How to increase the bioavailability of Fisetin

Jesper de Meeuw 

Where did you get the Phosal 50?  A quick web search showed some information but no sources.

Paul Tozour JGC Jesper de Meeuw  I am also trying to find ways to increase bioavailability of Fisetin besides spculative use of oil and piperine. I am thinking of ordering liquid phosphatidylcholine and PEG400 both can easily be bought on amazon. And of course ethanol (which I think I know where to buy :)

Phosal is hard for me, as consumer in Europe, to find a good place to buy. I wonder if it will be very differnt to use liguid phosphatidylcholine instead of PHOSAL? What do you think?

http://www.lipoid.com/en/phosal

"The Lipoid PHOSAL® brand name encompasses unique liquid compounds based on phosphatidylcholine. They can act as solubilizers for components that are either insoluble or barely soluble in aqueous solutions or function as a source of phosphatidylcholine with essential fatty acids. The PHOSAL® products can be incorporated directly into oral or dermal formulations."

Staffan Olsson 

Phosal 50 seems to be a mix of 50% phosphatidylcholine and 50% propylene glycol, both of which can be ordered from Amazon.  In particular, they sell phosphatidylcholine  for $14.09 for 100 x 420 mg liquid-filled gel caps and propylene glycol for $14.47 per quart bottle.  Therefore, you should be able to mix up your own equivalent of Phosal 50, if that's what you want.  I think I'll try olive oil first.

In June, my wife and I plan to do another Fisetin senolytic session, and for this I have purchased 100 grams of >98% pure Fisetin powder.  I also bought a $17 digital scale that reads in milligrams.  I'll put a small glass of warm olive oil on the scale, zero it, and add the Fisetin powder until I get the desired dose, then stir and drink.  We will first take a 10 mg capsule of Bioperine.  An hour later we will dissolve 2.0 grams of Fisetin powder in warm olive oil and take that.  We will do this in the morning for three consecutive days.

We are shooting for a total 6 gram dose because we previously experienced no ill effects from 5 grams taken over four days and because there seems to be a threshold effect with the senolytic effects of Fisetin and we would like to be over that threshold for as many senescent cell-types as possible.

JGC where did you purchase your Fisetin powder? Thanks in advance.

djmichel 

I bought the 100 g of Fisetin for $196 including shipping from vitaspace.com, which seems to be located in New York. I was dealing with a person named Peter. The URL is https://www.vitaspace.com and the phone number is (631) 342-1883.

JGC How do you plan to use the Fisetin?  That is an awful lot for senolytic doses.  Will you also take smaller doses daily?

Dan Nave 

Senolytic research with mice indicates that there is a threshold all-at-once dose of Fisetin, below which there is not much action in clearing senescent cells, so small daily doses probably have no senolytic effect.  Further, a big unknown is whether that threshold level varies significantly for different cell types.  Therefore, we are taking doses on the large side (2 g) for several days, then nothing more for 6 months.

We had planned to start this session last week, but there is a significant bruise on the back of my hand from competing at a dog agility trial (my hand accidentally hit a jump post).  I am waiting for that to fade before starting the session.

In response to another question, I have not yet personally determined whether 2 g of my Fisetin powder will easily dissolve in warm olive oil, but there is a post here somewhere saying that this works.  I will report my own experience, one way or the other, probably next week.

Paul Tozour 

Yes, apparently Amazon sells suppository molds, and one can fill these with coconut oil sandwiched with the supplement of interest, solidify them in the freezer, and insert away.  This is reputed to be a good way of getting fragile supplement molecules into the bloodstream while avoiding stomach acid and breakdown enzymes in the intestines.  It's worth considering, but I think I'll hold off for now.

JGC 

That sounds good.  

I had absolutely no problem dissolving my Swanson (Novusetin) Fisetin in room temp olive oil, and also it worked with another kitchen/cooking oil I had when I ran out of olive oil.  If there are fillers in your product they may not dissolve.  However, mine looked well dissolved, as well as the Quercetin and Curcumin I had also gotten from Swanson Vitamins.  Didn't really taste too bad either.
 I think you are wise to wait until you heal up from anything going on in the body before taking the senolytic dose.  From my experience, I feel that it slows/stops healing for a week or two.
Also, I feel that a wait of 6 month between doses is also wise.  When I took a second dose in 1 month after the first (F+Q+C) it really seemed to hit me hard, and took 2 1/2 weeks to 3 weeks before I was feeling normal again.  (I took 1 gram each of F+Q for three days.  The second month I did the same with F+Q+C. This dissolved in olive oil, and also took approx 1/2 teaspoon freshly ground black pepper at the same time, no waiting.)

Dan Nave Dan Nave

Today I had my first dose of fisetin. To enhance bioavailability I made my own PHOSAL (I mixed 50% phosphatidylcholine with 50% propylene glycol) and then I added Polyethylene Glycol (PEG 400). Then I mixed it all with Fisetin.

The Fisetin dose I took today was slightly over 20 mg/kg. My weight is 78 kg and I used 1600 mg.

I have been ok all day. No negative feelings.

Maybe i slight feeling of increased wellbeing during the day. But that can be placebo.

I am not sure ithat acute and short term effects is something to aim for or if short term effects should be seen as an indication of Fisetin doing a good job. But it can be an indication that I have not got any acute negative reactions. 

Tommorrow I aim for 35 mg/kg. 

Dan Nave JGC

When it comes to bioavailability there is research going on with a nanoemulsion. It works fine with mice. If it is well tolerated by humans and is as effective in humans as in mice it will be a very attractive product.

“Pharmacokinetic studies in mice revealed that the fisetin nanoemulsion injected intravenously (13 mg/kg) showed no significant difference in systemic exposure compared to free fisetin. However, when the fisetin nanoemulsion was administered intraperitoneally, a 24-fold increase in fisetin relative bioavailability was noted, compared to free fisetin. Additionally, the antitumour activity of the fisetin nanoemulsion in Lewis lung carcinoma bearing mice occurred at lower doses (36.6 mg/kg) compared to free fisetin (223 mg/kg). In conclusion, we have developed a stable nanoemulsion of fisetin and have shown that it could improve its relative bioavailability and antitumour activity..”

https://www.ncbi.nlm.nih.gov/pubmed/22387278

ta take it intraperitoneally is not an option for us but at least this gives us an indication that the issue with low bioavailability can be handled in creative ways.

JGC I have done a large senolytic dose with Fisetin twice now but I also take 100mg a day.  I give my wife 100mg a day as well. Do you think it's a waste of money to take a small daily dose?

Another question for you as well. I am buying some liquid DMSO.  I was thinking about dissolving some Dr's Best Fisetin into it and applying it to my face. Do you know anyone who has done this and if so is it safe and how many 100mg pills should I mix in a 8 oz bottle. Will it have a positive effect on my skin?

Thanks!

John

JOHN Be careful with pure DMSO - at minimum you need to dilute.  Personally I wouldn't put DMSO on my face.  Full strength DMSO can cause serious burns and rashes / reactions.  

JOHN 

I agree that DMSO, while it does dissolve flavenoids, may produce problems on its own.  If you do try it on your face, start with a very small patch.

As for daily small doses of Fisetin, itwill not trigger the aptosis of senescent cells, but it could possibly have other benefits.

JGC 

Regarding your discussion regarding about the bioavailability of polyphenols. (In the resveratrol thread).  I have done two experiments with fisetin using homemade rectal suppositories. (Fisetin in coconut oil. First 300 mg and then 500 mg.) Though I have not much to say at this stage. But the experiments has made me consider the question: which is the most rational way to get bioactive polyphenolic substances into the bloodstream and then have bioactive substances reach target cells?

 And I am not sure how much of fisetin’s actions that can be attributed to the free substance and how much (if any) that can be attributed to metabolites from the metabolism that takes place in the liver when the fisetin absobed and make first pass through the liver.

The oral route is the one that has the science behind it and it is also what the mayo clinic use on both animals and humans. Then again we have reports that “nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice” this indicate that there is potential for bypassing the oral route. (But  not through intraven-injections).

“Pharmacokinetic studies in mice revealed that the fisetin nanoemulsion injected intravenously (13 mg/kg) showed no significant difference in systemic exposure compared to free fisetin. However, when the fisetin nanoemulsion was administered intraperitoneally, a 24-fold increase in fisetin relative bioavailability was noted, compared to free fisetin.

 https://www.ncbi.nlm.nih.gov/pubmed/22387278

The section “2. Bioavailability and pharmacokinetics of fisetin” in the paper below is a good short read and it made me consider that it might not only be free fisetin that gives as the effects we are looking for, but there might be metabolites contributing to the effects we want. How much of those metabolites are produced when using the oral route and how much will we get from using other routes (like the rectal route)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067175/

“Touil et al. [10] determined the pharmacokinetics and metabolism of fisetin in mice and studied the biological activities of its metabolites. Their studies showed that after an intraperitoneal (ip) dose of 223 mg/kg body weight the maximum plasma concentration (2.53 µg/ml) of fisetin was reached at 15 min which started to decline with a first rapid alpha half-life of 0.09 h and a longer half-life of 3.12 h. Three metabolites of fisetin were detected including the methoxylated metabolite geraldol. The latter was shown to achieve higher concentrations than fisetin in tumor-bearing mice and appeared more cytotoxic than the parent compound [10].”

When it comes to the bioavailability of fisetin, I still favor the oral route, then the sublingual route and lastly using rectal suppositories. If I  find facts or make experiences that point me in another direction, then I will of course change my mind.

I keep experimenting and when I have something with more substance to report from my experiments I will do it in this forum. 

Staffan Olsson 

The Fisetin metabolites may perhaps play a role in the in vivo results with animal models.  However, in the initial work on human senescent cell cultures that indicated the senolytic effectiveness of Fisetin and D+Q was done in vitro, and essentially no metabolism was involved, in that the cells were cultured in a Petri dish to which the flavenoids were directly added.

On the question of how to improve bioavailability of Fisetin, I note that RevGenetics in their Nitro Super Micronized Resveratrol capsules suspends the Resevratrol micro-particles in Tween 80 surfactant emulsifier, a commercial product that can be bought by the liter and that has a huge effect on bioavailability.  I am wondering if ingesting Fisetin emulsified in Tween 80 would similarly enhance its bioavailability.

JGC  you seem to have a lot of knowledge on here. I have done a couple of senolytic doses with fisetin and I'm on 1000mg of extended release metformin for longevity. My father in law is in late stage Copd and has some heart issues. Is it safe for a 77 year old copd patient with a weak heart to take senolytics?  Will it help him live longer?   Can there be a benefit or is it too risky?

JGC 

The cell metabolism in the human body is very complex and the complexity makes it , as we all know, difficult to create specific  and effective interventions.

When it comes to the bioavailability of polyphenols I find this paper “  Molecular Mechanisms and Bioavailability of Polyphenols in Prostate Cancer” being a very compact but good read. It is about prostate cancer. But it highlights the complexity and relates in a meaningful way to research about polyphenols like quercetin, resveratrol, apigenin, curcumin, EGCG etc.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429226/

Different methods of delivering a substance usually/probably creates different metabolites. This due to metabolism by the mircroflora in the intestine and also during the metabolic passage through the liver and then through metabolism by other metabolic pathways in our cells. we work with a lot of assumtions and partly unknown varaibles, but when it comes to senolytics like fisetin, D and Q  what we have  gained so far is very promising

When it comes to bioavailability of Fisetin I will try a few more experiments with rectal administration but now with higher doses.