Fisetin to Clear Senescent Cells

Following studies with mice that showed significant senolytic clearance of senescent cells following large doses of the readily available flavenoid supplement Fisetin,  my wife and I (ages 79 and 84) decided to try it.  We have just completed two sets of massive Fisetin doses.

We had Life Extension blood-work done in October before the start, and we will have more again next week to observe any changes.  The first set of Fisetin doses was on October 22-25 with 800 mg/day for three days followed by 600 mg on the fourth day, for a total of 4 g.  I didn't notice much in the way of effects.  Perhaps some reduction of small aches and pains and some increase in energy and mental acuity.

For the second set of doses done November 22-26, since we experienced no negative side effects in the first set we decided to increase the dosage a bit and to add 10 mg of BioPerine, a supplement that is reputed to magnify the effects and potency of flavenoids.  For five days starting on Thanksgiving we took 500 mg of Fisetin and 10 mg of BioPerine twice per day, for a total of 5 g of Fisetin.

This time. I did experience one negative side effect.  A few months ago, about 2 AM in the morning I awoke from a deep sleep and experienced a severe episode of vertigo.   I turned over in bed, and the the whole room seemed to tilt.  Suddenly, I didn't know which way was up.  I staggered to the bathroom and vomited.  The symptoms tapered off and disappeared in a few days, but it was a very distributing experience.

On the 2nd day of our 2nd Fisetin series, I experience a recurrence of that vertigo in the middle of the night, not as bad as my initial experience but still rather disturbing.  I tolerated this mild vertigo and continued the treatment.  My wife had no similar symptoms, and after my last dose I experienced no further vertigo symptoms.

On the positive side, following the second set of dosages I did feel very well, and very sharp and alert.  This past weekend I ran my Shetland Sheepdog Taliesin in an AKC Canine Agility Trial in Mt. Vernon, WA, and we did very well, qualifying in 7 runs out of 15 and getting various colored placement ribbons.  I was feeling quite sharp, and I even invented a new dog-handling technique that fixed an ongoing problem we were having.

Next week we will do the blood-work again, and I'll report any changes.

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  • I received an email recently from age reversal and it had a link to a video in which Bill Falloon gave an updated presentation.  In one of the slides shown in the video it showed the senolytic as dasatinib quercetin and fisetin.  That's the first I've seen him include fisetin with dasatinib.  I believe they are using combo for there study.  Does anyone know what dosage they are recommending?

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  • Karl Thanks.  I am aware of that study.  I looking for the dosage that Life Extension is using in its study wherein they use Fisetin and dasatinib and quercitin.  I've attached a slide from the video where Bill Falloon mentions it.  The slide is at 29:30 of the video which is at :

    https://www.youtube.com/watch?v=fPH0sBfUK5U&feature=youtu.be

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      • Karl
      • Karl.1
      • 1 yr ago
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      Mel I would think that life extension doesn’t have any more info than we do. You could use the dose from the study.

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      • Mel
      • Mel
      • 1 yr ago
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      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. 

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  • For group informational purposes.  I completed my first experiment with fisetin this weekend.  I weigh 157 lbs.  Took 2 grams of Swanson fisetin and 2 capsules of Life Extension Senolytic Activator.  No particular reason to add that other than I had ordered ten boxes some time ago, so I had it and just threw it into the mix.  I took this same cocktail over three days.  No dramatic effects were experienced.  Noticeably, a parallel to fasting where you feel a bit "charged" or mildly antsy and just want to do something.  I do have some non-arthritis joint pain in my back and hip and I was surprised to note that it eliminated that short term.  The following day it was back again.  Alleviated with second and third doses also.  This leads me to suspect an analgesic mechanism rather than a curative effect.  Also, just to note previously I had taken 8 of the LEF senolytic activator capsules and felt like I had five cups of coffee, short-lived jitters.  But no pain relief. 

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      • Karl
      • Karl.1
      • 1 yr ago
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      Dorian Gray thanks for the feedback. I would think it will take awhile to see the positive effects.

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  • Dan said:
    For example during a fast, at day 5 is when it's clinically been measured that heavy senolytic activity occurs.

     What's your evidence for this? I'm not aware of any evidence for fasting actually killing senescent cells, let alone a specific time-course.

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  • Latest Senolytic Sessions with Fisetin

        It has been 6 months since we last did senolytics with Fisetin and D+Q, and our body load of senescent cells has probably built up again, so it's time for more sessions.  This time, in the lead-up to this, I've been experiencing lower back pains and a "wry-neck" problem on the right side of my neck that interferes with sleeping and limits the amount I can turn my head while driving.  Popping Advil and Tylenol doesn't help much.   These are likely to be aspects of age-related inflammation (I'm 85), so I was curious as to whether the new senolytic session would have any impact on these symptoms.

        Yesterday and today my wife Pauline and I took 10 mg of BioPerine at 8 AM followed by 2 grams of Fisetin powder stirred into warm Trader Joe's extra-virgin olive oil at 9 AM.  The olive oil was put in a shot glass, heated in the microwave for 30 seconds, then put on a small digital scale while the yellow Fisetin powder was spooned in until an added weight of 2 grams was reached.  The result was stirred until the yellow powder was either dissolved or suspended in the oil, forming an unsavory-looking opaque green liquid.  This was drunk as thoroughly as possible, and the residue in the glass was scooped out with bread fragments and eaten, until the glass was clean.

        My observation this afternoon is that my back pains are gone and my stiff neck is much better, but not completely gone.  I also feel more energetic and alert.  This time (see previous reports above) there were no flu-like symptoms or other observed negative side effects, at least so far.

        We're doing AKC competition dog agility with our Shetland Sheepdog Taliesin at a facility north of Seattle this weekend, so I will also be able to observe how the senolytics affects our performance (which was a mediocre 7 Qs out of 16 runs last weekend).   We plan one more Fisetin session tomorrow, followed by two D+Q+F+P sessions, to be done in the next two weeks.

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      • JGC
      • JGC
      • 1 yr ago
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      Followup on Above

           At the dog agility competition I mentioned, we did better than in the previous competition with 9 qualifications (Qs) out of 18 runs and 3 more near misses (2 clean but overtime runs and 1 tail hitting last bar).  Still some lower back pain after sitting too long, but wry neck is gone.

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  • Anyone have any ideas where to get dasatinib without a prescription?  I do not live in Florida or another state where the Florida doctor can ship.  The anti aging site was hacked and bonhoa health will not ship to US or EU.

    Thanks

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  • I've tried several combinations of Fiestin with various  supplements.   Initial trial was with Fisetin and Qurecetin.    2 grams of each, twice a day for three days.   Learned that Quercetin has no senolytic value so switched to using Fisetin with Echinacea as an immune system booster on the assumption that it would increase microglia activity.  No immediate changes noted.   Third trial,  added Lecithin to the combination on the assumption that an emulsifier would increase the adsorption of Fisetin.  Noted improvements in cogitative functions, ambition, physical condition over next several weeks.  Now seems to have leveled off.   Wish someone would devise a simple means of measuring the senescent cells concentration and / or removal effectiveness.

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      • Dan Nave
      • Dan_Nave
      • 1 yr ago
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      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.

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      • JGC
      • JGC
      • 1 yr ago
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      Dan Nave 

           Who says that "quercetin is not senolytic"?  My understanding is the in the initial in vitro tests with cell cultures, both quercetin and dasatinib were found to show senolytic effects, but when they were combined into the D+Q cocktail, the senolytic effect was considerably stronger than the sum of the two individual effects.

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      • RAW
      • Ancient Sage
      • Robert_Weinhardt
      • 1 yr ago
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      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. 

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      • JGC
      • JGC
      • 1 yr ago
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      RAW 

      Read the link in my post above and the link that it provides.  The work was done by the Mayo Clinic and other institutions, and is as I described it.  Fisetin is better, but Quercetin has senolytic properties, particularly for the cells that line blood vessels.  There has been speculation and self-experiments with F+Q, but I am not aware of any studies in which the synergy of Fisetin + Quercetin has been rigorously investigated.

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      • RAW
      • Ancient Sage
      • Robert_Weinhardt
      • 1 yr ago
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      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.  

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  • Fisetin + Hydroxypropyl-Beta-Cyclodextrin? 

      Some of you may understand more about the arcane subject of biochemistry and molecular structure than does a simple-minded nuclear physicist like me, so perhaps you can answer a question about Cyclodextrins.

                             Beta-Cyclodextrin

        Cyclodextrins are a family of non-toxic glucose-based molecules (alpha, beta, gamma, ...) shaped like doughnuts.  They are hydrophylic (water-seeking) on the outside and hydrophobic and lipophylic in the doughnut hole.  I have read that these properties can be used to increase the bioavailability of water-insoluble supplements like the flavenoid curcumin.  It's a bit more complicated than that, however, because beta-cyclodextrin, which is about the right size for transporting such insoluble molecules, is so tightly bound that it also has water solubility problems.  Fortunately, this can be fixed by hanging  a propylene molecule on the basic beta-cyclodextrin molecule to make water soluble hydroxypropyl-beta-cyclodextrin.

        The supplement manufacturer Nature's Essentials of Suwanee, GA actually sells boosted versions of the supplements Tumeric/Curcumin, Resveratrol, and Melatonin that have hydroxypropyl-beta-cyclodextrin included for increased bioavailability.  I have bought and am taking these boosted supplements daily.  Unfortunately, Nature's Essentials does not sell versions of the senolytic flavenoids fisetin and/or quercetin that have been similarly boosted.

        So my question is, if I buy some hydroxypropyl-beta-cyclodextrin powder, mix it with fisetin or quercetin powder, and take this as a senolytic, will that have the desired boosted bioavailibility?  Or does one have to do some further chemistry to thread the flavenoid molecule into the doughnut hole?

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    • JGC I prepared a fisetin-cyclodextrin complex last year. Note I used gamma-cyclo instead of beta-cyclo. It's a bit trickier than just mixing the two together. You first need to dissolve the fisetin and then allow it to complex with the cyclo. I did this using ethanol, but it takes a decent amount to dissolve a dose. I also added piperine. You then add this to an aqueous cyclo solution (50:50 was what I used) and allow time to complex. However, it's important to remove the ethanol afterwards unless you want alcohol poisoning. A potential problem is that fisetin is extremely temperature sensitive, so I used a rotary evaporator, which allows you to evaporate the ethanol at low temp. You could ingest at this point. I took it a step further and lyophilized the solution to create a powder, which I stored for a while before dissolving in some water and ingesting.

      The dose I ingested was probably less than 400 mg fisetin (started w/ 500 mg but lost some during prep). I used ultra-pure compounds that were pretty expensive ($500 per dose!). I verified complexation in the lab using FT-IR. I was doing this on the side to see if it was effective and might be marketable, but the business relationship I was in didn't work out and I haven't done anything with this since. However, I recently gave my father a dose of fisetin mixed with olive oil (the cyclo is just too time consuming and needs scaled up equipment for bigger doses). He gets his bloodwork done a lot because he has leukemia (CLL), so I was really surprised when the very next test (a week after his last dose) he saw the biggest drop in lymphocytes he's ever had. Although an N of 1 means very little, his result raised my interest and I'm considering a making a large batch. Would love to hear your own experience.

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      • JGC
      • JGC
      • 1 yr ago
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      Jacques Mathieu 

      That's really interesting work, Jacques.  I received my order of 25 g of 2-Hydroxypropyl-beta-cyclodextrin last week, but I haven't done anything with it yet.  My plan was to first dissolve a stoichiometric quantity of 2.44 g of the cyclodextrin in water, then add 500 mg of fisetin powder and leave it overnight to combine with the cyclodextrin and dissolve.  Do you think that would work, or would one absolutely need to use the ethyl alcohol, as you did?

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    • JGC it's hard to say. When I add the fisetin/ethanol to cyclo/H2O, I assume some precipitates out, but almost all is eventually complexed. Without a solvent I don't know if complexation will occur, or if the fisetin will just aggregate. You could test using a small amount first - if it's complexed it shouldn't leave much residue.

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  • Partial Answer

        I found a paper by some researchers in Thailand in which they actually do a computer simulation to investigate how Fisetin threads through the hole in Beta-Cyclodextrin and how this effect the interaction with water.  There are four possible configurations, and they calculate their relative probability of formation.  Apparently cofigurations II and III are the most soluble because the "B" region is more enclosed.  Here's a figure:

     The bottom line seems to be that mixing Cyclodextrin and Fisetin in an aqueous solution does produce dual molecules with improved water solubility.  They use unmodified Beta-Cyclodextrin, not Hydroxypropyl-Beta-Cyclodextrin, and they do not give any solubility values, but after all, its a simulation.

         On this basis, I just ordered some Beta-Cyclodextrin and some 2-Hydroxypropyl-Beta-Cyclodextrin from Amazon.  I intend to do some self-experiments with the aqueous mix, and maybe try it with Quercerin also.

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      • JGC
      • JGC
      • 1 yr ago
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      Followup

      My experiment with Hydroxypropyl-Beta-Cyclodextrin (HBC) and Quercetin was a failure.  I dissolved the HBC in water, warmed it in the microwave, and then added a stociometrically correct amount of Quercetin.  It made an opaque mustard-colored liquid that, after a few hours, resolved itself into a yellow transparent liquid with a thick layer of yellow powder on the bottom.  Repeated heatings and stirrings made no change in the situation.  Finally, it went down the sink.

      It has been suggested that one should dissolve the Qurecetin (or Fisetin) in 200 proof alcohol before mixing with dissolved HBC.  Partly because of the COVID-19 self-isolation, I haven't tried that yet.

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    • JGC fisetin is only soluble in ethanol to 5 mg/ml, so unless you find a way to remove it you would need to ingest 400 ml ethanol to get a 2 g dose of fisetin. I suspect that would kill most people. I used a rotary evaporator to keep temperature low as fisetin is very sensitive to temperature

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  • I received dasatinib today from antiaging.clinic   - I paid via wire (which minimizes my risk as they did not receive my bank info.  Via wire was the only method offered.  

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  • I was able to get mine from Bonhoa.  

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  • I don't think there's any evidence that piperine/BioPerine enhances the 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. Bath1 Best Bathroom shower wall panels

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      • Dan Nave
      • Dan_Nave
      • 1 yr ago
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      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.

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      • JGC
      • JGC
      • 1 yr ago
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      Philip V. Anstett 

      It's deja vu all over again.  If you scroll up to posts from one year ago, you will find that I already answered this question, as asked by Iðunn, and gave a reference.  

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  • The Mayo Clinic did multiple human Fisetin trials on elderly people, Google it.  There dose was 20 mg/kg.  for 2 consecutive days.  I weigh 85 kg so I took 1700 mg for 2 consecutive days.  Took 1 tablespoon olive oil and pepper to help with bio-availability. (not in Mayo trial)

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  • I'm just to the west of you on Whidbey Island.  At 190lbs the dose is 1,700 milligrams or 1.7 grams.   I found 500 milligram capsules.  I take it with querctin.   I'm 69.5 so we'll see.  

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

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

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

    I don't try to increase bioavailability. I just pop 12 pills, usually Swanson, with a glass of water. I usually have it coincide with a 24 hour spiritual fast of no food or drink each month, taking it before start and then after. I take the second round of the month either in the morning or evening, basically whenever I remember, so sometimes it's on an empty stomach, sometimes not, but I eat often, so usually I have some food in me.

    My results have been obvious enough and consistent enough with just taking the pills that I feel no need to try to improve bioavailability. (I do take a tablespoon of omega 3 fish oil every day, so that could help!) I don't always take them together, but as I said, I have personally seen a big difference in fine lines and wrinkles before taking fisetin and after, regardless of when I take it.

    My uncle started taking 1500mg/day for 2 days each month, and he loves it. He has arthritis in his fingers, and he said that buttoning his top collar button was always really painful, but now it is no longer painful. I didn't tell him about my arthritis before he asked what I thought of fisetin (I didn't know he was taking it). I am usually very conservative in telling others about self-experimentation because I believe it's best done by those who read the studies and understand the risks rather than someone who just takes the word of a friend or family member.

    My husband takes it with me. He finishes the bottle- 1800mg/day for 2 days every 2 weeks. He grimaces every time I hand him the bottle and a glass of water, but he takes it. He had severe sepsis a year ago last December where he was a day away from dying before diagnosed. Since then, we started him up a few months later on fisetin again. He said his muscles felt sore like after a good weightlifting workout, but that was his only side effect.

    For reference, I also take 4500mg omega-3 daily as indicated above, Ellysium (NR), and just in May started taking 1 pill of Jarrow's Broccomax and 1 pill of Biotivia's Pteromax daily. I added the last 2 in order to promote daily mild stimulation of the NRF2 pathway and its cellular antioxidant properties, but also because when my husband and I took Pteromax and Mitoq 7 years ago, we noticed that neither of us got sunburned, and my husband normally burns very easily. We stopped taking Pteromax because it became unavailable for a while. Mitoq alone didn't have the same effect. We later added Biotivia's Trans resveratrol, and that didn't have the same effect either. We dropped the Trans resveratrol and only took Mitoq for a while, but stopped that shortly after starting fisetin, mostly because of cost and not seeing as significant results as with fisetin. With Pteromax again available, I decided to try it for the summer and see if it has a similar sun protective effect like we experienced before, since I mildly burned my face a few weeks ago on a hike and was reminded of the need for sun protection.

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    • 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.

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
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      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. 

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    • 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.

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      • Joe smith
      • Joe_smith
      • 1 yr ago
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      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.

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
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      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.

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
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      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.

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      • Joe smith
      • Joe_smith
      • 1 yr ago
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      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?

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
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      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!

      Like 1
    • 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,"

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    • 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.

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      • Joe smith
      • Joe_smith
      • 1 yr ago
      • Reported - view

      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?

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

      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

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      • Joe smith
      • Joe_smith
      • 1 yr ago
      • Reported - view

      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!

      Like
    • 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?

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

      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.

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
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      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.

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      • Joe smith
      • Joe_smith
      • 1 yr ago
      • Reported - view

      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. 

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
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      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.

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      • Joe smith
      • Joe_smith
      • 1 yr ago
      • Reported - view

      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.

      Like
  • This encompasses 3 senolytics, Fistein, Azithromycin, and Dasatinib.

    Dr. Green has a new website targeting https://senolyticstreatment.com/. He points out that there are 4 different types of senolytics. (zombie cells) and there are different treatments which target each one. He suggests using Fistein 1500 mg x 3 consecutive days x every 3 months for aging purposes. (they are using 20mg/kg in Mayo Clinic trials x 2 consecutive days in elderly patients, as yet unpublished results) Azithromycin 500 mg x 3 spread over 1 week x every 3 months. (targets fibroblast) Dasatinib 100 mg x 3 consecutive days x every 3 months. He has set up a compounding pharmacy to make Dasatinib affordable for his patients. I order powder from China. The frequency is more often for treating specific diseases. He believes that Rapamycin slows down senescence, but cannot remove them. Please refer to his website for additional info.

     

    The following is an interview by Dr. Blagosklonny for his Aging article.

     

    Aging, COVID-19 and more   Interview with Alan S. Green, M.D., who practices medicine in New York state, and who, in 2016, began to treat patients with rapamycin (Sirolimus), an anti-aging drug. Interview was taken via email on March 31, 2020, by Editor Dr. Blagosklonny for the journal Aging. Question 1: How many patients and for how long have you treated with rapamycin? Answer 1: Patient number 1 is myself, treated for 4 years. An additional 480 patients treated from 3 years to present. Question 2: Rapamycin (Sirolimus) and its analog Everolimus are FDA-approved drugs used in millions of patients with several severe diseases for many years. Based on a few murine models, some people believe that rapamycin may have unacceptable side effects, even though rapamycin extended the health span and life span of mice in these studies. Have you noticed side effects in your patients? Answer 2: Rapamycin in older persons is very beneficial for the brain, heart, muscle, joints, insulin sensitivity, decreasing visceral fat, and prevention various age-related diseases. Rapamycin is a very potent drug and good results dependent on proper dose and interval. My patients show good results with sirolimus [rapamycin] 2 to 8 mg once a week. Major side effect in that range is decrease in activity innate immune system. To extent chronic inflammation is harmful in aging, this is generally beneficial. The basic researchers I follow are Matt Kaeberlein and Veronica Galvan who have recently shown excellent protection against normative aging in heart (dogs) and brain (rats). I have observed those same beneficial results in older humans. Question 3: Z-pak (Azithromycin) that you prescribed to your patients (just in case of possible bacterial complications) is now considered a promising drug to treat COVID-19. Would you like to comment? Also, it was published in Aging by Sargiacomo et al, that Azithromycin and hydroxychloroquine are senolytics, drugs that selectively kill senescent cells. Answer 3: A natural tension always exists between treating physicians who use standard of "reasonable degree of medical certainty" and government scientists who use standard of "definitive proof" and dismiss anything short of definitive proof as "anecdotal". (Perfect is the enemy of Good). As regards recent paper in Aging by Sargiacomo et al, that was an extraordinary important paper connecting COVID-19, aging, senescent cells and senolytics. In 2017 paper, Blagosklonny noted role of Doxycycline and other antibiotics as anti-aging drugs. Azithromycin looks like major drug in prevention and treatment COVID-19. I use same dose used in Cystic fibrosis study (500 mg 3 times a week) in which Azithromycin appears to be acting as senolytic.

    https://paperchase-aging.s3-us-west-1.amazonaws.com/interviews/Aging%2C+COVID-19+and+more-+Interview+with+Dr.+Alan+S.+Green.pdf

    Like 2
      • JGC
      • JGC
      • 1 yr ago
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      Van 

      The paper to which Dr. Green refers in his interview, by Sargiacomo, Sotgia, and Lisanti, makes an interesting case for a strong link between COVID-19 mortality and age-related senescent cells.  This brings up an interesting question:  Does anyone on this Forum know of anyone who has done D+Q and/or Fisetin senolytic sessions (to clear their burden of senescent cells) and then come down with COVID-19?

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      • Van
      • Van
      • 1 yr ago
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      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/

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      • JOHN
      • JOHN.1
      • 1 yr ago
      • Reported - view

      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. 

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      • Randy B
      • Randall_Bagrowski
      • 1 yr ago
      • Reported - view

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

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      • JOHN
      • JOHN.1
      • 1 yr ago
      • Reported - view

      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.

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      • GEdwards
      • GEdwards
      • 1 yr ago
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      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.

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  • Hello Van. Thanks for this info. Are you able to advise the name of your Chinese supplier for dasatinib? Being in Canada, I cannot see, or be prescribed drugs by Dr. Green and don't know of any age-reversing docs up here. At the moment I am using several "natural" products that replicate a natural rapalogue from Germany as well as berberine/PQQ, Niagen and resveratrol. Due to almost daily migraines, I cannot fast beyond 12 hours. Applying apocynin to specific areas but not seeing or feeling any difference. My main problem seems to be lack of energy, which I attribute to having a few too many zombies.  Many thanks!

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      • Van
      • Van
      • 1 yr ago
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      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.

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      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 1 yr ago
      • Reported - view

      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. 

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      • David H
      • David_Hanson
      • 1 yr ago
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      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.

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      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 1 yr ago
      • Reported - view

      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.

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      • Van
      • Van
      • 1 yr ago
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      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.

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      • Van
      • Van
      • 1 yr ago
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      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.

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      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 1 yr ago
      • Reported - view

      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...

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      • Van
      • Van
      • 1 yr ago
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      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

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      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 1 yr ago
      • Reported - view

      Van  Thanks. I will try that.

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      • GEdwards
      • GEdwards
      • 1 yr ago
      • Reported - view

      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

      Like
      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 1 yr ago
      • 1
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      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!

      Like 1
    • 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.

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      • Michael
      • Michael.1
      • 1 yr ago
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      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)

      Like
      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 1 yr ago
      • Reported - view

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

      Like
      • Michael
      • Michael.1
      • 1 yr ago
      • Reported - view

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

      Like
      • GEdwards
      • GEdwards
      • 1 yr ago
      • Reported - view

      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

      Like
  • I ordered my Dasatinib and Fisetin powders from the following Alibaba supplier.  https://hhdpharm.en.alibaba.com/company_profile.html?spm=a2700.galleryofferlist.0.0.362a73f6ugETpH#top-nav-bar.  Used Emily.  This is the same supplier that furnished Rapa for other members in this forum.  Need to make sure that you get 98% Fisetin vs 50%.  Both are sold.  Dasatinib is 99% only, I believe.  I paid $245 for 5 grams Dasatinib, and 50 grams of Fisetin.  That includes $50 Fedex shipping.  So cost is Dasatinib = 120/5= $24 gram Fisetin   =  120/50 = $2.40 gram.  This includes shipping.  Saved on shipping by ordering both at same time.  This does not include Visa CC charge of 3% = $7.20 which is really the cheapest way to pay, and you have CC guarantees.  Will update group once I receive it.  Noticed that Fisetin on line is starting to get expensive vs just a few months ago.  The word is getting out.  It takes around 5 grams for one quarterly dose of Fisetin, so those little 30 tab bottles (100mg) they sell are worthless, and expensive.  I had no problem with receiving my Rapa order from China which was only a business size envelope delivered by Fedex, but this one is going to be larger.  Will have to wait and see.  For those without experience using powders, this is the way to go.  Buy a jewelers scale that measures to .001 gm. = 1 mg. for about $30.  Usually includes calibration weights.  The lower the max weight, the more accuracy you get.  Mine has a max weight of 20 grams, but goes to 1/1000.  You only need to weigh once a week for Rapa and quarterly for  senolytics.

    Like 3
      • David H
      • David_Hanson
      • 1 yr ago
      • 2
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      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.

      Like 2
      • Van
      • Van
      • 1 yr ago
      • Reported - view

      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

      Like
  • I'm hearing that sulforafane may be more powerful than quercetin?  So why not take both.

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

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

      Like
  • Fairy8i8 Per Dr Rhonda Patrick Broccomax is pretty much useless. When tested it doesn't contain at all what its labels claims; Throne contains 10% claimed amounts  and Avmacol 40%. 

    Like
    • 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?

      Like
      • David H
      • David_Hanson
      • 1 yr ago
      • Reported - view

      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. 

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      • Joe smith
      • Joe_smith
      • 1 yr ago
      • Reported - view

      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.

      Like
      • David H
      • David_Hanson
      • 1 yr ago
      • 1
      • Reported - view

      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.

      Like 1
      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

      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. 

      Like
      • Joe smith
      • Joe_smith
      • 1 yr ago
      • Reported - view

      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?

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      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

      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. 

      Like
      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

      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.

      Like
      • Joe smith
      • Joe_smith
      • 1 yr ago
      • 1
      • Reported - view

      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.

      Like 1
      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

      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. 

      Like
    • 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.

      Like 1
      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • Reported - view

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

      Like
      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • 1
      • Reported - view

      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.

      Like 1
    • 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.

      Like 1
      • Fairy8i8
      • Fairy8i8
      • 1 yr ago
      • 1
      • Reported - view

      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.

      Like 1
      • Joe smith
      • Joe_smith
      • 1 yr ago
      • 1
      • Reported - view

      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.

      Like 1
      • Joe smith
      • Joe_smith
      • 1 yr ago
      • 1
      • Reported - view

      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.

      Like 1
    • 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

      Like
      • J Man
      • J_Man
      • 6 mths ago
      • Reported - view

      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.    

      Like
      • Fairy8i8
      • Fairy8i8
      • 6 mths ago
      • Reported - view

      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.

      Like
      • Fairy8i8
      • Fairy8i8
      • 6 mths ago
      • Reported - view

      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.

      Like
      • J Man
      • J_Man
      • 6 mths ago
      • Reported - view

      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.  

      Like
  • A UK doctor did his evaluation of the best sulforaphane to purchase: https://www.youtube.com/watch?v=qAb1eQbRAe0&t=18s

    Like
  • David H

    Dr Brad Stanfield (New Zealand) is great and I follow him as well. My comment to him was the same as on this thread. You just can't read ingredient list and believe manufacturer. The supplements in the US are unregulated; hence, no oversight and you need the third-party testing. With respect to Dr. Rhonda Patrick's second statement about efficacy, it is not her personal opinion but it is indeed fact and test based. It came from Jed Fahey at John Hopkins. Basically it seems that Dr. Patrick first  sprouted her broccoli then she became too busy and started uing BroccoMax instead. At this point she may have made a few statements about it but then subsequently checked with Dr Fahey and found out what's really in the product and changed her mind on it. The moral of the story: don't put any supplement or medicine in your mouth unless manufacturing monitored by FDA / equivalent reg body in other countries or reliable lab tested.  

    Like 1
  • I need some help on this topic. My aim is to take take 1.5 g of Fisetin on 3 consecutive days.

    Today was the first day. I took 15 capsules a 100 mg after a 20h water fast with 2 spoons of native olive oil, a capsule of curcumin containing perperin and an omega-3 capsule. First i wanted to dissolve Fisetin within the olive oil but seeing the small capsules i thought just to swallow it with oil, no problem. Afterwards i ate 500g of strawberries and ate as usual 1 h later.

    So far i recognized some slight stomach pain. Any hints how to improve the intake besides dropping the strawberries? Should i dissolve Fisetin completely in some oil? Take everything on an empty stomach or after a meal, at the beginning of a fast or at the end, or split the intake?

     

    Thank you in advance.

    Like 1
      • Jennifer Smith
      • We are all responsible for our own health, wealth, and happiness
      • Jennifer_Smith
      • 1 yr ago
      • Reported - view

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

      Like
  • I'm about to try fisetin. Has anyone used that available on Amazon (Axe-NIC)? It says Pharma Grade, not for human consumption. The Philly company won't ship to Canada. Any Canadians here? The RevGenetics 500 is $99 for us on Amazon plus $10.99 shipping.  I just lost my account due to the virus, so don't want to go overboard on something that's encapsulated and costs much less over the border. Thanks all.

    Like
      • JGC
      • JGC
      • 1 yr ago
      • 1
      • Reported - view

      Antonia Gauer 

      Last year I ordered 100 gm of >98% pure powdered Fisetin from VitaSpace for $190 plus $6 shipping.  That's $0.19 for 100 mg, still a lot better than $0.47 per 100 mg from Drs Best.  Further, it's already in powder form, removing the need for breaking open capsules before dissolving in olive oil.  They are located in New York, and I have no idea if delivery to Canada is a problem.

      Like 1
      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 1 yr ago
      • Reported - view

      JGC 

      Like
      • David H
      • David_Hanson
      • 1 yr ago
      • Reported - view

      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.

      Like
      • Moonlitnight
      • Medical Writer working on age reversal for over 20 yrs
      • Moonlitnight
      • 1 yr ago
      • Reported - view

      JGC Thank you. I will try that one.

      Like
      • JGC
      • JGC
      • 1 yr ago
      • Reported - view

      David H 

      I don't find ageless.one on ebay.  Do you have a link?

      Like
      • David H
      • David_Hanson
      • 1 yr ago
      • Reported - view

      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"

      Like
      • Greg
      • Greg
      • 1 yr ago
      • Reported - view

      David H 

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

      Like
  • I'm hearing that berberine and metformin up regulate autophagy where the body recycles garbage, including senescent  cells.

    Like 1
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