731 replies to this topic

[Andey]

I do see a clear performance boost with MK-677 at the gym, especially in the area of muscle building (weights or bodyweight lifting). I can sort of see why you would want to boost GH after a round of senolytics so that's sort of why I'm doing it. I have a contact that's a reliable source, he only takes bitcoin though. People have lab tested his stuff as I recall, on reddit.

 

That's basically what the doctor said on Louis CK's show about lower back pain, we just weren't meant for this kind of thing for that long. I've been suffering from lower back pain since I was 29, so this is definitely not a problem of age. The only reason why I was hoping dasatinib would help with it was lowering inflammation. 

 

Another wild guess - have you tried inversion table or boots ?

Or ELDOA stretching ?

I am working now with chiropractor and all this combine slowly and steadily improves my spine health.

ELDOA L5 - S1 is a good place to start

 

P.S. I know...offtopic, but this topic derailed ages ago, group buy have ended successfully  and it not even from Nyles

Edited by Andey, 20 April 2017 - 05:19 AM.

[Longevitarian]

Hi Guys"

 

This posting is regarding Navitoclax and its effect on the sertolli cells, and an idea

how to protect them.

My earlier posting suggested that cooling the "goods" to temperature below 10C would

alleviate the problem by upregulation of the Bcl-2, which essentially would locally do exactly

opposite action to what Navitoclax normally does in the cells thus cancelling its negative

effects on gonads, while still allowing its senolytic effects everywhere else.

To continue on this note I propose adaptation of a beer can cooler  as a contraption

which, with little ingenuity and modification could  implement such cooling strategy and

allow precise temperature regulation via your computer. Here it is:

http://www.thisnext....everage-Chiller

 

I think I should patent this solution and make $$$$$$$ to finance purchase of Nav.....He He He

 

 

[DareDevil]

Unfortunately that chiller seems to be out of production. Regarding Navitoclax regenerating our stem cells here is an interesting article from Japan where I believe it is the Year of Anti Aging:

Preventing aging with stem cell rejuvenation: Feasible or infeasible?

https://www.ncbi.nlm...les/PMC5253185/

 

DD

[Longevitarian]

DD'

 

Sorry to hear the beer coolers were discontinued. Fortunately there is huge selection of

other models and designs available on the internet. Moreover you don't need entire

device to fit ypur parameters....I is enough that ypu pull out the cooling element from

any of the devices and place it in a more comfortable wrapping ....eg adult diaper or

whatever .....this should work. The cooling element is extremely simple and will work

stand alone.......So , don"t ge discouraged......

 

https://www.google.c...GqamIEYT_GAH9M:

[Andey]

Unfortunately that chiller seems to be out of production. Regarding Navitoclax regenerating our stem cells here is an interesting article from Japan where I believe it is the Year of Anti Aging:

Preventing aging with stem cell rejuvenation: Feasible or infeasible?

https://www.ncbi.nlm...les/PMC5253185/

 

DD

 

There is a lot going on in that article.

Personally, I would wait until induced autologous pluripotent stem cells hit the mass market.

Inducing differentiation could be two age sword as you could gain short term benefits but deplete stem cells pool much faster. 

Fetal or placenta stem cells could be highly beneficial but yet to see commercially available service to match donor immunogenecity at least by HLA type. Unfortunately whole approach became shady before needed research was done and now it stagnated on the level of some sketchy clinics.

[DareDevil]

Hi Longetarian,

 

Yes that's true it should be easy. Plus I have medical icepacks that plastic surgeons give out to prevent swelling that are in my freezer. Judicious placement of these, a few minutes at a time to prevent sub-zero temperatures, could also be done manually despite it being a bit fastidious.

 

 

Hi all,

 

While apparently off topic, this subject isn't that far removed from that of your new quest, a Group Buy of Navitoclax to cleanse our Stem Cells so that we have healthier life giving bodily repair potential. In this vein, we would also need to see how to rebuild more quickly, because I've noted that cellular lysis brings short to medium term effects which are akin to those of chemotherapy. My family was so alarmed at my shape this weekend at a family gathering that many later inquired and my sister-in-law couldn't sleep all night afterwards. So we must address more holistically how to reduce and remand the effects of potent stem cell senolytics and kick-start rebuilding. After stopping old age, it serves well to reboot youth.

 

 

Hi Andey,

 

Thanks for your analysis. I see you're in Ukraine. That's where I am thinking of going since both EmCell and Infinity Clinic in Kiev have already replied, offering me Embryonic Stem Cell treatments. I am about to jump the gun, explode my credit card and book a 3-day session there. They offer multiple IV infusions of umbilical stem cells as well as screened and cultivated pre-differentiated tissue-targeting stem cells for specific treatment areas. One of these that appeals to me after losing considerable facial fat from D+Q and suddenly looking 10 years older, is their "facial skin stem cells" which, if true, would make all the injected stem cells concentrate their action on rejuvenating one's face from the inside, our blood irrigation bringing the building blocks for a new young and fresh pulpy face. Is this a pipe dream or can it hold true to promise?

 

Noteworthy, although expensive these clinics in Ukraine cost only a fraction of what I was quoted in Thailand. The cheaper options elsewhere are said to be just as good for therapeutic efforts, but they are less effective at reversing aging. These are based on Autologous Stem Cell Treatments from your own fat or bone marrow, but they come without the powerful Nanog gene that can reverse aging in adult stem cells. Making our stem cells young sounds like a plus.

 

These clinics in Kiev have received many awards and enjoy a strong reputation. One even has a special facility just for wealthy Middle-East patients, showing their success among the elite. They claim to have devised formulations that reduce rejection issues from incompatibilities. I would have access to my personal stash of Rapamycin, that I could possibly use at slightly higher doses than the usual low-dose anti-aging protocol to reduce rejection, which is the main indication for this drug. But these clinics surely have their own pharmaceutical strategies to handle this.

 

Please tell us if you've heard anything good or bad regarding the clinics offering treatment in Ukraine. At least the pricing might be justified if the claims are true. Is it marketing hype like the Stem Cell Facelift, where many doctors simply do standard old-school fat grafting to your cheeks or wherever, assuming a few stem cells will be inside? I hope not because it doesn't seem likely that the induced autologous pluripotent stem cells created by Robert Lanza are about to hit the market anytime soon. That could be for a second intervention in maybe 5 to 10 years time.

 

Meanwhile, I'd really like to clear my senescent stem cells BEFORE doing any stem cell infusions. So a Group Buy for Navitoclax would be great, as it isn't easy to source in other ways. I would however plan on scheduling a boosting of stem cell activity in the weeks following a Navitoclax stack, to heal from the inside after unleashing the Grim Reaper.

 

Cheers,

 

DareDevil

[Andey]

Hi Longetarian,

 

Yes that's true it should be easy. Plus I have medical icepacks that plastic surgeons give out to prevent swelling that are in my freezer. Judicious placement of these, a few minutes at a time to prevent sub-zero temperatures, could also be done manually despite it being a bit fastidious.

 

 

Hi all,

 

While apparently off topic, this subject isn't that far removed from that of your new quest, a Group Buy of Navitoclax to cleanse our Stem Cells so that we have healthier life giving bodily repair potential. In this vein, we would also need to see how to rebuild more quickly, because I've noted that cellular lysis brings short to medium term effects which are akin to those of chemotherapy. My family was so alarmed at my shape this weekend at a family gathering that many later inquired and my sister-in-law couldn't sleep all night afterwards. So we must address more holistically how to reduce and remand the effects of potent stem cell senolytics and kick-start rebuilding. After stopping old age, it serves well to reboot youth.

 

 

Hi Andey,

 

Thanks for your analysis. I see you're in Ukraine. That's where I am thinking of going since both EmCell and Infinity Clinic in Kiev have already replied, offering me Embryonic Stem Cell treatments. I am about to jump the gun, explode my credit card and book a 3-day session there. They offer multiple IV infusions of umbilical stem cells as well as screened and cultivated pre-differentiated tissue-targeting stem cells for specific treatment areas. One of these that appeals to me after losing considerable facial fat from D+Q and suddenly looking 10 years older, is their "facial skin stem cells" which, if true, would make all the injected stem cells concentrate their action on rejuvenating one's face from the inside, our blood irrigation bringing the building blocks for a new young and fresh pulpy face. Is this a pipe dream or can it hold true to promise?

 

Noteworthy, although expensive these clinics in Ukraine cost only a fraction of what I was quoted in Thailand. The cheaper options elsewhere are said to be just as good for therapeutic efforts, but they are less effective at reversing aging. These are based on Autologous Stem Cell Treatments from your own fat or bone marrow, but they come without the powerful Nanog gene that can reverse aging in adult stem cells. Making our stem cells young sounds like a plus.

 

These clinics in Kiev have received many awards and enjoy a strong reputation. One even has a special facility just for wealthy Middle-East patients, showing their success among the elite. They claim to have devised formulations that reduce rejection issues from incompatibilities. I would have access to my personal stash of Rapamycin, that I could possibly use at slightly higher doses than the usual low-dose anti-aging protocol to reduce rejection, which is the main indication for this drug. But these clinics surely have their own pharmaceutical strategies to handle this.

 

Please tell us if you've heard anything good or bad regarding the clinics offering treatment in Ukraine. At least the pricing might be justified if the claims are true. Is it marketing hype like the Stem Cell Facelift, where many doctors simply do standard old-school fat grafting to your cheeks or wherever, assuming a few stem cells will be inside? I hope not because it doesn't seem likely that the induced autologous pluripotent stem cells created by Robert Lanza are about to hit the market anytime soon. That could be for a second intervention in maybe 5 to 10 years time.

 

Meanwhile, I'd really like to clear my senescent stem cells BEFORE doing any stem cell infusions. So a Group Buy for Navitoclax would be great, as it isn't easy to source in other ways. I would however plan on scheduling a boosting of stem cell activity in the weeks following a Navitoclax stack, to heal from the inside after unleashing the Grim Reaper.

 

Cheers,

 

DareDevil

 

 

Hi DareDevil

 

Unfortunately I dont have much to share.

Those clinics are pretty much non existent on local healthcare market.

Emcell dont have ukrainian language as an option on their site.  http://infinityclinic.com/ opens empty for me. Lol. Its not a good sign for me as local residents are more likely to complain or take a legal action against them. Good luck if you are foreigner and want to prove something in Ukrainian court ))

Only clinic that I know is http://www.stemcellclinic.com, they advertise more as a cryobank service for 'own' placenta. I havent heard any real reports about them though. 

Stem cells are less immunogenic then a transplanted organ but without HLA matching their long term survival in the host body is problematic.

Less so in joints because they are less accesible to blood flow and immune system in those locations. There is also a technology to induce stem cells from hosts fat cells and inject in joints. Those cells would be not pluripotent but their type would be compatible with joint tissue (I forgot their exact naming). I remember that some time ago some clinic marketed this service here(dont sure is it still in business). As a downside - this approuch needs time to induce stem cells and to grow them in quantity for treatment, its far easier to inject random placenta cells and get money from a patient.

 

For me its not worth it right now coz I dont even get to the end of 20% effort according to Pareto principle, and stem cell therapy is definitely not in this range by cost/effect ratio.

If I were a multimillionaire it would be an another case though )

[Longevitarian]

Something to consider"

 

Google is looking for 10000 volunteers to participate in extensive testing of

their body over a period of 4 years. Sounds like excellent opportunity for

any proactive life extensionist.

http://www.naturalbl...-screening.html

 

[SearchingForAnswers]

If there is a group buy for navitoclax, please let me know - I want in!


Sent from my iPhone using Tapatalk

[Logic]

...my back hurts but always has for at least 12 years, after sleep...

 

Antibiotics could cure 40% of chronic back pain patients:

http://www.longecity...-pain-patients/

As everything in longevity is connected and I enjoy 'connecting the dots';  things are getting  ...'a little out of hand' in this thread!
Plz use GoogleSiteSearch (In the Search dropdown menu at the top of the page) to find an appropriate thread for subjects 'unrelated' to senolytics, or start a new thread.  Then post a link to said thread here, as I have done.

 

Edit:
Soz Nate I've just read your later post and linked new thread.  
 

Edited by Logic, 23 April 2017 - 04:08 PM.

[Logic]

If there is a group buy for navitoclax, please let me know - I want in!

 

There may well be!  

I got a quote on 100 grams of Navitoclax of:  $ 442.00/g.

Thats without shipping and testing:                $     6.70/g

Total:                                                              $ 448.70/g excluding postage from the USA ($ 6.80 local)

Thats not spare change, but as fasting is so good for one; I might just be able to afford the ~1 gram required for 1 treatment!  

As you can imagine it's going to be a hell of a lot of work to do ~100, 1 gram orders to get that gram, if we can get to 100 grams,  but such is the price of ...immortality..?  

I think we'll manage to pull it off!?

I have started (in Google docs) writing a forum post to this end and it would be up already were it not for a recovered stolen car having to be fetched and fixed.
I hope to get it up tonight if I manage to catch up on all the correspondence etc that piles up so quickly.

Edited by Logic, 23 April 2017 - 05:25 PM.

[DareDevil]

Hi Logic,

 

This maybe seems expensive but is cheap compared to stem cell treatment costing from $5000 to $25000. Plus this drug does things that stem cell IV infusions can't do, getting rid of the damaged senescent stem cells. My only hesitation is whether to buy 1 or 2 grams of Navitoclax in the Group Buy. Thanks for your efforts.

 

DareDevil

[mikey]

Hi Logic,

 

This maybe seems expensive but is cheap compared to stem cell treatment costing from $5000 to $25000. Plus this drug does things that stem cell IV infusions can't do, getting rid of the damaged senescent stem cells. My only hesitation is whether to buy 1 or 2 grams of Navitoclax in the Group Buy. Thanks for your efforts.

 

DareDevil

 

I apologize, but I haven't had time to keep up on reading this thread.

 

Is Navitoclax superior to DQ for senolytic effects and less potential side-effects?

 

Thank you!

[Andey]

Hi Logic,

This maybe seems expensive but is cheap compared to stem cell treatment costing from $5000 to $25000. Plus this drug does things that stem cell IV infusions can't do, getting rid of the damaged senescent stem cells. My only hesitation is whether to buy 1 or 2 grams of Navitoclax in the Group Buy. Thanks for your efforts.

DareDevil

What is the basis to compare Navitoclax vs stem cells ? Looks like they have nothing in common.
I am, personally, found somewhat perplexing that so many members are ready to take a plunge on Navitoclax ignoring sertoli cells die off and possibility of other side effects. Longevity is not red or black betting. Year or two waiting doesnt mean much but irreversible damage is very real.

Edited by Andey, 24 April 2017 - 06:55 PM.

[Rocket]

Hi Logic,

This maybe seems expensive but is cheap compared to stem cell treatment costing from $5000 to $25000. Plus this drug does things that stem cell IV infusions can't do, getting rid of the damaged senescent stem cells. My only hesitation is whether to buy 1 or 2 grams of Navitoclax in the Group Buy. Thanks for your efforts.

DareDevil

What is the basis to compare Navitoclax vs stem cells ? Looks like they have nothing in common.
I am, personally, found somewhat perplexing that so many members are ready to take a plunge on Navitoclax ignoring sertoli cells die off and possibility of other side effects. Longevity is not red or black betting. Year or two waiting doesnt mean much but irreversible damage is very real.

A couple years of waiting might not be a big deal if you're 25 or 30, but if you're 65 a couple years is entirely different; things are happening much faster.

[jmorris]

To all experimenters taking oral quercetin:

 

If you are taking quercetin orally in hopes of having some effect on senescent cells, you are not going to have any luck. I hate to be blunt but quercetin aglycone is just not orally bioavailable.

 

What's quercetin aglycone?

 

Quercetin aglycone is quercetin that has not been modified by the liver. 

 

Graefe, E. U. et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans. The Journal of Clinical Pharmacology 41, 492–499 (2001).

 

"The bioavailability of the aglycone quercetin is, however, very poor. No free quercetin could be detected in human plasma after oral intake of high amounts of quercetin. Quercetin circulates in plasma only in conjugated form, [...] Furthermore, after oral intake of the aglycone, even the total quercetin plasma concentrations measured after [analytical enzymatic] hydrolysis of quercetin conjugates [in plasma samples] were very low."

 

Notice that they did not say "5% free quercetin could be detected."

 

Also notice that they did not say "1% free quercetin could be detected."

 

They said "No free quercetin could be detected". 

 

None, zero, zilch, nada. 

 

When you eat quercetin (the aglycone), after it leaves your digestive system, it enters your liver and is immediately glycosylated. The studies that show quercetin killing senescent cells are for the aglycone, meaning quercetin with NO glycosylation. Once you attach a sugar molecule to quercetin (or really anything), it's a different molecule. It's a >really< different molecule. Glycosylation is how the liver inactivates toxic molecules like quercetin and other toxins and drugs in general. Once a toxin has a sugar attached to it, it makes it really hard for the toxin to make it across cell membranes, makes it impossible to bind to its pharmacophore and very easy to be washed out of the kidneys. Flavones like quercetin are extremely common in nature. Thus, our livers have had millions of years to get very, very good at quickly inactivating them.

 

It's no small coincidence that the Phase I clinical trial using quercetin in chemotherapy with people who actually have cancer used it intravenously. Please check out:

 

Ferry, D. R. et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin. Cancer Res. 2, 659–668 (1996).

 

From the article above, quercetin aglycone is pretty much insoluble in water. They reference a study in in 1975 where quercetin was given intravenously dissolved in ethanol. The researchers finally ended up dissolving it in DMSO and giving that intravenously. I don't know how much you all know about the wisdom of injecting ethanol or DMSO into a vein. I can tell you one does not even consider doing some thing so crazy/stupid unless 1) Someone is going to die otherwise and 2) There is absolutely no other way to get the drug into you. That is sadly the case with quercetin aglycone. All quercetin aglycone going into your digestive system has to make it passed your liver. Quercetin aglycone does not make it passed the liver, at all. Hence, the decision to go the dangerous intravenous route in the trial referenced above.

 

If you still don't believe me, take a look at the paper above to see the side effects of actual unmodified quercetin aglycone at doses expected to kill senescent cancer cells: Renal toxicity and severe nausea. Any of you experiencing those two? Probably not, since you all likely have functional livers attached between your digestive systems and hepatic veins.

 

"I've taken a bunch of quercetin and dasatinib and noticed not a lot has happened except now I'm thinner. What does this mean?"

 

Congratulations, your dasatinib has probably worked just fine to kill your harmful senescent fat cells. You are one of the first humans on earth to do this. However, the quercetin you took probably did jack squat. Be happy those senescent cells are gone. If you really want to kill senescent cells other than preadipocytes you are going to have to either:

 

1) Find a way to take quercetin IV. 

    Difficult but not recommended. I have a background as a chemist and biomedical scientist and I'm still afraid of all the ways that might kill me. (I have a plan that does not involve DMSO for those reckless and irresponsible enough to attempt this.)

 

2) Find another drug to supplement dasatinib. 

 

Navitoclax doesn't kill pre-adipocytes so it makes a good partner to dasatinib. Yeah, I know it's expensive. Did you really think this was going to be easy?

 

Edited by jmorris, 25 April 2017 - 03:28 AM.

[aribadabar]

 

I got a quote on 100 grams of Navitoclax of:  $ 442.00/g.

Thats without shipping and testing:                $     6.70/g

Total:                                                              $ 448.70/g excluding postage from the USA ($ 6.80 local)

Thats not spare change, but as fasting is so good for one; I might just be able to afford the ~1 gram required for 1 treatment!  

What is the suggested dosage for Navitoclax? 10 days x 100mg/d?

 

And why is it so much more expensive than D, like ~50x more?

 

Thanks!

[jmorris]

 

What is the suggested dosage for Navitoclax? 10 days x 100mg/d?

 

And why is it so much more expensive than D, like ~50x more?

 

Thanks!

 

 

The price to synthesize a drug is (very roughly):

 

(price of the precursors in $ per gram) / (% yield of step 1 * % yield of step 2 * % yield of step 3 * % yield of step n.....)

 

(For simplicity, this formula leaves out the cost of additional precursors.)

 

This means that the more steps involved to change a commonly available precursor into your final product, the more expensive it will be. The math scales exponentially with the number of steps. Navitoclax is a pretty big molecule. You don't get to pick what the yield is on any given synthetic step. You do research to find the best yielding reagent and procedure for what you are trying to do. Some of the steps you will be able to get 95 or 99% yield. Some others, you may not get better than 30%. Like I said, navitoclax is big, much bigger than dasatinib. I'm guessing at least ten steps to build that monster.  If two or three of the steps are 30%, well then things get expensive fast.

 

Oh yeah, and as the molecule gets bigger, your choice of reagents goes down because of having to pick reagent that do not cross react with functional groups that are already on the molecule. Or you have to add protecting groups to the sensitive parts and then remove them later which adds even more steps.

 

If I have time this week, I'll draw out the scheme with yields so we can do the calculation and see for ourselves.

Edited by jmorris, 25 April 2017 - 05:08 AM.

[Nate-2004]

 

1) Find a way to take quercetin IV. 

    Difficult but not recommended. I have a background as a chemist and biomedical scientist and I'm still afraid of all the ways that might kill me. (I have a plan that does not involve DMSO for those reckless and irresponsible enough to attempt this.)

 

2) Find another drug to supplement dasatinib. 

 

 

What about liposomal quercetin?

[Agent0023]

EMIQ is a more promising form of quercetin for oral use. Natural Factors brand is available OTC. _Enzymatically modified isoquercitrin, alpha-oligoglucosyl quercetin 3-O-glucoside, is absorbed more easily than other quercetin glycosides or aglycone after oral administration in rats._ https://www.jstage.j...32_12_2034/_pdf

[Iuvenale]

This study found quercetin in plasma after taking 1095 mgs. It also found that taking quercetin with a high fat meal improves bioavailability. 

 

Dietary fat increases quercetin bioavailability in overweight adults. SCOPE:

Epidemiologic evidence supports that dietary quercetin reduces cardiovascular disease (CVD) risk, but its oral bioavailability is paradoxically low. The aim of this study was to determine whether dietary fat would improve quercetin bioavailability in adults at high risk for CVD and to assess lipid-mediated micellarization of quercetin in vitro.

METHODS AND RESULTS:

In a randomized, cross-over study, overweight/obese men and postmenopausal women (n = 4 M/5 F; 55.9 ± 2.1 years; 30.8 ± 1.4 kg/m(2) ) ingested 1095 mg of quercetin aglycone with a standardized breakfast that was fat-free (<0.5 g), low-fat (4.0 g), or high-fat (15.4 g). Plasma was obtained at timed intervals for 24 h to measure quercetin and its methylated metabolites isorhamnetin and tamarixetin. Compared to the fat-free trial, plasma quercetin maximum concentration (Cmax ), and area under curve (AUC0-24 h ) increased (p < 0.05) by 45 and 32%, respectively, during the high-fat trial. During the high-fat trial, isorhamnetin Cmax and AUC0-24 h also increased by 40 and 19%, respectively, whereas Cmax and AUC0-24 h of tamarixetin increased by 46 and 43%, respectively. Dietary fat dose-dependently increased micellarization efficiency of quercetin aglycone in vitro.

CONCLUSION:

Dietary fat improves quercetin bioavailability by increasing its absorption, likely by enhancing its micellarization at the small intestine.

[mikey]

 

To all experimenters taking oral quercetin:

 

If you are taking quercetin orally in hopes of having some effect on senescent cells, you are not going to have any luck. I hate to be blunt but quercetin aglycone is just not orally bioavailable.

 

What's quercetin aglycone?

 

Quercetin aglycone is quercetin that has not been modified by the liver. 

 

Graefe, E. U. et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans. The Journal of Clinical Pharmacology 41, 492–499 (2001).

 

"The bioavailability of the aglycone quercetin is, however, very poor. No free quercetin could be detected in human plasma after oral intake of high amounts of quercetin. Quercetin circulates in plasma only in conjugated form, [...] Furthermore, after oral intake of the aglycone, even the total quercetin plasma concentrations measured after [analytical enzymatic] hydrolysis of quercetin conjugates [in plasma samples] were very low."

 

Notice that they did not say "5% free quercetin could be detected."

 

Also notice that they did not say "1% free quercetin could be detected."

 

They said "No free quercetin could be detected". 

 

None, zero, zilch, nada. 

 

When you eat quercetin (the aglycone), after it leaves your digestive system, it enters your liver and is immediately glycosylated. The studies that show quercetin killing senescent cells are for the aglycone, meaning quercetin with NO glycosylation. Once you attach a sugar molecule to quercetin (or really anything), it's a different molecule. It's a >really< different molecule. Glycosylation is how the liver inactivates toxic molecules like quercetin and other toxins and drugs in general. Once a toxin has a sugar attached to it, it makes it really hard for the toxin to make it across cell membranes, makes it impossible to bind to its pharmacophore and very easy to be washed out of the kidneys. Flavones like quercetin are extremely common in nature. Thus, our livers have had millions of years to get very, very good at quickly inactivating them.

 

It's no small coincidence that the Phase I clinical trial using quercetin in chemotherapy with people who actually have cancer used it intravenously. Please check out:

 

Ferry, D. R. et al. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin. Cancer Res. 2, 659–668 (1996).

 

From the article above, quercetin aglycone is pretty much insoluble in water. They reference a study in in 1975 where quercetin was given intravenously dissolved in ethanol. The researchers finally ended up dissolving it in DMSO and giving that intravenously. I don't know how much you all know about the wisdom of injecting ethanol or DMSO into a vein. I can tell you one does not even consider doing some thing so crazy/stupid unless 1) Someone is going to die otherwise and 2) There is absolutely no other way to get the drug into you. That is sadly the case with quercetin aglycone. All quercetin aglycone going into your digestive system has to make it passed your liver. Quercetin aglycone does not make it passed the liver, at all. Hence, the decision to go the dangerous intravenous route in the trial referenced above.

 

If you still don't believe me, take a look at the paper above to see the side effects of actual unmodified quercetin aglycone at doses expected to kill senescent cancer cells: Renal toxicity and severe nausea. Any of you experiencing those two? Probably not, since you all likely have functional livers attached between your digestive systems and hepatic veins.

 

"I've taken a bunch of quercetin and dasatinib and noticed not a lot has happened except now I'm thinner. What does this mean?"

 

Congratulations, your dasatinib has probably worked just fine to kill your harmful senescent fat cells. You are one of the first humans on earth to do this. However, the quercetin you took probably did jack squat. Be happy those senescent cells are gone. If you really want to kill senescent cells other than preadipocytes you are going to have to either:

 

1) Find a way to take quercetin IV. 

    Difficult but not recommended. I have a background as a chemist and biomedical scientist and I'm still afraid of all the ways that might kill me. (I have a plan that does not involve DMSO for those reckless and irresponsible enough to attempt this.)

 

2) Find another drug to supplement dasatinib. 

 

Navitoclax doesn't kill pre-adipocytes so it makes a good partner to dasatinib. Yeah, I know it's expensive. Did you really think this was going to be easy?

 

 

The marketplace provides both encapsulated liposomal quercetin and thick liquid micellized quercetiin, which should each absorb much better than unmodified quercetin.

 

I prefer the capsules.

 

RevGenetics makes an absorption claim for their micellized quercetin - "We Estimate This Product To Have An 85 Fold Absorption Over Regular Quercetin. This Estimate Makes A 10mg Serving Equivalent To About 850 Mg Of Regular Quercetin."

 

Perhaps one of the chemists here can clarify the details about these two methods of delivery.

[jmorris]

The marketplace provides both encapsulated liposomal quercetin and thick liquid micellized quercetiin, which should each absorb much better than unmodified quercetin.

 

I prefer the capsules.

 

RevGenetics makes an absorption claim for their micellized quercetin - "We Estimate This Product To Have An 85 Fold Absorption Over Regular Quercetin. This Estimate Makes A 10mg Serving Equivalent To About 850 Mg Of Regular Quercetin."

 

Perhaps one of the chemists here can clarify the details about these two methods of delivery.

 

 

Liposomal quercetin and micellized quercetin attempt to increase the level of quercetin that makes it through your intestinal lumen into the blood supply going to the liver. Both methods do so by surrounding quercetin in a double-layered droplet of phospholipid. 

 

Unfortunately even if you you engineer quercetin to absorb 100% into the intestine, this still does not solve the fact that once in the liver, the quercetin is glycosylated to a form that has not been shown to be active against senescent cells.

 

 

This study found quercetin in plasma after taking 1095 mgs. It also found that taking quercetin with a high fat meal improves bioavailability. 

 

Dietary fat increases quercetin bioavailability in overweight adults. SCOPE:

Epidemiologic evidence supports that dietary quercetin reduces cardiovascular disease (CVD) risk, but its oral bioavailability is paradoxically low. The aim of this study was to determine whether dietary fat would improve quercetin bioavailability in adults at high risk for CVD and to assess lipid-mediated micellarization of quercetin in vitro.

METHODS AND RESULTS:

In a randomized, cross-over study, overweight/obese men and postmenopausal women (n = 4 M/5 F; 55.9 ± 2.1 years; 30.8 ± 1.4 kg/m(2) ) ingested 1095 mg of quercetin aglycone with a standardized breakfast that was fat-free (<0.5 g), low-fat (4.0 g), or high-fat (15.4 g). Plasma was obtained at timed intervals for 24 h to measure quercetin and its methylated metabolites isorhamnetin and tamarixetin. Compared to the fat-free trial, plasma quercetin maximum concentration (Cmax ), and area under curve (AUC0-24 h ) increased (p < 0.05) by 45 and 32%, respectively, during the high-fat trial. During the high-fat trial, isorhamnetin Cmax and AUC0-24 h also increased by 40 and 19%, respectively, whereas Cmax and AUC0-24 h of tamarixetin increased by 46 and 43%, respectively. Dietary fat dose-dependently increased micellarization efficiency of quercetin aglycone in vitro.

CONCLUSION:

Dietary fat improves quercetin bioavailability by increasing its absorption, likely by enhancing its micellarization at the small intestine.

 

This paper attempts to do the very same thing as RevGenetics, but rather than sell you a product, they say you can make micellized, (liposomal) quercetin just by eating with a high fat diet.

 

And yes, it does help just like before to increase the level of quercetin that makes it into the intestinal circulation.

 

And no, that still does not solve the problem that 100% of blood leaving the intestine must pass through the liver.

 

All quercetin that makes it through the liver will be glycosylated and therefore unfit and unable to act on the cellular targets that kill senescent cells. This is because

 

1) The sugar molecule attached to quercetin is too hydrophilic to diffuse across cell membranes.

 

2) The sugar molecule attached to quercetin introduces a steric hinderance that makes it unable to bind to it's molecular target. i.e. it is now the wrong shape. 

 

EMIQ is a more promising form of quercetin for oral use. Natural Factors brand is available OTC. _Enzymatically modified isoquercitrin, alpha-oligoglucosyl quercetin 3-O-glucoside, is absorbed more easily than other quercetin glycosides or aglycone after oral administration in rats._ https://www.jstage.j...32_12_2034/_pdf

 

 

Again, enzymatically modified isoquercetin, alpha-oligoglucosyl quercetin 3-O-glucoside does absorb better but it is a different molecule than the one we are interested in: quercetin aglycone.

 

 

 

What about liposomal quercetin?

 

 

Answered above.

 

 

Anybody else?

[Nate-2004]

Might as well throw all my quercetin away to make room then. What a waste. 

[jmorris]

The problem here is an issue of naming.

 

There are hundreds of ways that you can modify quercetin by attaching sugar molecule to it. 

 

Sadly, none of those conjugated molecules are "quercetin". They have the word "quercetin" in their names but that is about it.

 

If you want quercetin, you have to go IV.

 

I'm sorry to be such a wet blanket.

[Nate-2004]

The day I turn to needles for my anti-aging addiction is the day I have surely hit rock bottom.

[eigenber]

I'm not sure what happens after I do this, but I've dumped a heaping teaspoon of quercetin under my tongue and let it dissolve, which it does completely. I'm assuming it has entered the bloodstream without any liver modification, at least initially.

[Nate-2004]

I'm not sure what happens after I do this, but I've dumped a heaping teaspoon of quercetin under my tongue and let it dissolve, which it does completely. I'm assuming it has entered the bloodstream without any liver modification, at least initially.

 

You likely just swallowed it all eventually. Good point though, surely there's some other entry point without needles.

 

What's the difference between quercetin dihydrate and quercetin aglycone? The kind I was taking orally was dihydrate.

Edited by Nate-2004, 25 April 2017 - 06:56 PM.

[jmorris]

I'm not sure what happens after I do this, but I've dumped a heaping teaspoon of quercetin under my tongue and let it dissolve, which it does completely. I'm assuming it has entered the bloodstream without any liver modification, at least initially.

 

Yes, the sublingual route is one way to bypass the liver. The question then is: What is the sublingual bioavailability of quercetin? 

 

Answer: I have absolutely no idea.

 

It could be 30% but I would be very surprised. Probably close to 0%.

 

Even if it was, say 30% which sounds unlikely considering how insoluble it is, there is a limit to how much drug you can absorb that way. The area under the tongue will saturate. (If you put 10mg under your tongue, the % absorbed will be greater than if you put 20 grams there. )

 

Certainly something to look into.

Edited by jmorris, 25 April 2017 - 07:29 PM.

[jmorris]

 

 

What's the difference between quercetin dihydrate and quercetin aglycone? The kind I was taking orally was dihydrate.

 

 

For all intents and purposes, the aglycone and dihydrate are the same thing.

 

Many molecule bind a few water molecules tightly. In quercetin's case, it's two, hence dihydrate.

 

When you run a chemical reaction, sometimes you need the chemical to be anhydrous (not be hydrated) due to some reagent in your reaction being spoiled by water. (There are many like this.) Also, the molecular weight of a hydrated molecule will be a little more than the anhydrous version. If you are running a chemical reaction and want to add a stoichiometric amount of the chemical to your reaction, knowing the right molecular weight is crucial. The dihydrate will be 36 AMU's heavier than the anhydrous.

 

So, manufacturers make sure to write "anhydrous" or "dihydrate" on the bottle so that you will know.

Edited by jmorris, 25 April 2017 - 07:11 PM.