Liver Toxicity - Methylated products Q ?

[notoriousmjc]

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[wedgylx]

Hmm...could not find the best place to post this but here goes:

How do you identify if a product will/is toxic to the liver (as in superdrol), and at what dose it becomes toxic, as apposed other methylated products that are not purported to be toxic???

Might dig through my texts, but have seen nothing specific so far.

Thanks

probably by giving differing doses to people and testing values

[LAZ]

Well anything methylated is hard on the liver because i believe the methylation is a barrier around the substance that keeps the liver from destroying it. There for the liver is working hard to break down a substance it cant break down. Someone correct me if i am wrong. I hate giving out incorrect info.

[wedgylx]

Well anything methylated is hard on the liver because i believe the methylation is a barrier around the substance that keeps the liver from destroying it. There for the liver is working hard to break down a substance it cant break down. Someone correct me if i am wrong. I hate giving out incorrect info.

I think that the toxicity can increase or decrease(to the point where it can be negligable) based on the carbon number to which the methyl group is bound. I'm not 100% on this but I'm fairly certain.

[Robboe]

Methylation of an androgenic compound is what is liver toxic.

[dinoiii]

Liver toxicity includes but is NOT LIMITED to methylated products. There has been citation of something as seemingly "benign" (in quotes due to the way I am using it - not implying it versus malignant here) as saw palmetto.

It is quantitatively a byproduct of how extensive and/or exclusive hepatic metabolism is. In regards to supplements - you will NOT find this in a "textbook" setting, however, there is a dose-limited hepatotoxic response seen with anything that exhibits this property. What I mean is - the severity of hepatotoxic effects will depend on how much you take of a designated supplement, however this is NOT to imply even the smallest dose will not have "some" effect on the liver.

Review the topic of Effective vs. Lethal Dose in a Pharm text and you can apply this kind of info there.

Hope this aids your quest. If you have more specific questions on a particular supp, I am sure I could potentially be of more assistance.

[TheKoos]

Assuming two methylated products have similar liver toxicity, which would be harder on the liver?

40mg ED of compound A

or

10mg ED of compound A combined with 10mg ED of compound B

[dinoiii]

Well given the hypothetical scenario of fictitious cpds., please comment on both the half-lives of Cpd A and Cpd B as well as volume of distribution for each and I will supply an answer. Prior to this knowledge, I would be guessing at best.

[TheKoos]

Lets say approx. 8 hour half life for both A and B.

Volume of distribution? Is that something other than the 40mg ED vs 10mg + 10mg?

20mg Ed of A and 20mg Ed of B vs 40mg ED of A would also be interesting.

Also how would the effects differ with the stacked compounds dosage split by 8-10 hours vs taking them at the same time?

[notoriousmjc]

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[dinoiii]

First Koos,

The volume of distribution of a drug/supplement is the size of the "compartment" into which a drug apparently has been distributed following absorption. If this is identical for each - the calculations can get complicated - then

your first scenario 40 mg A vs. 10 mg A + 10 mg B with the same half life could imply the former to be MORE hepatotoxic, however would you see greater efficacy in a scenario of 10 mg + 10 mg versus 40 mg....now you are talking effective dose.

second scenario 20 mg A + 20 mg B vs. 40 mg A would show potentially identical hepatotoxicity, but what would come into play more in this argument is how extensive the metabolism and what is the MOA of the various metabolites which likely would not be identical or you may as well be taking the 40 mg of A in the first place.

In both cases, the 8 hour half life being identical btw is highly unlikely.

Split 8-10 hours apart should not necessarily have the biggest effect as metabolites can be more active and potentially additive. In the same sense, the liver is an organ that is for the most part very quiescent (re: mitotic capactiy) despite its regenerative capacity...hehe, I am simply saying give it a break.

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Notorious

A few comments off the bat...methylation does not necessarily act the same with different cpds. Methylation outside a steroidal cpd in the C17 posistion is not necessarily the same as a -CH3 as a simple end group.

More on this topic later with specifics re: your particular supps. I have to present a case for a Tumor Board meeting in 15 minutes.

[TheKoos]

Thank you for the reply Dinoiii.

For my simple mind....does the last part of your response mean a single 40mg dose may be less stressful on the liver than 40mg spread out 20/20 or 10/10/10/10 because the liver has more time between each dose?

If the above statement is true would the benefit to the liver outweigh the possible decrease in effectiveness of the compound.

If the half-life is 8 hours how much difference would there be in the effectiveness of a single dose vs splitting the doses?

[dinoiii]

Because we are dealing with purely hypotheticals, you need to create the properties of your compounds before I could move forward.

Lets revisit the 40 mg vs. spread out again:
- If a 40 mg dose (what may be called a stress dose, but this too is a misnomer here) has 23 hours to offer recoup (i.e. - regeneration of glutathione), this may be the case that 40 mg is LESS hepatotoxic in the long run
- Now wipe out what I just said, however, if that same item doesn't allow for proper mitotic recoup of liver cells which is likely more a person dependent property anyway and why some chronic alcoholics don't develop cirrhosis and others do
- The truth of the matter is that with hypotheticals, this remains a daunting task and virtually impossible to answer without knowing more, but at this time, I could continue to offer a qualified - "it depends" statement.


What you said about outweighing effectiveness and the like...this is where that discussion of Lethal versus Effective doses would likely benefit you - but that is virtually a whole topic in its own right and something I cannot unfortunately get into now without spending the night on it.

Half-life remains dependent on activity of metabolites. In theory, the stress dose would make more sense from an efficacious standpoint. But heres another trick - receptor saturation as well as enzyme substrate saturation if we are talking about a PH or the like.




About the specific compounds you mention Notorious, I am simply trying to be careful the way I word a discussion of another company's products - in lieu of one of last year's battles with another supplement company owner as you may or may not be aware. It really is a needless headache, but in my next post, I will address the compounds you mention AS GENERIC, not to be identified with any company.

[notoriousmjc]

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[pbk]

Great thread. Dinoiii, this gives me the opportunity to ask about specific products, as I had been thinking of starting a thread to ask you these questions. This is for anyone else who has knowledge of this as well.

In particular, the two products I am most interested to find more info are M1T and 2a,17a di methyl etiocholan 3-one, 17b-ol (aka Methyl-Drol, SuperDrol). I have searched for answers, but have been left unsatisfied.

I realize there are many variables, including how the liver of different people handles these things, but I am just looking for good general info. Certainly, some PH's must be more liver toxic in general than others. In 2004, M1T was all the rage, but now that it is gone, a lot of people on the forums talk about how bad it was on the liver.

So, I really would like a general idea of how toxic M1T is and how "2a,17a di methyl etiocholan 3-one, 17b-ol" compares to it.

And while I have your attention on this, how about PP or MP, the PH that is often stacked with it. And how much more toxic is the stack vs the stand alone.

Don't want to get this too complicated, but let's keep in mind the dosing and cycle lengths as well. I.E., for M1T, 20mg per day for no more than two weeks. SD or MD...from 20 to 40 mg per day up to 3 to 4 weeks, or a stack with PP or MP for up to 6 weeks.

Dinoiii, I can't believe all the time and effort you spend here to help educate us, so I do not want to "hit" you with too much all at once, so this is all for now. What would be really great if there were some place to go online and have all this info on toxicity, a comparison of all the PH's that have been out in the past several years.

[Robboe]

Assuming two methylated products have similar liver toxicity, which would be harder on the liver?

40mg ED of compound A

or

10mg ED of compound A combined with 10mg ED of compound B

When stacking methylated androgenic compounds, it is the metabolites that can be the most damaging, so its not so straight forward.

[dinoiii]

bumping this to the top so I don't forget to revisit...