Why milk thistle hinders results

**Grunt76** · 12-06-2005, 10:18 PM

Why Milk Thistle hinders results!

OK, here's some more info on Milk Thistle. I was wondering how one might come to the conclusion that MT might hider results of a cycle. The idea of MT hindering uptake of drugs by the body didn't seem to stick with what was observed at all. It turns out that the pathway through which it hinders results is via an inhibition of the enzymes that convert arachidonic acid to prostaglandins, of which PGF-2a is.

I haven't had time to highlight the good parts, as it's time to eat. I will put the good parts in bold later. Oh, and this is just the abstracts that describe how milk thistle hinders results. I have plenty of other abstracts that describe the good effects too.

Now at first this one seems to say that the COX are super-activated, but it turns out it isn't the case.

Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin.

Dehmlow C, Erhard J, de Groot H.

Institut fur Physiologische Chemie, Universitatsklinikum, Essen, Germany.

The flavonoid silibinin, the main compound extracted from the milk thistle Silybum marianum, displays hepatoprotective properties in acute and chronic liver injury. To further elucidate the mechanisms by which it acts, we studied the effects of silibinin on different functions of isolated rat Kupffer cells, namely the formation of superoxide anion radical (02-), nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E(2) (PGE(2)), and leukotriene B(4) (LTB(4)). Production of 02- and NO were inhibited in a dose-dependent manner, with an 50 percent inhibitory concentration (IC(50)) value around 80 micro mol/L. No effect on TNF-alpha formation was detected. Opposite effects were found on the cyclooxygenase and 5-lipoxygenase pathway of arachidonic acid metabolism. Whereas no influence on PGE(2) formation was observed with silibinin concentrations up to 100 micro mol/L, a strong inhibitory effect on LTB(4) formation became evident. The IC(50)-value for inhibiting the formation of this eicosanoid was determined to be 15 micro mol/L silibinin. The strong inhibition of LTB(4), formation by silibinin was confirmed in experiments with phagocytic cells isolated from human liver. Hence, while rather high concentrations of silibinin are necessary to diminish free radical formation by activated Kupffer cells, significant inhibition of the 5-lipoxygenase pathway already occurs at silibinin concentrations which are achieved in vivo. Selective inhibition of leukotriene formation by Kupffer cells can at least partly account for the hepatoprotective properties of silibinin.

PMID: 8666328 [PubMed - indexed for MEDLINE]

In this study I have only highlighted where they say how PGF is dependent upon those enzymes:

Up-regulation of prostaglandin biosynthesis by leukotriene C4 in elicited mice peritoneal macrophages activated with lipopolysaccharide/interferon-{gamma}.

Rossi A, Acquaviva AM, Iuliano F, Di Paola R, Cuzzocrea S, Sautebin L.

Department of Experimental Pharmacology, 'L. Califano', University of Naples Federico II, Naples, Italy.

Leukotrienes (LT) and prostaglandins (PG) are proinflammatory mediators generated by the conversion of arachidonic acid via 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways. It has long been proposed that the inhibition of the 5-LO could enhance the COX pathway leading to an increased PG generation. We have found that in in vitro models of inflammation, such as mice-elicited peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma), the deletion of the gene encoding for 5-LO or the enzyme activity inhibition corresponded to a negative modulation of the COX pathway. Moreover, exogenously added LTC(4), but not LTD(4), LTE(4), and LTB(4), was able to increase PG production in stimulated cells from 5-LO wild-type and knockout mice. LTC(4) was not able to induce COX-2 expression by itself but rather potentiated the action of LPS/IFN-gamma through the extracellular signal-regulated kinase-1/2 activation, as demonstrated by the use of a specific mitogen-activated protein kinase (MAPK) kinase inhibitor. The LT-induced increase in PG generation, as well as MAPK activation, was dependent by a specific ligand-receptor interaction, as demonstrated by the use of a cys-LT1 receptor antagonist, although also a direct action of the antagonist used, on PG generation, cannot be excluded. Thus, the balance between COX and 5-LO metabolites could be of great importance in controlling macrophage functions and consequently, inflammation and tumor promotion.

PMID: 16046553 [PubMed - in process]

And here too:

Pharmacological intervention of cyclooxygenase-2 and 5-lipoxygenase pathways. Impact on inflammation and cancer.

Claria J, Romano M.

DNA Unit, Hospital Clinic, and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain. jclaria@clinic.ub.es

Eicosanoids are potent biologically active arachidonic acid-derived lipid mediators that are intimately involved in inflammation and cancer. Cyclooxygenase (COX), the key enzyme in prostaglandin (PG) biosynthesis, controls one of the major pathways of arachidonic acid metabolism and is the main target for non-steroidal anti-inflammatory drugs (NSAIDs). COX exists in two distinct isoforms, COX-1 and COX-2, the latter being primarily involved in inflammation and cell proliferation. For this reason, in recent years, selective COX-2 inhibitors, that achieve the same anti-inflammatory efficacy as traditional NSAIDs but minimize the risk of unwanted side-effects, have been developed. On the other hand, emerging information has appreciated the role of other arachidonic acid metabolic pathway (the 5-lipoxygenase (5-LO) pathway) in producing and maintaining inflammation. Moreover, it is now being perceived that COX-2 and 5-LO have converging functions not only in inflammation but also in cell proliferation and neo-angiogenesis. In this regard, there is evidence that COX-2 and 5-LO are co-expressed and up-regulated in a number of inflammatory and neoplastic disorders, and that COX-2 as well as 5-LO inhibitors have beneficial effects in inflammatory diseases and are being investigated as potential anticancer drugs. This review provides an overview and an update of the progress achieved in the knowledge of COX-2 and 5-LO pathways and their involvement in inflammation and cancer. It also proposes a model of integrated pharmacological intervention on these pathways and reviews the information available regarding the use of the novel dual COX-2/5-LO inhibitors that block both pathways equally well.

PMID: 16250846 [PubMed - in process]

Well, so, that's that. NAC, k-r-ALA...

About Picrorhiza kurroa

Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds.

Zhang Y, Dewitt DL, Murugesan S, Nair MG.

Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA.

A bioassay guided phytochemical study of the ethyl acetate extract of the seeds of Picrorhiza kurroa afforded a new triterpenoid, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-O-beta-D-glucoside (1), along with five known triterpenoids, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-oic acid (2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-O-beta-d-glucoside (3), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3beta, 19beta, trihydroxyolean-12-en-28-oic acid (5), and 2alpha, 3beta, 6beta, 23-tetrahydroxyolean-12-en-28-oic acid (6). Their structures were established by extensive NMR spectral studies. The acetyl derivatives, compounds 7 and 8, were prepared from compounds 1 and 2, respectively, to aid in their structure elucidation. The inhibition of cyclooxygenase-2 (COX-2) enzyme by compounds 1--6 at 100 microg/mL was 38.3%, 39%, 37%, 49.6%, 25%, and 45.0%, respectively. However, compounds 1--6, at 100 microg/mL, did not inhibit cyclooxygenase-1 (COX-1) enzyme. Compound 1 is a novel triterpenoid and compounds 1--6 are isolated for the first time from the seeds of P. kurroa.

PMID: 15979098 [PubMed - indexed for MEDLINE]

Now, of course, I don't know if COX-1 or COX-2 is more important for the synthesis of PGF2a and the resulting anabolism. Will search. EDIT : This says that COX-2 is much more important in inflammation mechanisms than COX-1. What this means for muscle growth I do not know. Maybe someone can help? Here's the excerpt:

Distribution of cyclooxygenase isoforms in murine chronic granulomatous inflammation. Implications for future anti-inflammatory therapy.

Appleton I, Tomlinson A, Mitchell JA, Willoughby DA.

Department of Experimental Pathology, William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, U.K.

Inhibition of the enzyme cyclooxygenase (COX) is the basis for the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs). COX exists as a constitutive (COX-1) and a mitogen-inducible (COX-2) isoform. The relative contribution of COX-1 and COX-2 to inflammation is unknown. This study investigated COX activity and the distribution of COX-1 and COX-2 during the development of a murine air pouch model of chronic granulomatous inflammation. COX activity progressively rose and was maximal at day 14. Of the COX metabolites measured, PGE2 was the greatest > 6-keto PGF1a > TXB2 > PGF2a. By day 7, COX-2-labelled fibroblast- and macrophage-like cells were observed and their number and distribution increased with time. At all time points, endothelial cells of venules in the loose connective tissue of the dermis showed immunoreactivity for COX-2. After day 14, labelling of capillaries in the granuloma was also observed. This study is the first to show that COX-2 is the predominant COX isoform in all stages of the inflammatory response. These results suggest that selective inhibition of COX-2 may prove more beneficial, with fewer gastric and renal side-effects, than existing NSAID therapy for the treatment of chronic inflammatory diseases.

PMID: 7562257 [PubMed - indexed for MEDLINE]

Stopping here, although it would be nice to know if all we need to look for is either COX-1 or COX-2 inhibition from whatever we take...

**DarkFalcon** · 12-07-2005, 06:37 AM

Man this rattles my brain. I'm going to have to read it over a few times.

**Grunt76** · 12-07-2005, 02:04 PM

Yeh, I'mma highlight the good parts, that way is much less rattle-ish...

nickhead76 · 12-08-2005, 03:14 PM

thats a nice article, but i dont know the difference between what i just read and a ham sammich.........

anyway....ok...so it hinders some gains, my question is, how much exactly is it hindering gains, and is it enough not to use it to help protect the liver.

and same thing for NAC.

**Grunt76** · 12-08-2005, 03:52 PM

NAC doesn't seem to impede gains, but does protect the liver.

Milk Thistle will hinder gains, period. I'll still use it, but instead of megadosing it, I'll preload it real good BEFORE the cycle, use it in moderation ON-cycle, and cut it off in PCT. Quite the contrary to what others do.

I'll save the NAC for ON and PCT.

nickhead76 · 12-08-2005, 04:32 PM

Quote:

Originally Posted by ss01

NAC doesn't seem to impede gains, but does protect the liver.

Milk Thistle will hinder gains, period. I'll still use it, but instead of megadosing it, I'll preload it real good BEFORE the cycle, use it in moderation ON-cycle, and cut it off in PCT. Quite the contrary to what others do.

I'll save the NAC for ON and PCT.

now i understand that kinda talk my man. :bigthumbu thanx.

**Grunt76** · 01-23-2006, 09:46 PM

Actually I stand corrected, NAC does inhibit COX-2, making it anti-anabolic.

**Grunt76** · 04-05-2006, 11:27 PM

Quote:

Originally Posted by Grunt76

Actually I stand corrected, NAC does inhibit COX-2, making it anti-anabolic.

Just a lot less so than MT.

Nitrous · 04-11-2006, 07:41 PM

intersting info..good post

comfortable_pants · 04-13-2006, 09:23 PM

Quote:

Originally Posted by Grunt76

Actually I stand corrected, NAC does inhibit COX-2, making it anti-anabolic.

so in your opinion you think something like liv-52 and krala would be better for liver protection?

**Grunt76** · 04-13-2006, 11:47 PM

I do not know what's in liv-52 and how it works. K-r-ALA is better in that it does not hinder results, however it probably isn't as good a hepatoportectant as MT or NAC. Straight glutathione is a good option instead of MT or NAC, but it is much pricier.

12-08-2005, 03:14 PM	#4
nickhead76 PLATINUM MEMBER Join Date: May 2005 Posts: 283 Recipes: 0 Rep Power: 8	thats a nice article, but i dont know the difference between what i just read and a ham sammich......... anyway....ok...so it hinders some gains, my question is, how much exactly is it hindering gains, and is it enough not to use it to help protect the liver. and same thing for NAC. __________________ PLATINUM MEMBER

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12-07-2005, 06:37 AM	#2
DarkFalcon I've got a RAGING clue! Join Date: May 2005 Location: dnyc99's cleaning staff Posts: 11,511 Recipes: 0 Rep Power: 299	Man this rattles my brain. I'm going to have to read it over a few times.

04-11-2006, 07:41 PM	#9
Nitrous Pro Stature Join Date: Dec 2005 Location: Atown, BC Posts: 169 Recipes: 0 Rep Power: 11	intersting info..good post