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Fisetin: Senolytic!

fisetin senolytic

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#91 Ducky-001

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Posted 08 October 2018 - 05:19 PM

I might do the olive oil thing too, makes sense.  I don't  think it's wise from a testing front to keep taking other supplements at the same time.  It confuses the situation.  But also, the whole point of this hype train is that Fisetin seems to be quite effective by itself, so I don't see the need to add in various stacks of other senolytics.  Maybe this is a legacy of the D+Q thing, because we have been told over and over that one senolytic is good for some tissues and not others, so a combination is needed.  Well, this is probably not true with Fisetin.  They tested quite a few tissues and it was effective in all of them as a senolytic.  I am quite happy to make things simpler when it can be done, and therefore don't plan to take any other senolytics until or unless something better and more proven comes along.

 

I added Quercetin just because I have a lot of it, and not so much Fisetin. It may or may not do anything. Will do only Fisetin today.



#92 OP2040

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Posted 08 October 2018 - 05:42 PM

"In the present study, the results of ALT and AST assays suggested that the fisetin dosage of 223 mg/kg may aggravate liver burden due to poor bioavailability. Further studies regarding increasing the bioavailability and reducing dose are required"

 

That's a huge amount to take - who in their right mind takes that much. Also, Fisetin has not been overlooked and some of these posts surprise me. I've been taking 100mg daily for several years, ever since I found out all the potential benefits it had. The results of the study only make take this stronger.

 

I think Fisetin has been on most people's radar.  But this is an exceptional study that changes a lot, hence the excitement.  Specifically it changes the idea that we need multiple or overly dangerous senolytics to do the job that Fisetin may be able to do alone and cheaply.  That is a huge difference compared to what we knew before, which was "well, Fisetin looks promising for this or that and it's a senolytic among many senolytics". 

 

Having said that, I'd love to hear more of your experience with it.  Any noticeable or measurable improvements since you started taking it?


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#93 brasscupcakes

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Posted 08 October 2018 - 05:51 PM

Hi there, questions: 

1. Dosage -- it was my possibly incorrect understanding that in calculating a mg / kg dosage with the potential for oral efficacy for humans, skin surface had to be calculated in addition to weight. Wrong?  

2. Senescence -- if you use Fisetin on a very occasional basis as part of a clean-up team, will you still get (or will there still be a potential to get) transient improvements in thought focus, memory, etc.

3. Okay -- this is a little squicky but ... supposedly only 50% of a drug delivered by the rectal route undergoes first-pass metabolism in the liver. Might rectal suppositories serve as a relatively effective means of administration until a better one is developed? It doesn't bypass the liver altogether and it's not a fun way to take your supplements, but you can formulate them at home or have a compound pharmacy make them for you. 

 

Also, an observation: Cheap is relative. No study ever that I know of has shown efficacy in humans at the 100 mg a day dosage suggested on the bottle of encapsulated brands of Fisetin. If you hold with the 10-to-25 mg / kg per day ratio (extrapolated mostly from effective rodent studies) it rates as costly for people in most income brackets. 

I shopped kilo prices for importing it over a year ago and they were quite high but I am happy to help with pricing research in future if there is interest in a group buy. 

 

Also: I thank you all. While I seldom ever post, I have learned a lot in these forums and enjoyed myself here immensely. 


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#94 OP2040

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Posted 08 October 2018 - 06:49 PM

Hi there, questions: 

1. Dosage -- it was my possibly incorrect understanding that in calculating a mg / kg dosage with the potential for oral efficacy for humans, skin surface had to be calculated in addition to weight. Wrong?  

2. Senescence -- if you use Fisetin on a very occasional basis as part of a clean-up team, will you still get (or will there still be a potential to get) transient improvements in thought focus, memory, etc.

3. Okay -- this is a little squicky but ... supposedly only 50% of a drug delivered by the rectal route undergoes first-pass metabolism in the liver. Might rectal suppositories serve as a relatively effective means of administration until a better one is developed? It doesn't bypass the liver altogether and it's not a fun way to take your supplements, but you can formulate them at home or have a compound pharmacy make them for you. 

 

Also, an observation: Cheap is relative. No study ever that I know of has shown efficacy in humans at the 100 mg a day dosage suggested on the bottle of encapsulated brands of Fisetin. If you hold with the 10-to-25 mg / kg per day ratio (extrapolated mostly from effective rodent studies) it rates as costly for people in most income brackets. 

I shopped kilo prices for importing it over a year ago and they were quite high but I am happy to help with pricing research in future if there is interest in a group buy. 

 

Also: I thank you all. While I seldom ever post, I have learned a lot in these forums and enjoyed myself here immensely. 

 

Hi Brass,  I wish you would post more, these are some thoughtful questions.

 

1. The formula for HED does take into account skin surface already, so most people just use the formula.  For mice it is:

     HED mg/kg = Mouse mg/kg (3/37)

     So for the 20 mg/kg that is a good starting point here, it would be HED = 1.62 mg/kg  which would then depend on your weight.

2.  Almost all of us just go by the studies, and there are good studies and bad studies, and unfortunately most are based on mice.  This

      means there is a high level of interpretation built into things, which is why we are always debating the details.  IMO this study was

      very good.  If the study is translatable to humans, and other similar studies, then yes you should get improvements in all those

      things with intermittent high doses.  But that is a big if.. and some like myself find it very compelling while others may not.

3. I'm so glad you brought this up because I have in the past as well, and not too many people cared to talk about it.  IMO it is a

    perfectly valid way to try to increase bioavailability.  I tried it with Trehalose, which has similar bioavailability issues, but it was tough

    to keep up day to day.  However, the beauty of the Fisetin is that you really shouldn't have to take it more than once a year, and

    probably not even that much.  I am thinking about this possibility as well.  The one other drawback is that you have to hold it in, and

    yes this is a bit "squcky" lol, but that means you should definitely try to do it on your #2 off-times. 

 

The reason I've been claiming it is cheap is because it only needs to be taken at most once a year if your goal is to clear senescent cells.  Yes, two bottles is a pretty sizable one-time hit, but compared to daily supplements, it comes out much cheaper in the end.  I think a lot of people are planning to make it into a daily supplement, but I don't see why if the goal is to clear senescent cells periodically. 


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#95 Oakman

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Posted 08 October 2018 - 07:07 PM

I think Fisetin has been on most people's radar.  But this is an exceptional study that changes a lot, hence the excitement.  Specifically it changes the idea that we need multiple or overly dangerous senolytics to do the job that Fisetin may be able to do alone and cheaply.  That is a huge difference compared to what we knew before, which was "well, Fisetin looks promising for this or that and it's a senolytic among many senolytics". 

 

Having said that, I'd love to hear more of your experience with it.  Any noticeable or measurable improvements since you started taking it?

 

Just a bit of counterpoint concerning the renewed excitement about Fisetin...because as wonderful as the new research all sounds...does it really change a lot of what is known?

 

1) This new study was done in mice, as we all know, which does not necessarily mean it works in humans to the same extent, or at all.

2) Fisetin is found in many fruits and vegetables, such as Strawberries, Mangoes, Cucumber with skin, Apples, Persimmons, Kiwi, Peaches, Grapes, Tomatoes, Onions, etc.

3) As common to so many foods, why has no one has noticed anything before relative to their aging after consuming them in quantites?

4) There is regularly a study or studies done that show great anti-aging effects in vitro on cells or in vivo in small lab animals with some natural or derived compound or other. Yet people are still aging and dying normally.

5) If this is so good, so unique, then what about all the other age-defying compounds in the literature? Do they not fit into the HUMAN aging picture as other researchers believe they have shown thru their own research?

6) Last, and most notably, the media LOVES to find the latest research on aging, and blow it all out of proportion to reality and offer to the unwashed masses the possibility of eternal youth against all odds. Google shows this happening right now to fiestin.

 

My suggestion is that fiestin, good as its possibilities MAY be, is simply one more small but important piece of the puzzle towards limiting aging to a graceful minimum. Perhaps in combination with other molecules, the maximum benefit would be obtained in humans... or at least something noticeable... which WOULD be exceptional!

 

Having taken fiestin for quite some time, although not in large doses, I couldn't say much of anything about it, good or bad. As is said, "The dose makes the poison", and I would be sceptical of taking large amts of this from a safety perspective. Nevertheless, I'm truly interested in all of you that are! I'm all for N=1 experimentation....Bravo!

 

Perhaps we can develop some educated ideas about combinations with other molecules worth investigating and trying that would intensify the benefits? This might allow using less fiestin and/or over a longer period with less possible side effects?


Edited by Oakman, 08 October 2018 - 07:07 PM.

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#96 smithx

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Posted 08 October 2018 - 08:03 PM

The study I initially quoted was done on mammalian tissue and therefore much more likely to be relevant to humans than a test done on bacteria, like the Ames test. Just discounting the evidence of double-strand breaks and chromosome loss out of hand seems reckless and ill-advised to me.

 

Pharma companies and regulatory agencies seem to agree with this too, given that the Comet test has become a standard compared to the Ames test, and some compounds which do not show mutigenicity on the Ames test do show it in Comet. This deficiency of the Ames test is one reason why Comet has become more widely used:

https://www.scienced...383571814002575

 

Also, it was pointed out to me that Fisetin actually did show mutigenicity in an Ames test:

http://citeseerx.ist...p=rep1&type=pdf

 

I am not saying people should avoid taking Fisetin, however there is evidence that at high doses it may be a non-specific agent of DNA and  chromosome damage.

 

 


Edited by smithx, 08 October 2018 - 08:09 PM.

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#97 OP2040

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Posted 08 October 2018 - 08:06 PM

I think it changes a lot because almost all the studies on other senolytics were also done on mice, and there was no lack of enthusiasm.  Specifically, it changes two things that are very important IMO.  First, it shows that, in mice, Ficetin is probably the most potent senolytic known. Second, it shows this effect in a multitude of tissues, which is something that has plagued the senolytic scene for quite some time now.  There was endless debate about combinations and which tissues are being targeted by which compound. 

 

Most of your statements seem to boil down to "this seems too common to be something important". 

 

For the record, this was by no means headline news.  The news always claims this or that as a cure for aging.  But we are on a forum of people who specialize in this sort of thing, so I feel no need to worry about people thinking that. 

 

However, it is NOT hype to say that, with some tweaking, this could be the answer to one of the 9 hallmarks of aging.  If it eliminates most senescent cells in a broad class of tissues in humans at some dose, then by definition that hallmark can be checked off.  Now, that hallmark may not mean as much as we thought, and it's rightly not considered a primary hallmark.  But it is a big deal and we are much closer to that goal after this study than before it.


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#98 smithx

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Posted 08 October 2018 - 08:28 PM

I see that someone marked my last comment, which cited two papers, as "ill-informed". Rather than being "ill-informed" I am actually trying to inform people!

 

I know that everyone would love to find a safe compound that would work against the effects of aging, but ignoring evidence that a compound could be harmful is just wishful thinking, and criticizing someone who presents evidence of potential issues is not a productive way to work together towards solutions.

 

 


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#99 OP2040

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Posted 08 October 2018 - 08:43 PM

The study I initially quoted was done on mammalian tissue and therefore much more likely to be relevant to humans than a test done on bacteria, like the Ames test. Just discounting the evidence of double-strand breaks and chromosome loss out of hand seems reckless and ill-advised to me.

 

Pharma companies and regulatory agencies seem to agree with this too, given that the Comet test has become a standard compared to the Ames test, and some compounds which do not show mutigenicity on the Ames test do show it in Comet. This deficiency of the Ames test is one reason why Comet has become more widely used:

https://www.scienced...383571814002575

 

Also, it was pointed out to me that Fisetin actually did show mutigenicity in an Ames test:

http://citeseerx.ist...p=rep1&type=pdf

 

I am not saying people should avoid taking Fisetin, however there is evidence that at high doses it may be a non-specific agent of DNA and  chromosome damage.

 

Ames tests are not meant to be used to determine what may cause cancer.  In your defense, you are not saying exactly that.  But I think you are still hoping that scary buzz words like mutagenicity will be enough to scare people away from a natural, effective, and most of all available substance.  As far as I'm concerned, tests on flavonoids that show mutagenicity in a lot of them can at most be considered a scientific curiosity and should probably be tossed in the bin.  That's not how cancer works.  And even if it was, Fisetin was much less mutagenic than Quercetin.

 

Just to demonstrate how absurd it is to interpret a study like this as a warning, most flavonoids are known for their anti-cancer activity in vivo,  Green tea, for example has no less than three mutagenic flavonoids, one of which is quercetin.  There are quite a few studies showing the anti-cancer effect of flavonoids, and especially Fisetin, in vivo!!  I don't know all the molecular mechanisms, nor do the studies, but results are results.  My guess is that many senolytics will show as mutagenic because they preferentially kill cancer cells, implying that the dna damage is part of that preferential killing.  Here's a good study to get started down that path:

 

https://onlinelibrar.../mnfr.201600025

 

 

Dietary flavonoid fisetin (3,3′,4′,7‐tetrahydroxyflavone) found in many fruits and vegetables has been shown in preclinical studies to inhibit cancer growth through alteration of cell cycle, inducing apoptosis, angiogenesis, invasion, and metastasis without causing any toxicity to normal cells.

 

I'm not going to look up a huge number of studies because it should be patently obvious that the studies you posted and the whole mutagen controversy is a gross error brought on by extreme reductionism.

 

Again, you are clear to say that you aren't trying to dissuade people.  But then why post the same sneaky agenda twice?  You are posting facts, but you clearly want to lead people to false conclusions.  I won't go so far as to accuse you of having an agenda.  Maybe you are just paranoid about cancer.  If that is the case, then you can thank me for allaying your fears.


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#100 smithx

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Posted 08 October 2018 - 08:52 PM

Firstly, I never mentioned cancer. I pointed out a study showing that fisetin was associated with double strand DNA breaks and chromosome loss. Many other issues can result from this sort of damage besides cancer.

 

Secondly, flavonoids seem to be beneficial in small doses, but what is being proposed here are megadoses, and it seems quite likely that megadoses could cause non-specific genetic damage. 

 

Also, what's with the ad-hominem attitude. You've used words like "nonsense", "sneaky", "agenda","paranoid", "false conclusions", etc. repeatedly. Attacking people for pointing out anything that disagrees with you is sucky behavior and shouldn't be tolerated in any serious discussion.

 

Why would I have an agenda? Why would I be sneaky? Why would I want to lead people to false conclusions? It's just crap to attack people like you're attacking me. Or is this how things work in the Trump era?

 

I'm presenting information. There is evidence that large doses of these compounds could be problematic. Use it as you will, but just discounting it, running over it, and trying to demonize anyone that presents information that may disagree with you is not productive.

 

 


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#101 OP2040

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Posted 08 October 2018 - 09:08 PM

The reason for the attitude is because you are posting facts without the proper context, thus inviting people to come to the wrong conclusions on their own.  It doesn't matter if your intention is to lead people to believe it is cancer-causing, damage-causing or just an unsophisticated "bad".  All of these conclusions are very wrong based on the science, and I think you know that because you seem intelligent and well-read.  So what am I supposed to conclude from that? 

 

I have no idea why you would have an agenda.  But apparently this forum is influential enough that we have movers, shakers and supplement makers coming here and communicating with all of us.  So someone coming here with an agenda is nothing new at all.

 

I am not running over it or around it, I destroyed the hypothesis that flavonoid mutagenicity can mean anything negative in vivo, and in fact may even be an anti-cancer mechanism.  The idea that you are just "presenting information" is a classic way to misinform people.  You either believe in what your saying or you don't.  So I'm asking you, do you believe flavonoids at the doses we are discussing cause cancer? 

 

As for the high doses, every single thing on this planet is toxic at some high enough dose.  Toxicity studies are much more relevant than Ames tests, and they have been done at quite high doses for most flavonoids, including FIsetin.


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#102 smithx

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Posted 08 October 2018 - 09:16 PM

The reason for the attitude is because you are posting facts without the proper context

 

The article I quoted is specifically ABOUT fisetin:

https://www.ncbi.nlm...les/PMC3689181/

 

And implying that I have some agenda because I might be working for some evil company is both aggressive and dumb, particularly if you were to look at my post history.

 

I may be "paranoid" but if something is known to cause chromosome loss and double strand breakage, I will err on the side of caution rather than to just jump in and assume that this damage is maybe somehow confined to cancer cells and therefore beneficial.

 

Again, go and do what you like, but if something causes this sort of damage in high doses, jumping into high doses seems reckless. And I say that as someone wo takes rapamycin :)


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#103 OP2040

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Posted 08 October 2018 - 09:48 PM

ok, fair enough.  But I hope you try to follow your own ideas to their logical conclusions in a serious manner.  The entire plant kingdom is full of natural pesticides, mutagens and other toxic compounds. 

 

Yes, doses matter and higher doses call for more caution..  So it seems our only disagreement then is what constitutes high doses.  To me, 20/30 mg/kg is nowhere near high enough dose to cause problems.  And the most frustrating part is that a toxicity study at that and higher level has already been posted! 

 

 


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#104 OP2040

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Posted 08 October 2018 - 10:10 PM

Just to be clear

 

https://www.ncbi.nlm...27824/#S16title

 

 

7. TOXICITY

Off-target effects that can contribute to toxicity are certainly a concern for any potential therapeutic. However, in the case of fisetin, there is no evidence for either short- or long-term toxicity. In a short-term study done by an outside laboratory, mice were orally administered 2000 mg/kg bw of fisetin, examined for 48 hr and sacrificed. No indications of toxicity were observed. The effects of long-term feeding of fisetin on health were also evaluated (18). No significant differences in body weights were seen between control and fisetin-fed animals given fisetin at 0.05% in their diets for 9 months (~25 mg/kg bw). Following sacrifice, multiple tissues (lungs, spleen, liver, kidneys, heart, stomach, intestine, testes and ovary) were examined using standard toxicological pathology criteria and no toxicity was associated with fisetin treatment. Furthermore, fisetin was negative in the Ames test. In addition, fisetin showed no inhibition of hERG activity at concentrations up to 10 μM, the highest concentration tested (unpublished results). It also showed no inhibitory effects on the activities of cytochrome P450s 3A4, 2C9 and 2D6 at concentrations up to 10 μM (unpublished results). Thus, at the present time, there is no indication of fisetin toxicity from either in vitro or in vivo tests.

 

Yes, I know this is mice, but mice are also much more cancer-prone than humans.  Now we can keep going round and round on this.  But the fact is that this already has an excellent safety profile, and if you discount this, you have to discount almost every current intervention, even the ones in mainstream medicine.  It would be a reductio ad absurdism based on caution.  Feel free to go down that road, but I don't want others to be dragged down it as well.

 

Not to add insult to injury, but here are the known side effects of your supplement of choice:

 

 

Adverse effects

The most common adverse reactions (≥30% occurrence, leading to a 5% treatment discontinuation rate) observed with sirolimus in clinical studies of organ rejection prophylaxis in individuals with kidney transplants include: peripheral edema, hypercholesterolemia, abdominal pain, headache, nausea, diarrhea, pain, constipation, hypertriglyceridemia, hypertension, increased creatinine, fever, urinary tract infection, anemia, arthralgia, and thrombocytopenia.[4]

The most common adverse reactions (≥20% occurrence, leading to a 11% treatment discontinuation rate) observed with sirolimus in clinical studies for the treatment of lymphangioleiomyomatosis are: peripheral edema, hypercholesterolemia, abdominal pain, headache, nausea, diarrhea, chest pain, stomatitis, nasopharyngitis, acne, upper respiratory tract infection, dizziness, and myalgia.[4]

The following adverse effects occurred in 3–20% of individuals taking sirolimus for organ rejection prophylaxis following a kidney transplant:[4]

System Adverse effects Body as a Whole Sepsis, lymphocele, herpes zoster infection, herpes simplex infection Cardiovascular Venous thromboembolism (pulmonary embolism and deep venous thrombosis), rapid heart rate Digestive Stomatitis Hematologic/Lymphatic Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), leukopenia Metabolic Abnormal healing, increased lactic dehydrogenase (LDH), hypokalemia, diabetes Musculoskeletal Bone necrosis Respiratory Pneumonia, epistaxis Skin Melanoma, squamous cell carcinoma, basal cell carcinoma Urogenital Pyelonephritis, ovarian cysts, menstrual disorders (amenorrhea and menorrhagia)

 

 

But then again, Rapamycin is patented, hard to get and expensive......hmm

 


Edited by OP2040, 08 October 2018 - 10:14 PM.

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#105 Kevnzworld

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Posted 09 October 2018 - 01:23 AM

A few additions..This is a pretty succinct analysis of the study with a link ( that works ) for the entire study.
Part of the study did test Fisetin on human fat tissue with a successful outcome.
The fact that aged mice had such a substantial life extension is pretty impressive. Essentially all the controls died befor the first of the Fisetin mice died.
Lastly the writers in the blog I’m sharing calculate a human dose of 600-900 mg.
http://www.ergo-log....m-the-body.html
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#106 extendcel

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Posted 09 October 2018 - 01:31 AM

There are always health risks with senolytics. The perfect senolytic won't cause damage to normal cells, but so far the senolytics we know of will kill normal cells too; that is the risk we take to clear out senescent cells.

Fisetin to me has one of the best safety profiles of the known potential senolytics because it also has protective effects. Quercetin seems to be a more risky compound than fisetin. If dosing is kept acute with long breaks in between, then I don't see much risk in it. Chronic dosing is much riskier. This is also considering we are taking a much smaller dose than used in toxicity studies. It is a natural substance much less potent than things like rapamycin and metformin, which have documented adverse effects.

The main risk you have to consider is potential kidney toxicity from the large doses you need to obtain bioavailability, though the senolytic effect should also benefit the kidneys.
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#107 DukeNukem

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Posted 09 October 2018 - 02:35 AM

>>> been trying to get folks on the fisetin band wagon and no one seems interested. This is a great flavonoid to supplement. <<<

Yup.

Been taking it since at least 2011, when I learned of its glycation reduction properties:

https://www.ncbi.nlm...pubmed/21738623

Definitely happy to hear about this new potential benefit.

(Regardless, nothing reduces glycation like the reduction of carbs--this is tactic number one in the reduction of AGEs.)


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#108 Ducky-001

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Posted 09 October 2018 - 07:23 AM

So, last night I took 15x100mg fisetin pills and emptied them into a shot glass. The content was a fine yellow powder. I filled the shot glass almost to the brim with extra virgin olive oil and stirred well. Most of the powder dissolved in the olive oil, or formed a sort of emulsion. The taste was bad, but not undrinkable. About 30 minutes after taking the mixture I felt a bit nauseous, and went to lay down on the coach. For the next few hours I felt nauseous and a bit viped out. I went to bed a bit later and woke up fine the next morning. I have some age spots on the back of my hand (my first age spots at the age of 49) that I'm watching to see if they will fade and go away. They may be a bit lighter already, but more time will tell. 

 

There was for sure a big difference between first try(as pills) and after emptying the content. I reckon that the bare powder is faster absorbed by the body.

 


Edited by Ducky-001, 09 October 2018 - 07:27 AM.

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#109 Andey

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Posted 09 October 2018 - 11:50 AM

So, last night I took 15x100mg fisetin pills and emptied them into a shot glass. The content was a fine yellow powder. I filled the shot glass almost to the brim with extra virgin olive oil and stirred well. Most of the powder dissolved in the olive oil, or formed a sort of emulsion. The taste was bad, but not undrinkable. About 30 minutes after taking the mixture I felt a bit nauseous, and went to lay down on the coach. For the next few hours I felt nauseous and a bit viped out. I went to bed a bit later and woke up fine the next morning. I have some age spots on the back of my hand (my first age spots at the age of 49) that I'm watching to see if they will fade and go away. They may be a bit lighter already, but more time will tell. 

 

There was for sure a big difference between first try(as pills) and after emptying the content. I reckon that the bare powder is faster absorbed by the body.

 

  A lot of pure oil could distress the stomach, esp if you don't used to it.  It started immediately when there was little to no absorption yet so it hints to a digestive distress.

I like lecithin + olive oil + water better. (adding some alcohol would be better yet)

Lecithin works as an emulsifier for an oil(not a lot of it needed) and allows to add water to the solution, it also removes the dependence on bile for absorption (still need lipase though).

 

I recall a year ago Fafner55, tried D+Q topically with DMSO and reported that his age spots vanished.


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#110 OP2040

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Posted 09 October 2018 - 11:53 AM

There are always health risks with senolytics. The perfect senolytic won't cause damage to normal cells, but so far the senolytics we know of will kill normal cells too; that is the risk we take to clear out senescent cells.

Fisetin to me has one of the best safety profiles of the known potential senolytics because it also has protective effects. Quercetin seems to be a more risky compound than fisetin. If dosing is kept acute with long breaks in between, then I don't see much risk in it. Chronic dosing is much riskier. This is also considering we are taking a much smaller dose than used in toxicity studies. It is a natural substance much less potent than things like rapamycin and metformin, which have documented adverse effects.

The main risk you have to consider is potential kidney toxicity from the large doses you need to obtain bioavailability, though the senolytic effect should also benefit the kidneys.

 

I worry a lot about kidney stuff, so this is kind of a red flag for me. It pops into my head as well. I start thinking.... all of this mess is being excreted somehow and all at once, logically it could damage your kidneys.  But I try to go by the studies because I don't want my fears to guide my decision.  Lucky for us, as you hinted at, all the senolytic studies show better kidney health to the extent that they measure it at all.

 

I do plan to take NAC beforehand to protect my liver, and I think it works the same for kidney.  It's probably not necessary, but I have some I'm not using, so why not. 


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#111 OP2040

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Posted 09 October 2018 - 11:59 AM

So, last night I took 15x100mg fisetin pills and emptied them into a shot glass. The content was a fine yellow powder. I filled the shot glass almost to the brim with extra virgin olive oil and stirred well. Most of the powder dissolved in the olive oil, or formed a sort of emulsion. The taste was bad, but not undrinkable. About 30 minutes after taking the mixture I felt a bit nauseous, and went to lay down on the coach. For the next few hours I felt nauseous and a bit viped out. I went to bed a bit later and woke up fine the next morning. I have some age spots on the back of my hand (my first age spots at the age of 49) that I'm watching to see if they will fade and go away. They may be a bit lighter already, but more time will tell. 

 

There was for sure a big difference between first try(as pills) and after emptying the content. I reckon that the bare powder is faster absorbed by the body.

 

I was thinking age spots would be a great way to measure.  It would be a very simple measurement, and a study just came out that you probably saw as well, showing that age spots def consist of senescent cells.  Even if it doesn't have an effect on them this way, I may try directly on the skin itself later just out of curiosity.  I've tried similar before/after things and I find that I have to take before/after pics to make it more accurate.  Memory just doesn't cut it, for me anyway.



#112 Turnbuckle

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Posted 09 October 2018 - 12:43 PM

I was thinking age spots would be a great way to measure.  It would be a very simple measurement, and a study just came out that you probably saw as well, showing that age spots def consist of senescent cells.  Even if it doesn't have an effect on them this way, I may try directly on the skin itself later just out of curiosity.  I've tried similar before/after things and I find that I have to take before/after pics to make it more accurate.  Memory just doesn't cut it, for me anyway.

 

If senescent cells do not divide and skin cells are constantly being replaced at the basal layer and eroding away at the top layer, how can age spots be senescent?  I don't know if the following paper explains it satisfactorily, but it obviously isn't senescent cells, but more likely a case of a morphological change (more rete ridges) that brings about a lower rate of melanin removal -- Molecular and histological characterization of age spots


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#113 OP2040

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Posted 09 October 2018 - 01:14 PM

If senescent cells do not divide and skin cells are constantly being replaced at the basal layer and eroding away at the top layer, how can age spots be senescent?  I don't know if the following paper explains it satisfactorily, but it obviously isn't senescent cells, but more likely a case of a morphological change (more rete ridges) that brings about a lower rate of melanin removal -- Molecular and histological characterization of age spots

 

This is the article I am remembering, but you're right it looks like I didn't even read the title all that well, as it says "contribute to"

https://www.fightagi...ency-treatment/

 

Given how fundamental senescent cells are for the entire microenvironment, I wouldn't be surprised if it did help eliminate them over time as skin turns over pretty quickly.  There's got to be some easily observable parameter directly related to senescence that we can do a before/after on.



#114 stefan_001

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Posted 09 October 2018 - 05:10 PM

Woke up in morning:

- slight painfull feeling in lungs, some cough

- skin on my hands is bit tighter but this is somewhat similar to using 300mg, its was not permanent then. My speculation is Fisetin at 300mg reduces SASP activity which is good too but means you need to use Fisetin constantly. Lets see what happens over the days with this higher dose.

- overall tired

 

At risk of spoiling the effect I did take NR in the morning. If Fisetin is selective it should have killed some cells during the 12 hour window. NR to help recover collateral damage. Will use another dose of 1000mg tonight and skip dinner.

 

3 days done. Similar pattern as described. Eyesight better. Now going to have a break and lets see do any plusses persist.
 


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#115 OP2040

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Posted 09 October 2018 - 06:25 PM

3 days done. Similar pattern as described. Eyesight better. Now going to have a break and lets see do any plusses persist.
 

 

myopia, presbyopia, or both?



#116 smithx

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Posted 09 October 2018 - 09:17 PM

Rapamycin when not taken very intermittently has a horrible safety profile. This is why I take very small doses on an 8-9 day frequency. The study you posted is not germane to that dosing regimen. I don't want to contaminate this thread with rapamycin info, but the intermittent dosing studies are referenced in the rapamycin threads. And people here who take it often get it from India, not from expensive US pharma companies.

 

 

Your characterization of 20mg/Kg as not a high dose has to be compared to the quantity one would get from dietary sources.

 

- The highest source of fisetin seems to be strawberries, at 160mcg/g. (see: https://www.ncbi.nlm...es/PMC3689181/)

- For a 150lb person, 20mg/Kg is 1367mg of fisetin

- To obtain 1367 mg of fisetin one would have to eat 8.5Kg of strawberries, which is probably 90x a normal quantity for a person to eat.

 

So the 20mg/Kg dosage is quite a bit higher than one would encounter in a normal diet.

 

Again, it may be completely safe. I just start getting paranoid when I read about double strand DNA breaks and chromosome loss.

 

 

 

 

Just to be clear

 

https://www.ncbi.nlm...27824/#S16title

 

 

Yes, I know this is mice, but mice are also much more cancer-prone than humans.  Now we can keep going round and round on this.  But the fact is that this already has an excellent safety profile, and if you discount this, you have to discount almost every current intervention, even the ones in mainstream medicine.  It would be a reductio ad absurdism based on caution.  Feel free to go down that road, but I don't want others to be dragged down it as well.

 

Not to add insult to injury, but here are the known side effects of your supplement of choice:

 

 

 

But then again, Rapamycin is patented, hard to get and expensive......hmm

 


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#117 Ducky-001

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Posted 10 October 2018 - 08:35 AM

Yesterday night I took the rest of my Fisetin 1g (10 x 100mg pills) and opened them and dissolved in EVO. No nauseousness this time, and little reaction generally. So it may be that my sweet spot is around 1,5g dissolved in oil. I have reordered more, and will try again next month. Age spots are still there.

 


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#118 Andey

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Posted 10 October 2018 - 10:27 AM

If somebody wants to quantify the effect of SC removal, measuring blood pressure before and two weeks after the intervention would be a good start.

New cells improve the elasticity of the tissue and all other things equal it should improve the result.


Edited by Andey, 10 October 2018 - 10:28 AM.


#119 ryukenden

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Posted 10 October 2018 - 12:59 PM

 

The Mayo Clinic is doing a study of Fisetin 

Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults (AFFIRM-LITE)
Fisetin 20/mg/kg/day, orally for 2 consecutive days, for 2 consecutive months.

 

 

What does it mean? Orally for 2 consecutive days for 2 consecutive months?

 

2 consecutive days per week for 2 months?
 


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#120 triguy

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Posted 10 October 2018 - 01:39 PM

what is the consensus on the highest quality brand FISETIN.        message me if it is more appropriate







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