TeamSavage
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Everybody seems to agree that stacking 17-aa methylated orals will cause increased liver toxicity and is generally a dumb idea. It seems prudent to avoid doing so. But I’m wondering why this might be a case? What’s the evidence that stacking two or more methylated compounds is really worse than taking just one? Is there a theoretical reason, clinical research, or blood work behind this? Before you flame me, please allow me to clarify…
If 20mg PP or 10mg Superdrol alone are liver toxic, then it stands to reason that taking both – each at the same dose (20mg PP + 10mg superdrol) - would be significantly more hepatoxic. (I’m not questioning this.) What I’m wondering about is why taking both at lower doses would be more hepatoxic than taking one alone at higher doses. Is there an interaction or synergy that makes the combination inherently more hepatoxic?
To simplify for the point of illustration, let’s say that Superdrol, mg per mg, is twice as liver toxic as PP. (Maybe it is or isn’t, but let’s assume for now.) So in terms of hepatoxicity, 1mg SD = 2mg PP. From what I read on AM about stacking methyls, taking 10mg SD + 20mg PP is assumed to be more liver toxic than taking higher doses of either alone. (For instance, under our assumption, the “hepatoxically-equivalent” doses of 20mg SD or 40mg PP.) But this may or not be the case. If the mechanisms of hepatoxicity are distinct for each compound, then combining them may have some multiplicative effect (making 10mg SD + 20mg PP worse than either 20mg SD or 40mg PP alone). But if the hepatoxicity for both is mediated by the same mechanism, then there might NOT be a multiplicative effect by combining both, making stacking them (at lower doses) no more damaging than taking one (at a higher dose).
An analogy:
Scenario A:
Both vodka (V) and acetaminophen (Tylenol, T) are liver toxic when taken alone. But they’re toxic through different mechanisms, and the risk of liver toxicity is significantly increased by combining them. Taking 6 vodka shots + 6 Tylenol daily is more liver toxic, in the long-term, than taking either 12 vodka shots or 12 Tylenol daily. 6V + 6T > 12V or 12T. (This analogy is muddied a little by the fact that high acute doses of Tylenol taken within a single 24-hour period can present severe cases of short-term liver toxicity, but hopefully you get my drift.)
Scenario B:
But vodka (V) and beer (B), while both liver toxic, are hepatoxic through identical mechanisms. In terms of long-term liver toxicity, 10 vodka shots + 10 beers are no more liver toxic than 20 vodka shots or 20 beers. 10V + 10B = 20V = 20B. There’s nothing inherently more toxic about “stacking” vodka and beer, as the toxicity of both is due to the same cause, alcohol.
So is there any evidence that stacking two 17-aa methyls is more similar to scenario “A”? The discussion of stacking methylated orals on this board seems to assume a situation similar to “A”. But “B” could in fact provide a more accurate representation, in which case stacking methyls would not be any worse than using a single methyl, provided that the doses of each methyl were reduced accordingly (cut in half with two methyls, cut to 1/3 with three methyls, etc.).
I’m certainly not an expert on steroid metabolism, which is why I’m asking this question. But my limited understanding is that the hepatoxicity of 17-aa methylated orals results from the production of a 17-glucuronide metabolite that causes cholestasis. (Oxandrolone, while 17-aa, doesn’t exhibit similar toxicity because it is not metabolized into a 17-glucuronide metabolite.)
If this is accurate, it would appear that the liver toxicities of all 17-aa methylated compounds are mediated through the same mechanism: 17-glucuronide metabolites. In other words, a situation closer to Scenario “B” than “A”. In this case, it seems reasonable that combining multiple 17-aa methyls, at lower doses, would be no more hepatoxic than taking a single methyl at a higher dose. In other words, if 1mg SD = 2mg PP in terms of liver toxicity, then 10mg SD + 20mg PP = 20mg SD = 40mg PP.
(The obvious response to this is, "Small, subtle differences in chemical structure can result in significant differences in action. Thus, even if the liver toxicities of 17-aa orals result from the same general mechanism (17-glucuronide metabolites), the various 17-glucuronide metabolites might differ in the specific way that they interact with the ATP bind cassette transporters to cause cholestasis, possibly making them more toxic in combination." The first sentence is undoubtedly true. The second, maybe, maybe not. Again, do we have reason to suspect one way or the other?)
To be clear, I’m not advocating stacking multiple 17-aa methylated compounds. And I’m not even claiming that it is or isn’t worse, that it’s situation “A” or “B”. But do we have REASON to believe that stacking is worse (theoretical, clinical, or otherwise)? Why? How? Or is this simply assumed?
I’d like some discussion and clarification of this issue.
(We do know that the beneficial effects of various 17-aa methylated orals are not all mediated by identical mechanisms. For the purposes of building LBM and strength, PP, SD, HD and others work through somewhat distinct mechanisms to provide unique benefit profiles. In many cases, stacking multiple synergistic methyls – at lower doses – might provide greater benefits than any single one at a higher dose… Of course, this doesn’t really matter if the combo eats your liver.)
P.S. I’ve been reading at AM for some time, although I just recently started posting. I originally came across BB.com first, but found it less than helpful. I remember reading a post at BB.com that said something along the lines of, “those guyz over at AM.com were talking about this but I couldnt understand them cuz they were using all sorts of science and studys and complacated words and s**t like their all supersmart doctors and scientists or somthing.” That was the final post I ever read at BB.com.
If 20mg PP or 10mg Superdrol alone are liver toxic, then it stands to reason that taking both – each at the same dose (20mg PP + 10mg superdrol) - would be significantly more hepatoxic. (I’m not questioning this.) What I’m wondering about is why taking both at lower doses would be more hepatoxic than taking one alone at higher doses. Is there an interaction or synergy that makes the combination inherently more hepatoxic?
To simplify for the point of illustration, let’s say that Superdrol, mg per mg, is twice as liver toxic as PP. (Maybe it is or isn’t, but let’s assume for now.) So in terms of hepatoxicity, 1mg SD = 2mg PP. From what I read on AM about stacking methyls, taking 10mg SD + 20mg PP is assumed to be more liver toxic than taking higher doses of either alone. (For instance, under our assumption, the “hepatoxically-equivalent” doses of 20mg SD or 40mg PP.) But this may or not be the case. If the mechanisms of hepatoxicity are distinct for each compound, then combining them may have some multiplicative effect (making 10mg SD + 20mg PP worse than either 20mg SD or 40mg PP alone). But if the hepatoxicity for both is mediated by the same mechanism, then there might NOT be a multiplicative effect by combining both, making stacking them (at lower doses) no more damaging than taking one (at a higher dose).
An analogy:
Scenario A:
Both vodka (V) and acetaminophen (Tylenol, T) are liver toxic when taken alone. But they’re toxic through different mechanisms, and the risk of liver toxicity is significantly increased by combining them. Taking 6 vodka shots + 6 Tylenol daily is more liver toxic, in the long-term, than taking either 12 vodka shots or 12 Tylenol daily. 6V + 6T > 12V or 12T. (This analogy is muddied a little by the fact that high acute doses of Tylenol taken within a single 24-hour period can present severe cases of short-term liver toxicity, but hopefully you get my drift.)
Scenario B:
But vodka (V) and beer (B), while both liver toxic, are hepatoxic through identical mechanisms. In terms of long-term liver toxicity, 10 vodka shots + 10 beers are no more liver toxic than 20 vodka shots or 20 beers. 10V + 10B = 20V = 20B. There’s nothing inherently more toxic about “stacking” vodka and beer, as the toxicity of both is due to the same cause, alcohol.
So is there any evidence that stacking two 17-aa methyls is more similar to scenario “A”? The discussion of stacking methylated orals on this board seems to assume a situation similar to “A”. But “B” could in fact provide a more accurate representation, in which case stacking methyls would not be any worse than using a single methyl, provided that the doses of each methyl were reduced accordingly (cut in half with two methyls, cut to 1/3 with three methyls, etc.).
I’m certainly not an expert on steroid metabolism, which is why I’m asking this question. But my limited understanding is that the hepatoxicity of 17-aa methylated orals results from the production of a 17-glucuronide metabolite that causes cholestasis. (Oxandrolone, while 17-aa, doesn’t exhibit similar toxicity because it is not metabolized into a 17-glucuronide metabolite.)
If this is accurate, it would appear that the liver toxicities of all 17-aa methylated compounds are mediated through the same mechanism: 17-glucuronide metabolites. In other words, a situation closer to Scenario “B” than “A”. In this case, it seems reasonable that combining multiple 17-aa methyls, at lower doses, would be no more hepatoxic than taking a single methyl at a higher dose. In other words, if 1mg SD = 2mg PP in terms of liver toxicity, then 10mg SD + 20mg PP = 20mg SD = 40mg PP.
(The obvious response to this is, "Small, subtle differences in chemical structure can result in significant differences in action. Thus, even if the liver toxicities of 17-aa orals result from the same general mechanism (17-glucuronide metabolites), the various 17-glucuronide metabolites might differ in the specific way that they interact with the ATP bind cassette transporters to cause cholestasis, possibly making them more toxic in combination." The first sentence is undoubtedly true. The second, maybe, maybe not. Again, do we have reason to suspect one way or the other?)
To be clear, I’m not advocating stacking multiple 17-aa methylated compounds. And I’m not even claiming that it is or isn’t worse, that it’s situation “A” or “B”. But do we have REASON to believe that stacking is worse (theoretical, clinical, or otherwise)? Why? How? Or is this simply assumed?
I’d like some discussion and clarification of this issue.
(We do know that the beneficial effects of various 17-aa methylated orals are not all mediated by identical mechanisms. For the purposes of building LBM and strength, PP, SD, HD and others work through somewhat distinct mechanisms to provide unique benefit profiles. In many cases, stacking multiple synergistic methyls – at lower doses – might provide greater benefits than any single one at a higher dose… Of course, this doesn’t really matter if the combo eats your liver.)
P.S. I’ve been reading at AM for some time, although I just recently started posting. I originally came across BB.com first, but found it less than helpful. I remember reading a post at BB.com that said something along the lines of, “those guyz over at AM.com were talking about this but I couldnt understand them cuz they were using all sorts of science and studys and complacated words and s**t like their all supersmart doctors and scientists or somthing.” That was the final post I ever read at BB.com.
