731 replies to this topic

[roguereason]

But wasn't the equivalent mouse to human dosage from the study around 30 mg for a 70 kg person? Thought I read that calculation in past pages. If so, you took 10 times that amount in the 300 mg dose.

 

I agree that it should be taken very infrequently.

 

Thanks for bringing this up, and reminding me to re-examine the dosage.

 

The general conversion from mouse to human dosage is really a fudge factor meant to be used to determine the baseline starting point for phase 1 testing of safety and pharmacokinetics.  It does give around 30mg.  

 

It is very conservative.

 

But good news, there is already pharmacokinetic information about dasatinib in humans and we can base our speculation on that.

 

This is a very interesting analysis that was done when they first wanted to test dasatinib in humans for cancer:

 

http://clincancerres...3/7180.full.pdf

 

There's a lot of information packed in there and will take me a while to fully digest, but here are a couple key points as I see it.  Please anyone correct my assumptions.  I'm a novice at this.

 

Two alternative trains of thought:

 

1. In mice they were testing dosages of 1.25, 2.5, and 5 mg/kg at different intervals.  They determined minimum effective was 1.25 twice a day or 2.5 once a day.  After considering what was already known about the human pharmacokinetics they determined that 70mg twice a day or 140mg of dasatinib would be ideal for humans.  Which initially did end up as being the starting point for human use I think.  Today (I think) the preferred starting dose is 100mg once a day, rather than 70mg twice.

 

2. Looking at the pharmacokinetics in mice vs humans the "area under the curve" (blood concentration over time) is pretty close for 5mg ==> 100mg.

 

Following the logic of #1 I would probably end up with 200mg as it seems like 2.5mg ==> 100mg or 140mg.  And in our study the mice took 5mg/kg.

 

But #2 is actually pretty convincing.  So might want to stick with the 100mg range.

 

Of course one could then tailor the values to individual body masses, for example I'm quite a bit more than 70kg.

Edited by roguereason, 19 October 2017 - 03:43 PM.

[roguereason]

Quercetin in phytosome (phosphatidylcholine) is much better orally available then quercetine alone. Lipid carriers enhance the quercetin uptake up to 6-fold. 

https://www.ncbi.nlm...pubmed/27756627

https://www.ncbi.nlm...pubmed/23514412

 

Thanks Alpharius.  That's a lot of information to weed through.  WIll take me a while and hope it will be worth it.

 

Generally if I were a mouse I'd probably live forever.  I really wish someone could provide the human plasma concentrations (cmax and auc) after supplementing with various (or any) forms of Q.  A table would be nice.

 

I found something for EMIQ a while back, but sometimes I'm afraid I'm reading marketing materials rather than peer reviewed studies.

[roguereason]

 

Quercetin in phytosome (phosphatidylcholine) is much better orally available then quercetine alone. Lipid carriers enhance the quercetin uptake up to 6-fold. 

https://www.ncbi.nlm...pubmed/27756627

https://www.ncbi.nlm...pubmed/23514412

 

Thanks Alpharius.  That's a lot of information to weed through.  WIll take me a while and hope it will be worth it.

 

Generally if I were a mouse I'd probably live forever.  I really wish someone could provide the human plasma concentrations (cmax and auc) after supplementing with various (or any) forms of Q.  A table would be nice.

 

I found something for EMIQ a while back, but sometimes I'm afraid I'm reading marketing materials rather than peer reviewed studies.

 

 

FYI, here is the one study I've found for EMIQ that does mention human plasma concentrations after supplementation.  I wish I had more information like this.

 

Check out Figure 6.

 

http://www.sciencedi...32389301530719X

 

"Here, we showed that the serum levels of quercetin and its major metabolites, isorhamnetin and tamarixetin28 were elevated at 2 hours after EMIQ intake and quercetin concentration reached around 90 ng/ml, indicating that EMIQ was indeed absorbed."

[xEva]

So people have been experimenting with D+Q for quite a while now, and at some point Logic was promising to post the results -- did I miss them?  I saw a few reports --thank you very much for them!-- but it seems more people have tried this, no?

 

I'm very interested to read about the results, good or bad.

Did it make you look younger? If so, how soon after the experiment the changes became apparent?

 

@DareDevil: has you friend shed the gaunt look after his October experiment? 

 

And where is Logic with his summary? Maybe it's in another thread?

 

 

[Iuvenale]

Crickets. I'm starting my third round. I haven't noticed any miracles. However, for me, noticing subtle antiaging effects is difficult. From my subjective stance, I can look ten years older from one day to the next.

 

Anyone else? 

[ClarkSims]

When I got my dasatinib, I put the bag in another plastic bag. I put water absorbing packets with it, so that the original bag is surrounded by the water absorbing packets.  I then put the double bagged dasatanib in my freezer.

 

I just assumed this was the best way to store it.

 

The internet says to store dasatinib tablets at room temperature.

 

Is the method I chose, a good way to store pure dasatinib?

[Moondancer]

Would be very interested to read about the experience with D+Q of more members too.

[Nate-2004]

Got a question. In the FOXO4 DRI thread it's been stated a couple of times with references that at least the FOXO4 DRI synolitic is more effective during higher amounts of inflammation. In other words, it's better to eat badly and not exercise for a week or two before, during and after all the dosing. Would this also be as true for the Dasatinib? I was about to go on another round of D+Q soon.

[Andey]

Got a question. In the FOXO4 DRI thread it's been stated a couple of times with references that at least the FOXO4 DRI synolitic is more effective during higher amounts of inflammation. In other words, it's better to eat badly and not exercise for a week or two before, during and after all the dosing. Would this also be as true for the Dasatinib? I was about to go on another round of D+Q soon.

I believe it’s unknown at a moment.
BTW ketogenic diet is also a mTor inhibitor.

As far as inflammation goes, LPS mentioned in Foxo thread is a potent inducer of inflammation. IL-6 goes from undetectable to thousands pg/ml, these levels are unachivable wi5h just a poor diet, its on par with solid flu.

[Nate-2004]

How would one utilize LPS (lipopolysaccharide) to achieve what we want here? 

Edited by Nate-2004, 04 March 2018 - 04:32 PM.

[XRT doc]

give yourself a really bad bacterial infection? 

[Rocket]

Got a question. In the FOXO4 DRI thread it's been stated a couple of times with references that at least the FOXO4 DRI synolitic is more effective during higher amounts of inflammation. In other words, it's better to eat badly and not exercise for a week or two before, during and after all the dosing. Would this also be as true for the Dasatinib? I was about to go on another round of D+Q soon.

I lift weights as long as I don't feel ill. No issues. No injuries.

The only reason to avoid 2 weeks in the gym is illness/injury or taking a break from over training. There is never an excuse for living on junk food.

Why are you taking both D and FOXO4? I thought F was superior?

2 drugs equals 2 sets of side effects.

Edited by Rocket, 05 March 2018 - 01:51 AM.

[Nate-2004]

I'm not taking both, I don't have any FOXO4-DRI. All I have is D+Q right now.

[xEva]

I was about to go on another round of D+Q soon.

 

 

How did the first round go? If you posted this already, pls show us where  

[StanG]

This is why I believe you never take too much of the "D" or too frequently.

 

https://www.ncbi.nlm...pubmed/29280266

 

 

2018 Apr;17(2). doi: 10.1111/acel.12711. Epub 2017 Dec 27.

Senescence promotes in vivo reprogramming through p16^INK4a and IL-6.

Mosteiro L¹, Pantoja C^1,2, de Martino A¹, Serrano M^1,2,3.

Author information

 

Abstract

Cellular senescence is a damage response aimed to orchestrate tissue repair. We have recently reported that cellular senescence, through the paracrine release of interleukin-6 (IL6) and other soluble factors, strongly favors cellular reprogramming by Oct4, Sox2, Klf4, and c-Myc (OSKM) in nonsenescent cells. Indeed, activation of OSKM in mouse tissues triggers senescence in some cells and reprogramming in other cells, both processes occurring concomitantly and in close proximity. In this system, Ink4a/Arf-null tissues cannot undergo senescence, fail to produce IL6, and cannot reprogram efficiently; whereas p53-null tissues undergo extensive damage and senescence, produce high levels of IL6, and reprogram efficiently. Here, we have further explored the genetic determinants of in vivo reprogramming. We report that Ink4a, but not Arf, is necessary for OSKM-induced senescence and, thereby, for the paracrine stimulation of reprogramming. However, in the absence of p53, IL6 production and reprogramming become independent of Ink4a, as revealed by the analysis of Ink4a/Arf/p53 deficient mice. In the case of the cell cycle inhibitor p21, its protein levels are highly elevated upon OSKM activation in a p53-independent manner, and we show that p21-null tissues present increased levels of senescence, IL6, and reprogramming. We also report that Il6-mutant tissues are impaired in undergoing reprogramming, thus reinforcing the critical role of IL6 in reprogramming. Finally, young female mice present lower efficiency of in vivo reprogramming compared to male mice, and this gender difference disappears with aging, both observations being consistent with the known anti-inflammatory effect of estrogens. The current findings regarding the interplay between senescence and reprogramming may conceivably apply to other contexts of tissue damage.

 

[Rocket]

More good news about Dasatanib.

 

https://www.scienced...80709111137.htm

[mkp6019]

Anyone thinking of a group buy? I would be interested.

[Rocket]

I think if you look around a little, you will find it not necessary for a group buy.

[mikey]

Would be very interested to read about the experience with D+Q of more members too.

 

REDUCTION IN BLOOD PRESSURE
I reported this many months ago, but I'll reiterate for you, Moondancer.

 

I've taken D with Q twice. 
 

However, I take a higher absorbing Q as liposomal Q (LQ). (Thorne Research Quercetin Phytosome)

(Numerous studies confirm that LQ has much greater bioavailability that plain Q.)

https://www.ncbi.nlm...pubmed/22607534

https://www.asiaphar...article/view/58

I apologize, as I don't mean to insult anyone's sensitivity. However, I continue to see mention of using plain Q, when I expect this website's scientists to see the advantages of taking  Q in a liposomal format.

 

The first time I took D/LQ I miscalculated and took 300 mg (an overdose) of D with 2,000 mg of LQ.

Overdosing D caused a problem with the QT-interval of my heart beat, which felt terrible. So I recalculated the dose and saw that 300 mg was far too much D.
I thought that I had really screwed myself up.

However, the heavy, odd heart beat lasted for 8 days and then went back to normal.

 

The second time, a few weeks later, I took 50 mg of D and 1000 mg of LQ.

I did feel a little bit like my bones were "leaden" for a couple days, an adverse effect of D I expect.

 

Then about two weeks later something happened that has never occurred before.

 

My blood pressure, which had been rising with age (64 then) and could hit hypertensive numbers, dropped significantly.

 

The drop exhibited was averaging about 115/60, like a teenager. This continued for about two months, then it started to rise again, but slowly and, here it is, about a year later and it isn't as high as it was before the two exposures to D/Q.

 

I assume that D/Q "cleaned" the endothelium/lining of my arteries to some significant extent via senolytic action so that the endothelium regenerated with improved, more youthful flexibility.

 

I haven't repeated D because of the potential toxicity that feeling like my bones were "leaden" signified.

 

I see that some are taking small amounts of Q somewhat frequently but I am waiting for a senolytic agent that has no potential for toxicity. 

 

Nothing that I've done or taken has caused a significant, consistent, measurable improvement in blood pressure, except D/Q.

[mikey]

I think if you look around a little, you will find it not necessary for a group buy.

 

Yes. A quick search for "buy Dasatinib" shows that it apparently can be purchased for as little as $11+ per gram in 70 mg tablets on the internet.

http://www.cancercur...ount-Price.aspx

[Rocket]

My mouse felt great after my D+Q experiments. There was an initial feel like being hit by a freight train for a day that sent my mouse home from work early, but then things got better from there,  My mouse's EGFR went up (i.e. got better) over previous blood work. Its the real deal unlike that junk people spent $900 on in the FOXO4 group buy. I believe the feeling ill came from all the crap that my body had to eliminate after the senescent cells were killed.

[StanG]

My mouse felt great after my D+Q experiments. There was an initial feel like being hit by a freight train for a day that sent my mouse home from work early, but then things got better from there,  My mouse's EGFR went up (i.e. got better) over previous blood work. Its the real deal unlike that junk people spent $900 on in the FOXO4 group buy. I believe the feeling ill came from all the crap that my body had to eliminate after the senescent cells were killed.

 

Hi Rocket,

 

I was curious as to why you compared "D+Q" (don'forget to also take vitiman D to promote apoptosis. After the first go round I heard a rumor that you should take only 50-60mg as there should be much less senescent cells to get ird of (they take guite a while to build up again).

 

Stan 

[Rocket]

Hi Rocket,

I was curious as to why you compared "D+Q" (don'forget to also take vitiman D to promote apoptosis. After the first go round I heard a rumor that you should take only 50-60mg as there should be much less senescent cells to get ird of (they take guite a while to build up again).

Stan

I take 2 very large doses over 2 days. Day 3 *can* suck. Repeat every 6 months. Maybe when I get into my late 40s or 50s it should be repeated less than every 6 months...

[Ibbz]

My mouse felt great after my D+Q experiments. There was an initial feel like being hit by a freight train for a day that sent my mouse home from work early, but then things got better from there,  My mouse's EGFR went up (i.e. got better) over previous blood work. Its the real deal unlike that junk people spent $900 on in the FOXO4 group buy. I believe the feeling ill came from all the crap that my body had to eliminate after the senescent cells were killed.

 

Did the mouse have any osteoarthritis? And has D+Q made any difference that you could tell?

[Longevitarian]

Despite it's excellent performance on rejuvenation of the fat tissue, muscles, cardiovascular system,

bones (osteoporosis) and probably other tissues I am pretty sure D+Q is useless in treatment of

osteoarthritis.

 

However NAVITOCLAX has been found to treat osteoarthritis in mice via senolytic action. There are

companies which are about to start human trials of Nav in treatment of osteoarthitis.....There are

press releases from last 4 months about it, but I don't have them handy.

[Ibbz]

Despite it's excellent performance on rejuvenation of the fat tissue, muscles, cardiovascular system,

bones (osteoporosis) and probably other tissues I am pretty sure D+Q is useless in treatment of

osteoarthritis.

 

However NAVITOCLAX has been found to treat osteoarthritis in mice via senolytic action. There are

companies which are about to start human trials of Nav in treatment of osteoarthitis.....There are

press releases from last 4 months about it, but I don't have them handy.

 

Yeah there's a number on the horizon such as the what's been developed by Unity Biotech which just started phase 1 trials, and obviously FOXO4-DRI.

[StanG]

I take 2 very large doses over 2 days. Day 3 *can* suck. Repeat every 6 months. Maybe when I get into my late 40s or 50s it should be repeated less than every 6 months...

 

I truly wonder if what you feel the third day is just your natural killer cells etc eliminating the senescent cells or something more,.especially at your young age. People like Daredevil. Mickey and you may be doing the rest of us a huge favor the way they take cancer drugs, peptides etc.  I hope that's the case.

 

Stan

[StanG]

Did the mouse have any osteoarthritis? And has D+Q made any difference that you could tell?

At 75 years of age, everyone has some. I thought I had more of a problem in my right knee. A scan showed it merely to be some arthritis. It has been two years and I have helped it by taking various supplements and figuring out beneficial exercises to where I now can run up the stairs and jog a bit. I don't test it further than that.

 

Stan

[extendcel]

What seems to be consensus with the D+Q combo? The results don't seem to be life changing but is it still worthwhile to use? I know quercetin is now suspect with recent studies. Have we abandoned navitoclax because of the cost plus the potential testicular toxicity?

[Fafner55]

I have found this combination to be effective.

1. 120 mg dasatinib (for a 70 kg individual. Scale by body weight not to exceed 140 mg.)
2. 2000 mg quercetin phytosome 
3. 2000 mg curcumin phytosome
4. 2000 mg honokiol

Expect diarrhea from killing senescent cells in the intestines, fatigue lasting a few days, and possibly nausea and a slight fever.

 

All one month recovery and regeneration between treatments.

 

Keep in mind that this treatment can be dangerous, particularly for older people with a heavy load of senescent cells, and for those with COPD for instance. I don't think either of my parents, who are nearly 90, would survive it.

 

Another possible danger is killing off and depleting stem cells. Again, the very old would be vulnerable.

 

Senolytic treatment should be supervised by a doctor. I am not a doctor.