Re: Phase II liver detox-, you misunderstand

[Guest guest]

You are quite right that Milk Thistle affects phase I, but it affects it in

the way YOU WANT IT TO!!! That is, as it says below in the abstract you

sent me, it INHIBITS PHASE I enzymes, thus SLOWING DOWN Phase I.

if you have a speedy Phase I, MILK THISTLE IS EXACTLY WHAT YOU WANT! I

have no idea why your doctor told you otherwise. He is simply wrong.

When you have an unbalanced Phase I/Phase II ratio, you want to INCREASE

PHASE II enzymes but DECREASE PHASE I enzymes.

Detox in the liver works like this: A chemical is altered in the liver by

Phase I enzymes to some intermediate chemical. This intermediate chemical

is then further altered by Phase II enzymes to a final chemical that is

much less toxic than the original, which can then be excreted. The PROBLEM

is that the INTERMEDIATE produced after Phase I alteration is often MORE

TOXIC than the original chemical! That is usually fine because it doesn't

hang around long, being almost immediately altered again by Phase II

enzymes to the final, non-toxic form. HOWEVER, when PHASE I is FAST and

PHASE II is slow, a LOT of the toxic intermediate is made quickly, but the

final, non-toxic version is made slowly. Therefore, these TOXIC

INTERMEDIATES build up and cause trouble.

In this case, you want to, FIRST, increase PHASE II enzymes, and SECOND,

DECREASE PHASE I enzymes.

Milk Thistle does BOTH of these things. As it says below, it INCREASES

glucuronidation (a PHASE II process) and INHIBITS PHASE I enzymes.

All the abstracts on MEDLINE that I have found say exactly this.

Please show me otherwise, if you find anything.

-Greg

Title

Tissue distribution of silibinin, the major active constituent of

silymarin, in mice and its association with enhancement of phase II

enzymes: implications in cancer chemoprevention.

Author

Zhao J; Agarwal R

Address

Center for Cancer Causation and Prevention, AMC Cancer Research

Center, Denver, CO 80214 and University of Colorado

Cancer Center, University of Colorado Health Sciences Center, Denver,

CO 80262, USA.

Source

Carcinogenesis, 20(11):2101-8 1999 Nov

Abstract

Polyphenolic antioxidants are being identified as cancer preventive

agents. Recent studies in our laboratory have identified and

defined the cancer preventive and anticarcinogenic potential of a

polyphenolic flavonoid antioxidant, silymarin (isolated from milk

thistle). More recent studies by us found that these effects of

silymarin are due to the major active constituent, silibinin, present

therein. Here, studies are done in mice to determine the distribution

and conjugate formation of systemically administered silibinin in

liver, lung, stomach, skin, prostate and pancreas. Additional studies

were then performed to assess the effect of orally administered

silibinin on phase II enzyme activity in liver, lung, stomach, skin

and small bowel. For tissue distribution studies, SENCAR mice

were starved for 24 h, orally fed with silibinin (50 mg/kg dose) and

killed after 0.5, 1, 2, 3, 4 and 8 h. The desired tissues were

collected, homogenized and parts of the homogenates were extracted

with butanol:methanol followed by HPLC analysis. The

column eluates were detected by UV followed by electrochemical

detection. The remaining homogenates were digested with

sulfatase and beta-glucuronidase followed by analysis and

quantification. Peak levels of free silibinin were observed at 0.5 h after

administration in liver, lung, stomach and pancreas, accounting for

8.8 +/- 1.6, 4. 3 +/- 0.8, 123 +/- 21 and 5.8 +/- 1.1 (mean +/-

SD) microg silibinin/g tissue, respectively. In the case of skin and

prostate, the peak levels of silibinin were 1.4 +/- 0.5 and 2.5 +/-

0.4, respectively, and were achieved 1 h after administration. With

regard to sulfate and beta-glucuronidate conjugates of silibinin,

other than lung and stomach showing peak levels at 0.5 h, all other

tissues showed peak levels at 1 h after silibinin administration.

The levels of both free and conjugated silibinin declined after 0.5

or 1 h in an exponential fashion with an elimination half-life

(t((1/2))) of 57-127 min for free and 45-94 min for conjugated

silibinin in different tissues. In the studies examining the effect of

silibinin on phase II enzymes, oral feeding of silibinin at doses of

100 and 200 mg/kg/day showed a moderate to highly significant

(P < 0.1-0.001, Student's t-test) increase in both glutathione

S-transferase and quinone reductase activities in liver, lung, stomach,

skin and small bowel in a dose- and time-dependent manner. Taken

together, the results of the present study clearly demonstrate

the bioavailability of and phase II enzyme induction by systemically

administered silibinin in different tissues, including skin, where

silymarin has been shown to be a strong cancer chemopreventive agent,

and suggest further studies to assess the cancer preventive

and anticarcinogenic effects of silibinin in different cancer models.

Language

Eng

Unique Identifier

20014762

At 02:34 PM 11/14/2000 -0500, you wrote:

>Mechanisms of Action

>

>Silymarin's hepatoprotective effects are accomplished via several mechanisms

>including antioxidation,8 inhibition of lipid peroxidation,9 enhanced liver

>detoxification via inhibition of Phase I detoxification and enhanced

>glucuronidation,10,11 and protection of glutathione depletion.12 Studies have

>also shown silymarin exhibits several anti-inflammatory effects, including

>inhibition of leukotriene and prostaglandin synthesis, Kupffer cell

>inhibition, mast cell stabilization, and inhibition of neutrophil

>migration.13-17 >>>>>>>>

>

>This is showing that milk thistle effects phase 1. I have actually seen it

>cited on several different research articles online. Just do I search. I am

>extremely tired right now, maybe I will do it tonight. My doctor also told

>me that I have speedy phase 1 to stay AWAY from milk thistle.

>

>

>This list is intended for patients to share personal experiences with each

>other, not to give medical advice. If you are interested in any treatment

>discussed here, please consult your doctor.

Bravo

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