Any Non-Responders Out There?

[Warrior21]

What, be able to get allergy shots? I don't have allergies. Not any that I know of. They prick you a few times in your back to test for allergies. maybe it's worth a shot.

I'm researching the DMMS, it ties into what we are researching. The DMMS is Cytochrome P450 and it's enzymes. CYP3A4 is responsible for metabolism of about 50% of human drugs. And you saw on the HIV site that steroids are metabolized by CYP3A4. I think we are on to something big here.

I think this is why some people grow extremely well off of a low amount of gear, and some need huge amounts to see crap gains. Maybe some people metabolize the drugs quick, just not fast enough to not see any gains. We might be the "overrapid metabolizers" as they call them.

If we can slow or stop the metabolism of steroids, small doses we take would build up to huge amounts in our blood. We might even have to lower doses after a while. Of course there's nothing wrong with this. For people who want to run anavar , it would save a hell of a lot of money.

The way I see it is there is a way to solve this, we are just going to have to research our asses off. My social life is over until this is taken care of.

[guest589745]

What, be able to get allergy shots? I don't have allergies. Not any that I know of. They prick you a few times in your back to test for allergies. maybe it's worth a shot.

I'm researching the DMMS, it ties into what we are researching. The DMMS is Cytochrome P450 and it's enzymes. CYP3A4 is responsible for metabolism of about 50% of human drugs. And you saw on the HIV site that steroids are metabolized by CYP3A4. I think we are on to something big here.

I think this is why some people grow extremely well off of a low amount of gear, and some need huge amounts to see crap gains. Maybe some people metabolize the drugs quick, just not fast enough to not see any gains. We might be the "overrapid metabolizers" as they call them.

If we can slow or stop the metabolism of steroids, small doses we take would build up to huge amounts in our blood. We might even have to lower doses after a while. Of course there's nothing wrong with this. For people who want to run anavar , it would save a hell of a lot of money.

The way I see it is there is a way to solve this, we are just going to have to research our asses off. My social life is over until this is taken care of.

I dont know why we havent recieved more replies, I honestly dont think we are blowing this out of proportion.

Im looking too.....

[Warrior21]

try looking up how or if allergy meds such as claritin inhibit CYP3A4. I found this:

Metabolism: In vitro studies with human liver microsomes indicate that loratadine (Claritin) is metabolized to descarboethoxyloratadine predominantly by cytochrome P450 3A4 (CYP3A4) and, to a lesser extent, by cytochrome P450 2D6 (CYP2D6). In the presence of a CYP3A4 inhibitor ketoconazole, loratadine is metabolized to descarboethoxyloratadine predominantly by CYP2D6. Concurrent administration of loratadine with either ketoconazole, erythromycin (both CYP3A4 inhibitors), or cimetidine (CYP2D6 and CYP3A4 inhibitor) to healthy volunteers was associated with substantially increased plasma concentrations of loratadine (see Drug Interactions section).

Yea I've looked all of those up. I have Ketoconazole here. It's Nizoral shampoo. I've stayed away from using Nizoral shampoo because it's said to lower testosterone levels . But If I was only going to use it on cycle where I'm adding testosterone to my body I guess there's nothing wrong with it, right.

Just so you know you can get the Nizoral (Ketoconazole) over the counter now-a-days. It's funny my mom just came home with a big ole' bottle of it last night from Wal-Mart. Check Wal-Mart for some. Maybe I will shower with it today.

So a CYP3A4 inhibition stack could be Grapefruit Juice with each dosage. Nizoral with daily shower. What do ya think?

[Warrior21]

I dont know why we havent recieved more replies, I honestly dont think we are blowing this out of proportion.

Im looking too.....

I have to agree. Nark kinda left us too. I think we are truly onto something. I mean look Tai has researched this extensively now. He said it's our DMMS. Before he mentioned DMMS we said it's Cytochrome P450 family. Well... it just turns out that the DMMS IS the Cytochrome P450 family!

I think it's possible that people are scared by these big terms were throwing around hehe.

[Warrior21]

Here we go, for anabolics this is exactly what we want to hear!


"DRUG INTERACTIONS

Ketoconazole is a potent inhibitor of the cytochrome P450 3A4 enzyme system. Coadministration of NIZORAL® Tablets and drugs primarily metabolized by the cytochrome P450 3A4 enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic and adverse effects. Therefore, unless otherwise specified, appropriate dosage adjustments may be necessary. The following drug interactions have been identified involving NIZORAL® Tablets and other drugs metabolized by the cytochrome P450 3A4 enzyme system:"

Notice increased or prolonged therapuetic effects of the drug are mentioned. Of course there could be adverse effects as well, but we know how to handle those.

[Bar barian]

the only thing I can think of why someone would be a non responder is because they dont have very sensitive AR receptors.. or they were down regulated during puberty??

[guest589745]

But wait, does the inhibition of CYP3A4 by grapefruit juice still aplly to injected steroids ?

[stupidhippo]

I mean these guys are presenting their findings pretty logically, and they might be on to something... BUT there are many BUTS still... about that post that mentions prolonged therapeutic effects etc... it DOES include the word MAY... What Im having the most problems is the theory that previously huge amounts did nothing to u and by drinking some grapejuice or whatever there would be a huge difference.. I have hard time believing there would be that huge of a differeńce.. these are pretty complex things in the end and not nearly all is known about them.. also previously there was sumin about premetabolizing in the small intestine, now this would only apply to orals... Keep digging guys, its interesting to say the least..

[stupidhippo]

But wait, does the inhibition of CYP3A4 by grapefruit juice still aplly to injected steroids?

by that post no.. is there still additional places ways CYP3A4 plays a part in this.. who knows..

[guest589745]

Yea I've looked all of those up. I have Ketoconazole here. It's Nizoral shampoo. I've stayed away from using Nizoral shampoo because it's said to lower testosterone levels . But If I was only going to use it on cycle where I'm adding testosterone to my body I guess there's nothing wrong with it, right.

Just so you know you can get the Nizoral (Ketoconazole) over the counter now-a-days. It's funny my mom just came home with a big ole' bottle of it last night from Wal-Mart. Check Wal-Mart for some. Maybe I will shower with it today.

So a CYP3A4 inhibition stack could be Grapefruit Juice with each dosage. Nizoral with daily shower. What do ya think?

Yea I remember seeing nizoral on a list. Well, I mean it looks good on paper, the only way we will know is trying it. Isnt nizoral supposed to help with balding too? I am not sure if it helps with DHT/19nor combo though but, if its still ok to take that with a dht/19nor, then that and the juice could work and probly would be rather safe I would think.

[guest589745]

by that post no.. is there still additional places ways CYP3A4 plays a part in this.. who knows..

Ok but what part of the statement are you getting that conclusion from?

[guest589745]

I mean these guys are presenting their findings pretty logically, and they might be on to something... BUT there are many BUTS still... about that post that mentions prolonged therapeutic effects etc... it DOES include the word MAY... What Im having the most problems is the theory that previously huge amounts did nothing to u and by drinking some grapejuice or whatever there would be a huge difference.. I have hard time believing there would be that huge of a differeńce.. these are pretty complex things in the end and not nearly all is known about them.. also previously there was sumin about premetabolizing in the small intestine, now this would only apply to orals... Keep digging guys, its interesting to say the least..

Yea I know what you mean, I agree. We are going to have to try it to see.

[guest589745]

I think people who could be useful on this subject are seeing the title and sayin "Well that aint me" and not even bothering to take a look lol. Damnit.

[guest589745]

For anyone Chiming in now, to help save you time of reading the now 4 pages of this thread.......

Our basic purpose of this thread now I think is to find out as much as possible about increasing the bioavailability of steroids or how and if inhibition of CYP(s) (CYP3A4) or (CYP2D6) (cytochrome P450 ) will possibly increase the effect of steroids both injectable and/or oral. Or how/why someone may not respond well to steroids considering training/diet is well enough to support growth and what to do about it. Thats basically it.

[Warrior21]

Okay sorry my comp wasn't letting me log in again. I switched over to a
different comp.

Anyways I know it seems grapefruit juice would not have that much effect on
CYP3A4 inhibition. But keep in mind that there are studies on PubMed showing
the seriousness of grapefruit juice. It has several compounds in it which
inhibit CYP P450 enzymes.

Also, the link I posted to on the HIV site shows that injected steroids also
are metabolized by CYP3A4. CYP3A4 is responsible for metabolism of over 50% of
human drugs. CYP2D6 comes in at a close second. I say we inhibit these 2 and we
are onto something.

Hippo I understand you may think the interactions aren't serious. Cuz you never
hear about them right? It's because doctors don't let drug-drug or food-drug
interactions happen. They take precautions to avoid them. But in our case we
are trying to elicit drug-drug and food-drug interactions.

SKullsmasher, yes Nizoral does help with balding. Thats why I had it in the
first place. I think I mentioned I was balding. So I bet on-cycle Nizoral would
work great. Wikipedia says Nizoral is a 'potent inhibitor of CYP3A4'.

And the commenbt about this not pertaining to other people, therefore they
don't care seems pretty true to me.

[Warrior21]

"CYP3A4 is the predominant cytochrome P450 (P450) expressed in human liver, accounting for up to 60% of total hepatic P450 protein (Shimada et al., 1994). CYP3A4 is involved in the metabolism of an extensive range of endogenous substrates and xenobiotics, making a significant contribution to the termination of the action of steroid hormones (Brian et al., 1990), detoxification of bile acids (Araya and Wikvall, 1999), elimination of xenobiotics, and activation of several potent carcinogens (Nebert and Gonzalez, 1987). It has been estimated that in excess of half of all therapeutic drugs are metabolized in full or in part by this enzyme (Maurel, 1996).
CYP3A4 expression exhibits substantial interindividual variation that cannot be explained by genetic polymorphism (Lamba et al., 2002; Spurdle et al., 2002) and seems to result from the intrinsic transcriptional regulation of this gene. Ten-fold or higher differences in hepatic mRNA expression and 20-fold differences in enzyme activity between healthy adults have been observed (Schuetz et al., 1994; Shimada et al., 1994; Maurel, 1996; Koch et al., 2002). This variability in expression of CYP3A4 has a significant impact on drug metabolism (Watkins et al., 1989). In the case of drugs with a low therapeutic index, such as agents used for cancer chemotherapy or organ transplantation, this variability has significant consequences and adds considerable complexity to clinical therapeutics. It is therefore evident that a basic understanding of how the CYP3A gene subfamily is regulated is of considerable relevance to clinical medicine as well as issues of endobiotic homeostasis. "

I can post a link to the the whole article if need be.

[Warrior21]

Bump, I can use some help. I'm also considering helping you write that article Taiboxa. Skullsmasher, why not we take part in that article? We already have substantial evidence that we are facing an overactive CYP3A4 enzyme. I wish I could destroy it completely

These websites show CYP3A4 inhibitors and there effects;

http://www.thedrugmonitor.com/interactionstable.html

http://www.thedrugmonitor.com/food-d...eractions.html

Notice cyp3a4 inhibitors; Slow down metabolism of drugs, increase bioavailability of drugs, prolong the time drug stays in blood.

St.John's Wort is an inducer. I have been taking St.John's Wort for a couple weeks now to help me sleep, I will take this shit no more.

[stupidhippo]

you may think the interactions aren't serious. Cuz you never
hear about them right? It's because doctors don't let drug-drug or food-drug
interactions happen. They take precautions to avoid them. But in our case we are trying to elicit drug-drug and food-drug interactions.

no.. thats not what I meant.. what I mean is that grapefruit for example does indeed have effect on serum levels of certain drugs... but not that many are altered in a very serious way. And by your percentages grapefruit would effect much more seriously to a lot diverse group of drugs than it actually does.. Statins are one group where u should avoid grapejuice (to prove your point)... IMO u are overinterpratating some of these facts.. I dont think its probable grapejuice could effect AAS serum concentrations in such a drastic way u are hoping... but I could be wrong... Also maybe in your case not the same logic applies than in normal ppl (by normal I mean if u indeed have some sort of abnormality in ur cytochrome P450 system).
BTW, Im gonna work as a doctor in a year.. So I have some knowledge on these subjects, I admit that its pretty limited in very detailed context but still...

[guest589745]

Sounds good, I am at work right now, trying to read and work at the same time.

Still, if injections bypass the intestinal tract all together, how can inhibiting this still apply to injectables? Does CYP still effect them?

[GetHugeDieTrying]

No STD's, thanks for caring tho =-)

All real stuff, except for some shit from IP back in the day.
First run: Test E/Dbol 8 weeks. Nothing, a whole bunch of headaches.
Second try: RF2 (Rocket Fuel 2). It's Test/Deca 200/mg per ml each. I did 2ml's of that a week for 8 weeks and nothing again. Actually I gained 8 lbs in the first week but I'm thinking that was placebo/increased cals.
Third try: Fina, made by me with an Animal kit. 5 weeks, again about 6 lbs in first week after that nothing.
Current try: Var only, I'm at 90mg daily. Been on for about 4 weeks. All I notice is a very, very slight pump. And a few of my lifts are up. But then again I just switched to a different routine so it's probably the routine/ more focus on nutrition as well.

My experience with AS has been shit. I've never had any gains where I could say "Wow I feel the steroids."

try some real gear thats all i got to say. *pay more if u have really have too..

[stupidhippo]

Sounds good, I am at work right now, trying to read and work at the same time.

Still, if injections bypass the intestinal tract all together, how can inhibiting this still apply to injectables? Does CYP still effect them?

yes.. if they are indeed metabolized in the liver by the P450 system... in the intestine if they were premetabolized (rendered inactive) before entering circulation... or thats how I understood it while glancing at it... Its also logical..

[Warrior21]

Yes CYP is involved in metabolism of injectables. I posted tons of reseach above to prove it. If you're at work I bet i would be hard for you to read all of it. But when you have a chance you should definately look at the links posted above.

Hippo I understand what you're saying. But I'm not going to rely on Grapefruit juice only. I'm going to discover a cocktail of drugs/foods which will help increase the bioavailability of AS. Due to the fact that I only have to take them on-cycle, I think I can get away with it and keep my health.

But Hippo if you check out PubMed you will see that grapefruit juice and drug interactions are serious. One of the links I posted about 2 posts up also shows grapefruit juice and it's interactions.

[Warrior21]

try some real gear thats all i got to say. *pay more if u have really have too..

Wow, ignorance my friend. Read the studies, overwhelming evidence here.

[Warrior21]

Another note. I started taking Grapefruit juice with the Var as of last night. My pee is looking slightly yellow throughout the day now. Before grapefruit juice, I would immediately pee and it would look like mountain dew once. The rest of the day it was clear.

Why is this significant you ask? Think about it. Darker pee=pee with more toxins in it. I used to pee really dark just several minutes after my Var capsule, then the rest of the day my pee was completely clear (I drink alot).

Now I have a lighter shade of yellow, throughout the day. I'm getting rid of the Var little by little, not all at once. I bet 3-5 days I will be feeling the Anavar . But I'm not going to stop with grapefruit juice only. I'm going to come up with a cocktail so that I can use measly doses, and have it not metabolize for a while.

If you think about it, slowing down drug metabolism will cause a nice buildup effect. Even off of small doses, it would just take more time with smaller doses. Orals are active immediately, so it wouldn't take all that much time.

[stupidhippo]

Hippo I understand what you're saying. But I'm not going to rely on Grapefruit juice only. I'm going to discover a cocktail of drugs/foods which will help increase the bioavailability of AS. Due to the fact that I only have to take them on-cycle, I think I can get away with it and keep my health.

But Hippo if you check out PubMed you will see that grapefruit juice and drug interactions are serious. One of the links I posted about 2 posts up also shows grapefruit juice and it's interactions.

Im not trying to say that they arent serious. With some drugs there are serious interactions, especially with some drugs that have a small therapeutic window.. All Im saying is that IMO it seems like u are stil probably expecting too much out of this. But I do believe u can probably influence the bioavailability of AS... just dunno to what a degree it will actually show in results..its the quantity here Im a lil skeptical about..

[Warrior21]

Im not trying to say that they arent serious. With some drugs there are serious interactions, especially with some drugs that have a small therapeutic window.. All Im saying is that IMO it seems like u are stil probably expecting too much out of this. But I do believe u can probably influence the bioavailability of AS... just dunno to what a degree it will actually show in results..its the quantity here Im a lil skeptical about..

Well if it means I have to use 70 or 80mg of Var instead of 200mg of Var to see results then I consider it a triumph. Taiboxa has even done over 200mg Anavar /day and not seen results! Ridiculous damnit.

[stupidhippo]

Another note. I started taking Grapefruit juice with the Var as of last night. My pee is looking slightly yellow throughout the day now. Before grapefruit juice, I would immediately pee and it would look like mountain dew once. The rest of the day it was clear.

Why is this significant you ask? Think about it. Darker pee=pee with more toxins in it. I used to pee really dark just several minutes after my Var capsule, then the rest of the day my pee was completely clear (I drink alot).

Now I have a lighter shade of yellow, throughout the day. I'm getting rid of the Var little by little, not all at once. I bet 3-5 days I will be feeling the Anavar . But I'm not going to stop with grapefruit juice only. I'm going to come up with a cocktail so that I can use measly doses, and have it not metabolize for a while.

If you think about it, slowing down drug metabolism will cause a nice buildup effect. Even off of small doses, it would just take more time with smaller doses. Orals are active immediately, so it wouldn't take all that much time.

there can also be compensatory reactions to stop the buildup... also the peeing thing is not necessarily so as u concluded.. Im not saying u are wrong.. All im saying is I wont get my hopes up yet about this. The best hint that u might be on to something is when the gear starts working with u (if it previously hasnt). also its another question then if the same logic applies to ppl with no abnormalities in the P450 system (assuming u have some there)

[stupidhippo]

Well if it means I have to use 70 or 80mg of Var instead of 200mg of Var to see results then I consider it a triumph. Taiboxa has even done over 200mg Anavar /day and not seen results! Ridiculous damnit.

that would be a good result.. Im not expecting it to be such a huge effect.. But if u are right Ill be the first to congratulate u..

[Warrior21]

Heh thanks. Remember when you said there is something deactivating AS in my body before they can work? Well I did read an article that does state that the P450 system are the enzymes that can deactivate drugs, therefore stopping their therapuetic effects.

Am I the only one with this case? No. Doctors prescribe medicine everyday that patients do not respond to. They just find other medication with the same purpose. The hard part about this is obviously I cannot go to a doctor and tell him to figure out why I'm not responding to roids you know.

So it's up to me, and anybody who wants to help, to figure out what is going on...and what is deactivating/metabolizing these hormones so quickly. Later on tonight I'm going to my friends house (shes gorgeous hehe). She worked with a pharmacy who produces anabolic steroids and has several books on steroid metabolism. It's just too bad I guess I have to tell her why I'm there huh.

[guest589745]

I have a feeling all of this may only apply to orally administed aas.

[stupidhippo]

dont tell her.. just ask that in a btw manner... especially if she is hot Probably not the most easy to read text, u are gonna be busy for some time with the book..

[stupidhippo]

I have a feeling all of this may only apply to orally administed aas.

I doubt it.. the steroids are inactivated in the liver.. in the orals case it was in the smallintestine where they possibly were premetabolized to a degree. This part only applies to the orals but in the end they will still be deactivated in the liver.. but this is a complex issue and I would be very surprised if someone here just works it out... this simply..

[Warrior21]

Well the chick has always thought I used anyway. I always denied it, I mean nothing ever worked for me anyway. But still she thinks I'm huge and I've got to be on stuff.

Skull don't lose hope bro. I already posted the fact that CYP P450 chromosomes deal with metabolism of ALL drugs, even injectibles bro. The girl I'm going to talk with tonight is pretty smart when it comes to this stuff. She will let me know for sure I bet. Don't lose hope, let's keep researching.

Wikipedias list of CYP3A4 inhibitors is a god place to start If you missed any of the links I posted above is suggest you check em out.

[guest589745]

FYI I wouldnt recomend taking more than 4 ounces of grapefruit juice with your orals as it could cause an overdose.

http://repositories.cdlib.org/cgi/vi...nutritionbytes


Yup, right here, Grapefruit juice only effects drugs administered orally and not intravenously.
Theres that. But you are talking about var here, so I conclude that grapefruit juice will cause a large increase in the bioavailability of it, around 60% from just 250ml of juice. The above link says it all.

As for intravenously administered aas, we have to look somewhere else now......

[Warrior21]

FYI I wouldnt recomend taking more than 4 ounces of grapefruit juice with your orals as it could cause an overdose.

http://repositories.cdlib.org/cgi/vi...nutritionbytes

Hehe, thats awesome info to hear bro. I'd down a whole damn gallon of it now. Seriously, that's what were trying to buildup in our blood until we get results bro. Good looking out too.

[guest589745]

I already posted the fact that CYP P450 chromosomes deal with metabolism of ALL drugs, even injectibles bro.

You need to point me exactly to where that is because I am finding conflicting studies.

[guest589745]

Hehe, thats awesome info to hear bro. I'd down a whole damn gallon of it now. Seriously, that's what were trying to buildup in our blood until we get results bro. Good looking out too.

re read it, I added to it.

[Warrior21]

Skull I find some info that goes contradicts that.

Check this link, there are injectables in there;
http://aidsinfonyc.org/hivplus/issue1/ahead/p450.html

Test Enanthate is metabolized by CYP3A4

[guest589745]

Skull I find some info that goes contradicts that.

Check this link, there are injectables in there;
http://aidsinfonyc.org/hivplus/issue1/ahead/p450.html

Test Enanthate is metabolized by CYP3A4

So is var, primo and deca from what I can tell hmmmm..........

and it specifically says "Primobolan DEPOT" hence, injectble, correct?

[guest589745]

Here is an article from hooker from 4 years ago that talks about this, with orals.

http://www.professionalmuscle.com/fo...p?t=1596&highl