Fisetin to Clear Senescent Cells

Mel don’t know Bill’s source of info.  I have in my notes Fisetin 1 to 1.5 gms per day for 2 days.

https://clinicaltrials.gov/ct2/show/NCT03430037?cond=fisetin&cntry=US&draw=1&rank=2

Mel I would think that life extension doesn’t have any more info than we do. You could use the dose from the study.

Karl life extension is conducting the study from the slide so they must have dosages.  But just haven't published them yet to my knowledge. 

Dorian Gray thanks for the feedback. I would think it will take awhile to see the positive effects.

RAW My feeling is that even if it is true that quercetin is not senolytic, it might be valuable to take it along with the fisetin.  My reasoning is that it has a "a moderate to strong inhibitory effect on CYP3A4 activity activity." "cytochrome P450 (CYP) enzymes that play an important role in drug metabolism and/or toxicology."

For this reason, even if it is only a sacrificial substance, it may increase the bioavailability of Fisetin when taken with it by reducing the effect of the CYP3A4 enzymes.

JGC Quercetin was originally used with Dasatinab because it appeared to enhance the effectiveness of Dasatinab.     (I don't recall which research group published the information)    Once Fisetin was discovered to be a more effective senolytic than Dasatinab, it became apparent that Quercetin didn't help Fisetin penetrate the intestinal wall and didn't have any synergistic effect with Fisetin. 

JGC Thanks very much for the information and the link.  I've been absolutely swamped with unrelated issues for the last several weeks and haven't had time to follow up on much of the information that's available.    I'll probably be in the 'body shop' for hip replacement and other repairs for the next several weeks and recovering for a while after that.   Hope to be back online in  a couple of weeks.  

Philip V. Anstett 

https://www.hindawi.com/journals/omcl/2015/854015/

Interactions between CYP3A4 and Dietary Polyphenols

https://www.ncbi.nlm.nih.gov/pubmed/12130727

Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4

I expect BioPerine is the same as piperine.  You can Google it.  Plenty of info on the net.

Fairy8i8 What do you think the fisetin is doing that is only lasting a few weeks? It cant be senescent cells building back up that quickly especially at your age of 38.

Fred Cloud Of course senescent cells can build up that quickly if you review the studies. Also, you need to assume that not all senescent cells were removed, and senescent cells still in the body promote more cells to become senescent. That, and I am basing it off of skin cells and visual queues. I live at a high elevation and have only started to use sunscreen this past week. Being above 3000 feet, I am exposed to more UVA than people at lower elevations, and UVA has been shown to be a major cause of skin wrinkling. So while I have cleared senescent skin cells, I haven't cleared 100%, and the UVA continues its damage, with repair capabilities decreasing as you age. I also live in a dry climate, which exacerbates the wrinkling. Apparently women living in Florida appear 10 years younger than women in my state because of the humidity. I have seen an increase in aging in the last year. Bodies age through multiple means, not just senescence. 

Fairy8i8 I am starting to realize you are right, after reading others reporting that the effects last a few weeks and then they have a reversion into the sasp mode. I have been reading alot and have seen the experts just assume you would only need to kill off senescent cells maybe once or twice a year and that seemed plausible but I don't think it is true. You need to listen to your body and see how long the results last and adjust your timing based on reversion of symptoms.

Fairy8i8 Looking at some studies technically it is a rate of clearing senescent cells that decreases with aging and slows down 5x. So, our immune system leaves senescent cell around for much longer as we age. As I see it there could be three approaches to solve it 1) Intervention leading to fewer senescent cells through inhibition of CD38 and promotion of increase in intracellular NAD+ levels. This leads to boosting immune system to be able to clear more cells. It doesn't appear to be a favorite topic on this forum. But it is an elegant approach and I suspect a part of real solution. I think it is better to clear the senescent cells that need to be cleared continuously and only do being cleaning occasionally.  2) Senolytics (Fisetin and others). Utilizing mega doses of some harsh senolytics just seems to drastic.  Also, human body is not lab mouse body. Even if senolytics work (remove all cells that need to be removed), this doesn't address the rate of immune system slowing down clearing the cells. So basically, you would need to use senolytics at least every 5 days? 3) suppressing senescence. Rapa, my preferred mode (only because it works and it is clearer on what to do and can be used topically too)

How about EltaMD UV Clear Broad-Spectrum SPF 46? It has good UVA protection and is moisturizing too. Retin-A over 6-12 months’ period can eradicate 40% of wrinkles too. Both are scientifically proven and supported by substantial amount of research to achieve what they claim to achieve.

Fred Cloud Many of the experts are starting companies to clear senescence, so they are looking at making drugs that would clear a lot more cells than just fisetin alone. Also, they are anticipating an expensive treatment (possibly using drugs like dasatinib), so of course they know most people would not take it monthly, nor might it be advised. That's what I like about fisetin - it has a history of human use, we have not yet found a toxic limit, though that may be studied more in the future as people take higher doses, and it is quite effective and cheap.

In the mouse studies, fisetin did not clear 100% of the senescent cells, so I do not expect it to clear all of them, which means more are being produced in the body regularly around the existing senescent cells. (Also, it does not clear all types of senescent cells, but does clear fat and skin senescent cells.) When they pulsed the dose every 2 weeks, by the last dose, the number of senescent cells increased from one cycle to the next, but at a small rate, so especially as you age, you should still expect some accumulation. The last trial in the study gave a higher dose, I think over 5 days, if I remember correctly, and then the animals were sacrificed and examined. This group had the greatest decrease in senescent cell number, but we do not know the lifetime effects because they were sacrificed soon after the dose.

I began with 2 days monthly because that was what the human study was doing at the time, so I figured that if researchers could get approval to give it to healthy 70+ year old women, then it would probably be okay for me too. As I said, the skin, particularly on my face, showed improvements, but the improvements would go away after a month. Skin has a pretty short turnover rate, and at my age, it is probably around 30 days, so seeing results diminish over this period is understandable, especially with regular UVA exposure. I decided that I didn't want to stay "steady state," but wanted continual improvement and clearing, so I began a 2 week cycle, and I am happy with it.

There are other ways to play with dosing - increasing the dose and doing it for 5 consecutive days, for example, but I am relatively young, so I do not feel the need to rush into something like that before there is a clinical trial, or we at least see the results of the human trials at the 2 days/month for 2 months level.

Joe smith You bring up some interesting points.

1) I am not familiar with CD38 inhibition, but I do take Elysium (a nicotinimide riboside supplement) to increase NAD+ production. I am interested in Nuchido Time+ to increase NAD+, but I haven't read of anyone using it or their results.

2) There is a minimum effective dose of Fisetin that makes it effective as a senolytic, and the mouse studies do show that increasing the dose does increase clearance. I wasn't sure myself, but seeing the nickel sized mole on my mom's face go away convinced me that fisetin, even at the about 100mg/pound dose for 2 days (just pills swallowed with water, no fancy mixing with oil or adding peperine) definitely does SOMETHING. She only took it for 2 days and didn't do it the following month, either, and I saw her 5 months later.  I think every 5 days would be too often. My husband, who had severe sepsis last year and was a day away from dying, says that taking it makes his muscles feel sore like a good weight lifting workout. The cells need time to rebuild and recover as well. Taking it too often would interrupt the rebuilding phase. 

It would be interesting to see if fisetin had a positive effect on clearing senescent immune cells and improving the immune response. At the very least, it could make the cells easier to clear. We do not know the mechanism, but it sure helped my mom and her mole, and she was 69.

I think UltaMD products are great, but I have a 4% nicotinamide cream that I use that already has the spf 50 in it, so I am starting there because I'd rather just use 1 cream on my face. I have not tried Retin-A because when I read the study, it reduced the appearance of fine lines and wrinkles in 40% of patients, NOT 40% of wrinkles. That means 60% of study participants saw NO fine line or wrinkle reduction at all. Because of the significant reddening and other side effects, I didn't want to go that route. I know that some inflammation can induce a healing response, but I'd rather do something periodically and have my skin heal completely than have something that creates chronic inflammation and irritation. My uncle had skin cancer, and he goes in to his dermatologist every year to have the area lasered. He has the doctor do his whole face at the same time, and he looks AMAZING. I would rather a treatment like that once a year - no underlying redness  or thin skin like you often get with Retin-A, just thick healthy looking skin and even skin tone.

Fairy8i8 1) Nuchido is quite interesting as the company is built around more modern concept important to the point I’m trying to convey here but clearly failing i.e. the single intervention by itself like taking NMN or NR or (I believe also senolytics) is counterproductive you take one step forward (your mole will shrink or you get more energy) and two steps back. Read her blog to get an idea https://nuchido.com/blogs/articles/ageing-nad-and-biological-complexity I don't know if her formula works, we need more testing but her scientific concept of network is very very interesting.
2) I want to apply the same concepts of networks to reducing senescence. What I believe you and other people on this forum and thread are accomplishing is short term positive gain but long term negative effect. Why? because you have to use two much senolytics and too often. I total agree with that every five days is too often but how with senolytics alone you can mimic what your body is doing when you are young? I don’t know and after reviewing a lot of the research on the subject I believe the researchers got no clue either. Hence, if anything you will need to accomplish it either through some senolytics which don’t yet exist or perhaps through network effect with other supplements and drugs together. Maybe all the ingredients already exist but cookbook is lacking? We need to make sure we don't take 2 steps backs.
3) Retin -A please don't look at one study but rather look at metastudy and drill down to individual studies. Also, what is the study that you are quoting? Please provide the link. Further I must disagree with you vigorously on your conclusions/statement son the subject. Please check out this metastudy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699641/ Tretinoin will reduce wrinkles and melasma in nearly all if not all the subjects that stick to it. The degree of it will of course vary. After a month or so you will look bad due to redness peeling etc. but then with long term use results show up. And no, your skin doesn't get thinner. If anything, it may get a bit thicker overall. The outer layer of course initially will do get thinner but then after 6-12 months it goes back to normal. If you have too much redness peeling go with weaker dose until your skin acclimates. And yes, both fractionated laser and RF micro needling work very well and produce beautiful results. Much more spectacular than Tretinoin. Also, they partially achieve their results by reducing number of senescent cells in the skin? Can you see the potential network effect here if you combine fractioned laser with senolytic or CR?

Joe smith Thanks! I'll look at the metastudy. I was referring to the study information included with the drug, which referenced the 40% of people saw a reduction (no specific amount of reduction given). There is also quality research on niacinamide as a topical. I follow some cosmetic chemists (thebeautybrains), and both Retin-A and 4% niacinamide were given an A rating by them as to quality double blind placebo controlled studies published in peer reviewed journals. I decided to go with the niacinamide first because it is over the counter and didn't cause irritation for me. All in all, I don't need redness and peeling when there are other options at this time and people still think I'm a college student. Topicals may enhance some things, but I prefer an overall health approach that will help not only my facial skin, but vital organs and other such functions. I'm not so into beauty to want to spend a bunch of money on it alone. I might try laser down the road, mostly because of the phenomenal results I saw with my uncle, and because I had a lot of sunburns on my face and shoulders as a child. If the laser his doctor is using prevents his skin cancer from coming back, then I am all about getting that done to prevent any problems of my own in the future. Besides, I already spend plenty on my anti-aging routine LOL!

Fairy8i8 Did I read this right, you wrote senescent cells increased when they pulsed the dose every 2 weeks? How could they end up with more senescent cells after the round of senolytics?

 "When they pulsed the dose every 2 weeks, by the last dose, the number of senescent cells increased from one cycle to the next,"

Joe smith So you feel increased senescent cell populations are mainly a lack of immune system clearance? Lets back up first, senescent cells are thought to occur from reaching hayflick limit and aged cells that dysfunction from age and telomere shortening, so as as a result senescent cells should occur at a higher rate in general but I agree it is certainly aggravated by a declining immune clearance rate.

Fred Cloud I don't feel. (well sometimes I do 🙂.) I'm only interested in the scientific proof, research and reason . Check this out Senescent cell turnover slows with age providing an explanation for the Gompertz law: https://www.nature.com/articles/s41467-019-13192-4

What do you think?

Fred Cloud Yes, you read that right. Fisetin does NOT get rid of 100% of senescent cells. It decreases the number.

Here is the study. Look at Figure 2B & 2C. Even at higher doses, like in Figure 4, it's still not 100%.

https://www.sciencedirect.com/science/article/pii/S2352396418303736

Fairy8i8 NAM is good and as you pointed out it has a solid research support behind it. It is meant to reduce irritation. In your dry climate I'd combine it with triglycerides for good skin barrier. And as you may know, you can buy quite potent retinoic acid OTC - adapalene 0.1%. OTC, It is a gel so it may be too drying for you but a cream version is the mildest of all retinoic acids and was meant to avoid skin irritation. You know people start retinoic acids in early twenties and I saw beautiful maintenance results after 15/20 years of continuous use. Anyway I agree with you that overall health approach is even more important. My issue is that we need to bridge the gap between research studies on senolytics on mice and what we need to do ourselves. In my mind it starts with simple testing on small short lived primates to establish safety and then drill down into dosages and safe amount. No efficacy for now. Just safety. I believe we need to do it ourselves. before some people die. Now!

Fairy8i8 Sorry for the confusion. I did not mean or question the 100% clearance. I was referring to when you said senescent cell amounts increase after taking a round of senolytics.

"senescent cells increased when they pulsed the dose every 2 weeks"

How is that possible that would you have more senescent cells after killing some of them off with a senolytic round?

Joe smith They have done safety studies on fisetin. The standard ones to determine toxicity of a substance. It doesn't seem to be very toxic. It's also been a supplement and taken for over a decade at lower doses by humans. I'm not worried about safety, but I also read various studies where they looked at potential toxicity and didn't find it. I think each person needs to investigate and decide for themselves. It's because of these previous studies that they went right into clinical trials in humans. I don't need to look at a primate when there are human study results coming soon. 

Glad the retin-A has worked well for you. It's good to hear people's positive results. I think I would go with the prescription form rather than an OTC form if I go that route.

Fred Cloud If you look at the Figures 2, it will be clear that it IS possible when you are looking at specific time points. After the first round, the number decreased. Then during the period of no fisetin, the senescent cells increased, but remained lower than the control group (indicating clearance, not suppression). After 4 weeks, when they were given the fisetin again in their diet over a 2 week period, the rate of increasing senescent cells declined, but there was still a net increase, just less. The body is constantly making new senescent cells, so this is no surprise. The researchers were excited that after the first round, the number of senescent cells stayed lower than the control group, which indicates senescent cell clearance, and not just a suppression mechanism where fisetin must be taken constantly. It did continue to increase, but at the second round, the rate flattened a bit, though still a slight increase. Just look at the graph. 

What this tells me is that a higher dose may be needed for effective clearing as you age. 2 months is quite a few years in mouse age. But overall, there was about a 40% reduction in senescent cells compared to the control group, and that is HUGE.

The implications of reducing the number of sick, inflammation producing cells by almost half in the body means a lot. Just ask my uncle with rheumatoid arthritis who started taking 1500mg for 2 days each month last fall, just half a bottle of pills swallowed with water. He can button his shirt without pain. Not having finger joint pain in an arthritis sufferer is a big deal in terms of increased quality of life.

I have sport injury onset arthritis in my big toe joint. Since taking fisetin, it doesn't hurt. I used to not be able to walk a block without serious pain. Today, I just hiked a mountain with my kids with no pain. 

I am taking fisetin because it has helped me. I feel the difference. My orthopedic surgeon told me that my toe flexion would just steadily decline and the pain would increase until I needed a joint replacement when my toe would no longer flex. Between omega-3 and the fisetin, I don't have pain, and I have full flexion 8 years later. 40% reduction of senescent cells feels great.

Fairy8i8 Yes, this thread is titled fisetin to clear senescent cells, but we are really  talking here about  at least 3 key senolytics: Fisetein, Azithromycin, and Dasatinib. And some others too.  Basically a cocktail taken concurrently whose safety is not at all established in humans.  That's what i want to test asap. And if there are studies please share. With respect of fisetin, yes I have seen statements in a research paper saying that it is relatively safe. And yes people are supplementing with the Fisetin as it is readily OTC available. However, it is logical non sequitur to say it is safe when taken 3 days in a row 1.5 gr a day, monthly or even quarterly for the next 5 years. There is no such study in humans and won't be any time soon because it is too dangerous and Dr Josef Mengele is currently not available to conduct such a study. Now you can test marmosets for 9 months which is equivalent of 5 years in humans to establish safety record for fisetin and combo (F+A+D+Q) which I'm much more concerned about. 

Joe smith Are you personally taking any of these senolytics? It would be nice to get a study combing the 3. However, I think cocktails like that are more likely to be studied by one of the many startups because they would be drugs registered with the FDA, and we would not see those results for about 10 years or more.

Fairy8i8 Well I have quercetin and Fisetin in the fridge. But I'm not taking them now. I'm taking prescribed low-dose Rapa for anti-aging and I'm concerned about interactions. I don't have the other ones like D or A. More serious stuff for sure. That said I'd love to test them all on marmosets to establish the safety first. And then if it checks out then why not? I would test them on me and few other willing volunteers but do super extensive monthly blood tests and med supervision and take it from there. And yes, I don't want to wait for some startup 10 years from now to show you and me the results and try to charge us arm and a leg. I want to do it openly now for everybody to benefit.

JGC   I know here in Spain, only 5% of population is estimated to have had Covid-19, and then what are the odds that someone in the general population practicing senolytics.  Not impossible, but probably a much greater chance they were using Azithromycin to treat Covid-19 which is not only can protect from bacterial infection, but blast fibroblast  in the lungs also.  If you go to Dr. Green's Rapa website, it discusses treatment of Covid-19 with senolytics.    https://rapamycintherapy.com/

JGC I just talked to Dr. Green a few days ago. I was patient 517. He hasn't talked to anyone who is a patient of his that has contracted covid. He said if any of his patients contracted it the symptoms were not big enough to get a test to verify they had it. 

JOHN Business is picking up in spite of the Wuhan. I saw him in March and i was patient 480.

Randy B Interesting! I was very impressed with him. My wife and I saw him as a couple. I have been going on and on about him to her for the past year. She was a little reserved until we met him. We spent 5 hours in his office. It was fantastic. I talked to him about a bunch of studies that I had questions about and he had clear and concise answers.  He's a brilliant guy. He finished med school at the age of 24 and has a law degree. He said getting his law degree was a piece of cake compared to a medical degree. He looks great for his age as well and I hope I'm a patient of his for a long time.

JOHN JOHN Saw Dr Green the first time 3.5 years ago.....glad I had made the trip....just had appt with him 3 weeks ago....referred a few new patients to him....yes, instead of fading, he is really quite sharp....worried about that.....but he is definitely holding up well.

Antonia Gauer My supplier no longer ships Dasatinib.  I am working up a new order, with a new supplier for Dasatinib and Fistein powder and will post my order here in the next week.  Of course, anyone can check with Alibaba and there are many suppliers of these drugs including Rapamycin.

Van  thank you. I regularly buy from AliBaba but feel uncomfortable with the powder quality. You are the guinea pig that survived :). The other issue is the Canadian inspection system. Anything powdery coming in from China is opened and I wonder if this scheduled drug would be confiscated. More likely than not it would. Back to the rapalogue I guess. And trying to fast. 

Antonia Gauer I am concerned about the purity but I also don’t feel qualified to make doses such as a 4mg to 6mg dose from a 1kg bag of rapamycin powder.

David H  Do you have one of those scales that people use for drugs? They are very accurate. I used one for my husband's IV cocktail when he was very ill. Sadly, his condition had gone too far, but the scales were very accurate. They come with little weight testers for accuracy.

Antonia Gauer I was suspect of China also at the beginning until I read an article that most of the drug manufactures in US order there raw materials from China.  They were running out of reagents for testing for Covid-19.  The reagents came from China.  If it is good enough for Merck and Pfizer, it's good enough for me.  Alibaba which is bigger than Amazon guarantees that you will get the product you order and they take CC.   I ordered by Rapa from China and I got exactly what I ordered at a very reduced price.  Remember China is 4 x the size of US and has 1,000 of companies competing for your dollars.

There is no mixing powders here.  You simply weigh the grams/milligrams that you are taking and put in glass, add water, and drink it.  Not too difficult.  My Rapa was a little more complex, but not applicable here.

David H It is not difficult to mix the 2 powders together.  Just take 1 gram of Rapa and mix with 250 grams of Lactose powder per these instructions.  You can use a large tablespoon and a large ceramic or glass bowl and follow this video.

video.https://www.youtube.com/watch?v=k-3DoyKy0zE

   Once you are finished mixing.  You would simply weight out .25 gram (250 mg) per mg. Rapa.  If taking 5 mg that would work out to be 5 x .25 = 1.25 grams per week of the mixture.  The reason for mixing with a lot of lactose is so you can measure accurately.

   If I can do it at 74 yo's most others can also.  Ordering Rapa tablets from Canada and using grapefruit juice or not, also works.  The main thing is to slow the aging down and feel better physically and mentally.

Van  Interesting. I have purchased pharmaceuticals from India for the same reason. Unfortunately, the pharmacy no longer delivers to Canada. Also, whenever I have had any powders delivered from China, they come with a huge "Opened by Customs Canada" sticker and some of the product is missing due to testing for naughties. I wonder if dasatinib can be identified as a prescription drug as there are huge penalties for importing scheduled drugs. By the way, after I mentioned the scale on this site yesterday, in response to a comment, it appeared in my "Amazon suggestions." I have never searched nor have I purchased anything to do with measurement on Amazon. Big Brother...

Antonia Gauer Well it is clear that this web site is selling your info to others.  Guess that is the way they support there cost to run this site.  If you ordered dasatinib, 3-5 grams from China it would come in an business envelope delivered by Fedex.  It is really the same size as a letter.  I live in Spain and they are also very strict, but I got my Rapa without a problem, but one never knows.  You can ask them if they have ever delivered to Canada and try to make an informed decision from there.  Good Luck

Van  Thanks. I will try that.

Moonlitnight If you can make the trip to La Guardia and UBER out to him in Littleneck it is worth the time....stay in a local hotel near by if need by, I have....seen him for 3 years.....not sure but if you get the first visit you can likely do televisit followups......I did that last month...televisit..... But you have to go in for first visit....but a great investment

GEdwards  Thank you for this info. It would be cost prohibitive for me at this point and the latest set of rules regarding the virus wont permit "non-essential" travel. But in the future maybe!

Moonlitnight Well you don't need to see him, you can just procure the rapamycin on your own and skip Dr Green altogether. I assume seeing Dr green is for people who dont know how to obtain the rapa on their own or dont feel comfortable in doing so.

Fred Cloud Moonlitnight

https://www.dropshipmd.com/buy/rapacan/

Said it could take 30 days = arrived in one week

30 1mg tabs = $117 (including WU fee)

Michael  Thank you! I will check to see if they deliver above the 49th.

Moonlitnight Send me your address. I'll mail you half of mine. Strictly for academic purposes. 

Moonlitnight Moonlitnight Hi MLNight,. Understood about cost having been laid off due to CV19 and my company being sold for assets. I never know the varying restrictions and just saw my nephew and family FaceBook sharing their flight to Orlando from Houston for vacation...all masked up but on vacation nonetheless. 

Please be cautious about foreign supplies, wasted a fair amount of time and done money buying foreign Biocon brand 'rapamune' that priced to be very very low dose vs the label. I have arthritis in both hands that respond results to Pfizer Rapamune and generic Sirolimus bought thru pharmacies..... There is very good quality control from regulated sourced or many transplanted patients would be doing of severe organ rejection. After taking the fake 'Rapamune' my hand began to ache again with a return to sharp intermittent pain. Even doing this phone text to you would have been a real challenge! I asked my wife to give me either another dose of Biocon or generic Sirolimus for the next two weekly cycles '3mg' with Grape fruit juice (white 10oz) and within 36 the pain abated till the next dose of Biocon sourced 'Rapamune' the next week when my hand quickly became problematic. In that Rapamycin addresses systemic inflammation this is understandable. My wife confirmed what my hands 'told' me.  I had to then take 10 Biocon pills with GF juice to get any positive response.... That would have been about 30mgs if on fact the Biocon pills were full dose 1mg strength.  They clearly were not.  There is a list of doctors on this web site (not this blog) for Doctors that help patients address aging and I'd hope you might find one regionally available.  I was checking this option here in Colorado when a friend that I referred to Dr. Green said he got a telemedicine visit and I could do the same since I was already a patient.  

I visited with Dr. Green and he asked me to try a Sirolimus 3mg pill that a compounding pharmacy was providing.  I took it Friday with GF juice (which should be the biologically available equivalent to 10mgs) as what would be my normal dose and so far it looks good but I need to track my response thru this Thursday to get an idea on actual strength of it.

I also get my Dasatinib thru this same counting pharmacy and it's too is potentiated by GF juice so both these meds are easily stretched on cost by GF juice helping with that cost issue.... But both require a prescription.

Best of luck and I'd enjoy hearing more from you.

Greg

Van Thank you for the Alibaba link. Today, I ordered 1 gram of rapamycin from them.  I already had Dasatinib from IAS.   Easy ordering process - now to buy a milligram scale.

David H When you order the .001 mg scale, try and buy one with calibration weights.  Also, you will need some lactose powder.  250 grams should do it.  Good Luck

Fairy8i8 and I am 40 now. Robert Olin I take Broccomax daily and fisetin pulsed every 2 weeks.

Joe smith Fairy8i8  Thats terrible information. If the content of products are so missleading then a link about the fake content must be spread. Do you have a link to Dr Rhonda Patrik so we can refer directly to her statement?

Staffan Olsson Maybe not so terrible - from a twitter tweet "

Dr. Rhonda Patrick

@foundmyfitness·

Apr 7, 2017

Avmacol has high concentration, broccomax has much less but is ok." 

Dr. Rhonda Patrick

@foundmyfitness

Dec 13, 2016

Broccoli sprouts are most concentrated form. Supps are not as good...avmacol is best one in U.S. Broccomax is decent."

From a February 2017 Joe Rogan podcast with Rhonda Patrick"

"Supplements: Hard to do right, only 1 in France  – Prostaphane with 70% bioavailability

• Avmocal has 40% bioavailability, Crucera only 10% bioavailability
• Broccomax isn’t great."

She said Broccomax is "ok" and "decent", and "isn't great".  The "isn't great" is concerning bioavailability".  Her favorite is Prostaphane but it is only available in France.  You can buy it using a shipping service because someone has either order it or go to a store where it is sold.  Then they ship it to you.  Those service fees are high. 

David H You are good at research 🙂 . Net net when you can get Avmacol for $24.95 for 60 capsules off Nutramax website and Broccomax on iherb for $18.87 as of today the choice at least for me is clear. I go with the readily available product used in multiple studies with good bioavailability vs isn't great.

Joe smith Thank you, I am a fan on Dr. Rhonda Patrick and am a member of FoundMyFitness. (I consider her my paid researcher - members join so we can benefit from her research.) Also I have a premium account with podcastnotes.org where I found the notes I cited from the Joe Rogan podcast.

Joe smith I agree. I would be very interested to know who did the testing and under what conditions. I would also be interested to see how it compares to broccoli sprouts, which she personally takes. The Broccomax bottle has testing claims, so it would be interesting to see if there is an independent study. 

Fairy8i8 Hi, see my follow up below. Basically the tests were done by Dr Jed Fahey lab at John Hopkins, #1 authority on the subject in the world. I didn't dig deeper into how they test and under what conditions. Perhaps  David H  as he is a member of FoundMyFitness could reach out to Dr Patrick and find out more? My understanding is  based on what she said is that broccoli sprouts are more effective/better. That said I'm curious too and we don't know for sure. It would be interesting to conduct the study of efficacy of broccoli sprouts vs Prostaphane/Avmacol. With respect of BroccoMax testing claims, let's find out more. Could you reach out to Jarrow and get the test(s) results?

David H I looked up the podcast. The Alpha Brain reference is linked to Onnit's Alpha Brain supplement. I would be cautious of relying on a competitor's testing as a reliable source for potency. I would take more stock in an independent lab. A PhD, especially a popularized one, citing a competitor's study doesn't make it more reliable. Note: I do enjoy her videos. It's true that Broccomax is less potent per capsule than some. However, I take several things that turn on the NRF2 pathway, and as the resveratrol researchers found, too much of a good thing is actually just toxic to the body. Sulphoraphane is a toxin that stimulates a certain response, but I used standard mouse to human scaling to get human equivalencies from the studies, so the amount you take depends on what you are looking at it doing, and also assumes you are not taking other things. I am taking other things, hence the conservative dose. I am looking for more of a nutritional boost effect than a drug effect from it, as I take it daily and have just started in the last month and want to see how I do. Ideally, I will feel no change. 

Joe smith Sorry, did not see this sooner. I found a 2.5 hour interview Dr. Patrick did with  with Fahey. 

https://youtu.be/Q0lBVCpq8jc

I haven't looked at it yet, but figured it would be interesting to some here.

Here is his FAQ page in response to all the questions he got from the interview.

http://chemoprotectioncenter.org/frequently-asked-questions/

I can see if Jarrow does batch testing. Even Fahey admits that potency levels will vary based on crop and growing conditions that naturally vary from year to year, even just buying and sprouting seeds.

Fairy8i8 You make two interesting points : 1) The more sometimes is not more effective 2) Interaction with the other supplements/drugs.

I think both of these have to do with the fact that we are trying to act on complex human organism. Hence there is a braking point. The drugs/interventions may be good by themselves with limitations of diminishing or even negative returns when saturation point is reached. This is even more complex and need to be adjusted when combined e.g. too much exercise may be counter productive where risk of injury goes up and benefits go down. The same with calorie restriction. When you combine two it is very beneficial but the amounts of exercise and calorie restriction need to be adjusted downward. Also clearly you wouldn't exercise and fast every day unless you want to die prematurely. We understand CR/exercise fairly well but much less so with respect of supplements/drugs and their combined effects. For instance, is it beneficial to combine fisetin (senolytics + NRF2 activator in strawberries) and broccoli (  sulforaphane NRF2 activator and senolytic) in megadoses at the same time? My gut feeling is that it will be counterproductive. Nature just didn't make humans to be so responsive with respect of such interventions like CR/exercise demonstrates. I'd bet everything on that eating 10 pounds of broccoli (or equivalent supplement) and 10 pound of strawberries (or equivalent supplement) per day won't make you live longer. Further it will most likely shorten your lifespan. Perhaps smaller doses are beneficial and/or rotating supplements to mimic mother nature and your specific epigenetics (i suspect that optimal doses of chemical compounds may be different depending on where you grew up and what you ate then) . Basically personalized medicine which starts with personalized testing.

Joe smith The only problem is that it takes 2 capsule of Avmacol to get at least the same listed amount as Broccomax. I looked a little deeper, and Broccomax used to not have myrosinase, so it used to be much less effective. They now have it. Also, Avmocol made their to suit Fahey's needs in that it is a tablet that can be crushed, which was beneficial for his research on autistic children who couldn't swallow a pill. Broccomax has recently been used in clinical trials and is currently the product of choice for a trial in prostate cancer patients in the US. Fahey never directly said that Broccomax didn't have it's claimed amount to Patrick, but insinuated it wasn't the best to her. The purity comment was an add on in podcast discussion and wasn't necessarily directed at Broccomax. They have since changed their supplier and how it's formulated to include myrosinase. Also, Fahey supplies broccoli seeds and was in the business. He has since had to distance himself from executive decisions of his company because of conflicts of interest, but he does hold a financial stake. Fahey did test various products, but I do not think he will give out the data or make a specific statement because of the legal ramifications. 

Fairy8i8 Thank you for your effort in bringing clarity to this issue. it looks like broccomax after all is an ok product. I have been looking for Avmacol on sites here in Europe but I have not found it.  Broccomax is much easier to buy.

Staffan Olsson Glad to hear you can get Broccomax, although if you are ever in France, Prostaphane could be even better.

Joe smith I agree with you on combining things. Fahey did do a study comparing sulphoraphane with curcumin, but I haven't looked at it yet. High doses of curcumin have some senolytic effects, but I do not know the dose used in the study or the results. Apparently many things activate the Nrf2 pathway, like even the omega-3 fish oil I take. Initially, I thought I was taking things that worked on different pathways, but there is a lot of crossover. One Broccomax has about as much sulphoraphane as 100mg of broccoli sprouts. I take as much fish oil as is in about a serving or two of salmon. I'm comfortable with those amounts, as it's comparable to food levels, but more convenient for me. It's hard to know the best route.

My dad (70 years old) got deep vein thrombosis. His doctor couldn't figure why because he has an awesome cardiovascular system. However, he was taking high doses of Vitamin K to get the various forms like MK-4 amd MK-7- thought to have no known upper limit- and guess what blood thinners block? Vitamin K uptake in the body. Here he thought he was doing something good for his body getting a variety of Vitamin K and improving calcium absorption and reducing calcification of blood vessels, even promoted by the likes of Dr. Patrick, and his doctor thinks it contributed to his deep vein thrombosis. Now he is on blood thinners for a year and gets terrible headaches from them. When self experimenting, you have to be comfortable with significant risk, and sometimes it may indeed cause more health problems than it fixes. That's why I appreciate this forum- people looking out for me on a possibly bad product, shared experience. I don't discuss this much with people around me because I know most won't bother to inform themselves and understand that there is some risk involved. That said, trials in children are very difficult to get approved, so I feel much more comfortable taking a product that has shown to improve many children's lives.

Fairy8i8 Joe smith I lookad at that interview some time ago and I remember that Fayey mentioned that when broccoli sprouts (or supplements) activate the Nrf2 pathway the pathway will stay activated for 48 or 72 hours.  When I learned that, I started to take sprouts or supplements intermittently every two or every third day.

Staffan Olsson Thanks for reminding me! I only take 1 Broccomax capsule a day, which is a low dose (autistic children were given more daily than me), so I won't be in a hurry the increase my dose. I think Fisetin has a much faster half life, if I remember correctly.

Fairy8i8 It sounds like we came to similar realization with respect of supplements and their interactions. They can be very useful but you need to be very cautious and conservative while applying sound overall principles like homeostasis. Also as you pointed out optimal dosing for some supplements is unclear we do know a bit about D3 optimal dosage curve but clearly not so much about K2. Interestingly that you brought up K2 . I have Innovixlabs K2 (MK4+MK7) 750% daily RDA. The last bottle I finished, I put it aside a couple of weeks ago to take a break from over supplementation.

Staffan Olsson Very useful piece of information. I think we should put more precision and engineering approach to the supplementation if we ever want to achieve repeatable and predictable results. A following spreadsheet, could be a start, showing:

1. compound (e.g. fisetin)

2. What we are trying to achieve: short , medium , long term

3. human activation amount

4. half/time and/or how long pathway stays activated

5. Interaction(s) with other compounds

6. Any advice on what to do and not to do when taking the supplement: e.g. take it with olive oil for better absorption, don't take it a day before or after going to gym, etc.   

7. Frequency of supplementation: e.g. once a week, supplementation cycle 

8. Side effects, things to watch out, etc.

9. What to do if you encounter such side effect e.g. stop supplementation for 2 weeks

Feel free to contribute. If you guys think it make sense, I will set it up on google docs so we can all edit it and contribute as needed.

Fairy8i8 Joe smith

yes the half life of fisetin is short. But its effects are long lasting because the effect of the "fisetin punch" produce a structural change in the human body by knocking out senescent cells. A bit like when surgery or the editing of genes are done there are long lasting effects of those kinds of procedures.

And yes, it is very logical that we should use different strategies when it comes to finding the optimal dosing for different purposes. Like when it comes to using broccoli extracts for treating autism or when we use the extract for improved general health and as a preventive measure.

There are many questions that we cant find answers to in our lifetimes so we have to rely on the research at hand and apply concepts of physiology. I will try to locate the segment in the interview with Fahey were Dr Patrick and him tlk about the long lastning effecs by broccoli extracts on the Nrf2 pathway

Fairy8i8 I read this post several times because one point confused me.  You stated, "However, he was taking high doses of Vitamin K to get the various forms like MK-4 amd MK-7- thought to have no known upper limit- and guess what blood thinners block? Vitamin K uptake in the body. "  Did you mean he was taking blood thinners at the same time he was taking the vitamin K2 (MK-4 and MK-7) or only after he experienced the DVT?  Was he taking any doctor prescribed medicines during the time he was taking the high dose vitamine K2( MK-4 and MK-7)?  

I've been taking high dose vitamin K2 + high dose vitamin D3 for over two years with no bad side effects, but I want to be aware of potential bad side effects.    

Jay Orman He wasn't on blood thinners at all before getting deep vein thrombosis. I was saying that blood thinners work by blocking vitamin K. He got deep vein thrombosis- a blood clot. His doctor was surprised that he got one. He has chronic fatigue syndrome, but takes good care of himself. He has excellent cardiac stress tests results and is a healthy weight, but he does have elevated cholesterol that he manages with careful diet. The only thing the doctor thought could be a factor in his getting DVT was the very high vitamin K and sitting in a car driving across country. He had to go on blood thinners for a year afterwards to get rid of the clot, and the doctor told him to stop taking his vitamin K supplement because the blood thinners work by blocking the Vitamin K receptors (which means that part of Vitamin K's action in the body is to assist in clotting). 

I would say to just watch for clot symptoms. Also, get up and move around frequently and if you are traveling, take frequent stops to move around. 

I get a ton of Vitamin K through diet, so I have never felt the need to supplement.

Jay Orman Also, he us was not taking any prescription medications during the time he took vitamin K. He did take the blood thinners for a year after DVT, but is now off them. I don't think he will supplement with Vitamin K again, though, and he has an alarm on his watch to make sure he gets up and moves around frequently because he is the type to get lost researching something on the computer and sit all day.

Fairy8i8 Thanks very much for both clear and precise answers.  I suspect inactivity and sitting may play an important role in DVT.  The K2, maybe?  I'll investigate further.  It reminds me of the death of Tim Russert a few years ago after he passed a stress test, but was sitting for an extended period on a long flight.  Very unfortunate.  

Need  I eat my fisetin on buttered toast and snack on dehydrated strawberries. I have just started. 

JGC 

JGC  A little lower price than ageless.one on ebay - their fisetin is $49 for 25gm plus $3 for shipping. They reduce the shipping charge for more than one item.  I ordered 3 last time and they charged $4.50 for shipping.

JGC Thank you. I will try that one.

JGC Sorry! Try this: https://www.ebay.com/itm/FISETIN-98-pure-powder-extract-no-fillers-cost-effective-ANTI-AGING/293083396786?ssPageName=STRK%3AMEBIDX%3AIT&var=592361881380&_trksid=p2057872.m2749.l2649

Title of ebay listing is: "FISETIN, +98% pure powder extract, no fillers, cost-effective, ANTI-AGING"

David H 

That particular product is from CHINA. I don't know if we can fully trust what the ingredients say.