4 status and it changes the way that cells create and process energy. APOE2 actually extends life.

Just to be clear the dosing of 3x700 mg EGCG is just what works in our instance, and it's not just about AD, it's really about any chronic brain inflammation. Brain inflammation is common in head traumas, bacterial infections, etc. I believe that it is the the primary cause of the spike in medical workers suicides, though that is only speculation on my part. More and more, research shows that real physical depression is also due to brain inflammation as well.

When you consider how often medical workers are around infections and bacteria is reasonable to theorize that they could be picking up the same kinds of things their patients often have.

One other thing .. we found Green Tea Max to be pretty useless, perhaps because of dose, but it seems that more likely that it's missing some critical poly phenol or something. Within a few days it was evident that it didn't measure up so we bailed on it then. I have a few bottles sitting around.

In a similar vein LEF makes a product called Cytokine Suppress. We tried that for bed time hours but the performance was the same and the half life seemed equivalent. I was hoping for a longer half life but no luck. It's much pricier than than Mega Green Tea Extract.

Thanks again!

John Whitling 

Thank you for your respons. When it comes to brain inflammation. I remember being at a stroke conference some 10 years ago. At that time they had brain inflammation after stroke as one of the subjects. (Depression is common after stroke). And one of the doctors proposed that brain inflammation also should be targeted in other forms of depression than just poststroke depressions.  I have not really followed up on that lead. But it is always great to remember persons who are decades ahead of the mainstream folks. "I hope we have quite a few in this forum".

And Systemic inflammation as well as brain protection are two of my targets when it comes to anti aging. (Targeted with Omega 3, curcumin, Senolytic treatments and more).

It is interesting to hear about your experience of green tea max. Liposomes have a much greater availability then standard green tea. But it might not be metabolized in ways that makes it equivalent to regular green tea. Sometimes it is the metabolites of a substance that are responsible for the major effects that we can get from a substance.  

BTW, when it comes to Ferulic acid and EGCG they used quite small doses. Good luck with your research.

John Whitling Maybe you should try a Senolytic on your friend. Dasatinib and Quercitin are cheap and with the latest study shown to be safe in humans. Look at this study: 

Scientists at the University of Texas have implicated a type of cellular stress for the first time as a player in Alzheimer's disease. And their discovery could lead to treatments for more than 20 human brain diseases including Alzheimer's and traumatic brain injury. One author of the study went as far as to say the treatment that researchers used on mice to rid them of the stressed cells actually stopped Alzheimer's disease "in its tracks."

After three months of treatment, UT Health said their findings were “exciting.” Orr said in a statement that the Alzheimer’s mice were 20 months old and had advanced brain disease when researchers started the therapy. “After clearing the senescent cells, we saw improvements in brain structure and function. This was observed on brain MRI studies (magnetic resonance imaging) and postmortem histology studies of cell structure. The treatment seems to have stopped the disease in its tracks,” she said.

Senolytic drugs only target and only kill senescent cells. They are cleared quickly by the body, and researchers saw no side effects.

Mice were treated with a drug combination including Dasatinib every other week. "So in the three months of treatment, they only received the drug six times," Orr said. "The drug goes in, does its job and is cleared. Senescent cells come back with time, but we expect that it would be possible to take the drug again and be cleared out again. That's a huge benefit -- it wouldn't be a drug that people would have to take every day."

Musi said he anticipates many further studies to understand the process using senolytic drugs. “Because these drugs are approved for other uses in humans, we think a logical next step would be to start pilot studies in people,” he said.

https://www.forbes.com/sites/robinseatonjefferson/2018/09/24/senolytic-therapies-seem-to-stop-alzheimers-disease-in-its-tracks/#1a871c8c1c1b

Larry D&Q appears to be safe and effective in humans (small study but larger studies are ongoing) 

https://www.fightaging.org/archives/2019/09/senolytic-treatment-with-dasatinib-and-quercetin-confirmed-to-reduce-the-burden-of-senescent-cells-in-human-patients/

Larry That is my plan. That's why I've been lurking on this post for a few months. As for D being cheap and available, I am clueless about that. I saw the write up where you could get D without a prescription but only in FL and only to FL residents. Before my readings here on this post I was not aware that it was high acute dosing.

Where can I get D. I am in Ohio, BTW, if it matters. I understand that the dose is small in comparison to Q .. maybe a 10 to 1 ratio.

John Whitling John Whitling I got mine here: https://www.dropshipmd.com/

I had quick and impressive results so I am confidant it is real. I also used them for Rapamycin. Use Western Union.

Larry Thanks!

Larry FYI, they say that cannot ship generic dasatinib to the USA. They mentioned sprycel ( a generic version) but said they were out of stock on that too.

John Whitling They must have got pushback from the USA. You can try this Doctor. He started a new practice called Qalytude. I'm not sure if he is writing prescriptions now but he says he will in the future. https://www.youtube.com/watch?v=pRhOYL_n9lk

For those interested in dosing of chlorogenic acid. They studied the metabolism of chlorogenic acid by giving 2000 mg to the participants. So that (2000 mg) is defintely a tolerable dose. if (and a big IF) chlorogenic acid t can be used as senolytic the dose would probably be much higher. 

Ajax would you mind sharing your bodyweight.  Would like to know the mg/kg.  Thanks!

Ajax I'm one of those who had no reaction from fisetin and great results form D&Q. I will try your protocol, thanks. 

Mel Always a question people enjoy answering. 😉 I'm 110kg.

Ajax How old is your aged mother?  My mother is 93 and cannot walk anymore.  My father has Alzheimers and is 88. I have asked their Dr if I can give them Fisetin becuase they live in an assisted living home and I cannot just hand them pills.  The Dr. said there was no indication for giving them Fisetin.  I may fight it.  But I'm really interested in how your mom fared and how old she is , etc etc....

JOHN My mother is in her early 80s. 

It's hard for me to pinpoint any beneficial effects specifically to fisetin (aside from the disappearance of the scar and skin tags) because we've also been taking NR.

That said, she reports a great improvement in her gluten sensitivity (which showed up in her later years), a reduction in fine wrinkles (I see the same in both of us), a thickening of her hair, and an overall increase in energy and well-being. Relatives have recently asked her if she had "work done".

Prior to taking NR we both had chronic fatigue, and what NR did to combat that was amazing. However, these last few months if I miss a few days of NR I don't notice the same return to fatigue. I'm not entirely sure if it's the fisetin treatments that have done that, or if I've just managed to bank up a lot of NAD.

Doctors will never recommend any of this stuff. They don't follow studies, and the studies that do get brought to their attention are via the drug companies.

For your Dad, I'd actually make NR more of a priority than fisetin. It's been shown to help with an Alzheimer’s model in mice, and NADH (reduced NAD) has been shown to help Alzheimer's in people.

Ajax thanks Ajax. Can you send me a link to the nad you take? There's a lot of stuff out there, precursors, nmn, etc so I'm not sure which one to take. I have taken a high dose Fisetin regimen once and I'm in the middle of my second one now. I did 2100mg with 850mg quercetin, 165mg bromelain. 10mg BioPerine and a tablespoon of olive oil. Day two it today. I haven't noticed much from the first one which was a much lower dose 800mg over 3 days. I take 100mg a day as well. Still waiting on results. Thanks for your input. I'm 51 old male by the way. 

JOHN 

I've been taking Tru Niagen (NR) which I order through amazon. My reasoning for using NR is because it's the most studied in humans, and overall cost. It has an FDA GRAS (generally recognized as safe) designation, so it's probably easier to get the assisted living staff to give it.

The recommended amount on the label is two pills, but it's better to start off with one and see how it goes. Also, best to take them early in the day, as they can disrupt sleep in some people if they take them too late in the day. (NAD influences circadian rhythms)

Good luck with your folks, John.

JOHN 

Fight that Doctor. Make him justify why not and what the risk is. I would want my advocate to do this for me.
Many of these elderly care doctors are SO out of touch, IMO

BobM I don't know if I could ever live with myself if I ended up giving them high doses of Fisetin and they ended up getting sick or drying.  Unfortunately it's not as easy of a decision when it involves somebody else. 

BobM yes, we’re so out of touch.

Koo I've posted some interesting inflammatory cell count results from a blood test recently, which credit to fisetin. Have a look at my post in the "Test results" category.

Koo 

Milk takes up to 4 hours to digest.  When it hits the stomach it immediately curdles and forms a mass which slows its digestion.  Anything taken with milk or mixed with milk will likewise take a long time to digest or be absorbed as it will be surrounded by the slowly digesting milk proteins, etc.  Don't take anything with milk if you want quick digestion.

300 mg of fisetin is not a particularly high dose.  I suspect you are experiencing a food sensitivity or intolerance (similar to an allergy, but limited to the digestive system) to either fisetin or the plant from which the fisetin is extracted.  The burning throat is a good clue, not to mention the really bad diarrhea  for 3 1/2 hours which you reported.

Dan Nave 

I don't think it's clear that milk is problematic for fisetin delivery. Milk is used to increase the bio-availability of fat soluble vitamins (fortified milk), and unbound fisetin has a half life of 3h in the blood (in mice, with their fast metabolism), so there's likely a bit of time to get to that critical dose.

I used cream with fisetin, mainly because the salicylates in coconut oil and olive oil makes me extremely nauseous and gives me the runs. It was my hope that some of the cream might act as a crude liposomal coating, but either way it worked very well for me. I had clear signs of senolytic action. (mentioned earlier in this thread)

I do agree that the dose here seems low. I think even the Mayo protocol dose is conservative, and it's much higher.

Ajax Thanks again for your feedback on having salicylate sensitivity. I finally plucked up the courage to try the coconut oil on its own yesterday, about 1/4 cup, and it wasn’t pleasant hehe. I have discovered an interesting fact about myself – I appear to be sensitive to salicylates! As before, my heart rate and blood pressure shot up soon after taking the oil, and a little later the diarrhoea started. OhBoy!

If you hadn’t mentioned it I wouldn’t have had a clue what was going on. On the bright side, it means I’m feeling a lot better about taking the fisetin! And the interesting thing about salicylate sensitivity is that it arises from the COX genes/enzymes not functioning properly, and I have a condition associated with chronic inflammation. So there is potential for treatment.

Koo I'm glad you figured it out, and that my post was helpful!

Ajax I would love to hear from anybody who dissolves fisetin in oil. How much oil are you using? I want to know if I was using way too much, it was around 60 mL, or if others use this much without any problem.

Thanks.

Koo I was using a bit less than that - about a shot glass worth - so maybe 45ml.

I don't see smaller amounts being used. Even at these amounts, it looks like the fisetin is suspended, rather than dissolved.

Ajax Thanks very much, that's good to know.

John W Thanks for posting that. Lots of good info indeed!

I was especially glad to read the toxicology section, though given the widespread lower-dose supplemental use of fisetin, I'm not too surprised.

Ajax I was particularly floored by the work on Alzheimer's and the idea that it raises cognitive abilities even among normal people. Fisetin could really be a game changer, way beyond just senescent cells. I haven't digested it all yet but I am on board, having just purchased a lot of it to see how it goes. My wife is APOE4/4 so this is welcome news to me.

John W 

When I translate the doses used on mice it quals a daily dose for humans of 2 mg/kg. 

Staffan Olsson I was reading 25 mg per kg. I really take a deep dive into this study. I have read  a few of them on fisetin but this has the most useful info. Here's what I found in the Alzheimer's section ..

Two groups each of wild type and AD mice were used for these studies. Fisetin was fed to one set of wild type and one set of AD mice between the ages of 3 and 12 months in their food at 0.05%, resulting in a daily dose of approximately 25 mg/kg body weight (bw). This dose of fisetin was chosen based on earlier studies on fisetin and cognitive function in mice (21).

By my way of thinking that would be the same for humans but is that correct?

Also there's a comment on 40 mg per kg being equivalent to donepizel in response for AD.

John W 

 When it comes to translate the animal doses that is used in experiments it is a science of itself. Difference in size as well as differences in metabolism. I post a link to a guide to basic calculations.

In table one they show that a basic approach to translate a dose given to mice is to divide the animal dose by 12,3. They you get to HED = human equivalent dose.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/

So 25 mg/kg to a mouse equals 25/12,3=2,03 to a human.

Staffan Olsson I would have never guessed! Thanks much for explaining and posting that link.

John W 

When using fisetin as a geroneuroprotector, most humans would need to take at least 150 - 200 mg fisetin daily. this based on to the above posted link and according to a basic dose translation. That is a very reasonable amount to take every day. But we will not reach strong (if any) senolytic effect when dosing is in this range. 

Staffan Olsson Thanks to that dosing study you posted that is the plan but I do have enough to do some spiking sessions maybe in concert with quercitin. I am excited to begin.

Mixing with olive oil would be a daily pain though, but we'll see how it goes. I used to make a poor man's lipo vitamin C for my dad who had T4a cancer. I was a lot of effort.

 I got it from same place most presumably.  The only uses I really found for apocynin were topical claims to skin rejuvenation.  Anyone else?

Zack Lonetree   Hi Jack, what is the amount of apo you are using in the saline?

Antonia Gauer 

For the topical Apocynin solution I started out by dissolving 50mg in 10 ounces of a light saline solution.

Mel Hi Mel,

I'm new to this, but my feeling is that you should wait longer, at least a month before you have a blood test. This will give the fisetin time to have noticeable effects. As others have said, it will most likely take some time, and you most likely want to keep the number of blood tests you have to a minimum.

Koo thanks for your thoughts.   Why would one want keep the number of blood tests to a minimum?   Thanks again. 

Florin I am not familiar with those studies. Would you please provide links to them? Also, most people here are following a conservative approach aligned with the Phase 2 trials being conducted by the Mayo Clinic. Those results are not yet published, so data on the effect on humans is still lacking. Also, one study indicated a toxic accumulation in the liver of mice at a high dose, which may have been a result of the DMSO delivery, but it is still unknown, so people are being conservative until more clear long term toxicity studies are conducted. Toxicity is being studied as part of one of the newer Phase 2 human trials, but we are still probably 2 years away from those results, and it is following the Mayo Clinic protocol, not the much more aggressive one you suggest.

As for myself, I have been very happy with the Mayo Clinic protocol. I have less arthritis symptoms and can see the moles and wrinkles in my skin lightening and diminishing. I have upped consumption to 2 days every 2 weeks because I was seeing a regression if I waited a full month. However, I am relatively young, so don't feel the need to be aggressive in my treatment. I also consider fisetin like weight lifting. A stimulus is good, but you need recovery time to allow the adaptation to occur. Off time is when the body regenerates and heals. Fisetin is causing a stress response and literally killing cells in the body, and that process takes its toll, so recovery is important. Senolytics cause a stress response. Your body needs to be able to adapt. Too much, and you get other negative side effects, like with the chemotherapy drugs. High doses kill the cancer, but they also begin to affect healthy cells and stress the body's ability to process and eliminate both the chemotherapeutic and the destroyed cells.

Fairy8i8 Very nice summary and thank you. Agree with what you said, and I have also gone to 2  Mayo  treatments/month ( 20mg/kg bodyweight for two consecutive days)

My own personnel experience is that there was initially an immediate response  to the Mayo protocol in that my endurance, strength and color vision were almost instantaneously enhanced. This immediate response did not increase after my first treatment, but it has not diminished either. Others on this forum have reported similar experiences.  It seems to me that there has to be more than removal of senescent cells and/or mTOR inhibition to explain the initial response.  I have done a minor literature search and have not found an explanation my initial response. I wonder if there is some sort of impact on mitochondria. It may be that my age  (80 yr old) has something to do with the initial response. 

Fairy8i8 Do you have a link to the study? Thank you

Fairy8i8 It's the same study that this entire discussion is based on. Here's the relevant info:

Ercc1−/∆;p16Ink4a-luciferase mice were fed a standard Teklad 2020 chow diet with or without supplementation with 500 ppm (500 mg/kg) of fisetin, ad libitum (approximately 60 mg/kg fisetin per day)

To determine if fisetin-mediated clearance of senescent cells impacts the health or lifespan of mice, WT f1 C57BL/6:FVB mice were fed a diet containing 500 ppm fisetin beginning at 85 wks of age, roughly equivalent to age 75 years in humans. This resulted in an extension of median as well as maximal lifespan (Fig. 5A-B).

So, 500 ppm = 60 mg/kg fisetin per day.

The WT (wild-type) mice were the only ones demonstrated to have any lifespan extension. You might think that this effect was probably all due to the elimination of senescent cells, but it might also have been caused by other factors such as chronic admin of fisetin affecting the microbiome which the paper also speculated about.

Regarding toxicity, I'm not sure what would be more toxic: acute, mega doses of (possibly contaminated) fisetin or lower chronic doses? Mega doses might be safer if heavy metal contamination would be the only concern, but what about stuff like hinokiflavon (where the dose might make the poison)? Although I'd like some human data (I did request blood test results for liver function in another thread), I'm not too concerned about fisetin accumulation in the liver; chronic administration in this study was beneficial, not harmful. The study which suggested liver toxicity used 223 mg/kg, whereas I'm referring to 60 mg/kg which apparently didn't have any toxicity. That same study also mentioned that there was no observed toxicity even at 112 mg/kg. And as for the Mayo Clinic's protocol, the reason it's going for acute admin rather than chronic is probably because it wants to avoid drug interactions (several drugs and substances were contraindicated) and perhaps hoping that acute admin would produce faster results than chronic.

Whatever happens with stress and recovery, the data we have suggests that chronic admin might be better than acute for lifespan extension. Isn't maximum efficacy what everyone wants, given the same level of safety?

Fisetin is a senotherapeutic that extends health and lifespan
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/

Anti-cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034928/

Florin Thanks for clarifying. I'm really glad you commented! I always got so caught up with the initial groups, that I failed to contemplate the significance of the final group. Refreshing to see a decrease in oxidative stress in the liver. However, we do not know how the different methods compare to longevity because the first 3 groups of mice on various diets were sacrificed rather than allowed to live. Also, there is a standard chart for adjusting dosing of animal subjects to human subjects. I don't have it off hand, but it's not 1 to 1, so 60mg/kg for humans would not be the indicated amount from this study.

Also, I will add a third day to our dose round (today) because I just took doses the last 2 days, based on the Mayo Clinic update and see how it goes. I have wondered about increasing a high dose to more days as the group of mice that was given the higher dosage for 5 days had more senescent clearance than the group given the 500ppm chow ad libidum pulsed on and off.  I never liked how that group had an initial decrease in senescent cells, but then a slow increase thereafter, even when given the chow again. It's too bad they didn't do the same imaging on the other groups to see senescent accumulation over time. If only I had money to fund research!

I had discussed which way to take fisetin with my dad. The nice thing about intermittent doses is that it is cheaper as well. As I said, I am young (40) so I have time to wait and see what becomes of the research while having benefitted on the Mayo Clinic protocol. Also, I take Biotivia Pteromax and Jarrow Broccomax daily, so I do take things that stimulate the nrf2 pathway on a daily basis already. At this point, I am more concerned with healthspan rather than lifespan.

 Michael To which study are you referring?

Fairy8i8 The only empirically-proven endpoints is that the chronic group had increased longevity and health. So, there's going to be a risk in assuming that intermittent or acute admin will provide the same or better results.