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Fisetin: Senolytic!

fisetin senolytic

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#811 osris

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Posted 02 November 2019 - 10:22 PM

Another question...

 

In the mouse and human study of fisetin, was fisetin taken with another substance to enhance its bioavailability?

 

If not, then how come the mouse study showed good results for fisetin in mice? In other words, if bioavailability is a problem, and the mice were not given another substance to compensate for it, how come fisetin worked well on the mice?

 

Obviously, we'll have to wait for the results of the human study to come in. 

 

Does anyone have an answer to this?



#812 sedentary

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Posted 03 November 2019 - 01:42 AM

IMHO the ingredients and composition look fine but the dosages are woefully underpowered at the recommended daily serving size. Taking 400mg quercetin, 300mg theaflavins and 100mg Fisetin per day won't make any dent to senescent cells population - the purpose of senolytic protocols are to stress all cells and the dysfunctional ones like the senescent ones to fail the stress test and thus be destroyed. To achieve this, one needs to reach decent serum levels of these compounds - given their low bioavailability, these dosages won't do much, if anything.

 

what about IV? how safe is fisetin if IVed? you will need micro doses too.


Edited by sedentary, 03 November 2019 - 01:43 AM.

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#813 tolerant

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Posted 03 November 2019 - 11:17 AM

Hi everybody,

 

I would like to share my experience with fisetin.

 

I'm riddled with depression and dementia-like symptoms, both of which are constantly deteriorating. Late last year, after the seminal Nature study came out, out of desperation willing to take anything that had any chance at all of making me better, I took a dose of 1400 mg before bed. If I remember correctly, the dose was extrapolated from the said study. When I woke up the next day, I felt a huge difference. I wasn't cured, but in terms of mental health I felt much, much better. It was like a miracle. I don't remember if the dementia-type symptoms also improved. I just remember the overall sense of well-being.

 

Amazed with the results, I decided to take another dose of 1400 mg that night. Unfortunately, when I woke up the day after my second 1400 mg dose, I was back to square one. That really scared me off fisetin, but about a month later, out of desperation I again took a 1400 mg dose, and that time it made no difference. I didn't feel any better or worse after having taking it. I never tried it again since then.

 

Now I haven't followed this thread because my emotional and cognitive state makes it almost impossible. I hope that my experience with fisetin is helpful, and perhaps someone can put forward a theory on why it unfolded the way it did. Should I try taking it again? Maybe try a different dosing regimen? A number of years ago, before I even knew what "senolytic" meant I did take one 100 mg capsule of the stuff on days I remembered to do it, and eventually made it through a 60 capsule bottle. That sort of dosing did not have any effect of me.


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#814 aribadabar

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Posted 03 November 2019 - 05:36 PM

what about IV? how safe is fisetin if IVed? you will need micro doses too.

 

To my knowledge, there are no IV grade offerings of these compounds and besides, it is not a DIY thing to do.


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#815 osris

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Posted 03 November 2019 - 06:39 PM

 

 


Hi everybody,

 

I would like to share my experience with fisetin.

 

I'm riddled with depression and dementia-like symptoms, both of which are constantly deteriorating. Late last year, after the seminal Nature study came out, out of desperation willing to take anything that had any chance at all of making me better, I took a dose of 1400 mg before bed. If I remember correctly, the dose was extrapolated from the said study. When I woke up the next day, I felt a huge difference. I wasn't cured, but in terms of mental health I felt much, much better. It was like a miracle. I don't remember if the dementia-type symptoms also improved. I just remember the overall sense of well-being.

 

Amazed with the results, I decided to take another dose of 1400 mg that night. Unfortunately, when I woke up the day after my second 1400 mg dose, I was back to square one. That really scared me off fisetin, but about a month later, out of desperation I again took a 1400 mg dose, and that time it made no difference. I didn't feel any better or worse after having taking it. I never tried it again since then.

 

Now I haven't followed this thread because my emotional and cognitive state makes it almost impossible. I hope that my experience with fisetin is helpful, and perhaps someone can put forward a theory on why it unfolded the way it did. Should I try taking it again? Maybe try a different dosing regimen? A number of years ago, before I even knew what "senolytic" meant I did take one 100 mg capsule of the stuff on days I remembered to do it, and eventually made it through a 60 capsule bottle. That sort of dosing did not have any effect of me.

 

I’ve yet to take fisetin so have no personal experience of it, but a few posters to this thread have said that fisetin shouldn’t necessarily produce any mood changes—for good or bad.

 

So your initial feeling of well being when you first took it could have been a placebo affect, otherwise this feeling would have been repeated when you took more fisetin subsequently.

 

If it does have any positive effects on dementia, then presumably it would take a while for such to be noticeable—maybe after taking fisetin three times a year for two years? Maybe less, who can say?

 


Edited by osris, 03 November 2019 - 06:39 PM.


#816 Empiricus

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Posted 04 November 2019 - 09:02 AM

Hi everybody,

 

I would like to share my experience with fisetin.

 

I'm riddled with depression and dementia-like symptoms, both of which are constantly deteriorating. Late last year, after the seminal Nature study came out, out of desperation willing to take anything that had any chance at all of making me better, I took a dose of 1400 mg before bed. If I remember correctly, the dose was extrapolated from the said study. When I woke up the next day, I felt a huge difference. I wasn't cured, but in terms of mental health I felt much, much better. It was like a miracle. I don't remember if the dementia-type symptoms also improved. I just remember the overall sense of well-being.

 

Amazed with the results, I decided to take another dose of 1400 mg that night. Unfortunately, when I woke up the day after my second 1400 mg dose, I was back to square one. That really scared me off fisetin, but about a month later, out of desperation I again took a 1400 mg dose, and that time it made no difference. I didn't feel any better or worse after having taking it. I never tried it again since then.

 

Now I haven't followed this thread because my emotional and cognitive state makes it almost impossible. I hope that my experience with fisetin is helpful, and perhaps someone can put forward a theory on why it unfolded the way it did. Should I try taking it again? Maybe try a different dosing regimen? A number of years ago, before I even knew what "senolytic" meant I did take one 100 mg capsule of the stuff on days I remembered to do it, and eventually made it through a 60 capsule bottle. That sort of dosing did not have any effect of me.

 

 

In the Amazon reviews there are a couple reports of people saying their brains worked better after taking fisetin.  

 

It may matter when you take it.  A few times a month I have been taking 200 mg of fisetin before bed.  My reason for taking it at night was that it might complement natural autophagy of sleep. The next morning I generally feel refreshed, both mentally and physically.  Sometimes I take it with a fish oil capsule.  At least one study looked at taking fistein with fish oil -- which alone has positive cognitive effects on me.  

 

Oddly, the time I took 500 mg before bed, I didn't notice anything.  It might not be advantageous to take huge dose at one time.  

 

I don't need to take much fistetin to notice an effect.  The predictably good results I get from a very low dose have kept me from experimenting with higher doses. Though the past 2 days I have been trying a little experiment with 500-600 mg spread throughout the day.  Too early to say much except that I had trouble sleeping last night, but don't feel it has made me drowsy.  It's as if fisetin causes sleeplessness, but counteracts the effects of sleeplessness.  

 


Edited by Empiricus, 04 November 2019 - 09:14 AM.


#817 osris

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Posted 04 November 2019 - 09:12 AM

It may matter when you take it.  A few times a month I have been taking 200 mg of fisetin before bed.  My reason for taking it at night was that it might complement natural autophagy of sleep. The next morning I generally feel refreshed, both mentally and physically.  Oddly, the time I took 500 mg before bed, I didn't notice anything. Sometimes I take it with fish oil.  At least one study looked at taking fistein with fish oil (which alone has positive cognitive effects on me).  

In the Amazon reviews there are reports of people experiencing more clarity of thought from taking fisetin.  

 

I don't need to take much fistetin to notice an effect.  That's kept me from experimenting with higher doses.  Though the past 2 days I have been trying a little experiment with 500-600 mg spread throughout the day.  It might not be advantageous to take huge dose at one time.  

 

I wonder if there have been any experiments on mice etc to see if fisetin has any senolytic effects in low dosages? 

 

Going by your experience, low dosages have some sort of "brain activity" effect. I wonder if this activity indicates any underlying senolytic effect?



#818 sedentary

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Posted 04 November 2019 - 06:52 PM

when you say "their brains worked better" after taking fisetin, what do you mean by that? im curious about it being relation to depression? or just general cognitive enhancement, for example concentration maybe?

i was going to get the product i mentioned on amazon, but after a reply saying its too low of dose of each and it wont too long with high price tag, i gave up. now im curious how to proceed from here. i really thought this product was the bomb at first. so i checked amazon again for reliable fisetin and again the bad reviews keep turning me off. i use fakespot.com and it shows a lot of deceit too on the few with good reviews. jeez, im sick of dark side of business.



#819 Dstein

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Posted 04 November 2019 - 09:13 PM

Hi everybody,

 

I would like to share my experience with fisetin.

 

I'm riddled with depression and dementia-like symptoms, both of which are constantly deteriorating. Late last year, after the seminal Nature study came out, out of desperation willing to take anything that had any chance at all of making me better, I took a dose of 1400 mg before bed. If I remember correctly, the dose was extrapolated from the said study. When I woke up the next day, I felt a huge difference. I wasn't cured, but in terms of mental health I felt much, much better. It was like a miracle. I don't remember if the dementia-type symptoms also improved. I just remember the overall sense of well-being.

 

Amazed with the results, I decided to take another dose of 1400 mg that night. Unfortunately, when I woke up the day after my second 1400 mg dose, I was back to square one. That really scared me off fisetin, but about a month later, out of desperation I again took a 1400 mg dose, and that time it made no difference. I didn't feel any better or worse after having taking it. I never tried it again since then.

 

Now I haven't followed this thread because my emotional and cognitive state makes it almost impossible. I hope that my experience with fisetin is helpful, and perhaps someone can put forward a theory on why it unfolded the way it did. Should I try taking it again? Maybe try a different dosing regimen? A number of years ago, before I even knew what "senolytic" meant I did take one 100 mg capsule of the stuff on days I remembered to do it, and eventually made it through a 60 capsule bottle. That sort of dosing did not have any effect of me.

 

I take 4 gms/day (mixed with stuff to make it more bioavailable) for 5 consecutive days then I take a month or two off.  My sleep is now the best that it has been in many decades, and I suspect that my mental functions have also improved--but that is difficul to mesasure.
 



#820 Empiricus

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Posted 05 November 2019 - 05:40 AM

when you say "their brains worked better" after taking fisetin, what do you mean by that? im curious about it being relation to depression? or just general cognitive enhancement, for example concentration maybe?

 

I was summarizing the gist of several reviews on Amazon.  I dug up some of the examples related to mental activity:

  • I've been taking this Fisetin supplement for a couple of weeks and have definitely noticed an improvement in my alertness
  • I have notice a difference in my mental clarity, I'm not as foggy as before, it's good
  • After taking it for a couple of weeks I feel like some of the brain fog that came to me with age has lifted and I'm feeling more "sharp" than I had in the past. That's enough to convince me. Many of the supplements I take have not obvious effect... Fisetin is different because I have seen a noticeable improvement.
  • so far I have discovered that the product is working pretty well. I am able to focus better during a long day, particularly towards the end of the day. 
  • Within the first week I noticed that the need to take that afternoon nap started to decline and my workflow started to increase. I could sit at the computer for long periods without fatigue. The thing I noticed most of all was how easy it was to make a commitment and stick with it.

The above reviews were from Revjuvenation Therapeutics brand.

  • Works. I notice cognitive improvement. 
  • Within days my mental performance returned ... well, not to baseline, but 75% of the way, which is amazing considering how cheap and safe this stuff is. I am pretty certain it's not a placebo effect as I tried perhaps 40 other supplements along the way with results only from a scant handful, and none comparable to this. Fisetin definitely also seems to increase general stress resistance, though that may be a side effect of more normal cognitive functioning.
  •  after taking Fisetin for a few months, I think my reasoning has improved and I've come up with some ideas that I really enjoyed.
  • Works well for my focus and all around mood. 
  • I am doing a protocol get rid of calcium Oxalates and calcium phosphates that have been deposited all over my body including the brain due to multiple polymorphisms of the AGXT AND KLOTHO genes. This causes various symptoms including microglial activation resulting in inflammation and swelling in the brain. I purchased Fisetin and take 2 per day morning and evening and it has greatly improved my brain symptoms. I just ordered 2 more bottles!!!
  • This reversed my grand daddy's dementia. Powerful pills.

Above are Doctor's Best reviews.

  • I am using it for it's effects on mood improvement and brain health. It puts me in a better mood and I feel more productive and social. Took about a week of using fisetin before I started to notice improvement in this area. I have tried hundreds of supplements, and this one is unique and I believe I will be sticking with it for a long time. 
  • I've been taking this for a few weeks now. What I noticed almost immediately is that I have more energy. This last year, I've been struggling with "brain fog", having difficulty finding the right words, experiencing forgetfulness, etc. I am already feeling a difference since taking this supplement. 

Above for Fisetin Plus.

 

One question I have is whether the high doses at infrequent intervals delivers thee kinds of performance results. I assume most of the reviewers were taking it daily as directed on the bottles. 


Edited by Empiricus, 05 November 2019 - 05:53 AM.

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#821 osris

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Posted 05 November 2019 - 03:36 PM

I take 4 gms/day (mixed with stuff to make it more bioavailable) for 5 consecutive days then I take a month or two off.  My sleep is now the best that it has been in many decades, and I suspect that my mental functions have also improved--but that is difficul to mesasure.
 

 

How do we know it’s not bioavailable, though?
 
Been trying to get an answer to this question for a while here.
 
The mouse experiments don’t mention whether the mice were given anything else with fisetin to improve bioavailability.
 
Maybe in mice bioavailability isn’t an issue—is that right?

Edited by osris, 05 November 2019 - 03:38 PM.

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#822 sedentary

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Posted 05 November 2019 - 11:36 PM

I was summarizing the gist of several reviews on Amazon.  I dug up some of the examples related to mental activity:

  • I've been taking this Fisetin supplement for a couple of weeks and have definitely noticed an improvement in my alertness
  • I have notice a difference in my mental clarity, I'm not as foggy as before, it's good
  • After taking it for a couple of weeks I feel like some of the brain fog that came to me with age has lifted and I'm feeling more "sharp" than I had in the past. That's enough to convince me. Many of the supplements I take have not obvious effect... Fisetin is different because I have seen a noticeable improvement.
  • so far I have discovered that the product is working pretty well. I am able to focus better during a long day, particularly towards the end of the day. 
  • Within the first week I noticed that the need to take that afternoon nap started to decline and my workflow started to increase. I could sit at the computer for long periods without fatigue. The thing I noticed most of all was how easy it was to make a commitment and stick with it.

The above reviews were from Revjuvenation Therapeutics brand.

  • Works. I notice cognitive improvement. 
  • Within days my mental performance returned ... well, not to baseline, but 75% of the way, which is amazing considering how cheap and safe this stuff is. I am pretty certain it's not a placebo effect as I tried perhaps 40 other supplements along the way with results only from a scant handful, and none comparable to this. Fisetin definitely also seems to increase general stress resistance, though that may be a side effect of more normal cognitive functioning.
  •  after taking Fisetin for a few months, I think my reasoning has improved and I've come up with some ideas that I really enjoyed.
  • Works well for my focus and all around mood. 
  • I am doing a protocol get rid of calcium Oxalates and calcium phosphates that have been deposited all over my body including the brain due to multiple polymorphisms of the AGXT AND KLOTHO genes. This causes various symptoms including microglial activation resulting in inflammation and swelling in the brain. I purchased Fisetin and take 2 per day morning and evening and it has greatly improved my brain symptoms. I just ordered 2 more bottles!!!
  • This reversed my grand daddy's dementia. Powerful pills.

Above are Doctor's Best reviews.

  • I am using it for it's effects on mood improvement and brain health. It puts me in a better mood and I feel more productive and social. Took about a week of using fisetin before I started to notice improvement in this area. I have tried hundreds of supplements, and this one is unique and I believe I will be sticking with it for a long time. 
  • I've been taking this for a few weeks now. What I noticed almost immediately is that I have more energy. This last year, I've been struggling with "brain fog", having difficulty finding the right words, experiencing forgetfulness, etc. I am already feeling a difference since taking this supplement. 

Above for Fisetin Plus.

 

One question I have is whether the high doses at infrequent intervals delivers thee kinds of performance results. I assume most of the reviewers were taking it daily as directed on the bottles. 

 

 

did you run them through fakespot.com ? i usually do that with the many fake reviews on amazon, you cannot ever know

 


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#823 Heisok

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Posted 06 November 2019 - 12:10 AM

"Our engine has profiled the reviewer patterns and has determined that there is high deception involved." D for rejuvenetics Fisetin D for the Company based on 17 products

C for Drs Best Fisetin

 

 



#824 sedentary

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Posted 06 November 2019 - 05:34 AM

its terrible this supplement business. highly unregulated! im not going to offtopic this but i cant help and mention that it has been killing me for all the fakes on the market regarding supplements. i keep finding problems in all supplements i have brought. sooner or later some independent lab shows weak results or personally i found out by simply questioning the companies too much as they put it in some cases.

not including just the fisetin studies on all the benefits out there being likely pretty reliable but the fact we just cannot get the real pure stuff to know. its all business! why would a company spend money to get a product and develop and sell it for cheap price without some profit? considering, a company to flourish needs A LOT OF PROFIT. so they will always find shortcuts inevitably. perhaps fisetin has real good value but none of the people who have used it could get 100% good quality. at most, perhaps 50% maybe if lucky?

If I was some asshole I can put some powder out there and claim its fisetin or any obscure substance that has good research behind it. How would any of you know what it is? You would personally test it? Who will test it for you? Not even independent labs are keeping up with the latest cool new supplements out there to be able to identify them. It will take FDA a year or so to figure its some crap. Few of the supplements I brought 10 years ago went off business when FDA caught up.

 

anyway, just wanted to let my frustration out on this problem. apologies for the off topic. if the world worked PERFECT we would have experienced REAL quality fisetin and other highly researched and supported by science supplements and seen real results. but that from my point of view, is almost impossible as it stands with the business side of things. *sigh*


Edited by sedentary, 06 November 2019 - 05:47 AM.

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#825 Empiricus

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Posted 06 November 2019 - 07:04 AM

"Our engine has profiled the reviewer patterns and has determined that there is high deception involved." D for rejuvenetics Fisetin D for the Company based on 17 products

C for Drs Best Fisetin

 

The main concern I had was that product descriptions of some products ("mental sharpness") may have influenced perception.  

 

Doctor's Best Fisetin has only a score of 3.5 which is pretty lame if they were paying commenters!  

 

I don't think we should blindly trust Amazon reviews, but the same goes for automated fake-spotters. Who knows how many false positives they report?  If "fake spotters" had acceptable false positive rates, Amazon would probably be using their algorithms to reject the comments.  

 

But fake reviews do slip by Amazon. One easy way to spot them is to look for date clusters.  Another is the reviewer's level of banality.  Certainly, once you've used a product, the honest reviews become easier to identify.  When specific details pertaining to the effects of a product mirror your experience, the probability of fraud goes down. That's why I don't dismiss a number of the fisetin reviews I quoted.  

 

I have personally experienced fisetin to be the rarest of supplements: one that has an impact on cognition, mood and even motivation. Even at the "suggested dose" (100mg). Even the next day (effects don't require weeks to kick in).  One would expect a number of extremely positive reviews.  And that's what we have.  


Edited by Empiricus, 06 November 2019 - 07:55 AM.

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#826 Rays

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Posted 06 November 2019 - 09:07 AM

 

How do we know it’s not bioavailable, though?
 
Been trying to get an answer to this question for a while here.
 
The mouse experiments don’t mention whether the mice were given anything else with fisetin to improve bioavailability.
 
Maybe in mice bioavailability isn’t an issue—is that right?

 

 

 

There were two mice studies in the study that this thread started with:
  • "For diet studies, mice were fed Teklad 2020 chow (Envigo, Madison, WI) prepared with or without 500 ppm (500 mg/kg) of fisetin"
  • "For oral administration of fisetin, mice were dosed with 100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol or vehicle only by gavage."
 
The ingredients of the Teklad chow (wheat, corn and soy oil) you can find here:
Maybe the mixing of the fisetin with the soy oil in the chow is beneficial for bio availability.
 
The mice in the oral gavage group were administered fisetin in: 
  • 60% Phosal 50 PG
  • 30% PEG400
  • 10% ethanol
 
Phosal 50 PG is used as a "bioavailability-enhancer in oral drug delivery". See link below.
It contains at least 50% Phosphatidylcholine.
Phosphatidylcholine (PC) is "a phospholipid attached to a choline particle. Phospholipids contain fatty acids, glycerol, and phosphorous. The phosphorous part of the phospholipid substance — the lecithin — is made up of PC".
 
PEG400 "is very hydrophilic, which renders it a useful ingredient in drug formulations to augment the solubility and bioavailability of weakly water-soluble drugs". See link below.
 
Together with the ethanol it reminds me of making a liposomal. It may be possible to do that yourself using the process described here:
 
 
References:

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#827 William Sterog

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Posted 06 November 2019 - 12:16 PM

My brain feels better than ever when I take Fisetin. But I think than it is because of the anti-inflammatory actions. I talked about it some pages ago.
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#828 osris

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Posted 06 November 2019 - 01:06 PM

 

There were two mice studies in the study that this thread started with:
  • "For diet studies, mice were fed Teklad 2020 chow (Envigo, Madison, WI) prepared with or without 500 ppm (500 mg/kg) of fisetin"
  • "For oral administration of fisetin, mice were dosed with 100 mg/kg of fisetin in 60% Phosal 50 PG:30% PEG400:10% ethanol or vehicle only by gavage."
 
The ingredients of the Teklad chow (wheat, corn and soy oil) you can find here:
Maybe the mixing of the fisetin with the soy oil in the chow is beneficial for bio availability.
 
The mice in the oral gavage group were administered fisetin in: 
  • 60% Phosal 50 PG
  • 30% PEG400
  • 10% ethanol
 
Phosal 50 PG is used as a "bioavailability-enhancer in oral drug delivery". See link below.
It contains at least 50% Phosphatidylcholine.
Phosphatidylcholine (PC) is "a phospholipid attached to a choline particle. Phospholipids contain fatty acids, glycerol, and phosphorous. The phosphorous part of the phospholipid substance — the lecithin — is made up of PC".
 
PEG400 "is very hydrophilic, which renders it a useful ingredient in drug formulations to augment the solubility and bioavailability of weakly water-soluble drugs". See link below.
 
Together with the ethanol it reminds me of making a liposomal. It may be possible to do that yourself using the process described here:
 
 
References:

 

 

Thanks, Rays. That chow might have made the difference. Can the public buy it for themselves I wonder?


My brain feels better than ever when I take Fisetin. But I think than it is because of the anti-inflammatory actions. I talked about it some pages ago.

 

Do you make the fisetin bioavailable to get that result?



#829 Florin

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Posted 06 November 2019 - 08:34 PM

Here's another reason to worry about supplemental fisetin: it might be contaminated with the cytotoxin hinokiflavon.

 

https://forum.age-re...al.net/t/63bxk5


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#830 osris

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Posted 07 November 2019 - 01:22 AM

That's a very long thread. Have you a direct link to the reference you make?



#831 Florin

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Posted 07 November 2019 - 02:53 AM

That's a very long thread. Have you a direct link to the reference you make?

 

https://forum.age-re...63bxk5?r=x1ay46


Edited by Florin, 07 November 2019 - 02:58 AM.


#832 osris

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Posted 07 November 2019 - 05:01 AM

 

Is the following the post you intended to link to? I can’t see anything in it related to your concerns about fisetin being contaminated with toxins. I’m not a scientist, though, so might be missing something obvious. Can you spell it out for me?
 
 
"I mean "bold" by feeding some stuff to your dogs which has never been fed to dogs before (at least not in the recorded science literature--I cannot find one report of dogs and fisetin). You really need some regular lab tests (liver and kidney) and a dose-escalation study for that.
 
Senolytics are from animal data, but those animals are RODENTS. Which are omnivores and famously capable of eating just about anything, quite like pigs and humans. But animals differ in their sensitivity to plant products, which is why rabbits and ruminants can feast on the nightshade plants and berries that would kill you or me. And humans and rodents can eat all the chocolate, garlic, onions, grapes and raisins that we like, and we have a good tolerance to ethanol, but these things are toxic (sometimes astonishingly toxic) to meat-eating cats and dogs, which cannot easily metabolize things like thiosulfate, caffeine, theobromine, and the like.
 
Here's another one: xylitol which is used as an artificial sweetener, is tolerated by rats and mice, who eat as much as they like. As do your kids on Halloween. But just a few candies can take out your dog.
 
So you never know. Dogs cannot eat many raisins and grapes, but apparently tolerate grapeseed extract. And sillymarin and some citrus bioflavonoids. So you got away with fisetin, it appears. But don't ever think that just because rats eat something in a study, and you eat it in unregulated pills from the supplement company, that you can feed the stuff to Rover. Next time, especially with plant-based products, you may guess wrong."

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#833 Florin

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Posted 07 November 2019 - 06:46 PM

 

 

Is the following the post you intended to link to?

 

No. The text is correct but not the URL. This one should work:

 

https://forum.age-re...63bxk5?r=x1ay46

 

Sorry for the confusion.



#834 osris

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Posted 08 November 2019 - 01:05 PM

Thanks for the link. I’ve pasted the post below so others can see it quicker.
 
Assuming that the post is correct about the toxicity of the plant that the Swanson fisetin product contains, this toxicity is probably how fisetin can kill senescent cells—a bit like chemotherapy drugs. 
 
The risk of death or serious illness from this toxicity is minutely small and possibly only theoretical. And this will especially be the case during the minimal times one would actually need to take fisetin for its senolytic effect—for two days once or twice a year. So I’m not too concerned about it.
 
The benefits of fisetin are too good to not take it for this low risk. Besides, there are probably many other supplements that have a notional toxicity risk, yet people no doubt find them beneficial. 
 
 
 
 
"Okay, here's the new Chinese bulk fisetin source from eBAY found by djmichel djmichael and discussed above:
 
Pure fisetin Powder at a cost of 22 dollars for 10 grams. link attached.
 
 
The source is Herba Link and the cost is roughly $50 for 25 grams ($2 a gram). I got a plastic packet today which is 25 grams, and the bulk weight of the plastic resealable packet was 27.2 g including the plastic, so net weight is good.  The time from order to receipt was just 4 days.
 
The source is Chinese. Manufacture date 1/21/2019. There is a certificate of analysis which claims 98.13 % fisetin by HPLC. It's a yellow powder and looks good, no odor. Taste is a bit reminiscent of pine. There is a heavy metal screen and a microbial screen.
 
It is a true herbal extract, done with water and ethanol. The plant source is stems of Rhus succedanea, the Japanese Wax Tree. This is a rather large and hardy shrub you can read about on Wikipedia. Its coating is the source of a lipid (not a wax) used as part of Japanese lacquer. The more common Linaean name these days is Toxicodendron succedaneum, a name it gets because the the plant is toxic to a number of herbivores. Nevertheless, the Rhus genus plants (many known as "sumacs," from a Syrian word meaning "red"), and anything in the larger Anacardiaceae family, are all quite high in fisetin (which is yellow-- the sumac red color is something else).
 
R. succedanea (this same wax tree) is the source of fisetin in the Swanson product, too. And I would bet Swanson gets it from the same Chinese source and just encapsulates it, so if you're looking to get out of all risk that way, it won't work.
 
It isn't clear to me why the wax tree R. succedanea is toxic. Other members of the family, like the infamous poison sumac (perhaps the most poisonous plant in N. America), contain urushiol, the same stuff that makes poison oak and ivy so bad. On the other hand, there are many sumacs with fruits used in spices and dyes, and sumac pink is actually what gives the traditional pink lemonade of colonial days, its color.
 
The fruit and stems of R. succedanea contains a flavonoid related to fisetin and to apigenin, called hinokiflavone. This stuff may be the toxicity source. It is far more toxic than fisetin, and is fascinating because its cytotoxic properties seem related to why we're interested in fisetin-- it goes to the mitochondria and increases production of reactive oxygen species, and induces apoptosis. It has been tested as an anticarcinogenic in melanoma, and shows some promise. It makes melanoma cells apoptose, with less toxicity in healthy cells.
 
Somebody badly needs to test hinokiflavone as a senolytic. I can't find that anybody has done so.
 
Do makers of fisetin from R. succedanea test for hinokiflavone content? They don't say so. Would it show up clearly on HPLC? I don't know. How much more toxic is it? I don't know. So if you are planning on eating fisetin from this source with gravy like mashed potatoes, just remember that there is no such things as a totally pure chemical. Natural product extracts are especially worisome. If you've been getting away with taking grams of Swanson fisetin, it's this same extract, so you're probably fine.
 
That's all I've been able to find out. I'll update when I have more.
 
And just for entertainment for this gerontology list, here is a poem about an old cow in the fall, who is tired of life. It was written by Robert Hillyer and was a favorite of my father's. It mentions sumac. It's called "Moo!""
 


#835 sedentary

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Posted 09 November 2019 - 02:43 AM

My brain feels better than ever when I take Fisetin. But I think than it is because of the anti-inflammatory actions. I talked about it some pages ago.

 

how can you tell it apart from all the other supplements you take?


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#836 William Sterog

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Posted 09 November 2019 - 01:10 PM

how can you tell it apart from all the other supplements you take?


I have been taking it on its own several times.
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#837 Empiricus

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Posted 14 November 2019 - 08:17 AM

Previously to last week had never taken more than 0.5 grams. My usual dose was 0.2 grams, and I had gone through several bottles earlier in the year. 

- Taking it usually at night, main thing was more motivation next day, more positive state of mind.  

- On the other hand, a wound got badly infected and healed slowly. Got injured working out at the gym (never happens to me, so I mention it).    

 

Last week I took 5 grams of fisetin (Doctor's Best). Days 1-3 I took 0.5 g, 4th day 1 g, 5th day 2.5 g.  I took it with fish oil and/or probiotic rich yogurt.

up to 1 grams, positive mental state. 

- day after last day (2.5g day), I got diarrhea, felt totally wiped out.  

- 2nd-4th day after, I felt light on my feet but I still looked sickly. Eyes sunken. Slept deeper. Libido higher. Motivation higher, but not particularly elated as after small doses.

 

Question: After stopping fisetin, how to increase speed of healing (slower healing being one of side effects of fisetin)?

Some ideas: Take curcumin, B-vitamins (particularly B5), most days. Anything else that could be helpful post-fistetin?



#838 Kentavr

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Posted 14 November 2019 - 04:48 PM

Previously to last week had never taken more than 0.5 grams. My usual dose was 0.2 grams, and I had gone through several bottles earlier in the year.
- Taking it usually at night, main thing was more motivation next day, more positive state of mind.
- On the other hand, a wound got badly infected and healed slowly. Got injured working out at the gym (never happens to me, so I mention it).

Last week I took 5 grams of fisetin (Doctor's Best). Days 1-3 I took 0.5 g, 4th day 1 g, 5th day 2.5 g. I took it with fish oil and/or probiotic rich yogurt.
- up to 1 grams, positive mental state.
- day after last day (2.5g day), I got diarrhea, felt totally wiped out.
- 2nd-4th day after, I felt light on my feet but I still looked sickly. Eyes sunken. Slept deeper. Libido higher. Motivation higher, but not particularly elated as after small doses.

Question: After stopping fisetin, how to increase speed of healing (slower healing being one of side effects of fisetin)?
Some ideas: Take curcumin, B-vitamins (particularly B5), most days. Anything else that could be helpful post-fistetin?


Try the combination: Curcumin + Ashwagandha + Quercetin + Fisetin.

All these ingredients have anti-inflammatory effect, + can give synergy.

Therefore, start with small doses.
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#839 Empiricus

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Posted 15 November 2019 - 11:24 AM

Question: After stopping fisetin, how to increase speed of healing (slower healing being one of side effects of fisetin)?

Some ideas: Take curcumin, B-vitamins (particularly B5), most days. Anything else that could be helpful post-fistetin?

 

Taking even low doses of curcumin so soon after a high dose of fisetin has turned out to be not a good idea.

Just ending 2 days of quite low dose curcumin (2 capsules/day theremin brand with fish oil). 

 

My hair suddenly became shockingly dry (fisetin had dried it out already) and my face looks even more drained and sickly. 

 

Low dose curcumin following high dose fisetin seems to amplify fisetin's impact to an astonishing extent.  Won't do that again!  


Edited by Empiricus, 15 November 2019 - 11:59 AM.


#840 osris

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Posted 15 November 2019 - 11:35 AM

Taking even low doses of curcumin so soon after a high dose of fisetin has turned out to be not a good idea.

Just ending 2 days of quite low dose curcumin (2 capsules/day theremin brand with fish oil). 

 

My hair suddenly became shockingly dry (fisetin had dried it out already) and my face looks even more drained and sickly. 

 

Low dose curcumin following high dose fisetin amplify the impact to an astonishing extent. Won't do that again.  

 

How can you be sure that fisetin was the cause of your hair and face drying? And if it was, why did it cause this do you think?


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