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Milk Thistle possibly anti-androgenic

JudoJosh

JudoJosh

Pro Virili Parte
possibly.. :dunno:

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.
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Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells.
Zi X, Zhang J, Agarwal R, Pollak M.

Lady Davis Research Institute of Jewish General Hospital and Department of Oncology, McGill University, Montreal, Quebec, Canada.

Silibinin, a naturally occurring flavonoid antioxidant found in the milk thistle, has recently been shown to have potent antiproliferative effects against various malignant cell lines, but the underlying mechanism of action remains to be elucidated. We investigated the effect of silibinin on androgen-independent prostate cancer PC-3 cells. At pharmacologically achievable silibinin concentrations (0.02-20 microM), we observed increased insulin-like growth factor-binding protein 3 (IGFBP-3) accumulation in PC-3 cell conditioned medium and a dose-dependent increase of IGFBP-3 mRNA abundance with a 9-fold increase over baseline at 20 microM silibinin. An IGFBP-3 antisense oligodeoxynucleotide that attenuated silibinin-induced IGFBP-3 gene expression and protein accumulation reduced the antiproliferative action of silibinin. We also observed that silibinin reduced insulin receptor substrate 1 tyrosine phosphorylation, indicating an inhibitory effect on the insulin-like growth factor I receptor-mediated signaling pathway. These results suggest a novel mechanism by which silibinin acts as an antiproliferative agent and justify further work to investigate potential use of this compound or its derivatives in prostate cancer treatment and prevention.</div>
which would be the IGF-reduction Group I) was talking about ... and there is another study I just cannot find atm which is about the way milk thistle inhibits the conversion of androgens after receptor binding.
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There's no possibility about it, it's a proven fact already - been many threads on AM and in general in many other forums about this issue.
 
Yaz said:
There's no possibility about it, it's a proven fact already - been many threads on AM and in general in many other forums about this issue.
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Ya. Tbh I don't take milk thistle. I take ALA and NAC. Nac far from my workouts though and only if I feel my liver is having a hard time. Other than that I just eat reasonably clean.
 
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mattrag said:
Ya. Tbh I don't take milk thistle. I take ALA and NAC. Nac far from my workouts though and only if I feel my liver is having a hard time. Other than that I just eat reasonably clean.
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Highly unlikely
Pretty good choices both NAC & ALA.
 
Actually that study supports the opposite. It's preventing testosterone hydroxylation and glucoronidation. Both good things.

Also these in vitro studies on milk Thistle are very hairy... Because the kinetics of milk Thistle are terrible. The only time you might get close to comparable plasma levels is with a siliphos product or a milk Thistle product like primordial.
 
When on cycle i try and avoid any more than 500mg a day, the only i reason I take any of it is because it is in every all in one cycle support. Forged liver and Liver52 are my liver supps. ALA & NAC are great too if you need something extra
 
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