12 replies to this topic

[sensei]

From personal experience:

I consume several cups of coffee per day. I performed a senolytic experiment with combined high doses over several days of fisetin & quercetin liposomal plus curcuminoids.

I ended up feeling as if I had drank 20 cups of coffee.

Research showed that all are potent inhibitors of caffeine metabolism.

After 36 hours with no coffee I felt normal.

:text=Quercetin%20is%20abundant%20in%20plants,might%20produce%20herb-drug%20interactions' class='bbc_url' title='External link' rel='nofollow external'>https://www.ncbi.nlm...ug interactions

[Phoebus]

Interesting. what were your dosages of F and Q? 

 

did you notice any benefits from the senolytic experiment? 

 

 

[sensei]

Interesting. what were your dosages of F and Q?

did you notice any benefits from the senolytic experiment?

4000mg fisetin 800mg quercetin liposomal formulation

Per day

Edited by sensei, 07 February 2022 - 03:33 AM.

[Phoebus]

thanks, and notice any benefits? 

[Moondancer]

4000mg fisetin 800mg quercetin liposomal formulation

Per day

 

 

4000mg of Fisetin per day for your senolytic treatment, sounds like a high dose. I'd be interested to know how you came up with that dose, is it because you have concerns about the bioavailability of Fisetin?

Did you use such a high before, and do you feel it gave more 'effects' than using a lower dose? 

 

You also mention it was a liposomal formulation; did you make it yourself, or did you buy a liposomal supplement with Fisetin & Quercetin?

 

Many thanks in advance!

[TheFountain]

If they "inhibited" Caffeine Metabolism you would feel no effects of Caffeine. Actually they ENHANCE Caffeine metabolism through Autophagy, which is why you felt more Caffeine sensitive.

 

People have Caffeine metabolism ass backwards. When you have MORE of the Caffeine metabolizing enzyme you Metabolizing it better, thus requiring LESS Caffeine. When you have LESS of the Enzyme, you Metabolize Caffeine worse thus require more of it. 

 

So, those of you who brag about absorbing a gallon of Coffee a day and think you have stout Caffeine pathways are full of shit. You're actually weaker at metabolizing it and someone who is "caffeine sensitive" is BETTER at metabolizing it! Get that straight now, tough guys. You're weaker, not stronger. 

[sensei]

No they inhibit CYP1A2 the enzyme that metabolizes caffeine.

You have it ass backward.

Inhibiting the metabolism of A DRUG besides a PRODRUG. INCREASES the effects and duration of effects.
It's why PEOPLE AVOID drinking lots of grapefruit juice - because it impairs CYP3A4 and can cause OVERDOSE.
https://www.pharmacy...ication-potency

And, you are incorrect. Caffeine is psychoactive WITHOUT metabolism.

Edited by sensei, 07 February 2022 - 12:11 PM.

[TheFountain]

No they inhibit CYP1A2 the enzyme that metabolizes caffeine.

You have it ass backward.

Inhibiting the metabolism of A DRUG besides a PRODRUG. INCREASES the effects and duration of effects.
It's why PEOPLE AVOID drinking lots of grapefruit juice - because it impairs CYP3A4 and can cause OVERDOSE.
https://www.pharmacy...ication-potency

And, you are incorrect. Caffeine is psychoactive WITHOUT metabolism.

 

 

Let's first discuss what Caffeine Metabolism MEANS! 

 

Caffeine gets BROKEN DOWN by the CYP!A2 enzyme which converts 95% of said Caffeine into Theobromine, Theophylline and Paraxanthine and who knows what else. Which leaves you with only a tiny little fraction of Caffeine that does what you THINK it's doing to your brain. In other words, Caffeine metabolism is the BREAK DOWN of Caffeine into various other Metabolites which makes caffeine LESS EFFICACIOUS to the consumer!

 

Therefor someone whose CYP!A2 pathways are more activated are going to break down Caffeine a fuck ton more than someone who's CYP!A2 is not, which means that the vast majority of that Caffeine being consumed is useless to their brains anyway and why are they even drinking it to begin with?

 

So if we are calling "caffeine Metabolism" the break down and lack of effectiveness of Caffeine availability on the brain then sure, you can ride home with that medal. But it doesn't mean a person is better at using Caffeine, it means their enzymes are ridding them of having to use it to begin with since less than 5% of it gets to the brain anyway! 

 

So people with a less active CYP1A2 are actually BETTER at using the caffeine, because they have nothing breaking it down nearly as much. 

 

Yes, I am being a bit of a dick right now, because I am sick of the whole tough guy Caffeine mentality. The singular reason you can drink more without it causing "sensitivity" is merely because you don't have to deal with the actual caffeine itself because your body doesn't let you!

 

This also applies to A2 receptor polymorphisms which are genetic in origin. People with this particular receptor polymorphism are BETTER at taking in caffeine than those who DON'T have this polymorphism, which means they are SENSITIVE to it because their A2 Receptor likes it better than someone who doesn't have the Polymorphism! 

 

So these incredible Hulk coffee drinkers out there who think they're gods gift to tolerance are full of shit. They don't HAVE TO tolerate it due to the genes being shut off (receptor site polymorphism)! 

Edited by TheFountain, 07 February 2022 - 09:25 PM.

[sensei]

You're being a dick and you're wrong.

The average elimination half-life of caffeine ranges from 1.5-9 hours, so people are VERY HETEROGENEOUS with respect to CYP1A2 metabolism of caffeine.

VERY LITTLE of that has ANYTHING to do with the EFFECT of caffeine on people.

It only has to do with DURATION, and potential accumulation.

Effect depends entirely on receptor affinity and receptor density.

And you are ASS BACKWARDS AGAIN.

Genetic polymorphisms may initially affect receptor sensitivity.

HOWEVER, the MAIN DRIVER of sensitivity for receptors is receptor density, and LONG TERM POTENTIATION.

We can debate all day long, but regardless

INHIBITION IF THE CYP1A2 receptor INHIBITS METABOLISM of caffeine, leads to a LARGER AREA UNDER THE CURVE due to INCREASED LENGTH OF T1/2 elimination, FURTHERMORE, depending on the DEGREE of inhibition, ACCUMULATION of caffeine to an INTOXICATING CONCENTRATION may occur.

People who drink lots of caffeine likely downregulate receptors and definitively alter adenosine and andrenergic receptors.

[TheFountain]

You're being a dick and you're wrong.

The average elimination half-life of caffeine ranges from 1.5-9 hours, so people are VERY HETEROGENEOUS with respect to CYP1A2 metabolism of caffeine.

VERY LITTLE of that has ANYTHING to do with the EFFECT of caffeine on people.

It only has to do with DURATION, and potential accumulation.

Effect depends entirely on receptor affinity and receptor density.

And you are ASS BACKWARDS AGAIN.

Genetic polymorphisms may initially affect receptor sensitivity.

HOWEVER, the MAIN DRIVER of sensitivity for receptors is receptor density, and LONG TERM POTENTIATION.

We can debate all day long, but regardless

INHIBITION IF THE CYP1A2 receptor INHIBITS METABOLISM of caffeine, leads to a LARGER AREA UNDER THE CURVE due to INCREASED LENGTH OF T1/2 elimination, FURTHERMORE, depending on the DEGREE of inhibition, ACCUMULATION of caffeine to an INTOXICATING CONCENTRATION may occur.

People who drink lots of caffeine likely downregulate receptors and definitively alter adenosine and andrenergic receptors.

 

Nope, all the pathways I discussed and how they scientifically function, and the polymorphisms that exist in A2 genetics is very FUCKING real, scientifically speaking of course. Re-read it. 

 

PS none of what you say changes the fact that so called "caffeine sensitive" people take in more Caffeine to their brains than wannabe incredible Hulk Coffee drinkers who aren't even feeling the effects barely. 

 

I am challenging you to prove this statement false. You can't because it's not.

Edited by TheFountain, 07 February 2022 - 11:27 PM.

[sensei]

PS none of what you say changes the fact that so called "caffeine sensitive" people take in more Caffeine to their brains than wannabe incredible Hulk Coffee drinkers who aren't even feeling the effects barely.

I am challenging you to prove this statement false. You can't because it's not.

You can't prove it to be true. HOWEVER, I can falsify your argument in at least one case.

I show below that some persons have caffeine sensitivity independent of caffeine absorption, rather it is associated idiosyncratic hyper-responses.

Known biological processes independent of caffeine absorption can lead to increased excitatory neurotransmission.

In fact, in persons with a polymorphism that causes for example, -- more calcium release than others in RESPONSE to caffeine, excess excitatory neurotransmission is purely dependent on idiosyncratically increased calcium release - independent of caffeine "absorption". Furthermore, downstream effects of increased calcium on the glutamate and gaba receptors would be caffeine absorption independent as well.

[TheFountain]

Al "metabolism" really amounts to here is the break down of useful caffeine by the body which does not enter the brain the same way it does for somebody who is "caffeine sensitive". 

 

Another term we can use instead of Caffeine sensitive is FAST CAFFEINE RESPONDERS. Because that paints a more accurate picture of what is really going on. Metabolism is is a bit of a tricky term in this context. It really just means they aren't being affected by the caffeine. Not that they're able to handle more caffeine. How the hell can they handle what's not hitting the brain? Duh

 

 

 

[TheFountain]

I don't think quercetin and fisetin are potent inhibitors of CYP1A2 because if you drink a little coffee every day the Caffeine in the coffee itself is an inducer of CYP1A2 and would overthrow the relatively weak affects of these compounds inhibitory properties. 

 

Unless of course there are some inexplicable AHR polymorphisms.