Alpine
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I have seen a lot of posts regarding Milk Thistle lately. Obviously a lot of ppl take NAC/MT to help the liver when using 17aa/methyls. Numerous posts have mentioned that it is Anti-androgenic and could hurt gains. Nobody really backs any of it up but just refers to this or that. I really didnt understand how this could be and decided to look into it a bit.
Silybum (MT) inactivates cytochromes P450 (P450) 3A4 and 2C9 preventing the metabolism of testosterone to 6-beta-hydroxytestosterone. This would seem to potentiate testosterone. Perhaps this is way off though.
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Drug Metab Dispos. 2004 Jun;32(6):587-94. Related Articles, Links
Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases.
Sridar C, Goosen TC, Kent UM, Williams JA, Hollenberg PF.
Department of Pharmacology, The University of Michigan, Ann Arbor, MI 48109, USA.
Silybin, a major constituent of the milk thistle, is used to treat several liver disorders. Silybin inactivated purified, recombinant cytochromes P450 (P450) 3A4 and 2C9 in a mechanism-based manner. The inactivations were time-, concentration-, and NADPH-dependent. The inactivation of the 7-benzyloxy-4-(trifluoromethyl-)coumarin O-debenzylation activity (P450 3A4) was characterized by a K(I) of 32 microM, a k(inact) of 0.06 min(-1), and a t(1/2) of 14 min. Testosterone metabolism to 6-beta-hydroxytestosterone (P450 3A4) was also inactivated with a K(I) of 166 microM, a k(inact) of 0.08 min(-1), and a t(1/2) of 9 min. The 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of purified human P450 2C9 was inactivated with a K(I) of 5 microM, a k(inact) of 0.14 min(-1), and a t(1/2) of 7 min. Parallel loss of heme was observed with both P450s. Activity of both P450 enzymes was not recovered after removal of silybin either by dialysis or by spin gel filtration. In addition, silybin inhibited the glucuronidation of 7-hydroxy-4-trifluoromethylcoumarin catalyzed by recombinant hepatic UDP-glucuronosyltransferases (UGTs) 1A1, 1A6, 1A9, 2B7, and 2B15, with IC(50) values of 1.4 microM, 28 microM, 20 microM, 92 microM, and 75 microM, respectively. Silybin was a potent inhibitor of UGT1A1 and was 14- and 20-fold more selective for UGT1A1 than for UGT1A9 and UGT1A6, respectively. Thus, careful administration of silybin with drugs primarily cleared by P450s 3A4 or 2C9 is advised, since drug-drug interactions cannot be excluded. The clinical significance of in vitro UGT1A1 inhibition is unknown.
credit to jboldman @ CEM for pointing this out
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I attribute a lot of this to Poliquin's reference to it (made famous by the Heavy Metal Detox log @ AM) in his interview with William Llewelyn.
http://www.bodyofscience.com/issues/...5_poliquin.pdf
http://www.bodyofscience.com/issues/...summer2005.pdf
In a semi-related note I have read that undenatured whey protien isolate is MUCH more effective than what most people assume. Besides being good for numerous other reasons it also boosts GSH (Glutathione, master antioxidant) levels considerably higher than anything else available (NAC, MT, ALA..). Until now I had not heard of uWPI used in regard to this subject. There is said to be a great deal of valid info on Pubmed regarding it but I havent ever looked and Im running out of time now. I have no doubt that uWPI is amazing but its so expensive. Im in college, 5lb of ON is about all I can validate at the moment.
Bump for more info...Bobo, Dr. D
Silybum (MT) inactivates cytochromes P450 (P450) 3A4 and 2C9 preventing the metabolism of testosterone to 6-beta-hydroxytestosterone. This would seem to potentiate testosterone. Perhaps this is way off though.
------------------------------
Drug Metab Dispos. 2004 Jun;32(6):587-94. Related Articles, Links
Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases.
Sridar C, Goosen TC, Kent UM, Williams JA, Hollenberg PF.
Department of Pharmacology, The University of Michigan, Ann Arbor, MI 48109, USA.
Silybin, a major constituent of the milk thistle, is used to treat several liver disorders. Silybin inactivated purified, recombinant cytochromes P450 (P450) 3A4 and 2C9 in a mechanism-based manner. The inactivations were time-, concentration-, and NADPH-dependent. The inactivation of the 7-benzyloxy-4-(trifluoromethyl-)coumarin O-debenzylation activity (P450 3A4) was characterized by a K(I) of 32 microM, a k(inact) of 0.06 min(-1), and a t(1/2) of 14 min. Testosterone metabolism to 6-beta-hydroxytestosterone (P450 3A4) was also inactivated with a K(I) of 166 microM, a k(inact) of 0.08 min(-1), and a t(1/2) of 9 min. The 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of purified human P450 2C9 was inactivated with a K(I) of 5 microM, a k(inact) of 0.14 min(-1), and a t(1/2) of 7 min. Parallel loss of heme was observed with both P450s. Activity of both P450 enzymes was not recovered after removal of silybin either by dialysis or by spin gel filtration. In addition, silybin inhibited the glucuronidation of 7-hydroxy-4-trifluoromethylcoumarin catalyzed by recombinant hepatic UDP-glucuronosyltransferases (UGTs) 1A1, 1A6, 1A9, 2B7, and 2B15, with IC(50) values of 1.4 microM, 28 microM, 20 microM, 92 microM, and 75 microM, respectively. Silybin was a potent inhibitor of UGT1A1 and was 14- and 20-fold more selective for UGT1A1 than for UGT1A9 and UGT1A6, respectively. Thus, careful administration of silybin with drugs primarily cleared by P450s 3A4 or 2C9 is advised, since drug-drug interactions cannot be excluded. The clinical significance of in vitro UGT1A1 inhibition is unknown.
credit to jboldman @ CEM for pointing this out
------------------------------
I attribute a lot of this to Poliquin's reference to it (made famous by the Heavy Metal Detox log @ AM) in his interview with William Llewelyn.
http://www.bodyofscience.com/issues/...5_poliquin.pdf
http://www.bodyofscience.com/issues/...summer2005.pdf
While this may be true (is it?) to some degree, I dont see how it could significantly alter levels enough to make any difference. Poliquin is known for doing crazy and extreme things (super extreme megadoses of IV vitC). Many of his ideas seem radical to the mainstream. He is somewhat of a mad scientist to many. I would not be quick to label him as the ultimate authority in AAS related health/science. Still, his remarks on milk thistle are interesting and he seems to be known for amazing things at his training facility. AA (X-factor) conversion is a known link in building muscle (althogh the AA supplement doesnt seem to do well). Inhibiting this and "messing" with androgen receptor sites doesnt sound good. The only problem is I have never heard of this (any of it) from anyone besides Poliquin.
In a semi-related note I have read that undenatured whey protien isolate is MUCH more effective than what most people assume. Besides being good for numerous other reasons it also boosts GSH (Glutathione, master antioxidant) levels considerably higher than anything else available (NAC, MT, ALA..). Until now I had not heard of uWPI used in regard to this subject. There is said to be a great deal of valid info on Pubmed regarding it but I havent ever looked and Im running out of time now. I have no doubt that uWPI is amazing but its so expensive. Im in college, 5lb of ON is about all I can validate at the moment.
Bump for more info...Bobo, Dr. D
