1079 replies to this topic

[manofsan]

Fore the last 4 days I have been using 1000 mg of fisetin, 250 mg turmeric and 5 mg piperine. 

I mixed the fisetin and turmeric in 5ml of DMSO and then diluted it with water.  I felt a little fatiuged

and almost like I had a hangover plus I had a mild headache. It seems that I didn't feel as much

reaction the 3rd day and almost no reaction yesterday so I may end my experiment today. I did 

go to the gym yesterday and found it a little more fatiguing than it usually is for me and didn't get

any extra energy later on like you did. 

 

Hi, regarding DMSO - hasn't this stuff been found to be harmful to cells, and especially harmful to mitochondria in particular?

 

https://www.ncbi.nlm...les/PMC4169574/

 

I realize you're taking it because it's a membrane disruptor, but there may be damaging side-effects from this. Are you sure you want to take that risk?

 

Mitochondria and their health are very important to our overall health and longevity.

[OP2040]

I would like to know if the many studies on D+Q are down to the actual science,, or if they simply ignore other compounds because they are not locked down and unavailable.  I've looked into D before, but it has a horrible safety profile and of course very hard to get.  I'm almost 100% certain it's the latter.  Clinical trials cost millions of dollars so you can really imagine anyone getting behind a trial for Fisetin or Quercetin alone. 

 

I did a search and can't find anything like this, but it would be extremely useful to have a simple chart based on all the senolytics and the cell types they are known to work with, possibly also including specificity.  The literature review required my be the hardest part, but once it is made, it would be easy to maintain.  I may do this myself.

Edited by OP2040, 26 March 2019 - 02:39 PM.

[Florin]

I did a search and can't find anything like this, but it would be extremely useful to have a simple chart based on all the senolytics and the cell types they are known to work with, possibly also including specificity.  The literature review required my be the hardest part, but once it is made, it would be easy to maintain.  I may do this myself.

 

An Overview of the Present State of Development of Senotherapeutics
https://www.fightagi...notherapeutics/

[Krell]

Has anyone tried this? 

 

Any suggestions on amounts (by weight or volume?) required?  

 

Since I have a scale, how about these weights:

 

90 grams water

4 grams d-limolene - https://www.ebay.com/itm/131548129653

6 grams tween 80 - https://www.ebay.com/itm/302575005257

1.7 grams fisetin (83kg*20mg/kg=1.66gm) - https://www.amazon.c...uct/B0081NXW1C/

 

Does it make any difference in what order you mix them?

 

My latest experiments:

 

I bought 4 oz of both d-limolene and tween 80.

See picture of bottles below.

 

I mixed 30 ml of d-limolene with 45 ml of tween 80.

They form a slightly yellowish clear liquid.

 

I added 300 mg fisetin (3 capsule contents) into the mixture and stirred off and on for 2 days.

This is about 10mg/ml concentration of fisetin in the d-limonene (300mg/30ml).

The fisetin was mostly dissolved, but with a fine powder left in the bottom of the glass.

I added another 300mg fiseting into the mixture and stirred off and on for 2 days.

This additional fisetin did not appear to dissolve in the mixture.  See picture below on left.

Conclusion is that fistein is soluble at somewhat less than 10mg/ml in d-limonene.

 

Add 270grams of water to 30ml of the fluid mixture while stirring for about 5 minutes.

(10 parts mixture (30ml) to 90 parts water (270ml or gram)

See picture of glass with yellow fluid below.

The nano-emulsion did not settle out over night.

Conclusion is that a stable emulision can be formed easily by this technique.

 

When I tasted a drop, it was like a super powerful lemon burning sensation. 

Conclusion is this emulsion is not drinkable in any significant quantity.

 

Comments?

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[Oakman]

As long as you got the fisetin in solution, it shouldn't hurt to mix it with, say, orange juice, and gulp the whole thing, would it. Probably on a totally empty stomach to get fastest absorption. BTW, thanks for experimenting!

[Woody42]

Are there any studies showing water fasting clears senescent cells ?

 

Now for a laugh.  Another plant compound Luteolin  may have some 

senolylic  properties.  One source of this is ragweed the same ragweed

mentioned in a couple of 1970 sifi books as a source of the fictional 

longevity drug booster spice.   

[manofsan]

 

When I tasted a drop, it was like a super powerful lemon burning sensation. 

Conclusion is this emulsion is not drinkable in any significant quantity.

 

Comments?

 

 

Mix it with booze?

[Daniel Cooper]

 

 

When I tasted a drop, it was like a super powerful lemon burning sensation. 

Conclusion is this emulsion is not drinkable in any significant quantity.

 

Comments?

 

I'm guessing that is the d-limonene that is giving that effect. 

 

Ideally you'd want to put it in a gel cap.  That's what you'd do if you were making a commercial product and indeed how d-limonene supplements are sold.  

 

I have no idea if anyone has come up with a way to DIY a gel cap though.

[LarryG]

I should have considered the difficulty of swallowing d-limonene.  It is usually sold as a capsule and I've take it so I never thought of the taste.  Here an article on something that doesn't have that problem...cyclodextrins.  https://www.tandfonl...44.2016.1245366

[Daniel Cooper]

For what it's worth, it does look like you can make your own gel caps by filling a regular old two part gelatin capsule with a dropper or syringe.  The only caveat being that whatever you use must not dissolve gelatin, which d-limonene might.

 

 

 

[Krell]

For what it's worth, it does look like you can make your own gel caps by filling a regular old two part gelatin capsule with a dropper or syringe.  The only caveat being that whatever you use must not dissolve gelatin, which d-limonene might.

 

Seems like too much liquid to consider capsules!

 

For example, 300mg fisetin (not much, 3 capsules) requires about 30ml d-limolene and 45ml tween 80, plus 9*75ml=675ml water, for a total of 750ml of nano-emulsion.

 

That would be a lot of capsules for not much fisetin dose.
 

[Daniel Cooper]

Yeah, that would be beaucoup capsules.  I hadn't noticed the total volume you guys are trying to consume.  

 

I've tasted raw d-limonene and yeah, that would be very difficult to get down.  Would probably burn your throat for a while if you managed to swallow it.  I doubt you would want to do it on a regular basis.

 

Never mind ......

 

 

 

 

[maxwatt]

I would like to know if the many studies on D+Q are down to the actual science,, or if they simply ignore other compounds because they are not locked down and unavailable.  I've looked into D before, but it has a horrible safety profile and of course very hard to get.  I'm almost 100% certain it's the latter.  Clinical trials cost millions of dollars so you can really imagine anyone getting behind a trial for Fisetin or Quercetin alone. 

 

I did a search and can't find anything like this, but it would be extremely useful to have a simple chart based on all the senolytics and the cell types they are known to work with, possibly also including specificity.  The literature review required my be the hardest part, but once it is made, it would be easy to maintain.  I may do this myself.

 

Interesting that genestein targets tyrosine kinase, the same target of dasatinib.  In addition, it appears to target other types 0f senescent cells.

 

"There is no information about senolytic activity of genistein but its inhibitory effect on tyrosine kinase [152] (the same target of dasatinib) would deserve appropriate consideration." reference

 

The reference above contains information on a dozen other potential senolytics. https://www.hindawi....i/2018/4159013/

 

I would not take genestein continuously due to mimetic estrogenic effects, but for intermittent use as a senolytic therapy, it might be worthwhile.  Pending further studies.

[scooterboy]

I am planning to take 3000mg of fisetin in olive oil for five days . I am going to add about 30mg of BioPerine per dose for absorption . My question is would it be better to open the capsules an add them to the mix or take them separately 

 

[LarryG]

Do you have any info on whether or not bioperine will increase absorption of fisetin?  To my understanding, it doesn't work with everything.  I have read but not confirmed that it works with quercetin, but that was with iso-quercetin, not quercetin per se.  I just read, but haven't been able to confirm, that Mayo Clinic used the following solution to increase absorption... 60% Phosal 50 PG:30% PEG400:10% ethanol.  I just did a two day test of 2G daily of fisetin.  It floated in the water, so I added into the 1/2 cup of the water the following: 1/8t of d-limonene, 1/8t PEG-40, and 3Tbs of red wine (5% alcohol).  The fisetin mixed easily into the water in this solution.  The fisetin I used was 50% fisetin powder from Pure Bulk.  2 teaspoons of this powder = approximately 2 grams of fisetin.  I bought 25 grams for $26.75, which is 12.5 grams of fisetin from the Smoke Tree plant.

 

 

[Woody42]

I used 1000 mg of fisetin with 250 mg of turmeric for 5 days. Now 

I wonder how long it takes for any senescent cells that this has targeted

to be killed and removed . Is this process likely to be over in a week or 

2 or take months. 

[scooterboy]

Do you have any info on whether or not bioperine will increase absorption of fisetin?  To my understanding, it doesn't work with everything.  I have read but not confirmed that it works with quercetin, but that was with iso-quercetin, not quercetin per se.  I just read, but haven't been able to confirm, that Mayo Clinic used the following solution to increase absorption... 60% Phosal 50 PG:30% PEG400:10% ethanol.  I just did a two day test of 2G daily of fisetin.  It floated in the water, so I added into the 1/2 cup of the water the following: 1/8t of d-limonene, 1/8t PEG-40, and 3Tbs of red wine (5% alcohol).  The fisetin mixed easily into the water in this solution.  The fisetin I used was 50% fisetin powder from Pure Bulk.  2 teaspoons of this powder = approximately 2 grams of fisetin.  I bought 25 grams for $26.75, which is 12.5 grams of fisetin from the Smoke Tree plant.

 

Are you using the 60% Phosal 50 PG:30% PEG400:10% ethanol mix with the 1/8t of d-limonene, 1/8t PEG-40, and 3Tbs of red wine   ?  Is it 1/8t of a cup to 1/2 cup of water ? Didn't you say d-limonene was not drinkable ?
 

Edited by scooterboy, 05 April 2019 - 06:15 PM.

[LarryG]

D-limonene is consumable and is sold as a supplement, or as an adjunct to another supplement, like, CoQ10+d-limonene.  The problem was with the solution I proposed.  It had so much d-limonene that it was just too much.  Far to strong to drink comfortably.  LIfe Extension sells the Jarrow version of d-limonene as a 500mg gel cap with a dose of 2, or 1gm.  [take 2, plus PEG-40, plus fisetin?) FYI...you need food grade d-limonene.  LEF sells Kanka Q-10 + d-limonene 100/100mg to increase absorption of the Q10 due to d-limonene being an emulsifier.  That's why the mix I made above (water, fisetin, d-limonene, PEG-40) dispersed in the water.  PEG40 is castor oil based Polyethylene Glycol and is a surfactant and emulsifier.  Another thing...PEG is a laxative in a large dose, say, 70g.  Miralax (polyethylene glycol 3350) is a laxative, for instance.  So, now that I think of it, I'm disinclined to take a large dose of PEG40.   So, at the level I used d-limonene in lemonade, I barely tasted it.  I may increase it next time to see what my tolerable limit as far as taste is.  FYI, after each of two doses of 2gm, I felt amazingly good for some reason, perhaps because it's anti inflammatory and I have osteoarthritis.  Mechanism of action in that aspect is unknown as far as I know but it inhibits COX-2 (not COX-1) and MAPKs, as well as IL-KB, and activates SIRT1 (mice).  https://www.ncbi.nlm...pubmed/28213268

[scooterboy]

D-limonene is consumable and is sold as a supplement, or as an adjunct to another supplement, like, CoQ10+d-limonene.  The problem was with the solution I proposed.  It had so much d-limonene that it was just too much.  Far to strong to drink comfortably.  LIfe Extension sells the Jarrow version of d-limonene as a 500mg gel cap with a dose of 2, or 1gm.  [take 2, plus PEG-40, plus fisetin?) FYI...you need food grade d-limonene.  LEF sells Kanka Q-10 + d-limonene 100/100mg to increase absorption of the Q10 due to d-limonene being an emulsifier.  That's why the mix I made above (water, fisetin, d-limonene, PEG-40) dispersed in the water.  PEG40 is castor oil based Polyethylene Glycol and is a surfactant and emulsifier.  Another thing...PEG is a laxative in a large dose, say, 70g.  Miralax (polyethylene glycol 3350) is a laxative, for instance.  So, now that I think of it, I'm disinclined to take a large dose of PEG40.   So, at the level I used d-limonene in lemonade, I barely tasted it.  I may increase it next time to see what my tolerable limit as far as taste is.  FYI, after each of two doses of 2gm, I felt amazingly good for some reason, perhaps because it's anti inflammatory and I have osteoarthritis.  Mechanism of action in that aspect is unknown as far as I know but it inhibits COX-2 (not COX-1) and MAPKs, as well as IL-KB, and activates SIRT1 (mice).  https://www.ncbi.nlm...pubmed/28213268

 

Are you using food grade d-limonene ?

[Oakman]

Seems like the current discussion is getting pretty convoluted. What do you think of this alternative method of improving bioavailability?

 

It seems that "fisetin strongly binds between the polar head and hydrophobic tail of the phospholipids around the interfacial region of the egg phosphatidylcholine liposomes (59). "  Here is a pretty picture showing fisetin in the lipid bilayer .

 

 

So as l-α-Dimyristoylphosphatidylcholine (DMPC) or egg phosphatidylcholine (PC) is easily obtainable, for example in capsules containing 70 mgs each with other lipids, Might not that be a possibly easier avenue to bioavailability? I bought some but haven't has a chance to play with it yet. It is a yellow powder, looks like powdered egg yolk. I'm not sure how two powders would interact to get integrated? Anyone have thoughts on this?

Edited by Oakman, 06 April 2019 - 01:29 AM.

[Woody42]

Any idea where to buy a small quanity of phosal 50 ?

[LarryG]

Phosal 50 is just 50% Phosphatidylcholine plus polyethelene glycol and PC is available for sale all over the web and EBay as a pill, or as a liquid.  Phosal is made in 35% PC as well.  Here's a link to a liposomal form with small drop size and enhanced absorption by QuickSilver.  Other brands available on EBay.... https://www.quicksil...oducts/pure-pc/

[scooterboy]

The lPhosphatidylcholineooks liposomal form may be the best choice to add to Fisetin . Any guess on how much for 2 grams ?

[scooterboy]

The lPhosphatidylcholineooks liposomal form may be the best choice to add to Fisetin . Any guess on how much for 2 grams ?

[LarryG]

Don't know how much to dissolve 2g because I have no science background, but enough to dissolve it easily.  What I did above did dissolve easily (sugar free lemonade, PEG400, d-limonene, 2g of fisetin).  Of course, I have no idea how this affected absorption but I am assuming it would be better than raw powder.  I would likely use the formula above, namely 60% Phosal 50 PG:30% PEG400:10% ethanol if I do this one formula, and I assume this would disperse in lemonade as well.  This substitutes Phosal 50 for d-limonene.  I do use food grade PEG400 (USP grade) from Amazon.  It's cheap.  I'm unsure what I'll do next dose.  Still looking at ideas.  Not sure if bioperine will help or not.  What improves absorption is dependent on the substance.  For instance, berberine absorption is improved by taking milk thistle extract as well.  I think adding bioperine is worth it based on the fact that it improves the absorption of quercetin by 3x.  https://restorativem...nal-absorption/

[extendcel]

I have around 5kg of 94%+ defatted Phosphatidylcholine to produce liposomes. At that quantity it cost me $265/kg.

Edited by extendcel, 07 April 2019 - 12:22 PM.

[Oakman]

A reminder: egg phosphatidylcholine ≠ any old phosphatidylcholine

Phosal 50 PG = Compound of 50% phosphatidylcholine from soybean with propylenglycol, fluid

 

 

Edited by Oakman, 07 April 2019 - 01:18 PM.

[Oakman]

A reminder: egg phosphatidylcholine ≠ any old phosphatidylcholine

Phosal 50 PG = Compound of 50% phosphatidylcholine from soybean with propylenglycol, fluid

 

References are in my original post #530

[scooterboy]

So are you saying both egg phosphatidylcholine and 50% phosphatidylcholine from soybean will work with Fisetin ?

[Oakman]

So are you saying both egg phosphatidylcholine and 50% phosphatidylcholine from soybean will work with Fisetin ?

 

I'm not an expert in the chemistry of PL, however the references I mentioned say that Fisetin has an affinity for egg PL, and so there must be something different about it from other PLs. In fact, upon further searching -this is so - as stated here in this study...

 

A review on phospholipids and their main applications in drug delivery systems

 

"Phospholipids are molecules in which hydrophilic head group and hydrophobic acyl chains are linked to the alcohol. The variation in head groups, aliphatic chains and alcohols leads to the existence of a wide variety of phospholipids. In addition, the different sources of phospholipids also enhance the species of phospholipids. Various phospholipids, such as soybean phosphatidylcholine, egg phosphatidylcholine, or synthetic phosphatidylcholine, as well as hydrogenated phosphatidylcholine, are commonly used in different types of formulations. Phospholipids become intriguing as they can offer various options. However, the species diversity of phospholipids make how to select an appropriate phospholipid to achieve the therapeutic purpose become a crucial problem in the design of DDS, so we summarized the structures, main sources, properties of phospholipids which can give a guideline in the design of DDS."

 

So what this indicated to me is that just taking some PL, any old PL ,will likely not make a good formulation for Fisetin. There's no harm in trying, but how can you be sure? Alternatively, someone has done the work to find that egg PL does work... so why not use that type. Just saying.

 

More chemistry from the same article....

 

"However, soybean and egg yolk have differences in the contents and species of phospholipids, mainly including: 1) egg yolk lecithin contains a higher amounts of PC; 2) phospholipids in egg yolk exist long chain polyunsaturated fatty acids of n-6 and n-3 series, primarily arachidonic acid (AA) and docosahexaenoic acid (DHA), which are absent in soybean lecithins; 3) animal lecithins have characteristic of the presence of SM [18]; 4) the saturation level of egg yolk lecithins is higher than that of soybean lecithins [19], so their oxidative stability is better than that of soybean lecithins; 5) for egg yolk phospholipids, saturated fatty acid is usually at sn-1 position, and unsaturated fatty acid is at sn-2 position [9], while for soybean lecithin, sn-1 and sn-2 position can be both unsaturated fatty acids"